Stress-induced diabetic ketoacidosis in concurrent ectopic pregnancy: A case report

Abstract

Ectopic pregnancy occurs in 1–2% of all pregnancies. The majority occur in the fallopian tube, requiring intervention in the form of methotrexate or surgery. Ruptured ectopic pregnancies can lead to hemodynamic instability, requiring immediate surgical intervention. In the case reported here, the patient presented in diabetic ketoacidosis with a pregnancy of unknown location. Upon further evaluation she was found to have a ruptured ectopic pregnancy and was taken to the operating room for surgical management. We discuss the rarity of these concurrent disorders, the pathophysiology behind stress-induced diabetic ketoacidosis, the effects of elevated glucose in peri-operative management, and the importance of multi-disciplinary approaches to urgent clinical decision-making.

Highlights

• •Hemorrhage can cause a stress response that leads to diabetic ketoacidosis.
• •Peri-operative glycemic control is vital in preventing surgical complications.
• •Ectopic-induced diabetic ketoacidosis is exceedingly rare, with only one case previously reported in the literature.
• •Unlike that case, in the present case the patient made a full recovery after surgical management.

1. Introduction

Ectopic pregnancy occurs in 1–2% of pregnancies [1], with approximately 18% eventually rupturing [2]. With over 90% of ectopic pregnancies occurring within the fallopian tubes [1], these are by far the most common site. Some ectopic pregnancies (e.g. cesarean scar ectopic pregnancies) may result in live births with significant maternal morbidity. Tubal ectopic pregnancies require intervention; conservative management is not a viable option. Ectopic pregnancies account for up to 3% of pregnancy-related deaths and is the leading cause of hemorrhagic maternal mortalities [1]. Ruptured ectopic pregnancy is a true gynecologic surgical emergency. Ectopic rupture can rapidly lead to hypovolemic shock and warrants surgical exploration of the abdomen. If methotrexate is contraindicated, treatment typically involves laparoscopic salpingectomy with excision of the ectopic pregnancy. In cases of severe hemodynamic instability, laparotomy may be warranted. Given such acute physiologic changes, the patient may present in a variable manner. We present a case of an adult patient without history of diabetes, found to be in diabetic ketoacidosis (DKA) with concurrent ectopic pregnancy.

2. Case presentation

A 35-year-old woman, gravida 1 para 0, at 5 weeks and 3 days of gestation dated by last menstrual period, presented with sharp, diffuse abdominal pain and nausea. She endorsed increased thirst, but denied fevers, vaginal bleeding, or discharge. She had no significant past medical or surgical history and was aware of her current pregnancy.

Her blood pressure was 92/65 mmHg, heart rate 138 bpm, temperature 36.6 °C, respiratory rate 34, and oxygen saturation 100%. She appeared anxious and pale, and spoke in short phrases. Her abdomen was diffusely tender to palpation in all quadrants, with mild distention and voluntary guarding.

Her blood glucose was 431 mg/dL, white blood cell count 29.3 × 10³/uL, hemoglobin 10.0 g/dL, creatinine 2.2 mg/dL, bicarbonate 9 mmol/L, lactate 17.9 mmol/L, venous pH 6.830 mm, anion gap 33.0 mEq/L, and beta human chorionic gonadotropin of 23,358 miU/mL. Her urinalysis showed many bacteria and white blood cells. Transvaginal ultrasound showed no contents in the uterus and a 7.4 × 2.8 cm left-sided complex collection without free fluid in the cul-de-sac (Fig. 1).

Fig. 1.

Transvaginal pelvic ultrasound.

The differential diagnosis at this time included pregnancy of unknown location favoring ectopic pregnancy, ruptured ectopic pregnancy, intraabdominal abscess, DKA, hypovolemic shock, septic shock, and acute kidney injury. The presumed source of sepsis was from her urinary tract versus pelvic collection. Pan cultures were obtained, she was given ceftriaxone, started on an insulin drip, and given intravenous hydration while awaiting transfer to a hospital with obstetric care.

Upon arrival she was started on meropenem for presumed septic shock. An obstetrician-gynecologist deemed her abdomen to be non-acute at that time, so magnetic resonance image (MRI) of the abdomen and pelvis was obtained for better characterization of the pelvic collection. It revealed a 20x17x9 cm ill-defined material surrounding the uterus with questionable active extravasation of contrast adjacent to a cystic structure in the left adnexa (Fig. 2).

Fig. 2.

Pelvic Magnetic Resonance Imaging T2-weighted, sagittal view.

Repeat hemoglobin resulted at 7.2 g/dL. The patient was consented for surgery and taken to the operating room. Transfusion of two units of packed red blood cells were initiated en route. Given the MRI findings, acute blood loss, and the patient's critical condition, the patient received an exploratory laparotomy, evacuation of hemoperitoneum, left salpingectomy, and removal of ectopic pregnancy. Some 1500 cc blood and clot was immediately expressed from the abdomen, with an actively bleeding ectopic pregnancy on the left fallopian tube. She was transfused an additional one unit of packed red blood cells and one unit of fresh frozen plasma. Fig. 3 details the timeline of events from hospital admission to conclusion of surgery.

