Br.J. Anaesth. (97),, 463 DROPERIDOL, FENTANYL AND MORPHINE FOR I.V. SURGICAL PREMEDICATION J. T. CONNER, G. HERR, R. L. KATZ, F. DOREY, R. R. PAGANO AND D. SCHEHL SUMMARY. mg and morphine mg alone and in combination with and. mg were studied for i.v. surgical premedication in 4 patients. Relief of anxiety, sedation, lack of recall, patient acceptance and side-effects were evaluated. The addition of to fentanyl and morphine produced greater sedation and relief of anxiety before operation, but did not improve patient acceptance or lack of recall. We have studied the effect of fentanyl and morphine alone and in combination with given i.v. for premedication. Relief of anxiety, sedation, lack of recall, patient acceptance and side-effects were evaluated. METHODS Two hundred and forty (4) patients, in good general health, in the age range -6 yr were studied. The method of anaesthesia was not standard and the patients were undergoing a variety of surgical operations, except cardiac- and neurosurgery. Patients with a history of sensitivity to the drugs under study, those under going surgery of the biliary tract and patients in pain were excluded also. No patient had received any previous sedative or narcotic on the day of surgery. One hour before surgery an i.v. infusion was started, and the drugs were administered i.v. over a -min period. The drugs were administered doubleblind using a randomized Latin square sequence: fentanyl. mg and morphine mg alone and in combination with mg and. mg. Each drug group consisted of 4 patients. All observations were made by a trained nurse observer. Before premedication, the patient was asked to evaluate his level of anxiety as negligible, mild, moderate or severe. Four minutes after premedication his sedation was rated, compared with the unpremedicated state, as (unchanged), +, +, 3 +, 4+ (improved), or -, -, 3- or 4- (worse). The patient was asked to rate his level of anxiety in comparison with his unpremedicated state, using a similar scale, and asked if the overall sensation of the drug was pleasant, unpleasant or neutral. The evaluation of sedation and relief of anxiety was repeated at, 6 and 3 min. Any signs of drug sensitivity, side-effects or symptoms were noted. Recall was tested by showing the patient a randomized series of "memory cards" (familiar objects or scenes) at,,4,,6 and 3 min. Recovery data were collected by the recovery nurses. The frequency of postoperative nausea, vomiting and agitation, and the time of responsiveness to a command after general anaesthesia were noted. Twenty-four hours after surgery the nurse observer, unaware of the drugs given, asked the patient to rate the premedication as poor (), fair ( + ), good ( + ) or excellent (3 + ). Each patient was asked if he would like to receive the drug again in the event of another operation. Each patient was asked to identify the "memory cards" from a composite of eight pictures. Evidence of recall of drug administration, the operating room or the recovery room was sought. At 4 h after operation the i.v. site was examined for evidence of thrombophlebitis. Statistical analysis was performed by transforming the raw scores to ridits based on the fentanyl and morphine scores, and using an analysis of variance procedure (Selvin, 977). RESULTS There was an even distribution of variables such as height, weight, sex, race, type of anaesthesia and surgery among the groups (table I). JAMES T. CONNER, M.D.; GEORGE HERR, M.D.; RONALD L. KATZ, M.D.; FRED DOREY, PH.D.; RICHARD R. PAGANO, M.D.; DONNA SCHEHL, R.N.; Department of Anesthesiology, U.C.L.A. School of Medicine, Los Angeles, California 94, U.S.A. 7-9/7/-463 $. Anxiety The changes in anxiety as scored by the patient are shown in table II and figures and. The drug effect was significant (chi-square on mean ridit score) Macmillan Journals Ltd 97
