Baclofen is a GABA-receptor agonist with strong antispastic activity. It has been used intrathecally to resolve tetanus-induced rigidity , and to avoid tracheotomy and mechanical ventilation of the lungs in severe tetanus . We report the first case of successful treatment of severe tetanus with intrathecal baclofen in a pregnant woman.
A 17-year-old primigravid (about 28weeks of gestation) African woman, with no previous medical history, was admitted to the Intensive Care Unit (in Bobo Dioulasso, Burkina Faso). Clinical symptoms of tetanus had begun two days before admission. She had never been immunized with tetanus toxoid. The portal of entry for C. tetanii was most likely an intramuscular injection 6 days earlier. She presented with complete lockjaw, neck and general contracture in opisthotonos with frequent paroxysms. The invasion period was 24 h, and her body temperature was 38.5°C. Subcutaneous (s.c.) serotherapy (heterologous serum 1500IU twice; Sérum antitétanique®, Pasteur vaccins, Marnes la Coquette, France), s.c. anatoxinotherapy (Tétavax®, Mérieux, Lyon, France), and intravenous (i.v.) penicillin G were started. Sedation was obtained by diazepam i.v. (20 mg h−1). The protocol of intrathecal baclofen administration and of catheter management has been described in a previous report . First a 19-gauge intrathecal catheter (Epidural Minipack®, Portex Ltd, England, UK) was implanted using aseptic conditions via the L3-L4 vertebral interspace and was advanced 3cm in the intrathecal space; correct placement was assessed by an aspiration test. Then, a first bolus of 750 μg of baclofen (Lioresal®, Novartis, Rueil Malmaison, France) was administered intrathecally through an antibacterial filter. Her muscular contracture and paroxysms disappeared within 90 min after this injection and did not recur for 24h: consciousness remained unaltered. Finally, baclofen was infused from day 1 to day 21 after her admission as boluses of 250-1500 μg once daily (mean daily dose 1350 μg). Doses were chosen to control muscle rigidity, to prevent laryngeal and diaphragmatic spasms and to keep the patient comfortable. Supplementary i.v. diazepam was used for sedation when necessary. Because there was no evidence of meningeal contamination, the same catheter was used during the entire course of the disease. Mild drowsiness lasting a few hours occurred frequently after the spinal injections, but no severe maternal side-effects related to baclofen (respiratory depression, bradycardia, or hypotension) were observed. On day 4, tracheotomy had to be performed because of laryngospasm, but mechanical ventilation of the lungs was not necessary. Baclofen therapy was stopped on day 21. The rate of i.v. diazepam was then increased to 200 mg day−1, without recurrence of the contractures. The tracheal cannula was removed on day 28. The fetus was regularly monitored with cardiotocography and an umbilical cord Doppler. Acute fetal distress was never observed. Aortocaval compression was prevented by positioning the patient on her side and changing sides frequently. On day 29, at about 32 weeks of gestation and three days after the end of the diazepam infusion, labour started spontaneously, and the patient delivered a 1500 g male baby with no muscular weakness. Clinical examination was normal, showing neither respiratory nor neurological distress; the Apgar score was 10/10 at 5min. The patient was discharged home on day 38 with her 9-day-old healthy baby.
The efficacy of intrathecal baclofen in suppressing spasms due to severe tetanus has been strongly suggested in several reports, including 14 cases that we observed in our institution in Burkina Faso . However, this is the first reported use of intrathecal baclofen for tetanus in a pregnant woman. In this instance, intrathecal baclofen, in association with i.v diazepam, was effective in resolving the spasms and thus it was possible to avoid mechanical ventilation of the lungs, although it is difficult to discriminate the role of each drug.
Tetanus occurring during pregnancy is not uncommon (6% of cases of maternal tetanus ) but has been poorly described. In our patient, because ultrasonographic examination was unavailable, we could not detect any complications during pregnancy related to possible fetal tetanus. However, no evidence of tetanus (or of the treatment we gave to the mother) was observed in the neonate after delivery.
Long-term sedation of pregnant patients in the Intensive Care Unit is also poorly documented . Diazepam largely crosses the placenta because it is a lipophilic molecule . During late pregnancy and labour, diazepam may induce a decreased fetal heart beat-to-beat variation , a low Apgar score, and a floppy infant syndrome (hypotonia, sucking difficulties, hypothermia and cyanosis) . For example, diazepam (up to 10 mg h−1, total dose 5725 mg) has been used for sedation in a case of Guillain-Barré syndrome that occurred in the third trimester . The newborn suffered from floppy infant syndrome during the first days, and plasma concentrations of desmethyldiazepam were high until the 6th day of life. However, the neonate did not require mechanical ventilation of the lungs and his psychomotor development was excellent.
To date, one case of intrathecal (but none of oral) baclofen administration in a pregnant woman has been reported . That patient was chronically treated by continuous intrathecal baclofen (1000 μg day−1) for spastic quadriplegia. The treatment was maintained during pregnancy, and a healthy girl was born by Caesarean section. Moreover, premature uterine contractions were controlled by increments in dose. The effects of pregnancy on the pharmacokinetics of baclofen have never been studied. In rats, placental transfer of baclofen is about 40% of the plasma concentration one hour after i.v. injection and is proportional to maternal plasma concentration . No tissue accumulation of baclofen was detected after 2-12 days of daily i.v. administration . Animal studies on the potential teratogenicity of baclofen produced controversial results. In three studies in rodents, baclofen was not found to have any teratogenic effect . However in rats, omphaloceles, ossification disorders and spina bifida have been reported after high doses . Because no data are available in humans, baclofen is a grade C drug in the Food and Drug Administration classification of teratogenicity in the USA . The effects of baclofen on the course of pregnancy are also unknown. In rabbits, GABAB receptors have been demonstrated in the uterus  so baclofen might directly increase the contraction of smooth muscle cells.
Finally, as it has been shown that the plasma transfer of intrathecal baclofen is extremely low , the risk of the use of intrathecal baclofen in a pregnant woman with tetanus seems theoretical, and should not limit the use of this drug in this maternal life-threatening situation.
An increasing number of observations suggests that intrathecal baclofen may be an effective treatment of tetanus with an acceptable risk of adverse effects. Thus it may be a valuable alternative in areas where mechanical ventilation of the lungs is seldom available. In this first report of tetanus occurring in a pregnant woman, intrathecal baclofen was efficient to control spasms, and was safe for both the mother and the fetus.
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