Transcript CO Poisoning - Calgary Emergency Medicine

Toxicology Grand Rounds:
Carbon Monoxide Poisoning
Mark Yarema, MD FRCPC
Poison and Drug Information Service
Calgary, Alberta
PADIS/Emergency Medicine/Critical Care Rounds
January 27, 2011
Acknowledgements
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PADIS: Rosalee Sears-Ford, Nina Walny
Critical Care: Paul Boiteau, Sid Viner
Emergency Medicine: Ian Rigby, Jay Green, Kevin
Hanrahan
Miscericordia Hospital: Malcolm Young
HBOT Clinics: Terry Stewart, Karen Keats, Caroline Bain
AHS Telehealth
PLP: Marianna Hofmeister, Holly Donaldson, Kyle Dormer
Podcast website: http://www.ucalgary.ca/plppodcasts/
Disclosure
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I have no commercial interest in any of the
products or therapies discussed in this presentation.
Outline
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Cases
Intro to CO
Pathophysiology
Clinical features
Diagnosis
Management
Special presentations:
 Misericordia Hospital HBO Unit
 HBOT Clinics Inc.
Q and A
Case 1
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63 y.o. male
Last seen July 1
Found by wife July 2 AM in garage with riding
tractor running
EMS called, pt. in cardiorespiratory arrest
Intubated, ventilated, CPR
Return of spontaneous circulation 15 minutes after
resuscitation initiated
Case 1
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In E.D.:
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ABG: pH < 6.8 PC02 58, p02 31, HC03 15,
Lactate > 20, COHb 61%
ST depression on EKG
Another cardiac arrest  resuscitated
Multiple pressors
PADIS consulted: candidate for HBO?
Case 1
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d/w PADIS: meets accepted criteria for HBO.
Recommended speaking with Misericordia HBO
MD on call
Transferred to Misericordia
1 HBO treatment given July 2
Transferred to ICU July 3
Died 19:29 hours July 3
Case 1.5
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4 days after death of Case 1
21 y.o. male
Texted girlfriend at 0400, found asystolic in car by
EMS at 0500
ROSC after 30 minutes CPR by EMS
In E.D.:
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intubated, unresponsive
ABG pH 6.82, COHb 57.3%, Lactate 22
Case 1.5
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d/w PADIS: meets accepted criteria for HBO.
Recommended speaking with Misericordia HBO
MD on call
Pt. deemed not appropriate candidate
Died 1700 hrs July 7th
Case 2
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62 y.o. female, 16 y.o. male, 35 y.o. male
Hx of ‘faulty furnace’ in home
Furnace turned on during last period of Canucks
game, then everyone fell asleep
4.5 hour ‘soaking period’
Case 2
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1:00am: 16 y.o. gets up to go to fridge, falls
62 y.o. hears the fall and wakes up
EMS called
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16 y.o. and 35 y.o.: headache, nausea, no other symptoms
62 y.o.: disoriented, combative, vomiting, headache
Does anyone need HBO?
Case 2
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d/w PADIS: 62 y.o. most concerning, meets
accepted criteria for HBO. Recommended speaking
with HBOT Clinics MD on call
MD speaks with HBOT clinics HBO MD on call
Patient accepted by HBOT, treated with HBO
Intro to CO
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Colorless, odorless, tasteless gas
Formed by incomplete combustion of carboncontaining compounds
Normal byproduct of hemoglobin degradation
Many different sources of exposure
Sources of CO
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Fires
Auto exhaust
Cigarette smoke
Malfunctioning water heaters, gas stoves, furnaces
Wood-burning fireplaces, blocked chimneys
Propane forklifts
Ice resurfacing machines
Generators
Inappropriate heat sources (e.g. barbecues)
www.coolestspringbreak.com
Source: The Arizona Republic,
November 29, 2000 (Maureen West and
Judd Slivka, reporters)
Deadly houseboats
CO concentration
in ppm
Scenario
25
Maximum exposure allowed by Can. OSHA for 8 hours
300
Home CO detector cutoff level (10 minute exposure)
800
CNS symptoms, Death ~ 2 hours
1200
Immediately Dangerous to Life and Health (IDLH)
5000-10,000
12,000
7000-30,000
Measured in open air near swim platform
Death within 2-3 minutes
Measured under houseboat swim platforms
Physiology
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Rapidly diffuses across alveolar-capillary
membranes
Binds to hemoglobin with 200-250X greater affinity
than oxygen
10-15% of total body CO taken up by tissue, bound
to extravascular proteins
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Myoglobin
Cytochrome oxidase
Catalase
Peroxidases
Pathophysiology
Pathophysiology
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Left shift oxyhemoglobin dissociation curve
Binding to cytochrome oxidase
Activation of excitatory amino acids
Binding to myoglobin
Nitric oxide (NO)
Left shift
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CO increases the affinity of oxygen for hemoglobin
Oxygen not displaced by CO is bound more tightly
to Hb
Lower oxygen delivery to cells
Hypoxia
www.modernmedicine.com
Left shift / hypoxia
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Does not explain all manifestations of poisoning
Patients may remain comatose even after COHb
undetectable
Dissolved CO in plasma and delivery to target
organs also important
Cytochrome oxidase inhibition
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CO interferes with cellular respiration
Decreased ATP production
Initiates inflammatory cascade
Lipid peroxidation
Ischemic brain injury
Binding may be increased under hypotensive or
hypoxic conditions
Cytochrome oxidase
Yong-Ling P. Ow, Douglas R. Green, Zhenyue Hao & Tak W. Mak
Nature Reviews Molecular Cell Biology 9, 532-542 (July 2008)
Activation of excitatory amino acids
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Tissue hypoxia increases excitatory amino acid
levels
Glutamate stimulates NMDA receptors and causes
intracellular Ca++ release
Delayed neuronal cell death
Myoglobin
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CO binds with 60X > affinity than O2
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Binding enhanced under hypoxic conditions
Leads to myocardial depression
Carboxymyoglobin may explain dysrhythmias and
ischemia that may occur with mild exposures
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Especially with pre-existing CAD
Oh NO!
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CO displaces nitric oxide (NO) from platelets
Actions of NO:
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Vasodilator
Forms peroxynitrite radicals  inactivate cytochrome
oxidase
Formation of platelet-neutrophil aggregates 
neutrophil adhesion in brain microvasculature
End result: delayed lipid peroxidation
Weaver. NEJM 2009
Simpler version of previous slide
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Too much CO = Bad
Clinical features of poisoning
Clinical features
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Early symptoms very nonspecific
Often confused with other illnesses:
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Influenza
Food poisoning
Gastroenteritis
Colic
Neurologic
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Initial
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Headache, dizziness, nausea
Later (higher levels/longer exposures)
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Syncope, focal neuro sx suggesting CVA, LOC,
confusion, seizures, coma
Persistent neurologic sequelae
Delayed neurologic sequelae (DNS)
Delayed Neurologic Sequelae
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Incidence between 2-43%
2 days – 5 weeks after initial poisoning
Neurologic and psychiatric symptoms
 amnesia
■ headaches
 psychosis
■ apraxia
 parkinsonism
■ incontinence
 paralysis
■ periph. neuropathy
 chorea
■ dementia
50-75% of cases resolve (may take months  1 year)
Who is at risk for DNS?
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post-hoc analysis of Weaver 2002 RCT
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plus additional pts treated only with NBO not in trial
Those most at risk of DNS:
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History of LOC
Patients with long exposures (> 24 hours)
Age > 36
COHb > 25%*
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*Randomized trial data only, not separate NBO patients
Weaver et al. Am J Resp Crit Care Med 2007;176:491-7.
