Hyperosmolar Hyperglycemic State Treatment & Management
- Author: Robin R Hemphill, MD, MPH; Chief Editor: George T Griffing, MD more...
Diagnosis and management guidelines for hyperglycemic crises are available from the American Diabetes Association.[15, 16, 4]
The main goals in the treatment of hyperosmolar hyperglycemic state (HHS) are as follows:
To vigorously rehydrate the patient while maintaining electrolyte homeostasis
To correct hyperglycemia
To treat underlying diseases
To monitor and assist cardiovascular, pulmonary, renal, and central nervous system (CNS) function
In an emergency situation, whenever possible, contact the receiving facility while en route to ensure preparation for a comatose, dehydrated, or hyperglycemic patient. When appropriate, notify the facility of a possible cerebrovascular accident. Initiation of insulin therapy in the emergency department (ED) through a subcutaneous insulin pump may be an alternative to intravenous (IV) insulin infusion.
Airway management is the top priority. In comatose patients in whom airway protection is of concern, endotracheal intubation may be indicated. Cervical spine immobilization is necessary if head or neck injury is a possibility. In patients with HHS, consider other procedures, including nasogastric tube placement, thoracentesis, paracentesis, and spinal tap, as appropriate.
Rapid and aggressive intravascular volume replacement is always indicated as the first line of therapy for patients with HHS. Isotonic sodium chloride solution is the fluid of choice for initial treatment because sodium and water must be replaced in these severely dehydrated patients.
Although many patients with HHS respond to fluids alone, IV insulin in dosages similar to those used in diabetic ketoacidosis (DKA) can facilitate correction of hyperglycemia. Insulin used without concomitant vigorous fluid replacement increases the risk of shock. Adjust insulin or oral hypoglycemic therapy on the basis of the patient’s insulin requirement once serum glucose level has been relatively stabilized.
All patients diagnosed with HHS require hospitalization; virtually all need admission to a monitored unit managed by medicine, pediatrics, or the intensive care unit (ICU) for close monitoring. When available, an endocrinologist should direct the care of these patients.
Frequent reevaluation of the patient’s clinical and laboratory parameters is necessary. Recheck glucose concentrations every hour. Electrolytes and venous blood gases should be monitored every 2-4 hours or as clinically indicated.
When an underlying disease is responsible for HHS, it must be promptly identified and treated. Resolution of HHS often lags while the underlying process remains to be resolved. Some authors advocate prophylactic heparin treatment and broad-spectrum antibiotic coverage, but these measures have not yet been studied thoroughly enough to allow recommendation of their use.
Standard Care for Dehydration and Altered Mental Status
Standard care for dehydration and altered mental status is appropriate, including airway management, IV access, crystalloid fluid replacement, and administration of any medications routinely given to coma patients.
Protection of the airway is mandatory in patients with obtundation or unconsciousness. Many patients present with respiratory failure and circulatory collapse and must be ventilated mechanically.
Because of the underlying metabolic acidosis that is frequently present, take care to hyperventilate patients when mechanical ventilation is instituted. Hyperventilation generates respiratory alkalosis, which compensates for the metabolic acidosis and also decreases the risk of cerebral edema.
IV access, large bore if possible, or central venous access is useful, provided attempts to obtain it do not significantly delay transfer to the nearest ED. Insertion of a central venous catheter is the only procedure that should be considered routinely in patients with HHS. A centrally placed catheter offers an avenue for vigorous rehydration. Findings from monitoring of the pulmonary capillary wedge pressure or the central venous pressure may help guide intravenous rehydration therapy.
Large-bore IV or central venous access may be especially helpful in cases in which hemorrhage is a precipitant and blood products are likely to be required or when inotropic agents may be necessary.
Fluid deficits in HHS are large; the fluid deficit of an adult may be 10 L or more. If a recent record of the patient’s weight is available for comparison, the difference between the admission weight and the preadmission weight may provide a rough estimate of the degree of dehydration.
Infuse enough volume to allow the perfusion of vital organs and the kidneys. A reasonable goal of treatment is to replace half of the estimated volume deficit in the first 12 hours of therapy. The remainder of the volume deficit may then be replaced over the second 12-hour period.
A 500-mL bolus of 0.9% isotonic saline is appropriate for nearly all adults who are clinically dehydrated. Administer 1-2 L of isotonic saline in the first 2 hours. A higher initial volume may be necessary in patients with severe volume depletion. Slower initial rates may be appropriate in patients with significant cardiac or renal disease. Caution should be taken to not correct hypernatremia too quickly, as this could lead to cerebral edema. As much as 2 L of 0.9% isotonic saline may be infused safely over the first hour of treatment.
After the initial bolus, some clinicians recommend changing to half-normal saline, whereas others continue with isotonic saline. Either fluid likely will replenish intravascular volume and correct hyperosmolarity; a good standard is to switch to half-normal saline once blood pressure and urine output are adequate.
