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Diagnosis And Management Of North American Snake And Scorpion Envenomations Case #1: A 45-year-old man presents, via rural EMS, with a chief complaint of “snakebite.” EMS reports that the patient ran over a 6 to 8ft snake with his pickup truck, cutting it in half. The patient doubled back to pick up the dead snake (foreseeing a nice new pair of snakeskin boots) and when he grabbed it, the snake “came around” and bit his hand. He has two puncture wounds almost 7cm apart on his right hand surrounded by dark purple ecchymosis and the start of bullae formation. He has edema and erythema of his hand and arm to the elbow and is having fasciculations of most of his large skeletal muscle groups. He is in pain and EMS reports that he seemed to be getting progressively confused and lethargic during their 70 minute transport. He is hypotensive, tachycardic, and is oozing blood from his IV sites. You realize that his life depends on your actions... Case #2: A 30-year-old man presents with a chief complaint of “snakebite.” About 30 minutes prior to arrival he was wading in murky water cleaning debris out of a stream and felt a bite on his hand. As he pulled his hand out of the water, he briefly caught a glimpse of a snake as it swam away; he gives a fairly good description of a small copperhead. He has two small punctures on his right index finger about 1 cm apart. He is currently pain free, without erythema, swelling, or ecchymosis. His vitals and remaining physical exam are normal. He wants to know if he can go home... Case #3: A 39-year-old man presents to your Florida ED about four hours after being bitten on the forearm by a small red, yellow, and black snake while clearing brush. The snake escaped and was thought to be a king snake. There was minimal pain at the site of the bite and no swelling or bleeding, so he continued working. The patient started to get worried when he developed twitching in his arms and face about one hour before arrival at the ED. Soon after the twitching started, he began having difficulty talking and swallowing and had an episode of double vision, prompting him to call 911. On arrival, the patient is awake, alert, Editor-in-Chief Andy Jagoda, MD, FACEP, Professor and Vice-Chair of Academic Affairs, Department of Emergency Medicine; Mount Sinai School of Medicine; Medical Director, Mount Sinai Hospital, New York, NY. Associate Editor Health Science Center, New Orleans, LA. Wyatt W Decker, MD, Chair and Associate Professor of Emergency Medicine, Mayo Clinic College of Medicine, Rochester, MN. Francis M Fesmire, MD, FACEP, Director, Heart-Stroke Center, Erlanger Medical Center; Assistant Professor, UT College of Medicine, Chattanooga, TN. HSC/Jacksonville, FL. Gregory L Henry, MD, FACEP, CEO, Medical Practice Risk Assessment, Inc; Clinical Professor of Emergency Medicine, University of Michigan, Ann Arbor. Keith A Marill, MD, Instructor, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA. John M Howell, MD, FACEP, Clinical Charles V Pollack, Jr, MA, MD, FACEP, Professor of Emergency Medicine, Michael J Gerardi, MD, FAAP, FACEP, Professor and Chair, Department of George Washington University, Director, Pediatric Emergency Emergency Medicine, Pennsylvania Washington, DC; Director of Academic Medicine, Children’s Medical Center, Hospital, University of Pennsylvania Affairs, Best Practices, Inc, Inova Atlantic Health System; Department of Health System, Philadelphia, PA. Fairfax Hospital, Falls Church, VA. Emergency Medicine, Morristown Memorial Hospital, NJ. Michael S Radeos, MD, MPH, Editorial Board Assistant Professor of Emergency Michael A Gibbs, MD, FACEP, Chief, Medicine, Lincoln Health Center, William J Brady, MD, Associate Department of Emergency Medicine, Bronx, NY. Professor and Vice Chair, Department Maine Medical Center, Portland, ME. of Emergency Medicine, University of Robert L Rogers, MD, FAAEM, Steven A Godwin, MD, FACEP, Virginia, Charlottesville, VA. Assistant Professor and Residency Assistant Professor and Emergency Director, Combined EM/IM Program, Peter DeBlieux, MD, LSUHSC Medicine Residency Director, University of Maryland, Baltimore, Professor of Clinical Medicine; LSU University of Florida MD. September 2006 Volume 8, Number 9 Authors Melissa W Costello, MD Assistant Professor of Emergency Medicine, University of South Alabama, Mobile, Alabama Alan Heins, MD Assistant Professor of Emergency Medicine, University of South Alabama, Mobile, Alabama Daniel A Zirkin, MD Resident Physician, Department of Emergency Medicine, Emory University, Atlanta, Georgia Peer Reviewers Frank Lovecchio, DO, MPH, FACEP Medical Director, Banner Good Samaritan Regional Poison Center; Research Director, Maricopa Medical Center, Department of EM; Associate Professor, AZ College of Osteopathic Medicine Robert Barish, MD Professor of Emergency Medicine, Vice Dean for Clinical Affairs, University of Maryland School of Medicine, Baltimore, MD Charles Stewart, MD, FAAEM, FACEP Emergency Physician, Colorado Springs, CO CME Objectives Upon completion of this article, you should be able to: 1. Name the types of venomous snakes native to the United States. 2. Describe the key characteristics for identifying venomous versus non-venomous snakes. 3. Explain the grading system for envenomations. 4. Describe the indications and administration of CroFabTM. 5. Effectively evaluate and manage severe snake and scorpion envenomations. 6. Prevent and treat adverse effects of antivenom administration. 7. Describe multiple resources available to assist in the management and treatment of snake envenomations. Date of original release: September 12, 2006. Date of most recent review: September 1, 2006. See “Physician CME Information” on back page. Alfred Sacchetti, MD, FACEP, Assistant Clinical Professor, Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA. Beth Wicklund, MD, Regions Hospital Emergency Medicine Residency, EMRA Representative. Corey M Slovis, MD, FACP, FACEP, Professor and Chair, Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN. Valerio Gai, MD, Senior Editor, Professor and Chair, Dept of EM, University of Turin, Italy. Jenny Walker, MD, MPH, MSW, Assistant Professor; Division Chief, Family Medicine, Department of Community and Preventive Medicine, Mount Sinai Medical Center, New York, NY. International Editors Peter Cameron, MD, Chair, Emergency Medicine, Monash University; Alfred Hospital, Melbourne, Australia. Amin Antoine Kazzi, MD, FAAEM, Associate Professor and Vice Chair, Department of Emergency Medicine, University of California, Irvine; American University, Beirut, Lebanon. Ron M Walls, MD, Professor and Chair, Hugo Peralta, MD, Chair of Emergency Department of Emergency Medicine, Services, Hospital Italiano, Buenos Brigham & Women’s Hospital, Boston, Aires, Argentina. MA. Research Editors Nicholas Genes, MD, Mount Sinai Emergency Medicine Residency. Maarten Simons, MD, PhD, Emergency Medicine Residency Director, OLVG Hospital, Amsterdam, The Netherlands. snakebites and scorpion stings is unclear, supported by large, but not population-based studies. The American Association of Poison Control Centers (AAPCC) compiles data from their Toxic Exposure Surveillance System (TESS) and publishes a comprehensive annual analysis of all toxic exposures, including envenomations, reported to all of the US Poison Control Centers. These reports include information on exposures, ED use, and clinical outcomes including death.1-2 In spite of this centralized clearinghouse/reporting system, the consensus among experts in the field is that relying on self-reported data in the cases of envenomations that do not require ED visits results in a true incidence on envenomation that is as high as three to four times the number reported by TESS.3-5 The body of current literature on North American snake envenomations can generally be divided into two categories; pre-CroFabTM and postCroFabTM. The Crotalidae Polyvalent Immune Fab Ovine (CroFabTM) was approved by the US Food and Drug Administration in October of 2000 essentially replacing the older Antivenom Crotalidae Polyvalent (ACP) available since 1954. Indications and administration of CroFabTM will be discussed in detail later in this article. Dozens of articles have been published on the topic of snake envenomations since the approval of CroFabTM, but the vast majority are review articles by a small pool of authors. Very little original research has been done since the CroFabTM research in 1999. The research that has been done has typically been in small populations and does not include a single randomized, blinded clinical trial of any medication, device, or technique for snakebite management. The most recent comprehensive review identified was “North American snake envenomation: diagnosis, treatment and management” by Gold, Barish, and Dart in the Emergency Medicine Clinics of North America.4 This group of authors has written extensively in the emergency medicine and wilderness medicine literature on the topic of snake envenomations. In addition to the review article above, they participated in a four article symposium in the Annals of Emergency Medicine6 (presenting the data from the October 1999, North American Congress of Clinical Toxicology’s, “Advances in the Management of Snakebite” Symposium), and a full review of venomous snakebites in the New England Journal of Medicine.5 Most of the recent research-based literature has focused on the limited areas of field man- and anxious. His heart rate is 92, blood pressure 140/85, temperature 98.2°F orally, respiratory rate 22, and oxygen saturation 95% on room air. You note right eye ptosis; the pupils are equal, round, and reactive to light, but the right eye does not move past the midline on lateral gaze. Mild dysarthria is present. There are two tiny puncture marks on the right forearm with 1-2cm of surrounding ecchymosis, but no swelling. During your exam, respirations became shallower and labored, with some snoring upper airway sounds. You realize that this might be more than just the bite of a king snake... S nakes, both native and imported, and scorpions produce clinically important envenomations in the United States. While envenomations have long been considered the purview of the Southeastern US and the desert Southwest, the widespread and evergrowing population of people who maintain these animals in collections and as “pets” has made the presentation of a snakebite or scorpion sting possible in any emergency department (ED) in the country. These animals can produce devastating injuries and must be recognized promptly and treated appropriately to prevent significant morbidity and death. Not all envenomations need treatment. Indeed, there are times when the risk of treatment outweighs the benefit. However, failure to aggressively treat in the appropriate situation may result in a disastrous outcome for the patient and for the clinician who does not meet the standard of care expected of the emergency medicine specialist. This article will divide the discussion of snakes and the management of snake and scorpion envenomations into two sections. The first section will deal exclusively with pit vipers (Crotalids), their identification, envenomation signs and symptoms, and treatment with CroFabTM. Changes and controversies in the care of patients with Crotalid envenomations will also be addressed. The second section will deal with coral snakes and the identification and treatment issues that they present, along with a brief discussion of scorpion stings and the “exotics:” The non-native captive snakes that are found more and more commonly in the US, both in zoos and as pets. Critical Appraisal Of The Literature Unfortunately, evidence from well-conducted clinical research is in short supply to guide the management of envenomations. The literature supporting the ED evaluation and treatment of envenomations is generally weak, with few randomized trials or meta-analyses, and many review articles rehashing the same weak literature. Even the epidemiology of Emergency Medicine Practice© 2 September 2006 • EBMedice.net agement changes, trials of venom extraction devices, surgical management, and the expansion of the use of CroFabTM to non-Crotalidae envenomations; all of which will be discussed in this article. Coral snake envenomations are not treated with CroFabTM and thus will be reviewed separately. It is fairly rare and human treatment studies include only case series.7 Additionally, one well-designed animal model study explored a technique for first aid of coral snake envenomations.8 Similarly, the evaluation and management of scorpion envenomations is supported by only one randomized, placebo-controlled trial from Tunisia that enrolled a group with few severely affected people, and a systematic review including a randomized trial and three cohort studies.9,10 Non-native venomous snakes represent a heterogeneous group of animals kept by collectors and zoos. These snakes cause some dangerous envenomations each year in the United States, but the majority of the literature on evaluation and treatment of these snakes is published in the countries where the snakes are native. Most of these reports are low quality, but a few randomized, controlled trials support practice and are available through online databases by searching the specific species of snake responsible for the envenomation. Clinical guidelines are of virtually no help in guiding the assessment and treatment of envenomations. A search of the National Guidelines Clearinghouse using various key words, including snakebite, envenomation, rattle snake, coral snake, scorpion, cobra, krait, venom, etc. yielded only one relevant guideline, entitled, “First aid: 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations,” published in Circulation.11 The two suggestions for the first aid of snakebites are: 1) First aid providers should not apply suction to snakebite envenomation sites; this recommendation is supported by a few Class II and III studies. 