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\title{Renal Parameters as Predictors of Morbidity and Mortality in Snake Bite Patients in a Tertiary Care Hospital in Southern India}
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             \author[1]{Imtiaz  Pasha}

             \affil[1]{  Kempegowda institute of medical sciences,Bangalore-560011}

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\date{\small \em Received: 7 December 2013 Accepted: 31 December 2013 Published: 15 January 2014}

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\begin{abstract}
        


Background: Snake bite is predominantly an occupational hazard and a common cause of morbidity and mortality. Acute renal failure has been associated with venomous viper and sea snake bites.AIMS: This study was carried out to study the incidence and clinical profile of the snake bite patients who develop acute renal failure;and to identify the predictors of morbidity and mortality in these patients.Material and methodology: We carried out prospective study on fifty (50) cases of definitive snake bite admitted to Department of Medicine/Emergency medicine, Kempegowda institute of medical sciences, Bangalore from May 2012 to November 2013.Statistical analysis: SPSS for Windows version 17.0 (SPSS, Inc, Chicago, Ill) was used for statistical analysis. The Pearson Chi-Square Test was used to analyze parametric variables. A P value of 0.05 or less was considered statistically significant.

\end{abstract}


\keywords{snake bite, acute renal failure, oliguria, morbidity, mortality.}

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\section[{Introduction}]{Introduction}\par
nake bite is predominantly an occupational hazard in the rural tropics and a common cause of morbidity and mortality \hyperref[b0]{1,}\hyperref[b1]{2} .The majority of victims initially are treated by professional snakebite healers, snake charmers, and religious men, who use herbal remedies, chant divine "mantras," and apply "snake stone," all of which are supposed to magically draw out the venom from the victim \hyperref[b2]{3} . Death often occurs even before the patient can be brought to the hospital.\par
Globally, at least 421,000 envenomations and 20,000 deaths occur each year due to snake bite. These figures may be as high as 1,841,000 envenomations and 94,000 deaths. Based on the fact that en¬venoming occurs in about one in every four snakebites, be¬tween 1.2 million and 5.5 million snakebites could occur an¬nually \hyperref[b3]{4} . In many parts of Southeast Asian region, snake bite is a familiar occupational hazard of farmers, plantation workers and others, resulting in tens of thousands of deaths each year and innumerable cases of chronic physical handi¬cap  {\ref 5} . India accounts for about 30,000 deaths per year due to snake bite \hyperref[b4]{6} .\par
More than 2,700 species of snakes are recognized the world over, but only about 450 of these have front fangs that make them capable of injecting venom during the bite7. The venomous snakes belong to four families: Elapidae, Viperidae, Hydrophiidae, and Colubridae.\par
Elapids are land snakes, the venom of which contains a high concentration of neurotoxins. The elapids, encountered in Africa and Asia 7 include cobras, kraits, mambas, and coral snakes. Renal involvement is uncommon in victims of bites from members of this family.\par
Vipers include the Russell's viper, Echis carinatus (sawscaled viper), puff adder, pit vipers, and rattlesnakes. The vipers are the most widely distributed species. Russell's viper is found in India, Burma, Pakistan, Thailand, and other areas of Asia; Echis carinatus in Africa, India, Pakistan, Sri Lanka, and the middle east; and the puff adder (Bitis arietans) in Africa The carpet or saw-scaled viper, Echis carinatus, justifiably can be labeled the most dangerous snake in the world. The factors contributing to its deadliness are its widespread distribution, abundance in farming areas, diurnal habits, good camouflage, and its highly toxic venom.\par
Hydrophid or sea snake bites are reported mainly among fishing folk of Malaysia, Thailand, and western pacific coastal areas  {\ref 7,11,12,13,14.} Sea snake venom is primarily myotoxic.\par
Colubrids include the boomsiang (Dispholidus typus), and the bird snake (Thelotornis kirtlandi), which are back-fanged African species. Back-fanged colubrids are usually harmless to humans but are occasionally known to cause serious and fatal poisoning 2 .\par
Renal lesions have been associated with bites from members of the last 3 families, including the Russell's viper  {\ref 15-19,} Echis carinatus  {\ref 10,16,18,} puff adder \hyperref[b17]{20,}\hyperref[b18]{21} , pit viper \hyperref[b19]{22,}\hyperref[b20]{23,}\hyperref[b21]{24,}\hyperref[b22]{25} and sea snake  {\ref 11,}\hyperref[b9]{12} .\par
Acute renal failure (ARF), the most significant of all the renal manifestations, has been reported with varying frequency in different studies. . In India, the most widely distributed vipers are Echis carinatus and Russell's viper 3. Most Indian patients are victims of Russell's viper or Echis Carinatus bites15-21\par
In India, the incidence of ARF is 13\% to 32\% following Echis carinatus or Russell's viper bite \hyperref[b13]{16,} {\ref 28,} {\ref 29} .\par
A variety of histopathological findings have been described in snake bite patients. The most common of them have Acute tubular necrosis 3,7-9,30, Acute cortical necrosis 31 ,Acute diffuse interstitial nephritis 32,33, Proliferative glomerulonephritis.  {\ref 34} .\par
The aim of this study were to describe the incidence and clinical profile of the snake bite patients who develop acute renal failure; and to identify the predictors of morbidity and mortality in these patients. 
\section[{II.}]{II.} 
\section[{Materials and Methods}]{Materials and Methods}\par
Fifty (50) cases of definitive snake bite consecutively admitted to Department of Medicine/Emergency medicine, Kempegowda institute of medical sciences, Bangalore from May 2012 to November 2013 were taken up in this prospective obsvervational study. a) Inclusion Criteria 1. Definitive history of snake bite 2. Clinical picture consistent with snake bite, as presence of fang marks or cellulitis or coagulopathy or neuroparaly¬sis 3. Presence of Acute Renal Failure, defined as an abrupt (within 48 hours) absolute increase in the t t t . baseline value measured after admission to our hospital or elsewhere after snake bite, before referral to our hospital, or a percentage increase in t t t t t above base¬line, or oliguria of less than 0.5 mL/kg per hour for more than six hours .Serum creatinine more than 1.5 mg/dL or oli¬guria (urine output less than 400 mL/day)35. b) Exclusion Criteria 1. Patients with pre-existent renal disease (Serum creatinine > 1.5 mg/dL prior to snake bite or ultrasonography of abdomen suggestive of bilateral small kidneys/loss of corticomedullary differentiation / obstruc¬tive nephropathy/other renal pathology) 2. Diagnosed cases of hypertension/diabetes mellitus 3. Exposure to nephrotoxic drugs/toxins. Data was collected by using pre-tested proforma meeting the objectives of the study. Purpose of the study was carefully explained to the patients and consent was taken.\par
