Critical presentation and management of an acute gastrointestinal haemorrhage as a result of an arterioenteric fistula secondary to a failed pancreatic allograft

Background

Pancreatic transplantation is a standard of care for type 1 diabetes mellitus. Successful transplantation offers the potential for euglycaemia, exogenous insulin independence and prevents the progression of diabetes-related complications.1

There are three approaches to pancreatic transplants. The most common is a simultaneous pancreas–kidney transplant for individuals younger than 55 years who have insulin-dependent diabetes and end-stage renal disease. The second approach is a pancreas-after-kidney transplant where the pancreas is transplanted after successful kidney transplantation, in an effort to guarantee long-term kidney graft function. It is recommended for individuals younger than 55 years with severe secondary complications and hypoglycaemic unawareness. The third approach is pancreas transplant alone (PTA), which is reserved for patients with poorly controlled type 1 diabetes who have not yet developed diabetic nephropathy. The principal indication for PTA is recurrent episodes of life-threatening hypoglycaemic unawareness.2 Patients with hypoglycaemic unawareness do not experience normal hypoglycaemic warning signs because they fail to trigger epinephrine secretion in response to low blood sugar. Thirty per cent of patients with PTA will eventually require a kidney transplant due to the adverse effects of immunosuppressive therapy used to prevent allograft rejection.1

In a pancreatic transplant, the donor pancreas with duodenal cuff is transplanted into the recipient’s right lower quadrant. Enteric anastomosis for exocrine drainage is made via a duodenojejunostomy (figure 1A) or a duodenocystostomy. Venous anastomosis is created between the donor portal vein and the vena cava, superior mesenteric or iliac vein of the recipient. Arterial anastomosis is created by using a Y-graft conduit of the donor common iliac artery, including its internal and external iliac branches. The donor internal and external iliac branches are connected to the donor splenic artery and superior mesenteric artery (figure 1B), while the donor common iliac artery is anastomosed to the common iliac or external iliac artery of the recipient (figure 1A).2 The recipient’s native pancreas remains untouched.

Figure 1

Schematic of the pancreatic transplant and its anastomoses. (A) Systemic vascular anastomosis with duodenojejunostomy. Venous anastomosis is with the iliac vein, and arterial anastomosis is with the external iliac artery. (B) Donor pancreas and donor Y-graft. A, recipient aorta; Dc, donor duodenal cuff; EI, recipient external iliac artery; IVC, recipient inferior vena cava; PV, donor portal vein; SA, donor splenic artery; SI, recipient small intestine; SMA, donor superior mesenteric artery; SMV, donor superior mesenteric vein; SV, donor splenic vein; Y, Y-graft consisting of the donor common iliac artery and its external and internal iliac branches; xxx, indicates sites of anastomosis. (Images drawn by AN.)

Postoperatively, pancreatic transplants have patient survival rates of >95% at 1 year and >88% at 5 years; and graft survival rates of ~85% at 1 year and >60% at 5 years.3 Despite the survival rate, severe complications can arise, including allograft rejection, haemorrhage from failed anastomosis, vascular graft thrombus, infection, pancreatic leak, pseudoaneurysms, arterial dissection, arterial stenosis, arteriovenous fistula formation, graft pancreatitis, small bowel obstruction, and arterioenteric (AE) fistula formation.1

Here, we present a fatal case of a massive gastrointestinal (GI) haemorrhage caused by an AE fistula between the right external iliac artery and the terminal ileum in a patient with a history of failed pancreatic transplant due to allograft failure.

Case presentation

A 60-year-old woman with a history of insulin-dependent type 1 diabetes mellitus status post pancreatic transplant in 2005, allograft rejection in 2019, end-stage renal disease secondary to immunosuppressive therapy, dialysis-dependent and idiopathic thrombocytopenic purpura presented to the emergency department with acute onset 9/10 right lower extremity (RLE) and abdominal pain. She also reported constipation prior to arrival.

