Elsevier

The Lancet

Volume 399, Issue 10338, 14–20 May 2022, Pages 1867-1875
The Lancet

Articles
Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial

https://doi.org/10.1016/S0140-6736(22)00182-9Get rights and content

Summary

Background

Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection.

Methods

We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low–medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671.

Findings

From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0·48, 95% CI 0·38–0·61; p<0·0001). Among patients treated according to the algorithm, compared with patients who received usual care there was a decrease in bleeding that required intervention (47 [5%] patients vs 51 [6%] patients; RR 0·65, 0·42–0·99; p=0·046), organ failure (39 [5%] patients vs 92 [10%] patients; 0·35, 0·20–0·60; p=0·0001), and 90-day mortality (23 [3%] patients vs 44 [5%] patients; 0·42, 0·19–0·92; p=0·029).

Interpretation

The algorithm for the early recognition and minimally invasive management of complications after pancreatic resection considerably improved clinical outcomes compared with usual care. This difference included an approximate 50% reduction in mortality at 90 days.

Funding

The Dutch Cancer Society and UMC Utrecht.

Introduction

Postoperative complications occur in more than 20% of patients after major surgery and are the greatest contributors to health-care use and costs.1, 2 Despite continuous improvements in a wide range of health-care processes during the past decades, postoperative complications are not always preventable.2 It has been suggested that the focus on improving outcomes should therefore include the timely recognition and management of complications.2, 3, 4 However, recognising the early signs of complications before they lead to clinical deterioration is a challenge. Noticing subtle changes in vital signs, biochemical markers, and radiological features requires members of a multidisciplinary medical team to have the appropriate training and experience.5 Improving the failure to rescue rate (ie, reducing mortality after major complications) has emerged as a main target for quality improvement by the international surgical community.2, 3, 4 There is a clear need for studies to develop effective interventions that can be implemented broadly to improve failure to rescue rates worldwide.2, 3, 4

Research in context

Evidence before this study

We searched PubMed, Embase, and the Cochrane Library for articles in any language published from database inception to June 20, 2016, before the start of this study, and updated the search on August 1, 2021 with search terms “diagnosis”, “management”, “pancreatic resection”, and “complications”, and synonyms. We found no studies that evaluated a multimodal intervention for recognition and management of complications after pancreatic resection. We found many observational studies that evaluated different diagnostic modalities for postoperative pancreatic fistula. We published a systematic review on this topic in 2020. Our 2020 review included all diagnostic tests that showed an association with postoperative pancreatic fistula in at least two cohorts. Identified variables were body temperature, C-reactive protein, white blood cell count, serum amylase amount, drain amylase amount, non-serous drain efflux, and peripancreatic fluid collections on CT scan. To our knowledge, no randomised trials have been published on complication management after pancreatic resection. However, several observational studies suggested the superiority of a minimally invasive treatment strategy compared with reoperation.

Added value of this study

To our knowledge, our study provides the first high-quality evidence that early recognition and minimally invasive management of complications after pancreatic resection, before they become clinically relevant, can interrupt the cascade of events that lead to organ failure and death. This effect was measured both in high-volume centres and in low–medium volume hospitals.

Implications of all the available evidence

The multidisciplinary, multimodal algorithm for daily bedside use was designed using data from our mandatory nationwide audit, guideline inventories, Dutch national meetings and international consensus meetings, and a comprehensive systematic review of the literature. The algorithm was therefore based on the best available evidence. After combining this evidence with our study findings, we believe that after pancreatic resection, all patients should receive a structured daily evaluation to aid the early recognition and management of complications before these become clinically relevant. This provision will considerably improve clinical outcomes and decrease the failure to rescue rate, which is an international priority in surgical practice and among policy makers. Our simple to use and low-cost algorithm, and the method for its implementation, can be modified easily for use in other types of surgery. Future studies could evaluate further improvements to the algorithm and the adaptation of the algorithm in other clinical contexts.

Pancreatic resection is an example of a complex operation with a high risk (30–73% of patients) of postoperative complications.6, 7 The most common complication is pancreatic fistula, which results in an intra-abdominal leak of amylase-rich fluid8 that can lead to life-threatening consequences, such as sepsis, bleeding, and multiple organ failure.8, 9 In patients with clinically relevant pancreatic fistula, mortality is 12–18%.9, 10, 11 Outcomes after pancreatic resection have improved since the centralisation of such surgery to high-volume centres owing to a focus on the technical aspects of the surgery, process measures, and institutional factors, such as improvements in prehabilitation, anaesthesiology, and the quality of postoperative support in intensive care units.6, 12 Nevertheless, even in high-volume centres, complications after pancreatic resection remain a serious problem.6, 10, 11 Furthermore, most patients worldwide have such surgery in low-volume or medium-volume centres.13, 14, 15 Reported nationwide 90-day mortality rates after pancreatic resection range from 7% to 12%.15, 16, 17 Improving failure to rescue rates has therefore been prioritised in pancreatic surgery.18, 19

We designed a multimodal algorithm for the early recognition and minimally invasive management of postoperative complications in patients having pancreatic resection for all indications. We hypothesised that implementation of this multimodal algorithm would result in better clinical outcomes than after usual care.

Section snippets

Study design and participants

The Care After Pancreatic Resection According to an Algorithm for Early Detection and Minimally Invasive Management of Pancreatic Fistula versus Current Practice (PORSCH) trial is a Dutch, nationwide, stepped-wedge cluster-randomised controlled trial.20 In the Netherlands, pancreatic surgery is centralised to centres that do at least 20 pancreatoduodenectomies per year. All 17 Dutch centres doing pancreatic surgery, including all eight university hospitals, participated in this study, and we

Results

All 17 centres doing pancreatic surgery in the Netherlands were randomly assigned a crossover date. One centre stopped doing pancreatic surgery before crossover to the intervention. From Jan 8, 2018, to Nov 9, 2019, a total of 1805 patients had pancreatic resection in the Netherlands and all of these patients were eligible and included in this study. 885 (49%) patients received usual care (control group), 57 (3%) patients underwent resection during the wash-in phase, and 863 (48%) patients

Discussion

This stepped-wedge cluster randomised trial showed that the use of a novel algorithm for the early recognition and management of postoperative complications in patients undergoing pancreatic resection greatly improved clinical outcomes, including an approximate 50% reduction of mortality nationwide. Our findings support a strategy in which all patients have a structured daily evaluation to identify and treat complications before they become clinically relevant. The smartphone app that was

Data sharing

Data (anonymised) from this study will be made available upon request, subject to review and approval by the study steering committee, the Dutch Pancreatic Cancer Group, institutional review boards (if appropriate), and a signed data access agreement. Requests including a detailed study proposal should be directed to [email protected].

Declaration of interests

CvdL is the Secretary of the Dutch Society of Interventional Radiology (unpaid position). CHvW's institution received payments from Pfizer, Biomerieux, Da Volterra, and MSD and he has a European Patent Application with Da Volterrra, University Antwerp, and University Medical Centre Utrecht Holdings. All other authors declare no competing interests.

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