The North American pit vipers include [9,13,15,18,21,47]:

By far, most bites to humans occur in the spring and summer. Snakes are cold-blooded, so they seek warmth underground or among rocks in cold weather. In the spring they are quite active, so one may see relatively many bites as the ground warms. More bites occur in the evenings, as people are more active outside and as the snakes become more active in seeking food during the time of day that better meets their temperature requirements. Wingert notes that [37]:

Although snakes prefer nocturnal activity, a major proportion of the bites (approximately 45%) occur between 3 p.m. and 9 p.m. Males are bitten in a ratio of 4:1 over females. [Male humans suffer from a prefrontal cortex that matures later than that of the female, and many of this subset when bitten have recently consumed alcohol and/or other mind-altering drugs.] Fifty percent of bites occur in children or young adults younger than 20 years of age, with the highest proportion in the 16 to 24 year age group. Of all bites, 65% occur in the upper extremities (usually the hands or fingers) and 34% in the lower extremities. Approximately one-third of all bites are non-accidental; that is, the patient was purposefully handling or playing with a venomous snake.

Exposure to snakes occurs in a variety of places—gopher holes, open air conditioning ducting under buildings, on the roadside, commercial nurseries after the snakes are transported in potted plants, garages, gutter downspouts, corn fields, tall grass, woodpiles, and flowerbeds. According to experts at the Arizona Poison and Drug Information Center, 25% of rattlesnake bites are dry bites—no venom is injected. In another 25%, so little is injected that antivenom is not required [3]. Of an estimated 8,000 bites reported in the United States each year, only 8 to 15 result in death. Most of these deaths can be attributed to complications of the injury, errors in management, or other factors not directly related to snake venom [24].

The venom of rattlesnakes is responsible for more deaths, more hospitalizations, and more injuries than the venom of any other animal in North America [24]. The eastern diamondback rattlesnake accounts for the majority of deaths from snakebite in the United States [51]. Unlike the less complex neurotoxic venom of elapids, pit viper venoms, particularly those of the rattlesnakes (crotalids), are composed of as many as 20 different components.

Envenomation by the massasauga (Sistrurus catenatus) in general causes edema that is far less severe than with crotalid bites, although it may sometimes be marked in an untreated case. Ecchymosis is not unusual, and blebs may form. Necrosis is minimal. Patients do not complain of paresthesia, nor is fasciculation seen. In most cases, there is some immediate pain [11]. Nausea and vomiting may occur. Lethal toxicity is significant [13].

The bite from a pit viper usually causes some degree of swelling around the bite area within 5 to 10 minutes. Nearly all bites cause pain, and pain that is initially mild usually increases in severity as edema progresses. The bite of a non-venomous snake may also be painful, but the pain results simply from the trauma of the bite and is of limited severity and duration, in contrast to the dull, constant pain and tenderness caused by envenomation. As local tissue damage increases, there is progressive swelling and ecchymosis.

Local swelling resulting from a deposit of venom may be immediate, greatly delayed, or absent, depending on the venom load and the depth of the bite. Deeper bites that penetrate muscle are more likely than subcutaneous bites to swell less, especially early on, but the venom is likely to make a more rapid entry into the systemic circulation due to the greater vasculature of muscle. This increases the likelihood of rapid clinical deterioration and more severe clotting abnormalities.

