Study of role of serum ferritin in predicting outcome in children with severe sepsis at a tertiary hospital

 

Manjushree S Kulkarni^1*, Deepak A Shukla²

 

Abstract              Background: Severe sepsis is defined as sepsis plus one of the following: Cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions (renal, neurologic, hematologic, or hepatic). The present observational study was aimed to evaluate serum ferritin as in predicting outcome in children, critically ill with sepsis and whether serum ferritin is associated with unfavorable outcomes. Material and Methods: Present prospective and observational study was conducted in children 1-5 years age group with severe sepsis. Serum ferritin level was considered raised if the result was >300 mg/L. Results: In present study 60 children satisfying study criteria were studied. Boys (63.3 %) were more than girls (36.7 %) and mean age was 36.46 ± 13.64 months. Mean duration of illness before admission and duration of fever before admission was 5.37 ± 1.26 days and 4.23 ± 3.48 days respectively. 58.3 % children received antibiotics before admission and 18.3 % children had malnutrition. Common suspected source of infection was pneumonia (35.0 %), Urinary tract infection (18.3 %), Meningitis (18.3 %), Intra-abdominal infection (6.7 %) and from other focus (21.7 %). Blood culture was positive in 23.3 %. Mean serum ferritin levels were 172.56 ± 118.3 ng/mL and ferritin ≥ 300 ng/mL was noted in 26.7 %. According to severe sepsis criteria cardiovascular organ dysfunction (65.0 %) was most common, followed by one or more Organ dysfunctions (40.0 %) and acute respiratory distress syndrome (36.7 %). We compared variables between cases with serum ferritin < 300 ng/ml (n=46) and cases with serum ferritin ≥ 300 ng/ml (n=14). We noted a statistically significant difference in cases of survivors, non-survivors, cases of multiorgan dysfunction syndrome (MODS), pediatric risk of mortality score (PRISM III) at 24 h and length of Pediatric intensive care unit (PICU) stay. While duration of mechanical ventilation and need of mechanical ventilation on day 1 were comparable in both groups and difference was not significant statistically. Conclusion: Serum Ferritin levels can be helpful predictive marker of mortality in severe sepsis and higher ferritin is associated with increasing organ dysfunction.

Keywords: serum ferritin, PICU, multiorgan dysfunction syndrome, severe sepsis,

 

INTRODUCTION

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.¹ Severe sepsis is defined as sepsis plus one of the following: Cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions (renal, neurologic, hematologic, or hepatic). In 2017, almost half (20 million) of all estimated sepsis cases worldwide occurred in children under 5 years of age. The study estimated that 41.5% (20.3 million) of incident sepsis cases and 26.4% (2.9 million) deaths related to sepsis worldwide were among children younger than five years.³ The three most common causes of sepsis-related deaths among children were infections related to neonatal disorders (for example, preterm birth, encephalopathy, hemolytic disease), lower respiratory infections and diarrheal diseases.⁴The increase in plasma ferritin concentration paralleled the increase in plasma CRP during acute pneumonia, tuberculosis, rheumatoid arthritis and neutropenic sepsis, suggesting that ferritin was acting as an acute phase protein.⁹ The present observational study was aimed to evaluate serum ferritin as in predicting outcome in children, critically ill with sepsis and whether serum ferritin is associated with unfavorable outcomes.

              

MATERIAL AND METHODS

Present prospective and observational study was conducted in department of pediatrics, at XXX medical college and hospital, XXX, India. Study duration was of 1 year (April 2020 to March 2021). Study was started after obtaining approval from institutional ethics committee

Inclusion Criteria

Children 1-5 years age group with severe sepsis. Severe sepsis² was defined as sepsis plus one of the following: Cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions (renal, neurologic, hematologic, or hepatic).

• Cardiovascular organ dysfunction - Despite >40 ml/kg of isotonic intravenous fluid in 1 hour ‑ Hypotension ≤5th percentile for age or systolic blood pressure <2 SD below normal for age;

OR Need for vasoactive drug to maintain blood pressure;

OR 2 of the following 5:

• Unexplained metabolic acidosis: Base deficit>5 meq/L
• Increased arterial lactate: >2 times upper limit of normal
• Oliguria: Urine output <0.5 ml/kg/hour
• Prolonged capillary refill: >5 sec
• Core to peripheral room temperature gap >3°C.
• Acute respiratory distress syndrome (ARDS) was defined by ‑ the presence of a PaO2/FiO2 ratio ≤300 OR PaCO2 65 torr or 20 mm Hg over baseline PaCO2 OR Need for non‑elective invasive or noninvasive mechanical ventilation
• Organ dysfunctions (neurological, renal, hepatic or hematologic) was defined as ‑
• Neurological: GCS score ≤ 11 or acute change in mental status with GCS of ≥ 3 points from abnormal baseline.
• Renal: Serum creatinine >2 times upper limit of normal or 2 fold increase in baseline creatinine.
• Hepatic: Total bilirubin ≥ 4 mg/dl or ALT level twice the upper limit of normal for age.
• Hematological: Platelet count < 80,000 or a 50% decline in the platelet count from the highest value recorded over the last 3 days or INR >2.

Exclusion Criteria

Non-infective causes that alter the levels of inflammatory markers, such as chronic inflammatory conditions (including rheumatoid arthritis, inflammatory bowel disease, and Wilson’s disease).

Conditions with iron overload whether primary, e.g., hereditary hemochromatosis or secondary, e.g., transfusion overload, porphyria cutanea tarda, and ineffective erythropoiesis (in sideroblastic anemia or thalassemia), and hematological malignancy. Study was explained to parents/relatives and written consent was taken. Detailed history regarding symptoms, past/medical history was collected from parents/relatives. All children underwent anthropometric measurements, detailed general/systemic examination. Relevant laboratory investigations were done at admission, such as total white blood cells count, differential count, erythrocyte sedimentation rate, platelet count and serum ferritin levels. Serum ferritin level was considered raised if the result was >300 mg/L. 5 ml of blood was collected with aseptic precautions and blood culture was performed by using agar based growth mediums and into bile broth using standard techniques. All children received antibiotics and ICU care as per standard operating procedures of department. Treatment details, clinical course were noted in proforma. Follow up was kept till 1 month of discharge. Data was collected and compiled using Microsoft Excel, analysed using SPSS 23.0 version. Difference of proportions between qualitative variables were tested using chi- square test or Fisher exact test as applicable. P value less than 0.5 was considered as statistically significant.

 

RESULTS

In present study 60 children satisfying study criteria were studied. Boys (63.3 %) were more than girls (36.7 %) and mean age was 36.46 ± 13.64 months. Mean duration of illness before admission and duration of fever before admission was 5.37 ± 1.26 days and 4.23 ± 3.48 days respectively. 58.3 % children received antibiotics before admission and 18.3 % children had malnutrition. Common suspected source of infection was pneumonia (35.0 %), Urinary tract infection (18.3 %), Meningitis (18.3 %), Intra-abdominal infection (6.7 %) and from other focus (21.7 %). Blood culture was positive in 23.3 %. Mean serum ferritin levels were 172.56 ± 118.3 ng/mL and ferritin ≥ 300 ng/mL was noted in 26.7 %.

 

 

 

 

 

 

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