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Indian Pediatr 2015;52: 583 -586 |
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Russell’s Viper Envenomation-associated Acute
Kidney Injury in Children in Southern India
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Sriram Krishnamurthy, Kuralvanan Gunasekaran,
Subramanian Mahadevan, *Zachariah Bobby and
#Ajith Prabhu Kumar
From Departments of Pediatrics, *Biochemistry and
#Community Medicine; Jawaharlal Institute of Postgraduate Medical
Education and Research (JIPMER), Puducherry, India.
Correspondence to: Dr. Subramanian Mahadevan,
Professor, Department of Pediatrics, JIPMER,
Puducherry 605 006, India.
Email:
[email protected]
Received; August 12, 2014;
Initial review; October 21, 2014;
Accepted: April 23, 2015.
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Objectives: To determine the frequency and risk factors of acute
kidney injury in children with Russell’s viper envenomation using Acute
Kidney Injury Network definition and classification system.
Methods: A prospective
observational study recruiting 61 subjects managed as per the National
Snakebite Protocol.
Results: 45.9% of envenomed
children had acute kidney injury. The median (IQR) of the maximum serum
creatinine level during hospitalization was 2 (1.3-4.8) mg/dL. The
distribution of stages 1, 2 and 3 of acute kidney injury was 32.1%,
17.9% and 50% respectively. Dialysis was required in 35.7% of the
children with acute kidney injury.
Conclusions: Acute kidney injury
is common with Russell’s viper envenomation. Native treatments and
bleeding manifestations were associated with acute kidney injury in our
patient population.
Keywords: Bleeding, Complications,
Management, Outcome, Snakebite.
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A cute Kidney injury (AKI) is a common complication
of Russell’s viper envenomation [1,2]. The quantum of Russell’s viper
envenomation-associated AKI, using the revised consensus Acute Kidney
Injury Network (AKIN) definition and classification system [3] is not
well documented in children. We conducted this study to determine the
frequency and risk factors of AKI associated with Russell’s viper
envenomation in children.
Methods
This prospective observational study was conducted at
a referral hospital in Southern India from January 2013 to July 2014.
Sixty-one children below 13 years of age with systemic features of
Russell’s viper envenomation were included. The study was approved by
the Institutional Ethics Committee. Informed consent was obtained prior
to enrolment of subjects. The primary objective of the study was to
determine the incidence of AKI using the AKIN definition and
classification system in children with Russell’s viper envenomation [3],
while the secondary objectives were to study the predictors of AKI, and
to compare the clinico-biochemical profile in Russell’s viper
envenomation cases with AKI versus those without AKI.
Russell’s viper envenomation was diagnosed when [4]:
(i) the snake was brought to the hospital dead or alive, or (ii)
the victim or witnesses identified it as a Russell’s viper with a
matched description in the form of images or photographs; and the victim
had a typical clinical presentation (including bleeding manifestations,
or limb edema with fang marks); and a positive 20-minute whole blood
clotting time (20 WBCT). Patients with known chronic kidney disease were
excluded. Indications for renal replacement therapy included fluid
overload (e.g pulmonary edema or uncontrolled hypertension), anuria for
more than 12 hours, altered sensorium, pericarditis, hyperkalemia (serum
potassium >5.5 mEq/L) and refractory metabolic acidosis.
At admission, serum creatinine was measured in all
children by modified Jaffe method [5] using autoanalyzer. Repeat serum
creatinine was done every 24 hours after admission for 3 days.
Thereafter, serum creatinine was measured at intervals of 48 hours (or
whenever clinically indicated, whichever was earlier) till discharge or
death. Clinical parameters such as bleeding manifestations, limb edema,
duration of hospitalization, number of vials of Anti-snake venom serum
(ASV) required, AKI stage, requirement of mechanical ventilation, blood
products or dialysis, and mortality were recorded. ASV was administered
as per the National Snake bite Protocol and World Health Organization
guidelines for management of snake bites [6,7]. The 20 WBCT was measured
every 6 h till normalization. Patients received polyvalent ASV (Bharat
Serum and Vaccines, Ltd). The initial dose administered was 10 vials
dissolved in 10 mL/kg of normal saline and intravenously infused over 1
hour. If the 20 WBCT did not decrease to less than 20 min after 6 hours,
additional 10 vials were administered. This was repeated after 6 hours
if the 20 WBCT was still not normal.
Complete renal recovery was defined as normal serum
creatinine for age (0.2-0.4 mg/dL for infants, 0.3-0.7 mg/dL for 1-12
years, 0.5-1 mg/dL for >12 years) [8] and normal blood pressure for age
[9]. Residual renal injury was defined as elevated serum creatinine for
age [8] or persistent hypertension at discharge [9]. The proportion of
Russell’s viper envenomation-associated AKI was estimated to be 20%
[1,2]. Assuming a variability of 10% and 95% confidence, the sample size
required was calculated as 61 children.