All patients were interviewed, detailed history was taken with respect to risk factors and detailed physical examination were carried out. Appropriate investigations were carried out.\par
Laboratory investigations in¬cluded hemoglobin, total and differential leucocyte counts, platelet counts, red cell counts, bleeding and clotting time, coagulation profile including prothrombin time, activated partial thromboplastin time and international normalised ra¬tio (INR), urine microscopy, urinary protein, kidney and liver function tests and serum electrolytes. Radiological investi¬gations included X-ray chest and ultrasonography of abdo¬men.\par
Statistical analysis: SPSS for Windows version 17.0 (SPSS, Inc, Chicago, Ill) was used for statistical analysis. The Pearson Chi-Square Test was used to analyze parametric variables. A P value of 0.05 or less was considered statistically significant. 
\section[{III.}]{III.} 
\section[{Results}]{Results}\par
During the study period of 18 months a total of 50 patients were admitted for snake bite, out of which 36(72\%) were males and the male: female was 2.5:1.A majority were from rural areas 37(74\%) and the rest from urban areas 13(26\%). The mean age of the male patients was 41.81 years and that of the female patients was 48.29 years.\par
A majority of the patients were farmers (54 \%), labourers (18\%) and housewife (16 \%).The biting species identified were viper (70\%),cobra (6\%) and unknown species (14\%).\par
The peak incidence in the snake bite cases occurred during the months of july to September. Most of the patients were bitten during the day time (78\%).The most frequently bitten site was the lower extremity (70\%).\par
Definitive fang marks were seen in (66\%) of the cases. Tourniquet was applied in (10\%) of patients.Cellulitis was seen in patients, out of which patients developed compartment syndrome, requiring fasciotomy.\par
Only 12\% of patients presented to hospital within 2 hours of bite and the mean lapse of time from bite to hospitalisation in males was 17.  {\ref 39}    Laboratory data showed anemia (hemoglobin<10gm\%) in 13(26\%), leucocytosis in 32(64\%), thrombocytopenia in 24(48\%), coagulopathy in 18(36\%), hematuria in 20(40\%), proteinuria in 26(52\%), and hyperkalemia in 9(18\%) .\par
Mean urine output at baseline, 24hrs, 48hrs and 72hrs were 651.37 ml, 1436.59 ml, 1751.46 ml and 1956.22 ml. Mean Blood urea at baseline, 24hrs, 48hrs and 72hrs were 44.66 mgs\%, 53.71mgs\%,51.49 mgs\% and 47.86 mgs\% and mean serum creatinine at baseline, 24hrs, 48hrs and 72hrs were 1.641mgs\%, 1.827mgs\%,1.756mgs\% and 1.780 mgs\% respectively.\par
There was no significant between group differences in creatinine between those with INR<1.5 and INR>1.5\par
Out of these 50 patients, 20(40\%) patients developed acute kidney injury and 13(26\%) required hemodialysis and 1 patient progressed to chronic kidney disease. The mortality rate was 4\%. 
\section[{IV.}]{IV.} 
\section[{Discussion}]{Discussion}\par
Snakebite is a common medical emergency and an occupational hazard. Renal manifestations include proteinuria, hematuria, pigmenturia, and acute renal failure.\par
In India, the incidence of ARF is 13\% to 32\% following Echis carinatus or Russell's viper bite  {\ref 16, 28, 29.} A variety of histopathological findings have been described in snake bite patients.The most common of them have Acute tubular necrosis 3,7-9,30, Acute cortical necrosis 31, Acute diffuse interstitial nephritis 32, 33, Proliferative glomerulonephritis.  {\ref 34} .\par
Most of the patients were found to be men in working age group, especially from rural population. Majority of the snake bites occurred between 6 am to 6 pm, i.e., during working hours in the field. As expected, the snake bites more commonly involving lower limbs. So, this also shows that use of protective footwear can reduce the snake bites.\par
In our study, out of 50 number of snake bite patients, 20(40\%) patients developed acute renal failure. This prevalence is higher compared to the other studies from India \hyperref[b13]{16,} {\ref 28,} {\ref 29} . The higher prevalence probably due to higher number of viper bites and delay in administration of ASV, as there is a delay in taking the patient to hospital after snake bite. 45(90\%) of the patients had local cellulitis, indicating the vasculotoxic nature of envenomation.\par
There was a significant increase in duration of hospitalization in those with Creatinine >1.5 (18 days) compared to those with creatinine<1.5 (32 days).\par
The other common symptoms were swelling/inflammation of bite area (90\%), muscle pain/tenderness (60\%), oliguria (50\%), fever (26\%) and vomiting(26\%), hematuria(40\%) and bleeding from site was present in 40\% patients. Similar figures have been reported previously also  {\ref 38} .\par
Common findings on examination were tachycardia (38\%), breathlessness (34\%), and hypotension (36\%) and Proteinuria ( 52\%) patients. Common laboratory findings were Anaemia (26\%);, Leucocytosis (64\%); Thrombocytopenia(48\%), Coagulopathy (36\%). Coagulopathy is an important factor contributing to increased mortality. The prevalence of coagulopathy in this study (36\%) is comparable to that noted by Athappan et al 39 i.e., 27.7\%, whereas it is less as compared to other series (60-80\%)  {\ref 40} . By itself, coagulopathy is a marker of the vasculotoxicity and hemotoxicity of the poison, which means that these patients will have nephrotoxicity due to damage to renal microvasculature. Also coagulopathy leads to bleeding and hypotension which, further leads to renal insufficiency as a result of prerenal insult.\par
The mortality of snake bite induced acute renal failure is found to be 4\% in this study. This is less compared to estimates from other studies from India (22-50\%) 39 . Kalantri et al reported an overall mortality of 11\% in venomous snake bite patients 41 . The mortality can be prevented by intervention at various levels, which include early transfer of the patient to a primary health care facility, where ASV should be administered at the earliest. The high risk patients should be identified early and referred to higher centre.\par
The limitations of this study were a smaller sample size and lack of investigations like renal biopsy.\par
This study concludes that acute renal failure occurs in 40\% victims of snake bite and is associated with significant increase in the number of hospilisation days. Common manifestations in¬clude cellulitis, oliguria, proteinuria, coagulopathy and thrombocytopenia. The overall mortality of snake bite in¬duced acute renal failure is 4\%. Presence of coagulopa¬thy and increase in the number of hospitisation days are predictors of morbidity and mortality in snake bite patients who develop acute renal failure.\begin{figure}[htbp]
\noindent\textbf{1} \par 
\begin{longtable}{P{0.85\textwidth}}
Year 2014\\
Volume XIV Issue II Version I\\
( ) B\\
Medical Research\\
Global Journal of\end{longtable} \par
 