2) Properly performed pressure immobilization is recommended for first aid treatment of Elapid snakebites. The first aid provider creates this pressure by applying a snug bandage that allows a finger to slip under the bandage; this recommendation is supported by a single Class III study in a porcine model of a coral snake envenomation. EBMedicine.net • September 2006 Epidemiology And Etiology Given the multitude of people who have an intense and occasionally irrational fear of snakes, it is hard to believe that snakebites are a relatively infrequent occurrence. Even harder to believe, is that fatalities from snake envenomations are exceedingly rare. It is estimated that there are approximately 45,000 snakebites per year in the United States.12 Seven thousand to 8000 of these bites are attributed to venomous snakes, but these bites only result in five to six deaths annually.3,12 The Toxic Exposure Surveillance System (TESS) report for 2004 breaks down snakebites by species, with 98% of bites by venomous snakes in the US from the Crotalids; there were a total of 5046 reported bites, with 167 major complications and two deaths. TESS reported 97 coral snake envenomations in 2004, with four major complications and no deaths. Envenomations by poisonous exotic snakes resulted in 131 reported cases in 2004. These bites were more severe than coral snakebites with morbidity and mortality rates similar to that of rattlesnakes; about 35% moderate injury, 7% major injury, and one death. One of the major limitations of the data reported by TESS is that, generally speaking, the data is compiled only from snake envenomations that result in visits to a physician (ED or other) or a call to the regional or national Poison Control Center. Many people who sustain minor envenomations or dry bites (bites where no venom is injected) will not seek medical care. It is reasonable to conclude that the patients who do not seek medical care generally will not take the time to report their envenomation to TESS. Thus, authors of scientific and medical writings are left to speculate on the true incidence of envenomations. The current consensus seems to be based on the estimate given by Parish in a 1954 report on the incidence of treated snakebites in the US (45,000),12 and a report by Langley and Morrow estimating that the actual incidence and death rate from snakebites was three to four times that reported by TESS.3 The majority of deaths occur among children and the elderly, among those for whom antivenom is not given, is postponed, or is administered in insufficient quantities, and among members of fundamentalist religious groups who handle poisonous snakes during religious rituals.13 Rattlesnakes, with their presence in virtually all of the continental US and the high potency of their venom, are responsible for the majority of snakebite 3 Emergency Medicine Practice© fatalities with the diamondback rattlesnake accounting for 95% of these fatal bites.14-15 Snakebites are more common during the spring and summer months when both snakes and people are more active outdoors. Very little has changed in the literature regarding the demographics of snake envenomations since 1966, when Parish published one of the first comprehensive survey results in Public Health Reports.12 Best summarized by Gold et al, “the majority of victims remain men between the ages of 17 and 27 years. More than 95% of the bites are on the extremities, and most occur between April and October, the peak months being in July and August.”4 Nonetheless, an emergency physician in any part of the country can potentially see snakebites at any time of the year, often from deliberate exposure to captive snakes.16 Of the nearly 3000 species of venomous and nonvenomous snakes worldwide, there are less than 40 species of venomous snakes in North America. To simplify things even further for the non-herpetologist, the venomous species of North America can be divided into four main types: Rattlesnakes (consisting of species from both the Crotalus and the Sistrurus genus), copperheads (genus Agkistrodon), cottonmouths (genus Agkistrodon), and coral snakes. The first three types are members of the Viper family and the Crotalinae subfamily; coral snakes are North America’s only native member of the family of snakes called Elapids.4,17 The family Elapidae also includes many of the most dangerous snakes in the world including cobras, kraits, adders, and mambas. Three different species of Elapids can be found in North America from North Carolina to Arizona and as far south as several hundred miles south of the US-Mexican border. The Eastern coral snake (Micrurus fulvius) is the most dangerous of the coral snakes. The highest concentrations are found in Florida, but it has also been found from North Carolina to Louisiana. The Western coral snake (Micruroides euryxanthus) is found in the Sonoran Desert of Arizona, northern Mexico, and the southwest corner of New Mexico below 5800 feet. The third Elapid in the US is the Yellow-bellied sea snake (Pelamis platurus). It has weak venom relative to the other Elapids, but it can still be dangerous to humans. The range of this sea snake in North America is limited to the southernmost areas of California and the northern pacific coast of Mexico. Exotic snakes are held by collectors and zoos in scattered places throughout the country and may repreEmergency Medicine Practice© sent any of the venomous species found in the world, but are most commonly cobras, kraits, and true vipers (as opposed to the pit vipers). Scorpions Scorpions are arthropods in the class Arachnida, sharing some characteristics with spiders, and are found worldwide. Most species of scorpions deliver venom that is not dangerous to humans, but there are a noteworthy few that deliver a potent, although not deadly, venom. In the US, scorpions are found primarily in the desert Southwest, with only one species, the Bark scorpion Centruroides sculpturatus (aka exilicauda), dangerous to humans. The Bark scorpion is only found in Arizona and Northern Mexico. The South African and Tunisian scorpions are very different from the Southwestern scorpion. In the US, most envenomations are treated at home, with very few advancing to pulmonary edema or shock. Most of the large case series and controlled trials have been performed outside the US, and caution must be used when extrapolating these studies to the management of patients in the US. Pathophysiology Pit Vipers/Crotalids Crotalid venom is a stunningly complex mixture of proteins that include proteolytic enzymes, collagenases, phospholipases, nucleotidase, hyaluronidase, acetylcholinesterase, and amino acid oxidase. In addition, it contains elemental metals, amino acids, carbohydrates, lipids, serotonin, and even histamine.18 Local toxic effects include swelling, pain, ecchymosis, and blebs; systemic effects result in coagulopathy, myocardial injury, muscular paralysis, and central nervous system injury. 4,6 See Table 1 for a more detailed description of venom effects. Crotalid venom has multiple effects on many organ systems and one of the most prominent is the venom’s power as an anticoagulant. Recently, it has been the subject of studies looking into clinical applications of a number of proteins isolated from venom for development of new anticoagulant drugs. These proteins have shown to inhibit platelet adhesion by interfering with the binding of vWF to the GPIb receptor and may provide an entirely new target for antiplatelet agents.19 Venom composition will change depending on the species of snake, age, diet, geographic location, 4 September 2006 • EBMedice.net and time of the year.4 Several types of Crotalids, once mature, have the ability to vary the amount of venom injected during a strike. Generally, the younger the snake, the more potent their venom.20 scorpion antivenom conducted in Tunisia, 82.4% of 825 patients had only local effects. The other 17.6% exhibited systemic effects, primarily autonomic instability, e.g. hypertension, sweating, and fever. Nine (1%) of 825 patients experienced cardiogenic shock, six (0.8%) had pulmonary edema, and two (0.25%) died.23 Coral Snakes Coral snake venom is a heterogeneous mixture of peptides and enzymes with primarily neurotoxic effects on nerve conduction and neuromuscular transmission.7 The mechanism of action and pharmacodynamics of coral snake venom is unclear and has apparently not been the subject of any published research. It is unlikely that this uncertainty will be addressed unless, like the Crotalids, a researcher determines a potential clinical use for Elapid venom or one of its components. Some cytotoxic effects may occur but are usually minor especially when compared to Crotalid venom. Often, there are no symptoms for one to five hours but, once they begin, systemic signs and symptoms may progress rapidly. Tremors and cranial nerve dysfunction resulting in ptosis, dysarthria, and dysphagia are common in substantial envenomations. Respiratory depression occurs more rarely and late in the course. Section 1. The Pit Vipers (Family Viperidae, Subfamily Crotalidae): Rattlesnakes, Cottonmouths (Water Moccasins), And Copperheads Identification Identification of the snake that produced the bite can be extremely helpful. Accurate information about the identity of a snake can provide information on the potency of the venom (rattlesnake venom being the most potent among native US snakes) and the patient’s expected clinical course and response to antivenom. Often, well-meaning patients or bystanders will bring in the snake for identification; it goes without saying that unless you have significant experience handling snakes it is best not to handle specimens that are brought in...alive or dead! If Non-native Venomous Snakes Imported snakes of the family Elapidae share some of the characteristics of coral snakes, including a tendency for elapid venom to cause mostly neurotoxic effects. Snakes of the family Viperidae, including Central and South American and Asian pit vipers and the true vipers of Africa, the Middle East, and Europe, are similar in effect to the Crotalid pit vipers of North America, with primarily cytotoxic venom, resulting in local tissue damage, coagulopathy, and organ dysfunction. Scorpions Scorpion venom is delivered through a tail stinger from two venom glands and is a combination of peptides and proteins with proteolytic and neurotoxic effects. Neurotoxic effects are proposed to be mediated by effects at sodium and potassium channels of neurons.21-22 Most envenomations produce only local effects of pain and swelling. In a randomized, placebo-controlled trial of EBMedicine.net • September 2006 Table 1: Snake Venom Components And Their Effects *Refers to quantity of the envenomation. Though not comprehensive, this table is designed to provide an easy reference in clinical practice. Reprinted from Kiran S, Senthilnathan TA Update in Anesthesia, Issue 16 (2003) Article 6. 