Snakebite is a common problem in tropical
countries, affecting nearly 6 million people every year, with
nearly 10% of these fatalities occurring in India [1].
Russell’s viper (RV) (Daboia russelii), the foremost
cause of morbidity and mortality [2], and is responsible for
both hemato-toxicity and neuro-toxicity. Local tissue damage,
venom induced coagulopathy, platelet dysfunction,
phospholipase A2 induced
rhabdomyolysis, hyperkalemia, acute kidney injury (AKI) and
multi-organ dysfunction, all are effects of RV venom [3].
Direct toxic action of the venom may also be responsible for
AKI [4].
Different studies have estimated that the incidence
of AKI following hematotoxic bite ranges from 10-32% [4].
Recently, it was reported that there is a geographical
variation in the venoms of snake and this variation is
responsible for different efficacies of ASV in different parts
of country [5]. There is scarcity of data regarding the
factors responsible for AKI following hematotoxic
envenomation, especially in children. Hence this study was
conducted to find out the incidence of renal complications
following hematotoxic snake bites and to identify the clinical
and laboratory indicators which help in predicting AKI early.
METHODS
A comparative study was conducted in the pediatric emergency
ward of a tertiary care centre in between January, 2016 to
December, 2017. Prior approval was taken from the
institutional ethics committee. Hemato-toxic envenomation was
identified by identification of snake by the victim/ relatives
or witness, and features of intoxication characterized mainly
by a positive 20 minute whole blood clotting test (WBCT).
On admission, all the children received 10 vials of
ASV diluted with 100 mL/ 200 mL normal saline (0.9% NaCl).
Depending on correction of coagulopathy and clinical
indication, upto 30 vials of ASV were used. Serum urea and
creatinine, electrolytes and an electrocardiogram were
obtained at the time of admission. These were repeated once
daily or when clinically indicated, till discharge or
normalization of the value in three repeated tests. Acute
kidney injury was defined according to KDIGO guidelines
(Kidney disease: Improving global outcome) [6]. Dialysis
(peritoneal dialysis in this institution and hemodialysis in a
referral hospital) was used when the patient developed signs
of fluid overload, developed oliguria/ anuria (defined as
urine output <0.5 mL/kg/h for last 24 hours), hyperkalemia
(defined as >5.5 mEq/L with ECG changes or >6 mEq/L). If these
values were not normalized even after 6 months of discharge or
there was persistent hypertension, it was assumed that there
is permanent renal damage. The follow-up period was 6 months
or till normalization of renal function, whichever was later.
Statistical analysis:
Shapiro-Wilk test was used to check normal distribution.
Chi-square test was used to find the significance of
difference between attributes in contingency tables, whereas
one-way ANOVA was used to check the significance of difference
between means. Kruskal Wallis H test was used for skewed data.
Pearson’s product moment correlation coefficient (r) was
calculated to find the degree and direction of relationship of
dependent and independent variables. Significantly correlated
variables were considered for a binary logistic regression
model taking AKI, permanent renal damage and mortality as
dependent /outcome variable to calculate the adjusted odds
ratio. P<0.05 was taken as statistically significant.
Analysis was done by SPSS version 19.0 (Statistical Packages
for Social Sciences Inc, Chicago, IL, US).
RESULTS
During the study period, 371 children were admitted with
hematotoxic envenomation. Children with known kidney disease,
who were severely ill and died immediately, and those with
parental refusal of consent were excluded from the study (7
children were excluded; 1 with end stage renal disease due to
lupus nephritis, 2 were severely ill and died immediately, and
4 refused consent). Finally, 364 children (69% males) were
included. Mean (SD) age of the study population was 8.9 (2.3)
years. Majority of them belonged to lower socioeconomic status
(60.7%). Out of the 364 children, 139 (38.2%) developed AKI
following envenomation. Out of these 48 (34.5%), 55 (39.5%)
and 36 (26.0%) children developed stage 1, 2 & 3 AKI,
respectively. Sixteen children (4.4%) died and 59 (16.2%)
children developed permanent renal damage. Different clinical
and laboratory parameters of two groups of children (with AKI
and without AKI) are presented in Table I.
