Abstract
IntroductionMidazolam is used routinely to sedate patients in the intensive care unit (ICU). We suspected that midazolam over-sedation was occurring in the ICU of the Guy's and St. Thomas' Trust and that it could be difficult to differentiate this from underlying neurological damage. A sensitive assay for detecting midazolam and 1-hydroxymidazolam glucuronide (1-OHMG) in serum was developed and applied in the clinical setting.MethodsIn the present study we evaluated a series of cases managed in a mixed medical, surgical and trauma ICU. Serum was collected from 26 patients who received midazolam, were 'slow to wake' and in whom there was suspicion of neurological damage. Patient outcome was followed in terms of mortality, neurological recovery and neurological damage on discharge.ResultsOut of 26 patients, 13 had detectable serum levels of midazolam and/or 1-OHMG after a median of 67 hours (range 36–146 hours) from midazolam cessation. Of these 13 patients in whom midazolam/1-OHMG was detectable, 10 made a full neurological recovery. Of the remaining 13 patients with no detectable midazolam/1-OHMG, three made a full neurological recovery; 10 patients were subsequently found to have suffered neurological damage (P < 0.002), eight of whom died and two were discharged from the ICU with profound neurological damage.ConclusionThese findings confirm that prolonged sedation after midazolam therapy should be considered in the differential diagnosis of neurological damage in the ICU. This can be reliably detected by the assay method described. The effects of midazolam/1-OHMG persist days after administration of midazolam has ceased. After prolonged sedation has been excluded in this patient group, it is highly likely that neurological damage has occurred.
Highlights
Midazolam is used routinely to sedate patients in the intensive care unit (ICU)
A wide interpatient variability in the pharmacokinetic properties of midazolam in critically ill patients with multiple organ failure has been reported [5], which can lead to prolonged sedation after midazolam therapy is stopped
We previously developed a rapid assay for measuring midazolam and its glucuronide metabolite simultaneously [1]
Summary
Midazolam is used routinely to sedate patients in the intensive care unit (ICU). Midazolam is an intravenous sedative that is commonly used during ventilation in critical illness It is often regarded as the sedative of choice in the intensive care unit (ICU). According to the findings of our recent electronic survey (93% respondents) [1], midazolam is still routinely used in the UK as a sedative in ICUs. ICU = intensive care unit; 1-OHMG = 1-hydroxymidazolam glucuronide. Midazolam is 94–98% bound to plasma albumin and has a volume of distribution of 1.7 l/kg in healthy individuals [2] It is extensively metabolized first via cytochromes p450, 3A4 and 2B6 to 1-hydroxymidazolam, before undergoing glucuronidation to form 1-hydroxymidazolam glucuronide (1-OHMG), which has sedative properties and is excreted in the urine [3,4]. Patients with multiple organ failure are at high risk for neurological damage because they frequently have episodes of hypotension and dysrhythmia, and may have significant coagulopathy during the course of their critical illness
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have