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No IV, No Problem! Practical Approaches to Alternative
Routes of Administration
Objectives
• Evaluate the need for alternative routes of drug administration
• Utilize proper technique and identify medications appropriate for intranasal administration
• Evaluate the risks and benefits with drug administration via intraosseous route
• Recommend appropriate medications, doses, and techniques for endotracheal tube administration
• Recommend appropriate techniques, fluids, and adjunctive agents for hypodermoclysis
Feeling the Need for Speed!
Laurimay L. Laroco, Pharm.D.
Pharmacy Clinical Coordinator – Adult ED and Clinical Evaluation Areas
WakeMed Health and Hospitals
Raleigh, NC
Does your ED and/or institutionprovide access to alternate routes of medication administration other than
IV for emergent meds/fluids?
Yes
No
I don’t know
Working on it…
What alternate routes are utilized for emergent med/IV administration at your
institution/ED?
Intraosseous
Intranasal
Subcutaneous
Endotracheal
Establishment of Vascular Access• Vascular Access
• Considered a standard of emergency care• Both pre‐hospital and acute hospital settings
• One of the most common procedures ordered in an Emergency Department (ED)• Reported top selected procedure of 2009 ED visits
• High priority procedure for critically ill and unstable patients
• Success rate and time to vascular access is crucial to optimal resuscitation of the most critical patients
Emergency Vascular Services: Technology, Economics, and Deployment in a Multi‐Dimensional Setting. Vidacare Corporation. 2006Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 1
Access Time Expectations
• Average time necessary for peripheral IV cannulation is 2.5‐13 minutes
• Average time necessary for “difficult access” is as much as 30 minutes
• Goal for time to vascular access in emergent/urgent situations: Immediately!
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.
Common Needs for Emergent Vascular Access
• Prompt resuscitation
• Reliable delivery of emergent/urgent medications, electrolytes, nutrition, and fluids
• Route for contrast needed in diagnostic imaging
• Blood tests for monitoring and diagnostic purposes
• Monitoring of hemodynamicsEmergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Rauch D, et al. Clinical Pediatrics; 48(9): 895‐901.
Difficult Venous Access (DVA)• Definition
• Multiple attempts and/or special interventions are anticipated or required to achieve and maintain peripheral venous access
• Emergent Intravenous Access Failure• Failure rate of 10‐40%• One of the major limitations of out‐of‐hospital resuscitation
• Pediatric patients• Number of attempts in pediatric patients ranges from 1‐10 • Average child required 2.2 sticks to achieve venous access• Average time for venous access can range 10‐33 minutes
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24.
Risk Factors for DVA
Patient Related
• Weight
• Age
• Dark or scarred skin
• Pain, anxiety, fear
• IV drug abuse patients
• Mental/Emotional Status
• Multiple hospitalizations
Treatment‐Related
• Long term or repeated intravenous treatments
• Chemotherapy patients
• Steroid therapy
• Long term IV antibiotics
• Shunts
• Fistulas
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24.
Risk Factors for DVA
Illness/Injury Related
• Acute conditions• Multiple injuries/trauma
patient
• Dehydration/Hypotension
• Sepsis, Septic Shock
• Vasoconstriction
• Burns
• Peripheral edema
• Hypothermia
Illness/Injury Related
• Chronic conditions
• Diabetic patients
• Tumors
• Vasculopathies
• Dermatologic abnormalities
• Sickle cell disease
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24.
Effects of DVA
• Patient related effects
• Increased on‐scene times
• Multiple needlesticks
• Delayed IV fluid support
• Delayed medication delivery
• Delay in diagnosis and initiation of treatment
• Increased frustration and productivity loss of ED staff
• Other complications
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 2
Effects of DVA
• Central Venous Catheterization
• Common alternative approach when venous access establishment has failed
• Associated consequences• Delayed time to establishment
• Venous thrombosis
• Arterial puncture
• Associated bloodstream infections
• Pneumothorax
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Institute for Healthcare Improvement. http://www.ihi.org/knowledge/Pages/Measures/MeasuresPreventCentralLineInfection.aspx Last accessed: 2/25/13
Effects of DVA
• Central Venous Catheterization
• Associated bloodstream infections
• As high as 20% mortality rate
• Costly – up to $56,000 per episode
• May add 7‐14 days to a hospital stay
• Institute of Health Improvement
• Reduction of central line infections initiative to reduce patient harm in healthcare settings
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Institute for Healthcare Improvement. http://www.ihi.org/knowledge/Pages/Measures/MeasuresPreventCentralLineInfection.aspx Last accessed: 2/25/13Center for Disease Control and Prevention. MMWR 2002; 52 (RR‐10): 1‐26.
Effects of DVA
• 2012 Prospective Cohort Study• Objective
• Estimate the incidence of intravenous access difficulty (IVAD) and its associated delays in an urban ED
• Methods• Recorded the time from the initial skin puncture to IV line establishment
• Results• 125 patients enrolled, 107 had an IV placed in ED• Incidence and delays associated with IVAD were as follows
• None: 61%/1min• Mild: 11%/5 min• Moderate: 23%/15 min• Severe: 5%/120 min
Witting MD. J Emerg Med. 2012; Apr 42(4): 483‐87.
