Management hyperglycemia (DKA/HHS) in ICU

byAbdelwahab Ward, BS Pharm, PharmD - last updated
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OVERVIEW ã…¡ Hyperglycemia is a common finding in critically ill patients with and without diabetes. However, hyperglycemic crisis is a medical emergency that frequently leads to ICU admission. Two syndromes have been described Diabetic ketoacidosis (DKA) and Hyperglycemic hyperosmolar syndrome (HHS). Although the treatment is similar. The most common cause of DKA/HHS is non-adherence to insulin therapy, but an infection, cardiac ischemia, trauma, or other acute illness can also be a trigger.

ASSESSMENT AND DIAGNOSIS

Diabetic ketoacidosis occurs in the face of insulin deficiency, usually in patients with type 1 diabetes, but has also been described in conjunction with use of sodium glucose cotransporter 2 (SGLT-2) inhibitors. Diabetic ketoacidosis is characterized by metabolic acidosis with an elevated anion gap due to excessive ketone (acetone, beta-hydroxybutyric acid, and acetoacetate) production from lipolysis. Measurement of beta-hydroxybutyric acid has been suggested for a specific diagnosis of ketoacidosis.

SYMPTOMS AND SIGNS ã…¡ Hyperventilation, hyperglycemia (glucose 500-800 mg/dL) cause intravascular volume depletion from osmotic diuresis, tachycardia, hypotension, shock, and confusion/coma. Hypokalemia may be masked by acidosis and extracellular potassium shift. A pro-inflammatory state is manifest and may contribute to complications such as venous thromboembolism or a sepsis-like picture. Metabolic acidosis [Mild acidosis (pH 7.25-7.3), Moderate (pH 7-7.24), Severe (pH < 7) with concurrent worsening of mental status].

          Patients with euglycemic DKA (glucose < 300 mg/dL) do not have elevated glucose concentrations but elevated ketones from relative insulin deficiency brought on by SGLT-2 inhibitor-induced glucosuria and reduced carbohydrate intake (often with an acute illness or surgery). Clinicians should be suspicious of this syndrome with growing utilization of these drugs presenting with metabolic acidosis. It may be prudent to discontinue use of SGLT-2 inhibitors several days prior to a planned surgery. Patients with HHS usually have only a mild acidosis (lactic or mild starvation ketosis) but:
      • More significantly elevated glucose levels (> 600 mg/dL).
      • More significant dehydration and hyperosmolarity (> 320 mOsm/kg).
      • Significant stupor or coma compared with DKA.

MANAGEMENT

FLUID + POTASSIUM + INSULIN ã…¡ The therapeutic goals of DKA management include optimization of volume status, hyperglycemia and ketoacidosis, electrolyte abnormalities and potential precipitating factors. The majority of patients with DKA present to the emergency room. Therefore, emergency physicians should initiate the management of hyperglycemic crisis while a physical examination is performed, basic metabolic parameters are obtained, and final diagnosis is made. Several important steps should be followed in the early stages of DKA management:
      • Collect blood for metabolic profile before initiation of intravenous fluids.
      • Infuse 1 L of 0.9% sodium chloride over 1 hour after drawing initial blood samples.
      • Ensure potassium level of > 3.3 mEq/L before initiation of insulin therapy (supplement potassium intravenously if needed).
      • Initiate insulin therapy only when steps 1–3 are executed.

The protocol for the management of patients with DKA is presented in (Figure 1). It must be emphasized that successful treatment requires frequent monitoring of clinical and metabolic parameters that support resolution of DKA (see Table 1).

Table (1). Checklist of DKA management milestones
Phase I (0–6 h) Phase II (6–12 h) Phase III (12–24 h)
Perform history and physical exam and order initial laboratory studies Continue biochemical and clinical monitoring Continue biochemical and clinical monitoring
Implement monitoring plan (biochemical and clinical) Change isotonic fluids to hypotonic fluids if corrected Na normal/high Adjust therapy to avoid complications
Give intravenous bolus of isotonic fluids If glucose is < 200–250 mg/dL, add dextrose to intravenous fluids Address precipitating factors
Start insulin therapy (after fluids started and only if K > 3.3 mmol/L) Adjust insulin infusion rate as needed If DKA resolved, stop intravenous insulin and start subcutaneous insulin
Consult diabetes team Maintain K at 3.3–5.3 mmol/L range Consult diabetes educator
Abbreviations: DKA, diabetic ketoacidosis; h, hours.