Physical examination showed a thin and ill-appearing woman, moaning in pain. Vital signs were blood pressure (BP) 194/100 mm Hg, pulse 105 bpm, respiratory rate (RR) 22, O₂ saturation 95% on room air and temperature 37°C. Her right leg and lower abdomen were mottled. Abdominal examination revealed lower quadrant tenderness, right greater than left. Hydromorphone was administered for the pain. She had a large bowel movement, and shortly after, became increasingly confused and hypotensive at 66/35 mm Hg with a pulse of 105 bpm. On re-examination, she had large volume, bright red rectal bleeding. She was put in the Trendelenburg position and massive transfusion protocol (MTP) with uncrossed match blood was initiated.

The patient’s home medications included tacrolimus, romiplostim, insulin lispro, latanoprost, losartan, bumetanide, pantoprazole, glucagon and ondansetron. Haemodialysis was last performed the day prior to presentation. She was previously on prednisone therapy to prevent transplant rejection. Steroid use worsened her glucose control.

Investigations

Blood work revealed lactic acid of 1.8 mmol/L, troponin of 0.01 ng/mL and normal coagulation studies. Comprehensive metabolic panel (CMP) was significant for glucose of 333 mg/dL, blood urea nitrogen (BUN) of 24 mg/dL, creatinine of 3.63 mg/dL, calcium of 7.8 mg/dL and alkaline phosphatase of 280 U/L . Initial complete blood count (CBC) revealed a white blood cell (WBC) count of 1.8×10⁹/L, haemoglobin of 105 g/L, haematocrit of 35% and platelets of 95×10⁹/L. Haemoglobin and haematocrit decreased to 88 g/L and 28%, respectively, during active haemorrhaging.

The patient was sedated with rocuronium and etomidate and intubated due to her pain and restlessness. A bedside abdominal ultrasound did not reveal any abnormalities of the aorta. On abdominal CT angiography (CTA), the aorta was patent with no evidence of intramural haematoma, dissection or penetrating atherosclerotic ulcer. Right and left lower extremity runoff was unrevealing, excluding deep vein thrombosis or other vascular emergencies. The abdominal and pelvic CTA did reveal active extravasation of contrast into the lumen of adjacent distal ileum from a presumed arterial graft stump for pancreatic transplant arising from the right external iliac artery (figure 2). Multiple small and large bowel loops were dilated with intermediate density fluid, reflecting potential blood products. There was an ill-defined, non-enhancing soft tissue structure in the right pelvis with multiple calcifications (figure 3). This was suspicious for devitalised pancreatic allograft of unknown chronicity. The findings were concerning for an AE fistula supported by active haemorrhaging from an arterial stump off of the right external iliac artery into the lumen of the distal ileum.

Figure 2

CT angiography of abdomen and pelvis suggesting an arterioenteric fistula as the cause of the massive gastrointestinal haemorrhage. (A) Sagittal view revealing active extravasation of contrast into the lumen of the distal ileum (red arrow) from an arterial graft stump arising from the right external iliac artery (blue arrow). (B) Axial view showing contrast within the lumen of the distal small bowel, and an arterial graft stump (yellow arrow) arising from external iliac artery.

Figure 3

Coronal view of abdominal CT angiography revealing an ill-defined, non-enhancing soft tissue structure in the right pelvis with multiple calcifications (purple arrow), suggestive for devitalised pancreatic allograft of unknown chronicity.

Treatment

MTP was continued to prevent the development of hypovolaemic shock. In addition, norepinephrine was initiated for persistent hypotension, and tranexamic acid was administered to promote clotting. After 12 units of packed red blood cell (PRBC) product, along with platelets and cryoprecipitate, her BP improved, although she continued to have large volume rectal bleeding. A repeat CBC showed haemoglobin of 124 g/L, haematocrit of 39%, platelets of 36×10⁹/L and WBC count of 7.1×10⁹/L. CMP was significant for hypocalcaemia at 5.9 mg/dL and hypomagnesaemia at 1.4 mg/dL. An arterial blood gas (ABG) revealed a pH of 7.288, pCO₂ of 31.1 mm Hg, pO₂ of 98.8 mm Hg and bicarbonate of 14.8 mmol/L. Bicarbonate, calcium gluconate and magnesium were administered to correct for deficiencies.

