-
Search
 
 
  
 Other POC-IT Resources
 

POC-IT Center
ABX Guide
HIV Guide

 Related Sites
 

PAHO
Medical Association of Trinidad
CHRC guidelines
Trinidad and Tobago Ministry of Health
CDAP - The Chronic Disease Assistance Programme

 Guide Editors
 Editor In Chief
    Christopher D. Saudek, M.D.

Managing Editor
    Rita Rastogi Kalyani, M.D., M.H.S.

Advisor
    Frederick L. Brancati, M.D., M.H.S.
 

Management> Emergencies>
Diabetes Guide Home PageEmail this module to a friend

Hyperosmolar Hyperglycemic State

Vanessa Walker Harris, M.D. and Rita Rastogi Kalyani, M.D., M.H.S.
02-03-2011

DEFINITION

  • Characterized by severe hyperglycemia, hyperosmolality, and dehydration, in the absence of significant ketoacidosis (plasma glucose >600 mg/dL, arterial pH > 7.30, serum bicarbonate >18 meq/L, effective serum osmolality >320 mOsm/kg) (Kitabchi)
  • Initiated by osmotic diuresis due to hyperglycemia. Maintained by insulin levels sufficient to prevent lipolysis and subsequent ketogenesis, but inadequate to appropriately reduce blood glucose levels (Stoner).
  • Associated with proinflammatory state, reversed by effective hydration and insulin treatment (Kitabchi).
  • Usually seen in patients with type 2 diabetes (T2DM), in whom it may be the initial presentation. Rarely occurs in children or patients with type 1 diabetes (Stoner; Nugent).

EPIDEMIOLOGY

  • Mortality rates 5 - 20%; significantly higher > 70 years of age. Early mortality (<72 hrs) more common and likely due to sepsis, shock, or underlying illness. Late mortality (>72 hrs) usually due to thromboembolic events or the effects of therapy (Kitabchi; Trence; Magee; Nugent).
  • Infection (e.g. pneumonia, urinary tract infection) most common precipitating factor. Other common causes: medication noncompliance, undiagnosed diabetes, myocardial infarction, pancreatitis, cerebrovascular accident, medications (calcium channel blockers, thiazide diuretics, atypical antipsychotics), and drug use (alcohol, cocaine). Endocrine causes include thyrotoxicosis, Cushing's syndrome, and acromegaly.
  • In children, long-term steroid use and gastroenteritis common causes (Kitabchi; Stoner; Trence)
  • Underlying medical illnesses that compromise access to water or promote release of counterregulatory hormones (i.e. catecholamines, glucagon, cortisol, growth hormone) can result in severe dehydration, and predispose to HHS (Kitabchi).
  • Mean age of presentation 57 - 69 years.
  • Common in nursing home residents (28%) (Delaney; Nugent)

DIAGNOSIS

  • Usually evolves over several days to weeks
  • Thorough history and physical examination, looking for signs (below), and an underlying precipitant (listed above)
  • Plasma glucose (>600 mg/dL), electrolytes with calculated anion gap (serum bicarbonate >18 meq/L), osmolality (>320 mOsm/kg), arterial blood gas to assess acidosis (pH >7.30), serum and urinary ketones to identify ketosis (may be present from dehydration)
  • Corrected serum sodium calculated by adding 1.6 meq/L to the measured Na+ for each 100 mg/dL of glucose above 100 mg/dL. Elevated corrected serum sodium reflects dehydration, and the value can be used to calculate free water deficit:  Total Body Water (TBW) X [(Current Na/Desired serum Na)-1], where TBW is weight (kg) * % water (varies by gender and age; ~60%). Example: TBW 0.6 X 70 kg man = 42, Corrected Serum Sodium = 160 mEq/L, Free Water Deficit = 42 X [160/140 - 1] = 6 L.
  • Additional laboratory: blood urea nitrogen (mean 65 mg/dL); serum creatinine (mean 3 mg/dL)[ RENAL FUNCTION]; complete blood count with differential (leukocytosis may be present even in the absence of infection); electrocardiogram; chest X-ray; toxicology; transaminases (abnormal in up to one-third of patients with uncontrolled diabetes); lipase and amylase (elevations may suggest pancreatitis); creatine kinase (abnormal in up to two-thirds of patients) and urine, sputum, or blood cultures to exclude infection
  • Anion gap is calculated as Na - (Cl- + HCO3-) (meq/L). Use uncorrected Na+. Normal anion gap = serum albumin x 3. About 50% of patients have mild anion gap acidosis (Stoner; Magee).
  • Effective serum osmolarity reflects tonicity and is calculated as (2 x Na meq/L) + Glucose (mg/dL)/18 + BUN (mg/dL)/2.8. Note that serum Na is the main contributor to osmolarity.
  • Serum levels of potassium, magnesium, and phosphate are typically normal or elevated despite actual total body depletion due to shifts from the intracellular to the extracellular space due to insulin deficiency (Stoner; Magee).
  • Pre-renal azotemia (elevated BUN out of proportion to elevated creatinine) often present.
  • Elevated creatine kinase usually due to dehydration, but need to consider rhabdomyolysis.

