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).

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).

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study.

STUDY OBJECTIVE: Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. DESIGN: Multicenter cohort study. SETTING: Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. PATIENTS: We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. INTERVENTIONS: No interventions were carried out. MEASUREMENTS: Principal values collected included measurements of peripheral perfusion index and hemoglobin values. METHODS: The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. MAIN RESULTS: We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231). Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62-5.45]) and 90-day mortality (3.13, [1.45-7.11]). A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57-162.10]). CONCLUSION: High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.

"The peripheral perfusion index discriminates haemodynamic responses to induction of general anaesthesia".

Induction of general anaesthesia is often accompanied by hypotension. Standard haemodynamic monitoring during anaesthesia relies on intermittent blood pressure and heart rate. Continuous monitoring systemic blood pressure requires invasive or advanced modalities creating a barrier for obtaining important information of the circulation. The Peripheral Perfusion Index (PPI) is obtained non-invasively and continuously by standard photoplethysmography. We hypothesized that different patterns of changes in systemic haemodynamics during induction of general anaesthesia would be reflected in the PPI. Continuous values of PPI, stroke volume (SV), cardiac output (CO), and mean arterial pressure (MAP) were evaluated in 107 patients by either minimally invasive or non-invasive means in a mixed population of surgical patients. 2 min after induction of general anaesthesia relative changes of SV, CO, and MAP was compared to the relative changes of PPI. After induction total cohort mean(± st.dev.) MAP, SV, and CO decreased to 65(± 16)%, 74(± 18)%, and 63(± 16)% of baseline values. In the 38 patients where PPI decreased MAP was 57(± 14)%, SV was 63(± 18)%, and CO was 55(± 18)% of baseline values 2 min after induction. In the 69 patients where PPI increased the corresponding values were MAP 70(± 15)%, SV 80(± 16)%, and CO 68(± 17)% (all differences: p < 0,001). During induction of general anaesthesia changes in PPI discriminated between the degrees of reduction in blood pressure and algorithm derived cardiac stroke volume and -output. As such, the PPI has potential to be a simple and non-invasive indicator of the degree of post-induction haemodynamic changes.

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.

Fluid-responsiveness, blood volume and perfusion in preoperative haemodynamic optimisation of hip fracture patients; a prospective observational study.

BACKGROUND: Preoperative resuscitation strategies in patients with hip fracture (HF) are lacking. We aimed to investigate fluid-responsiveness, peripheral perfusion index (PPI) and blood volume (BV)-status in patients with HF undergoing resuscitation in the preoperative phase. METHODS: In a prospective observational study, we evaluated preoperative fluid-responsiveness, indices of perfusion and BV before and after lumbar epidural analgesia in 50 patients with HF shortly after admittance. RESULTS: Initially, 18 (36%) patients were fluid-responsive (≥10% increased SV in response to 250 ml fluid bolus) and 13 (26%) presented hypovolaemia (deviation of measured BV from estimated BV ≤ 0.9). According to fluid-responsiveness, no difference in absolute values of cardiac index (CI) (2.7 L [2.1-3.3] vs. 2.8 L [2.3-3.4], p = .5) was seen, but cardiac output (CO) rose significantly in the hypovolaemic patients: 9% [5-18] vs. 1% [-3-7], p = .004. After epidural analgesia, 26 (52%) patients were again fluid-responsive and 15 (30%) were hypovolaemic. CI was now significantly lower in fluid-responsive patients (2.2 L [1.7-2.7] vs. 2.9 L [2.3-3.5], p = .001). Prior to epidural analgesia, no significant trend towards hypovolaemic patients having lower indices of perfusion was seen. After epidural analgesia, more patients with hypovolaemia presented with PPI≤1.5 (8 (53%) vs. 3 (9%), p = .001) and absolute values of PPI were also significantly lower if IBV was low (1.4 [0.9-3.2] vs. 3.2 [2.4-4.8], p = .01). PPI correlated with hypovolaemia after epidural analgesia (rho 0.4 [0.1-0.7], p = .007). CONCLUSIONS: Preoperative fluid-responsivity in HF patients might be attributable to elements of hypovolaemia and sympathetic compensatory ability conjointly, confounding the use of SV-guided resuscitation. PPI could be associated with BV, which may support clinicians during perioperative haemodynamic optimisation.

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.

The effect of vasoconstriction on intestinal perfusion is determined by preload dependency: A prospective observational study.

