Basics
Description
- Results from a relative insulin deficiency in the undiagnosed or untreated diabetic
- Sustained hyperglycemia creates an osmotic diuresis and dehydration:
- Extracellular space maintained by the osmotic gradient at the expense of the intracellular space
- Eventually profound intracellular dehydration occurs.
- Total body deficits of H2O, Na+, Cl-, K-, PO4-, Ca2+, and Mg2+
- In contrast to diabetic ketoacidosis (DKA), severe ketoacidosis does not occur:
- Circulating insulin levels are higher.
- The elevation of insulin counter-regulatory hormones is less marked.
- The hyperosmolar state itself inhibits lipolysis (the release of free fatty acids) and subsequent generation of keto acids
- Most commonly seen in elderly type II diabetics who experience a stressful illness that precipitates worsening hyperglycemia and reduced renal function
- In the elderly, 30-40% of cases are associated with the initial presentation of diabetes.
Hyperosmolar hyperglycemic states (HHS) rare in pediatric patients
Etiology
- Hyperosmolar state precipitated by factors that:
- Impair peripheral insulin action
- Increase endogenous or exogenous glucose
- Decrease patients ability to replace fluid loss
- Infection is the most common precipitating factor in 32-60% of cases.
- Other precipitating causes include:
- Inadequate diabetes therapy
- Medication omission
- Diet indiscretion
- Infections
- Pneumonia
- UTI
- Sepsis
- Medications/drugs
- Diuretics
- β-blockers
- Calcium channel blockers
- Phenytoin
- Cimetidine
- Amphetamines
- Ethanol
- Myocardial infarction
- Stroke
- Renal failure
- Heat stroke
- Pancreatitis
- Intestinal obstruction
- Endocrine disorders
- Burns
- Heat stroke
Diagnosis
Signs and Symptoms
History
- Progression of signs and symptoms typically occur over days to weeks.
- Polyuria/polydipsia/weight loss
- Dizziness/weakness/fatigue
- Blurred vision
- Leg cramps
Physical Exam
- Dehydration
- Tachycardia
- Sunken eyes
- Hypotension
- Orthostasis
- Dry mucous membranes
- Decreased skin turgor
- Collapsed neck veins
- Coma/lethargy/drowsiness
- Urinary output maintained until late
- Seizures/focal neurologic deficits
- Concurrent precipitating medical illness
Essential Workup
Diagnostic criteria:
- Serum glucose ≥600 mg/dL (usually >1,000 mg/dL)
- Minimal ketosis
- pH ≥ 7.30, HCO3 ≥15 mEq/L
- Effective serum osmolality >320 mOsm/kg:
- = 2 — Na+ + glucose/18
- BUN not included because it is freely permeable between fluid compartments
Diagnosis Tests & Interpretation
Lab
- Broad testing indicated to evaluate hyperosmolar syndrome and for precipitating causes
- Electrolytes:
- K+ may be elevated even in the presence of total body deficit owing to shift from intracellular space to extracellular space.
- Mild anion gap metabolic acidosis owing to lactic acid, β-hydroxybutyric acid, or renal insufficiency
- Increased sodium-correct for hyperglycemia: Corrected [Na+] = [Na+] + 1.6 — [(glucose in mg/dL) - 100]/100
- BUN, creatinine:
- Azotemia with elevated BUN/creatinine ratio owing to prerenal and intrarenal causes
- Venous blood gas (VBG) or arterial blood gas (ABG) to rapidly determine pH:
- ABG necessary to evaluate mixed acid-base disorders
- Serum ketones, β-hydroxybutyrate, and lactate level if pH < 7.3 or significantly elevated anion gap to evaluate mixed acid-base disorder
- Serum osmolarity
- CBC:
- Leukocytosis due to infection, stress, or hemoconcentration
- Increased hemoglobin and hematocrit due to hemoconcentration
- Lipase and amylase:
- Pancreatitis common
- Elevated amylase and lipase with no evidence of pancreatitis common
- May be due to increased salivary secretion, hemoconcentration, or decreased renal clearance
- Urinalysis:
- Check for ketones/glucose.
