Devastating Effects of Combined DKA and Acute Pancreatitis in Select Patients: Two Cases

Abstract

Most cases of acute pancreatitis are routinely managed in the hospital without complications. However, management could become very complicated when patients present with a combination of acute pancreatitis and diabetic ketoacidosis (DKA). In fact, triad of acute pancreatitis, DKA, and hypertriglyceridemia in patients could result into systemic complications which may lead to fatal consequences. We report 2 cases in which patients presented with acute pancreatitis and DKA. Clinical course was complicated for both cases. While one of the patients expired, the other patient could not be extubated. This combination must be avoided at all costs because the clinical outcome for affected patients is difficult to predict.

Introduction

Acute pancreatitis (AP) is a leading cause of hospitalization in the United States. It is an inflammatory disease characterized with abdominal pain, nausea, vomiting, and elevated levels of pancreatic enzymes. Acute pancreatitis is caused by inappropriate activation of pancreatic enzymes and autodigestion. Most common etiology include alcohol abuse, gallstones, and hypertriglyceridemia. ¹ Meanwhile, bidirectional relationship between AP and hyperglycemia has been described. ² Acute pancreatitis triggered by any mechanism can result in beta cell dysfunction, transient insulin deficiency, and insulin resistance which can possibly trigger diabetic ketoacidosis (DKA).^3,4 Regardless of the mechanisms involved, the combined effect of DKA and AP in patient could lead to systemic insults which may be difficult to treat. We hereby report 2 cases underscoring the devastating effect of combined DKA and AP.

Case 1

A 46-year-old male with a past medical history of hypertension, type 2 diabetes, gout, gastroesophageal reflux disease (GERD), morbid obesity, obesity hypoventilation syndrome, and hepatic steatosis presented to the emergency department (ED) with altered mental status, generalized weakness, severe heartburn, chest tightness, and nausea. Physical exam was significant for agonal breathing; Glasgow coma scale was 3. Patient was immediately intubated and placed on mechanical ventilation for airway protection. Initial vitals showed tachycardia, tachypnea, low blood pressure, and low-grade fever. Labs revealed leukocytosis, elevated blood glucose, hyponatremia, hypocalcemia, low CO₂, elevated creatinine, positive acetone, lactic acidosis, high lipase level, and elevated triglycerides (see Table 1). Severe metabolic acidosis was seen on arterial blood gas (ABG; see Table 1). Urinalysis showed leukocyte esterase, nitrite, ketones, and hyaline casts. Bibasilar infiltrates and atelectasis were seen on chest x ray. Computed tomography (CT) abdomen and pelvis revealed fatty changes of the liver. Computed tomography head was unremarkable. Electrocardiogram (EKG) showed sinus tachycardia and prolonged PR interval. Patient was diagnosed with severe DKA, high anion gap metabolic acidosis (HAGMA), acute pancreatitis secondary to hypertriglyceridemia, acute kidney injury (AKI), and septic shock secondary to urinary tract infection (UTI). He was started on DKA protocol, intravenous (IV) fluids, bicarb drip, pressors, and broad-spectrum antibiotics. Hemodialysis was initiated for severe acidosis and anuria. Despite some improvement (Figures 1 and 2), neurological status remained the same and patient could not be extubated. He was transferred to “in network” hospital for further care.

Table 1.

Initial Laboratory Results of the Patients With Respective Reference Ranges.

Laboratory parameters	Case 1	Case 2	Reference range
WBC	15.8	20	4.8-10.8 × 103/uL
Hemoglobin	14.7	11.7	13.7-17.5 g/dL
Hematocrit	51.5	37.5	38.8%-50%
Platelets	207	391	150-4508 × 103/uL
Sodium	134	141	136-145 mmol/L
Potassium	6.6	4.8	3.5-5.3 mmol/L
Magnesium	2.7	1.8	1.5-2.5 mg/dL
CO2	7.1	5	20-31 mmol/L
BUN	44	13	6-24 mg/dL
Creatinine	2.6	1	0.6-1.2 mg/dL
Random blood glucose	863	512	70-140 mg/dL
Hemoglobin A1C	12.2	10.1	4.0%-5.6%
Serum lipase	34 385	1598	114-286 U/L
Triglycerides	681	151	0-150 mg/dL
HDL	13	36	>=40 mg/dL
C reactive protein	11.2	68	0.0-0.8 mg/dL
Ketone	2+	3+	Negative
Acetone	Positive	Positive	Negative
pH	6.87	7.16	7.35-7.45
PaCO2	35.5	15.1	35-45 mmHg
HCO3	6.3	5.3	22-26 mmol/L
Anion gap	20.9	24.7	8-16 mmol/L

Abbreviations: BUN = blood urea nitrogen; HDL = high-density lipoprotein; WBC = white blood cell.

