Analgesic-Potentiating Effect of Chlorpromazine During Labor A study of 2093 patients JOHN E. LINDLEY, M.D., STANLEY F. ROGERS, M.D., and JOHN H. MOYER, M.D. ees undertaken for the pur- pose of evaluating the analgesic effect of chlorpromazine during labor. It appeared that chlorpromazine would be desirable in labor because of its known potentiating ef- fect on analgesics, and its use might allow a reduction in dosage, or possibly {he elim- ination of the more depressant-type medica- tion, such as barbiturates and narcotics. Also, the sedative, tranquilizing, and anti- emetic, effects of chlorpromazine should be very desirable for the patient in labor who frequently is nauseated. Since this study has been in progress, several reports,"*"® have been published which present favorable evidence for the use of chlorpromazine in labor. The present re~ port confirms this work to a large extent, especially with regard to the optimal dosage of chlorpromazine required to produce a maximum potentiating effect on meperidine and scopolamine. Harer presented a well- controlled study of 500 patients receiving chlorpromazine during labor. He arrived at From the Departments of Obstetries and Gyne- cology, and Pharmacology, Baylor University Col- lege of Medicine, and the Obstetrical Service of Jefferson Davis Hospital, Houston, Texas. Present address (J. E. L.): Department of Ob- stetries and Gynecology, University of Mississippi School of Medicine, Jackson, Mi ** 10-(3-dimethylaminopropyl)-2-chlorphenothia- zine hydrochloride. Supplied by Smith, Kline & French Laboratories as ‘Thorazine, 582 an effective dose of 50 mg. of chlorproma- zine, as compared to 25 mg. in the present series. METHOD AND MATERIAL The study includes 1881 charity patients who delivered at the Jefferson Davis Hos- pital, a city-county hospital, and 212 of the authors’ private patients. In the charity group all obstetric patients who were in labor were given chlorpromazine, except those with hy- pertension, The hypertensive patients were omitted because of a concomitant study in which reserpine was used for the treatment of toxemia of pregnancy. No barbiturates were given to the patients because it was thought that the primary sed- ative effect of chlorpromazine would act as an effective substitute, and thereby eliminate the known fetal respiratory depressant re- sponse to barbiturates. All drugs were given intramuscularly, and the first dose was given as soon as the patient began to complain of significant pain. The drugs were repeated every 2 to 3 hours, as needed. The drugs— chlorpromazine, meperidine, and scopola- ‘mine—were combined in the same syringe and given as a single injection, Five different therapeutic programs were used in an effort to determine the optimal regimen for the maximum potentiating eflect of chlorproma- zine, The first program’ consisted of chlor- promazine alone, while the other four con-CHLORPROMAZINE DURING Taste 1. Resuurs Onrainen Fox PAIN R CiLonrromazine DuntinG Lavon; Five DIFFERENT Dosac LABOR LLIEF AND SEDATION IN 1881 PatuENrs wert Reaimens Were EVALUATED By PHYSICIAN aT END OF LAWOR, AND HY PATIENT ON Fikst PosrpaRruM DAY Drugs and dosage (given intramuscularly «as needed for pain) Total no, patient Chlorpromazine only, 25 mg. 79 Chlorpremazine, 25 mg., and meperidine, 25 mg, 187128 68 Chlorpromazine, 25'mg., meperidine, 25 mg,, and scopolamine, 0.4 mg, 520453. 87 Chlorpromazine, 12.5 1 meperidine, 50 mg., and scopolamine, 0.4 mg. 46 41 89 Chlorpromazine, 25 mg., meperidine, $0 mg., and scopolamine, 0.4 mg. 1049 93189 sisted of various combinations of meperidine, scopolamine, and chlorpromazine. A good result in pain relief is defined by the patient being asleep, or nearly so, be- tween uterine contractions, and suffering a minimal amount of discomfort during con- tractions, that is, not complaining of pain and showing no unusual restlessness or ob- jective evidence of pain, The evaluation of pain relief, side effects, etc., was made by the obstetric resident physician on duty in the labor suite. The patient’s own evaluation was obtained by careful questioning on the first postpartum day. CHARITY PATIENTS Observations During Labor Table 1 presents the results obtained with regard to relief of pain with the use of five different drug-dosage combinations, Evalu- ation was made by both the physician and the patient, In the initial phase of the study chlor promazine alone was used in 25-mg. doses in 79 patients. In this group the physicians evaluated 49 per cent good results, 9 per cent fair, and 42 per cent poor results, The patients’ evaluation of pain relief showed less Yel. 10, Now 8 November, 1957 Evaluation of pain relief and sedation by physician Evaluation of pain relief and sedation by patient 16 62 5 3 66 35 10 424 82 14 3 82 16 204 9 0 8 2 4 4 9 121 106 10 881 84 20 148 14 favorable results, with 37 per cent good, 9 per cent fair, and 54 per cent poor results In the next group, 187 patients, 25 mg. of meperidine were administered along with 25 mg. of chlorpromazine. Physician evaluation: 68 per cent good results, 3 per cent fair, and 29 per cent poor results. Patient evaluation in this group: 62 per cent good, 3 per cent fair, and 35 per cent poor results, In the next group of 520 patients, 0.4 mg of scopolamine was added to the 25 mg. of meperidine and 25 mg. of chlorpromazine. Physician evaluation: 87 per cent good re- sults, 3 per cent