Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol

Abstract

BackgroundAcute pancreatitis (AP) is associated with high morbidity and mortality in its most severe forms. Most patients with severe AP require intubation and invasive mechanical ventilation, frequently for more than 7 days, which is associated with the worst outcome. Recent increasing evidence from preclinical and clinical studies support the beneficial effects of epidural analgesia (EA) in AP, such as increased gut barrier function and splanchnic, pancreatic and renal perfusion, decreased liver damage and inflammatory response, and reduced mortality. Because recent studies suggest that EA might be a safe procedure in the critically ill, we sought to determine whether EA reduced AP-associated respiratory failure and other major clinical outcomes in patients with AP.Methods and analysisThe Epidural Analgesia for Pancreatitis (EPIPAN) trial is an investigator-initiated, prospective, multicentre, randomised controlled two-arm trial with assessor-blinded outcome assessment. The EPIPAN trial will randomise 148 patients with AP requiring admission to an intensive care unit (ICU) to receive EA (with patient-controlled epidural administration of ropivacaine and sufentanil) combined with standard care based on current recommendations on the treatment of AP (interventional group), or standard care alone (reference group). The primary outcome is the number of ventilator-free days at day 30. Secondary outcomes include main complications of AP (eg, organ failure and mortality, among others), levels of biological markers of systemic inflammation, epithelial lung injury, renal failure, and healthcare-associated costs.Ethics and disseminationThe study was approved by the appropriate ethics committee (CPP Sud-Est VI). Informed consent is required. If the combined application of EA and standard care proves superior to standard care alone in patients with AP in the ICU, the use of EA may become standard practice in experienced centres, thereby decreasing potential complications related to AP and its burden in critically ill patients. The results will be disseminated in a peer-reviewed journal.Trial registration numberNCT02126332.

Pharmacists in Critical Care

“…Medication bags and syringes should be labeled clearly with information regarding the route of administration if other than IV (eg, wording such as “epidural use only”). Independent double-checks should be implemented at the bedside when epidural medications are initiated and when rates or doses are changed [ 47 - 49 ].…”

Management of Severe Acute Pancreatitis

“…In patients with SAP requiring intensive care unit, there is early evidence for mortality benefit [58•]. A randomized clinical trial is underway to investigate the benefits of thoracic epidural analgesia in AP patients requiring intensive care unit admission [59]. In our clinical practice, opioids remain the most effective short-term analgesic agents for alleviation of pain in SAP; however, they should be administered judiciously, especially in the presence of ileus.…”

Management of the patient with acute pancreatitis

“…12 An international multicentre RCT investigating the role of epidural anaesthesia in patients with AP admitted to ICU is currently ongoing. 13 Non-steroidal analgesics should be avoided; parenteral opioids and paracetamol should be used instead until reliable gut absorption is demonstrated. Multimodal antiemetic drugs are given as required.…”