Can PreHospital Vitamins Help Us Survive Smoke Inhalation

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Can Pre-Hospital Vitamins Help Us Survive Smoke
Inhalation ?

• December 2008

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Todays Agenda

• Prelude
• Act I Chandra Manuelpillai, MD
• Act II Kar-mun Woo, MD
• Act III K. Sophia Dyer, MD
• Coda

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Where there is smoke

• Every 17 seconds a fire department responds to a
  fire somewhere in the US
• The US has one of the highest fire death rates in
  the world
• Smoke inhalation is the leading cause of death
  from fire

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Novembers Journal Club
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Chemical Asphyxiation

• Chemical asphyxiants exert their effects at
  tissues distant from the lung
• Carbon monoxide (CO)
• Cyanide (CN)
• Baud FJ 1991325761

BMC EM Journal Club
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Chemical Asphyxiation

• Chemical asphyxiants exert their effects at
  tissues distant from the lung
• Carbon monoxide (CO)
• Cyanide (CN)

BMC EM Journal Club
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Chemical Asphyxiation CN

• Wool
• Silk
• Nylon
• Plastics

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Chemical Asphyxiation CN

• CNS
• Agitation
• Coma
• Seizures

• Cardiac
• Tachycardia
• Bradycardia
• Dysrhythmias
• Hypotension

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Chemical Asphyxiation CN

• CNS
• Agitation
• Coma
• Seizures

• Cardiac
• Tachycardia
• Bradycardia
• Dysrhythmias
• Hypotension

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ED Treatment
BMC EM Journal Club
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Cyanide Antidote Kit

• Chen KK JAMA 1952

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Cyanide Antidote Kit

• Amyl nitrite
• Use pre-IV via inhalation
• Sodium nitrite
• 10mL of 3 300mg
• Sodium thiosulfate
• 50mL of 25 12.5g

• Cyanomethemoglobin
• Thiocyanate

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Hydroxocobalamin

• Hydroxocobalamin (Vitamin B12a)
• Now available in US

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Hydroxocobalamin

• Hydroxocobalamin (Vitamin B12a)
• Now available in US

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Todays Agenda

• Prelude
• Act I Chandra Manuelpillai, MD
• Act II Kar-mun Woo, MD
• Act III K. Sophia Dyer, MD
• Coda

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Clinical Toxicology 200644 37-44

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Cyanide Antidote kit

• Only available antidote in the United States at
  the time of articles publication
• Consists of amyl nitrite (inhaled), sodium
  nitrite (IV), sodium thiosulfate (sulfur donor)
• Potential disadvantages
• amyl nitrite and sodium nitrite excess metHb
• sodium nitrite can cause severe hypotension
• sodium thiosulfate slow onset of action

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Hydroxocobalamin

• Precursor of Vitamin B12
• Directly binds to cyanide to form cyanocobalamin
  and is excreted in urine
• Cyanokit 250mL vial with 2.5g of lyophilized
  hydroxocobalamin
• Used in Europe for decades and received
  regulatory approval in France in 1996

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Objective

• The purpose of this paper was to assess the
  survival status and clinical parameters used for
  the treatment of smoke inhalation-associated
  cyanide poisoning with hydroxocobalamin in the
  prehospital setting

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Methods

• Retrospective, open-label, case review
• Enrollment 101 consecutive patients
• Inclusion criteria all patients treated in the
  prehospital setting with hydroxocobalamin for
  smoke inhalation

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Methods

• Head MD at Paris Fire Brigade reviewed scene
  reports and hospital records from 1995-2003
• Pre-antidotal and post-antidotal
• Clinical status
• Vital signs
• Glasgow coma scale scores

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Methods

• Outcomes
• Survival rate as a whole and within subgroups
• Recovery of cardiac function s/p arrest at scene
• Hemodynamic improvement (SBP gt90)
• Changes in GCS in those who did not require
  sedation

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Key Results
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Results

• Overall 41.7 survival rate
• That excludes the 29 unknown outcomes
• Subgroups
• Cardiac arrest 21 of 38 with spontaneous
  recovery of circulation, however 19 of 21
  eventually died in ICU
• Adverse events
• Red/pink discoloration of urine/skin 1
• Rash 1

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Authors Conclusion

• Hydroxocobalamin has a riskbenefit
• ratio rendering it suitable for prehospital
• use in the management of acute cyanide
• poisoning caused by smoke inhalation.

