337 The cardiovascular effects of high-dose butorphanol- nitrous oxide anaesthesia before and during Theodore H. Stanley MD, Parsad Reddy MD, Stephen Gilmore as, George Bennett MD operation The cardiovascular effects of high doses of butorphanol Butorphanol (Stadol) is a new synthetic agonist- (0.3-.0.45 mg.kg 1) plus 60 per cent NzO anaesthesia antagonist opioid which has become popular as a were measured at unconsciousness, following tracheal postoperative analgesic because of its reduced intubation, and immediately before and at one and ten liability for producing respiratory depression, t-3 minutes after surgical stimulation in 17A. S.A. class I and Butorphanol is also being used as the intravenous II patients undergoing elective gastric or gall bladder analgesic component of nitrous oxide-narcotic- surgery. Butorphanol atut NzO produced unconscious. oxygen anaesthesia in a number of centres. 4-6 We ness with only small decreases in heart rate and cardiac previously measured the cardiovascular effects of output but did not result in sufficient analgesia to block or morphine-N20, meperidine-NzO and fentanyl-N20 treat stimulation of the cardiovascular system secondary in man and found that nitrous oxide plus any of the to tracheal intubation or surgical incision, even when above pure agonist opioids results in cardiovascular supplemented with additional butorphanol to high cumu- depression both before and during operation. 7-1~ lative dose levels (1.0 mg.kg-l ). The data suggest that The objective of this investigation was to measure even high dose butorphanol - N20 anaesthesia requires the cardiovascular effects of high doses of butor- supplementation with other anaesthetics or anaesthetic phanol (up to 1.0 mg'kg <) plus N20 in man before adjuvants to prevent cardiovascular stimulation during and during surgical stimulation to determine if they general abdominal surgery. were different from those of the other commonly used opioids plus N20. Key words ANALGESICS, NARCOTIC: butorphanol, mepeddine, Methods moiphine, fentanyl, SURGERY:general, abdominal, The investigation was approved by the University CARDIOVASCULARDYNAMICS: stimulation, of Utah Human Research Committee. Informed depression. consent for performance of the study was obtained the night before operation from 17 A. S.A. class I or II patients taking no cardiac, pulmonary or renal medication and scheduled to undergo elective gas- From the Department of Anesthesiology, The University tric or gall bladder surgical operations. None of the of Utah School of Medicine, Salt Lake City, Utah patients were receiving any medication except 84132, antacid preparations or sedatives. Premedieation Address correspondence to: Theodore H. Stanley, included pentobarbital (l mg'kg -1) and atropine M.D., Professor of Anesthesiology, The Department of (0.1 mg-kg-1) intramuscularly 90 minutes before Anesthesiology, The University of Utah School of the scheduled operation. Medicine, Salt Lake City, Utah 84132. Prior to anaesthetic induction, an intravenous Supported in part by Stanley Research Foundation, infusion of lactated Ringers solution was started in Salt Lake City, Utah. an upper extremity and given at 200 ml/hr. A CAN ANAESTH SOC I 1983 / 30: 4/pp337-34| 338 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL central venous pressure catheter was placed percu- pancuronium (0.1 mg'kg -l) was given intraven- taneously into the right atrium from the antecubital ously over a five-minute period. fossa or neck, and a catheter was inserted into the All patients were questioned 24 to 48 hours radial or brachial artery percutaneously and thread- postoperatively with regard to their memory of the ed 30 to 40 cm into the central aorta. The aortic anaesthetic induction and operative procedure. pressure catheter was attached via an arterial pres- Data were analyzed for statistical significance using sure transducer to a central digital computer substa- analysis of variance. P < 0.05 was considered tion in the operating room. Warner's method ~l of statistically significant. analyzing the central aortic pulse-pressure curve, which was recently validated by English et al., 12 Results was used to determine cardiac output (QT), stroke Buto~hanol (mean 0.13 -+ 0.02mg.kg -l) and volume (SV), heart rate (HR), mean arterial blood nitrous oxide produced unconsciousness in all pressure (BP), systolic arterial blood pressure patients in an average of 7 -+ 0.5 minutes. Five (SBP), and systemic vascular resistance (SVR). minutes after induction HR and QT were slightly but Initial cardiovascular data were recorded 15 significantly reduced but all other variables re- minutes after all catheters were implanted with the mained unchanged (Table). Tracheal intubation patients awake and breathing room air. Following resulted in marked increases in SBP, BP, SV and this, the patients were given N20 (60 per cent) in QT above control values. These variables were only oxygen to breathe, and butorphanol (0.1-0.15 mg- slightly decreased with additional butorphanol, kg -l) was given slowly intravenously over a ten- SBP, BP and SV increased