The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients
- Conditions
- Methanol Poisoning
- Interventions
- Device: isocapnic hyperventilation
- Registration Number
- NCT06173817
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Adult patients, men & women diagnosed with methanol poisoning
- Serum-methanol ā„ 50 mg/dL (16 mM)
- pH ā„ 7.0, and correctable by bicarbonate infusion
- no (newly developed) visual disturbances
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Isocapnic hyperventilation (iHV) isocapnic hyperventilation 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. ā 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)
- Primary Outcome Measures
Name Time Method Characterization of methanol elimination kinetics, when iHV is utilized 0-40 hours T1/2 S-methanol (t1-t2) during iHV: Half-life of methanol in blood from start (t1) to end (t2) of treatment with iHV
T1/2 S-methanol (t0-t1) before iHV): Half-life of methanol in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics
- Secondary Outcome Measures
Name Time Method Tolerability by self reporting by patient 0-40 hours Patient tolerability of iHV as self reported by patient
This will be recorded using a five-level Likert Scale
1 Did not tolerate iHV at all 2: Tolerated iHV sin shorter periods, but below therapeutic level 3: Barely tolerated iHV enough for therapeutic level 4 Tolerate iHV enough for therapeutic level 5: No discomfort and good toleration of iHVElimination ratio of formate 0-40 hours Evaluation of elimination ratio of formate through breath vs. urine with or without iHV
Elimination ratio of methanol 0-40 hours Evaluation of elimination ratio of methanol through breath vs. urine with or without iHV
Feasibility of use of iHV in Iran 0-40 hours iHV is new in Iran. The process requires training to be implemented correctly. This will be evaluated by assessing protocol deviations related to iHV equipment and by interviewing study workers on their perceived competency using the iHV equipment.
This will not be reported in one value, but presented as text and used as an exploratory outcome to guide any future implementation of iHV in IranNeed for haemodialysis 0- 40 hours Document type and degree of haemodialysis. Indication for such treatment is by the discretion of the local investigator. If S methanol \>5mM after 26hrs (T1/2 50-80hrs during fomepizole treatment without haemodialysis (8)) or if patient becomes increasingly acidotic in spite of adequate antidote treatment.
Adverse events through study completion, estimated 2 years Adverse events, including death, will be defined according to Good Clinical Practice guidelines by the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use. All adverse events will be registered in this trial and reported in accordance with local regulations in Iran.
Adverse events also include medical device deficiency of the isocapnic hyperventilation systemCharacterization of methanol elimination kinetics, prior to iHV is utilized 0-40 hours T1/2 S-methanol (t0-t1) before iHV): Half-life of methanol in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics
Serum formate kinetics 0-40 hours T1/2 S-formate before (t0-t1) before and after (t1-t2) (iHV): Half-life of formate in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics
Implementation of fomepizole in Iran through study completion, estimated 2 years Perception of simplicity of use of fomepizole amongst doctors involved in the study This will be recorded using a five-level Likert Scale
1 Fomepizole can not be used in the Iranian healthcare system 2: Fomepizole is difficult and require significant extra efforts to be used in the Iranian healthcare system 3: Fomepizole may be used the Iranian healthcare system with some extra effort 4 Fomepizole can easily be used the Iranian healthcare system with little extra effort 5: Fomepizole can easily be used the Iranian healthcare system with no extra effortEvaluation of fomepizole elimination during iHV 0-4 hours S-fomepizole analyzes from t1-t2. Pending availability of fomepizole analyzes
Length of ICU- and hospital stay from stdy start to death or discharge ICU, expected average 30 hours Length during treatment with iHV
Trial Locations
- Locations (1)
Loghman-Hakim Hospital,
š®š·Teheran, Iran, Islamic Republic of