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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 6  |  Page : 1222-1235
Peritoneal dialysis for the prevention of fluid overload in infants after cardiac surgery – A systematic review and meta-analysis


1 Department of Pediatrics, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
2 Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
3 Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

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Date of Submission07-Jul-2018
Date of Acceptance13-Aug-2018
Date of Web Publication9-Jan-2020
 

   Abstract 


The objective is to compare peritoneal dialysis with standard care therapy for the prevention of fluid overload in infants after cardiac surgery. We searched published literature through the major database up to December 2017. Randomized controlled trials (RCTs), quasi-randomized trials, and observational studies were included in the study. The primary outcome measures were as follows: all-cause mortality and duration of hospitalization. Of the 392-citation retrieved, full text of 7 was finally assessed for eligibility. Of these, a total of five studies (RCTs = 3, and observational studies = 2) were included. There was no significant difference between the prophylactic PD and the standard therapy group for any of the primary outcomes. The present systematic review shows that prophylactic PD is not beneficial compared to standard care in infants postcardiac surgery for congenital heart disease. The GRADE evidence generated was of “very low quality.”

How to cite this article:
Bhatt GC, Das RR, Chaudhary B, Satapathy AK, Malik S. Peritoneal dialysis for the prevention of fluid overload in infants after cardiac surgery – A systematic review and meta-analysis. Saudi J Kidney Dis Transpl 2019;30:1222-35

How to cite this URL:
Bhatt GC, Das RR, Chaudhary B, Satapathy AK, Malik S. Peritoneal dialysis for the prevention of fluid overload in infants after cardiac surgery – A systematic review and meta-analysis. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Apr 9];30:1222-35. Available from: http://www.sjkdt.org/text.asp?2019/30/6/1222/275466



   Introduction Top


Congenital heart disease (CHD) is defined as “a gross structural abnormality of the heart or intrathoracic great vessels that is actually or potentially of functional significance.[1]” Incidence of CHD varies from 4 to 50 per 1000 live births in various studies.[2],[3] Of these, 25% of the neonates require immediate surgical intervention whereas many others require it during later part of infancy.

In the postoperative period, fluid overload is an important risk factor for morbidity and mortality in these groups of children. Fluid overload in postoperative period is attributed to acute kidney injury, capillary leak, or hemo-dilution. To overcome this fluid overload and acute kidney injury, various treatment modalities have been implicated which include diuretics, passive peritoneal drainage, and early (prophylactic) renal replacement therapy (RRT).

In infants, peritoneal dialysis (PD) is the preferred mode of RRT in view of small intravascular volume. However, there is insufficient evidence available in these groups of infants and the results of the randomized controlled trials (RCTs) have been conflicting.[4],[5],[6],[7] This systematic review was carried out to synthesize the evidence regarding the effect of prophylactic PD on fluid overload in postcardiac surgery infants.

Objective

Our objective is to compare prophylactic peritoneal dialysis with standard care therapy (peritoneal drainage and/or diuretics) for the prevention of fluid overload in infants after cardiac surgery


   Methods Top


Types of studies

RCTs, quasi RCT’s and nonrandomized controlled studies were considered for the analysis.

Types of participants

Children with age <1 year with CHD who underwent cardiac surgery were included. Patients with preexisting kidney disease, interventions combining drug therapy with PD, without any control group were excluded from the study as those with preexisting genitourinary abnormality, serum creatinine >1 mg/ dL, active urinary tract infections, requiring >72 h of nephrotoxic medications, premature neonates <37 weeks gestation and weight <2 kg, urine output <0.5 mL/kg/H over 24 h in the 48 h before procedure, abdominal defects, chromosomal abnormalities, preoperative extracor-poreal life support (ECLS), planned PD catheter (PDC) not placed and the patient dying or requiring a second operation.

Types of intervention

The type of intervention is the prophylactic use of PD for the prevention of fluid overload in postoperative period of infants with CHD undergoing cardiac surgery.

Types of comparison/control The type of comparator/control is the use of passive drainage (no prophylactic PD) or diuretics or both (passive drainage and diuretics).