\caption{\label{tab_1}Table 1 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{2} \par 
\begin{longtable}{P{0.6762942779291553\textwidth}P{0.10422343324250681\textwidth}P{0.06948228882833787\textwidth}}
Hematological\tabcellsep Number of patients\tabcellsep \%\\
parameters\tabcellsep \tabcellsep \\
Hemoglobin (Hb in gms)\tabcellsep \tabcellsep \\
<10.0\%\tabcellsep 13\tabcellsep 26\\
>10.0\%\tabcellsep 37\tabcellsep 74\\
Total count(/mm3)\tabcellsep \tabcellsep \\
<11000\tabcellsep 18\tabcellsep 36\\
>11000\tabcellsep 32\tabcellsep 64\\
Platelet count(/mm3)\tabcellsep \tabcellsep \\
<100000\tabcellsep 24\tabcellsep 48\\
>100000\tabcellsep 26\tabcellsep 52\\
Prothrombin time ( in secs)\tabcellsep \tabcellsep \\
< 15 sec\tabcellsep 11\tabcellsep 22\\
>15 sec\tabcellsep 39\tabcellsep 78\\
\multicolumn{2}{l}{Activated partial thromboplastin time( APTT in secs)}\tabcellsep \\
< 30 sec\tabcellsep 9\tabcellsep 18\\
>30 sec\tabcellsep 41\tabcellsep 82\\
INR\tabcellsep \tabcellsep \\
< 1.5\tabcellsep 26\tabcellsep 52\\
>1.5\tabcellsep 24\tabcellsep 48\\
\multicolumn{2}{l}{Fibrin degradation products( FDP)}\tabcellsep \\
Positive\tabcellsep 22\tabcellsep 44\\
Negative\tabcellsep 28\tabcellsep 56\end{longtable} \par
 
