SEPTIC SHOCK

Dr. VENKAT NARAYANA GOUTHAM.V

In 1914, Schottmueller wrote, “Septicemia is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness.”

Definitions…

Infection A microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms.

Bacteremia The presence of viable bacteria in the blood.

SIRS systemic level of acute inflammation, that may or may not be due to infection, and is generally manifested as a combination of vital sign abnormalities.

Severe SIRS SIRS in which at least 1 major organ system has failed

Sepsis SIRS which is secondary to infection.

Severe sepsis Severe SIRS which is secondary to infection.

Shock It is a serious, life threatening medical condition characterized by a decrease in tissue perfusion to a point that is inadequate to meet cellular metabolic needs.

Septic shock sepsis with hypotension(arterial bp<90mm hg systolic) for 1 hr despite adequate fluid resuscitation.( Or ).need for vassopressors to maintain systolic bp>=90mm or mean arterial pressure >=70mmhg.

Multiple Organ Dysfunction Syndrome (MODS) The presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

Criteria for SIRS…

Requires 2 of the following 4 features to be present:o Temp >38° or <36.0° Co Tachypnea RR>20 o Tachycardia (HR>90, in the

absence of intrinsic heart disease)

o WBC > 12,000/mm3 or <4,000/mm3 or >10% band forms on differential

Criteria for Severe SIRS

Must meet criteria for SIRS, plus 1 of the following:

o Altered mental statuso SBP<90mmHg or fall of >40mmHg from baselineo Impaired gas exchange (PaO2/FiO2 ratio<200-

250)o Metabolic acidosis (pH<7.30 & lactate > 1.5 x

upper limit of normal)o Oliguria (<0.5mL/kg/hr) or renal failure o Hyperbilirubinemiao Coagulopathy

o platelets < 80,000-100,000/mm3, o INR >2.0, PTT >1.5 x control, o elevated fibrin degredation products

Identifying Acute Organ Dysfunction as a Marker of Severe Sepsis

TachycardiaHypotensio

n CVP PAOP

Jaundice Enzymes Albumin

PT

Altered Consciousness

ConfusionPsychosis

TachypneaPaO2 <70 mm

HgSaO2 <90%

PaO2/FiO2 300

OliguriaAnuria

Creatinine

Platelets PT/APTT Protein C D-dimer

Relationship Between Sepsis and SIRS

TRAUMA

BURNS

PANCREATITIS

SEPSIS SIRSINFECTION SEPSIS

BACTEREMIA

Pathophysiology…

It is not precisely understood, but it involves a complex interaction between the pathogen and the host's immune system.

Physiological response to localized infection:o Influx of activated PMN leukocytes & monocytes release of inflammatory

mediatorso Local vasodilatation & increased endothelial permeabilityo Activation of the coagulation cascade.

The same occurs in septic shock but at a systemic level. Diffuse endothelial disruption Increased vascular permeability Vasodilatation Thrombosis of end organ capillaries

Infection

InflammatoryMediators

Endothelial Dysfunction

Vasodilation

Hypotension Vasoconstriction Edema

Maldistribution of Microvascular Blood Flow

Organ Dysfunction

Microvascular Plugging

Ischemia

Cell Death

Risk Factors for SIRS/Sepsis

1. Extremes of age2. Indwelling lines/catheters3. Immunocompromised states4. Malnutrition5. Alcoholism6. Malignancy 7. Diabetes8. Cirrhosis9. Male sex10. Genetic predisposition?

Clinical Manifestations…

Recognition of Septic Shock: Inflammatory triad-

Fever Tachycardia flushed skin

Hypoperfusion Altered sensorium Urine output Wide pulse pressure.......bounding

pulses

Warm

shock

Clinical Manifestations…

Hypotension Cold and clammy skin Mottling Tachycardia Cyanosis Narrow pulse pressure Hypoxemia Acidosis.

Cold shock

Localizing symptoms that are most useful clues to the etiology sepsis: Head and neck infections - Severe headache, neck stiffness,

altered mental status, earache, sore throat, sinus pain or tenderness, cervical or submandibular lymphadenopathy

Chest and pulmonary infections - Cough (especially if productive), pleuritic chest pain, dyspnea.(Streptococcus pneumoniae,Klebsiella pneumoniae,Staphylococcus aureus)

Abdominal and GI infections - Abdominal pain, nausea, vomiting, diarrhea(E coli,Acinetobacter species,Enterobacter species,Salmonella species)

Pelvic and genitourinary infections - Pelvic or flank pain, vaginal or urethral discharge, dysuria, frequency, urgency(E coli,Proteus species,Klebsiella species)

Bone and soft-tissue infections - Focal pain or tenderness, focal erythema, edema, fluctuance(S aureus,Staphylococcus epidermidis,Streptococci)

Work-up…

Laboratory studieso CBCo Comprehensive chemistry panelo Coagulation studieso Blood & urine cultures

Imaging studieso Chest radiographyo Abdominal radiographyo Others according to the suspected cause.

