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From the JAMA Network |

Insulin Dosing in Pediatric Diabetic Ketoacidosis Where to Start?

David Carmody, MB BCh1; Rochelle N. Naylor, MD1; Louis H. Philipson, MD, PhD1
[+] Author Affiliations
1Departments of Medicine and Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, Illinois
JAMA. 2015;313(22):2274-2275. doi:10.1001/jama.2015.135.
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JAMA Pediatrics

Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical Trial

Karthi Nallasamy, MD, DM; Muralidharan Jayashree, MD; Sunit Singhi, MD; Arun Bansal, MD

Importance The standard recommended dose (0.1 U/kg per hour) of insulin in diabetic ketoacidosis (DKA) guidelines is not backed by strong clinical evidence. Physiologic dose-effect studies have found that even lower doses could adequately normalize ketonemia and acidosis. Lowering the insulin dose may be advantageous in the initial hours of therapy when a gradual decrease in glucose, electrolytes, and resultant osmolality is desired.

Objective To compare the efficacy and safety of low-dose insulin against the standard dose in children with DKA.

Design, Setting, and Participants This was a prospective, open-label randomized clinical trial conducted in the pediatric emergency department and intensive care unit of a tertiary care teaching hospital in northern India from November 1, 2011, through December 31, 2012. A total of 50 consecutive children 12 years or younger with a diagnosis of DKA were randomized to low-dose (n = 25) and standard-dose (n = 25) groups.

Interventions Low-dose (0.05 U/kg per hour) vs standard-dose (0.1 U/kg per hour) insulin infusion.

Main Outcomes and Measures The primary outcome was the rate of decrease in blood glucose until a level of 250 mg/dL or less is reached (to convert to millimoles per liter, multiply by 0.0555). The secondary outcomes included time to resolution of acidosis, episodes of treatment failures, and incidences of hypokalemia and hypoglycemia.

Results The mean (SD) rate of blood glucose decrease until a level of 250 mg/dL or less is reached (45.1 [17.6] vs 52.2 [23.4] mg/dL/h) and the mean (SD) time taken to achieve this target (6.0 [3.3] vs 6.2 [2.2] hours) were similar in the low- and standard-dose groups, respectively. Mean (SD) length of time to achieve resolution of acidosis (low vs standard dose: 16.5 [7.2] vs 17.2 [7.7] hours; P = .73) and rate of resolution of acidosis were also similar in the groups. Hypokalemia was seen in 12 children (48%) receiving the standard dose vs 5 (20%) of those receiving the low dose (P = .07); the tendency was more pronounced in malnourished children (7 [88%] vs 2 [28%]). Five children (20%) and 1 child (4%) receiving standard- and low-dose infusion (P = .17), respectively, developed hypoglycemia. Treatment failure was rare and comparable. One child in the standard-dose group developed cerebral edema, and no deaths occurred during the study period.

Conclusions and Relevance Low dose is noninferior to standard dose with respect to rate of blood glucose decrease and resolution of acidosis. We advocate a superiority trial with a larger sample size before 0.05 U/kg per hour replaces 0.1 U/kg per hour in the practice recommendations.

JAMA Pediatr. 2014;168(11):999-1005. doi:10.1001/jamapediatrics.2014.1211

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