5 Emergency Medicine Practice© the animal is brought in dead or in parts, keep in mind that snakes retain the ability to strike, bite, and potentially cause a significant envenomation for several minutes after death or decapitation. If you have been provided a specimen that is fairly intact and is in an appropriate container to allow for safe inspection (and you don’t develop profound cataplexy at the thought of handling a snake), then knowing a few good resources can be helpful in accurate identification; see Table 5 on page 18. Figure 1 shows some of the characteristic features that help distinguish the venomous pit vipers from the thousands of non-venomous species of snakes in the US. In general, pit vipers will have a triangular shaped head, elliptical pupils, and a heat sensing pit in front of the eye. These snakes will also have a set of retractable fangs and may or may not have a rattle on the tail. The body markings on the Crotalids are widely variable and can be helpful in identifying the specific species of snake. The fourth species of native venomous snake, the coral snake, is in a totally different subfamily of snakes and does not have any of this characteristic set of pit viper features despite possessing very potent venom. The clinically important feature to know with coral snakes is the difference in the markings between a coral snake (venomous) and a king snake (non-venomous) which has evolved very similar markings to the coral snake in order to fool its prey. The old saying, “red on yellow kills a fellow; yellow on black, venom lack,” works well to differentiate the corals from the king snakes in North America ONLY. Both species are found throughout the geographical distribution of the coral snake. Generally speaking, if you see more than two or three snakebites a year or if you are the regional referral center for snake envenomations (like we are), you may also want to keep a field guide specific to your region in your ED reference library. Peterson Field Guides publishes two titles on reptiles and amphibians, one for Eastern and Central North America and one for the Western US.24-25 These guides are recommended by several herpetology sources and are inexpensive (approximately $15 each) references to keep handy. Other potentially useful resources are poison control centers, medical toxicology divisions of large hospitals, state agriculture departments, university veterinary programs, and local zoos that keep and care for reptiles. Emergency Medicine Practice© Prehospital / Wilderness Care Multiple methods for treating snakebites in the field have gone in and out of vogue over the years, and have been discussed at length both in the medical and non-medical literature. Recently, the recommended first aid measures for snakebites have been revised to exclude many treatments of the past. Arterial tourniquets, aggressive wound incision/excision, electric shock, and ice submersion/cryotherapy may all worsen a patient’s condition.16-17 Current recommendations for field care call for very little beyond rapid transportation; see Table 2. Field care by bystanders or emergency medical services should include removing the patient from the area where the bite occurred. It is not recommended to try to catch or kill the offending snake simply to bring it to the hospital. In other words, common sense and discretion should prevail. A snake that has taken up residence under the slide on a school playground is very different from a snake that strikes because you stepped on its home in the middle of the woods. A good description of the snake in combination with the patient’s signs and Table 2: Prehospital Care of Snake Envenomations 6 September 2006 • EBMedice.net Figure 1: Comparison Of Venomous Snakes (Pit Vipers) And Nonvenomous Snakes In The US From Gold BS, Dart RC, Barish RA. Bites of venomous snakes. N Engl J Med 2002;347(5):347-58; with permission. EBMedicine.net • September 2006 7 Emergency Medicine Practice© symptoms is generally adequate to initiate in-hospital treatment. Patients should be reassured, placed at rest, kept warm, and transported immediately to the closest medical facility. The bitten extremity should be immobilized and kept at or below the level of the heart, and all constrictive clothing, jewelry and watches should be removed.4,15,26 Closely monitor vital signs to assess for hypotension as a sign of systemic toxicity and hypotension should prompt a bolus of intravenous isotonic fluids.5,17 Incision and suction, once the standard of care for the treatment of snakebites, is no longer recommended and may, in fact, pose more risk than benefit.27 Incision has never been shown to be beneficial for extracting venom and can cause unintended and potentially disabling injury to digital nerves, arteries, and tendons even when performed by an experienced provider.28 Oral suction of the venom is strongly discouraged both for its lack of effectiveness in removing venom and because of the possibility of introducing oral flora into the wound, potentially complicating treatment. There are several commercial snakebite kits on the market containing a multitude of items for the treatment of snakebites. Generally there is some combination of venous and/or arterial tourniquets, lancets or scalpels, antiseptic wipes, and various suction devices. Most of the kits were developed and marketed since before the “incision and suction” treatment went out of vogue. The most recognized and researched of these suction devices is the Sawyer Venom Extractor®. The marketing information available on the internet for this product references its ability to remove “up to 30%” of the snake venom based on two small studies (one animal in 1985 and one human in 1986) by Bronstein et al.29-30 A well-designed, 2004 human study by Alberts et al27 using simulated radiolabeled snake venom demonstrated minimal (0.04%) venom extraction from a simulated snakebite wound and only a 2% reduction of total body venom load. Given the poor performance of this device in the controlled trials and the elimination of most of the former interventions from the field treatment recommendations, Johnson said it best when he stated, “the best snakebite kit is probably the keys to a car that runs.”15 EMS may be faced with a snakebite victim who has had one or more well-intentioned field interventions by a bystander and it is important to know which should be discontinued and which should remain until hospital evaluation is complete. Incision is one of the most likely field interventions Table 3: Severity Grading69 Emergency Medicine Practice© 8 September 2006 • EBMedice.net the EMS provider may encounter. In cases where an incision has been made, control bleeding and apply a moist dressing.17 If an extractor device is correctly in place it should be left in place until the arrival at the hospital.17 Arterial tourniquets should be removed due to the potential for limb ischemia but venous tourniquets or “constriction bands,” defined as wide, flat bands that restrict venous and lymphatic flow to impede absorption of venom, can be left in place. These constriction bands, which should be loose enough to allow two fingers to slip easily underneath, have shown some benefit in delaying absorption of venom in experimental models and have been suggested as therapy in patients with prolonged transport times.17,31 If a device has been applied and it is not causing vascular compromise, it should be left in place by EMS during transport. EMS personnel should frequently reassess the tension of any constrictive device to ensure that progressive limb edema does not result in a venous constriction band becoming an inadvertent arterial tourniquet.10 omations. Patients with significant envenomations will have considerable pain both from the local cytotoxic effects of the venom and the diffuse muscle fasciculations caused by the neurotoxins and myotoxins in Crotalid venom. It is acceptable to give narcotics and benzodiazepines for comfort while antivenom is being prepared except in the cases of a coral snake, Mojave rattlesnake, or Eastern Diamondback rattlesnake envenomation where the neurotoxic effects of the venom can result in severely impaired mental status. There are no good, evidence-based recommendations in the literature for choice of drugs or dosing. NSAIDs should be avoided due to their antiplatelet effects potentially worsening venominduced coagulopathy. History Once the patient arrives in the ED, key pieces of information pertaining to the snakebite itself must be ascertained; see Table 4. Ask the patient about symptoms that may indicate a significant envenomation; particularly pain, numbness, nausea, tingling around the mouth, metallic taste, muscle cramps or fasciculations, dyspnea, diplopia, or dizziness.4,14-15,18-28 Additionally, ascertain the traditional components of a patient history including a comprehensive review of any co-morbid medical conditions (particularly cardiac disease and coagulopathy), a list of current medications, allergies (especially to papain or papaya based extracts, latex, and horse-based or sheep-based products), the time of last oral intake and the patient’s tetanus status. Obtaining the history should not interfere with the initiation of treatment in the critically ill or clinically deteriorating patient. ED Management And Stabilization Initial Stabilization Upon arrival in the ED, whether by ambulance or by personal vehicle, a rapid assessment of the patient should obviously include an evaluation of airway, breathing, and circulation. Barring a situation in which these are compromised and need to be addressed immediately, the initial stabilization of a snakebite victim includes many of the interventions that are recommended for the field providers. Obtain an initial set of vital signs, place the patient on continuous cardiac, BP, and pulse oximetry monitoring (on an unaffected extremity), remove constrictive clothing and jewelry, establish intravenous access, and draw blood for labs including tubes for a type and screen and coagulation studies. Supplemental oxygen can be given on a case-by-case basis. Use a Sharpie® or surgical marker to mark and time the leading edge of erythema. Also, mark two to three sites above the bite as locations for serial measurement of limb circumference. Once a clinically significant envenomation has been identified, rapidly begin the process of obtaining the appropriate antivenom and begin the mixing process, and/or arrange for rapid transfer of the patient to a facility capable of handling snake enven- EBMedicine.net • September 2006 Table 4: Key Questions In The History Of A Patient With A Snakebite • The location of the wound or wounds • The time of the bite • The type of snake • Treatment provided by prehospital bystander or EMS • Changes in the patient’s condition since the time of the bite 9 Emergency Medicine Practice© tration of antivenom), liver function tests, total creatine kinase, serum myoglobin, arterial blood gases, and chest radiography.4,14-15,18,28 This second set of tests can be ordered judiciously on a case-by-case basis, taking into account severity of the envenomation and co-morbid disease. Grading severity of envenomations will be discussed in detail in the next section. Physical Exam Focus the initial physical exam on the evaluation of the ABCs and provision of adequate resuscitation. Once the adequacy of all elements of the primary survey is established and the steps outlined in the initial stabilization are completed, the evaluation of the bite site can commence. As mentioned, onefourth of snakebites are dry. Examine the site of the bite for fang marks or scratches and consider the possibility of other types of animal bites or injuries if the diagnosis of a snake envenomation is in doubt. Pay particular attention to any local signs of envenomation, i.e. edema, petechiae, ecchymosis, or bullae formation.18 Document circumferential measurements at several sites above and below the bite site.16 Mark a line at the site of each measurement to ensure accurate reproducibility. Repeat these measurements every 15 to 30 minutes during the course of treatment. Also, mark and time the edge of the swelling to serve as an index of local progression.4 Focus the remainder of the physical exam primarily on the cardiovascular, pulmonary, and neurologic systems. Patients may be hypotensive due to third space losses and hemorrhage. Initial treatment for hypotension is intravenous isotonic fluids.28 The neurologic exam becomes particularly important in severe envenomations, especially in cases of Mojave rattlesnake, coral snake, or non-native/exotic envenomations where altered mental status and neurologic impairment can be a significant and often delayed feature of the envenomation.18 Compartment pressures: The other diagnostic test that can be performed in selected cases is the measurement of compartment pressures. Most envenomations involve only subcutaneous deposition of venom. In the rare intramuscular envenomation, compartment syndrome may develop but it is often impossible to distinguish the symptoms of compartment syndrome (classically the 5 “P’s:” pain out of proportion, pallor, parasthesia, paralysis, and pulselessness) from the symptoms of a significant envenomation. Formerly, fasciotomy was the recommended treatment for snakebites with suspected compartment syndrome, but current review suggests a more conservative treatment plan involving serial Stryker measurement for compartment pressures. Treatment General Principles The treatment of patients with snake envenomations entails aggressive supportive care and early administration of adequate doses of antivenom when indicated.4 Airway, breathing, and circulation are of primary importance. Establish peripheral intravenous access in an unaffected extremity. Hypotensive patients should receive fluid boluses to replace third space losses and may require blood transfusion if a venom-induced coagulopathy has resulted in significant hemorrhage. The transfusion of blood products will only temporize coagulopathy and ongoing blood losses until the venom is neutralized by antivenom. To be clear...fresh frozen plasma does not fix an envenomation induced coagulopathy. Diagnostic Studies The number and type of recommended diagnostic studies in a patient with a snake envenomation varies throughout the snakebite literature. However, the majority of authors agree that a core group of tests is indicated: A baseline complete blood count (CBC) with platelet count, coagulation studies including prothrombin time, partial-thromboplastin time, activated partial-thromboplastin time, fibrinogen level, fibrin split products (fibrin degradation products), basic electrolytes, blood urea nitrogen, serum creatinine, and urinalysis. Patients bitten by an unknown species with no evidence of toxicity require, at a minimum, coagulation studies which are necessary for the grading of the envenomation. Various sources also recommend obtaining an electrocardiogram, a specimen for type and screen or type and crossmatch for blood products (as crossmatch may be more difficult following the adminisEmergency Medicine Practice© Analgesics Consider analgesics part of the standard therapy for envenomations. Pain control will usually require parenteral narcotics for the first 24 to 48 hours of therapy in patients that are receiving antivenom.33 Skeletal muscle fasciculations can be treated with parenteral benzodiazepines. 