Laboratory studies

CBC:o The WBC count and differential.o Hemoglobin concentration dictates oxygen-carrying

capacity in blood.o The goal is to maintain hematocrit >30% and hemoglobin >10

g/dL.

o Platelets are an acute-phase reactant and are typically elevated in the setting of inflammation. However, platelet counts may decrease in the setting of DIC.

Comprehensive chemistry panel

Sodium and chloride levels are abnormal in severe dehydration.

Decreased bicarbonate can point to acute acidosis.

Increased BUN and creatinine levels can point to severe dehydration or renal failure.

Glucose control is important in the management of sepsis, with hyperglycemia associated with higher mortality.

• LFTs and bilirubin, alkaline phosphatase, and lipase levels are important in evaluating multiorgan dysfunction or a potential source (eg, biliary disease, pancreatitis, hepatitis).

Serum lactate…

It is the best serum marker for tissue perfusion.

There is also evidence that lactate can be elevated in sepsis in the absence of tissue hypoxia due to mitochondrial dysfunction and down-regulation of pyruvate dehydrogenase, which is the first step in oxidative phosphorylation.

Lactate levels >2.5 mmol/L are associated with an increase in mortality.

It has been hypothesized that lactate clearance is a measure of tissue reperfusion and an indication of adequate therapy.

Coagulation studies (PT/aPTT) o PT and activated aPTT are elevated in DIC.o Fibrinogen levels are decreased and FDP are increased in the setting of DIC.

Blood cultures o Blood cultures should be obtained in patients who have suspected sepsis in order to

isolate a specific organism and tailor antibiotic therapy. o Positive in < 50% of cases of sepsis.o A set of cultures from an indwelling intravenous catheter is especially

important, as these catheters are a frequent source of bacteremia.

Urinalysis and urine culture o Urinary tract infection is a common source of sepsis, especially in elderly patients. o Febrile adults without localizing symptoms or signs have a rate of occult urinary tract

infection of 10-15%.

Gram stain and culture, when applicable o Sputum specimen should be obtained if pneumonia is suspected.o Any abscess should be drained promptly, and purulent material sent to the

microbiology laboratory for analysis.o CSF specimen should be obtained if meningitis is suspected.

Imaging studies

• CXR routine in the workup of fever with an unclear etiology.o Infiltrates are detected with a chest radiograph in about

5% of febrile adults without localizing signs of infection.

Abdominal plain films should be obtained if clinical evidence of bowel obstruction or perforation exists.

Abdominal ultrasonography is indicated when evidence of acute cholecystitis or ascending cholangitis exists

Management…

The initial treatment of sepsis and septic shock

involves the administration of supplemental oxygen and volume infusion with

isotonic crystalloids

Broad spectrum antibiotics

Abscess should be drained, necrotic tissue excised

Blood glucose levels normalized

Replacement-dose corticosteroids

Patients with septic shock should be treated in an ICU. Apache score

The following should be monitored frequently: o systemic pressureo CVPo pulse oximetryo ABGso blood glucoseo lactate, and electrolyte levels o renal function

o Urine output, a good indicator of renal perfusion, should be measured, usually with an indwelling catheter

An initial assessment of airway and breathing is very important in a patient with septic shock.

Supplemental oxygen should be administered to all patients with suspected sepsis.

Fluid therapy…

Patients with suspected septic shock require an initial crystalloid fluid challenge of 20-30 mL/kg (1-2 L) over a period of 30-60 minutes with additional fluid challenges at rates of up to 1 L over 30 minutes.

Crystalloid administration is titrated to a CVP goal between 8 and 12 mm Hg or signs of volume overload (dyspnea, pulmonary rales, or pulmonary edema on the chest radiograph).

A fluid challenge refers to the rapid administration of volume over a particular time period followed by an assessment of the response.

Patients with septic shock often require a total 4-6 L or more of crystalloid resuscitation.

It is also important to monitor urine output (UOP) as a measure of dehydration.

UOP <30-50 mL/h should prompt further fluid resuscitation

Vasopressor agents…

Vasopressor administration is required for persistent hypotension once adequate intravascular volume expansion has been achieved.

