Surgical Intensive Care Unit Module

Christiana Care Health System

Introduction

Time in the Surgical Intensive Care Unit can be brutal and beautiful. Like most things in life, it is what you make it…

One way to make it more rewarding and an overall smoother experience is to pay attention to the details. As a mentor of mine used to say “details, details, details.” If you are diligent and pay attention to the details I guarantee your experience in the SICU will be significantly enhanced.

Basic expectations: 1. Communication is key. Everything discussed on rounds and throughout the day should be completed and that

means communicated efficiently through the team to ensure tasks are done. Tasks should not be signed out to night resident. Most of the work occurs when a new patient arrives. Always see the patient immediately, if something immediate needs to be done, do it. Put in orders, make sure they are on our lists (powerchart, e-signout), obtain ICU consents and Goals of Care discussion (document), and make sure there is a consult note:

- If from surgical team, they should do the note (contact if needed) - If Emergency General Surgery (EGS) or Trauma, NO consult note (some exceptions) - If from anyone else, we are responsible for the note 2. No job is above anyone, period. 3. When you need help, ask for it. This is a team, including the fellows and attendings.

Daily Routine: 1. Days start at 0500 sharp. Nights can be awful in the SICU so it’s not fair to keep the night resident there longer

than they should be, so please be on time. Meet by room 12 in the “Monkey Cage” at 0500. Night resident will be responsible for rounding on new admits from the day prior (0800) and overnight (**SCC patients).

2. You will run the list with the night resident and split up the remainder of patients who need to be rounded on. 3. Full sign out takes place in the SCCC Conference Room at 0800 (back of SICU). This is where we present any

significant issues, overnight events, critical patients, patients being posted out of the unit, or patients going to the OR. This should be brief (i.e. posted to 2C)

4. Formal walking rounds usually start around 0900 but this can vary depending on day and rounding attending. Basic format includes presenting overnight events followed by systems-based issues (ie, present your note from the morning), however, each attending will have their own style on rounds and we will adjust accordingly.

5. Whoever saw the patient will be presenting the patient. Another team member will be on e-Signout updating the list – be thorough! This makes everyone’s lives much easier when we have to do discharge summaries or go over daily plans. Another team member will be on PowerChart placing orders. It is critical that we get orders and e-signout updates in during rounds or the rest of the day we are playing catch-up.

6. Following completion of rounds, the flow of the day will really depend on what cases/procedures/tasks there are left to get done. We’ll address these on the fly. But ideally we’ll sit down as a team and quickly re-run the list, divide up tasks, and keep things running smooth. I may have to step out of rounds to take care of things at times.

7. Sign out to the night resident is at 1700 (except Wednesdays short call when it is 1900). This should be thorough and detailed.

Daily Orders: Make sure to order labs and chest x-rays when appropriate for the next day while rounding. Make sure to order a BMP with Ionized Ca, CBC, Mg, and Phos and any other appropriate labs. You must also select nurse vs. lab collect. If the patient has any sort of line: PICC, CVC, or arterial line, make sure the labs are nurse collect. CXRs should be ordered on appropriate patients for “Next Day AM.”

Call Schedule: On Wednesday one person stays for “short call” until 1900 instead of the usual 1700 because the night residents is in lecture until 1100 those days and needs the extra 2 hours to avoid violating work hours. On weekends we take either Friday night / Sunday morning or Saturday 24 hour call. Sunday night shift starts at 1500 (not 1700 like most days). Typically the trauma chief will be able to help round at 0500 on weekends in addition to the two people on call. The resident on the night before is free to go once they round, write notes and sign out to incoming resident. You are not expected to stay for table sign-out.

Always Have a Plan for a Problem: Generally, less is more in the ICU. A lot of what we do to patients is or can be harmful in one way or another, even if it is necessary (i.e. over sedation, positive pressure ventilation, antibiotics, polypharmacy, etc.) If we are doing something to a patient we should have a plan for either fixing the problem so they no longer need that intervention or have a stop date. Doing otherwise would be equivalent to indefinitely transfusing a patient that is actively bleeding.

Efficiency and Details: It is typically easiest to divide everything into systems and address each system while keeping in mind that they all work together. (Please see next page for example note and one way to keep things more organized)

NEUROLOGIC: (past medical history relevant to each system) - GCS: - Sedation: _ - Pain: _ - Neurologic Injury: - Seizure ppx: Keppra 500 BID (if indicated) - Neurosurgery Plan: - Plan: no active issues

PULMONARY: (PMH) - Intubated/Ventilated: plan for daily SBT with RSBI, pulmonary toilet - Vent Mode/Settings: _ - Chest Tube: yes_no

GENITOURINARY: (PMH) - Net Positive/Negative: _ - UOP: _ - Foley: yes_no - Electrolytes: _

CARDIOVASCULAR: (PMH) - Vasopressors: - Cardiac Meds:

HEMATOLOGY: (PMH) - Hgb: _ (I add each number for the day, 8.7 - 7.5 - 1U RBC - 8.8 - 8.9 etc. and include product given, i.e. 1U RBC) - Plts: _ (same as Hgb) - DVT ppx: PCBs/_

INFECTIOUS DISEASE: (PMH) - Temp: _ - WBC: _ - Cultures: _ - Antibiotics (stop date): _

GASTROINTESTINAL: (PMH) - Diet: _ - Last BM: _ - Bowel Regimen: _ - Stress Ulcer ppx: _

ENDOCRINE: (PMH) - Always think about acute and chronic issues. Consider home medications such as Synthroid or steroids - Steroids: yes_no - Diabetic: yes_no

LINES & TUBES: can you remove any of them to reduce risk of infection? - Central line: yes_no - Arterial line: yes_no - Foley: yes_no - Chest Tubes: yes_no

WOUNDS: assessing traumatic, surgical or pressure wounds and optimizing healing

Goals of Care: not_completed ICU Consent: not_completed

DISPOSITION: the most important question is “do they need to be in the SICU?” If yes, then ask “why” and assess ways to fix it. If no, then post them out of the SICU and stop charging them $4,000 per night.

Table of Contents

Neurology A. Pain Control, Sedation, Delirium, Agitation B. Neuromuscular Blocking Agents C. Traumatic Brain Injury / Traumatic Spine Injuries D. Seizures and Status Epilepticcus E. End of Life Care and Organ Donation F. Brain Death and Death in the SICU

Pulmonology G. Oxygen Delivery Devices and Goals of Oxygenation H. Noninvasive Mechanical Ventilation I. Mechanical Ventilation and the Different Modes J. Discontinuing Mechanical Ventilation K. Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Associated Lung Injury L. Pneumonia: Community-Acquired, Nosocomial and Ventilator-Associated Pneumonia M. Tracheostomy (and PEG): Optimal Timing and Management N. Chest Tube Management O. How to Read a Portable CXR

Cardiology P. Vasopressor & Inotropic Therapy Q. Shock and PA Catheter, PA Catheter Guide (click here) R. Hypertensive crisis

Nephrology / Urology S. Acid Base Disorders T. Diuresis and Diuretics U. Severe Electrolyte Abnormalities V. Renal Replacement Therapy

Endocrinology W. Diabetes, Diabetic Ketoacidosis and HONK

Gastroenterology X. Nutrition in Critical Illness Y. Stress Ulcer prophylaxis Z. Gastrointestinal Bleeding and Massive Transfusion AA.Acute Pancreatitis BB.Compartment Syndromes

Infectious Disease CC.Sepsis & Septic Shock DD.Clostridium Difficile

Hematology EE.Venous Thromboembolism: Prophylaxis and Treatment FF. Blood Products in the ICU and TEG

Procedures GG. Procedures in the SICU (Exploratory Laparotomy, Tracheostomy, PEG, Bronchoscopy)

Click on the “heading” of any page and it will return you to the Table of Contents

Resources

Helpful Resources:

- ACS (American College of Surgeons) TQIP Best Practice Guidelines (click here for link) - EAST (Eastern Association for the Surgery of Trauma) (click here for link) - Drug Reference: CCHS Portal -> Formulary -> CCHS Formulary -> Search Specific Drug - CCHS Trauma Management Guidelines: CCHS Portal -> Depts -> Trauma Program -> Christiana -> Trauma

Management Guidelines -> select specific guideline

Apps: - “MediCode” - Algorithms for BLS, ACLS, PALS, CPR and NRP - Christiana “CareRef” app - MedCalx - “ICU Trials” - brief summary of high yield literature

Literature (High Yield):

Neurology - PADIS Guidelines - Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/ mobilization), and Sleep

(disruption) (click here for link) - Guidelines for the Management of Severe Traumatic Brain Injury 4th Edition. The Brain Trauma Foundation,

2016 - ACS TQIP - Best Practice in the Management of Traumatic Brain Injury, 2017

Pulmonology - Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice

Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Infectious Disease Society of America Guidelines, 2016

- Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 2012 - ARDSnet.org (includes discussion and links to studies related to ARDS) - TRACMAN Trial - Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving

Mechanical Ventilation. Caring for the Critically Ill Patient, 2013 Cardiology

- POISE Trial - Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery: a randomised controlled trial. The Lancet, 2008

- Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock. CHEST, 2016 - Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive

care (PAC-Man): a randomised controlled trial. The Lancet, 2005 - Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit. Journal of

Cardiovascular Pharmacology and Therapeutics, 2015 Nephrology / Urology

- SAFE Trial - A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit. NEJM, 2004

- Continuous Renal-Replacement Therapy for Acute Kidney Injury. NEJM, 2012 Endocrinology

- NICE-SUGAR Trial - Intensive versus Conventional Glucose Control in Critically Ill Patients. NEJM, 2009 - CORTICUS Trial - Hydrocortisone Therapy for Patients with Septic Shock. NEJM, 2015

Gastroenterology - ASPEN Guidelines - Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult

Critically Ill Patient. Society of Parental and Enteral Nutrition, 2016 - CALORIES Trial - Trial of the Route of Early Nutritional Support in Critically Ill Adults. NEJM, 2014

Infectious Disease - STOP-IT Trial - Trial of Short-Course Antimicrobial Therapy for Intra-abdominal Infection. NEJM, 2015 - PRORATA Trial - Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units: a

multicentre randomised controlled trial. The Lancet, 2010 Hematology

- PCC - Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation. Journal of Critical Care, 2016

- ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. American College of Cardiology, 2017

- Idarucizumab for Dabigatran Reversal. NEJM, 2015 - Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. NEJM, 2019 - TRICC Trial - A Multi-center Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care.

NEJM, 1999

Neurology

A. Pain Control, Sedation, Delirium, Agitation

Commonly Used Non-Opioid Pain Medications

I. acetominophen (Tylenol): PO (liquid or tab) A. MOA: anelgesic mechanism not completely understood, antipyretic effect via direct action on the

hypothalamic heat-regulating center B. Dose: typically 650 mg q4h (do not exceed 4g/day) C. Metabolism: liver D. Excretion: urine (5-10% unchanged) E. Half-life: 2-4 hours (toxic metabolites accumulate in renal failure) F. Acetaminophen is largely converted to nontoxic glucuronate or sulfate conjugates and secreted in

the urine. A minor amount of acetaminophen is metabolized via the cytochrome P450 system to intermediates that can be toxic, particularly N-acetyl-p-benzoquinoneimine. Ordinarily, this intermediate is rapidly conjugated to reduced glutathione, detoxified and secreted. If levels of glutathione are low or the pathway is overwhelmed by high doses of acetaminophen, the reactive intermediate accumulates and binds to intracellular macromolecules that can lead to cell injury, usually through apoptotic pathways. Factors that increase the metabolism of acetaminophen through the P450 system (certain drugs, chronic alcohol use) or that decrease the availability of glutathione (fasting, malnutrition, alcoholism) can predispose to acetaminophen toxicity. Factors that affect downstream toxicity of acetaminophen metabolic intermediates may also affect toxicity. These factors are important in designing therapies for acetaminophen hepatotoxicity. (Detailed review found through the NIH)

G. CCHS does NOT currently carry IV acetaminophen (Ofirmev)

II. ketorolac (Toradol): NSAID - IV A. MOA: exact mechanism unknown, inhibits cyclooxygenase, reducing prostaglandin and

thromboxane synthesis B. Dose: 15-30 mg IV q6h (max 120mg/day, do not exceed 5 days) C. Metabolism: liver primarily D. Excretion: urine 91%, bile/feces 6%, Half-life: 5.3 hours E. Complications: acute kidney injury - decreased prostaglandin synthesis can lead to reversible

renal ischemia, a decline in glomerular hydraulic pressure (the major driving first of glomerular filtration), and AKI. Prostoglandin synthesis typically increases in setting of prolonged renal vasoconstriction (CKD, hypovolemia, older age, hypercalcemia), which can be inhibited by NSAID

III. gabapentin: PO A. MOA: exact mechanism largely unknown, blocks voltage-dependent calcium channels,

modulating excitatory neurotransmitter release B. Dose: neuropathic pain - 100-400 mg PO TID C. Metabolism: none D. Excretion. urine (100% unchanged), Half-life: 5-7 hours E. Complications: can cause changes in mental status F. Literature: Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory

Neurons with Additive Effects When Co-applied with Paracetamol (Acetaminophen). The Scientific World Journal, 2017

IV. ketamine: IV or PO - typically for intractable pain, often in patients with neurologic trauma A. Bolus (not intubated) or continuous (intubated) infusion (see power chart order set for specifics) B. Bolus: 0.5-3.5 mg/kg/hr, titrate by 0.25-0.5 mg/kg/hr as needed to reach target (Ideal BW) C. Continuous: 0.1-0.5 mg/min IV D. MOA: Ketamine exerts its analgesic, antidepressant, and psychomimetic effects via myriad

pathways. Its primary mechanism is as a noncompetitive antagonist at the phencyclidine binding site of N-methyl-D-aspartate (NMDA) receptors residing in the central nervous system (CNS), particularly in the prefrontal cortex and hippocampus, where it decreases the frequency of channel opening and duration of time spent in the active, open state.

E. Metabolism: liver F. Excretion: urine primarily (4% unchanged), feces <5%, Half-life: 2.5 hours

Neurology

G. 2018 Regional Anesthesia & Pain Medicine Guidelines: (click here for link)

Commonly used Opioids

I. oxycodone: PO A. MOA: bind to various opioid receptors, producing anesthesia and sedation B. Dose: 2.5-15 mg q4h C. Metabolism: liver D. Excretion: urine primarily (up to 19% unchanged), Half-life: 3.5-4 hours E. Complications: constipation, respiratory depression

II. hydromorphone (Dilaudid): PO/IV/PCA A. MOA: bind to various opioid receptors, producing anesthesia and sedation B. Dose: 0.5-4 mg IV q2-4h, 2-8 mg PO q4h, PCA (0.2 mg q12min, 0.1 mg continuous = 4.4mg/4h) C. Onset: IV ~15 minutes, PO ~30 minutes D. Metabolism: liver E. Excretion: urine primarily, Half-life: 2.4 hours F. Complications: constipation, respiratory depression

III. morphine: PO/IV/PCA A. MOA: bind to various opioid receptors, producing anesthesia and sedation B. Dose: 2.5-10 mg IV q2-6h, 15-30 mg PO q4h C. Onset: IV ~15 minutes, PO ~45 minutes D. Metabolism: liver E. Excretion: urine primarily (up to 2-12% unchanged), bile/feces 7-10%, Half-life: 2-4 hours F. Complications: constipation, respiratory depression

IV. fentanyl: IV/drip A. MOA: bind to various opioid receptors, producing anesthesia and sedation B. Dose: 25-100 mcg IV every 15-30 minutes until desired effect, drip in intubated patients C. Onset: 1-2 minutes D. Metabolism: liver E. Excretion: urine 75% (<10 unchanged), feces 9%, Half-life: 3.7 hours F. Complications: constipation, respiratory depression

Management of Constipation in the ICU I. Bowel Regimen:

A. All patients on opioids should be ordered for a bowel regimen that combines a stool softener and mild peristaltic stimulant unless otherwise contraindicated

B. Example: docusate sodium 100 mg po bid PLUS senna 2 tablets po qhs C. Bowel regimen should be adequately titrated with increasing opioid dose D. Typically will add Miralax +/- Dulcolax suppository (PR) for persistent constipation lasting >3

days unless otherwise contraindicated E. STAY AHEAD OF THE GAME (think of it like VTE prophylaxis)

Sedatives

I. midazolam (Versed): IV, pushes or drip A. MOA: binds to benzodiazepine receptors, enhances GABA effects B. Dose: 1-2 mg IV q2-5 minutes, 0.01-0.05 mg/kg/h IV for intubated patients C. Metabolism: liver D. Excretion: urine (<1% unchanged), Half-life: 2.5 hours (can be significantly prolonged with

drip, particularly in obese patients secondary to distribution) E. Complications: respiratory depression, bradycardia, tachycardia, bronchospasm

II. propofol (Diprivan): IV/drip A. MOA: induces hypnosis B. Dose: 100-200 mcg/kg/min IV drip, 20-50 mg IV prn C. Metabolism: liver D. Excretion: urine, Half-life: 3-12 hours, 1-3 days (after 10 day infusion), >70% during distributive

phase (with half-life of 2-30min) E. Complications: hypotension, respiratory depression, bradycardia, pancreatitis

Neurology

III. dexmedetomidine hydrochloride (Precedex): A. MOA: produces centrally mediated sympatholytic, sedative and analgesic effects (selective

alpha-2 adrenergic agonist) B. Dose: 0.2-1.4 mcg/kg/h IV C. Metabolism: liver D. Excretion: urine 95% (none unchanged), feces 4%, Half-life: 2 hours E. Complications: reflex bradycardia, hypotension, respiratory depression F. Good for weaning off ventilator and if short course of intubation is predicted G. Also frequently utilized for patients with EtOH withdrawal refractory to standard CIWA

Reversal Agents – Flumazenil and Naloxone • flumazenil (Romazicon)

1. Flumazenil is NOT intended for routine reversal of benzodiazepine-related sedation or to diagnose benzodiazepine-induced sedation.

2. Indications and Dosage: Suspected benzodiazepine overdose • Initial dose: 0.2 mg IV over 30 sec • If desired level of consciousness not obtained after 30 sec: 0.3 mg IV over 30 sec • Wait another 30 sec to determine level of consciousness • Further doses (if necessary): 0.5 mg IV over 30 sec at 1 min intervals • Maximum cumulative dose: 3 mg

• naloxone (Narcan) 1. To be used for complete or partial reversal of narcotics in suspected overdose or for

diagnostic / therapeutic purposes. 2. Dosing:

• Initial dose: 0.1-0.2 mg IV • Repeat doses of 0.4-2 mg every 2-3 min to a total dose of 10 mg. • Naloxone may be given IM or SC if IV route is not possible.

Delirium: DELIRIUMS mnemonic

D - Drugs (less is more) E - Emotional (anxiety, depression, psych) L - Lack of Drugs (EtOH, medication or drug withdrawal) I - Infection (UTI, PNA, etc) R - Retention (urinary, fecal) I - Intracranial Problems (TBI, CVA, Meningitis, Seizure) U - Uncontrolled Pain M - Metabolic (electrolytes, B12, thiamine, thyroid, adrenal, etc) / Myocardial (MI, Arrhythmia, CHF) S - Sensory (blindness, deafness, etc)

Agitation: When verbal techniques and soft restraints are not effective consider the following options - Three Major Classes include Benzodiazepines, 1st and 2nd Generation Antipsychotics - QT prolonging medications (i.e. antipsychotics) need EKG, generally avoid if QTc > 500 I. Mild: ensure patient is on home medications including anxiety and antipsychotic/depression meds

A. Seroquel 12.5 - 100 mg TID - PO (QT prolonging) II. Moderate: typically try single agent first

A. Droperidol 2.5-5mg q20min until effect reached - IM/IV (QT prolonging) - 1st Gen Antipsychotic B. Haloperidol 5mg q20min until effect reached - IV (QT prolonging) - 1st Gen Antipsychotic C. Zyprexa 5mg - PO/IM (QT prolonging) - 2nd Gen Antipsychotic (atypical) D. Geodon 10 - 20 mg - PO/IM (QT prolonging - 2nd Gen Antipsychotic (atypical) E. Midazolam 2.5-5mg q3-5min - IM/IV (rapid onset, 1-2 hour effect) F. Lorazapam 0.5-2 mg q10-30min - IM/IV (longer onset and longer effect, half-life 10-20 hours)

III. Severe: Consider combination of Antipsychotic and Benzodiazepine and/or switch class of medication

Link: UpToDate Algorithm

Neurology

B. Neuromuscular Blocking Agents Short-Acting:

I. Succinylcholine: - The only depolarizing NMB (acts like Ach and depolarizes membrane) - Resistant to acetylcholinestrase, not metabolized at junction leads to initial fasiculations followed

by flaccid paralysis (facial muscles first, diaphragm last) - Depolarization causes cells to lose K+ ions, typically increasing K by 0.5-1.0 mEq/L life-threatening

hyperkalemia has occurred in patients with denervated muscle caused by upper and lower motor neuron disease (spinal cord injury, stroke, demyelinating disease) and in burn and trauma patients (thought to be safe to give within 24 hours of trauma or burn)

- Dose: 0.3-1.1 mg/kg IV once for induction - Metabolism: plasma - Excretion: urine (10% unchanged), Half-life unknown

Intermediate-Acting:

I. cisatracurium (Nimbex): Commonly used in the SICU - Benzylisoquinolinium structure - binds motor end-plate cholinergic receptors - Minimal (if any) cardiovascular effects - Dose: 150-200 mcg/kg IV once for induction (typically use 10-20 mg for one dose) - Metabolism: Hoffman degradation (i.e. safe in setting of renal or hepatic impairment), 80% (pH

and temperature dependent break down -- acidosis/hypothermia will affect metabolism and prolong effect) and liver

- Excretion: urine 95% (<10 unchanged), feces 4%, Half-life: 22-29 minutes - Most commonly used in SICU for Trach, PEG, Bedside Abdominal Exploration or ARDS

II. roceronium (Zemuron): - MOA: antagonizes motor endplate acetylcholine receptors - Dose: 0.6 mg/kg IV once for induction - Metabolism: liver - Excretion: urine, bile, Half-life: 1.4-2.4 hours - Adverse Reactions: hypersensitivity, arythmies

III. vecuronium (Norcuron) - MOA: antagonizes motor endplate acetylcholine receptors (structural analogue of pancuronium) - Not vagolytic (minimal effect on BP and HR) - Dose: 80-100 mcg/kg IV once for induction - Metabolism: liver (50% excreted in bile), 35% renal excreted - Excretion: 25-50% in bile, 35% renal, Half-life: 65-75 minutes - Metabolite: 3-desacetylvecuronium (50% activity) - Adverse Reactions: prolonged blockade once discontinued compared to other agents