Effects of DVA
• Healthcare Worker Effects
• Needle‐free drug delivery
• Addresses concerns over bloodborne pathogens
• Broader scope of healthcare workers can deliver drugs by other routes vs. having to access a vein
• Reduces cost associated with needlestick injury
• Reduces time spent reporting needlestick injuries
• Reduces the amount of time off work secondary to a needlestick injury
Royal College of Nursing, Needlestick Injury in 2008. http://www.rcn.org.uk. Last accessed 3/10/13.Study of nurses’ views on workplace safety and needlestick injuries. http://www.nursingworld.org/safeneedles. Last accessed 3/10/13..
Management of DVA
• Technique chosen will depend on urgency of case
• ACLS guidelines
• Emergency Nursing Resource Guideline
• Ultrasound‐guided IV access
• Intraosseus vascular access
• Subcutaneous rehydration therapy
• Warming
• Alternative methods
ENA Emergency Nursing Resources Development Committee. Emergency nursing resource: difficult intravenous access. Emergency Nurses Association; 2011 Dec
Barriers to Management of DVA
• Inadequate availability of staff
• Lack of available expertise
• Limited access to or training in advanced technologies that facilitate peripheral venous access
Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011..
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 3
Alternative Routes: Need for Options
• Rapid establishment of vascular access is more important than the site of access
• The need for availability of alternative routes• Immediate vascular access required• DVA situations• Mass casualties• Delay or prevent central line placement• Hospital protocols that limit the number of IV
establishment attempts• Decrease in occupational exposures• “The Perfect Storm” scenarios…
Emergency Vascular Services: Technology, Economics, and Deployment in a Multi‐Dimensional Setting. Vidacare Corporation. 2006Emergency Nursing Resource: Difficult Intravenous Access. Emergency Nursing Resource Development Committee, 2011.Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24; American Heart Association. Vascular Access Procedures. 2006
Alternative Routes: The Need for Options
Route Fluids Medications
Intraosseous X X
Transmucosal (inc. Intranasal)
X
Subcutaneous X X
Inhalation (inc. Endotracheal)
X
Intravenous X X
PICC X X
Central Venous Cannulation X X
Central Venous Cutdown X X
Intramuscular X
Oral X X
Naso/orogastric X X
Transdermal X
Kuensting LL, et al. J Emerg Nurs. 2009; 35: 419‐24
What are examples of risk factors for DVA?
Dark skin
IV drug abuse patients
Dehydration
All of the above
Key Takeaways
• Alternate routes of administration is essential to deliver urgent/emergent medications in DVA situations
• Identification for risk factors for DVA is key in the preparation for utilizing alternate routes of administration
No IV Access, Get MAD!
Christi Jen, PharmD, BCPSClinical Pharmacist – Emergency Medicine
PGY1 Residency Program DirectorBanner Boswell Medical Center
A Sarah Case
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 4
Why Intranasal (IN)?
Safety
• Needleless
• Pain‐free
• No sterile technique needed
• Patient tolerated
Efficacy
• Transmucosal drug absorption
• Nose‐to‐brain pathway
• Relatively rapid onset of action
Mechanism of IN Drug Absorption
Image from: http://training.seer.cancer.gov/anatomy/respiratory/passages/nose.htmlImage from: http://care.american‐rhinologic.org/sinus_anatomy
Variability IN Drug Absorption
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79.
• Formulation
• Physicochemical properties
Drug
• Transepithelial passage
• Drug degradation & elimination
• Other
Patient
Drug Formulation
• Volume less than 200 µL to avoid runoff
• Concentrated, potent drug
• ≥ 10 µm in diameter to ensure adsorption
• Viscosity indirectly related to size of spray
• 30°angle of drug administration demonstrated 90% deposition efficiency
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79.
Physicochemical Drug Properties
• Molecular weight
• Rapid absorption: < 300 Da
• Slow absorption: >1000 Da
• Hydrophilicity vs lipophilicity
• Lipophilic = transcellular
• Hydrophilic = paracellular > transcellular
• Degree of ionization
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79.
Image from: http://publications.nigms.nih.gov/findings/oct04/sasisekharan_files/textmostly/slide8.html
Transepithelial Passage
• Must overcome mucus barrier on epithelium
• Mucociliary clearance:
• Biphasic
• Transcellular vs. paracellular passage
• Nasal blood flow
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79http://www.nlm.nih.gov/medlineplus/ency/imagepages/9674.htm.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 5
Degradation and Elimination
• Means of elimination:
• Sneezing
• Run‐off
• Difficulty in penetration epithelial cells and tight junctions
• Nasal first‐pass effect: enzymes, efflux proteins
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79.
Patient Factors
Mucosal Health
• Dysfunction in mucociliary clearance: CF
• Rhinosinusitis
• Radiation to head/nasal cavity
• Cigarette smoking
Drug Interactions
• Vasoconstrictors: phenylephrine, oxymetazoline
• Considered relative contraindications
Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79.
Ideal Conditions for IN Drug Administration
Relatively healthy nasal
mucosa
Lipophilic drug
< 1000 Da
Types of IN Devices
Nose Drops
Atomizers
Aerosol
Syringe and
Cotton Ball
Wolfe TR, Bernstone T. J Emerg Nurs 2004;30:141‐7.
