BY SAAD CHAUDHRY; CHI ZHANG; AHMED RAZIUDDIN, MD
A 62-year-old tall, thin African American man presented to the emergency department after four days of constipation and vomiting. He had decreased mental status, and was unable to provide a complete medical background. His spouse reported that the patient had diffuse abdominal pain for the past four days, and had been experiencing increased thirst and excessive urination for the past four weeks.
She reported that the patient was unresponsive to over-the-counter laxatives and had been unable to produce bowel movements. The patient had no prior abdominal surgery, medication use, or primary care visits. The patient used to be a 20-pack-a-year smoker, but he had quit smoking almost 10 years earlier. The patient also had shortness of breath for the past day but no fever, chills, or chest pain.
Patient's vital signs had a blood pressure of 150/77 mm Hg, heart rate of 58 beats/minute, temperature of 98.1°F, and oxygen saturation of 99%. The patient later admitted to drinking two cans of beer a day and smoking marijuana habitually, but denied any family history of diabetes or hypertension.
The patient appeared lethargic during the physical exam. He also had rapid deep breathing that required increased respiratory efforts. Vesicular breath sounds were heard bilaterally with the use of accessory muscles observed. The abdominal exam revealed a diffusely tender abdomen on palpation. There was no guarding, rebound tenderness, or organomegaly. Bowel sounds were present but hypoactive.
Multiple finger stick glucose tests revealed levels exceeding the instrument's testing parameter of 500 mg/dL; later laboratory testing confirmed the actual glucose value to be 1,750 mg/dL. In the first hour of the patient's ED visit, laboratory studies ordered included comprehensive metabolic panel (CMP), serum troponin I, lactic acid, complete blood count (CBC), ketone panel, serum lipase, arterial blood gas (ABG), and an electrocardiogram (ECG). (Table 1.) The ECG revealed sinus tachycardia with an atrial rate of 104, a long QT interval, and a right bundle branch block.
The patient soon became more lethargic, and was immediately given a 1,000 mL intravenous bolus of normal saline (0.9% sodium chloride) for his dehydration. To alleviate nausea and vomiting and to prevent any complications of acid reflux, the patient was given 4 mg IV-push ondansetron and 20 mg IV-push famotidine. One hour after the initial medications were given, another round of 1,000 mL normal saline and 4 mg ondansetron was given IV-push. A rectal temperature taken two hours after admission to the ED revealed a core body temperature of 97.2°F.
After the first round of labs, 50 mEq sodium bicarbonate IV-push was given to the patient to help reduce his acidotic state. A 2,000 mL IV saline bolus was given to further assist with his dehydration. To decrease his hyperglycemia, the patient was given 8 units of regular insulin and started on an insulin drip at a rate of 6 units/hour. Additionally, 3.375 grams IV-piggyback (PB) of piperacillin/tazobactam and 1 gram IV-PB of vancomycin was given to prevent any bacteremia or infection. Another 30 grams of Kayexalate (sodium polystyrene sulfonate) at a concentration of 15g/60mL were also given to help adjust electrolyte imbalance caused by pseudohyperkalemia.
The patient's condition further deteriorated in the third hour. IV medications were ineffective in preventing the patient's lapse into a diabetic coma due to the severity of the patient's hyperosmolar state at admission. The patient became unresponsive to auditory stimuli and could be aroused only by a sternal rub. A finger stick glucose test was repeated, and the patient's results still exceeded the testing parameters of the instrument. Unable to accurately assess the patient's true glucose value by point-of-care testing, efforts were then focused on stabilizing the patient's vital signs. The patient's condition remained stable but unimproved.
Just as the patient lapsed into a diabetic coma during the fourth hour, his body temperature dropped abruptly. Rectal thermometer revealed a decrease in core body temperature from 96.2°F to 92.0°F within one hour. (Table 2.) Warming blankets were promptly applied; blood culture, urine culture, urinalysis, and urine microscopy were ordered to rule out other organic causes of hypothermia.
