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ABSTRACT |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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CASE REPORT |
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On arrival at the toxicologic service, the patient’s vital signs were normal; however, the swelling had progressed to her left thigh. Routine laboratory examinations showed leukocytosis with a white blood cell count of 13,400/mm3 and a positive result on a urine pregnancy test. One vial of equine-derived hemotoxic bivalent F(ab')2 antivenom was given 12.5 hours after the snake bite, and she was admitted to the clinical toxicology ward. She did not develop any adverse reactions to the antivenom, and the local swelling disappeared promptly after the administration of antivenom. On day two, her thrombin time and activated partial thromboplastin time were normal. Monitoring of the fetus did not find any evidence of hypoxia, and there was no vaginal bleeding. The patient was discharged uneventfully on the fourth day after admission and delivered a normal baby at 40 weeks of gestation (23 weeks after the snake bite). Telephone follow-up 10 years later showed no developmental delay of the child.
Case 2. A 36-year-old pregnant woman who was at 8 weeks of gestation was bitten by a green habu over proximal part of her right middle finger on December 12, 1996. Thirty minutes later, she was sent to a community hospital with local pain, bleeding, and swelling around the fang marks. Antivenom was not administered at the community hospital because of the fear of possible adverse effects. She had persistent pain and progressive swelling of right hand and was transferred to our toxicologic service approximately four hours after the snake bite.
On arrival, her vitals signs were normal. Physical examination showed that bleeding had stopped at the bite site, but ecchymosis and swelling of right forearm were noted. Laboratory data, including liver enzyme levels, renal function, pro-thrombin time, activated partial thromboplastin time, and complete blood counts were unremarkable except for mild leukocytosis with a white blood cell count of 11,600/mm3 and a positive result on a urine pregnancy test. Because mild local envenoming was suspected without evidence of further progression, a clinical toxicologist recommended only supportive care. Her condition continued to improve, and she was discharged on the third day after admission. During hospitalization, monitoring of the fetus’s condition did not show any abnormality. The patient gave birth to a normal baby girl at 39 weeks of gestation (31 weeks after the snake bite). Telephone follow-up of the child eight years later showed no growth retardation or intellectual disabilities.
Case 3. A 22-year-old pregnant woman who was at 28 weeks of gestation was bitten by green habu over right wrist on April 20, 1999. She came to a local hospital with swelling of right wrist and hand one hour after the snake bite and received one vial of equine-derived hemotoxic bivalent F(ab')2 antivenom. However, the symptoms rapidly worsened, and she was transferred to our emergency department two hours after the snake bite.
On arrival at the emergency department, physical examination showed local erythema, bleeding from fang marks, and progressive swelling of right forearm. Laboratory examinations were remarkable for mild leukocytosis with a white blood cell count of 13,900/mm3 and mild anemia with a hemoglobin level of 11.3 g/dL. Two vials of hemotoxic bivalent antivenom were administered 4 hours after the snake bite, and patient was admitted to the surgical ward for further observation and management. Another two vials of anti-venom were given 17 hours after the snake bite because of slow but steady progression of right arm swelling. On day two, the swelling extended to the right upper arm 10 cm above the elbow, and the surgeons gave her two more vials of anti-venom. In an attempt to treat patient’s toxic manifestations, she was given four more vials of antivenom two hours later and was treated with another two vials of antivenom on day three. Although she received a total of 13 vials of antivenom during the hospitalization, she did not develop any adverse effects and was discharged on day six. Fetal evaluation by ultrasonography showed normal development of the fetus. She had an uncomplicated delivery at 37 weeks of gestation (nine weeks after the venomous snake bite). Follow-up of the child by telephone after six years showed a well-developed boy.
