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ORIGINAL ARTICLE OPEN ACCESS

The value of postoperative measurement of amylase in abdominal drainage fluid after pancreatic surgery

F Safi, S Bakathir, M Taha, T Lange, H El Salhat, F Branicki

ABSTRACT serum amylase (≥100 IU/l) was found in 20/52 (38%) patients following pancreatic surgery. Introduction: Clinical symptoms accompanied The elevated amylase levels returned to normal by a continuous increase of amylase within four days. Abdominal drainage fluid concentration in abdominal drainage fluid and amylase values were found increased in 19/47 change in color of drainage fluid may indicate (40%) of patients. All elevated levels returned to the presence of fistula or leakage. Aims: To normal by the tenth post­operative day. The investigate the clinical relevance and utility of color of abdominal drainage fluid was sero­ post­operative (PO) monitoring of amylase and sanguinous in all cases. No clinical pancreatic lipase estimations in the serum and abdominal fistula or anastomotic leakage was evident (0/55 drainage fluid following pancreatic surgery. patients), all patients were discharged home. Methods: Seventy patients (37 males, 33 Conclusion: Documentation of transient females) who underwent duodenum­preserving elevation of serum amylase and abdominal pancreatic head resection [n = 12 (GI)], pylorus drainage fluid amylase levels did not appear to preserving Whipple’s procedure [n = 39 (GII)], be of clinical significance. segmental resection of the body of the pancreas [n = 4 (GIII)] and pancreas tail/body resection Keywords: Pancreatic anastomosis, Leakage, [n = 15] were enrolled in the study prospectively. Fluid amylase level. In G I, II and III (n = 55) duct mucosa anastomosis with the remnant of distal pancreas ********* was fashioned. The serum amylase and lipase levels and levels of amylase in drainage fluid Safi F, Bakathir S, Taha M, Lange T, Salhat HE, Branicki were measured pre­operatively and from PO day F. The value of postoperative measurement of amylase 1, until removal of the drain. Only 32 patients in abdominal drainage fluid after pancreatic surgery. received subcutaneous octreotide, 100 µg three International Journal of Hepathobiliary and Pancreatic times daily for five days. Results: Elevation of Diseases 2012;2:31–37.

Article ID: 100009IJHPDFS2012 1 F Safi, 2S Bakathir, 3M Taha, 4T Lange, 2H El Salhat, 1 F Branicki Affiliations: 1 Department of Surgery, United Arab Emirates University; 2Department of Surgery, Tawam Hospital, Al ********* Ain, UAE; 3Department of Internal Medicine (Division Gastroenterology), Tawam Hospital, Al Ain, UAE; 4Weimer doi:10.5348/ijhpd­2012­9­OA­7 Hospital, Germany. Corresponding Author: Dr. Farouk Safi, Professor Department of Surgery, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 1 7666, Al Ain, United Arab Emirates; Email: INTRODUCTION [email protected] The three fundamental techniques for reconstruction to enable pancreatic exocrine secretion after proximal Received: 27 December 2011 pancreas resection are end to side pancreatico­ Accepted: 03 April 201 2 Published: 08 November 201 2 jejunostomy, end to side pancreatico­gastrostomy and end to end invaginating anastomosis.

