A Comparison of Pentamorphone and Fentanyl in Balanced Anaesthesia

703 A comparison of pentamorphone and fentanyl in balanced

William B. Kelly MD, Michael B. Howie MO, anaesthesia during Vincent A. Romanelli MO, Jose A. Duarte MD, Hamid Rezaei MS, Thomas D. McSweeney BS general surgery

The purpose of our randomized, double-blind study of 64 un- respectively. In addition, the 1 t~g" kg -I pentamorphone group premedicated healthy patients undergoing surgical procedures had significantly (P < 0.05) lower peak isoflurane concentra- with a duration of at least 60 min was to compare 0.75 I~g" kg -j tions than the 5 #g" kg-* fentanyl study group (0.9 + 0.5 and 1 lzg" kg -1 pentamorphone with 5 tzg" kg -t and 7.5 MAC~ vs L5 5:0.3 MACe/o). In conclusion, we found pen- I~g" kg-* fentanyl to determine which dose of opioid would tamorphone to be a haemodynamically stable, isoflurane- reduce the requirement for isoflurane supplementation needed sparing opioid analgesic. Pentamorphone's major advantage to maintain haemodynamic stability. At 21 points during the over fentanyl was its lower requirement for inhalation agent procedure, the haemodynamic variables of heart rate and sys- in a balanced anaesthesia technique. tolic, diastolic, and mean arterial pressures were recorded. The use of isoflurane was quantified; the number of patients re- Cette ~tude randomis~e et h double aveugle portait sur de 64 quiring inhaled anaesthetic, concentration peaks, MAC min- patients en bonne sant~ non pr~m~diqu~s soumis ?t des in- utes, and duration of isoflurane use were noted. The number terventions d'une dur~e minimale de 60 min. Son objectif of equal-volume supplemental opioid analgesic doses, post- consistait ?~ comparer 0.75 t,g" kg -t et 1 ~tg. kg -I de pen- operative analgesics, occurrence ofpostoperative nausea, emesis, tamorphone avec 5 I~g" kg -let 7,5 I~g" kg -1 de fentanyl dans and antiemetic doses were compared. The four groups exhibited le but de d~terminer la dose de morphinique capable de r~duire similar patient demographics, total dose of muscle relaxants, le besoin de supplementation ~ l'isoflurane n~cessaire au main- types of surgical procedures, and duration of surgery or anaes- tien de la stabilit~ h~modynamique. A 21 ~tapes pendant l'in- thesia. Haemodynamic variables were stable with no difference tervention, on enregistr~ les variables h~modynamiques repr~- among the four study groups. The patients given pentamor- sentdes par la fr~quence cardiaque et les pressions systoliques, phone demonstrated both delayed requirement (P < 0.05) and diastoliques et moyennes. L'utilisation de l'isoflurane est quan- shorter duration (P < 0.05) of isoflurane supplementation. Pa- tifi~e de la fafon suivante; le nombre de patients ayant besoin tients given either 5 Izg" kg -t or 7.5' ttg" kg -t fentanyl needed de l'agent inhalatoire, les concentrations maximales, le CA3,I- isoflurane supplementation within 12:1:16 rain and 12 :t: 17 minute et la durde d'utilisation. On compare le nombre de rain from induction respectively; while patients given either 0.75 doses ~ volumes ~gaux de morphiniques en supplement, le be- #g" kg -~ or 1 #g" kg -I pentamorphone did not require iso- soin d'analg~siques postop~ratoires, l'occurrence des vomisse- flurane supplementation for 37 :i: 10 rain and 43 d: 26 rain ments et des naus~es postop~ratoires, ainsi que les doses d'an- ti~m~tiques. Les donn~es d~mographiques, les doses totales de myorelaxants, le type d'intervention et la dur~e de l'anesth~- Key words sie ~taient les m~mes pour les quatre groupes. Les variables ANAESTHETICS,INTRAVENOUS: fentanyl, pentamorphone; sont demeur~es stables sans differences entre les quatre groupes. ANAESTHETICS,VOLATILE: isoflurane. Les patients des groupes pentamorphone ont eu des besoins From the Department of Anesthesiology, Division of retardes (P < 0,05) et de plus courte dur~e (P < 0,05) d~- Cardiothoracic Anesthesia, Clinical Anesthesia Research soflurane. Les patients recevant 5 tLg" kg -t ou 7,5 t~g" kg -I Laboratory, The Ohio State University Medical Center, Doan de fentanyl on eu besoin d'une suppldmentation ~ l'isoflurane Hall, Room N429, 410 West Tenth Avenue, Columbus, OH en def~ de 12 + 16 min et 12 + 17 min aprbs l'induction 43210-1228. respectivement; par contre, les patients qui avaient refu 0,75 Supported in part by a grant from Anaquest Inc., Madison, #g" kg -~ ou I I~g" kg -1 de pentamorphone n'ont pas eu besoin WI. de suppldment d'isoflurane pendant 37 + 10 min et 43 q- 26 Address correspondence to: Dr. Wilfiam B. Kelly. rain respectivement. De plus, le groupe pentamorphone 1 Acceptedfor publication 30th April, 1994. #g" kg -~ a re~u des concentrations isoflurane maximales moins