Statistical methods: Data were analyzed using
Mann Whitney U test. Categorical variables were expressed as proportions
and compared using chi-square test or Fisher exact test. Data were
evaluated using SPSS version 19. Predictive risk factors for AKI were
determined by univariate analysis, followed by stepwise logistic
regression analysis.
Results
Sixty-one children (34 males) with Russell’s viper
envenomation were enrolled. Their mean (SD) age was 7.2 (1.8) years. The
median (IQR) time to ASV administration was 4 (2.3, 7) hours, while the
mean (SD) number of ASV vials required were 10.9 (7.6). Fourteen
children (23%) required mechanical ventilation, 12 (19.7%) required
inotropic support, while blood products were administered in 9 (14.8%)
children. Bleeding manifestations were encountered in 23 (37.7%)
children, including hematuria (24.6%) and hematemesis (9.3%).
Twenty-eight (45.9%) children developed AKI. The
characteristics of these 28 children are summarized in Table I.
Fourteen children with AKI (50%) were in stage 3 of AKI. Of these, 10
required renal replacement therapy.
TABLE I Clinical and Biochemical Profile of Children with Russell’s Viper Envenomation-associated AKI (N=28)
Characteristics |
|
Age (y), median (IQR) |
8 (6.7-10) |
Males# |
15 (53.6) |
Oliguria# |
8 (28.6) |
Onset of oliguria after the bite (h), median (IQR) |
36 (30-72)
|
Anuria# |
9 (14.8) |
Time for recovery from oliguria (d), median (IQR) |
6 (4.5-5.5) |
Hypertension# |
2 (7.1) |
Dialysis requirement#* |
10 (35.7) |
Serum creatinine (mg/dL), median (IQR) |
Maximum |
2 (1.3-4.8) |
At discharge |
0.85 (0.7-1.2) |
AKI stage# |
Stage 1 |
9 (32.1) |
Stage 2 |
5 (17.9) |
Stage 3 |
14 (50) |
Hyperkalemia# |
4 (14.3) |
Hyponatremia# |
3 (10.7) |
Time to ASV administration (h), median (IQR) |
4 (3-8.25) |
In children requiring dialysis (n=10) |
8 (3-10) |
In children with AKI stage 3 (n=14) |
7 (4-9) |
Pre-ASV treatment sought
|
(tourniquet /native medications)# |
27 (96.4)
|
Length of hospital stay (d), median (IQR) |
8 (6-12) |
Limb edema# |
11 (39) |
Residual renal injury at discharge# |
9 (32.1) |
#Values in No. (%); *9 children were managed with
peritoneal dialysis, and 1 child underwent hemodialysis. |
Native treatment, bleeding manifestations and shock
were found to be predictors of AKI on univariate analysis. On stepwise
logistic regression analysis, bleeding manifestations (OR 3.6; 95% CI
1.21, 10.7; P=0.016) and native treatment (OR 6.2; 95% CI 1.19,
32.23; P=0.01) were found to be independent predictors of AKI.
There were 4 deaths out of 28 children with AKI,
whereas there were no deaths in the 33 children without AKI. The
frequency of bleeding manifestations and proteinuria was significantly
higher with AKI. The median (IQR) values of the highest blood urea and
serum creatinine values reached during hospital stay in children with
AKI (n=28) were 105 (71.3, 205.5) mg/dL and 2 (1.3-4.8) mg/dL
respectively, as compared to the corresponding values of 28 ( 22-34) mg/dL
and 0.7 (0.6-0.8) mg/dL in children without AKI (n=33) (Table
II).
