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Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial

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Abstract

Objective

To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA).

Design

Randomized, double-blind controlled clinical trial.

Setting

Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018.

Participants

Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded.

Intervention

Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion.

Outcome measures

The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema).

Results

Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred.

Conclusions

Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

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Acknowledgments

Dr. Poovazhagi V (Head of Department. Pediatric Intensive Care Unit, Professor of Pediatrics, Institute of Child Health, Chennai, India) for critical review of the manuscript; Mrs. S. Raja Deepa B.Com, MCA (JIPMER Campus, Puducherry, India) for data handling, review 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) helping with statistical analysis and Mrs. Harpreet Kaur (Punjab University, Chandigarh, India), and Mrs. Neelima Chadha (Tulsi Das Library, PGIMER, Chandigarh, India) helping with the medical literature search. The preliminary data were presented at the 9th World Congress of Pediatric Intensive and Critical Care (PICC 2018, Singapore). Ethics approval: Institute Ethics Committee of JIPMER, Puducherry; No. JIP/IEC/2014/4/308, dated 27 June, 2014. Contributors: RR: conceptualized the study, reviewed the literature, and critically reviewed the manuscript; JA, PS, PJ, SA, SS: data collection, reviewed the literature and contribution of manuscript writing; NP, SM: protocol development, review of literature and manuscript writing. All authors involved in the management of the patients and approved the final version of the manuscript. RR, SM: study supervision.

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Authors and Affiliations

  1. Division of Pediatric Critical Care, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605 006, India

    Ramachandran Rameshkumar, Ponnarmeni Satheesh, Puneet Jain, Jagadeesh Anbazhagan, Shilpa Abraham, Seenivasan Subramani, Narayanan Parameswaran & Subramanian Mahadevan

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  1. Ramachandran Rameshkumar
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  2. Ponnarmeni Satheesh
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  3. Puneet Jain
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  4. Jagadeesh Anbazhagan
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  6. Seenivasan Subramani
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  7. Narayanan Parameswaran
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  8. Subramanian Mahadevan
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Corresponding author

Correspondence to Ramachandran Rameshkumar.

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Funding

Supported in part by the institutional and departmental fund

Competing interest

None stated.

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Rameshkumar, R., Satheesh, P., Jain, P. et al. Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial. Indian Pediatr 58, 617–623 (2021). https://doi.org/10.1007/s13312-021-2255-x

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