CAN J ANAESTH 1994 / 41:8 / pp 703-9 704 CANADIAN JOURNAL OF ANAESTHESIA dlev~es (P < 0,05) que le groupe fentanyl 5 I~g" kg -1 (0,9 + 0,5 MAC~ versus 1,5 -I- 0,3 MAC%). En conclusion nous avons trouv$ que le pentamorphone procurait une bonne stabilit$ h~modynamique et r$duisait les besoins d'isoflurane. Dans une technique anesthdsique ~quilibr~e, l'avantage majeur du pentamorphone sur le fentanyl r~side dans sa capacit~ de diminuer le besoin d'agent inhalatoire.

The current most widely used opioid analgesic anaesthetics for general surgery are the piperidine derivatives sufentanil and fentanyl. Pentamorphone is an opioid that produces analgesia and sedation more rapidly than the FIGURE 1 The chemical structure of pentamorphone [7,8- closely related opioid analgesic, morphine. Several studies didehydro-4,5-epoxy-3 hydroxy- 17-methyl-I 4-(pentylamino)-(5)- have described varying results as to the relative potency morphinan-6-one; Anaquest, Murray Hill, NJ] is very similar to that of pentamorphone compared with other opioids. An ini- of morphine. tial human volunteer study of pentamorphone using a calibrated spring rod indicated that it was 400 to 500 times as potent as morphine, with similar effects on blood and has demonstrated a lower degree of undesirable pressure and heart rate. A second human volunteer study side effects in previous studies. Structurally (Figure compared two doses of pentamorphone and fentanyl for 1), pentamorphone is a 14-13-n-pentylaminomorphinone analgesic tolerance to five noxious stimuli and determined [IUOAC name 7,8-didehydro-4,5-epoxy-3 hydroxy-17- an analgesic potency of pentamorphone at five times that methyl-14-(pentylamino)-(5)-morphinan-6-one]. Pentam- of fentanyl. ~ When administered postoperatively, pentamorphone is a pale, yellow solid that is only slightly soluble orphone in doses from 0.08 to 0.24 ~g-kg.-'~ were not in water. It can be easily detected by high performance sufficient to relieve acute postoperative pain after major liquid chromatography. With these effects in mind, we abdominal or orthopaedic surgery when compared to a performed a randomized, double-blind isoflurane-sparing placebo. 2,3 Another human volunteer study demonstrated study in 64 healthy surgical patients between the ages that when pentamorphone was administered in increasing of 18 and 70 yr, who were given pentamorphone (0.75 doses, it produced a linear increase in pain threshold as ~tg. kg -~ or 1 ~tg. kg -l) or fentanyl (5 ~tg-kg -z or 7.5 well as a concurrent respiratory depression, which was ~g. kg-I) as the analgesic during general anaesthesia for similar to other opioids. 4 A patient controlled analgesia elective procedures of at least 60 min duration. Anaes- study placed the relative analgesic potency of pentam- thetic depth can often be ascertained from patients' hae- orphone at 170 times greater than morphine. 5 Pentam- modynamic responses and the need for analgesics. There- orphone given as a constant infusion in very high doses fore, we compared the haemodynamic profdes and the in canines displayed slight, direct myocardial depressant supplemental dose requirements of patients given fentanyl effects on heart rate, mean arterial pressure and cardiac with those given pentamorphone. output. 6 As the sole anaesthetic in patients undergoing elective coronary artery bypass grafting surgery, the time Me~hods to loss of consciousness placed the relative analgesic po- After protocol approval by the Human Subjects Review tency of pentamorphone at five to six times greater than Committee, all patients underwent routine preoperative fentanyl.7 Animal studies have compared pentamorphone physical examination and medical history. Patients were with fentanyl and report an analgesic potency of two to excluded from the study if they (1) were undergoing cra- eight times greater than that of fentanyl, s However, when niotomies, major surgical procedures involving the central large doses are given to a dog, pentamorphone has been nervous system, or open thoracic surgical procedures; (2) shown to be epileptogenic. The study demonstrated my- were < 18 yr old; (3) had a haematocrit of <25%; (4) otomic activity at dose levels of -->125 ~g. kg -l, with had an oral temperature <35~ or >37.5~ (5) had EDs0 for analgesia in the same study at 12 p.g. kg -l. a personal or family history of malignant hyperthermia; The seizure activity was demonstrated in a single animal (6) had a history of unusual reaction or sensitivity to monitored with EEG at a dose level of 350 ~g. kg -m opioid analgesics or anaesthetics; (7) were chronically (unpublished data: in Anaquest Investigator's Brochure). using drugs known to affect anaesthetic requirement; (8) Pentamorphone, formerly designated RX77989 and had angina pectoris or myocardial infarction within the A4492, is a synthetic opioid with strong analgesic effects past six months; or (9) were pregnant or breast-feeding. Kelly et al.: PENTAMORPHONEVERSOS FENTANYL 705

