- Email: [email protected]
Reply to Drs. Barclay and Weinberg
CORRESPONDENCE
Effect of meperidine on uterine contractility To the Editors: Res ipsa loquitur reasoning and propter hoc thinking have no place in physiologic research. The article, "Effect of Meperidine on Uterine Contractility," by DeVoe, DeVoe, Rigsby, and McDaniels which appears in the December 1 issue of your JouRNAL is an example par excellence of faulty experimental design, inadequate statisti= cal evaluation, and invalid conclusion. The criteria for selection of subjects were not specified. No mention was made of parity. The population could be quite nonhomogeneous. Some patients were in spontaneous labor. Other patients had labor induced with Pitocin or sparteine sulfate by one of three different routes. May we assume that the labor pattern each of these routes and agents produce is similar? Amniotomy adds yet another uncontrolled factor. At the outset, therefore, the study involves five, and with the addition of meperidine six, independent variables. Using an apparently arbitrary level of significance of 15 per cent change in uterine activity, the authors found "increased" uterine activity following the administration of large doses of meperidine in 22 of 45 patients. At what level of probability is a 15 per cent difference a statistically significant variation? By what statistical test are the 22 who showed "increased" uterine activity different from the 23 who did not show "increased" activity? The most important shortcoming in this paper is the assumption that the coincidental administration of meperidine at the onset of the phase of maximum acceleration of labor is the cause of the acceleration. This may be likened to the statement: The dock stopped and grandfather died. The temporal relationship between the clock stopping and grandfather dying is unquestionable. Only a child, however, would insist that grandfather died because the clock stopped.
Although the expression has become somewhat worn with use, it is important to remember that, statistically, correlation does not imply causation. The authors have anticipated such criticism in their discussion but did not anticipate the effects of a myriad of uncontrolled factors which make their study both inconclusive and not greatly significant. Mel L. Barclay, M.D. Jerrold H. Weinberg, M.D. Department of Obstetrics and Gynecology Sinai Hospital of Detroit Detroit, Michigan 48235 6767 West Outer Drive December 24, 1969
Reply to Drs. Barclay and Weinberg To the Editors: The point of our paper ("Effect of Meperidine on Uterine Contractility," 105: 1004, 1969) has clearly eluded Drs. Barclay and Weinberg. It is simply that meperidine could not reasonably be accused of retarding labor. We did not suggest that meperidine caused the accelerations demonstrated, and, indeed, we carefully refrained from making that implication. We merely pointed out that the administration of meperidine is often associated with an increase in uterine activity and certainly not the decrease traditionally assigned to it. A change in uterine activity of ± 15 per cent in Montevideo units (M.U.) is commonly accepted as a significant variation, based on the experience of Hendricks.1 Our experimental group v:as composed of forty-five unselected volunteers of various parities from the obstetric clinic whose labors were managed in a variety of manners, permitting evaluation of meperidine in a number of situations typical of its use in clinical obstetrics. Since we were measuring uterine contractility,
1269
1270
Corresponde1ce
Amer.
not cervical dilatation, against time, we do not feei that parity is a significant variable. REFERENCE
1. Hendricks, Charles: Personal communication to Keith DeVoe, Jr. Siephen
f.
De v· oe) lvf.D.
Department of Obstetrics and Gynecology
Hospital of the Unive;jity of Pennsylvania Philadelphia, Pennsylvania 19104 February 20, 1970
Effect of meperidine on uterine contractility To the Editors: Reference is made to DeVoe and associates' paper, "Effect of Meperidine on Uterine Contractility" (AMER. J OnsTET. GYNEC. 105: 1004, 1969). May I call the readers' attention to the article of Sica-Blanco, Rozada, and Remedio: "Effect of Meperdine on Uterine Contractility During Pregnancy and Prdabor" (AMER. J. 0BSTET. GYNEC. 97: 1096, 1967) where the subject was originally explored. That this reference was not included in DeVoe and associates' article is an oversight which I tmst the authors will correct. My congradulations to Dr. DeVoe for a wellconducted study.
Silvio Aladjem, M.D.
Case Western Reserve University
Cleveland, Ohio 44106 December 12, 1969
Reply to Dr. Aladjem To the Editors: The communication of Dr. Aladjem is noted with appreciation. Though our study was limited to the effect of meperidine on uterine contractility during active tabor, the article mentioned (Effect of Meperidine on Uterine Contractility During Pregnancy and Prdabor, AMER. J. OllSTET. GYNEC. 97: 1096, 1967) makes a worthwhile addition to our bibliography. Stephen J. DeVoe, M.D. Department of Obstetrics and Gynecology Hospital of the University of Pennsylvania Philadelphia, Pennsylvania 19104 February 20, 1970
The oversuppression syndrome To the Editors: The article by Dr. MacLeod and colleagues on "The Oversuppression Syndrome" stresses
J.
