Envenomations and antivenom during pregnancy

22.1

General principles about envenomation

Envenomation is the exposure to a poison or toxin resulting from a bite or sting from an animal. The medically important venomous animals consist of several major categories: snakes, spiders, scorpions, hymenoptera (bees, wasps, and ants), and marine animals (some fish and cnidarians, such as jellyfish, anemones, and corals). Information about a bite or sting is often obtained secondhand from patients or primary caregivers, and additional exposures may go unreported.

US poison control centers assist in the assessment and management of envenomations. The national database (National Poison Data System) is a source of demographic and clinical data regarding such cases, although it is subject to a number of limitations; the database does not include all envenomations, as there is no mandatory reporting requirement, and the source of information on clinical effects and treatments is secondhand, often incomplete, and variably documented [ ]. Shown in Table 22.1 are the 3555 exposures to the most common venomous animals in pregnancy from 2009 to 2018 as reported to US poison control centers. A retrospective observational study of the American Association of Poison Control Centers (AAPCC) between 2009 and 2018 revealed most venomous animal exposures in pregnancy had no effects or minor effects, there were no maternal deaths, and three fetal demises were reported following snake envenomations, although a direct correlation could not be drawn. This same study documented an increased likelihood of antivenom administration in pregnant patients with rattlesnake (85.0% vs. 58.9%) and black widow envenomations (4.8% vs. 2.2%) and decreased use of antihistamines in scorpion and hymenoptera stings [ ].

Symptoms from an envenomation often produce a characteristic reaction, depending on the venomous animal involved, which may be the same as in the nonpregnant patient, or may be more pronounced during pregnancy due to physiologic circulatory changes. For example, black widow envenomation may produce hypertension, tachycardia, sweating, and other signs of adrenergic excess in both the pregnant and nonpregnant patient [ ]. Scorpion stings can have a wide range of outcomes, from localized pain and swelling to fatal neuromuscular or cardiotoxic effects. In pregnancy, pelvic pain has been reported [ ] with animal studies showing increase in frequency and amplitude of contractions mediated by kinins [ ].

Pharmacologic therapy of envenomations is directed at symptomatic and supportive care, as well as specific therapy, if available and appropriately indicated. In general, symptomatic and supportive drugs are used sparingly and at the lowest effective doses in order to avoid confounding clinical assessment [ ]. The need for tetanus toxoid should be assessed and administered to people at risk of tetanus regardless of pregnancy status. The current American College of Obstetricians and Gynecologists recommendations include administering the Tdap vaccine between 27 and 36 weeks during every pregnancy. However, it is appropriate to administer the vaccine outside of this window during extenuating circumstances such as wound management for infection prevention [ ].

Routine use of antibiotics (e.g., dicloxacillin, cefazolin, and metronidazole) after envenomation is questionable unless signs suggestive of infection are present [ ], which is unlikely to be seen prior to 24–48 h after a bite or sting. There is no evidence in support of the administration of prophylactic antibiotics, even in snake envenomation, with its extensive tissue injury effects, unless tissue necrosis occurs. Any short-term course of standard antibiotics is presumed to be safe during pregnancy.

Any decision to use a specific antidotal therapy—antivenom—must take into account the potential for allergic reactions, either Type 1 (anaphylaxis or anaphylactoid) or Type 3 (serum sickness) and the risk–benefit assessment in pregnancy includes the potential for adverse effects on the fetus. Antivenoms, currently available for some snake, spider, and scorpion envenomations, are generally indicated when there is (1) evidence of systemic envenomation (e.g., neurotoxicity, coagulopathy, rhabdomyolysis, persistent hypotension, or renal failure) or (2) severe local envenomation effects; for example, extensive local tissue injury in snakebite [ , ]. Antivenoms have not been specifically evaluated in pregnant patients, but despite limited evidence, long experience and observation have not demonstrated any particular risks. Antidotes should be used when there is a clear maternal indication to decrease the morbidity and mortality associated with envenomation [ ] and, in general, the management which is most beneficial to the mother will provide the best outcome for the pregnancy. Consultation with a poison center and its medical toxicologist or other clinician with expertise in managing envenomations is recommended when treating an envenomated pregnant patient. The poison center can also be helpful in locating and obtaining antivenom for unusual or nonnative (exotic) species, which may not be stocked routinely at a hospital pharmacy.

Pregnancy tests are recommended for any woman of reproductive age who is envenomated. Other laboratory studies are guided by the usual assessment of any particular envenomation. Additional serum testing (electrolytes, coagulation tests, liver enzymes, etc.) may be needed depending upon the scenario and clinical course. As an example, it is standard to obtain a complete blood count, platelets, and coagulation studies with certain Crotalinae [WU3] (rattlesnake, copperhead, and cottonmouth) snakebites.