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The mortality rate after pancreatic resection has drainage fluid postoperatively or during deteriorating decreased to less than 5% but reported morbidity clinical status of the patient are essential for the remains high [1]. Even today, following resection, diagnosis of anastomotic failure, 3) to follow up the morbidity ranges from 6–57%. Fistula rate after patients with high abdominal drainage/serum amylase resection is 0–20% with a morbidity of 0–13% [1]. The levels in order to document whether the patient main cause of serious morbidity and mortality is developed surgical complications in the form of postoperative anastomotic leakage due to intra­ anastomotic or stump failure and, 4) to evaluate the peritoneal release of enterokinases and activation of value of octerotide in reducing failures. pancreatic enzymes that lead to sepsis and hemorrhagic complications. Failure of the remnant proximal pancreatic duct closure after left sided pancreatic MATERIALS AND METHODS resection causes milder complications as compared to anastomotic failure of an entero­entero anastomosis but A prospective study was conducted which included it can result in fistula formation or an intra­abdominal all patients undergoing pylorus preserving proximal fluid collection [1]. pancreaticoduodenectomy (PD), duodenum preserving The failure in the integrity of an anastomosis pancreas head resection (DPPHR), segmental resection between the remnant pancreas and the gastrointestinal of the pancreas with anastomosis (SR) and distal tract can result in a fistula with leakage of pancreatic pancreatectomy (DP) by the same surgeon between secretions outside the abdominal cavity. This may occur January 2000 ­ July 2011. Data collected included without significantly affecting the general condition of patient demographics, type of operation carried out, the patient or it may prolong in­hospital treatment or hospital mortality, morbidity, and the need for lead to discharge of the patient with the fistula until reoperation and readmission. spontaneous closure occurs. Failure of anastomotic Instructions were given to nurses and residents integrity may well give rise to intra­abdominal fluid regarding the need to measure the serum and collections, sepsis, hemorrhage, peritonitis and death. abdominal drainage fluid amylase and lipase Strasberg et al. classified pancreatic anastomotic failure concentrations daily starting from the first postoperative into five grades depending on the clinical course day and to inject octereotide subcutaneously in a dosage following this complication. Pancreatic anastomotic of 3x100 µg; 3x200 µg or 3x300 µg for variable periods. failure grade I requires normal post­operative therapy All patients who underwent pancreatic resection and without any need for additional treatment; in grade II anastomosis had two drains (without suction), one there is need for pharmacological support; grade III placed in a sub­hepatic location, the second adjacent to requires interventional therapy; grade IV requires the pancreatic anastomosis. A single abdominal drain surgical and intensive care treatment and grade V is was used for patients undergoing DP and was placed death [2]. adjacent to the pancreatic stump. The decision to The International Study Group for Pancreatic Fistula remove the drains was dependent on the levels of Definition reviewed several previous scores/definitions amylase recorded postoperatively, the color of the of pancreas anastomotic failure on the basis of two abdominal fluid and the general clinical condition of the parameters; 1) daily output in ml, 2) and amylase patient. The upper limit of the reference range of concentration in the drained abdominal fluid, and 3) the amylase in our laboratory was 100 IU/L. duration of the fistula. Suspicion of and diagnosis of Surgical technique: Pancreaticojejunostomosis fistula depends on monitoring the output of the was performed by the same surgeon (FS) in all patients abdominal drainage system, the concentration of as follows. A retro­colic jejunal limb was brought amylase in drainage fluid more than three times the through a window in the transverse colon, an end to side serum concentration after third post­operative day, pancreatico­jejunal anastomosis was fashioned in two color of the fluid, general condition of the patient, and layers; a duct to mucosa anastomosis was made using radiologic documentation. The Group also proposed an PDS® 5/0 or 6/0 interrupted sutures; all knots were A, B or C clinical grading system: a) well patient, b) placed outside the lumen. The second layer involved a often well, and c) appearing ill [1]. pancreas parenchyma­seromuscular interrupted sutures Theoretically, the drainage fluid should be rich in using 4/0 PDS®. This technique was performed amylase when pancreatic fluid leaks from the pancreatic regardless of the diameter of the pancreatic duct. stump and anastomotic failure. Therefore, ‘amylase rich’ Following distal pancreatectomy, the pancreatic duct drainage has been one of the most popular definitions of was closed separately using prolene® 4/0 U shaped pancreatic duct leakage used in the literature [3]. The sutures, followed by parenchyma­parenchyma suturing purpose of are study was: 1) to investigate the value of using interrupted prolene® 4/0 sutures. measurement of amylase concentration in serum and abdominal drainage fluid in diagnosing anastomotic or stump failure after pancreatic surgery and to determine RESULTS if a correlation exists between the dynamics of post­ operative changes in amylase concentration in drainage Results are summarized in table 1–4. The tables fluid with clinical outcome, 2) identify whether high show the number of patients with serum amylase values concentrations of amylase in the serum or in abdominal of more than 100 IU/L. There was missing data for

