HYDROGEN SULFIDE : Does Hyperbaric Oxygen work? Case of the week December 12, 2003 Rob Hall MD

H2S Knock-down case of the week!

How is H2S toxic? Inhibits cytochrome oxidase Thus inhibits oxidative phosphorylation Anaerobic metabolism can ’ t keep up! > CELLULAR HYPOXIA EARLY DEATH Respiratory paralysis due to toxic effect at the respiratory centers

Permanent Neurologic Sequelae Prolonged coma Recurrent seizures Chronic vegatative states Tremors Cognitive impairment

Why might HBOT be effective? Increased oxygen delivery to tissues Increased oxyhemoglobin which increases the auto-oxidation of sulfide

What are the TEXTBOOK recommendations for HBOT? Haddad “ May be beneficial in patients in whom CNS symptoms do not resolve spontaneously or with prompt nitrite therapy ” Ford. “ Should be used in neurologically compromised or acidemic patients refractory to conventional therapy ” Goldfrank 2003 “ All patients should receive HBOT if readily available; transport solely for HBOT is unnecessary ”

H2S and HBOT …… So what is the evidence??

1) Vicas. Vet Hum Toxicol yo male H2S contaminated petroleum Unconcscious on arrival in ED 3 HBO treatments 13 hr post exposure 2 further HBO treatment Increased LOC, memory, verbal interaction, problem solving Persistent retrograde amnesia

2) Al-Mahesneh. Vet Hum Toxicol 1989 Acute exposure to known high [H2S] Comatose, unresponsive, F/D pupil on arrival in the ED Flown to hyperbaric chamber (?delay) HBOT for 3 hours NO improvement Patient died at 56hrs after exposure

3) Snyder. Am J Emerg Med 1995 Construction pit on of New Jersey coast Two men knocked – down, several other rescuers knocked down, 1 Dead on scene Worker 1 GCS 3 on arrival, sent for HBO 12 hour delay until HBOT started

3) Snyder. Am J Emerg Med 1995 Day1 One session of 2ATA for 45 min GCS 3 -> 5 Day 2 Two sessions of 1.5 ATA for 90 min each Day3 – 7 Two sessions of 1.0 ATA for 90 min each Day 3 GCS 7, Day 5 GCS 11, Day 7 GCS 15 Day 8-16 One session of 1.0 ATA for 90 min

3) Snyder. Am J Emerg Med 1995 Persistent Neurological Sequelae Slow speech, flat affect, inability to concentrate, impaired visual memory, easily distractible, confabulation Neurologic Sequelae unchanged at 12 and 18 months

4) Schneider. Occ Med yo male Building a sewer system in New Jersey Rescuer died at the scene GCS 3 on arrival at ED Transfer for HBOT 10hrs after exposure 2 ATA for 45 min bid X “ several ” days Regained consciousness on day 5 GCS 11 on day 7 then improved to 15 Similar neurological sequelae to last case noted at one month and 4yrs post incident

Neuroimaging CT head was normal in this case on day of exposure MRI was normal at 17 months despite persistent neurological sequelae PET scan at 3 years showed marked decrease in perfusion to thalamus, basal ganglia and abnormal metabolic patterns in the temporal and parietal lobes

NOTE Normal CT or MRI of brain does not preclude permanent neurologic sequelae!

5) Smilkstein. J Emerg Med yo male Oil pump waste collection tank GCS of 7 on arrival to ED HBOT started 10hrs after exposure Total of 12 HBOT treatments over 6 days #1: 2.5 ATA for 45 min #2: 2.0 ATA for 75 min #3-12: 2 ATA for min Outcome: stepwise improvement, awake/alert by 48hrs, slight difficulty with complex tasks persisted

6) Harefuah Another Case report of H2S treated with HBOT Hebrew!

The RATS have the last word! Bitterman. Tox Appl Pharm 1986 Rat model: several groups with 20 rats each LD 75 dose of intraperitoneal sodium sulfide Various treatments after sulfide injection Group 1: no treatment Group 2: sodium nitrite + room air Group 3: 100% oxygen Group 4: HBOT at 2 ATA Group 5: sodium nitrite + 3 ATA HBOT Various treatments before sulfide injection Group 7: HBOT 3 ATA Group 8: sodium nitrite and HBOT 3ATA

The RATS have the last word! Bitterman. Tox Appl Pharm 1986 pretreatement rescue treatments

The RATS have the last word! Bitterman. Tox Appl Pharm 1986 Conclusions from the rats Methemoglobinemia alone not beneficial Oxygen beneficial HBOT + methemoglobinemia beneficial

SUMMARY: H2S and HBOT 6 Case reports: 5 +ve, 1 -ve Case reports have significant delay from exposure to HBOT: does this matter? 1 Animal model NO case series NO controlled trials

Summary HBOT may have a role in the management of H2S toxicity but it ’ s efficacy is LARGELY UNKNOWN