\caption{\label{tab_2}Table 2 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{3} \par 
\begin{longtable}{P{0.5555555555555556\textwidth}P{0.2111111111111111\textwidth}P{0.08333333333333333\textwidth}}
Sr creatinine\tabcellsep No patients\tabcellsep \%\\
<1.5\tabcellsep 30\tabcellsep 60\\
>1.5\tabcellsep 20\tabcellsep 40\\
\multicolumn{3}{l}{Table 4 : WBCT in minutes of patients studied}\\
WBCT in minutes\tabcellsep Number of\tabcellsep \%\\
\tabcellsep patients\tabcellsep \\
<20 min\tabcellsep 14\tabcellsep 28\\
>20 min\tabcellsep 36\tabcellsep 72\\
Total\tabcellsep 50\tabcellsep 100\end{longtable} \par
 
\caption{\label{tab_3}Table 3 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{5} \par 
\begin{longtable}{P{0.5626760563380282\textwidth}P{0.21549295774647886\textwidth}P{0.07183098591549296\textwidth}}
End results\tabcellsep No of patients\tabcellsep \%\\
Discharged\tabcellsep 47\tabcellsep 94\\
Death\tabcellsep 2\tabcellsep 4\\
Chronic kidney\tabcellsep 1\tabcellsep 2\\
disease\tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_4}Table 5 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{6} \par 
\begin{longtable}{P{0.13795811518324608\textwidth}P{0.1424083769633508\textwidth}P{0.1424083769633508\textwidth}P{0.01780104712041885\textwidth}P{0.04895287958115183\textwidth}P{0.36047120418848166\textwidth}}
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Year 2014\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Volume XIV Issue II Version I\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep B )\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep (\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Medical Research\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Global Journal of\\
Sr\tabcellsep Number of\tabcellsep \multicolumn{3}{l}{\% Mean SD}\tabcellsep P\\
.Creatinine\tabcellsep hospitalization\tabcellsep \tabcellsep \tabcellsep \tabcellsep value\\
\tabcellsep days\tabcellsep \tabcellsep \tabcellsep \\
<1.5*\tabcellsep 32\tabcellsep 64\tabcellsep 9.88\tabcellsep \multicolumn{2}{l}{7.534 0.003}\\
>1.5*\tabcellsep 18\tabcellsep \multicolumn{4}{l}{36 15.94 4.659 0.001}\\
*p<0.005\tabcellsep \tabcellsep \tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_5}Table 6 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{7} \par 
\begin{longtable}{P{0.255\textwidth}P{0.425\textwidth}P{0.17\textwidth}}
Blood urea\tabcellsep Mean ± SD\tabcellsep P value\\
Baseline\tabcellsep 44.66 ± 32.677\tabcellsep 0.180\\
24hrs\tabcellsep 53.71 ± 39.688\tabcellsep 0.90\\
2 nd day\tabcellsep 51.49 ± 42.390\tabcellsep 0.186\\
3 rd day\tabcellsep 47.86 ± 45.155\tabcellsep 0.105\end{longtable} \par
 