August 15, 1970 Obstet. Gynec.
that the post oral contraceptive amenorrhea is always seen wlln only the combination type drugs. 1 While this is generally true, it has been reported with a sequential oral contraceptive. 2 - 4 The authors also state that women should be allowed to ovulate every 2 years to prevent this problem. Aiihough this is an interesting concept, there is no proof to support it. How does one select a 2 year interval to continue the drugs when many of the amenorrhea cases reported occurred after only 3 to 12 months of treatment? Indeed, there can still be some question whether oral contraceptives cause the amenorrhea as its occurrence in the literature amounts to only approximately 105 cases out of millions of women using these drugs. 1 ·5 Even if only a small fraction of the cases are reported, the actual numbers may be lower than expected from the spontaneous occurrence of secondary amenorrhea of 6 months' duration. The authors limit the workup of these patients presumability on the hypothesis that the amenorrhea is caused by the drugs. Since the etiology may not be the oral contraceptives, it would seem that a thorough in-depth gynecologic endocrine evaluation of each case is in order. Finally, since effective therapy is available for this small group, one wonders about the wisdom of discontinuing the drugs on millions of women to perhaps aid a few. REFERENCES
1. MacLeod, S. C., Parker, A. S., and Perlin, I. A.: AMER. J. 0BSTET. GYNEC. 106: 359, 1970. 2. Baillie, P.: S. Afr. ]. Obstet. Gynec. 6: 71, 1f\CO 1JUU.
3. Spellacy, W. N.: Southern Med. 1968. 4. Halbert, D. R., and Christian, C. Gynec. 34: 161, 1969. 5. Reyniak, ]. V., Sedlis, A., Stone, Rrunieri, J.: Surg. Forum 20: 414_,
]. 61: 542, D.: Obstet. M. L., and 196ft
William N. Spellacy, M.D. Department of Obstetrics and Gynecology School of Medicine P. 0. Box 875 Biscayne Annex Miami, Florida 33152
Reply to Dr. Spellacy To the Editors: I would like very much to respond to Dr. Spellacy's letter regarding our recent report in the AMERICAN JoURNAL OF OBSTETRICS AND GYNECOLOGY on "The Oversuppression Syn· drome."
Effect of meperidine on uterine contractility To the Editors: Res ipsa loquitur reasoning and propter hoc thinking have no place in physiologic research. The article, "Effect of Meperidine on Uterine Contractility," by DeVoe, DeVoe, Rigsby, and McDaniels which appears in the December 1 issue of your JouRNAL is an example par excellence of faulty experimental design, inadequate statisti= cal evaluation, and invalid conclusion. The criteria for selection of subjects were not specified. No mention was made of parity. The population could be quite nonhomogeneous. Some patients were in spontaneous labor. Other patients had labor induced with Pitocin or sparteine sulfate by one of three different routes. May we assume that the labor pattern each of these routes and agents produce is similar? Amniotomy adds yet another uncontrolled factor. At the outset, therefore, the study involves five, and with the addition of meperidine six, independent variables. Using an apparently arbitrary level of significance of 15 per cent change in uterine activity, the authors found "increased" uterine activity following the administration of large doses of meperidine in 22 of 45 patients. At what level of probability is a 15 per cent difference a statistically significant variation? By what statistical test are the 22 who showed "increased" uterine activity different from the 23 who did not show "increased" activity? The most important shortcoming in this paper is the assumption that the coincidental administration of meperidine at the onset of the phase of maximum acceleration of labor is the cause of the acceleration. This may be likened to the statement: The dock stopped and grandfather died. The temporal relationship between the clock stopping and grandfather dying is unquestionable. Only a child, however, would insist that grandfather died because the clock stopped.
Although the expression has become somewhat worn with use, it is important to remember that, statistically, correlation does not imply causation. The authors have anticipated such criticism in their discussion but did not anticipate the effects of a myriad of uncontrolled factors which make their study both inconclusive and not greatly significant. Mel L. Barclay, M.D. Jerrold H. Weinberg, M.D. Department of Obstetrics and Gynecology Sinai Hospital of Detroit Detroit, Michigan 48235 6767 West Outer Drive December 24, 1969
Reply to Drs. Barclay and Weinberg To the Editors: The point of our paper ("Effect of Meperidine on Uterine Contractility," 105: 1004, 1969) has clearly eluded Drs. Barclay and Weinberg. It is simply that meperidine could not reasonably be accused of retarding labor. We did not suggest that meperidine caused the accelerations demonstrated, and, indeed, we carefully refrained from making that implication. We merely pointed out that the administration of meperidine is often associated with an increase in uterine activity and certainly not the decrease traditionally assigned to it. A change in uterine activity of ± 15 per cent in Montevideo units (M.U.) is commonly accepted as a significant variation, based on the experience of Hendricks.1 Our experimental group v:as composed of forty-five unselected volunteers of various parities from the obstetric clinic whose labors were managed in a variety of manners, permitting evaluation of meperidine in a number of situations typical of its use in clinical obstetrics. Since we were measuring uterine contractility,
1269
1270
Corresponde1ce
Amer.
