Journal Club slides

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.
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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.
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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 standarddose (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.
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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.
• Open-label design.
• Adolescent children not enrolled.
• A possibly stringent noninferiority margin of 18 mg/dL/h.
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Trial Flow
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Baseline Demographic and Biochemical Characteristics
Low-Dose Group
Standard-Dose Group
(n = 25)
(n = 25)
7.3 (3.8)
6.5 (3.6)
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)
6.2 (2.6)
7.0 (3.1)
133.0 (7.0)
134.5 (10.0)
4.8 (0.8)
4.7 (0.7)
292.0 (13.8)
298.2 (21.2)
Age, mean (SD), y
Male/female, No.
Bicarbonate, mean (SD), mEq/L
Sodium, mean (SD), mEq/L
Potassium, mean (SD), mEq/L
Effective osmolality, mean (SD), mOsm/kg
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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)
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Mean BG Decrease With
Insulin Therapy
Secondary Outcome Measures
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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).
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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.
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Contact Information
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.
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