Transcript 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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Introduction
Background
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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.
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Physiologic dose-effect studies have found that even lower doses could
normalize ketonemia and acidosis.
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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
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To compare the efficacy and safety of low-dose insulin against the standard
dose in children with DKA.
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Methods
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Study Design: Prospective, open-label randomized clinical trial.
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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.
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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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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.
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Results
Trial Flow
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Results
Baseline Demographic and Biochemical Characteristics
Characteristic
Low-Dose Group
Standard-Dose Group
(n = 25)
(n = 25)
7.3 (3.8)
6.5 (3.6)
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)
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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Results
Primary Outcome for Low-Dose vs
Standard-Dose Insulin
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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.
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Mean (SD) time taken to achieve this
target: 6.0 (3.3) vs 6.2 (2.2) hours.
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Mean (SD) BG decrease in the first hour
of insulin: 39.2 (25.5) vs 61.3 (37.7)
mg/dL/h.
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Mean BG Decrease With
Insulin Therapy
Results
Secondary Outcome Measures
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Comment
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Low-dose insulin achieved a clinically effective BG reduction that was
comparable to the standard dose.
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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.
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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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Conclusions
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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.
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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
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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
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None reported.
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