George Ford MD MS Assistant Professor Pediatric Endocrinology ETSU and Niswonger Children s Hospital

Transcription

1 George Ford MD MS Assistant Professor Pediatric Endocrinology ETSU and Niswonger Children s Hospital

2 Disclosure Statement of Financial Interest I, George Ford MD MS, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

4 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

5 5-10% of diabetes patients 1:400 children Peak incidence puberty (10-12 girls, boys) Autoimmune destruction of insulin producing beta cells Higher risk of celiac and thyroid disease Risks of DM1: 5% if sibling has DM1, 13-33% chance if identical twin with DM1 Highest incidence in Caucasians

6 Type one diabetes is T cell mediated T cells drive B lymphocytes to make antibodies to islet

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9 Unknown is the short answer Some genetic predisposition to islet cell autoimmunity and progression to DM1 HLA-DR3, HLA-DR4, PTPN22, UBASH3A SNPs (Steck, 2012, Pediatric Diabetes, 15;355) Environmental factors unproven: viruses, vitamin D, timing of food introduction (Cow s milk)

10 Incidence of type one diabetes is rising 2-5% per year

11 Normal Pre-diabetes Diabetes Hemoglobin A1c < Fasting Blood Sugar < > 126 Oral Glucose Tolerance Test < > 200

12 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

13 Type 1 Weight loss Slender Presents with ketoacidosis Low insulin level Honeymoon on insulin Type 2 Obese Acanthosis nigricans Non-Caucasian Teen age Normal to elevated insulin level (limited usefulness) BP Ketoacidosis variable

14 Humoral Autoantibodies Glutamic acid decarboxylase (GAD-65) Insulin autoantibodies Phosphatase related IA-2 (IA-2) Zinc Transporter autoantibodies (ZnT8)

15 May be clinically obvious Look for markers of islet cell autoimmunity Anti GAD (glutamic acid decarboxylase) Ab + 80% Type 1 Anti-insulin % Type 1 However, 5-10% of adults with Type 2 have one or more positive antibody Look for residual islet cell function Serum insulin or C-peptide Look at subsequent clinical course on insulin Type 1 kids - honeymoon period Type 2 kids- larger per kilo insulin doses

16 Polyuria Polydipsia Polyphagia Unusual weight loss Fatigue Irritability

17 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

18 Hyperglycemia Plasma glucose > 250 mg/dl Metabolic Acidosis ph < 7.3 and/or bicarbonate < 15 mmol/l Moderate to large ketonemia and ketonuria

19 Wide range for rates of DKA at diagnosis of DM1 (15-70%) Inversely correlated with regional incidence of DM1 Rates of delayed diagnosis United States: SEARCH for Diabetes Study Overall DKA rate: 25.5% at diagnosis Type 1 > type 2 (29.4% vs 9.7%) Kids age 0-4 DKA rate higher (37.3%) vs Age with lowest rate of DKA at diagnosis. (14.7%) Rewers et al. Pediatrics 2008; 121;e1258

20 With established diabetes: 1-10% per patient year Risk factors: Poor metabolic control Previous episode DKA Peripubertal/teen girls Psychiatric disorders Difficult family circumstances

21 Clinical Case: DKA ID: 13.5 yr. old previously healthy Caucasian girl presents with a 1 week history of polyuria and vomiting, and went to an outside ER due to mental status and a glucose=812. Labs: ph 7.1,HCO 3 6.5, Cr 2.5, Lg Ketones PE: Weight. 82 kg (>>95%), BP 98/44 Dry mucous membranes Cool hands and feet Delayed cap refill= 3 seconds Altered mental status

22 Hyperglycemia Hyperosmolar State (HHS) Plasma glucose > 600 mg/dl ph > 7.25 and bicarbonate > 15 mmol/l Effective serum osmolarity > 320 mosm/kg Urine and serum ketones negative Stupor or coma Severe dehydration

23 Correct Dehydration slowly over 48 hours Correct Acidosis/Reverse ketosis Restore glucose to near normal Identify and treat precipitating events Avoid complications of therapy

24 General recommendations: Mild/Moderate dehydration: Start with 10 ml/kg fluid bolus over 1-2 hours Severe Dehydration: If in hypovolemic shock, initiate 0.9% NaCl bolus ml/kg over 30 minutes. When serum glucose reaches < 300 initiate dextrose containing fluids. Titrate glucose to keep glucose in range of Consider changing to NaCl 0.45% + electrolytes after perfusion restored of if hypernatremia (usually after 6+ hours)

25 If Potassium < 5 and urine output established Add 20 meq KCl and 20 meq Kphos to fluids after initial fluid resuscitation No urine output: NS only without electrolytes Fluid rate: 1.5 MIVF is a good rule of thumb. Q2H VBG, Q4H BMP, Mg, PO4 until acidosis resolved