The team transferred the patient to a tertiary facility with a transplant team. On arrival, the patient’s skin was mottled and she was still actively haemorrhaging. Repeat CBC showed haemoglobin of 116 g/L, haematocrit of 35.2%, platelets of 62×10⁹/L and WBC count of 6.6×10⁹/L. The CMP was significant for hypocalcaemia at 7.4 mg/dL, hyperglycaemia at 421 mg/dL and hypocapnia at 16 mmol/L. She also had an elevated BUN and creatinine at 27 mg/dL and 3.03 mg/dL, respectively. MTP was continued, and she received an extra eight units of PRBCs, two units of fresh frozen plasma and one unit of platelets. The patient remained on pressors for hypotension. She also received a dose of ketamine to maintain sedation in preparation for surgery.

The patient was transported to the operating room, where vascular surgery performed an angiogram via the right common iliac artery. The angiogram confirmed arterial extravasation from the midexternal iliac artery near the site of the pancreas graft anastomosis. They then performed percutaneous endovascular revascularisation by placing a transluminal covered stent graft into the right iliac artery, sacrificing the failed pancreatic graft. A completion iliac angiogram demonstrated excellent angiographic result with no evidence of active arterial extravasation. Concern for abdominal compartment syndrome secondary to haemoperitoneum warrented urgent exploratory laperotomy by the surgical team. Intra-abdominal exploration revealed mild ascites, dilated loops of viable small bowl filled with blood and no haemoperitoneum. Once the abdomen was open, and the ascitic fluid evacuated, the patient’s BP improved, and she began weaning off of pressors. The pancreatic jejunal anastomosis was identified and circumferentially dissected and transected, releasing the small bowel, but resulting in a quarter-sized hole within the jejunum. Subsequently, a 7 cm jejunectomy was performed with no primary anastomosis. An open abdomen negative pressure therapy dressing was placed for temporary abdominal closure. Intraoperatively, the patient received transfusion products, lactated ringer, and 35 units of insulin. The patient tolerated the procedures well without complications. The patient was anticipated to return for jejunal anastomosis and total allotransplant pancreatectomy after stabilisation and recovery.

Postoperatively, the patient was transferred to the intensive care unit for further management. She arrived in stable condition, sedated and intubated, with a BP of 190/92 mm Hg, pulse of 80 bpm, RR of 14 and a temperature of 34°C. Physical examination revealed normal sinus rhythm, weakly palpable pulses ×4 extremities, decreased air movement bilaterally, absent bowel sounds, distended abdomen with wound vacuum-assisted closure draining serosanguineous fluid, mottling of bilateral lower extremities right greater than left, and ongoing passage of blood from rectum without evidence of brisk arterial bleed. A CBC revealed WBC of 3.3×10⁹/L, haemoglobin of 118 g/L, haematocrit of 35.4% and platelets of 41×10⁹/L. CMP showed sodium of 148 mmol/L, potassium of 2.7 mmol/L, chloride of 116 mmol/L, BUN of 24 mg/dL, creatinine of 2.6 mg/dL, glucose of 312 mg/dL, calcium of 11.9 mg/dL, anion gap of 14 mmol/L and glomerular filtration rate of 19 mL/min. ABG was pH of 7.26, pCO₂ of 35 mm Hg and pO₂ of 91 mm Hg. Lactic acid was 7.4 mmol/L. Her persistent metabolic and lactic acidosis despite adequate blood transfusion and fluid resuscitation was due to end-stage renal failure and prolonged ischaemia of the RLE. Serial CBC and CMP remained relatively unchanged overnight, with the exception of potassium rising to 5.7 mmol/L, and lactic acid decreasing to 3.0 mmol/L.

Outcome and follow-up

On postoperative day 1, the patient became hypotensive and bradycardic into the 30’s. CBC revealed a significant drop in haemoglobin to 66 g/L and haematocrit to 14.3%. The patient was observed to be in disseminated intravascular coagulation evidenced by her low platelet count of 41×10⁹/L, elevated prothrombin time of 13.5 s, and bloody output from her Foley catheter, nasogastric tube and femoral catheter site. Despite resuscitation with vasopressors and blood products, she continued to decompensate. The family was made aware of her condition, and agreed to make her comfort measures only. The patient expired shortly after extubation, approximately 24 hours after initial presentation. The patient received approximately 40 units of PRBCs, 11 units of plasma, 4 units of platelets and 2 units of cryoprecipitate.