Atomization
• Delivers small drug particles to nasal mucosa
• Rapid administration
• No regard for positioning
• Devices available:
• Mucosal Atomization Device (MAD)
• Accuspray Nasal Spray
• Kurve Controlled Particle Dispersion
Del Pizzo J, Callahan JM. Ped Emerg Care 7 Jul 2014;30(7):496‐501
DDAVP Drops
• Delivered posteriorly
• Rapid clearance
• Immediate swallowing
• Delivered posteriorly
• Rapid clearance
• Immediate swallowing
DDAVP Spray
• Delivered anteriorly
• Slow nasopharynx clearance
• 2‐3 fold increase in relative bioavailability
• Delivered anteriorly
• Slow nasopharynx clearance
• 2‐3 fold increase in relative bioavailability
Harris AS, Nilsson IM, Wagner ZG, et al. J Pharm Sci. 1986 Nov;75(11):1085‐8.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 6
Ketamine Spray vs. Drops
• 34 uncooperative children with ASA Grade 1 requiring dental treatment
• 2‐stage crossover trial
• Patient acceptance: (p<0.0001)
• Onset of sedation (p<0.05)
• Recovery time (p<0.05)
Ketamine Drops
Atomized Ketamine
Pandey RK, et al. J Clin Pediatr Dent. 2011;36(1):79‐84.ASA: American Society of Anesthesiologists
Pharmacokinetic (PK) Study of Haloperidol in Healthy Adults
Dose: haloperidol 2.5 mg Log P= 3.2, MW 370 Da
Miller JL, Wesson Ashford J, Archer SM, et al. Pharmacotherapy. 2008;28(7):875‐82..
*Mucosal Atomization Device not used
Midazolam PK Study
Midazolam IN IV IM
Bioavailability (%)
72.5 100% 93%
Tmax (mins) 10.3 12.4 29.2
Wermeling DP, et al. Anesth Analg 2006;103:344‐9.
• Sedative properties: IV > IN > IM
• Adverse effects:• Nasal irritation
• Taste disturbance
• Eye watering
• Dizziness
• No severe e.g., respiratory depression
New Therapeutic Uses of IN Drugs
Patient Population & Indications
• Pediatrics & adults
• Life‐threatening situations
• Seizures
• Hypoglycemia
• Analgesia
• Opioid overdose
• Epistaxis
• Anesthesia
Medications
• Opioids
• Fentanyl
• Sedative
• Benzodiazepines
• Ketamine
• Other
• Naloxone
• Lidocaine
Considered off‐label use of medications!
IN Midazolam
• Anxiolytic and treatment of seizure
• Properties:
• log P = 2.5, MW = 326 Da
• Tmax: 5 – 10 mins
• Usual dose: 0.2 mg/kg (max 10 mg)
• Adverse Effects:
• Nasal irritation
• Dysgeusia, nausea, vomiting, salivation
• Visual and gait disturbancesDel Pizzo J, Callahan JM. Ped Emerg Care 7 Jul 2014;30(7):496‐501Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79
EMS Treatment of Peds Seizures
IN midazolam
◦Median seizure time: 11 mins (p<0.003)
PR diazepam
◦Median seizure time: 30 mins
◦ Repeat seizure in ED
◦ ED intubation
◦ Other seizure meds
◦ Hospital admission
◦ PICU admissionHolsti M, Sill BL, Firth SD, et al. Ped Emerg Care. Mar 2007;23(3):148‐53.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 7
Treatment of Acute Peds Seizures at Home
IN Midazolam
• Dose: 0.2 mg/kg (max 10mg) x 1
• Median time to seizure cessation: 3 mins
• Median total seizure time: 10.5 mins
• Easier to administer*
• No difference in adverse drug effects
PR Diazepam
• Dose: 0.3‐0.5 mg/kg (max 20mg) x 1
• Median time to seizure cessation: 4.3 mins
• Median total seizure time: 12.5 mins
Holsti M, Dudley N, Schunk J, et al. Arch Pediatr Adolesc Med. Aug 2010;164(8):747‐753.*Statistically significant
IN Fentanyl
• Analgesia
• Properties:
• log P = 4.05, MW = 336 Da
• Tmax = 5 – 15 mins
• Dosing:
• 1.7 mcg/kg (1 – 2 mcg/kg)
• Adverse Effects:
• Epistaxis, dysgeusia, nasal irritation
Del Pizzo J, Callahan JM. Ped Emerg Care 7 Jul 2014;30(7):496‐501Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79
IN Fentanyl vs. IV Morphine
• Age 7‐15 with clinically deformed closed long‐bone fractures (N=67)
• Morphine 10mg/mL IV or fentanyl 150 mcg/mL IN• Mean doses: morphine 0.11 mg/kg, fentanyl 1.7
mcg/kg
• Results:• Statistically significant reductions in combined pain
scores at 5, 10, and 20 mins • No serious adverse events reported between two
groups• Minor: bad taste
Borland M, et al. Ann Emerg Med. Mar 2007;49(3):335‐40.
IN Ketamine
• Sedation and analgesia
• Properties
• log P = 2.9, MW = 237 Da
• Dosing: not established in peds
• 0.5 – 9 mg/kg have been studied
• 5 mg/kg (usual)
• Adverse effects:
• Nasal irritation
• Emergence phenomenaDel Pizzo J, Callahan JM. Ped Emerg Care 7 Jul 2014;30(7):496‐501Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79
IN Ketamine (INK)
• Analgesia in adults (moderate to severe pain)
• Sub‐dissociative dose: 0.7 – 1 mg/kg
• Only 56% efficacious (N=72)
• Analgesia in ≥ 6 years old (moderate‐severe pain)
• 0.5 to 0.75 mg/kg
• 88% treatment success (N=40)
• Procedural sedation in peds
• Dose: 3 – 6 mg/kg (5 mg/kg)Yeaman F., et al. Emerg Med Austral 2014;6:237‐42.Andolfatto G, et al. Acad Emerg Med Oct 2013;20:1050‐4.Tsze DS, et al. Ped Emerg Care. Aug 2012;28(8):767‐70.