TABLE I Demographics

5 #g" kg-t F 7.5 t~g" kg-t F 0.75 #g" kg-I P l #g" kg-I P n 16 16 16 16 ASA Class I 5 7 5 6 ASA Class II 11 9 11 10 Surgical types - Orthopaedic 6 5 5 5

- lntraabdominal,laparotomy 5 3 5 4

- Intraabdominal,laparoscopic 1 1 2 3 - Other(urology, gynaecology, ENT) 4 5 4 6 Age (yr) 40 -t- 15 34 • 14 38 -I- 15 42 + 15 Weight (kg) 74 • 12 69 + 11 72 + 16 77 -t- 18 Height (cm) 168 + 10 171 • 12 169 + 11 168 + 13 Body Surface Area (m2) 1.8 + 0.2 1.8 -I- 0.2 1.8 • 0.2 1.9 + 0.3 Duration of surgery(min) 115 + 51 138 • 59 114 + 48 103 + 43 Duration of anaesthesia (min) 136 4- 53 155 4- 54 141 + 53 125 4- 45

Values are mean + standard deviations or counts. Abbreviations: F - fentanyl; P - pentamorphone.

No patient received any sedative or analgesic medi- minute intervals until heart rate or blood pressure re- cation before entering the operating room. After preoxy- turned to within 15% of preoperative baseline levels. genation, a total of 64 ASA class I and II patients with Ventilation was adjusted to maintain a PETCO2 be- written consent were randomized into four equal groups tween 30 and 40 mmHg as measured by capnography to receive a loading dose of 0.75 ~g-kg -I pentamor- (model 78345A; Hewlett-Packard, Andover, MA) with phone, 1 ~g. kg -1 pentamorphone, 5d I~g" kg -~ fentanyl, a gas mixture of 70/30% N20 / 02. We recorded the fol- or 7.5 ~tg. kg -~ fentanyl prepared by the pharmacy to lowing haemodynamic variables: heart rate and systolic, equal dose volumes of 0.15 ml. kg-l just before induction diastolic, and mean arterial pressure using a Dinamap of anaesthesia. The choice of opioid was blinded to both blood pressure monitor with printer (model 1846SX/P, the patient and the anaesthetist. Thiopentone was given Critikon, Inc. Tampa, FL). Haemodynamic variables in a sufficient dose to induce loss of eyelash reflex and were recorded at baseline, induction and then once a min- was followed by 1.5 mg. kg -I succinylcholine/v (Table ute for three minutes, ten minutes before incision and I). Vecuronium, 0.05 mg. kg -l, followed by supplemental at two-minute intervals until incision, incision and every boluses of 0.01 mg. kg -l, was administered as required minute for five minutes, and finally every 15 rain until to maintain muscular relaxation (Table I). Using a nerve 80 min after incision. In addition, recovery variables, nau- stimulator positioned over the ulner nerve, relaxation was sea, vomiting, respiratory rate, need for antiemetics, or judged as adequate with the presence of 0 or 1 twitch need for analgesics were noted. In the recovery room, in response to train-of-four stimulation. droperidol was administered only to treat nausea and When arterial blood pressure or heart rate was 15% vomiting. greater than preoperative baseline levels, supplemental Statistical Analysis System, Inc. (SAS Raleigh, NC) doses of 0.15 Isg" kg -1 pentamorphone or 1.5 ~tg. kg -l computer programmes were used to perform statistical fentanyl prepared by the pharmacy to equal dose volumes analysis. Haemodynamic, demographic, and drug dose of 0.03 ml. kg -z were administered at five-minute in- data were analyzed using standard tests (Bartlett's test tervals. Isoflurane could then be administered in response and Shapiro and Wilk's W-test) to determine whether to elevations in blood pressure if the patient's response deviations from normal distributions and homogeneity of was deemed inadequate after four supplemental doses of variance were present. None was found, permitting use opioid. Dosing of volatile anaesthetic progressed incre- of two-way analysis of variance of each haemodynamic mentally with increases of up to 0.5% at five-minute in- variable to detect significant interactions between the fac- tervals to a maximum of 1.5% (calibrated vaporizer set- tors patient group and time. Only if an interaction was ring). If these supplemental doses of opioid analgesic and found were post hoc analyses of variance for repeated changes in isoflurane level were insufficient to control measures (ANOVA) with Duncan's multiple range tests increased heart rate or blood pressure, a rescue bolus used to assess the significance of the results over time of up to 10 mg labetolol could be administered at five- and among patient groups. Based on haemodynamic 706 CANADIAN JOURNAL OF ANAESTHESIA

