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Nifedipine as a safe and effective tocolytic agent in

the treatment of preterm labor

To the Edi tors:We read with interest the article by Carr et

al (Carr DB, Clark AL, Kernek K, Spinnato JA. Mainte-

nance oral nifedipine for preterm labor: A randomized

clinical trial. Am J Obstet Gynecol 1999;181:822-7). The

data of only 74 patients were shown in the original arti-

cles Tables I throug h II I, altho ugh there were 86 patients

randomly assigned. This opens the questions of whether

the 12 patients were equally divided between the two

groups an d whet her th e cha racteristics of Tables I

throu gh II I were similar.

We agree with the con clusion of C arr et al tha t adju-

vant to colytic thera py with nifed ipine in this group of pa-tients after initial intravenous magnesium sulfate tocoly-

sis showed no beneficial value. The question remains,

however, as to whether t he pa tients that were selected by

this enrollment procedure were the patients who nor-

mally would require maintenance therapy. Patients were

enrolled in the study after uterine quiescence had been

achieved. In how many cases could uterine quiescence

not be a chieved with intra veno us magn esium sulfate, and

therefore the patient could n ot be en rolled in the study,

and how many of these patients were delivered preterm?

Again, p atients who can be successfully managed with in-

travenous magnesium sulfate and antibiotics may repre-

sent a group no t in need o f any further th erapy. The on ly

correct way to perform such a trial is to randomly assignpatients on admission, rather than studying only the pa-

tients in whom uterine quiescence could be achieved

with intravenous magn esium sulfate.

There have been some questions lately about the effi-

cacy and safety of calcium-chan nel blockers in the treat-

ment of preterm labor. In our study1 that compared the

tocolytic efficacies of nifedipine and ritodrine we had to

discontinue ritodrine medication in 12 cases because of

severe maternal side effects. These patients were given

nifedipine instead. Because we were primarily interested

in the toco lytic efficacies of both drug s, we decided to in-

clude in the analysis only patients who actually only re-

ceived the tocolytic agent to which they had been ran-

dom ly assigned . To a void a bia s including th ese 12patients (that is, there could be a beneficial effect of

nifedipine in th is group o f 12 patients), we decided to ex-

clude th em fro m th e an alysis. Table I shows the r esults of

delay of delivery of that study1 accord ing to an intent-to-

treat analysis. There was a statistically significant differ-

ence in favor of nifedipine as compared with ritodrine in

delay of delivery for 24 hours, 48 hours, 1 week, and 2

weeks after starting to colysis. When the data for d elay of

delivery for 48 hours as mention ed in Table I were a dd ed

to th e da ta o f the meta-ana lysis of Ray,2 meta-analysis

showed that there was a pooled odds ratio in favor of

American Journal of Obstetrics and Gynecology August 2000 513

nifedipin e for delaying delivery compared with -agonists

of 1.54, with a 95% confidence interval from 1.06 to 2.24,

which is statistically significant (P= .03).

We agree with Carr et a l that the in cidence of m ater-

nal side effects with nifed ipine is significantly lower tha n

with -agonists.1, 2 In contrast to suggestions from some

anima l studies, studies in hum an bein gs did not show any

significant a lterations in uterine blood flow.3

In the late 1980s and early 1990s there were some re-

ported cases of profound hypotension, maternal death,

and neuromuscular blockade resulting from the combi-

nation of nifedipine and magnesium sulfate. The risk of

severe hypotension can be explain ed by the fact that bo thdrugs are effective calcium antagonists. However, the

clinical experience during the last decade has shown that

the a ctual risk of th is comb ination is probably limited. We

recommend caution when using high tocolytic doses of

nifedipine in combination with a bolus of intravenous

magnesium sulfate. In our opinion, nifedipine could be

used as a safe, well-tolerated and effective toco lytic agen t.

D.N.M . Papatsoni s, MD, H .P. van Geij n, M D, PhD, and

G.A. Dekker, MD, PhD

Division of Maternal-Fetal Medicine, Department of Obstetr ics and Gy-

necology, Free University H ospital, De Boelelaan 1117, 1081 HV

Amsterdam, The Netherlands

REFERENCES1. Papatsonis DN, Van G eijn H P, Adr H J, Lange FM, Bleker OP,

Dekker GA. Nifedipine versus ritodrine in th e man agement of

preterm labor: a randomized multicenter trial. Obstet Gynecol

1997;90:230-4.

2. Ray JG. Meta-an alysis of nifed ipine versus beta-sympat hom imetic

agents for tocolysis during preterm labor. J Soc Obstet Gynaecol

Ca n 1998;20:259-69.

3. Han retty KP, Whittle JM, Howie CA, Rubin P C. Effects of

nifedipine on Doppler flow velocity waveforms in severe pre-

eclampsia. BMJ 1989;299:1205-6.

6/ 8/105047

doi:10.1067/ mob.2000.105047

LETTERS TO THE EDITORS

Table I. Com parison of d elay of delivery after tocolysis

between nifedipine and ritodrine

Nifedipine Ritodrine

(n = 95) (n = 90)

Statistical

Delivery timing No. % No. % significance*

Within 24 h 11 12 23 26 P= .02Within 48 h 21 22 33 37 P= .04Within 1 wk 36 38 52 58 P= .008Within 2 wk 43 45 59 66 P= .008