1. Dr. Wong Oi Fung Journal Club Presentation ICU TMH
Journal Club: Increased long-term mortality among survivors of acute carbon monoxide poisoning (Crit Care Med 2009;37(6):1-7)
Dr. Wong Oi Fung
Journal Club Presentation
ICU TMH

2. Spectrum of effects of acute CO exposure
NEJM 2009;360(12):

3. NEJM 2009;360(12):

4. Long term outcome from CO poisoning??

5. Background
Estimated annual ED visits of carbon monoxide poisoning in US ~ 50,000
2nd leading cause of unintentional poisoning deaths
Death from intentional +unintentional ~2700 annually
An increase risk of long-term mortality from causes other than CO in patients with myocardial injury after an episode of acute CO poisoning was demonstrated in a recent study
?reason
JAMA 2006;295(4):

7. Mortality of CO poisoned patients with myocardial injury
Frequent consequence of myocardial injury in patients with moderate to severe CO poisoning
37% w/ elevated cardiac biomarkers and/or diagnostic ECG change
Low in-hospital mortality 5%
Increased mortality in CO-poisoned patients with myocardial injury
JAMA 2006;295(4):

8. Henry’s study…..
Objective: to determine the association between myocardial injury and long-term mortality in patients following moderate to severe CO poisoning
Population: 230 adult patients treated in the Hennepin County Medical Center for moderate to severe CO poisoning with HBO2 from 1/1994 to 1/2002
Intervention: Followed up through 11/2005
Comparison: patients w/ myocardial injury Vs w/o myocardial injury
Outcome: all-cause mortality
Study Design: prospective cohort study

9. 230 patients
85 w/ myocardial injury
145 w/o myocardial injury
6 died in hospital + 26 died following hospital discharge
6 died in hospital + 16 following hospital discharge
Total 54 deaths (24%)
Standard mortality ratio 3.0
**3 times more likely to die during the follow-up period compared with age- and sex-specific US mortality rate
4 dies (18%) of presumed cardiovascular causes
14 (44%) died of presumed cardiovascular causes (cardiac arrest, myocardial infarction, CHF, fatal arrhythmia, stroke or natural causes in association with cardiovascular complications

10. Cardiovascular risk
Mode of exposure
Severity of illness
Myocardial injury
**myocardial injury significant independent predictors**

11. Uncertain mechanism for the increase of mortality
More common death from cardiovascular causes for patient with myocardial injury (44% Vs 18%)

13. -LVEF: 8 < 45%; 12  >45%
-Among those patient with impaired LVEF 2 had global wall motion impairment; 6 had regional wall motion impairment in left ventricle
-Coronary angiography in 7 patients all normal

14. Crit Care Med 2009;37(6):1-7

15. Objective
To investigate the potential impact on long-term mortality of CO-poisoned patients treated at a medical center over 3 decades.
1) to determine whether patients treated with HBO2 for acute COP are at increased risk for long-term mortality
2) to determine which underlying causes of death affect long-term mortality

16. Populations
Patient treated for acute CO poisoning with HBO2 therapy at the Center for Hyperbaric Medicine of Virginia Mason Medical Center from May 1978 through December 2005
Exclusion:
Patients <18 at the time of poisoning
Missing data on any of the predictor variables
Comparison and analysis
Analysis of standardized mortality ratio (SMR) & SMRs by major and minor cause-of-death classications
The State of Washington population as referent population
Strata by dichotomization of severity of COP (COHB <25% Vs > 25% & LOC +ve Vs LOC-ve ), age at COP(18-45 Vs > 46) and intentional Vs accidental
Outcome
All cause of death
Study Design
Retrospective cohort

17. General indications for HBO2
Transient or prolonged unconsciousness
Abnormal neurologic findings on physical examination
Evidence of cardiac ischemia
COHb level >25 to 30%