Two hours after the blankets were applied, the patient's temperature increased to the normal baseline at 98.5°F, and the patient awoke and muttered under his breath about excessive warmth. The blanket was disconnected and reapplied in intervals to stabilize the patient's body temperature.
A new set of labs was drawn during the 11th hour, and the patient was transferred to the ICU for further management. After three hours of continuous ICU care, the patient was finally stabilized and regained full consciousness.
Etiology and Presentation
Diabetic ketoacidosis (DKA) and hyperosmolar state (HSS) are major acute complications in patients with diabetes mellitus, and both may occur in patients with type 1 or type 2 diabetes. (Diabetes Care 2004;27 Suppl 1:S94.) Risk factors include infection, alcohol abuse, pancreatitis, myocardial infarction, trauma, drugs, and selective racial backgrounds. African Americans and Hispanics are at the greatest risk of developing acute diabetic complications. (Ann Intern Med 2006;144:350.)
DKA and HSS occur due to the absence or deficiency of the net effective concentration of insulin. Dysfunction of the insulin pathway shifts body metabolism toward lipolysis. Breakdown of lipids increase ketone serum concentration, which, along with elevated serum glucose, results in classic DKA/HSS signs and symptoms such as nausea, vomiting, abdominal pain, polyuria, polydipsia, Kussmaul breathing, and altered mental status. (Robbins and Cotran Pathologic Basis of Disease, 9th Edition. Philadelphia: Elsevier; 2015.) The basic pathophysiology of both conditions can be seen as a consequence of osmotic diuresis due to hyperglycemia. (Diabetes Care 2004;27[Suppl 1]:S94.)
A significant number of patients present with DKA as the initial symptom of diabetes mellitus because they do not seek medical care for the initial polyuria and polydipsia. (Diabetes Spectrum 2002; 15: 28.) Many of these patients are older than the average age of diabetes patients, especially among African Americans. In fact, a community study has determined that more than 40 percent of DKA patients were over age 40, and as many as 20 percent of DKA patients were over age 55. (Arch Intern Med 1997;157:669.)
The mortality rate for DKA is about five percent, while the mortality for HHS is around 15 percent; both conditions are significantly more severe in those over age 65 and in the presence of diabetic coma. (Diabetes Care 2004;27[Suppl 1]:S94.) Most DKA patients have type 1 diabetes, but a subset of patients with type 2 diabetes are afflicted with “ketosis-prone” diabetes, which account for 20-50 percent of all DKA patients. These patients are usually obese, elderly, male, and African American or Hispanic. (Ann Intern Med 2006;144:350.)
The most common electrolyte imbalance in DKA is the phenomenon of pseudohyperkalemia. Two mechanisms falsely elevate serum potassium in diabetic patients. Insulin directly stimulates the sodium-potassium ATPase pump, so insulin deficiency causes a predictable decrease in the driving force of extracellular potassium intracellularly, resulting in potassium accumulating extracellularly. Acidosis stimulates the exchange of intracellular potassium with extracellular protons. An elevated potassium value in laboratory tests is, therefore, considered “normal” in DKA/HSS patients because it is a compensatory physiological mechanism.
If such patients were to present with potassium in the ranges of 3.5-5.5 mEq, they should promptly receive potassium infusion because they actually are suffering from hypokalemia. DKA/HSS patients with low body temperature, however, may also present with low to normal potassium due to hypothermia and the subsequent induction of hypokalemia. (Mil Med 1998;163:719.) This patient's inability to produce a bowel movement, even with the aid of laxatives, was most likely due to his intrinsic hypokalemic state.
Complications and Coma
Hypothermia is a reduction in core temperature below 95°F (35°C), with the most accurate reading taken by rectally. (Med Sci Law 1969;9:231.) Hypothermia can be caused by starvation, malnutrition, immobility, myocardial infarction, pulmonary embolism, and endocrine disorders such as hypopituitarism and hypothyroidism. A British study determined that DKA-induced hypothermia (11.8% of all cases of hypothermia admissions) is more common than hypothyroidism-induced hypothermia (8% of all cases of hypothermia admissions). (Br Med J 1978;2:1387.)
