Copperhead and Cottonmouth Envenomation

Updated: Apr 09, 2021
Author: Sean P Bush, MD, FACEP; Chief Editor: Joe Alcock, MD, MS 



Moccasins are new world pit vipers (family Viperidae, subfamily Crotalinae), which may be identified by a heat-sensing pit anteroinferior to each eye, elliptical pupils, a triangular head, and undivided subcaudal scales. See the image below.

Snake envenomations, moccasins. Copperhead (Agkist Snake envenomations, moccasins. Copperhead (Agkistrodon contortrix). Photo courtesy of Sean Bush, MD.

Moccasins comprise the genus Agkistrodon, which includes the cottonmouth (Agkistrodon piscivorus) and copperhead (Agkistrodon contortrix) in the southeastern United States; the cantil (Agkistrodon bilineatus) in Mexico and Central America; the mamushi (Agkistrodon blomhoffii), Siberian pit viper (Agkistrodon halys), and Central Asian pit viper (Agkistrodon intermedius) in central and northeastern Asia; and the Malayan pit viper (Calloselasma rhodostoma) and hundred-pace snake (Deinagkistrodon acutus) in southeastern Asia. See the image below. This article specifically addresses the management of envenomation by the moccasin snakes found in the United States, A contortrix and A piscivorus.

Snake envenomations, moccasins. Cottonmouth or wat Snake envenomations, moccasins. Cottonmouth or water moccasin (Agkistrodon piscivorus). Photo courtesy of Sean Bush, MD.


Envenomation occurs when the moccasin injects venom via hollow movable fangs located in the anterior mouth. The effects of moccasin envenomation are generally similar to rattlesnake envenomation. However, in most cases, moccasin envenomation is generally less serious than envenomation by rattlesnakes. For further discussion of more severe pit viper envenomation, see Rattlesnake Envenomation.

Moccasin venom is complex, with nearly 50 identified components. These can be broken down into the following four major categories[1] :

  • Proteolytic enzymes that directly destroy tissue, as happens in digestion of prey animals
  • Inflammatory mediators, including histaminelike and bradykininlike factors, that cause pain, erythema, swelling, and, occasionally, distributive shock
  • Fibrinolytic enzymes that cleave fibrin into ineffective D-dimers, resulting in coagulopathy
  • Antiplatelet factors that cause thrombocytopenia

Although neurotoxic factors can be detected in moccasin venom, clinically significant neurotoxicity does not occur with envenomation by copperheads or cottonmouths.


A large percentage of bites are considered intentionally interactive—they occur when the snake is handled, kept as a pet, or abused. Many bites are associated with ethanol use.



United States

Approximately 9,000 patients are treated in US emergency departments (EDs) for snake envenomation each year.[2] Based on poison center data, moccasin snakes account for 56% of this total (50% copperheads and 6% water moccasins).[3] In portions of the southeastern United States, copperheads account for 85% of all reported snake envenomations.[4, 5] See the image below.

Snake envenomations, moccasins. Copperhead (Agkist Snake envenomations, moccasins. Copperhead (Agkistrodon contortrix). Photo courtesy of George Bush.


An estimated 1.8-2.7 million venomous snakebites occur each year worldwide.[6]  The proportion of these caused by Agkistrodon species is not known.


Incidence of snakebite is higher in males than in females.


Young adults are bitten most commonly.[7]


The American Association of Poison Control Centers (AAPCC) previously reported only two deaths from moccasin envenomation since its first annual report in 1983. In two retrospective studies of copperhead victims, patients missed a median of 2-6 weeks of work. Treatment with Crotalidae Polyvalent Immune Fab (ovine) was found to reduce limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation.[8]  Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation.[9]

Nearly all patients fully recover after moccasin envenomation, although long-term disability has been reported.[10]

Some patients have long-term problems with limb pain and/or swelling, particularly after physical exertion. The proportion of patients who develop these sequelae and the relationship with initial clinical severity and treatment are not known.

Patient Education

Call professionals, such as animal control, to move snakes.

Never attempt to handle, possess, or kill venomous reptiles.

For patient education resources, see the patient education article Snakebite.




