Which findings are associated with DKA?

Type 1 Diabetes Mellitus [Without Ketoacidosis or After Ketoacidosis Has Resolved]

Insulin is the mainstay of treatment for T1DM. Intensive insulin therapy has become the standard of care for patients with T1DM. Typically a long-acting basal insulin—such as glargine [Lantus, Toujeo, Basaglar], detemir [Levemir], or degludec [Tresiba]—along with premeal boluses of rapid-acting insulin—such as lispro [Humalog, Admelog], aspart [NovoLog, Fiasp], or glulisine [Apidra]—is instituted.

Required total daily insulin dosing [TDD] is dependent on age at presentation, pubertal stage, and the presence of acidosis at diagnosis. Total daily insulin requirements range from about 0.25 to 1.0 U/kg per day [Table 1]. Long-acting or basal insulin is typically 50% of TDD; the remaining 50% is bolus insulin. Bolus rapid-acting insulin dosing is calculated by the following formulas [Fig. 1]:

To cover meal carbohydrates, acarbohydrate ratio is derived from the formula

500 divided by total daily insulin dose

To correct hyperglycemia, acorrection factor is derived from the formula

1500 divided bytotal daily insulin dose

Correction doses should not be given more frequently than every 3 hours.

For new-onset patients, atarget glucose of 150 mg/dL is assigned, whereas more established patients typically use 120 mg/dL. Correction at bedtime or during the night should be less aggressive and a higher target may be assigned—for example, 150 to 200 mg/dL.

Carbohydrate ratios, correction factors, and targets are adjusted on the basis of fasting and postprandial glucose levels. High postprandial glucose levels would require a lower carbohydrate ratio. High blood glucose levels that do not correct after a correction dose has been given would require a lowering of the correction factor. High morning fasting glucose levels would require an increase in the long-acting insulin dose.

Implicit in these recommended treatment regimen is that [1] the patient or family is able to count carbohydrates correctly, and [2] the family is able to calculate insulin dosing correctly using the carbohydrate ratio, correction factor, and target. If the patient or family is unable or unwilling to perform these calculations a simplified insulin regimen should be devised using fixed doses of intermediate-acting insulin and a sliding scale of rapid-acting insulin.

Less complex insulin regimens include NPH and rapid-acting insulin given at breakfast, dinner, and bedtime [Fig. 2]. NPH and rapid-acting insulin are given at breakfast [no insulin at lunch if glucose 200 to 300 mg/dL] and base deficit of −4 mEq/L or greater.

As many as one-third of patients in the early or very late stages of DKA have initial blood glucose levels lower than 200 mg/dL. A pregnant diabetic patient with a history of poor food intake or vomiting for longer than 12 to 16 hours should have a thorough workup for DKA, including a complete blood cell count and electrolyte determinations. A serum bicarbonate level lower than 18 mg/dL or an anion gap exceeding 10 to 15 mEq/L should prompt performance of an arterial blood gas analysis. In all cases of DKA, the diagnosis is confirmed by arterial blood gases demonstrating a metabolic acidemia with base excess exceeding −4 mEq/L.80

Table 59.4 contains a protocol for treatment of DKA. The important steps in management include the following:

Search for and treat the precipitating cause. Typical initiators include pyelonephritis and pulmonary or gastrointestinal viral infections.

Perform volume resuscitation that is both vigorous [3 to 4 L of physiologic intravenous fluid over the first 2 hours] and sustained [a total of 6 to 8 L is frequently required over the first 24 hours]. The patient will continue to generate vascular volume deficits until her glucose levels and acidosis are largely resolved. A physiologic fluid such as 0.9% NaCl or lactated Ringer solution should be used and continued until the acidosis is substantially corrected. Potassium chloride should be added to the infusate when the plasma potassium level nears the lower limit of normal.

Use insulin to correct hyperglycemia. Although intermittent injections may be used, a continuous infusion of regular or short-acting insulin [i.e., lispro or aspart] allows frequent adjustments. When given as a continuous infusion, insulin 1 to 2 U/h gradually corrects the patient's glucose abnormality over 4 to 8 hours. Attempts to normalize plasma glucose levels rapidly [i.e., in less than 2 to 3 hours] may result in hypoglycemia and physiologic counter-regulatory responses.

Monitor serum bicarbonate levels and arterial blood gas base deficits every 1 to 3 hours to guide management. Even after the plasma glucose level is normalized, acidemia may persist, as evidenced by continuing abnormalities in the patient's electrolyte concentrations. Unless volume therapy is continued until the patient's electrolyte stores and plasma concentrations have substantially returned to normal, DKA may reappear, and the cycle of metabolic derangement will be renewed.

Epidemiology

Diabetic ketoacidosis [DKA] classically occurs in patients with type 1 diabetes mellitus but may also occasionally develop in patients with type 2 diabetes. Type 1 diabetes refers to insulin deficiency due to autoimmune destruction of the insulin‐producing beta‐cells of the pancreas. In the past, type 1 diabetes was called “juvenile” or “insulin‐dependent” diabetes. However, these terms are no longer used because this disease can present at any age [patients in their 80s can develop type 1 diabetes], and patients with type 2 diabetes can also be “insulin‐dependent.” Type 2 diabetes accounts for more than 90% of all cases of diabetes, and it is characterized by relative insulin deficiency and insulin resistance. Type 2 diabetes has been called “non‐insulin dependent” or “adult‐onset” diabetes, but these terms are also outdated since these patients usually become insulin‐dependent as their disease progresses and are presenting at younger ages [even in childhood] because of the increasing obesity epidemic.

