PD without routine intraperitoneal drainage was associated with a higher morbidity (Table 3). There was an increase in the number of complications per patient, an increase in the number of patients who had at least 1 grade 2 or more complication, and a higher mean complication severity score. PD without routine intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess, severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. There was no difference between drain and no-drain groups in quality of life when assessed at baseline and at 30 days after surgery (see Supplemental Digital Content Table 1, available at http://links.lww.com/SLA/A521).
The study was stopped early by the Data Safety Monitoring Board because of excess mortality in the patients undergoing PD without routine intraperitoneal drainage. After 90 days of follow-up, there were 8 deaths (12%) in the no-drain group and only 2 deaths (3%) in the drain group (P = 0.097) (Table 4). Among the 10 patients who died, 90% were male, 80% had a soft pancreatic texture, 60% had a pancreatic duct of 3 mm or less, and 80% developed a pancreatic fistula. Two patients (20%) had a combined biliary and pancreatic fistula and 70% developed an intra-abdominal abscess. Five deaths (50%) were associated with intra-abdominal hemorrhage (see Supplemental Digital Content Table 2, available at http://links.lww.com/SLA/A522).
Percutaneous drains were placed in 3 (30%) of the patients who died. Seventy percent of the patients who died were returned to the operating room on average at POD 11 (range: 1–24). One patient who died had a percutaneous drain but was not returned to the operating room. (See Supplemental Digital Content 1, available at http://links.lww.com/SLA/A520, which describes the postoperative course of the 10 patients who died.)
Two deaths, 1 in the drain group and 1 in the no-drain group, were related to recurrent cancer. One patient in the no-drain group had a laparoscopic PD, did not have a documented pancreatic leak, and was discharged on POD 10. However, the patient returned on POD 24 in shock and died from postoperative hemorrhage from the hepatic artery. The remainder of the deaths, 70%, occurred in the setting of a pancreatic fistula associated with sepsis, multisystem organ failure, and/or hemorrhage (Table 4 and Supplemental Digital Content Table 2, available at http://links.lww.com/SLA/A522).
This is the first randomized prospective multicenter trial to evaluate the outcome of PD without routine intraperitoneal drainage. Experienced pancreatic surgeons from 9 high-volume (≥50 PD/yr) academic pancreas centers in the United States enrolled 137 patients who were randomly assigned to either receive (n = 68, drain group) or not receive (n = 69, no-drain group) intraperitoneal drains at the time of the resection. The balance between the groups in all factors thought to potentially affect outcome afforded by the randomized prospective design of this trial supports the conclusion that the difference in outcomes is caused by omitting the abdominal drain at the time of resection. Elimination of intraperitoneal drains at the time of PD was associated with increased morbidity and mortality.
Intraperitoneal drainage after PD has been the common practice for pancreatic surgeons, which is understandable given the frequency of pancreatic fistula and its associated complications. Jeekel9 was the first to question this practice in the literature more than 2 decades ago with a case series of 22 patients who underwent PD without drainage with acceptable results. In recent years, the practice of routine intraperitoneal drainage after PD has been further scrutinized.
Enthusiasm for pancreatectomy without routine intraperitoneal drainage has been promoted in part by several publications from the Memorial Sloan-Kettering group.3,7,8 In 1998, Heslin et al8 published a retrospective review of 89 patients, 51 undergoing PD with drains and 38 without drains. There was no difference in the rate of major complications between the 2 groups. The only previous randomized prospective trial was a single-center study published by Conlon et al7 from the same institution in 2001. This study included patients undergoing PD (n = 139) and distal pancreatectomy (n = 40), with 88 randomized to drainage and 91 randomized to pancreatic resection without drainage. There was no significant difference in the mortality rate or the number or type of complications experienced by the 2 groups. In addition, drainage at the time of resection did not reduce the need for subsequent percutaneous drainage or reoperation. The authors concluded that routine drainage after pancreatic resection should no longer be considered mandatory.