Most bites occur on the extremities. Upper extremity bites predominate in males and are often associated with deliberate handling of the snake. Other findings may include the following:

  • Pain around the bite site
  • Swelling
  • Nausea, vomiting, or diarrhea
  • Syncope, near syncope

Co-intoxication with alcohol is common and may affect the patient's judgment and ability to comply with therapy.

Physical Examination

Although moccasin envenomation usually is associated with less severe local effects than rattlesnake envenomation, severe envenomations do occur.[11]

Fang marks are common, but they may be absent.

Hemorrhagic vesicles may be present at the envenomation site.

Tenderness surrounding bite site is almost always present.

Use a pen to mark and time the border of advancing edema and tenderness often enough to gauge progression.

Rapidly progressive swelling is usually indicative of a more severe envenomation.

Erythema at the bite site, proximal to the bite site, and along patterns of lymphatic drainage may be noticed.

Ecchymosis and bullae may also be noted.

Bleeding into the tissues of the bite site is common. Systemic bleeding is uncommon in moccasin envenomations.

Tachycardia is common and due to pain, anxiety, and third-spacing of fluids due to inflammation.

Hypotension is uncommon and usually due to intravascular volume depletion.


Complications of envenomation may include the following:

  • Coagulopathy (uncommon in moccasin envenomations), thrombocytopenia (uncommon), and bleeding (rare)
  • Lymphatic injury, leading to prolonged or permanent swelling of the envenomated limb, particularly after exertion
  • Skin and soft-tissue necrosis
  • Infection (affects ~2% of patients with viperid snake envenomation)
  • Death (extremely rare)

Also see Complications in Treatment.





Laboratory Studies

Coagulopathy, specifically hypofibrinogenemia and thrombocytopenia, may occur with pit viper envenomation. However, these problems are much less common after copperhead envenomations than after cottonmouth and rattlesnake envenomations. Laboratory evidence of coagulopathy and/or thrombocytopenia occur in approximately 10% of copperhead envenomations; clinically significant bleeding occurs very rarely. For a more detailed discussion of coagulopathy induced by pit viper venom, see Rattlesnake Envenomation. Perform the following laboratory tests:

  • CBC count including platelet count
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Fibrinogen concentration
  • Type and screen, only if severe coagulopathy/thrombocytopenia is present or clinical bleeding is suspected

Additional laboratory and other diagnostic data should be obtained on a case-by-case basis. Factors to consider may include severity of envenomation, physician preference, and cost. Bacterial cultures are rarely helpful. The incidence of infection in these envenomations is approximately 2%. Patients who develop shock, respiratory failure, or signs suggesting rhabdomyolysis may benefit from measurements of electrolytes, BUN, creatinine, and creatine phosphokinase (CPK) on a case-by-case basis. Elevations of CPK are common after moderate-to-severe rattlesnake and possibly cottonmouth envenomations, less so with copperheads.

Imaging Studies

Plain radiographs may depict teeth or fangs retained in the wound. However, this finding is uncommon and of limited clinical utility; routine radiography is not recommended.

Other Tests

Skin testing for allergy to antivenom is not necessary prior to administration of commercially available antivenoms for US pit vipers.

Pregnancy testing may be indicated in reproductive-aged female patients, as snake envenomation can cause miscarriage.

Because moccasin venom is not cardiotoxic, routine examination with ECG is not required. An ECG may be useful in cases of shock or if otherwise clinically indicated.


Fasciotomy is rarely, if ever, indicated in cases of moccasin envenomation.

Because envenomation produces limb swelling, severe pain, and pain with passive stretch, it is common for envenomated limbs to appear similar to limbs with compartment syndrome. However, true compartment syndrome is present in less than 2% of moccasin envenomations.

Compartment pressure monitoring is indicated in cases of suspected compartment syndrome.

The preferred therapy for compartment syndrome due to moccasin envenomation is administration of antivenom. Crotaline Fab antivenom has been shown to improve perfusion pressures in an animal model and in human case reports.

Fasciotomy should be reserved for cases in which compartment pressures remain elevated despite administration of adequate doses of antivenom or in cases of compartment syndrome when antivenom cannot be obtained.[12]

Because tissue pressures in the fingers and toes cannot be measured accurately, the diagnosis of suspected compartment syndrome in the digits is difficult. If capillary refill is poor, administer antivenom to reduce swelling and attempt to restore perfusion. If capillary refill remains poor after administration of adequate doses of antivenom, digit dermotomy may be indicated.[12]



Prehospital Care

Do nothing to injure the patient or impede travel to the ED.