Pit viper envenomation can rise to the level of a complex poisoning, affecting every organ system, resulting in coagulopathy and hemoconcentration (early) followed by a decrease in erythrocytes (anemia), thrombocytopenia, hematuria, proteinuria, hematemesis, melena, hemoptysis, epistaxis, and hypotension [19]. Hypofibrinogenemia and thrombocytopenia are common findings. Physiologic responses to envenomation, such as release of bradykinin, contribute to the severity of pain and, short of a shock state, may cause significant but transient hypotension [15]. Difficulty swallowing (dysphagia), blurred vision, and marked thirst may occur, and the patient may experience significant weakness after eastern and western diamondback envenomation [12]. The patient may feel faint, nauseated, and/or numb or tingly around the mouth, tongue, scalp, fingers, toes, or site of the bite [19]. Such paresthesias indicate that a significant envenomation exists. Fasciculations are very common in human victims, and when present after a bite by an unidentified snake should suggest the eastern diamondback, the Mojave, or the southern Pacific rattlesnake as the offending reptile. Fasciculations in severe cases may become generalized, especially with eastern diamondback rattlesnake bites [15]. Transient myosis is said to be a symptom of severe envenomation due to the bite of the eastern diamondback rattlesnake [15]. Convulsions are particularly common in children [12]. Prolongation of bleeding and clotting times may occur [19]. In addition to visible tissue destruction (including blebs, sloughing, and gangrene), changes in capillary permeability may occur, leading to great fluid loss and hypovolemic shock as well as pulmonary edema (both of which are frequent causes of death) and swelling of entire limbs. Anaphylaxis and Kounis syndrome are unlikely but possible results of snakebite and should be considered in the overall assessment of the patient.

While local swelling in the region of the snakebite may be the most visible sign used to identify progression or lack of progression of envenomation, it is important to bear in mind that an occasional patient will have scant or even no swelling and yet a severe coagulopathy demonstrated by a plummeting fibrinogen level and likely plummeting platelet count as well. The impact of the venom on the blood coagulation cascade, coupled with the possibility of hypovolemic shock resulting from leakage of intravascular fluid into the tissues, constitutes the greatest threat to the victim. Incipient coagulopathy following envenomation is, in a sense, a "stealth attack," because coagulopathy cannot be felt by the patient or seen by the clinician unless overt bleeding is present. This, along with the fact that an occasional coagulopathy develops only after a surprising number of hours, is the reason that all pit viper snakebite victims who have and continue to have no swelling or other signs or symptoms should be evaluated for coagulopathy and monitored clinically by an informed staff in an urgent care setting with the ability to perform all required laboratory studies for 8 to 12 hours before being discharged home. Typical urgent care units are unlikely to be able to perform timely fibrinogen or FDP testing and thus would be an inappropriate setting for pit viper snakebite evaluation. As such, patients typically initially present to a hospital-connected emergency center, and those who begin to demonstrate any signs or symptoms of envenomation should be admitted to an ICU for a minimum of 24 hours.

Antivenoms currently in use (CroFab and Anavip) that target pit viper venom are suspensions of venom-neutralizing antibodies prepared from the serum of animals hyperimmunized against specific venoms [33]. Protherics Inc., the manufacturer, describes Crotalidae Polyvalent Immune fragment antigen binding (Fab) (Ovine) (CroFab) as [9]:

…a sterile, nonpyrogenic, purified, lyophilized preparation of ovine Fab (monovalent) immunoglobulin fragments obtained from the blood of healthy sheep flocks 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). To obtain the final antivenin product, the four different monospecific antivenins are mixed. CroFab is a venom-specific "Fab" fragment of immunoglobulin G (IgG) that works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body.

Because of the variable composition of pit viper venoms, the systemic manifestations of poisoning are variable in onset and progression; optimal management requires careful, frequently repeated clinical assessment over an extended period while anticipating the serious complications that may be associated with snake envenomation [39]. Hurlbut et al. make three fundamental and critical points about assessment of the snakebite victim [50]:

Weakness, dizziness, cold and clammy skin, tachycardia, nausea, vomiting, and diarrhea are all nonspecific symptoms and may be manifestations of an emotional or anxiety reaction (Table 1), in which case they appear almost immediately after the bite. Such symptoms may also reflect systemic envenomation, in which case they generally occur after 30 to 60 minutes, or longer[15]. Importantly, "nausea and diaphoresis accompanied by dizziness and weakness are probably not primary neurologic signs but indications of early hypotension due to intravascular volume depletion," in which case treatment with antivenom and a normal saline bolus would be indicated [25].

"Trivial" envenomation exists when swelling is localized 30 to 60 minutes after a bite and the patient ultimately exhibits no paresthesias, fasciculations, or ecchymoses; no symptoms other than minor pain; and no abnormal serial laboratory findings [12]. Antivenom is not indicated for apparent trivial envenomation. Instead, the affected part should be cleaned and immobilized and the patient should be immunized against tetanus and studied for at least 12 hours or overnight to ensure that delayed progression does not develop [12].

