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

Spectrum of effects of acute CO exposure NEJM 2009;360(12):1217-1225

NEJM 2009;360(12):1217-1225

Long term outcome from CO poisoning??

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):398-402

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):398-402

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

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

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

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

-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

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

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

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

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

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

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

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

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

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

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, 2.2-3.7) 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, 1.2-1.9) As above Pancreatic cancer, mental and psychiatric disorders and alcolism ** NO excess deaths for heart disease in either category of age

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

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

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

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)

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

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

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

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

Thank you