TABLE II Anaesthesiamaintenance

5 gg" kg-t F 7.5 ~g. kg-t F 0.75t~g. kg-I P l gg" kg-t P 0.03 ml'kg-I supplementalopioid analgesic doses given (n) 43 20 22 21 Patients requiring supplemental opioid analgesicdoses (n) 15 10 14 13 Patients requiring isoflurane (n) 16 16 14 15 Patients requiting labetolol (n) 2 1 2 2 Time from induction to when isoflurane was given (min) 12 -t- 16 12 + 17 37-t-10' 43-1-26" Duration isoflumne administered (rain) 104 -I- 45 104 -6 50 25+24* 22+15" Duration isoflurane as a % of duration of anaesthesia(%) 77 + 14 68 + 22 18 + 14' 18 + 11" Peak isoflurane concentration (%) 1.5 5:0.3 1.1 5:0.5 1.1 -t- 0.7 0.9 + 0.5* MAC rain isoflurane (min) 49 5:31 58 + 28 32 + 30 33 + 26 Total labetolol administered (nag) 10 + 5 5 15-1-5 " 8+3 Amount of veeuronium (mg) 7 5:5 9 5:4 6+5 8+5 Amount of thiopentone (mg" kg-I) 3.6 5:0.4 3.8 5:0.5 3.7 5:0.5 3.8 5:0.4 Values are mean 5: standard deviations or counts. Abbreviations: F - fentanyl; P - pentamorphone. *P< 0.05 versus 5 ~tg- kg-I fentanyl. baseline values, a power curve at an a = 0.05 level of tory, as the haemodynamic profdes of the four groups significance and for four patient groups of 15 subjects showed no differences among heart rate (Figure 2), mean was used to estimate the detectable difference (/5) with arterial pressure (Figure 3), systolic arterial pressure (Fig- 90% power. 9 The minimal difference (8) in haemodynamic ure 4), or diastolic arterial pressure (Figure 5). means detectable among patient treatment groups was Only one patient in the 5 ~tg. kg-~ fentanyl group did >_.25% of their baseline haemodynamic means. Therefore, not require supplemental doses of opioid, with the re- differences in haemodynamic means less than 25% of maining 15 patients receiving a mean number of 2.7 + their baseline value were not detectable using our sample 1.5 supplemental doses. Six patients in the 7.5 ~tg. kg -~ size. One-way ANOVAs were used to compare demo- fentanyl group did not require supplemental doses of graphic, peak isoflurane concentration, duration of iso- opioid analgesic, with the remaining ten patients receiving flurane as a percent of duration of anaesthesia, and drug 3.8 + 2.4 supplemental doses. Two patients in the 0.75 dose data among the patient groups using the Bonferroni I~g" kg -I pentamorphone group did not require supple- method to correct for the ten multiple comparisons. Du- mental doses of opioid analgesic, with the remaining 14 ration time and MAC min data were compared among patients receiving 3.2 -t- 1.9 supplemental doses. Three patient groups using the distribution-free Kmskal-Wallis patients in the 1.0 ~g. kg -~ pentamorphone group did rank sum statistic using the Bonferroni method to correct not require supplemental doses of opioid analgesic, with for the six multiple comparisons. Categorical comparisons the remaining 13 patients receiving 3.1 + 1.8 supplemen- were analyzed using the nonparametric Mantel-Haenszel tal doses. There was no difference among the four study chi-squared tests using the Bonferroni method to correct groups in the total number or the mean number of sup- for the fifteen multiple comparisons. Differences were con- plemental doses (Table II). sidered statistically significant if P < 0.05. Values are Two patients in the 5 ~g. kg-t fentanyl group (mean reported as means with standard deviations or counts. total dose, 10 + 5 mg), one patient in the 7.5 ~tg-kg -j fentanyl group (mean total dose 5 mg), two patients in Results the 0.75 ~tg. kg -I pentamorphone group (mean total dose No differences in demographic data, duration of surgery mean 15 + 5 mg), and two patients in the 1.0 ~tg. kg -I or anaesthesia, or types of surgery were noted among pentamorphone group received labetolol (mean total dose the four study groups (Table I). No differences in thio- 8 + 3 mg). There was no difference in the number of pentone dose to loss of eyelash reflex or vecuronium re- patients requiring labetolol or in the amounts of labetolol quirement were noted among the four study groups (Table administered (Table II). II). No patient experienced recall or change in respiratory When considering the use of isoflurane, the pentam- rate (Table III). Both analgesics were clinically satisfac- orphone groups differed from the fentanyl groups. Pa- Kelly et al.: PENTAMORPHONE VERSUS FENTANYL 707

