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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 4  |  Page : 1841-1848

Fluid balance among children with sepsis and its relation to prognosi


1 Department of Pediatric, Faculty of Medicine, Menoufia University Hospital, Menoufia, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University Hospital, Menoufia, Egypt

Date of Submission25-Aug-2022
Date of Decision06-Sep-2022
Date of Acceptance12-Sep-2022
Date of Web Publication04-Mar-2023

Correspondence Address:
Sara S El-wazer
El-Mostkbal, Nozha
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_288_22

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  Abstract 


Objectives
To assess fluid imbalance among critically septic children and its relation to the prognosis of these critically ill children.
Background
Fluid imbalance is a common adverse event in critically ill children, which may lead to oxygenation failure, mortality, and in bad need for more fluid for resuscitation.
Patients and methods
This prospective cohort study was conducted on 74 critically septic children admitted into the Pediatric Intensive Care Unit. Pediatric Index of Mortality II, Pediatric Risk of Mortality, and Pediatric Sequential Organ Failure Assessment scores were calculated. Fluid measurements were assessed daily for 5 days. Children were subgrouped regarding the balance of fluid into a balanced fluid versus unbalanced fluid either hypovolemia or hypervolemia.
Results
Normovolemic cases represented 43 (58.1%) children, 14 (18.9%) children were in the hypovolemic group, and 17 (23%) children were in the hypervolemic group. There was a highly significant increase in mechanical ventilation need, Pediatric Sequential Organ Failure Assessment, and incidence of mortality in hypovolemic children compared with other groups (P < 0.001 for all); moreover, Pediatric Risk of Mortality and Pediatric Index of Mortality II showed a significant increase in hypovolemic children compared with the other two groups (all P < 0.05). Pediatric Intensive Care Unit showed a significant increase in hypervolemic children compared with other children (P = 0.041).
Conclusion
Fluid imbalance is a common adverse effect during fluid therapy in septic children and is linked to substantial morbidity and mortality.

Keywords: fluid balance, mortality, pediatric, Pediatric Index of Mortality II


How to cite this article:
Saleh NY, Rizk MS, El-wazer SS, Abo Hola AS. Fluid balance among children with sepsis and its relation to prognosi. Menoufia Med J 2022;35:1841-8

How to cite this URL:
Saleh NY, Rizk MS, El-wazer SS, Abo Hola AS. Fluid balance among children with sepsis and its relation to prognosi. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1841-8. Available from: http://www.mmj.eg.net/text.asp?2022/35/4/1841/371019




  Introduction Top


Sepsis is defined as a potentially fatal organ dysfunction caused by an abnormal host response to infection, characterized by vasodilation and hypovolemia, which is treated with early antibiotics and fluid resuscitation [1].

The Pediatric Sepsis Consensus Congress classified age into six subgroups to account for age-specific vital signs and risk factors for invasive infections, which affect antibiotic coverage guidelines [2].

Sepsis is the primary cause of death in the pediatric population worldwide, accounting for an estimated 7.5 million deaths each year. The WHO states the top four causes of sepsis-related childhood mortality: severe pneumonia, serious diarrhea, serious malaria, and serious measles [3].

Physiologic differences also play a role in fluid therapy. The changes that occur as a child grows have a significant effect on fluid requirements, making fluid therapy a critical component of pediatric pharmacotherapy. Fluid therapy is classified into three types: deficit, maintenance, and replacement. Each component of fluid therapy should be carefully considered when selecting the type of fluid and volume to be administered [4].

Fluid therapy aids in the restoration of normal body fluid volume and composition in terms of water–electrolyte balance. Fluid overload is common in critically ill children and may contribute to oxygenation failure and overall mortality. Because increasing disease severity frequently necessitates more fluid for resuscitation, it is unclear whether fluid overload causes morbidity or merely an indicator of disease severity [5].

So, this study aimed to assess the fluid imbalance status among septic children and whether it is related to the prognosis of these critically ill children.