26 Half life of IV insulin is 4-5 minutes Starting dose: Recommended: 0.05 units/kg/hour--more gradual reduction in plasma osmolarity and possible reduction in Cerebral edema Typical range: 0.05 units/kg/hour-0.1 units/kg/hr Titrate insulin up in 0.01 units/kg/hour with goal to drop blood sugar by about mg/dl per hour Invariably IV fluids alone drop the blood sugar prior to insulin administration by about mg/dl. DO NOT BOLUS INSULIN Al Hanshi et al., 2011, Pediatric Critical Care, 12(2)

27 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

28 Mortality rate: % Cerebral Edema in 60-90% of deaths Other uncommon causes: Pulmonary Edema, ARDS, Aspiration pneumonia Cardiac arrhythmias, hypo/hyperkalemia CNS Thrombosis Rhabdomyolysis Sepsis, mucormycosis

29 Major Cause of death in childhood DKA 20% with clinically evident cerebral edema die 20% have mild to severe neurological outcomes At risk: Initial ph < 7.1, more severe DKA Higher BUN, lower PCO2, higher K Baseline mental status abnormal New diagnosis (3X risk all, greater if age less than 5)

30 Additional risk factor factors Bicarbonate administration Avoided but if ph < 7 after initial hydration AND the patient has cardiac instability may be considered Insulin within the first hour of therapy. Early significant drop in plasma osmolality Rapid rehydration (> 50 cc/kg in first 4 hours) Persistent hyponatremia and hypernatremia

31 Clinical Manifestationsusually in first 24H Altered mental status Severe headache Seizure Bradycardia Pupillary changes Clinical worsening DESPITE improving lab values

32 Usefulness of Brain CT CT/MRI changes may NOT be seen in early cerebral edema May confirm cerebral edema Can be focal or diffuse Initial scan is normal 40% of the time Subsequent scans: Often demonstrate edema, hemorrhage, or infarction Take home: Not always diagnostic

33 Diagnostic Criteria Major Criteria Minor Criteria Cranial Nerve Palsy (III, IV, and VI especially) Decorticate or decerebrate posturing Abnormal motor or verbal response to pain Abnormal neurogenic respiratory pattern (grunting, tachpnea, Cheyne-stokes respirations, apneusis) Acute altered mentation/fluctuations in level of consciousness Heart rate decelerations (more than 20 bpm) not attributed to improved hydration/sleeping Age inappropriate incontinence Vomiting Headache Lethargy (not easily aroused from sleep) Diastolic blood pressure > 90 Age less than 5 years. Tx: 1 diagnostic or 2 major or 1 major and 2 minor criteria. (Adapted from Muir et al. Diabetes Care 2004;27;1541)

34 Reduce rate of fluid administration Raise had of bed Intubate if necessary to protect airway Avoid hyperventilation (associated with worse neurological outcomes) Two choices: IV mannitol g/kg over 15 minutes, repeat in 15 minutes if no improvement. 3% NaCl (5-10 ml/kg) over 30 minutes

35 3% vs Mannitol for cerebral edema Use of 3% began in 2001 (Curtis et al, Pediatric Diabetes, 2001, 2(4) No consensus, failure to respond to one should prompt the other. (Tasker et al, Pediatric Diabetes, 2014, 15(4) Consider Sodium level?

36 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

37 Recognizing new onset diabetes Increase awareness Check UA and/or bedside CBG Often missed in younger children Look for precipitating factors and treat

38 DKA prevention after diagnosis: Need for ongoing diabetes education Regular psychosocial evaluation Appropriate adult supervision Recognizing pump failures early and giving insulin by injections to treat high blood sugars and ketosis

39 1. Type 1 diabetes 2. Type 1 vs. Type 2 diabetes 3. Diabetic Ketoacidosis 4. Cerebral Edema 5. Preventing DKA 6. Basal/Bolus dosing after diagnosis

40 DKA resolved Anion gap < 13 HCO3 > Hemodynamically stable Neurologically intact Electrolytes improving with no significant derangement Discontinue labs, follow ketones for insulin dosing Transition to Lantus and Humalog/Novolog

41 Based on age, weight, and glycemic response to insulin drip. Rules of thumb: Age < units/kg/day, adjusted for very young children Age units/kg/day Age units/kg/day Half of insulin dosing should be basal and the rest should be calculated as bolus insulin

42 14 year old male, 60 kg Insulin starting dose: 1 unit/kg/day Basal Insulin with Lantus: 30 units Carbohydrate Ratio: Often dosed by experience Can use rule of 500 (500/total daily dose of insulin) 500/60 = 8 grams of carbs for every 1 unit of insulin Often round up to CR of 1:10

43 14 year old male, 60 kg Correction Factor/Sliding Scale: Rule of 1800/total daily dose of insulin 1800/60 = 1 unit for every 30 > 150 Quick rules of thumb: ½ unit for 50 > 200 or 250 in toddlers 1 unit for 75 > 150 in school aged children 1 unit for 50 > 150 for teens

44 Acknowledgments: Dr. Cheryl Hanna MD, OHSU, some materials adapted from David Maahs, MD ppt, Barbara Davis Center for Childhood diabetes