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Carbon Monoxide

Gavin Greenfield

Mark Yarema

March 21, 2002

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Carbon Monoxide - Overview

• Sources

• Pathophysiology (3 effects)

• Acute Presentation

• Delayed Neurological Sequelae presentation

• Co-oximeter – what is it?

• Treatment – NBO vs HBO

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CO – What is it?

• colourless poisonous gas• generated through incomplete combustion

of carbon containing products – anything that contains carbon and is burned

• most common cause of fire related death• responsible for more morbidity and

mortality than any other toxin (in industrialized countries); leading cause of poisonous deaths in the U.S.

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Examples of Exposurenote

• smoke from fires• smoke from cigarettes• indoor burning of charcoal (bbq’s)• fossil fuel engine exhaust • gas or coal heater emissions• formaldehyde producing plants• CO also produced from hepatic metabolism of

methylene chloride vapour (paint removers and other solvents)

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Pathophysiology – Carboxyhemoglobin

note

• CO binds to hemoglobin 240 times as strongly as oxygen

• amount of oxygen that can be carried by the hemoglobin is inversely related to the number of binding sites occupied by CO

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Oxygen Dissociation Curve

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Pathophysiology – Oxygen Dissociation Curve

note

• Shifted to the left (as does low body temperature and alkalosis)

• caused by change in structure of the Hb molecule after CO binds it – results in Hb more tightly holding on to remaining oxygen molecules

• results in hemoglobin being unable to release its bound oxygen to tissues

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Pathophysiologynote

• Binding of hemoglobin by CO (with induction of carboxyhemoglobin and shifting of curve to left) does not account for all of the consequences observed

• animals transfused blood with highly saturated carboxyhemoglobin but minimal free CO do not get symptoms

• the small free portion that is dissolved in plasma likely has a major role

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Quick Review of Kreb’s Cycle

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Pathophysiology – Toxic effects of CO on respiratory pigments and

mitochondrial cytochromesnote• CO results in the cessation of cytochrome

oxidative phosphorylation– at a cellular level get a switch to anaerobic

metabolism (pyruvate utilization switches from aerobic Kreb’s cycle to being metabolized to lactate)

• CO pathologically activates neutrophils leading to vascular adherence and a reperfusion injury manifested by lipid peroxidation

• CO also binds myoglobin and disrupts its activity– decreased myocardial contractility

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Summary of Pathophysiologynote

• 1. Carboxyhemoglobin + Shift of Oxygen Dissociation Curve to left results in decreased tissue oxygen delivery

• 2. Cellular toxin – impairment of oxidative phosphorylation resulting in anaerobic metabolism and impairment of myoglobin

• 3. Lipid peroxidation

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Typical Presentationsnote

• benign headache syndrome or viral illness– particularly if group of people have similar

symptoms or if it improves after leaving an exposure site

• seizures, coma, myocardial ischemia

• everywhere in between

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Clinical Featuresnote

• Tissues that have high oxygen utilization are more severely affected (heart and brain)

• severe CO toxicity– brain: altered mental status, coma, seizures– heart: hypotension, cardiac arrest

• mild CO toxicity– headache, nausea, vomiting, dizziness, confusion, emotional

ability, weakness– chest pain, palpitations, mottled skin from decreased cardiac

output

• symptoms exacerbated during times of increased neurologic or myocardial oxygen demand

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Clinical Features – Delayed Neurological Sequelae

• typically develop 2 to 40 days post exposure

• may include headache, difficulty concentrating, lethargy, emotional lability, amnestic syndromes, dementia, psychosis, parkinsonism, chorea, apraxia, agnosia, peripheral neuropathy, urinary incontinence

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Diagnosis (in addition to history and physical examination)

• Pulse oximetry not useful – why?• oxygen saturation displayed is the ratio of

oxyhemoglobin to total (oxy + deoxy) hemoglobin• pulse oximeters use only two wavelengths of light

therefore each hemoglobin molecule is classified as oxyhemoglobin or deoxyhemoglobin

• carboxyhemoglobin absorbs approximately the same light as does oxyhemoglobin therefore the pulse oximeter misinterprets carboxyhemoglobin as oxyhemoglobin

