The effectiveness of anti-emetic agents: a comparison of the anti-activity of trifluopromazine (vesprin®), perphenazine (trilafon®), and trifluoperazine (stelazine®) with that of dimenhydrinate (gravol®) in postanaesthetic vomiting

I. E. Pur Krs M.B. B.S. F.F.A.R.C.S.(ENG) M. Isrrtl ~.D. THE EFFECTIVENESSof individual anti-emetic drugs in reducin~ the incidence of postoperative vomiting in patients who would otherwise receive no +an}i-emetic is readily established. This has led to a proliferation of anti-emetic agents, making the choice of one agent for any patient extremely difficult. Bellevillet has pointed out the difficulties of making coroparisons between well-controlled studies of different investigators, and recommends further controlled comparative studies. However, unless consideration is given to the large numbers of interacting factors affecting the incidence of postoperative vomiting, it may be impossible to grade the effectiveness of the test agehts, and recommendations on the choice of agent may have to be based upon the absence of undesirable side-effects.2 In this study, in addition to recording the incidence of side-effects, an attempt has been made to reduce the number of variables by selecting certain operations, using standard anaesthetic techniques, and a standard pre-anaesthetic medication, in the hope that clearer d~tinctions might appear regarding the anti-emetic activity of the agents used. The an!i-emetic activity of dimenhydrinate (Gravol| has been well documented 3-6 and this agent was the one most frequently used in this hospital to control postoperative nausea and vomiting. It was included in the survey as a "control" agent against which to measure the activity "of the three newer drugs. Investigation of trifluoperazine (Stelazine| showed prolonged protection against apomorphine-induced vomi9ti~"ng,7 good results in nausea and vomiting of pregnancy,s and in the suppression of seasickness.9 Pe.rphenazine (Trilafon| was 16.6 to 47.8 times more effective than chlorpromazine in preventing apomorphineinduced vomiting,1~ and substantially reduces postoperative vomiting.11,12,13 Significant reduction in postoperative vomiting has been demonstrated by a number of workers using trifluopromazine (Vesprin| *From the Department of Anaesthesia, Victoria General Hospital and Dalhousie University, Halifax, Nova Scotia. The statistical analyses presented in this paper were provided by Smith K~ine and French Laboratories., - THE EFFECTIVENESS OF ANTI-EMETIC AGENTS: A COMPARISON OF THE ANT~-EMETIC ACTIVITY OF TRIFLUOPROMAZINE (VESPRIN| PERPHENAZINE (TRILAFON| AND TRIFLUOPERAZINE (STELAZINE| WITH THAT OF DIMENHYDRINATE (GRAVO L| IN POSTANAESTHETIC VOMITING* selected. The selection was based on the site of operation, and on the expected age and sex distribution of patients undergoing th~ operation, factors known to influence the incidence of vomiting.T M All patients included in the survey received a standard narcotic premedication (meperidine 50-100 rag. with atropine 0.4-0.6 mg. roughly according to body weight), which has been reported to increase the incidence of postoperative vomiting.1 Data were collected from 9,491 patients, of w~om 345 were excluded, 269 because they received a premedieation other than ~neperid/ne and atropine, and 76 because of inadequate data. The age and sex distribution, distribution among operations, and incidence of nausea and vomiting of those patients excluded were similar to those of the patients retained. With the exception of those patients whose condition was unsatisfactory preoperatively (physical status 3 or 4) or postoperatively (marked hvpotension or underventilation ), aft patients scheduled to undergo one of the selected operations were included in the survey. The distribution of the remaining 2146 patients according to sex and operation is presented in Figure 1 and shows the preponderance of female patients arising from the method of selection, especially in the intra-abdominal and perineal groups. FICURE1. Patient distribution by operation type. Allocation of Drugs The test agents were placed in separate multi-dose vials, the concentration of the solution being adjusted as shown in Table I, to-allow an effecti~ e anti-emetic dose when given at the rate of 0.01 ml. per lb. of body weight (0.02 ml./kg.). )A master list of trial numbers containing four anaesthetic types (nitrous oxide/ oxygen, halothane, eyclopropane, ether) for each of the ten operations was used to select the appropriate drug. As each patient arrived m the recovery room, he was identified as to operation and anaesthetic given, and allocated the next available trial number under that heading. Againsteaeh trial number was a code letter identifying the vial to be given. The code letters were arranged in sequence, with a space at every fifth trial number, where no anti-emetiC was given. From the appropriate vial 0.01 ml. per pound of body weight w~s withdrawn land injected intramus6ularly. Thus the selection of anti-emetic agent was not biased by file selection of the administering nurse, or by the obs4rver, fTables II and III, showing the distribution of patients by operation, anaesthetic, and anti-emetic, reflects the incidence of the four anaesthetic techniques used l and ifldieates an even distribution of anti-emetic drugs. DRUG CONCENTRATIONS Dimenhydndate Trifluopromazme Perphena:z,ne Trifluoperazme DISTRIBUTION OF PATIENTS BY OPERATION AND ANAESTHETIC ! DISTRIBUTION OF PATIENTS BY OPERATION AND ANTI-EMETIC AGENT Total (2146) Observations Using a special proforma, recovery rpom nurses observed the patient at 15minute intervals. In addition, every episode Iof retching or vomiting occurring after the first 15 minutes was recorded. A score system was used, nausea having a value of 1, retching 2, and vomiting 8. After discharge from the recovery room, nausea and emesis recorded on the patient's ch~Lrt were scored in a similar manner. In order to assess subjective responses, patients were visited between 24 and 48 hours postoperatively and questioned as to the extent of the vomiting remembered, which was graded as mild whege patients reported nausea only, or one episode of vomiting, moderate where t}vo episodes of vomiting had been experienced, and severe when there had been Ithree or more remembered episodes of vomiting. While discrepancies did occur between the score value and the vomiting reported by the patient, these wer%not frequent, and occurred equally in either direction. Those patients who had h~d previous anaesthesia were invited to compare their experiences, and to state Whether they had experienced less, more, or the same amount of vomiting with this anaesthetic. Additional data recorded included the occurrence of hypotension during the anaesthetic and in the recovery room, the tlming and number of postoperative analgesic and subsequent anti-emetic injectio/~s, and the duration of postoperative sleep, judged by the ability to respond to veroal commands. The main effect of an anti-emetic agent gi@n prophylactically may be to reduce the numbers of patients with a positive seor~ for nausea and vomiting, while the main effect of a drug given therape (...truncated)