fair, and 10 per cent poor results. Patient evaluation: 82 per cent good, 3 per cent fair, and 16 per cent poor results. ‘The next group of 46 patients received 12.5 mg. of chlorpromazine, 50 mg. of me- peridine, and 0.4 mg. of scopolamine, Phy- sician evaluation in this group: 89 per cent good, 2 per cent fair, and 9 per cent poor. Evaluation by the patient: 87 per cent good, 4 per cent fair, and 9 per cent poor results. ‘The final group of 1049 patients received 25 mg. of chlorpromazine, 50 mg. of meperi- dine, and 0.4 mg. of scopolamine. Physician evaluation of pain relief in this group: 89 per cent good, 1 per cent fair, and 10 per cent poor. Patient evaluation: 84 per cent 583LINDLEY ET AL. good, 2 per cent fair, and 14 per cent poor results, In all five groups of patients, the 0.4 mg. of scopolamine was given only with the initial injection, and was not repeated. This was done to keep the patient as cooperative as le, so that saddle-block anesthesia could be used with greater ease, Also, the amount of nursing care required is reduced when the scopolamine effect is not excessive, Had repeated doses of scopolamine been given, it is probable that there would have been much greater amnesia, and thus better results in the patient evaluation, From Table 1 it can be seen that the percentage of good results obtained by patient evaluation is con- sistently lower than that of the physician in all groups, However, the correlation becomes closer as the amount of medication is in- creased. It was the general impression that these patients showed very little apprehension and the incidence of nausea arid vomiting was markedly decreased. The type of sleep ex- perienced by these patients was different from the usual barbiturate sedation in that they could usually be aroused easily to con- verse, and were able to maintain a more co- operative attitude, We believe that the most consistently ef- fective dosage schedule was that which was administered to the final group, i.e., an initial dose of 25 mg. of chlorpromazine, 50 mg, of meperidine, and 0.4 mg. of scopolamine, repeating the dosage of chlorpromazine and meperidine every 2 to 3 hours, as needed for pain, It is probable that in private patients in whom general anesthesia is commonly used, and greater amnesia is more desirable, it would be wise to repeat the initial dose of scopolamine. Certainly, some of the poor results ob- tained can be explained by the relatively high percentage of indigent patients who pre- sented themselves in an advanced stage of labor and delivered before the medication could be regulated properly. This would ob- 584 ‘Tante 2. CONDIrION oF 1887 INFANTS DELIVERED ny Morners Wao Received CHLORPROMAZINE ‘During Lanor Poor Stillborn _ viously be true of any type of analgesia eval- uated in a charity hospital. Condition of the Infant There were 1887 infants delivered by the 1881 patients, including 3 sets of twins. Table 2 presents the condition of these in- fants at birth. There were 83.8 per cent in good condition, 11.9 per cent in fair condi- tion, 2.6 per cent in poor condition, and 1.6 per cent stillborn, The infants classified in poor condition were so classified largely be- cause of apnea neonatorum for 2 minutes or more, requiring active resuscitation Those in fair condition were only in a mod- erately depressed condition and required no active resuscitation, Possible Drug Side Effects he undesirable side effects thought to be due to chlorpromazine are presented in Table 3. There were 0.85 per cent patients who developed secondary uterine inertia, apparently solely as a result of having been given the drug. These rsponded well to intra- venous Pitocin. In 0.48 per cent, profound ‘Tape 3, UNbESIRAULE ErrEcrs THoucHT Due TO CHLORPROMAZINE IN 1881 PATIENTS IN LAnOR Ne % Secondary uterine inertia thought due ‘to drug 16 0.85 Profound maternal sedation 9 048 Hypotension 6 032 Uncooperative and disoriented with hyperactive behavior (excess scopolamine effect) 191,01 ‘Transient nuchal rigidity 2 OL Urticaria 1 0.05 ‘Torat, Sipe Errects 532.82 Oba ‘GrreccteayCHLORPROMAZINE DURING LABOR, sedation beyond that thought to be desir able was observed. There was a transient nuchal rigidity in 0.1 per cent of these pa- tients, for which no other cause could be found. This is probably due to involvement of the extrapyramidal nervous system. There were 1.01 per cent who were uncooperative and disoriented with hyperactive behavior. ‘This latter side effect occurred in none of the patients to whom chlorpromazine alone had been administered and was the type of be- havior usually attributable to scopolamine. However, in view of only 1 initial dose of scopolamine having been given, it is felt that chlorpromazine was a definite contributory factor where this side effect occurred. One patient had a transient urticaria, which re- sponded well to antihistamine therapy. Although saddle-block anesthesia _ was used in 1030 patients, or 55 per cent of these 1881 deliveries, there were only six (0.32 per cent) instances of significant hypotension, and one of these was in a pa- tient who had bled ‘considerably from an abruptio placentae. This low incidence of hypotension is due, most likely, to the fact that all patients remained supine during the therapy, thus eliminating the postural hypo- tension that is associated with the use of chlorpromazine in ambulatory patients. No jaundice was observed and no