Types of outcome measures

Primary outcomes

  1. All-cause mortality
  2. Duration of hospitalization


Secondary outcomes

  1. Proportion of infants with 10% fluid overload
  2. Duration of mechanical ventilation/time to extubation
  3. Time to achieve negative fluid balance
  4. Adverse events


Definitions

Percentage fluid overload is defined as cumulative fluid balance that is expressed as percentage and a cutoff of ≥10% has been associated with increased mortality in critically ill pa-tients.[8] Fluid overload percentage is calculated by the following formula:[9] % fluid overload: [(Total fluid in-Total fluid out)/Admission weight] × 100.

A deficit in fluid volume is known as negative fluid balance.[10]

Data extraction (selection and coding)

Data extraction was done by using a pilot tested data extraction form. The first two authors independently extracted data including author, type of population, exposure/intervention (PD or diuretic infusion), results (outcome measures, effect, significance), and sources of funding/support. Any disagreement in the extracted data was resolved through discussion with the third author.

Risk of bias (quality) assessment

Two review authors independently assessed the methodological quality of the selected trials by using Cochrane methodological quality assessment forms.[11] The handbook has seven criteria, which include -random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and any other bias. Any disagreements between the two review authors were resolved through discussion with the third author.

Strategy for data synthesis

The data from various studies were pooled and expressed as mean difference (MD) with 95% confidence interval (CI) in case of continuous data and risk ratio (RR) with 95% CI in case of categorical data. P <0.05 was considered statistically significant. The assessment of heterogeneity was done by I2 statistics.[12] If there was a high level heterogeneity (>50%), we explored the cause. A fixed-effects model was initially conducted. If significant heterogeneity existed between trials, potential sources of heterogeneity were considered and where appropriate a random effects model was used. Review Manager version 5.2 was used for all the ana-lyses.[13] Where data were provided as median with range or interquartile range (IQR), these were converted to mean and standard deviation as per standard methods described recently.[14],[15],[16]

Search methods for identification of studies

Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, Google Scholar, Cochrane renal group were searched from 1970 to December 2017. Following search strategy was applied: Peritoneal dialysis (PD) AND prevention OR prophylaxis OR controlled AND infants OR neonates OR children.

Publication bias

This was looked for by construction of the inverted funnel plot as suggest by Egger et al.[17]

Grade of evidence

For assessment of the quality of evidence we used GRADE Profiler software (version 3.2, McMaster University and Evidence Prime Inc, Canada).[18] The software uses five parameters for rating the quality of evidence. The parameters used were -limitations to design of RCTs, inconsistency of results or unexplained heterogeneity, indirectness of evidence, imprecision of results, and publication bias. The rating was done as -no, serious, and very serious limitation.


   Results Top


Of 392 citations retrieved, full text of 16 articles was assessed. Of these, a total of three RCTs[6],[19],[20] and two nonrandomized studies[4],[21] were included in qualitative synthesis. The three RCTs were open-label studies with moderate-to-high risk of bias. The detailed flow of the studies is shown in [Figure 1]. All of the studies were conducted in cardiac intensive care unit (CICU) of USA (n = 4) and Canada (n = 1). Most of the participants were <6 months of age and had critical CHD. The characteristics of the included studies are shown in [Table 1]. There were three comparisons of prophylactic PD versus standard care (PD vs. passive drainage, PD vs. furosemide, and PD vs. passive drainage plus furosemide) as follows.
Figure 1: PRISMA flow diagram.

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Table 1: Characteristics of included studies.

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Prophylactic peritoneal dialysis versus passive drainage

A total of three studies (2 RCTs, and 1 observational study) reported these outcomes.[4],[19],[20]

Primary outcomes

  1. All-cause mortality: Two RCTs with 42 participants reported this outcome,[6],[19] and the pooled data showed no difference in mortality among PD group compared to supportive therapy group (RR 3.26; 95% CI: 0.37 to 29.01) [Figure 2]. One observational study with 84 participants reported this outcome,[4] and the pooled data showed no difference in mortality among PD group compared to supportive therapy group (RR 2.00; 95% CI: 0.54 to 7.47).
  2. Duration of hospitalization: One RCT with 22 participants reported this outcome,[6] and the pooled data showed no difference between the two groups (MD -7.30; 95% CI: -21.14 to 6.54) [Figure 3]. Another observational study with 84 participants reported this outcome,[4] and the pooled data showed no difference between the two groups (MD -0.98; 95% CI: -5.49 to 3.53).
Figure 2: All-cause mortality (peritoneal dialysis vs. passive drainage).

