In the United States, approximately 6% of the reported toxic exposures during pregnancy are the result of bites or envenomations. The latter term is used to describe toxic exposures resulting from the contact with biologic substances (toxins or venoms) produced in specialized glands or tissues from animals, usually by cutaneous (eg, in the case of jellyfish) or transdermal (parenteral) injection (in the case of snakebites, scorpion stings or bee stings).
In the assessment of a potentially venomous bite, one must distinguish the bite from one from a nonvenomous snake, bites from other animals, and puncture wounds caused by inanimate objects. In occasions the animal responsible for the envenomation is not seen or recognized. In these cases, the circumstances of the envenomation including the geographical location of the sting or bite and the clinical presentation assist in making a presumptive diagnosis.
The clinical manifestations and severity of an envenomation depend on the particular species of the animal responsible (and therefore the geographical location of the incident), the amount of toxin(s) exposed to, the size of the victim, the site of exposure, and the implementation or not of supportive and specific treatment (in the form of an antidote), if available. Anaphylactic shock can result from the repeated exposure to certain stings (eg, bees), the management of which is not addressed here as it is dealt with in a specific chapter of this book.
Though the number of animals responsible for envenomations is large (including species of fish, lizards, insects, and jellyfish) we will limit the discussion to snakebites, spider bites, and scorpion stings in North America. Given the increasing popularity of exotic animals (snakes, spider, and scorpions) as pets the possibility of envenomation by a nonendemic species exists. In these cases, expert consultation with a herpetologist or arthropod expert will be beneficial. Most zoos or poison control centers have specific information on unusual breeds of snakes. Timely consultation is highly recommended.
Snakebites during pregnancy are an uncommon event. Most fatalities associated to snake bites occur in developing countries where venomous snakes are plentiful, human populations are dense, and rapid transport and intensive medical treatment facilities are lacking.
Of the more than 120 species of snakes indigenous to the United States only 25 are venomous. The majority of these snakes belong to the subfamily Crotalinae (pit vipers: rattlesnakes, cottonmouths, and copperheads). The coral snake (Elapidae) is the only other native venomous snake. Common pit vipers in the United States include the rattle snakes (Sistrurus and Crotalus) and the moccasins snakes: cotton-mouths (Agkistrodon piscivorus) and copperheads (Agkistrodon contortrix).
Rattlesnakes cause two-thirds of all bites by identified venomous snakes in the United States.
Snake venoms are primarily composed of mixtures of proteins and polypeptides with various properties. Many proteins have enzymatic activities, whereas others produce toxic cellular effects. Actions of snake venoms can be broadly classified as inflammatory, cytotoxic, neurotoxic, and hemotoxic though this is an oversimplification as the peptides of snake venom appear to bind to multiple receptor sites in the prey. The composition of venom varies with the species and age of the snake, geographic location and time of year. Venom usually is injected into subcutaneous tissue via fangs; occasionally, intramuscular or intravenous injection can occur.
Clinically, local effects most commonly predominate, progressing from pain and edema to ecchymosis and bullae. Hematologic abnormalities, including benign defibrination with or without thrombocytopenia, may result, but severe generalized bleeding is uncommon. Local or diffuse myotoxicity and edema may result in complications such as rhabdomyolysis or compartment syndromes. Other rare general effects include cardiotoxicity, fasciculations, and shock.
About 25% of all pit viper bites and 50% of all coral snakebites in the United States do not result in envenomation and are considered “dry" bites. In the absence of positive identification, objective symptoms and signs of an envenomation become the focus of diagnosis. In some cases the appearance of the bite can be of assistance to expert herpetologists in the identification of the snake responsible for it.
The case-fatality rate of reported snake envenomations during pregnancy is approximately 4% to 5%. The case-fatality rate for fetus and neonates is approximately 20%. Both figures represent an improvement over previously reported numbers (38%-43% and 10%, respectively).
The vast majority of these losses are in utero fetal deaths. The deaths in the neonates may occur from 30 minutes to 8 days after birth.
