Frequency of Hypophosphatemia in Children Presenting with Sepsis in a Tertiary Care Hospital: A Cross-sectional Study

Aim: To determine the frequency of hypophosphatemia in the children presenting with sepsis in a tertiary care hospital. Study Design: A cross-sectional study. Place and Duration: Department of paediatric, civil hospital, Karachi, Pakistan from october 2020 to april 2021. Original Research Article Qadri et al.; JPRI, 34(39A): 68-73, 2022; Article no.JPRI.87473 69 Methodology: A total of 190 children with clinical sepsis were included in the study. Serum phosphate level, CBC, CRP, and blood culture of all children were sent within 24 hours of admission. Serum phosphate level less than 2.5mg/dL was labeled hypophosphatemia. It was categorized as mild, moderate and severe at level of 2-2.5 mg/dL), 1-2 mg/dL), and < 1 mg/dL respectively. Results: Mean ± SD age of study participants was 2.69±3.19 years. Out of 190 patients 106 (55.8%) were male while 84 (44.2%) were female. Hypophosphatemia was found in 36 (18.9%) patients among them. Mild and moderate hypophosphatemia was noted in 18 (50%) of the children from each category of patients. Conclusion: This study concluded that hypophosphatemia was documented in considerable number of children who presented with clinical sepsis. Serum phosphate levels should be checked in children who present with sepsis. To avoid the issues of a double burden of disease in these patients, strategies to prevent these diseases should be supported.


INTRODUCTION
A dysregulated host response to the infection causes the sepsis, which is a life-threatening organ failure. Sepsis represents a significant socioeconomic burden worldwide [1]. Severe sepsis is one of the primary cause of the admission to the intensive care units (ICUS) [2][3]. The incidence and rate of hospitalization for the severe sepsis is increasing every year. In studies published in the previous decade, the incidence of sepsis in all patients admitted to ICUs ranges from 9 to 37 percent, and severe sepsis remains a prominent cause of the death. Severe sepsis mortality rates in patients admitted to intensive care units range from 30 to 50% [4][5].
Blood Culture remains the gold standard but has limitations due to final report after seven days. Hematological and inflammatory markers such as ESR, CRP, raised total leukocyte count, ANC, band cells, toxic granulations are better indicator for the sepsis but have certain limitations [6-8].
Phosphate is a component of adenosine triphosphate, 2, 3-diphosphoglycerate and intracellular chemical messengers among other intermediate molecules involved in critical physiological processes [9]. Hypophosphatemia (HP) has been linked to sepsis and has been suggested as a useful diagnostic tool [10]. During the first 24 hours of admission, patients with sepsis had a high rate of HP [10]. Phosphate (P) values of less than 2 mg/dl were particularly indicative of gram-negative sepsis. The exact process by which HP develops in sepsis is uncertain. The elimination of the illness was linked to an increase in P levels [11][12][13].
In the majority of the cases, hypophosphatemia symptoms are nonspecific and include fatigue and irritability [14]. During childhood, the normal level of phosphorus in the blood changes. Normal blood phosphorus levels in children aged one to three years are (3.8 mg/dl to 6.5 mg/dl), four to eleven years (3.7 mg/dl to 5.6 mg/dl) and twelve to fifteen years (3.7 mg/dl to 5 Patients with phosphate derangements primarily focus on the association of hypophosphatemia [19,20] and the critically ill population but in our area ,there is scarcity of the studies related to the sepsis and related markers hence we aimed to conduct the study to find correlation between hypophosphatemia and severity of the sepsis.

METHODOLOGY
This cross-sectional study was conducted at department of paediatric, civil hospital Karachi by non-probability consecutive sampling technique from october 2020 to april 2021. The sample size was calculated by taking prevalence of hypophosphatemia in septic children P=(58.8%). 6 Using margin of error(d)=7% the total calculated sample size was 190 patients with the help of WHO software for sample size calculation taking 95% confidence level. Children of either gender presenting with clinical sepsis age 1 month to 15 years were included in the study. Children having chronic renal failure, congenital renal disease and severe malnutrition were excluded from the study. Hypophosphatemia was defined as the serum phosphate level less than 2.5mg/dL. It was categorized as mild: 2-2.5 mg/dL, moderate: 1-2 mg/dL and severe :< 1 mg/dL. Patients were labeled as clinical sepsis if two or more of the following criteria were fulfilled: Axillary Temperature >38°C or <36°C, tachycardia or fast breathing, White blood cell count >12,000/mm2 , or 10% immature (band) forms, on complete blood count report.
Complete history and detailed examination of the septic children were taken at the time of admission. Serum phosphate level, CBC, CRP, and blood culture of all included children were sent within 24 hours of admission. The sepsis was diagnosed as per operational definitions. The final outcome i.e. hypophosphatemia was labeled when the serum phosphate level was less than 2.5mg/dL. It was categorized as mild, moderate and severe showing range of 2-2.5 mg/dL, 1-2 mg/dL), < 1 mg/dL) respectively. Biasness and confounder were controlled by strictly following the inclusion criteria. All patients were given supportive and definitive management as per hospital protocols. All data was kept strictly confidential. The data was compiled and analyzed using SPSS version 21.
For qualitative factors such as gender, culture, hypophosphatemia and levels of hypophosphatemia, frequencies and percentages were calculated.
Age, serum phosphate, axillary temperature, heart rate, respiration rate, white blood cell count, and CRP were all provided as the mean SD quantitative variables. Stratification was used to control the effect modifiers such as age, gender, axillary temperature, heart rate, respiration rate, white blood cell count, and CRP. The Chi-square test was used to determine whether category variables were related. The significance level was set at P 0.05.

RESULTS
In this study, 190 patients were included to assess the hypophosphatemia in clinical sepsis children.  Hypophosphatemia is linked to a worse prognosis in critically ill adults and children, according to various studies (prolonged length of stay and the need for respiratory support, and higher mortality). However, there was inadequate information as to when hypophosphatemia becomes essential and requires treatment [25].
In an international investigation, 98 (46.4%) of the females had the average age of 10.51 days. The average phosphorus concentration was 4.39 0.67± mg/dL. Phosphorus levels in girls and boys were substantially different. The difference in mean phosphorus between positive and negative blood culture patients was likewise significant. However, phosphorus levels were not linked with type of feeding, ESR, urine culture, or CRP status [26].

CONCLUSION
Hypophosphatemia was documented in the considerable number of the children in the clinical sepsis. Serum phosphate levels should be checked in children who present with sepsis. To avoid the issues of a double burden of disease in these patients, the strategies to prevent these diseases should be supported.

LIMITATIONS
The sample population represents a single institutional experience; but the study sample can be generalized as the sample came from various areas of Pakistan. Serum procalcitonin should also be done in suspected sepsis children.

ETHICAL APPROVAL
Permission was taken from the ethical review committee of the institute.

CONSENT
Informed consent was taken from the care takers.