European Journal of Internal Medicine 17 (2006) 24 – 27 www.elsevier.com/locate/ejim
Original article
Snake venom poisoning in Greece. Experiences with 147 cases Christos Y. Frangides a, Vasilios Koulouras a, Sophia N. Kouni c,*, Gerasimos V. Tzortzatos b, Athanasios Nikolaou a, John Pneumaticos a, Christos Pierrakeas b, Constantinos Niarchos b, Nicholas G. Kounis c, Constantinos M. Koutsojannis c a
c
Department of Internal Medicine, ‘‘Saint Andrews’’ State General Hospital, Patras, Greece b Department of Cardiology, ‘‘Saint Andrews’’ State General Hospital, Patras, Greece Section of Medical Sciences, School of Health Sciences, Patras Highest Institute of Education and Technology, 7 Aratou Street, Queen Olga’s Square, Patras 26221, Greece Received 3 February 2005; received in revised form 10 June 2005; accepted 31 October 2005
Abstract Background: Snake venom poisoning is a medical emergency requiring immediate attention. Bites from poisonous European snakes can lead to local tissue damage and systemic symptoms. Vipera ammodytes accounts for the most envenomation in Greece. Methods: The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome of 147 consecutive victims of V. ammodytes admitted to our hospital from 1988 to 2003 were reviewed and analyzed. Results: The most common symptoms and signs included fang marks (100%), pain (100%), swelling (98.64%), ecchymosis (60.54%), tachycardia (32.65%), fainting or dizziness (29.93%), fever (23.13%), enlargement of regional lymph nodes (17.69%), nausea (16.33%), hypotension (13.61%), and vomiting (12.93%). The main complications were reduced range of motion, thrombophlebitis, local hemorrhagic blister formation, skin bleeding, rhabdomyolysis, reduced sensation, acute renal failure, necrosis with tissue loss, carpal tunnel syndrome, compartment syndrome, Kounis syndrome, and digit amputation. Conclusions: A V. ammodytes bite is a potentially serious event that requires immediate hospital care. Yet, the majority of victims can be treated successfully with conservative methods. No deaths occurred in our series. D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. Keywords: European snakes; Snake venom; Vipera ammodytes poisoning; Kounis syndrome; Rhabdomyolysis
1. Introduction Greece is home to poisonous snakes of the Viperidae family, which belongs to the subgroup Viperinae (adders) that includes Vipera ammodytes, Vipera xanthine, Vipera labetina, Vipera berus, and Vipera ursinii. V. ammodytes is the most common snake found in all parts of the country and it is responsible for the vast majority of envenomation. Other snakes are located in specific geographic regions of the country. Snakes in Greece start their activity at the end of winter and remain active until the end of autumn.
* Corresponding author. Tel./fax: +30 2610 279579. E-mail address:
[email protected] (S.N. Kouni).
V. ammodytes has, in its upper jaw, two movable poisonous teeth, and one single bite can release about 20 mg of poison. The snake poison is rich in proteins, of which neurotoxin, cytotoxin, and hematoxin are the most important. It also has large amounts of enzymes that are proteolytic or hydrolytic and contain hyaluronidase. In addition, the poison stimulates the release of histamine or similar substances that can cause gas gangrene and infection from Clostridium species [1,2]. Bites from poisonous European snakes of the Vipera order can lead to local tissue damage and systemic symptoms such as generalized edema, hypotension, gastrointestinal symptoms, hemolysis, and renal dysfunction. Allergic symptoms, such as utricaria, localized angioedema asthma, and even Kounis syndrome, have been observed
0953-6205/$ - see front matter D 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2005.10.001
C.Y. Frangides et al. / European Journal of Internal Medicine 17 (2006) 24 – 27 Table 1 Demographic characteristics of the snakebite victims
Table 3 Clinical symptoms and signs
N = 147 Gender Employment Farmers or shepherds Other professions Age
25
Male Female
85 62
57.82% 42.17%
Male Female Male Female Male Female
57 54 28 8 16 – 83 years 16 – 80 years
38.77% 36.73% 19.04% 5.44% 48.11 T17.71 52.13 T 15.92
[3]. Anaphylactic reactions following snakebites may be IgE-mediated [4]. The purpose of this retrospective study was to review the demographic, epidemiological, clinical and laboratory findings, as well as the treatment and outcome, of 147 consecutive cases of snakebite envenomation treated in our hospital.
