F Jasmijn Smits1, Anne Claire Henry1, Marc G Besselink2, Olivier R Busch2, Casper H van Eijck3, Mark Arntz4, Thomas L Bollen5, Otto M van Delden6, Daniel van den Heuvel5, Christiaan van der Leij7, Krijn P van Lienden5, Adriaan Moelker8, Bert A Bonsing9, Inne H Borel Rinkes1, Koop Bosscha10, Ronald M van Dam11, Wouter J M Derksen1, Marcel den Dulk11, Sebastiaan Festen12, Bas Groot Koerkamp3, Robbert J de Haas13, Jeroen Hagendoorn1, Erwin van der Harst14, Ignace H de Hingh15, Geert Kazemier16, Marion van der Kolk17, Mike Liem18, Daan J Lips18, Misha D Luyer15, Vincent E de Meijer19, J Sven Mieog9, Vincent B Nieuwenhuijs20, Gijs A Patijn20, Wouter W Te Riele1, Daphne Roos21, Jennifer M Schreinemakers22, Martijn W J Stommel17, Fennie Wit23, Babs A Zonderhuis16, Lois A Daamen1, C Henri van Werkhoven24, I Quintus Molenaar1, Hjalmar C van Santvoort25. 1. Department of Surgery, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, Utrecht, Netherlands. 2. Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 3. Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands. 4. Department of Radiology, Radboud University Medical Centre, Nijmegen, Netherlands. 5. Department of Radiology, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, Utrecht, Netherlands. 6. Department of Radiology, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 7. Department of Radiology, Maastricht University Medical Centre, Maastricht, Netherlands. 8. Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, Rotterdam, Netherlands. 9. Department of Surgery, Leiden University Medical Centre, Leiden, Netherlands. 10. Department of Surgery, Jeroen Bosch Hospital, Den Bosch, Netherlands. 11. Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands. 12. Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands. 13. Department of Radiology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands. 14. Department of Surgery, Maasstad Hospital, Rotterdam, Netherlands. 15. Department of Surgery, Catharina Hospital, Eindhoven and GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands. 16. Department of Surgery, Cancer Centre Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 17. Department of Surgery, Radboud University Medical Centre, Nijmegen, Netherlands. 18. Department of Surgery, Medisch Spectrum Twente, Enschede, Netherlands. 19. Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands. 20. Department of Surgery, Isala, Zwolle, Netherlands. 21. Department of Surgery, Reinier de Graaf Hospital, Delft, Netherlands. 22. Department of Surgery, Amphia Hospital, Breda, Netherlands. 23. Department of Surgery, Tjongerschans Hospital, Heerenveen, Netherlands. 24. Julius Centre for Health Sciences and Primary Care, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, Utrecht, Netherlands. 25. Department of Surgery, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, Utrecht, Netherlands. Electronic address: h.vansantvoort@umcutrecht.nl.
Abstract
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.
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.