Bleeding diathesis results from pit viper envenomation. Fetal and placental effects from the anticoagulation are postulated to produce the fetal losses. Although the specific effects of venom on the human fetus are unknown, there is evidence that snake venom may cross the placenta affecting the fetus even without evidence of envenomation in the mother. Snake venom has been shown to have uterotonic properties and fetal loss during early gestation may be due to intrauterine bleeding, hypoxia, and pyrexia.
Local measures include positive identification of the type of snake (venomous snakes generally have a triangle-shaped head). Following a bite from a venomous snake, the victim should be moved beyond striking distance, placed at rest, reassured, kept warm, and transported to the nearest medical facility as soon as possible for definitive medical care. The injured area should be immobilized in a functional position below the level of the heart. All rings, watches, and constrictive clothing should be removed. No stimulants such as caffeine or alcohol should be administered. Signs and symptoms of an envenomation might not develop immediately, which makes transportation to the nearest medical facility essential to ensure prompt and ongoing evaluation and necessary treatment if envenomation has occurred. Previously recommended first aid measures involving the use of tourniquets, incision and suction, cryotherapy, and electric shock therapy are strongly discouraged. Paramedical personnel should focus treatment on support of airway/breathing, circulation, administration of oxygen, establishment of intravenous (IV) access on the contralateral side, and transportation of the victim to the nearest medical facility. Tourniquets are not recommended but those that are not producing limb-threatening ischemia and constriction bands that have been placed as first aid should be left in place until the victim is evaluated. Because venom may be transported, a loose constriction bandage may be used to delay spread of the venom.
The snake (dead or alive) can be brought in with the victim. If possible they should be placed in a canvas bag or container. Snake parts should not be handled directly since even dead or decapitated snakes retain a bite reflex rendering them capable of inflicting a secondary bite.
Local and supportive measures for poisonous snakebite include careful cleaning of the wound, maintaining the extremity in neutral position, supportive care, potential use of antibiotics, and tetanus prophylaxis. Tetanus prophylaxis is not contraindicated in any pregnant snakebite or trauma victim who otherwise would be a candidate for the toxoid booster or antiglobulin. Mouth suction is contraindicated.
The management of snakebites is summarized in the algorithm included in Fig. 23-8. It pertains to the treatment of patients bitten by pit viper snakes (family Viperidae, subfamily Crotalinae) in the United States, including the rattlesnakes (genus Crotalus), pygmy rattlesnakes (Sistrurus), and moccasin snakes (genus Agkistrodon). Within the Agkistrodon genus are the copperhead snakes (A. contortrix) and the water moccasin (cottonmouth) snake (A. piscivorus). This proposed algorithm is not a substitute for clinical judgment. The care of these victims may vary based on the patient presentation, available treatment resources, patient comorbidities, and patient preference among other factors. Because of the many variables inherent in the management of snakebite victims, consultation with a physician specialist is recommended.
Emergency Department and Hospital Management of Pit Viper Snakebite. (Reproduced with permission from Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop, BMC Emergency Medicine 2011, 111:2. http://biomedcentral.com/1471-227X/11/2.)
From the obstetric standpoint, there should be concern for threatened abortion, vaginal bleeding, and fetal distress (revealed by fetal bradycardia). Monitoring of uterine contractions (with fetal heart rate monitoring if indicated) is recommended.
Immunotherapy (antivenom) is based on administration of antibodies produced by an animal that has been previously hyper-immunized against the venom of the corresponding or a very close species.
Most cases are mild and do not preclude continued administration of antivenom. When considering its use, the risk of adverse reaction to antivenom must be weighed against the benefits of reducing venom toxicity. While the safety of antivenom in pregnancy is unclear, the risks of withholding likely outweigh the risks of administering in correct clinical scenarios. Because copperheads carry a lesser potent venom, their bites may not require antivenin. Hypersensitivity reactions are common with antivenin use. Symptoms of acute anaphylactoid reactions, such as pruritus, urticaria, or wheezing occur in approximately 6% of patients. However, severe acute allergic reactions, including reactions involving airway compromise, have been described. For these reasons, antivenom should not be given in the field.
