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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 174-178

Retrospective study on 48-h fluid balance and outcome in mechanically ventilated critically ill children


Department of Pediatrics, Division of Pediatric Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Submission19-May-2020
Date of Decision18-Jun-2020
Date of Acceptance27-Jun-2020
Date of Web Publication13-Jul-2020

Correspondence Address:
Dr. Ramachandran Rameshkumar
Department of Pediatrics, Division of Pediatric Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPCC.JPCC_83_20

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  Abstract 


Background and Aim: There is limited data on the outcome of mechanically ventilated critically ill children in low- and middle-income countries. The aim was to study the association of fluid balance in mechanically ventilated critically ill children and outcomes.
Methodology: This retrospective study was conducted in an academic hospital's pediatric intensive care unit (PICU) from January 2015 to December 2016. Children aged 1 month to 12 years ventilated for more than 24 h with 48-h fluid balance were included in the study. Patients were divided into ≤10% and >10% fluid overload (FO) groups. The primary outcome was all-cause PICU mortality. The secondary outcomes were the durations of mechanical ventilation, PICU and hospital stay; organ failure; and extubation failure.
Results: A total of 107 patients (23 in >10%-FO and 84 in ≤10%-FO groups) were enrolled. The median (interquartile range) age and pediatric risk of mortality III score were similar in both groups (12, 7–36 months vs. 11, 3–32 months; P = 0.37; and 16, 12–20 vs. 15, 12–18; P = 0.71, respectively). The most common indication for ventilation was disordered control of breathing (55% vs. 42%) followed by respiratory pathology (30% vs. 39%). In >10%-FO group, higher proportion of patients had acute respiratory distress syndrome (13 [56%] vs. 28 [35%], P = 0.06) and acute kidney injury (15 [65%] vs. 37 [44%)], P = 0.07), of which a significant number required renal replacement therapy (10 [43%] vs. 15 [17%], P = 0.01). More patients had septic shock in >10%-FO group (13 [56%] vs. 27 [32%], P = 0.03). There was no significant difference in all-cause PICU mortality in >10%-FO groups (13 [57%]) as compared to ≤10%-FO group (32 [38%]) (relative risk = 1.2, 95% confidence interval [CI]: 1.0–1.5, P = 0.11; and adjusted hazard ratio = 1.52, 95% CI: 0.78–2.97, P = 0.22). No differences were noted in other outcome variables.
Conclusion: There was no significant difference in mortality and morbidity noted in 10% FO cutoff in critically ill mechanically ventilated children. A larger sample size, preferably a multicentric study, is warranted.

Keywords: Children, fluid overload, morbidity, mortality, ventilation


How to cite this article:
Ravikumar N, Rameshkumar R, Satheesh P, Mahadevan S. Retrospective study on 48-h fluid balance and outcome in mechanically ventilated critically ill children. J Pediatr Crit Care 2020;7:174-8

How to cite this URL:
Ravikumar N, Rameshkumar R, Satheesh P, Mahadevan S. Retrospective study on 48-h fluid balance and outcome in mechanically ventilated critically ill children. J Pediatr Crit Care [serial online] 2020 [cited 2020 Aug 9];7:174-8. Available from: http://www.jpcc.org.in/text.asp?2020/7/4/174/289527




  Introduction Top


Fluid resuscitation is an essential step in the management of critically ill children and forms the basis of early goal-directed therapy in pediatric septic shock.[1] In children on mechanical ventilation, maintenance fluid requirement is reduced due to lesser insensible water loss. Overestimation of the fluid deficit and excessive replacement could lead to positive fluid balance and fluid overload (FO). Pediatric and adult studies have shown adverse outcomes with a positive cumulative balance, especially in acute respiratory distress syndrome (ARDS).[2],[3],[4] However, there is limited data on the outcome of children ventilated for other indications.

In children with ARDS, early FO is known to be independently associated with increased mortality and duration of mechanical ventilation.[3] If FO affects through pulmonary dysfunction, then all children on mechanical ventilation are likely to have poor outcomes due to cumulative positive balance. Because patients with severe disease tend to receive more fluid during resuscitation, the severity of disease could also affect the outcome and needs to be considered during analysis.[5] Although a positive balance is shown to have adverse outcomes in mechanically ventilated children regarding respiratory morbidity and duration of hospital stay, most studies fail to show a significant difference in mortality.[3],[6]

The association of fluid balance and clinical outcomes has not been previously studied in critically ill mechanically ventilated children from low- and middle-income countries. Sufficient evidence is required to prove the poor outcome of positive fluid balance in children ventilated for various indications to make fluid restriction a significant part of the management protocol. Our study attempts to provide a better understanding of the threshold of fluid balance and outcome in critically ill mechanically ventilated children during the pediatric intensive care unit (PICU) stay.