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Strengths of Article

• Clear outcome measures
• Decent number of a patients

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Limitations of Article

• Single data extractor
• No control group
• Lack of cyanide concentrations
• Risk-benefit ratio no analysis and never
  calculated
• Multiple unreferenced statements

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Further Questions

• Hydroxocobalamin often given in conjunction with
  sodium thiosulfate in Paris, but unknown if
  combined
• Any studies comparing hydroxocobalamin treatment
  with current cyanide antidote kit
• Who is Jane Saiers?

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Final Comments

• I didnt hate this article, but feel topic needs
  further study
• However, given low side effects and potential
  benefit, there may not be harm in its use until
  then
• 1 ½ Joes

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Todays Agenda

• Prelude
• Act I Chandra Manuelpillai, MD
• Act II Kar-mun Woo, MD
• Act III K. Sophia Dyer, MD
• Coda

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Annals of Emergency MedicineJune 2007 Vol
49(6)794

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Objective

• To assess outcomes in patients treated with
  hydroxocobalamin in the out-of-hospital setting
  or in the ICU for smoke-inhalation-associated
  cyanide poisoning.

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Methods

• Prospective open-label case series
• Enrollment
• Smoke inhalation patients with suspected cyanide
  poisoning who were admitted to Fernand Widal
  Hospitals Toxicology ICU
• Exclusion
• Out-of-hospital deaths
• Severe burns
• June 1987 to Feb 1994

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Intervention

• 5g IV hydroxocobalamin (on-scene or ICU)

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Comparison

• An active control group was not included because
  of the lack of a safe alternative cyanide
  antidote in France. A placebo control group was
  not included because it was not considered
  ethical to withhold potentially lifesaving
  antidotal treatment from patients assigned to
  placebo.

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Outcomes

• Survival
• - Analyzed in predefined subgroups by
  cyanide-poisoning status (gt or lt 39 µmol/L) and
  cardiorespiratory status on presentation
• Adverse events
• - As recorded by a pre-made data collection form

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Patient characteristics

• Only 67 (42/63) had confirmed cyanide toxicity
  (gt 39 µmol/L)
• 20 (13/63) found in cardiac arrest
• Correlated with higher cyanide levels

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Antidote Outcomes

• 72 (50/69) overall survival after antidote
• 67 (28/42) survival in those with confirmed
  cyanide poisoning
• 13 (2/15) survival in those presenting in
  cardiac arrest

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Adverse Events

• 28 (19/69) had adverse events identified as
  possibly related to antidote, none of which were
  considered serious
• Chromaturia (n6)
• Pink/red skin discoloration, erythema (n6)
• Increased blood pressure (n5)
• No allergic reactions reported
• Transient lab alterations of no clinical
  significance

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Authors Conclusion

• Hydroxocobalamin is well-tolerated in smoke
  inhalation victims without significant risk of
  harm, regardless of eventual confirmed cyanide
  toxicity and including patients with concomitant
  carbon monoxide poisoning.
• The safety profile of hydroxocobalamin allows it
  to be used empirically in the out-of-hospital
  setting for cases in which cyanide poisoning is
  suspected but cannot be confirmed within the
  short time available for initiating effective
  intervention.

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Since study data collected

• Dec 2006 study data cited in FDA approval of
  Cyanokit (first presented at 2005 ACEP Research
  Forum)
• June 2007 article published in Annals
• March 2008 Cyanokit available in US
• Dec 2008 discussed at BMC Journal Club

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Favorite Sentence

• All patients surviving to the hospital were
  admitted to the Toxicology ICU except those dead
  at the scene.

