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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2008  |  Volume : 19  |  Issue : 3  |  Page : 404-410
Acute Renal Failure in Snake Envenomation: A Large Prospective Study


Department of Medicine, Madurai Medical College, Madurai, India

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   Abstract 

Venomous snakebite is a common problem in India. The aim of this study is to assess the prevalence, risk factors and prognostic factors in snakebite induced acute renal failure and to determine their outcome from a tertiary care center in India. A total of 1548 cases of snakebite admitted to adult medical wards of Government Rajaji hospital from January 2003 to December 2004, were studied from hospitalization to discharge or death. There were 1180 poisonous and 368 nonpoisonous snakebites. Among the poisonous, there were 1121 viperidae and 59 elapidae bites. A total of 159 (13.5%) patients (M = 98, F = 61) developed acute renal failure; of them 72 (45.3%) required dialysis and 36 (22.6%) expired (of them, 23 required dialysis). ARF patients were older than non ARF (39.1 vs. 35.4 years, p = 0.03). Cellulites (OR 9.20, p = 0.032), regional lymphadenopathy (OR 22.0, p= 0.001), intravascular hemolysis (OR 3.70, p = 0.004) and bite to needle time more than 2 hours (OR 2.10, p = 0.001) were identified as independent risk factors for the development of acute renal failure. Bite to needle time more than 2 hours (OR 2.10, p = 0.01), presence of intravascular hemolysis (OR 13.0, p = 0.004) and hypotension (OR 22.2, p = 0.04) and the presence of bleeding manifestations (OR 7.91, p = 0.032) were identified as independent predictors of poor outcome in snakebite victims. We conclude that our study demonstrates several risk factors and predictors for the development and outcome of ARF in patients with snakebites.

Keywords: Snakebite, Acute, Renal, Failure, Dialysis, India

How to cite this article:
Athappan G, Balaji M V, Navaneethan U, Thirumalikolundusubramanian P. Acute Renal Failure in Snake Envenomation: A Large Prospective Study. Saudi J Kidney Dis Transpl 2008;19:404-10

How to cite this URL:
Athappan G, Balaji M V, Navaneethan U, Thirumalikolundusubramanian P. Acute Renal Failure in Snake Envenomation: A Large Prospective Study. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Aug 24];19:404-10. Available from: http://www.sjkdt.org/text.asp?2008/19/3/404/40501

   Introduction Top


Poisonous snakebites are a serious health challenge in tropical regions due to their inci­dence, morbidity and mortality. [1] World Health Organization (WHO) estimates that there are approximately 125,000 deaths out of 2,500,000 poisonous snakebites worldwide every year [1] of which India accounts for 10,000 deaths. [2]

The majority of snakebite's victims are ini­tially treated by professional snakebite healers, snake charmers and religious men, who use herbal remedies, chant divine "mantras" and apply "snake stone" causing delay in seeking medical aid. Ignorance of snakebite treatment among primary health care personnel is ano­ther factor responsible for the high morbidity and mortality.

Acute renal failure is mainly observed follo­wing bites by the viperidae group but less with sea snakes and the colubridae group. Most Indian patients are victims of Russell's viper or Echis carinatus bites, causing ARF. [3],[4],[5]

Although there were a number of studies on acute renal failure in snakebite victims, from India there have been no prospective large studies on the risk factors in the development and outcome of ARF. This study aims to eva­luate the prevalence, risk and prognostic fac­tors in snakebite induced acute renal failure.


   Materials and Methods Top


We studied prospectively 1548 consecutive victims of snakebites, who were admitted to Government Rajaji Hospital, a tertiary care teaching institute with bed capacity and bed occupancy rate of 2200 and 95%, respectively, in Madurai, India from January 2003 to December 2004.

The diagnosis was based on identification of snake and/or a clinical picture consistent with snake envenomation within 24 hours after hospitalization. A typical clinical picture was defined as the presence of fang marks, clini­cally significant bleeding tendencies with local swelling, erythema, cellulites and abnormal clotting time.

Acute renal failure was defined as a rise in serum creatinine level of 50% or more of the previous baseline value, performed at our hospital or elsewhere after snakebite. [6] We ex­cluded from the study patients who had clini­cal and/or laboratory evidence of chronic kid­ney disease or history of recent non-steroidal anti-inflammatory drugs (NSAID) intake. Chronic kidney disease was defined as the baseline creatinine value more than 2 mg/dl, decreased kidney size or loss of cortico­medullary differentiation renal ultrasound, and/or past history of active renal disease. The ethical committee of the hospital approved the present project.

All patients received tetanus toxoid in the emergency room. The snake anti-venom (SAV) was obtained from Serum Institute and/or Haffkine Institute, Mumbai, India. We classi­fied the cases of snakebite as mild, moderate, and severe [7] and administered SAV 20-40 ml in mild, 50-90 ml in moderate, and 100 ml or more in the severe cases cautiously by intravenous drip after an initial bolus over 30 minutes.