The incidence of DKA is 46 to 80 per 10,000 person‐years among patients with diabetes, and the estimated mortality rate of DKA is 4% to 10%. Only 20% of DKA episodes occur in patients with new‐onset diabetes. Furthermore, 20% of patients with DKA have multiple annual episodes. Therefore, patient education and compliance are crucial for reducing the incidence of DKA.

Pathophysiology

Diabetic ketoacidosis occurs when cellular energy needs cannot be met by glucose supplied by an insulin-requiring transport mechanism. The body then must use fat stores as energy. The two major components of DKA are [1] hyperglycemia caused by inability of glucose to cross the cellular membrane when insulin is inadequate and [2] acidosis caused by the metabolic products of fat oxidation as the body is forced to change its energy source. Thus it follows that not all hyperglycemia results in ketoacidosis if the relative amount of insulin available is sufficient to meet cellular energy needs but is insufficient to facilitate cellular uptake of enough glucose from the plasma and tissue compartments to achieve normoglycemia. Ketoacidosis without hyperglycemia is possible if the body uses fat as an energy source in the face of relatively little glucose delivered to the plasma and tissue compartments. This can occur under circumstances of nausea, vomiting, and reduced intake. In general, however, counterregulatory hormones [cortisol, growth hormone, glucagons, catecholamines] produce hyperglycemia even with relatively limited intake if insulin is inadequate.

Table 71-2 lists the mechanism of action on blood glucose of hormones that are believed to contribute to metabolic decompensation in DKA. It is important to note that the effects of all these hormones together is greater than the sum of individual effects in the experimental situation. The relative contributions of each of these hormones to the metabolic decompensation of DKA under facilitative precipitating conditions cannot be determined with any accuracy by measuring the hormones. Counterregulatory hormonal contribution to emotionally or psychologically precipitated DKA is poorly understood.

Figure 71-1 depicts the metabolism of glucose and pathway leading to ketoacid production [Chapter 67]. The most relevant ketones produced are β-hydroxybutyrate, acetoacetate, and acetone. Under fasting conditions and under conditions of acidosis, formation of β-hydroxybutyrate is favored over acetoacetate causing significant increases in the ratio between the two compounds. Because the common urinary test for ketones measures primarily acetoacetate, this test can significantly underestimate the ketoacid burden. Although urine test may be useful for monitoring, serum ketones are more helpful for quantitative purposes.

Figure 71-2 shows the basic pathophysiology of DKA through effects of insulin deficiency on tissue metabolism that result in the observed signs and symptoms of DKA.

In addition to ketoacidosis, lactic acidosis may be present if there is significant dehydration and resultant poor tissue perfusion. If acidosis is present, there is often a compensatory respiratory alkalosis accompanied by the classic deep respirations through pursed lips described as Kussmaul respirations.

The absolute and relative fluid and electrolyte deficits of patients with DKA can be calculated in a number of standard ways. Table 71-3 lists the ranges of expected fluid and electrolyte deficits. It is important to recognize that observed hyponatremia in patients with DKA reflects not only sodium deficits but factitious measurement caused by hyperglycemia and hyperlipidemia. The observed sodium can be corrected for this artifact by the following formula:

Na+corrected=Na+observed+[[Glucosein mmol/L-5.6]/5.6]×1.6.

or

Na+corrected=Na+ observed+[[Glucoseinmmol/L-5.6]/5.6]×1.6.

Case 1: Diabetic Ketoacidosis

A 37-year-old G5P3 presented at approximately 31 weeks of gestation complaining of nausea, vomiting, diarrhea for 2 days, and decreased fetal movement followed by no fetal movement for 24 hours. She gives a history of only one prenatal visit, and no previous prenatal blood work.

She was admitted with diagnosis of gastroenteritis with dehydration. On admission, the patient was dizzy and tachypneic with a respiratory rate of 26 beats per minute [bpm]. Her temperature was 98.6° F, pulse was 127 bpm, and blood pressure of 124/80 mm Hg.

Laboratory blood tests revealed a glucose level of 983 mg/dL, K+ of 5.3 mEq/L, anion gap of 34, and creatinine of 1.8 mg/dL. A complete blood count and platelet count were normal. Arterial blood gas revealed a pH of 7.26, a bicarbonate of 13 mEq/L, and base excess of −11.2. Serum and urine ketones were positive. Electrocardiogram [ECG] revealed sinus tachycardia. Fetal heart rate monitoring revealed absent accelerations, absent variability and presence of spontaneous decelerations [Fig. 12-1A]. Ultrasound examination revealed normal fluid and a biophysical profile [BPP] of 2/10.

A diagnosis of DKA was made, and the patient received 15 µ of regular insulin as a loading dose followed by continuous IV infusion at a rate of 10 µ/hr. She also received large doses of fluids [4 L of normal saline during first 5 hours] and potassium replacement. After control of plasma glucose levels and correction of maternal acidosis and electrolytes, fetal heart rate tracing continued to be nonreassuring [see Fig 12-1B] and repeat BPP was still 2/10. Despite that, delivery was not performed. Over the next several hours the fetal tracing continued to be nonreassuring and was followed by reduced base line and repetitive decelerations [see Fig. 12-1C]. Umbilical artery Doppler revealed absent diastolic flow, BPP was still 2/10. A decision for cesarean section was made, but the fetus died 20 minutes after the last testing and the patient underwent induction of labor with subsequent vaginal delivery of a stillborn fetus weighing 2000 g.