Critical Care Obstetrics part 57 pps

Overdose, Poisoning and Envenomation During Pregnancy 549 maternal monitoring capabilities. Priorities for evaluation and resuscitation should not differ from those established for the patient who is not pregnant. As with multiple other critical situations, the best chance for fetal survival is maternal survival [174] . Local measures include positive identifi cation of the type of snake and rapid transport to defi nitive medical care. There is no universally applicable method to reliably delay the transport of venom from the bite site to the systemic circulation [169] . Calming the patient, immobilization, and splinting of the extremity bitten are crucial. A loose constriction bandage may be used to delay spread of the venom by compressing lymphatic vessels. If care is available within 60 minutes, wound incision and suc- tioning are not recommended. Unfortunately negative pressure venom extraction devices have shown no benefi t [175] . Tourniquets are not recommended as they can contribute to severe tissue destruction [169] . 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 [174] . Circumferential measurement at several points along the affected limb should be started shortly after the patient ’ s arrival and repeated hourly until progression has ceased [172] . In general indications for antivenom use are: (a) hypotension or other signs and symptoms of autopharmacological reactions, (b) hemostatic abnormalities or spontaneous systemic bleeding, (c) paralysis, (d) rhabdomyolysis, (e) cardiovascular signs and symptoms, and (f) renal compromise [169] . In local envenomation, antivenom is indicated if: (a) the species involved is known to cause local tissue necrosis, (b) there is swelling involving more than half of the bitten limb, (c) there is rapidly progressive swelling, and (d) there are bites on fi ngers and/or toes [169] . Although there is no universal grading system for snakebites, a I – IV grading scale is clinically useful as a guide to antivenom administration (Table 39.26 ). When considering the use of antivenom, the risk of adverse reaction to its administration must be weighed against the benefi ts of reducing venom toxicity. In general, antivenom should USA include the rattlesnakes ( Sistrurus and Crotalus spp.) and the moccasins snakes: cotton - mouths ( Agkistrodon piscivorus ) and copperheads ( Agkistrodon contortrix ). Overall, rattlesnakes cause two - thirds of all bites by identifi ed venomous snakes in the USA. Venom usually is injected into subcutaneous tissue via fangs; occasionally, intramuscular or intravenous injection can occur. Dry bites (no envenomation) occur in as many as 50% of strikes. Venom generally is composed of several digestive enzymes and spreading factors, which result in local and systemic injury. The venom may be cytotoxic, hematotoxic, neurotoxic, rhab- domyolytic, cardiotoxic, nephrotoxic, or may cause an autoim- mune reaction (complement activation). In general, viper (Crotalidae spp.) venom is mainly cytotoxic, whereas elapid venom is mainly neurotoxic, colubrid venom predominantly hemotoxic, and sea snake venom chiefl y myotoxic [174] . Subdivision of symptoms into local, autopharmacological, antihemostatic, neurological, muscular, cardiac, and renal effects help to stage the patient. In conjunction with information on geographical distribution, habitat, and behavior of the snake, the clinical pattern of symptoms and signs is useful to identify the culprit of the envenomation [169] . Clinically, local effects most commonly predominate, progressing from pain and edema to ecchymosis and bullae. Hematologic abnormalities, including benign defi brination with or without thrombocytopenia, may result, but severe generalized bleeding is uncommon. Local or diffuse myotoxicity may result in complications such as compartment syndrome or rhabdomyolysis. Neurotoxins produce neuromuscular blockade and nerve conduction. Prodromal symptoms of neurotoxicity (drowsiness, hypersalivation, diaphoresis, fasciculations and circumoral paresthesias) are often followed by specifi c effects on cranial nerves. Progressive respiratory paralysis is the most serious neurotoxic effect [174] . Other rare general effects include cardiotoxicity, fasciculations, and shock. In the event of