Pit viper venom does not cross the blood brain barrier and thus does not affect the brain directly. The presence of mental status changes suggests a comorbidity, prescription or recreational drug use, or the possibility of a cerebral bleed as a result of coagulopathy. Other complications of envenomation that may lead to mental status change include hypoxia secondary to pulmonary edema, cardiac failure, or hypovolemic shock. Aberrant behavior and seizure point to hypoxia, the etiology of which should be immediately explored.

As noted, IV fluid resuscitation with normal saline (at least 20 mL/kg in both children and adults) is usually adequate for the treatment of hypotension in patients with snakebite envenomation. It is advisable to give IV fluids cautiously, monitoring cardiac function and pulmonary signs so as not to exacerbate peripheral edema or precipitate pulmonary edema, especially in the treatment of severe envenomation. Vasopressors should be used only as short-term agents for the treatment of shock and only after hypovolemia as the likely cause of shock has been considered and addressed [12].

Risk of significant bleeding as a result of urinary catheter insertion is not of great concern in patients envenomed by pit vipers. Hematuria due to coagulopathy does not preclude urinary catheter insertion. Some risk of bleeding obviously exists; however, for patients with severe envenomation and those who are unable to void every one to two hours, the benefits of catheterization include:

In the prehospital setting, emergency responders should remain calm and reassure the patient continually. Death from snakebite is very rare. If the patient is stable and the hospital is close, avoid lights and sirens, as less excitement keeps capillary pressure (and thus the pressure gradient) lower, resulting in slower absorption of the venom. The patient should be instructed to avoid any unnecessary activity and movement.

If possible, the snake should be photographed and identified, but the animal should only be transported if its identity is in question and if it is safe to do so. Reflexes persist even after beheading, so all snakes should be treated as if alive.

Jewelry should be removed, but any constricting band or tourniquet should remain until removal is instructed by a physician's order. The extremity should be lightly splinted/immobilized after marking and timing the leading edge of swelling or tenderness. The extremity should be positioned slightly below heart level. If a suction pump device (e.g., the Sawyer Venom Extractor) is used, it should be limited to one minute to prevent further tissue damage.

If pain is severe, morphine sulfate should be administered (slowly, to avoid nausea), unless the patient has a history of allergy. One large-bore IV should be started away from the bitten extremity with warmed normal saline (as cold fluids can contribute to shock) administered and titrated to keep the patient's blood pressure within normal limits and pulse less than about 110–120 beats per minute in an adult; loss of vascular fluid volume should be considered. If circumstances allow for perfect sterile technique, start an IV lock away from the bitten extremity. Blood should be drawn using a large clot tube first, followed by tubes of all colors. All tubes should be fully labeled and signed, and a blood bank form (with phlebotomist signature) should be completed on arrival at the hospital.

For all patients with known or suspected snakebite, assessment is based on laboratory values and progression, if any, of signs and symptoms. It is important to remember that even asymptomatic patients should be studied for 8 to 12 hours from the time of the bite [13].

A blood band should be applied, and the blood requisition is labeled "Snakebite: hold clot tube only." The signed blood sample and requisition are sent to the blood bank, but type and screen or crossmatch should be performed only if it becomes necessary. Differential, creatine kinase (CK), and ethanol (if indicated) tests should also be included in the initial laboratory assessment. The following tests should be performed immediately and every six hours thereafter:

All patients with any signs/symptoms of envenomation should be admitted to an ICU. These patients are kept NPO and on strict bed rest initially, with vital signs taken every 15 minutes (including pulse oximetry); automated blood pressure measurements should be avoided. Morphine sulfate may be administered as needed for pain if the patient has no history of allergy. Infection is rarely an issue in the early management of snakebite, and prophylactic antimicrobials are not indicated. If there is uncertainty about the diagnosis or if objective signs (e.g., purulent discharge, fever) develop as a late complication of tissue breakdown, antimicrobial therapy may be indicated, guided by cultures [12].