IJHPD – International Journal of Hepatobiliary and Pancreatic Diseases, Vol. 2, 201 2. ISSN – [2230 - 901 2] IJHPD 201 2;2:31 –37. Safi et al. 33 www.ijhpd.com amylase drainage fluid later in the post­operative course considering the color of the fluid, normalizing or when drains had been removed or no samples were sent decreasing amylase concentrations and the general for testing to the laboratory. The study included 70 condition of the patient. Neither abdominal sepsis nor patients. There male to female ratio was 1.12:3. Means intra­abdominal collections of fluid were documented in age of all patients was 57.4 years. any patients (Tables 3, 4). There were no post­operative deaths. Morbidity not related to pancreatic surgery was observed in 18 patients (26%). Four patients (5.7%) required re­ DISCUSSION operation for control of hemorrhage. None of the patients developed any clinical signs of fistula and or The mortality rate following duodeno­ anastomotic/stump leakage. No abdominal collection pancreatectomy has been reported between 3%–5% in was documented based on clinical signs and symptoms. some large series [3, 4]. A mortality rate of zero has Pancreatic surgery caused post­operative been reported in some series of more than a hundred amylasaemia in about 40% patients without any clinical patients [5–7]. The major cause of mortality is sepsis signs of pancreatitis. The elevated serum amylase values and/or hemorrhage resulting from failure of return to normal, less than 100 IU/L, within one week pancreatico­jejuno or gastrostomosis [8]. To prevent of operation. High serum values were as high as 10 fold this life threatening complication after surgery, various the normal levels (Table 2). No patient exhibited clinical modifications for pancreatico­enteric reconstruction signs of acute pancreatitis. have been proposed like pancreatico­jejunostomy or More than 50% operated patients showed elevated pancreatico­gastrostomy, invagination or duct to amylase values in the abdominal drainage fluid mucosa anastomosis, stented or nonstented collections. The concentration of the amylase was as anastomosis, end to end or end to side anastomosis and high as 200 fold the normal value. All increased levels the use of fibrin glue. However, no universal consensus returned to normal within 7–10 days. The color of has been reached as to which particular variation of collected body fluid was initially serosanginous then pancreatico­enteric reconstruction is safer and less serous. The observed amylase levels did not play any prone to anastomotic failure. Randomized controlled role in the decision as to when the drain can be trials and metaanalysis showed no difference in leak removed. The decision to remove the drain was made rates between pancreatico­gastro or jejunostomosis [9,

Table 1: Patient demographic data (n = 70).

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Table 2: Serum amylase levels pre­ and post­pancreatic resection (n = 70).

Table 3: Postoperative abdominal drainage amylase levels (subhepatic drain).

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Table 4: Postoperative abdominal drainage amylase Levels (drain adjacent to pancreatic anastomosis).