  Patients and methods Top


Study design

This prospective observational study was conducted on 74 children admitted to the Pediatric Intensive Care Uni (PICU) from June 2021 to December 2021. Children were included in the study if their ages ranged from 1 month to 18 years and diagnosed with sepsis based on the international pediatric sepsis consensus criteria [6]. Exclusion criteria were (a) age under 1 month or over 18 years; (b) primary renal diseases such as nephrotic syndrome, chronic kidney disease, primary cardiac disease, and primary hepatic disease; and (c) lack of parental consent to participate in the study.

Ethical approval

Informed consent was obtained from children's legal guardians in advance of enrollment in this study, and the study protocol was approved by the Menoufia University Research Ethics Committee (a member of Egyptian Network Research Ethics Committee). The study approval number is 10/8 2022 PED.

Sample size determination

Based on past reviews of literature, it is estimated that the mortality among children with septic shock is 33% with a hazard ratio for %FO at 96 h to be 5.7 [7]. The sample size has been calculated at power 80% and 95% confidence interval, and it was 74 patients.

Study methods

All included children were subjected to the following: full history taking; general examination of heart rate, respiratory rate, temperature, and blood pressure as vital signs; weight, height/length, head circumference, and BMI as anthropometric measurements; and local examination was also performed to evaluate the respiratory, cardiovascular, nervous, and gastrointestinal systems. Mortality predictive scores were calculated for all patients at baseline which included the Pediatric Risk of Mortality (PRISM score) which is an objective way of defining and quantifying illness severity and prediction of mortality [8],[9]; Pediatric Index of Mortality II (PIM II score), which is a recalibrated form of PIM score used to predict mortality risk [10]; and Pediatric Sequential Organ Failure Assessment (pSOFA score), which is a screening tool to evaluate and assess the severity of organ dysfunction [11].

Samples of 9–10 ml of venous blood were collected using a needle and syringe after the application of skin disinfectant for laboratory investigations (one was an EDTA blood sample and another one was a plain blood sample). The laboratory investigations included complete blood count [12]; random blood sugar [13] using Pentra-80 automated blood counter (GMI , 6511 Bunker Lake Blvd. Ramsey, MN 55303 USA); C-reactive protein [14]; liver function tests (alanine transaminase, aspartate transaminase, serum albumin, and total bilirubin) [15] measured by kinetic ultraviolet optimized method IFCC (Pentra C-400; Horiba, s: Parc Euromédecine, 390 Rue du Caducée, 34790 Grabels, France); serum electrolytes (admission sodium level, serial sodium level during the first week, potassium, and calcium), kidney functions (urea and creatinine) [16] using standard colorimetric methods; and blood culture [17] (blood sample of 10 ml) and other body fluid cultures were taken as clinically indicated.

Fluid measurements were assessed daily for 5 days using the prespecified formula (repeat weight–PICU admission weight)/(PICU admission weight) mentioned by Selewski et al.[18].

Study outcomes

Our primary outcome was mortality during hospitalization or during the 30-day postdischarge follow-up period. The secondary outcomes were the length of PICU and hospital stay, need and duration of mechanical ventilation (MV), and occurrence of organ dysfunction.

Statistical analysis

Statistical presentation and analysis of this study were carried out, using the mean ± SD, median, and interquartile range. Unpaired Student's t test was used to test continuous data, Mann–Whitney (U test) for skewed continuous data, and χ2 test for categorical data. All analyses were performed by the IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, New York, USA). Correlations between analyzed data were tested by Pearson's correlation. For all of the data analyzed, a P value less than 0.05 was considered significant.


  Results Top


Regarding demographic and clinical data of children based on fluid state, we found only significant increase of weight and BMI in hypervolemic children compared with normovolemic and hypovolemic ones (P = 0.045 and 0.035, respectively). On the contrary, there was no significant difference regarding to age, sex, and height [Table 1].
Table 1: Demographic data of the studied groups

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Regarding clinical outcomes between included children based on their fluid state, there was a highly significant increase in MV need, pSOFA, and incidence of mortality in hypovolemic children compared with other two groups (P < 0.001 for all); moreover, there was a significant increase in PRISM and PIM II in hypovolemic children compared with other groups and a significant increase in PICU stay in hypervolemic children compared with others (P < 0.05).

