Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: Results of a prospective randomized double-blinded placebo-controlled trial

doi:10.1016/j.ejso.2008.01.014

European Journal of Surgical Oncology (EJSO)

Volume 34, Issue 8, August 2008, Pages 868-875

https://doi.org/10.1016/j.ejso.2008.01.014 Get rights and content

Abstract

Aims

To evaluate the impact of prophylactic octreotide on gastric emptying in patients undergoing pancreaticoduodenectomy. Postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) are common complications after pancreaticoduodenectomy. Whereas several prospective randomized trials propose the prophylactic use of octreotide to prevent pancreatic fistula formation, somatostatin has, however, been associated with delayed gastric emptying after partial duodenopancreatectomy.

Methods

In this prospective, randomized, double-blinded, placebo-controlled trial we analyzed the influence of prophylactic octreotide on delayed gastric empting after pancreaticoduodenectomy. Patients were randomized to the placebo group (n = 32) and the octreotide group (n = 35). Primary endpoint was the incidence of delayed gastric emptying, secondary endpoints included perioperative morbidity other than DGE. DGE was measured by clinical signs, gastric scintigraphy and the hydrogen breath test. Risk factors for DGE other than octreotide were analyzed by univariate and multivariate analyses.

Results

DGE measured by clinical signs was similar between both groups studied (∼20% of the patients). Gastric scintigraphy (T_1/2) was 76.3 ± 15.2 min in the octreotide group and 86.7 ± 18.0 min in controls at day 7, respectively. The H₂ breath test was 65.0 ± 6.5 min in octreotide treatment group and 67.0 ± 5.7 min in controls at day 8. POPF grade C occurred in ∼3% of the patients, although prophylactic treatment of octreotide did not reduce the incidence of POPF. Multivariate analysis showed that postoperative intraabdominal bleeding and infection were independent risk factors for DGE. Furthermore preoperative biliary stenting reduced postoperative DGE after partial duodenopancreatectomy.

Conclusion

Prophylactic octreotide has no influence on gastric emptying and does not decrease the incidence of postoperative pancreatic fistula after pancreaticoduodenectomy.

Introduction

Partial duodenopancreatectomy has become a safe treatment modality for various benign and malignant pancreatic diseases with mortality rates below 5% in most high volume centers.¹ Research has therefore focused on prevention and treatment of complications such as postoperative pancreatic fistula (POPF) formation and delayed gastric emptying.2, 3 While POPF might become life threatening in the case of vascular erosions, DGE after pancreaticoduodenectomy is usually self-limiting, but significantly contributes to patient discomfort and prolongs hospital stay.4, 5, 6, 7 Morbidity secondary to DGE, such as aspiration of gastric contents, depletion of caloric reserves or infection of feeding catheters, however, might further aggravate the postoperative course.8, 9, 10

The etiology of DGE after pancreaticoduodenectomy is discussed controversially, with diabetes mellitus, malnutrition and pancreatic fibrosis3, 11 being associated with postoperative DGE. Other studies focus on surgical factors like trauma of the pylorus,5, 12 resection of duodenal pacemakers with decreased motilin production,13, 14 as well as different types of gastrointestinal reconstruction contributing to DGE.10, 15, 16 Furthermore, postoperative intraabdominal complications,¹⁰ treatment with dopamine¹⁷ and early jejunal feeding might influence gastric emptying.¹⁸

Somatostatin inhibits gastroenteropancreatic exocrine secretion. Octreotide, its long-acting analogue, has been studied in multiple randomized controlled trials and is thought to prevent POPF formation after pancreatic surgery, however, results are controversial. While some European studies found a significant reduction of POPF after pancreas resection in octreotide treated patients,19, 20 several international studies failed to demonstrate a beneficial effect.2, 21, 22, 23

Besides the secretory effects, octreotide decreases gastric motility and prolongates orocaecal transit time in healthy humans2, 24, 25 and has therefore been used in the treatment of dumping syndrome after gastric surgery.²⁶ We therefore studied the effect of octreotide prophylaxis on delayed gastric empting after pancreaticoduodenectomy.

Section snippets

Inclusion criteria, randomization and study drugs

Sample size was calculated based on the incidence of delayed gastric emptying for 40% of the patients with somatostatin and for 12% without somatostatin treatment.²⁷ This ratio reflects our experience in >400 patients undergoing partial pancreaticoduodenectomy. The level of statistical significance was set to 0.05 and a power of 0.80, using a post hoc 2-sample t test with Bonferroni correction.