Figure 1.

Rapid decline in lipase level following admission for Case 1.

Figure 2.

Changes in the patient’s arterial pH and serum glucose levels following admission for Case 1.

Case 2

A 63-year-old female with a past medical history of hypertension, type 2 diabetes, hyperthyroidism, homelessness, and polysubstance abuse presented to the emergency department (ED) with shortness of breath (SOB), generalized weakness, and vomiting. Initial vitals showed tachycardia, tachypnea, and elevated blood pressure. Physical examination revealed superficial ulcers on the right foot along with mild lower extremity edema. Labs revealed leukocytosis, very low bicarb, elevated blood glucose, high anion gap, positive acetone, and elevated lipase (see Table 1). Arterial blood gas was significant for metabolic acidosis (see Table 1). Electrocardiogram showed sinus tachycardia. Initial chest x ray showed mild left lower lobe atelectasis. Computed tomography abdomen and pelvis revealed minimal peripancreatic fat stranding consistent with acute pancreatitis. Patient was diagnosed with DKA, HAGMA, and acute pancreatitis. She was started on DKA protocol and admitted into intensive care unit (ICU). During the hospital course, patient went into cardiac arrest. She was resuscitated with cardiopulmonary resuscitation (CPR), epinephrine, and bicarb. Patient was intubated for airway protection, started on bicarb drip, and placed on pressors. Hypothermic protocol was initiated. Repeat chest x ray was significant for widespread pneumonic infiltrates. Vancomycin and Zosyn were started for possible pneumonia and septic shock. On completion of hypothermic protocol and resolution of DKA along with AP (Figures 3 and 4), patient remained obtunded and unresponsive when examined off sedation. Computed tomography head showed multiple infarcts in the bilateral cerebellum and pons of the brainstem. Multiple electroencephalogram (EEGs) showed some epileptiform activity and diffuse slowing; Keppra was added to treatment regimen. Hemodialysis was initiated by nephrology for uremia. Patient did not show any signs of neurological recovery despite intensive management and eventually expired.

Figure 3.

Rapid decline in lipase level following admission for Case 2.

Figure 4.

Changes in the patient’s arterial pH and serum glucose levels following admission for Case 2.

Discussion

Diabetic ketoacidosis, a serious complication of diabetes miletus, may occur at the time of diagnosis of diabetes or may be triggered by a variety of events including medication noncompliance, infection, trauma, and physiological stress. It is an acute metabolic derangement which is characterized by hyperglycemia, ketonemia, metabolic acidosis, and elevated anion gap. ⁵ While it is mostly seen in patients with type 1 diabetes due to absolute insulin deficiency, DKA may also occur in patients with type 2 diabetes due to relative insulin deficiency. ⁶ Meanwhile, in patients with poorly controlled blood glucose, DKA can trigger hypertriglyceridemia (HTG), a leading cause of AP. Consequently, a triad of DKA, HTG, and AP may coexist. This phenomenon was first described in 1997 as an “enigmatic triangle.” ⁷ Profound lack of insulin can increase lipolysis in adipose tissue with the release and delivery of free fatty acid (FFA) to the liver. This may result in production of high output of very-low-density lipoprotein (VLDL), which, when combined with the inhibition of lipoprotein lipase in peripheral tissues results into HTG. ⁸ Our first patient presented with this “enigmatic triangle” of DKA, HTG, and AP. And regardless of the association of AP with a triglyceride level over 1000 mg/dL, AP has been reported in patients with DKA and lower triglyceride levels. ⁹ Although our second patient has the history of type 2 diabetes, the presence of AP may further worsen insulin resistance and result into DKA. Acute pancreatitis triggered by any mechanism can result into beta cell dysfunction thereby causing transient insulin deficiency (T1DM) or insulin resistance (T2DM) thus possibly triggering DKA. ¹⁰ Both patients received insulin infusion and IV fluids with obvious resolution of DKA and AP. However, they were obtunded and could not be extubated. Concomitant presence of DKA and AP could result into devastating systemic complications and multiorgan failure which could complicate recovery despite intensive management. In addition to anoxic encephalopathy and uremia which were seen in these patients, pancreatic encephalopathy, a serious complication of severe acute pancreatitis is also a possibility and it may have worsened their prognoses.

Conclusion

Acute pancreatitis with DKA may have devastating consequences with undesirable outcome for patients. Clinical findings in these cases reinforce the need to adequately educate diabetic patients on strict glycemic control while avoiding various trigger for acute pancreatitis.