snakebite during pregnancy, all patients should be transported (left lateral decubitus since a maternal death after snakebite has been reported for presumptive supine hypotensive syndrome) to a medical care facility with appropriate fetal and Type of snake No. Minor effect Moderate effects Major effects No. follow - up Copperhead 2 2 (100%) 0 0 0 Rattlesnake 3 2 (67%) 0 1 (33%) 0 Nonpoisonous 8 3 (37%) 0 0 5 (63%) Unknown snake 5 3 (60%) 1 (20%) 0 1 (20%) Total 18 10 (56%) 1 (5%) 1 (5%) 6 (34%) Minor effects are signs or symptoms developing from the exposure but minimally bothersome and generally resolving without residual disability. A moderate effect is one that is more pronounced or prolonged than minor effects, usually requiring some form of treatment. Major effects are life - threatening signs or symptoms of the exposure that result in signifi cant disability or disfi gurement. (Reproduced by permission from Toxic Exposure Surveillance System (TESS). Exposures in Pregnant Women, 1999. AAPCC 2000.) Table 39.25 Snake envenomation during pregnancy by type of snake and maternal effects, US: 1999. Chapter 39 550 are unknown, there is evidence that snake venom may cross the placenta affecting the fetus even without evidence of envenomation in the mother [178] . The effects of venom on the human fetus are unknown. Venom exposure during pregnancy may result in teratogenesis, fetal growth retardation, or even mutagen- esis. It is also undetermined what effect the different types of venom, the amount and the route of exposure have on the fetus. Snake venom has uterotonic properties and fetal wastage during early gestation may be due to intrauterine bleeding, hypoxia and pyrexia [174,179] . The absence of short - term and long - term vari- ability in the fetal heart rate is an ominous sign and along the lack of fetal movements, suggest depression of the CNS of the fetus [174] . We were unable to fi nd any English - language reports of coral snakes (characterized by a black snout and an alternating pattern of black, yellow, and red) envenomation during pregnancy. Coral snakes and sea snakes of the Elapidae family are much less effi - cient in injecting venom into large prey; thus, their poor effi - ciency at envenomation, coupled with their relatively small size and shy nature, may play a role in the paucity of information concerning these snake bites during pregnancy. Coral snake bites often show little local reaction. Systemic effects may be delayed for several hours. Because of the neurotoxicity of coral snake venom, coral snake antivenin is usually recommended for its victims. Of note, the net effect of these neurotoxins is a curare like syndrome, thus contraindicating the use of magnesium sulfate as a tocolytic if patient develops preterm labor. Occasionally, a victim will present with the bite of a rare, exotic snake. Most zoos or poison control centers have specifi c information on unusual breeds of snakes. Timely consultation is highly recommended [180] . not be given in the fi eld because of the risk of severe allergic complications. Hypersensitivity reactions are common with antivenin use (23 – 56%) [172] . Skin testing (which may be unreliable) and careful monitoring must be available and used when antivenin is given. The quality of the antivenoms and its frequency of severe side effects (nearly 50% of patients treated) makes monitoring and treatment of side effects an important part of the management of these patients. Crotalidae polyvalent immune Fab antivenom (CroFab or FabAV, a sheep - derived antigen - binding fragment) is more specifi cally tailored for crotalids of North America and is less aller- genic than equine - derived whole immunoglobulin antivenoms. With pit viper poisoning, antivenin is usually recommended for grade III or IV bites. Crotalidae polyvalent immune Fab antivenom effectively controls the effects of envenomation; however, initial control of coagulopathy is diffi cult to achieve in some cases, and recurrence or delayed - onset hematotoxicity is not uncommon [176] . Because copperheads carry a lesser potent venom, their bites usually do not require antivenin. Fasciotomies may be required occasionally but only after con- fi rmation of the presumptive diagnosis of compartment syndrome (pressures above 30 mmHg) and