In the United States, mainly 2 types of poisonous spider bites are of concern, the black widow and the brown recluse. These spiders bite only when trapped or crushed against the skin. In 90 percent of suspected spider bites, the actual arachnid has been unavailable for identification. The diagnosis of spider bites is mainly clinical.
The black widow spider occasionally has been reported to envenomate a pregnant victim. The adult female black widow spider (Latrodectus mactans) has a highly neurotoxic venom (α-latrotoxin), which destabilizes the cell membranes and degranulates the nerve terminals resulting in massive noradrenaline (norepinephrine) and acetylcholine release into synapses causing excessive stimulation and fatigue of the motor end plate and muscle.
In contrast to the dermo-necrotic effects of the Loxosceles bite, the site lesion secondary to Latrodectus is unremarkable (similar to coral snake’s bite). Within about 1 hour of the bite, patients develop an autonomic and neuromuscular syndrome characterized by hypertension, tachycardia and diaphoresis, abdominal pain and tenderness, and back, chest or lower extremity pain (painful muscle spasms and cramping), and weakness within minutes to hours of envenomation These neuromuscular symptoms progress over several hours, then subside over 2 to 3 days. Severe Latrodectus envenomation is characterized by: generalized muscular pain in the back, abdomen, and chest refractory to analgesics, diaphoresis remote from envenomation site, abnormal vital signs (blood pressure >140/90 mm Hg, pulse >100), nausea and vomiting and headache. Black widow envenomations can mimic acute intra-abdominal processes and preeclampsia (abdominal pain, headache, hypertension, and proteinuria).
Laboratory workup may include a CBC, acute abdominal series, ECG and CPK to evaluate acute abdominal and chest pain syndromes.
General supportive management (airway protection, breathing and circulation per Advanced cardiac life support [ACLS] protocols) must be instituted as soon as possible. Most widow spider envenomations may be managed with opioid analgesics and sedative-hypnotics. Analgesics (morphine) and benzodiazepines (midazolam) are effective adjuvant treatment for the neuromuscular symptoms. Studies suggest benzodiazepines are more efficacious than muscle relaxants for treatment of widow spider envenomation. Antibiotics are not indicated. Tetanus immunization should be instituted following a black widow spider bite.
Though a specific antivenin for black widow bites is available and can result in resolution of most symptoms within 30 minutes from administration and decrease the need for hospitalization, it should be cautiously restricted for severe envenomation (eg, severe hypertension, unstable angina). Due to hypersensitivity, anaphylaxis, and serum sickness reactions, it should be given only in the hospital setting. The antivenin must be diluted and administered slowly (200 mL over an hour) after skin testing and antihistamines (diphenhydramine) is administered to reduce acute adverse reactions to the antivenom. Symptoms have been shown to improve within 1 hour of antivenom administration and for as long as 48 hours after envenomation. No more than 1 vial of antivenom is usually required.
There are 11 species of native Loxosceles spiders in North America. Loxosceles reclusa, also known as the brown recluse spider (BRS), are found in the United States widely, though not in the whole country. Characteristic violin-shaped markings on their backs have led brown recluses to also be known as “fiddle-back" spiders. A more distinguishing feature is the number of eyes. Whereas most spiders have 8, L. reclusa has 6 eyes arranged in a distinctive pattern of 3 pairs, known as dyads. They are nocturnal and are considered to be house spiders, as their habitat includes attics, basements, boxes, sheds, and woodpiles. The spiders are not known to migrate out of their native areas, but may be moved from place to place by humans, leading to reports of bites in nonendemic areas. Nonetheless, many bites attributed to BRS are likely not arachnid accidents or caused by other species of spiders. Physicians should be especially cautious of a history of presumptive Loxosceles envenomation from a patient in an area in which BRS are not endemic.
In South America, the more potent venom of the species Loxosceles laeta is responsible for several deaths each year.