At a serum osmolality below 320 mOsm/kg, the IV fluids may again be switched to 0.9% isotonic saline. When the blood glucose concentration, initially checked hourly, reaches 300 (or, as some prefer, 250) mg/dL, change the infusion to 5% dextrose in 0.9% isotonic saline again. This helps prevent a precipitous fall of glucose, which may be associated with cerebral edema. In pediatric patients with suspected HHS, correcting fluid deficits over a longer period (48 h) may help reduce the risk of cerebral edema.
In most patients, adequately monitoring volume status entails the use of a urinary catheter. In patients with preexisting or acute cardiac disease or with diseases in which third-spacing is a problem, use findings from pulmonary capillary wedge pressure monitoring to guide rehydration therapy. Patients with hypotension may require pressor support in the ICU while rehydration is being accomplished.
Medications for coma patients
Basic medications given to coma patients in the field may include dextrose (50 mL of % dextrose in water [D50]). This is of benefit to many comatose patients with few adverse effects.
When possible, fingerstick glucose measurement is obtained before dextrose administration. Whenever fingerstick glucose measurement is unavailable or is likely to be delayed, D50 must be administered to comatose patients on an empiric basis without delay. Undiagnosed and untreated hypoglycemia, which may present with signs and symptoms very similar to those of HHS, is readily reversible but can be rapidly lethal if not treated promptly.
Insulin Therapy for Correction of Hyperglycemia
All patients with HHS require IV insulin therapy; however, immediate treatment with insulin is contraindicated in the initial management of patients with HHS. The osmotic pressure that glucose exerts within the vascular space contributes to the maintenance of circulating volume in these severely dehydrated patients. Institution of insulin therapy drives glucose, potassium, and water into cells. This results in circulatory collapse if fluid has not been replaced first.
After the kidneys show evidence of being perfused, initiating insulin therapy is safe. This is accomplished most effectively in the ICU, where cardiovascular and respiratory support is available if needed. Infuse insulin separately from other fluids, and do not interrupt or suspend the infusion of insulin once therapy is started.
The following steps may be used as a guideline for insulin infusion:
Begin a continuous insulin infusion of 0.1 U/kg/h
Monitor blood glucose by means of bedside testing every hour; if glucose levels are stable for 3 hours, decrease the frequency of testing to every 2 hours
Set the target blood glucose level at 250-300 mg/dL; this target level may be adjusted downward after the patient is stabilized
For a blood glucose concentration lower than 250 mg/dL, decrease the insulin infusion rate by 0.5 U/h
For a blood glucose concentration of 250-300 mg/dL, do not change the insulin infusion rate.
For a blood glucose concentration of 301-350 mg/dL, increase the insulin infusion rate by 0.5 U/h
For a blood glucose concentration higher than 350 mg/dL, increase the insulin infusion rate by 1 U/h
Do not discontinue the insulin drip
If the blood glucose concentration decreases by more than 100 mg/dL between consecutive readings, wait to increase the insulin infusion rate
When the glucose level has been between 200 and 300 mg/dL for at least 1 day and the patient’s level of consciousness has improved, glycemic control may be tightened. The recommended level of glycemia for most patients with type 2 diabetes mellitus (DM) is 80-120 mg/dL. This correlates to the hemoglobin A1c value of 7% recommended by the American Diabetes Association.
All patients who have experienced HHS will probably require intensive management of their diabetes initially, and this includes insulin therapy. The severe hyperglycemia with which these patients present implies profound beta cell dysfunction. In most instances, sufficient recovery of endogenous insulin production is a reasonable expectation, with safe dismissal of the patient from the hospital on oral therapy. After maintaining adequate glycemic control with insulin for several weeks after HHS, consider switching patients to an oral regimen.
Initiation of insulin therapy in the ED via subcutaneous insulin pump may be an alternative to intravenous insulin infusion.
Profound potassium depletion necessitates careful replacement. With rehydration, the potassium concentration is diluted. With the institution of insulin therapy, potassium is driven into cells, exacerbating hypokalemia. A precipitous drop in the potassium concentration may lead to cardiac arrhythmia.
Potassium may be added to the infusion fluid and should be started at a level of 5 mEq/L or less. Hypokalemia at the onset of rehydration requires up to 60 mEq/L to correct the serum potassium concentration. Check the potassium level at least every 4 hours until the blood glucose concentration is stabilized.
Phosphate, magnesium, and calcium are not replaced routinely, but a patient who is symptomatic with tetany requires replacement therapy.
Monitoring During Treatment
The mortality associated with HHS remains high. The profound electrolyte and metabolic abnormalities present during treatment warrant careful cardiorespiratory monitoring. When gas exchange has been compromised, endotracheal intubation and mechanical ventilation are indicated.