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Figure 3: Duration of hospitalization (peritoneal dialysis vs. passive drainage).

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Secondary outcomes

  1. Proportions of patients with 10% fluid overload: This outcome was not reported by any of the studies
  2. Duration of mechanical ventilation/time to extubation (d): One RCT with 22 participants reported this outcome,[6] and the pooled data showed no difference between the two groups (MD 1.5; 95% CI: -2.26 to 5.26). One observational study with 84 participants reported this outcome (4) and the pooled data showed no difference between the two groups (MD -0.88; 95% CI: -2.3 to 0.54)
  3. Time to negative fluid balance: One RCT with 22 participants reported this outcome,[6] and the pooled data showed no difference between the two groups (MD 0.03; 95% CI: -0.72 to 0.78). One observational study with 84 participants reported this outcome,[4] and the pooled data showed a significantly shorter duration in the PD group (MD -0.91; 95% CI: -1.24 to -0.58)
  4. Adverse events: Two studies reported the adverse events. One RCT with 22 participants reported four serious adverse events only in the PD group, of which, three required cardiopulmonary resuscitation followed by ECLS and one died.[6] One observational study with 84 participants reported three adverse events only in the PD group (one major and 2 minor) in the form of bloody effluent in the catheter, replacement of catheter, and omental evisceration requiring partial omentectomy followed by secondary closure of the abdominal wall.[4]


Prophylactic peritoneal dialysis (versus Furosemide

One RCT with 73 participants reported the outcomes.[20]

Primary outcomes

  1. All-cause mortality: There was no significant difference between the two groups (RR 0.26; 95% CI: 0.03 to 2.38) [Figure 4]
  2. Duration of hospitalization (d): There was no significant difference between the two groups (MD -2.78; 95% CI: -8.5 to 2.94) [Figure 5].
Figure 4: All-cause mortality (peritoneal dialysis vs. furosemide).

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Figure 5: Duration of hospitalization (peritoneal dialysis vs. furosemide).

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Secondary outcomes

  1. Proportions of patients with 10% fluid overload: This was significant lesser by 78% in the PD group (RR 0.22; 95% CI: 0.07 to 0.67)
  2. Duration of mechanical ventilation (d): There was no significant difference between the two groups (MD -1.00; 95% CI: -2.17 to 0.17)
  3. Time to negative fluid balance (d): There was no significant difference between the two groups (MD -0.28; 95% CI: -0.6 to 0.04)
  4. Adverse events: Only two minor adverse events in the PD group noted.


Prophylactic peritoneal dialysis versus passive drainage and furosemide

A single-observational study with 52 participants reported the outcomes.[21]

Primary outcomes

  1. All-cause mortality: There was no significant difference between the two groups (RR 3.24; 95% CI: 0.36 to 29.15) [Figure 6]
  2. Duration of hospitalization (d): This outcome was not reported.
Figure 6: All-cause mortality (peritoneal dialysis vs. passive drainage and furosemide).

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Secondary outcomes

  1. Proportions of patients with 10% fluid overload: This outcome was not reported
  2. Duration of mechanical ventilation: There was no significant difference between the two groups (MD -1.84; 95% CI: -3.73 to 0.05)
  3. Time to negative fluid balance: The study described in figure that PD group had lesser time to negative fluid balance than the control group
  4. Adverse events: peritonitis, hyperglycemia, catheter leak, hypokalemia, hemoperitoneum, chyloperitoneum, hypoglycemia, hypophos-phatemia, and omentum herniation occurred in both groups without any significant difference.


Publication bias

As there were few trials, we could not construct funnel plot to denote any chance of publication is there or not.

Grade of Evidence

We constructed the GRADE table mainly for the primary outcomes as most of the secondary outcomes were reported by single studies which inherently generate “very low” quality evidence. The grade evidence generated for primary outcomes was also of “very low” quality [Table 2], [Table 3], [Table 4].
Table 2: Peritoneal dialysis compared to passive drainage for fluid overload in postcardiac surgery infants.