IN Naloxone
• Opioid reversal
• Properties:
• log P = 2.09, MW = 327 Da
• Tmax = 6 – 9 mins
• Usual dosing: 2 mg
• Adverse effects:
• Nasal irritation
Del Pizzo J, Callahan JM. Ped Emerg Care 7 Jul 2014;30(7):496‐501Grassin‐Delyle S, et al. Pharmacol and Therap 2012;134:366‐79Dowling J, et al. Therap Drug Monitor Aug 2008;30(4):490‐6.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 8
Saved by the Nose: Bystander IN Naloxone Study
• 385 bystanders over 15 months• Opioid use: 24.1 out of 30 days
• Overdose Kits• Instructions: 1 mg/nostril; may repeat x 1• 2 Luer‐lock, prefilled syringes with naloxone 2mg/2mL
• Mucosal atomization device (MAD)
• Results: 50 participants reported overdose• 74 successful reversals• Participants used multiple kits
Doe‐Simkins M, Walley AY, Epstein A, et al. Am J Pub Health. May 2009;99(5):788‐91.
Re‐visiting Sarah
To get MAD or not to get MAD
Pros
• Easy to use without regard to patient position
• Upright vs supine
• Healthcare vs. lay personnel
• Relatively inexpensive
Cons
• One size‐fits all
• Single‐use only
• Cumulatively expensive
How to Use the MAD Device
• Obtain and prepare all supplies.
• Drug
• 3 mL syringe and needle
• Atomization device
• Calculate the dose needed.
• Draw up the volume needed.
• Add 0.1 mL to account for “dead space.”
• Remove needle and replace with atomization device using Luer‐lock system.
• Monitor the patient.
How to Use the MAD Device
• Utilize both nostrils to maximize absorptive area
• Aim slightly up and towards middle nasal turbinate in 30°angle
• Bioavailability similar to IV
• Drug dosing
• Monitoring
• Single‐use; one size fits all
MAD
Key Takeaways
• Ideal conditions for IN administration• Lipophilic drug with MW less than 300 Da
• Relatively healthy nasal mucosa
• Concentrated drug; volume up to 1 mL
• Administration technique• 30° angle towards middle nasal turbinates
• Safety:• Monitor for severe adverse effects e.g., respiratory
depression
• Counsel the patient on possible burning sensation and discomfort
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 9
Atomization Device
Image from: http://intranasal.net/DeliveryTechniques/default.htm#How_should_one_deliver_medications_to_the_nose
Indication Drug Dose Factors to Consider
Analgesia1 Fentanyl 50 mcg/mL 1.5 – 2 mcg/kg Respiratory depressionRe‐dose in 15 mins*Smallest wt: 10 kg
Anxiolysis1 Midazolam 5 mg/mL 0.4 – 0.5 mg/kg(max 10 mg)
Burning sensation for 30 seconds
Seizures1 Midazolam 5 mg/mL 0.2 mg/kg (max 10 mg)
Provide airway support
NG Insertion2 Lidocaine 4% (PF) Injection 5 mL
0.5 – 1 mL1.5 mL
In addition to pharyngeal and topical lidocaine 2% jelly
Opioid Reversal
Naloxone 1 mg/mL 2 mg Avoid using less concentrated 0.4 mg/mL vial
Sedation3,4 Ketamine 100 mg/mL
5 mg/kg (peds)(0.5 – 9 mg/kg
have been studied)
Monitor for emergence phenomena, HTN
1. Wolfe TR, Braude DA. Pediatrics Sept 2010;126(3):532‐7.2. Gallagher EJ. Ann Emerg Med 2004;44:138‐41.3. Pandey RK, et al. J Clin Pediatr 2001;35(1):79‐844. Tsze DS, et al. Ped Emerg Care. Aug 2012;28(8):767‐70.
Appendix: IN Dosing Table
No IV Access? Get the IO!
Suprat S. Wilson, PharmD, BCPS
Pharmacy Coordinator, Emergency Medicine Services
Detroit Receiving Hospital
Detroit, MI
55 y/o M with
out‐of‐hospital cardiac arrest
RN unable to obtain peripheral IV access
What is the first line alternative access according the ACLS recommendations?
Endotracheal
Central venous catheter
Intraosseous
Intramuscular
Current Recommendations
• ACLS1
• “It is reasonable for providers to establish IO access if IV access is not readily available (Class IIa, LOE C).”
• PALS2
• “IO access is a rapid, safe, effective, and acceptable route for vascular access in children, and it is useful as the initial vascular access in cases of cardiac arrest (Class I, LOE C).”
1. Neumar, et al. Circulation. 2010; 122: S729‐S7672. Kleinman, et al. Circulation. 2010;122:S876‐S908
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 10
When to Consider IO
• Cardiac or respiratory arrest
• Shock, including sepsis
• Respiratory distress (need RSI)
• Multitrauma patients
• Status epilepticus
Lewis, et al. Emerg Med Clin N Am. 2013;31:59–86
Why IO?