Support the airway, breathing, and circulation per advanced cardiac life support (ACLS) protocol with oxygen, monitors, large-bore intravenous lines, and fluid challenge. Minimize activity (if possible), remove jewelry or tight-fitting clothes in anticipation of swelling, and transport the patient to the ED as quickly and as safely as possible. Use a pen to mark and time the border of advancing tenderness often enough to gauge progression (suggest about every 15 minutes at first).

Studies have demonstrated no benefit when a negative-pressure venom-extraction device (eg, The Extractor, Sawyer Products) was evaluated; additional injury can result.[13, 14] Incision across fang marks is not recommended. Mouth suction is contraindicated.

Lymphatic constriction bands and pressure immobilization techniques may inhibit the spread of venom, but whether they improve outcome after viper envenomation is not clear. These techniques may actually be deleterious for pit viper envenomation if they increase local necrosis or compartment pressure. Tourniquets are not recommended.

Maintain the limb in a neutral position of comfort.

First aid that lacks therapeutic value or is potentially more harmful than the snakebite includes electric shock, alcohol, stimulants, aspirin, ice application, and various folk and herbal remedies.[15, 16]

Cost and risk of acute adverse reactions generally preclude field use of antivenom.[15]

Attempts to capture or kill the snake are not recommended because of the risk of additional injury.

If the venomousness of a particular snake is uncertain, consider taking photographs of the snake from a safe distance of at least 6 feet away using a cell phone or digital camera. Species identification can be helpful and can sometimes guide the choice about antivenom, but is not necessary for appropriate management.

Emergency Department Care

Adequate hydration with intravenous fluids is indicated. Patients with hypotension should be resuscitated first with two isotonic sodium chloride solution challenges (eg, 20 mL/kg) while receiving antivenom. Persistent shock may require evaluation for bleeding, pressors, and additional antivenom,

Managing envenomations is a dynamic process; administer additional antivenom as indicated by a worsening clinical course. When considering the use of antivenom, the risk of allergy to antivenom must be weighed against the benefits of reducing venom toxicity. See the algorithm below.[17]

Crotaline treatment algorithm. Crotaline treatment algorithm.

Inpatient Care

Patients believed to have dry bites, in which no venom effects develop, should be observed for at least 8 hours. Close follow-up and/or recheck examination is recommended.

Patients who have minimal snake envenomation are probably best managed with overnight observation. They may be discharged if signs of envenomation do not progress for at least 12-24 hours, with instructions to return if venom effects progress. Several reports have documented instances in which patients who were initially discharged with mild envenomation returned in several hours with progressive venom effects requiring antivenom.

Patients whose envenomation is severe enough to require antivenom should be admitted to the hospital or an ED observation unit.

Patients who are discharged should be instructed to return to the hospital if pain or swelling increases or if new symptoms develop. Because patients at home rarely elevate their envenomated limbs consistently, some increase in swelling is expected during the first 1-3 days after the patient goes home. If not accompanied by increasing pain or other signs/symptoms, this is generally not a concern.

Certified specialists in poison information and medical toxicologists are available to provide consultation through a regional poison center: 1-800-222-1222.

If indicated, patients may require transfer after stabilization to a facility where antivenom can be administered and/or where medical toxicologists or other physicians experienced in the management of snake envenomation are available.


This agent neutralizes toxins from snakebites. Two antivenoms are currently marketed in the United States, one of which has US Food and Drug Administration (FDA) approval for use in Agkistrodon snake envenomation.[18]

Crotaline Fab antivenom (CroFab; Crotaline polyvalent immune Fab (ovine), BTG International Inc, West Conshohocken, Penn) is a highly purified product derived from sheep hyperimmunized with the venom of four crotaline snakes, including A piscivorus. A relatively pure IgG fraction is extracted from the sheep serum and cleaved with papain to remove the antigenic Fc portion. Column affinity purification is then used to produce a product consisting almost entirely of Fab fragments with specific affinity to snake venom.[19] CroFab is approved by the FDA for treatment of both rattlesnake and moccasin (Agkistrodon) snakebites.