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Table 3: Peritoneal dialysis compared to furosemide for fluid overload in postcardiac surgery infants.

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Table 4: Peritoneal dialysis compared to passive drainage and furosemide for fluid overload in postcardiac surgery infants.

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   Discussion Top


Summary of evidence

A detailed literature search retrieved five studies which were included in the present systematic review. The result indicates that prophylactic PD compared to standard care (either passive drainage or diuretics or both) in infants postcardiac surgery for CHD neither decreases all-cause mortality nor decreases the duration of hospitalization. Regarding the secondary outcomes, proportion of infants with 10% fluid overload was lesser as reported by a RCT. Other outcomes like time to achieve negative fluid balance, duration of mechanical ventilation/ time to extubation, and adverse events were not significantly different between the two groups when data from RCTs were considered. Only, time to achieve negative fluid balance was significantly lesser in the prophylactic PD group when data from observational studies were considered. Adverse events were common in the prophylactic PD group though it was not significantly different from the standard care group.

Studies have shown that positive fluid positive balance is associated with higher morbidity (prolonged ventilation and prolonged hospital stay) and increased mortality independent of illness severity.[22] A fluid overload between 10% and 20% has been determined as clinically significant threshold for adverse outcomes in children with critical illness.[23],[24],[25] A number of interventions such as diuretic use, theophylline[26] fluid restriction, early use of RRT,[2] etc. has been tried to achieve a negative fluid balance but with variable success. A recent trial comparing furosemide with peritoneal dialysis in infants undergoing cardiopulmonary bypass found that furosemide group had three times odds of 10% fluid overload, more likely to have prolonged ventilator use, longer duration of inotrope use and higher electrolyte abnormality score as compared to PD group.[20] However, in this unblinded trial the authors had given lower furosemide dosage and also the study was not powered to determine difference in clinical outcome. Another randomized controlled trial on use of PD after Norwood paliations reported no significant clinical outcomes associated with PD, but found more adverse effect in PD group.[6] They reported four patients in the PD group have one or more serious adverse events. However, three of the patients in the PD group had cardiac arrest before the initiation of PD and this group had worse preoperative cardiac function and lactate levels.[6],[20] Another limitation was a small sample size in this study.


   Strengths and Limitations Top


The major strengths of the present systematic review are: it is the first systematic review conducted to show the clinical utility of PD for prevention of fluid overload in infants undergoing cardiac surgery, and the use of GRADE evidence to further strengthen the recommendations. Potential limitations include: inclusion of few eligible trials with small sample size, inclusion of studies from high income countries only, and very low grade evidence generated (due to potential biases in the included study). Further adequately powered randomized multicenter clinical trials with the inclusion of novel biomarkers of AKI and determining the cost-effectiveness of interventions are required before any firm recommendations can be made[27].


   Conclusions Top


The present systematic review shows that prophylactic of PD is not beneficial compared to standard care in infants postcardiac surgery for CHD. As the GRADE evidence generated was of “very low quality,” good quality RCTs with larger sample size are needed before any firm recommendations are made.


   Acknowledgment Top


Dr Girish C Bhatt was awarded the Indian Council of Medical Research (ICMR) international fellowship (ICMR-IF) for the year 20172018 in young scientist category for undergoing short term training in Pediatric Nephrology at Montreal Children’s Hospital, McGill University Health Centre, Canada.

Conflict of interest: None declared.



 
   References Top

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Mitchell SC, Korones SB, Berendes HW. Congenital heart disease in 56,109 births. Incidence and natural history. Circulation 1971;43:323-32..  Back to cited text no. 1
    
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Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890-900.  Back to cited text no. 2
    
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Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr 2008;153:807-13.  Back to cited text no. 3
    
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Kwiatkowski DM, Menon S, Krawczeski CD, et al. Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg 2015;149:230-6.  Back to cited text no. 4
    
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Sampaio TZ, O’Hearn K, Reddy D, Menon K. The influence of fluid overload on the length of mechanical ventilation in pediatric congenital heart surgery. Pediatr Cardiol 2015;36:1692-9.  Back to cited text no. 5
    
