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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Acute Kidney Injury; Neurotoxicity; Critical Care; Therapeutic Drug Monitoring; Beta Lactams

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Amiens-Picardie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens
• Investigators: Principal Investigator: Youssef BENNIS, PU-PH, CHU Amiens

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: critical care; neurotoxicity; Sepsis; Acute Kidney Injury; therapeutic drug monitoring; beta lactams
• Additional Relevant MeSH Terms: Urogenital Diseases; Nervous System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Chemically-Induced Disorders; Renal Insufficiency; Poisoning; Pathological Conditions, Signs and Symptoms; Acute Kidney Injury; Sepsis; Neurotoxicity Syndromes
• Other Study ID Numbers: PI2017_843_0036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No