• Quick access
• Reliability
• Safety
• Laboratory studies
Access Type Average Time (min)
1st Attempt Success Rates
Peripheral IV (n=57)
3.6 73.7 %
Central IV (n=5)
15.6 20 %
Intraosseous (n=30)
1.5 80.6 %
Paxton, et al. J Trauma. 2009;67: 606–611)
Intraosseous Success Rates
Study Patients IO Site(s) Outcomes
Glaeser, et al. Ann Emerg Med.1993;22:1119‐1124
Observational study
Pediatrics (n= 152) and adults (n= 13)
Proximal tibia76% overall success rate
12% infiltration
Reades, et al. Ann Emerg Med.2011;58:509‐516
Randomized study
cardiac arrest adults (n = 182)
Tibial (n = 64)
Humeral (n = 51)
Peripheral IV (n = 67)
First attempt success
91% tibia
51% humeral
43% peripheral IV
Gazin, et al. Resuscitation2011;82:126–129
Observational study
Adults (n = 34) and pediatrics (n = 5)
Unknown
84% first attempt success
97% second attempt success
Laboratory Studies
• Serum chemical analysis• Na+, Cl‐, BUN/Scr, Mg, Phos, Total Ca++, bicarb
• Albumin, bilirubin, total protein
• ? K+, glucose, lactate
• Hgb/ Hct
• Blood gas analysis
• Blood typing
Paxton. Trauma 2012;14(3):195‐232
• Dogs (n=21)
• Distal femur (14G)
• Femoral vein (16G)
• Peripheral IV (16G)
• Drugs
• Epinephrine 0.01 mg/kg
• Bicarb 1 mEq/kg
• CaCl 10 mg/kg
• Lidocaine 1 mg/kg
• D50W 0.25 mg/kg
• IO IV CVC
Drug Delivery of IO
~_~_
Orlowski, et al. AJDC. 1990;144:112‐117
• Humans (n=22)
• Iliac crest
• Peripheral IV
• Morphine 5 mg
• Similar AUC with IO & IV
• Monkeys (n=6)
• Proximal tibia (15G)
• Endotracheal tube
• Peripheral IV (18G)
• Atropine 0.03 mg/kg
• Plasma atropine
• IV > IO > ET
Prete, et al. Am J Emerg Med. 1987;5(2):101‐04
Van Hoff, et al. Am J Emerg Med. 2008;26:31‐38
Contraindications
• Bone with a fracture
• Recent history of orthopedic surgeries
• Extremity with vascular injury
• Active infection
• Recent IO access attempt
• History of prior sternotomy (for sternal site)
Buck, et al. Ann Pharmacother 2007;41:1679‐86Paxton. Trauma 2012;14(3):195‐232
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 11
Intraosseous Anatomy
Dev , et al. N Engl J Med 2014;370:e35.
IO Insertion Sites
Proximal humerus
Distal femur
Proximal tibia
Distal tibia
Clavicle
Radius & Ulna
Iliac crest
Calcaneus
Sternum(adults only)
Hock, et al. Am J Emerg Med. 2009;27:8‐15Paxton. Trauma 2012;14(3):195‐232
What type of intraosseous device do you have at your hospital?
EZ‐IO®
BIG®
FAST1®
Manual needles
Mechanical Devices
FAST1®
BIG®
EZ‐IO®
Luck, et al. J Emerg Med. 2010;39(4): 468–475
Manual Needles
The Sur‐Fast® needleThe Sussmane–Raszynski needleThe modified Dieckmann needle
The modified Dieckmann needle
The Jamshidi needle
Luck, et al. J Emerg Med. 2010;39(4): 468–475
Approved Sites for IO Needles
Device Pediatric Adult Sites
Manual ✔ ✔
Sternum, humeral head, distal radius and ulna, ilium, femur, proximal and distal tibia,
including malleoli
FAST® ✔ ✔For sternal use only in ≥ 12 years
old
BIG® ✔ ✔Proximal humerus in adults
Proximal tibia in both adults and children
EZ‐IO® ✔ ✔Proximal and distal tibia,
humeral head
Adapted from Luck, et al. J Emerg Med. 2010;39(4): 468–475
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 12
Verification of Proper Placement
• Firm placement
• Aspiration of bone marrow (?)
• Easy to flush
• Ultrasound to identify misplaced needles
Luck, et al. J Emerg Med. 2010;39(4): 468–475Buck, et al. Ann Pharmacother 2007;41:1679‐86Paxton. Trauma 2012;14(3):195‐232
IO placed into the proximal tibia
20 min resuscitation
Echo: dilatation of right ventricle and a collapsed left ventricle
Suspected PE – tPA given
55 y/o M with out‐of‐hospital cardiac arrest
48 hours later
Landy, et al. Resuscitation. 2012;83:e149‐e150
Complications
• Extravasation
• Soft tissue necrosis
• Compartment syndrome
• Cellulitis / skin abscesses
• Osteomyelitis
• Bone injury
• Embolic complications
Christensen, et al. Ped Emerg Care. 1991;7(5):289‐290Paxton. Trauma 2012;14(3):195‐232
Launay, et al. J Trauma. 2003;55:788 –790
Depot Effect
• Drug remain in medullary cavity
• Lower serum peak concentration
• Longer time to peak concentration
• Drugs (animal models)
• Phenytoin
• Vancomycin
• Ceftriaxone
• Tobramycin
How Fast Can You Infuse?