After approval by the local ethical committee, patients 18 years or older undergoing partial

Patient characteristics and operation

After full workup and control of preoperative conditions, 67 consecutive patients were randomized to the study and underwent elective pancreaticoduodenectomy. Thirty-five patients received appropriate prophylactic octreotide and 32 patients' saline doses. Both groups were comparable with respect to demographics (Table 1). The mean age was 59.9 ± 2.0 in the octreotide group and 64.8 ± 2.0 in the control group. There was no difference between groups in terms of gender, body weight and relevant

Discussion

The major findings of the presented, prospective, randomized, double-blinded, placebo-controlled study are that the application of prophylactic octreotide does not delay gastric emptying after pancreaticoduodenectomy. Even though this study was not aimed to test for POPF, no decrease in the incidence of postoperative pancreatic fistula was found in this study. Interestingly, the omission of preoperative biliary drainage in jaundiced patients was associated with delayed gastric emptying (DGE)

Acknowledgements

We appreciate the statistical assistance of P. Ziehen. The excellent linguistic assistance of B. Tilton is gratefully acknowledged.

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Cited by (77)

Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis
2024, Surgery (United States)
Clinically relevant postoperative pancreatic fistula remains a common complication after pancreatoduodenectomy. The fistula risk score is a validated tool to predict the risk of clinically relevant postoperative pancreatic fistula. To mitigate complications, we have implemented an extended antibiotic pathway for patients at increased risk of clinically relevant postoperative pancreatic fistula (fistula risk score ≥3). We report outcomes after pancreatoduodenectomy in patients at increased risk for clinically relevant postoperative pancreatic fistula who received extended antibiotic therapy compared to those who received standard perioperative antibiotics (single dose before incision).
Single-institution analysis of 87 patients who underwent elective pancreatoduodenectomy (2018–2022) with soft gland texture and fistula risk score ≥3 and were treated with (n = 34) or without (n = 53) 10 days of broad-spectrum antibiotics (piperacillin/tazobactam converted to amoxicillin/clavulanic acid at discharge) after surgery. Associations between extended antibiotics and postoperative outcomes were analyzed.
Baseline clinicodemographic factors were similar between cohorts. Patients who received extended antibiotics had shorter index days (6 vs 8 days, P = .004) and 90-day composite length of stay (8.5 vs 12 days, P = .018). Patients who received extended antibiotics had lower rates of clinically relevant postoperative pancreatic fistula (11.8% vs 37.7%; odds ratio = 0.17, 95% confidence interval: 0.04–0.68), wound infections (8.8% vs 30.2%; odds ratio = 0.08, 95% confidence interval: 0.01–0.50), organ space infections (14.7% vs 43.4%; odds ratio = 0.15, 95% confidence interval: 0.04–0.52), and image-guided drain placement (8.8% vs 34.0%; odds ratio = 0.15, 95% confidence interval: 0.04–0.62). There were no Clostridium difficile infections in the extended antibiotic group.
Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula and associated complications after pancreatoduodenectomy in patients with a fistula risk score ≥3. These results form the basis of a randomized controlled trial (NCT05753735).
Does pancreatic duct stent placement lead to decreased postoperative pancreatic fistula rates after pancreaticoduodenectomy? A meta-analysis
2022, International Journal of Surgery
Citation Excerpt :
A lot of risk factors have been reported to be linked to an increased risk of postoperative pancreatic fistula, which included but not limited to factors related to surgical procedures (types of anastomosis, methods of pancreaticojejunostomy, operative time and the surgeon's technological levels) and patient characteristics (age, gender, obesity, pancreatic texture, pancreatic duct diameter, tumor pathological type and pancreatic juice output) [10–14]. Although various techniques have been proposed to prevent postoperative pancreatic fistula, which include reconstruction with pancreaticogastrostomy, modification of the pancreaticojejunal anastomosis technique, pancreatic duct stent placement, use of fibrin glue and somatostatin analogue octreotide, the optimal surgical strategy to reduce POPF rates is still held in suspension [15–18]. In addition, with the new technological advancements, minimally invasive techniques (e.g., laparoscopic, total laparoscopic or robotic-assisted) have been also adapted for pancreaticoduodenectomy, which is demonstrated to be beneficial for improving the perioperative and surgical outcomes, with a significant learning curve effect [19–21].
To evaluate the effectiveness of pancreatic duct stent placement for preventing postoperative pancreatic fistula after pancreaticoduodenectomy.
PubMed, the Cochrane Central Register of Controlled Trials, Embase and ClinicalTrials.gov databases were searched up to February 26, 2022. Studies comparing outcomes following pancreaticoduodenectomy with or without pancreatic duct stents were included. The primary outcome measured was postoperative pancreatic fistula rate, and secondary outcomes were in-hospital mortality rate, reoperation rate, delayed gastric emptying rate and wound infection rate.
Seven RCTs involving 847 patients met the inclusion criteria. No statistically significant difference between the stent group and non-stent group was detected in the incidence of postoperative pancreatic fistula (RR = 0.85, 95%CI: 0.57–1.26, P = 0.41), in-hospital mortality, reoperation, delayed gastric emptying rate and wound infection. Subgroup analyses revealed that use of an external stent significantly reduced the incidence of pancreatic fistula (RR = 0.61, 95%CI: 0.43–0.86, P = 0.005).
Our preliminary results from this systematic review and meta-analysis revealed that pancreatic duct stents did not reduce the risk of POPF and other complications after pancreaticoduodenectomy compared with no stents. External stents were associated with a reduced POPF rate compared with no stents. Large-scale RCTs are required to assess the effectiveness and assist in clarifying the real role of pancreatic duct stents with respect to the POPF rates after pancreaticoduodenectomy.
Do somatostatin-analogues have the same impact on postoperative morbidity and pancreatic fistula in patients after pancreaticoduodenectomy and distal pancreatectomy? – A systematic review with meta-analysis of randomized-controlled trials
2020, Pancreatology
Citation Excerpt :
