Neurotoxic snake bite in pregnancy

Case report

A 32-year-old female in her third pregnancy was bitten by a black mamba at 29 weeks of gestation. She was an undocumented immigrant from a neighbouring country, working as a seasonal worker on a farm. She was known to be HIV positive with a suppressed viral load. She stepped on the snake and, despite wearing gumboots, was struck on her upper calf. Her employer applied a tight tourniquet around her upper thigh and rushed her to the nearest hospital. During this journey to the hospital, he threatened her with immediate dismissal if she were to tell anyone where she worked or lived.

She developed respiratory failure with agonal breathing within 2.5 h of the bite. She was intubated using a rapid sequence induction, ventilated and antivenom was initiated. A fetal heart was identified but not monitored further.

As the district level hospital had no critical care facilities, she was transported to a tertiary hospital (with 800 beds and 53 ICU beds), approximately 300 km away. She received multidisciplinary care from obstetrics, critical care and emergency medicine. Upon arrival in the medical ICU, fasciculations were observed in the affected leg, in keeping with pre-synaptic blockade, that lasted another 8 h. She received 10 vials of antivenom intravenously within 20 h. It was administered two vials at a time, monitoring for anaphylactic reactions, 2 h apart. Once neurological improvement was apparent, antivenom infusions were ceased. She was not sedated and was successfully extubated within 28 h. Neostigmine and glycopyrrolate were administered prior to extubation to assist with the reversal of any post-synaptic blockade.

Localised cytotoxic oedema was developed at the site of the bite. Her creatinine kinase levels peaked at 700 U/l (normal: 22–198 U/l) and myoglobin level at 1100 ng/ml (normal: 85 ng/ml). She received intravenous fluids and maintained a good urine output. Her clotting profile remained normal throughout with a platelet count of 118 (150–400 × 10⁹/l). This mild thrombocytopenia was ascribed to pregnancy and/or HIV and was not further investigated. No arrhythmias were identified on electrocardiographic monitoring in the ICU.

She was admitted to the tertiary centre for a total of six days. Her fetus showed good growth and appeared to be unaffected by the neurotoxins. Unfortunately, due to her employer’s threats, she did not share her contact details or home address and was lost to follow-up.

Discussion

Snakebites in rural areas of low to middle income countries are relatively common. A single-centre cohort in rural South Africa reported 983 bites in five years. ¹ Approximately 16% of these bites were deemed severe bites where a form of systemic involvement was present.

An estimated 400 cases of snakebites in pregnancy have been reported in the English literature. A literature review published in 2010 reported 213 venomous snake bites in pregnancy from 1966 to 2009. ² Many of these cases were venomous bites; however, none of them were black mamba (Dendroaspis polylepis) bites. There was a total of nine maternal deaths (3.9%), and 41 fetal and neonatal deaths (19.2%). Ninety-six women received antivenom. Of the 96 women, 2 women died (2.1%) and 29 fetuses/infants died (30.2%). One hundred and six cases did not state whether antivenom was given, and not all snake species are reported. A review of the American Association of Poison Control Centres data system between 2009 and 2018 reported 191 snakebite cases in pregnancy, as opposed to 7733 non-pregnant controls. ³ No maternal deaths and three fetal deaths were reported. Different case series report between 21% and 43% fetal loss. ²

Toxic snakebites can be divided into cytotoxins (most common), neurotoxins or hemotoxins. Mamba venom causes paralysis in three different ways: polypeptides competing with acetylcholine to bind to post-synaptic nicotinic receptors of skeletal muscle; polypeptides (dendrotoxins) which facilitate the release of acetylcholine from the nerve endings and toxins (fasciculins) inhibiting synaptic acetylcholinesterase. Lastly, muscarinic receptor blockade has also been described in mamba bites. ⁴

First aid management of a snake bite includes reassurance of the victim, immobilisation of the affected limb with bandages or clothing, like splinting of a sprained ankle and urgent transfer to a medical facility. Arterial compression with a tourniquet is not advised. ⁵ If a pregnant woman is supine, the left lateral position is preferred, keeping the affected limb lower than the heart. ⁶

Patients bitten by neurotoxic snakes may develop flaccid paralysis within 1–8 h. ⁴ They need to be monitored every 15 min (Figure 1) for signs of paralysis including ptosis, facial weakness, blurred vision and peripheral paraesthesia. ⁷

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Figure 1.

