Therapeutic Management of Trauma-related Acute Pancreatitis in a Heart Transplant Recipient

COSMIN BANCEU1, SIMONA GURZU2, MARIUS HARPA1*, KLARA BRINZANIUC1, MIHAELA ISPAS1, VASILE BUD3, JUDIT KOVACS1, MARIAN POP1, MARIUS CIORBA5, HUSSAM AL HESSEIN1, HORATIU SUCIU1 1Institute for Cardiovascular Diseases and Transplantation of TarguMures, University of Medicine, Pharmacy, Science and Technology of Targu Mures, 50 Gheorghe Marinescu Str., 540136, Targu Mures, Romania 2University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, Department of Pathology, 38 Gheorghe Marinescu Str., 540139, Targu Mures, Romania 3University of Medicine, Pharmacy, Sciences and Technology of Targu Mures,Department of General Surgery, Gheorghe Marinescu Str., 540139, Targu Mures, Romania 4University of Medicine, Pharmacy, Sciences and Technology of Targu Mures,Department of Gastroenterology, Gheorghe Marinescu Str., 540139, Targu Mures, Romania

Pancreatitis is associated with high mortality in patients with heart transplantation(HTx) after infections and rejection complications [1]. The mortality rate is very high even if acute necrotizing pancreatitis benefits from suitable treatment [2]. 3% of patients with transplant can develop acute pancreatitis after heart transplant versus 0.1% of patients with other cardiac surgery [3], which means a high risk of death [2]. Several complications like shock, renal failure, sepsis and respiratory dysfunction can be caused by acute pancreatitis [4]. These complications are determined by the activation of the inflammatory pathway that develops a systemic inflammatory response syndrome (SIRS) [5]. Due to the immunosuppression drugs in heart transplantation, patients with acute pancreatitis have a very low survival rate [6]. Two groups of gastrointestinal complications may appear after cardiac surger y: mesenteric ischemia and pancreatitis [7]. More than 50% of patients die during hospitalization for gastrointestinal complications after cardiac surgery [8] and about 40% for pancreatitis if the patient develops this complication much later post cardiac surgery [7]. Hyperamylasemia after open heart surgery is a sign of acute pancreatitis and the percentage of those who develop severe pancreatitis with hemorrhagic pancreatitis or pancreatic abscess in the case of elevated amylases it's high [9]. After cardiac surgery, pancreatitis is a serious complication with significant morbidities and mortality, its incidence being even higher in patients with heart transplantation than in those with other cardiac surgeries [9][10][11]. The evolution of pancreatitis after HTx develops a sterile infection with pancreatic pseudo-cysts followed by systemic sepsis and multiorgan failure [1,5,12,13].
The aim of this paper was to highlight the severity of this pathology especially because the patient is immunosuppressed after cardiac transplant.
Signed informed consent was obtained for publication of scientific data.

Experimental part
A 32 -year old man with end-stage heart failure (ischemic heart disease, left venricular aneurysm with massive ventricular thrombus, 20% ejection fraction) was evaluated for cardiac transplant. He was treated with loop diuretics (Furosemide 160 mg/day), potassium sparig diuretics (Spironolactone 50 mg/ day), beta-blockers drugs (Carvedilol 12.5 mg/ day), anticoagulant treatment with Sintrom 1 mg/ day. After 1 year on the waiting list an orthotropic transplantation was performed with bicaval technique. After 34 days, the patient was discharged from our service without special problems, with immunosuppressive treatment (Prograft 6 g/day, Cellcept 2g/day, Prednison 20 mg/day), antiviral drug (Valcyte 450 mg/day) antibiotic medication (Sulfamethoxazole-Trimethoprim 800/160 mg/ day, loop diuretics (Furosemide 80 mg/day), potassium sparing diuretics (Spironolactone 50 mg/ day). The patient is without reject signs at the heart biopsy (ISHLT 0). The patient is in our transplant follow up program and his evolution is without reject signs but with chronic renal failure developed two years after immunosuppression treatment was started (creatinine level 1.87 mg/dL, urea 64 mg/dL), controlled with low doses of loop diuretics Furosemide 20 mg/day with monitoring of electrolytes, renal and hepatic function.
Three years later, he presented to the Emergency Department, with severe abdominal pain and abdominal distention which started after a traumatic accident. The laboratory investigation reveals hemoglobin (Hgb) 8.4g/ dL (11-17 g/dL), hematocrit (Htc) 23.3% (34-54%),  Emergent surgery consisted on removing all the necrotic peri and intrapancreatic tissue and pancreatogenic exudate in order to avoid the systemic release of toxic and vasoactive substances. Also it was perform a classic cholecystectomy to avoid biliary pancreatitis. A drainage tube was installed and the patient was transferred to ICU. After two weeks of favorable evolution, patient started to have sanguineous drainage and laboratory investigations showed decreased levels of Hgb from 11.2 g/dL to 8.0 g/ dL, hematocrit from 33 to 23.2% and increased levels of leukocytes from 11.2x10 3 µL to 25.6 x10 3 µL,. Surgical reintervention, for a diffuse pancreatic and peripancreatic hemorrhage was necessary. After long hemostasis, the patient was transferred in the ICU. Two weeks later the laboratory investigations showed increasing serum levels of amylases to 935 U/L. CT-exam ( fig. 3) . 4).

Results and discussions
Patients with heart, liver, intestinal kidney or bone marrow transplantation have a higher prevalence of developing acute pancreatitis compared to the others patients either by exogenous mechanism or by the druginduced pancreatitis mechanism [10,11,14]. The pathophysiology is altered by the immunosuppressive treatment, which increases mortality risk in transplanted versus non-transplanted patients [6,11].
For example, even though pancreatitis is not among the clear side effects, it has been reported as a possible rare and fatal effect of long-term administration of tacrolimus [16]. Due to the absence of specific diagnostic tests, the diagnosis of acute drug-induced pancreatitis is difficult to establish, [10] but in this case we knew that the symptomatology started after an accident, so etiology was clearly post-traumatic.
One of the most serious complications after cardiac surgery is acute pancreatitis and this complication has significant morbidities and mortality [1,2,10]. Severe acute pancreatitis can be associated with systemic inflammation, compensator y immunesuppression, secondary infections, vital organ dysfunction, and death [12]. The diagnosis and treatment can be delayed because transplanted patients are under immunosuppression treatment and they can develop a crypto-symptomatic acute pancreatitis, a fact that increases mortality in orthotropic heart transplant patients [1,11,14,15]. Even with aggressive and appropriate care, the patient can develop acute necrotizing pancreatitis witch has a high mortality rate [2].
Even with an optimal management, acute pancreatitis is a disease with a high mortality, regardless of etiology or treatment, due to the complications that can arise [19].

Conclusions
Less commonly, pancreatitis after cardiac transplantation has a very high mortality, especially since there is no specific protocol to manage this pathology and the risk of rejection of the allograft is increased.