Hypothermia is the result of severe decompensation during hypoglycemia as well as lactic acidosis. The main mechanism of decreased body temperature in DKA/HSS is due to impaired metabolism of glucose to produce heat. Diabetic Kussmaul breathing impairs adequate oxygen intake, further contributing to the development of hypothermia because oxygen is needed for thermoregulation. Hypothermia results in suboptimal conditions for insulin to function, another detriment to the body's attempt to re-establish homeostasis. (Recent Advances in Medicine. London: Churchill; 1968.) The tendency of diabetic patients to experience hypothermia produces a vicious cycle that exacerbates hyperglycemic states and induces severe diabetic coma in susceptible patients.
Treatment and Prognosis
As many as 25 percent of elderly patients above age 65 suffer from diabetes mellitus (Centers for Disease Control and Prevention. National Diabetes Fact Sheet, 2011), and the management protocol for these patients was created in 2012 by the American Diabetes Association (ADA). Late presentation of diabetes mellitus is positively correlated to the likelihood of developing ketosis-prone diabetes or latent autoimmune diabetes of the adult (LABA). (Diabetes Care 2001;24:1460.) Depending on the patient population, LABA could account for a large portion of diabetic patients, and this proportion is magnified in the elderly. To aid in diagnosis, further testing such as detection of glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulinoma-associated (IA-2) autoantibody, and zinc transporter autoantibody (ZnT8) as well as low C-peptide levels are required. (Diabetes Care 2012;35:2650.) GAD is absent (patients with Aβ+ phenotype) in many African American patients with LABA, and should not be used to rule out ketosis-prone diabetic presentations in African Americans. (Diabetes Care 2009;32:1335.)
Diabetic ketoacidosis is managed with multiple IV medications and saline aimed at reducing symptoms of dehydration, hyperglycemia, and electrolyte imbalance. The most crucial therapies are normal saline at a rate of 1 to 1.5 L/hour and insulin at 0.14 units per kilogram of body weight per hour (approximately 10 units per hour in a 70kg patient). (Diabetes Care 2009;32:1335.) Uncomplicated DKA may be reversed when patient's pH is greater than 7.3 with a glucose level of 200 mg/dL, and bicarbonate levels greater than 18 mmol/L. These patients may be discharged and managed at home with prescribed insulin. (Emerg Med 2015;47:410.) If DKA does not resolve with treatment, further care should be aimed at reducing comorbid precipitating events and complications such as hypokalemia and hypothermia.
Uncomplicated and complicated DKA carry significant mortality risk, with complicated DKA more likely to occur in the elderly. Both conditions may adversely contribute to long-term complications such as diabetic retinopathy and nephropathy. African American and Hispanic patients with LABA belong to a particularly high-risk patient group because there is no accurate method of expressing how long their condition has existed. Hemoglobin A1c (HgbA1c) is often used as a prognostic tool in determining long-term complications in these patients. HgbA1c's predictive value for risk of long-term diabetic complications tapers off at around 65 years of age, and further glycemic control as monitored by this index does not significantly improve patient's quality of life. (Clin Diabetes 1999;17.)
This case demonstrates the severity of DKA in a patient who has never experienced any symptoms of diabetes mellitus before his ED visit. Prompt diagnosis and proper management of the patient yielded favorable results with reversal of DKA, despite the patient's temporary hypothermic event. Treatment of DKA includes IV therapy of fluids and insulin to improve hydration and electrolyte balance, as well as management of potential hypothermia. Diligent monitoring of patient laboratory values and vital signs allows clinicians to take prompt measures that will minimize the damage caused by DKA before restoring the patient to normal functional status.
Diabetes mellitus can occur in any patient, and the onset can occur at any age, though the average age of onset for diabetes mellitus is 45 to 64. (Centers for Disease Control and Prevention, National Diabetes Statistics Report, May 15, 2015.) The patient in this case was 62. A late presentation suggests a diagnosis of ketosis-prone latent autoimmune diabetes of adults (LADA) or type 1.5 diabetes mellitus, but confirmatory testing is required for definitive diagnosis and proper long-term management of such patients.