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Case study - Mrs B.. 40 year old female presenting after a syncopal episode at homeHeadache, 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 mo
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1. CO - The Silent Killer Martin Laliberté MD FRCP ( C ) ABEM
McGill University
Centre Anti-Poison du Québec
2. Case study - Mrs B. 40 year old female presenting after a syncopal episode at home
Headache, nausea, dizziness x 2 weeks
Lives in a condominium building downtown
Heard the alarm of the CO detector installed in her apartment ( 100 - 150 ppm )
3. Incidence of CO poisoning Leading cause of poisoning mortality
Most common cause of death in combustion related inhalation injury
1000 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
4. 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
5. 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
6. Pathophysiology - Tissue hypoxia Binding to Hb to form COHb
Hb affinity for CO 250 times affinity for O2
Effect on oxyHb dissociation curve
left shift, distortion of shape
Impaired release of oxygen at tissue level
Increased minute ventilation with subsequent increased CO uptake
7. 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
8. 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 perfusion
Ischemic reperfusion injury
9. 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- )
10. 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
11. 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
12. Severity of CO intoxication Inhaled CO concentration
Duration of exposure
Individual susceptibility
minute ventilation
pregnancy
Presence of systemic illnesses
cardiac and pulmonary diseases
Initial COHb not predictive
13. 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
14. 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
15. Shimazu et al. ( 2000 ) CO elimination : two-compartment model
Short 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
16. Delayed or persistent CO toxicity Persistent : present from exposure
Delayed : 2 to 40 days post-exposure
Dementia, psychosis, memory deficit
Parkinsonism, paralysis, chorea
Personnality changes, gait disturbance
Cortical blindness, apraxia, agnosia
Peripheral neuropathy, urinary incontinence
17. Delayed or persistent CO toxicity Reported neurologic impairment varies widely
between 3 % and 44 %
Reported at 10 % to 30 % at 1 year
Neuropsychologic deficits often subtle
Can be identified by psychometric testing
Spontaneous recovery
mild poisoning : 100 % resolve at 2 months
severe poisoning : 75 % resolve at 1 year
18. Delayed CO toxicity Lesions of cerebral white matter
globus pallidus, cerebellum, hippocampus
perivascular injury with blood flow abnormalities
Often associated with LOC in acute phase
Hypotension is essential to cause white matter lesions in animal model
Patients > 30 year old more susceptible to delayed CO toxicity
19. 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
20. Clinical evaluation Maintain a high level of suspicion
History of exposure can be absent
COHb
< 3 % non-smokers or < 10 % in smokers
not predictive of outcome
correlation with symptoms useless
ABG : metabolic acidosis ( lactate )
ECG : ischemia, arrythmias
21. 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
22. Neurologic evaluation Neurologic examination
Mental status examination
Folstein
Psychometric testing
CO Neuropsychological Screening Battery
Neuroradiologic imaging : CT, MRI
23. Psychometric testing Lack of standardized methods
Normalisation 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 ?
24. 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 exposure
Susceptibility of individual to CO
25. Case study - Mrs B. Patient is given O2 100 % on arrival
HBO facility is contacted for consultation
Based on the history of LOC and persistent confusion, transfer for admission is advised
Patient receives 4 treatments of HBO
26. Management of CO poisoning Identify the source to correct the problem
Domestic 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 !