Symptoms and signs
N = 147
%
Fang marks Pain Swelling Ecchymosis Tachycardia Fainting or dizziness Fever Swelling of regional lymph nodes Nausea Hypotension Vomiting Paresthesia Allergic reactions Swollen reactions Blurred vision Convulsions Kounis syndrome
147 147 145 89 48 44 34 26 24 20 19 10 4 4 4 1 1
100.00 100.00 98.64 60.54 32.65 29.93 23.13 17.69 16.33 13.61 12.93 6.80 2.72 2.72 2.72 0.68 0.68
regression analysis. A P-value below 0.05 was considered to represent a statistically significant difference.
2. Patients and methods One hundred forty-seven individuals treated at ‘‘Saint Andrew’s’’ State General Hospital in Patras, Greece, from January 1988 to December 2003, for V. ammodytes bites were included in this study. Data were collected from their medical records. All of the patients exhibited evidence of envenomation. The severity of the reaction to a snakebite depends on the degree of envenomation. The classification of our cases was based on a system described by Downey et al. [5]. According to this system, grade 0 indicates there is no envenomation but swelling and erythema around the fang marks below 2.5 cm, grade 1 indicates swelling and erythema of 2.5 – 15 cm but no systemic signs, grade 2 swelling and erythema of 15– 40 cm with mild systemic signs, grade 3 swelling and erythema greater than 40 cm with systemic signs, and grade 4 indicates severe systemic signs including coma and shock. The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome were analyzed. Statistical analysis was performed using the v 2 test and with Spearman’s rho correlation coefficient and stepwise
Table 2 Severity of the snakebite according to Downey et al.’s system Grade
N
%
0 1 2 3 4 Total
0 91 45 9 2 147
0.0 61.90 30.61 6.12 1.36 100
3. Results 3.1. Demographic and epidemiological characteristics of the victims As expected, the snakebites showed a well-defined seasonal pattern, with all cases occurring from March through October. Half of the cases were noted during the summer months of June, July, and August. The offending snake was seen in the majority of cases (93.5%); 37 patients brought the dead snake to the hospital for identification. The largest incidence was during the warmest midday hours. The anatomical locations of the bites were the upper extremities (finger and hand) and the feet (ankle, heel, tibia). Table 1 shows the demographic characteristics. Table 2 shows the severity of the snakebite according to Downey et al.’s system.
Table 4 Complications of snakebite victims Complication
N = 147
%
Wound infection Reduced range of motion Thrombophlebitis Skin bleeding Local hemorrhagic blister formation Rhabdomyolysis Reduced sensation Acute renal failure Local necrosis with tissue loss Carpal tunnel syndrome Compartment syndrome Digit amputation
20 19 15 9 9 8 6 4 4 3 2 1
13.60 12.92 10.20 6.12 6.12 5.44 4.08 2.72 2.72 2.44 1.36 0.68
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3.2. Clinical symptoms, signs, and laboratory aspects All patients were seen within 1 h of the bite, either in the regional medical center or in the hospital. Table 3 shows the clinical symptoms and signs, and Table 4 shows the main complications of the snakebite victims. The laboratory findings of our patients are summarized in Table 5. The duration of hospitalization ranged from 1 to 28 days, with a mean duration of 4.03 T 3.53 days. One hundred ten patients (74.82%) were in the hospital for fewer than 5 days and 13 (10.56%) for more than 5 days. 3.3. Treatment and outcome On admission to the hospital, the wound was cleansed thoroughly and covered with a sterile dressing. The injured extremity was immobilized in a position at heart level. The patients were put in bed, not allowed to walk, and kept warm. Vital functions, size of local swelling, ecchymosis, development of systemic symptoms and signs or delayed toxicity including coagulopathy and estimation of urine output were noted for all patients. Prophylaxis with tetanus toxoid and/or tetanus immune globulin at a dosage of 250 IU intramuscularly was administered at separate sites in separate syringes. All patients received supportive and symptomatic treatment, with special care in the maintenance of fluid and electrolyte balance and urine output. Analgesics, antiemetics, antiallergics, and mild sedatives were given when necessary. All patients received antibiotics (a combination of penicillin and metronidazole) in order to prevent microbial contamination because the majority of victims had made the incisions themselves in the bite area using non-sterilized knives. Renal dialysis was not required in cases of mild acute renal failure. There were not any serious coagulation disorders. Platelet transfusion and replacement with specific clotting factors and fresh whole plasma were not required. Intravenous administration of antivenin was only given in 12 (8.16%) cases. The antivenom available in Greece Table 5 Laboratory aspects of snakebite victims Lab findings
N = 147
%
Leukocytosis Neutrophilia Ureac CPKj PT/PTTj SCOT/SGPTj LDHj Hematuria/proteinuria Creatininej Thrombocytopenia Bilirubinj Myoglobinemia Aldolase Myoglobinuria
104 102 40 38 34 33 32 32 22 12 12 8 7 7
70.74 69.38 27.21 25.85 23.12 22.44 21.76 21.76 14.96 8.16 8.16 5.44 4.76 4.76
contains antibodies for all Greek snakes. Skin testing with horse serum was performed before administration of the antivenin. All patients were successfully treated and recovered completely. There were no deaths.