not cervical dilatation, against time, we do not feei that parity is a significant variable. REFERENCE
1. Hendricks, Charles: Personal communication to Keith DeVoe, Jr. Siephen
f.
De v· oe) lvf.D.
Department of Obstetrics and Gynecology
Hospital of the Unive;jity of Pennsylvania Philadelphia, Pennsylvania 19104 February 20, 1970
Effect of meperidine on uterine contractility To the Editors: Reference is made to DeVoe and associates' paper, "Effect of Meperidine on Uterine Contractility" (AMER. J OnsTET. GYNEC. 105: 1004, 1969). May I call the readers' attention to the article of Sica-Blanco, Rozada, and Remedio: "Effect of Meperdine on Uterine Contractility During Pregnancy and Prdabor" (AMER. J. 0BSTET. GYNEC. 97: 1096, 1967) where the subject was originally explored. That this reference was not included in DeVoe and associates' article is an oversight which I tmst the authors will correct. My congradulations to Dr. DeVoe for a wellconducted study.
Silvio Aladjem, M.D.
Case Western Reserve University
Cleveland, Ohio 44106 December 12, 1969
Reply to Dr. Aladjem To the Editors: The communication of Dr. Aladjem is noted with appreciation. Though our study was limited to the effect of meperidine on uterine contractility during active tabor, the article mentioned (Effect of Meperidine on Uterine Contractility During Pregnancy and Prdabor, AMER. J. OllSTET. GYNEC. 97: 1096, 1967) makes a worthwhile addition to our bibliography. Stephen J. DeVoe, M.D. Department of Obstetrics and Gynecology Hospital of the University of Pennsylvania Philadelphia, Pennsylvania 19104 February 20, 1970
The oversuppression syndrome To the Editors: The article by Dr. MacLeod and colleagues on "The Oversuppression Syndrome" stresses
J.
August 15, 1970 Obstet. Gynec.
that the post oral contraceptive amenorrhea is always seen wlln only the combination type drugs. 1 While this is generally true, it has been reported with a sequential oral contraceptive. 2 - 4 The authors also state that women should be allowed to ovulate every 2 years to prevent this problem. Aiihough this is an interesting concept, there is no proof to support it. How does one select a 2 year interval to continue the drugs when many of the amenorrhea cases reported occurred after only 3 to 12 months of treatment? Indeed, there can still be some question whether oral contraceptives cause the amenorrhea as its occurrence in the literature amounts to only approximately 105 cases out of millions of women using these drugs. 1 ·5 Even if only a small fraction of the cases are reported, the actual numbers may be lower than expected from the spontaneous occurrence of secondary amenorrhea of 6 months' duration. The authors limit the workup of these patients presumability on the hypothesis that the amenorrhea is caused by the drugs. Since the etiology may not be the oral contraceptives, it would seem that a thorough in-depth gynecologic endocrine evaluation of each case is in order. Finally, since effective therapy is available for this small group, one wonders about the wisdom of discontinuing the drugs on millions of women to perhaps aid a few. REFERENCES
1. MacLeod, S. C., Parker, A. S., and Perlin, I. A.: AMER. J. 0BSTET. GYNEC. 106: 359, 1970. 2. Baillie, P.: S. Afr. ]. Obstet. Gynec. 6: 71, 1f\CO 1JUU.
3. Spellacy, W. N.: Southern Med. 1968. 4. Halbert, D. R., and Christian, C. Gynec. 34: 161, 1969. 5. Reyniak, ]. V., Sedlis, A., Stone, Rrunieri, J.: Surg. Forum 20: 414_,
]. 61: 542, D.: Obstet. M. L., and 196ft
William N. Spellacy, M.D. Department of Obstetrics and Gynecology School of Medicine P. 0. Box 875 Biscayne Annex Miami, Florida 33152
Reply to Dr. Spellacy To the Editors: I would like very much to respond to Dr. Spellacy's letter regarding our recent report in the AMERICAN JoURNAL OF OBSTETRICS AND GYNECOLOGY on "The Oversuppression Syn· drome."