Improvement of pancreatic tissue oxygenation and survival rate and time after isovolemic hemodilution with hydroxyethyl starch plus bovine hemoglobin in swine with acute pancreatitis

Introduction

Acute hemorrhagic necrotizing pancreatitis (AP) is still an essential problem with a high mortality. Disturbed microcirculation and as a consequence decreased tissue oxygenation is a crucial effect in the cascade from the self-limiting mild edematous to the often fatal form of AP. The aim of the study was to evaluate the therapeutic approach of isovolemic hemodilution (IHD) with hydroxyethyl starch (HES) alone and in combination with HBOC-301 and with Ringer's solution with regard to pancreatic tissue oxygen tensions and survival in pigs suffering from acute pancreatitis.

Methods

After approval of the local ethics committee, 39 pigs were anesthetized, endotracheally intubated and normoventilated (FIO₂ = 0.3). After laparotomy and splenectomy the pancreatic duct was cannulated. The pancreatic tissue oxygen tension (tpO₂) was measured using a silicon catheter (Licox Medical Systems, GMS, Germany). After 30 min equilibration, AP was induced by a combination of intravenous cerulean and intraductal glycodeoxycholic acid. Fifteen and 75 min after induction of AP, animals were randomized and isovolemically (PAOP constant) hemodiluted with 10% HES 200.000/0.5 plus HBOC-301 (+ 0.6 g/dl plasmatic hemoglobin; Oxyglobin^®, Biopure, USA) (HES/HBOC group), 10% HES 200.000/0.5 (HES group) or Ringer's solution (RINGER group) to a hematocrit (Hct) of 15%. tpO₂ was measured every hour 30 min after reaching Hct of 15%. After 6 hours catheters were removed, the abdomen was closed and animals were extubated. After 6 days (144 hours) animals were sacrified. Statistical analyses were performed using the Kolmogorov–Smirnov test for normal distribution, Student's t test was used for normally distributed data and the chi-square test for the survival rate (significance, P < 0.05).

Results

After induction of AP, tpO₂ decreased in all groups and increased significantly after IHD with HES/HBOC in comparison with the HES and RINGER groups (P < 0.001). tpO₂ remained low in the HES and RINGER groups and decreased after 5 hours (P = 0.046) and 6 hours (P = 0.015) in the Ringer group in comparison with the HES group. The survival rate at the end of the observation period was higher in the HES/HBOC group (10/13) (P = 0.002) in comparison with the RINGER group (2/13) (P < 0.001), and between the HES (8/13) vs RINGER groups (P = 0.016).

Conclusion

Only IHD with HES plus HBOC-301 was able to normalize pancreatic tissue oxygen tensions in comparison with IHD with HES or Ringer's solution after induction of severe AP. The complementary strategy of IHD and additional application of HBOC-301 as combination of rheologic and O₂-delivering therapy may represent a novel therapeutic option for the treatment of acute pancreatitis in the future.