The incidence of post pancreatectomy hemorrage in our study was 22.2% which is comparable with the previous studies. In previous studies, the incidence of PPH Grades A to C as per ISGPS criteria ranges from 3% to 29%. [9-11] In our study, out of 27 patients, 6 patient develop PPH, all were late PPH develop 24hr after the surgery. Late PPH has a different mechanism as compare to early PPH and requires a surgical or radiological intervention for its management. One of the reason behind PPH is erosion or ulceration of peripancreatic vessels at anastomotic site by enzyme rich pancreatic juice leaked from pancreatic fistula or due low gastric pH which may cause direct mucosal or blood vessels injury or lysis of blood clots. Out of 6, 5 patients manifest as intraluminal bleed either as Ryle’s tube bleed or as hematemesis and 1 patient presented as intraluminal and extraluminal bleed with Ryle’s tube and abdominal drain bleed, detailed characterictics as shown in Table 4.
3 patients had grade B PPH, in all endoscopy and angiograpy was done but bleeding source could not identified and managed conservatively with blood transfusion and resuscitation. Other 3 patients develop grade C PPH and taken up for reexploration in view of hemodynamic instability, one patient had bleed from pancreatic stump, another from anastomotic site which was ligated. Another patient had bleed from common hepatic artery in which PG anastomosis leak was present and patient presented with both Ryle’s tube and drain bleed. Bleeder was ligated but patient expired on POD 10.
In a study done by Darnis et al, it was found that associated POPF, type of resection, older age patient, and patient with poor nutritional status were the risk factors for PPH.[12] In another study Feng et al found independent risk factors for late PPH after pancreaticoduodenectomy such as male gender, diameter of pancreatic duct, end-to-side invagination PJ, associated POPF, and intra-abdominal abscess[13] Nine indicators can strongly predict the probability of PPH Grade C, according to research done by Wellner et al. after major pancreatic surgery. The following risk variables for bleeding complications were: advanced age, male gender, body mass index, vascular resection, multivisceral resection, and concomitant POPF. Appropriate care, intraoperative blood transfusions, and preoperative biliary drainage, however, were important protective factors. [14] Etiology of PPH is multifactorial as discussed above, also in our study it may be multifactorial and low gastric pH is one of the factor associated with increased risk of PPH. In our study on applying Chi Square test as pH value of 4.1 as cutoff 75%(3/4) patients had PPH while in patients with pH >4.1 only 13%(3/23) had PPH. Also on applying unpaired t test there is significant difference in pH values, 3.39 among bleeders as compared to 6.33 among non bleeders. Two patients had low pH values less than 2 ,both of them had grade C PPH.To the best our knowledge no previous study was done to find out association between gastric pH and PPH,Our study is first of its kind showing definitive association between PPH and low gastric pH. The possible reasons of association may be lysis of clots by pepsin at low pH, impaired blood clotting at low gastric pH,impaired platelet aggression at low pH and direct injury by pepsin at low ph as described in literature.
In a study done by Berstad et al it was found that in an acidic medium, pepsinogen converted to its active form pepsin, which can easily dissolve the freshly formed blood clots within short time.[15] Also, in acidic medium, plasmin-mediated fibrinolysis is also increased, which may blunt the reinforcement of the initial platelet clot by a fibrin clot.[16] A platelet clot will sustain hemostasis for several hours but will dissolve unless supported by a fibrin clot.Also ,in vitro studies it was found that a neutral pH is prerequisite for good platelet aggregation. However, in a slightly acidic medium, platelet aggregation is blunted, and at pH 6, it is virtually lost. [17-19] According to earlier research, keeping the pH at 4 is sufficient to stop mucosal bleeding in those with acute stress ulcers. In a pilot research, intermittent pantoprazole IV treatment in high-risk ICU patients efficiently regulated gastric pH and prevented upper GI bleeding without any tolerance..[20]
In our study gastric pH varies from 1.1 to 8.4 which is similar in study done by Fuchs and DeMeester, in which the gastric pH ranges from 1 to 8.[21] In a study done by Shinchi et al,Gastric pH demonstrated two distinct patterns during the night-time period: first is acid- type patients exhibited a persistent acid pH, whereas second one is alkaline-type patients had cyclic variations between an acid and an alkaline pH.[22] Acid-type patients had a significantly more acidic profile as compare to alkaline-type patients. In our study low pH values may be due the presence of acidic type of patients. The small sample size of our study is one of its limitation ,while the strength of the study is that it is first study of its kind done at tertiary care center, also the cause of PPH is multifactorial but low gastric pH is showing significant association in all cases of PPH