464 BRITISH JOURNAL OF ANAESTHESIA TABLE I. Characteristics of the patients studied {mean values ±SD where appropriate). mg mg mg mg mg mg Age (yr) Sex (M/F) Race (colour) White Black Other Weight (kg) Height (cm) 43.3 ±4.6 6/4 33 66. ±. 6 ±.7 3.4 ±4. / 37 69. ±6. 6 ± 9.4 4. ±. / 3 4 66.4 ±.4 64 +.9 4.9±. / 36 4 6.6+.4 67 ±. 4. ±. /9 3 4 69. ±6. 69 ± 37.9 ±3. 7/3 37 3 6.9 ±4.4 67 ± 9. Patient anxiety scored by patient 6 min 3 min Ridit scores 6 min 3 min Patients sedation scored by nurse 6 min 3 min Ridit scores 6 min 3 min TABLE II. Anxiety and sedation mean scores on scale ± 4. mg mg mg mg mg mg....67.49.3.6.43 observer.44..3.7.37.44.46.3.7..7.4.46.479.4.3.9.9..7.463.479.4.374.7..9 3..64.6.6.6....76.69.743.797.77.6 7.6.6.49.6.67.64.. 9.33.6.76.77.7..73.63.4.63.644.6.7.6.46..6.697.74.6.4.7.3.99.6.634.67..37..63.76.77.769 at (P<.), 6 min (P<.) and 3 min (P<.). At (paired z tests on mean ridit scores) the following were better than morphine alone: fentanyl + mg (P<.), morphine + mg (P<.3), morphine + mg (P<.). mg was better than fentanyl alone (P<.). At 6 min: fentanyl + mg was better than morphine or fentanyl (P<.); morphine+ mg better than fentanyl (P<.) and morphine (P <.) alone; fentanyl+ mg better than morphine (P<.4) or fentanyl (P<.); morphine + mg better than morphine (P<.). At 3 min the following were better than morphine: morphine + mg, morphine+ mg, fentanyl+ mg and fentanyl + mg (P<.); better than fentanyl: fentanyl + mg (P<.), fentanyl+ mg (P<.), morphine + mg (P<.) and morphine + mg (P<.6). Sedation The change in sedation scored by the observer is shown in table II (raw data and the ridit transformed data) and figures 3 and 4 (ridit data). The drug effect was significant (chi-square on transformed
I.V. PREMEDICATION 46. r.7 Droperidol mg..7 Droperidol mg.6.6 Droperidol. nig cc. :..4 **...4 '. #.3-6 3 FIG.. Mean change in anxiety scored by patient as compared with unpremedicated state: fentanyl. mg alone and with mg and. mg. The higher the score the greater the relief of anxiety..3-6 3 FIG. 3. Mean change in sedation scored by observer as compared with the patient's unpremedicated state: fentanyl. mg alone and with mg and. mg. The higher the score the greater the sedation..7 r / - Oroperidpl mg. r Droperidol mg.6.^. -o Droperidol.mg.7.6 Droperidol.mg.4.3h 6 3 FIG.. Mean change in anxiety: morphine mg alone and with mg and. mg. data) at (P<.), (P<.), 6 min (P<.) and 3 min (P<.). At (z test) fentanyl + mg was better than fentanyl (P<.4) or morphine (P<.). mg was better than morphine (P<.4). At fentanyl + mg was better than fentanyl (P<.) and morphine (P<.). + mg.4.3-6 3 FIG. 4. Mean change in sedation: morphine mg alone and with mg and. mg. was better than fentanyl (P<.) and morphine (P<.). mg was better than fentanyl (P<.) and morphine (P<.);
466 BRITISH JOURNAL OF ANAESTHESIA morphine + mg was better than fentanyl (P<.) and morphine (P<.). At 6 min fentanyl+ mg was better than fentanyl (P<.) and morphine (P<.), fentanyl + mg was better than fentanyl (P<.) and morphine (P<.). mg was better than fentanyl (P<.) and morphine (P<.) and morphine + mg was better than fentanyl (P<.) and morphine (P<.). At 3 min fentanyl + mg was better than fentanyl (P<.) and morphine (P<.) and fentanyl + mg was better than morphine or fentanyl (P<.). + mg was better than fentanyl (P<.) and morphine (P<.); morphine + mg was better than fentanyl or morphine (P<.). Peak scores for the narcotics alone appeared to have occurred within the first min while those for the narcotic- combinations occurred at 6 and 3 min. Patient acceptance 4 h after surgery {table HI and fig. (ridit score)) The overall Chi-square was not significant (P<.3). mg was better than fentanyl + mg (paired z test; P<.74) and better than morphine +.6 r. CC.4 3- - - Droperidol Dose (mg) + +. FIG.. Mean patient acceptance as scored by the patient 4 h after surgery: with fentanyl. mg or morphine mg. The patient acceptance of fentanyl and morphine alone is shown. The higher the score the greater the patient acceptance. mg (P <.3); morphine was better than morphine + mg (P<.); fentanyl better than morphine + mg (P<.4) and fentanyl + mg (P<.). Most patients did not rate the study drugs as pleasant after injection (table III); fentanyl rated highest while morphine rated least. As for willingness to take the drug again, fentanyl scored highest while morphine + scored least. TABLE III. Patient acceptance. mg mg mg + mg mg mg Patient acceptance (-3) at 4 h (% of patients) Poor () Fair(l+) Good ( + ) Excellent (3 + ). 7. 7. 4. 7. 7. 3. 7. 7.. 4. 7. 3. 7. 3.. 3. 4. Patient acceptance Mean Raw score Ridit score.76..64.4.7.3.7.47.4.43.3.377 Patient's subjective rating at (%) Pleasant Unpleasant No opinion 4. 3. 3.. 69.. 3.. 9. 43. 4. 7. 4.. 36. 33.. 7. Patients who would take again (%) (at 4 h) 79. 6. 7. 6. 63. 7.
