surviving the hyperglycemic crisis · surviving the hyperglycemic crisis 2 august 2018 brian lee,...
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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