Discussion
inflammation, liver injury, kidney injury, sepsis, pancreatitis-related
INFLAMMATION, SEPSIS, ACUTE PANCREATITIS, COMPLICATIONS
In this trial, there was no difference in ventilator-free days at day 30 between intensive care unit patients with acute pancreatitis receiving thoracic epidural analgesia combined with usual care and those receiving usual care alone. There was no between-group difference in the incidence of acute pancreatitis-related complications, and patients who received epidural analgesia were less likely to receive opioids despite similar between-group analgesia scores. However, the duration of invasive ventilation was higher in the intervention group than in the control group in patients intubated within 30 days from randomization.Our trial did not confirm the hypothesized benefits of epidural analgesia. In animal models of acute pancreatitis, epidural analgesia improved arterial oxygenation, decreased systemic inflammation and liver injury, increased gut barrier function, and improved splanchnic, pancreatic, and renal perfusion [Several hypotheses could explain the differences between the current results and our initial assumptions. First, a major limitation is that our population does not correspond to the population in which the trial hypothesis was generated, since the observed number of ventilator-free days at day 30 was higher than initially assumed. Therefore, no definitive conclusion can be drawn from the current study on the efficacy of epidural analgesia in improving clinical outcomes in a population of patients who would have higher rates of intubation requirements. The less-frequent need for invasive ventilation at day 30 in our trial (41–42%), as compared to that in the study from Jung et al. (58%) [Secondary analyses found that the duration of mechanical ventilation was higher in patients who received epidural analgesia than in those who did not. It is possible that the intervention directly affected weaning from mechanical ventilation and may be harmful in our trial population, although potential mechanisms remain unreported to date. In addition, epidural analgesia had no effect on biomarkers of lung or kidney injury over time and it reduced opioid requirements while providing efficient analgesia. Whether a reduction in opioid requirements could benefit a population of patients with higher intubation rates warrants further investigation. Although our sample size is limited and our study underpowered to bring definitive conclusions, this is concordant with previous findings supporting the potential safety of epidural analgesia when administered for multiple days in intensive care unit patients, including those with sepsis or under sedation [This trial has limitations. It did not have detailed protocols addressing each single aspect of the management of patients with acute pancreatitis, such as fluid therapy or the initiation, route of administration, and dose of enteral feeding [This study also has strengths. It is the first multicenter randomized trial of epidural analgesia in acute pancreatitis. Despite its open-label design, final assessors of clinico-biological data, statistical analyses, and outcome assessment remained masked to the treatment group. However, many questions remain on the timing and duration of epidural analgesia [