TABLE 11I Recoveryfrom anaesthesia

5 #g. kg-l F 7.5 l~g. kg-l F 0.75~g. kg-t P l l~g. kg-t P

Patients with postoperative nausea (n) 4 6 2 5 Patients experiencing recall (n) 0 0 0 0 Patients with postoperative vomiting (n) 4 3 2 2 Patients receiving 0.625 mg of droperidol (n) 3 2 1 1 Patients requiring postoperative morphine (n) 5 9 9 6 Time from end of N20to extubation (mitt) 5 5:6 9 5:8 45:2 115:17 Postoperative morphine dose (mg) 6.5 5:6.0 4.8 5:2.4 7.1 5:3.6 3.7 -I- 2.0 Values are mean + standard deviations or counts. Abbreviations: F - fentanyl; P - pentamorphone.

FIGURE 3 Comparisonof mean arterial pressures (mmHg). The FIGURE 2 Comparisonof heart rates (bpm). The data are displayed data are displayed as means and standard deviations. The fentanyl as means and standard deviations. The fentanyl patients' data are patients' data are shown as solid lines while pentamorphone patients' shown as solid lines while pentamorphone patients' data are shown as data are shown as dashed lines. dashed lines.

study groups (Table III). The time from the end of N20 tients receiving 0.75 ~g" kg -1 pentamorphone did not re- administration to extubation was shortest for the 0.75 quire isoflurane supplementation until 37 + 10 min after ~g. kg-l pentamorphone group. There was no difference the start of anaesthesia, and patients receiving 1 Ftg" kg-' in the use or dose of postoperative morphine among the pentamorphone did not need isoflurane supplementation four groups. until 43 + 26 min (Table II). However, the patients given either 5 or 7.5 ~g. kg-' fentanyl required isoflurane Discussion sooner (12 + 16 and 12 -F 17 min, respectively) (P < The primary goal in the development of any new an- 0.05). Thetotal time of isoflurane administration for the algesic is increasing effectiveness against pain in a dose- 5 or 7.5 ~g. kg-' fentanyl groups was longer (104 + dependent manner without haemodynamic or respiratory 45 and 104 + 50 rain, respectively) than either the 0.75 depression. Ideally, any new analgesic should provide an or 1 Ftg-kg -l pentamorphone groups (25 -F 24 and 22 advantage over previously available drugs. The haemo- -I- 15 min, respectively) (P < 0.05). No differences in dynamic stability we found with pentamorphone is sup- MAC min of isoflurane were noted among the four study ported by a similar study with balanced anaesthesia. 13 groups (Table II). Our study demonstrated that pentamorphone's advantage Recovery from anaesthesia was satisfactory for all four over fentanyl was in the lower requirement for inhalational 708 CANADIAN JOURNAL OF ANAESTHESIA

