Intoxication by Drug
Conditions
Keywords
Benzodiazepine, Tricyclic antidepressant, Intoxication, Hemadsorption
Brief summary
In this trial the investigators 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.
Detailed description
In this prospective interventional study with medical device, the investigotors 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.
Interventions
DEVICEHemadsorption filter
Plasma titers neurodepressing drug: * At admission to the hospital (standard of care) * 2 hours after admission (+/- 15 minutes) * 4 hours after admission (+/- 15 minutes) * 6 hours after admission (+/- 15 minutes) * 8 hours after admission (+/- 15 minutes) * Just before start hemadsorption Hemadsorption via dialysis catheter in patients still fulfilling inclusion criteria 8 hours after admission. Subsequent plasma titers pre- and post-hemadosorption filter: * 15 minutes after start of hemadsorption (+ 15 minutes) * 4 hours after start of hemadsorption (+/- 15 minutes) * 8 hours after start of hemadsorption (+/- 15 minutes) * 12 hours after start of hemadsorption (+/- 15 minutes) * 16 hours after start of hemadsorption (+/- 15 minutes) * 20 hours after start of hemadsorption (+/- 15 minutes) * 24 hours after start of hemadsorption (+/- 15 minutes) * Every other 24 hours until cessation of hemadsorption or normalization of the plasma titer (+/- 15 minutes)
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in time to upper limit of normal of the dosed drug with versus without hemadsorption | From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days | Based on plasma titers before start of hemadsorption the half life of the drug can be calculated. A theoretical intersection with the upper boundary of normal of the intoxicated drug plasma titer can be calculated. This will be statistically compared to the real time of attaining this titer after start of hemadsorption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to saturation of hemadsorption filter | From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days | Comparing the pre- and post filter titer of the neurodepressing drug the time to saturation can be observed |
| Catheter related complications | From enrollment to the removal of the dialysis catheter +/- 3 days | Catheter related complications (eg bleeding, infection) will be noted |
| Seizures during hemadsorption therapy | From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days | Seizures during hemadsorption therapy will be noted |
| Bleeding during hemadsorption therapy | From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days | Bleeding during hemadsorption therapy will be noted |
| Adsorbability of the individual neurodepressing drugs | From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days | Comparing the pre- and post filter titer of the neurodepressing drug the adsorbability can be observed. |
| Duration mechanical ventilation | From enrollment to extubation (+/- 3 days) | Time to extubation and stop of flumazenil will be noted |
| Duration ICU stay | From enrollment to discharge from ICU (+/- 1 week) | Time to discharge will be noted |
| Need and duration vasopressors | From enrollment to stop of vasopressors (+/- 3 days) | Time untill discontinuation of vasopressors will be noted |
| Cost effectiveness of applying a Cytosorb® hemadsorption filter | From enrollment to discharge from ICU (+/- 1 week) | Duration of ICU stay, duration of ventilation, cost of a hemadsorption filter and disposables amongst others will be used for an evaluation of cost effectiveness |
Countries
Belgium
Contacts
Primary ContactMarie-Claire vanmalderen, Study coordinator
Backup ContactMerel Stevens, Study coordinator
Outcome results
None listed