CHLORPROMAZINE (" LARGACTIL") AS AN ANALGESIC IN LABOUR

Transcription

1 Brit. J. Anaesth. (9), 27, 46. CHLORPROMAZINE (" LARGACTIL") AS AN ANALGESIC IN LABOUR A Report of 27 controlled cases BY DAVID SAVAGE Charing Cross Hospital Obstetric Unit OF the many pharmacological properties third of the cases, retarded in another of chlorpromazine (" Largactil", May & third, and not altered in the remainder. Baker, Ltd.), its sedative action on the Rottger (9) administered chlorprocentral nervous system, and its potentiat mazine in combination with promethazine ing effects on analgesics would seem to and pethidine (the " lytic cocktail") by indicate that it might be of value in reliev intramuscular injection to 0 patients in ing pain in labour. labour. Good relief of pain was achieved The effect of chlorpromazine in poten in per cent of cases, fair alleviation in tiating analgesic drugs and its " pharma 4 per cent, while 28 per cent obtained no cological leucotomy " action have recently benefit. No ill effects were observed on the been put to use in the treatment of other baby. Labour was slightly prolonged in painful conditions. Administered to primiparae but was of normal duration in patients with malignant disease chlorpro multiparae. mazine relieved pain, muscle spasm, apprehension, and promoted a sense of wellbeing and a decrease in need for narcotics (Albert, Bateman and Klopp, 94). Sadove, Levin, Rose, Schwartz and Witt (94) found that pain was relieved by narcotics plus chlorpromazine when narcotics alone had failed and that the patients seemed more relaxed and spoke of pain as an objective phenomenon which they no longer minded although it was still present. The first reported use of chlorpromazine in labour was in 92 when it was given together with pethidine to 7 patients with good effect in 79 cases (Lacomme, Laborit, Le Lorier and Pommier, 92). Labour was hastened in a THE TRIAL The aim of this trial of chlorpromazine was twofold: () To assess the analgesic effect of the drug in combination with pethidine and compare it with a control series of patients receiving pethidine, quinalbarbitone ("Seconal") and chloral. (2) To observe the effect of chlorpromazine on uterine action. Alternate patients in a series of 24 consecutive cases at Kingsbury Maternity Hospital were allocated on admission in labour into " Largactil" and " Control" groups. Those admitted for elective Caesarean section or delivered before arrival at hospital were excluded. 46 Downloaded from at Pennsylvania State University on May 2, 6

2 CHLORPROMAZINE AS AN ANALGESIC IN LABOUR 47 Patients admitted for antenatal treatment were not grouped until the onset of labour. Abnormal obstetric cases (breech presentations, twins, emergency admissions, trials of labour) were included in the series without selection. Parity, Maternal Age and Birth Weights of Infants. Apart from a slight preponderance of primigravid patients in the " Largactil" group (70 cases compared with 6 in the "Control" group), there was "LARGACTIL' 2 6 "CONTROL" Previous Pregnancies (over 28 weeks) 4 < 2 2 > < 2 2 > Maternal Age (years) < >0 < >0 Birth weight (pounds) FIG. Parity, maternal age and birth weights of infants in " Largactil" and " Control" groups Downloaded from at Pennsylvania State University on May 2, 6

3 48 BRITISH JOURNAL OF ANAESTHESIA little difference in parity, maternal age made by Rottger (9) that administraand the birth weight of the infants in the tion of the drug in early labour with weak two groups (fig ). and irregular uterine contractions will result in labour ceasing, was confirmed. Method of Administration and dosage of Following the initial dose, chlorproma Chlorpromazine. zine was given by mouth (in the absence There were 27 cases allocated to the of vomiting) in doses of 2 to 0 mg and " Chlorpromazine " group and of these this was repeated at not less than 6hourly 0 received chlorpromazine. The re intervals. Pethidine, loomgintramuscumaining 22 patients were admitted in larly, was given from half to one hour advanced labour, at or near full dilatation after the initial dose of chlorpromazine, of the cervix, and too late for administra and repeated as required at not less than tion of the drug to be of benefit. To have 4hourly intervals, excluded these mothers, who mainly had easy and rapid labours, would have ad Assessment of Pain Relief. versely affected results in the " Lar Patients in both groups were intergactil" group and they were therefore viewed on the third day of the puerincluded. perium. The questions and replies are Chlorpromazine was given to 0 cases, shown in table II. Eightyfour received the drug by mouth, It was noticed that there was an ex 8 by intramuscular injection and by tremely variable response to chlorproboth routes. The total dosage given is mazine. Some patients were unaffected shown in table I. whilst others receiving the same dose of Orallv Route Intramuscularly Orally and Intramuscularly TABLE I Route and total dose of chlorpromazine Dose (mg) In the earlier cases in the series, rela the drug were deeply sedated. The tively small doses of chlorpromazine were amount of pain relief was similar in both given, i.e. 2 mg orally at 6hourly inter groups but rather more " Largactil " cases vals. had a hazy recollection of labour. The initial dose was later increased to 7 mg orally or 0 mg by intramuscular The " Largactil" group (27 cases). injection and this was given when labour Twentytwo of these patients were adwas well established. The observation mitted too late for chlorpromazine and Total 84 8 Downloaded from at Pennsylvania State University on May 2, 6