Persistent hypotension is typically defined as systolic blood pressure (SPB) <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg with altered tissue perfusion.

The goal of vasopressor therapy is to reverse pathologic vasodilation and altered blood flow distribution.

The recommended first-line agent for septic shock is either norepinephrine or dopamine

Norepinephrine: Has predominant alpha-receptor agonist effects results in

potent peripheral arterial vasoconstriction without significantly increasing heart rate or cardiac output.

So it is preferred in warm septic shock where peripheral vasodilatation exists in association with normal or increased cardiac output.

Dose: 5-20 mcg/min

Dopamine: has a much greater effect on beta-receptors increasing

mean arterial pressure primarily through increasing myocardial contractility, stroke volume, and heart rate.

At high doses it has some alpha-receptor effect and so causing peripheral vasoconstriction.

It is more useful in the setting of cold shock, where peripheral vasoconstriction exists and cardiac output is too low to maintain tissue perfusion.

Doses range from 2-20 mcg/kg/min.

Antibiotics…

Antibiotics should be administered within the first hour of recognition of septic shock, and delays in antibiotic administration have been associated with increased mortality.

Selection of particular antibiotic agents is empirically based on an assessment of the patient's underlying host defenses, the potential source of infection, and the most likely responsible organisms.

Antibiotic choice must be broad spectrum, covering gram-positive, gram-negative, and anaerobic bacteria when the source is unknown.

WHEN the source is unknown. Clinical condition Antibiotics

regimens(intravenous therapy)

Immunocompetent adult Ceftriaxone(2g q24h) or piperacillin-tazobactum(3.375g q4-6h)or meropenem(1g q8h) or(cefepime 2g q12h)

AIDS piperacillin-tazobactum(3.375g q4-6h)or meropenem(1g q8h) or(cefepime 2g q12h)

One regimen for septic shock of unknown cause is

Ceftriaxone(2g q24h) or piperacillin-tazobactum(3.375g q4-6h)or meropenem(1g q8h) or(cefepime 2g q12h)

Vancomycin must be added if resistant staphylococci or enterococci are suspected.

If there is an abdominal source, a drug effective against anaerobes should be included “metronidazole”

Antibiotics are continued for at least 5 days after shock resolves and evidence of infection subsides

Abscesses must be drained and necrotic tissues (eg, infarcted bowel, gangrenous gallbladder, abscessed uterus) surgically excised.

Steroid therapy…

It has theoretical benefits in the setting of severe sepsis by inhibiting the massive inflammatory cascade.

Recent guidline is that steroids should be administered only in patients with septic shock whose hypotension is poorly responsive to fluid resuscitation and vasopressor therapy.

Hydrocortisone 200–300 mg/day, for 7 days in three or four divided doses or continuos infusion.

Activated protein C…

Recombinant drug with fibrinolytic and anti-inflammatory activity, seems beneficial for severe sepsis and septic shock if begun early; benefit has been shown only in patients with significant risk of death.

Dose: 24 mcg/kg/h by continuous IV infusion for 96 h. Bleeding is the most common complication;

Contraindications include: hemorrhagic stroke within 3 mo, spinal or intracranial surgery within 2 mo, acute trauma with a risk of bleeding intracranial neoplasm.

Blood sugar…

Normalization of blood glucose improves outcome in critically ill patients, even those not known to be diabetic.

A continuous IV insulin infusion (crystalline zinc 1 to 4 U/h) is titrated to maintain glucose between 80 to 110 mg/dL .

This approach necessitates frequent (eg, q 1 to 4 h) glucose measurement.

Renal Replacement

Intermittent haemodialysis and continuous veno venous haemofiltration (CVVH) are considered equivalent. CVVH offers easier management in haemodynamically unstable patients.

DVT prophylaxis

Use either low-dose unfractionated heparin or low-molecular weight heparin.

Use a mechanical prophylactic device, such as compression stockings or an intermittent compression device, when heparin is contraindicated.

Use a combination of pharmacologic and mechanical therapy for patients who are at very high risk for DVT.

Consideration forlimitation of support

Discuss advance care planning with patients and families.

Describe likely outcomes and set realistic expectations.

As sepsis progresses to septic shock,the risk of dying increases substantially.

Sepsis is usually reversible whereas patients with septic shock often succumb despite aggressive therapy.

So prevention offers the best oppurtunity to reduce mortality and morbidity.

Special consideration must be given to neonates, infants, and small children with regard to fluid resuscitation, appropriate antibiotic coverage, intravenous (IV) access, and vasopressor therapy.