10 September 2006 • EBMedice.net cally break envenomations into four or five categories, ranging from “dry bite” or nonenvenomation to severe/very severe. Table 3 on page 8 is a synthesis of several scoring systems from different authors and can be used to grade the envenomations of all pit viper or suspected pit viper envenomations3. Envenomations are graded based on the symptom or sign that places the patient in the highest (most severe) category.4 Treat moderate and severe/very severe envenomations (Grades II-IV) with antivenom. We have combined the Grade III and IV categories for simplicity since the treatment remains the same and the signs and symptoms differ only in matter of degree. CroFab™ was FDA approved in 2000 for the treatment of all “mild to moderate North American Crotalidae envenomations;” however, all of the research upon which this approval was based was done with rattlesnake envenomations.37,40 Copperheads, while a member of the Crotalidae subfamily of vipers, are a separate species from the rattlesnakes and copperhead venom is not used in the preparation of CroFab™. As recently as 2004, authors have recommended against the administration of CroFab™ for copperhead bites because the venom effects were not “serious enough” and the risks of antivenom outweighed the benefits.40 One retrospective review of copperhead bites by a group at Carolinas Medical Center showed that CroFab™ administration resulted in an improvement in local symptoms.41 Unfortunately, this was a small study involving only 32 patients. The selection criteria for treating with antivenom were not standardized and the “treatment group” represented only 8% of the copperhead envenomations that presented to Carolinas Medical Center during the review period. A larger, multicenter, randomized controlled study of CroFab™ in the treatment of copperhead bites is certainly warranted and needs to include comparisons not only of local symptoms, but also of short- and long-term disability and adverse events associated with treatment versus non-treatment. After the severity of the envenomation has been determined, patients with an indication to receive CroFab™ should have the drug administered as soon as possible. Early (< 6 hrs) administration of CroFab™ has been clinically shown to reduce clinical decline and systemic coagulopathy. Reassess and admit these patients to the ICU for monitoring and the completion of the CroFab™ treatment. When the possibility of an envenomation by a Wound Care Even in the absence of a clinically significant envenomation, snakebites are puncture wounds and therefore require local wound cleansing and tetanus prophylaxis. Interestingly, there is good data to show that snakebites have very low rates of infection.34-35 In spite of a broad spectrum of oral flora cultured from the mouths of snakes, the venom is postulated to have antibacterial properties.36 Based on these studies, prophylactic antibiotics are not currently recommended for snakebites.33 Compartment Syndrome In cases with documented pressures above 30mmHg, give an additional four to six vials of antivenom along with 1 to 2gm/kg of mannitol over 30 minutes; limb elevation and re-evaluation of pressures after one hour should occur prior to consideration of fasciotomy.4,28,32 It is recommended that the appropriate service that handles fasciotomy in your facility (generally, surgery or orthopedics) be consulted early in the course of treatment despite the rarity of envenomations that ultimately require this procedure. Crotalidae Polyvalent Immune Fab (CroFab™) CroFab™ was approved by the FDA in October of 2000. CroFab™ is a preparation of ovine Fab (monovalent) immunoglobulin fragments obtained from the blood of healthy sheep flocks. These sheep are immunized with one of the following North American snake venoms: Crotalus atrox (Western Diamondback rattlesnake), Crotalus adamanteus (Eastern Diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), and Agkistrodon piscivorus (Cottonmouth or Water Moccasin).37 Note that copperhead venom is not included in the immunizations. According to the CroFab™ package insert, patients with allergies to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may be at risk for an allergic reaction to CroFab™. In addition, it has been noted in the literature that some dust mite allergens and some latex allergens share antigenic structures with papain and patients with these allergies may be allergic to papain.38-39 Indications: Initiating treatment of an envenomation with CroFab™ is largely based on physical findings, their severity, and development over time. Classically, envenomation severity has been determined based on symptoms and quantified using one of a few accepted grading scales. These scales typiEBMedicine.net • September 2006 11 Emergency Medicine Practice© reconstitution of CroFab™ can begin prior to patient arrival. Nonetheless, the eagerness to begin the process of mixing needs to be tempered by the possibility of not needing to use a treatment which has an average cost of nearly $1000 per vial. The recommended initial dose of CroFab™ is four to six vials. Dosage requirements are dependent upon the individual patient response. The use of the recommended adult dosages in the pediatric population appears to be safe.43-44 The initial dose should not be reduced in a pediatric patient because, despite their smaller size, the volume of venom to be neutralized is not reduced. Anecdotal experience with the older ACP venom indicates that antivenom requirements may, in fact, be higher in pediatrics; but no clear clinical correlation between age, size, weight, or snake species and antivenom requirement has ever been demonstrated with either antivenom preparation. However, the fluid status of the pediatric patient should be taken into account when deciding on the initial dilution of the dosage to be given. Most children can handle the 250cc volumes without difficulty as this correlates to a 20cc/kg bolus for a 12.5kg child, but fluid status may become an issue in children less that 10kg.44 Unfortunately, there are no controlled studies to provide guidance on the delivery of higher concentrations. Deliver the initial dose at a rate of 25 to 50mL/hr for the first ten minutes. If no acute allergic reaction is noted after this initial time; deliver the remainder of the first four to six vial dose at the full rate of 250mL/hr. If a reaction occurs, administer both H1and H2-receptor blockers. If the symptoms resolve and the reaction was mild, the infusion can be continued with close monitoring. In a retrospective review of CroFab™ safety by Dart and McNally, the two patients with severe reactions (cough and widespread urticaria +/- wheezing) had infusions discontinued, diphenhydramine and an H2-receptor blocker given, and then infusions restarted. In one patient the reaction recurred and no further antivenom was given. In the other patient, the infusion was restarted and completed without incident with the precaution of an epinephrine infusion which is only described as being administered “in standard doses”45-46 or as a “low dose infusion” which was stopped 30 minutes after the completion of the infusion of CroFab™.47 After the initial dose of four to six vials, “initial control” is achieved when an adequate clinical response has occurred, i.e. no further progression of coral snake or Mojave rattlesnake exists, the scale presented in Table 3 should not be used. The signs and symptoms of such venom may be significantly delayed and have their primary effects on the nervous system. In these cases, extend the observation period to at least 12 hours from the time of the injury to account for this delay.4-5,18 Confusing matters somewhat, some authors recommend admission of all suspected coral snake envenomations for close monitoring.4 Presumably the authors are differentiating “observation” in the ED from “admission” meaning 23 hours or more. Unfortunately, there is no good clinical data upon which these recommendations are based. Preparation and Administration: If possible, obtain written, informed consent prior to the administration of CroFab™, advising the patient primarily of the risks of anaphylaxis, delayed serum sickness, and/or death. In the initial clinical studies of CroFab™, the rates of allergic reaction were low and skin testing was not done. Skin testing done in the setting of the older polyvalent antivenom administration (which had a much higher anaphylaxis rate) has been shown to have both high false-positive rates and false-negative rates, 33% and 10 to 36% respectively. As clinical experience and comfort with CroFabTM have increased, the need for skin testing prior to administration has never been shown to be useful. Additionally, skin testing delays the onset of definitive treatment and the risk of true anaphylaxis with CroFab™ is substantially lower than with the older Antivenom Crotalid Polyvalent (ACP).42 Despite this data, the treating physician should always be prepared for an anaphylactic reaction to antivenom with basic supplies such as epinephrine, diphenhydramine, airway equipment, oxygen, and pressors. CroFab™ is packaged as a shelf-stable lyophilized powder in a vial. Reconstitute each vial of CroFabTM with 10mL of Sterile Water for Injection USP (diluent is not included). After being thoroughly mixed, further dilute each of the reconstituted vials to be used in a given dose in a single 250mL bag of 0.9% Sodium Chloride USP. Use this reconstituted and diluted product within four hours of mixing. The reconstitution and dilution process is time consuming; even in the most practiced hands, preparation of an initial dose of CroFab™ takes more than 30 minutes. Given this, our recommendation is that the mixing of CroFab™ should begin as soon as the patient demonstrates evidence of a significant envenomation. Occasionally, in select scenerios, when patients are being transported for treament, the Emergency Medicine Practice© 12 September 2006 • EBMedice.net any local symptoms, systemic symptoms, or coagulopathy. Observe the patient while administering two additional vials every six hours for three additional doses. If, after completion of the initial dose, the patient’s symptoms continue to progress (worsening of the local injury or systemic effects such as muscle fasciculation, parasthesias, abnormal mental status, tachypnea, tachycardia, or hypotension), an additional four to six vials is recommended. This additional dose is also warranted if laboratory studies show prolonged coagulation times, decreasing fibrinogen levels, or worsening platelet count. If a second four to six vial dose is given, the patient needs to be reassessed for “initial control” and a third round of four to six vials may be needed in the most severe cases. Multiple studies of CroFab™ indicate that the dose required for initial control can range from 4 to 18 vials. If three rounds of four to six vials fail to achieve control of an envenomation, consider an alternative diagnosis, such as another type of envenomation, a toxic overdose, or an exotic species. The elimination half-life for CroFab™ is estimated to range from 12 to 23 hours.37 Further study has shown that Fab molecules have a shorter half-life than the IgG used in traditional polyvalent antivenom.45 Early studies of CroFab™ reported cases of recurrence of signs and symptoms of the original envenomation after intital control. This may be due to a Fab half-life that is shorter than the elimination half-life of snake venom, thus the administration of CroFab™ includes three additional doses to prevent symptom recurrence. Once initial control is obtained, admit the patient to the ICU and give two vials of CroFab™ at 6, 12, and 18 hours after the completion of the control doses. incidence and severity of reactions to CroFab™ appears to be significantly reduced. In the initial clinical studies discussed above, seven of the first 42 patients treated had an early, though relatively minor, reaction (five urticaria, one cough, one urticaria/dyspnea and wheezing). However, it is important to note that there have been case reports of serious reactions and serum sickness related to CroFab™.46-47 Disposition Patients who have no findings of