SIGNS AND SYMPTOMS

  • Signs: poor skin turgor, dry mucous membranes, cool extremities, tachycardia, hypotension, low grade fever or hypothermia, tachypnea, abdominal distention (possibly due to gastroparesis induced by hypertonicity), focal neurologic signs such as seizures, hemianopia, hemiparesis, aphasia, myoclonus, dysphagia (Kitabchi; Stoner; Magee)
  • Symptoms: polyuria, polydipsia, weakness, weight loss, visual disturbance, leg cramps, nausea, vomiting, and abdominal pain (less common in HHS and may suggest intraabdominal pathology), lethargy, confusion, stupor, coma (occurs with effective serum osmolality >350 mOsm/L) (Kitabchi; Stoner; Magee)
  • The presence of coma or hypotension is associated with poor prognosis. Mortality increases with increasing age and with higher levels of serum osmolality (Nugent).

Tables/Images

CLINICAL TREATMENT

Fluid therapy

  • Goal to expand intravascular, interstitial, and intracellular volume and restore renal perfusion (Kitabchi).
  • On average, fluid deficits 100-200 mL/kg, 20-25% of body water, 12% of body weight, or approximately 9 L. One half of the calculated deficit should be replaced in the first 18 - 24 hours, and the remainder over the next 24 hours (Kitabchi; Trence; Stoner).
  • In absence of cardiac compromise, isotonic saline (0.9% NaCL) infused at 15-20ml*kg body wt-1*h-1 or 1-1.5 L during the first hour (Kitabchi).
  • Normal or elevated corrected serum sodium: 0.45% NaCl infused at 250-500mL/h after the first hour (Kitabchi)
  • Low corrected sodium: 0.9% NaCl at 250-500 mL/h after the first hour (Kitabchi)
  • Successful fluid replacement assessed by hemodynamic monitoring, measuring fluid input/output, laboratory values, and clinical examination (Kitabchi).
  • In patients with cardiac or renal compromise, monitor serum osmolality and clinical exam more frequently to avoid iatrogenic volume overload (Kitabchi).
  • Fluids alone can decrease serum glucose levels by 80 to 200 mg/dL/hour. Once serum glucose <300 mg/dL, change fluid to 5% dextrose with 0.45% NaCl to prevent cerebral edema from too rapid correction of hyperosmolality (Delaney; Stoner; Trence).
Insulin therapy

  • Adequate fluids must be given before initiation of insulin, otherwise hypotension, vascular collapse, or death can occur due to intracellular shifting of water (Stoner; Kitabchi; Delaney; Trence).
  • Continuous intravenous infusion of regular insulin is preferred due to its short half-life and easy titration; capillary blood glucose should be checked by glucometer every hour while on IV insulin infusion by glucometer and plasma glucose at least every 2 to 4 hours (Stoner; Kitabchi).
  • Give an initial bolus of 0.1 units/kg, followed by a continuous insulin infusion of 0.1units/kg/hr or 0.14 units/kg continuous insulin infusion without bolus (Stoner; Kitabchi).
  • If glucose level does not fall by 50-75 mg/dL/hr, then increase the insulin infusion rate until a steady glucose decline is achieved (Stoner; Kitabchi).
  • When plasma glucose <300 mg/dL, decrease insulin infusion to 0.02-0.05 units/kg/hr to keep glucose between 250 -300 mg/dL until patient mentally alert (Kitabchi, Stoner).
  • Once hyperosmolar state resolves and patient able to eat, initiate subcutaneous insulin. To transition to subcutaneous insulin, allow an overlap of 1-2 hours between administration of subcutaneous insulin and discontinuation of the intravenous insulin drip. If patient NPO, continue IV insulin (Stoner; Kitabchi).
  • In insulin naïve patients, total daily dosage should be 0.5-0.8 units/kg divided into multiple doses (Kitabchi).
  • Some patients can be controlled on small doses of subcutaneous insulin and may be later transitioned to oral hypoglycemic agents upon discharge (Delaney; Stoner; Kitabchi).
Correction of electrolyte imbalances

