co - the silent killer martin laliberté md frcp ( c ) abem mcgill university centre anti-poison du...
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CO - The Silent Killer
Martin Laliberté MD FRCP ( C ) ABEM
McGill University
Centre Anti-Poison du Québec
Case study - Mrs B.
40 year old female presenting after a syncopal episode at home
Headache, nausea, dizziness x 2 weeksLives in a condominium building downtownHeard the alarm of the CO detector installed in
her apartment ( 100 - 150 ppm )
Incidence of CO poisoning
Leading cause of poisoning mortalityMost common cause of death in combustion
related inhalation injury1000 to 2000 deaths / year ( USA )Difficult diagnosis
incidence of unrecognized cases higher estimated > 42 000 visits / year ED visit rate 16.5 / 100 000 population
Sources of CO
Motor vehicle exhaust running engine in closed space faulty exhaust systems
Propane-powered equipement lift, water heater, concrete saw, polishers
Combustion for heating or cooking camping equipment, heating systems
Smoke inhalation in fires
Xenobiotics metabolism
Methylene chloride peak of 50 % in humans
Dibromomethane peak of 27 % in rodents
Diiodomethane peak of 14.2 % in humans
Bromochloromethane peak of 11 % in rodents
Pathophysiology - Tissue hypoxia
Binding to Hb to form COHbHb affinity for CO 250 times affinity for O2Effect on oxyHb dissociation curve
left shift, distortion of shape
Impaired release of oxygen at tissue levelIncreased minute ventilation with subsequent
increased CO uptake
Pathophysiology - Cellular level
15 % of CO bound to extravascular heme-containing proteins
Cytochrome oxidase ( aa3 ) alteration in ATP production intracellular acidosis persists after exposure
Cardiac and skeletal myoglobin occuring at COHb 2 % alteration in tissue O2 uptake
Pathophysiology - Cardiovascular
Myocardial depression consequence of hypoxic stress cytochrome a3 dysfunction CO binding to cardiac myoglobin
Arterial hypotension myocardial depression NO-related peripheral vasodilatation
LOC with reduction of cerebral perfusionIschemic reperfusion injury
Pathophysiology - Neurovascular
CO in circulation associated with massive increase in NO in perivascular tissues
NO released from vascular endothelial cells and platelets
Production of oxygen radicals from impaired mitochondrial function
Reaction NO with oxygen radicals to form peroxynitrite ( ONOO- )
Pathophysiology - Neurovascular
Peroxynitrite binds to perivascular tissue proteins causing injury
Increased capillary permeability in CNS and pulmonary vascular beds
Endothelial injury causing expression of adherence molecules - beta 2 integrins
Leucocytes bind to injured endothelium reducing cerebral perfusion
Initiation of CNS lipid peroxidation
Clinical manifestations
General headache, nausea, vomiting, weakness
Cardiovascular chest pain, tachypnea, tachycardia, hypotension pulmonary edema, arrythmias, cardiac arrest
Neurologic dizziness, ataxia, seizures, coma
Others retinal hemorrhages, metabolic acidosis
Severity of CO intoxication
Inhaled CO concentrationDuration of exposureIndividual susceptibility
minute ventilation pregnancy
Presence of systemic illnesses cardiac and pulmonary diseases
Initial COHb not predictive
Case study - Mrs B.