Concerns about pregnancy, or obvious pregnancy-related risks or effects, may prompt providers to observe envenomated patients longer in an emergency department, or to admit them to the hospital for monitoring or additional treatment. There are little data on pregnancy outcomes in most envenomations. Some studies and reports of high rates of fetal loss in other parts of the world may be secondary to venomous animals with higher degrees of maternal or fetal toxicity or may be secondary to a lack of appropriate medical care in their native environments. In the United States, there are few reports of adverse pregnancy outcomes with envenomations, other than when there is significant maternal toxicity. Regardless, before discharge from a health facility, patients should be coherent, tolerate oral intake, have no progression of symptoms, and any pain should be adequately controlled with oral analgesics. Pregnant patients should have no pregnancy-related risks, and appropriate discharge instructions and follow-up care should be given. More long-term evaluations of individual cases are encouraged to better characterize the long-term results of specific envenomations in pregnancy and to determine any additional strategies other than standard therapies.

22.2

Snake bites

The World Health Organization reports there is evidence that 4.5–5.4 million people a year are bitten by snakes, 1.8–2.7 million of them develop clinical illness, and the death toll could range from 81,000 to 138,000 [ ]. There are five major families of venomous snakes: Atractaspididae, Colubridae, Elapidae, Hydrophiidae, and Viperidae. In the United States, Viperidae are represented by three genera and over 30 species of the subfamily Crotalinae (rattlesnakes, copperheads, and cottonmouths) and two genera and three species of one elapid (family: Elapidae), the coral snake.

Crotalinae generally produce a syndrome characterized by local tissue injury, which may include necrosis and hematologic toxicity, including thrombocytopenia, hypofibrinogenemia, and other coagulation abnormalities. There may be systemic effects, such as nausea and diaphoresis or hypotension and, rarely, neurotoxicity such as muscle fasciculation or weakness, that usually do not result in respiratory compromise. The coral snake generally does not produce significant local tissue effects and primarily produces neurotoxicity, which can include respiratory arrest. In other parts of the world, elapids may produce significant local tissue injury, rhabdomyolysis, renal injury, or other effects [ ].

Knowledge about the toxicity profiles of local snake species is vital. Expert advice should be sought managing a snake envenomation in a pregnant patient if the envenomation is unfamiliar to the clinician or severe or unusual effects occur. Snakes vary widely in appearance, and identification is rarely possible by the clinician. A digital photo taken at a safe distance may be useful. In places where numerous genera or species overlap, and species-specific antivenom is available, such as Australia, venom detection kits can be useful in determining the appropriate monovalent antivenom [ ]. If there is doubt about the snake's identity, treatment should be administered for an unidentified snake bite.

22.3

Spider bites

Spider bites are rare medical events, since only a handful of species cause difficulties in humans. Very few species have muscles powerful enough to penetrate human skin, and most of those spiders bite humans only in rare circumstances. Furthermore, the venom of most spiders has little or no effect. The most likely to inflict significant bites in humans are Latrodectus (“widow”) spiders and Loxosceles species (“recluse”) spiders. A spider bite usually presents acutely as a localized solitary papule, pustule, or wheal. Systemic symptoms can accompany some envenomations. Allergic reactions typically result from contact with spiders.

Widow venom contains α-latrotoxin, which provokes a massive presynaptic release of acetylcholine, dopamine, norepinephrine, epinephrine, and glutamate. After a bite, the wound site may become painful, erythematous, and edematous and can have a classic appearance of isolated diaphoresis within an area of central clearing. Neuromuscular symptoms, including severe muscle pain and cramping, usually occur within an hour. Increased autonomic functions leading to tachycardia, tachypnea, and hypertension are also associated and are often correlated with increased pain. Some patients may progress to systemic manifestations (latrodectism) with symptoms including diffuse muscle rigidity and cramping, tenderness, and burning around the bite, truncal and abdominal tenderness, nausea, and vomiting [ ].

Bites from Loxosceles spiders are customarily necrotic. Their venom contains hyaluronidase and sphingomyelinase D enzymes that along with platelet aggregation and neutrophil activity exacerbate necrosis. Local manifestations of the bite include edema, inflammation, hemorrhage, damage to the vessel wall, thrombosis, and necrosis [ ]. Systemic loxoscelism can include acute renal failure, rhabdomyolysis, intravascular hemolysis, and coagulopathy [ ] although very few cases and no associated mortalities have been reported in pregnancy. Given extensive differential diagnosis for skin necrosis, and low prevalence of spider bites, the diagnosis of loxoscelism syndrome should be considered only when a spider is caught in the act of biting or otherwise reliably associated with a lesion [ ].

Most patients' reports of spider bites are unreliable unless directly witnessed and retrieved for identification. Those who did not clearly witness the bite should be presumed to have some other disorder, and the finding of multiple skin lesions essentially excludes the diagnosis of spider bite. Papules and pustules should be carefully unroofed and cultured to identify infectious causes. Common infections that could be mistaken for spider bites include staphylococcal and streptococcal infections, a skin lesion of early Lyme disease, and atypical presentations of herpes zoster or herpes simplex.