envenomation (dry bites/Grade 0) can be discharged after a four to six hour observation period.18 Patients who have limited local signs of envenomations but do not meet the criteria for CroFab™ need to be monitored for progression of symptoms in the ED or observation unit for a minimum of 8 to 12 hours from the time of the bite4-5,18,28 Although most patients with Crotalidae envenomations begin to manifest local symptoms within 10 minutes of a bite and virtually all have some findings within 30 to 60 minutes, there are some patients who will not manifest symptoms for several hours, although the mechanism for this is unclear.4 In those cases where the patient does not initially meet treatment criteria, observation and intermittent reassessment is critical since local findings or symptoms that would upgrade the envenomation into a treatment category may be absent initially. Patients who receive CroFab™ are admitted to the hospital as discussed in the previous section. The half-life of CroFab™ is less than that of polyvalent antivenom. This fact, coupled with the persistent activity of the depot-style delivery of the venom, can lead to recurrent coagulopathy despite appropriate antivenom treatment.68 Such recurrence is characterized by decreased platelets, elevated prothrombin time, and decreased fibrinogen. During the initial trials, such a recurrent coagulopathy was observed only in those patients experiencing coagulation abnormalities at initial presentation. After initial treatment, this coagulopathy may be present for weeks. Therefore, post treatment, monitor those patients presenting with coagulopathy for signs and symptoms of recurrent coagulopathy after discharge every two to three days until the coagulopathy resolves48-49 Advise patients to contact their physician immediately if they experience new symptoms or unusual bruising or bleeding after hospital discharge as additional antivenom treatment may be needed. Monitoring: After stabilization and initial control of the patient’s symptoms have been achieved, and the administration of the scheduled doses has begun, continue close surveillance of the patient’s condition. Observation includes monitoring of limb circumference, both above and below the bite, and using a pen to outline the edematous area every 30 to 60 minutes. Obtain laboratory determinations of the patient’s coagulation status every four hours.28 If symptoms or laboratory data warrants, the treating physician can give an additional two vials. Any unscheduled re-dosing after initial control does not reset the 6, 12, 18 hour schedule to the beginning. When compared to polyvalent antivenom, the EBMedicine.net • September 2006 13 Emergency Medicine Practice© Emergency Medicine Practice© 14 September 2006 • EBMedice.net EBMedicine.net • September 2006 15 Emergency Medicine Practice© Emergency Medicine Practice© 16 September 2006 • EBMedice.net Boyer et al recommend retreatment with two vials of CroFab™ in the event of fibrinogen level < 50mcg/mL, platelet count < 25,000, INR > 3.0, aPTT > 50 seconds, multicomponent coagulopathy, worsening trend in patients with prior severe coagulopathy, high risk behavior for trauma, or comorbidities that increase the risk of hemorrhage.49 Instruct patients to report any signs or symptoms of delayed allergic reactions or serum sickness after hospital discharge. Serum sickness is a delayed hypersensitivity reaction to antivenom characterized by fever, rash, arthralgias, and lymphadenopathy which typically begin 7 to 21 days following antivenom administration. It is much more rare with CroFab™ than with the older polyvalent antivenom (3% versus more than 80%) and responds well to a tapering course of prednisone starting at 60mg daily and tapering over seven to ten days.4,33,45 Serum sickness is the only indication from steroids in the treatment of snake envenomation. toms of compartment syndrome and it is clinically impossible to establish the difference without direct measurement of compartment pressures.53 Even in the cases where compartment pressures exceed 30 to 40mm Hg, additional antivenom administration (four to six vials) has been shown to reduce compartment pressures, avoiding an unnecessary and disfiguring fasciotomy. Fasciotomy should only be considered in the extraordinarily rare cases where additional antivenom doses have failed to reduce measured pressures. In the authors’ opinion, given the ”assess, treat, reassess, treat” management strategy, and the scheduled dosing nature of current management, a medical ICU service may be more appropriate than a surgical service. Clearly, in the rare case of true elevated compartment pressures, a consultation to orthopedics or surgery is warranted. That said, snake envenomations present such a complex interaction of multisystem toxicologic effects that the determination of the best admission service should be handled on a caseby-case and hospital-by-hospital basis. Controversies Alternative Treatment Several studies have addressed specific techniques used in the care of snake envenomations and have shown that many of the devices and techniques traditionally used in care of snake envenomations were either of no benefit or were, in fact, harmful. Incisions, suction devices, packing in ice (cryotherapy), application of heat, and even application of electrical shocks have all historically been used to treat snake envenomations. While the application of a stun-gun or “gasoline engine spark plugs” to a patient may be intriguing, there is no clinical benefit, and a handful of case studies show the danger of this therapy, even in controlled settings.50 As discussed in detail above, little role remains for any field treatment beyond immobilization, reassurance, and rapid transport. Section 2. Coral Snakes (Elapidae), Exotic Snakes, And Scorpions Prehospital Care As with Crotalid envenomations, there are no specific prehospital interventions for scorpion or nonCrotalid snake envenomations, other than removal from danger, and rapid, safe transport. Immobilization of the affected limb may be helpful. An interesting experiment testing a novel immobilization technique in a porcine model of a coral snake envenomation has been published.8 The pressure-immobilization technique is not a tourniquet, but uses an elastic bandage applied from the envenomation site and extended proximally. The goal is to impede lymphatic flow, not venous or arterial flow. Apply the bandage about as tight as a wrap for an acute sprain, yet loose enough to allow a finger to be inserted between skin and bandage without difficulty. Also, splint the limb to limit motion. Elapid snakebites in other countries, primarily Australia, are treated with a similar pressure immobilization technique.54-55 Because of the low quality evidence, this technique must be considered experimental, even though it has been included in a clinical guideline for the snakebite section of an emergency care guide- Fasciotomy Once considered part of the primary treatment of snake envenomations, fasciotomy is the other controversial issue that has yet to be addressed in this discussion. Good clinical data from animal studies have shown that in snake envenomations, rabbits that receive fasciotomy (with or without antivenom) have poorer outcomes than those treated with antivenom alone.51-52 The signs and symptoms of a significant envenomation closely mimic the symp- EBMedicine.net • September 2006 17 Emergency Medicine Practice© line, the 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations.11 occur over a few minutes. Tremors, ptosis, dysphonia, dysphagia, and decreased deep tendon reflexes are the most common neurologic signs and may indicate impending respiratory paralysis.7 Emergency Department Evaluation Non-native Venomous Snakes Depending on the species, envenomations may produce mostly neurotoxic effects, especially from the other Elapids, e.g. cobras, kraits, and mambas. Cytotoxic and coagulopathic effects may predominate from bites of other snakes, especially the Viperidae (both pit and true vipers). Once identification is made, a poison center consultation and/or accessing one of the available web resources will help guide clinical decision making; see Table 5. Coral Snakes Coral snakebites produce little, if any, pain and local reaction. Assessment of signs of neuropathy must be aggressively sought, as progression to bulbar paralysis and respiratory failure may be rapid. The onset of neurological symptoms may be delayed one to four hours, but once neurological signs appear, progression to paralysis and respiratory failure may Table 5: Useful Websites For Snake Identification And Bite Management Black and white photographs of snakes do very little to help in the identification of snakes and thus, are not reproduced in this article. Fortunately, the internet has proven to be extremely useful for snake identification with many sites that provide a variety of full color pictures and tools to help identify venomous snakes and differentiate them from their non-venomous counterparts. Using a search engine and the topic "snake" or "snake identification" will result in websites that discuss the snakes that are indigenous to your region and will aid in identification. This table lists some of the useful websites for snake identification and bite management. • http://mdg.ext.msstate.edu/Tom_Snake/ index.html: One of the most user friendly sites as it has been designed for identification of snakes by the non-herpetologist. Snakes are identified by name or features. It is based at Mississippi State University and will identify the snakes of the Southeast and the majority of the snakes nationwide. unknown snake, but if you have a good idea of what you are looking for, this is an excellent site for quick confirmation. • http://trailquest.net/SNpoi.html: Avid hikers will recognize this site as an excellent resource for all things related to hiking. It also happens to contain a complete list of "poisonous" and "nonpoisonous" snakes that may be encountered while hiking throughout the continental United States. Like the previous site, it requires that you choose a species to see a photo, but it does have better descriptions of habitat and distributions of species by state/region. • www.snakesandfrogs.com: This site provides excellent descriptions (with photos) of the various characteristics that identify snakes. Follow the links to "How to Identify Snakes." It is a South Carolina based site that will work for most snakes indigenous to the US East and Southeast. It is an excellent site if you have the specimen in front of you but tougher to navigate if you are working solely from a patient’s description. • www.aza.org: The American Zoo and Aquarium Association (AZA) can be particularly helpful when exotics are involved in an envenomation. The AZA maintains the Antivenom Index, a list of the types and locations of all species-specific antivenoms for any of the venomous exotics housed in US zoos and larger private collections. The Antivenom Index is a members-only list, but national and regional Poison Control Centers maintain active memberships and can access the information needed to provide patient care (American Association of Poison Control Centers, www.aapcc.org, 800-222-1222). • http://www.pitt.edu/~mcs2/herp/SoNA.html: This site’s common name is "Snakes of North America" and it can be found easily by searching "snake identification" on Google. It is a comprehensive list of every snake native to North America with a picture. Each snake only has one photo and requires that you choose the species in order to see the photo. This can prove to be a challenging way to identify an Emergency Medicine Practice© 18 September 2006 • EBMedice.net Non-native Venomous Snakes Again, guidance on testing will depend on the identification of the snake. Bites from other members of the family Elapidae will likely require no testing. Patients with bites from other Viperidae snakes will probably require testing similar to that recommended previously for Crotalid envenomations, e.g. complete blood count, comprehensive metabolic panel, prothrombin time, partial thromboplastin time, fibrinogen level, blood type and antibody screening. Compartment pressure measurement is indicated if compartment syndrome is suspected. Scorpions Children are at the greatest risk of severe effects because of low body weight to venom ratios. Elderly people may also have lower reserves against the physiologic insult of the toxins. Evaluation of local, systemic, and neurological effects is essential. Deaths occur from cardiopulmonary collapse or respiratory paralysis. Identification of impaired tissue perfusion, tachycardia, tachypnea, hypoxemia, hypotension, agitation, altered mental status, and/or cranial and somatic neuromuscular dysfunction are a prompt for aggressive treatment. A retrospective study of 428 patients admitted to the intensive care unit in Tunisia for scorpion envenomations found that respiratory rate > 30 breaths per minute, agitation, and sweating were predictors of pulmonary edema.56 Scorpions A complete blood count and plasma protein concentration may help predict the presence of pulmonary edema, as will a chest x-ray. Cardiac enzymes may demonstrate cardiac damage. Liver enzymes may show liver damage which was correlated with poor prognosis in a study of 951 patients admitted to a Tunisian ICU.57 Echocardiography may be necessary to evaluate cardiogenic shock or suspected cardiac dysfunction. Diagnostic Studies Coral Snakes There is no adequate evidence to support the use of any specific laboratory or imaging tests in cases of coral snake envenomations. Since there are generally few cytotoxic effects, there is probably no need for testing. However, if the patient requires endotracheal intubation and mechanical ventilation for respiratory failure, a chest x-ray to assess tube position and arterial or venous blood gases to assess ventilation status are indicated. Treatment Prompt administration of specific antivenom, when available and indicated, and supportive care of airway, breathing, circulation, and neurologic function are the foundation of ED care for these envonomations and stings. Tetanus prophylaxis should be Key Points 1. Venomous snakes (domestic and imported) and scorpions can produce devastating injuries and must be recognized promptly and treated appropriately to prevent morbidity and death. 