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Diagnosisnote

• Arterial Blood Gas – what do you expect?• P02 should be normal or high if on O2• is useful for demonstrating metabolic

(lactic) acidosis• can do venous COHb level as it correlates

well with arterial • CBC

– give hemoglobin level so can estimate arterial oxygen content

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Diagnosis – Co-oximetry

• Co-oximetry is the investigation– co-oximeters use four rather than two

wavelengths of light– detect oxyhemoglobin, deoxyhemoglobin,

carboxyhemoglobin, methemoglobin– co-oximeters require a sample of whole

arterial blood

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Co-oximetry

• signs and symptoms of CO injury correlate with on-scene co-oximeter determination of COHb

• very little correlation with emerg carboxyhemoglobin levels

• healthy non-smokers have baseline level of 1-3%

• smokers commonly have levels of 10% and in some cases may exceed 15%

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Other Investigationsnote

• EKG to detect myocardial ischemia• If clinically indicated

– cardiac enzymes– serum CK, serum myoglobin, urine myoglobin to

detect rhabdo– CXR– CT / MRI modestly sensitive for CNS ischemic injury 6

h after exposure

• Other routine investigations to exclude alternative diagnoses

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Treatment – 100% Oxygennote

• nonrebreather with reservoir• PO2 increases resulting in increased total

oxygen content of blood and increased oxygen delivery

• half life of carboxyhemoglobin is inversely related to P02 – the higher the PO2 the shorter the half life of carboxyhemoglobin– 320 min breathing room air– 60 -130 min breathing 100% oxygen at normal

atmospheric pressure– 23 min breathing 100% oxygen at 2.8 atmospheres of

pressure (hyperbaric)

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100% Oxygen

• Tintinalli recommends treating for 4 hours

• Rosen recommends treating until resolution of symptoms or substantial fall of COHb levels and then changing to low-flow oxygen (<50%)

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Treatment – Hyperbaric Oxygen (HBO)

note

• dramatic improvement in symptoms and signs but +++ debate with regard to HBO resulting in improved short and long term outcomes compared with NBO (normobaric oxygen)

• Carboxyhemoglobin levels are not used to determine eligibility for HBO (Tintinalli)

• some institutions use arbitrary COHb levels as one determinant of referral for HBO therapy (Edmonton) regardless of presence of symptoms (Rosen)

• consider costs and risks of transport

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HBO – MOA and Complicationsnote

• shortens half life of carboxyhemoglobin• improves oxygen delivery to ischemic tissue (by

increasing PO2)• may regenerate cytochrome oxidase• lessens CO induced reperfusion injury

• complications rare and include oxygen induced seizures (1 in 1000), ear and sinus barotrauma, pulmonary barotrauma, vascular gas embolism

• possible higher seizure risk with higher pressure• only absolute contraindication is untreated

pneumothorax

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HBO

• standard HBO treatment uses 100% oxygen at 2.4-2.8 atmospheres of pressure for 90 min

• most respond to one treatment although some may require more

• efficacy may decrease if delayed more than 6 hours after exposure

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HBO – History and Research“Carbon monoxide” and

“Hyperbaric”• Pre-1989

– multiple studies claimed benefit– all uncontrolled or retrospective

• 1989 – first randomized study– Trial of Normobaric and Hyperbaric Oxygen for Acute Carbon

Monoxide Intoxication. The Lancet, August 19, 1989• Prospective, randomized nonblinded clinical trial in 629 patients• no benefit of HBO over NBO in pt’s with no history of LOC (therefore

likely less severe poisoning)• reported incidence of delayed neurological sequelae in more than

40% of both treatment groups• outcome measured was recovery (self assessment questionnaire

and physical examination) at one month (delayed neurological sequelae diagnosed when pt’s reported any of a variety of complaints on the questionnaire)

• pt’s randomized for treatment at a mean time of almost 6 hours

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HBO - Literature

• 1995– Delayed Neurological Sequelae After Carbon Monoxide

Poisoning: Prevention by Treatment With Hyperbaric Oxygen. Annals of Emergency Medicine, 25(4), April 1995