Cardiac
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PVC’s and other dysrhythmias
Myocardial ischemia
Myocardial stunning
With CAD, exacerbation of angina and arrhythmias
can occur with COHb < 10%
Acute mortality from CO usually from ventricular
arrhythmias
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230 pts with moderate/severe poisoning all treated with HBO
Indications for HBO:
 LOC
 Seizure
 Focal neuro deficit
 Ischemic chest pain
 Dysrhythmias
 COHb > 40%
 COHb> 25% with Hx CV disease, age > 60, Hgb < 100,
exposure > 2 hours
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85 (37%) had elevated TnI or CK-MB or diagnostic
EKG changes of ischemia
32 (38%) eventually died compared with 22 (15%)
of patients who had no myocardial injury
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Effect persisted over many years
Diagnosis
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History and physical
 Mini mental status exam
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Laboratory tests
CO pulse oximetry
 COHb / VBG
 Select patients: EKG, cardiac markers
Imaging
 CT
 MRI
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COHb pulse oximeters
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Accurate 3% from COHb of 0-40%
Some false +ves
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Pre-hospital
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More during early use?
Incident response paramedics
Calgary Zone availability
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FMC, PLC, RGH triage
UCC’s
www.masimo.com
[COHb]
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Measured with co-oximeter
Venous blood as accurate as arterial
Normal levels 0-5%, up to 10% in smokers
Wide variation in clinical manifestations with identical levels
Inaccurate predictor of peak levels
 Variations in half lives
 Effect of 02 given prior to sampling
Not predictive of symptoms or final outcome
Blood gas
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Some HBO trials have used lactate > 2.5 or base
excess < -2 as indications for HBO
Metabolic acidosis (hydrogen ion concentration) on
presentation a better predictor of need for multiple
HBO treatments than COHb*
*Turner et al. J Accid Emerg Med 1999
Neuroimaging
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Abnormalities may be seen within 12 hours of CO
exposure causing LOC
Basal ganglia most commonly affected
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Caudate
Putamen
Globus pallidus
Also subcortical white matter and hippocampus
caudate
globus
pallidus
cerebellum
www.learningradiology.com
Management
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ABC’s
O2 via nonrebreather
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Alters t ½ of COHb
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5-6 hours at room air
40-90 minutes on 02 via NRB
Hyperbaric oxygen
HBO
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100% O2 while exposed to increased atmospheric
pressure
Reduces the half-life of COHb to 23 minutes
Mechanisms:
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Increases dissolved plasma [02] tenfold
May help regenerate cytochrome oxidase
Inhibits leukocyte adherence to the microvascular
endothelium
Does HBO prevent development of delayed
neurologic sequelae?
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Non-blinded, randomized study of 629 adults, Rx within 12 h
exposure
 pregnant women, pts < 15 y.o. excluded
Patients separated into LOC vs. no LOC prior to
randomization into one of four groups
 No LOC: 6h NBO vs 4h NBO +1 HBO Rx (2.0 ATA X 1
hour)
 LOC: 4h NBO + 1 HBO vs 4h NBO + 2 HBO Rx (all +
4h NBO)
Self-assessment questionnaire at 1 month following Rx re:
neurologic sequelae
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% complete recovery at 1 month:
 No LOC: 66% NBO vs 68% HBO
 LOC: 54% 1 HBO vs 52 % 2 HBO
Conclusion: HBO not useful in pts with no LOC, and 2
sessions not useful in those who did have LOC
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Randomized, non-blinded, 65 patients with mild poisoning , <6
hours of removal from exposure
 LOC, cardiac compromise excluded
1 HBO Rx (120 mins, 2.8 ATA) vs NBO until Sx resolved
Mean time from randomization to HBO 2 hours
Neuropsych tests done after Rx (baseline) then 3-4 weeks after
poisoning
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Incidence of DNS: 23% NBO group, 0% HBO group
Conclusion: HBO decreased incidence of DNS after
CO poisoning
Scheinkestel et al, Med J Aust March 1999
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Randomized, double-blind trial with 191 patients, all
severities included
 pregnancy, peds excluded
Time to treatment 6.6-7.5h
HBO: 3 days of 60 min Rx at 2.8 ATA + continuous NBO
 potentially 3 more HBO Rx if clinically abN after the
first 3
NBO: continuous hi flow 02 for 3 days + sham dives
Scheinkestel et al, Med J Aust March 1999
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46% lost to follow up
Incidence of DNS: HBO 5/104; NBO 0/87
Conclusion: No benefit from HBO and may have
worsened outcome, cannot be recommended
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Randomized trial of 152 patients
Extensive inclusion criteria
HBO group: 3 treatments (1 X 2.8 ATA, 2 X 2.0 ATA)
NBO group: 100% 02 via NRB during 3 sham dives
Neuropsych testing after chamber sessions 1 and 3, then 2
wks, 6 wks, 6 mos, 12 mos
Primary outcome: cognitive sequelae at 6 wks.