5. Zoos maintain a stock of antivenoms for many exotic, venomous snakes and may be a source for treating envenomations from those snakes. 6. Your local poison control center has access to multiple sources for identifying venomous snakes and obtaining specific antivenom. Call them. 2. Identification of the snake that inflicted the bite is important but not essential for appropriate management 7. Children and elderly are at the highest risk of severe morbidity and death from scorpion stings and require close observation. 3. Crotalid envenomations are graded based on the most severe sign or symptom, and CroFab™ should be administered for all moderate and severe envenomations. 8. Equipment and medications for management of anaphylaxis should be in place during the administration of any antivenom. 4. Once a coral snake bite is confirmed, antivenom should be given immediately, even if no symptoms are present. EBMedicine.net • September 2006 19 Emergency Medicine Practice© offered if there is no clear history of tetanus immunization within five years and encouraged if it has been more than ten years. Critical care services including mechanical ventilation, pressor and inotrope administration, intravenous hydration and nutrition, and prolonged sedation are sometimes required in severe envenomations. No credible evidence supports the use of prophylactic antibiotics or steroids in scorpion, coral snake, or non-native venomous snake envenomations. Consideration of special needs for individual cases is discussed later in this article. Adverse effects of antivenom administration, often anaphylaxis, occur in the majority of patients who receive antivenom derived from animal serum. Universal preparation to treat these reactions is required for all patients receiving antivenom. Two prospective case series, one from Australia and one from South Africa, found over a 70% occurrence of immediate hypersensitivity reactions, with about half of these anaphylaxis, after administration of (non-Fab derived) snake antivenom.58-59 In a study of 181 patients who received Antivenom Crotalid Emergency Medicine Practice© Polyvalent (ACP), 56% experienced a rash 3 to 21 days after antivenom with several experiencing subjective fever, itching, and arthralgias as well. These findings appeared dose related with nearly all patients receiving 30 or more vials of antivenom experiencing a rash. Serum sickness, discussed previously, is much more common with the horse serum derived antivenoms used for coral snake, exotic snake, and scorpion envenomations than with CroFab™.4 In a prospective observation study of 116 patients receiving scorpion (Centruroides) antivenom for severe envenomations, four patients had immediate reactions: Three cases of rash and one case of anaphylaxis. Follow-up of the 99 patients was conducted at one year; 61% experienced delayed hypersensitivity reaction and serum sickness, which responded to steroids and antihistamines.60 A prednisone taper, beginning at 60mg per day over seven to ten days, along with oral antihistamines, is the most common treatments for serum sickness.61 One randomized, controlled trial and a systematic review of that trial concluded that the administration of 0.25mg of 1:1000 epinephrine sub- 20 September 2006 • EBMedice.net cutaneously in the forearm immediately before antivenom infusion is started markedly reduced the incidence of immediate hypersensitivity reactions; absolute risk reduction 30%, number-needed-to-treat was 3.3, with no significant adverse effects attributable to epinephrine.62-63 before and after depletion of stocks of antivenom, suggest that use of antivenom in children may prevent some hospital and intensive-care unit admissions.64-65 Coral Snakes Place coral snake specific antivenom at the bedside of all patients with a suspected coral snake bite. Observe and treat at the first sign of envenomation, however minor. The antivenom is derived from horse serum and may result in an immediate or delayed hypersensitivity reaction. The incidence data for adverse reactions is not available. A provocative pilot study was conducted in children admitted to the hospital for a scorpion envenomation, using a before-after, quasi-experimental analysis of an intervention using prazosin, an alpha-receptor blocker. Unfortunately, this study was done in Tunisia, involving severe envenomations by North African scorpions and a control therapy using insulin and dextrose which is not standard in the US. Prazosin dosing was 30 micrograms/kg/dose orally at the time of presentation and repeated three hours after the first dose and every six hours thereafter as needed to alleviate signs of autonomic instability. Before beginning the prazosin intervention “standard therapy” was to use an insulin and dextrose mixture, intravenous fluids, and treatment of associated complications. Standard therapy was given in addition to prazosin. With 20 patients in the “before cohort” and 16 patients in the “after cohort,” the authors reported that the prazosin group experienced fewer episodes of hypoglycemia and hyperkalemia; although, it is unclear if this is an effect of the scorpion venom or a side effect of the insulin/dextrose therapy. Only one of 16 patients in the prazosin group died, compared to seven of 20 in the control group. Hospital length-of-stay was reduced in the prazosin group from a mean of 71.5 hours to 46.3 hours.66 With the unavailability of scorpion antivenom in Arizona, there is a pressing need for a well designed, randomized, controlled trial of prazosin in the treatment of scorpion envenomations with systemic signs. A randomized clinical trial of scorpion antivenom is currently being conducted. A two-year clinical trial of 50 patients, supported by a FDA grant to the University of Arizona, to study the effect of a new scorpion FAB fragment antivenom has been completed but was only reported in a Tuscon, Arizona newspaper.67 The drug, Anascorp™, is made in Mexico and not yet approved for use by the FDA. The clinical trial overseen by researchers at the University of Arizona and the Arizona Poison Center in Tucson reported that the drug used in > 100 Arizona children demonstrated benefit. Controversies/Cutting Edge Non-native Venomous Snakes Early and sufficient antivenom administration is the key to treatment of non-native venomous snakebites. Again, positive identification of the snake is essential so that specific antivenom can be obtained. Local zoos are required to store antivenom, when available, for every venomous species in their collection. Call your local zoo for availability of antivenom or call the American Zoo and Aquarium Association (301-562-0777) for access to their antivenom index. Collectors of venomous snakes are not bound by these same regulations, so a search for antivenom must be conducted, after identification of the snake, through local poison control centers or the American Association of Poison Control Centers (800-222-1222). Scorpions Supportive care is the cornerstone of treatment. Scorpion antivenom for Centruroides sculpturatus (aka exilicauda), the only scorpion species in the US dangerous to humans, was previously available only in Arizona, but production stopped in 2001. Stocks became outdated in 2004, and are not FDA approved for the treatment of scorpion envenomations. In addition, there are contradictory findings from studies of the effectiveness of antivenom in treating scorpion stings. Complicating this, is the fact that most studies have been done on non-North American scorpion envenomations. For example, one randomized, placebo-controlled trial in Tunisia and a systematic review including the randomized trial and three cohort studies concluded that there was no benefit to administering antivenom.9-10 More relevant to US practice, but weaker evidence, a case series and a natural before-after analysis of cohorts EBMedicine.net • September 2006 21 Emergency Medicine Practice© Case #1: This case represents a very severe envenomation (Grade III/IV). This patient needed 12 vials of CroFab™ to achieve initial control and resolve the coagulopathy. He was admitted to the medical ICU and monitored for several days. His pain was controlled with narcotics and benzodiazepines; he ultimately did well and was discharged home. He did not get a new pair of boots. Case #2: This patient required eight hours of observation. The bite was a “Grade 0” at presentation and he remained asymptomatic for the eight hour stay. The patient was discharged home after wound cleansing and administration of tetanus prophylaxis. Case 3: In this case, the patient was experiencing neurotoxic effects of a coral snake envenomation and was at a high risk for respiratory failure. Three vials of North American coral snake antivenom were given, with additional doses made available at the bedside. Aggressive supportive care, including endotracheal intubation and mechanical ventilation were required. The patient made an uneventful recovery. He decided to hire someone the next time the brush needed clearing. Disposition Coral Snake Any time a patient with a coral snake envenomation exhibits severe systemic or neurological signs, admit the patient to the intensive care unit. If the patient does not exhibit any systemic symptoms or signs at the end of a 12 hour ED observation period, the patient may be discharged home.4 If the patient has systemic signs after four hours and is requiring any supportive care, admit the patient for at least a 24 hour observation period. At the end of the observation period, patients no longer requiring supportive care may be discharged. Patients with continuing systemic signs and supportive needs should continue to receive antivenom and be managed in an ICU setting. Non-native Venomous Snakes Because of the wide variety of snakes and venom effects, no firm disposition criteria can be determined. Consult a poison control center to assist in medical management decisions.68 References Scorpions Any time a patient with a scorpion envenomation exhibits severe systemic signs, admit the patient to the intensive care unit. If the patient does not exhibit any systemic symptoms or signs at the end of a four hour ED observation period, the patient may be discharged home with no specific discharge instructions. If the patient has systemic signs or requires supportive care, admit for at least a 12 to 24 hour observation period. At the end of the observation period, patients no longer requiring supportive care may be discharged. Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report. To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available. 1. Conclusion There are approximately 8000 venomous snakebites in the US each year. The vast majoity of these bites are from rattlesnakes, copperheads and water mocosins. Management is based on early recognition, envenomation assessment, and administration of the appropriate antivenom. Current concepts in care have relenquished incision and suction techniques to history books and have promoted antivenom that is immunotherapy based. The three cases presented at the beginning of this article illustrate scenarios that may confront any emergency medicine physician. The case outcomes show the benefit of proper clinical management. Emergency Medicine Practice© 2. 3. 4. 5. 