After exclusion of this RCT, the heterogeneity level dropped to 0% and revealed an overall RR of 0.55 (95%-CI: 0.47–0.65, P < .001) (data not shown). Six studies [18,21–24,39] with mixed cohorts and eleven studies [11,12,14,15,17,19–21,28,38,40] with patients after PD could be identified and pooled in the meta-analysis of the impact of somatostatin analogues on the occurrence of intraabdominal abscesses. Here, the overall pooled RR of studies with mixed cohorts was not able to reveal any relevant impact of somatostatin analogues on intraabdominal abscesses (RR: 1.00, 95%-CI: 0.62–1.62, P = 1.00; eFig. 1a).
Postoperative pancreatic fistula/POPF is the most feared complication in pancreatic surgery. Although several systematic reviews investigated the impact of somatostatin analogues on POPF, no stratification was performed regarding type of pancreatic resection (pancreaticoduodenectomy/PD; distal pancreatectomy/DP) and different somatostatin analogues.
This study was planed according to the Preferred-Reporting-Items-for-Systematic –Review-and-Meta-Analysis/PRISMA-guidelines. After screening databases for randomized controlled trials/RCT, studies were stratified into pancreatic resection techniques and data were pooled in meta-analyses containing subgroups of octreotide, somatostatin, lanreotide, pasireotide and vapreotide.
The meta-analysis of studies with a mixed cohort of patients after pancreatic resection revealed a protective effect of somatostatin analogues for morbidity (RR: 0.71, p < .00001) but not for mortality (RR: 1.07, = 0.78) or intra-abdominal abscesses (RR: 1.00, p = 1.00). Moreover, no effect was visible for mortality (RR: 1.57, p = .15), morbidity (RR: 0.87, p = .15) and intra-abdominal abscesses (RR: 0.92, p = .48) after PD. The meta-analysis of patients after PD revealed no impact of somatostatin analogues on POPF (RR: 0.87, p = .19) and clinically relevant POPF (RR: 0.69, p = .30). However, treatment with somatostatin analogues in the mixed cohort showed less POPF (RR: 0.60, p < .00001) and clinically relevant POPF (RR: 0.47, p = .02), which was also the case after DP (RR: 0.41, p = .03).
Somatostatin analogues did not affect POPF and clinically relevant POPF after PD, but seemed to be associated with less POPF after DP. As no sufficiently powered RCT could be identified by the systematic review, further RCTs are urgently needed to investigate the effect of somatostatin analogues after DP.
CRD42018099808.
Somatostatin analogues and the risk of post-operative pancreatic fistulas after pancreatic resection - A systematic review & meta-analysis
2020, Pancreatology
Post-operative pancreatic fistula (POPF) is a common complication of pancreatic resection. Somatostatin analogues (SA) have been used as prophylaxis to reduce its incidence. The aim of this study is to appraise the current literature on the effects of SA prophylaxis on the prevention of POPF following pancreatic resection.
The review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from studies that reported the effects of SA prophylaxis on POPF following pancreatic resection were extracted, to determine the effect of SA on POPF morbidity and mortality.
A total of 15 studies, involving 2221 patients, were included. Meta-analysis revealed significant reductions in overall POPF (Odds ratio: 0.65 (95% CI 0.53–0.81, p < 0.01)), clinically significant POPF (Odds ratio: 0.53 (95% CI 0.34–0.83, p < 0.01)) and overall morbidity (OR: 0.69 (95% CI: 0.50–0.95, p = 0.02)) following SA prophylaxis. There is no evidence that SA prophylaxis reduces mortality (OR: 1.10 (95%CI: 0.68–1.79, p = 0.68)).
SA prophylaxis following pancreatic resection reduces the incidence of POPF. However, mortality is unaffected.
Bacterial smear test of drainage fluid after pancreaticoduodenectomy can predict postoperative pancreatic fistula
2019, Pancreatology
Citation Excerpt :
Furthermore, POPF increases medical costs and the duration of postoperative hospitalization [14,15]. It has recently been suggested that POPF may be prevented by the performance of pancreatico-enteric anastomosis methods such as pancreaticogastrostomy [16] or invagination via pancreaticojejunostomy [17], and by prophylactic somatostatin analog use (e.g. octreotide [18], and pasireotide [19]); however, the effectiveness of these methods remains controversial [20–22]. To predict the development of POPF, a risk scoring system has been described based on the presence or absence of four factors (small duct, soft pancreas, high-risk pathology, and excessive blood loss) [6,23].
It is widely accepted that postoperative pancreatic fistula (POPF) accompanied by bacterial infection results in a worse outcome than POPF alone. However, few studies evaluating predictive indicators of POPF have focused on bacterial infection.
A consecutive 100 patients who underwent pancreaticoduodenectomy at our institute for periampullary disease were enrolled. POPF was assessed according to the International Study Group of Pancreatic Fistula consensus guidelines; grades B and C were defined as clinically relevant POPF (CR-POPF). The patients’ characteristics, perioperative surgical factors, and laboratory data including the results of culture and smear testing performed using drainage fluid on postoperative days (PODs) 1 and 3 were analyzed.
The overall incidence of CR-POPF was 25%. Univariate analyses revealed that the factors associated with CR-POPF were male sex, soft pancreas, MPD diameter, higher serum C-reactive protein concentration and white blood cell count on POD 3, higher amylase concentration in drainage fluid, and culture and/or smear positivity of drainage fluid. Multivariate analysis newly revealed that the smear positivity of drainage fluid on POD 3 was the independent risk factors for CR-POPF (p = 0.027).
Smear positivity of drainage fluid on POD 3 after pancreaticoduodenectomy may be a new predictor of CR-POPF.
Efficacy of octreotide in the prevention of complications after pancreaticoduodenectomy in patients with soft pancreas and non-dilated pancreatic duct: A prospective randomized trial
2018, Hepatobiliary and Pancreatic Diseases International
The efficacy of octreotide to prevent postoperative pancreatic fistula (POPF) of pancreaticoduodenectomy (PD) is still controversial. This study aimed to evaluate the effect of postoperative use of octreotide on the outcomes after PD.
This is a prospective randomized controlled trial for postoperative use of octreotide in patients undergoing PD. Patients with soft pancreas and pancreatic duct < 3 mm were randomized to 2 groups. Group I did not receive postoperative octreotide. Group II received postoperative octreotide. The primary end of the study is to compare the rate of POPF.
A total of 104 patients were included in the study and were divided into two randomized groups. There were no significant difference in overall complications and its severity. POPF occurred in 11 patients (21.2%) in group I and 10 (19.2%) in group II, without statistical significance (P = 0.807). Also, there was no significant differences between both groups regarding the incidence of biliary leakage (P = 0.083), delayed gastric emptying (P = 0.472), and early postoperative mortality (P = 0.727).
Octreotide did not reduce postoperative morbidities, reoperation and mortality rate. Also, it did not affect the incidence of POPF and its clinically relevant variants.

