Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

BACKGROUND: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. METHODS: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. RESULTS: Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15-30] and 30 days [18-30], respectively; median absolute difference of - 0.0 days, 95% CI - 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5-28] versus 6 days [2-13], p = 0.02). CONCLUSIONS: In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter Propensity Analysis.

OBJECTIVE: Recent preclinical and clinical data suggest that thoracic epidural analgesia, a technique primarily aimed at decreasing pain, might exert anti-inflammatory effects, enhance splanchnic and pancreatic blood flow during acute pancreatitis; however, the influence of epidural analgesia on mortality remains under investigated in this setting. This study was therefore designed to assess the impact of epidural analgesia on mortality in ICU patients with acute pancreatitis. DESIGN: Multicenter retrospective, observational, cohort study. SETTING: Seventeen French and Belgian ICUs. PATIENTS: All patients admitted to with acute pancreatitis between June 2009 and March 2014. INTERVENTIONS: The primary exposure was thoracic epidural analgesia versus standard care without epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses were used to control for bias in treatment assignment and prognostic imbalances. MEASUREMENTS AND MAIN RESULTS: One thousand three ICU patients with acute pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia was used in 46 patients and was associated with reduced mortality in unadjusted analyses (4% vs. 22%; p = 0.003). After adjustment for baseline variables associated with mortality, epidural analgesia was still an independent predictor of 30-day mortality (adjusted odds ratio, 0.10; [95% CI, 0.02-0.49]; p = 0.004). Using propensity score analysis, the risk of all-cause 30-day mortality in patients with acute pancreatitis receiving epidural analgesia was significantly lower than that in matched patients who did not receive epidural analgesia (2% vs. 17%; p = 0.01). CONCLUSIONS: Among critically ill patients with acute pancreatitis, mortality at 30 days was lower in patients who received epidural analgesia than in comparable patients who did not. These findings support ongoing research on the use of epidural analgesia as a therapeutic intervention in acute pancreatitis.

Lung real time three-dimensional imaging in critically ill ventilated patients: a global diagnosis concordance study.

Lung ultrasound (LUS) increases clinical diagnosis performance in intensive care unit (ICU). Real-time three-dimensional (3-D) imaging was compared with two-dimensional (2-D) LUS by assessing the global diagnosis concordance. In this single center, prospective, observational, pilot study, one trained operator performed a 3-D LUS immediately after a 2-D LUS in eight areas of interest on the same areas in 16 ventilated critically ill patients. All cine loops were recorded on a computer without visible link between 2-D and 3-D exams. Two experts blindly reviewed cine loops. Four main diagnoses were proposed: normal lung, consolidation, pleural effusion and interstitial syndrome. Fleiss κ and Cohen's κ values were calculated. In 252 LUS cine loops, the concordance between 2-D and 3-D exams was 83.3% (105/126), 77.6% (99/126) and 80.2% (101/126) for the trained operator and the experts respectively. The Cohen's κ coefficient value was 0.69 [95% Confidence Interval (CI) 0.58-0.80] for expert 1 meaning a substantial agreement. The inter-rater reliability was very good (Fleiss' κ value = 0.94 [95% CI 0.87-1.0]) for 3-D exams. The Cohen's κ was excellent for pleural effusion (κ= 0.93 [95% CI 0.76-1.0]), substantial for normal lung diagnosis (κ = 0.68 [95% CI 0.51-0.86]) and interstitial syndrome (κ = 0.62 [95% CI 0.45-0.80]) and fair for consolidation diagnoses (κ = 0.47 [95% CI 0.30-0.64]). In ICU ventilated patients, there was a substantial concordance between 2-D and 3-D LUS with a good inter-rater reliability. However, the diagnosis concordance for lung consolidation is poor.

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

BACKGROUND: Acute 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 ANALYSIS: The 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 DISSEMINATION: The 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 NUMBER: NCT02126332.