ferences were apparent in length of MAC anaesthesia as well as the amount of inhaled anaesthetic requirement. The drug group's mean difference of approximately 20 MAC min was not significant because the standard deviations were all over 25 MAC min. Therefore more studies at higher doses are indicated to delineate the actual effective dose of pentamorphone. Although pentamorphone has been shown to depress ventilatory responses to hypoxia and hypercapnia, i i we found that pentamorphone demonstrated potent analgesic effects and effective blunting of the haemodynamic response to surgery, without increased incidence of respiratory rate change or perioperative haemodynamic com- plication. We found patients tolerated pentamorphone FIGURE 4 Comparisonof mean systolicarterial pressures (mmHg). well and it appears to offer isoflurane-sparing advantages The data are displayedas means and standard deviations.The fentanyl over fentanyl in general anaesthesia. patients' data are shown as solid lines while pentamorphonepatients' data are shown as dashed fines. Acknowledgments We would like to express our appreciation to the Samuel J. Roessler Memorial Medical Research Scholarship for financial support of the medical students Ernst W. Lisek, Martin J. Kungl, Lisa Bohman Egbert, Brad S. Efaw, Brian S. Myers, Todd N. Cardwell, Carofine J. Caine, and Bradley D. Egbert. In addition, we wish to acknowl- edge Anaquest Inc. for their support in this study.

References 1 Glass PSA, Doherty MA, Helms MJ. Relative analgesic potency of pentamorphone and fentanyl. Anesthesiology 1989; 71: A761. 2 Parker RK, Holtmann B, White PE Initial clinical evaluation of pentamorphone: a new opioid analgesic. Anesth Analg 1990; 70: $298. FIGURE 5 Comparisonof mean diastolicarterial pressures 3 Wong HY, Parker RK, Fragen R, White PF. (mmHg). The data are displayedas means and standard deviations. Pentamorphone for management of postoperative pain. The fentanylpatients' data are shown as solid lines while Anesth Analg 1991; 72: 656-60. pentamorphonepatients' data are shown as dashed fines. 4 Glass PSA, Carnporesi EM, Shafron D, Quill T, Reves JG. Evaluation of pentamorphone in humans: a new potent agent in a balanced anaesthesia technique. The most ap- opiate. Anesth Analg 1989; 68: 302-7. parent differences in inhaled anaesthetic requirements 5 Ginsberg B, Muir M, Damask M, Quill TJ, Glass PSA. were the duration of isoflurane use and interval of in- Assessment of the analgesic efficacy of pentamorphone to duction to initiation of volatile anaesthetic (Table II). morphine. Anesthesiology 1990; 73: A836. Lowdon et al. Jo also demonstrated an increased interval 6 Ho WM, Ashburn MA, Liu WS, et al. Cardiovascular ef- from induction to initiation of volatile anaesthetic with fects of large doses of pentamorphone in the dog. J Cardio- the use of pentamorphone compared with fentanyl. We thorac Vasc Anesth 1990; 4: 326-31. feel that pentamorphone was responsible for these dif- 7 Falinski BA, Sebe! PS, Hug CC Jr, Klochany A. ferences in volatile anaesthetic use because we found no Pharmacodynamics of pentamorphone during coronary ar- differences in recovery time, number of patients requiting 9tery bypass grafting in humans. J Cardiothorac Vase labetolol, or number of patients requiring supplemental Anesth 1992; 6: 168-72. intraoperative opioid analgesic doses. Although the mean 8 Rudo FG, Wynn RL Ossipov M, et al. Antinocieeptive difference in total MAC min was not found to be different activity of pentamorphone, a 14-beta-aminomorphinone de- among the fentanyl and pentamorphone groups, this was rivative, compared to fentanyl and morphine. Anesth Analg most likely a result of our sample size. Individual dif- 1989; 69: 450-6. Kelly et al.: PENTAMORPHONE VERSUS FENTANYL 709

9 Howie MB, McSweeney TD, Lingam RP, Maschke SP. A comparison of fentanyl-O2 and sufentanil-O2 for cardiac anesthesia. Anesth Analg 1985; 64: 877-87. 10 Lowdon JD, Sebel PS, Murphy MR. Pentamorphone in balanced anesthesia: comparison with fentanyl. Anesthesiol- ogy 1989; 71: A225. 11 Afifi MS, Glass PSA, Cohen NA, Shook JE, Camporesi EM. Depression of ventilatory responses to hypoxia and hypercapnia after pentamorphone. Anesth Analg 1990; 71: 377-83.