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DISCUSSION |
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Because the prevalence of snake bite during pregnancy is low, the toxic effects and optimal management of snake envenoming in this population remain unclear. A few literature reports indicate a high rate of fetal death, mainly due to spontaneous abortion.7 Dunnihoo and others reviewed 30 reported cases of snake bite in pregnancy and found that envenoming in pregnancy by the vipers produced fetal wastage in 43% of the patients.7 Possible mechanisms for venom-related fetal death include direct effect of the venom on the fetus, fetal hypoxia due to maternal hypotension, placental bleeding due to coagulopathy, venom- or stress-induced uterine contraction, and pyrexia or cytokine release secondary to tissue damage and necrosis.6,8–10 In Taiwan, T. stejnegeri belongs to the crotaline (pit viper) subfamily and mainly produces the hemorrhagic type of venom. It causes various hemotoxic effects, ranging from mild local symptoms (e.g., pain, swelling, and bruising) to systemic complications (e.g., coagulopathy, rhabdomyolysis, and renal impairment).1,2
Although it is understandable that any major maternal complications would likely affect the fetus, it is unclear whether and how the venom components, if any, may cross the placenta. In our report, the three women were all envenomed by T. stejnegeri and were in different trimesters of their pregnancy. Although systemic manifestations were possible after T. stejnegeri envenoming, these three patients had only mild-to-moderate local symptoms and signs. Venom exposure during pregnancy may also cause teratogenesis, fetal growth retardation, or even mutagenesis.9 However, none of our patients had major maternal or fetal complications, including one patient who did not receive antivenom therapy. To our knowledge, snake bite during pregnancy has not been previously discussed in any case report in Taiwan. Our report is the first in Taiwan to suggest that T. stejnegeri envenoming does not have a strong tendency to cause venom-related spontaneous abortion, which is similar to another case report on pit viper envenoming in United States.11
Species-specific antivenom is the main therapy in the management of snake envenomation.12 Administration of antivenom in pregnant patients is a complex issue because treatment can simultaneously affect the mother and the fetus.8 The issue is further complicated by the fact that little information is currently available regarding the safety of antivenom therapy in pregnant patients. High incidence of adverse reactions, ranging from 30% to nearly 70%, for less-purified antivenom had been previously reported.6 There were also case reports of fetal hypoxic-ischemic encephalopathy or intra-uterine death from episodes of anaphylaxis to antivenom during pregnancy.13–15 In addition, the ethylmercury, one material in the thimerosal preservative of antivenom, is an organic mercury compound that crosses the placenta and causes central nerve dysfunction of the fetus.11 These findings had raised concerns about the liberal use of antivenom in pregnancy. Most researchers nevertheless still recommend that antivenom therapy of pregnant patients should be the same as for other patients because antivenom generally poses far less risk than snake envenoming in pregnancy.7,9,16
In Taiwan, the antivenom for T. stejnegeri is an equine-derived bivalent F(ab')2 antivenom specifically developed for T. stejnegeri and P. mucrosquamatus and has been shown to have a low rate of allergic reaction.17 Two patients in our current report received the F(ab')2 antivenom therapy with favorable response and did not develop any adverse effects or fetal complications, even with higher dosage of antivenom (13 vials). In addition, we did not observe any psychomotor retardation or cerebral palsy in the two children 6 and 10 years later, respectively. Our case report thus suggested a relatively high safety profile of equine-derived bivalent F(ab')2 anti-venom for pregnant women, which is consistent with prior finding for the general population in Taiwan.
The management of snake envenoming in pregnant patients should be based primarily on toxic manifestations of the mother because the clinical course of the mother seems to determine the fetal outcome. Close observation of maternal clinical symptoms and a full fetal assessment should be undertaken early and intensively during the patient’s hospital stay. Antivenom therapy should not be withheld because of pregnancy status unless the risk of anaphylaxis outweighs the benefit of alleviating the symptoms of snake envenoming. Based on our experience, the less antigenic and more purified equine-derived F(ab')2 antivenom could be a safe antidote in treating pregnant patients with T. stejnegeri envenoming. Such viewpoint of using more refined ovine-derived Fab antivenom for pit viper envenoming during pregnancy was also advocated in the case report by Chang and others.11
Received March 31, 2007. Accepted for publication April 27, 2007.
* Address correspondence to Chun-I Huang, Department of Emergency Medicine, Taipei Veterans General Hospital, 201, Shih-Pai Road Section 2, Taipei 112, Taiwan, Republic of China. E-mail: cihuang{at}vghtpe.gov.tw 
Authors’ addresses: Yen-Chia Chen, Lee-Min Wang, and Chun-I Huang, Department of Emergency Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, Republic of China, Telephone: 886-2-2827-9582, Fax: 886-2-2873-8013, E-mails: ycchen4{at}gmail.com, lmwang{at}vghtpe.gov.tw, and cihuang{at}vghtpe.gov.tw. Min-Hui Chen, Center for Drug Evaluation, Taiwan, 1F, No. 15-1, Section 1, Hang-Jou Southern Road, Taipei, Taiwan 100, Republic of China, Telephone: 886-2-2322-4567, Fax: 886-2-2327-9135, E-mail: chen.minhui{at}gmail.com. Chen-Chang Yang, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, Republic of China, Telephone: 886-2-2876-5725, Fax: 886-2-2873-9193, E-mail: ccyang{at}vghtpe.gov.tw. Yen-Wen Chen, Department of Respiratory Therapy, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, Republic of China, Telephone: 886-2-9332-41960, E-mail: albert6369{at}gmail.com.pe.gov.tw
Reprint requests: Yen-Chia Chen, Department of Emergency Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, Republic of China, Telephone: 886-2-2827-9582, Fax: 886-2-2873-8013, E-mail: ycchen4{at}gmail.com.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