Table I Characteristics of the Study Population and Acute Kidney Injury (N=364)
Variables |
No AKI (n=225) |
AKI (n=139) |
Age#, y |
9.1 (1.7) |
5.8 (1.0) |
Males sex |
170 (67.7) |
81 (32.3) |
Rural residence |
116 (53.5) |
101 (36.5) |
Bite on trunk |
49 (46.2) |
57 (53.8) |
Single Bite |
221 (73.7) |
79 (26.3) |
Time b/w bite and ASV#, min |
36.4 (5.9) |
74.5 (8.3) |
Vials of ASV required* |
10 (10-30) |
20 (10-30) |
Local reaction |
<5 cm |
106 (84.1) |
20 (15.9) |
5-10 cm |
72 (66.0) |
37 (34.0) |
>10 cm |
47 (36.4) |
82 (63.7) |
System involvement |
No |
203 (83.2) |
41 (16.8) |
One system |
17 (26.6) |
47 (73.4) |
>1 system |
5 (8.9) |
51 (91.1) |
Neurotoxicity |
24 (20.5) |
93 (79.5) |
Alteration of K+ |
No |
158 (89.8) |
18 (11.2) |
After 6 h |
23 (43.4) |
30 (56.6) |
2-6 h |
32 (42.1) |
44 (57.9) |
<2 h |
12 (20.3) |
47 (79.7) |
K+ level# (mEq/L) |
3.9 (0.3) |
5.7 (0.6) |
Altered WBCT |
6 h |
202 (96.2) |
8 (3.8) |
12 h |
21 (25.3) |
62 (74.7) |
>12 h |
2 (2.8) |
69 (97.2) |
Bleeding |
48 (32.7) |
99 (67.3) |
Ventilation |
7 (8.0) |
81 (92.0) |
Blood product |
55 (34.8) |
103 (65.2) |
Inotropes |
88 (42.5) |
119 (57.5) |
All values in no. (%) except #mean (SD) and * median (IQR); WBCT –whole blood clotting test, K+- serum potassium; All comparisons P<0.01 except P<0.001 for rural residence and bite on trunk; b/w – between. |
Administration of ASV following 1 hour of bite
emerged as the most significant predictor of AKI (adjusted
OR=23.4, 95% CI=22.1-24.8), permanent renal injury (adjusted
OR=19.7, 95% CI=18.9-20.5) and mortality (adjusted OR=15.2,
95% CI=14.7-15.7) (Table II). Our model can
correctly predict 67.2%-78.9% variation of AKI, 62.1-70.3%
variation of permanent renal injury and 53.1-61.7% variation
of mortality. Renal histopathology was done in 48 (81.4%)
children suffering from permanent renal damage and 16 children
(100%) who died. Acute tubular necrosis (25, 39.1%) was the
most common finding in histopathology, followed by renal
cortical necrosis (12.5%).
Table II Acute Kidney Injury, Permanent Renal Injury and Mortality in Children with Hematotoxic Snakebite (N=364)
Variables |
AKI (n=139 ) |
Permanent renal injury (n=59 ) |
Mortality (n=16) |
Anti-snake venom after 1 h |
23.4 (22.1-24.8) |
19.7 (18.9-20.5) |
15.2 (14.7-15.7) |
Need of mechanical ventilation |
18.1 (17.4-18.9) |
16.2 (15.8-16.6) |
13.8 (12.6-15.0) |
Bleeding |
15.6 (15.3-15.9) |
12.9 (12.1-13.7) |
9.5 (8.5-10.6) |
Blood products |
13.2 (12.5-13.9) |
8.7 (8.5-9.0) |
1.8 (0.3-2.9) |
Serum potassium level >6 mEq/L |
9.9 (8.2-11.6) |
7.5 (6.9-8.1) |
1.7 (0.6-2.1) |
Alteration of pH in first 2 h |
8.7 (8.1-9.3) |
5.7 (5.1-6.4) |
1.2 (0.7-1.8) |
Requirement of inotropes |
5.5 (4.7-6.3) |
1.1 (0.8-1.3) |
1.1 (0.6-1.5) |
Rural residence |
5.1 (3.8-6.4) |
1.2 (0.7-1.5) |
0.9 (0.3-1.4) |
Values in adjusted odds ratio (95% CI). |
DISCUSSION
In this study conducted to detect the incidence and predictors
of renal complications due to hematotoxic envenomation, we
found that 38.2% children developed AKI following bite and 26%
of them developed stage 3 AKI. Acute tubular necrosis was the
most common finding in renal histopathology.
Measurement of serum venom level was not possible
in our setting. Nearly 20%, 30% and 40% variation of AKI,
permanent renal injury and mortality still remained
unexplained. Renal histopathology could not be done in all the
children due to invasive nature of the investigation and lack
of consent.
Previous studies report 14.6-45.9% children
developing AKI after hematotoxic envenomation and 24.5%
developing permanent renal injury [7-9]. Mortality was lower
in the current study than previous Indian reports of 6.6-22.3%
[7-9]. This variability may be due to local variation of
venom, heterogeneity of population and availability of
resources [5,9]. Similar to the finding of current study,
other authors have also noted that the time between
administration of ASV and the snakebite was the most
significant predictor of AKI [8,9]. Howarth, et al.
[10] determined that mean periphery to systemic circulation
time of venom was 58 (7) minutes. Hence, administration of ASV
after 1 hour was less effective in prevention renal
impairments. However, Krishnamurthy, et al. [7]
did not found any significant association between delayed
administration of ASV and development of AKI. AKI was more
common among the younger children may be due to their
ambulatory nature leading to more circulation of toxin [11].
Similar to the findings of current study, multiple researchers
have also reported pre-hospital factors, alteration of 20 WBCT
for prolonged time, neurotoxic signs and severe illness
(characterized by bleeding, requirement of mechanical
ventilation, blood products and inotropes) predict adverse
outcome [9, 12-15].
To conclude, delay in administration of ASV was the
most significant predictor of renal complications and
mortality following hematotoxic bite. Prompt hospitalization
after bite leads to early initiation of treatment and lesser
fatality. As the composition of venom varies according to
geographic location [5] and present study includes children
from part of Bengal, Bihar and Jharkhand only, further
multi-centric research should be undertaken before
generalization of findings of this study.
Ethical Clearance:
Institution Ethics Committee, Burdwan Medical College,
BMC/PG/4456 dated 14/12/2015.
Contributors:
KI: writing manuscript, collection of data, analysis of data;
SS: collection of data, analysis of data, designing study; AR:
collection of data, writing and revising manuscript. AKD:
planning study, revising manuscript.
Funding:
None; Competing interest: None stated.
What This Study Adds? |
• Administration of ASV
following 1 hour of bite is the most significant
predictor of acute kidney injury, permanent renal
injury and mortality.
|
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