Long-Acting:

I. pancuronium (Pavulon) - MOA: antagonizes motor endplate eacetylcholine receptors - Vagolytic (add about 10 BPM on average to HR) - Avoid in patients with cardiovascular disease (risk of myocardial ischemia) - Dose: 60-100mcg/kg IV once for induction - Metabolism: 60-80% renal, 15-40% hepatic - Excretion: urine primary, bile/feces, Half-life: 1.4-2 hours - Metabolite: 3-hydroxypancuronium (50% activity)

Factors altering the effects of NMB - There are many drugs that can affect the action of neuromuscular blockers (potentiating or

antagonizing)

Neurology

- Aminoglycosides and clindamycin -- both decrease Ach release by blocking calcium influx - Increased magnesium levels - phenytoin, theophylline, hypercalcemia all can antagonize the effects of NMB

Acute Quadriplegic Myopathy Syndrome - Diffuse weakness persists long after drug and active metabolites are eliminated - Global motor deficit affecting muscles in both upper and lower extremities and decreased motor

reflexes - Presents as clinical triad of acute paresis, myonecrosis with increased CPK concentration,

abnormal EMG - No clear evidence of what places patients at risk - Possibly secondary to concurrent drugs (aminoglycosides, cyclosporine), hyperglycemia, or renal/

hepatic dysfunction - Concurrent administration of corticosteroids and NMB: NMB administration beyond one or two days

increases risk - Estimates approach 30% with greater than 3 days concurrent use shown to occur with all NMB's

when used with corticosteroids

NMB Selection is Based On: - Indication

- Rapid sequence intubation: - Etomidate - Succinylcholine - Rocuronium

- Non-rapid intubations - Vecuronium - Cisatracurium

- Drug characteristics (pharmacokinetics) - Patient characteristics - Adverse effects - Cost effectiveness

ALWAYS PROVIDE ADEQUATE SEDATION AND PAIN RELIEF TO PATIENTS ON NMB AGENTS

Neurology

C. Traumatic Brain Injury: Adapted from the Brain Trauma Foundation (2016) and ACS TQIP (2017)

Triage and Transport: Patients with a Glasgow Coma Scale (GCS) ≤ 13 or with a combination of TBI (GCS score ≤ 15) and moderate to severe extra-cranial anatomic injuries and Abbreviated Injury Score (AIS) ≥3 should be rapidly transported directly from the scene to the highest level trauma center available in a defined trauma system to allow for expedient neurosurgical assessment and intervention

Glasgow Coma Scale (GCS): I. GCS = Opens Eyes (none = 1, to pressure/pain = 2, to sound = 3, spontaneous = 4) Verbal (none =

1, Sounds = 2, Words = 3, Confused = 4, Oriented = 5) Motor (none = 1, extension/decerebrate = 2, abnormal flexion/decorticate = 3, normal flexion = 4, localization = 5, obeys commands = 6)

II. The GCS provides a reliable tool for assessing disturbances of consciousness across care paths III. Standardized approaches to GCS assessment and reporting are essential IV. The GCS should specify the score for each of the three components (eye, verbal, motor) when

reporting on individual patients; however, the motor portion correlates most strongly with the GCS as whole and is most predictive

V. The sum of the component scores (GCS 3-15) is relevant for comparisons at the group level for purposes of classification and prognosis

Mild brain injury = GCS ≥13 Moderate brain injury = GCS 9 - 12 Severe brain injury = GCS ≤8 = Intubation for airway protection

Intracranial Pressure Monitoring: rarely used in SICU at CCHS I. ICP monitoring is important, but it does not replace careful neurological and radiographic examination II. ICP monitoring is generally indicated in comatose patients (GCS ≤ 8) and if there is evidence of

structural brain damage on initial CT imaging III. ICP monitoring is generally not indicated in comatose patients without evidence of structural brain

damage or elevated ICP (compressed/absent basal cisterns) on initial CT imaging. Patients may be observed with repeat CT imaging and forego ICP monitoring if there is no progression

Neurology

IV. ICP monitoring should be considered in patients with a GCS > 8 whohave structural brain damage with high risk for progression (large/ multiple contusions, coagulopathy)

V. ICP monitoring should be considered in patients who require urgent surgery for extracranial injuries,who need mechanical ventilation because of extracranial injuries, or who evidence progression of pathology on CT imaging or clinical deterioration

VI. The preferred method for ICP monitoring is an external ventricular drain (EVD) because it is both diagnostic (measures ICP) and therapeutic (allows for drainageof cerebrospinal fluid (CSF)

Management of Intracranial Hypertension: I. ICP is a global measure that cannot identify the specific mechanism(s) of pressure elevation.

Additional neuro-monitoring and assessment of cerebral auto-regulation may help to individualize treatment

II. The recommended “3-tiered” approach to ICP management utilizes various treatments to target different mechanisms. Higher tiers reflect more intensive management that is associated with increased complications

III. Failure to control ICP/CPP within one tier, should prompt rapid progression to the next tier’s treatment options

IV. Repeat CT imaging and neurological examination should be considered to rule out the development of surgical lesion and guide management

Tier 1: 1. Head of bed elevated at 30 degrees (reverse Trendelenburg) to improve cerebral venous outflow 2. Sedation and analgesia using recommended short-acting agents (for example, propofol, fentanyl,

midazolam) in intubated patients 3. Ventricular drainage performed intermittently. Continuous drainage is not recommended unless an

additional ICP monitor is placed, as when the drain is open, it does not accurately reflect the true ICP 4. Repeat CT imaging and neurological examination should be considered to rule out the development

of a surgical mass lesion and guide treatment 5. If ICP remains ≥ 20 - 25 mmHg proceed to Tier 2

Tier 2: 1. In patients with a parenchymal ICP monitor an EVD should be considered to allow for intermittent

CSF drainage 2. Hyperosmolar therapy should be given intermittently as needed for ICP elevation and not on a routine

schedule. - Mannitol should be administered in intermittent boluses (0.25 - 1 gm/kg body weight). Caution

should be taken in the hypovolemic patient when osmotic diuresis is instituted with mannitol. The serum sodium and osmolality must be assessed frequently (every 6 hours) and additional doses should be held if serum osmolality exceeds 320 mOsm/L. Mannitol may also be held if there is evidence of hypovolemia

- Hypertonic saline may be administered in intermittent boluses of 3% sodium chloride solution (250 ml over 1⁄2 hour) or other concentrations (e.g., 30cc of 23.4%). Serum sodium and osmolality must be assessed frequently (every 6 hours) and additional doses should be held if serum sodium exceeds 160 mEq/L

3. Cerebral autoregulation should be assessed (see Advanced Neuromonitoring section). If the patient is not autoregulating, the CPP goal should be lowered to reduce ICP (to no less than 50 mm Hg). Additional neuromonitoring (e.g., PbtO2, SjvO2, CBF) may help determine optimal CPP

4. PaCO2 goal of 30 - 35 mmHg should be maintained, as long as brain hypoxia is not encountered. Additional neuromonitoring(e.g., PbtO2, SjvO2, CBF) may help determine optimal PaCO2

5. Repeat CT imaging and neurological examination should be considered to rule out development of a surgical mass lesion and guide treatment

6. Neuromuscular paralysis achieved with a bolus “test dose” of a neuromuscular blocking agent should be considered if the above measures fail to adequately lower ICP and restore CPP. If there is a positive response, continuous infusion of a neuromuscular blocking agent should be employed (Tier 3)

7. If ICP remains ≥ 20 - 25 mmHg proceed to Tier 3

Neurology

Tier 3: 1. Decompressive hemi-craniectomy or bilateral craniectomy should only be performed if treatments in

Tiers 1 and 2 are not sufficient or are limited by development of side effects of medical treatment 2. Neuromuscular paralysis via continuous infusion of a neuromuscular blocking agent can be employed

if there is a positive response to a bolus dose. The infusion should be titrated to maintain at least two twitches (out of a train of four) using a peripheral nerve stimulator. Adequate sedation must be utilized

3. Barbiturate or propofol (anesthesia dosage) coma may be induced for those patients who have failed to respond to aggressive measures to control malignant intracranial hypertension, however it should only be instituted if a test dose of barbituate or propofol results in a decrease in ICP, thereby identifying the patient as a “responder.” Hypotension is a frequent side effect of high dose therapy with these agents. Meticulous volume resuscitation should be ensured and infusion of vasopressor/inotropes may be required. Prolonged use or high dose of propofol can lead to propofol infusion syndrome. Continuous EEG may be used to ensure targeting of the infusion to burst suppression

4. Hypothermia (<36 °C) is not currently recommended as an initial TBI treatment. Hypothermia should be reserved for “rescue” or salvage therapy after reasonable attempts at ICP control via the previous Tier 3 treatments have failed

Indications for Surgical Intervention: I. Epidural Hematoma (EDH)

A. Indications: 1. EDH greater than 30 cm3 or with greater than 5 mm midline shift should be surgically

evacuated regardless of the patient’s Glasgow Coma Scale (GCS) score. 2. EDH less than 30 cm3 and with less than a 15-mm thickness and with less than a 5 mm

midline shift (MLS) in patients with a GCS score greater than 8 without focal deficit can be managed nonoperatively with serial computed tomographic (CT) scanning and close neurological observation in a neurosurgical center.

B. Timing/Method: 1. It is strongly recommended that patients with an acute EDH in coma (GCS score < 9) with

anisocoria (unequal pupils) undergo surgical evacuation as soon as possible. 2. There are insufficient data to support one surgical treatment method. However, craniotomy

provides a more complete evacuation of the hematoma. II. Subdural Hematoma (SDH)

A. Indications: 1. An acute subdural hematoma (SDH) with a thickness greater than 10 mm or a midline

shift greater than 5 mm on computed tomographic (CT) scan should be surgically evacuated, regardless of the patient’s Glasgow Coma Scale (GCS) score.

2. All patients with acute SDH in coma (GCS score < 9) should undergo intracranial pressure (ICP) monitoring.

3. A comatose patient (GCS score < 9) with an SDH less than 10-mm thick and a midline shift less than 5 mm should undergo surgical evacuation of the lesion if the GCS score decreased between the time of injury and hospital admission by 2 or more points on the GCS and/or the patient presents with asymmetric or fixed and dilated pupils and/or the ICP exceeds 20 mm Hg.

B. Timing/Method: 1. In patients with acute SDH and indications for surgery, surgical evacuation should be

performed as soon as possible. 2. If surgical evacuation of an acute SDH in a comatose patient (GCS < 9) is indicated, it should

be performed using a craniotomy with or without bone flap removal and duraplasty. III. Skull Fractures

A. Indications: 1. Patients with open (compound) cranial fractures depressed greater than the thickness of

the cranium should undergo operative intervention to prevent infection. (i.e. if outer cortical layer of bone segment is depressed deeper than the inner cortical layer of the skull)

2. Patients with open (compound) depressed cranial fractures may be treated non-operatively if there is no clinical or radiographic evidence of dural penetration, significant intracranial

Neurology

hematoma, depression greater than 1 cm, frontal sinus involvement, gross cosmetic deformity, wound infection, pneumocephalus, or gross wound contamination.

3. Nonoperative management of closed (simple) depressed cranial fractures is a treatment option.

B. Timing/Methods: 1. Early operation is recommended to reduce the incidence of infection. 2. Elevation and debridement is recommended as the surgical method of choice. 3. Primary bone fragment replacement is a surgical option in the absence of wound infection at

the time of surgery. 4. All management strategies for open (compound) depressed fractures should include

antibiotics.

Tracheostomy: I. If level of consciousness remains persistently depressed, TBI patients should undergo tracheostomy

to facilitate liberation from mechanical ventilation; this can decrease the time on the ventilatory and ventilator-induced lung injury

II. Relative contraindications to tracheostomy include high intracranial pressure, hemodynamic instability, and severe respiratory failure with significant ventilatory requirements

III. All TBI patients deemed not likely to improve rapidly should be considered for early tracheostomy, within 7-8 days of injury

Timing of Pharmacologic Venous Thromboembolism Prophylaxis: I. Patients with TBI are at high risk for venous thromboembolism (VTE), with rates as high as 20-30% II. VTE prophylaxis should be considered within the first 72 hours following TBI in most patients. Earlier

initiation of pharmacologic prophylaxis (<72 hours) appears to be safe in patients at low risk for progression of intracranial bleeding and have a stable repeat head CT scan. We generally start at 48 hours after stable imaging, see trauma guidelines on portal.

III. Placement of a prophylactic inferior vena cava (IVC) filter should be considered in patients at highrisk for progression of intracranial hemorrhage who cannot receive pharmacologic prophylaxis, including those with lower extremity long bone fractures or pelvic fractures in addition to TBI

IV. Please see CCHS Guidelines through the home portal and trauma department

Seizure Prophylaxis: will generally give Keppra 500mg q12h PO or IV for 7 days for TBI - Goal is to reduce further injury/metabolic stress to the brain from potential seizure

Reversal of anticoagulation: See anticoagulation reversal guidelines through trauma department on home portal including indications for K-centra (See “Helpful Resources” on page 3) - K-centra, Reversal of Oral Anticoagulants, Intracranial Hemorrhage (Traumatic and Non-Traumatic)

Traumatic Spinal Injures: ASIA Impairment Scale (click link)

The extent of spinal cord injury (SCI) is defined by the American Spinal Injury Association (ASIA) Impairment Scale (modified from the Frankel classification), using the following categories:

A = Complete: No sensory or motor function is preserved in sacral segments S4-S5

B = Incomplete: Sensory, but not motor, function is preserved below the neurologic level and extends through sacral segments S4-S5

C = Incomplete: Motor function is preserved below the neurologic level, and most key muscles below the neurologic level have a muscle grade of less than 3/5

D = Incomplete: Motor function is preserved below the neurologic level, and most key muscles below the neurologic level have a muscle grade that is greater than or equal to 3/5

E = Normal: Sensory and motor functions are normal

Neurology

D. Seizures and Status Epilepticcus

Seizure – sudden change in baseline electrical activity resulting in physiologic change in patient

Types - Simple (no loss of consciousness) versus complex (loss of consciousness) - Partial versus generalized

Causes of status epilepticus: Number one cause is medication non-compliance. - Withdrawal syndrome - Ischemia - Remote structural changes - Electrolyes – Na, Ca, Mg - Endocrine – hypoglycemia, hyperthyroid - Hypercarbia

- Hypoxia - Uremia - Fulminate Hepatic failure - Complication of medication- theo/ buproprian/

lithium - Traumatic Brain Injury

What tests are needed? - EEG/CT/MRI - Imaging is not needed for ETOH withdrawal unless clinical picture suggests another

cause (e.g not waking up, head laceration) - Lumbar puncture is only useful when malignancy, subarachniod bleed or infection is suspected

Definitions: I. Status epilepticcus - The term status epilepticcus refers to the occurrence of a single unremitting

seizure with duration longer than 5 to 10 minutes or frequent clinical seizures without interictal return to baseline.

II. Refractory status epilepticcus - continual seizures after 1-2 meds have been tried 20% of these patients go on to have persistent neurological defects - behavior, memory, emotional

III. Incidence of status epilepticcus - Less than 1 % of all seizures

Management: ABC’s (as always) 1. Protect the airway 2. Aspiration precautions (roll the patient to the side if vomiting) 3. Move to icu (if you are not already in the ICU) 4. Suppress fever 5. Control seizures with medications

Medications: 1. Benzodiazepines:

- Ativan- gets to the brain quickly and stays around for 4-6 hours, dose – 2mg , repeat PRN - Valium- lipid soluble, gets to brain quickly, but goes to fat stores quickly 20 min needs re-dosing.

Stable in vial for long time so usually in code cart 7mg followed by 7mg - Versed

2. Barbiturates 3. Phenytoin (Dilantin) 20mg/kg – side effects include hypotension and skin irritation 4. Fosphenytoin – parent compound, hydrolyzed to phenytoin, same dose, for pts who are hypotensive,

no skin irritation 5. Propofol 6. Etomidate 7. Halothane

CALL NEURO-CRITICAL CARE AND CONSIDER EEG

Neurology

E. End of Life Care and Organ Donation

I. Introduction: 20% of all deaths in the US occur in the ICU. The majority of these deaths occur in the setting of life-support withdrawal. ICU care enlists the input of patients’ family more than any other setting. Much of the care of our ICU patients includes building trust, as well as bereavement/emotional support of the family. The most important/yet least achieved factor associated with family satisfaction with their loved-ones’ care is communication. (Levy et al Crit Care Med 2006)

II. Communication: Arrange formal family meeting for dying patients, in addition to informal updates 1. Plan ahead: who will be there, family can write down questions in preparation 2. Utilize a comfortable room away from ICU when possible 3. Offer opportunity for family to tell you about the patient’s life - this will help you and them

understand pt and their values. (i.e. “Can you tell me about your loved one”) 4. Find out what family understands about diagnosis, treatments, prognosis 5. Provide additional information about diagnosis treatments, prognosis in straightforward

manner. It is Ok to use words like ‘dying’. 6. Try to align medical team’s goals to family’s wishes, different families want different levels of

decision-making and it is useful to assess this early to avoid delaying decision making 7. Don’t use terms like ‘withdraw care’, instead, talk about changing direction of care from cure

to palliative/comfort care. 8. Acknowledge emotional burden on families, offer spiritual assistance 9. Summarize - diagnosis, prognosis, plan decided on at the end of the meeting 10. Family satisfaction is higher when the family does most of the talking.

III. Palliation: pain control and patient comfort are paramount at end-of-life. Prolonging inevitable death is NOT palliative. A. Our palliative care team is an extremely helpful resource and involving them can be helpful

in answering families questions and facilitating the best care for the patient . B. Stopping all interventions will not necessarily result in increased comfort (labs, radiographs,

frequent vitals, aggressive pulmonary toilet, frequent turning, antibiotics, pressors) C. Mechanically ventilated patients may be terminally extubated to humidified air or 02, or terminally

weaned to T piece. The method is often attending preference-though terminal extubation is probably preferable allowing for greater interaction between the patient and family. Terminal weaning may be used if a patient has copious secretions.

D. Dying patients experience no increased discomfort after discontinuing artificial hydration or nutrition.

E. Morphine is first line treatment of pain and dyspnea and should not be withheld for fear of hastening death. Benzos for anxiety. Antiemetics as needed.

IV. Gift of Life (GOL): Organ Donation A. Do not initiate discussion of organ donation with patients or family. This should be brought

up and addressed by the Gift of Life team separately to avoid any potential ethical or legal dilemmas.

B. It is ok to draw labs, etc in order for the GOL team to assess potential donation for a patient C. Once a patient/family has made the choice to pursue GOL and documentation has been signed

we will often perform more detailed assessment of potential for organ donation via labs, imaging (ECHO), and procedures (bronchoscopy) which will often be requested by the GOL team.

D. GOL has an extensive team including physicians and surgeons who will request certain interventions to optimize potential for organ donation and should be followed if family has agreed to pursue organ donation and appropriate documentation has been completed.

E. Depending on family preference and certain protocol (dictated by GOL), care can either be withdrawn in the ICU or in the Operating Room, or care can be continued with the understanding that if patient does die, despite our efforts, that we would be prepared to pursue organ donation.

Neurology

F. Brain Death and Death in the SICU

Clinical diagnosis: if complete and irreversible cessation of all brain function (including Brainstem); confirmatory testing not needed.

Who: Adults and children > 5 yr of age (if < 5, consult pedi neurologist or neurosurgeon)

Notify: Organ Bank (Federal Law) when anticipated (1-800-446-6362)

Testing Performed by Neuro-Critical Care Certified Personal: Giberson, Cipolle, Fulda or NCC attending

Prerequisites: if “NO” to any of the below, confirmatory testing in addition to clinical exam is is required I. Absence of any neuromuscular paralyzing drug II. T > 32.2 degrees C = 90 degrees F, (CCHS T>36 degrees C) III. Absence of endogenous metabolic intoxication IV. Negative toxicology screen if indicated (negative drug screen required), Barbiturate level < 1 mg% V. Absence of severe hypotension (SBC >100), significant cardiopulmonary or neurological disease VI. Absence of hypoxia, PaO2 > 50 mm Hg or SaO2 > 85%

Clinical Criteria: I. Unresponsive coma, cerebral unresponsiveness; No movement to painful stimuli, withdrawal,

seizures, posturing, or other muscular movement. May have spinal cord reflexes. II. Apnea testing: No spontaneous respiration in presence of adequate CO2 drive

A. Apnea test is done at bedside; tests medullary/brainstem response to p CO2 drive (in absence of significant cardiopulmonary disease or neuromuscular paralysis/disease).

B. Procedure: requires passive oxygenation of trachea with 100% O2 (4 L/m; no MV) to allow CO2 to rise without hypoxia. ABG is drawn at 0, 5, 10 min and pt observed; placed back on MV at 10 min. Baseline paCO2 = 35-45 torr, and PaO2 >80 torr (orSaO2 >95%)

C. Pt is observed for duration of test: if there is no spontaneous respiratory efforts and paCO2 has risen to > 60 torr, apnea is present

D. STOP the test if SaO2 falls to < 90%, if loss of V.S., or if respiratory efforts noted. E. DOCUMENT test results in Progress Note and ICU Flow Sheet; include times, V.S., ABG, SaO2,

observations and personnel present. III. Absent brainstem reflexes; absence of pupillary response to light, corneal reflex, gag reflex,

oculocephalic and oculovestibular reflex IV. Duration of Observation; Persistence for > 24 h. Observation < 24 hr is permissible if structural brain

damage and dx is certain.

Confirmatory Testing: (not required for clinical dx of brain death) I. Four vessel cerebral angiogram demonstrating absence of blood flow to cerebrum and brainstem II. Radionuclide blood flow study (not adequate alone in some situations) III. Electrocerebral silence on EEG, may supplement clinical testing.

DOCUMENTATION: MUST BE COMPLETED ON ALL PATIENTS WHO DIE IN THE SICU 1. Death Note: brief progress note in PowerChart with exam, cause and time of death 2. Autopsy Form (nursing will provide): includes cause of death and autopsy request forms

- Attending can sign the following morning after patient leaves the ICU 3. Discharge Summary: needs to be completed on all patients the same as if they were discharged

Pulmonary

G. Oxygen Delivery Devices and Goals of Oxygenation

I. Oxygen cascade: describes the process of declining oxygen tension from atmosphere to mitochondria. At sea level, atmospheric pressure is 760mmHg. Oxygen makes up 21% of atmospheric gases (760mmHg x 0.21) so the partial pressure of oxygen in the atmosphere is 159mmHg. During respiration air is humidified reducing atmospheric pressure by 47mmHg to 713mmHg so the maximal inspired partial pressure of oxygen is 149mmHg. Once air enters the lungs it meets up with carbon dioxide, which further dilutes oxygen concentration (see alveolar air equation, part VI). Therefore, the maximal oxygen concentration in the alveolar space depends on barometric pressure, the fraction of oxygen in inspired air, and the concentration of CO2 in the alveolar space.