Clinical trial data show that copperhead victims treated with ovine Fab antivenom recovered more quickly and had a shorter duration of opioid analgesic use than those who received placebo.[8, 20] Patients who received Fab antivenom soon after envenomation recovered more quickly than those who received Fab antivenom in a delayed fashion.[6]

An F(ab’)2 antivenom (Anavip; Crotalidae Immune F(ab’)2 (equine), Instituto Bioclon S.A. de C. V., TlapIan CXMX, Mexico) may also be effective for moccasin envenomation. Anavip is produced from the serum of horses hyperimmunized with venom from two Central American rattlesnakes, and the IgG molecule is cleaved below the hinge region to produce 100 kd F(ab’)2 molecules. Although Anavip is only FDA approved for the treatment of rattlesnake envenomation, both copperhead and water moccasin victims were included in the Anavip clinical trials.[21] The impact of F(ab’)2 antivenom on recovery from venom-induced limb injury has not been studied,

The antivenom dose is titrated to clinical effect. The initial dose of CroFab is 4-6 vials infused intravenously over 1 hour; most copperhead patients respond well to a 4-vial dose.[18, 22] If using Anavip, the initial dose is 10 vials.[23] Doses are repeated as needed until initial control of the signs and symptoms of envenomation are achieved: swelling is no longer progressing, the patient is clinically stable, and coagulation parameters are normal or clearly trending towards normal. At this point, the FDA-approved dosing recommendations call for administration of 2-vial doses of CroFab 6, 12, and 18 hours later to maintain initial control. Some data suggest that this maintenance dosing may not be necessary when treating copperhead patients.[18] Because of its longer half-life, maintenance dosing is not required when using Anavip. Recurrence of swelling or worsening coagulation parameters are treated with repeat doses of antivenom.

Antivenoms can be associated with acute and delayed allergic reactions (see Complications below).

Modern antivenoms are costly. Ideally, patient-centered decision-making should include discussions of benefits, risks, cost, and patient preferences. Although risk-benefit calculations favor antivenom administration in most clinical situations, both antivenom products are expensive, and formal cost-benefit studies have not been conducted.


Medically significant bleeding is uncommon in water moccasin envenomation and very rare following copperhead bites. Consider transfusion, in conjunction with ongoing antivenom administration, if antivenom alone does not correct severe coagulopathy or if the patient has active severe bleeding. Transfusion is generally recommended for life-threatening bleeding (rare), a platelet count of less than 20,000/μL, fibrinogen less than 50 mg/dL, or a hemoglobin value of less than 7 g/dL. Use transfusion as a temporizing measure only after adequate antivenom therapy because antivenom may correct coagulopathies more definitively. Coagulopathy and thrombocytopenia often recur and may persist for as long as 2 weeks after envenomation. Recurrence of coagulopathy and thrombocytopenia may be less common in F(ab’)2 than in Fab recipients.

Discharge Instructions

Keep the envenomated extremity elevated.

Return immediately if swelling worsens or pain becomes severe.

Return immediately if any abnormal bleeding or bruising, dark tarry stools, or severe headache occurs.

Return for signs of wound infection, such as fever, worsening redness, or swelling immediately adjacent to the bite site, or drainage of pus. Because tenderness at the bite site, more generalized swelling, and lymphangitic streaking are common manifestations of the envenomation itself, these are less useful as signs of infection.

Return or follow up if a fever, itchy rash, joint pain, or swollen lymph nodes occur any time during the next few weeks.

Acetaminophen or a prescribed pain medication is typically used for analgesia following snake envenomation. NSAIDs are probably safe to administer in cases of copperhead envenomation.[24, 25]

Do not participate in contact sports, undergo elective surgery, or have dental work for 2 weeks after the snakebite.

Drink plenty of liquids. Return if urine decreases in amount or becomes cola colored.

Referral to a physical therapist or surgeon may be indicated.

Patients who developed coagulopathy or thrombocytopenia should have these studies rechecked in 2 days, again in another 2-3 days, and as needed for signs of coagulation problems (eg, bleeding gums, easy bruising).