adequate treatment with antivenom [172] . In their review of snakebites during pregnancy, Dunnihoo et al [177] . reported an overall fetal wastage of 43% and a maternal mortality of 10%. Bleeding diathesis resulted from pit viper envenomation. Possible mechanisms for the fetal losses may be anoxia associated with shock, bleeding into the placenta and uterine wall and uterine contractions initiated by the venom [174] . Although the specifi c effects of venom on the human fetus Table 39.26 Grading of snakebite poisoning. Grade Envenomation Skin effects Symptoms Lab abnormalities I None 1 inch of edema or erythema, puncture wounds None None II Minimal 1 – 5 inch of edema or erythema within fi rst 12 h None None III Moderate 6 – 12 inch of edema or erythema within fi rst 12 h Minimal (nausea, vomiting, paresthesias, metallic taste, and fasciculations) Platelets < 90 000/ µ L Fibrinogen < 100 mg/dL) PT > 14 s CK > 500 – 1000 U/L IV Severe Rapidly involves the entire part; potential compartment syndrome Systemic effects may include shock, diffuse or life - threatening bleeding, renal failure, respiratory diffi culty, and altered mental status Platelets < 20 000/ µ L Any abnormal coagulation parameter associated with potentially life - threatening bleeding Rhabdomyolysis Myoglobinuric renal failure PT, prothrombin time; CK, creatine kinase. (From Wood JT, Hoback WW, Green TW. Poisonous snakebites resulting in lack of venom poisoning. Va Med Monthly 1955;82:130; and Dunnihoo DR, Rush BM, Wise RB, Brooks GG, Otterson WN. Snake bite poisoning in pregnancy: a review of the literature. J Reprod Med 1992;37:653 – 658.) Overdose, Poisoning and Envenomation During Pregnancy 551 ing is a characteristic fi nding associated with black widow envenomation [172] . Other symptoms include: perspiration, nausea, vomiting, diarrhea, sialorrhea, and headache [182] . The neuromuscular manifestation of the envenomation progress over several hours and then subside over 2 – 3 days [185] . The evaluation of these patients may include a complete blood count, abdominal ultrasound or CT, EKG, and creatine kinase (CPK) to evaluate acute abdominal and chest pain syndromes. General supportive management (airway protection, breathing and circulation per advanced cardiac life support protocols) must be instituted promptly. Most black widow spider envenomations may be managed with opioid analgesics and sedative - hypnotics. A specifi c antivenin for black widow bites is available. Although it results in resolution of most symptoms 30 minutes after administration and has been shown to decrease the need for hospitalization signifi cantly, it should be cautiously restricted for severe envenomations, due to hypersensitivity, anaphylaxis, serum sick- ness reactions, and even risk of death [1,185,187] . Antivenom should be considered when envenomation seriously threatens pregnancy or precipitates potentially limb - or life - threatening effects (e.g. severe hypertension, unstable angina). As is the case with snake antivenoms, it should be given only in the hospital setting for the possibility of anaphylactic reactions [172] . The antivenin is derived from horse serum must be diluted (in 2.5 ml of normal saline) and administered slowly (200 ml over an hour) after skin testing and antihistamines to reduce acute adverse reactions to the antivenom [182] . One to two vials are generally suf- fi cient to counteract the nanomolar concentrations of circulating black widow spider venom; however additional dosing may be necessary in patients who do not demonstrate adequate recovery [188] . Symptoms have been shown to improve within 1 hour of Spider b ites In the USA, spider bites during pregnancy are reported four times more frequently than snake bites (see Tables 39.25 and 39.27 ). In the USA only two 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 [181] . The adult female black widow spider ( Latrodectus mactans ) has a highly neurotoxic venom ( α - latrotoxin), which destabilizes the cell membranes and degranulates nerve terminals resulting in massive norepinephrine and acetylcholine release into synapses, causing excessive stimulation and fatigue of the motor endplate and muscle [172,182] . Membrane receptors that bind α - latroxin have been identifi ed: neurexin and latrophilin/CIRL (calcium - independent receptor for α - latrotoxin). Although the nervous system is the primary target of low doses of α - latrotoxin, cells of other tissues (placenta, kidney, spleen, ovary, heart, and lung) are also susceptible to the toxic effects of α - latrotoxin because of the presence of CIRL - 2, a low - affi nity receptor of the toxin [183] . Although it is known that this venom does not affect the CNS due to its inability to cross the blood – brain barrier, it is not known whether it crosses the placenta or has direct fetal effects [182] . The diagnosis of a black widow spider bite is mainly clinical. The venom does not contain infl ammagens so the site of the envenomation is usually unremarkable except for a small circle of erythema and induration [172,182] . Within about one hour of the incident (minutes to hours), 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 [181,184,185,186] . Muscle cramp- Table 39.27 Insect and arthropod envenomation by category of exposure and maternal effects, US: 1999. Category of exposure Total No effect Minor effects Moderate effects No follow - up Ants/fi re ants 14 1 (7.1%) 3 (21.4%) 3 (21.4%) 7 (50%) Bee/wasp/hornet 66 1 (1.5%) 23 (34.8%) 1 (1.5%) 41 (62.1%) Miscellaneous insects 97 6 (6.1%) 31 (31.9%) 3 (3.1%) 56 (57.7%) Caterpillar/centipede 9 1 (11.1%) 4 (44.4%) 0 4 (44.4%) Scorpion 165 1 (0.6%) 67 (40.6%) 3 (1.8%) 94 (56.9%) Ticks 11 0 5 (45.4%) 0 6 (54.5%) Black widow spider 22 2 (9.1%) 11 (50%) 5 (22.7%) 4 (18.1%) Brown recluse spider 23 0 7 (30.4%) 3 (13.0%) 13 (56.5%) Other spiders 77 0 20 (25.9%) 8 (10.3%) 49 (63.6%) Miscellaneous arthropods 41 0 13 (31.7%) 1 (2.4%) 27 (65.8%) Total: 524 12 (2.3%) 184 (35.1%) 27 (5.1%) 301 (57.4%) Minor effects are signs or symptoms developing from the exposure but minimally bothersome and generally resolving without residual disability. A moderate effect is one that is more pronounced or prolonged than minor effects, usually requiring some form of treatment. Major effects (exposure resulting in life - threatening signs or symptoms or results in signifi cant disability or disfi gurement) were not reported in this series. (From Gei AF, Van Hook JW, Olson GL, Saade GR, Hankins GDV. Arthropod envenomations during pregnancy. Report from a national database — 1999. (Abstract no. 0662). Annual Meeting of the Society for Maternal – Fetal Medicine, Reno, Nevada, 2001.) Chapter 39 552 Systemic involvement, although uncommon, occurs within 24 – 72 hours of the bite more frequently in children than in adults. These systemic envenomations may be life threatening, and present with fever, constitutional symptoms (low - grade fevers, diarrhea, vomiting), petechial eruptions, thrombocytopenia, and hemolysis with hemoglobinuric renal failure, seizures or coma, and usually associated with minimal skin changes [191] . This presentation is more common seen after a bite by L. laeta , prevalent in Peru, Chile, and part of Brazil [190] . Treatment of envenomations is hindered by the delayed presentation of the victims to a medical facility and overdiagnosis. Unfortunately by the time a necrotic ulcer develops it may be too late for interventions. The treatment of local envenomations is mainly conservative (immobilization and elevation, application of ice, local wound care, tetanus prophylaxis, analgesics, and close follow - up). The application of ice in theory decreases the damage and infl ammation and local spread of the venom through vaso- constriction (application of heat results in more severe damage). Severe brown recluse spider bites produce dermonecrosis within 72 – 96 hours. Early surgical management in general has been found to be ineffective and sometimes harmful as an initial management technique [172,190] . Skin grafting may be necessary after 4 – 6 weeks of standard therapy or until the lesion borders are well defi ned. Given its leukocyte inhibiting properties, dapsone has frequently been recommended for the treatment of local lesions. However, because of the potential for adverse effects associated with dapsone use, especially in the setting of glucose - 6 - phosphate dehydrogenase defi ciency, hypersensitivity, cross - reactivity with sulfa allergies and methemoglobinemia, appropriate caution should be exercised if using this medication. To date, no well - controlled