Study Patients IO Site(s) Outcomes
Hock Ong, et al Am J Emer Med.
2009;27:8‐15
Observational study
24 ED adults
Proximal tibia (n = 24) vs. proximal humeral (n = 11) via EZ‐IO
Tibia:
PB 165 vs No PB 93 mL/min
Humeral:
PB 153 vs. No PB 84 mL/min
No difference between sites
Tan, et al. Am J
Emerg Med.2012;30:1602‐1606
Observational study
22 ED adults Proximal tibia (n = 20) vs. distal tibia (n = 22) via EZ‐IO
Proximal tibia:
PB 7.7 vs no PB 4.96 mL/min
Distal tibia:
PB 3.8 vs. no PB 2.07 mL/min
PB = Pressure bags
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 13
Drug Administration Pearls
• Minimize pain
• Lidocaine (preservative free)
• Medication / fluid infusions
• Pressure bags
• Infusion pumps
• Standard intravenous doses
• Flush with saline between medications
Buck, et al. Ann Pharmacother 2007;41:1679‐86Paxton. Trauma 2012;14(3):195‐232
54 y.o. male with septic shock currently on norepinephrine and vasopressin
PMH: ESRD with recent infected graft (MRSA)
In the ICU• permacath (x 2)
In the ED • 20 G, right hand• ultrasound guided lines (x 4)
Patient remains hypotensive & requires norepinephrine
What about IO?
Medications Given via IO
• ACLS medications
• Adenosine
• Amiodarone
• Atropine
• Calcium salts
• Epinephrine
• Lidocaine
• Naloxone
• Sodium bicarbonate
• Vasopressin
• RSI medications
• Etomidate
• Thiopental
• Rocuronium
• Succinylcholine
• Vecuronium
• Resuscitation fluids
• Albumin
• Blood products
• Dextrose solutions
• Saline, Lactated ringersPaxton. Trauma 2012;14(3):195‐232
Medications Given via IO
• Vasopressors
• Dobutamine
• Dopamine
• Norepinephrine
• Analgesics & Sedatives
• Diazepam
• Midazolam
• Fentanyl
• Morphine
• Antibiotics
• Penicillin
• Ampicillin
• Cefotaxime
• Vancomycin
• Miscellaneous
• Phenytoin
• Tenecteplase
• Heparin
• Insulin
• FurosemidePaxton. Trauma 2012;14(3):195‐232
Key Takeaways
• Get the IO kits ready!
• Lidocaine to minimize pain
• Pressure bags for faster infusions
• Standard IV medications dosing
• Watch for EXTRAVASATION!
No IV, No IOUse the Tube? Joseph Halfpap, PharmD, BCPS
Clinical Pharmacist‐ Emergency MedicineUniversity of Wisconsin Hospitals and Clinics
Madison, WI
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 14
Case ‐ It Could Happen• Code Blue called
• 68 y.o. diabetic patient recently admitted for pneumonia
• Found on floor V.Fib arrest • IV ripped out in fall• CPR in progress, defibrillated 2x, anesthesia intubating
• Patient well‐known to unit and requires IV access team for IV’s
• Only IO kit is locked in the ED 10 minutes away• 3rd year medical resident running code is requesting amiodarone
What would we recommend to our resident about route of
administration?
Wait until we can get an IV
Wait until we can get an IO
Use the ETT tube
Current Recommendations
• PALS
• “Vascular access (IO or IV) is the preferred method for drug delivery during CPR, but if it is not possible, lipid‐soluble drugs, …can be administered via an endotracheal tube.”
• ACLS
• “If IV or IO access cannot be established, epinephrine, vasopressin, and lidocaine may be administered by the endotracheal route during cardiac arrest (Class IIb, LOE B).”
Kleinman, et al. Circulation. 2010;122:S876‐S908Neumar, et al. Circulation. 2010; 122: S729‐S767
What medication would we recommend to our resident?
Give amiodarone via ETT
Give epinephrine via ETT
Give lidocaine via ETT
Medications for ET Administration
•Naloxone•Atropine•Vasopressin• Epinephrine• Lidocaine
Neumar, et al. Circulation. 2010; 122: S729‐S767
Administration
• Volume
• Peds 5ml/Adults 10ml
• Diluent
• Sterile water may improve absorption of epinephrine/lidocaine
• 0.9% Saline may not decrease PaO2 as much as sterile water
Prengel AW, et al. Anesth Analg. 2001;92(6):1505‐9Efrati O, et al. Resuscitation. 2003;59(1):117‐22Naganobu K, et al. Anesth Analg. 2000;91(2):317‐21Kleinman et al Circulation 2010;122:S876 S908
Neumar, et al. Circulation. 2010; 122: S729‐S767
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 15
Administration
• Direct instillation vs. Endobronchial Tube
• Endobronchial tube administration may increase absorption
• LMA administration may further decrease absorption
• Ventilation Post Administration
• 5‐10 positive pressure ventilations immediately post administration
Prengel AW, et al. Anesth Analg. 2001;92(6):1505‐9Efrati O, et al. Resuscitation. 2003;59(1):117‐22Naganobu K, et al. Anesth Analg. 2000;91(2):317‐21Kleinman et al Circulation 2010;122:S876 S908
Neumar, et al. Circulation. 2010; 122: S729‐S767
What dose of medication would we recommend to our resident?
