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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 4  |  Page : 1381-1386

Hypoalbuminemia as a predictor of adverse outcome in critically ill children: a prospective cohort study


1 Department of Pediatrics and Neonatology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pediatrics and Neonatology, Ministry of Health, Sirs-Ellayan Hospital, Menoufia, Egypt

Date of Submission26-May-2021
Date of Decision31-Jul-2021
Date of Acceptance08-Aug-2021
Date of Web Publication24-Dec-2021

Correspondence Address:
Abeer Y El-Shamy
MBBCh, Sirs Ellayan, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_105_21

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  Abstract 


Objectives
To evaluate the incidence of hypoalbuminemia as a predictor of clinical outcome in critically ill pediatric patients.
Background
Hypoalbuminemia is a common finding in critically ill patients associated with a high risk of poor outcome, but there is limited data on its role in pediatric patients. The aim of this study was to investigate the effect of low albumin levels in pediatric patients on poor prognosis and high risk of mortality in the pediatric intensive care unit (PICU).
Patients and methods
This was a prospective cohort study conducted at the PICU at El-Bagour Hospital from November 2018 to November 2020. The aim was to evaluate low albumin level as a predictor of poor prognosis and clinical outcome in 150 critically ill children aged 1 month up to 18 years. Receiver operating characteristic curve was used to assess the discriminatory ability of scoring systems for patients' mortality.
Results
In total, 148 patients were included in the final analysis where the incidence of hypoalbuminemia in the first 48 h postadmission was 44.6% with an overall mean serum albumin level of 3.34 ± 0.78. Moreover, we found that children with hypoalbuminemia had higher mortality rate (P < 0.001), higher PICU stays (P = 0.016), lower Glasgow Coma score (P = 0.0017), and more need of mechanical ventilation (P < 0.001).
Conclusion
Hypoalbuminemia may be used as a significant predictor of mortality and risk assessment in critically ill children.

Keywords: hypoalbuminemia, intensive care unit, organ dysfunction, predicted index of mortality, risk of mortality


How to cite this article:
Khattab AA, El-Shamy AY, Abdelaziz AA. Hypoalbuminemia as a predictor of adverse outcome in critically ill children: a prospective cohort study. Menoufia Med J 2021;34:1381-6

How to cite this URL:
Khattab AA, El-Shamy AY, Abdelaziz AA. Hypoalbuminemia as a predictor of adverse outcome in critically ill children: a prospective cohort study. Menoufia Med J [serial online] 2021 [cited 2024 Mar 28];34:1381-6. Available from: http://www.mmj.eg.net/text.asp?2021/34/4/1381/333221




  Introduction Top


Albumin represents the most abundant protein in plasma with more than two-third of plasma protein composition, thus, it contributes about 75% or higher of the colloid osmotic pressure of plasma [1].

Also, albumin plays an important role in the transport and binding of many molecules such as bilirubin, bile salts, hormones, and even drugs. About two-thirds of albumin remains in the extravascular space with only one-third in the intravascular space as it is highly water-soluble [2].

Hypoalbuminemia is a complex disease characterized by lack of synthesis in malnutrition, malabsorption, and even hepatic dysfunction or excessive loss, which happens in nephropathy or protein-losing enteropathy [3].

In critical illness, the permeability of capillaries increases much caused by proinflammatory mediators such as histamine or bradykinin or by damage to the integrity of capillary structures so that they may become leakier. Thereby, there is an exchange between albumin in the extravascular and intravascular compartments, so hypoalbuminemia is a common finding in critical ill patients [4].

A meta-analysis study, conducted on critically ill patients, showed that hypoalbuminemia was associated with higher mortality rate, higher length of pediatric intensive care unit (PICU) stay along with the higher need of mechanical ventilation [5].

It also showed that hypoalbuminemia is anchored with adverse outcomes in adults [6]. There is a paucity of data regarding the incidence and significance of hypoalbuminemia in critically ill children, but show conflicting results [7].

The aim of this study was to evaluate the incidence of hypoalbuminemia as a predictor of clinical outcome in critically ill pediatric patients.