studies have shown dapsone to affect clinical outcome in human brown recluse envenomations; therefore, it is not rou- tinely recommended [172,190] . antivenom administration and for as long as 48 hours after envenomation [182,188] . Analgesics (morphine) and benzodiazepines (midazolam) are effective adjuvant treatment for the neuromuscular symptoms [172,184] . Calcium gluconate is no longer recommended for black widow spider envenomation [1] . Antibiotics are not indicated unless specifi c signs of cellulitis are noted. A booster of the tetanus toxoid should be given following a black widow spider bite. In the particular case of pregnancy, black widow envenomations can mimic acute intra - abdominal processes [186,189] and preeclampsia (abdominal pain, headache, hypertension, and pro- teinuria) [182] . Hospitalization and treatment with specifi c antivenom is recommended given that maternal mortality has been postulated to be as high as 5% [174,186] . In 1999, 22 bites by black widow spiders were reported to Poison Control Centers in the USA (Table 39.27 ). Half of the women reported only minor effects and another fi ve women (18.7%) reported effects requiring some form of treatment. The outcome was not known in four cases [170] . Loxosceles spiders have a worldwide distribution in temperate and tropical regions. There are approximately 50 recognized Loxosceles species in North America [190] . Loxosceles recluse is perhaps the best known member of the family and along with Loxosceles deserta are endemic and responsible for the majority of documented bites. Characteristic violin - shaped markings on their backs have led brown recluses to also be known as “ fi ddle- back spiders ” though these markings may not be visible without magnifi cation and may vary according to spider variable color. In South America, the more potent venom of the species Loxosceles laeta is responsible for systemic loxoscelism and several deaths each year. The usual habitat of the brown recluse is in dark closet corners and the sides of cardboard boxes and can infest in large numbers. Although not aggressive, the spider will bite when trapped [190] . The venom of these spiders has variable toxicity depending on the species. It contains at least nine enzymes, consisting of various lysins (facilitating venom spread), hyaluridonidase, and sphingo- myelinase D, which causes cell membrane injury and lysis, thrombosis, local ischaemia, and chemotaxis [172,190] . Loxosceles venom is also capable of inducing systemic intravascular clotting, which can result in hemolysis and renal failure [190] . Although most bites are asymptomatic, envenomation can begin with severe burning pain (characteristic of these envenomations) 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) (see Figure 39.5 ). The differential diagnosis includes arterial injection injury, herpes simplex, Stevens – Johnson syndrome, vasculitis, purpura fulminans, necrotizing fasciitis, and toxic epidermal necrolysis among others [190] . Loxoscelism is the term used to describe the systemic clinical syndrome caused by envenomation from the brown spiders. Figure 39.5 Effects of Loxosceles reclusa bite. (Photograph courtesy of Dr. Ramon L. Sanchez; Galveston, Texas.) Overdose, Poisoning and Envenomation During Pregnancy 553 clinical effects of envenomations are neuromuscular and neuro- autonomic [175] . A grade III envenomation is characterized by either cranial/autonomic or somatic skeletal neuromuscular dysfunction, including blurred vision, nystagmus, hypersalivation, tongue fasciculations, dysphagia, slurred speech, respiratory dis- tress; restlessness and severe involuntary shaking or jerking of extremities that may be mistaken for a seizure. A grade IV com- bines cranial/autonomic and somatic nerve dysfunction [175] . Most commonly, an infl ammatory local reaction occurs with the envenomation, which is treated with wound debridement and cleaning, tetanus prophylaxis, and antihistamines [185] . Antivenom is recommended for grade III and IV envenomations [195] . In Israel and India control of the overstimulated autono- mous system has been successfully achieved with the use of β - blockers (prazosin), calcium - channel blockers (nifedipine), and angiotensin - converting enzyme (ACE) inhibitors (captopril) [169] . In 1999, 165 scorpion envenomations were reported by pregnant women in the USA. In those patients with known outcome, minor symptoms were predominant. No life - threatening symptoms or signs were reported (see Table 39.27 ) [170] . Summary 1. Poisoning during pregnancy represent a third of a percent of all toxic exposures reported in the USA. 2. The number of reported toxic exposures has increased by about 25% over the past 6 years both in the pregnant and non - pregnant population. 