Regarding laboratory findings, we found a highly significant decrease regarding platelets, albumin at day 2, and albumin at day 5 in hypovolemic children compared with other two groups (P < 0.001); moreover, there was a significant increase of absolute neutrophil count in hypovolemic children compared with other children (P = 0.029) [Table 2].
Table 2: Laboratory findings of the studied groups

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Regarding demographic data and clinical characteristics of survivor and nonsurvivor children, we found no statistical significant differences among all three groups in terms of age, sex, and anthropometric measures. Moreover, there was a highly significant increase in the nonsurvivor group than survivors regarding ventilation need, pSOFA score, nosocomial infection, incidence, and incidence of hypervolemia and hypovolemia (P < 0.001 for all). We found a significant increase in PICU stay in the nonsurvivor group compared with other children (P = 0.028) [Table 3].
Table 3: Demographic and clinical characteristics of survivors and nonsurvivors

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Regarding laboratory findings of survivor and nonsurvivor children, we found that there was a highly significant decrease in albumin and platelets, being higher in survivors (all P < 0.001) [Table 4]. However, there was no significant difference between both groups regarding hemoglobin, C-reactive protein, or bicarbonate.
Table 4: Laboratory findings of survivors and nonsurvivors

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On doing a multivariate logistic regression for mortality prediction between children, there was a highly significant increase in the adjusted odds ratio of unbalanced fluid status, presence of nosocomial infection, and low albumin level (all P = 0.001) [Table 5].
Table 5: Multivariate logistic regression analysis for prediction of mortality

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  Discussion Top


The current study aimed to assess the incidence of fluid imbalance among septic children and whether it is associated with the prognosis of the PICU patients.

This prospective cohort study included 74 critically ill children admitted to the PICU with a mean age of 42.2 ± 45.6 months.

We categorized the patient group into balanced fluid subgroup (n = 43) and unbalanced fluid subgroup (n = 31) either hypovolemia or hypervolemia based on follow-up of central venous pressure measurements, body weight measurements, presence of edema, and related clinical picture, of which we reported higher BMI and weight in hypervolemic than normovolemic and hypovolemic children (all P < 0.05).

Most of hypovolemic children in our study had neurological problems and acute respiratory distress syndrome (ARDS), whereas all of them had septic shock and nosocomial infection and all of them needed MV.

This is in agreement with Abdelhalim et al.[19], who reported that central nervous system infection in septic children was about 18.4%; moreover, they reported that pneumonia was the highest infection, with 44.8%, followed by bronchopneumonia with 23.7%. This may be due to timing of their study with high prevalence of chest diseases at that time and random selection by the candidate.

In Gonzales et al.[20], they also reported that most of their septic children required MV as most of them developed ARDS, which was supported by our results.

We reported a higher score of pSOFA (on days 2 and 5) and PIM II in hypovolemic children in which the mortality rate was 100% compared with lower scores in hypervolemic children, of which the mortality rate was about 58.8% (P < 0.05).

In agreement with our findings, Lalitha et al.[21] showed that pSOFA scores, either on day 1 or day 3, clearly predicted hospitalization mortality among septic children admitted to the PICU. Moreover, they figured out a proportionate increase in mortality percentage in septic children with critical illness which correlated with the increase in pSOFA score on days 1–3.

Another study by El-Mashad et al.[22] reported that the Sequential Organ Failure Assessment (SOFA) score was higher in nonsurvivors (P < 0.001) and mortality increased progressively among children subgroups from lower to higher SOFA scores.

PRISM score was significantly increased in hypovolemic children compared with hypervolemic and normal children (P = 0.005). Expected mortality of PRISM in hypovolemic children was the highest compared with other groups, which could be attributed to the higher the PRISM score, the higher the expected percentage of mortality. Moreover, actual mortality did not differ compared with expected deaths.

To our knowledge, no previous studies had reported PRISM and PIM II in hypovolemic and hypervolemic children which need further confirmation and validation.