  Patients and methods Top


Study design: this was a prospective observational cohort study conducted at the PICU of Menoufia Teaching Hospital from November 2018 to November 2020. The study protocol was approved by the Ethical Committee of Menoufia Hospital under the code of 9114485, as well as a written confirmed consent was gained from guardians before the inclusion process after explanation of the study. Inclusion criteria: our inclusion criteria were children who were critically ill and admitted to the PICU aged 1 month up to 18 years. We also excluded children in whom hypoalbuminemia was expected to be a result of preexisting diseases such as severe protein-energy malnutrition characterized by either weight or height less than third centile according to the WHO guidelines in 2007 [8]. Also, children who had chronic diseases such as chronic liver disease and chronic kidney disease. Children who experienced second-burn and third-burn degrees, or who had received blood product or albumin within the last 4 weeks before admission, were excluded too. Study process: all children had done the admission albumin-level test within the first 48 h of admission. The exact estimation of the albumin level in plasma was done according to the guidelines (dye-binding method) [9]. We defined hypoalbuminemia based on the guidelines as serum albumin level less than 2.5 g/dl for children less than 7 months of age and less than 3.4 g/dl for whom age is more than 7 months [10]. The data collected from children were age, sex, weight, height, diagnosis categorized regarding the organ system, complete blood count, C-reactive protein, Glasgow Coma score (GCS), blood glucose, Na, K, urea creatinine, SGOT, SGPT, and blood culture. Children were allocated into two groups based on their albumin level to hypoalbuminemic group (children with low level of albumin) and normoalbuminemic group (children with normal albumin level). Based on the purpose of analysis, children were also assigned to two subgroups regarding age into less than 7 months and more than 7 months. Children who were discharged against medical advice were excluded from the final analysis of outcome. Outcomes: our primary outcomes were the length of PICU stay, the need for mechanical ventilation, and the fate of patients in PICU. Pediatric Risk of Mortality 2 (PRISM2), Pediatric Logistic Organ Dysfunction 2 (PELOD2), and Pediatric Index of Mortality 2 (PIM2) scoring systems were used to assess the severity of illness. Statistical analysis: data were collected, tabulated, and statistically analyzed using an IBM personal computer with Statistical Package of Social Science (SPSS), version 19 (SPSS Inc., Chicago, Illinois, USA), where the following statistics were applied: descriptive statistics in which quantitative data were presented in the form of mean, SD, and range, while qualitative data were presented in the form of numbers and percentages. Analytical statistics: used to find out the possible association between studied factors and the targeted disease. The used tests of significance included χ2 test: was used to study the association between two qualitative variables. Mann–Whitney test (nonparametric test) is a test of significance used for comparison between two groups not normally distributed having quantitative variables. Kruskal–Wallis test (nonparametric test): is a test of significance used for comparison between three or more groups not normally distributed having quantitative variables. Spearman's correlation (r) is a test used to measure the association between quantitative and qualitative ordinal variables: P value of less than or equal to 0.05 was considered statistically significant.


  Results Top


Baseline data: 150 children were included out of 167 children admitted to the PICU during the study time. In total, 17 children were excluded from our study as they matched the exclusion criteria and two children were discharged against medical advice [Figure 1]. The mean age for all children was 4.03 ± 4.35 years (range: 1.5 months–15 years). In total, 73 (48.7%) children were male and 77 (51.3%) were female. The mean serum albumin for all children was 3.34 ± 0.78 g/dl.
Figure 1: Temporal profile of patients admitted to the pediatric intensive care unit.

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The incidence of hypoalbuminemia was found in 67 (44.6%) children out of 150 children. When the children were allocated regarding their age, it was found that 13 (36.1%) out of 36 children in the younger group were hypoalbuminemic, whereas 54 (47.4%) out of 114 in the older group were hypoalbuminemic, making the incidence of hypoalbuminemia in children older than 7 months significantly higher (P = 0.26, RR = 0.76). The incidence of hypoalbuminemia in children with predicted death rate more than 5% (55.4%) was higher than the incidence observed in children with predicted death rate calculated by PIM2 less than 1% (23%) (P < 0.001, RR = 2.399). Diagnostic categories: the diagnostic categories of 150 children showed that the incidence of hypoalbuminemia in the neurological disease category was higher than other illnesses (20 out of 40) followed by the respiratory-disease category (20 out of 43), while in normoalbuminemic group, the respiratory-disease category has the highest number of pediatric patients (23 out of 43) than the neurological-disease category (20 out of 40) [Table 1].
Table 1: Baseline demographics data of the study population at admission, and diagnostic categories between studied groups

