Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Insulin in Pediatric Diabetic Ketoacidosis Nallasamy K, Jayashree M, Singhi S, Bansal.

Copyright restrictions may apply

JAMA Pediatrics Journal Club Slides:

Insulin in Pediatric Diabetic Ketoacidosis

Nallasamy K, Jayashree M, Singhi S, Bansal A. Low-dose vs standard-dose insulin in pediatric diabetic ketoacidosis: a randomized clinical trial. JAMA Pediatr. Published online September 29, 2014. doi:10.1001/jamapediatrics.2014.1211.


Background

• Standard recommended dose (0.1 U/kg/h) 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

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 osmolality is desired.

Study Objective

• To compare the efficacy and safety of low-dose insulin against the standard

dose in children with DKA.

Introduction


• Study Design: Prospective, open-label randomized clinical trial.

• Setting: Pediatric emergency department and intensive care unit of a

tertiary care teaching hospital in northern India from November 1, 2011,

through December 31, 2012.

• Patients: Fifty consecutive children 12 years or younger with a diagnosis of

DKA were randomized to low-dose (0.05 U/kg/h; n = 25) and standard-dose

(0.1 U/kg/h; n = 25) groups.

– Children were excluded if they had symptomatic cerebral edema, septic

shock at presentation, anuria for longer than 6 hours, or insulin

treatment before admission.

Methods


Methods

Primary Outcome

• Rate of decrease in blood glucose (BG) until a level of 250 mg/dL or

less is reached.

Secondary Outcomes

• Time to resolution of acidosis.

• Episodes of treatment failures.

• Incidences of hypokalemia and hypoglycemia.

Limitations

• Open-label design.

• Adolescent children not enrolled.

• A possibly stringent noninferiority margin of 18 mg/dL/h.


ResultsTrial Flow


ResultsBaseline Demographic and Biochemical Characteristics

Characteristic Low-Dose Group

(n = 25)

Standard-Dose Group

(n = 25)

Age, mean (SD), y 7.3 (3.8) 6.5 (3.6)

Male/female, No. 9/16 11/14

Children with malnutrition, No. (%) 7 (28) 8 (32)

New-onset DKA, No. (%) 13 (52) 16 (64)

BG, mean (SD), mg/dL 485.3 (133) 524.4 (103)

pH, mean (SD) 7.08 (0.12) 7.05 (0.11)

Bicarbonate, mean (SD), mEq/L 6.2 (2.6) 7.0 (3.1)

Sodium, mean (SD), mEq/L 133.0 (7.0) 134.5 (10.0)

Potassium, mean (SD), mEq/L 4.8 (0.8) 4.7 (0.7)

Effective osmolality, mean (SD), mOsm/kg 292.0 (13.8) 298.2 (21.2)


Results

Primary Outcome for Low-Dose vs Standard-Dose Insulin

• Mean (SD) rate of BG decrease until 250

mg/dL or less is reached: 45.1 (17.6) vs

52.2 (23.4) mg/dL/h.

• Mean (SD) time taken to achieve this

target: 6.0 (3.3) vs 6.2 (2.2) hours.

• Mean (SD) BG decrease in the first hour

of insulin: 39.2 (25.5) vs 61.3 (37.7)

mg/dL/h.

Mean BG Decrease WithInsulin Therapy


Results

Secondary Outcome Measures


Comment

• Low-dose insulin achieved a clinically effective BG reduction that was

comparable to the standard dose.

• Time to resolution of acidosis was similar in both groups, suggesting that

the low dose could be as effective as the standard dose in suppressing

lipolysis and ketogenesis.

• Gradual BG decrease in the initial hour and a tendency toward fewer

episodes of hypokalemia suggest that the lower dose could be safer

(higher insulin in the first few hours can cause a precipitous BG decrease

and rapid electrolyte shifts, thus increasing the risk of cerebral edema).


Conclusions

• Low-dose insulin is noninferior to standard-dose insulin with respect to the

rate of BG decrease and resolution of acidosis.

• This study opens the door for a subsequent superiority trial with a larger

sample size to explore differences in the rate of BG decrease before 0.05

U/kg/h replaces 0.1 U/kg/h in the practice recommendations.


• If you have questions, please contact the corresponding author:– Muralidharan Jayashree, MD, Department of Pediatrics,

Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India 160012 ([email protected]).

Conflict of Interest Disclosures• None reported.

Contact Information

Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Insulin in Pediatric Diabetic Ketoacidosis Nallasamy K, Jayashree M, Singhi S, Bansal.

Documents

insulin dose

standard dose

standard dose

copyright restrictions

mean sd bg

comment lowdose insulin

mean sd time

mean bg decrease