Feeling the Need for Speed! - …€¢ Evaluate the need for alternative routes of drug ... •Drug...

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


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


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




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..



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



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


Physicochemical Drug Properties

• Molecular weight

• Rapid absorption: < 300 Da

• Slow absorption: >1000 Da

• Hydrophilicity vs lipophilicity

• Lipophilic = transcellular

• Hydrophilic = paracellular > transcellular

• Degree of ionization


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.



Degradation and Elimination

• Means of elimination:

• Sneezing

• Run‐off

• Difficulty in penetration epithelial cells and tight junctions

• Nasal first‐pass effect: enzymes, efflux proteins


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


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.



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.



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:


• 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:


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.



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



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



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



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



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



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



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




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


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.



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.



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



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


Adverse reactions

• Common

• Edema ‐ 9‐14%

• Erythema ‐ 9‐14%

• Inflammation ‐ 3‐5%

• Pain ‐ 3‐5%

• Rare

• Cellulitis

• Abcesses


Courtesy of Laura L. Kuensting DNP



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



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