SURVIVING THE

HYPERGLYCEMIC CRISIS

2 August 2018

Brian Lee, MD

Division of Endocrinology & Metabolism

Srinakharinwirot University

Annual SWU Medical Conference 2018

& 5th SWU Annual Conference in Medicine

CASE 1

• A 30 yo woman

with T1DM

• Nausea, abdominal pain

1 day PTA

• Ran out of insulin

3 days ago

PHYSICAL EXAMINATION

• BP 100/60 mmHg

• Kussmaul breathing with fruity odor

• Dry lips, flat jugular vein

• Abdomen: soft, mildly tender at periumbilical

area

INVESTIGATIONS

• Plasma glucose 800 mg/dL

• Serum K 6.0, HCO3 10 meq/L

• Serum ketones positive

• Arterial blood gas: pH 6.5, CO2 30 mmHg

• Urine exam: Sp.gr 1.030, glucose 4+, ketones 3+

WHAT IS THE DIAGNOSIS?

CASE 2

• A 70 yo man

with T2DM

• Cough & fever

Polyuria

1 week PTA

• Drowsy

1 day

PHYSICAL EXAMINATION

• T 39 C, HR 120/min, BP 80/50 mmHg

• Drowsy, not pale

• Dry lips, flat jugular vein

• Lungs: crepitation at RLL

INVESTIGATIONS

• Plasma glucose 1,200 mg/dL

• Serum Na 150, K 4.0, Cl 80, HCO3 20 mEq/L

• Effective serum osmolality: 366 mOsm/kg

• Arterial blood gas: pH 7.35, CO2 30 mmHg

• CBC: WBC 30,000/mm3, PMN 90%

• CXR: new infiltration at RLL

WHAT IS THE DIAGNOSIS?

PATHOPHYSIOLOGY

/ thin

Family Hx more

common

absolute

INSULIN ACTION

PATHOPHYSIOLOGY

INSULIN DEFICIENCY → LIPOLYSIS → FFA →

KETONES

Main keto-acid in DKA: Beta-hydroxybutyrate.

PRECIPITATING FACTORS

Most common

● Infection

● Discontinuation / inadequate insulin

○ Fear of hypoglycemia

○ Fear of weight gain

○ Stress of chronic disease (non-

compliance)

CLINICAL PRESENTATION

• Signs of hyperglycemia:

Polyuria, polydipsia, weight loss

• Signs of dehydration

• Mental status change

CLINICAL PRESENTATION

• T2 DM, older, more comorbidities

• Onset: several days to weeks • More severe dehydration

(water deficit 9 L vs 6 L)

• Drowsy / coma (due to hyperosmolarity)

• Focal neurologic signs (due to severe hyperglycemia)

- hemiparesis, seizures

• Usually T1DM

T2DM + severe stress

• Shorter onset 1-2 days

• Nausea, vomiting, diffuse

abdominal pain (due to

acidosis)

• Drowsy / coma (due to

severe acidosis)

• Kussmaul respirations

• Fruity odor (acetone breath)

HHS DKA

INITIAL LAB INVESTIGATIONS

• Complete blood count • Plasma glucose

• Blood urea nitrogen/creatinine

• Electrolytes (with calculated anion gap)

• Calculate effective serum osmolality

• Serum and urinary ketones

• Urinalysis

• Arterial blood gas

• Electrocardiogram, chest x-ray

• Lactate, cultures (if suspect infection)

Criteria for diagnosis

Diabetic Ketoacidosis (DKA) Hyperglycemic Hyperosmolar State (HHS)

Plasma glucose >250 mg/dL Plasma glucose >600 mg/dL

Arterial pH ≤7.3 Arterial pH >7.3

Bicarbonate <18 mEq/L Bicarbonate >18 mEq/L

Moderately positive ketones by nitroprusside method in blood or urine Serum beta-hydroxybutyrate (β-OHB) ≥ 3.0 mmol/L

No significant ketonuria and ketonemia

Anion gap >12 mEq/L Na - (Cl + HCO3)

Effective serum osmolality >320 mOsm/kg (2 x Measured Na + Glucose / 18)

21

CRITERIA FOR DIAGNOSIS

Diabetes Care 2009

WIDE ANION GAP MET ACIDOSIS (AG > 12)

• Normal anion gap is <12 mEq/L • In ketoacidosis, the “delta” of the anion

gap above 12 mEq/L is composed of anions derived from keto-acids (B-hydroxybutyrate, acetoacetate)

HYPERCHLOREMIC METABOLIC ACIDOSIS

• Normal gap acidosis • Common during DKA resolution due to

– Fluid replacement with saline (NaCl)

