Insulin
As previously noted, insulin therapy is required to treat hyperglycemic crises from DKA and HHS. In DKA there is an absolute insulin deficiency, whereas in HHS, there is a relative insulin deficiency. In HHS, there is not enough endogenous insulin to move glucose into the cells, but there is enough insulin to block a catabolic state. That is why the breakdown of fats and proteins does not occur, and why ketoacidosis and hyperkalemia are not seen in HHS. On the other hand, glucose elevations do occur, and are usually more extreme in HHS than DKA. There are five major therapeutic actions of insulin in DKA (Table 5), and it is imperative to determine serum potassium before starting an insulin infusion as insulin will drive potassium into the cell, worsening hypokalemia and promoting the development of life-threatening arrhythmias, including ventricular fibrillation, ventricular tachycardia, and torsades de pointes. The electrocardiogram does not accurately predict severity of hypokalemia and should not be used as a substitute for direct potassium measurement.
Loading Dose and Drip Rate. When treating adult patients with DKA or HHS, the ADA recommends an IV push loading dose of 0.1 U/kg insulin, followed by an hourly maintenance dose of 0.1 U/kg. Alternatively, a continuous infusion of 0.16 U/kg/hr can be used without a bolus. The rationale behind a bolus is the rapid saturation of insulin receptors, followed by a drip to maintain saturation of receptors. However, a recent prospective observational cohort study by Goyal et al15 questions the utility of the initial insulin bolus. The study compared DKA patients who received an initial insulin bolus to those who did not. Both groups were similar at baseline and received equivalent IV fluids and insulin drips. They found no statistically significant differences in the incidence of hypoglycemia, rate of serum glucose change, anion gap change, or length of stay in the ED or hospital. The authors concluded that administration of an insulin bolus has no significant benefit to patients and does not change clinically relevant end-points.15 At this time, there is no proven benefit to giving DKA patients an IV insulin bolus; moreover, doing so may further increase hypoglycemia. The use of an insulin bolus is particularly not recommended for use in pediatric patients with DKA due to a higher incidence of hypoglycemia in this patient population.16
As with DKA, the ADA3 recommends giving HHS patients an insulin bolus of 0.1 U/ kg followed by a continuous infusion at 0.1 U/kg per hour. It is crucial to monitor patients closely to ensure glucose levels do not fall too rapidly. Glucose levels should be kept between 150 to 200 mg/dL for patients with DKA and 200 to 300 mg/dL for patients with HHS until the conditions resolve; this may necessitate lowering the infusion rate to 0.02 to 0.05 U/kg per hour. In addition to frequent glucose monitoring, a basic metabolic panel and venous pH should be obtained every 2 to 4 hours while a patient is on an insulin drip.3
Subcutaneous Vs Intravenous Insulin for DKA. Several small studies evaluating patients with mild-moderate DKA demonstrated similar outcomes when subcutaneous (SQ) insulin was used instead of IV insulin. However, SQ injections require more frequent dosing (every 1 to 2 hours) and still require close monitoring of blood glucose. This monitoring frequency is usually not feasible on a hospital floor, but may be feasible on step-down units, thus avoiding admission to the intensive care unit (ICU) for patients who do not otherwise require ICU-level of care.17 Subcutaneous insulin should not be given to patients with severe acidosis, hypotension, or altered mental status. The ADA consensus statement continues to recommend IV infusion of regular insulin as the preferred route due to its short half-life and easy titration.3
Determining When to Switch to Subcutaneous Insulin. Ideally, patients are not in the ED long enough to have their metabolic abnormalities corrected, as this usually requires several hours. In DKA, the insulin drip should continue until the blood glucose is less than 200 and at least two of the following conditions are met: the anion gap is less than 12, venous pH greater than 7.3, and serum bicarbonate >15. In HHS, osmolality and mental status should both return to normal prior to stopping the infusion. In both cases, subcutaneous insulin should be administered at least 1 to 2 hours before stopping the drip to prevent recurrent crisis.1,3
Refractory Acidosis. First and foremost, refractory acidosis should prompt a diligent source for dead gut, abscess, and underlying sepsis. While vomiting and diffuse abdominal pain are common in DKA and are related to ketoacidosis, these symptoms are atypical of HHS and should raise suspicion for underlying pathology.3 Additionally, a lower than expected bicarbonate level can also occur from resuscitation with large volumes of normal saline, resulting in a hyperchloremic non-gap metabolic acidosis.