Hemadsorption to Enhance Drug Elimination in Intoxications

In this trial we assess the effectiveness of applying a hemadsorber (cytosorb®) in removing benzodiazepines or tricyclic antidepressants in intoxicated patients admitted to ICU with prolonged impaired consciousness. This is a one arm interventional investigation where a hemadsorption filter is applied in patients fulfilling inclusion criteria 8 hours after admission. Plasma titer of the neurodepressing drug will be collected sequentially both before and after start of hemadsorption to evaluate the speed of drug elimination before and after application of a hemadsorption filter. Pre- and post filter titers will be obtained to evaluate adsorbability and to evaluate time to saturation of the filter.

In this prospective interventional study with medical device, we would include 18 patients admitted to ICU after an intoxication with a quantifiable neurodepressing drugs (type benzodiazepines or tricyclic antidepressants) and with impaired consciousness defined as need for intubation or need for Flumazenil to prevent intubation. Naloxone is administered per standard of care to identify if opioid intoxications is the main reason of neurodepression. Patients requiring mechanical ventilation for other reasons than impaired consciousness due to this intoxication or indication for prolonged use of sedatives are excluded.

Patients with at least one risk factor for delayed drug elimination (Chronic kidney disease G3b or CHILD-Pugh B or C) and persisting impaired consciousness after eight hours (including patients with persisting need for flumazenil) and having 5 plasma titers of the neurodepressing drug with intervals of 2 hours will be initiated on a hemadsorption filter after contact between the treating team and either dr. Michaël Mekeirele or dr. Tim Balthazar to verify inclusion criteria. Patients fulfilling inclusion criteria but lacking the 5 plasma titers will get additional plasma titers with intervals of 2 hours until 5 plasma titers are obtained. If these patients still fulfill inclusion criteria at that time then a hemadosorption filter will be initiated.

After starting hemadsorption a plasma titer pre- and post filter will be obtained after 15 minutes and every 4 hours after starting hemadsorption for the first 24 hours. After this timepoint additional plasma titers will be obtained every 24 hours until stopping hemadsorption or normalisation of the plasma titer.

Eligibility Criteria:
Inclusion Criteria:

1. older than18 years
2. Admission to ICU
3. GCS \< 8 or requiring Flumazenil 8 hours after hospital admission
4. Having an intoxication with a benzodiazepine or tricyclic antidepressant that we can measure/quantify
5. Having a risk factor for delayed drug elimination defined as either Cirrhosis CHILD B/C or chronic kidney insufficiency KDIGO 3b or worse

Exclusion Criteria:

1. Pregnant patient
2. Patients in chronic dialysis before admission
3. Need for mechanical ventilation for other reasons than intoxications (e.g. pneumonia, neurotrauma)
4. Concomitant pathology requiring continued intravenous sedation
5. Known history of seizures
6. Contra-indication to heparin use
7. DNR restricting the use of mechanical ventilation or dialysis