18. 1502 patients treated with HBO2 for acute COP from 5/1978 to 12/2005
32 patients with insufficient demographic information in records to submit for an NDI search
239 <18 at the time of poisoning
38 found by NDI direct result of death from the poisoning episode
Patients with missing information on one or more of the predictor variables: 99 missing race; 17 missing COHb levels; 5 unknown intent; 1 unknown LOC status total 122
Remained 1073 patients
11741 person-years follow-up
162 deaths records

19. Result COHb <25% >>COHB > 25% LOC +ve >> LOC –ve
accidental >>intentional accident

20. Standardized Mortality Ratio Analyses
No elevated mortality
SMR: Probability of fatality in individuals with exposure/ probability of fatality in individuals without exposure
Higher mortality for the entire cohort than expected mortality experience of residents of the State of Washington
Increased risk of death from alcoholism, motor vehicle accidents involving pedestrians, motor vehicle accidents of an other or unspecified nature, accidental posioning and intentional self harm

21. Most of the excess mortality in the group of intentional CO poisoning
Increased risk of death for alcoholism, cirrhosis and other liver diseases, other diseases of the digestive system, machine injuries, accidental poisonings, other injuries of undetermined intent and intentional self-harm

22. Analysis of conventional measures of CO poisoning severity: COHb levels & presence of LOC
Significant increase of all cases of mortality in both levels of COHb and for both level of consciousness categories
Significant increase in mortality of alcohlism and intentional self-harm

23. Effect of CO poisoning on long term mortality in different age of exposure
Age at exposure
SMR
Significant excess deaths in both groups
Significant causes of death in individual groups
18-45
2.9 (95% CI, )
Other injuries (predominantly accdiental poisonings) & violence (predominantly intentional self-harm)
Lymphatic/ hematopoietic cancer, diabetes, transportation/motor vehicle injuries, & falls from ladders or scaffolding
>46
1.5 (95% CI, )
As above
Pancreatic cancer, mental and psychiatric disorders and alcolism
** NO excess deaths for heart disease in either category of age

24. Direct Comparisons within Cohort
Unadjusted survival curves by COHb level showed significant difference in survival time (log-rank p=0.018)

25. Control of age of exposure, race, sex and intentionality of poisoning patient followed up for >1 year to <17 years after exposure had no significant difference in mortality rates regardless of COHb and the presence of LOC

26. Discussion
Significant increase risk for long-term mortality for patients > 18 who survived an acute episode of CO poisoning of moderate to severe degree with HBO2
Underlying causes may not actually be result of the CO poisoning event
?acute CO poisoning  marker of risk for death from other coexistent disease processes, psychiatric illness and behaviors

27. Causes of long-term mortality from episode of acute CO poisoning
Most excess mortality from patient with intentional exposure
35% of death due to completed suicides
**average subsequent death rate from completed suicide following attempted suicide 30% (similar)
NOT particular higher rate of long-term completed suicidal deaths for intentional exposure (no significant different in death rate from suicide for accidental exposure)

28. Causes of long-term mortality from episode of acute CO poisoning
Mental illness and high-risk behavior
Mental and psychiatric illnesses, alcoholism, tabacco-related deaths
Likely to be pre-existing problems rather than the result from the CO poisoning
Accidental traumatic injuries
***interpretation in cautious (small no. of deaths and excess deaths )
?impaired judgment, abnormal coordination, residual cognitive impairment

29. Limitation
Possibility of inaccurate coding of the cause of death in the NDI
Unmatched comparison group
risk factors for mortality: smoking status, BMI, socieconomic status

30. Recommendation from the paper
Close follow-up of CO poisoning with psychiatric and psychological evaluations
? CO-induced cognitive impairment

31. Applicability to local situation
Intentional exposure contributed to majority of cases of CO poisoning in HK
?? Different result if similar study performed in HK as less chronic alcoholic in the local situation
Patients with intentional CO exposure are more likely to have underlying psychiatric/psychological illness
Higher long term mortality from causes related to the high risk behaviors, i.e. self-harm, in this group of patients is expected

32. Thank you