Midazolam in Combination with Propofol for Sedation during Local Anesthesia Ellis Taylor, MD,* Ahmed F. Ghouri,_F Paul F. White, PhD, MD, FFARACSS Division of Clinical Research, Department of Anesthesiology, versity School of Medicine, St. Louis, MO.

Washington

Uni-

To compare the sedative, anxiolytic, and amnestic effects, as well as the recovery characteristics, when midazolam (vs. a placebo) is administered to patients receiving a propofol infusion for sedation during local anesthesia. Design: Randomized, double-blind, placebo-controlled study to evaluate the perioperative effects of intravenous (IV) midazolam. Setting: Outpatient surgery center of a university-affiliat medical center. Patients: One hundred thirty-nine consenting, ASA physical status I, II, and III outpatients undergoing elective surgical procedures under local anesthesia. Interventions: Patients were randomly assigned to receive either midazolam 2 mg IV or saline 2 ml IV prior to injection of local anesthesia. Intraoperative sedation was maintained using a variable-rate propofol infusion. Measurements and Main Results: Preoperative assessment of sedation, anxiety, and amnesia was performed before and after IV midazolam. Intraoperative evaluations included level of sedation, as well as cardiovascular and respiratory measurements, at I - to 5-minute intervals during the operation. Postoperatively, recovery of psychomotor function and patients’ subjective feelings were assessed using the visual analog scale and questionnaires. Amnesia was assessed using picture recall during the perioperative period. In the operating room, midazolam 2 mg IV, compared with the placebo, produced a significantly greater increase in patients’ level of sedation (7 2 13 mm to 49 2 21 mm for midazolam vs. 8 + I1 mm to 19 4 21 mm for the placebo; p < 0.01) and a greater decrease in anxiety level (62 2 25 mm to 21 f 21 mm for miduzolam vs. 54 5 27 mm to 53 2 22 mm for the placebo; p < 0.01). Although the propofol dosage requirements to maintain comparable levels of sedation were similar in both groups, midazolam decreased patients’ recall of intraoperative events (e.g., propofolinduced pain on injection and discomfort with local anesthetic injection) without sig-

Study Objective:

*Instructor

in Anesthesiology

tMedica1 Student, Research Associate $Professor of Anesthesiology, Clinical Research

Director

of

Address reprint requests to Dr. White at the Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8054, St. Louis MO 63110, USA. This study was supported in part by a grant from the Ambulatory Anesthesia Research Foundation, Los Altos, CA. Dr. White is a member of the Board of Directors. Received for publication September 13, 199 1; revised manuscript accepted for publication October 23, 1991. 0 1992 Butterworth-Heinemann

J. Clin. Anesth. 421%416,

1994.

nzficantly altering cardiorespiratory parameters or prolonging times to ambulation and discharge from the outpatient facility. Conclusions: Premeditation with midazolam 2 mg IV produced increased sedation, amnesia, and anxiolysis when administered immediately prior to the propofol infusion as part of a sedation technique for outpatient surgery. This combination did not prolong the recovery room stay when compared with propofol alone.

Keywords: Anesthesia, local; infusions, benzodiazepines (midazolam); propofol;

intravenous; monitored

J. Clin. Anesth.,

sedation, anesthesia

vol. 4, May/June

care. 1992

213

Original

Contributions

Introduction Adjuvant intravenous (IV) sedative-hypnotic infusions during local and regional anesthesia can enhance patient comfort and provide for improved recovery profiles.‘.’ In addition, IV anesthetics are more controllable and associated with a more rapid recovery when administered by a continuous variable-rate infusion.” The IV anesthetic propofol (Diprivan) has recently been approved for clinical use as a sedative during local and regional anesthesia. Preliminary studies have suggested that propofol is an acceptable alternative to other available sedative-hypnotics for sedation during local and regional anesthesia.-‘-7 A recent comparative study demonstrated that propofol infusion was as effective as midazolam (Versed) infusion for sedation during local and regional anesthesia in outpatients undergoing short surgical proceduresX Although midazolam produced less pain on injection and more effective intraoperative amnesia, these authors found that propofol was associated with less postoperative sedation, drowsiness. confusion, and clumsiness, as well as a more rapid recovery ofcognitive function. It was suggested that administration of a small dose of midazolam prior to initiation of the propofol infusion might offer advantages over either drug alone when used for sedation in the outpatient setting. Therefore, we designed a randomized, double-blind, placebo-controlled study to evaluate the perioperative effects and recovery characteristics when midazolam (or a placebo) was administered prior to the propofol infusion for sedation during monitored anesthesia care.

Materials and Methods One hundred thirty-nine consenting, ASA physical status I, II, and III outpatients scheduled to undergo elective general surgical procedures with local infiltration were randomly assigned to receive either midazolam 01 a placebo (saline) prior to initiation of a propofol infusion for intraoperative sedation. The protocol was approved by the Human Studies Committee at the Washington University School of Medicine, and the study was performed in the Outpatient Surgery Center at Barnes Hospital in St. Louis, Missouri. Upon arrival in the preoperative holding area, patients were asked to complete a 100 mm visual analog scale (VAS) to assess their baseline level of each of the following variables: anxiety (0 = calm; 100 = extremely nervous), sedation (0 = wide awake; 100 = almost asleep), tiredness (0 = none, 100 = extremely fatigued), clumsiness (0 = well-coordinated; 100 = extremely clumsy), pain (0 = none; 100 = severe), and nausea (0 = none; 100 = severe).g Prior to receiving the study medication in the operating room (OR), patients were shown a picture, and the anxiety and sedation VAS were recorded. The patients were shown a second picture 3 to 5 minutes after injection of the study drug (prior to initiating the propofol loading infusion), and the anxiety and sedation VAS were repeated. Subsequently, the anesthesiologist 214

J. Clin. Anesth., vol. 4, May/June 1992

assessed the patients’ level of consciousness (sedation score) at 5- to lo-minute intervals during the operation using a five-point scale: 1 = awake and fully alert: 2 = awake but drowsy; 3 = sleeping but easily aroused; 4 = sleeping but difficult to arouse; 5 = asleep and unresponsive to verbal or tactile stimulation. All patients were monitored with an electrocardiogram, a noninvasive automatic blood pressure cuff’ (Dinamap, Tampa, FL), a digital pulse oximeter (Nellcor, Hayward, CA), and a precordial stethoscope. The COIItinuous variable-rate infusion of propofol was administer-et] using a Bard InfusOR pump (Bard, Reading, MA). Following entry into the OR, patients received either midazolam 2 mg IV (2 ml) or saline (placebo) 2 ml I\’ according to a randomized, double-blind protocol. After reassessing the sedative, anxiolvtic, and amnestic effects of’ the study medication, a loading infusion of propofol 200 ~gikglmin was administered to achieve a sedation score of 3 (i.u., patient sleeping but easily aroused). The maintenance infusion was then initiated at a rate of’ 100 kgikgimin. Subsequently, the propofol infusion rate was varied between 25 and 120 pgikgimin to maintain a stathe operation. ble le\~~l3 of’ consciousness throughout Fencanyl 50 kg IV was administered 3 to :i minutes priorto local anesthetic infiltration. ‘I‘he sedation score, as well as mean arterial pressure (MAP). heart rate (HK), recpiratory rate (RK), and oxy