6.
Ryerson LM, Mackie AS, Atallah J, et al. Prophylactic peritoneal dialysis catheter does not decrease time to achieve a negative fluid balance after the Norwood procedure: A randomized controlled trial. J Thorac Cardiovasc Surg 2015;149:222-8.  Back to cited text no. 6
    
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Dittrich S, Aktuerk D, Seitz S, et al. Effects of ultrafiltration and peritoneal dialysis on pro-inflammatory cytokines during cardiopulmo-nary bypass surgery in newborns and infants. Eur J Cardiothorac Surg 2004;25:935-40.  Back to cited text no. 7
    
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Claure-Del Granado R, Mehta RL. Fluid overload in the ICU: Evaluation and management. BMC Nephrol 2016;17:109.  Back to cited text no. 8
    
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Bagshaw SM, Cruz DN. Fluid overload as a biomarker of heart failure and acute kidney injury. Contrib Nephrol 2010;164:54-68.  Back to cited text no. 9
    
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Scales K, Pilsworth J. The importance of fluid balance in clinical practice. Nurs Stand 2008; 22:50-7.  Back to cited text no. 10
    
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Assessing Risk of Bias in Included Studies. Ch. 8. Available from: http://handbook.cochrane. org/ chapter_8/8_assessing_risk_of_bias_in_include d_studies.htm. [Last accessed on 2016 Aug 30].  Back to cited text no. 11
    
12.
Higgins JP, Green S; Cochrane Collaboration, editors. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, England, Hoboken, NJ: Wiley-Blackwell; 2008. p. 649.  Back to cited text no. 12
    
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RevMan 5 | Cochrane Community. Available from: http: /tools/review-production-tools/ revman-5. [Last accessed on 2017 Aug 26].  Back to cited text no. 13
    
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Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5:13.  Back to cited text no. 14
    
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Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 2018;27:1785-805.  Back to cited text no. 15
    
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Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014;14:135.  Back to cited text no. 16
    
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Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.  Back to cited text no. 17
    
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Cochrane Community. Available from: http:/ tools/review-production-tools/gradepro-gdt. [Last accessed on 2017 Aug 26].  Back to cited text no. 18
    
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Riley AA, Jefferies JL, Nelson DP, et al. Peritoneal dialysis does not adversely affect kidney function recovery after congenital heart surgery. Int J Artif Organs 2014;37:39-47.  Back to cited text no. 19
    
20.
Kwiatkowski DM, Goldstein SL, Cooper DS, Nelson DP, Morales DL, Krawczeski CD. Peritoneal dialysis vs. furosemide for prevention of fluid overload in infants after cardiac surgery: A randomized clinical trial. JAMA Pediatr 2017;171:357-64.  Back to cited text no. 20
    
21.
Sasser WC, Dabal RJ, Askenazi DJ, et al. Prophylactic peritoneal dialysis following cardiopulmonary bypass in children is associated with decreased inflammation and improved clinical outcomes. Congenit Heart Dis 2014;9:106-15.  Back to cited text no. 21
    
22.
Santos CR, Branco PQ, Gaspar A, et al. Use of peritoneal dialysis after surgery for congenital heart disease in children. Perit Dial Int 2012;32: 273-9.  Back to cited text no. 22
    
23.
Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: A retrospective analysis. Crit Care Med 2004;32:1771-6.  Back to cited text no. 23
    
24.
Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE, et al. Fluid overload and mortality in children receiving continuous renal replacement therapy: The prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 2010;55:316-25.  Back to cited text no. 24
    
25.
Gillespie RS, Seidel K, Symons JM. Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol 2004;19:1394-9.  Back to cited text no. 25
    
26.
Bhatt GC, Gogia P, Bitzan M, Das RR. Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review. Arch Dis Child 2019: 104:670-679  Back to cited text no. 26
    
27.
Bhatt GC, Das RR. Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review meta-analysis of randomized controlled trials. BMC Nephrol 2017;18:78.  Back to cited text no. 27
    

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Correspondence Address:
Girish Chandra Bhatt
Department of Pediatrics, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh
India
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DOI: 10.4103/1319-2442.275466

PMID: 31929269

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    Figures

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