  Methodology Top


Study design and setting

The retrospective study was undertaken in the PICU of a tertiary care academic hospital. The medical records from January 2015 to December 2016 were screened. Our PICU is a 19-bedded intensive care unit (ICU) and accepts both medical and surgical patients. The institute's ethics committee (IEC) approved the study with a waiver of written consent (JIP/IEC/2016/1042).

Participants

All children aged 1 month to 12 years admitted to the PICU and mechanically ventilated for more than 24 h with documented input–output balance for at least 48 h from the start of mechanical ventilation were included in the study. Children with stay in PICU <48 h, mechanical ventilation duration <24 h, incomplete/missing data about fluid balance data, and ventilated outside PICU (other ICU) before admission were excluded from the study.

Data collection and outcome variables

Baseline variables (age, sex, and severity score by the pediatric risk of mortality [PRISM-III][7]), the indication of ventilation, fluid balance, shock, acute kidney injury (AKI) (by p-RIFLE), ARDS (by Pediatric Acute Lung Injury [ALI] Consensus Conference – PALICC classification),[8] and intervention details were collected. The SpO2/FiO2 ratio, oxygen saturation index, and organ failure score (by Sequential Organ Failure Assessment [SOFA] and Pediatric Logistic Organ Dysfunction [PeLOD] score[9]) were noted in a pro forma. FO percentage was calculated as = ([fluids administered in milliliter − fluid output in milliliter]/weight at admission in gram] ×100).[10] The primary outcome was all-cause PICU mortality. The secondary outcomes were (i) durations of mechanical ventilation, PICU and hospital stay; (ii) organ failure; and (iii) extubation failure.

Statistical analysis

The normality of data was checked with the Kolmogorov–Smirnov Z-test. Continuous variables between the two groups were checked by the Mann–Whitney U-test for nonnormally distributed data. The proportion was compared by the Chi-square test (Fisher's exact test if cell frequency is small). The relative risk with 95% confidence interval (CI) was calculated as appropriate. Kaplan–Meier curve with a log-rank test was used to analyze the time to event data followed by Cox regression analysis to adjust prespecified factors (age, sex, and PRISM-III). The relative risk and hazard ratio, with a 95% CI, were calculated wherever appropriate. All tests were two tailed, and P < 0.05 was considered statistically significant. SPSS 20.0 software (SPSS Inc. Chicago, IL, USA) and Epi Info™ 7 (7.0.9.7, Centers for Disease Control and Prevention) were used for data analysis. The statistician was blinded for treatment group classification until the preparation of the first draft of the manuscript.


  Results Top


The study flow is depicted in [Figure 1]. After screening of 295 patients, 107 eligible patients were enrolled (>10%-FO group, n = 23; and ≤10%-FO group, n = 84). The baseline characteristics and clinical data of the study participants are summarized in [Table 1] and comparable. Half of the patients (55% vs. 42%) were ventilated for the disordered control of breathing followed by respiratory pathology (30% vs. 39%) and shock (9% vs. 2%). Most of the patients belonged to the younger age group (median age, 12 months, interquartile range [IQR]: 4–36 months). The median (IQR) SpO2/FiO2 ratio was lower in >10%-FO group as compared to ≤10%-FO group (240, 170–280 vs. 250, 220–330; P = 0.09). There was no difference in the median (IQR) oxygen saturation index between the groups (5.4, 2.9–6.6 vs. 3.6, 2.8–5.2; P = 0.14). The all-cause PICU mortality was higher in >10%-FO group (13 [57%]) as compared to the ≤10%-FO group (32 [38%]). However, there was no statistical difference achieved (relative risk = 1.2, 95% CI: 1.0–1.5; P = 0.11; and adjusted hazard ratio = 1.52, 95% CI: 0.78–2.97, P = 0.22) [Figure 2]. There was no significant difference noted in the other outcomes. The outcomes of the study groups are summarized in [Table 2].
Figure 1: Study flow. PICU – Pediatric intensive care unit, FO – fluid overload

