Lormetazepam Versus Midazolam in Critically Ill Patients: a Retrospective Cohort Trial

Study Overview
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Brief Summary
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The aim of this retrospective cohort study is to evaluate the effect of lormetazepam versus midazolam on hospital mortality, intensive care unit outcomes and sedation management. The hypothesis is that patients receiving midazolam have a 5% higher hospital mortality in comparison to patients receiving lormetazepam.

Detailed Description
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Sedation is an integral part of modern intensive care medicine and has seen a tremendous development throughout the last years. Current guideline recommendations are targeted at an awake critically ill patients (target Richmond Agitation-Sedation Scale 0/-1) as early deep sedation has been shown to negatively affect the outcome. Nevertheless, is an adequate and individualized anxiolysis still an important intervention that can be achieved via process optimization, modifications to the infrastructure of the ward and pharmacologic therapy. Bolus application of benzodiazepines is a recommended pharmacologic measure to achieve proper anxiolysis. Midazolam is currently the most commonly used benzodiazepine in European intensive care units. Midazolam accumulates after repetitive application due to its pharmacokinetic properties, which increases the likelihood for side effects and makes targeted sedation increasingly difficult. Lormetazepam is used with increasing frequency as it is eliminated independent of the patients age and has few relevant metabolites. It is therefore thought to be better suited for targeted sedation management, which in turn would be beneficial for the patients. The aim of this retrospective cohort study is to evaluate the effect of lormetazepam versus midazolam on hospital mortality, intensive care unit outcomes and sedation management.

Official Title
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The Effect of Lormetazepam Versus Midazolam in Critically Ill Patients on Hospital Mortality: a Retrospective Cohort Trial

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Midazolam vs. Lormetazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intensive care unit patients at the Charité - Universitätsmedizin Berlin Age ≥ 18 years Intensive care unit length of stay ≥ 48 hours Duration of mechanical ventilation > 0 hours Midazolam or lormetazepam application during the ICU stay Exclusion Criteria: Number of application < 2 Midazolam and lormetazepam application during the intensive care unit stay Neurosurgical intensive care unit patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Midazolam<br>Critically ill intensive care unit patients receiving midazolam | Drug: Midazolam vs. Lormetazepam<br>* In this retrospective analysis we compared critically ill ICU patients receiving midazolam to those receiving lormetazepam.<br>|
| Lormetazepam<br>Critically ill intensive care unit patients receiving lormetazepam | Drug: Midazolam vs. Lormetazepam<br>* In this retrospective analysis we compared critically ill ICU patients receiving midazolam to those receiving lormetazepam.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Mortality | Proportion of patients that between hospital admission and hospital discharge | On average 20 days, for each study subject measured up to study completion day 12-31-2018 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of delirium during the intensive care unit stay | Incidence of delirium diagnosed on the intensive care unit | On average 7 days, for each study subject measured up to study completion day 12-31-2018 | 
| Duration of delirium during the intensive care unit stay | Duration patients had a delirium on the intensive care unit | On average 3 days, for each study subject measured up to study completion day 12-31-2018 | 
| Hospital length of stay | Time patients spend admitted to the hospital | On average 30 days, for each study subject measured up to study completion day 12-31-2018 | 
| Intensive care unit length of stay | Time patients spend admitted to the intensive care unit | On average 7 days, for each study subject measured up to study completion day 12-31-2018 | 
| Duration of mechanical ventilation | Time patients are mechanically ventilated | On average 4 days, for each study subject measured up to study completion day 12-31-2018 |