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Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: Results of a prospective randomized double-blinded placebo-controlled trial

Abstract

Aims

Methods

Results

Conclusion

Introduction

Section snippets

Inclusion criteria, randomization and study drugs

Patient characteristics and operation

Discussion

Acknowledgements

Surgery

J Am Coll Surg

Gastroenterology

Am J Surg

J Gastrointest Surg

J Gastrointest Surg

J Lab Clin Med

Surgery

J Am Coll Surg

1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience

J Gastrointest Surg

The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers

Gut

Pancreatic fibrosis correlates with delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy

Ann Surg

Delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy

Surg Gynecol Obstet

Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes

Ann Surg

Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy

Ann Surg

Sepsis delays gastric emptying following pylorus-preserving pancreaticoduodenectomy

Hepatogastroenterology

Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness

Crit Care Med

Is pylorospasm a cause of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy?

Ann Surg Oncol

Role of the duodenum in postprandial release of pancreatic and gastrointestinal hormones

Pancreas

Delayed gastric emptying after standard pancreaticoduodenectomy versus pylorus-preserving pancreaticoduodenectomy: an analysis of 200 consecutive patients

J Am Coll Surg

Pylorus-preserving pancreatoduodenectomy: influence of a Billroth I versus a Billroth II type of reconstruction on gastric emptying

Dig Surg

Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study

Ann Surg

Dopamine delays gastric emptying and prolongs orocaecal transit time in volunteers

Eur J Anaesthesiol