The venom contains at least 8 enzymes, consisting of various lysins (facilitating venom spread) and sphingomyelinase D, which causes cell membrane injury and lysis, thrombosis, local ischemia, and chemotaxis.
Although most bites are asymptomatic, envenomation can begin with pain and itching that progresses to vesiculation (single clear or hemorrhagic vesicle) with violaceous necrosis and surrounding erythema, and ultimately ulcer formation and necrosis (dermonecrotic arachnidism). Differential diagnosis includes several bacterial infections, herpes simplex, Stevens-Johnson syndrome, factitious injuries, and toxic epidermal necrolysis.
Treatment of local envenomations is conservative (local wound care, cryotherapy, elevation, tetanus prophylaxis, and close follow-up). Bites may be cleaned and treated with rest-ice-compression-elevation (RICE). Mild bites may be treated symptomatically with analgesics and antihistamines. Most BRS bites heal without aggressive medical treatment.
Severe brown recluse spider bites produce dermonecrosis within 72 to 96 hours, which might be treated with rest, ice compresses, antibiotics, dapsone, and surgery delayed for several weeks. There is no consensus concerning the efficacy of any reported therapy including dapsone, colchicine, steroids, antivenom, nitroglycerin patches, surgical excision, and hyperbaric oxygen. Insufficient data exist to support their clinical use at this time. Skin grafting may be necessary after 4 to 6 weeks of standard therapy or until the lesion borders are well defined. Antivenom is not commercially available for L. reclusa. The only commercially available antivenom is for L. laeta in South America.
Loxoscelism is the term used to describe the systemic clinical syndrome caused by envenomation from the brown spiders. Systemic involvement, although uncommon, occurs more frequently in children than in adults. Systemic envenomations may be life threatening, and present with fever, constitutional symptoms, petechial eruptions, thrombocytopenia, and hemolysis with hemoglobinuric renal failure, seizures or coma, usually associated with minimal skin changes. Systemic envenomation requires supportive care and treatment of arising complications, corticosteroids to stabilize red blood cell membranes, and support of renal function.
Cases of envenomation by L. reclusa in pregnant patients have been reported. No special risks or complications resulted from these bites when managed conservatively only with low-dose prednisone No episodes of hemolysis, disorders of coagulation, or renal damage have been described.
The estimated global incidence of scorpion envenoming is about 1.5 million involving 2600 deaths per year, the majority of which occur in the Middle East and North of Africa. Over 650 species of scorpions are known to cause envenomation, of which about 30, all belonging to the family Buthidae, are potentially dangerous to humans. Scorpions are endemic mostly in arid and tropical areas. They are shy creatures, active at night during the hot season, but often live in houses or near inhabited areas which explains the high incidence of scorpion stings involving children in many parts of the world. Different venoms and clinical presentations are seen across different species. The most important clinical effects of envenomations are neuromuscular, neuroautonomic, or local tissue effects. Systemic envenoming is caused by members of the genera Centruroides (found in the Southwest region of the United States and in Mexico); Tityus (in Brazil and Trinidad); Androctonus, Buthus, Leiurus, and Nebo (in North Africa and the Near and Middle East); Hemiscorpius (in Iran, Iraq, and Baluchistan); Parabuthus (in South Africa); and Mesobuthus (in the Indian subcontinent).
The first symptom of scorpion envenoming is localized pain, which reflects the penetration of the venom and is a valuable warning signal. Systemic manifestations occur in less than a third of victims of scorpion stings.
Overstimulation of the sympathetic system results in a characteristic “adrenergic (autonomic) storm” with cardiac (tachycardia, peripheral vasoconstriction, hypertension, diaphoresis), metabolic (hyperthermia, hyperglycemia), urogenital (bladder dilatation, urinary retention), respiratory (bronchial dilation, tachypnea), and neuromuscular (mydriasis, tremor, agitation, convulsions) manifestations. In contrast, a cholinergic (or muscarinic) syndrome can occur with the combination of a hypersecretion syndrome (salivation, sweating, vomiting, urinary incontinence, bronchial hypersecretion, and diarrhea), abdominal pain, myosis, bronchospasm, bradycardia with hypotension. This syndrome seems to be rarer, delayed, or masked by the adrenergic storm. In addition, the release of inflammatory substances or vasodilators (kinins, prostaglandins) reinforces and exacerbates some symptoms (fever, dyspnea, visceral, particularly infarction) which can become dominant.