– Renal loss of HCO3

• May persist after anion gap has closed

• Closing of anion gap is better sign of recovery from DKA than correction of metabolic acidosis

Ketone Body Equilibrium in DKA

AcAc β-OH B

• DKA

resolution:

balance shifts

to acetoacetic

acid (AcAc)

• DKA (before

Rx)

• Lactic acidosis

• Alcoholic

ketoacidosis

Molar Ratio of β-OH B to AcAc

Normal health 2 to 1

DKA 3-4 to 1

DKA with high redox state

-poor tissue perfusion /

lactic acidosis

-alcoholic ketoacidosis

7.7-7.8 to 1

TESTS FOR SERUM KETONE

Nitroprusside test B-hydroxybutyrate level

• Measures only AcAc,

acetone

• May wrongly indicate

that DKA is not

improving or getting

worse

• F/U ketone is not

recommended

● B-OH B level > 3.0

mmol/L is diagnostic

of DKA

● Anion gap narrowing

is best indicator of

reduced keto-acids

DIFFERENTIAL DIAGNOSIS IN DKA

• Wide gap acidosis (unmeasured anions):

Lactic acidosis (lactate - poor perfusion, sepsis)

Renal failure / Uremia (phosphates, sulfates)

Ketoacidosis (alcohol)

Poisonings / Overdoses (methanol, ethanol,

ethylene glycol, aspirin, paraldehyde)

• Normal gap acidosis

Hyperchloremic metabolic acidosis (rapid, large

volume saline infusion)

Diarrhea, RTA

DIFFERENTIAL DIAGNOSIS IN DKA

Potassium Balance in DKA

• Potassium is mostly intracellular

• Urinary losses during DKA (due to glycosuria)

• Potassium shifts to extracellular (plasma), serum K usually high before treatment due to – Insulin deficiency

– In presence of high blood glucose

– In metabolic acidosis (exchange with H+)

• After insulin Rx → Hypokalemia

33

Be Aware of Conditions that may make DKA Diagnosis Difficult

Conditions that ↑ bicarbonate (eg.

vomiting)

Pregnancy SGLT2 inhibitor

Significant osmotic diuresis

↑ β-hydroxy

butyrate

Mixed acid-base so pH not as low

Normal or mildly ↑ glucose (euglycemic

DKA)

Loss of keto anions

Normal anion gap

Negative serum

ketones

Order serum

β-hydroxy

butyrate

TREATMENT

• Correction of dehydration, hyperglycemia, and

electrolyte imbalances

• Identification of comorbid precipitating events

• Frequent patient monitoring

TREATMENT

• IV fluids:

0.9% NaCl 1,000 ml in 1 hr --> 500-1,000 ml/h

ประเมิน volume status เป็นระยะ: JVP, lung: crepitations?,

urine output > 0.5-1 ml/kg/hr

• เมื่อแก้ไข dehydration แล้ว: เปลี่ยนเป็น 0.45% NaCl 1,000 ml

drip 250-500 ml/hr

• เมื่อ DTX < 200-250 (HHS < 300) mg/dL เปลี่ยนเป็น 5%DN/2

drip 150-250 ml/hr

• Be careful of volume overload in heart disease, renal

insufficiency, elderly patients

Suggested Initial Rate of Fluid

Replacement

39 Chaithongdi N et al. Hormones (Athens). 2011;10:250-260.

Hours Volume

1st hour 1000 – 2,000 mL

2nd hour 1000 mL

3rd-5th hours 500 – 1000 mL/hour

6th-12th hours 250 – 500 mL/hour

TREATMENT

• Regular insulin: 0.1 u/kg iv stat then drip 0.1 u/kg/hr

If BW 50 kg: RI 5 u iv stat, then drip 5 u/h (ไล่สาย 20-30

ml ก่อนเริ่ม drip)

• DTX q 1hr: if DTX ลดลง <50-75 mg/dL/h: bolus RI 0.14

u/kg หรือเพิ่ม insulin 2x

เพิ่ม rate iv fluid ถ้ายังมี dehydration, แก ้precipitating

• เมื่อ DTX < 250 mg/dL: ลด insulin drip ลงครึ่งหน่ึง และปรับ

insulin q 1hr keep DTX 150-200 (HHS 250-300) จนกว่าจะ resolution of DKA / HHS

• K replacement: aim keep K 4-5 mEq/L

• K shifts into cells with insulin Rx and correction of

acidosis → severe hypokalemia may occur

• Serum K 3.3-5.2: NSS 1000 ml + KCL 20-40 mEq/L

• ถ้า serum K < 3.3 mEq/L: หยุด insulin และให ้KCL 10-20

mEq/hr

• ถ้า serum K > 5.2 mEq/L: หยุด KCL drip และ F/U serum

K q 2 hr

• ก่อนให้ KCL: Urine output > 1 ml/h, serum K < 5.2

meq/L, ระวังถ้าท ีrenal insuff

ADA. Diabetes Care. 2003;26:S109-S117.