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Table 1: Baseline characteristics and clinical variables in the study participants

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Figure 2: Survival curve showing mortality in the study groups

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Table 2: Outcome variables of the study participants

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  Discussion Top


In this retrospective cohort study, we compared critically ill children based on their fluid balance at 48 h, namely ≤10%-FO and >10%-FO. The all-cause PICU mortality was higher in the >10%-FO group; however, no statistically significant difference was achieved. No significant differences were noted in the length of mechanical ventilation, PICU, and hospital stay; organ failure rate; and extubation failure rate. Adult studies on FO have shown decreased survival in patients with ARDS.[11],[12],[13]

The result was comparable to a study by Sinitsky et al., who found that although there was progressively higher mortality with increasing FO (FO groups: 0–5, 5–10, 10–15, and >15), this was not significant.[6] Flori et al. showed that an incremental increase in FO by 10 ml per kg per day had increased mortality in children with ALI.[2] Their study included all children admitted to the PICU with ALI regardless of the need for mechanical ventilation. The pediatric study analogous to the Fluids and Catheters Treatment Trial conducted by Pediatric ALI and Sepsis Investigators Network concluded that positive FO was independently associated with lesser ventilator-free days but with no difference in mortality.[3] In a systematic review by Alobaidi et al., FO was associated with increased in-hospital mortality and a 6% increase in the odds of mortality for every 1% increase in FO after adjusting for illness severity.[14] Similar to our setting, a study by Samaddar et al. found that >15%-FO at any time during the first 14 days of PICU was associated with higher mortality but not statistically significant but significantly longer duration of ventilation and PICU stay.[15] Nevertheless, this observation was in contrast to our study, where the duration of ventilation, PICU, and hospital stay was similar between the study groups.

The longer duration of ventilation and PICU stay in ≤10%-FO group could be due to the earlier mortality in the >10%-FO group. The different fluid balance groups in Sinitsky et al.'s study showed the increasing duration of ventilation with higher FO.[6] Vidal et al., in their study, showed that >13%-FO is independently associated with prolonged ventilation.[16] Alobaidi et al.'s review found a higher risk of prolonged ventilation (>48 h) and AKI with positive fluid balance.[14] In our study, the proportion of children having ARDS and AKI was higher in the >10%-FO group, of which a significant number had renal replacement therapy (RRT), but we did not analyze these as outcome parameters.

The organ dysfunction scores were comparable between the two groups in our study. Contrast results were reported by Samaddar et al., which found that >15%-FO had a higher maximum PELOD score.[15] The extubation failure was higher in the >10%-FO group among the survivors though this was not statistically significant. A similar observation was reported by Randolph et al. in their study that showed that cumulative FO did not predict extubation failure following low tidal volume ventilation and established weaning protocols.[17]

Our study had higher SpO2/FiO2 ratios and lowered oxygen saturation indices in the ≤10%-FO group, implying higher respiratory morbidity in children with >10%-FO group. We used the worst values of these ratios and indices, but daily comparisons were not made. Arikan et al. in children on ventilation for >24 h found that ≥15%-FO was independently associated with the particular day's oxygenation index.[5] Samaddar et al. did not find a significant association of FO and oxygenation index.[16] In our study, the most common indication for mechanical ventilation was nonrespiratory, i.e., disordered control of breathing, and hence the majority of children required normal lung ventilation. We have not done a separate analysis for children ventilated for respiratory causes as the sample size would be too small to derive any conclusions.

The strengths of our study were the comparison of two groups of critically ill children admitted to a general PICU for ventilation based on their fluid balance at 48 h with a cutoff of 10%-FO without excluding children requiring RRT. Most other studies focus on children with ALI and postoperative surgical cases and have excluded children on RRT. The present study incorporates the recent definition of pediatric ARDS and has picked up many cases of mild ARDS, which would have been missed if previous definitions had been used.[8]

However, there were a few limitations. With the data collection being retrospective, incomplete records could not be included in the analysis, cutting short our sample size. The relatively stable children with expected shorter stays in PICU were not catheterized, and the balance was not available, which could be a source of bias. We were also unable to include children who were moribund at admission and died within 48 h as a minimum of 48-h balance was required for inclusion. Further larger studies preferably multicentric are required to make conclusions regarding the harmful effects of positive FO in children on mechanical ventilation so that early achievement of zero or negative fluid balance can be prescribed as standard therapy in future.