I.V. PREMEDICATION 467 TABLE IV. Failure to recall (%). mg mg mg mg mg mg Memory card min min 6 min 3 min 3 6 7 7 7 3 Operating room 9 min 3 Recovery room 39 3 44 3 TABLE V. Side-effects before operation (%). mg mg mg mg mg mg None Nausea Vomiting Dizziness Flushing Heavy feeling chest and neck Dyspnoea Tingling, etc. of membranes Anxiety Agitation/restlessness Pain on injection 4. 7. 4..... 4. 47. 7. 3. 6... 7. 3 3 3.. 3. 3....... 7. 7... Recall (table IV) There was a lack of recall with reaching a peak at 6-3 min. There was no difference between any of the groups. There was no lack of recall of the operating room (mean time of entrance 9 min) in any group. Droperidol did not affect lack of recall of the recovery room. Side-effects (table V) Nausea and vomiting was infrequent in all groups. Flushing, sensations of heaviness over the chest and neck and sensations of tingling or numbness were associated with morphine. The frequency of these complaints was decreased by. Agitation, restlessness and increased anxiety were not common, occurred only in patients who received and were more frequent with the larger dose. The frequency of pain on injection was % or less in all the groups. Only two of 34 patients had signs of clinical thrombophlebitis 4 h after surgery. DISCUSSION Droperidol (Janssen et al., 963) is a popular tranquillizer in the technique of neuroleptanalgesia. Several studies of i.m. - mg alone concluded that it had no place in surgical premedication (Morrison, Clarke and Dundee, 97; Ellis and Wilson, 97). Morrison (97) stated that "the addition of to fentanyl was to increase the sedative effect over that of either drug given alone, while the unpleasant subjective effects and restlessness associated with given alone were also reduced by combination with the opiates". In the late 96's and fentanyl in a : ratio was marketed (Thalamonal). Today, and fentanyl are also available separately. Over the past few years, dysphoria ascribed to both and Thalamonal has been described. These have been largely anecdotal, but Briggs and Ogg (973) and Lee and Yeakel (97) cited a number 3
46 BRITISH JOURNAL OF ANAESTHESIA of cases in which patients who had received Thalamonal for premedication refused surgery. It was postulated that was the component which caused this problem. In our study, the addition of to fentanyl or morphine improved the relief of anxiety and sedation scores in the period before operation. There was no significant advantage of the.-mg over the -mg dose. Patient acceptance of. mg with either fentanyl or morphine was no better than combinations with mg or even fentanyl or morphine alone. While the raw relief of anxiety and sedation scores seen in this study are high and comparable with those obtained with other drug combinations we have studied with the same method (Conner et al., 976, 977a, b), the raw patient acceptances scores are poor. We recognize the inherent weakness of comparing drugs across studies. It is our impression that the relationship of preoperative sedation and relief of anxiety scores to patient acceptance in this study is not highly correlated. In published (Conner et al., 976, 977b) and unpublished studies of lorazepam and diazepam, the sedation and anxiety scores were comparable with those for the combinations in this study, but the patient acceptance scores were much greater. In many cases patients who received the narcotic combination scored it high before, but low after surgery. Several patients in this group described a "paranoid feeling" and "panicky sensations" in their rejection of the drug. Only 3 of the 6 patients who received described increased anxiety before operation, while this was a common complaint after operation. It may be that causes difficulty in expressing feelings of the drug: an anaesthetist observing the sedation produced by the -narcotic combination may easily mistake the patient's outward calmness for mental tranquillity. For all the groups in this study there were few instances in which the effects of the drugs were judged pleasant at. The addition of to either fentanyl or morphine did not increase the number of patients who would ask for the drug again compared with that favouring the narcotic alone. Sixty-three per cent of the patients who received. mg plus morphine said they would decline this combination in the future. The low patient acceptance ratings for fentanyl alone were chiefly because of the short duration of the drug effects, while low scores for morphine alone were related to the sensations produced by the injection of this narcotic i.v., warmth, heaviness of the body, tightness in the chest and neck, and a general sensation of tingling. Reasons for low patient acceptance scores for groups receiving plus a narcotic were a combination of those seen with the narcotics alone plus the complaint of increased anxiety and restlessness. Would the patients have fared better if the drugs had been given i.m. rather than i.v.? There are few data for comparison, but studies of narcotics given i.m. have reported similar frequencies of nausea, vomiting and dizziness. The sensations produced by i.v. injection would be expected to be less severe or non-existent with i.m. morphine because of gradual onset of activity and lower plasma drug concentrations. Cressman, Plostnicks and Johnson (973) "would expect the response to following intramuscular administration to be almost equivalent to that observed following intravenous administration". The complaints of patients receiving in this study are similar to previous studies of i.m. injection. In some circles it is believed that patient acceptance can be improved by using large doses of (.-. mg kg - ). In our study, patient acceptance of mg combinations scored less than mg. However, further studies would be needed to demonstrate if there is an advantage of larger doses of for premedication. Lack of recall in this study appeared to be a lack of recognition of information rather than a disturbance of memory consolidation or retrieval of that information. Patients were often too heavily sedated to identify the cards, but lack of recall of the operating room, a more potent stimulus, was uniformly uncommon with all drug combinations (% or less). Many anaesthetists find the passive and cooperative attitude of the patient following desirable when undertaking procedures such as regional analgesia. If and narcotic combinations are not acceptable, perhaps the addition of a tranquillizer such as diazepam to might be acceptable. REFERENCES Briggs, R. M. and Ogg, M. J. (973). Patients' refusal of surgery after Innovar premedication. Plast. Reconstr. Surg.,,. Conner, J. T., Bellville, J. W., Wender, R., Schehl, D., and Katz, R. L. (977a)., scopolamine and atropine for intravenous surgical premedication. Anesth. Analg. (Cleve.), 6, 66.