Age, gender, history of co-morbid illnesses, use of concomitant drugs, time of onset of oliguria, hospitalization time, the bite site, presence of cellulites, bleeding manifesta­tions, regional lymphadenopathy, blood pres­sure, the severity of envenomation and the type of snakebite were recorded. Administered amounts of anti-venom, time elapsed between the snakebite and administration of antivenom (bit to needle time), dialysis treatment, and mortality were also noted. Weight (Kg), urine output (ml/hr) and systolic and diastolic blood pressure (mm Hg) were evaluated daily.

A blood specimen was collected at admi­ssion and everyday till discharge or death in order to measure sodium, potassium, create­nine, blood urea nitrogen, blood coagulation time, hemoglobin, hematocrit and platelet count. Liver function test and peripheral smear were performed in all the patients along with reti­culocyte count to detect intravascular hemo­lysis.


   Statistical Analysis Top


Patients were classified into two groups according to the presence and absence of ARF. Differences between the two groups were compared using Chi square test or student t­test wherever required. Risk factors for both development and outcome of ARF were de­termined by univariate and multivariate ana­lysis with logistic regression. P < 0.05 was considered statistically significant.


   Results Top


Of the 1548 snakebites, 1180 were due to poisonous snakebites. Among them, 1121 cases were due to viper bite and 59 to elapidae bite. All the 159 cases (13.5%) of ARF were from viper bites and none from elapidae during the study period.

The characteristics of snakebite victims are provided in [Table - 1]. Among the 159 (98 males, 61 females) cases of ARF, 72 (45.28%) re­quired dialysis and 36 (22.5%) expired, where­as none in the non-dialyzed group expired.

The bite to needle time was significantly more in patients who developed ARF than in those who did not. When the time interval for the administration was less than 12 hours, 81/981 (8.3%) patients developed acute renal failure, however, when the interval was more than 12 hrs 78/140 (55%) cases were affect­ted, and the difference was significant. There was no difference in the amount of anti-venom administered in both groups.

Disseminated intravascular coagulation was observed in 44 (27.8 %) patients in the ARF vs. 68 (6.7%) in the non-ARF group, (p < 0.001). In the patients in the ARF group, hema­turia was the predominant bleeding manifes­tation (70%) followed by bleeding from the fang mark site in 20 % and multiple bleeding sites in 10%. The ARF group developed lower systolic (ARF, 90 (70-170) mmHg vs. non ARF, 110 (100-180) mm Hg, p = 0.8) and diastolic (ARF, 60 (40-100) mmHg vs. non ARF, 80 (60-120) mmHg, p = 0.4) blood pre­ssure on admission, however, the difference was not significant. Nobody in the study groups developed evidence of rhabdomyolysis.

All the patients with ARF developed oligu­ria. In the ARF group, the mean peak of crea­tinine and blood urea nitrogen levels were 4.2 (1.5-16.7) and 47.2 (18.7-90.2) mg/dl, respec­tively.

Among the variables entered into univariate analysis, the following were found to predict the development of ARF: age of the patient, cellulites, regional lymphadenopathy, the pre­sence of bleeding manifestations, intravascu­lar hemolysis, hypotension, and bite to needle time. These seven variables were entered into Logistic Regression analysis, which revealed that cellulites (OR 9.90, C.I 1.21-70.5, p = 0.02), regional lymphadenopathy (OR 21.6, C. I 6.83-73.5, p = 0.001) and bite to needle time more than 2 hrs (OR 2.10, C.I 2.05­2.17, p = 0.001) and intravascular hemo­lysis (OR 3.2, C.I 1.53-8.90, p = 0.01) were identified as independent risk factors for the development of acute renal failure.

Among the variables entered into univa­riate analysis for the outcome of ARF, the following were found to predict the out­come of ARF: time for AV administration (bite to needle time), the presence of blee­ding manifestations, intravascular hemolysis, development of hypotension and high urea and creatinine values. These variables were entered into Logistic Regression analysis. In logistic regression analysis, hypotension (OR 22.2, C.I 1.21-495, p = 0.05), bleeding manifestation (OR 7.905, C.I 1.196-52.252, p = 0.03), intravascular hemolysis (OR 13.0, C.I 2.20-76.0, p = 0.01) and bite to needle time (OR 2.10, C.I 1.84-2.0, p = 0.001) were identified as independent risk factors for predicting mortality in ARF. The charac­teristics of the patients remaining alive and the expired ones following the development of ARF are provided in [Table - 2].