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Strengths of Article

• Prospective approach
• Systematic assessment of adverse events
• Took advantage of a unique collaboration with the
  Paris Fire Brigade system
• Author awareness of study limitations
• A causal relationship between survival and the
  administration of hydroxocobalamin cannot be
  established.

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Limitations of Article

• Data is OLD
• Absence of a control, unclear efficacy
• Unclear of on-scene deaths
• Unclear timing of antidote administration

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Further Questions

• Which patients at a fire scene should receive
  empiric administration?
• duration/environment of smoke exposure, ? utility
  for less ill patients as well as patients
  excluded in study
• Is there a way to determine the true efficacy of
  hydroxocobalamin?
• ? case control possibilities by looking at cities
  that do not yet stock hydroxocobalamin
• How much evidence is required to support routine
  administration of hydroxocobalamin?

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Further Questions

• Who is Jane Saiers, PhD?

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Final Comments

• Efficacy of hydroxocobalamin in human populations
  is still largely undetermined, although it has an
  attractive safety profile for use as an empiric
  antidote in suspected cyanide poisoning patients
  due to smoke inhalation.
• Final rating

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Todays Agenda

• Prelude
• Act I Chandra Manuelpillai, MD
• Act II Kar-mun Woo, MD
• Act III K. Sophia Dyer, MD
• Coda

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Empiric Prehospital Hydroxocobalamin Is Paris
Different?

• Sophia Dyer, MD
• Associate Medical Director, Boston EMS
• Medical Toxicologist Boston Police, Fire and EMS
• Hazardous Materials-Specialist Level
• Associate Medical Director-Boston Medflight

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Is Paris Different?

• In these studies-Very different Prehospital
• Both Borron and Fortin, mobile ICU- Critical Care
  MD and RN staff

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US EMS Systems

• Outside of urban, suburban area-many volunteer
  based
• No MDs on ambulances
• Vast variations on transport times
• Vast variations on education and skill sets
• But more aeromedical?

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Borron, et al.

• Transplantable to some prehospital systems?
• Missing datatime to treat, time to hospital and
  On scene time
• Unique-All admitted to specialized ICU, level of
  HBO
• 19 protocol violations?
• No children under 15
• Excluded gt20TBSA burns and face/neck burns

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Fortin, et al.

• Included children, but unclear age split
• Included burns, but no extent of burns
• ? Similar ICU care and HBO
• Missing data-29 outcomes missing
• Lack of blood cyanide levels
• Cardiac Arrest-poor outcomes 19/21 with ROSC
  later died

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Other missing points in this decision

• No human clinical trials of sodium thiosulfate
  alone
• No randomized control trial of sodium thiosulfate
  vs. hydroxocobalamin
• Are these results better than just excellent ICU
  level care?
• Differences in skin discoloration between Borron,
  Fortin and prior volunteer studies

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Where it might be clear?

• Prehospital-difficulty in dosing and safety of
  dosing of sodium nitrite for children
• Unfortunately, missing pedi data from Borron and
  pedi specifics in Fortin are lacking

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What can be predicted to be driving this?

• Heavy marketing campaign to fire services
• Focusing on force protection
• But should force protection be the issue?

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In the fire service CO and CN.

• ..should be considered a preventable exposure

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FinallyIts the Economy!

• Cost of Cyanokit-740.00 x 2 per BEMS ALS trucks
  back up14,200
• Training 4,200
• Total18,200
• Shelf life-31 months
• Cost of prevention?

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Next Journal Club January 13

• Curriculum Topic Head and ENT
• Morsal Tahouni (EM2)
• Shane Ruter (EM1)
• February 10 Hematology Meguerdichian and
  Huancahuari
• March 10 Lopez and Dresden

BMC EM Journal Club
BMC EM Journal Club
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