          FLUID REPLACEMENT ã…¡ Immediate resuscitation with crystalloid fluids (0.9% NaCl or Ringer’s lactate) is needed, based on the degree of hypotension, with ongoing fluid replacement to correct the 10 to 12 L potential deficit using hypotonic fluid unless the corrected sodium deficit is severe (Figure 1). Hydration alone improves glycemic control and acid–base balance. A recent review concluded that data are insufficient to recommend one crystalloid over another, although balanced salt solutions are favored in most critical care patients. While sodium chloride solutions may increase the risk of hyperchloremia and a lower urine output, addition of potassium and dextrose can be done more readily. In one small study, use of Ringer’s lactate was associated with a longer time to achieve glucose control in DKA perhaps related to lactate serving as a substrate for gluconeogenesis, but there was no difference in time to closure of the anion gap.

INSULIN REPLACEMENT ã…¡ Is not geared toward normalization of glucose, rather to replace a basal insulin deficit. A fixed rate of infusion is preferred to titrated insulin using 0.1 U/kg/h with an optional intravenous bolus of 0.1 U/kg for obese or significantly insulin-resistant patients. An infusion of 0.14 U/kg/h without a bolus dose has also been suggested. Preparation of the intravenous tubing by flushing an extra 20 mL of the insulin infusion has been suggested to saturate insulin-binding sites and maximize insulin delivery. The maintenance fluid should include dextrose 5% once the glucose level has fallen to below 250 mg/dL in DKA and 300 mg/dL in HHS to protect against hypoglycemia and osmotic shifts (Figure 1). Insulin resistance may be reduced with resuscitation and falling glucose levels, necessitating a reduction in insulin infusion rate to 0.05 U/kg/h or increase in glucose dose. Patients with hyperglycemia typically have low sodium levels reported due to a lab anomaly. The reported serum sodium should be increased by 2.4 mEq/L for each 100 mg/dL elevation in glucose above normal. Sodium bicarbonate is only used for severe acidosis (pH < 6.9), as ketones will be metabolized to bicarbonate. Potassium is replaced acutely, prior to any insulin therapy, if the level is less than 3.3 mEq/L, and should be added to maintenance fluids if the level is less than 5.3 mEq/L and urine output is adequate (more than 0.5 mL/kg/h).

ELECTROLYTE REPLACEMENT ã…¡ Additional electrolyte replacement is typically needed, so phosphorus and magnesium should be monitored routinely. Insulin and dextrose combine to shift phosphorus intracellularly, so levels less than 1.5 mg/dL warrant therapy to prevent severe hypophosphatemia and muscle weakness or injury. Magnesium therapy should be individualized based on concentrations and potential for arrhythmias. Subcutaneous insulin may be prescribed for the management of DKA in patients with uncomplicated cases using lispro insulin (Humalog) 0.3 U/kg followed by 0.1 U/kg administered hourly in non-ICU settings.Subcutaneous insulin therapy in conjunction with a DKA protocol did not produce comparable patient outcomes compared with intravenous insulin but was significantly less costly for patients who were not persistently hypotensive, comatose, and did not have complications such as myocardial infarction, heart failure, end-stage renal disease, or dementia.


          Studies in children and adults have also examined the potential utility of early treatment with glargine insulin (Lantus), concurrently with insulin infusion. A pilot study using insulin glargine 0.3 U/kg subcutaneous within 2 hours of the initiation of insulin infusion demonstrated safety and similar outcomes. The Joint British Diabetes Societies guideline expert opinion suggests that home basal insulin be continued throughout insulin infusion therapy in DKA to minimize rebound hyperglycemia after the infusion. Typically, in the United States, transition to a basal and bolus insulin regimen is done after the anion gap has closed in DKA or after rehydration, glycemic control, and osmotic stabilization in HHS. The basal insulin is ideally given 2 hours prior to stopping the infusion to account for time to onset of action and avoid rebound hyperglycemia or recurring ketosis. In HHS, mental status may take quite a bit longer to normalize. A patient who remains unstable may be transitioned to a titrated insulin infusion for ongoing management.

Osmotic shifts are an important consideration in DKA or HHS and renal failure. Hemodialysis will lower both the glucose and blood urea nitrogen, potentially causing significant osmotic shifts and a more rapid decline in glucose concentration than with insulin alone. Although cerebral edema is reported in children more than adults, this catastrophic adverse effect is a potential with concurrent therapies. Further, dialysis patients will not need the same degree of fluid and potassium repletion, so treatment should be individualized.

REFERENCES

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