Give epinephrine 1mg ETT
Give epinephrine 3mg ETT
Dosing• Optimal dosing is unknown via ETT
• ACLS• Recommend 2‐2.5x the IV dose• Equipotent epinephrine dose 3‐10x IV in animals
• PALS• Double or triple dose of lidocaine, naloxone, atropine
• Give a 10‐fold increase dose of epinephrineKleinman, et al. Circulation. 2010;122:S876‐S908Neumar, et al. Circulation. 2010; 122: S729‐S767
DD
O
S
E
ACLS/PALS Dosing Via ET
• Add text
Adapted from Kleinman, et al. Circulation. 2010;122:S876‐S908Neumar, et al. Circulation. 2010; 122: S729‐S767
Drug Adult IV Dose
Adult ETDose
Pediatric IV Dose
PediatricET Dose
Naloxone 0.4‐2 mg 0.8‐5 mg 0.1 mg/kg 0.1‐0.3 mg/kg
Atropine 1 mg 2‐3 mg 0.02 mg/kg 0.04‐0.06 mg/kg
Vasopressin 40 units 40‐100 units NA NA
Epinephrine 1 mg 2‐10 mg 0.01 mg/kg 0.1 mg/kg
Lidocaine 100 mg 200‐300 mg 1 mg/kg 1‐3 mg/kg
Medication Considerations
• Epinephrine – Don’t be low on the dose
• β2 effects have caused transient hypotension
• Vasopressin‐ IV dose may be adequate via ET
• Lidocaine‐ only antiarrhythmic with data
• Dosing may be limited by availabilityKleinman, et al. Circulation. 2010;122:S876‐S908Neumar, et al. Circulation. 2010; 122: S729‐S767Wenzel V, et al. Anesthesiology. 1997;86(6):1375‐81.
ET Kinetic Considerations
• Decrease pulmonary blood flow
• Arrest <20% of normal
• Delayed onset of action
• 1‐2 min compared to IV
• Prolonged action with ROSC
• Possible depot effect
Wyckoff MH Clin Perinatol. 2006;33(1):153‐60Niemann JTResuscitation. 2002;53(2):153‐57.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 16
Efficacy
• Add textNiemann JT, Crit Care Med. 2000;28(6):1815‐9.
Niemann JT, Resuscitation. 2002;53(2):153‐57.
3 year retrospective review 5 year retrospective review
Out‐of‐hospital arrest ‐ Asystole Out‐of‐hospital arrest ‐ All rhythms
n=78 IV drugs, n= 43 ET drugs n=495 IV drugs, n=101 ET drug
Epinephrine/Atropine dose 2mg ET Epinephrine/Atropine dose 2mg ET
ROSC 17% IV vs. 0% ET (p = 0.005)
No difference in survival to discharge
ROSC 27% IV vs. 15% ET (p = 0.01)
Survival to Discharge 5% IV vs. 0% ET (p = 0.01)
Key Takeaways
• IV/IO preferred
• ET route last resort
• Use high doses
• Use enough volume
• Don’t stress over diluent
• Hyperventilate briefly after drug given
Lost IV? Check Under the Skin
Joseph Halfpap, PharmD, BCPSClinical Pharmacist‐ Emergency Medicine
University of Wisconsin Hospitals and ClinicsMadison, WI
Case• 2 y.o. male
• 3 days of diarrhea, vomiting, and poor oral intake. • 1 wet diaper in the last 24 hours.
• Exam• fatigued
• mucus membranes are dry
• extremities are cool
• capillary refill is prolonged (2 seconds)
• Ondansetron ODT given‐ continued vomiting
• ED RN’s unable to establish IV access after 1 attempt
What are the options?
• Repeat IV attempt – RN ultrasound guided, IV access team and IV rehydration?
• Nasogastric tube placement – oral rehydration?
• Subcutaneous administration of fluid?
• Intraosseous administration of fluid?
Background
• Hypodermoclysis
• Administration of subcutaneous fluids ‐ SQ hydration
• Used historically 1930’s‐50’s
• Fell out of favor
• Adverse case reports
• Improved IV technology
• Currently used in palliative care and new research in pediatrics
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6Remington R. J Am Geriatr Soc. 2007;55(12):2051‐5.
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 17
Indications
• Mild to moderate dehydration in pediatrics and adults unable/unwilling to tolerate oral rehydration and…
• IV therapy not available
• IV therapy failure/expected failure
• No other needs for IV access
• Facilitate IV access
• Equally effective as IV rehydration in these patients
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6Remington R. J Am Geriatr Soc. 2007;55(12):2051‐5.
Efficacy Hypodermoclysis ‐ AdultStudy Population S
QIV Design Results
O’Keeffe/Lavin
HospitalizedElderlyMild
Dehydration
30 30 RCT1.5L/day48 hours
No difference between routes in serum urea (P=0.3) or creatinine (P=0.5) More agitation with IV (P<0.001)
Slesak et al.
HospitalizedElderly
Mild/Mod Dehydration
48 48 RCT1L/day6 days
No difference between routes in discomfort, cardiac failure, hyponatremia, local side effects, or improvement in ADL performance (P=0.25, P=0.68, P=1.0, P=1.0, P=0.74)
Duems/Arino
Hospitalized Elderly
Mild/ModDehydration
34 33 RCT1.5L/day72 hours
No difference between routes in posthydration serum urea, creatinine, osmolality (P=0.96, P=0.60, P=0.43)
Challineret al.
