Hyperbaric oxygen for carbon monoxide poisoning

Reviewed and revised 27 December 2013

OVERVIEW

• The indications for, and effectiveness of, hyperbaric oxygen for carbon monoxide poisoning are controversial.
• RCTs are conflicting and hyperbaric oxygen therapy cannot be routinely recommended, but an undefined subgroup of patients who my benefit from treatment cannot be ruled out.
• severe CO poisoning patients are those generally considered most likely to benefit from hyperbaric oxygen therapy, but this needs to balanced by the hazards and logistically difficulties of transferring critically ill patients to a hyperbaric chamber

MECHANISM OF CARBON MONOXIDE TOXICITY

Effects of CO toxicity include those of acute hypoxia as well as delayed neurological sequelae, that are more prominent with chronic exposure

• CO has 210 times greater affinity for haemoglobin than does O2.
• CO causes cellular hypoxia by impairing haemogloin-mediated oxygen delivery to tissues
• CO also binds cytochromes, causes endothelial oxidative injury, lipid peroxidation and triggers inflammatory cascades

RATIONALE FOR HYPERBARIC OXYGEN THERAPY

CO elimination half-life varies with the dissolved oxygen tension in the blood due to competitive binding with haemoglobin

• FiO2 0.21 -> 240 min
• FiO2 1.0 -> 90 min
• 100% O2 at 3 atmospheres -> 23 min

HIGH RISK PATIENTS

Patients at high risk of persistent neurological sequelae are those for whom hyperbaric oxygen may be considered:

• significant loss of consciousness or coma
• persistent neurological dysfunction (e.g. confusion)
• abnormal cerebellar examination
• metabolic acidosis
• myocardial ischaemia
• age >55 years
• pregnancy

Outcome does not correlate well with COHb levels

STANDARD TREATMENT

• administration of high-flow oxygen via a non-rebreather mask until all symptoms resolved
• continue for 24 hours in pregnant patients while fetal well-being is assessed
• follow up at 1-2 months for neuropsychiatric assessment

HYPERBARIC OXYGEN TREATMENT

• protocols vary, which is a source of controversy when assessing the effectiveness of therapy
• The Scheinkestel et al (1999) study used daily 100-minute treatments with 100% oxygen in a hyperbaric chamber–60 minutes at 2.8 atmospheres for 3 days, extended to 6 days if there were neurological abnormalities.

EVIDENCE SUMMARY

Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041. doi: 10.1002/14651858.CD002041.pub3. Review. PubMed PMID: 21491385.

• Systematic review
• 7 RCTs of varying quality and all had design or analysis flaws, one excluded as no clinical outcomes studied
• n = 1361 from 6 studies
• 2 RCTs  found a beneficial effect of HBO for the reduction of neurologic sequelae at one month, while 4 others did not.
• Pooled random effects meta-analysis does not suggest a significant benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12)
• Significant methodological and statistical heterogeneity was apparent among the trials
• Positive trials particularly flawed — e.g. not adjusting for multiple hypotheses or stopped early
• Negative trials limited by low power or limited follow up
• Only the Scheinkestel et al (1999) and the Weaver et al (2001) studues exposed control groups to ‘sham dives’
• Insufficient evidence to support the use of hyperbaric oxygen for CO poisoning -> suggests MCRCT needed

Scheinkestel CD, Bailey M, Myles PS, Jones K, Cooper DJ, Millar IL, Tuxen DV. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust. 1999 Mar 1;170(5):203-10. Review. PubMed PMID: 10092916.

• RCT
• n = 191 (73% had severe poisoning and 76% had attempted suicide)
• Inclusion critieria: all patients referred for CO poisoning
• Comparison: Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber–60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group–for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments.
• Outcome: Neuropsychological performance at completion of treatment, and at one month where possible.
  — HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients).
• Criticisms:
  — delay before most patients received hyperbaric oxygen (about 7 hours) might have reduced its effectiveness
  — patients in both arms of the trial were treated with continuous normobaric oxygen for 3 days, which is not generally accepted as standard practice
  — only 46% of patients randomised to treatment were followed up at 4 to 6 weeks -> this makes this study difficult to interpret as delayed neurological sequelae are the key concern on CO poisoning
  — Pregnant women, children, burns victims and those refusing consent were excluded
  — external validity limited to acute CO poisoning

Weaver LK, Hopkins RO, Chan KJ, Churchill S, Elliott CG, Clemmer TP, Orme JF Jr, Thomas FO, Morris AH. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002 Oct 3;347(14):1057-67. PubMed PMID: 12362006.

• quadruple-blinded RCT with blocked, stratified randomisation
• ITT
• n= 152
• Inclusion criteria included COHb level elevation or exposure to ambient CO elevation OR an obvious CO exposure with symptoms of CO poisoning
• comparison: hyperbaric O2 vs high flow O2
• intervention: three chamber sessions within a 24-hour period, consisting of either three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air.
• control: Oxygen treatments were administered from a high-flow reservoir through a face mask that prevented rebreathing or by endotracheal tube.
• primary outcome: cognitive sequelae six weeks after carbon monoxide poisoning
  — hyperbaric-oxygen group (19 of 76 [25.0 percent]) had more cognitive sequelae than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007) -> NNT = 5
  — Cognitive sequelae were less frequent in the hyperbaric-oxygen group at 12 months
• Criticisms:
  — trial stopped early for benefit – which likely inflates the reported benefit
  — baseline differences between groups were present: cerebellar dysfunction before treatment was more frequent in the normobaric oxygen group (15% vs. 4%, p=0.03) (p. 1060) and there was also a significant difference in duration of CO exposure (13 hours in the HBO vs. 22 hours in NBO group) – however HBO was still favoured when these were adjusted for
  — excluded children, pregnant patients and moribund patients
  — significant number of patients refused randomisation (these were not analysed further)
  — no assessment of cost-effectiveness
  — no validation of neuropsychiatric assessment
  — bias likely as the study reports a primary outcome of all neurologic sequelae, yet the originally intended endpoint was delayed neurologic sequelae (for which there was no difference)
  — the very different chamber-related adverse event rates in the two arms suggest that anyone with access to the comparison of the rates of these outcomes would have been able to identify treatment allocation

References and Links

Journal articles

• Annane D, Chadda K, Gajdos P, Jars-Guincestre MC, Chevret S, Raphael JC. Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Med. 2011 Mar;37(3):486-92. PMID: 21125215.
• Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041.PMID: 21491385. [Free Full Text]
• Scheinkestel CD, Bailey M, Myles PS, Jones K, Cooper DJ, Millar IL, Tuxen DV. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust. 1999 Mar 1;170(5):203-10. PMID: 10092916.
• Weaver LK, Hopkins RO, Chan KJ, Churchill S, Elliott CG, Clemmer TP, Orme JF Jr, Thomas FO, Morris AH. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002 Oct 3;347(14):1057-67. PubMed PMID: 12362006.]

FOAM and web resources

• ALIEM —Carbon Monoxide Poisoning: Common Questions and Dilemmas (2013)
• TPR — Hyperbaric oxygen for carbon monoxide poisoning? Eminence-based recommendations not evidence-based (2012)
• TPR — Review of carbon monoxide toxicity misses some key references (2012)
• TPR — Does delayed hyperbaric oxygen therapy improve neurological outcome in carbon monoxide toxicity? (2011)
• TPR — Hyperbaric oxygen for carbon monoxide poisoning: do we know the answer (2011)