4. Discussion This study shows that snakebites are, in large proportion, an occupational risk in middle-aged persons. Lack of concentration, overconfidence, and a lack of protective measures, such as wearing gloves, boots, or long pants, in activities and work in places where snakes are hidden are some of the causes of snakebites. The relatively high proportion of middle-aged men and women bitten by snakes is attributed to the fact that, in rural areas in Greece, men and women are equally employed in the fields, and the possibility of accidentally bothering a snake is high. In contrast, other reports show that in other parts of the world, the most common victims are children and teenagers [6] or young adults [7]. The degree of protection afforded by responsible behavior and protective clothing is remarkable. Iserson [8] reported on the incidence of snakebites in three groups of experienced outdoor workers. Members of the Southern Arizona Rescue Association worked for 115,00 person – hours in the field without a snakebite. The personnel of the La Selva Biological Station in Costa Rica worked for 350,000 person – hours in the field without a bite. Graduate students in tropical studies, also in Costa Rica, worked for 660,000 person –hours in the fields with only one bite. The risk of someone being bitten by a snake is small and so is the risk of dying from a snakebite. Although there are an estimated 45,000 bites from all snakes in the United States each year, only 6800 persons are treated for snake poisoning [9]. In a 6-year period (1975 –1980), the number of deaths from snakebites in the United States ranged from 9 to 14. Most of the deaths occurred in people who were elderly, mistreated, untreated, complicated by other serious diseases, or members of religious sects who handle serpents as part of their worship exercises and refuse medical treatment [10]. The severity of the reaction to a snakebite depends on the nature, location, depth, and number of bites, the amount of venom injected, the species and the size of the snake involved, the age and size of the victim, and the victim’s sensitivity to the venom [11]. Larger snakes of the same species tend to have more venom, although the larger snake may have learned to ration its venom while a smaller and younger animal may be more likely to inject the full load. Moreover, the venom is stronger when the snake awakens from hibernation. Our findings suggest that the majority of V. ammodytes bites in Greece produce mild local and systemic manifestations. In our series, the time interval between snakebite and hospital admission was 40.95 T 24.06 min and is relatively
C.Y. Frangides et al. / European Journal of Internal Medicine 17 (2006) 24 – 27
short in comparison with other series. This should be attributed to the fact that snakebite is always a hot topic, leading to an unwarranted fear of impending death and necessitating immediate medical care. It must be pointed out that some of the local signs presented, such as edema, redness, and ecchymosis, might be produced or deteriorate from improper or unnecessary applications, such as tied tourniquets, pressured dressings, suctions by mouth, local incisions, and the use of ice. The complications of incision and suction, especially in the hands of untrained individuals who do not know the anatomy of the body, include damage to the underlying structures, vascular compromise to the extremity, and infection. The blade in a snakebite kit is of sufficient size and quality to damage underlying blood vessels, nerves, tendons, and muscles. Incisions or suctions in the area of the snakebite do not increase mortality but may increase morbidity through improper application [7]. Although rhabdomyolysis is a very rare complication in European snakebites, in our series, there were eight cases of mild rhabdomyolysis with favorable outcome. We attributed this complication to the direct action of the venom on the myocytes. Acute renal failure of short duration was encountered in three cases, probably due to the toxic action of the venom or secondary to dehydration due to fluid loss from vomiting. One of the patients developed acute myocardial infarction 1 h following the snakebite with increased cardiac enzymes, troponins, and serum tryptase. We attributed this complication to an IgE-mediated hypersensitivity reaction to the venom and the action of tryptase or histamine on the coronary arteries, the so-called Kounis syndrome [3]. This report shows that snake venom poisoning is a medical emergency that may involve multiple organ systems
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of the human body in addition to the site of the bite. The course of the envenomation syndrome requires careful monitoring and clinical decision-making. Although there were no deaths in our series, we agree with others [12] that consultation with a physician experienced in the diagnosis and treatment of snake bites is essential.
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