FEATURE Early Versus Late Drain Removal After Standard Pancreatic Resections Results of a Prospective Randomized Trial Claudio Bassi, MD, FRCS,* Enrico Molinari, MD,* Giuseppe Malleo, MD,* Stefano Crippa, MD,* Giovanni Butturini, PhD,* Roberto Salvia, PhD,* Giorgio Talamini, MD,† and Paolo Pederzoli, MD* Summary of Background Data: The role of surgically placed intra- abdominal drainages after pancreatic resections has not been clearly estab- lished. In particular, their effect on morbidity rates and the optimal timing for their removal remains controversial. Methods: A total of 114 eligible patients who underwent standard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol (amylase value in drains 5000 U/L on postoperative day POD 1) were randomized on POD 3 to receive either early (POD 3) or standard drain removal (POD 5 or beyond). The primary end point of the study was the incidence of pancreatic fistula. Secondary endpoints included abdominal complications, pulmonary complications, in-hospital stay, and perioperative mortality. Cost-analysis between the 2 groups was also made. Results: Early drain removal was associated with a decreased rate of pancreatic fistula (P = 0.0001), abdominal complications (P = 0.002), and pulmonary complications (P = 0.007). Median in-hospital stay was shorter (P = 0.018), and hospital costs decreased (P = 0.02). Mortality was nil. A significant association with pancreatic fistula was found for timing of drain removal (P  0.001), unintentional weight decrease before surgery (P = 0.022), type of pancreas texture (P = 0.015), serum amylase levels on POD 1(P = 0.001), and albumin levels on POD 1 (P = 0.039). Multivariate analysis showed that timing of drain removal (P = 0.0003) and unintentional weight decrease before surgery (P = 0.02) were independent risk factors of pancreatic fistula. Conclusions: In patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after standard pancreatic resections. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs. The manuscript is a randomized trial, registered in the NLM database as NCT00931554. (Ann Surg 2010;252: 207–214) I n the field of pancreatic surgery, controversy regarding operatively placed drains has recently emerged. Even though intra-abdominal drains act as a warning of anastomotic leak and hemorrhage, the risk of infection and the potential damage that may be induced by mechanical pressure, erosion, or suction led to their role being questioned. In particular, the question as to whether drains should be placed after pancreatic resections was addressed by Conlon et al in a prospective randomized trial, which represents the first evidence- based approach supporting that intra-abdominal drains should not be considered mandatory or standard. 1 However, as in clinical practice the principle of postoperative drainage remains constant, it is of paramount importance to understand what is the effect of drain placement on morbidity rates, to what extent do drains influence the development of pancreatic fistula and, accordingly, what is the optimal timing for their removal. Surgically placed drains are in fact normally removed at the surgeon’s discretion when the occurrence of pancreatic fistula has been excluded, although some authors advocated an early removal to prevent intra-abdominal infections. In this regard, Kawai et al showed in a prospective study that early drain removal after pancreaticoduodenectomy (PD) was an indepen- dent factor in reducing the incidence of abdominal complications. 2 Therefore, appropriate drain management may represent a key factor for improving “fast-track” protocols, reduce in-hospital stay, and ultimately, provide a high-quality, cost-effective care. We recently demonstrated that an amylase value in drains 5000 U/L on postoperative day (POD) 1 identifies a subgroup of patients who are not likely to develop a pancreatic fistula and in whom continued drain management beyond the early postoperative period may be detrimental. 3 As a result, we designed a prospective, randomized clinical trial to test the hypothesis that, in patients with amylase value in drains 5000 U/L, early drain removal (POD 3) is associated to a lower rate of pancreatic fistula and abdominal complications after standard pancreatic resections as opposed to drain removal according to our standard policy (POD 5 or beyond). PATIENTS AND METHODS Study Design This prospective randomized trial was approved by the Eth- ical Committee on Clinical Investigation of Verona Medical Uni- versity Hospitals (protocol n°1637) and registered at National Insti- tutes of Health as NCT00931554. Patients with pancreatic and periampullary tumors who underwent standard pancreatic resections (PD or distal pancreatectomy DP with or without spleen preser- vation) were recruited into the study if amylase value in drain(s) was 5000 U/L on POD 1. Specific exclusion criteria consisted in (i) reconstruction of the pancreatic remnant by pancreaticogastrostomy; (ii) clinical suspect of postpancreatectomy hemorrhage (defined according to ISGPS) 4 or relaparotomy within 72 hours from index operation; (iii) “sinister” appearance of drain effluent (defined as dark brown, to milky water to clear “spring water” fluid that looks like pancreatic juice) or clinical suspect of biliary fistula (defined as output of biliary fluid from at least 1 abdominal drain) within 72 hours from index operation; (iv) peripancreatic fluid collection 5 cm (maximum diameter) at a routine transabdominal ultrasound performed before randomization. After obtaining informed consent, eligible patients were randomized on POD 3 by a computer-gener- ated allocation schedule to receive either early or late drain removal. In the former group (group A), drain(s) were removed on POD 3 itself, whereas in the latter (group B) drain management was based on our institutional protocol, as previously reported. 3 Briefly, amy- lase value in drain(s) was again measured on POD 5, with drains From the *Departments of Surgery and †Surgery and Biomedical Sciences, “G.B. Rossi” Hospital, University of Verona, Verona, Italy. Reprints: Claudio Bassi, MD, FRCS, Department of Surgery, “G.B. Rossi” Hospital, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy. E-mail: claudio.bassi@univr.it. Copyright © 2010 by Lippincott Williams & Wilkins ISSN: 0003-4932/10/25202-0207 DOI: 10.1097/SLA.0b013e3181e61e88 Annals of Surgery • Volume 252, Number 2, August 2010 www.annalsofsurgery.com | 207