Potassium Replacement

• K+ = > 5.5 mEq/L: no K supplement

• K+ = 4 - 5 mEq/L: 20 mEq in NSS 1L

• K+ = 3 - 4 mEq/L: 40 mEq in NSS 1L

If admission K+ = <3 mEq/L give 10-20 mEq/h until

K+ >3 mEq/L, then add 40 mEq/L to replacement fluid

• Bicarbonate เฉพาะกรณ ีpH < 6.9, Serum HCO3 <10:

5%DW 400 ml + 7.5% NaHCO3 100 ml + KCl 20

mEq iv drip in 2 hr

• Blood gas, serum K q 2 hr (อาจเกิด hypoK; bicarb --> K

shift เข้า cell)

ให ้bicarb q 2 hr จนกว่า pH ≥ 7

• Treat precipitating cause เช่น antibiotics ถ้าม ีinfection

ADA. Diabetes Care. 2003;26:S109-S117.

Phosphorus Administration

• Phosphorus level maybe low (insulin Rx

→ shift into cell)

• If serum phosphorus < 1 mg/dL:

30-40 mmol K-Phos over 24 h

• Monitor serum calcium level

(hypocalcemia may occur)

Resolution of DKA / HSS

DKA

• Blood glucose < 200

mg/dl

• and two of the

following criteria :

⬜ Serum HCO3 ≥ 15

meq/L

⬜ Venous pH > 7.3

⬜ Anion gap ≤ 12

meq/L

HSS

• Blood glucose <

300 mg/dl

• Normal

osmolality

• Normal

consciousness

• Continue insulin infusion until anion gap closes

Transition to subcutaneous insulin

• Good consciousness, no N/V, bowel sounds +

• Insulin dose = insulin in past 6 hours (units)

x 4 x 80%

• RI-RI-RI-NPH or glargine

• Overlap of 1-2 h

PHOSPHATE

• Phosphate concentration decreases with insulin

therapy

• Patients with cardiac dysfunction, anemia, or

respiratory depression and serum phosphate

concentration 1.0 mg/dl : 20-30 mEq/l potassium

phosphate can be added to replacement fluids

• Maximal rate of phosphate replacement :

4.5 mmol/h (1.5 ml/h of K2PO4)

COMPLICATIONS DURING RX

• Hypoglycemia

• Hypokalemia

• Cerebral edema: Rare in adult patients

SYMPTOMS AND SIGNS OF CEREBRAL

EDEMA

• Starts with headache

• Gradual deterioration in level of consciousness,

• Seizures

• Sphincter incontinence

• Pupillary changes

• Papilledema

• Bradycardia

• Elevation in blood pressure

• Respiratory arrest

Causes of Morbidity and Mortality

• Shock

• Hypokalemia during

treatment

• Hypoglycemia during

treatment

• Cerebral edema

during treatment

• Hypophosphatemia

• Acute renal failure

• Adult respiratory

distress syndrome

• Vascular thrombosis

• Precipitating illness,

including MI, stroke,

sepsis, pancreatitis,

pneumonia

53

DKA Management Pitfalls

• Not assessing for and/or treating underlying cause of the DKA

• Not watching K+ closely enough and/or not replacing K+ aggressively enough

• Following serial serum ketone concentrations

• Following serum bicarbonate instead of the anion gap, with misinterpretation of expansion acidosis as “persistent ketoacidosis”

• Interrupting IV insulin too soon (eg, patient not yet eating, anion gap not yet closed)

54

DKA Management Pitfalls

• Occurrence of rebound ketosis consequent to

inadequate insulin dosing at transition (eg,

failure to give SC insulin when glucose is “low”

or injudicious use of sliding scale insulin)

• Inappropriate extension of hospitalization to

“fine-tune” an outpatient regimen

• Inadequate patient education and training

• Inadequate follow-up care 55

Predischarge Checklist

• Diet information

• Glucose monitor and strips

(and associated prescription)

• Medications, insulin, needles

(and associated prescription)

• Treatment goals

• Contact phone numbers

• “Survival Skills” training

56

Summary

• DKA and HHS are life-threatening

emergencies

• Management involves

– Attention to precipitating cause

– Fluid and electrolyte management

– Insulin therapy

– Patient monitoring

– Prevention of metabolic complications during

recovery

– Transition to long-term therapy

• Patient education and discharge planning

should aim at prevention of recurrence

57