II. Causes of low blood oxygen. A. Atmospheric causes

1. Decreased fraction of inspired oxygen (FiO2) - easiest to control 2. Decreased barometric pressure - hyperbaric oxygen therapy

B. Cardiopulmonary causes 1. V/Q mismatch (normal ventilation and perfusion but mismatched) 2. Shunt (perfusion without ventilation) 3. Diffusion defect (think interstitial edema, etc.) 4. Decreased cardiac output

III. Oxygen carrying capacity: Ca02 A. Ca02 = [1.34 x Hb x (SaO2/100)] + 0.003 x PaO2

1. We can control Hb and SaO2 to some degree, PaO2 has minimal effect on CaO2 (see below) B. Oxygen is carried in blood in two forms.

Pulmonary

1. Bound (Saturation) to hemoglobin (Sa02 - largest component) - Each gram of hemoglobin can carry 1.34ml of oxygen. Hemoglobin has 4 binding sites for oxygen, and if all are occupied then the oxygen capacity would be saturated. Under normal conditions, the hemoglobin is 97% to 98% saturated. Assuming a hemoglobin concentration of 15g/dl O2 content is approximately 20ml/100ml. With a normal cardiac output of 5 l/min, the delivery of oxygen to the tissues at rest is approximately 1000 ml/min: a huge physiologic reserve.

2. Dissolved (Pressure) in blood (Pa02) - Dissolved oxygen follows Henry’s law – the amount of oxygen dissolved is proportional to the partial pressure. For each mmHg of PO2 there is 0.003 ml O2/dl (100ml of blood). If this was the only source of oxygen, then with a normal cardiac output of 5L/min, oxygen delivery would only be 15 ml/min or roughly 1.5% of total

IV. Oxygen Delivery: D02 A. DO2 = [1.39 x Hb x SaO2 + (0.003xPaO2)] x CO = Ca02 x CO B. The Delivery of oxygen (DO2) to the tissues is determined by:

1. The amount of oxygen in the blood (Ca02) - mainly determined by Hb and SaO2 2. The cardiac output (CO = SV x HR)

V. Oxygen Extraction: A. Fick equation: This is computed by determining the amount of oxygen that has been lost between

the arterial side and the venous side and multiplying by the cardiac output. In the following equation, VO2 is the oxygen consumption per minute, CaO2 is the content of oxygen in arterial blood, and CvO2 is the content of oxygen in venous blood. Since hgb remains constant in the equation, you only need to obtain SaO2 and SvO2 to calculate VO2.

VO2 = CO x (CaO2-CvO2) mlO2/min

VI. What is the alveolar air equation? A. PA02 = PiO2 - (PaCO2 / R) = 150 - (40 / 0.8) = 100 at sea level (99.7 to be exact)

1. Barometric pressure - the pressure at any point in the Earth's atmosphere (760 at sea level) 2. PiO2 = pressure of inspired oxygen = FiO2 x (barometric pressure – saturated vapour

pressure of H20) = 0.21 x (760 – 47) = 150 3. R = Respiratory Quotient = CO2 eliminated / O2 consumed = 0.8 4. What is the highest PaO2 you can achieve on RA? Assuming a CO2 40.

Answer: 100 but dependent on A-a gradient

VII.What is A-a gradient? A. A-a gradient = PAO2 - PaO2 B. What is the highest PaO2 you can achieve on RA? Assuming a CO2 40 and an A-

a gradient of 10. Answer: 90 C. Normal A-a gradient = (Age+10) / 4 = 2.5 + (2.5 x every decade old)

VIII. How much oxygen should I administer to a hypoxic patient? A. Only marginal increases in oxygen content occur with saturations above 88-90% so this should be

your goal. In the severely hypoxemic pt always start with 100% oxygen, and wean FiO2 as tolerated. Remember: oxygen toxicity occurs over a longer period of time (i.e. short-term risk of low oxygen is greater than short-term risk of administering too much oxygen)

IX. Oxygen Toxicity: Initial concern for oxygen toxicity came from the discovery that therapeutic oxygen causes blindness in premature babies with respiratory distress syndrome. Observational studies in adults suggest that high inspired oxygen may lead to acute lung injury. These observations are supported by animal models of oxygen- induced lung toxicity. In animal models, the extent of injury appears to depend on 1) The FiO2, 2) The duration of exposure, 3) The barometric pressure under which exposure occurred. It appears that the critical FiO2 for toxicity is above 60 mm Hg. Since oxygen is a drug, the goal should always be to minimize FiO2. We can control FiO2 (keep less than 60 mm Hg) and time of exposure (minimize).

Pulmonary

X. Oxygen Delivery Devices- Oxygen can be delivered to the upper airway by a variety of devices. The performance of a particular device depends: 1) flow rate of gas out of the device, and 2) inspiratory flow rate created by the patient. In the ideal device, gas flow exceeds the patient’s peak inspiratory flow so as not to entrain air from the atmosphere (i.e. patient only gets desired FiO2 delivered). A. Variable performance devices: all function by creating an oxygen reservoir

1. Nasal cannula: The premise behind nasal cannula is to use the dead space of the nasopharynx as a reservoir for oxygen. When the patient inspires, atmospheric air mixes with the reservoir air in the nasopharynx. The final FIO2 depends on the flow of oxygen from the nasal cannula, the patient’s minute ventilation and peak flow. For most patients, each addition 1 liter per minute of O2 flow with nasal cannula represents an increase in the FiO2 by 3%. So 1 liter is 24%, 2 liters is 27% and so on. At 6 liters (40%), it is not possible to raise the FiO2 further, due to turbulence in the tubing and in the airway. There are a couple of problems with nasal cannula: 1) they need to be positioned at the nares, 2) effectiveness is influenced by the pattern of breathing - there appears to be little difference whether the patient is a mouth or a nose breather, but it is important that the patient exhale through their mouth to maintain the reservoir. The advantage of nasal cannula is patient comfort.

2. Face mask: Standard oxygen masks provide a larger reservoir than the nasopharynx. In individual patients FIO2 can vary greatly depending on flow oxygen into the mask and the flow rates generated by the patient.

3. Non-rebreather face masks and High-flow oxygen: Oxygen enters these masks at a very high flow rate. For non-rebreather masks a large reservoir is attached to the mask to store oxygen. Theoretically these devices could provide 100% FiO2 to the patient; however, because patients using these devices tend to have very high inspiratory flow rates and the seal of the mask around the patients mouth is never complete FiO2 is often significantly less than 100% (usually in 70-80% range).

Pulmonary

H. Noninvasive Mechanical Ventilation: Definition: The delivery of mechanical ventilation to the lungs without an endotracheal tube or tracheostomy in the airway (i.e. ventilation without a completely sealed system which is typically only provided with a cuff on an endotracheal tube or tracheostomy)

Modes of noninvasive ventilation (NIV): I. Negative pressure:

A. Mechanism of negative pressure ventilation: delivery of sub-atmospheric pressure around chest and abdomen (creating a vacuum effect), which results in the expansion of the chest and air being drawn into the lungs through the mouth and nose. Expiration will occur passively when the pressure around the chest walls returns to normal atmospheric pressure. Negative Pressure ventilation attempts to simulate normal breathing and causes the least trauma to the lungs.

B. Drawbacks with negative pressure ventilation: 1. Problems with correct fitting and portability 2. Difficulty in application and removal of the device-requiring attendants 3. Must sleep in supine position

C. Indications for negative pressure ventilation: (Not used very often since the development of positive pressure nasal/face interfaces) 1. Chronic respiratory failure secondary to neuromuscular disease (i.e polio, muscular

dystrophy). Generally used for nocturnal ventilatory support, with the patient breathing spontaneously during the day.

2. Acute respiratory failure- there are 2 different studies which examined the use of the iron lung and poncho wrap (respectively) in COPD patients with acute respiratory failure. Both studies demonstrated the effectiveness of negative pressure ventilation to correct CO2 retention.

D. Types of negative Pressure Ventilation 1. Iron lung: Used primarily during the polio epidemic in the 1950’s 2. Cuirass/shell: A shell or cage surrounds the chest and is connected to a portable ventilator 3. Raincoat/poncho: A tight fitting suit connected by hoses to a portable ventilator 4. Pneumowrap 5. Rocking bed: Patient is placed on a bed which rocks rapidly flat to upright which also induces

diaphragmatic motion as the abdominal contents shift 6. Pneumobelt: A device designed as a belt with a bladder which inflates and deflates with air in

a cyclic pattern. The diaphragm moves in response to changes in intra- abdominal pressure

II. Positive pressure A. This is the most common mode of noninvasive ventilation utilized presently. The interface with

the patient can be a full face mask, a nasal mask, nasal pillows or BiPAP.

B. Mechanism of positive pressure ventilation: delivery of either a supra-atmospheric pressure or a preset tidal volume which then inflates the lungs. Exhalation is also a passive event, relying on the elastic recoil of the lung to deflate the lung until equilibration with atmospheric pressure or PEEP.

C. Benefits of positive pressure noninvasive ventilation 1. Avoid intubation and the associated risks and complications 2. Preservation of swallowing and speech 3. Preservation of cough reflex 4. Improve gas exchange 5. Reduction of work of breathing by resting respiratory muscles

D. Absolute/Relative contraindications: 1. Decreased mental status 2. Uncooperative 3. Unstable hemodynamics

Pulmonary

4. Copious secretions and unable to protect airway.

E. Drawbacks to positive pressure ventilation: 1. Interface difficulties- discomfort from mask, headgear, or straps 2. Air leak 3. Nasal pain, erythema, or skin breakdown from mask 4. Nasal congestion or dryness 5. Nasal bridge ulceration 6. Eye irritation from air leak blowing into eyes 7. Gastric distention - especially important in patients status post GI surgery 8. Aspiration

F. Types of Positive Pressure: 1. BiPap 2. Portable ventilator (LP-6, LP-10)

III. Initiation of Non-invasive Positive Pressure Ventilation (NIPPV): A. BiPAP (Bilevel Positive Airway Pressure)

1. Uses a pressure targeted strategy: 2. Inspiratory pressures (IPAP) can be set from 8-20 cm H20 of pressure (think of IPAP as

pressure support). As the pressure increases, the more uncomfortable it will feel for the patient. Generally start between 8-11 cm H20.

3. Expiratory pressure (EPAP) is set at 3-6 cm H20. Think of this as PEEP. 4. The difference or “step” between the IPAP and EPAP is the amount of support the patient is

getting. If the patient requires more ventilation, gradually increase the IPAP level. 5. The ventilator rate can also be set- a back-up rate can be chosen below the patient’s

spontaneous rate to be assured the patient will not develop apnea. One can choose a higher ventilator rate to prevent periods of prolong apnea and allow rest of respiratory muscles.

6. If oxygenation needs to be improve, one can either increase the amount of oxygen in the circuit, or one can increase the EPAP level. Remember if EPAP level is increased TV will decrease. To offset this, one can increase the IPAP level the same increment as the increase in the EPAP.

7. CPAP (Continue Positive Airway Pressure) - single pressure setting that is continuous

B. Portable ventilator (LP-6, LP-10, LTV) 1. Essentially mechanical ventilation with a poor seal compared with ETT or Trach 2. Set up a volume targeted strategy - tidal volumes need to be higher than invasive ventilation 3. Tidal volume 10-15cc/kg is used. This compensates for air leak through the mouth and

around the mask 4. A respiratory rate can be chosen as in standard ventilation. Check adequacy of ventilation/

oxygenation with ABG. 5. Increase the tidal volume or the respiratory rate if the minute ventilation needs to be

increased. Similarly, decrease the tidal volume or the respiratory rate if the patient is being over-ventilated.

6. Oxygen supplementation is provided in line with the circuit.

C. Patients when initiated on NIPPV are often anxious and initially uncomfortable. They usually require 1:1 assistance by a respiratory therapist to become acclimated to the technique and make fine tuning adjustments to the flow rate and pressures. It may take an hour for the patient to become comfortable. Monitoring of the heart rate, respiratory rate and ABGs will determine the effectiveness of NIPPV in correcting acute respiratory failure. If at any point, the patient is worsening conversion to endotracheal tube should be considered.

IV. To wean a patient from noninvasive ventilation: A. Improved oxygen saturation on a low oxygen flow rate B. Respiratory rate < 24/min C. Interrupt for short periods for talking, eating, drinking and assess tolerance

Pulmonary

I. Mechanical Ventilation and the Different Modes

I. 1. Initiating Mechanical ventilation A. Aim: Provide adequate ventilation and oxygenation without inducing barotrauma/volume trauma.

Allow respiratory muscles to rest if patient is too fatigued to continue breathing independently. B. After intubation: Confirm ETT placement by:

1. End tidal CO2 monitor (single best test) - quantitative or color 2. Auscultation: Listen for bilateral breath sounds (unilateral breath sounds - consider right main-

stem bronchus intubation or pneumothorax) 3. CXR - confirm position (5 +/- 2 cm above the carina) 4. Order sedation medications and restraints if needed

II. Initial Settings: generally start with volume based settings (Assist Control - see part III below) A. FiO2: Start with 100% FiO2, wean to goal of less than 60% (see previous “Chapter A”) B. Respiratory Rate (RR): 12-14 b/min (higher rates if prior metabolic acidosis or ARDS, lower rates

with severe obstructive lung disease) C. PEEP (intubated) / CPAP (not intubated patient): Initial level 5-8 cmH20 D. Tidal Volume (TV): 6-8 ml/kg IBW (may use higher TV if no lung disease (e.g. CVA or overdose)

but this should be your goal in most patients or set pressure (below) E. Pressure Support (PS): set pressure (titrate PS to ensure spontaneous TV are 6-8 ml/kg)

III. Types of Ventilator Settings and Modes: A. Volume: set volume, RR, flow rate resulting in variable pressure

1. Assist Control (AC) / Continuous Mandatory Ventilation (CMV): set rate or have patient trigger breath at set volume, monitor for high airway pressure

2. Synchronized Intermittent Mandatory Ventilation (SIMV): set rate but patient can breath in addition to this at independent volumes, vent will try to synchronize with patient (comfortable)

B. Pressure: set pressure, RR, flow rate resulting in variable volume 1. Pressure Control (PC): set rate and pressure, monitor for low tidal volume 2. Pressure Support (PS): patient determines volume and frequency up to set pressure (popular

weaning mode) 3. Airway Pressure Release Ventilation (APRV): inverse ratio (I:E), pressure controlled,

intermittent mandatory ventilation with unrestricted spontaneous breathing, improved recruitment and oxygenation. Often used in ARDS a) P High at the P Plateau (or desired P Mean + 3 cmH2O). If your are switching to APRV

from a different mode, then P High can be set at the previous mean airway pressure. A good starting level would be 28 cmH2O. Higher transalveolar pressures recruit additional alveoli, but, try to keep P High below 35 cmH2O.

b) T High at 4.0-6.0 seconds. This is the inspiratory time. The respiratory rate should be 8 to 12 breaths per minute (never more or you start to loose benefit of inverse ratio)

c) P Low at 0 cmH2O to optimize expiratory flow. The large pressure difference allows for tidal ventilation in very short expiratory times.

d) T Low at 0.5-0.8 seconds. The expiratory time should be short enough to prevent de-recruitment and long enough to obtain a suitable tidal volume. A tidal volume target is between 4 and 6ml/kg. If the tidal volume is inadequate, the expiratory time is lengthened; if it is too high (>6ml/kg) the the expiratory time is shortened.

IV. What to watch out for: A. High airway Pressures (PIP): Peak Pressures > 35 cm H2O.

1. Measure plateau pressure (goal <30 cm H2O) a) If plateau pressure also high: problem with lung compliance / alveoli:

(1) ARDS (2) CHF (3) PTX (4) PulmonaryHemorrhage (5) Large effusion (6) Right mainstem intubation

Pulmonary

b) If plateau pressure low: problem with airway: (1) Kink in tubing (2) Mucus plug (3) Bronchospasm (4) Obstructive lung disease (asthma, COPD)

B. Unstable hemodynamics: Hypotension is common after intubation – probably multi-factorial including pre–intubation hypovolemia which is increased by peri-intubation analgesia and anesthesia, immediate effects of positive pressure ventilation on venous return; acidosis (hyperventilate pre-intubation). Usually responds to fluids – if persistent and life threatening consider air-trapping or pneumothorax (temporary hypoventilation at rate of 4 or disconnect vent from ETT to assess if BP improves / obtain CXR). Go through ABC’s

C. Agitation: Don’t forget that if paralytic agent has been used ensure patient also receives an anxiolytic/anmesic agent like Versed, propofol, benzodiazepine etc. and restraints if needed

V. Daily Assessment A. Oxygenation requirement (O2): Determined by FiO2 and PEEP

1. If decreasing requirements: reduce FiO2 (goal less than 60 mmHg) 2. If increasing requirements: use methods to improve oxygenation

a) Increase Alveolar O2 concentration: Increase FiO2, Decrease CO2 (hyperventilate).

b) Ventilator maneuvers to facilitate alveolar recruitment: (1) PEEP increases functional residual capacity (FRC) by recruiting and stabilizing alveoli

that may have been collapsed at normal end- expiratory pressures. This improves V/Q matching allowing better gas mixing. (a) Optimal PEEP - difficult to assess even with sophisticated techniques include

Pressure Volume Curve (compliance curve) and Estimating Lung Compliance (TV mls / Pressure)

(b) Potential Complications: Decrease venous return causing hypotension and Barotrauma

(2) Sighs: Intermittent high volume breaths to recruit gas exchange units (3) Pressure Control Ventilation: uses Square Pressure wave form-hypothetically allows

for recruitment of alveolar gas exchange units by maintaining inspiratory pressures for longer periods.

(4) Lengthen inspiratory time (inverse ratio ventilation) Normal I:E ratio is set at 1:2 on ventilator. Prolonged inspiratory time can increase recruitment of alveolar units.

3. Other Ways to Increase Oxygen Delivery = {O2 Content x 10} x CO a) O2 Content = CaO2 = Hb x SaO2 x 1.36 + [0.003 x pO2] b) Although in cardiac disease optimizing O2 delivery appears to be beneficial this may not

be the case in septic patients. In fact, attempts at increasing cardiac output in sepsis may be associated with worse outcomes.

B. Ventilation requirements (CO2): Determined by respiratory rate (RR) and tidal volume (TV) 1. If CO2 low: either patient is hyperventilating or need to decrease RR or TV 2. If CO2 high: either patient is too sedated and/or need to increase RR or TV

C. Prone Position: Typically reserved for patient with ARDS where lung involvement is heterogeneous but dependent areas are more affected than non-dependent regions. Turning patient to prone position results in recruitment of previously collapsed alveoli - the majority of patients respond within 30 minutes. 50% maintain improvement when turned supine again (usually after 2 hours). Typically prone position is only a temporizing measure.

VI. Ventilatory requirement A. Alveolar Minute Volume = RR x [TV - dead space] B. Normal Minute Volume is 6 L/min, but we tolerate <10 - 12 L/min when assessing whether a

patient is ready to wean from the ventilator.

Pulmonary

VII.Patient–Ventilator Synchrony / Dyssynchrony A. Perfect synchrony is virtually impossible (i.e. duration of neural inspiration should equal

mechanical inflation and neural expiration should equal mechanical inactivity) B. There are many potential reasons for tachypnea on ventilator: Pain, Anxiety, Sepsis...... but poor

interaction with delivered breaths may play a role C. Is patient getting enough Minute Volume - PCO2, pH. D. Is patient having difficulty triggering the Ventilator

1. Mode: AC may be better tolerated than IMV. On IMV, add some Pressure Support. 2. Trigger: Threshold of negative pressure required to trigger breath - RT can lower the

triggering threshold. Auto-PEEP raises the triggering threshold but Applied PEEP does not. 3. Flow Rates: Some patients need higher flow rates, 80 - 120L.min.

VIII. Barotrauma: Signs (decrease breath sounds, hypotension, increase O2 requirements, chest pain) A. Barotrauma takes two forms:

1. Alveolar Injury (aka ARDS) 2. Pneumothorax.

a) Aim to keep plateau pressure < 30 cm H20. b) Clinical evidence:

(1) High plateau pressures (>30 cm H20) are associated with lung injury (baro- or volu-trauma) in experimental animals.

(2) RCT showed that low volume / low pressure ventilation resulted in decreased mortality in ARDS (some confusion in literature reflects heterogeneous studies- mortality benefit only seen when control group has plateau pressure exceeding 30 cm H20). Keep plateau less than 30.

(3) Increased peak airway pressure w/o increased plateau unlikely to cause lung injury as this likely reflects a compliant lung, but no evidence to support this statement

IX. Air-trapping A. AUTO-PEEP (Dynamic hyperinflation)

1. Clinical Situations: Reflects inadequate time for expiration. a) Prolonged Expiration - Bronchospasm. b) Shortened Expiratory Time (high RR or Prolonged Inspiratory time e.g. ARDS)

2. Measure: Expiratory Pause Pressure (occlude expiratory port of ventilator at end expiration- if persisting airflow at end-expiration a pressure will register).

3. Problems: a) Hemodynamic Compromise (Decreased venous return) b) Hypoventilation (air-trapping implies less gas mixing and exchange) c) Difficulty triggering ventilator.