Blebs, vesicles, and superficial necrotic tissue should be aseptically debrided on the fourth or fifth day, per local protocol, if coagulation values are normal. Active and passive rehabilitation therapy should be initiated as soon as the patient is able to tolerate it to prevent contractures, and the patient with significant injury should be referred to rehabilitation therapy at discharge.

Antivenom treatment should be initiated in the presence of any of the following signs or symptoms [86]:

Progression of circumferential or linear (leading edge) swelling measuring 1 cm/hour is considered to be significant, regardless of the site of the bite. Without early and adequate treatment, swelling and healing can take weeks to return to a level of maximum improvement. With early and adequate treatment, swelling can be expected to subside in approximately 10 days [4]. It is therefore important to not wait hours to see how far swelling progresses before beginning antivenom administration, because further and perhaps irreversible tissue destruction may well be occurring during that time. Swelling can occur haltingly as the venom dissolves different types and layers of tissue and can be thought to have stopped, only to become obvious again. One should not wait for multiple episodes of such a pattern to pass before beginning treatment.

Each vial of CroFab should be reconstituted with 18 mL of 0.9% saline drawn from an IV bag of normal saline containing the volume of fluid the patient is to receive over the next hour (minimum: 250 mL) [4]. The diluent should be instilled gently along the wall of each vial to avoid foaming. To hasten mixing, release pressure after all diluent is added. Each vial of CroFab should be mixed by continuous, gentle manual inversion at a rate no faster than two complete inversions per second, until no solid material is visible in the vial; to prevent foaming, it should not be shaken. The reconstituted antivenom is then returned to the IV bag.

Regardless of patient age, in severe envenomation CroFab is initially administered approximately each hour in increments of 10 vial doses to gain control (rather than the routine 6 vial doses discussed later) until initial control is achieved. Consultation should be sought early with severe envenomation, particularly if initial control is not achieved by the administration of two 10-vial doses of CroFab.

After swelling appears to have ceased and coagulation studies have normalized or are trending substantially toward normal, one should continue to measure and mark the zone of local swelling every 30 minutes to 2 hours for the next 48 hours. Importantly, recurrence or delayed-onset of one or more venom effects occurs in up to approximately half of patients treated with CroFab antivenom [87]. Recurrence can also occur after treatment with Anavip. Local tissue recurrence typically develops within 6 to 36 hours of initial control. The onset of recurrent or delayed-onset hematologic venom effects typically occurs 2 to 7 days after initial control, with some cases up to 10 days after initial control [88].

Epinephrine is the drug of choice for anaphylaxis and should be administered as first-line therapy. Epinephrine may rarely be used prophylactically in patients known to be acutely sensitive to antivenom or its components and who have a life-threatening envenomation.

Massive fluid shifts can occur rapidly in anaphylaxis due to increased vascular permeability, with transfer of up to 35% of the intravascular volume into the extravascular space within minutes [82]. Any patient who does not respond promptly and completely to injected epinephrine should be assumed to have intravascular volume depletion causing persistent hypotension despite maximum vasoconstriction. Large-volume warmed fluid resuscitation should be initiated immediately in patients who present with orthostasis, hypotension, or incomplete response to IM epinephrine [81]. Adults may require 1–2 L normal saline administered at a rate of 5–10 mL/kg in the first five minutes. Children should receive up to 30 mL/kg in the first hour [98].

Boyer et al. recommend that patients who have received antivenom should be re-evaluated at least once within five days after treatment [5]. If the results of laboratory testing remain normal, recurrence is unlikely. However, patients at risk for recurrence (i.e., with abnormal coagulation during the first 36 hours) should be reassessed every 48 hours after the last antivenom dose, until coagulation values are clearly stable or improving for several days [5].

If coagulation values become significantly abnormal on follow-up, or if there is a definite downward trend, then laboratory test results should be monitored daily and consideration should be given to re-treatment with antivenom. Until more data are available, re-treatment with FabAV should be considered in patients with any of the following [5]: