Preoperative high dose of dexamethasone in emergency laparotomy: randomized clinical trial.

BACKGROUND: Patients undergoing emergency laparotomy present with a profound inflammatory response, which could be an independent pathophysiological component in prolonged recovery. The aim of this study was to investigate the effects of a single preoperative high dose of intravenous dexamethasone on the inflammatory response and recovery after emergency laparotomy. METHODS: In this double-blinded placebo-controlled trial, patients were prospectively stratified according to surgical pathology (intestinal obstruction and perforated viscus) and randomized to preoperative 1 mg/kg dexamethasone or placebo at a ratio of 1 : 1. The primary outcome was C-reactive protein on postoperative day 1. Secondary outcomes were postoperative recovery, morbidity, and mortality. RESULTS: A total of 120 patients were included in the trial. On postoperative day 1, the C-reactive protein response was significantly lower in the dexamethasone group (a median of 170 versus 220 mg/l for dexamethasone and for placebo respectively; P = 0.015; mean difference = 49 (95% c.i. 13 to 85) mg/l) and when stratified according to intestinal obstruction (a median of 60 versus 160 mg/l for dexamethasone and for placebo respectively; P = 0.002) and perforated viscus (a median of 230 versus 285 mg/l for dexamethasone and for placebo respectively; P = 0.035). Dexamethasone administration was associated with improved recovery (better haemodynamics, better pulmonary function, less fatigue, and earlier mobilization). Furthermore, the dexamethasone group had a lower 90-day mortality rate (7% versus 23% for dexamethasone and for placebo respectively; relative risk 0.33 (95% c.i. 0.11 to 0.93); P = 0.023) and a decreased incidence of postoperative major complications (27% versus 45% for dexamethasone and for placebo respectively; relative risk 0.62 (95% c.i. 0.37 to 1.00); P = 0.032). CONCLUSION: A single preoperative high dose of intravenous dexamethasone significantly reduces the inflammatory response after emergency laparotomy and is associated with enhanced recovery and improved outcome. REGISTRATION NUMBER: NCT04791566 (http://www.clinicaltrials.gov).

Perioperative changes in fluid distribution and haemodynamics in acute high-risk abdominal surgery.

BACKGROUND: Understanding the pathophysiology of fluid distribution in acute high-risk abdominal (AHA) surgery is essential in optimizing fluid management. There is currently no data on the time course and haemodynamic implications of fluid distribution in the perioperative period and the differences between the surgical pathologies. METHODS: Seventy-three patients undergoing surgery for intestinal obstruction, perforated viscus, and anastomotic leakage within a well-defined perioperative regime, including intraoperative goal-directed therapy, were included in this prospective, observational study. From 0 to 120 h, we measured body fluid volumes and hydration status by bioimpedance spectroscopy (BIA), fluid balance (input vs. output), preload dependency defined as a > 10% increase in stroke volume after preoperative fluid challenge, and post-operatively evaluated by passive leg raise. RESULTS: We observed a progressive increase in fluid balance and extracellular volume throughout the study, irrespective of surgical diagnosis. BIA measured variables indicated post-operative overhydration in 36% of the patients, increasing to 50% on the 5th post-operative day, coinciding with a progressive increase of preload dependency, from 12% immediately post-operatively to 58% on the 5th post-operative day and irrespective of surgical diagnosis. Patients with overhydration were less haemodynamically stable than those with normo- or dehydration. CONCLUSION: Despite increased fluid balance and extracellular volumes, preload dependency increased progressively during the post-operative period. Our observations indicate a post-operative physiological incoherence between changes in the extracellular volume compartment and inadequate physiological preload control in patients undergoing AHA surgery. Considering the increasing overhydration during the observational period, our findings show that an indiscriminate correction of preload dependency with intravenous fluid bolus could lead to overhydration. Trial registration clinicaltrials.gov. (NCT03997721), Registered 23 May 2019, first participant enrolled 01 June 2019.

AHA STEROID trial, dexamethasone in acute high-risk abdominal surgery, the protocol for a randomized controlled trial.

INTRODUCTION: Existing multimodal pathways for patients undergoing acute high-risk abdominal surgery for intestinal obstruction (IO) and perforated viscus (PV) have focused on rescue in the immediate perioperative period. However, there is little focus on the peri-operative pathophysiology of recovery in this patient group, as done to develop enhanced recovery pathways in elective care. Acute inflammation is the main driver of the perioperative pathophysiology leading to adverse outcomes. Pre-operative high-dose of glucocorticoids provides a reduction in the inflammatory response after surgery, effective pain relief in several major surgical procedures, as well as reduce fatigue and improving endothelial dysfunction. AIM: To evaluate the effect of high-dose glucocorticoid on the inflammatory response, fluid distribution and recovery after acute high-risk abdominal surgery in patients with IO and PV. METHODS: AHA STEROID trial is a sponsor-initiated single-center, randomized, double-blind placebo-controlled trial, assessing preoperative high-dose dexamethasone (1 mg/kg) versus placebo (normal saline) in patients undergoing emergency high-risk abdominal surgery. We plan to enroll 120 patients. Primary outcome is the reduction in C-reactive protein on postoperative day 1 as a marker of successful attenuation of the acute stress response. Secondary outcomes include perioperative changes in endothelial and other inflammatory markers, fluid distribution, pulmonary function, pain, fatigue, and mobilization. The statistical plan is outlined in the protocol. DISCUSSION: The AHA STEROID trial will provide important evidence to guide the potential use of high-dose glucocorticoids in emergency high-risk abdominal surgery, with respect to different pathophysiologies.

Inflammatory response, fluid balance and outcome in emergency high-risk abdominal surgery.

BACKGROUND: The main disease etiologies requiring emergency high-risk abdominal surgery are intestinal obstruction and perforated viscus and the differences in immune response to these pathologies are largely unexplored. In search of improvement of patient assessment in the perioperative phase, we examined the inflammatory response in this setting, focusing on potential difference in pathophysiology. METHODS: The electronic medical records of 487 patients who underwent emergency abdominal surgery from year 2013-2015 for intestinal obstruction and perforated viscus were reviewed. We evaluated the relationship between pre- and postoperative C-reactive protein (CRP) trajectory, fluid balance, and perioperative morbidity and mortality according to type of surgery, intervention, and surgical pathology. RESULTS: A total of 418 patients were included. Pre- and postoperative absolute CRP values were significantly higher in patients with perforated viscus (n = 203) than in intestinal obstruction (n = 215) (P < .0001). Relative changes at hour 6 and POD 1 were non-significant (P = .716 and P = .816 respectively). There was significant association between both pre- (quartile 1 vs 4, OR 5.11; P < .01) and postoperative (quartile 1 vs 4, OR 4.10; P < .001) CRP and adverse outcome, along with fluid balance and adverse outcome in patients with obstruction but not in those with perforation. Fluid balance and CRP had statistically significant positive correlation in patients with obstruction. CONCLUSIONS: In this explorative study, a high pre- and postoperative CRP and a high positive fluid balance were associated with worse outcome in patients with intestinal obstruction, but not in patients with perforated viscus. Future studies should address the different inflammatory and fluid trajectories in these specific pathologies.

Inflammatory response after transanal total mesorectal excision.

INTRODUCTION: The advantages of transanal total mesorectal excision (taTME) would be a reduction of the hernia rate and surgical trauma. The present study reports data for patients undergoing taTME and compares the post-operative immune response in taTME with those of conven-tional laparoscopic surgery (CLS) and single-port laparo-scopic surgery (SPLS). METHODS: A comparative cohort study in patients with rectal cancer undergoing taTME. C-reactive protein (CRP) and white blood cell count (WBC) were measured pre-operatively and on post-operative days one, two, three and four. RESULTS: A total of 40 patients were included in taTME, 20 patients in CLS and 20 in SPLS. Patients' demographics (except for clinical staging), R0 resection and post-operative complication rates were comparable. The length of abdom-inal incisio-n was significantly lower by taTME than by both SPLS and CLS (p < 0.001). Distant resection margin was shorter in the taTME group (p < 0.01), and the quality of specimen differed between groups (p < 0.01). CRP and WBC increased significantly in each group (p < 0.05), but there was no difference between the groups. CONCLUSIONS: There is no difference in the inflammatory response in patients with rectal cancer undergoing taTME surgery compared with CLS and SPLS. We therefore conclude that the length/presence of abdominal incision does not further reduce the post-operative inflammatory stress response in minimally invasive procedures. The surgical trauma extends beyond the abdominal incision and depends on the intra-abdominal handling of the tissue. FUNDING: none. TRIAL REGISTRATION: ID NCT00157972, ethical approval ID H-1-2011-007, H-15000540.