Report on oxymorphone in obstetrics

Report on oxymorphone in obstetrics DONALD L. SNOW, M.D. EDWARD SATTENSPIEL, M.D. Phoenix, Arizona

maternal gain in relief of pain. The careful selection and appropriate use of analgesic agents in obstetrics is therefore mandatory if reduction in fetal morbidity and mortality is to be accomplished. It was with these principles in mind that we undertook an obstetrical investigation of oxymorphone (Numorphan), the hydrochloride of 14-hydroxydihydromorphinone, a new synthetic derivative of morphine. It differs from dehydromorphinone hydrochloride by an hydroxyl group at the fourteenth carbon atom.

WITH modern prenatal care, the advent of antibiotics, the use of blood transfusions, and hospital delivery, maternal mortality in obstetrics has been reduced to a very low level. However, the hazards of labor and birth to the child have not been materially altered in the past 10 to 20 years, and perinatal mortality and morbidity continue to present two of the most serious problems in obstetrics. Clinical evidence suggests a correlation between asphyxia at birth and the subsequent appearance of defects in infants and children. 1 It is reasonable to conclude that permanent, although sometimes subtle, impairment of nervous function is infinitely

Methods and materials

Oxymorphone was administered to pa-

1nore v:idespread. Unfortunately, no experi-

tients on the Obstetrical Service at the

mental conditions can be created to establish the relationship in human beings and postnatal pathophysiologic abnormalities. In animal experiments, however, changes in

Maricopa County General Hospital, Phoenix, Arizona. All patients admitted in labor from October 1, 1959, through April 15, 1960, were included in this study. These patients

function as \vel! as in structure \vere demon-

were clinic or nonclinic service patients;

strated when guinea pigs were subjected to asphyxiation. 1 Of utmost concern to the physician, therefore, are those factors which can cause significant respiratory depression of the fetus. The use of narcotic drugs which may contribute to fetal hypoxia is one of these. The injudicious administration of most such agents involves risks for the mother and and particularly for the child, which occasionally are out of all proportion to the

there are no private patients at Maricopa County General Hospital. Observations of the effects of the medications were recorded by a total of 12 different physicians who were attending the patients during part or all of the period covered by this study. Due to the number of persons involved in the determination of results of this study, there has necessarily been some element of variability. The group factor, however, has helped to reduce bias. The drug was given alone in subcutaneous doses of 0.5, 0. 75, or 1.0 mg. and repeated as needed at intervals of not less than 4

From the Department of Obstetrics and Gynecology, Maricopa County General Hospital. Presenied at the Pan American Medical Congress Section on Obstetrics and Gynecology, Mexico City, Mexico, May 3, 1960.

hours. It was also used in the san1e closes

with 50 mg. of promazine, a tranquilizing agent which potentiates the action of nar-

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Volume 83 Number 1

Oxymorphone in obstetrics 23

cotics. For purposes of comparison, meperidine alone was administered in doses of 50 and 75 mg., or also in combination with 50 mg. of promazine. During the first 4 months of our study, oxymorphone and meperidine were used in alternate months. Thereafter, oxymorphone was used exclusively. A total of 262 patients received oxymorphone while 87 received meperidine. The time interval was charted between administration of drugs and subjective response. Untoward effects on the fetus during labor as manifested by alterations in fetal heart rate, fetal movements, passage of meconium, etc., were noted. Duration of each labor was determined. The elapsed time from birth to spontaneous respirations of the babies was recorded. The possible relationship between the drugs used during labor and any evidence of perinatal morbidity and mortality was explored and relative information analyzed. Analgesia was evaluated as follows: good, marked relief of pain and discomfort; fair, adequate relief; poor, minimal relief. Results and comment

Maternal factors. This study comprises 349 patients ranging in age from 13 to 42 years. The average age of multigravidas was 26 years; of primigravidas, 18. At the time

of the initial dose the average cervical dilation was 5 em. The majority of patients received only one injection throughout labor, indicating adequate duration of effective analgesia. A combination of pudendal block and trichloroethylene (Trilene) analgesia was most often used at delivery; 42 patients had spinal block (saddle) . The time interval between the administration of the drugs and the first signs of response by the patients was recorded. Of the group given oxymorphone, 188 patients ( 72 per cent) gave evidence of relief of pain in 10 minutes; and 7 (3 per cent) in over 20 minutes. In comparison, only 29 ( 33 per cent) of the patients receiving meperidine showed indications of analgesic effect in 10 minutes or less; 45 (52 per cent) in 11 to 20 minutes; and 13 (15 per cent) in 20 minutes. Seventy per cent of patients receiving varying doses of oxymorphone alone or in combination with promazine had marked relief of pain as compared to 49 per cent of patients given meperidine alone or with promazine (see Tables I and II). Another 27 per cent of the patients given oxymorphone and 35 per cent of those given meperidine obtained fair relief. Thus a total of 97 per cent of patients receiving oxymorphone had satisfactory relief of pain and discomfort

Table I. Effectiveness of oxymorphone

Result

Oxy· morphone, 1 mg.