The severity of scorpion envenoming may be evaluated by a scoring system. Three grades are generally used, that is, grade I for local events, grade II for mild systemic symptoms, and grade III for life-threatening envenoming.(see Table 23-3)
TABLE 23-3.Clinical Score of Scorpion Envenoming and Corresponding Treatment. ||Download (.pdf) TABLE 23-3. Clinical Score of Scorpion Envenoming and Corresponding Treatment.
|Grade ||Symptoms ||Treatment* |
|I ||Local pain (sometime associated with local paresthesia, erythema, ecchymosis, blisters) ||Aspirin 10 mg/kg orally every 4 h |
|II || |
Mild systemic envenoming
Idem grade I + hyperthermia
Cardiovascular and respiratory symptoms: tachycardia, arrhythmia, dyspnea, hypertension/hypotension, electrocardiographic abnormalities, Hypersecretory syndrome (salivation, sweating, bronchorrhea, nausea, vomiting, diarrhea, urination)
Digestive tract: abdominal distension, abdominal cramps
Neuromuscular disorders: dysfunction of either skeletal or cranial muscles: confusion, agitation, fasciculation, dystonia, vision disorders, ptosis, aberrant eye movements
Biological disorders: hyperleukocytosis, hyperglycemia, acidosis
Immunotherapy: dose depending on antivenom titer
Prazosin 30 μg/kg orally every 6 h
Midazolam 0.05–0.2 mg/kg orally or IV (or diazepam 0.5 mg/kg IV or rectally) every 12 h
|III || |
idem grade II + multivisceral failure
Cardiovascular symptoms: heart failure, cardiogenic shock, pulmonary edema
Neuromuscular disorders: dysfunction of both skeletal and cranial muscles: convulsions, paralysis, Glasgow score 6 (in absence of sedation)
Biological disorders: Sao2, 90%, increasing biomarkers of cellular necrosis, electrolytic anomalies (decrease of Na+ and Ca++, increase of K+)
Transfer to ICU
Symptomatic treatment only is recommended in grade I (local) envenoming, for which immunotherapy is not helpful and too expensive. Acetaminophen and even a short course of NSAID’s can be considered during pregnancy. Use of analgesics, even if they are not the most essential drugs in envenoming, is still important because pain is frequent and intense. Morphine or its derivatives or analogs (codeine, tramadol), although very effective, should be avoided because the opioid receptor agonists inhibit noradrenaline reuptake, which may potentiate their effects; these agents also cause respiratory depression, worsening the patient’s respiratory condition. Systemic envenoming (grade II and III) require immunotherapy. The antivenom dosage depends on its neutralizing titer. Administration should be done via the intravenous route, either as a direct slow intravenous push in cases of severe envenoming (grade III) or by infusion in 250 mL of saline administered over 30 minutes. Immunotherapy might be repeated after 2 hours if cure is not obtained on the first attempt. In cases of cardiac arrhythmia or hypertension, prazosin (30 μg/kg orally every 6 hours for 48 hours or until clinical improvement) can be used. Prazosin is more effective than nifedipine which blocks calcium ion influx of smooth muscle cells in the arterioles and inhibits their contraction. Hydralazine inhibits release of calcium ions in the smooth muscle of the vascular wall. Although effective, hydralazine has several disadvantages, including sympathetic stimulation which increases heart rate, with a risk of myocardial infarction, and an increase in plasma renin, leading to urinary retention requiring treatment with a β2-adrenergic blocker and diuretic. Further, hydralazine administered parenterally produces a prolonged hypotensive response which is difficult to control. Clonidine could be an alternative to prazosin as it causes a decrease in heart rate and peripheral blood pressure. Dobutamine can be used alone or in combination with diuretics or antiarrhythmics in cases of heart failure (infusion of 10 μg/kg/minute until normalization of left ventricular ejection fraction, then 5 μg/kg every 12 hours). Neuromuscular disorders (tremors, cramps, convulsions) may be treated with benzodiazepines, based on clinical signs and response to treatment, that is, midazolam (0.05–0.2 mg/kg orally or intravenously) or diazepam (0.5 mg/kg intravenously or rectally) every 12 hours.