10]. Observational clinical studies demonstrate that the In such cases amylase levels return to normal within one surgeon’s experience and preferences play to influence week post­operatively [13]. Measurement of serum operative outcome. Having become familiar with amylase after pancreatic surgery is not mandatory and principles relating to pancreatic surgery the same should be done only if there is clinical suspicion of technique has been used to connect the remnant pancreatitis. In all our patients with hyperamylasaemia pancreas with the jejunum and employs an end to side no clinical features of pancreatitis were documented. duct mucosa double layer with interrupted 4/0 PDS® The volume of drainage fluid per day has been sutures. No evident leakage in our study with our selected as one indicator of pancreatic fistula. In the surgical technique provides evidence for the selection of review reported by Shinchi et al. [14], some authors this safe anastomotic procedure [11]. chose 50 ml/day as a ‘cut­off’ value, others selected 30 Pancreatic fistula remains a significant cause of post­ ml/day and in some publications the volume is not operative morbidity and mortality in patients undergoing defined, as in our analysis. We decided to remove drains pancreatic head resection [12]. Traditionally, the after three to four days according to the color of the diagnosis of a fistula has been made on the basis of drainage fluid and the general condition of the patient. amylase rich drainage fluid or radiological evidence of A drain producing serous fluid with a normal amylase disruption of the pancreatic anastomosis. The reported concentration can be removed independent of the incidence of post­operative pancreatic fistula is between volume of drainage fluid. 0–30% [1]. The true incidence is, however, unknown High concentrations of amylase in body fluids do not because of the varying definition as to what constitutes a always indicate anastomotic or stump failure. The post­operative pancreatic fistula [1]. Anastomotic or measurement of amylase concentration only once stump failure after pancreatic surgery is a serious surgical postoperatively in the third, fifth, seventh or tenth post­ complication. It occurs in immediate or easy operative day in body fluid is also of no value for the postoperative period causing deviation from the normal diagnosis and definition of anastomotic fistula or post­operative course requiring careful management [2]. anastomotic failure. Some authors have chosen two fold, Whether the diagnosis of this complication can be made two and half fold, three fold, five fold or absolute values on clinical grounds or by measurement of amylase levels of ≥1000, 2000, or 5000 for amylase concentration as merits consideration. cut off values for the recognition of this complication We analyzed data relating to amylase levels in serum [15, 16]. Our study is consistent with the reports from and abdominal drainage fluid to determine how useful Hiroyuki et al. [14] and Yi­Ming Shyr et al. [17] that these are to identify anastomotic or stump failure. there are patients without any clinical signs of leakage or Hyperamylasaemia has been reported after many symptoms who have high amylase value in body fluids surgical procedures. Occasionally, the origin is salivary even seven to 10 days post­operatively. Perhaps, in some amylase and this does not reflect injury of the pancreas. patients, pancreatic juice leaks from needle hole sites or

IJHPD – International Journal of Hepatobiliary and Pancreatic Diseases, Vol. 2, 201 2. ISSN – [2230 - 901 2] IJHPD 201 2;2:31 –37. Safi et al. 36 www.ijhpd.com from the anastomosis itself, which has not fully healed. S Bakathir – Minor contribution in Conception, and It may be that amylase levels are high and do actually Acquisition of data, Minor contribution in drafting the indicate leakage of pancreatic fluid but this is article, Minor contribution in final approval of the subclinical in nature without overt manifestation of version to be published leakage like large intra­abdominal collections or M Taha – Minor contribution in Conception, and features of systemic sepsis. Acquisition of data, Minor contribution in drafting the The dynamic and course of amylase concentration in article, Minor contribution in final approval of the each patient during the complete post­operative period version to be published is of more diagnostic value than the estimation of T Lange – Major Contribution in conception and design, amylase on a particular post­operative day. In all our Acquisition of data, Analysis and interpretation of data, patients without leakage the high amylase Minor contribution in drafting the article, Minor concentration returned to normal levels. Yi­Ming Shyr contribution in final approval of the version to be et al. [17], reported that all patients without leakage published showed a continuous decrease in amylase levels. In H El Salhat – Minor contribution in Conception, and addition, patients without leakage reported by Hiroyuki Acquisition of data, Minor contribution in drafting the et al had a reduction in amylase concentration and near article, Minor contribution in final approval of the normalization by the 13th post­operative day. version to be published Decreasing concentrations of amylase re­increasing F. Branicki – Minor contribution in Conception, and were found only in patients with clinical leakage [14] Acquisition of data, Minor contribution in drafting the with very high values beyond the 10th post­operative article, Major contribution in final approval of the day. version to be published Neither the isolated estimation of amylase in serum, nor the volume or amylase concentration of abdominal Guarantor drainage fluid, on a single post­operative day appears to The corresponding author is the guarantor of be indicative of the complications of fistula, submission. anastomotic failure or leakage. More important is the dynamic of daily evaluation of the amylase Conflict of Interest concentration, which after 10 days, is more likely to be Authors declare no conflict of interest. of diagnostic value. Suspicion of these complications may be raised clinically on daily patient rounds. The Copyright diagnosis can be confirmed, better delineated and © F Safi et al. 2012; This article is distributed under the followed by additional laboratory tests, imaging studies terms of Creative Commons Attribution 3.0 License and monitoring of the course of measuring amylase which permits unrestricted use, distribution and concentrations in body fluids [18, 19]. reproduction in any means provided the original authors and original publisher are properly credited. (Please see www.ijhpd.com/copyright­policy.php for CONCLUSION more information.)

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