B. Measures to Decrease Auto-PEEP 1. Decreasing RR is more helpful than lowering tidal volume. 2. Decrease Inspiratory Time (higher flow rates) 3. Bronchodilators 4. PEEP match

Pulmonary

J. Discontinuation of Mechanical Ventilation: (around 40% of ICU patients at any given time)

I. Definitions: concepts of “Weaning”, “Liberation”: Protocol is better than No Protocol A. Like everything in ICU: generate hypothesis (this patient is ready to wean) and test hypothesis

(perform assessment and spontaneous breathing trial) II. Steps in discontinuation of mechanical ventilation:

A. Assessing Readiness to Wean: General Rules 1. Is patient improving? Is underlying cause of ventilator requirement improving? 2. Neurologic

a) Can control secretions (i.e can clear them, has good cough strength) b) No excessive sedation or obtundation, (i.e. follows commands, GCS)

3. Cardiovascular a) No significant hypotension or unstable arrhythmia b) No active coronary ischemia (extubation could cause more stress / ischemia)

4. Metabolic a) No major electrolyte disturbance (eg., K+ normal, phosphorus >1.0) b) No signs of adrenal insufficiency

5. Pulmonary a) Oxygenation requirement:

(1) PEEP ≤ 8 (2) O2 sat > 90% on 0.4 Fi02 (Pa02/Fi02 ratio > 200)

b) Ventilation requirement: (1) RR <35 (2) Tidal Volume >5mL/kg (3) RSBI <105 = {RR / TV(L)} sensitivity 97%, specificity 64%, positive predictive value

(PPV) 78%, and negative predictive value (NPV) of 95% (Rapid shallow breathing index. Manjush Karthika, Farhan A. Al Enezi, and Yaseen M. Arabi, 2016)

(4) Minute ventilation 4 - 12 (need to ventilate on their own but not be working too hard) (5) No significant respiratory acidosis (change from baseline) (6) If concern for neuromuscular disease, want Negative Inspiratory Force (NIF) < 20

B. Perform Spontaneous Breathing Trial (SBT): 1. Suggestion is to perform with inspiratory pressure augmentation (5-8 cm H2O) rather than T-

piece or CPAP. Higher rate of successful SBT, higher rate of successful extubation and was associated with a trend towards lower ICU mortality (CHEST guidelines, 2016), however there is bias in studies on this topic.

2. Stop pressure support and PEEP a) If ETT is <7 may consider PS 5 or automatic tube compensation to decrease ETT

resistance b) PEEP of 5 is OK, or can use no PEEP

3. Duration of 30 minutes, no significant difference from 120 min SBT in randomized trials, (Zeggwagh. Intens Care Med 1999, Perren. Intens Care Med 2002)

C. If patient still meets ‘liberation’ criteria, and has passed SBT they should be ready to extubate. 1. 13% of patients passing SBT vs 40% not getting SBT need to be re-intubated 2. Place back on supportive vent setting once SBT passed (or not passed!)

D. A Failed SBT: This heralds a difficult to wean patient 1. International Consensus Conference Classification:

a) Simple (~50-60%): Successful SBT after the first attempt b) Difficult (~30-40%): Failed SBT at first attempt and required up to three trials or required

<7 days to reach successful SBT c) Prolonged (~10%): Required > 7 days to reach successful SBT

2. Must Evaluate the CAUSE OF SBT FAILURE a) Pulmonary

(1) Lack of resolution of underlying disease (ARDS, PNA, Effusion, etc.) (2) Muscle fatigue (increasing RR, decreasing TV? See also neurologic causes below if

no clear pulmonary issue.

Pulmonary

b) Neurologic (1) Uncontrolled anxiety, delirium, agitation (2) Inadequate central respiratory drive (sedation?) (3) Inadequate peripheral muscle strength (low NIF, steroids, NMBs)

c) Cardiovascular (1) Did pulmonary edema develop after PEEP removal? (2) Unstable arrhythmia, angina, hypo/hypertension or tachycardia during SBT

d) Other: metabolic (metabolic acidosis, adrenal insufficiency), nutrition, glycemic control 3. Always place back on supportive vent mode after weaning attempt is complete. 4. Different strategies:

a) Can use AC mode with daily SBT or b) Can use gradual PSV wean c) Avoid SIMV d) Just make sure you do a daily attempt!

5. Passed a SBT…Extubation? a) 2016 CHEST guidelines suggest performing cuff leak test in patients deemed high risk for

post-extubation stridor b) The Cuff Leak Test:

(1) Make sure cuff is inflated. (2) Suction above cuff so secretions aren’t aspirated (3) Proper cuff leak test: set vent to AC 8cc/kg, and make sure patient is

getting proper TV (4) Deflate cuff and measure expired TV on six breaths, take average of

lowest 3-6 breaths. (5) Assessment: an adequate cuff leak is defined as <75% inspired TV measured by the

vent (i.e >25% cuff leak or volume >110mL), turbulent flow heard without a stethoscope, or ability to breath with ETT occluded. (a) Only 2% of patients with cuff leak >25% will have post-extubation stridor

compared with 30% for patients without a cuff leak (6) Solumedrol 40 IV increases cuff leak volume after 6hrs and reduces post- extubation

stridor (no evidence for reduced need for reintubation) (7) Francois Lancet 2007: Solumedrol 20 mg x1 12 hours prior to extubation for everyone

intubated >36h only strategy which reduces re-intubation for laryngeal edema (8% vs 54%)

6. Patient is extubated and is not doing well 1. Consider NIPPV - especially for pure hypercarbic failure2. Can treat laryngeal edema with steroids, histamine blockers, heliox, racemic epinephrine. LOW threshold for immediate re-intubation (always protect the airway when needed)

7. Risk factors for failed extubation: (Weaning Patients from the Ventilator. John F. McConville, M.D., and John P. Kress, M.D., 2012) a) Failure of 2 or more consecutive SBTs b) Chronic heart failure c) More than one coexisting condition other than heart failure d) Partial pressure of partial carbon dioxide >45mm Hg after extubation e) Weak cough f) Upper-airway stridor at extubation g) Age > 65 years h) APACHE II score >12 on the day of extubation i) Pneumonia as cause of respiratory failure

Literature: 1. Rapid shallow breathing index. Manjush Karthika, Farhan A. Al Enezi, and Yaseen M. Arabi, 2016 2. Methods for performing spontaneous breathing trial. CHEST guidelines, 2016 3. Length of SBT. Zeggwagh. Intens Care Med 1999, Perren. Intens Care Med 2002 4. 12-h pretreatment with methylprednisolone versus placebo for prevention of post-extubation laryngeal

oedema: a randomised double-blind trial. Bruno François, MD. The Lancet, 2007 5. Weaning Patients from the Ventilator. John F. McConville, M.D., and John P. Kress, M.D., 2012

Pulmonary

K. Acute Respiratory Distress Syndrome (ARDS): (click here for ARDSnet link)

Definition: Acute lung injury leading to increased vascular permeability and impaired gas exchange.

I. ARDS criteria include: PaO2/FiO2 ratio is NOT diagnostic on its own A. Widespread bilateral radiographic infiltrates (i.e. diffuse) B. PaO2/FiO2 ratio < 300 mm Hg (regardless of PEEP Level)

1. Mild: <300 mm Hg 2. Moderate: <200 mm Hg 3. Severe: <100 mm Hg

C. No clinical evidence of left atrial hypertension (i.e. no cardiac etiology)

II. There are over 60 documented causes of ARDS. The most common causes include: 1. Sepsis 2. Aspiration of gastric contents 3. Pneumonia 4. Severe trauma 5. Burns 6. Massive blood transfusion

7. Lung and bone marrow transplantation

8. Drugs 9. Leuko-agglutinan reactions 10. Near drowning 11. Pancreatitis

III. Pathophysiology of ARDS Inflammatory injury to the alveoli produces diffuse alveolar damage. Inflammatory mediators such as TNF-alpha, IL-1, and IL-6 are released leading to inflammatory cell (neutrophils thought to be primary mediator of injury) recruitment, which lead to damage to the capillary endothelium and the alveolar epithelium. Protein-rich fluid escapes into the alveolar space and interstitial space leading to impaired lung compliance and gas exchange. High compliance = large change in volume with minimal change in pressure

Compliance = change in Volume / change in Pressure

IV. Pathologic Stages of ARDS A. Exudative phase: diffuse alveolar damage, usually first week of illness. B. Proliferative phase: pulmonary edema resolves, Type II alveolar cells proliferate, there is

squamous metaplasia and myofibroblasts infiltrate the interstitium and begin laying down collagen C. Fibrotic stage: normal lung architecture is not seen. There is diffuse fibrosis and cyst formation.

V. Clinically: A. Patients usually develop syndrome 4-48 hours after precipitant injury, and may persist for

days to weeks. B. Severe hypoxemia, with rapidly worsening tachypnea, dyspnea, increasing oxygen

requirements and worsening lung compliance. C. CXR will demonstrate diffuse bilateral alveolar infiltrates. D. Differential diagnosis includes:

1. Cardiogenic pulmonary edema 2. Diffuse alveolar hemorrhage 3. Acute eosinophilic pneumonia 4. Hamman-Rich syndrome

E. Most patients require mechanical ventilatory support because of the severe hypoxemia, high minute ventilation requirements, and poor lung compliance.

VI. Pulmonary goals in ARDS A. Improve oxygenation B. Decrease the work of breathing C. Avoid ventilator-induced lung injury

VII.Ventilation in ARDS: utilize a lung-protective strategy to reduce risk of further lung injury A. Tidal volumes of 6 mL/kg vs 12 mL/kg = mortality 31 vs 39.8% (New Eng J Med 2000; 342: 1301) B. Use of PEEP to prevent cyclic atelectasis (i.e. keep alveoli from collapsing)

Pulmonary

C. Keep plateau pressures < 30 cm H20 to reduce risk of barotrauma D. Hypercapnia may be needed to ventilate with low TV (permissive hypercapnea)

VIII. Oxygenation in ARDS: A. Increase FIO2 (still try to keep <60 cm H2O) B. Increase PEEP (No difference in high vs low PEEP (N Engl J Med 351:327, July 22, 2004) C. Pressure control ventilation may be needed to keep peak pressures <30 cm H2O D. Lengthening inspiratory time (Inverse ratio/APRV) to allow recruitment of more alveoli may be

needed to improve oxygenation. E. Prone positioning: improves blood flow to better ventilated lung units and promotes expansion of

collapsed lung units. F. Deep sedation +/- paralytics (earlier is better if using paralysis) G. Nitric Oxide (NO) improves numbers but not outcomes H. Suppress fever and inflammatory cause if able

IX. Complications of ARDS: A. Barotrauma: (13%) B. Nosocomial infection C. Myopathy from NMB and/or critical illness

X. Mortality: A. Estimated at 35-40% B. Long term survivors of ARDS are usually asymptomatic from a pulmonary standpoint, but may

have mild abnormalities seen on pulmonary function testing

XI. ARDSNet Protocol (THE Guide for ARDS vent management Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network (N Engl J Med 2000; 342:1301-8)

A. Initial ventilator settings: 1. Calculate ideal body weight (IBW):

a) Male = 50 + 2.3 [height (inches) - 60] b) Female = 45.5 + 2.3 [height (inches) - 60]

2. Set mode to assist-control ventilation (ACV) and set initial tidal volume to 8 cc/kg (IBW). Reduce to 7 cc/kg (IBW) after 1-2 hours and then to 6 cc/kg (IBW) after another 1-2 hours.

XII.The plateau pressure (PPL) goal is < 30 cm H20. Adjust the tidal volume to reach this goal: A. Ask RT to check PPL with 0.5 sec. inspiratory pause q4h and after each change in tidal

volume or PEEP. B. If PPL > 30, decrease tidal volume to 5 cc/kg IBW or even 4 cc/kg IBW if necessary. C. If PPL < 25 and the tidal volume < 6 cc/kg IBW, increase tidal volume until PPL > 25 or tidal

volume = 6 cc/kg. D. If the patient is breath stacking or has severe dyspnea, tidal volume may be increased to 7 or 8

cc/kg IBW as long as the PPL < 30.

XIII. Oxygenation goal = PaO2 55-80 mmHg or SaO2 88-95% in order to avoid oxygen-induced lung injury. Basically, you will want to use a high level of PEEP for any given FiO2 setting:

XIV. pH goal = 7.30 - 7.45:

Pulmonary

A. If pH 7.15 - 7.30, increase the set rate until pH > 7.30 or PaCO2 < 25 (max rate = 35). If the set rate = 35 and the pH is still < 7.30, consider giving NaHCO3.

B. If pH < 7.15, set rate to 35. If the set rate = 35 and pH is still < 7.15, consider NaHCO3. In addition, increase tidal volume at 1 cc/kg IBW increments until pH > 7.15. It is okay to go above the target PPL at this point (i.e. you have to ventilate the patient and have run out of options)

C. If pH > 7.45, decrease set rate until patient’s respiratory rate < set vent rate. Minimum set rate=6.

XV. The goal I:E ratio is 1:1 - 3:1. Adjust flow rate and inspiratory flow wave-form to achieve this goal.

XVI. Conduct a weaning trial daily if the patient meets all of the following criteria: A. FiO2 < 0.4 and PEEP < 8 (as long as these values are < values from previous day). B. Patient can take spontaneous breaths (turn down the set vent rate and see). C. Systolic BP > 90 mmHg without pressors.

Literature/Source: 1. For more specifics on the weaning protocol and management of ARDS, go to (click here for link) or

(click here for link)

Pulmonary

L. Pneumonia

Community Acquired Pneumonia (CAP): Out of an estimated 878,000 adults 45 years and older who were hospitalized with a primary diagnosis of CAP in 2010, 71% were 65 years or older, and 10% to 20% required admission to the intensive care unit (ICU)

Adapted from the ATS/IDSA Guidelines (2007) and AAFP Guidelines for CAP (2016)

I. For all definitions below, pneumonia equals a new infiltrate, signs/symptoms of infection (fever, leukocytosis), purulent sputum, and/or worsening oxygenation.

II. Most hospitalized patients with CAP in the United States are treated empirically with no etiologic diagnosis. A review of the experience of Medicare for 17,340 patients hospitalized for CAP in 2009 showed a microbial diagnosis was made in only 7.6 percent of cases (Diagnostic tests for agents of CAP. Bartlett JG. SO, Clin Infect Dis. 2011;52 Suppl 4:S296.)

III. Community-Acquired Pneumonia (CAP) A. Direct admission to the ICU:

1. Required for patients with any major criteria, septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence.)

2. Recommended for patients with 3 of the minor criteria for severe CAP listed in table 4. (Moderate recommendation; level II evidence.)

Pulmonary

B. Following Diagnostic studies should be obtained on ICU patients: 1. CXR 2. Blood cultures 3. Urine legionella antigen: most common atypical bug in the ICU 4. Sputum cultures 5. Influenza testing in appropriate clinical setting 6. Thoracentesis if effusion >5cm on lateral

IV. Recommended Antibiotic regimens for ICU CAP: A. Streptococcus pneumoniae is the most common organism, however, 30-40% of testing testing

shows no definitive organisms. PCR detection up to 86% for bacteria and virus B. A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sul-bactam) plus either azithromycin (level II

evidence) or a fluoroquinolone (level I evidence) (strong recommendation) 1. For penicillin-allergic patients, a respiratory fluoroquinolone and aztreonam are

recommended. C. For Pseudomonas infection, use an antipneumococcal, antipseudomonal b-lactam (piperacillin-

tazobactam, cefepime, imipenem, or meropenem) PLUS either: 1. Ciprofloxacin or 2. Levofloxacin (750-mg dose) or 3. The above b-lactam plus an aminoglycoside and azithromycin or 4. The above b-lactam plus an aminoglycoside and an an- tipneumococcal fluoroquinolone (for

penicillin-allergic patients, substitute aztreonam for the above b-lactam). (Moderate recommendation; level III evidence.)

D. For community-acquired methicillin-resistant Staphy- lococcus aureus infection, add vancomycin or linezolid. (Moderate recommendation; level III evidence.)

Hospital Acquired Pneumonia (HAP): Adapted from Adapted From ATS/IDSA Guidelines (2016)

I. Diagnosis: A. We suggest noninvasive sampling with semiquantitative cultures to diagnose VAP, rather than

invasive sampling with quantitative cultures and rather than noninvasive sampling with quantitative cultures (weak recommendation, low-quality evidence). 1. Remarks: Invasive respiratory sampling includes bronchoscopic techniques (ie,

bronchoalveolar lavage [BAL], protected specimen brush [PSB]) and blind bronchial sampling (ie, mini-BAL). Noninvasive respiratory sampling refers to endotracheal aspiration.

II. Antibiotic Treatment: A. We suggest that patients with suspected HAP (non-VAP) be treated according to the results of

microbiologic studies performed on respiratory samples obtained noninvasively (i.e. endotracheal aspiration), rather than being treated empirically (weak recommendation, very low-quality evidence).

B. For patients with suspected HAP/VAP, we recommend using clinical criteria alone, rather than using serum PCT plus clinical criteria, to decide whether or not to initiate antibiotic therapy (strong recommendation, moderate-quality evidence).

C. We recommend that all hospitals regularly generate and disseminate a local antibiogram, ideally one that is specific to their intensive care population(s) if possible.

D. We recommend that empiric treatment regimens be informed by the local distribution of pathogens associated with VAP and their antimicrobial susceptibilities.

III. Empiric Treatment: In patients with suspected VAP, we recommend including coverage for S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli in all empiric regimens (strong recommendation, low-quality evidence). A. MRSA: we suggest including an agent active against MRSA for the empiric treatment of

suspected VAP only in patients with any of the following: a risk factor for antimicrobial resistance (Table 2), patients being treated in units where >10%–20% of S. aureus isolates are methicillin resistant, and patients in units where the prevalence of MRSA is not known (weak recommendation, very low-quality evidence). 1. If empiric coverage for MRSA is indicated, we recommend either vancomycin or linezolid

(strong recommendation, moderate-quality evidence).

Pulmonary

B. MSSA: we suggest including an agent active against methicillin-sensitive S. aureus (MSSA) (and not MRSA) for the empiric treatment of suspected VAP in patients without risk factors for antimicrobial resistance, who are being treated in ICUs where <10%–20% of S. aureus isolates are methicillin resistant (weak recommendation, very low-quality evidence). 1. When empiric treatment that includes coverage for MSSA (and not MRSA) is indicated, we

suggest a regimen including piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem (weak recommendation, very low-quality evi- dence). Oxacillin, nafcillin, or cefazolin are preferred agents for treatment of proven MSSA, but are not necessary for the empiric treatment of VAP if one of the above agents is used.

C. Pseudomonas auruginosa: we suggest prescribing 2 antipseudomonal antibiotics from different classes for empiric treatment of suspected HAP/VAP in patients with any of the following:

a) Patients with increased risk of pseudomonas infection (see algorithm below) b) Patients in units where >10% of gram-negative isolates are resistant to an agent being

considered for monotherapy, or where there is an abundance of GNR on gram stain c) Patients in an ICU where local antimicrobial susceptibility rates are not available (weak

recommendation, low-quality evidence).

D. In patients with suspected HAP/VAP, we suggest avoiding aminoglycosides if alternative agents with adequate gram-negative activity are available (weak recommendation, low-quality evidence).

E. In patients with suspected VAP, we suggest avoiding colistin if alternative agents with adequate gram-negative activity are available (weak recommendation, very low-quality evidence).

F. Remarks: High risk of death in the meta-regression analysis was defined as mortality risk >25%; low risk of death is defined as mortality risk <15%. For a patient whose septic shock resolves when antimicrobial sensitivities are known, continued combination therapy is not recommended.

Pulmonary

Pulmonary Critical Care Medicine: IDSA Guidelines 2016: HAP, VAP & It’s the End of HCAP as We Know It (And I Feel Fine)

Pulmonary

M. Tracheostomy (and PEG): Optimal Timing and Management

I. Introduction: Tracheostomy is a procedure commonly performed on critical patients that will likely require prolonged mechanical ventilation. Controversy exists over the optimal timing of this procedure. Ideally, the procedure is performed when only benefits ascribed to the procedure outweigh the risks.

II. Benefits of tracheostomy: A. Improves patient comfort (long-term) - reduces agitation and sedation requirements B. Improves patient communication (does not cross vocal cords, can use speaking valve) C. Reduces time on the ventilator D. Reduce laryngeal ulceration E. Reduce vocal cord injury F. Improves patient’s ability to rehabilitate G. Lower incidence of nosocomial pneumonia (theoretical) H. May reduce length of ICU stay and/or pneumonia in theory but no high level evidence

III. Risks A. Bleeding B. Pain (short-term) C. Stomal infections

D. Pneumothorax/Hemothorax E. Pneumomediastinum F. Death (Tracheo-Innominate Fistula etc.)

IV. Timing A. Early - Less than 7 days B. Late - Greater than 7-14 days

V. Outcomes: A. Time on ventilator – reduced with early (Griffiths et al BMJ 2005, Rodriquez et al J Trauma 1997,

Arabi et al Critical Care 2004, Rumbak et al Critical Care Med 2004) B. Time in ICU: reduced with early tracheostomy (Griffiths et al BMJ 2005, Rodriquez et al surgery

1990, Rumbak et al Critical Care Med 2004) C. Pneumonia: mixed results, trend toward reduction with early tracheostomy (Rodriquez et al

surgery 1990, Kluger et al Eur J Emerg Med 1996, Sugerman HJ, Wolfe L, Pasquale MD, et al. Multicenter, randomized, prospective trial of early tracheostomy. J Trauma 1997)

D. Mortality: No difference in mortality (Griffiths et al BMJ 2005) E. TracMan Trial: no benefit of early (<4 days) vs late (>10 days) tracheostomy but 91.9% in early

group ended up receiving tracheostomy vs 44.9% in late group.

VI. Conclusion: Early tracheostomy appears to reduce time on ventilator and LOS in ICU but does not alter mortality. It is also more comfortable for patients in the long term. Early tracheostomy may reduce the incidence of nosocomial pneumonia but there is no high quality evidence at this time. The optimal timing for tracheostomy in ICU needs further study but there appears to be benefit to early (<7 days) tracheostomy when patient will need one for an extended time. However, as the TracMan trial showed, we are not very good at evaluating who will need a trace and only about half the patient we think will need tracheostomy end up needed one if we wait more than 10 days to perform tracheostomy.

Tracheostomy Video Link: Blue Rhino Percutaneous Tracheostomy Set and Technique - We typically use Fentanyl, Versed and Nimbex for sedation and paralysis - We typically utilize a bronchoscope to assist during the procedure but is not mandatory

PEG Tube Video Link (often performed with trach): PEG Tube Placement - We use a modified technique / true Seldinger technique over a wire but otherwise it is the same

Literature: 1. Tracheostomy: Epidemiology, Indications, Timing, Technique, and Outcomes. Respiratory Care, 2014 2. Timing of tracheostomy for critically ill patients who are predicted to be on long-term artificial

respiration. Cochrane Review. 2015

Pulmonary

3. Evidence-based guidelines for the use of tracheostomy in critically ill patients. Néstor Raimondi. Journal of Critical Care, 2016.

