Recommended dosages of analgesic and sedative drugs in intensive care result in a low incidence of potentially toxic blood concentrations

Abstract

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.

Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).

Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.

Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Keywords: Analgesia; critical care; drug concentrations; drug dosages; intensive care medicine; sedation.

Figure 1

Flowchart of inclusion and exclusion (n = ICU admissions).

Figure 2

RASS values measured within 1, 2, 3, and 4 h from the sampling time. The marked line is the median RASS value.

Figure 3

Propofol concentrations with corresponding RASS value within 4 h of sampling time. Panel A: with and without dexmedetomidine. Panel B: with and without fentanyl.

Figure 4

Panel A: morphine concentrations with corresponding NRS value within 4 h of sampling time. Panel B: fentanyl concentrations with corresponding NRS value within 4 h of sampling time.