In the United States, the nationwide Poison Help! number, 1-800-222-1222, connects the caller to the nearest poison control center. Certified poison centers have trained personnel to assist physicians in the management of toxic exposures, including snake bites, with 24-hour access to medical toxicologists for specific questions.

In addition, medical toxicologists are available to provide bedside patient care at some medical centers. Medical toxicologists have specific training and expertise in snakebite management.

The manufacturer of Crotaline Fab antivenom provides a technical assistance hotline at 1-877-SERPDRUG (877-377-3784).

Consider consulting a surgeon (eg, general, orthopedic, hand) if, in the subacute phase of illness, debridement of clearly necrotic tissue is required.

Occupational therapy, physical therapy, physiatry (rehabilitative medicine), and/or pain management consultation may be helpful to assist patients with persistent pain, swelling, or other limitations.


Antivenom-associated complications may include immediate hypersensitivity reactions and delayed hypersensitivity reactions.[26] In a randomized controlled trial of FabAV for copperhead bites, the incidence of hypersensitivity reactions was low. Most reactions were mild skin reactions.[27]

Immediate hypersensitivity reactions

Although true anaphylaxis can occur, most acute hypersensitivity reactions are rate-related anaphylactoid reactions resulting in histamine release. These occur in approximately 8% of CroFab-treated patients.[28] The proportion of Anavip recipients who develop anaphylactoid reactions is not as well established, but clinical trial data suggest the rate is similar to CroFab-treated patients.[21] If urticaria, wheezing, swelling, or hypotension develop, take the following steps:

  1. Stop the antivenom infusion.
  2. Administer antihistamines (eg, diphenhydramine), epinephrine, and/or corticosteroids as clinically indicated.
  3. Reassess the need for antivenom, involving local experts or experts from the regional poison center as needed.
  4. If antivenom administration is resumed, do so at a reduced infusion rate.

Almost all patients who develop an anaphylactoid reaction are able to complete antivenom therapy.

Delayed hypersensitivity reactions

Serum sickness is a delayed-type hypersensitivity reaction, characterized by rash, myalgias, flulike symptoms, and, occasionally, fever, developing 3-14 days after antivenom administration. Serum sickness is reported in approximately 12% of CroFab recipients.[28] The rate of serum sickness following Anavip administration is less well-established, but probably similar. Treatment is with oral corticosteroids.


Never handle a venomous snake, even if it is believed to be dead.

Do not reach or step into places outdoors that are not visible.

At home, remove debris in which snakes might hide (eg, log piles). Remove items, such as bird feeders, that might attract snakes—seeds that fall from bird feeders attract rodents, which attract snakes.

Heavy clothing (such as hiking boots) may retard some strikes.

Young children should be closely supervised, and older children should be educated to avoid snakes.[7]



Medication Summary

The physician must be prepared to support the patient's cardiovascular and respiratory systems after any venomous snakebite.


Class Summary

Indications for antivenin use in crotalid envenomation include significant or progressive local tissue findings, hematologic laboratory abnormalities, and/or evidence of systemic toxicity (eg, airway swelling, neurological toxicity, cardiovascular collapse). The sooner antivenin is initiated, the more effective it is.

Crotalidae polyvalent immune FAB (ovine) (CroFab)

It is indicated for envenomation caused by North American pit vipers, including rattlesnakes, copperheads, and cottonmouths (water moccasins).

Crotalidae immune FAB (equine) (Anavip)

Crotalidae immune FAB (equine) contains venom-specific F(ab’)2; fragments of immunoglobulin G (IgG) that bind and neutralize venom toxins, thereby facilitating redistribution away from target tissues and elimination from the body. It is indicated for envenomation caused by North American pit vipers, including rattlesnakes, copperheads, and cottonmouths (water moccasins).


Class Summary

These agents immunize patients against tetanus.

Diphtheria-tetanus toxoid (dT)

Diphtheria-tetanus toxoid is used to induce active immunity against tetanus in selected patients. Tetanus and diphtheria toxoids are the immunizing agents of choice for most adults and children older than 7 years. Booster doses are necessary to maintain tetanus immunity throughout life because tetanus spores are ubiquitous.

Pregnant patients should receive only tetanus toxoid, not a diphtheria antigen–containing product. In children and adults, immunization may be administered into the deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the mid thigh laterally.