- Assess for UTI.
- Magnesium, calcium, phosphate
- Blood cultures in sepsis
- Creatine kinase for rhabdomyolysis:
- Urine pregnancy test in females of childbearing years
- Cardiac enzymes and troponin for myocardial infarction
Imaging
- CXR to evaluate for possible underlying pneumonia
- Head CT: When indicated for AMS or with focal neurologic deficit
Diagnostic Procedures/Surgery
ECG:
- Evaluate for electrolyte abnormalities causing conduction impairment
- Evaluate for signs of ischemia as triggering event
Differential Diagnosis
Differentiate from DKA:
- If acidosis or significant anion gap present, must determine cause (i.e., ketosis, DKA, lactic acidosis, [hypoperfusion, sepsis, or postictal], or other causes of metabolic acidosis)
- Mixed disorder of HHS and DKA present in up to 33% of patients
Treatment
Pre-Hospital
IV fluid resuscitation and initial stabilization
Initial Stabilization/Therapy
ABCs:
- Secure airway in comatose patients.
- Cardiac monitor and 18G IV
- Naloxone, thiamine, and blood glucose for coma of unknown cause
- Restore hemodynamic stability with IV fluids.
- 0.9% NS 1-2 L over the 1st hr
- Larger volumes of fluid may be needed to normalize the vital signs and establish urine output.
Ed Treatment/Procedures
- General strategy:
- Frequent reassessment of volume and mental status
- Electrolyte assessment difficult:
- Serum levels of Na+, K+, PO4- do not accurately reflect the total body solute deficits or the intracellular environment.
- Repeat electrolyte and glucose levels hourly.
- Search for a precipitating illness.
- Fluids:
- Begin resuscitation with 0.9% NS 1-2 L over 1-2 hr to restore intravascular volume and achieve hemodynamic stability.
- Use 0.45% saline after initial resuscitation
- Calculate total body water (TBW) deficit using corrected serum sodium:
- TBW deficit = 0.6 — weight (kg) — (1 - 140/corrected Na+)
- Average fluid deficit is 9 L.
- Replace 50% of the fluid deficit over the next 12 hr.
- Change fluid to D5 1/2 NS when serum glucose is <250 mg/dL.
- Potassium:
- Anticipate hypokalemia:
- Total body deficit of ~5-10 mEq/kg body weight (replace over 3 days)
- Begin potassium repletion after urine output is established. Do not start in anuric patients or if initial K+ level is >5 mEq/L.
- If the initial K+ is normal (4-5 mEq/L), give 20-30 mEq KCl in the 1st L of fluids, then give 20 mEq/hr.
- If the initial K+ is low (3-4 mEq/L), give 40 mEq in 1st L
- If serum K+ is <3 mEq/L hold insulin and give 10-20 mEq/h until K+ >3.3, then add 40 mEq to each lister
- Follow repeat serum K+ levels q1-2h and adjust treatment accordingly.
- Insulin:
- No role in the early resuscitation
- Earlier use of insulin may cause rapid correction of hyperglycemia with collapse of the intravascular space, hypotension, and shock or hypokalemia and dysrhythmias.
- Some patients will not require insulin.
- Use insulin as sole therapy in patients with fluid overload (i.e., acute renal failure [ARF]).
- Begin only after achieving hemodynamic stability and evaluating for hypokalemia:
- Do not use unless serum K+ >3.3 mEq/L
- SC or IM insulin not recommended due to erratic absorption
- Titrate drip to optimally decrease serum glucose by 50-90 mg/dL/hr. More rapid correction places the patient at risk for developing cerebral edema.
- Decrease drip rate by 1/2 when serum glucose <250 mg/dL.
