Perphenazine in clinical anaesthesia

0 Can. Anaes. See. J., ,eel. 6, no. 4, October, 1959 1 1Read at the Annual Meeting of the Western Dlvaslon of the Canadian Anaesthetasts' Society , n Saskato.on, March 19 , 1959. 2Department of Anaesthesaa, Umvermty of Saskatchewan College of Medicine and Umversity Hospital , Saskatoon PEtlPHENAZINE ( T r i l a f o n | is 1-(2-hydroxyethyl)-4-[3-(2-chloro-10-phenothiazyl)propyl]-plperazine. The chlo, ophenoth,azme derivative is obtained as a white crystalline solid which is soluble m organic and inorganic acids. It combines with hydrochloric or maleic acid to give crystalline salts whica are water soluble. Tablets for oral admmistratmn contain 2, 4, and 8 mg. The; intramuscular and intravenofls preparation is provided m colourless ampoules containing 5 rag. in 1 ml. The pH of this solution is 5 9 and causes no irritation whq~n injectec by vein or into the muscles. Perphenazane is one of the "broad spectrum" group of tranquflhzers. The s t r u c ~ r a l relationship to chlorpromazine is shown below: Following initial reports of the wide r~nge of neuro- and psycho-sedative effects and the potent anh-emetac activity of perphenazine (1, 2), a preliminary trial was made with this drug in assocmtion with anaesthesia. Perphenazine was reported to provide a satasfactory sedative response without excessive hypnosis, and it appeared to be effectree m alleviating nausea and vomiting, at a dose level wbach did not cause a significant change in blood pressure, pulse rate, or resplrataon (3). A more extensive lxiaI was-therefore undertaken to test perphenazinc for two specific aj?phcations in anaesthesia. Anmaal studies were carried out to determine whether perphenazine was effective m sup]?ressmg epinephrineprovoked cardiac arrhythmms m dogs under anaesthesia (,t, 5). Clinical studies were carried out mainly to determine the anta-emetac effects of perphenazine in associatton with anaesthesia. - CHLOI~ROMAZINE ( LAI~GA~IL| ) PERem~NAZmE (TitmAFo~r~J CANADIAN ANAESTIIETISTS' SOCIETY JOURNAL retching, and vomiting in the early postoperative period were treated with perphenazine either intravenously or intramuscularly to determine whether these symptoms could be alleviated immediately wh]Lle the patient was under direct supervision in the postanaesthetic recovery ward. The study was set up in this way because many of the patients who were scheduled for major operations were premedicated with other phenothiazine derivatives (promethazme, levomepromazine, promazine, and proclorperazine) which would reduce the incidence of nausea and vomiting postoperatively. From July, 1956, to October, 1957 (16 months), the over-all incidence of nausea and vomiting among patients admitted to the recovery room, excluding those who arrived with gastric suction, was 705 in a total of 4,563 (i5.5 per cent). Perphenazine was under trial from November, 1957, to February, 1959 (16 months). During this time the incidence of nausea and vomiting was 818 in a total of 5,383 (15.2 per cent). Aside from the introduction of Fluothane, and Fluothane-ether anaesthesia, there were no reraarkable changes in the types of anaesthetics used in the second period. In the first period, over 14 per cent received a phenothiazine for premedlcatuon, while in the second period over 16 per cent received a phenothiazine for premedication. This dad not materially affect the data that were analysed, because most of these patients underwent major abdominal operations and gastric suction was used in many of them. Since it was not desirable to administer additional drugs as a routine prophylactic against symptoms which might require treatment in less than 15 per cent of patients, it was left up to the senior nurses ot~,the recovery room to request treatment for those patients who were having peraistent nausea, retching, and vomiting, and to record whether administration of perphenazine intravenously or intramuscularly was effective in relieving the patient promptly. This method was considered valid in handling a situ~/cion where the course of the untreated symptom is notoriously variable, and where the trap of post hoc reasoning might be fallen into ff every patient received the same treatment. During this trial, 107 patients had a definite previous history of vomiting after general anaesthesia. Perphenazine was used for premedication intramuscularly about one hour before scheduled operation in each of these. Postoperative vomiting occurred in 11 patients of this group (10 per cent). During the course of regional anaesthesia, 73 patients were given perphenazine 5 rag. intramuscularly or intravenously as supplementary sedation In each patient the resulting sedation was satisfactory and two of these vomited postoperatively. Perphenazine was administered to 54 patients in whom nausea or vomiting developed during spinal anaesthesia, with prompt and complete relief in all but one. In 233 other patients who received low spfiaal anaesthesia, nausea and vomiting occurred in 29 (13 per cent). Hiccough was treated only seven times, with prompt relief in six patients. Persistent nausea, retching, and vomiting was treated in 411 of 818 patients in the recovery room. Of these, 362, received perphenazine. A1- but 18 obtained prompt and complete relief (95 per cent effective). The othe: 49 patients were given a variety of other anti emetic drugs by choice of the surgeon, and will not be considered here. Many of the pattents who were not given specific drug therapy had a long period of vomiting and were treated with gastric suction. During the period that perphe:aazine was under trial, it was noted that the onset of nausea and vomiting in the recovery room followed the administration of pain-relieving drugs (meoeridine, morphine, and codeine) in 212 patients ( 26 per cent). Nausea and vomiting are often regarded as a protective fimction for the removal of noxious substances in the gastro-mtestinal tract and an important diagnostic sign. However, the development of these symptoms in the immediate postanaesthetm period serves no apparent useful purpose, and often may be detrimental to the pataent. Retching and emests during this period may increase pain at the operative site, aggravate emotional upsets related to the operation, and, ff persistent, may upset water and electrolyte balance. Fear and anxiety associated with vomiting may also rapidly exhaust the postoperative l~atient. Many drugs are available to the anaesthetist now which~ have sedative and anti-emetic activity when used for premedicatlon. It is also thought that with the newer anaesthetic agents, and improvements in technique, the incidence of nausea and vomiting directly related to the effect of anaesthesia itself is in sharp decline. For these reasons, the mare part of this study was directed to evaluating the effect of perphenazine on nausea, retching, and vomiting after their development. It has become apparent that even vrith the use of a variety of tranquillizing drugs, (...truncated)