4 CHLORPROMAZINE AS AN ANALGESIC IN LABOUR 49 most of these (8 cases) had gas and air. Labour was tolerable in cases and in 6 it was intolerable; in 9 cases memory of events was clear and in 2 it was hazy. Of the 0 cases who received chlorpromazine: received chlorpromazine alone; 74 received chlorpromazine and pethidine; received chlorpromazine with quinalbarbitone or chloral. In addition to the four questions set out Question Was your labour tolerable or intolerable? Is your memory of the labour clear or hazy? Was your labour better or worse than you expected? (Primiparae only) Are your willing to have another baby? (Primiparae only) Was this better or worse than your last labour? {Multiparae only) Drugs Chlorpromazine alone ( cases) Subjective effect Chlorpromazine and pethidine (74 cases) Chlorpromazine and " Seconal " or chloral ( cases) TABLE II Questions and replies at third day interview Tolerable 0 Clear 8 Worse ibetter 7 Willing Worse 9 " Largactil " Intolerable Hazy 7 2. Same 2 Not willing 8 Better 28 in table II, the 0 patients were asked oa the third day after delivery what effect they noticed after receiving chlorpromazine. Their answers, together with the degree of pain relief and memory, are recorded in table III. With the increase in dosage of chlorpromazine, the results are improved (table IV). The drug appeared to have a cumula 9 22 Same 0 Tolerable 02 Clear 04 Worse 7 Willing 6 Worse TABLE III of chlorpromazine as recorded at third day, interview e O H 80% 6 8% 60 9% 0 Analgesia Memory G = c oq % ico/ J /o qo/ * A c o' >,o 0% 0 70% 4 6% ICO' > m % 26 6% 4 Co/ > /o 0% 0 24 j.s % 8% 28 46% Better " Control Intolerable Hazy 2 24 Same 9 Not willing Better Subjective effect of chlorpromazine c s i. % 7.% 9% 0% 2 7.% 27% Same 4 % 9 2% 7 8% 2 c % 0% 0 Downloaded from at Pennsylvania State University on May 2, 6

5 0 BRITISH JOURNAL OF ANAESTHESIA tive effect and patients having prolonged labours remained remarkably cheerful and unconcerned. TABLE IV Effect of increasing chlorpromazine dosage on analgesia and memory Dose of chlorpromazine 20 mg (70 cases) 70 mg ( cases) rable Analgesia 80% 6 86% 0 erable o c 6% % 4 t know c o Q % y O 67% 47 9 Memory 29% ct know 0O % o/ Chlorpromazine on " Gas Analgesia. It was expected that the effect of gas and air might well be potentiated by the previous administration of chlorpromazine, and patients who had used the Minnitt's apparatus in labour were questioned as to its efficiency at the thirdday interview. The relief of pain obtained by breathing gas and air from the Minnitt's apparatus was not influenced by the previous administration of chlorpromazine. In the "Largactil" group 9 per cent experienced good relief with gas and air and 28 per cent found it ineffective. In the "Control" group 7 per cent obtained good relief and 24 per cent found it ineffective. The effect of Chlorpromazine on Uterine Action. The total length of labour was significantly prolonged by chlorpromazine. Labours lasting for more than 24 hours were twice as numerous in the " Largactil " group (fig. 2), and the average length of labour was increased from 2 hours 2 minutes in the "Control" group, to 8 hours 0 minutes in the " Largactil" group. The second stage of labour was similarly prolonged. In 9 cases the second stage lasted for more than 2 hours, whilst only cases occurred in the " Control" group (fig. ). The average length of the second stage was 4 minutes in the " Control" group and 60 minutes in the " Largactil" group. This prolongation of labour due to chlorpromazine occurred in primigravidae only. The length of labour in tnultigravidae in both "Largactil" and " Control " groups was the same. Many of the patients who received more than 00 mg of chlorpromazine were indifferent to their surroundings and to their labour pains. During the second stage of labour this indifference resulted in poor expulsive efforts being made with a consequent increase in the number of forceps deliveries. There were 6 forceps deliveries in the " Largactil" group and 4 in the " Control " group. In the " Largactil" group, 4 of the 6 forceps deliveries were performed wholly, or in part, because of uterine inertia. The effect of Chlorpromazine on the Infant. The condition of the newborn infant was unaffected by the administration of chlorpromazine to the mother in labour as judged by: () The time interval between the birth of the infant and its first breath. This Downloaded from at Pennsylvania State University on May 2, 6