A follow-up study from the same group published in 2013 showed that this concept was not universally accepted even in their own institution, with drains still being placed in half of pancreatic resections.3 However, this single-center retrospective study of 1122 patients concluded that operative drains were associated with increased grade 3 or more complications, pancreatic fistula, readmission, and a longer hospital stay, and elimination of drains did not affect mortality. The authors concluded that routine prophylactic drainage after pancreatic resection can be safely abandoned.
Other groups, including participants in this study, have previously reported retrospective studies supporting the concept that pancreatic resection without drains is safe. Fisher reported on 2 consecutive cohorts of patients who underwent pancreatic resection with (n = 179) and without (n = 47) intraperitoneal drainage.6 Elimination of routine intraperitoneal drainage did not increase the frequency or severity of serious complications. However, when all grades of complications were considered, the number of patients who experienced any complication (65% vs 47%, P = 0.020) and the median complication severity grade (1 vs 0, P = 0.027) were increased in the group that had drains placed at the time of surgery. Eliminating intraoperative drains was associated with decreased delayed gastric emptying (24% vs 9%, P = 0.020) and a trend toward decreased wound infection (12% vs 2%, P = 0.054). The readmission rate (9% vs 17%, P = 0.007) and the number of patients requiring postoperative percutaneous drains (2% vs 11%, P = 0.001) were higher in patients who did not have operatively placed drains, but there was no difference in the reoperation rate (4% vs 0%, P = 0.210). The authors concluded that abandoning the practice of routine intraperitoneal drainage after pancreatic resection may not increase the incidence or severity of severe postoperative complications.
A recent larger retrospective study by Mehta et al4 also supported PD without drainage. A series of 709 consecutive PDs, 251 without drainage, was reviewed. There was no increase in 30-day mortality (2% vs 2.5%) and patients with drains experienced higher rates of morbidity (68.1% vs 54.1%, P < 0.01), particularly pancreatic fistula. The authors concluded that the data supported elimination of routine primary operative drainage at the time of PD.
It seems that the results of this study are in contrast to most of the recent literature on this subject. However, careful consideration of the available data is required. In a recent meta-analysis of the available literature, van der Wilt et al5 determined that it was premature to conclude that omitting drainage after pancreatic resection leads to a decrease in the risk for complications. This study, which is the only multicenter randomized prospective trial involving multiple high-volume pancreas centers, also strongly supports the conclusion that primary operative drainage at the time of PD should not be abandoned. Of all the available literature, this study is the least likely to be influenced by bias. The randomization process is critical in avoiding selection bias. In retrospective studies, patients may be selected for PD without drains on the basis of a perceived or real decreased risk for pancreatic fistula or other complications. In this study, all patients, regardless of anticipated pancreatic texture, duct size, or comorbidities were randomly assigned to the treatment groups. The comparability of the 2 groups is as close to identical as possible. Differences in rare outcomes, such as mortality, are difficult to detect in retrospective cohort studies and require a large sample size. Retrospective and single-institution studies can also be confounded by the evolution of a surgeon's technique and an institutional learning curve over time. The design of this trial with multiple expert surgeons at multiple high-volume pancreas centers eliminated these confounding factors.
Another strength of this study is the completeness and length of follow-up. It is interesting to note that 6 of the deaths (60%) occurred more than 30 days after surgery and 3 of the deaths (30%) occurred more than 60 days after surgery. Clearly, previous studies that reported only 30- or 60-day mortality figures may not be capturing the true mortality after PD. If this study followed the patients only for mortality to 30 or even 60 days, the 4-fold increase in mortality would not have been apparent. Although the mortality rate of 3% is in the expected range, a mortality rate of 12% was unacceptable and led the Data Safety Monitoring Board to conclude that it was not ethical to continue the study.
Careful analysis of the deaths in this study showed that among the 8 patients with no drain, 6 died of sepsis/multisystem organ failure in the setting of a pancreatic fistula. These patients were aggressively managed when they first had evidence of a complication in the postoperative period. However, absence of an operatively placed drain may have resulted in a period of time in which a fistula was occurring and the fluid remained undrained. One patient died of postoperative hemorrhage 24 days after an apparently uncomplicated laparoscopic PD. One patient died of early cancer recurrence 59 days after surgery. Even if the latter 2 patients were excluded, the excess mortality in the group without drains would remain very worrisome.