   Discussion Top


Acute renal failure complicates the course in 5% to 32% of victims of severe viper poisoning. [3],[8],[9] No consensus exists on the single mechanism causing acute renal failure after viper bite. It is known, however, that viper venom induces several clinical abnor­malities that favor the development of acute renal failure. These alterations include a va­rying degree of bleeding, hypotension, circu­latory collapse, intravascular hemolysis [3],[10] and disseminated intravascular coagulation [3],[10] with or without microangiopathy. E. carinatus venom directly activates prothrombin to thrombin. [11],[12] Viper venom produces activation of Factor V with fibrinolysis leading to disseminated intravascular coagulation (DIC). This can result in hemorrhage, hypo­volemia and thrombin in the microvascu­lature and glomerular capillaries and a mic­roangiopathic hemolytic anemia with subse­quent ARF. [13] A direct cytotoxic action of snake venom on the kidney may occur, [10] however, convincing evidence is still lacking. Hypersensitivity to venomous or antiveno­mous protein occasionally causes acute renal failure. [14]

The renal lesions of clinical significance in envenomed patients are acute tubular and patchy or diffuse cortical necrosis. [3],[10] Glo­merulonephritis, interstitial nephritis, and papillary necrosis and occasional cases of necrotizing arteritis of the interlobular arte­ries have been reported. [15] Since the multi­tude of mechanisms of ARF exist and there is varying histological involvement, the out­come of a patient cannot be determined by a single factor.

The prevalence of ARF in the present study was 13.5% which is comparable to other reported series in India (13-32%), [3],[16] while the incidence reported from Nigeria, [8] Israel [9] and Thailand [17] were 1-10, 6.2, and 5%, respectively.

The finding that delay to administer an adequate dose of anti-venom increases the risk for developing ARF more than 2 times (odds ratio 2.10) is not unexpected because the venom continues to act until it is neu­tralized. In fact, early administration of anti-venom has been demonstrated to com­pletely reverse all clinical manifestations of snake envenomation. [18] Hence, anti-venom should be available in health centers and emergency services of small communities, rather than being concentrated in reference hospitals. Delay in seeking medical aid or ignorance among the public and health care personnel can contribute to increased mor­bidity and mortality.

Another significant independent factor re­lated to development of ARF in our study was the presence of cellulites. The earliest symptoms in patients bitten by vipers are pain and swelling of the bitten part, appea­ring within a few minutes. In severe poiso­ning, the swelling can spread to involve the whole limb within 24 hours. However, severe envenomation without much swelling can occur if the venom directly enters the blood stream. [19]

Regional lymphadenopthy was another sig­nificant independent factor for ARF. Just as cellulites, regional lymphadenopthy can be a bedside indicator of the amount of toxin released by the snakebite.

Intravascular hemolysis is a well-known cause of renal injury [3],[10] that can be more lethal when combined with other adverse factors such as dehydration, hemorrhage or hypotension. in our present study, hemoly­sis was identified as an independent predic­tor for development of ARF.

In our study, 44 (27.7%) patients with ARF developed bleeding, which was less than that in other reports ( 60-65%). [16] Hematemesis, melena, hemoptysis, hematu­ria, epistaxis are well known manifestations and may lead to severe hypovolemic shock. Bleeding in snake-bite victims is usually due to DIC. Platelet count was low in 40 (25.2%) patients with ARF, which could also ex­plain the bleeding due to DIC as noticed in the study.

Hypotension is another major factor to cause ARF. [19] Bleeding, either into tissues or externally, and loss of plasma into the bitten extremity can produce hypotension and circulatory collapse. The latter was, however, not observed in our present study. Russell's viper can cause hypotension and collapse by releasing bradykinin. In our study, intravascular hemolysis and bleeding due to DIC were more important pathogen­netic factors in the development of ARF and hypotension did not contribute much to it. In general, early pre hospital treatment of hypotension with fluids and inotropic support could have prevented the develop­ment of ARF in at least some of the pa­tients. This warrants aggressive treatment of hypotension.

In our study, patients with ARF due to snakebite developed hypotension within the first 24 hours, intravascular hemolysis, bleeding manifestations due to DIC, com­bination of hypotension and intravascular hemolysis, and venom induced direct nephro­toxicity in similar percentages reported else­ where. [10]

Mortality rate was elevated among our ARF patients, especially the dialyzed ones. There were significant statistical differences between patients with ARF who recovered as against patients who died. Recovered cases of ARF had a shorter mean bite to needle time as was observed by Sharma et al, [20] less bleeding manifestations as noticed by Soe et al [21] and intravascular hemolysis and elevated serum ceatinine as stated by Kalantri et al. [22]

Some limitations of our study included the study of only selected parameters, the lack of renal biopsies that would demonstrate the histological pattern of renal involvement, the lack of complete coagulation profile for evidence of DIC, and the lack of ELISA test to identify the snake venom due to technical constraints.