Neurologic examination reveals that the patient is confused and disoriented
COHb measured on admission is 15 %Patient is a non-smoker Head CT Scan and ECG is normal
COHb elimination half-life
O2 20.9 % 1 atm 320 min ( 128-409 ) - Peterson
O2 100 % 1 atm 131 min ( 27-462 ) - Myers 72 min ( 26-146 ) - Weaver
O2 100 % HBO 3 atm : 23 min - Peterson 1.58 atm : 27 min - Jay 2.5 atm : 22 min - Pace
Shimazu et al. ( 2000 )
CO elimination : two-compartment modelShort term exposure
initial phase - half life 5.7 minutes slower phase - half life 103 minutes
Long terme exposure initial phase - half life 21.5 minutes slower phase - half life 118 minutes
Two compartments intravascular and extravascular
Delayed or persistent CO toxicity
Persistent : present from exposureDelayed : 2 to 40 days post-exposureDementia, psychosis, memory deficitParkinsonism, paralysis, choreaPersonnality changes, gait disturbanceCortical blindness, apraxia, agnosiaPeripheral neuropathy, urinary incontinence
Delayed or persistent CO toxicity
Reported neurologic impairment varies widely between 3 % and 44 %
Reported at 10 % to 30 % at 1 yearNeuropsychologic deficits often subtleCan be identified by psychometric testing Spontaneous recovery
mild poisoning : 100 % resolve at 2 months severe poisoning : 75 % resolve at 1 year
Delayed CO toxicity
Lesions of cerebral white matter globus pallidus, cerebellum, hippocampus perivascular injury with blood flow abnormalities
Often associated with LOC in acute phaseHypotension is essential to cause white matter
lesions in animal modelPatients > 30 year old more susceptible to
delayed CO toxicity
Low dose / chronic CO exposure
CO 61 ppm and COHb 4 % - effect on memory and learning abilities
COHb 2 - 3.9 % - worsening ischemia in patients with pre-existing CAD
COHb 6 % - exercise-induced ventricular arythmias in patients with CAD
CO 38 ppm - 35 % cardiovascular mortality excess in workers
Clinical evaluation
Maintain a high level of suspicionHistory of exposure can be absentCOHb
< 3 % non-smokers or < 10 % in smokers not predictive of outcome correlation with symptoms useless
ABG : metabolic acidosis ( lactate )ECG : ischemia, arrythmias
Pulse oximetry in CO poisoning
Pulse oximetry : HbO2 and RHb at two wavelengths : 660 nm and 940 nm
Unreliable with significant amount of abnormal Hb : MetHb, COHb, SHb
Pulse oximetry overestimates true fractional arterial oxygen saturation
Elevation of COHb level falsely elevates the SaO2 by an amount less than the COHb level
Neurologic evaluation
Neurologic examinationMental status examination
Folstein
Psychometric testing CO Neuropsychological Screening Battery
Neuroradiologic imaging : CT, MRI
Psychometric testing
Lack of standardized methodsNormalisation of psychometric testing
practice effect when repeated decreasing effect of other toxins with time very subjective, tester can be biased
Abnormal testing : at risk of persistent or delayed neurologic sequelae
Predictive of need for HBO therapy in mild toxicity ?
Severity of CO poisoning
COHb level does not correlate with severity or outcome
Severity of neurologic lesions correlate better with hypotension than with hypoxia
Duration of exposure as important as concentration
Total CO load = [ ] x ventilation x exposureSusceptibility of individual to CO
Case study - Mrs B.
Patient is given O2 100 % on arrivalHBO facility is contacted for consultationBased on the history of LOC and persistent
confusion, transfer for admission is advisedPatient receives 4 treatments of HBO
Management of CO poisoning
Identify the source to correct the problemDomestic exposition
verification of heating or cooking appliances
Occupational exposition CSST investigation
CO poisoning : mandatory reporting to public health services
Making the diagnosis can save lives !
Case study - Mrs B.
Case reported to public healthHigh CO concentrations measured in buildingTwo other cases diagnosed in building
needing treatmentInvestigation identifies serious flaws in
ventilation system in the basement garage and inadequate CO dectors
Management of CO poisoning
Oxygen 100 % ASAPABGCOHbECGCXRCardiac enzymesCardiac monitoring
Hyperbaric oxygen therapy
Enhanced elimination of COHbImproved tissue oxygenationEnhanced dissociation of CO from
cytochrome oxidaseInhibition of B2 integrin adhesion to vascular
endothelium Prevention of CNS lipid peroxydation
HBO vs NBO studies
Isolated case reportsUncontrolled clinical observationsStudies
small non-randomized unblinded assessment of outcome incomplete assessment of outcome
Raphael et al. - 1989
Prospective randomised clinical trial of NBO ( n=170 ) vs HBO ( n=173 )
Patients without LOC admitted within 12 hours of CO exposure
NBO : 6 hrs of NBO O2HBO : 2 hrs of O2 at 2.0 atm, 4 hrs of NBOEvaluation at 1 month : interview, telephone
Raphael - Results
Time to randomisation shorter in HBO groupLost to follow up : NBO 12.9 % HBO 8.0 %Recovering at 1 month