BACKGROUND: The effects of vasoconstriction on cardiac stroke volume (SV) and indices of peripheral and intestinal perfusion are insufficiently described. METHODS: In a non-randomized clinical study, 30 patients undergoing elective rectal surgery were exposed to modulation of preload. The primary endpoint was intestinal perfusion (flux), measured by single-point laser Doppler flowmetry. Secondary endpoints were central cardiovascular variables obtained by the LiDCO rapid monitor, the peripheral perfusion index (PPI) derived from the pulse oximetry signal and muscle (StO2 ) and cerebral oxygenation (ScO2 ) determined by near-infrared spectroscopy. RESULTS: For the whole cohort (n = 30), administration of Phenylephrine during HUT induced a median [IQR] increase in SV by 22% [14-41], p = .003 and in mean arterial pressure (MAP) by 54% [31-62], p < .001, with no change in PPI, StO2 and ScO2 or flux. In patients who were preload dependent during HUT (stroke volume variation; SSV >10%; n = 23), administration of phenylephrine increased SV by 29% [12-43], p = .01 and MAP by 54% [33-63], p < .001, followed by an increase in intestinal perfusion flux by 60% [15-289], p = .05, while PPI, StO2 and ScO2  remained unchanged. For non-preload dependent patients (SSV <10%; n = 7), no changes in hemodynamic indices were seen besides an increase in MAP by 54% [33-58], p = .002. CONCLUSION: The reflection of vasoconstrictive modulation of preload in systemic cardiovascular variables and indices of perfusion was dependent on preload responsiveness. Administration of phenylephrine to increase preload did not appear to compromise organ perfusion.

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.

Association of the intraoperative peripheral perfusion index with postoperative morbidity and mortality in acute surgical patients: a retrospective observational multicentre cohort study.

BACKGROUND: We hypothesised that in acute high-risk surgical patients, a lower intraoperative peripheral perfusion index (PPI) would indicate a higher risk of postoperative complications and mortality. METHODS: This retrospective observational study included 1338 acute high-risk surgical patients from November 2017 until October 2018 at two University Hospitals in Denmark. Intraoperative PPI was the primary exposure variable and the primary outcome was severe postoperative complications defined as a Clavien-Dindo Class ≥III or death, within 30 days. RESULTS: intraoperative PPI was associated with severe postoperative complications or death: odds ratio (OR) 1.12 (95% confidence interval [CI] 1.05-1.19; P<0.001), with an association of intraoperative mean PPI ≤0.5 and PPI ≤1.5 with the primary outcome: OR 1.79 (95% CI 1.09-2.91; P=0.02) and OR 1.65 (95% CI 1.20-2.27; P=0.002), respectively. Each 15-min increase in intraoperative time spend with low PPI was associated with the primary outcome (per 15 min with PPI ≤0.5: OR 1.11 (95% CI 1.05-1.17; P<0.001) and with PPI ≤1.5: OR 1.06 (95% CI 1.02-1.09; P=0.002)). Thirty-day mortality in patients with PPI ≤0.5 was 19% vs 10% for PPI >0.5, P=0.003. If PPI was ≤1.5, 30-day mortality was 16% vs 8% in patients with a PPI >1.5 (P<0.001). In contrast, intraoperative mean MAP ≤65 mm Hg was not significantly associated with severe postoperative complications or death (OR 1.21 [95% CI 0.92-1.58; P=0.2]). CONCLUSIONS: Low intraoperative PPI was associated with severe postoperative complications or death in acute high-risk surgical patients. To guide intraoperative haemodynamic management, the PPI should be further investigated.

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.

Protocol for a multicentre retrospective observational cohort study in Denmark: association between the intraoperative peripheral perfusion index and postoperative morbidity and mortality in acute non-cardiac surgical patients.

INTRODUCTION: Perioperative haemodynamic instability is associated with postoperative morbidity and mortality. Macrocirculatory parameters, such as arterial blood pressure and cardiac output are associated with poor outcome but may be uncoupled from the microcirculation during sepsis and hypovolaemia and may not be optimal resuscitation parameters. The peripheral perfusion index (PPI) is derived from the pulse oximetry signal. Reduced peripheral perfusion is associated with morbidity in critically ill patients and in patients following acute surgery. We hypothesise that a low intraoperative PPI is independently associated with postoperative complications and mortality. METHODS AND ANALYSIS: We plan to conduct a retrospective cohort study in approximately 2300 patients, who underwent acute non-cardiac surgery (1 November 2017 to 31 October 2018) at two Danish University Hospitals. Data will be collected from patient records including patient demographics, comorbidity and intraoperative haemodynamic values with PPI as the primary exposure variable, and postoperative complications and mortality within 30 and 90 days as outcome variables. We primarily assess association between PPI and outcome in multivariate regression models. Second, the predictive value of PPI for outcome, using area under the receiver operating characteristics curve is assessed. ETHICS AND DISSEMINATION: Data will be reported according to the Strengthening the Reporting of Observational Studies in Epidemiology and results published in a peer-reviewed journal. The study is approved by the regional research ethics committee, storage and management of data has been approved by the Regional Data Protection Agency, and access to medical records is approved by the hospital board of directors (ClinicalTrials.gov registration no: NCT03757442).

Effect of head rotation on cerebral blood velocity in the prone position.

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P < 0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.