• prospective, randomized, nonblinded study of 65 pt’s with mild to moderate (no history of LOC or cardiac instability) CO poisoning who presented within 6 hours

• outcome was delayed neurological sequelae tested by a neuropsychologic screening battery (not defined), and simply asking for the presence of symptoms

• no difference between groups immediately after treatment• 7 patients in the ambient pressure group had DNS diagnosed• 0 patients in the HBO group had DNS diagnosed (p<0.05, 95% CI

on the difference between the proportion of pt’s in whom DNS developed in the two groups (23% vs. 0%) was 8.2% to 38.4%

• pt’s treatment begun at a mean time of 2.0 hours

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HBO – Literaturenote

• 1995 (cont’d)– Non-comatose patients with acute carbon monoxide

poisoning: hyperbaric or normobaric oxygenation? Undersea & Hyperbaric Medicine, Vol. 22, No. 1, 1995

• 26 patients randomized to either 6h 100% NBO + 6h 50% NBO or 2h HBO + 4h 100% NBO + 6h 50% NBO

• no patient blinding; ?investigators blinded• clinical signs and symptoms assessed at 2h and at 12h• less clinical abnormalities at both 2h and 12h in HBO group• no clinical abnormalities in any pt at hospital discharge• mean time to treatment 53 minutes

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HBO - Literature

• 1999– Hyperbaric or normobaric oxygen for acute carbon

monoxide poisoning: a randomized controlled clinical trial. Medical Journal of Australia, 170:203-210, 1999

• randomized controlled double-blind trial of 191 patients• included all pt’s (minus pregnant women, children and burn

victims) irrespective of severity of poisoning• daily 100 minute treatments with 100% oxygen in a

hyperbaric chamber (either at 2.8 atm for 60 min or 1.0 atm) for 3 days

• main outcome was neuropsychologic performance (tests) at completion of treatment and at one month (where possible)

• no benefit and possible harm in HBO group

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HBO - Literature

• 1999 (cont’d)– Hyperbaric or normobaric oxygen for acute carbon

monoxide poisoning: a randomized controlled clinical trial. Medical Journal of Australia, 170:203-210, 1999

• criticisms: cluster randomization, more intense and higher pressure oxygen therapy may have resulted in oxygen toxicity, some authors questioned the appropriateness of the neuropsychological testing, 54% of pt’s lost to follow up, another author subsequently reviewed their statistics and using the exact same data found a benefit to HBO therapy

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HBO – Literaturenote

• 2000– Hyperbaric oxygen for carbon monoxide poisoning.

Cochrane Database of Systematic Reviews, Jan 01, 2000.

• included all randomized controlled trials (6) involving non-pregnant adults acutely poisoned with carbon monoxide, regardless of severity. Trials with a score of 3 out of 5 or higher on the validity instrument of Jadad were included

• no evidence that unselected use of HBO is helpful; however, evidence is insufficient to provide clear guidelines for practice

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HBO - Literature

• 2000 (cont’d)– Hawkins et al. – another retrospective review

that did show benefit to HBO

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HBO - Literature

• 2002– Hyperbaric Oxygen Does Not Prevent

Neurologic Sequelae after Carbon Monoxide Poisoning. Academic Emergency Medicine. 9(1), January 2002

• mice study• no benefit to HBO

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HBO – Literature Summary

• all reported non-randomized studies have suggested benefit from HBO

• of the 4 published randomized studies, two report benefit (the two from 1995) and two report no benefit (1989, 1999)

• So what the heck do we do?