NBO 66 % HBO 68 % p=0.75
> 90 % patients functional at 1 monthHBO at a low pressure ( 2 vs 2.5-3 atm )HBO after > 6 hours in 50 % casesSoft outcome measures at 1 month
Ducasse et al. - 1995
Prospective randomised clinical trial of NBO ( n=13 ) vs HBO ( n=13 )
Patients exposed to CO without LOCDiscovery to admission < 2 hrsNBO : O2 100 % x 6 hrs, 50 % x 6 hrsHBO : O2 100 % 2.5 atm x 2 hrs, 100 % x 4
hrs, 50 % x 6 hrs
Ducasse - Results
Clinical abnormalities at 2 hrs reflex impairment, headache, asthenia NBO 9 HBO 2 p < 0.01
Clinical abnormalities at 12 hrs headache, moderate pulmonary edema NBO 5 HBO 0 p < 0.05
Patients treated with HBO at 3 weeks ( n=18 ) fewer EEG abnormalities abnormalities normal reactivity to CO2 on SPECT scans
Thom et al. - 1995
Prospective randomized study NBO ( n=32 ) vs HBO ( n=33 )
Reffered patients with mild to moderate CO poisoning no history of LOC no cardiac instability
Outcome : delayed neurologic sequelaeNeither patients nor investigators blinded to
treatment
Thom - Interventions
NBO : 100 % O2 until all symptoms resolvedHBO : 100 % O2 at 2.8 atm x 30 minutes and
at 2.0 atm x 90 minutesTreatment given within 6 hours in all cases
Thom - Results
NBO : 7 / 30 patients ( 23 % ) with DNSHBO : 0 / 30 patients ( 0 % ) with DNSDNS persisted for a mean of 41 daysAll patients eventually recovered
Scheinkestel et al. - 1999
Randomised controlled double-blind trialReferred patients, all severity of poisoningCluster randomisation to HBO ( n=104 ) vs
NBO ( n=87 )73 % with severe poisoningStratified in 4 groups : suicide, accidental,
ventilated, not ventilatedPsychometric testing : 0 and 1 month
Scheinkestel - Interventions
All patients had daily txs x 3 days100 % O2 daily to everyone between txsHBO :100 % O2 x 100 min, 60 min at 2.8
atmNBO : 100 % O2 x 100 min at 1.0 atmPatients with abnormal clinical evaluation or
poor psychometric testing had 3 more txs
Scheinkestel - Results
HBO patients required more txsHBO patients had worse outcome in learning
testGreater % of severely poisoned patients in HBO
group had a poor outcome at end of txDNS restricted to HBO patientsNo difference if tx < 4 hours or with accidental
poisoning
Scheinkestel - Limitations
Mean delay to treatment 7.1 hours ( 95 % CI 1.9-26.5 )
Large number of severily poisoned patients46 % had 1 month follow up44 % with possibility of co-ingestantsHigh proportion of depressed patientsBaseline O2 100 % x 3 days different from other
studies
Weaver et al. - Abstract - 1995
Undersea Hyperbar Med 1995 ; 22 : 14Reported - Dr K. Olson - October 1st 1999Prospective double-blind RCT with 152
patients ( last update May 1999 )No difference in outcome between HBO vs
NBO
Mathieu et al. - 1996
Undersea Hyperbar Med 1996;23 (suppl) : 7-8Prospective unblinded RCT with 575 non-
comatose patientsRandomisation to HBO at 2.5 atm vs NBOTime to treatment < 12 hoursNo difference in outcome at 1 year between
HBO vs NBO
Uncontrolled case series
Relation suggested between favorable outcome and HBO therapy in severe poisoning
Severely poisoned patients ( comatose ) can have a normal outcome without HBO
Poisoned patients can have a bad outcome despite HBO
Variability in severity, treatment modalities, psychometric testing, length of follow up with potential for selection bias
Classic indications for HBO
Coma or loss of consciousnessNeurologic abnormalitiesCardiovascular dysfunctionSevere metabolic acidosisCOHb > 40 %COHb > 15 %
Timing of HBO
Patients treated at > 6 hours tend to do worse delayed CO toxicity : 30 % vs 19 % mortality : 30 % vs 14 %
Benefit shown as late as 21 days in anecdotal, uncontrolled case reports
Natural history of delayed neurologic toxicity mild poisoning : 100 % resolve at 2 months severe poisoning : 75 % resolve at 1 year
Adverse effects of HBO
Need for transfer to HBO facility with risk of deterioration
Otic barotrauma effusion, hemorrahge, TM rupture
CNS oxygen toxicity : seizuresEpistaxis
CO poisoning in pregnancy
High incidence of neurologic abnormalities and stillbirth after CO poisoning
Fetal Hb binds CO more avidly that Hb ACO absorption and elimination slower in fetal
circulationHBO felt to be safe in pregnancyNo scientifically established role for HBO in
pregnancy : COHb > 15 % suggested
Prevention of CO poisoning
Public education about CO poisoningIdentification of activities at riskTraining of workers for proper use of propane-
powered toolsAppropriate ventilation of confined placesIndustrial and domestic use of CO detectorsReporting to public health services
Problems in CO poisoning
Absence of reliable method to estimate prospectively the severity of CO poisoning
Difficulty in comparing results of studies because no staging in severity of disease
Misleading information and myths are perpetuated in the literature
Making the diagnosis and preventing further exposure to CO is too often forgotten