  • Potassium: establish adequate renal function (urine output >50 mL/hr). If K+ >5.2 meq, do not give K+, but check serum K+every 2 hrs. If K+ is 3.3-5.2 meq/L, give 20-30 meq K+ in each liter of IV fluid for goal serum K+ 4-5 meq/L. If K+ < 3 meq/L, hold insulin and give 20-30 meq/hr until K+ >3.3 meq/L (Kitabchi; Stoner; Delaney).
  • Phosphate and Calcium: no controlled data to suggest improved outcomes with phosphate replacement. Consider replacement with potassium phosphate if serum phosphate level < 1 meq/L and muscle weakness is a concern. Monitor serum calcium carefully due to risk of severe, symptomatic hypocalcemia (Delaney; Stoner).
  • Magnesium: often depleted in uncontrolled diabetes. Replace to maintain goal > 2 meq/dL. Correcting hypomagnesemia will aid in resolution of hypokalemia (Stoner).
  • Bicarbonate: No indication for repletion with bicarbonate unless lactic acidosis results in pH < 7 (Magee)
  • Serum electrolyte panel including BUN and creatinine should be checked every 2-4 hours to monitor electrolyte imbalances (Kitabchi).
Complications

  • Common: hypoglycemia, hypokalemia, inadequate volume replacement, sudden large volume shifts, premature discontinuance of insulin therapy (Delaney)
  • Vascular occlusions (mesenteric ischemia, myocardial infarction, disseminated intravascular coagulopathy) occur due to increased viscosity and hypercoagulability. Treat with full-dose heparin or low-molecular-weight heparin if there is clinical evidence of thrombosis (Magee; Stoner).
  • Atraumatic rhabdomyolysis with or without acute tubular necrosis may occur in patients with decompensated diabetes and is associated with increased mortality (Magee; Stoner).
  • Cerebral edema and acute respiratory distress syndrome due to overhydration are rare but often fatal in children and young adults. Treatment of cerebral edema includes intravenous mannitol, mechanical ventilation, and intravenous dexamethasone (Stoner).

FOLLOW UP

  • Patient education focused on encouraging adherence to blood glucose monitoring and compliance with prescribed medications coupled with adequate follow-up to establish a durable diabetes management regimen (Delaney; Stoner; Kitabchi)
  • Sick day management education to encourage early contact with health care providers; review of blood glucose goals and appropriate use of insulin; and starting liquid diet containing carbohydrates and salt when nauseated. (Kitabchi; Stoner; Trence)
  • Review with nursing home staff the importance of adequate fluid intake and close monitoring of hydration status in patients with diabetes (Trence; Stoner).
  • Avoid medications that interfere with effectiveness of insulin (Delaney).

EXPERT COMMENTS

  • Compared to diabetic ketoacidosis: mortality rates are considerably higher; symptoms develop over a longer period of time; usually less ketosis and greater hyperglycemia.
  • Suspect a mixed syndrome of DKA and HHS in patients with pH <7.3, ketonemia, osmolarity > 320 mOsm/L (Delaney; Magee).
  • Severe anion gap metabolic acidosis should prompt consideration of lactic acidosis or other non-HHS entities (Trence; Stoner).
  • Abdominal distention, abdominal pain, nausea, or vomiting that persist after rehydration may be related to an acute intraabdominal process (Stoner; Magee).
  • Focal neurologic signs such as seizures, hemiparesis, lethargy, coma often resolve with correction of fluid deficit and hyperglycemia (Stoner; Magee).
  • Patients with hemodynamic instability, compromised airway, obtundation, or acute abdominal symptoms should be managed in the intensive care unit (Stoner; Magee).
  • Mental status changes occur only with severe hyperosmolarity, coma usually only if osmolarity >360. Suspect other causes, e.g. stroke, if change in mental status with less severe hyperosmolarity.

Basis for Recommendations

  • Kitabchi AE, Umpierrez GE, Miles JM, et al.; Hyperglycemic crises in adult patients with diabetes.; Diabetes Care; 2009; Vol. 32; pp. 1335-43;
    ISSN: 1935-5548;
    PUBMED: 19564476
    Rating: Basis for recommendation
    Comments:Consensus statement outlining precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS.

REFERENCES

RELATED MODULES


 
 
Home
 
Overview
 
Management
 
Complications and Comorbidities
 
Medications
 
Clinical Tests
 
Trinidad and Tobago Specific Modules
 
View All Modules