Acute StrokeUnable to take
PO
17 17 RCT2L/day72 hours
No difference in post hydration osmolality (P=0.12)
Duems Noriega O. Rev Esp Geriatr Genotol 2014:49(3):103‐7O’Keeffe ST. Gerontology 1996;42:36‐39
Challiner Y. Post Grad Med J 1994:70‐195‐197
Efficacy Hypodermoclysis Pediatrics
• Infuse‐PEDS2
• Randomized non‐inferiority study
• Children 1 month – 10 years, n=148
• Compare IV and hyaluronidase (HDASE) facilitated SQ hydration
• 20 ml/kg isotonic fluids over 1 hour then as needed
Spandorfer PR, et al. Clin Ther. 2012;34(11):2232‐45.
Efficacy Hypodermoclysis Pediatrics• Results
• Primary endpoint mean total volume infused• 365.0 mL in the HDASE group over 3.1 hours vs. 455.8 mL in the IV group over 6.6 hours (p=0.51)
• Secondary endpoint volume administered in ED• 334 mL SQ vs. 299 mL IV = non‐inferior (p=0.03)
• Dehydration scores similarly improved• 2.6 SQ vs. 2.2 IV (p=0.07)
• Successful line 100% SQ vs. 78% IVSpandorfer PR, et al. Clin Ther. 2012;34(11):2232‐45.
Hyaluronidase (HDASE)
• Products
• Hylenex‐ recombinant human
• Vitrase‐ ovine derived
• Mechanism
• Enzymatic hydrolysis of hyaluronic acid
• Increased permeability of SQ tissue
• Dosing ‐ Clysis
• 100‐200 units‐ typically 150 units
• Duration
• 24‐48 hoursAllen CH, et al. Pediatrics. 2009;124(5):e858‐67Spandorfer PR, et al. Clin Ther. 2012;34(11):2232‐45.Thomas JR, et al. J Palliat Med. 2007;10(6):1312‐20.
Hyaluronidase (HDASE)• Adverse reactions
• <0.01% risk of allergic reaction • Benefits
• 3‐4x increased rate of SQ fluid administration• Comparable to IV infusions
• Increased rate of absorption?• Radiolabeled NSS faster ‐ no difference at 1hr
• Decreased pain scores?• 5.8 on 100mm VAS with HDASE• 9.6 on 100mm VAS w/o HDASE (p < 0.002)
Allen CH, et al. Pediatrics. 2009;124(5):e858‐67Spandorfer PR, et al. Clin Ther. 2012;34(11):2232‐45.Thomas JR, et al. J Palliat Med. 2007;10(6):1312‐20.Lipschitz S, et al. J am Geriatric Soc 1991:39:6‐9
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 18
Hypodermoclysis
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6Remington R. J Am Geriatr Soc. 2007;55(12):2051‐5.Barua P. Age Ageing. 2005;34(3):215‐7
Advantages Limitations
• No IV• Less staff time to place• Decreased needle sticks• Extremities free• Less pain• Decreased cost• Site lasts 24‐48 hours
• Cannot provide more than 3L/24 hours
• Limited choice of IVF• Systemic absorption delayed
Sites
• Abdomen
• Scapula
• Interscapular area best
for children
• Thigh
• Upper chest
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6Remington R. J Am Geriatr Soc. 2007;55(12):2051‐5.Barua P. Age Aging. 2005;34(3):215‐7
Fluids • Recommended
• Lactated Ringers, 0.9% Saline• Pediatrics and Adults
• Also used• D5W, D5NS, D51/2NS, 1/2NS• Acidic pH of dextrose solutions may cause more discomfort
• Potassium up to 30meq/L tolerated in adults• Hypertonic and electrolyte free fluid not recommended• Fluid/electrolyte shifts
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6Remington R. J Am Geriatr Soc. 2007;55(12):2051‐5.Barua P. Age Aging. 2005;34(3):215‐7
Technique
1. Prepare site as for IV
2. Pinch skin
3. Insert 24‐25g angiocath or butterfly at 30‐45 degree angle
4. Check for lack of blood return
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6
Technique
5. Inject hyaluronidase if desired
6. Prop catheter with gauze
7. Secure with occlusive dressing
8. Start infusion and titrate slowly to desired rate
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6
Adverse reactions
• Common
• Edema ‐ 9‐14%
• Erythema ‐ 9‐14%
• Inflammation ‐ 3‐5%
• Pain ‐ 3‐5%
• Rare
• Cellulitis
• Abcesses
Spandorfer PR. Pediatr Emerg Care. 2011;27(3):230‐6
Courtesy of Laura L. Kuensting DNP
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 19
Subcutaneous hydration is appropriate for which of the
following?
Mild Dehydration
Moderate Dehydration
Severe Dehydration
Hyaluronidase facilitates more rapid administration of subcutaneous fluids.
True
False
Key Takeaways
• Subcutaneous fluid administration offers advantages for rehydration in certain clinical situations for both adults and pediatrics
• Hyaluronidase increases the rate of fluid delivery
• Isotonic solutions are recommended – LR is better tolerated
No IV, No Problem! Practical Approaches to Alternative
Routes of Administration
2014 Midyear Clinical Meeting No IV, No Problem! Practical Approaches to Alternate Routes of Administration
© 2014 American Society of Health-System Pharmacists 20