  Conclusion Top


The study concludes that there was no significant difference in mortality or morbidity in association with positive fluid overload (FO) with a cutoff of 10%. Studies with larger sample size are required to obtain more evidence regarding the association of fluid overload and clinical outcomes in mechanically ventilated critically ill children.

Acknowledgment

We acknowledge the contribution of Mrs. S. Raja Deepa B. Com, MCA (JIPMER Campus, Puducherry, India) for support of data entry in a blinded manner and editing of the manuscript; Mr. Rakesh Mohindra (Punjab University, Chandigarh, India), and Mrs. Thenmozhi M (M. Sc, Ph.D., Senior demonstrator, CMC, Vellore, India) for helping with the statistical analysis and Mrs. Harpreet Kaur (Punjab University, Chandigarh, India) and Mrs. Neelima Chadha (Tulsi Das Library, PGIMER, Chandigarh, India) for helping with medical literature search.

Financial support and sponsorship

This study was financially supported in part by the institutional and departmental fund.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506.  Back to cited text no. 1
    
2.
Flori HR, Church G, Liu KD, Gildengorin G, Matthay MA. Positive fluid balance is associated with higher mortality and prolonged mechanical ventilation in pediatric patients with acute lung injury. Crit Care Res Pract 2011;2011:854142.  Back to cited text no. 2
    
3.
Valentine SL, Sapru A, Higgerson RA, Spinella PC, Flori HR, Graham DA, et al. Fluid balance in critically ill children with acute lung injury. Crit Care Med 2012;40:2883-9.  Back to cited text no. 3
    
4.
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564-75.  Back to cited text no. 4
    
5.
Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012;13:253-8.  Back to cited text no. 5
    
6.
Sinitsky L, Walls D, Nadel S, Inwald DP. Fluid overload at 48 hours is associated with respiratory morbidity but not mortality in a general PICU: Retrospective cohort study. Pediatr Crit Care Med 2015;16:205-9.  Back to cited text no. 6
    
7.
Pollack MM, Patel KM, Ruttimann UE. PRISM III: An updated pediatric risk of mortality score. Crit Care Med 1996;24:743-52.  Back to cited text no. 7
    
8.
Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: Consensus recommendations from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med 2015;16:428-39.  Back to cited text no. 8
    
9.
Gogia P, Koreti S, Patel GS. SOFA (sequential organ failure assessment) and PELOD (pediatric logistic organ dysfunction). Sch J App Med. Sci 2015;3:1645-8.  Back to cited text no. 9
    
10.
Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics 2001;107:1309-12.  Back to cited text no. 10
    
11.
Simmons RS, Berdine GG, Seidenfeld JJ, Prihoda TJ, Harris GD, Smith JD, et al. Fluid balance and the adult respiratory distress syndrome. Am Rev Respir Dis 1987;135:924-9.  Back to cited text no. 11
    
12.
Humphrey H, Hall J, Sznajder I, Silverstein M, Wood L. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest 1990;97:1176-80.  Back to cited text no. 12
    
13.
Schuller D, Mitchell JP, Calandrino FS, Schuster DP. Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome? Chest 1991;100:1068-75.  Back to cited text no. 13
    
14.
Alobaidi R, Morgan C, Basu RK, Stenson E, Featherstone R, Majumdar SR, et al. Association between fluid balance and outcomes in critically ill children: A systematic review and meta-analysis. JAMA Pediatr 2018;172:257-68.  Back to cited text no. 14
    
15.
Samaddar S, Sankar J, Kabra SK, Lodha R. Association of fluid overload with mortality in critically-ill mechanically ventilated children. Indian Pediatr 2018;55:957-61.  Back to cited text no. 15
    
16.
Vidal S, Pérez A, Eulmesekian P. Fluid balance and length of mechanical ventilation in children admitted to a single pediatric intensive care unit. Arch Argent Pediatr 2016;114:313-8.  Back to cited text no. 16
    
17.
Randolph AG, Forbes PW, Gedeit RG, Arnold JH, Wetzel RC, Luckett PM, et al. Cumulative fluid intake minus output is not associated with ventilator weaning duration or extubation outcomes in children. Pediatr Crit Care Med 2005;6:642-7.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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