27. Case study - Mrs B. Case reported to public health
High CO concentrations measured in building
Two other cases diagnosed in building needing treatment
Investigation identifies serious flaws in ventilation system in the basement garage and inadequate CO dectors
28. Management of CO poisoning Oxygen 100 % ASAP
ABG
COHb
ECG
CXR
Cardiac enzymes
Cardiac monitoring
29. Hyperbaric oxygen therapy Enhanced elimination of COHb
Improved tissue oxygenation
Enhanced dissociation of CO from cytochrome oxidase
Inhibition of B2 integrin adhesion to vascular endothelium
Prevention of CNS lipid peroxydation
30. HBO vs NBO studies Isolated case reports
Uncontrolled clinical observations
Studies
small
non-randomized
unblinded assessment of outcome
incomplete assessment of outcome
31. 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 O2
HBO : 2 hrs of O2 at 2.0 atm, 4 hrs of NBO
Evaluation at 1 month : interview, telephone
32. Raphael - Results Time to randomisation shorter in HBO group
Lost 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 month
HBO at a low pressure ( 2 vs 2.5-3 atm )
HBO after > 6 hours in 50 % cases
Soft outcome measures at 1 month
33. Ducasse et al. - 1995 Prospective randomised clinical trial of NBO ( n=13 ) vs HBO ( n=13 )
Patients exposed to CO without LOC
Discovery to admission < 2 hrs
NBO : O2 100 % x 6 hrs, 50 % x 6 hrs
HBO : O2 100 % 2.5 atm x 2 hrs, 100 % x 4 hrs, 50 % x 6 hrs
34. 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
35. 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 sequelae
Neither patients nor investigators blinded to treatment
36. Thom - Interventions NBO : 100 % O2 until all symptoms resolved
HBO : 100 % O2 at 2.8 atm x 30 minutes and at 2.0 atm x 90 minutes
Treatment given within 6 hours in all cases
37. Thom - Results NBO : 7 / 30 patients ( 23 % ) with DNS
HBO : 0 / 30 patients ( 0 % ) with DNS
DNS persisted for a mean of 41 days
All patients eventually recovered
38. Scheinkestel et al. - 1999 Randomised controlled double-blind trial
Referred patients, all severity of poisoning
Cluster randomisation to HBO ( n=104 ) vs NBO ( n=87 )
73 % with severe poisoning
Stratified in 4 groups : suicide, accidental, ventilated, not ventilated
Psychometric testing : 0 and 1 month
39. Scheinkestel - Interventions All patients had daily txs x 3 days
100 % O2 daily to everyone between txs
HBO :100 % O2 x 100 min, 60 min at 2.8 atm
NBO : 100 % O2 x 100 min at 1.0 atm
Patients with abnormal clinical evaluation or poor psychometric testing had 3 more txs
40. Scheinkestel - Results HBO patients required more txs
HBO patients had worse outcome in learning test
Greater % of severely poisoned patients in HBO group had a poor outcome at end of tx
DNS restricted to HBO patients
No difference if tx < 4 hours or with accidental poisoning
41. Scheinkestel - Limitations Mean delay to treatment 7.1 hours ( 95 % CI 1.9-26.5 )
Large number of severily poisoned patients
46 % had 1 month follow up
44 % with possibility of co-ingestants
High proportion of depressed patients
Baseline O2 100 % x 3 days different from other studies
42. Weaver et al. - Abstract - 1995 Undersea Hyperbar Med 1995 ; 22 : 14
Reported - Dr K. Olson - October 1st 1999
Prospective double-blind RCT with 152 patients ( last update May 1999 )
No difference in outcome between HBO vs NBO
43. Mathieu et al. - 1996 Undersea Hyperbar Med 1996;23 (suppl) : 7-8
Prospective unblinded RCT with 575 non-comatose patients
Randomisation to HBO at 2.5 atm vs NBO
Time to treatment < 12 hours
No difference in outcome at 1 year between HBO vs NBO
44. 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
45. Classic indications for HBO Coma or loss of consciousness
Neurologic abnormalities
Cardiovascular dysfunction
Severe metabolic acidosis
COHb > 40 %
COHb > 15 %
46. 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
47. Adverse effects of HBO Need for transfer to HBO facility with risk of deterioration
Otic barotrauma
effusion, hemorrahge, TM rupture
CNS oxygen toxicity : seizures
Epistaxis
48. CO poisoning in pregnancy High incidence of neurologic abnormalities and stillbirth after CO poisoning
Fetal Hb binds CO more avidly that Hb A
CO absorption and elimination slower in fetal circulation
HBO felt to be safe in pregnancy
No scientifically established role for HBO in pregnancy : COHb > 15 % suggested
49. Prevention of CO poisoning Public education about CO poisoning
Identification of activities at risk
Training of workers for proper use of propane-powered tools
Appropriate ventilation of confined places
Industrial and domestic use of CO detectors
Reporting to public health services
50. 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