In conclusion, our study demonstrates that the prevalence of ARF is 13.47% in snakebite victims. Risk factors for the development of ARF in this population include cellulites and regional lymphadenopathy, while pre­dictors of poor outcome are hypotension and bleeding. Early adequate administration of snake anti-venom may reduce the develop­ment of ARF.

 
   References Top

1.Chippaux JP. Snakebites: Appraisal of the global situation. Bull World Health Organ 1998;76(5):515-24.  Back to cited text no. 1    
2.Chugh KS. Snake bite induced acute renal failure in India. Kidney Int 1989;35(3):891-907.  Back to cited text no. 2    
3.Chugh KS, Pal Y, Chakravarty RN, et al. Acute renal failure following poisonous snake bite. Am J Kidney Dis 1984;4(1):30-8.  Back to cited text no. 3    
4.Mittal BV. Acute renal failure following poisonous snake bite. J Postgrad Med 1994; 40(3):123-6.  Back to cited text no. 4    
5.Varuganam T, Panaboke RG. Bilateral cortical necrosis of the kidneys following snakebite. Postgrad Med J 1970;46(537):449-51.  Back to cited text no. 5    
6.Albright RC Jr. Acute renal failure: A practical update. Mayo Clin Proc 2001;76 (1):67-74.  Back to cited text no. 6    
7.Norris RL, Auerbach PS. Disorders caused by reptile bites and marine animal exposure, Harrison's Principles Of Internal Medicine 16 th ed. McGraw-Hill: 2005.  Back to cited text no. 7    
8.Warrell DA, Ormerod LD, Davidson NM. Bites by the Puff-adder (Bitis arietans) in Nigeria and value of antivenom. Br Med J 1975;4(5998):697-700.  Back to cited text no. 8    
9.Efrati P, Reif L. Clinical and pathological observations on 65 cases of viper bite in Israel. Am J Trop Med Hyg 1953;2(6):1085-108.  Back to cited text no. 9    
10.Chugh KS, Aikat BK, Sharma BK, Dash SC, Mathew T, Das KC. Acute renal failure following snakebite. Am J Trop Med Hyg 1975;24(4):692-7.  Back to cited text no. 10    
11.Chugh KS, Mohanthy D, Pal Y, Das KC, Ganguly NK, Chakravarty RN. Haemostatic abnormalities following Echis Carinatus (Saw scaled viper) envenomation in the rhesus monkey. Am J Trop Med Hyg 1981; 30(5):1116-20.  Back to cited text no. 11    
12.Reid HA. Myoglobinuria and sea snake bite poisoning. Br Med J 1961;1(5235):1284-9.  Back to cited text no. 12    
13.Visweswaran RK, George J. Snake bite induced acute renal failure. Indian J Nephrol 1999;9:156-9.  Back to cited text no. 13    
14.Date A, Pulimood R, Jacob CK, Kirubakaran MG, Shastry JC. Haemolytic uremic syndrome complicating snake bite. Nephron 1986;42 (1):89-90.  Back to cited text no. 14    
15.Sitprija V, Suvanpha R, Pochanugool C, Chusil S, Tungsanga K. Acute interstitial nephritis in snake bite. Am J Trop Med Hyg 1982;31(2):408-10.  Back to cited text no. 15    
16.Chugh KS. Snakebite induced acute renal failure in India-Nephrology forum. Kidney Int 1989;35(3):891-907.  Back to cited text no. 16    
17.Sitprija V, Boonpucknavig V. Snake venoms and nephrotoxicity. In: Lee CY, (ed). Berlin, Springer Verlag, Snake Venoms, 1979:1951-3.  Back to cited text no. 17    
18.Reid HA. Animal Poisons, in Manson's Tropical Diseases. 18th ed, In: Manson­Bahr PE, Apted FI, (eds). London, Balliere Tindall,1982:544-66.  Back to cited text no. 18    
19.Ali G, Kak M, Kumar M, et al. Acute renal failure following echis carinatum (saw- scaled viper) envenomation, Available from: http://www.ijnephrol.com/octdec2004/17.html. (Last accessed on 2006 Jun 7).  Back to cited text no. 19    
20.Sharma SK, Chappuis F, Jha N, et al. Impact of snake bites and determinants of fatal outcomes in southeastern Nepal. Am J Trop Med Hyg 2004;71(2):234-8.  Back to cited text no. 20    
21.Soe P, Russels Viper bite: Correlation of different clinical criteria to peritoneal dia­lysis and clinical outcome, Regional Health Forum- Volume 9, Number 1, 2005.  Back to cited text no. 21    
22.Kalantri S, Singh A, Joshi R, et al. Clinical predictors of in-hospital mortality in patients with snake bite: A retrospective study from a rural hospital in central India. Trop Med Int Health 2006;11(11):22-30.  Back to cited text no. 22    

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Correspondence Address:
Ganesh Athappan
Department of Medicine, Madurai Medical College, Madurai – 625020, Tamilnadu
India
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