Rehydration interrupts the cycle of hyperglycemia and hypovolemia by restoring lost intravascular volume, increasing renal perfusion, improving glomerular filtration rate, and reducing glucosuria. Improved systemic perfusion decreases the release of counter-regulatory hormones such as catecholamines, cortisol, glucagon and growth hormone, which exacerbate hyperglycemia. Finally, rehydration decreases the peripheral insulin resistance that is caused by the hyperosmolar state [7]. The American Diabetes Association consensus statement for Hyperglycemic Crisis recommends isotonic saline (0.9 % sodium chloride) at a rate of 15–20 ml/kg body weight (wt) within the first hour [1]. Additional fluid therapy should be adjusted based on hemodynamics, sodium status and urinary output. Fluid deficits should be restored within 24 h. The free water deficit (FWD) may be calculated using the corrected serum sodium, and provide some guidance for free water repletion (Table 50.2). The importance of prompt fluid hydration is supported by the fact that normalization of the hyperosmolar state results in a more robust response to low-dose insulin therapy [7].

Current treatment protocols recommend starting either with an insulin IV bolus of 0.1 units/kg body wt followed by 0.1 units/kg/hour(h) infusion or 0.14 units/kg body wt/h continuous infusion [1, 8]. The low dose infusion rates are based on randomized controlled studies for DKA that showed low-dose or physiological insulin performed similarly to high dose insulin in terms of rate of resolution of hyperglycemia as well as reduction in counter-regulatory hormones, and had lower incidence of hypoglycemia and hypokalemia [9, 10]. A more recent study demonstrated that giving an initial insulin bolus prior to starting a continuous infusion, normalized blood glucose, pH and bicarbonate levels just as quickly as providing a continuous infusion at a slightly higher rate of 0.14 units/kg/h [11]. Therefore, solely providing a continuous infusion rate is equally recommended. If the glucose level does not decline by 10 % in the first hour, it is recommended to bolus 0.14 units/kg body wt and to continue infusion at the previous rate. Once the blood glucose reaches 300 mg/dL, the insulin infusion rate should be lowered to 0.02–0.05 units/kg body wt/h and supplemental dextrose infusion should be given to maintain blood glucose between 200 and 300 mg/dL until the patient’s mental status normalizes. This last step is a safeguard against the physiological threat of cerebral edema that may result from the rapid correction of serum hyperosmolality. With insulin treatment, brain osmolality decreases at a rate significantly slower than plasma, and there is a net movement of water into the brain [2]. Oftentimes, patients with HHS will present with a milder form of the metabolic derangements of DKA. These patients should also continue treatment with simultaneous dextrose and insulin infusion until ketogenesis ceases and anion gap acidosis resolves.