Antiparasympathetic drugs, such as atropine, are not recommended routinely in the treatment of scorpion envenoming. These cause blockage of sweating and potentiate the adrenergic effects of scorpion venom, increasing hypertension and ischemic complications.
Improvement of antivenomous sera is obtained by first separating the antibodies from other plasma components, followed by enzymatic digestion of IgG, then purification of the final product. As a consequence, efficacy and safety are significantly increased. Most of the antivenoms currently manufactured are purified fragments of immunoglobulin G (IgG) [F(ab’)2], which reduces potential adverse effects. However, poorly refined antivenoms may induce severe adverse reactions, such as shock or anaphylaxis.
A proportion of patients (usually 6%-10%), develop a reaction either early (within a few hours) or late (5 days or more) after being given an antivenom. The risk of reactions is dose-related, except in rare cases in which there has been sensitization (IgE-mediated Type I hypersensitivity) by previous exposure to animal serum, for example, to equine antivenom, tetanus-immune globulin, or rabies-immune globulin.
Early anaphylactic reactions: Usually within 10 to 180 minutes of starting antivenom, the patient begins to itch (often over the scalp) and develops urticarial, dry cough, fever, nausea, vomiting, abdominal colic, diarrhea, and tachycardia. A minority of these patients may develop severe life-threatening anaphylaxis: hypotension, bronchospasm, and angioedema. Some fatal reactions have probably been under-reported as death after snakebite is usually attributed to the venom. In most cases, these reactions are not truly “allergic". They are not IgE-mediated type I hypersensitivity reactions to horse or sheep proteins as there is no evidence of specific IgE, either by skin testing or radioallergosorbent tests (RAST). Complement activation by IgG aggregates or residual Fc fragments or direct stimulation of mast cells or basophils by antivenom protein are more likely mechanisms for these reactions.
Pyrogenic (endotoxin) reactions: Usually develop 1 to 2 hours after treatment. Symptoms include shaking chills (rigors), fever, vasodilatation, and a fall in blood pressure. Febrile convulsions may be precipitated in children. These reactions are caused by pyrogen contamination during the manufacturing process. They are commonly reported.
Late (serum sickness type) reactions: Develop 1 to 12 (mean 7) days after treatment. Clinical features include fever, nausea, vomiting, diarrhea, itching, recurrent urticaria, arthralgia, myalgia, lymphadenopathy, periarticular swellings, mononeuritis multiplex, proteinuria with immune complex nephritis and, rarely, encephalopathy. Patients who suffer early reactions and are treated with antihistamines and corticosteroid are less likely to develop late reactions.
Prophylaxis of Antivenom Reactions
There is no absolute contraindication to antivenom treatment, but patients who have reacted to horse (equine) or sheep (ovine) serum in the past (eg, after treatment with equine antitetanus serum, equine antirabies serum or equine or ovine antivenom) and those with a strong history of atopic diseases (especially severe asthma) are at high risk of severe reactions and should therefore be given antivenom only if they have signs of systemic envenoming.
In the absence of any prophylactic regimen that has proved effective in clinical trials these high risk patients may be pretreated empirically with subcutaneous epinephrine (adrenaline), intravenous antihistamines (both anti-H1, such as promethazine or chlorpheniramine; and anti-H2, such as cimetidine or ranitidine), and corticosteroids. In asthmatic patients, prophylactic use of an inhaled adrenergic β2 agonist such as salbutamol may prevent bronchospasm.