Case of the Week 41
Hemadsorption: A New Therapeutic Option for Selected Cases of Bromazepam Intoxication
Mekeirele M, Verheyen S, Van Lancker R, Wuyts S, Balthazar T. Case Reports in Nephrology and Dialysis 2022; 12(3):163-166
12/06/2022
New!Peer Reviewed Published DataCase reportCritical CareCRRT (pre or post filter)Drug removalIntoxicationLiver failure
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Summary
CoW 41/2022 – This case reports on an a 67-year-old woman with CHILD-C liver cirrhosis, who was admitted to the tertiary intensive care unit (ICU) after intoxication with bromazepam.
Benzodiazepine ingestion can account for around 21% of all intoxications requiring admission to Intensive Care (IC). Management is normally with a supportive approach and with the use of flumazenil, an antidote for benzodiazepines, however, flumazenil does not influence elimination. In this case report, a 67 yr old patient with impaired liver function (CHILD-C cirrhosis) was admitted after intoxication with the benzodiazepine, bromazepam. The initial plasma concentration was very high (874 mg/L, upper limit of normal 170 mg/L). She became increasingly drowsy with respiratory insufficiency so a flumazenil infusion was started resulting in her becoming more alert, however, the infusion rate could not be decreased due to her repeatedly relapsing into stupor. Due to her liver failure (and consequent slow metabolism), it was calculated that the half-life of bromazepam would be 10 days rather than 10 hrs, requiring a stay of 23 days on the ICU, so CytoSorb hemoadsorption was initiated using continuous venovenous hemofiltration (CVVHF). Pre and post CytoSorb adsorber blood levels were taken. Results showed that elimination of bromazepam by CytoSorb was quick and efficient (-31% after 1 h, -56% after 11 h). After the first 11 hrs there was a quick decline in adsorbing capacity suggesting saturation, however, by this time the patient was in the upper limit of normal for bromazepam, so no second hemoadsorber was needed and the flumazenil infusion could be quickly tapered off within 1 day. The authors conclude that hemadsorption is a viable option to reduce length of IC stay or need for intubation in slow metabolizers. They state that the cost of a prolonged stay in the intensive care unit is significantly higher than the cost of an adsorber.
Case presentation
The initial plasma concentration was 874 µg/L (upper limit of normal 170 µg/L)
The patient developed respiratory failure due to decreased consciousness
Given the expected slow decrease in plasma levels of bromazepam due to cirrhosis and the inherent risk of a prolonged need for mechanical ventilation, an infusion of flumazenil was initiated to avoid intubation
The patient regained consciousness and remained stable, but the flumazenil infusion rate could not be decreased due to a relapse in stupor following this intervention
As expected, only a very slow decrease in bromazepam titer was observed
Based on the decline in titer, the half-life of bromazepam was calculated to be 10 days rather than the expected 10 h. This implied that a reduction of the bromazepam titer to 170 µg/L could only be expected after 23 days of ICU admission, warranting a search for further therapeutic options
Hence hemadsorption was initiated in combination with continuous renal replacement therapy (CRRT)
Treatment
CytoSorb was used in conjunction with CRRT run in continuous veno-venous hemofiltration (CVVHF) mode using the Prismax® (Baxter, IL, USA) system
Measurements
Sequential quantifications of bromazepam levels from blood taken pre and post CytoSorb adsorber
Results
Application of CytoSorb resulted in the quick and efficient elimination of bromazepam (-31% after 1 h, -56% after 11 h). There was no rebound in plasma titer after cessation of the hemadsorption therapy and the patient attained the target level of bromazepam 13 days earlier than predicted without the hemoadsorber
Patient Follow-Up
After the first 11 hrs there was a quick decline in adsorbing capacity suggesting saturation. However, by this time the patient was in the upper therapeutic limit for bromazepam, so no second hemoadsorber was needed
The flumazenil infusion could be quickly tapered off within 1 day
Conclusions
The application of CytoSorb proved to be effective in eliminating bromazepam in a patient with CHILD-C cirrhosis
The authors conclude that hemoadsorption is a viable option to reduce length of ICU stay or need for intubation in slow metabolizers
They state that the cost of a prolonged stay in the intensive care unit is significantly higher than the cost of an adsorber.