- Adjust insulin drip to maintain serum glucose between 150-200 mg/dL, and continue until serum bicarbonate is >18 mg/dL and pH > 7.3
- Phosphate:
- Routine replacement not recommended
- If serum levels <1 mg/dL, give 20-30 mmol potassium phosphate over 24 hr
- Monitor serum calcium levels closely
- Magnesium:
- 0.35 mEq/kg magnesium in fluids for 1st 3-4 hr (2.5-3 g MgSO4 in 70 kg patient)
- Caution in ARF
- Anticoagulation:
- Arterial thrombosis may complicate hyperosmolar state:
- Consider SC heparin as prophylaxis.
- Remain vigilant to detect thrombotic complications (e.g., MI, pulmonary embolus, mesenteric ischemia).
Medication
- Insulin: Begin with 0.05-0.1 U/kg/h; modify after assessing clinical response.
- MgSO4 (magnesium sulfate): 50% (5 g/10 mL; dilute to at least 20% before IV use)
- Naloxone: 2 mg (peds: 0.1 mg/kg) IV push (IVP)
- Potassium phosphate IV: Phosphorous serum level <0.5 mg/dL: 0.5 mmol/kg IV infused over 4-6 hr; phosphorous serum level 0.5-1 mg/dL: 0.25 mmol/kg IV infused over 4-6 hr
- Potassium phosphate PO: Phosphorus 250 mg per tablet and potassium 1.1 mEq per tablet
- Thiamine: 100 mg (peds: 10-25 mg) IVP
Follow-Up
Disposition
Admission Criteria
- All but the mildest cases should be admitted to ICU:
- Frequent serial labs for the 1st 24 hr
- Rapid shifts in fluids and electrolytes and the potential for deterioration in mental status and arrhythmias mandate close monitoring.
- Mild cases may be managed in an observation unit over 12-24 hr.
Discharge Criteria
- Patients meeting the diagnostic criteria for hyperosmolar syndrome should not be discharged.
- Mild hyperglycemia patients with mild volume deficits and normal serum osmolarity can be discharged after hydration and correction of hyperglycemia.
Issues for Referral
Patient should follow-up with endocrinology and with their primary physician within 1 wk postdischarge for long-term blood glucose monitoring and insulin therapy.
Pearls and Pitfalls
- Failure to look for precipitating event or cause
- Too rapid correction of glucose-may lead to hypotension
- Continuing isotonic fluids after volume resuscitation-may lead to hypernatremia
- Continuing hypotonic fluids without frequent electrolytes-may lead to cellular edema, cerebral edema
- Failure to prevent hypokalemia: Respiratory depression, dysrhythmias
- Avoid phenytoin in the event of seizure activity:
- Inhibits the endogenous release of insulin
Additional Reading
- Gaglia JL, Wyckoff J, Abrahamson MJ. Acute hyperglycemic crisis in the elderly. Med Clin North Am. 2004;88:1063-1084.
- Kitabchi AE, Nyenwe EA. Hyperglycemic crisis in diabetes mellitus: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 2006;35(4):725-751.
- Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 2011; 94:340-351.
See Also (Topic, Algorithm, Electronic Media Element)
Diabetic Ketoacidosis
Codes
ICD9
- 250.20 Diabetes with hyperosmolarity, type II or unspecified type, not stated as uncontrolled
- 250.21 Diabetes with hyperosmolarity, type I [juvenile type], not stated as uncontrolled
- 276.0 Hyperosmolality and/or hypernatremia
ICD10
- E11.01 Type 2 diabetes mellitus with hyperosmolarity with coma
- E87.1 Hypo-osmolality and hyponatremia
SNOMED
- 20313009 hyperosmolality (disorder)
- 190331003 diabetes mellitus, adult onset, with hyperosmolar coma (disorder)
- 190330002 diabetes mellitus, juvenile type, with hyperosmolar coma (disorder)