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Hyperosmolar Syndrome, Emergency Medicine

Basics

Description

- Hyperosmolar state precipitated by factors that: - Impair peripheral insulin action - Increase endogenous or exogenous glucose - Decrease patients ability to replace fluid loss

- 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

  • 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 spaceEventually 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 actionIncrease endogenous or exogenous glucoseDecrease patients ability to replace fluid loss
  • Infection is the most common precipitating factor in 32-60% of cases.
  • Other precipitating causes include:Inadequate diabetes therapyMedication omissionDiet indiscretionInfectionsPneumoniaUTISepsisMedications/drugsDiureticsβ-blockersCalcium channel blockersPhenytoinCimetidineAmphetaminesEthanolMyocardial infarctionStrokeRenal failureHeat strokePancreatitisIntestinal obstructionEndocrine disordersBurnsHeat 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/18BUN 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 insufficiencyIncreased 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 hemoconcentrationIncreased hemoglobin and hematocrit due to hemoconcentration
  • Lipase and amylase:Pancreatitis commonElevated amylase and lipase with no evidence of pancreatitis commonMay 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 statusElectrolyte 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 resuscitationCalculate 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 LIf serum K+ is <3 mEq/L hold insulin and give 10-20 mEq/h until K+ >3.3, then add 40 mEq to each listerFollow repeat serum K+ levels q1-2h and adjust treatment accordingly.
  • Insulin:No role in the early resuscitationEarlier 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/LSC or IM insulin not recommended due to erratic absorptionTitrate 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 recommendedIf serum levels <1 mg/dL, give 20-30 mmol potassium phosphate over 24 hrMonitor 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 hrRapid 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)