6 CHLORPROMAZINE AS AN ANALGESIC IN LABOUR 70" 60" ; " LARGACTIL" "CONTROL' Total length of labour (hours) FIG. 2 Total length of labour in " Largactil " and " Control " groups. 49 " LARGACTIL" o "CONTROL" Second stage (hours) Fio. Length of second stage of labour in " Largactil " and " Control " groups. interval exceeded minute in 4 infants in the" Largactil" group and 7 in the " Control" group. (2) The infant's colour at birth. There were infants with white asphyxia in each group; 8 infants in the "Largactil" group and 24 infants in the " Control" group were cyanosed at birth. () The number of infants requiring active resuscitation (e.g. oxygen or nikethamide). There were 6 such infants in the "Largactil" group and 7 in the " Control" group. (4) The stillbirth and neonatal death rate. In the " Largactil" group there was stillbirth (undiagnosed disproportion) and neonatal death from intrauterine asphyxia due to placental separation. In the " Control" group there was also stillbirth (macerated twin,.24 kg) and neonatal death (prematurity,.4 kg) Downloaded from at Pennsylvania State University on May 2, 6

7 2 BRITISH JOURNAL OF ANAESTHESIA 60 0 JU "LARGACTIL" ?n "CONTROL' Post parcum blood loss (ounces) Fio. 4 Third stage haemorrhage in " Largactil " and " Control " groups. The third stage of labour. No unfavourable effects of chlorpromazine were observed during the third stage of labour. The postpartum haemorrhage rate was not increased (fig. 4). Side effects of Chlorpromazine. Vomiting followed oral administration of the drug in cases and 2 more complained of nausea. Pronounced tachycardia ( per minute) occurred in 2 cases. Sweating and dizziness occurred in case and skin pallor was noticeable in a number of cases. Some transient local pain was produced at the site of the intramuscular injection and, in one case, this persisted for three days. CONCLUSIONS Chlorpromazine has no adverse effects on the^ foetus or on the third stage of labour. It has no advantages over quinalbarbitone and chloral in producing sedation and appears to prolong the length of labour in primigravidae. The fourfold increase in the number of forceps deliveries in the "Largactil" group may have been due to the drug, and its routine administration as a sedative in labour is not advocated. In doses of over 7 mg chlorpromazine is a more effective sedative than quinalbarbitone and chloral and, in addition, it potentiates the analgesic effect of pethidine. In this effective dose chlorpromazine produces uterine inertia in primigravidae and increases the number of forceps deliveries fourfold. Consequently its routine administration to patients in labour is not advocated. SUMMARY () Alternate cases in a series of 24 patients in labour were allocated into "Largactil" and "Control" groups. The " Largactil" group received chlorpromazine and pethidine, and the "Control" group received quinalbarbitone, chloral and pethidine. (2) The sedation and analgesic action of chlorpromazine was assessed by ques Downloaded from at Pennsylvania State University on May 2, 6

8 CHLORPROMAZINE AS AN ANALGESIC IN LABOUR tioning the patient about her labour pains on the third day after delivery, and was compared with the effect obtained from quinalbarbitone and chloral. No significant difference in pain relief was noticed in the two groups of patients. () With larger doses of chlorpromazine, better sedation and analgesia were obtained, but uterine inertia occurred, labour was significantly prolonged and the forceps delivery rate was increased. (4) " Gas and air" analgesia was not potentiated by chlorpromazine. () Chlorpromazine had no adverse effects on the infants or on the third stage of labour and no severe side effects of the drug occurred. ACKNOWLEDGMENTS My thanks are due to Dr. Fairer of Charing Cross Hospital for his help at the commencement of this trial and for his advice regarding the dosage of chlorpromazine. I also wish to thank the staff of Kingsbury Maternity Hospital for their willing cooperation, and Mr. Everard Williams, Miss Josephine Barnes and Mr. Robert Rees, under whose care these patients were confined. Largactil (chlorpromazine hydrochloride) for this trial was generously supplied by May and Baker Ltd. REFERENCES Albert, N., Bateman, J. C, and Klopp, C. T. (94). Proc. A'mer. Ass. Cancer Res.,, 0. Lacomme, M., Laborit, H., Le Lorier, G., and Pommier, M. (92). Bull. Ass. Gynaec. Obstet. Langue. front., 4, 8. R&ttger, H. (9). Unpublished paper read at the 2th Session of the Lower Rhine and Westphalian Society for Gynaecology and Obstetrics, Dussoldorf,' November Sadove, M. S., Levin, M. L, Rose, R. F., Schwartz, L, Downloaded from at Pennsylvania State University on May 2, 6