Approach to snake bites in pregnancy.

Identification of the snake seems to be of less importance than the urgency with which a patient receives treatment. ² Antivenom should preferably be administered within 4 h of envenomation, but can be given up to 24 h afterwards. ⁶ Accessibility to antivenom is crucial to optimise the outcome. ⁸ Mothers who receive antivenom when bitten by poisonous snakes have a better outcome than those who do not. ⁷

Polyvalent antivenom contains antigens to puff and gaboon adders, rinkhals, mambas and cobras. It should not be used for the management of back-fanged snake bites. One vial contains 10 ml of antivenom and costs approximately R 986 ($63.50). Antivenom should be stored between 2 and 8°C and has a shelf life of three years. ⁹ Adder bites require smaller quantities; however, mambas require large quantities administered through continuous intravenous infusions until paralysis shows signs of reversal. Intramuscular injection of antivenom is not effective. This patient received a total of 100 ml over 16 h. Respiratory support is also essential for these individuals.

Antivenom as an immunoglobulin is a large particle (50,000 Da) and is thought not to cross the placenta. Drugs larger than 1000 Da cross the placenta poorly. ⁶ There is still debate about whether venom crosses the placenta. There have been reports of fetal affectation without maternal systemic affectation, suggesting transplacental transfer of venom. ¹⁰

Hypersensitivity reactions and serum sickness have been reported in 8 and 13% of patients, respectively, who have been treated with CroFab®, a brand of antivenom. ¹⁰ In Langley’s literature review, only 1 woman out of 96 women who received antivenom developed serum sickness. ² She delivered a healthy infant at term. Type I and III hypersensitivity reactions have previously been reported. Women should be observed for 24 h after cessation of antivenom for anaphylactic reactions, which can be managed with adrenaline. Type III hypersensitivity reactions may occur at a later stage and women should be counselled to seek help if they develop signs or symptoms.

The average gestational age at the time of fetal demise was 20.2 weeks. ² Some studies report poor fetal outcome if envenomation occurs in the first trimester; however, Langley reported 11 in the first trimester, 7 in the second and 10 in the third. The gestational age was not reported in many cases. In a case series by Seneviratne et al., they reported poor fetal outcome in women who received antivenom if envenomation took place at 18 weeks of gestation or earlier. ¹¹ Reported congenital malformations after envenomation included hydrocephalus with polydactyly, hydrocephalus and intracranial haemorrhage. Fetuses of mice and rabbit studies injected with venom developed cleft palate and facial deformities, hepatic and myocardial damage, pulmonary vascular congestion, bleeding into the intestinal lumen and death and resorption. ²

A number of mechanisms have been proposed for fetal death, either directly from venom in fetal circulation or indirectly from maternal illness and placental compromise. ⁶ These mechanisms include fetal hypoxia secondary to maternal shock, haemorrhage into the placenta and uterine wall leading to placental abruption, preterm contractions, either directly or indirectly from the toxin, maternal haemorrhage leading to acute fetal anaemia and potentially maternal anaphylaxis secondary to antivenom administration. ²

The recent UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2015–17 (MBRRACE) report highlighted inter-racial disparities in maternal outcomes. Black mothers are up to five times more likely to die than white mothers in the UK. ¹² This difference has not yet been investigated in South Africa; however, this case emphasises the difference in seeking help and follow-up for care of disadvantaged communities.

In summary, neurotoxic snakebites in pregnancy are rarely reported. Venomous bites are more common in rural communities where women have limited access to care. They may even choose to approach traditional healers for treatment and never be registered in hospital systems. ⁵ These cases are seldom reported and published, possibly skewing the current known literature. This woman was fortunate to receive rapid, appropriate care from her rural medical team. Fetal and early neonatal losses have been reported in all venomous snake bite victims. Polyvalent antivenom and supportive ventilation is essential in the care of neurotoxic snakebites.

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