\caption{\label{tab_6}Table 7 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{8} \par 
\begin{longtable}{P{0.17733812949640287\textwidth}P{0.2079136690647482\textwidth}P{0.24460431654676257\textwidth}P{0.15899280575539568\textwidth}P{0.06115107913669064\textwidth}}
\tabcellsep \tabcellsep 48hrs\tabcellsep 1.756 ± 1.545\tabcellsep 0.188\\
\tabcellsep \tabcellsep 72hrs\tabcellsep 1.780 ± 1.639\tabcellsep 0.201\\
Serum creatinine\tabcellsep Mean ± SD\tabcellsep P value from\\
\tabcellsep \tabcellsep Baseline\\
Baseline\tabcellsep 1.641± 1.319\tabcellsep 0.091\\
24hrs\tabcellsep 1.827 ± 1.362\tabcellsep 0.076\end{longtable} \par
 
\caption{\label{tab_7}Table 8 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{9} \par 
\begin{longtable}{P{0.02570194384449244\textwidth}P{0.13034557235421165\textwidth}P{0.1285097192224622\textwidth}P{0.0642548596112311\textwidth}P{0.04406047516198704\textwidth}P{0.091792656587473\textwidth}P{0.1799136069114471\textwidth}P{0.06792656587473002\textwidth}P{0.11749460043196544\textwidth}}
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{Urine output}\tabcellsep \multicolumn{2}{l}{Mean ± SD}\tabcellsep P value from\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Baseline\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Baseline\tabcellsep \multicolumn{2}{l}{651.37 ± 509.825}\tabcellsep 0.074\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 24hrs\tabcellsep \multicolumn{2}{l}{1436.59 ±}\tabcellsep 0.318\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{784.178}\tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 48hrs\tabcellsep \multicolumn{2}{l}{1751.46 ±}\tabcellsep 0.564\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{923.601}\tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 72hrs\tabcellsep \multicolumn{2}{l}{1956.22 ±}\tabcellsep 0.913\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{1331.394}\tabcellsep \\
\tabcellsep \tabcellsep \multicolumn{4}{l}{Table no 10 : INR VS Serum Creatinine}\tabcellsep \tabcellsep \tabcellsep \\
INR<1.5\tabcellsep \tabcellsep \tabcellsep \multicolumn{3}{l}{Serum creatinine}\tabcellsep \tabcellsep \tabcellsep \\
\tabcellsep \multicolumn{2}{l}{Baseline}\tabcellsep 24hrs\tabcellsep \tabcellsep \multicolumn{2}{l}{48hrs}\tabcellsep \multicolumn{2}{l}{72hrs}\\
\tabcellsep Mean±SD\tabcellsep P\tabcellsep Mean±SD\tabcellsep P\tabcellsep Mean±SD\tabcellsep P value\tabcellsep Mean±SD\tabcellsep P value\\
\tabcellsep \tabcellsep value\tabcellsep \tabcellsep value\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\tabcellsep \multicolumn{5}{l}{1.55±1.48 1.000 1.54±1.17 1.000 1.39±0.87}\tabcellsep 1.000\tabcellsep 1.43±1.17\tabcellsep 1.000\\
INR>1.5\tabcellsep Mean±SD\tabcellsep P\tabcellsep Mean±SD\tabcellsep P\tabcellsep Mean±SD\tabcellsep P value\tabcellsep Mean±SD\tabcellsep P value\\
\tabcellsep \tabcellsep value\tabcellsep \tabcellsep value\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\tabcellsep 1.91±1.5\tabcellsep \multicolumn{3}{l}{0.071 2.26±1.69 0.071}\tabcellsep 2.34±2.1\tabcellsep 0.352\tabcellsep 2.25±2.09\tabcellsep 0.728\end{longtable} \par
 
\caption{\label{tab_8}Table 9 :}\end{figure}
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\end{document}