TABLE II Comparison of Clinical Features and Laboratory Parameters in
Russell’s Viper Envenomation Cases with and without AKI
Characteristics
|
Children without AKI |
Children with AKI |
P
|
|
(N=33) |
(N=28) |
|
Age, y* |
7 (3-10) |
8 (6.7-10) |
0.336 |
Males# |
19 (57.6) |
15 (53.6) |
0.754 |
Length of hospital stay, d* |
3 (2-5) |
8 (6-12) |
0.004 |
Activity at the time of bite# |
|
|
|
Playing |
12 (36.4) |
10 (35.7) |
|
Sleeping |
6 (18.2) |
10 (35.7) |
0.232 |
Walking |
15 (45.5) |
8 (28.6) |
|
Site of bite# |
|
|
|
Leg |
25 (75.8) |
23 (82.1) |
|
Hand |
5 (15.2) |
4 (14.3) |
0.674 |
Trunk |
3 (9.1) |
1 (3.6) |
|
Pre ASV treatment sought# |
|
|
|
Tourniquet |
7 (21.2) |
10 (35.7) |
0.266 |
Native medications |
2 (6.1) |
8 (28.6) |
0.018 |
Immobilization# |
1 (3) |
3 (10.7) |
0.253 |
No. of ASV vials* |
10 (0-11) |
10 (8-19) |
0.083 |
ASV reaction# |
9 (27.3) |
13 (46.4) |
0.121 |
Requirement of mechanical ventilation# |
5 (15.2) |
9 (32.1) |
0.116 |
Requirement of inotropes# |
3 (9.1) |
9 (32.1) |
0.024 |
Requirement of blood products# |
1 (3) |
8 (28.6) |
0.005 |
Bleeding manifestations#$
|
8 (24.2) |
15 (53.6) |
0.019 |
Hematuria# |
2 (6.1) |
13 (46.6) |
0.001 |
Urine protein: Urinary creatinine (g/g of creatinine)# |
|
|
|
0.2 - 2 |
1 (3) |
6 (21.4) |
|
>2 |
1 (3) |
10 (35.7) |
0.001 |
Mortality |
0 (0) |
4 (14.3) |
0.039 |
*Values depicted as median (IQR); #values depicted as n (%);
$included hematemesis in 4, hematuria in 13, subconjunctival
hemorrhage in 2, epistaxis in 2, melena in 2, and bleeding from
bite site in 2 children.
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Discussion
In this descriptive study, we observed that AKI
occurred in almost half of the children with Russell’s viper
envenomation. Further, half of the cases of Russell’s viper envenomation-associated
AKI were in AKI stage 3, while about one-third each required dialysis,
mechanical ventilation and inotropes. Native treatments and bleeding
manifestations were independent predictors of AKI. The mechanisms of
Russell’s viper envenomation-associated AKI include direct nephrotoxic
effect of the venom [1,2], hypotension, disseminated intravascular
coagulation and intravascular hemolysis [4]. These may lead to acute
tubular necrosis, cortical necrosis or immune complex-mediated
glomerulonephritis. Though there are multiple studies on snake
envenomation in children [10,11], most have included hematotoxic or
neurotoxic snake bites.
The incidence of snake bite-associated AKI in an
adult population from Karnataka using the AKIN definition was 14.6%
[12]. This study included adults with snake envenomations irrespective
of species of snake. A study from Kolkata [4] studied the profile of
Russell’s viper envenomation-associated AKI in 61 children, but
incidence of AKI could not be determined as cases without AKI were not
recruited. Before the advent of the AKIN definition, ‘acute renal
failure’ was documented to occur in 13-22% of snake envenomation [1,2].
We could not demonstrate any association between
delayed administration of ASV and development of AKI. ASV administration
as soon as four hours after Russell’s viper envenomation did not prevent
renal failure in one earlier study. The authors had hypothesized that
once significant obstruction of renal micro-vessels with fibrin occurs,
ASV would not prevent AKI [13]. On the contrary, another study observed
the time to ASV initiation to be negatively correlated with requirement
for dialysis [4]. Variability in these results could be related to
heterogeneity in patient populations.
This is the first study from Southern India to
analyze the incidence of AKI in Russell’s viper envenomation using the
consensus AKIN definition in a cohort of exclusively pediatric patients.
The profile of patients in our study could have been limited by a
referral bias. The model for prediction of AKI explains only 25.1% of
all determinants. We also could not assess long term residual renal
injury in Russell’s viper envenomation; although this is being
increasingly recognized [14].
We conclude that AKI is common in Russell’s viper
envenomation, and children with bleeding manifestations and native
treatments are at risk for AKI. There is a need for prompt referral of
such patients to higher centres, in order to initiate timely
interventions.
Contributors: SK, KG, SM: were involved in
management of the patients; SK, KG: collected the data; SK: reviewed the
literature and drafted the manuscript; SK, SM: conceptualized the study
and reviewed the literature; SM: critically reviewed the manuscript and
shall act as guarantor of the paper; ZB: supervised the laboratory
tests; APK: performed the statistical analysis. All authors approved the
final version of the manuscript.
Funding: None; Competing interests:
None stated.
What is already known
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Acute kidney injury (AKI) is a common complication of
Russell’s viper envenomation.
What This Study Adds
•
The incidence of AKI (using AKIN definition) in Russell’s
viper envenomation is 45.9%.
• EEnvenomed children with bleeding manifestations and native
treatments are at risk for AKI.
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