Paradoxical effect of oral lorazepam in a premedication for ERCP

Abstract

Restlessness often complicates ERCP and may be a reason for premature termination of the procedure. To evaluate whether a premedication with orally administered lorazepam could reduce the need for sedatives and improve sedation quality, we studied 95 patients undergoing ERCP in a randomized double-blind trial. Methods: Inpatients scheduled for ERCP (age 20–85 years) received either 1mg lorazepam (n=47) or placebo (n=48). The sedation was induced by midazolam (0.03–0.10mg/kg) and propofol (0.3–1.0mg/kg) and maintained by bolus doses of propofol (20–50mg), S(+)-ketamine (25mg), and in longer procedures additional midazolam (1–5mg) administered by the endoscopist’s impression of the patient’s state. All patients were continuously monitored by pulse-oximetry, oscillometric blood pressure measurements, and assessment of a sedation score. The amount of sedatives needed to achieve an adequate sedation was protocolled. The endoscopist and after recovery the patients were asked to rate their impression of the procedure. Results: All patients were successfully sedated and the satisfaction with the sedation achieved highest rates in 87 vs. 71% (lorazepam vs. placebo) if rated by the endoscopist and 77 vs. 83% if rated by the patients. Heart rate, oxygen saturation and blood pressure did not differ between the groups. States of restlessness (44 vs. 46) and oxygen desaturation <85% (12 vs. 12) occurred similarly often and could all be handled within short time. The total amount of midazolam (2.4±.2 vs. 2.4±.2 μg/kg/min; mean±SEM) and propofol (71±5 vs. 63±4 μg/kg/min) needed to achieve an adequate sedation did not differ between the groups. Patients who had received lorazepam needed significantly more ketamine (15.8±1.4 vs. 11.3±1.2 μg/kg/min; P<.05) and propofol in the period 5–10 minutes after induction (275±39 vs. 159±37 μg/kg; P<.05). Discussion: The higher amounts of sedatives needed in the lorazepam group are most likely due to an occupation of the benzodiazepine receptor by lorazepam exerting a lower intrinsic activity than midazolam. Hence, the action of midazolam is assumed to be competitively antagonized by the premedication with lorazepam. The study indicates that orally administered lorazepam is contraproductive in a premedication for ERCP.