4. A guide to open surgical tracheostomy. Shanghai CHEST, 2017

Pulmonary

N. Chest Tube Management

I. Physiology of Chest Tubes: fundamentally chest tubes allow equalization of pressures between the intra-thoracic and extra-thoracic spaces. This connection can be accomplished with a simple whole in the chest wall (i.e. finger thoracotomy) but is kept sterile by utilizing a sterile chest tube and connecting it to a sterile atrium. A. Chest tubes also function to drain intra-thoracic fluid such as blood (hemothorax), infection

(empyema) or simple fluid (pleural effusion), often utilizing suction to help remove the fluid. B. Sometimes thrombolytics such as tPA (tissue plasminogen activator) and/or enzymes Dornase

(an enzyme that breaks down protein) are utilized to help drainage of complex collections (i.e. clotted blood or empyema).

II. Indications: A. Pneumothorax B. Hemothorax C. Pleural Effusion (simple, malignant, etc.) D. Empyema E. Abscess

III. Daily Assessment: STEP I: Assess for leak by having patient cough (not ventilated), breath/simulate cough (ventilated)

→ No leak present → Done, NO LEAK → Yes leak present → Need to assess further (suction induced leak vs. true leak)

• Take chest tube off suction if on suction and repeat STEP I → Constant Leak - persists throughout the breathing cycle → Intermittent Leak - present only at certain times (i.e. expiration) → Forced-Expiratory Leak - only present with cough, valsalva or ventilator simulation

STEP II: Assess location of leak → Clamp chest tube at the skin where tube enters chest wall

• Persistent leak = leak outside thoracic cavity (i.e. in tubing or atrium) - fix it • Resolution of leak = leak inside thoracic cavity (i.e. true leak)

STEP III: Management is dependent on the etiology of the leak and many will resolve on their own. • Reduce leak rate (place to water seal and reduce PEEP, etc if able). • Bronchial valve placement • Resection (wedge, lobe or lung)

IV. Assessing for Removal of Chest Tubes: A. Want patient to tolerate under water seal without increased pneumothorax or accumulation of fluid B. There should not be a leak present (this would lead to pneumothorax and even tension with time) C. Output: generally safe to remove when output < 150 cc/day (except: hemothorax, empyema)

V. Indications for Thoracotomy Following Chest Tube Placement in Trauma Patient: A. Initial output > 1500 cc B. 200 cc / hr x 4 hrs = 1L over 5 hours (this is a little easier to remember)

VI. Management of Hemothorax and Indications for Video Assisted Thoracotomy (VATs) - EAST (2011) A. All hemothoraces, regardless of size, should be considered for drainage (Level 3) B. Attempt of initial drainage of hemothorax should be with a tube thoracostomy (Level 3). 14F

appears equivalent to large bore tubes (literature 1) C. Persistent retained hemothorax, seen on plain films, after placement of a thoracostomy tube

should be treated with early VATS, NOT a second chest tube (Level 1). D. VATS should be done in the first 3 to 7 days of hospitalization to decrease the risk of infection and

conversion to thoracotomy (Level 2). E. Intrapleural thrombolytic may be used to improve drainage of subacute (6-day to 13-day duration)

loculated or exudative collections, particularly patients where risks of thoracotomy are significant (Level 3).

F. 1500 mL via a chest tube in any 24-hour period regardless of mechanism should prompt consideration for surgical exploration (Level 2)

Pulmonary

Literature: 1. 14 French pigtail catheters placed by surgeons to drain blood on trauma patients: Is 14-Fr too

small? Journal of Trauma and Acute Care Surgery, 2012 2. A Prospective Study of 7-Year Experience Using Percutaneous 14-French Pigtail Catheters for

Traumatic Hemothorax/Hemopneumothorax at a Level-1 Trauma Center: Size Still Does Not Matter. World Journal of Surgery, 2018

3. Chest tube care in critically ill patient: A comprehensive review. Egyptian Journal of Chest Diseases and Tuberculosis 2015

Pulmonary

O. How to Read a Portable CXR: 5 Step approach to reading the portable CXR:

Step 1: Confirm patient’s name, date of birth, and medical record number. Step 2: Take notice of penetration: Too white (under penetrated), too dark (over penetrated). Step 3: Take notice of inspiratory effort: Should see 10-11 ribs Step 4: Take notice of alignment: Step 5: Begin systematic approach: ABCDE

A. Airways Start at the top in the midline and review the airways ensuring that the trachea is overlying the spine. Start at the top and trace down the trachea to carina (is ETT 5 +/- 2cm above carina). Is it straight and midline? Trace down both main bronchi. Is the carina wide (more than 100 degrees)? Is there bronchial narrowing or dilatation?

B. Breathing Look for lung and pleural pathology. Both lungs should be well expanded and similar in volume. Can you count 10 posterior ribs bilaterally? Is one lung larger than the other? Compare the apical, upper, middle and lower zones in turn. Are they symmetrical? Are there areas of increased density? Trace the lateral margins of the lung to the costophrenic angles checking for pneumothorax. Are the costophrenic angles crisp? Trace the hemidiaphrams to the midline. Can you see the whole of the hemidiaphragm?

C. Circulation Look at the heart and vessels (systemic and pulmonary). Check the cardiac position. Assess cardiac size (<50% of the chest diameter on PA films and <60% on AP films) Check the position and size of the aortic arch. Check the width of the upper mediastinum Look at the hilar vessels. Can you see them clearly on both sides?

D. Disability Check for any bony pathology (fracture or metastasis). Trace along each posterior (horizontal) rib on one side of the chest. Is there a fracture or abnormal area? Repeat with the other side of the chest. Now trace lateral and anterior ribs on the first side. Repeat on the other side. Now, check the clavicles and shoulders. Can you trace around the cortex of the bones? Finally, check the vertebral bodies. Are they all rectangular and of a similar height? Can you see 2 pedicles per vertebral body? Are there disc spaces?

E. Exposure Everything else outside the thorax including the upper abdomen, soft tissues and lines or medical devices. Is there free gas under the diaphragms? Is there a hiatal hernia? Is there an absent breast shadow? Are there lines (i.e. chest tubes, pacer wires, central lines, etc) entering the thorax and are they appropriately positioned.

A few rules: - 95% of the time the right hemidiaphragm is higher than left hemidiaphragm. A left hemi- diaphragm

that is greater than 1 cm higher than the right is abnormal. - Diaphragm should be smooth and costophrenic angles should be sharp and there should be no air. - Heart should be less than 1⁄2 of hemithorax on a PA film. This does not hold true on portable AP film. - Left pulmonary artery should be less than 1⁄2 of aortic knob. - Azygous vein should not be visible in an upright film. - Finally, know your anatomy

If there is concern for a diaphragm injury consider SNIFF Test (fleuro)

Cardiology

P. Vasopressors

Drug Reference: CCHS Portal -> Formulary -> CCHS Formulary -> Search Specific Drug

Site of action: Adrenergic receptors A. α-1: Peripheral arteriolar vasoconstriction through vascular smooth muscle B. β-1: Increases HR, contractility and AV node conduction. Increases renin release. C. β-2: Promotes smooth muscle relaxation (respiratory (bronchodilation), uterine, vascular),

increases HR, contractility and AV node conduction D. Dopamine: Increases renal, splanchnic, cerebral blood flow via D1 and D2 receptors. Unclear if

any clinical meaning to these effects

Available Vasopressor Medications A. Phenylephrine

1. Pure α1 adrenergic receptor agonist stimulating smooth muscle and producing vasoconstriction (sympathomimetic). Increases SVR with a potential reflex bradycardia (maybe benefit in atrial fibrillation)

2. Metabolism: liver extensively 3. Excretion: urine 86% (16% unchanged), Half-life: 2-3 hours 4. Dose: 10-100 mcg/min 5. Indications: Hyperdynamic sepsis, drug-induced hypotension, neurogenic hypotension; not

used in cardiogenic shock 6. Complications: bradycardia, excessive afterload

B. Norepinephrine (first line agent in septic shock) 1. α1 activity with some β1-activity producing vasoconstriction, increases SVR with some

chronotropic and inotropic cardiac effect 2. Metabolism: liver, kidney, plasma 3. Excretion: urine (minimally unchanged), Half-life: 1 minute 4. Dose: 1-40 mcg/min 5. Indications Sepsis, cardiac related hypotension 6. Complications: vasoconstriction with hypoperfusion of tissues

C. Epinephrine 1. Acts on α1, β1 and β2 producing vasoconstriction, increases SVR with some chronotropic

and inotropic cardiac effect, and bronchodilation 2. Metabolism: liver, other tissues 3. Excretion: urine (minimally unchanged), Half-life: 1 minute 4. Dose: 1-40 mcg/min 5. Indications:

a) Anaphylactic shock: Continuous 1-40 mcg/min. Bolus: 1:10,000 adrenaline given iv in 1 ml doses until effective. If no iv access available then 0.5 ml of 1:1,000 im.

b) Acute severe asthma attack: unresponsive to normal treatment may require infusions of epinepherine, though 0.5ml of 1:1000 s/c may be used

c) Bronchospasm/Airway Edema: 2.25% racemic epinephrine 1-3 inhalations q3h prn d) ACLS: 1:10,000 adrenaline, 1 mg IV/IO q3-5 min prn, total of 5-10 mL

D. Vasopressin (typically start as second agent when norepinephrine at 10-20 mcg/min) 1. Directly stimulates V1 and V2 receptors, resulting in vasoconstriction and antidiuresis 2. Metabolism: Liver, kidney, extensively 3. Excretion: urine (5-6% unchanged), Half-life: <20 minutes 4. Dose: 0.01-0.04 units/min IV

E. Dopamine 1. Dose-dependant activity acting on dopaminergic, alpha, and beta receptors causing

chronotropic, inotropic, renal/splanchnic vasodilation (low dose) and vasoconstriction (high dose)

2. Metabolism: liver, kidney, plasma

Cardiology

3. Excretion: urine 80%, Half-life: 2 minutes 4. Dose – dose response varies between patients. 1-50 mcg/kg/min IV

- Renal: <5 mcg/kg/min - mostly D1/D2 receptors: natriuresis and renal vasodilation with modest increase in CO

- Cardiac: 5-10mcg/kg/min - mostly β receptors to increase contractility and cardiac output with minimal change in HR or SVR, some increase in renal/splanchnic blood flow

- Vasoactive: >10mcg/kg/min - additionally has effects on a1 receptors, causing vasoconstriction, increased HR with increase/decreased renal/splanchnic blood flow

5. Indications: ACLS, Sepsis with some cardiac dysfunction, cardiogenic shock, renal transplant 6. Complications: vasoconstriction with tissue hypoperfusion

F. Dobutamine 1. β-1 and β-2 2. It increases cardiac output and reduces afterload (b2 effects on skeletal muscle). 3. Cardiogenic shock. 4. Metabolism: liver 5. Excretion: urine, Half-life: 2 minutes 6. Dose: 2-20 mcg/kg/min 7. Indications: Cardiac decompensation 8. Complications: hypotension, tachycardia, arrhythmias

G. Midodrine 1. MOA: alpha-1 agonist, essentially an oral equivalent of phenylephrine 2. Dose: 2.5 - 20 mg q8h PO 3. Metabolism: Midodrine is an inactive prodrug, which is rapidly converted to its active

metabolite desglymidodrine. Levels of desglymidodrine peak within 1-2 hours 4. Excretion: renal, Half Life: 3-4 hours 5. Complications: rare bradycardia which resolves with cessation 6. Benefits: decreased duration and reinstitution of of IV vasopressors and decreased number of

days in the ICU. Does not change mortality. (Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock. Micah R. Whitson. 2016)

Angiotensin II (Giapreza) - $3,000 per day of therapy - FDA labeled Indication: used to increase blood pressure in patients with septic shock who fail to

maintain MAP goal with high dose norepinephrine/vasopressin therapy (must be on two medications) - Most beneficial in patients with septic shock with acute kidney injury requiring SLEDD therapy - Alaris pump concentration is 2.5 mg/250 mL NS (or 10,000 ng/mL). Expires in 24 hours after

compounding. Store either at room temperature or under refrigeration - Route of administration: Continuous IV infusion. Central line is preferred - Dosage/titration:

- Start at 20 ng/kg/min. Titrate q5min by increments of up to 15 ng/kg/min as needed during the first 3 hours to achieve MAP >65 (goal should be MAP 75-90 before weaning other vasopressors)

- Min dose: 1.25 ng/kg/min. Max dose: 80 ng/kg/min - Duration of therapy: Most patients achieve MAP goal within 3 hours after initiation of therapy. Most

therapy ends after 48 hours. Therapy may continue up to 7 days based on clinical trial - Side effects: Greater number of patients develop thromboembolic events vs placebo (12.9% vs. 5.1%)

Literature: 1. Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit.

Journal of Cardiovascular Pharmacology Care Jacob C. Jentzer, MD. 2015. 2. Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock. Micah R.

Whitson et al. CHEST. 2016

Cardiology

Q. Shock and PA Catheter

&

Determining Underlying Etiology of Shock:

Unfortunately, there is no single clinical tool that has been shown to be optimal for hemodynamic monitoring and assessment of shock. Many of the factors used include: heart rate, blood pressure, mean arterial pressure (MAP), urine output, lactic acid level and clearance, central venous pressure (CVP), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), delivery of oxygen (DO2), venous oxygen saturation (SvO2), and of course the Swan-Ganz catheter (discussed below), which helps measure or calculate many of these variables. As a result we use multiple variables to make clinical decisions on our patients who are in a state of shock, which is generally defined as a systolic blood pressure below 90 mmHg or MAP below 65 mmHg

FlowTrac (A-line needed): a tool for hemodynamic monitoring in sedated and ventilated patients I. Mechanical Ventilation: Currently, literature supports the use of SVV on patients who are 100%

mechanically (control mode) ventilated with tidal volumes of more than 8cc/kg and fixed respiratory rates.

II. Spontaneous Ventilation: Currently, literature does not support the use of SVV with patients who are spontaneously breathing.

III. Arrhythmias: Arrhythmias can dramatically affect SVV. Thus, SVV’s utility as a guide for volume resuscitation is greatest in absence of arrhythmias.

IV. Please see link for more information: (FlowTrac)

Cardiology

PA Catheter (Swan-Ganz): There is only evidence for increased complications without benefit for routine use of PA catheter in sepsis, ARDS, and cardiogenic shock. Rarely used, typically in cases with unknown source or mixed shock state. PA Cather Guide (click here)

Indications A. Need to measure PA pressure, PCWP, CO B. Precise diagnose Pulmonary Hypertension C. Unable to determine cause of shock after evaluation/CVP D. Complicated hemodynamic management (eg., sepsis plus CHF, plus ESRD) E. Need to precisely calculate Cardiac output/mixed venous 02 sampling for management

Contraindications (absolute and relative): A. Prosthetic TV or PV B. Known R cardiac tumor or clot C. R sided endocarditis D. LBBB (everyone needs EKG prior to PA Cath) E. Significant coagulopathy

- Complications: mortality rate 0.02%-1.5% (JAMA 2001 review). Complications are same as CVL, plus arrhythmia, PA rupture, valvular damage.

PA Catheter Insertion Basics A. Insertion: after consent, 7French “Cordis” is inserted in same manner as a triple lumen catheter.

Best sites to float a PA catheter through the Cordis are: 1. Right IJ 2. Left Subclavian 3. Femoral (usually need fluouroscopy for femoral and any other site)

B. After flushing the ports, testing the balloon, and testing the catheter for proper waveforms (‘fling’ catheter look for waves and ‘square root sign’ after catheter is flushed), you can float the catheter through the Cordis.

C. REMEMBER: when moving forward, Balloon must be ALWAYS UP. When moving backwards balloon must be ALWAYS DOWN.

PA catheter waveforms:

Cardiology

R. Hypertensive Crises

Definitions: I. Hypertensive Emergency - increased systolic and diastolic BP leading to end-organ damage

A. Hypertensive encephalopathy B. Acute aortic dissection C. Acute pulmonary edema D. Acute MI/unstable angina

E. Stroke F. Blindness G. Acute renal failure H. Microscopic hemolytic anemia

II. Hypertensive Urgency - elevated blood pressure without evidence of end-organ damage. A. The clinical differentiation between these two entities is the presence or absence of end organ

damage not the level of blood pressure elevation.

Epidemiology: I. Hypertensive crises will occur in < 5% of all hypertensive patients. The majority have pre-existing

diagnosis of HTN and have been prescribed medication, but have inadequate follow-up. II. Evaluation:

A. History (Prior hypertensive episodes, medication compliance, baseline BP, substance abuse-ETOH, cocaine).

B. PE – BP all limbs, don’t forget eye exam C. Labs: CBC, electrolytes, BUN, Cr, U/A, CK and isoenzymes, urine tox screen (check for use of

cocaine, amphetamines, phencyclidine) peripheral smear to detect microangiopathic hemolytic anemia

D. Other studies CXR, EKG, Consider Head CT for any neuro changes III. Treatment:

A. Hypertensive emergency requires immediate control of BP to stop end-organ damage. Control does not mean immediate normalization of BP. Usually intravenous medications are used to lower the diastolic BP by 10-15%, or to a diastolic BP 110 mm Hg. For aortic dissection this goal should be reached within 5-10 minutes. In other pts with hypertensive emergency, the goal should be reached within 30-60 minutes. Once the end-point is reached, maintenance therapy with an oral agent can be instituted.

B. Hypertensive urgency- BP is gradually reduced over 24-48 hrs usually with an oral medication

Recommended Antihypertensive Agents for Hypertensive Crises A. Uncomplicated patient: Labetolol, nicardipine, esmolol, nitroprusside. B. Pulmonary edema: nitroprusside with nitroglycerin and loop diuretic C. Acute myocardial ischemia: labetolol or esmolol with nitroglycerin D. Encephalopathy: labetalol, or nicardipine E. Acute aortic dissection: labetolol or combination of nitroprusside with esmolol.The aim is to lessen

pulsatile load and force of left ventricular contraction to slow the propagation of the dissection. Surgical consultation for possible repair.

F. Eclampsia: labetalol, nicardipine, or hydralazine. Immediate delivery. G. Acute renal failure/microangiopathic hemolytic anemia: fenoldopam or nicardipine H. Sympathetic crisis: Re-administer the discontinued drug. Or nicardipine, verapamil, or fenoldopam

Medications that should be avoided in HTN crisis: 1. Nitroglycerin – Classically, pt’s with hypertensive crisis are volume depleted.

Nitroglycerin can cause a precipitous drop in BP by decreasing preload. 2. Diuretics- Long acting, variable response. 3. Nifedipine- Cause precipitous drop in BP 4. Hydralazine: Direct vasodilator. Begins to work in 5-15 minutes. Can cause a precipitous drop

in BP. 1⁄2 life 3 hours but for some unknown reason pharmacologic effects can last for 10 hours in some individuals. Because of prolonged and unpredictable effects hydralizine should be avoided.

Nephrology / Urology

S. Acid-Base Disorders: “7.4” Quick Steps

Step #1: Gather the necessary data (ABG and serum chemistries). Step #2: Look at the pH:

2a: pH > 7.4, then pt has primary alkalosis, proceed to Step 3a. If 2b: pH < 7.4, then pt has primary acidosis, proceed to step 3b.

Step #3: Look at the PCO2: 3a: pH >7.4. If PCO2 is > 40, then pt’s alkalosis is metabolic; if PCO2 is < 40 then respiratory. 3b: pH <7.4. If PCO2 is > 40, then pt’s acidosis is respiratory; if PCO2 is < 40, then metabolic.

Step #4: Check if patient has a significant anion gap (> 12-18). (Formula for this is: Na – Cl – HCO3) When calculating AG pay attention to serum albumin values. For every 1 g/dL decline in serum albumin <4.4 g/dL, a 2.5 mEq/L reduction in AG occurs.

Step #5. For Metabolic Acidosis - Calculate Predicted PCO2 5a: WINTERS FORMULA: If pCO2 is different than predicted then there is an additional respiratory problems beyond mere compensation.

pCO2 predicted (+/-2) = (1.5 X HCO3) + 8

Step #6: If there is an anion gap calculate the corrected HCO3. (Pt’s gap – 12 + pt’s serum bicarb) If gap excess > 30, then pt has an underlying metabolic alkalosis in addition to whatever disorders Steps #1 through #5 yielded. If gap excess < 23, then pt has an underlying metabolic acidosis in addition to whatever disorders Steps #1 through #5 yielded.

Step #7: Figure out what’s causing the problem(s), using the differentials below and then FIX IT!!!

Bicarbonate (HCO3-): - Constantly under state of change between carbonic acid

(H2CO3) ⇤⇥ bicarbonate (HCO3-) + hydrogen ion (H+) ⇤⇥ carbon dioxide (CO2) + water (H2O). (image to right)

- Indications: pH < 7.1 or pH < 7.2 in setting of renal failure (crt 2x normal) or pH < 7.2 with vasopressors

- Complications: ↑ PCO2 (requiring increased ventilation, careful in poorly ventilated patient with already elevated PCO2), ↑ lactate, ↑ Na+, ↓ ionized Ca++

- Benefits: correcting acidosis ↑ sensitivity to catacholamines

Nephrology / Urology

T. Diuresis and Diuretics

Carbonic Anhydrase Inhibitors:

acetazolamide (Diamox) - Indications: Total body CO2 is used as a surrogate for bicarbonate as 95% of total body CO2 is

produced from bicarbonate. Normal levels are typically between 21-29. Typically carbonic anhydrase inhibitors are administered when CO2 (as surrogate for bicarbonate) level are greater than 30.

- MOA: inhibits carbonic anhydrase which prevents bicarbonate absorption. Carbonic acid (H2CO3) and bicarbonate (HCO3-) absorption in the proximal tubule is dependent on carbonic anhydrase to convert them to carbon dioxide (CO2) + water (H2O), which both rapidly diffuse across the cell membrane where they are rehydrated back to carbonic acid and bicarbonate within the tubular cell. The bicarbonate is then re-absorbed into the blood stream. Therefore, inhibition of carbonic anhydrase prevents absorption of bicarbonate.

- Location of effect: proximal tubule - Dose: 500mg BID/TID for 1-3 days - Complications: loss of NaHCO3, Hypokalemic metabolic acidosis, tolerance after 2-3 days

Nephrology / Urology

Loop Diuretics:

furosemide (Lasix), bumetanide (Bumex), torsamide, ethacrynic acid - Indications: Potent diuretic with less vasodilation than thiazide diuretics. Typically utilized in the SICU

for diuresis in edematous patients to reduce pulmonary edema and optimize pulmonary function. Also utilized to treat acute hyperkalemia, hypercalcemia, and hypernatremia

- MOA: inhibit Na/K/2Cl cotransporter. This reduces re-absorption of Na, K and Cl while altering the luminal voltage gradient which reduced re-absorption of divalent cations (Ca++ and Mg++)

- Location of effect: ascending limb of the loop of Henle - Dose: 20-80 mg PO or IV (IV 2x as potent) - Complications: loss of Na + H2O, hypokalemic metabolic alkalosis, hypocalcemia, hypomagnesemia.