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Outcomes: 148 children were included in the final analysis in which two children were excluded due to discharge against medical advice. The duration of the PICU stay was significantly higher in the hypoalbuminemic group than that in the normal albuminemic group [P = 0.016, mean difference = −8.08, 95% confidence interval (CI) −14.64 to −1.52]. The essential need for mechanical ventilation was significantly higher in hypoalbuminemic as compared with the normal group (odds ratio = 4.54,95% CI 2.22–9.26, P < 0.001). Moreover, mean serum albumin in ventilated children (55 children) was 2.92 ± 0.76, and 3.58 ± 0.69 in nonventilated children (113 children), and mean difference was 0.66 (P ≤ 0.001). In terms of GCS, there was a lower score in the hypoalbuminemic group compared with the normal group with mean of 11.71 ± 2.3 and 12.93 ± 2.32, respectively, and mean difference of 1.22 (95% CI 0.464–1.975) (P = 0.0017). Children with hypoalbumin levels had a mortality rate of 43.9% (29 out of 66), which was 2.78 times greater than the normal albumin group 15.8% (13 out of 82) (odds ratio = 4.16, 95% CI 1.93–8.95) (P = 0.0003) [Table 2].
Table 2: Comparison of albumin-level groups with reference to duration of pediatric intensive care unit stay, Glasgow Coma score, mechanical ventilation, and outcome

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We also assessed a comparison between survivors and nonsurvivor children regarding serum albumin level, PRISM2, PIM2, and PELOD2. Mean PRISM2 score in nonsurvivor group (13.74 ± 6.58) was higher compared with survivors' group (8.42 ± 4.96) with mean difference of − 5.32 (95% CI −7.28 to −3.358) (P < 0.0001). Mean PELOD2 score in nonsurvivor children (6.33 ± 2.99) was higher than survivor children (2.71 ± 1.94), and mean difference of −3.62 (95% CI −4.439 to −2.8) (P < 0.0001). Mean PIM2 score in nonsurvivors' group (2.64%±0.49) was higher compared with survivors' group (2.15%±0.61) with mean difference of −0.49 (95% CI −0.698 to −0.28). When using an independent sample t test for comparing the mean serum level in survivors' and nonsurvivors' children, it was found that the mean in survivors was 3.54 ± 0.7, and 2.82 ± 0.76 in nonsurvivors with mean difference of 0.72 (95% CI 0.46–0.977) (P < 0.0001) [Table 3].
Table 3: Comparison between survivors and nonsurvivors regarding scores and serum albumin level

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Statistical relations

We measured the correlation between albumin level and other parameters to assess the strength of the relationship between these variables and other parameters [Table 4]. A nonsignificant correlation was found between serum albumin level and GCS less than 8, and PRISM2 score (Rho = −0.128, 0.105, respectively, P > 0.05), and a positive correlation between serum albumin level and PIM2 score, PELOD2 score, need for mechanical ventilation, the mortality rate, and length of PICU stay (Rho = 0.216, 0.306, 0.351, 0.31, and 0.235, respectively, P < 0.05).
Table 4: Correlation between serum albumin level and other parameters

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Diagnostic accuracy

The optimal cut-off PIM2 score was at more than 1.6%, with 92.9% sensitivity and 75.5% specificity and area under receiver operating characteristic (ROC) curve of 0.78 (P < 0.001). The optimal cut-off PRISM2 score was at more than 4.5 with 92.9% sensitivity and 72.6% specificity and area under ROC curve of 0.73 (P < 0.001). Also, the optimal cut-off PELOD2 score was at more than 1.5 with 95.2% sensitivity and 84.9% specificity and area under ROC curve of 0.844 (P < 0.001) that yielded a good discrimination on predicting mortality and morbidity in the PICU [Table 5].
Table 5: The prognostic scoring performance for Pediatric Index of Mortality 2, Pediatric Risk of Mortality 2, and Pediatric Logistic Organ Dysfunction 2 scores as regards mortality

