Vasoconstriction with phenylephrine increases cardiac output in preload dependent patients.

General Anaesthesia (GA) is accompanied by a marked decrease in sympathetic outflow and thus loss of vasomotor control of cardiac preload. The use of vasoconstriction during GA has mainly focused on maintaining blood pressure. Phenylephrine (PE) is a pure α1-agonist without inotropic effects widely used to correct intraoperative hypotension. The potential of PE for augmenting cardiac stroke volume (SV) and -output (CO) by venous recruitment is controversial and no human studies have explored the effects of PE in preload dependent circulation using indicator dilution technique. We hypothesized that PE-infusion in patients with cardiac stroke volume limited by reduced preload would restore preload and thus augment SV and CO. 20 patients undergoing GA for gastrointestinal surgery were monitored with arterial catheter and LiDCO unity monitor. Upon stable haemodynamics after induction patients were placed in head-up tilt (HUT). All patients became preload responsive as verified by a stroke volume variation (SVV) of > 12%. PE-infusion was then started at 15-20mikrg/min and adjusted until preload was restored (SVV < 12%). Li-dilution cardiac output (CO) was initially measured after induction (baseline), again with HUT in the preload responsive phase, and finally when preload was restored with infusion of PE.At baseline SVV was 10 ± 3% (mean ± st.dev.), CI was 2,6 ± 0,4 L/min*m2, and SVI 43 ± 7mL/m2. With HUT SVV was 19 ± 4%, CI was 2,2 ± 0,4 L/min*m2, SVI 35 ± 7mL/m2. During PE-infusion SVV was reduced to 6 ± 3%, CI increased to 2,6 ± 0,5 L/min*m2, and SVI increased to 49 ± 11mL/m2. All differences p < 0,001. In conclusion: Infusion of phenylephrine during preload dependency increased venous return abolishing preload dependency as evaluated by SVV and increased cardiac stroke volume and -output as measured by indicator-dilution technique. (ClinicalTrials.gov NCT05193097).

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.

Triage and outcomes for a whole cohort of patients presenting for major emergency abdominal surgery including the No-LAP population: a prospective single-center observational study.

PURPOSE: This study aimed to characterize 252 consecutive patients with an indication for major emergency abdominal surgery including patients not proceeding to surgery (No-Lap). Patients who do not proceed to major emergency abdominal surgery and their clinical outcomes are not well characterized in the existing literature. Triage criteria may vary between centers, potentially impacting reported outcomes. METHODS: A single-center prospective observational study in a high-volume Danish surgical center including 252 patients presenting with an indication for major emergent abdominal surgery was conducted from the 15th of October 2020 to the 15th of August 2021. The primary outcome was to estimate the prevalence of No-Lap patients. RESULTS: Overall, 21 patients (8.3%) of our total study cohort did not proceed to surgery. These patients were significantly older, more comorbid with higher ASA scores, poorer performance status, and were more likely to have bowel ischemia. Poor functional performance and surgeons' consideration of futile intervention were the main reasons for deferring surgery in all 21 patients. Overall, 30-day mortality was 95% for the No-LAP cohort, 9% for the LAP cohort, and 16% for the whole cohort, respectively. CONCLUSIONS: The No-LAP group selection process could be one of the main determinants of reported postoperative outcomes. Prospective international multi-center studies to characterize the entire cohort of patients eligible for emergency laparotomy including the No-LAP population are needed, as large variations in triage criteria and culture seem to exist. Trial registration Retrospectively registered.

Electrolyte and Acid-Base Disturbances in Emergency High-Risk Abdominal Surgery, a Retrospective Study.

BACKGROUND: Patients undergoing emergency high-risk abdominal surgery potentially suffer from both systemic dehydration and hypovolaemia. Data on the prevalence and clinical impact of electrolyte disturbances in this patient group, specifically the differences in patients with intestinal obstruction (IO) versus perforated viscus (PV) are lacking. METHODS: Adult patients undergoing emergency high-risk abdominal surgery in a standardized perioperative pathway were included in this retrospective single-center cohort study. Electrolytes and arterial blood gas analysis were measured during the early perioperative period. Prevalence and clinical impact of electrolyte disturbances were assessed. RESULTS: A total of 354 patients were included in the study. Preoperative alkalemia dominated preoperatively, significantly more prevalent in IO (45 vs. 32%, p < .001), while acidosis was most pronounced postoperatively in PV (49 vs. 28%, p < .0001). Preoperative hypochloraemia and hypokalemia were more frequent in the IO (34 vs. 20% and 37 vs. 25%, respectively). Hyponatremia was highly prevalent in both IO and PV. Pre- and postoperative hypochloremia were independently associated with 30-day postoperative morbidity and mortality in patients with IO (OR 2.87 (1.35, 6.23) p = 0.006, OR 6.86 (1.71, 32.2) p = 0.009, respectively). Hypochloremic patients presented with reduced long-term survival as compared with the normo- and hyperchloremic patients (p < 0.05). Neither plasma sodium nor potassium showed a significant association with outcome. CONCLUSION: These observations suggest that acute high-risk abdominal patients have frequent preoperative alkalosis shifting to postoperative acidosis. Both pre- and postoperative hypochloremia were independently associated with both impaired short- and long-term outcome in patients with intestinal obstruction, with potential implications for the choice of resuscitations fluids.