Can also cause ototoxicity thought to be secondary to Na/K/2Cl cotransporter expressed on hair cells of the inner ear. Hyperuricemia, which may lead to Gout flair.

Nephrology / Urology

Thiazide Diuretics:

hydrochlorothiazide (HCTZ), chlorothiazide, chlorthalidone - Indications: hypertension, CHF, kidney stones (90% reduction in new calcium oxalate stones),

nephrogenic diabetes insipidus - MOA: inhibit the Na/Cl cotransporter in the distal convoluted tubule resulting in decreased re-

absorption of Na and Cl. There is also some loss of potassium and hydrogen during this process as a result of more distal exchange for Na occurs. There is also some degree of vasodilatory effect that is not fully understood but makes this class very good for treating hypertension and CHF

- Location of effect: distal convoluted tubule - Dose: 12.5 - 200 mg PO daily - Complications: hypokalemic metabolic alkalosis, hyperuricemia, hyperglycemia, hyperlipidemia

Nephrology / Urology

Potassium-sparing Diuretics:

spironolactone, eplerenone, amiloride (ENaC Blocker) - Indications: hyperaldosteronism, hypokalemia, drug-resistant hypertension - MOA: aldosterone receptor antagonist - Location of effect: aldosterone-sensitive distal nephron, including connecting tubule and collecting duct - Dose: 12.5-200 mg PO divided daily or BID - Complications: loss of Na + H2O, hyerkalemia, small risk of acidosis

Nephrology / Urology

Nephrology / Urology

U. Severe Electrolyte Abnormalities

Hyponatremia

I. Definition: Hyponatremia is generally defined as a plasma sodium level of less than 135 mEq per L (135 mmol per L). Symptomatic hyponatremia (usually < 120 mEq per L) leads to significant morbidity and mortality. Morbidity can also result from rapid correction of hyponatremia.

Evaluation: I. Step 1: Begin with the history and physical exam. Many conditions are causes are apparent just from

the history and physical exam (e.g. medications, cardiac dz, renal failure, etc) II. Step 2: Calculate serum osmolality. Normal plasma osmolality is 280 - 300 mOsm per kg.

Serum Osmolality = 2 X [sodium] + [urea] + [glucose]

A. Normal: if serum osmolality is normal consider: 1. Pseudohyponatremia: This condition results from increased percentage of large molecular

particles in the serum relative to sodium. These large molecules do not contribute to plasma osmolality resulting in a state in which the relative sodium concentration is decreased, but the overall osmolality remains unchanged. Severe hypertriglyceridemia and hyperproteinemia are two causes of this condition.

B. High: if serum osmolality is high (> 300 mOsm per kg of water) consider: 1. Severe hyperglycemia. Glucose molecules exert an osmotic force and draw water from the

intracellular compartment into the plasma, thereby causing a diluting effect. C. Low: if serum osmolality is low go to Step 3:

III. Step 3: Assess volume status: A. Blood Volume Analysis: nuclear medicine study (Blood Volume Analysis: A New Technique and

New Clinical Interest Reinvigorate a Classic Study. Timothy A. NEJM, 2007) 1. Hypervolemic hyponatremic conditions: congestive heart failure, liver cirrhosis, and renal

diseases such as nephrotic syndrome. 2. Hypovolemic hyponatremic conditions: drugs (e.g. thiazide diuretics) 3. Euvolemic hyponatremic conditions: SIADH, Beer potomania, psychogenic polydipsia,

adrenal insufficiency, hypothyroidism

Treatment: I. Step 1: Based on Na levels and severity of symptoms decide whether immediate treatment is

required. II. Step 2: Determine whether hyponatremia occurred acutely or developed over a longer period of time

(>48 hours). Timing is often difficult to determine. In patients with chronic hyponatremia, overzealous and rapid correction should be avoided because it can lead to Osmotic Demyelinating Syndrome (central pontine myelinolysis). In osmotic demyelinating syndrome, neurologic symptoms usually occur one to six days after correction and are often irreversible.

III. Step 3: Determine the most appropriate method of correcting the hyponatremia. In some conditions Na can be corrected by simple fluid restriction; however, in many situations Na supplementation is required. Can use hypertonic saline.

Hypernatremia

I. Definition: Hypernatremia is defined as plasma Na concentration > 145 mEq/L and is caused by a deficit of water relative to solute

II. Causes: A. Hypernatremia with hypovolemia Extrarenal losses – GI (Vomiting, diarrhea), Skin (fever, burns,

excessive sweating). Renal losses: Intrinsic renal disease, Loop diuretics osmotic diuresis (glucose, urea, mannitol)

B. Hypernatremia with euvolemia Extrarenal losses Skin (fever, excessive sweating). Renal losses - central diabetes insipidus, nephrogenic diabetes insipidus. Decreased intake- inability to access water, primary hypodipsia

Nephrology / Urology

C. Hypernatremia with hypervolemia Hypertonic fluid administration (hypertonic saline, NaHCO3, total parenteral nutrition), mineralocorticoid excess, adrenal tumors

Treatment: I. Acute vs Chronic

A. Acute hypernatremia (< 24 h) can be corrected within 24 h B. Chronic hypernatremia (<24-48 h) should be corrected over 48 h, and the plasma osmolality

should be lowered at a rate of no more than 2 mOsm/L/h to avoid cerebral edema II. The amount of water necessary to replace existing deficits may be estimated by the following formula:

Free water deficit = TBW × [(plasma Na/140) − 1]

III. This formula assumes constant total body Na content. In patients with hypernatremia and depletion of total body Na content (ie, who have volume depletion), the free water deficit is greater than that estimated by the formula.

IV. Replace free water A. Oral hydration is effective in patients without significant GI dysfunction (100cc q4h PO or NG/OG). B. In severe hypernatremia or in patients unable to get oral hydration, IV hydration is required.

V. In patients with hypernatremia and ECF volume overload - free water deficit can should be replaced with 5% D/W followed by a loop diuretic to remove excess NA

VI. In patients with hypernatremia and euvolemia, free water should be replaced with 0.45% saline VII. In patients with hypernatremia and hypovolemia 0.9% normal saline is preferred until volume replaced

Hyperkalemia

Hyperkalemia Management: I. Cardio protective: stabilizes cardiac membrane

A. calcium gluconate 1G IV over 10 minutes II. Push potassium into cells:

A. insulin regular 10 units once AND dextrose 25 G once (prevent hypoglycemia) B. albuterol 50 mg nebulizer over 5 minutes C. sodium bicarbonate 50 mEq over 5 minutes

III. Elimination of potassium from the body (must remove potassium or will keep recurring) A. Renal: furosamide (Lasix) - 40-80 mg IV once B. Fecal: sodium polystyrene sulfonate (Kayexelate) - increases fecal potassium excretion

through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels. The practical exchange ratio is 1 mEq K per 1 gram of resin 1. Can be given orally or rectally as enema 15-30 G once 2. May take hours to days to provide effect (i.e. not helpful for acute hyperkalemia)

C. Blood: dialysis IV. Remember to recheck potassium level to ensure treatment worked

Nephrology / Urology

V. Renal Replacement Therapy

Overview and Indications I. The management of patients with acute kidney injury (AKI) is supportive, with renal replacement

therapy (RRT) indicated in patients with severe kidney injury. Multiple modalities of RRT are available. These include intermittent hemodialysis (IHD); continuous renal replacement therapies (CRRTs); and hybrid therapies, also known as prolonged intermittent renal replacement therapies (PIRRTs), such as sustained low-efficiency dialysis (SLED) and extended-duration dialysis (EDD). Despite these varied techniques, mortality in patients with AKI remains high, exceeding 40 to 50 percent in severely ill patients

II. Indications for renal replacement therapy include the following when refractory to medical therapy: - Acidosis: intractable metabolic acidosis - Electrolyte disarray: hyperkalemia, hypercalcemia, etc. - Intoxicants: methanol, ethylene glycol, lithium, salicylates - Overload from fluid: (i.e. pulmonary edema, secondary hypertension, etc.) - Uremic complications (pericarditis, encephalopathy, bleeding) - Typically BUN >100, Crt >10mg/dL

Terminology III. Dialysis (diffusion): The movement of solutes from a high concentration compartment to a low

concentration compartment. Movement occurs along an electrochemical gradient. An electrolyte solution (dialysate) runs countercurrent to blood across a semi-permeable (small pore) filter. Small molecules in blood such as urea move along the concentration gradient into the dialysate fluid. Larger molecules are poorly removed by this process. Solute removal is directly proportional to the dialysate flow rate.

IV. Conventional hemodialysis blood flow is 350-450 ml/min and dialysate flow is 500-800 ml/min. In continuous hemodialysis (CVVHD) blood flow is usually set at 100-200 ml/min, and dialysate flows at 1000-2000 ml/hr.

V. Ultra-filtration (convection): Solute is carried (in solution) across a semipermeable membrane in response to a transmembrane pressure gradient (a process known as solvent drag). This mimics what actually happens in the normal human kidney. The rate of ultrafiltration depends upon the porosity of the membrane and the hydrostatic pressure of the blood. This is very effective in removal of fluid and middle-sized molecules.

Types of renal replacement therapy: I. Intermittent hemodialysis is the most efficient – Large amounts of fluid can be removed and

electrolyte abnormalities can be rapidly corrected. However, this is not suitable in unstable patients. Even in hemodynamically stable patients with ARF 20-30% become hypotensive during dialysis. Many ICU patients are too hemodynamically unstable for this therapy.

II. Continuous Renal Replacement Therapy (CRRT): The concept behind continuous renal replacement techniques is to dialyze patients in a more physiologic way, slowly, over 24 hours, just like the kidney. Intensive care patients are particularly suited to these techniques. In general, these therapies require that pts are on anticoagulation.

III. CVVH - continuous veno-venous hemofiltration. The ultrafiltration rate is high, and replacement electrolyte solution is required to maintain hemodynamic stability. This mode is also very effective for clearing mid sized molecules. It is hypothesized that removal of mid sized inflammatory cytokines may play a role in improving outcome in sepsis.

II. CVVHD - continuous venous venous hemodialysis- the dialysate is driven in a direction countercurrent to the blood. This provides reasonably effective solute clearance, although mostly small molecules are removed.

III. CVVHDF - continuous venous venous hemodiafiltration is the most popular method of dialysis in ICU. It combines convective and diffusive dialysis. Both small and middle molecules are cleared, and both dialysate and replacement fluids are required. CVVHDF is similar to IHD in slow motion: the blood flow is 100 – 200ml/min, the dialysate flow is 1000ml/hour, the filtration rate is 10-20ml/hour (very efficient), the urea clearance is 10-20ml/hour.

IV. Peritoneal dialysis has the advantage of being simple and cost effective.The major disadvantages of PD are poor uremia control, risk of peritoneal infection and mechanical obstruction of pulmonary and cardiovascular performance. Essentially never utilized in the ICU setting.

Endocrinology

W. Diabetes, Diabetic Ketoacidosis and Hyperosmolar Nonketotic Syndrome (HONK)

I. Glucose Control and Diabetes in the Critically Ill

Glucose control in the critically ill patient has been, and continues to be an area of debate. Initial interest started in 2001, when van den Berghe et al reported results from a single-center, prospective, randomized controlled trial in Leuven, Belgium, and changed the way that blood glucose was managed in intensive care units (ICUs) throughout the world. The overwhelmingly favorable results of the study - which, among critically-ill surgical patients, found a remarkable mortality benefit from the use of intensive insulin therapy targeting normoglycemia. However, the publication of the NICE-SUGAR trial in 2009, which reported that intensive insulin therapy may actually result in increased mortality among critically-ill patients, served as a major bookend to the era of tight glycemic control as a pillar of ICU management and has lead us to the generally accepted goal of blood glucose <180 in ICU patients.

Types of Insulin and Glucose Management 1. Rapid-acting insulin, begins to work about 15 minutes after injection, peaks in about 1 hour, and

continues to work for 2 to 4 hours. Types: Insulin glulisine (Apidra), insulin lispro (Humalog), and insulin aspart (NovoLog)

- Typically Aspart insulin sliding scale (mild, moderate or aggressive) with blood glucose checks AC+HS if on diet and controlled or every 4-6 hours if NPO or poorly controlled

2. Regular or Short-acting insulin usually reaches the bloodstream within 30 minutes after injection, peaks anywhere from 2 to 3 hours after injection, and is effective for approximately 3 to 6 hours. Types: Humulin R, Novolin R

3. Intermediate-acting insulin generally reaches the bloodstream about 2 to 4 hours after injection, peaks 4 to 12 hours later, and is effective for about 12 to 18 hours. Types: NPH (Humulin N, Novolin N)

4. Long-acting insulin reaches the bloodstream several hours after injection and tends to lower glucose levels fairly evenly over a 24-hour period. Types: Insulin detemir (Levemir) and insulin glargine (Lantus) \

- Typically add glargine if patient poorly controlled with aggressive sliding scale or if on long acting insulin at home. Want half of daily requirement to be long acting. (i.e. if total daily requirement is 60 units, give glargine 15 units BID in addition to sliding scale which will cover other 30 units)

5. Insulin drip is reserved for severe hyperglycemia or for patients with multiple factors such as changes in nutrition and steroids causing labile blood glucose levels. These patients need blood glucose checks every hour to help prevent hypoglycemia.

Literature: 1. Glucose Control in Critical Care. Jeremy Clain, Kannan Ramar, Salim R Surani. World J Diabetes

2015 August 10; 6(9): 1082-1091 2. “NICE-SUGAR TRIAL” - Intensive versus Conventional Glucose Control in Critically Ill Patients. Simon

Finfer et al. New England Journal of Medicine. 2009 March. Vol 360, No 13 3. American Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/

medication/insulin/insulin-basics.html

Endocrinology

II. Diabetic Ketoacidosis: A life threatening condition, mortality ranges from 2-10% in developed countries. Mortality was 100% before discovery of insulin

Pathophysiology: A. Deficiency of insulin

1. Induces increased hepatic production of glucose 2. Decreased peripheral utilization of glucose 3. Induces lipolysis which generates ketoacids (acetoacetate, B-hydroxybutyrate, and acetone)

which causes acidosis A. Increased counter regulatory hormones

1. Glucagon and catecholamine levels increase inducing glycogen phosphorylase to break down hepatic glycogen stores

2. Growth hormone levels increase which worsen hyperglycemia 3. Cortisol level is increased which stimulates protein catabolism which provides amino acids for

gluconeogenesis

As a result of the insulin deficiency and increased counter regulatory hormones, there is hyperglycemia. Glucosuria develops because the blood glucose levels exceed the glomerular reabsorptive capacity. Glucosuria induces an osmotic diuresis in which the patient loses 5-7 liters of free water, and electrolytes. This process causes the hyper-osmolarity seen in serum. Lipolysis as a consequence of insulin deficiency causes the formation of the ketoacids which accumulate and create the anion gap metabolic acidosis.

Clinical symptoms: Thirsty, weak, fatigued, abdominal pain (resolves when ketosis clears), vomiting, polydipsia, polyuria, air hunger, weight loss

Findings:Volume depleted, hypergylcemic, hyperosmolar, acidotic, ketonemia, ketonuria

Precipitants for DKA: - Noncompliance with insulin - New-onset DM - Infection - Myocardial infarction - Pancreatitis - Sympathomimetic drugs

- Steroids - GI bleeding - Trauma - CVA - Thromboembolic disease

Evaluation: Labs, Volume status, Acid-base status, Electrolytes, Osm, Glucose, Precipitants

Management: 1. Replace fluid losses over 24-48 hrs. Calculate free water deficit and use NS IV to expand

extracellular fluid volume without abrupt fall in plasma osmolality, then switch to hypotonic 1/2 NS once volume repleted (resolved orthostasis) NS 500cc/hr for 4 hrs, then 250cc/hr

2. Insulin is a must. It lowers glucagon level and counteracts gluconeogenesis in the liver. It stops lipolysis and the hepatic production of ketoacids. Loading dose 0.1-0.2units/kg IV then continuous infusion of 5-10 units/hr IV. Target the blood glucose level to decline by 75-90 mg/dl per hour.

3. Give glucose (IV D5 1/2NS) when the serum glucose level falls to 250-300 if ketosis persists as evident by acidic pH, persistent anion gap, or serum ketones.

4. Titrate the insulin drip down a unit per hour as needed to prevent hypoglycemia, but continue it until ketosis is resolved.

5. Replace electrolytes lost (potassium, magnesium, phosphate). 6. Bicarbonate use is controversial, no documented benefit. Would not give

unless pH is less than 7.0 or there is another indication for use. 7. Treat underlying precipitating cause for the DKA (i.e. infection)

Endocrinology

III. Hyperosmolar Nonketotic Syndrome (HONK): life-threatening acute metabolic complication of diabetes mellitus characterized by hyperglycemia, dehydration, organ failure, and electrolyte disturbance.

A. Typically seen in type 2 diabetics, but 40% in prior series had no previous diagnosis of diabetes. B. Metabolic derangements secondary to a relative insulin deficiency and elevated levels of stress-

responding, counter-regulatory hormones such as glucagon, catecholamines, growth hormone, and cortisol.

Epidemiology: A. HONK frequency of 17.5 cases per 100,000 person years. Mean age of presentation 57-69 yrs B. Mortality rate 12-46%. Risk factors for mortality include increasing age and higher levels of serum

osmolality. 1. Mortality rate of 7% if serum osm < 350 mOsm/L, 14% when 350-

374 mOsm/L, 32% when 375-399 mOsm/L, and 37% when > 400 mOsm/L.

Pathophysiology: A. Relative insulin deficiency leads to increased liver glucose production and a decrease in

peripheral use of glucose. B. Hyperglycemia exceeds the glomerular reabsorption capacity that results in a volume and

electrolyte diuresis. C. Generally no significant ketosis or acidosis, but have a higher degree of volume depletion that

causes prerenal azotemia, with further impairment of the glucose disposal with worsening hyperglycemia and hyperosmolality.

D. Basal insulin secretion is maintained in HONK, and the insulin levels are adequate to prevent peripheral lipolysis in adipose tissue, but the insulin levels are not adequate to allow peripheral uptake of glucose or to prevent liver overproduction of glucose.

E. Counter-regulatory hormones (cortisol) are elevated which stimulate protein catabolism to increase circulating amino acids to provide gluconeogenic precursors for the liver. Glucagon and catecholamines induce glycogenolysis in the liver further worsening the hyperglycemia. In HONK, glucagon levels correlate with the degree of hyperglycemia.

F. Hyperglycemia causes a significant osmotic diuresis which is associated with major urinary losses of electrolytes.

G. Hyperglycemia raises the extracellular osmolality and causes water to shift from the intracellular to extracellular compartment.

H. The total-body water deficit in HONK is generally in the range of 8-10 L. I. An intact thirst mechanism and access to free water should lead to

increased fluid intake in patients with an osmotic diuresis. J. Mental status changes occur when the hyperglycemia worsens and

hyperosmolality develops. K. A depressed level of consciousness will lead to a decrease fluid intake

and worsening of hyperglycemia/osmolality. L. In HONK, the degree of mental status change correlates with the degree

of hyperosmolality and dehydration.

Clinical Presentation: A. polyuria and polydipsia B. increasing lethargy C. mild confusion D. stupor E. seizures, aphasia, CVA F. hypotension, tachycardia, tachypnea, fever, dehydration, shock

Diagnostic criteria: A. Blood sugar > 600 mg/dl B. Osmolality > 330 mOsm/L C. Prerenal azotemia D. pH>7.3 E. Serum bicarbonate > 20 mEq/L

Endocrinology

Precipitants: A. Acute illness such as UTI or respiratory infection B. Noncompliance C. Stopping oral hypoglycemics or insulin, or inadequate dose of these meds D. Substance abuse may contribute to noncompliance

Evaluation: A. Assess volume and hydration status, B. Check baseline labs including lytes, BUN, Cr, ABG, serum osmolality C. Calculate anion gap, free water deficit D. Look for precipitating cause such as infection, myocardial infarction

Management: A. Replace fluid losses: Vigorous fluid replacement is vital. Generally in B. HONK, free water losses exceed sodium losses which causes a hypertonic dehydration.

1. Hypotensive patients should receive isotonic IV fluids until stable hemodynamics, then switched to hypotonic fluid. When serum osm > 330, give 1⁄2 NS at a rate of 1-2 L/hr for 1-2 hours, then 1 L/hr for 3-4 hrs monitoring response of blood pressure, and urine output. Once these parameters have improved, 1⁄2 NS is given at a rate to replace half of the free water deficit over the first 12 hrs, and the remainder in the next 24 hrs

C. Correct hyperglycemia: With volume and water repletion, glucose level will fall by 80-200 mg/dl/hr. 1. Insulin regimen of a 10-units regular IV bolus, then continuous infusion of 0.1-0.15 units of

insulin/kg/hr will decrease serum glucose from 80-100 mg/dl/hr. 2. Once blood sugar reaches 250-300 mg/dl, 5% dextrose can be added to the intravenous

fluids and the insulin infusion rate reduced. D. Replete electrolyte losses: pts will have whole body potassium deficits secondary to the osmotic

diuresis. Potassium levels will fall during treatment of HONK, so it must be monitored closely to maintain a serum level 4-5 meq/L. Don’t give K+ on presentation unless K+ is less than 4meq/L . Once urine output is adequate, 20-40 meq/L K+ can be added to the IV fluids given. 1. Detect and treat precipitating cause

Complications of Diabetic Ketoacidosis and Hyperosmolar Nonketotic Syndrome (HONK): A. Hypoglycemia B. Hypokalemia C. Cerebral edema resulting from rapid correction of BS is a rare complication, presents with

headache, progressive drowsiness, and lethargy in a patient with otherwise adequate resolution of hyperglycemia. Proposed mechanism is the development of an osmotic disequilibrium during correction of the hyperosmolar state. The CNS generates idiogenic osmols to adapt for intracellular dehydration. If correction of the extracellular hyperosmolality occurs faster than the dissipation of the idiogenic osmols, there is an osmotic gradient favoring brain cell swelling.

Gastroenterology

X. Nutrition in Critical Illness

Adapted from the 2016 ASPEN Guidelines

Overview: I. Although malnutrition in the ICU is associated with poor outcomes, the details of feeding critically ill

patients--when, what, where-is a much debated topic, with little evidence. Presented below are brief discussions of the major issues in critical care nutrition.

