Diabetic Ketoacidosis in ChildrenAn Intensivist’s Perspective for the Emergency Medicine Provider

September 12, 2020

Ashwin Krishna MD, MPH, FAAPAssistant Professor of PediatricsPICU/PCU Medical DirectorUniversity of Kentucky College of MedicineKentucky Children’s Hospital

I have no financial disclosures or conflicts of interest to report

Disclosure

• Epidemiology, Pathophysiology and Definition

• Risk Factors for Life Threatening Disease

• KCH DKA guideline

• Role of the Community Hospital Provider

Overview

• Leading cause of morbidity and mortality in patients with Type 1 Diabetes Mellitus (T1DM)

• Occurs at the time of diagnosis in 30% of Children in US and Canada

• Risk factors for DKA as initial presentation of T1DM:• Age <5 yo (heightened risk in age <2yo)• Low SES• Ethnic minorities (black, latinx, Native American)

• Occurs in 6-8% of Children with known T1DM per year

• Risk factors for DKA with known T1DM:• Poor glycemic/metabolic control• Immediate Hx gastroenteritis or other intercurrent illness• Peripubertal adolescents (F>M)• Hx psychiatric disorders• Low SES• Non-compliance to insulin regimen pump or SQ injection • Corticosteroid or atypical antipsychotic use

• Can occur in children with T2DM• Lower incidence than in patients with T1DM• Can present with mixed picture—DKA + hyperglycemic hyperosmolar state (HHS)

DKA

Kao KT, Islam N, Fox DA, Amed S. Incidence Trends of Diabetic Ketoacidosis in Children and Adolescents with Type 1 Diabetes in British Columbia, Canada. J Pediatr 2020; 221:165.Usher-Smith JA, Thompson MJ, Sharp SJ, Walter FM. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ 2011; 343:d4092.

Pathophysiology

T1DM: β-islet cells in pancreas cannotmake insulin

T2DM: Hepatocytes, adipose tissue andskeletal muscle cannot respond to secretedinsulin

Cohen et al. Major Topics in Type 1 Diabetes. Published November 2015

DKA• Hyperglycemia—Serum Glucose

>200 mg/dL (11mmol/L)• Metabolic Acidosis with elevated

anion gap• Venous pH <7.30 OR • Serum bicarbonate <15mEq/L

• Ketosis—presence of ketones in the blood

• BOHB>3mmol/L• Urine ketones of moderate/large is

sufficient in the presence of the other 2 criteria

HHS• Severe hyperglycemia—Serum

glucose>600mg/dL (>33.3mmol/L)• Mild acidosis

• Venous pH >7.25• NO elevated anion gap

• Absent or very mild ketosis• Marked elevation in serum

osmolality (>320mOsm/L)

Definition of DKA

Zeitler P, Haqq A, Rosenbloom A, et al. Hyperglycemic hyperosmolar syndrome in children: pathophysiological considerations and suggested guidelines for treatment. J Pediatr 2011; 158:9.Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018; 19 Suppl 27:155.

Anion Gap= (Serum Na+) – (Cl- + HCO3-)

Serum Osmolality= 2(Serum Na+) + (BUN/2.7) + (Glucose/18)

MUDPILESMethanol Tox.UremiaDKAParaldehyde/phenforminINH/Iron ToxLactic AcidosisEthylene GlycolSalicylates

Some quick calculations

• Fluid status—generally have 5-10% fluid deficit• Reasonable to assume 7% fluid deficit in moderate/severe DKA• Measure weight loss from pre-illness status

• Acidosis • Mild DKA pH 7.2-7.3• Moderate DKA pH 7.1-7.19• Severe DKA pH <7.1

DKA—Fluid Status and Acidosis

DKA—Ketones and Electrolytes

KetonesSerum BOHB—most accurate clinical test for ketosis Urine Ketones—can confirm presence but not severityAnion Gap—useful surrogate if BOHB not available. Abnormal ≥15

ElectrolytesSodium deficit almost always present, but serum sodium concentrations can vary

Hyperglycemia increases serum osmolalitywater moves to extracellular space via osmotic gradientNa+ diluted Glucosuria induces osmotic diuresisincreased water lossraises serum sodium

Potassium deficit though levels are usually normal or highK moves into extracellular space Insulin (when you start it) moves K intracellularly so anticipate replacement

Phosphate balance negative due to poor diet and decreased intake—however often normal levels in serum

Osmotic diuresis causes phosphaturiaInsulin (when you start it) moves Phos intracellularly so anticipate replacement

• Polyuria—presents differently at different ages• Polydipsia• Weight loss

• Anorexia (initially)• Nausea/Vomiting• Abdominal Pain

• Candida infections • Hyperventilation—compensation for metabolic acidosis

• Tachypnea • Deep, heaving breaths (Kussmaul Respirations)• Ketone breath

• Dehydration• Tachycardia• Poor perfusion• Decreased skin turgor

• Mental Status Change (late)• Drowsiness• Lethargy• Coma

DKA—Presentation

Considerations/Red Flags• New onset enuresis in apreviously toilet trained child

• Younger children may not have apparent polyuria/polydipsia if they are not toilet trained

• Dehydrated patients don’t have polyuria!!!

Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018; 19 Suppl 27:155.

Assessment of the DKA Patient• ABCs• Vital Signs• Mental Status • Evaluate for Evidence of Infection• Obtain weight—compare with pre-

illness weight if possible• Labs:

• Fingerstick Glucose• VBG—assess severity of acidosis• BOHB—best direct test• Urine Ketones• Full chemistry panel, including phos

Treatment of the DKA Patient• Gentle isotonic volume

expansion (limit fluid bolus to 10-20mg/kg) based on fluid status

• Initiation of an insulin infusion (.05-0.1u/kg/hr)

• Initiation of hourly fluids at supramaintenance but not excessive rate

Initial Assessment and Treatment

• 1% of children with DKA• 40-70% mortality• Most common cause of death from Diabetes

This Study:• Retrospective Case Control • 61 patients identified with Cerebral Edema and DKA• 174 Matched controls by age, sex, new onset vs known• 181 randomly selected controls

Other Risk Factors• Overadministration of fluid (>50ml/kg in first 4hrs)• Age <5yo • New onset T1DM

DKA—Cerebral Edema

RISK FACTORS FOR CEREBRAL EDEMA IN CHILDREN WITH DIABETIC KETOACIDOSISN Engl J Med, Vol. 344, No. 4

• Hypocapnia—cerebral vasoconstriction

• Dehydration

• Osmotic Changes with correction

• Bicarb: promotes osmotic shifts and cellular swelling AND precipitously drops serum K

DKA—Cerebral Edema

RISK FACTORS FOR CEREBRAL EDEMA IN CHILDREN WITH DIABETIC KETOACIDOSISN Engl J Med, Vol. 344, No. 4

DKA—Cerebral Edema

• Multi-center RCT

• 1389 DKA admissions

• Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design

• 0.9% NaCl vs 0.45% NaCl solution• Rapid versus Slow administration

• No Differences in complications or cerebral edema for either the fluids or rate of replacement

RISK FACTORS FOR CEREBRAL EDEMA IN CHILDREN WITH DIABETIC KETOACIDOSISN Engl J Med, Vol. 344, No. 4

• First KCH guideline created 2014• Revised in 2019• Reviewed by Critical Care and Endocrinology teams at KCH

Goal: Prevent complications with either aggressive correction or administration of therapeutics with a high risk of CE

DKA at KCH

DKA at KCH

• Inclusion and ExclusionCriteria

• Goals of Care

DKA at KCH

DKA at KCH

DKA at KCH—Management

• Insulin Drip (.05-0.1unit/kg/hr)

• 2 bag system• Without dextrose• With dextrose

• 1.5x Maintenance• 40/20/10 rule • For adult sized patients canrun at 150ml/hr

• Q1h fingerstick glucose• Repeat BMP in 4 hours if noK in fluids• Q8h labs otherwise or thereafter

DKA at KCH—Transitioning off Drip

• Transition with normal mental status AND:• AG≤16 OR• BOHB<1• Can also follow vital sign normalization (HR and RR)

DKA—Transitioning off drip

• Data reporting metrics

• Revision every 3-4 years based on new evidence

• Bedside BOHB testing—fingerstick + rapid turnaround time

• Outreach—We want to sync our practice with community providers

Future Plans with DKA

• No need to ever give a patient in DKA:

• Sodium Bicarbonate• Insulin bolus (can lead to rapid

drop in serum glucose) • Excessive fluids (>20ml/kg

unless in shock)• Any other adjunctive

medications

Community Provider Recommendations:• Primary and Secondary Assessment• Obtain VBG, BMP, UA, BOHB if

possible• Single (10-20ml/kg) fluid bolus with

isotonic crystalloid• Initiate Insulin infusion at .05-.1

units/kg/hr• Initiate 2 bags of fluids at 1.5x

maintenance rate• D10 ½ NS or NS with Kphos/KCl• ½ NS or NS with Kphos/KCl

• Q1h glucoses while on drip• If pH<7.2 or altered mental status, can

call PICU at KCH directly for admission o/w transfer to PED

Take Home Points for the Community Provider

Thanks