Fig. 3.

Timeline of events leading to surgery.

Post-operatively she had decreasing need for insulin, which was discontinued on post-operative day 1. Her blood glucose had reduced to normal range, in the 120 s. Her hemoglobin A1c resulted as 4.9%. Her blood cultures showed no growth and urine cultures grew Escherichia coli. Her antibiotics were discontinued after 48 h, and she was discharged on post-operative day 2. She was seen in the office one week and again one month later, when no complications noted. At her most recent appointment, the patient was hesitant to attempt pregnancy again due to this traumatic experience but planned to conceive in several months.

3. Discussion

Between 2009 and 2014, the average hospitalization rate for patients with diabetes and superimposed DKA was 6.3% [3], with approximately 2–5% of DKA cases resulting in mortality [4]. The probability of a simultaneous occurrence of DKA and ectopic pregnancy is expected to be exceedingly rare. There is one documented case study on ectopic pregnancy with superimposed DKA. This case study was published in the British Medical Journal in 1984, and details a 17-year-old girl with ruptured ectopic pregnancy and blood sugar measurements over 500 mg/dL. During surgical planning, the patient suffered a cardiac arrest. She was taken to the operating room and the ruptured ectopic pregnancy was confirmed and removed. The patient expired four hours later [5].

The present case report differs from the 1984 report in two respects. Firstly, while patients had elevated blood glucose levels and no history of diabetes, in the case of a 17-year-old, it is more likely that occult Type I diabetes is present than in a 30-year-old patient. This could explain the overlapping DKA in a 17-year-old patient as well as ectopic pregnancy. However, it is much less likely that DKA develops in a patient without a history of diabetes in our case report. Secondly, we will unfortunately never know the potential outcome and recuperation of the 17-year-old after removal of ectopic pregnancy as she expired shortly after surgery. In our case, we were able to determine that the patient had a normal hemoglobin A1C without occult diabetes, and her blood glucose normalized after resolution of the acute insulting event. This highlights the peri-operative risk of morbidity and mortality for patients with hyperglycemia requiring emergent surgery.

Patients with DKA are at high risk of morbidity and mortality peri-operatively. Diabetic patients are at a higher risk of peri-operative skin and soft-tissue infection, systemic infection, and other peri-operative procedures [6]. Estimated risk of peri-operative mortality in diabetic patients is 50% higher than that of non-diabetic patients [6]. A component of this estimated risk can be attributed to the longstanding complications of diabetes, including cardiovascular, neurologic, and ophthalmic complications, which would affect peri-operative morbidity. However, several studies have investigated peri-operative complications in hyperglycemic patients without diabetes. A study by Frisch et al. showed that hyperglycemic patients have a significantly increased length of hospital stay, hospital complications, and mortality regardless of diabetic or non-diabetic status [7]. Despite the outcomes in hyperglycemic patients, one study showed that hyperglycemic patients who receive insulin in the pre-operative period were at similar risk of adverse outcomes to those with normal blood glucose [8].

There is adequate physiologic evidence demonstrating that stress can lead to DKA. The most common cause of DKA is infection. Other common causes include alcohol, surgical procedures, inadequate insulin, and long fasting [4]. When these stressors interact with the body, stress hormones are released, including epinephrine, norepinephrine, catecholamines, cortisol, glucagon, and growth hormone. These increase the blood glucose concentration via gluconeogenesis, glycogenolysis, lipolysis, and ketogenesis. Additionally, the same hormones act to decrease pancreatic cell sensitivity to glucose, thus inhibiting insulin secretion [4]. Schade and Eaton summarize that stress-related hormones are pivotal in the development and decompensation of DKA. At least one of the stress hormones listed above are found to be elevated in patients with DKA. Blockage of hormone production or hormone receptor action decreases the severity and length of DKA. Additionally, in select circumstances, introduction of these stress hormones can induce DKA in patients with diabetes [9]. While serum stress hormone levels are not usually measured during an episode of DKA, typical laboratory findings in DKA include blood glucose of >11.0 mmol/L, venous pH <7.3, serum bicarbonate <15 mmol/L, as well as ketonemia, glycosuria, and ketonuria [10].

The case represents a unique clinical diagnosis, with a multidisciplinary approach. The consequences of surgery must be weighed against the peri-operative risk with DKA in a critically ill patient. Despite clinical condition, a ruptured ectopic pregnancy is a surgical emergency, and the patient needs to be taken to the operating room immediately. We hope to shed light on this intersection of anatomy, pathophysiology, and gynecologic surgery.