again with surgical minute period until the patients were non-respon- stimulation while HR returned to control values and sive to verbal command. When unconscious the SVR became elevated. Eight of the 17 patients palients were given an additional 0.2 mg.kg -I of moved with initial surgical stimulation. Frequent butorphanol intravenously. Respirations were first additional boluses of butorphanot stopped move- assisted and then controlled to maintain end-tidal ment and reduced Q'r and sv to control values but I'CO2, and then later PaCO2, between 4.3-4.9 kPa were ineffective in decreasing SBP, BP and SVR to (32-37 tore) as measured in aortic blood every preanaesthetic values. This was true even when 15-30 minutes. Fifteen minutes "after beginning butorphanol was given to a total dose above anaesthesia, when all patients had respirations 1.0 mg-kg-I. Thus, all 17 patients required diaz- controlled and were unconscious, succinylcholine epam or enflurane before the study was completed. (1.5 mg.kg -1, IV) was given and the trachea intu- The latter two comp.__ounds were effective in de- bated. Additional butorphanol (0.1 mg.kg -1) was creasing SBP and BP to desirable levels but also given five minutes later (before surgical stimulus) produced significant decreases in Q'r. and, following this, the surgical procedure began. When intensively questioned postoperatively, all Supplemental butorphanol (0.05-0.1 mg.kg-1 , IV) patients related that their last memory prior to was given after the operation began whenever operation was either coming into the operating systolic arterial blood pressure (SBP) became >20 room or having a face mask placed on their faces per cent of preoperative (control) values. If three and their first memory postoperatively was upon supplemental doses of butorphanol did not reduce recovering consciousness in the recovery room or SBP to within 20 per cent of control values in five to their hospital room. No patients recalled tracheal ten minutes, enflurane (0,3-1.5 per cent) or diaz- intubation or any aspect of the surgical procedure. epam (0.1-0.2mg-kg -~, IV) was added to the anaesthetic regime. Cardiovascular dynamics were Discussion measured before induction of anaesthesia, five The results of this study demonstrate that high dose minutes following anaesthetic induction with butor- butorphanoI-NxO produces unconsciousness with phanol and nitrous oxide, one minute after endo- only a minimum of cardiovascular depression. tracheal intubation, one minute after additional Unfortunately, the technique, even when supple- butorphanol (before surgical stimulation) and one mented with additional doses of butorphanol (up to and ten minutes after surgical stimulation (abdom- a total butorphanol dosage of 1.0 mg'kg-I), does inal incision). Following the last measurement not produce sufficient analgesia to block or effe~- Stanh;y etal.: ntG~ DOSE Bu'roRPHANOL 339 TABLE Cardiovasculareffects of butorphanolplus niUeus oxide bef~te and during operation(mean • SD) Following surgical 5 minutes after After additional stimulation induction with Following Butorphanol Control ButorphunolplusN20 intubation (0,1 rag) 1 rain lO rain Stroke volume (mI) 5 I 49 69t 63* 72? 54 -'- 8 + 7 + 10 -- 8 -+ 10 + 7 Heart rate (beats/mix) 79 70" 83 7g* 84 76 -+ 8 -+ 6 .4- 8 --- 7 • 9 • 7 Cardiac output (l/mirt) 4.4 3.5* 5.8* 5.0* 5.4 4,0 - 0.7 -+ 0.4 0.9 -+ 0.6 • 0.7 - 0,8 Systetaic vascular 2800 3384 3344 3192 3922* 4652* rcsislance (PRU) • -+610 -+520 ---480 -+590 -+560 Systolic blood 17.0 17.2 21.It 19.4" 21.87 19.7" pressure (kPa) • 1.3 -+ 1.2 -+ 19 -+ 1.6 -4- 1.9 + 1.5 Mean blood 12.5 12.6 15~21" 13,8" 16.17 14.0" pressure (kPa) • l_l + 1.2 -+ 1.5 • 1.9 --. 1.7 +- 1.3 *p <0.05, "~p < 0.01, analysis of variance. tively treat cardiovascular "stress responses" to but results in a ceiling effect on respiratory depres- tracheal intubafion and surgical stimulation. Our sion as well. 3'2~ These, plus other data which show data suggest, therefore, that high dose butorphanol- that intravenous butorphanol produces minimal N20 anaesthesia must be supplemented with other cardiovascular changes, suggest that the drug might agents (inhalation or intravenous) to prevent car- be effective as a component of nitrous oxide- diovascular stimulation during general abdominal narcotic-oxygen anaesthesia. surgery. Preliminary studies by Del Pizzo s and Zauder 6 in The advantages of nitrous oxide-narcotic- which butorphanol plus nitrous oxide were used in oxygen anaesthesia are said to be a minimum Of surgical patients yielded encouraging initial results. cardiovascular depression, a reasonably rapid re- Unfortunately, our data in this study are not so cover,/ time and an absence of pain in the early encouraging. While we are not completely sure why postoperative period, m't3-1s A significant dis- even extremely high doses of butorphanol were advantage of these techniques is early postoperative ineffective in producing sufficient levels of analge- respiratory depression, especially when high doses sia to block or treat hypertension with surgical of the narcotic are used intraoperativety.