Neurotoxicity Evaluation of Beta-lactams in Intensive Care Unit and Identification of the Risk Factors

Study Overview
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Brief Summary
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Beta-lactams are the most prescribed antibiotics in intensive care units. The lack of linearity between the dose administered and the exposition due to the very high variability of the pharmacokinetics in critically ill patients requires that the treatment be adapted on a case-by-case basis depending on the drug serum concentration. However, maximum concentrations not to be exceeded in order to limit beta-lactams toxicity are generally unknown. The main toxic risk of beta-lactams in intensive care is indeed neurological, but the neurotoxicity is probably underdiagnosed due to the variability of the signs observed, their time to onset, and confounding factors. Apart from recommendations for dose adjustment in the event of renal insufficiency, the procedures for the proper use of beta-lactams in intensive care are poorly established. The study presented here aims to assess the impact of the neurotoxic risk of beta-lactams in intensive care based on therapeutic drug monitoring, and thus to improve beta-lactam safety in critically ill patients. This is a prospective cohort study evaluating change in neurological status of patients admitted to the ICU and treated with a beta-lactam antibiotic with therapeutic drug monitoring. Neurological evaluation and scoring (Glasgow scale, CAM-ICU, Richmond agitation-sedation scale) and beta-lactam serum concentration assay are performed together 2 to 3 times a week.

Official Title
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Neurotoxicity Evaluation of Beta-lactams in Intensive Care Unit and Identification of the Risk Factors

Conditions
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Neurotoxicity, Sepsis, Beta Lactams, Therapeutic Drug Monitoring, Critical Care, Acute Kidney Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the ICU Treatment initiation by an antibiotic of the beta-lactam class Beta-lactam therapeutic drug monitoring Exclusion criteria: Any neurological disorder already present at admission Patients on mechanical ventilation who presented a neurological disorder before being intubated and sedated

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with a change in neurological status | the primary objective is to assess the frequency of beta-lactam neurotoxicity in a standardized use with therapeutic drug monitoring | one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| beta-lactam serum concentration according neurological status | beta-lactam serum concentration is assayed by a validated HPLC method | one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurotoxicity, Sepsis, beta lactams, therapeutic drug monitoring, critical care, Acute Kidney Injury