What is the Marx protocol for Hyperbaric Oxygen (HBO) therapy?

The Marx Protocol for Hyperbaric Oxygen Therapy

The Marx protocol for hyperbaric oxygen therapy consists of three hyperbaric oxygen treatments at 3.0 atmospheres absolute (atm abs) administered within 24 hours of carbon monoxide poisoning presentation, as established in the Weaver study, which demonstrated significant reduction in cognitive sequelae compared to normobaric oxygen therapy. 1

Protocol Details

The specific components of the Marx protocol include:

• First treatment: 3.0 atm abs for 1 hour followed by 2.0 atm abs for 1 hour
• Second and third treatments: 2.0 atm abs (typically for 90 minutes each)
• Timing: All three treatments administered within 24 hours of presentation
• Target population: Patients with carbon monoxide poisoning, particularly those with risk factors for cognitive sequelae

Evidence Base

The protocol is based on the highest quality evidence from the 2002 Weaver study, which showed:

• 21% absolute reduction in neurologic sequelae at 6 weeks (46% vs 25%) 1
• Number needed to treat (NNT) of approximately 5 patients to prevent one case of cognitive sequelae 1
• Benefits persisted at 6 weeks, 6 months, and 12 months after treatment 1

Clinical Application

Indications for the Marx Protocol

• Loss of consciousness during or after CO exposure
• Neurological symptoms (confusion, seizures, focal deficits)
• Pregnancy (regardless of symptoms)
• Severe CO poisoning (high carboxyhemoglobin levels, though levels alone do not determine treatment)
• Persistent symptoms despite normobaric oxygen therapy
• Age ≥36 years (risk factor for cognitive sequelae) 1, 2

Implementation Considerations

• Treatment should begin as soon as possible after CO exposure
• Continue 100% normobaric oxygen via non-rebreather mask until HBO therapy is available
• Patients should be carefully evaluated for contraindications to hyperbaric therapy
• Persistently symptomatic patients may benefit from the full three treatments 1

Special Populations

• Pregnant women: Should receive HBO₂ regardless of symptoms due to higher fetal risk
• Children: Those with impaired consciousness or neurological symptoms should be considered for HBO₂
• Patients with burns: Decision regarding HBO₂ should be deferred to burn surgeon 1, 2
• Intentional CO poisoning: Screen for co-ingestions with toxicology testing 1

Genetic Considerations

An important nuance in the application of the Marx protocol involves apolipoprotein E (APOE) genotype:

• Patients with the e4 allele (14-25% of population) may derive less benefit from hyperbaric oxygen therapy
• Those without the e4 allele show greater reduction in cognitive sequelae with HBO₂ 1

However, since most individuals do not carry the e4 allele and genotyping is not routinely available in emergency settings, the protocol is recommended for all eligible patients.

Common Pitfalls to Avoid

• Delaying treatment: Benefits diminish significantly with delays beyond 6 hours from exposure 1
• Relying solely on COHb levels: Levels do not reliably predict symptoms or outcomes 2
• Inadequate pressure: Using less than 3.0 atm abs for the first treatment may reduce efficacy 1
• Premature discontinuation: Completing all three treatments within 24 hours is essential for optimal outcomes
• Overlooking follow-up: All patients should be evaluated 1-2 months after exposure to screen for delayed neurological sequelae 2

The Marx protocol represents the most evidence-based approach to hyperbaric oxygen therapy for carbon monoxide poisoning, with demonstrated long-term benefits in reducing cognitive sequelae in affected patients.