II. Expert opinion recommends starting enteral nutrition in patients expected to be NPO for >7days (probably most ICU patients) within 24-48 hours unless otherwise contraindicated.

Enteral or Parenteral?

I. With the exception to contraindications to enteral feeding (bowel obstruction, severe ileus, intractable vomiting, severe GI bleeding, bowel ischemia, abdominal compartment syndrome, significant hemodynamic instability, etc.), enteral feeding is first line because it is associated with fewer infectious complications (Gramlich et al. Nutrition 2004). This may be due to maintenance of the integrity of bowel mucosa, or increased infections associated with hyperglycemia or central line of TPN.

Gastric or post-pyloric?

I. There is no evidence that post-pyloric feeding reduces risk of pneumonia or enhances tolerance of feeds in unselected patients (Ho et al Intensive Care Med 2006). Therefore, gastric feeds are suitable in most patients.

II. Post-pyloric feeds (naso-jejunal) are recommended in severe acute pancreatitis over TPN due to reduction in infectious complications and length of stay (ACG, AGA Guidelines). That being said one 50 pt study has shown no significant difference between NG and NJ feeds in pancreatitis (Eatock FC et al Am J Gastro 2005). If someone is sick enough to be in the ICU we will generally attempt to obtain post-pyloric feeding but if not will try gastric with NG.

Early or Late Initiation of Feeding?

I. Guidelines recommend initiation of feeds early, within 24hrs (National guidelines Clearinghouse). This is due related in part to results of the ACCEPT trial, which implemented early nutrition as part of multiple nutrition guidelines in a multicenter trial and found reduced mortality and hospital stay. Other retrospective studies show similar benefits to early feeds. Note that one 150pt randomized trial (Ibrahim JPEN 2002) found worse outcomes in early feeds.

II. Generally safe to go ahead and start patient on Promote at 20cc/hr (trickle) and wait for recommendations from nutrition. Osmolite 2.0 would be twice as concentrated (i.e. 2 kcal/mL)

III. Estimate Goal TF Rate: quick and easy formula is = (wt x 25) / 25 1. wt(kg) x 25-30 kcal/kg/day = 70kg x 25 kcal/kg/day = 1750 kcal/day 2. 1750 kcal/day / 24 hours = 73 kcal/hour ~ 75 kcal/hour = goal rate of 75 mL/hr (Promote)

High Gastric Residuals Volumes (GRV)/Intolerance with Enteral Nutrition (EN)?

I. We suggest that GRVs not be used as part of routine care to monitor ICU patients receiving EN. II. We suggest that, for those ICUs where GRVs are still utilized, holding EN for GRVs <500

mL in the absence of other signs of intolerance (see section D1) should be avoided. Signs of feeding intolerance include emesis, abdominal distention, constipation, and, if the patient is awake and alert, complaints of uncomfortable fullness, abdominal pain, or nausea. (2016 ASPEN)

III. Patient with concern for intolerance of enteral EN should receive treatment to try to improve tolerance. Evidence suggests Erythromycin is a superior prokinetic to Reglan in setting of critical care tube feed intolerance, but combination is even better (Nguyen Crit care med 2007). Tachyphylaxis develops to both. Use side effect profile of each when choosing (ie avoid raglan in patients w/seizure, erythromycin in long QT, etc). Post pyloric feeding is another option for intolerance.

Gastroenterology

Special Formulations?

I. There is some evidence that omega 3 acids and anti-oxidants added to feeds early improve outcomes in sepsis and ARDS (Berger Crit Care Med 2007 and Pontes- Arruda Crit Care Med 2007). An earlier meta-analysis found arginine reduces infectious complications (Heylan JAMA 2001). ARDSNet is currently running a large trial to further look at this exciting issue.

Enteral Nutrition in Patients on Vasopressors? (Literature 2)

I. Objective: To evaluate the tolerability and safety of EN in critically ill patients receiving intravenous (IV) vasopressor therapy.

II. Methods: A retrospective medical record review was conducted in an urban academic medical center and included adult ICU patients from 2011 who received concomitant EN and IV vasopressor therapy for ≥1 hour. EN tolerance was defined as an absence of gastric residuals ≥300 mL, emesis, positive finding on abdominal imaging, and evidence of bowel ischemia/perforation

III. Results: Two hundred fifty-nine (n = 259) patients received 346 episodes of concomitant EN and IV vasopressor therapy. Overall EN tolerability was 74.9%. Adverse events included rising serum lactate (30.6%), elevated gastric residuals (14.5%), emesis (9.0%), positive finding on kidney/ureter/bladder radiograph (4.3%), and bowel ischemia/ perforation (0.9%). An inverse relationship was found between maximum norepinephrine equivalent dose and EN tolerability (12.5 mcg/ min for patients who tolerated EN vs 19.4 mcg/min, P = .0009). This relationship remained statistically significant after controlling for other variables (P = .019).

IV. Conclusion: Enteral nutrition is generally felt to be safe in patient receiving a maximum norepinephrine equivalent dose of 12.5 mcg/min or less. Patients can be monitored with lactate levels, gastric residuals, emesis, positive imaging or evidence of ischemia/perforation

2016 ASPEN Guidelines Bundle Statements: • Early assessment of patients admitted to the Intensive Care Unit (ICU) for nutrition risk, and calculation

of energy and protein requirements to determine goals of nutrition therapy; • Initiation of enteral nutrition (EN) within 24−48 hours following the onset of critical illness and admission

to the ICU; • Take steps as needed to reduce risk of aspiration and improve tolerance to gastric feeding; • Implementation of enteral feeding protocols with institution-specific strategies to promote delivery of EN; • Elimination of the use of gastric residual volumes as part of routine care to monitor ICU patients

receiving EN; and • Initiation of parenteral nutrition early, when EN is not feasible or sufficient in high-risk or poorly

nourished patients.

Literature: 1. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill

Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Stephen A. McClave, MD. 2016

2. Tolerability and Safety of Enteral Nutrition in Critically Ill Patients Receiving Intravenous Vasopressor Therapy. Journal of Parental and Enteral Nutrition, 2013

3. ESPEN Guidelines on Enteral Nutrition: Intensive care. K.G. Kreymann. 2006

Gastroenterology

Y. Stress Ulcer Prophylaxis

History: Association between critical illness and development of gastrointestinal bleed has been recognized for > 100 years.

A. Cushings ulcer (1832)- Stress ulcer associated with head injury. B. Curlings ulcer(1842) –Stress ulcer associated with burn injury.

Incidence: Estimates to range from 1.5 to 8.5% among all intensive care unit (ICU) patients, but may be as high as 15% among patients who do not receive stress ulcer prophylaxis. However, this complication is rare, occurring in fewer than 1% of surgical ICU patients.

Pathogenesis: Stress ulceration generally begins in the proximal regions of the stomach within hours of major trauma or serious illness. Endoscopy performed within 72 hours of a major burn or cranial trauma reveals acute mucosal abnormalities in greater than 75% of patients. Multi-hit hypothesis: Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. (Crit Care Med. 2002 ;30:S351-S355). Possible factors include:

A. Decreased mucosal blood flow. B. Decreased synthesis of protective barrier (e.g. prostaglandin) by GI mucosa. C. Decreased proliferation of mucosal epithelial cells (baseline and in response to injury). D. Decreased food intake (buffering effect) E. Increased secretion of acid

Adapted from EAST Guidelines

Which patients should receive prophylaxis? Level 1 recommendations Prophylaxis is recommended for all patients with:

- Mechanical ventilation >48 hours (OR 15.6) - Coagulopathy (OR 4.3) platelet count <50,000/m3, an INR >1.5, or PTT >2 times normal - Severe Traumatic brain injury - these patients are typically intubated and ventilated (see above) - Major burn injury (>30%) - these patients are sent to burn centers

Level 2 recommendations Prophylaxis is recommended for all ICU patients with:

- Multi-trauma, Sepsis, Acute renal failure Level 3 recommendations Prophylaxis is recommended for all ICU patients with:

- ISS>15, Requirement of high-dose steroids (>250 mg hydrocortisone or equivalent per day), In selected populations, no prophylaxis is necessary

Is there a preferred agent for stress ulcer prophylaxis? If so, which? Level 1 recommendations

- There is no difference between H2 antagonists, cytoprotective agents, and some PPIs - Antacids should not be used as stress ulcer prophylaxis.

Level 2 recommendations - Aluminum containing compounds should not be used in patients on dialysis

Level 3 recommendations - Enteral feeding alone may be insufficient stress ulcer prophylaxis

What is the duration of prophylaxis? No level 1 or level 2 evidence regarding duration Level 3 recommendations

- Until able to tolerate enteral nutrition

However, some recent evidence questions the benefit for stress ulcer prophylaxis in ICU patients - Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. NEJM, 2018

- European, multicenter, parallel-group, blinded, randomized controlled trial (RCT) - 3298 patients were enrolled; 1645 assigned to the pantoprazole group, 1653 to the placebo group - Among adult pts in the ICU who were at risk for GI bleeding, mortality at 90 days and the number

of clinically important events were similar in those assigned to pantoprazole vs placebo

Gastroenterology

Z. GI Bleeding in the ICU

Management guidelines for CCHS can be found on home portal

CCHS Policy: Christiana Care is committed to improving the care of patients with High Risk Upper GI bleeding by requiring management by an inter-professional team, whether the patient presents to the Emergency Department (ED) or when the need arises in a patient already residing on a patient care unit.

Purpose: To provide guidelines for the resources and specialty personnel who are skilled at triage, resuscitation, diagnosis, and treatment of patients with High Risk Upper GI bleeding. Paramount is that the patient’s management has an identified Team Leader and a safe procedural environment if an emergent intervention is necessary.

Scope: Christiana Care Health Services and the Medical-Dental Staff

Definitions: For purposes of this policy the following definitions apply:

High Risk Upper GI Bleed A patient will be considered as having a High Risk Upper GI bleed if they have active hematemesis, bright red blood per nasogastric tube, or bright red blood per rectum, with at least one of the following:

- Hemodynamic instability despite reasonable resuscitation efforts, or - Signs of hypovolemia on presentation with transient response after reasonable resuscitation, or - Known or suspected portal hypertension

Potential Interventions Surgical or non-surgical procedures used in the diagnosis and/or management of a patient with a High Risk Upper GI bleed and may include, but is not limited to, the following: pharmacologic therapy, EGD, interventional radiology procedure, surgical procedure, and/or insertion of a Sengstaken-Blakemore tube.

Process: 1. Initial evaluation, resuscitation, and stabilization of the patient are the responsibilities of either the

Emergency Department or patient’s clinical care team for patients on a patient care unit. The Team Leader at this initial phase of patient management is either the ED attending, or the attending physician, respectively.

Christiana Hospital I. Emergency Department - The Christiana ED physician is required to make an initial triage

determination based upon their clinical judgment: A. If an intervention is required immediately, the Christiana ED Attending will activate a Trauma Code

along with a STAT Gastroenterology consultation. 1. Once the Trauma Team arrives at the patient’s bedside, the Trauma Attending will assume

responsibility for the patient’s care and the coordination of required consultants. These consultants are likely to include, but are not limited to, Anesthesiology, Gastroenterology, Critical Care Medicine, and Interventional Radiology.

2. Disposition of patient will be determined by Trauma Attending in collaboration with consultants.

B. For patients with high risk upper GI bleeding not meeting criteria for a Trauma Code, the Christiana ED Attending will call a MICU alert along with STAT Gastroenterology consultation. 1. Once the MICU Team arrives at the patient’s bedside, the MICU Intensivist will assume

responsibility for the patient’s care and coordination of required consultants. These consultants are likely to include, but are not limited to, Anesthesiology, Gastroenterology, Interventional Radiology, and Trauma Surgery.

2. Disposition of patient will be determined by the MICU Team in collaboration with consultants.

Gastroenterology

C. Inpatient- For patients on a Christiana patient care unit that develop an unstable upper GI bleed, the nursing staff, or the Attending physician, will activate a Rapid Response Team (RRT). 1. Once the RRT Team arrives at the patient’s bedside, the MICU Team lead will assume

responsibility for the patient’s care and coordination of required consultants. a) Consultants are likely to include, but are not limited to, Anesthesiology, Gastroenterology,

Interventional Radiology, and Trauma Surgery. If an intervention is required immediately, the RRT Team will activate a Trauma Code along with a STAT Gastroenterology consultation.

b) Disposition of the patient will be determined by the MICU Team in collaboration with consultants.

Wilmington Hospital I. Emergency Department - The Wilmington ED attending is required to make an initial triage

determination based upon their clinical judgment. A. If an intervention is required immediately, the Wilmington ED Attending will activate a Trauma

Code along with a STAT Gastroenterology consultation and the patient will be transferred to the Christiana ED for ongoing management as outlined above. 1. For patients with high risk upper GI bleeding not meeting criteria for a Trauma Code, the

Wilmington ED Attending will call a WICU alert along with STAT Gastroenterology consultation.

2. Disposition of patient will be determined by the WICU Team in collaboration with consultants. B. Inpatient - For patients on a Wilmington patient care unit who develop an unstable upper GI bleed,

the nursing staff, or the Attending physician, will activate a Rapid Response Team (RRT). 1. Once the RRT Team arrives at the patient’s bedside, the WICU Team lead will assume

responsibility for the patient’s care and coordination of required consultants. Consultants are likely to include, but are not limited to, Anesthesiology, Gastroenterology, Interventional Radiology, and Trauma Surgery. If an intervention is required immediately, the RRT Team will activate a Trauma Code along with a STAT Gastroenterology consultation and the patient will be transferred immediately to the Wilmington ED in preparation for transport to Christiana.

2. Disposition of the patient will be determined by the WICU Team in collaboration with consultants.

Settings for an EGD in patients with high risk of upper GI bleed:

When collaborative consultation between the Team Leader and the Gastroenterologist determines the patient requires an emergent EGD and Anesthesia support, these individuals will determine the optimal venue. The ED or non-ICU patient care units are not appropriate locations for this procedure.

Possible venues include: I. GI Lab during hours of normal operation

A. When the GI lab is determined to be the location for the EGD the Gastroenterologist will notify the appropriate parties within the GI Lab for scheduling/support.

B. The Team Leader will manage the pre, intra, and post procedure care of the patient in collaboration with all consultants.

II. Intensive Care Units 24/7/365 A. When the ICU is determined to be the location for the EGD the Team Leader will, in collaboration

with the endoscopist, determine timing of the procedure. B. The Team Leader will manage the pre, intra, and post procedure care of the patient in

collaboration with all consultants. III. Operating room 24/7/365, When the Operating Room is determined to be the location for the EGD,

the case will be posted by the endoscopist, or designee, by contacting OR at 733-2666 or the Charge RN at 733-3088, or the Anesthesia in Charge pager 733-1451. A. The case will be assigned an Operating Room Classification in order to activate OR resources to

meet patient’s needs: 1. Class 1 (20 minutes to Operating Room - Immediate) – Acute life- or limb-threatening

processes associated with on-going resuscitation and immediate need for surgical intervention.

Gastroenterology

2. Class 2 (< 2 hours or next available Operating Room, which ever sooner - Emergent) – Conditions that are anticipated to become life- or limb-threatening without prompt surgical intervention. These cases will be transported to the PACU for an evaluation by the anesthesia team. The attending surgeon/gastroenterologist must be available at the scheduled procedure time.

3. Class 3 (< 4 hours or next available Operating Room, which ever sooner - Urgent) – Conditions in which clinical deterioration is anticipated that would affect outcome without timely surgical intervention. The attending surgeon/gastroenterologist should be in- house and available at least one hour prior to anticipated starting time. The surgeon/gastroenterologist must be readily available for pre- operative discussion with the anesthesiologist.

B. The patient will be transferred to an ICU post-procedure as specified above. C. The patient’s Team Leader will provide and coordinate the peri-procedure care.

Massive Transfusion Protocol (MTP): #1819 or call #0 and ask for blood bank I. If you think you need or are going to need an MTP, call for it. You can always return it. II. What comes in MTP at CCHS = 1:1:1 resuscitation

A. pRBC - 6 units Packed red blood cells (RBCs) are prepared from whole blood by removing approximately 250 mL of plasma. One unit of packed RBCs should increase levels of hemoglobin by 1 g/dL (10 g per L) and hematocrit by 3 percent. In most areas, packed RBC units are filtered to reduce leukocytes before storage, which limits febrile non-hemolytic transfusion reactions (FNHTRs), and are considered cytomegalovirus safe

B. FFP - 6 units Plasma products available in the United States include fresh frozen plasma and thawed plasma that may be stored at 33.8 to 42.8°F (1 to 6°C) for up to five days. Plasma contains all of the coagulation factors. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Thawed plasma has lower levels of factors V and VIII and is not indicated in patients with consumption coagulopathy (diffuse intravascular coagulation)

C. PLTs - 1 unit (~6 units of whole blood) - increase platelet count by 5-10,000/uL Platelet transfusion may be indicated to prevent hemorrhage in patients with thrombocytopenia or platelet function defects. Contraindications to platelet transfusion include thrombotic thrombocytopenic purpura (TTP) and heparin-induced thrombocytopenia (HIT). Transfusion of platelets in these conditions can result in further thrombosis. One unit of apheresis platelets should increase the platelet count in adults by 30 to 60 × 103 per µL

Cryoprecipitate: Not included in MTP I. Cryoprecipitate is prepared by thawing fresh frozen plasma and collecting the precipitate.

Cryoprecipitate contains high concentrations of factor VIII, factor XIII, fibrinogen, von Willibrand Factor and fibronectin. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy (DIC). Each unit will raise the fibrinogen level by 5 to 10 mg per dL (0.15 to 0.29 µmol per L), with the goal of maintaining a fibrinogen level of at least 100 mg per dL (2.94 µmol per L)

Please see home portal for guidelines on reversal of anticoagulation. - K-centra Reversal of Oral Anticoagulatns, Intracranial Hemorrhage (Traumatic and Non-Traumatic)

Literature: 1. ASGE guideline: the role of endoscopy in acute non-variceal upper-GI hemorrhage. American Society

for Gastrointestinal Endoscopy. 2004; 60(4); 497- 504. 2. Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A

retrospective evaluation. Jonathan H. Sin et al. Journal of Critical Care. 2016.06.024

Gastroenterology

AA.Acute Pancreatitis

Adapted from American Gastroenterology Association Guidelines (2018)

I. Diagnosis: at least two of the following three A. Characteristic abdominal pain; biochemical evidence of pancreatitis (ie, amylase or lipase

elevated >3 times the upper limit of normal); and/or radiographic evidence of pancreatitis on cross-sectional imaging

II. General Classification: A. Interstitial Edematous Pancreatitis (90-95%) B. Necrotizing Pancreatitis (5-10%) with or without hemorrhage

III. Imaging: Generally CT is recommended modality (2016 Revised Atlanta Classification) A. Initial imaging is most useful when performed 5–7 days after hospital admission, when local

complications have developed and pancreatic necrosis (if present) should be more clearly seen. B. Types of Collections:

1. No Necrosis: a) <4 weeks = Acute Peripancreatic Fluid Collection (APFC) b) >4 weeks = Pseudocyst

2. Yes Necrosis: a) <4 weeks = Acute Necrotizing Collection (ANC) b) >4 weeks = Walled Off Necrosis (WON)

IV. Atlanta Classification: A. Mild (80%): acute pancreatitis without signs of organ failure or local complications B. Moderate: acute pancreatitis with local complications (pancreatic and peripancreatic collections) C. Moderately severe: transient signs of organ failure lasting < 48 hours D. Severe: acute pancreatitis with signs of organ failure lasting > 48 hours

V. Severity / Prognosis: A. Apache II >8 available immediately and consistent with ‘severe pancreatitis’ and high risk for

necrotizing pancreatitis (usually occurs 7-10d), which is associated with 20% mortality. These patients should be cared for in ICU.

B. Ranson’s Criteria: Score of 4 or more has LR of 2.5 for major complications/mortality, but takes 48hrs to complete.

Gastroenterology

VI. General Management: supportive for the most part A. Hydration with goal UOP > 0.5-1.0cc/kg/hr, Lactate <2.0 within 48 hours, etc B. Give nutrition when able, enteral is always better than parental nutrition it pt tolerates C. Frequent assessment (i.e. ICU level of care) with STEP UP approach if worsening

VII.Step-Up Approach (2010) A. 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue

randomized to either open necrosectomy or step up approach. 1. Step-up Approach: percutaneous drainage, followed, if necessary, by minimally invasive

retroperitoneal necrosectomy. B. Results: 35% able to be treated with percutaneous drainage only. New-onset multiple-organ

failure occurred less often in patients assigned to the step-up approach than those assigned to open necrosectomy (12% vs 40%). No difference in mortality.

VIII.Recommendations: A. Initial Resuscitation:

1. In patients with acute pancreatitis, the AGA suggests using goal-directed therapy for fluid management. Conditional recommendation, very low quality evidence.

2. Comment: The AGA makes no recommendation whether normal saline or Ringer’s lactate is used.

B. Nutrition: 1. In patients with acute pancreatitis, the AGA recommends early (within 24 hours) oral feeding

as tolerated rather than keeping the patient nil per os. Strong recommendation; moderate quality evidence.

2. In patients with acute pancreatitis and inability to feed orally, the AGA recommends enteral rather than parenteral nutrition. Strong recommendation, moderate quality evidence.

C. Infection and Antibiotics: 1. Infection should be considered in patients who fail to improve after 7-10 days with persistent

or increasing wbc count or who deteriorate dispite optimal supportive measures. Clinical signs of infection and abdominal imaging demonstrating the presence of gas within the necrosis are reasonably suggestive of infection and antibiotic therapy can be initiated without aspiration and culture.

2. Carbapenem (Imipenem) is first line. Second line agents include quinolone, ceftazidime, or cefepime combined with an anaerobic agent such as metronidazole) should be used

D. When to operate? 1. In patients with acute biliary pancreatitis, the AGA recommends cholecystectomy during the

initial admission rather than after discharge. Strong recommendation, moderate quality evidence.

Literature: 1. A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis. Hjalmar C. van Santvoort,

M.D, NEJM 2010 2. Revised Atlanta Classification for Acute Pancreatitis: A Pictorial Essay1. Bryan R. Foster, MD, 2016 3. American Gastroenterological Association Institute Guideline on Initial Management of Acute

Pancreatitis. Seth D. Crockett. 2018

Gastroenterology

BB.Compartment Syndromes

Definition: A group of syndromes characterized by increased pressure within a closed anatomical space resulting in local ischemia (limb compartment syndrome) or local and systemic complications (abdominal compartment syndrome).

The definitive treatment of both syndromes is emergent surgical decompression.