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.

Mortality and major complications after emergency laparotomy: A pilot study of risk prediction model development by preoperative blood-based immune parameters.

BACKGROUND: Emergency laparotomy is associated with high risk of postoperative complications and mortality. Preoperative identification of patients at high risk of adverse outcome is important. The immune response to conditions requiring emergency laparotomy is not understood in detail. The present study describes preoperative blood-based immune profiles and their potential value in surgical risk assessment. METHOD: Patients (N = 100) referred for emergency laparotomy at Hvidovre Hospital were consecutively included from 3 June 2013-11 April 2014. All patients had blood samples collected before surgery and the immune parameters c-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), interferon-γ induced protein 10 kDa (IP-10), tumor necrosis factor α (TNF-α) and soluble urokinase plasminogen receptor activator (suPAR) were determined. Patients were stratified according to major postoperative complications (including death), 30- and 180-day mortality. Using logistic regression models and receiver operating characteristics curves the predictive ability of the immune parameters were estimated. RESULTS: Major complications were recorded in 45 (45.0%) of the patients, whereas 30-day and 180-day mortalities were 17 (17.0%) and 25 (25.0%), respectively. Concentrations of suPAR and TNF-α were associated with major complications while CRP, IL-6, suPAR and TNF-α were associated with mortality. Adding the combined immune parameters to a regression model including age, sex, American Society of Anesthesiologists physical status and Eastern Cooperative Oncology Group Performance Status significantly improved the predictive ability for major complications, 30-day mortality and 180-day mortality. CONCLUSION: In emergency laparotomy, preoperative blood-based immune parameters added predictive power to regression models and could be considered in risk prediction model development.

Functional performance and 30-day postoperative mortality after emergency laparotomy-a retrospective, multicenter, observational cohort study of 1084 patients.

BACKGROUND: Despite the importance of predicting adverse postoperative outcomes, functional performance status as a proxy for frailty has not been systematically evaluated in emergency abdominal surgery. Our aim was to evaluate if the Eastern Cooperative Oncology Group (ECOG) performance score was independently associated with mortality following high-risk emergency abdominal surgery, in a multicentre, retrospective, observational study of a consecutive cohort. METHODS: All patients aged 18 or above undergoing high-risk emergency laparotomy or laparoscopy from four emergency surgical centres in the Capitol Region of Denmark, from January 1 to December 31, 2012, were included. Demographics, preoperative status, ECOG performance score, mortality, and surgical characteristics were registered. The association of frailty with postoperative mortality was evaluated using multiple regression models. Likelihood ratio test was applied for goodness of fit. RESULTS: In total, 1084 patients were included in the cohort; unadjusted 30-day mortality was 20.2%. ECOG performance score was independently associated with 30-day mortality. Odds ratio for mortality was 1.70 (95% CI (1.0, 2.9)) in patients with ECOG performance score of 1, compared with 5.90 (95% CI (1.8, 19.0)) in patients with ECOG performance score of 4 (p < 0.01). Likelihood ratio test suggests improvement in fit of logistic regression modelling of 30-day postoperative mortality when including ECOG performance score as an explanatory variable. CONCLUSIONS: This study found ECOG performance score to be independently associated with the postoperative 30-day mortality among patients undergoing high-risk emergency laparotomy. The utility of including functional performance in a preoperative risk assessment model of emergency laparotomy should be evaluated.

Prediction of Outcome After Emergency High-Risk Intra-abdominal Surgery Using the Surgical Apgar Score.

BACKGROUND: With current literature quoting mortality rates up to 45%, emergency high-risk abdominal surgery has, compared with elective surgery, a significantly greater risk of death and major complications. The Surgical Apgar Score (SAS) is predictive of outcome in elective surgery, but has never been validated exclusively in an emergency setting. METHODS: A consecutive prospective single-center cohort study of 355 adults undergoing emergency high-risk abdominal surgery between June 2013 and May 2014 is presented. The primary outcome measure was 30-day mortality. Secondary outcome measures were postoperative major complications, defined according to the Clavien-Dindo scale as well as the American College of Surgeons' National Surgical Quality Improvement Program guidelines, and intensive care unit admission. The SAS was calculated postoperatively. Cochran-Armitage test for trend was used to evaluate the incidence of both outcomes. Area under the curve was used to demonstrate the scores' discriminatory power. RESULTS: One hundred eighty-one (51.0%) patients developed minor or no complications. The overall incidence of major complications was 32.7% and the overall death rate was 16.3%. Risk of major complications, death, and intensive care unit admission increased significantly with decreasing SAS (P < .001). The score's c-statistics were 0.63. CONCLUSIONS: We have demonstrated the SAS to be significantly predictive but weakly discriminative for major complications and death among adults undergoing emergency high-risk abdominal surgery. Despite its predictive value, the SAS cannot in its current version be recommended as a standalone prognostic tool in an emergency setting.