Oxymorphone, 0.75 mg.

Oxymorphone, 0.5mg.

Oxymorphone, 1 mg., plus promazine, 50 mg.

Good Fair Poor

59 (88%) 8 (12%) 0 (0%)

60 (63%) 31 (33%) 4 (4%)

23 (SO%) 20 (44%) 3 (6%)

2 (100%) 0 (0%) 0 (0%)

Oxy· morphone, Oxy0.75 mg., morphone, plus 0.5 mg., plus promazine, promazine, 50 mg. 50 mg. 23 (88%) 3 (12%) 0 (0%)

18 (69%) 8 (31%) 0 (0%)

Total 185 (70%) 70 (27%) 7 (3%)

Table II. Effectiveness of meperidine

Result

Meperidine, 75mg.

Meperidine, 50 mg.

Good Fair Poor

3 (30%) 5 (SO%) 2 (20%)

6 (46%) 1 (8%) 6 ( 46%)

Meperidine, Meperidine, 75 mg., plus 50 mg., plus promazine, 50 mg. promazine, 50 mg.

6 (75%) 2 (25%) 0 (0%)

28 (SO%) 23 (41%) 5 (9%)

Total 43 (49%) 31 (35%) 13 ( 16%)

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January I, 1962 Am. j. Obst. & Gynec.

Snow and Sattenspiel

during labor. For meperidine this percentage was 84. The highest le\·e! of pain relief occurred in those patients to whom either 1.0 mg. oxymorphone alone (88 per cent marked relief) or 0. 75 mg. oxymorphone combined with promazine ( 88 per cent marked relief) was administered. It was the opinion of a!! observers that oxymorphone, in addition to analgesia, provided relief from apprehension and had a general quieting effect. No adverse effects on maternal respiratory rate or depth were observed, and none of the patients receiving either drug had nausea, Yormtmg, or other untoward reactions. In the oxymorphone series the average duration of labor was 9 hours m 64 primigravidas, and 7.7 hours in 198 multigravidas; in the meperidine series, 11.5 hours in 20 primigravidas, and 8. 7 hours in 67 multigravidas. Apparently the duration of labor is shortened by oxymorphone. Fetal factors. Six babies of 262 n1.others, 2.3 per cent receiving oxymorphone in labor, showed delay in respiration. After a brief interval, 3 babies breathed spontaneously while the other 3 had to be resuscitated. The delay in respiration varied from 2 to 4 minutes. Two babies of the 87 mothers, 2.4 per cent, to whom meperidine was given had a delay of respiration of 2 minutes. One required resuscitation. Analysis of the causes of the delay in both groups reveals the presence of factors such as tight cord, relative cephalopelvic disproportion, and administration of either analgesic too close to the time of delivery and implies that meperidine in the dose ranges used in this study contribute little if anything to the incidence of hypoxia and perinatal morbidity. There were 5 prenatal deaths. One antepartum death occurred prior to admission; of the other 4 infants lost in the entire series of 349 mothers, 3, including one set of twins, were very immature, while one death was associated with severe abruptio placentae. In no case could the drugs used be held responsible for the infant mortality. Oxymorphone appears to be both a safe

and effective analgesic agent for use in obstetrics. Noteworthy in this series has been the almost negligible depressing effect of the drug on the infants, the rapidity of onset of action, and the high percentage of patients obtaining marked relief of both pain and discomfort.

Summary and conclusions 1. Oxymorphone, a new and potent narcotic analgesic, was routinely administered by subcutaneous injection, alone or in combination with promazine, to 262 unselected patients in labor at the Maricopa County General Hospital. These were compared with 87 unselected obstetrical patients, who were given meperidine alone or meperidine with promazine. 2. Oxymorphone provides analgesia in labor characterized by rapid onset and adequate duration. 3. In addition to analgesia, oxymorphone provides a distinct sedative effect. It seems to shorten the first stage of labor as compared to that of patients given meperidine. 4. Of the patients receiving oxymorphone, 97 per cent had satisfactory relief of pain ( 70 per cent~ n1arked relief; 27 per cent. adequate relief) ; 84 per cent of patients receiving meperidine had satisfactory relief of pain (49 per cent, marked; 35 per cent. adequate\. 5. Neither oxymorphone nor meperidine caused nausea, Yomiting, or other untoward reactions. 6. The drug used in this study had an almost negligible respiratory depressing effect on the babies and thus did not increase perinatal morbidity or mortality. 7. The over-all fetal mortality was 1.2 per cent. None of the deaths could be attributed to the drugs used. 8. The routine use of oxymorphone in patients in labor is recommended as a safe and effective procedure. REFERENCE

1. Windle, William F.: Asphyxia Neonatorum, Springfield, Ill., 1950, Charles C Thomas, Publisher, pp. 54, 60.