Many studies have evaluated pancreatic resection with and without intraperitoneal drainage in patients undergoing distal pancreatectomy and PD.3,5–8,15 This combined approach may not be valid as PD is associated with a more severe morbidity and mortality than distal pancreatectomy. In the recent report by Correa-Gallego,3 exclusion of patients undergoing distal pancreatectomy and focusing the analysis on just the subset of 739 patients undergoing PD showed that mortality was significantly increased [3 (1%) vs 11 (3%), P = 0.02] when routine drainage was eliminated in the patients undergoing PD. We found that the 90-day mortality rate was increased in the no-drain group for the patients undergoing PD although it was only marginally significant (P = 0.097, Table 4), which is consistent with the report by Correa-Gallego et al.3
This study suggests that abandoning the practice of routine intraperitoneal drainage in all patients is not safe. Some surgeons have taken a compromise position by placing drains at the time of resection but removing them in the early postoperative period on the basis of drain amylase concentration. In this study, drains were removed when the amylase concentration was low and/or the volume of output was low and this was typically about POD 7, the time of discharge from the hospital. The University of Verona group has proposed that a concentration of amylase in fluid from intraperitoneal drains of greater than 5000 U/L on the first POD can be used to predict patients who were at risk for developing a clinically significant pancreatic fistula and allow early drain removal in those at low risk.16 The results of a randomized prospective trial suggest that in patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after pancreatic resection. These data suggest that a prolonged period of drain insertion may be associated with a higher rate of postoperative complications. However, this is perhaps true only in the subset of patients at low risk of pancreatic fistula. This approach is predicated on the assumption that drain amylase concentration can accurately predict which patients are at risk for fistula. Other studies have concluded that the early dynamic postoperative changes in drain volume and amylase concentration are not clearly correlated, with the later development of a clinically significant postoperative pancreatic fistula making this approach problematic.17,18
Other tools to predict the subsequent development of a pancreatic fistula are currently being evaluated. A 10-point fistula risk score based on intraoperative blood loss, duct size of less than 5 mm, soft pancreatic parenchyma, and certain pathologies were recently reported and may be highly predictive of which patients are at low risk for pancreatic fistula.19 Further studies are needed to determine whether intraperitoneal drainage can be safely eliminated in selected patients using predictive factors.
Based on the previous literature, we hypothesized that abandoning the practice of routine intraperitoneal drainage after pancreatic resection would not increase the incidence or severity of postoperative morbidity or mortality. This randomized prospective multicenter trial provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the severity and frequency of complications and contributed to a 4-fold increase in mortality from 3% to 12%. Furthermore, there is evidence that elimination of intraperitoneal drainage may directly increase mortality. The authors caution against abandoning the use of intraperitoneal drainage in all cases where PD is performed.
The authors thank Ericka Haverick, BSN, RN; Amber DelVisco, CCRP, CCRC; Gina Mateia, BA; Cynthia Allbritton, RN; Ben Maccaby, Jenna Gates, PA; Jerry Owens, CCRP; and Kenia Ramos, RN, who served as coordinators for the study and performed quality assurance functions and regulatory compliance. The authors also thank Jason Fleming, MD (Chair); Susan Hilsenbeck, PhD; F. Charles Brunicardi, MD; Kenneth Mattox, MD; Deborah McAbee, JD; Sarah McNees, PhD, CCRP; and Crystal Ross, who served on the Data Safety Monitoring Committee.
The following criteria define each of the author's contributions to the study and manuscript:
1. Contributed to design of the study
2. Contributed to acquisition of data
3. Contributed to analysis and interpretation of data
4. Participated in drafting of the paper
5. Participated in revising the paper critically for important intellectual content
6. Gave final approval of the version to be published
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drain; multicenter; pancreaticoduodenectomy; randomized; Whipple
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