22 Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2004;22(5):335-404. (Prospective; 2,395,582 patients) Watson WA, Litovitz TL, Rodgers GC, et al. 2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2005;23(5):589-666. (Prospective; 2,438,644 patients) Langley RL, Morrow WE. Deaths resulting from animal attacks in the United States. Wilderness Environ Med 1997;8:8-16. (Expert opinion) Gold BS, Barish RA, Dart RC. North American Snake Envenomation: diagnosis, treatment and management. Emerg Med Clin North Am 2004;22(2):423-43. (Review) Gold BS, Dart RC, Barish RA. Current Concepts: Bites September 2006 • EBMedice.net 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. of Venomous Snakes. N Engl J Med 2002;347: 347-356. (Review) Dart RC, Waeckerle JF. Introduction: “Advances in the Management of Snakebite” Symposium. Ann Emerg Med 2001;37:166-167. (Expert opinion) Kitchens CS, Van Mierop LH. Envenomation by the Eastern Coral Snake (Micrurus fulvius fulvius). A study of 39 victims. JAMA. 1987;258(12):1615-1618 German BT, Hack JB, Brewer K, et al. Pressure-immobilization bandages may delay toxicity in a porcine model of eastern coral snake (Micrurus fulvius fulvius) envenomation. Ann Emerg Med 2005;45(6):603-608. (Animal study, randomized, controlled) Abroug F, El Atrous S, Nouira S, et al. Serotherapy in scorpion envenomation: a randomized controlled trial. The Lancet 1999;354:906-909. (Prospective, randomized, controlled; 825 patients) Foex B. BestBETs: Scorpion envenomation: Does administration of antivenom alter outcome? Accessed 25 May 2006 at http://www.bestbets.org/cgibin/bets.pl?record=00567 . (Systematic review) ECC Committee, Subcommittees and Task Forces of the American Heart Association. First aid: 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation 2005;112(22 Suppl):1525. (Consensus conference report) Parrish HM. Incidence of treated snakebites in the United States. Public Health Rep 1966;81:269-276. (Survey) Russell FE, Banner W. Snake venom poisoning. Conn’s Current Therapy. Rakel RE (ed). Philadelphia, WB Saunders Co, 1988, p 1002. Juckett G, Hancox JG. Venomous Snakebites in the United States: Management Review and Update. Am Fam Phys 2002;65(7):1367-1374. (Review) Johnson CA. Management of Snakebite. Am Fam Phys 1991;44(1):174-180. (Review) Liebelt EL, Kazzi ZN. Timing and Toxicology Critical for Treating Snakebite Victims. UAB Insight 2006; Spring: 9-10. (Expert Opinion) McKinney PE. Out-of-hospital and Interhospital Management of Crotaline Snakebite. Ann Emerg Med 2001;37(2)168-174 (Review) Otten EJ. Venomous Animal Injuries. In: Marx JA, editor-in-chief. Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6th ed. Philadelphia: Mosby Elsevier; 2006. 894-913 (Textbook Chapter) Messmore HL, Jeske WP, Wehrmacher W, el al. Antiplatelet Agents: Current drugs and future trends. Hematol Oncol Clin N Am 2005;19:87-117. (Review) Suncoast Herpetological Society. Venom1 Antivenom Bank. May 2006. Accessed 12 September 2006 at http://www.kingsnake.com/suncoastherpsociety/SH Sven.htm. Cheng D. Scorpion Sting. Accessed 25 May 2006 at http://www.emedicine.com. (Review) EBMedicine.net • September 2006 22. Rodriguez de la Vega RC, Possani LD. Current views on scorpion toxins specific for K+ channels. Toxicon 2004;43(8):865-875. (Basic science) 23. Zuo XP, Ji YH. Molecular mechanism of scorpion neurotoxins acting on sodium channels: insight into their diverse selectivity. Mol Neurobiol 2004;30(3):265-278. (Basic science) 24. Conant R, Collins JT. Reptiles and Amphibians: Eastern and Central North America 3rd ed. New York: Houghton Mifflin; 1998. Peterson Field Guide Series. (Reference book) 25. Stebbins RC. A Field Guide to Western Reptiles and Amphibians 3rd ed. New York: Houghton Mifflin; 2003. Peterson Field Guide Series. (Reference book) 26. Venomous Snakes of North America. Accessed 12 September 2006 at http://www.geocities.com/ RainForest/2221/snakeid.html. 27. Alberts M, Shalit M, LoGalbo F. Suction for Venomous Snakebite: A Study of “Mock Venom” Extraction in a Human Model. Ann Emerg Med 2004; 43(2) 181-186. (Prospective;8 human volunteers) 28. Dart RC, Daly FS. Reptile Bites. In: Tintinalli J, editor. Emergency Medicine: A Comprehensive Study Guide, 6th ed. Chicago: McGraw Hill; 2004. p1200-1205. (Textbook Chapter) 29. Bronstein AC, Russell FE, Sullivan JB. Negative pressure suction in the field treatment of rattlesnake bite. Vet Hum Toxicol 1985;28:297 (Abstract) 30. Bronstein AC, Russell FE, Sullivan JB. Negative pressure suction in the field treatment of rattlesnake bite victims. Vet Hum Toxicol 1986; (Abstract) 31. Burgess JL, Dart RC, Egen NB, et al. Effects of constriction bands on rattlesnake venom absorption: a pharmacokinetic study. Ann Emerg Med 1992;21:10861093. 32. Hall EL. Role of surgical intervention in the management of crotaline snake envenomation. Ann Emerg Med 2001;37(2):175-180. (Review) 33. Singletary EM, Rochman AS, Bodmer JC, et al. Envenomations. Med Clin N Am 2005; 1195-1224. (Systematic review) 34. Clark R.F, Selden BS, Furbee B, The incidence of wound infection following crotalid envenomation. J Emerg Med 1993;11:583-586. (Prospective, observational; 54 patients) 35. Weed HG, Nonvenomous snakebite in Massachusetts: prophylactic antibiotics are unnecessary. Ann Emerg Med 1993; 22:220-224. (Prospective observational; 72 patients) 36. Talan DA, Citron D.M, Overturf G.D, et al. Antibacterial activity of crotalid venoms against oral snake flora and other clinical bacteria. J Infect Dis 1991;164:195-198. (Basic Science) 37. Protherics. “CROFAB® CROTALIDAE POLYVALENT IMMUNE FAB (OVINE)” Package Insert. 2006. (Package Insert) 38. Quarre JP, Lecomte J, Lauwers D, et al. Allergy to latex and papain. J Allergy Clin Immunol 1995; 95(4):922. 23 Emergency Medicine Practice© 53. American College of Surgery, Commission on Trauma and American College of Emergency Physicians. Guidelines for treatment (poster publication). Chicago, IL: American College of Surgery; 1994. (Clinical Consensus Statement) 54. Sutherland SK, Coulter AR, Harris RD. Rationalisation of first aid measures for elapid snakebite. Lancet 1979;1(8109):183-185. (Expert opinion) 55. Howarth DM, Southee AE, Whyte IM. Lymphatic flow rates and first aid in simulated peripheral snake or spider envenomation. Med J Aust 1994;161:695-700. (Animal study, randomized, controlled) 56. Bouaziz M, Bahloul M, Hergafi L, et al. Factors associated with pulmonary edema in severe scorpion sting patients—a multivariate analysis of 428 cases. Clin Toxicol (Phila) 2006;44(3):293-300. (Retrospective, cohort;428 patients) 57. Bahloul M, Chaari A, Khlaf-Bouaziz N, et al. Gastrointestinal manifestations in severe scorpion envenomation. Gastroenterol Clin Biol 2005;29(10):10011005. (Retrospective chart review; 951 patients) 58. Moran NF, Newman WJ, Theakston RD, et al. High incidence of early anaphylactoid reaction to SAIMR polyvalent snake antivenom. Trans R Soc Trop Med Hyg. 1998;92(1):69-70. (Prospective case series; 17 patients) 59. Isbister GK, Tankel AS, White J, et al. Med J Aus. 2006;184(8):419-20. (Prospective case series; 14 patients) 60. LoVecchio F, Welch S, Klemens J, et al. Incidence of immediate and delayed hypersensitivity to Centruroides antivenom. Ann Emerg Med 1999;34(5):615-619. (Prospective, cohort;116 patients) 61. Lo Vecchio F, Klemens J, Roundy EB, et al. Serum sickness following administration of Antivenin (Crotalidae) Polyvalent in 181 cases of presumed rattlesnake envenomation. Wilderness Environ Med 2003;14(4)220-221. (Retrospective;181 patients) 62. Premawardhena AP, deSilva CE, Fonseka MMD, et al. Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomized, placebo controlled trial. BMJ 1999;318:1041-1043. (Prospective, randomized, controlled;105 patients) 63. Nuchpraryoon I, Garner P. Interventions for preventing reactions to snake antivenom. Cochrane Database Syst Rev 2000;(2):CD002153. (Systematic review) 64. LoVecchio F, McBride C. Scorpion envenomations in young children in central Arizona. J Toxicol Clin Toxicol 2003;41(7):937-40. (Prospective case series; 483 patients) 65. Riley BD, LoVecchio F, Pizon AF. Lack of Scorpion Antivenom Leads to Increased Pediatric ICU Admissions. Ann Emerg Med 2006;47(4):398-399. (Before-after cohort; about 35,000 patients) 66. Gupta V. Prazosin: a pharmacological antidote for scorpion envenomation. J Trop Pediatr 2006;52(2):150151. (Prospective, before-after, quasi-experimental;36 (Case Report) 39. Baur X, Chen Z, Rozynek P, Düser D, et al. Cross-reacting IgE antibodies recognizing latex allergens, including Hev b 1, as well as papain. Allergy 1995;50(7):604609. (Clinical Trial, 58 patients) 40. Caravati EM, Copperhead bites and Crotalidae polyvalent immune Fab (ovine): Routine use requires evidence of improved outcomes. Ann Emerg Med 2004;43(2): 207-208. (Expert opinion) 41. Lavonas EJ, Gerardo CJ, O’Malley G, et al. Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med 2004;43:200-206. (Retrospective chart review;32 patients) 42. Jurkovich GJ, Luterman A, McCullar K, et al. Complications of Crotalidae antivenin therapy. J Trauma 1988;28(7):1032-1037. (Prospective, Cohort; 40 patients) 43. Schmidt JM. Antivenom therapy for snakebites in children: is there evidence? Curr Opin Pediatrics 2005;17(2):234-238. (Review) 44. Offerman SR, Bush SP, Moynihan JA, et al. Crotaline Fab antivenom for the treatment of children with rattlesnake envenomation. Pediatrics 2002;110: 968–971. (Prospective/Retrospective, pediatric cohort; 12 patients) 45. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med 2001;37(2):181-188. (Review) 46. Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med 2002; 39(6):677-679. (Case report) 47. Clark RF, McKinney PE, Chase PB. et al. Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom. Ann Emerg Med 2002;39(6):671-676. 48. Boyer LV, Seifert SA, Clark RF, et al. Recurrent and persistent coagulopathy following pit viper envenomation. Arch Intern Med 1999;159(7):706-710. (Retrospective chart review; 38 patients) 49. Boyer LV, Seifert SA, Cain JS. Recurrence phenomena after immunoglobulin therapy for snake envenomations: part 2. Guidelines for clinical management with Crotaline Fab antivenom. Ann Emerg Med 2001;37(2):196-201. (Review and clinical guidelines) 50. Holstege CP, Miller MB, Wermuth M, et al. Crotalid snake envenomation. Crit Care Clin 1997;13(4):889-921. (Review Article) 51. Stewart RM, Page CP, Schwesinger WH, et al. Antivenin and fasciotomy/debridement in the treatment of the severe rattlesnake bite. Am J Surg 1989;158:543-547. (Animal Study, randomized, controlled) 52. Tanen DA, Danish DC, Grice GA, et al. Fasciotomy worsens the amount of myonecrosis in a porcine model of Crotaline envenomation. Ann Emerg Med 2004;44(2):99-104. (Randomized, blinded, controlled animal; 20 pigs) Emergency Medicine Practice© 24 September 2006 • EBMedice.net d. Grade III/IV (severe/very severe envenomation) patients) 67. McClain C. 2-year scorpion-antivenin trials successful; FDA scrutiny next. Accessed 6 July 2006 at http://www.azstarnet.com/allheadlines/124591. (Unpublished, prospective, randomized, controlled; 50 patients) 68. Hughes A. Observation of snakebite victims: is twelve hours still necessary? Emerg Med (Freemantle) 2003;15(5-6):511-517. (Two phase case series; 360 patients) 69. Norris R. “Snake Venom Poisoning In The United States: A Medical Emergency!” Accessed 11 September 2006 at http://www.emed.stanford.education/didactics/snakebites.htm. 70. Gibly R, Williams M, Walter FG et al. Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation. Ann Emerg Med 1999;34(5): 669-670. 36. If the patient in question three developed no further symptoms, what is the correct management plan? a. Mix CroFabTM and administer four vials according to the treatment algorithm and then discharge home. b. Mix CroFabTM and administer four vials according to the treatment algorithm and then admit for the completion of the CroFabTM treatment regimen. c. Observe for four hours and discharge if unchanged. d. Observe for eight hours and discharge if unchanged. CME Questions 37. If the patient in question three developed significant altered mental status, but no other changes in his presentation, what grade should be assigned to his envenomation? 33. Which of the following anatomic regions is the location for more than 95% of snake envenomations? a. Back b. Extremities c. Head d. Torso a. Grade 0 (nonenvenomation) b. Grade I (mild envenomation) c. Grade II (moderate envenomation) d. Grade III/IV (severe/very severe envenomation) 34. Which of the following is a true statement? 38. An 8-year-old, 35kg female presents to the emergency department one hour after an identified cottonmouth/water moccasin bite to the leg while swimming in a local pond. She has marked pain, severe edema and erythema to her entire leg, and has an elevated INR and aPTT. Appropriate management should include which of the following? a. 25% of venomous snakebites in the US are fatal. b. 98% of venomous snakebites in the US are from Crotalids. c. Imported snakes account for the majority of fatal snakebites in the US. d. Up to 20% of the venomous snakebites in the US can be attributed to coral snakes. a. Three vials of CroFabTM, adjusted for weight, mixed in 250cc NS, and given according to the treatment protocol. b. Six vials of CroFabTM, with no weight adjustment, mixed in 250cc NS and given according to the treatment protocol. c. Pretreatment with epinephrine 0.25mg IM prior to CroFabTM administration. d. Skin testing to determine sensitivity to CroFabTM. 