Monitoring of sedation depth in intensive care unit by therapeutic drug monitoring? A prospective observation study of medical intensive care patients

Richard J Nies,Matthias Kochanek,Kathrin Kuhr,Roman Pfister,Guido Michels,Carsten Müller,Martin H J Wiesen,Philipp S Binder,Nicole Nosseir,Felix S Nettersheim

doi:10.1186/s40560-018-0331-7

Richard J Nies, Matthias Kochanek + Show 8 more

Open Access

https://doi.org/10.1186/s40560-018-0331-7

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Abstract

BackgroundAnalgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures.MethodsForty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman’s rank correlation coefficient rho (ρ).ResultsAverage age of the population was 57.8 ± 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (ρ = − 0.467) and Ramsay Scores (ρ = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (ρ = − 0.312) and Ramsay Scores (ρ = 0.295). Correlations between BIS index and serum concentrations of midazolam (ρ = − 0.252) and sufentanil (ρ = − 0.166) were low.ConclusionCorrelations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.

Highlights

Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU)
In deeper sedated patients, Richmond Agitation-Sedation Scale (RASS) Score is more precise than Ramsay Score, which is not recommended in the German Arbeitsgemeinschaft Wissenschaftlicher Medizinischer Fachgesellschaften (AWMF) guidelines anymore [4]
Bremer et al [23] investigated 648 critically ill patients by therapeutic drug monitoring, who received a combination of fentanyl and midazolam when they had to be mechanically ventilated > 24 h

Summary

Introduction

Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. Ill patients on intensive care units require regimens of analgosedation for several reasons such as mechanical ventilation. Low states of analgosedation can cause hypercatabolism, immunosuppression, hypercoagulopathy, awareness and increased sympathetic activity, or inadvertent extubation, whereas deep sedation can be responsible for extended mechanical ventilation, higher risk of nosocomial pneumonia, increasing costs, and neuropsychological dysfunction [1,2,3,4,5,6]. Monitoring of analgosedation is an elementary part of ICU procedures to avoid excessive sedation states, drug-induced delirium, and higher mortality [2, 4, 6]. The current state of analgesia, sedation, and delirium should be measured every 8 h using validated monitoring procedures [4]

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