The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients (iHV-Met)

University of Oslo (UIO)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Methanol Poisoning

Treatments: Device: isocapnic hyperventilation

Study type: Interventional

Funder types: Other

Identifiers

NCT06173817

475313 (Other Identifier)

IRCT20120629010133N5 (Registry Identifier)

U1111-1277-6360 (Other Identifier)

iHV-Met_2.0

Details and patient eligibility

About

The projects investigate if treatment with isocapnic hyperventilation can eliminate methanol from the body in a similar manner to dialysis. This is achieved by administering the antidote (fomepizole) and let the patient breathe on a isocapnic hyperventilation device while samples of blood, urine and maybe the breath are collected to measure the contents of methanol and its metabolites.

Full description

Isocapnic hyperventilation (iHV) The normal physiology breathing is a careful balance between the number of breaths per minute (rate/min) and the depth of each breath (tidal volume, Vt). Together they make up the minute ventilation (MV), where MV= rate x Vt). To maintain stable homeostasis in the organism, the minute ventilation is closely regulated to maintain adequate uptake of oxygen and adequate elimination of the carbon dioxide (CO2) that is produced by the metabolism. Too low minute ventilation leads to a buildup of CO2 and decrease in blood pH (respiratory acidosis), while hyperventilation (too high minute ventilation) leads to an excess loss of CO2 and increase in blood pH (respiratory alkalosis). The same mechanism will also enable the organism to compensate any metabolic disturbances (up to a certain point): A metabolic acidosis will be counteracted by a hyperventilation, whereas a metabolic alkalosis will be counteracted by a hypoventilation, both with the ultimate goal of keeping the acidity (as given by the pH) as closely regulated as possible.

The concept of isocapnic hyperventilation (iHV) allows the person to hyperventilate while keeping the CO2 within normal limits at the same time. The ClearMate (Thornhill Research Inc., Canada) adds CO2 to the inspired air to compensate to the increased loss induced by the increased minute ventilation. This means that hyperventilation can occur, and a wash-out of volatile substances such as methanol will happen without disrupting the important CO2 balance.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients, men & women diagnosed with methanol poisoning
• Serum-methanol ≥ 50 mg/dL (16 mM)
• pH ≥ 7.0, and correctable by bicarbonate infusion
• no (newly developed) visual disturbances

Exclusion criteria

• Acidosis requiring haemodialysis (pH <7.0), or acidosis that is not responding in spite of aggressive buffer (bicarbonate) treatment within maximum 1-2 hours.
• Comatose patients
• Newly developed visual disturbances
• ADH not fully blocked with antidotes, and not responding to additional dosing of fomepizole. Will be identified by a continuous or increasing anion gap (AG) or Base Excess (BE) on the blood gas machine.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Isocapnic hyperventilation (iHV)

Experimental group

Description:

Loading dose of fomepizole on clinical suspicion; A) History of intake of alcohol of unknown/illegal origin plus symptoms potentially occurring from methanol, or B) history as above and verified methanol poisonings among people drinking the same alcohol, or C) metabolic acidosis of unknown origin (where methanol cannot be excluded as the cause;or D) a combination of these. ● iHV started after a S-methanol concentration \> 50 mg/dL is obtained (typically within 4 hours) and initial acidosis is partly or fully corrected by sodium bicarbonate (BD \<15mM, HCO3- \>10mM)

Treatment:

Device: isocapnic hyperventilation