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Higher cerebellar dysfunction in NBO group (15% vs 4%)
At 6 wks, lower incidence DNS in HBO group (25% vs
46%)
 persisted when adjusting for cerebellar dysfunction and
also at 12 months (ITT analysis)
Conclusion: 3 HBO Rx within 24h period reduced risk of
cognitive sequelae at 6 weeks and 12 months
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Non blinded, randomized trial of 385 pts. aged 15 years and
up
Domestic CO poisoning only, October 1989- January 2000
Patients separated into LOC vs. coma prior to
randomization into one of four groups
 LOC: NBO vs NBO +1 HBO Rx (2.0 ATA X 1 hour)
 coma: NBO +1 HBO Rx (2.0 ATA X 1 hour) vs 2 HBO
Rx
Self-assessment questionnaire at 1 month re: neurologic
sequelae
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% complete recovery at one month following treatment
 LOC: 58% NBO vs. 61% HBO
 Coma: 68% HBO X 1 vs. 47% HBO X 2 (significant)
Conclusion: no evidence superiority of HBO > NBO in
patients with LOC. 2 HBO treatments associated with
worse outcomes.
HBO Clinical Trials
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Study design flaws:
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Randomization procedures
Blinding
Intent to treat analyses
Follow up (most 15-20% lost to f/u except one at 46%)
Outcomes (questionnaires vs neuropsych battery,
“complete recovery” vs. “cognitive sequelae”)
NBO and HBO therapies used (duration, number of
treatments)
Excluded patients (pregnant, peds)
Buckley et al. Toxicol Rev 2005;24(2):75-92
HBO-suggested indications*
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Syncope
Altered LOC
Coma
Seizure
Abnormal cerebellar function
Age > 36 years
Prolonged CO exposure (> 24 hours)
COHb > 25%
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Missing: myocardial ischemia
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Goldfrank’s Toxicologic Emergencies, 2011
Pregnant patients
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Fetal COHb concentrations tend to be higher
than maternal levels (animal studies)
Human studies suggest fetal Hgb affinity is similar
to maternal Hgb affinity in low 02 states
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More important issue is fetal hypoxia
Maternal COHb does not predict fetal outcome
Normal mental status with no LOC in mother =
good outcomes, normal deliveries
Pregnant patients
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NBO treatment of pregnant patients
 similar to nonpregnant patients
 treat until mother is asymptomatic
 benefit of prolonged Rx to mother unclear
Indications for HBO in pregnant patients
 same as for nonpregnant patients except:
 lower COHb in mother at which HBO recommended
(arbitrarily set at 15-20%)
 any features of fetal distress
Outcomes
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Cardiac arrest patients
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18 patients given HBO after cardiac arrest with ROSC
Resuscitation time range 19-45 min.
Mean time to HBO 4.3 hours post exposure
COHb range 14-55%
All patients died during hospitalization (range 9 hours-7 days
post discovery)
HBO director survey of fictitious CO-induced arrest case:
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100% recommended HBO
Chance of survival 74%
Chance of recovery w/o neurologic sequelae 28%
CO poisoning and cardiac arrest
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Quick summary of other studies:
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5 peds smoke inhalations: 0 survivors
10 peds CO patients: 8 died, 2 had DNS
10 adult smoke inhalations: 0 survivors
11 adult CO patients: 0 survivors
23 adult CO patients: 17 died, 6 unknown outcome
? Role of CN poisoning in smoke inhalation victims
Objectives
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By the end of the presentation, the participant should
be able to:
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List the mechanisms by which carbon monoxide (CO) causes
toxicity
Describe the clinical features seen with acute and delayed
toxicity from CO
Discuss the controversies in the management of CO
poisoning, including the role of hyperbaric oxygen (HBO)
How to reach us
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Poison and Drug Information Service:
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403- 944-1414 (Calgary)
1-800-332-1414 (Alberta)
[email protected]