Volume I:
First Thirty Minutes
- Section 1
  Acute Care Algorithm/ Treatment Plans/ Acronyms
- Section 2
  Universal Approach
  - CALS Universal Approach To Emergency Advanced Life Support
- Section 3
  Steps 1-6
- Section 4
  Preliminary Impression/Focused Clinical Pathways
Volume II:
Resuscitation Procedures
Volume III:
Definitive Care

Endocrine and Metabolic 5: Hyperosmolar (Hyperglycemic) Non-Ketotic State Portal

Introduction

This condition is commonly referred to as hyperosmolar hyperglycemic non-ketotic coma (HHNC) and more recently as hyperosmolar nonketotic state (HNS). Typically, HNS is a complication of a type-2 diabetes hyperglycemic episode that is set off by some precipitating event and develops over days. HNS can occur in patients without a previous diagnosis of diabetes. HNS also can present as a mixed disorder, with components of diabetic ketoacidosis (DKA). Fluid intake is inadequate in the face of the ensuing osmotic diuresis. The resultant dehydration is severe, and the mortality is high.

Patient Assessment

History. Typically HNS occurs in geriatric patients and develops more insidiously than does DKA. CNS changes such as coma, confusion, hallucinations, and/or seizures are often present. Fever, thirst, polydipsia, and polyuria are common. A serious underlying disease is often the precipitating event. These diseases include infection, burns, MI, pulmonary emboli, stroke, pancreatitis, hyperthyroidism, GI bleed, renal disease, and others. Other precipitating causes include recent surgery, hyperalimentation, dialysis, and numerous drugs (mannitol, diuretics, steroids, propranolol, loxapine, diphenylhydantoin, diazoxide, propranolol, calcium-channel blockers, and cimetidine).

Exam. Most patients appear seriously ill, and severe dehydration is present. Hypotension is common, as is fever and tachycardia. Neurological signs are commonly present, such as altered mental status, seizures, transient hemiparesis, myoclonus, nystagmus, aphasia, and other deficits. The patient may have visual hallucinations. The precipitating event will add further findings to the exam.

Diagnostic Studies and Laboratory Findings. This type of clinical presentation generates a broad differential diagnosis with an extensive work-up: electrolytes, ABGs, serum osmolality, CPK, coagulation profile, cultures, urinalysis, chest x-ray, ECG, cranial CT, spinal tap, and other tests.

HNS Diagnostic Criteria: plasma osmolarity > 320 mOsm/L; serum glucose > 600 mg/dL (often around 1000); and little to no ketosis. Other criteria include pH around 7.3 and HCO₃- >15 (which can vary if this condition is ‘mixed’ with DKA).

Sodium may be high or low. Note that the osmotic effect of hyperglycemia influences the measured sodium value. The sodium value without this influence can be estimated by adding 1.6 mEq/L to the measured sodium value for every 100 mg/dL increase in serum glucose.

Total body potassium is likely to be low, whatever the initial serum value is; a low initial serum K+ is life threatening in this context. Compare measured osmolarity with calculated osmolarity ([2 x Na] + [glucose/18] + [BUN/2.8]). If the calculated value is significantly less than measured value, look for other substances, such as toxic alcohols.

Disease Management

Management of the HNS patient is similar in a general sense to managing a patient with DKA: the goal of treatment is to restore homeostasis while aggressively searching for and treating the precipitating cause(s).

Restoring Homeostasis.
Restoring homeostasis is based on rehydration, insulin therapy, and electrolyte replacement. Significant physiologic changes in circulating volume, blood sugar, and electrolytes can occur rapidly. It is easy to overshoot/overcorrect on any one of the treatment parameters, to the detriment of the patient’s clinical status. (See Complications, this portal.) Close monitoring and frequent assessment is needed to gauge treatment effects, plan further interventions, and prevent complications. Blood glucose levels may need to be initially monitored as often as every half-hour, electrolytes every hour. Less frequent lab tests are required as the patient improves. For these reasons, use flow sheets to help you closely monitor therapy until the patient stabilizes. Simultaneously treat and monitor the following interacting areas of concern:

Dehydration and Fluid Replacement. Mean fluid deficit is 9 to 10 L, and circulatory collapse is a common terminal event. Restoring circulating volume is the first priority. Consider placing a central line for CVP monitoring, especially in geriatric patients or patients with cardiovascular or renal complications. These patients need customized fluid flows. (Vol II—Circ Skills 3 Central Venous Pressure Measurement) Strict monitoring of input and output (I & O) is necessary and may require bladder catheterization. Although one size doesn’t fit all, consider initially giving 2 to 3 L of NS over 1 to 2 hours. Once the patient is stabilized (good BP and urine output), switch to 1/2 NS at a rate to restore 1/2 of the remaining fluid deficit over next 12 hours and the second 1/2 over the following 12 to 24 hours. Switch IV fluid to D5 1/2 NS once glucose falls to < 300 mg/dL.