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  Discussion Top


Despite of the availability of many severity-score systems that can predict the mortality, there were only few studies that assess the mortality and morbidity in PICU in critically ill patients presented with hypoalbuminemia. This study focused on the incidence of hypoalbuminemia in PICU in critically ill pediatrics, as hypoalbuminemia is a common problem associated with higher mortality and morbidity rate [11]. In critical illness, the permeability of blood vessels increases much by the action of inflammatory mediators, as a result, there is a dramatic change in albumin level between extravascular and intravascular. There is about 300% rise in albumin-escape rate as a result of albumin-balance alteration. Also, there is a huge decrease in albumin synthesis in the liver by the effect of these inflammatory mediators, especially interleukin-6 and tumor necrosis factor-alpha [12].

The incidence of hypoalbuminemia in this study was 44.6% of children admitted to the PICU and this comes with the alignment of a study by Horowitz and Tai [13] that mentioned the incidence of hypoalbuminemia, which was about 33% at admission. Durward et al. [7] found that hypoalbuminemia was 57% at admission but after 1 day, it progressed to 76%. The frequency of hypoalbuminemia in another study by Tiwari et al. [12] was 21% at admission, then it increased to 34% after 1 week, and about 37% during the rest of the PICU stay. We could not perform repeated serum albumin to all children due to the lack of commitment from guardians, so we measured only the incidence of hypoalbuminemia at admission.

We used PIM2, PRISM2, and PELOD2 scores to assess the severity of illness 48 h postadmission [14],[15],[16]. PIM2 was found in a previous study by Qureshi et al. [16] to be the most effective pediatric scoring system with the highest accuracy rate among all other scores. PRISM2 and PELOD2 were also used to assess the severity of illness and give the highest accuracy rate in assessing the risk mortality as well.

There was a relation between hypoalbuminemia and mortality rate as PRISM2 score was much higher in the hypoalbuminemic group rather than the normal albumin-level group (10.82 vs. 7.71, P = 0.13), despite of the nonstatistical significance in P value, and high PELOD2 score in the hypoalbuminemic group versus the other group (3.24 vs. 1.35, P = 0.04). As regards the need for mechanical ventilation, there was a highly significant difference in favor of the hypoalbuminemic group (56 vs. 21.9%, P < 0.001) and a high mortality rate in the hypo-albumin-level group compared with the normal group (43.9 vs. 15.8%, P < 0.001). This comes with the alignment of another study by Tiwari et al. [12], which stated that hypoalbuminemic children had higher PRISM2 scores compared with normal ones (12.9 vs. 7.5, P < 0.001) with prolonged PICU stay (13.8 vs. 6.7, P < 0.001); and a higher need for mechanical ventilation was observed in the hypoalbuminemic group compared with the normal group (84.8 vs. 28.8%, P < 0.001) and a high risk of mortality between both groups in favor of hypoalbuminemic group (25.6 vs. 17.7%, P < 0.001).

Our findings on PRISM2 score offered good discriminative power with the area under the ROC curve being 0.73 (95% CI 0.638–0.822), which comes in alignment with other studies that mentioned the ROC curve analysis of PRISM (0.78, 0.90, 0.87, 0.86, and 0.95) as mentioned by Qureshi et al. [16], Pollack et al. [17], Martha et al. [18], Varma et al. [19], and Choi et al. [20], respectively. Also, there was a significant correlation between PELOD2 score and PIM2 score with 0.84, 95% CI, 0.767–0.921; and 0.78, 95% CI, 0.691–0.86, respectively, P value less than 0.001. So, overall, these three scores rendered good discriminative relation between survivors and nonsurvivors and further it may be used as a tool for prognostic evaluation beside their use in assessing the risk of mortality.

Limitations and recommendations

This study had several limitations. It was a single-center study with a small number of participants in each group. Also, we could not perform repeated serum albumin, so we can assign the incidence of hypoalbuminemia in the whole study duration. We recommend further high number of participants and multicenter studies to be approached, so we can conclude a better evaluation of such disease. We also recommend prospective studies and randomized controlled trials to be performed not retrospective, so we can get the highest possible accuracy.


  Conclusion Top


There is a relation between hypoalbuminemia in PICU and high mortality and morbidity rates as patients with hypoalbuminemia tend to have bad adverse outcomes and hence giving those high mortality rates.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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