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Hemorrhage complicating the course of severe acute pancreatitis

Backgrounds/Aims The course of severe acute pancreatitis (SAP) complicated by hemorrhage is associated with poor outcome. Methods Twenty-four (13%) out of 183 cases of SAP had hemorrhagic complications- 12 intraabdominal & 12 intraluminal, 13 had major & 11 had minor and 16 had de-novo & 8 post-surgical bleeding. The mean duration of pancreatitis prior to bleeding was 27±27.2 days. Results Predictors of haemorrhage on univariate analysis were delayed admission (0.037), more than one organ failure (p=0.008), presence of venous thrombosis (p=0.033), infective necrosis (0.001) and systemic sepsis – bacterial (0.037) & fungal (p=0.032). On multivariate analysis infected necrosis (OR=11.82) and presence of fungal sepsis (OR=3.73) were the significant factors. Patients presenting with more than one organ failure and bacterial sepsis had borderline significance on multivariate analysis. Need for surgery (50% vs. 12.6%), intensive care stay (7.4±7.9 vs. 5.4±5.2 days) and mortality (41.7% vs. 10.7%) were significantly higher in patients who suffered haemorrhage. Seven of the 13 with major bleeding had pseudoaneurysms-4 were embolized, 4 needed surgery including 1 embolization failure. Seven with intraabdominal bleeding required surgical intervention, 2 had successful embolization and 3 had expectant management. CT severity index and surgical intervention, were significantly associated with intraabdominal bleeding. Organ failure, presence of pseudoaneurysm and surgical intervention were associated with major bleeding. Conclusions Hemorrhage in SAP was associated with increased morbidity and mortality. Infected necrosis accentuated the degradation of the vessel wall, which predispose to hemorrhage. Luminal bleeding may be indicative of erosion into the adjacent viscera by the pseudoaneurysm.


INTRODUCTION
Severe Acute pancreatitis (SAP) carries a mortality of 15-20%. [1][2][3] Although gastrointestinal (GI) bleed is not considered as organ failure in the revised Atlanta classification, 4 still the consequences associated with it can sometimes be detrimental. Due to the rarity of this complication, there has been a lot of variability in its reporting.
The reported incidence is 1-23%. [5][6][7][8][9] However, whenever this complication is encountered, it can be fatal in onethird to half of the cases. [5][6][7] Haemorrhage in the peripancreatic area further complicates the course of necrosis and increases mortality. [5][6][7][8][9] Haemorrhage can arise secondary to erosion of the vascular wall, formation of pseudoaneurysms or microvascular ischaemic complications, spleno-porto-mesenteric venous thrombosis causing oesophagogastric varices 5,6 and following surgical debridement. 5,[10][11][12] Severe inflammation and activated enzymes which leak into the retroperitoneum in SAP can digest the viscus and vascular structure, including the relatively resistant arterial wall. This leads to acute erosion, disruption, or wall weakening and pseudoaneurysm formation which might eventually rupture and bleed. 5,6,8,10,12 Pancreatic necrosis, abscess and pseudocysts may produce similar damage to the vasculature. In addition to pancreatic debridement, timing of surgery and surgical technique have also been identified as risk factors for the occurrence of haemorrhage. 5,8,10,12 There is paucity of literature on the haemorrhagic complications arising as a result acute pancreatitis, so the present study was planned to classify and assess the outcome of the course of severe acute pancreatitis complicated by haemorrhage.

Statistical analysis
Descriptive statistics were used. Data was expressed as mean±SD or mean (range) as appropriate. Mann Whitney U test was used to evaluate ordinal data like CTSI. Chi square test was used for analysis of nominal data. Factors which were found significant on univariate analysis were entered into multivariate logistic regression analysis.
Statistical significance was set at ＜0.05.

RESULTS
A total of 183 patients of severe acute pancreatitis (SAP) were evaluated during the study period -86 pro-    Major versus minor bleeding: patients with major bleeding had lesser mean number of organ failure, higher incidence of pseudoaneurysms, and a higher need for surgery (Table 3).

De-novo versus post-surgical bleed:
Both the groups were comparable in terms of severity and need for interventions (Table 4).

DISCUSSION
The present study has proposed the classification system for haemorrhage associated with acute pancreatitis.   5,6,9,12 There has been a lot of variability in reporting the incidence of haemorrhage associated with pancreatitis due to the rarity of this complication and varied presentations. [5][6][7][8][9][10][11][12] Most of the large reports on pseudoaneurysms associated with pancreatitis include both acute and chronic cases. 5 week of onset of illness. 3 The management of these patients is challenging due to the presence of peripancreatic inflammatory process, ongoing sepsis, poor physiological status as a result of prolonged illness and inability to exactly localize the source of bleeding. Presence of pseudoaneurysms as localized on angiography is a favorable sit-uation as algorithm based directed therapy can be successfully carried out in this situation. 13 We reported splenic artery to be commonest site for pseudoaneurysm. Others have also observed similar findings. [5][6][7]9,[14][15][16] We reported pseudoaneurysms as the cause of haemorrhage in onethird of the cases. Others have reported haemorrhage due to pseudoaneurysms in 10% 11 and 18% 7 cases. A recent review has reported pseudoaneurysms as the cause of acute haemorrhage in 60% cases. 5 However, the exact management of non localized bleed still remains to be elucidated. A recent review has reported 20% incidence of capillary and venous bleeding. 5,6 In the present study, bleeding could not be precisely localized in seven (30%) of the patients. The cause is usually the slow diffuse venous or capillary oozing which is difficult to pin point. Those with major non localized have very limited surgical options and have a high mortality.
Concluding, the present study has proposed the classification system based on the nature, site, timing and severity of haemorrhage. Based on the classification, we have evolved the management algorithm to plan a treatment strategy.