Hyperglycemia and Insulin Therapy. Do not initiate insulin therapy until fluid therapy is begun and you have evidence that the kidneys are being perfused. In the absence of fluid therapy, insulin may contribute to circulatory collapse by taking away the osmotic support of glucose, water, and potassium from the already compromised circulating volume. Also, hold insulin therapy until hypokalemia is treated if it is initially present (see below).

HNS patients may be sensitive to exogenous insulin. On the other hand, obese patients may require larger doses. Set a target of 250 to 300 mg/dL. Consider a bolus of 0.1 U/kg IV. Start an infusion of 0.1 U/kg/h IV. Mix 100 U of regular insulin in 100 cc NS for a concentration of 1:1. Monitor glucose levels closely, adjusting infusion as needed to approach and maintain the target. Add dextrose to IV fluids once glucose falls to < 300 mg/dL. Do not discontinue the insulin drip until the patient has stabilized and improved, glucose levels have stayed within the 200 to 300 range for more than a day, and resources are in place to convert the patient to SQ insulin.

Electrolyte Disorders and Potassium Replacement. Hyperkalemia is often initially present. Monitoring the ECG for evidence of hyperkalemia is important if a serum level is unavailable. See Vol III—END/M7 Disorders of Electrolyte Concentration for ECG criteria and treatment of severe and symptomatic hyperkalemia.

As therapy begins and the dehydration and hyperglycemia improve, extracellular potassium moves into cells and the hypokalemic loss is unmasked. For this reason, most patients with moderate initial hyperkalemia who are receiving fluid and insulin therapy may be observed with serial K+ levels over several hours. Hold off on K+ replacement therapy until levels come down into the normal range (< 5 mEq/L). At that time, add up to 40 mEq K+ per liter to the IV that is dedicated to K+ replacement. For stable situations, a standard rate range is 10 to 20 mEq/h.

On the other hand, if the initial potassium is < or = 4.5 mEq, suspect severe K+ loss and begin replacement therapy as soon as it is established that the patient is making urine. (Remember: “no Pee = no K.”) This level of K+ loss may be life threatening and must be monitored closely with serum levels and cardiac monitoring as you are replacing it, using peripheral IV rates up to 40 mEq K+/hour total. (Never give K+ IV push.) Note that several IVs may be needed to customize therapy, as the K+ rate requirement may be too limiting a factor for the initially large intravenous fluid rate requirements.
In the rare case that the patient has significant initial hypokalemia, begin replacement therapy as soon as it is established that the patient is making urine BUT hold insulin therapy until K+ is restored to > 3.3 mEq/L in order to avoid adverse sequelae of hypokalemia: arrest, arrhythmia, respiratory muscle weakness.
PEDS note: Oral/NG liquid K+ replacement can supplement IV replacement therapy in severe cases of hypokalemia.
Patients with renal failure need even closer potassium monitoring. Other levels to monitor and replace if the patient has tetany include phosphate, magnesium, and calcium. See Vol III— END/M7 Disorders of Electrolyte Concentration for their considerations.

Precipitating Causes of HNS.

(Vol I—PATHWAY 1 Altered Level of Consciousness)

A common diagnostic trap is to assume that a certain aspect of the patient’s condition is due to HNS. For instance, is the altered mental status due to the hyperosmolar effects of HNS, or did a primary cranial/cerebrovascular event occur that precipitated this episode of HNS? Aggressive investigation is warranted in looking for treatable precipitating causes for HNS. Infection (the most likely cause) can be difficult to find in diabetics. If you suspect infection on clinical grounds, start empirical antibiotics without waiting for lab results. (Vol III—IN1 Adult Pneumonia)

Obtain CPK and its isoenzymes, as both MI and rhabomyolysis can be either a precipitating cause or a complication of HNS. Note that patients with diabetes can have silent MIs (no pain and no ECG changes), so obtain serial cardiac enzymes over the acute treatment period if the patient is old enough to have atherosclerotic disease and their serial ECGs are indeterminate or normal.

Complications
Close monitoring of the patient during the beginning and the initial phases of treatment cannot be overemphasized. Complications of (over)treatment are possible, such as CHF, pulmonary edema, hypoglycemia, hypokalemia, cerebral edema (rare), and seizures. Complications of the disease process include ischemia/infarction of target organs, thromboembolism, ARDS, DIC, and muti-organ dysfunction syndrome (MODS). See Vol I—PATHWAY 6 Adult Respiratory, #6 and Vol I—PATHWAY 6 Adult Respiratory, #10.

Consider subcutaneous prophylactic anticoagulant therapy in high-risk patients who don’t have contraindications to such therapy.

References