Abdominal Compartment Syndrome (ACS) • Increased intra-abdominal pressure (IAP) results in gut and renal ischemia, decreased venous

return, hypotension, decreased lung compliance and impaired ventilation from increased pleural pressures.

• Most common causes are abdominal trauma, intra-abdominal bleeding, AAA repair. Can occur with dilated loops of bowel in absence of trauma, rarely with ascites, peritonitis, pancreatitis.

• Symptoms: distended abdomen, hypotension, renal failure, increased peak airway pressures (PIP)

• Measuring IAP: most convenient/least invasive way is through Foley catheter port connected to CVP monitor. Paralysis of the patient prior to measuring bladder pressure is debated, however, it is likely more useful as a therapy due to the fact that we are attempting to measure the true abdominal pressure, not the pressure after initiation of a therapy such as paralysis (e.g. we would not measure the bladder pressure after surgical decompression and then close the abdomen if it were within normal limits). IAP > 20 with above symptoms is generally considered abdominal compartment syndrome. Abdominal perfusion pressure (MAP-IAP) > 60 is desirable.

• Treatment: surgical decompression leaving open abdomen with negative pressure therapy is the most definitive therapy. Alternative include drainage of ascites if contributing, paralysis to relax abdominal muscles, escharotomy in severe burns to the abdomen causing constriction

• Outcome: ~70% mortality

Limb Compartment Syndrome (LCS) • Causes

- Injury (trauma, hemorrhage, ischemia-reperfusion, venous obstruction) leads to swelling and increased pressure within a compartment. The increased pressure collapses venules, and as hydrostatic pressure increases, eventually collapses arterioles causing limb ischemia.

- Most common cause is fracture of tibia or distal radius/ulna, in which compartment syndrome has been described in 2-30% of fractures

- Crush injury is another important cause - Aortic balloon pumps can cause LCS~5% of the time through inducing LE ischemia

Large DVTs, phlegmasia cerulean dolens can cause LCS • Symptoms: (6 P’s)

- Early: pain out of proportion, paresthesia - 30 to 120 minutes after (early nerve ischemia) - Middle: poikilothermia, pallor - Late: pulselessness (arterial insufficiency), paralysis (late nerve ischemia)

• Signs: tense limb, pain with flexion/extension, loss of 2 point discrimination. Pulselessness implies late disease, limb injury has already begun.

• Measuring Compartment pressure: Must be done if LCS suspected in unresponsive patient. Multiple different techniques available. Most popular is a simple needle manometer-18G needle connected to CVP monitor. The ideal pressure for performing fasciotomy is unknown. Different cutoffs used are: compartment pressure >30, diastolic BP-compartment pressure<30 (i.e. delta pressure), MAP- compartment pressure<40.

• Ischemia lasting longer than 4-6 hours is generally irreversible • Treatment: Fasciotomy. In Phlegmasia celulea dolens, treatment is leg elevation and

anticoagulation. • Morbidity: 15-20% loss of motor function/strength assuming no necrosis found • Vascular patients on IV lytic (tPA) therapy require ICU care and compartment checks

Infectious Disease

CC.Sepsis/Septic Shock: (click here for link)

Definitions: • Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection • Septic shock: Sepsis with circulatory and cellular/metabolic abnormalities profound enough to

substantially increase mortality

Clinical Criteria: • Sepsis: Suspected or documented infection and an acute increase of ≥ 2 SOFA points (a proxy for

organ dysfunction: pulmonary, cardiovascular, hepatic, coagulation, renal, CNS) (must know baseline SOFA score to assess for acute change but The baseline SOFA score can be assumed to be zero in patients not known to have preexisting organ dysfunction).

• Septic Shock: Sepsis and vasopressor therapy needed to elevate MAP ≥ 65 mmg Hg and lactate > 2 mmol/L (18 mg/dL) after adequate fluid resuscitation

Mortality: • SOFA score of 2 points or more = in-hospital mortality greater than 10%. • SOFA score of 2 points or more + Septic Shock = hospital mortality rates greater than 40%

Where does the patient need to go?

quickSOFA (qSOFA): A parsimonious clinical model developed with multivariable logistic regression identified that any 2 of 3 clinical variables—Glasgow Coma Scale score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate 22/min or greater—offered predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) similar to that of the full SOFA score outside the ICU. Good bedside assessment. Essentially vital signs plus gestalt or mental status of patient and may be most useful for triaging patients (i.e. floor vs step-down vs ICU)

• Respiratory rate ≥22/min • Altered mentation (i.e. GCS <15 found to be equal to GCS <13)

Infectious Disease

• Systolic blood pressure ≤100 mm Hg (SBP more commonly recorded but MAP <65 likely more accurate)

For patients with suspected infection within the ICU, the SOFA score had predictive validity (AUROC = 0.74; 95% CI, 0.73-0.76) superior to that of this model (AUROC = 0.66; 95% CI, 0.64-0.68), likely reflecting the modifying effects of interventions (eg, vasopressors, sedative agents, mechanical ventilation). Addition of lactate measurement did not meaningfully improve predictive validity but may help identify patients at intermediate risk.

Resuscitation: • start broad spectrum antibiotics early (within 1 hours for sepsis and septic shock) • correct hypovolemia (30mL/kg crystalloid within the first 3 hours - 2L for 70kg patient) • restore perfusion pressure • and in some cases a little more may be required…

2016 Surviving Sepsis Guidelines: A few important statements…

Sepsis and septic shock are medical emergencies and we recommend that treatment and resuscitation begin immediately. (Best Practice Statement)

Antibiotics:

We recommend that administration of IV antimicrobials be initiated as soon as possible after recognition and within 1 h for both sepsis and septic shock. (strong recommendation, moderate quality of evidence).

We recommend empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens. (strong recommendation, moderate quality of evidence).

IV Fluid:

We recommend that in the resuscitation from sepsis-induced hypo-perfusion, at least 30ml/kg of intravenous crystalloid fluid be given within the first 3 hours. (Strong recommendation; low quality of evidence)

We recommend that following initial fluid resuscitation, additional fluids be guided by frequent reassessment of hemodynamic status. (Best Practice Statement)

We recommend crystalloids as the fluid of choice for initial resuscitation and subsequent intravascular volume replacement in patients with sepsis and septic shock (Strong recommendation, moderate quality of evidence). We suggest using albumin in addition to crystalloids when patients require substantial amounts of crystalloids (weak recommendation, low quality of evidence).

Vasopressors:

We recommend norepinephrine as the first choice vasopressor (strong recommendation, moderate quality of evidence).

We suggest adding either vasopressin (up to 0.03 U/min) or epinephrine to norepinephrine with the intent of raising MAP to target, or adding vasopressin (up to 0.03 U/min) to decrease norepinephrine dosage.(weak recommendation, low quality of evidence)

Steroids:

We suggest against using intravenous hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, we suggest intravenous hydrocortisone at a dose of 200 mg per day. (Weak recommendation; low quality

Infectious Disease

of evidence) - At CCHS, we typically use 50mg q6h in patients with suspected adrenal insufficiency on 2 or more vasopressors. Initial once time dose is 100mg followed by 50mg q6h.

Glycemic Control:

We recommend a protocolized approach to blood glucose management in ICU patients with sepsis, commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This approach should target an upper blood glucose level ≤180 mg/dL rather than an upper target blood glucose ≤110 mg/dL. (Strong recommendation; high quality of evidence)

We recommend that blood glucose values be monitored every 1 to 2 hrs until glucose values and insulin infusion rates are stable, then every 4 hrs thereafter in patients receiving insulin infusions. (Best Practice Statement)

Three major points: these can all occur simultaneously • Obtain source control (if able to do so) • Give early, broad spectrum, antibiotics (within 1 hour) • Resuscitation

Summary: • Start resuscitation early with source control, intravenous fluids and antibiotics. • Frequent assessment of the patients’ volume status is crucial throughout the resuscitation period. • We suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels as a

marker of tissue hypo-perfusion.

Literature: 1. Surviving Sepsis Guidelines: (click here for link)

Infectious Disease

DD.Clostridium Difficile Infection

Infectious Disease Society of America (IDSA) Guidelines - 2018 (click here for link)

What is the best-performing method (ie, in use positive and negative predictive value) for detecting patients at increased risk for clinically significant C. difficile infection in commonly submitted stool specimens? - Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin;

GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission (Figure 2) (weak recommendation, low quality of evidence).

What is the most sensitive method of diagnosis of CDI in stool specimens from patients likely to have CDI based on clinical symptoms? - Use a NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by

NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission (Figure 2) (weak recommendation, low quality of evidence).

What is the role of repeat testing, if any? Are there asymptomatic patients in whom repeat testing should be allowed, including test of cure? - Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool

from asymptomatic patients, except for epidemiological studies (strong recommendation, moderate quality of evidence).

What are important ancillary treatment strategies for CDI? - Discontinue therapy with the inciting antibiotic agent(s) as soon as possible, as this may influence the

risk of CDI recurrence (strong recommendation, moderate quality of evidence). - Antibiotic therapy for CDI should be started empirically for situations where a substantial delay in

laboratory confirmation is expected, or for fulminant CDI (described in section XXX) (weak recommendation, low quality of evidence).

What are the best treatments of an initial CDI episode to ensure resolution of symptoms and sustained resolution 1 month after treatment? - Either vancomycin or fidaxomicin is recommended over metronidazole for an initial episode of CDI.

The dosage is vancomycin 125 mg orally 4 times per day or fidaxomicin 200 mg twice daily for 10 days (strong recommendation, high quality of evidence) (Table 1).\

- In settings where access to vancomycin or fidaxomicin is limited, we suggest using metronidazole for an initial episode of nonsevere CDI only (weak recommendation, high quality of evidence). The suggested dosage is metronidazole 500 mg orally 3 times per day for 10 days. Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity (strong recommendation, moderate quality of evidence). (See Treatment section for definition of CDI severity.)

What are the best treatments of fulminant CDI? - For fulminant CDI*, vancomycin administered orally is the regimen of choice (strong recommendation,

moderate quality of evidence). If ileus is present, vancomycin can also be administered per rectum (weak recommendation, low quality of evidence). The vancomycin dosage is 500 mg orally 4 times per day and 500 mg in approximately 100 mL normal saline per rectum every 6 hours as a retention enema. Intravenously administered metronidazole should be administered together with oral or rectal vancomycin, particularly if ileus is present (strong recommendation, moderate quality of evidence). The metronidazole dosage is 500 mg intravenously every 8 hours.*

- *Fulminant CDI, previously referred to as severe, complicated CDI, may be characterized by hypotension or shock, ileus, or megacolon in which case surgery should be considered.

- If surgical management is necessary for severely ill patients, perform subtotal colectomy with preservation of the rectum (strong recommendation, moderate quality of evidence). Diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes is an alternative approach that may lead to improved outcomes (weak recommendation, low quality of evidence).

Hematology

EE.Venous Thromboembolism and Management of Massive Thromboembolism

At CCHS we use chemical prophylaxis with Lovenox 30 mg q12 hours with mechanical prophylaxis with PCBs in all trauma patients unless otherwise contraindicated. For patient with impaired renal function we use heparin 5,000 TID.

Risk Factors: spinal cord injury, lower extremity and pelvic fractures, need for surgical procedures, increasing age, femoral venous line insertion or surgical repair of venous injuries, prolonged immobility, long duration of hospital stay, severity of the trauma, and mechanism of injury

2013 Cochrane Review: significantly reduced risk for DVT in patients receiving prophylaxis compared with no prophylaxis (4 versus 9 percent; relative risk [RR] 0.52, 95% CI 0.32-0.84) [2]. The reduction in pulmonary embolism (PE) was not statistically significant (1.7 versus 3.3 %; RR 0.65, 95% CI 0.29-1.43). Mortality was low in both groups (1 versus 1.4%; RR 0.59, 95% CI 0.2-1.70). Other findings included: - Mechanical ppx reduced risk of DVT relative to no prophylaxis (five trials; RR 0.43, 95% CI 0.25-0.73). - Pharmacological ppx reduced the risk of DVT relative to mechanical prophylaxis (six trials; RR 0.48,

95% CI 0.25-0.95) but had a higher risk for minor (RR 2.37, 95% CI 1.13-4.98), but not major, bleeding. - LMW heparin reduced the risk of DVT relative to unfractionated heparin (two trials; RR 0.68, 95% CI

0.50-0.94) with similar rates of bleeding. - Combined (mechanical and pharmacological prophylaxis) reduced the risk of DVT relative to

pharmacologic prophylaxis alone (three trials; RR 0.34, 95% CI 0.19-0.60).

Massive Pulmonary Thromboembolism: I. Introduction: Massive pulmonary embolism is a rare but often fatal illness. Most patients die within

the first few hours so the immediate institution of effective therapy is critical. In fact, patients suspected of having a massive PE therapy should be initiated prior to performing diagnostic evaluation. Christiana Hospital has PERT Alert if indications met, see portal.

II. Treatment: A. Resuscitation: ABC’s (as always)

1. Airway: Hypoxemia and respiratory failure require immediate intubation. Caution: Positive pressure can lead to worsening of hemodynamic status.

2. Hemodynamic: a) IV fluids: may be necessary, be cautious because fluids can precipitate RV failure in an

already strained right side. This is in contrast to treatment of RV infarct where fluids are required.

b) Unless clearly volume depletion IV fluids should be limited to 1L. c) Begin vasopressors early. Norepinephrine and dopamine. Dobutamine should be used

with caution because of the risk of worsening hypotension. B. Anticoagulation: SubQ heparin is first line in hemodynamically stable patient. IV Heparin is

recommended in renal failure, morbid obesity and hemodynamically unstable patient (see below). C. Thrombolytics:

1. Accelerates lysis of clot, but associated with increased risk of major hemorrhage. 2. No study has been large enough to CONCLUSIVELY demonstrate mortality benefit. 3. Persistent hypotension and severe hypoxemia are accepted as indications for thrombolytic

therapy. (i.e. if everything else is failing) D. IV filters:

1. Indicated in patients with contraindication to anticoagulation. 2. Recurrent PE on anticoagulation 3. Bleeding on anticoagulation 4. Some physicians recommend IVC filters in patients with poor cardiac reserve because a

recurrent PE would likely be fatal. Consider in all pts with massive PE and + DVT E. Embolectomy: catheter or surgical

1. Performed with massive PE and contraindication to therapy or refractory to treatment.

Literature: 1. EAST Guidelines on Venous Thromboembolism 2. Antithrombotic Therapy for Atrial Fibrillation. CHEST. 2018 3. Thromboprophylaxis for trauma patients (Review). Barrera LM. Cochrane Review. 2013

Hematology

FF. Blood Products in ICU

The Products:

• Whole Blood: Only indicated in massive bleed (usually in military trauma setting)

• Packed Red Blood Cells: Each unit contains 200 ml of red cells, 300 ml of volume. One unit will raise the hgb by 1g/dL and hct by 3%. Hct is 55% in pRBC. Stored for up to 45 days. Half-life of RBC variable. Needs to be ABO compatible, crossmatched and Rh typing. In most areas, packed RBC units are filtered to reduce leukocytes before storage, which limits febrile nonhemolytic transfusion reactions (FNHTRs), and are considered cytomegalovirus safe

• Fresh Frozen Plasma (FFP): Plasma products available in the United States include fresh frozen plasma and thawed plasma that may be stored at 33.8 to 42.8°F (1 to 6°C) for up to five days but once thawed must be used within 24 hours. Plasma contains all of the coagulation factors. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Thawed plasma has lower levels of factors V and VIII and is not indicated in patients with consumption coagulopathy (diffuse intravascular coagulation) Needs to be ABO compatible.

• Platelets: Obtained from whole blood as a pooled product. Each bag increases platelets by 5-10 thousand in 70kg person. The presence of allo-antibodies may decrease the response to transfusion. Single donor platelets and HLA-matched may be more effective. Small amounts of RBC, WBC and plasma are transfused with platelets. This may sensitize the recipient and make future RBC transfusions more difficult. ABO matching in not mandatory but ABO incompatible platelets is believe to have shortened survival. Women of childbearing age should have Rh typing.

• Cryoprecipitate: prepared by thawing FFP at 4 degrees and collecting the white precipitate. Cryoprecipitate contains high concentrations of factor VIII, factor XIII, fibrinogen, von Willibrand Factor and fibronectin. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy (DIC). Each unit will raise the fibrinogen level by 5 to 10 mg per dL (0.15 to 0.29 µmol per L), with the goal of maintaining a fibrinogen level of at least 100 mg per dL (2.94 µmol per L)

• Factor VIII and IX precipitate: typically used for hemophilia

• Leukocyte reduced products: Leukocytes are the cause of many adverse consequences of blood transfusions. Immunologically mediated effects such as GVHD, and FNHTR. Infectious transmissions and reperfusion injury. Indicated for chronically transfused, transplant recipients, individuals with previous transfusion reactions, CMV negative individuals that are immunocompromised.

Threshold for Red Blood Cell Transfusions:

• Hebert in Canadian Critical Care Trials Group prospective randomized trial: 838 pts randomized to liberal transfusion 10-12 hgb (420) or restrictive 7-9 hgb (418.) Well designed, well matched. Pts in restrictive group received on average three fewer units of blood. Overall restrictive group received 50% less transfusions. No difference in mortality overall but in hospital mortality higher in liberal group. Subgroup analysis showed less severely ill and age <55 assigned to restrictive group were half as likely to die at 30 days. People with cardiac disease did the same in each group. Authors believe this strategy should be used in all populations, cerebrovascular disease included.

• Effect of massive transfusions is dilution of clotting factors. Clotting factors will fall by 10% for every 500 ml of blood loss. In normal host bleeding will only occur when clotting factors fall below 25% of normal. Most recommend to correct clotting factors but probably correcting reason for bleed (artery under ulcer base) would suffice. Platelets will fall by 25% with 6 units PRBC’s.

• Conclusion: potential risks include increased risk of infection and coagulopathy with transfusion with no evidence for increases complications in restrictive transfusion. Therefore it is generally recommended to follow restrictive transfusion practice (hgb <7-9).

Hematology

Platelet Transfusion: American Association of Blood Banks Guidelines - Patients having elective central venous catheter placement with a platelet count less than 20 × 109

cells/L. (Quality of evidence: low; strength of recommendation: weak) - Patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/

L. (Quality of evidence: very low; strength of recommendation: weak) - Patients have major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L.

(Quality of evidence: very low; strength of recommendation: weak)

Complications: • Acute Hemolytic reactions. Estimated to occur 0.016% of transfusions. Always ABO

incompatibility. Less than half are fatal. Pain at infusion site, dyspnea, hypotension, mental status changes. In critically ill pt consider this if pt becomes suddenly hypotensive. Stop transfusion. Send blood for free hemoglobin, haptoglobin and Coombs’ testing.

• Delayed reactions 0.025% of transfusions. May go undetected. Pts with prior alloimmunization or pregnancy. 35% asymptomatic. Minor antigens.

• Febrile nonhemolytic reactions. 7% of transfusions. Antileukocyte antibodies. • Allergic reactions. From mild reactions to anaphylaxis. No hemolysis. Secondary to serum

antigens. In IgA deficient patients may develop IgE antibodies to infused IgA. • Hypothermia. Make sure blood is warmed to at least 80 degrees. • Coagulopathy. Occurs in massive transfusions. 8-10 units pRBC’s. • Citrate Toxicity. Blood is anticoagulated with citric acid and sodium citrate (citrate binds to

calcium). Once transfused citrate can cause hypocalcemia. In addition, citrate metabolism results in production of HCO3. As a result, metabolic acidosis can develop. Typically this does not occur because transfused blood is acidotic to serum (pH 7.10).

• Hyperkalemia. Hyperkalemia leaks out of RBCs at rate of 1meq/d. Concentration is about 90meq/L in 1 unit of PRBC’s. Not usually a problem because of small volume of fluid transfused. Hypokalemia is usually transient and is a consequence of transfusion related alkalosis.

• Acute lung injury. Transfusion of alloreactive antibodies contained with red cell products or FFP can lead to agglutination and activation of leukocytes and resultant ARDS. More common with FFP.

Thromboelastogram (TEG): (click her for link)

Procedures

GG. Procedures in the SICU

Note: For each procedure make team members aware and set a time for the procedure so everyone is working toward a similar goal. This always included the nurse and typically the respiratory therapist in addition to the surgical team and surgical attending.

Bronchoscopy: Interactive Bronchoscopy (click here for link) - General Indications: patients with concern for mucous plugging is the most common. - Supplies: bronchoscopy tower and scope, BAL collection canister if needed, flush for scope (supplies

generally gathered by respiratory therapist) - Medications: typically utilize whatever the patient is on (i.e. Versed, Propofol, Fentanyl)

Tracheostomy: Blue Rhino Percutaneous Tracheostomy Set and Technique - General Indications: please see section above with details - Supplies: “Blue Rhino” percutaneous tracheostomy set, #6 Shiley, cuffed trach (consider proximal XL

Trach if indicated for thick/deep neck), bronchoscopy tower with bronchoscope, blanket roll for under the shoulders creating neck extension.

- Medications: typically Versed 2-10mg, Fentanyl 100-300mcg, and Nimbex 10-20mcg

Percutaneous Endoscopic Gastrostomy (PEG) Tube: PEG Tube Placement - General Indications: patients unable to swallow for a prolonged period of time (>4 weeks). Typically

neurocritical care patients with significant dysphagia. Should be evaluated by speech. - Supplies: Endoscope (from GI lab - bring patient sticker), endoscopy tower, PEG tube kit/set,

Chloraprep. - Medications: typically Versed 2-10mg, Fentanyl 100-300mcg, and Nimbex 10-20mcg (may not need) - Safe Technique

- 1:1 Depression: of stomach wall seen endoscopically when palpation of the stomach wall - Light reflex: able to see endoscopic light through the abdominal wall - Safe Pass: small gauge needle inserted slowly with fluid, if air seen in syringe before needle seen in

gastric lumen then likely that needle has entered other portion of the GI tract (i.e. transverse colon) and it is not safe to place PEG tube.

Exploratory Laparotomy (bedside): - General Indications: deteriorating patient with abdominal source/open abdomen, intestinal ischemia,

abdominal compartment syndrome, second look procedure in patient too unstable for OR - Supplies: Chloraprep (x2), blue towels, laparotomy drape, suction tubing with pool sucker, laparotomy

pads, irrigation, suture removal kit and consider having Bovie (Bovie cart needed, which is in SICU), bowel stapler, small laparotomy tray (may need to go to surgical “hard” goods for this with patient sticker)

- Medications: typically these patients are on sedative drips (see above section for these meds)