35. A 25-year-old male presents to the ED 60 minutes after a brown snake bit his hand. He says the snake had a triangular head and a rattle on its tail. Currently, the patient has local swelling around 2 fang marks, some mild pain in his hand, and minimal local swelling. His vitals and labs are normal. What Grade is this envenomation? a. Grade 0 (nonenvenomation) b. Grade I (mild envenomation) c. Grade II (moderate envenomation) EBMedicine.net • September 2006 39. All of the following patients have received a 25 Emergency Medicine Practice© surgery for fasciotomy if greater than 40mmHg. d. Measure compartment pressures and administer an additional four to six vials of CroFabTM with mannitol and arm elevation if pressures are greater than 40mmHg. dose of four to six vials of CroFabTM. Which of the following has achieved “initial control”? a. Swelling and redness have improved according to the pen marks, and repeat labs show an increase in INR from 2.5 to 3.0. b. Swelling and redness have progressed beyond the pen marks and the repeat labs have returned to baseline normal levels. c. Swelling and redness have remained the same according to the pen marks and the repeat labs are improved. d. Swelling and redness have remained the same according to the pen marks, the repeat labs are improved, and the patient has developed confusion. 42. Which of the following is a true statement? a. Mojave rattlesnake envenomations present in a similar fashion to other Crotalid envenomations and can be assessed using the grading scale in Table 1. b. Coral snake venom is classically considered to be primarily cardiotoxic. c. Crotalid venom is a complex mixture of proteins and other substances that affect the cardiac, neurologic, hematologic, and musculoskeletal systems. d. Venom extraction devices are an effective field treatment for envenomations and should be applied by bystanders or EMS providers that have them available in the field. 40. The patient has received six vials of CroFabTM and has achieved initial control of the envenomation. Three hours after his first two vial follow-up dose of CroFabTM, his altered mental status returns. What is the best course of action at this point? a. Administer two vials of CroFabTM and continue with his scheduled dosing regimen according to the original times. b. Administer two vials of CroFabTM and reset the follow vial timing for additional doses at 6, 12, and 18 hours following the newest dose. c. Administer four to six vials of CroFabTM and reassess in one hour. d. Wait until the next six hour incremental dose is due and administer two vials. 43. An 18-month-old, 12kg female was stung on the leg by a scorpion while playing on her porch in Tuscon, Arizona. Over the past few minutes, she has started getting agitated, sweating profusely, vomiting, and passing watery stools. On arrival to the ED by EMS, the patient was alert, agitated, diaphoretic, tachypneic at 48 breaths per minute with oxygen saturation 94% by pulse oximetry, and tachycardic at 160 beats per minute. After starting an IV line, placing oxygen by mask, and instituting continuous monitoring, your best initial course of action is to: 41. A patient who has received one dose of four vials of CroFabTM following a severe (Grade III) envenomation of the hand has developed increased pain, pallor, and numbness of his hand. Palpation of his forearm reveals a very tight compartment and he has pain out of proportion. What is the best course of action? a. Administer three vials scorpion antivenom intravenously immediately with a 20ml/kg bolus of normal saline. b. Give 0.12mg epinephrine 1:1000 intramuscularly in the thigh and 12.5mg diphenhydramine intravenously. c. Give midazolam intravenously, draw labs, and plan for pediatric intensive care unit admission. d. Give metoprolol 2.5mg intravenously every five minutes for three doses to establish betareceptor blockade, but hold for heart rate less than 60 beats per minute. a. Continue CroFabTM treatment according to timed protocol, elevate his arm, and reexamine in one hour. b. Immediate fasciotomy to relieve compartment sydrome. c. Measure compartment pressures and consult Emergency Medicine Practice© 26 September 2006 • EBMedice.net the patient is anxious, tachypneic at 32 breaths per minute, with faint wheezes bilaterally. After establishing IV access, placing oxygen by nasal cannula, and instituting continuous cardiac monitoring, what is the best initial course of action? 44. The patient is a 39-year-old man who was bitten on the hand while clearing brush at his Florida home by a red, yellow, and black snake, thought to be a coral snake. Injury occurred 30 minutes before ED arrival and the patient has no symptoms, no pain, no paresthesias, and no neurological deficits. What is the best course of action? a. Give 0.3mg epinephrine 1:1000 intramuscularly in the thigh and 50mg diphenhydramine intravenously. b. Give three more vials of coral snake antivenom intravenously for progression of symptoms. c. Perform neuro checks every hour to assess for progression of symptoms. d. Perform rapid sequence intubation for impending respiratory failure. a. Observe for 12 hours and, if no symptoms, discharge home. b. Obtain CBC, CMP, PT/PTT and fibrinogen at baseline and after four hours while monitoring for symptoms. c. Immediately give coral snake antivenom. d. Perform neuro checks every hour and give antivenom when and if symptoms appear. 47. The patient is a 44-year-old man who received polyvalent, horse serum-derived antivenom for bites from a Gaboon viper while working at the zoo two weeks ago. He presents to the ED for evaluation of an itchy, red rash on trunk and arms that has been increasing for the past three days. What is the best treatment plan for this patient? 45. The patient is a 26-year-old man who was cleaning up in the trailer of a circus snake handler and decided to “mess” with the snakes. A monocle cobra bit him at least twice and maybe three times on the right hand and forearm about two hours ago. He tried to conceal his injury from his boss, but started to have severe pain, muscle twitching, and difficulty swallowing so admitted the injury and was brought into the ED. The snake handler brings ten vials of polyvalent cobra antivenom with the patient. What is the best initial course of action? a. Obtain additional Gaboon viper antivenom to give additional treatment for unresolved envenomation. b. Give 0.3mg epinephrine 1:1000 intramuscularly in the thigh and 50mg diphenhydramine intravenously. c. Obtain CBC, CMP, PT/PTT and fibrinogen at baseline and after four hours while monitoring for symptoms. d. Give prednisone 60mg and diphenhydramine 50mg PO in the ED and prescribe a steroid taper for ten days and prn diphenhydramine. a. Call the poison control and the regional zoo for guidance in managing this patient. b. Give midazolam 4mg intravenously, draw labs, and plan for ICU admission. c. Give 0.25mg epinephrine subcutaneously to prevent immediate hypersensitivity reaction and three vials of cobra venom intravenously. d. Obtain CBC, CMP, PT/PTT, and fibrinogen at baseline and perform type and cross for packed red blood cells and fresh frozen plasma. 48. The patient is a 36-year-old collector of venomous snakes who was bitten by one of his black mamba (Dendroaspis polylepis) snakes about one hour ago. He has no clear symptoms, but says he feels funny and anxious. His vital signs are stable and he is in no distress. He reports that he has antivenom for almost all of his snakes, but he has never been able to obtain antivenom for this snake species. After establishing IV access, placing oxygen by nasal can- 46. The patient is a 52-year-old woman who was bitten by a coral snake two hours ago and given three vials of coral snake antivenom about ten minutes ago. She complains of an intensely itchy, blotchy rash all over the body and face and swelling of the lips. On exam, EBMedicine.net • September 2006 27 Emergency Medicine Practice© Committees of the American Heart Association and representatives from the resuscitation councils of ILCOR: How to Develop EvidenceBased Guidelines for Emergency Cardiac Care: Quality of Evidence and Classes of Recommendations; also: Anonymous. Guidelines for cardiopulmonary resuscitation and nula, and instituting continuous cardiac monitoring, what is the best initial course of action? a. Call your local poison center or national poison center hotline 800-222-1222 for help obtaining antivenom. b. Give coral snake antivenom three vials intravenously to capitalize on cross-reactivity of the species. c. Give 0.3mg epinephrine 1:1000 intramuscularly in the thigh and 50mg diphenhydramine intravenously. d. Obtain CBC, CMP, PT/PTT, and fibrinogen at baseline and after four hours while monitoring for symptoms. emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IX. Ensuring effectiveness of community-wide emergency cardiac care. JAMA 1992;268(16):2289-2295. Physician CME Information Credit Designation: The Mount Sinai School of Medicine designates this educational activity for a maximum of 48 AMA PRA Category 1 Credit(s)TM per year. Physicians should only claim credit commensurate with the extent of their participation in the activity. Credit may be obtained by reading each issue and completing the printed post-tests administered in December and June or online single-issue post-tests administered at EBMedicine.net. Target Audience: This enduring material is designed for emergency medicine physicians. Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians. Date of Original Release: This issue of Emergency Medicine Practice was published September 12, 2006. This activity is eligible for CME credit through September 12, 2009. The latest review of this material was September 1, 2006. Coming in Future Issues: Acutely Decompensated Heart Failure Weakness Complications In Pregnancy Discussion of Investigational Information: As part of the newsletter, faculty may be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration approved labeling. Information presented as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product. Disclosure of Off-Label Usage: This issue of Emergency Medicine Practice discusses no off-label use of any pharmaceutical product. Class Of Evidence Definitions Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions. Class I • Always acceptable, safe • Definitely useful • Proven in both efficacy and effectiveness Class III • May be acceptable • Possibly useful • Considered optional or alternative treatments Level of Evidence: • One or more large prospective studies are present (with rare exceptions) • High-quality meta-analyses • Study results consistently positive and compelling Level of Evidence: • Generally lower or intermediate levels of evidence • Case series, animal studies, consensus panels • Occasionally positive results Class II • Safe, acceptable • Probably useful Level of Evidence: • Generally higher levels of evidence • Non-randomized or retrospective studies: historic, cohort, or casecontrol studies • Less robust RCTs • Results consistently positive Faculty Disclosure: It is the policy of Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Dr. Costello, Dr. Heins, Dr. Zirkin, Dr. Lovecchio, Dr. Barish, and Dr. Stewart report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. For further information, please see The Mount Sinai School of Medicine website at www.mssm.edu/cme. Indeterminate • Continuing area of research • No recommendations until further research ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category 1 credit per annual subscription. Level of Evidence: • Evidence not available • Higher studies in progress • Results inconsistent, contradictory • Results not compelling AAFP Accreditation: Emergency Medicine Practice has been reviewed and is acceptable for up to 48 Prescribed credits per year by the American Academy of Family Physicians. AAFP Accreditation begins August 1, 2006. Term of approval is for two years from this date. Each issue is approved for 4 Prescribed credits. Credits may be claimed for two years from the date of this issue. Significantly modified from: The Emergency Cardiovascular Care AOA Accreditation: Emergency Medicine Practice has been approved for 48 Category 2B credit hours per year by the American Osteopathic Association. Emergency Medicine Practice is not affiliated with any pharmaceutical firm or medical device manufacturer. CEO: Robert Williford President and Publisher: Stephanie Williford Direct all editorial or subscription-related questions to EB Medicine: 1-800-249-5770 • Fax: 1-770-500-1316 • Non-U.S. subscribers, call: 1-678-366-7933 EB Practice, LLC • 305 Windlake Court • Alpharetta, GA 30022 E-mail: [email protected] • Web Site: EBMedicine.net Emergency Medicine Practice (ISSN Print: 1524-1971, ISSN Online: 1559-3908) is published monthly (12 times per year) by EB Practice, LLC, 305 Windlake Court, Alpharetta, GA 30022. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than substitute, professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials contained herein are not intended to establish policy, procedure, or standard of care. Emergency Medicine Practice is a trademark of EB Practice, LLC. Copyright © 2006 EB Practice, LLC. All rights reserved. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC. Subscription price: $299, U.S. funds. (Call for international shipping prices.) Emergency Medicine Practice© 28 September 2006 • EBMedice.net