Neurologic monitoring is indicated in all patients with HHS who present with altered mental status. Hyperosmolarity may trigger many neurologic syndromes. If a patient has seizures, phenytoin is not the agent of choice, because it inhibits endogenous insulin secretion and because, in general, it is ineffective in persons with HHS.
Provide adequate nutritional support for all patients. Most HHS patients with HNS are unable to eat for several days as a consequence of the comorbidities with which they present.
Patients in the ICU who require prolonged mechanical ventilation, patients with impaired airway defenses, and all patients with prolonged MS changes are candidates for enteral or parenteral nutrition. The use of parenteral nutrition often induces insulin resistance and leads to increased insulin requirements.
Once HHS is resolved, provide dietary counseling for all patients. This probably is most effectively delivered by a registered dietitian who has expertise in counseling patients with diabetes.
Generally, no consultation is absolutely required to manage HHS in the ED; however, in occasional cases, consultations may be useful.
A consultation with an endocrinologist is suggested for patients with HNS. Consider a consultation with a neurologist for most patients with altered mental status. A neurologist should monitor the cases of any patients with underlying neurologic disease (eg, cerebrovascular accident or a history of seizures). A pulmonologist or critical care specialist should monitor the cases of patients requiring intubation and mechanical ventilation. Other consultations (eg, with infectious disease or psychiatry) may be obtained as appropriate.
Primary care follow-up is necessary for additional diabetic teaching and any appropriate immunizations. Visiting home nurse referral may be necessary to enhance compliance.
After any episode of HHS, enroll patients in a program of routine diabetes care. Adhere to American Diabetes Association guidelines for the care of people with diabetes. For patients with diabetes that was unrecognized before HHS, perform a dilated eye examination. Advise patients treated with insulin to wear a bracelet or chain identifying them as having diabetes.
Nugent BW. Hyperosmolar hyperglycemic state. Emerg Med Clin North Am. 2005 Aug. 23(3):629-48, vii. [Medline].
Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan. 24(1):131-53. [Medline].
Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec. 30(4):817-31. [Medline].
Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec. 29(12):2739-48. [Medline].
Campanella LM, Lartey R, Shih R. Severe hyperglycemic hyperosmolar nonketotic coma in a nondiabetic patient receiving aripiprazole. Ann Emerg Med. 2009 Feb. 53(2):264-6. [Medline].
Ahuja N, Palanichamy N, Mackin P, Lloyd A. Olanzapine-induced hyperglycaemic coma and neuroleptic malignant syndrome: case report and review of literature. J Psychopharmacol. 2010 Jan. 24(1):125-30. [Medline].
MacIsaac RJ, Lee LY, McNeil KJ, Tsalamandris C, Jerums G. Influence of age on the presentation and outcome of acidotic and hyperosmolar diabetic emergencies. Intern Med J. 2002 Aug. 32(8):379-85. [Medline].
Kershaw MJ, Newton T, Barrett TG, Berry K, Kirk J. Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases. Diabet Med. 2005 May. 22(5):645-7. [Medline].
Bhowmick SK, Levens KL, Rettig KR. Hyperosmolar hyperglycemic crisis: an acute life-threatening event in children and adolescents with type 2 diabetes mellitus. Endocr Pract. 2005 Jan-Feb. 11(1):23-9. [Medline].
Singhi SC. Hyperglycemic hyperosmolar state and type 2 diabetes mellitus: yet another danger of childhood obesity. Pediatr Crit Care Med. 2005 Jan. 6(1):86-7. [Medline].
Middleton P, Kelly AM, Brown J, Robertson M. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J. 2006 Aug. 23(8):622-4. [Medline]. [Full Text].
Bartoli E, Sainaghi PP, Bergamasco L, Castello L. Hyperosmolar coma due to exclusive glucose accumulation: recognition and computations. Nephrology (Carlton). 2009 Apr. 14(3):338-44. [Medline].
Bartoli E, Bergamasco L, Castello L, Sainaghi PP. Methods for the quantitative assessment of electrolyte disturbances in hyperglycaemia. Nutr Metab Cardiovasc Dis. 2009 Jan. 19(1):67-74. [Medline].
Rosa EC, Lopes AC, Liberatori Filho AW, Schor N. Rhabdomyolysis due to hyperosmolarity leading to acute renal failure. Ren Fail. 1997 Mar. 19(2):295-301. [Medline].
Kitabchi AE, Nyenwe EA. Hyperglycemic crises in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 2006 Dec. 35(4):725-51, viii. [Medline].
Munoz C, Villanueva G, Fogg L, et al. Impact of a subcutaneous insulin protocol in the emergency department: Rush Emergency Department Hyperglycemia Intervention (REDHI). J Emerg Med. 2011 May. 40(5):493-8. [Medline].
Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis?. Diabetes Care. 2008 Nov. 31(11):2081-5. [Medline]. [Full Text].