In the present study, absolute neutrophil count was significantly higher in hypovolemic children compared with hypervolemic and normovolemic children (P = 0.029). On the contrary, platelet count and serum albumin levels at baseline, day 2, and day 5 were lower in hypovolemic children than hypervolemic and normovolemic children (P < 0.001).

Because sepsis promotes apoptosis of lymphocyte, septic shock may result in a specific dramatic increase in neutrophils. The exact mechanism of neutrophil elevation is unknown, but it is most likely a combination of catecholamines and endogenous cortisol (both of which have been shown to boost neutrophil counts while decreasing lymphocyte counts) [23].

Moreover, because platelets are an acute-phase reactant, platelets are frequently elevated in chronic, smoldering infections. Because septic shock frequently causes the consumption of platelet, thrombocytopenia is more common in hypovolemic shock [24].

This is explained by Acikgoz et al. [25], who stated that sepsis-associated thrombocytopenia is multifactorial. Inflammatory mediators and bacterial endotoxin can enhance platelet reactivity and adhesively, and also autoantibodies to specific platelet antigens have been detected.

We reported a mortality rate of 39%. There was a significant relation between diagnosis and mortality, of which 69% of not-survivors had neurological problems, whereas 60% of survivors had chest problems (P < 0.001). Moreover, there was a significant relation between presence of septic shock and mortality, of which 48.3% of nonsurvivors had septic shock and none of survivors had septic shock (P < 0.001).

This is in agreement with a study by Márquez-González et al.[26], who reported that 33% of septic children died. Other studies with similar conditions reported varying percentages based on eligibility criteria; however, if only patients with septic shock were eligible, as in the cohort studied by Chen et al.[27], the relationship with mortality was nearly identical (30%).

Another study by Charles et al.[28] reported that about 47.6% of nonsurvivors children had cardiovascular diseases, whereas about 30% of survivors children had diabetes mellitus; however, there was no significant difference (P > 0.05).

All nonsurvivors were mechanically ventilated and had significantly higher mean PICU stay versus the survivors group (14.4 ± 5.26 vs. 12.3 ± 6.79 days; P = 0.028), and there was a higher SOFA score in nonsurvivors compared with the survivor group (6.41 ± 1.93 vs. 4.66 ± 1.60 points; P < 0.001). Nosocomial infection and ARDS were significantly higher in nonsurvivors compared with survivors. Moreover, about 48.3% of nonsurvivors were hypovolemic (P < 0.001).

This is in agreement with a study by Márquez-González et al.[26], which found that all dead children required MV; however, only 83% of survivors required MV (P = 0.05).

Another study by Lalitha et al.[21] reported that all nonsurvivors children had MV, whereas only 50% of the survivor group had MV (P < 0.001). Moreover, a higher pSOFA score on days 1 and 3 were reported in the nonsurvivor group compared with the survivor group (P < 0.001). However, they reported a higher mean PICU stay in the nonsurvivor group compared with the survivor group, but it was not significant (P = 0.59).

Similarly, Charles et al.[28] reported that the SOFA score was higher at admission for the nonsurvivor children compared with survivors (P < 0.0001). Moreover, ~93.6% of the nonsurvivor children had MV compared with 69.1% of the survivor group (P < 0.0001).

We found that platelet count and albumin level were significantly lower in the nonsurvivor group compared with the survivor one (P < 0.001).

Similar to these results, Motalib et al.[29] found that there was a significant difference in platelet count among the nonsurvivor and survivor groups (P < 0.05), which was further supported by Fahmey et al.[30].

We assessed variables associated with mortality prediction via multivariate logistic regression analysis, and we found that unbalanced fluid, presence of nosocomial infection, and albumin level are independent predictors for mortality among the studied patients (all P < 0.001).

To our knowledge, our study is the first study to issue that fluid status is an independent predictor of mortality among septic children, and further studies should validate and confirm these results.

The limitations of the current study might be the small sample size included, and further studies with a larger sample size should be done to validate our results. Furthermore, further research should concentrate on interventions aimed at mitigating the potential hazard associated with fluid imbalance.


  Conclusion Top


Fluid imbalance is common in septic children as a result of fluid overload, which could be a predictor of substantial morbidity and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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