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HBO - Tintinalli Recommendations For Use

note

• If mild CO Toxicity then treat with NBO for 4 hours and only consider HBO if symptoms persist– mild toxicity listed as weakness, nausea, dizziness,

headache, mildly abnormal CONSB• If severe toxicity than HBO 90 minute treatment,

if symptoms persist repeat treatment in 3-6 h– severe toxicity listed as LOC or near syncope,

confusion (moderately normal CONSB), focal neuro changes, myocardial ischemia, persisting hypotension, persisting acidosis, pregnant mother with COHb > 15%, concurrent injury or intoxication

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HBO – Calgary vs. Edmonton

• Calgary– monoplace chamber in Calgary (HBOT clinics) but

can only take stable pediatric or pregnant patients, not intubated patients

• Edmonton– HBO located at Misericordia Hospital– Senior Therapist for The Chamber told me that it is

used regularly (maybe one patient q 2 months)– ER Doc consults Doc on call for the chamber who has

final decision as to the use of the chamber

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HBO - Edmonton

• No specific guidelines as to who gets the HBO– the ones mentioned include COHb>20%

(controversial and dependent on the MD on call), severity of presentation (syncope, seizures, metabolic acidosis, etc.)

• Pt gets 3.0 atm pressure x 90 min – up to tid in first 24 hours then prn at 2.0 atm x 90 min up to bid

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HBO - Calgary

• HBOT Clinic in south Calgary has monoplace chambers

• deals more with patients with DCS, diabetic wounds, osteonecrosis of mandible

• will dive stable pregnant and pediatric patients with CO poisoning but cannot take intubated patients

• can call HBOT clinic --> will be referred to MD on call to discuss case

• will usually treat at 2.5 ATA for 3-4 treatments, depending on patient

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Bottom Line re: HBO in Alberta

• Can call HBOT if patient is pregnant or a child, but if patient is unstable/intubated, must discuss with Misericordia MD on call as HBOT cannot take unstable patients

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Special Patients

• very young and very old more severely affected

• pregnant patients• fetus at greater risk due to greater affinity

of fetal hemoglobin than adult hemoglobin for CO

• pt’s with chronic exposures have greater risk of sequelae independent of COHb levels

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Pregnancy

• CO is known teratogen

• fetal hemoglobin binds CO more tightly than maternal hemoglobin

• longer elimination half life of carboxyhemoglobin in fetus

• lower threshold for HBO

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Dispositionnote

• Discharge (ensure not to same environment)– Mild symptoms with full resolution after 4 h of 100%

O2– Mild symptoms with full resolution after one HBO

treatment• Admit

– mild symptoms but persist– severe symptoms regardless of improvement with

treatment– pregnant pt’s for fetal monitoring

• All patients need follow up to evaluate for delayed sequelae

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note

CONSB (from Tintinalli)

Weaver LK should be publishing data on a randomized double blind study comparing HBO to

NBO

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CASE 1

• 28 year old female

• fight with significant other

• depressed

• locks self in garage with car running

• found in garage by friend

• no LOC or syncope reported

• transported on 100% 02 NRB by EMS

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CASE 1

• Vitals stable in ED, c/o headache only

• exam normal

• ABG normal, no acidosis

• COHb level 31%

• What would you do?

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CASE 2

• 42 year old male

• lives alone in Airdrie

• girlfriend comes over to visit nightly for a 7 day period - reports feeling nauseated, dizzy, and having a headache after leaving house each morning

• day 8 - arrives to find him unconscious in house

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CASE 2

• Intubated/ventilated by EMS. No CPR necessary.

• Fire department confirms presence of CO in home from furnace

• transferred to FMC

• COHb level 14% at FMC

• What would you do?

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CASE 3

• paramedic calls in stating there has been an outbreak of CO poisoning at a local skating rink because of a problem with the refrigeration mechanisms

• up to 25 people symptomatic, reporting headaches, nausea, vomiting

• 4 paramedics on scene, can treat 8 people at once with 02

• wants to know how to manage patients and whether they should all come to your emerg

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OUTCOMES

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CASE 1

• treated with 100% 02 NRB for 4 hours

• symptoms resolved

• no longer suicidal

• discharged to f/u with GP

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CASE 2

• Remained unconscious in ED

• case discussed with HBO MD in Edmonton

• flown to Edmonton by fixed wing for HBO therapy

• discharged the next day to f/u with GP

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CASE 3

• advised EMS not to transport anyone whose symptoms resolved once they went outside

• called all ED’s (adult and pediatric) to inform them of potential incoming cases

• 4 patients came to FMC, all had levels from 10-15% with mild symptoms

• treated with 100% 02 for 4 hours and discharged