evi- dence of blood dyscrasias noted clinically. This is as expected since the duration of treatment with chlorpromazine was so short. ‘There was a total of 53 (2.8 per cent) pa- tients in whom undesirable side effects from the use of the drug were observed. PRIVATE PATIENTS During the 2-year period in which the above study was undertaken, the authors used chlorpromazine in conjunction with meperidine and scopolamine in 212 private patients, In private practice the considera- tion of achieving complete relief from the pain and discomfort of labor was obtained in very nearly 100 per cent of the cases, and at ol. 10, Now 5 November 1957 the very least, a significant degree of relief was obtained. The only variable between the charity patients and the private patients was the amount of drug used to obtain this high order of relief in the latter. Dosage Schedule Currently, the following therapeutic pro- gram seems to be the most effective one. Primigravidas in early labor or patients ad- mitted for induction of labor should be given 50 mg. of chlorpromazine by mouth; follow- ing this, doses of meperidine ranging from 25 to 50 mg, and 0.3 mg. of scopolamine may be given. This latter dosage may be repeated once or twice during labor, as nec- essary. Patients already in active labor should be given 50 mg, of meperidine, 25 mg, of chlorpromazine, and 0.3 mg. of sco- polamine, all in one syringe, All these drugs may be repeated once, or perhaps twice, throughout the entire labor. In the entire group of patients, the highest total dosage of meperidine received was 150 mg. and 0.6 mg. of scopolamine along with a maximum of 100 mg. of chlorpromazine, throughout the duration of labor. Sixty-two per cent of the patients received only the initial dosage of the three drugs when they were in active labor and at approximately 4 to 5 em. cervical dilatation, Most of these patients also received saddle-block anesthesia when complete cervical dilatation was reached in primigravidas, and at 6 to 7 em. cervical dilatation in multigravidas. Eighteen per cent received 2 such doses, and the re- maining 20 per cent received the maximum dosage of 150 mg, of meperidine, 0.6 mg. of scopolamine, and 100 mg. of chlorproma- zine, Saddle-block anesthesia was also effec- tive in reducing the total quantity of drugs given. During the past 2 years no barbitu- rates have been given to patients in labor, and there have been no instances of serious apnea in the infants. The dosage requirement under this regi- men of medication represents approximately 585LINDLEY ET AL. a 50 per cent reduction in the total dosage of meperidine previously used by the authors. The dose previously varied from 100 to 300 mg, for patients in labor, and it is thought that a higher order of relief has been achieved in the patients in the current report when chlorpromazine was used. We have not ob- served anything to indicate that saddle-block anesthesia should not be used when chlor- promazine is employed, unless a marked hy- potensive effect occurs, and in our experience the few who became hypotensive were easily relieved by ephedrine or phenylephrine. SUMMARY AND CONCLUSIONS The use of chlorpromazine during labor was studied in 1881 charity patients, There were five different dosage regimens used. One was chlorpromazine alone, while the other four were a combination of chlorpromazine with meperidine and scopolamine, The most consistently effective dosage was found to be 25 mg, of chlorpromazine, 50 mg. of meperi- dine, and 0.4 mg. of scopolamine. There were 1049 patients treated under this regi- men, good results in pain relief and sedation being obtained in 89 per cent according to physician evaluation, and in 84 per cent ac- cording to patient evaluation on the first postpartum day. The incidence of apprehen- sion, nausea, and vomiting was reduced and the patients were able to maintain a more cooperative attitude, There were 1887 infants delivered by 586 these patients and their condition at birth has been discussed. The occasional undesirable side effects en- countered have been discussed and the inci- dence given, There were no patients with jaundice, Even though saddle-block anesthe- ia was used for 55 per cent of these deliv- eries, the incidence of hypotension was low (0.32 per cent). A series of 212 privately treated patients in labor has also been included, and the good results obtained have made chlorpromazine a standard of drugs used for the patient in labor. We believe that the administration of barbiturates to patients in labor is not only undesirable, but completely unnecessary. The ideal of obtaining relief from the discomforts of labor, with a minimal depressant effect on the infant, is certainly closer at hand with the use of chlorpromazine as background medication for analgesics. REFERENCES. 1. Anz, U.E., and Swirit, LJ. Clinical evatua- tion ‘of chlorpromazine’ in the management of labor. Am. J. Obst, & Gynec. 71:1242, 1956. 2. Harer, W. B, Chlorpromazine in normal labor. " Obst. & Gynec. 8:1, 1956 3. Karr, M., Lame, V. Ey and BENARON, H. B. The use of chlorpromazine in the obstetric pa. tient: A preliminary report. Am. J. Obst. & Gynec. 69:780, 1955. 4, Nortox, H. [., Wrinoantex, M., and Mo ‘The use of chlorpromazine ical sedation. Am. J. Obst. & Gynec. 7131251, 1956. 3. Scnarrer, A. L, ‘The use of chlorpromazine in labor.” Am. J. Obst. & Gynec. 7131247, 1956. Obstetrics ond ‘Grrecolony