3. Although slightly more frequent during the second trimester, toxic exposures during pregnancy are reported with similar frequency in all trimesters. 4. The emergency treatment and stabilization of the mother should take priority over the monitoring and treatment of the fetus. 5. A prompt consultation with the obstetric service is recommended in the emergent management of the compromised poisoned pregnant patient. The goals of this consult are: (a) the assessment of fetal viability and (b) the decision/skill to proceed with an emergent or perimortem cesarean section, if the resusci- tative efforts are not successful and/or the patient ’ s condition worsens. 6. The mechanism of exposure needs to be sought and established, since intentional toxic exposure usually indicates severe social, emotional and/or psychiatric pathology. When identifi ed, the need for additional and aggressive intervention (hospital admission, social and psychiatry consults, etc.) may prevent a potentially fatal recurrence. 7. Insect and arthropod exposures are not uncommon during pregnancy. The majority of these envenomations resulted in minor or no effects. Moderate effects are more likely when the cause of the exposure is a spider bite than with other arthropod exposures, including scorpion and bee stings. Other treatments, such as colchicine, steroids, antivenom, nitroglycerin patches, hyperbaric oxygen, and surgical excision, have been reported but insuffi cient data exist to support their clinical use [190] . Intradermal anti - loxosceles Fab fragments have been shown to attenuate dermonecrotic arachnidism in a rabbit model when given up to 4 hours after venom inoculation [192] . This treatment has not yet been applied clinically [190] . Antivenom is not commercially available for Loxosceles reclusa . There are four sources of commercial Loxosceles antivenoms, none of which is available in the USA [190] . In countries where antivenom is available the usual indication is systemic loxoscelism and it is likely that its use is capable of decrease the size of the lesion. Systemic envenomation requires supportive care and treatment of arising complications, corticosteroids to stabilize red blood cell membranes, and support of renal function. Patients with an isolated dermal lesion who will be discharged home should be instructed to watch carefully for a change in the color of the urine because the can develop a delayed systemic reaction [190] . Anderson [193] reported fi ve cases of envenomation by Loxosceles reclusa in pregnant patients. He concluded that no special risks or complications resulted from being bitten by the brown recluse during pregnancy when managed only with low - dose prednisone. No instances of hemolysis, disorders of coagulation, or renal damage were reported in this case series. In 1999, 23 bites by brown recluse spiders were reported to Poison Control Centers nationwide. Of those bites, the outcome is unknown in the majority (13) and moderate effects (more pronounced or prolonged than minimal; usually requiring some form of treatment) were reported in three cases [170] . Scorpions Over 650 species of scorpions are known to cause envenomation (mostly to children under 10 years); they are endemic mostly in arid and tropical areas. In developing countries scorpion stings are associated with mortality ratios of up to 0.2% [194] . Different venoms and clinical presentations are seen across the different species. Systemic envenoming is caused by members of the genera Centruroides (found in Southwest USA and Mexico), Tityus (Brazil and Trinidad), Androctonus , Buthus , Leiurus , and Nebo (North Africa, Near and Middle East); Hemiscorpius (Iran and Iraq); Parabuthus (South Africa), and Mesobuthus (Indian sub- continent) [169] . 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