Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.

Hypotension after general anaesthesia induction using remimazolam or propofol in geriatric patients undergoing sevoflurane anaesthesia with remifentanil: a single-centre, double-blind, randomised controlled trial.

BACKGROUND: The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients. METHODS: This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg-1 h-1) or propofol (0.025 mg kg-1 s-1) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age. RESULTS: Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37-2.46; P=0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups. CONCLUSIONS: Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr. CLINICAL TRIAL REGISTRATION: UMIN000042587.

Effect of subclavian vein diameter combined with perioperative fluid therapy on preventing post-induction hypotension in patients with ASA status I or II.

BACKGROUND: Perioperative hypotension is frequently observed following the initiation of general anesthesia administration, often associated with adverse outcomes. This study assessed the effect of subclavian vein (SCV) diameter combined with perioperative fluid therapy on preventing post-induction hypotension (PIH) in patients with lower ASA status. METHODS: This two-part study included patients aged 18 to 65 years, classified as ASA physical status I or II, and scheduled for elective surgery. The first part (Part I) included 146 adult patients, where maximum SCV diameter (dSCVmax), minimum SCV diameter (dSCVmin), SCV collapsibility index (SCVCI) and SCV variability (SCVvariability) assessed using ultrasound. PIH was determined by reduction in mean arterial pressure (MAP) exceeding 30% from baseline measurement or any instance of MAP < falling below 65 mmHg for ≥ a duration of at least 1 min during the period from induction to 10 min after intubation. Receiver Operating Characteristic (ROC) curve analysis was employed to determine the predictive values of subclavian vein diameter and other relevant parameters. The second part comprised 124 adult patients, where patients with SCV diameter above the optimal cutoff value, as determined in Part I study, received 6 ml/kg of colloid solution within 20 min before induction. The study evaluated the impact of subclavian vein diameter combined with perioperative fluid therapy by comparing the observed incidence of PIH after induction of anesthesia. RESULTS: The areas under the curves (with 95% confidence intervals) for SCVCI and SCVvariability were both 0.819 (0.744-0.893). The optimal cutoff values were determined to be 45.4% and 14.7% (with sensitivity of 76.1% and specificity of 86.7%), respectively. Logistic regression analysis, after adjusting for confounding factors, demonstrated that both SCVCI and SCVvariability were significant predictors of PIH. A threshold of 45.4% for SCVCI was chosen as the grouping criterion. The incidence of PIH in patients receiving fluid therapy was significantly lower in the SCVCI ≥ 45.4% group compared to the SCVCI < 45.4% group. CONCLUSIONS: Both SCVCI and SCVvariability are noninvasive parameters capable of predicting PIH, and their combination with perioperative fluid therapy can reduce the incidence of PIH.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Effect of phenylephrine rescue injection on hypotension after spinal anaesthesia for caesarean delivery when guided by both heart rate and SBP during an early warning window: A randomised controlled trial.

BACKGROUND: Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension. OBJECTIVE: To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability. SETTING: A teaching hospital. DESIGN: A randomised controlled trial. PATIENTS: One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study. INTERVENTIONS: All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion. MAIN OUTCOME MEASURES: The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events. RESULTS: The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P  = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ±â€Š9.49 vs. 86.7 ±â€Š11.16 mmHg, P   =  0.004). There was no significant difference in the incidence of hypertension between groups. CONCLUSION: After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension. TRIAL REGISTRATION: Chictr.org.cn; Identifier: ChiCTR 2100041812.

Effect of Remimazolam- versus Propofol-Based Total Intravenous General Anesthesia on Intraoperative Hemodynamic Stability for Major Spine Surgery in the Prone Position: A Randomized Controlled Trial.

Background and Objectives: Remimazolam offers advantages over propofol in terms of hemodynamic stability. However, it remains unclear whether remimazolam-based total intravenous anesthesia (TIVA) can reduce intraoperative hypotension compared to propofol-based TIVA, especially after prone positioning. In this study, we compared the effects of remimazolam- and propofol-based TIVA on intraoperative hemodynamic stability in patients undergoing surgery in the prone position. Materials and Methods: This study randomly assigned patients undergoing major spinal surgery in the prone position to the propofol or remimazolam group. Target-controlled infusion (2-3.5 µg/mL for induction and 2-3 µg/mL for maintenance) was used in the propofol group and continuous infusion (6 mg/kg/h for induction and 1-2 mg/kg/h for maintenance) was used in the remimazolam group; target-controlled infusion (3-5 ng/mL) of remifentanil was performed in both groups. The primary outcomes were the incidence of hypotensive episodes during the first hour after prone positioning. The secondary outcomes included the incidence of severe hypotension and the total amount of inotropic or vasopressor medication. Systolic and mean arterial pressure, heart rate, cardiac index and output, stroke volume, stroke volume variation, and pleth variability index were also evaluated. These variables were recorded per minute for the first 10 min after prone positioning, and every 10 min thereafter. Results: The study enrolled 94 patients (47 patients in each group). The incidence of hypotension or severe hypotension did not differ significantly between the two groups during the first hour after prone positioning. The total amount of ephedrine administered during the first hour after prone positioning was lesser (p = 0.020) and the mean arterial pressure during the initial 10 min after prone positioning was higher in the remimazolam group (p = 0.003). Conclusions: Our study uncovered no significant differences in the incidence of hypotension between remimazolam- and propofol-based TIVA in patients undergoing major spine surgery in prone position.

Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure.

[Figure: see text].

Effectiveness of cold HD for the prevention of HD hypotension and mortality in the general HD population.

BACKGROUND: Cold hemodialysis (HD) prevented intradialysis hypotension (IDH) in small, short-term, randomized trials in selected patients with IDH. Whether this treatments prevents IDH and mortality in the HD population at large is unknown. METHODS: We investigated the relationship between dialysate temperature and the risk of IDH, i.e. nadir blood pressure <90 mmHg (generalized estimating equation model) and all-cause mortality (Cox's regression) in an incident cohort of HD patients (n = 8071). To control for confounding by bias by indication and other factors we applied instrumental variables adjusting for case mix at facility level. RESULTS: Twenty-seven percent of patients in the study cohort were systematically treated with a dialysate temperature ≤35.5°C. Over a median follow-up of 13.6 months (interquartile range 5.2-26.1 months), a 0.5°C reduction of the dialysate temperature was associated with a small (-2.4%) reduction of the risk of IDH [odds ratio (OR) 0.976, 95% confidence interval (CI) 0.957-0.995, P = .013]. In case-mix, facility-level adjusted analysis, the association became much stronger (OR 0.67, 95% CI 0.63-0.72, risk reduction = 33%, P < .001). In contrast, colder dialysate temperature had no effect on mortality both in the unadjusted [hazard ratio (HR) (0.5°C decrease) 1.074, 95% CI 0.972-1.187, P = .16] and case-mix-adjusted analysis at facility level (HR 1.01, 95% CI 0.88-1.16, P = .84). Similar results were registered in additional analyses by instrumental variables applying the median dialysate temperature or the facility percentage of patients prescribed a dialysate temperature <36°C. Further analyses restricted to patients with recurrent IDH fully confirmed these findings. CONCLUSIONS: Cold HD was associated with IDH in the HD population but had no association with all-cause mortality.

Intraoperative arterial pressure management: knowns and unknowns.

Preventing postoperative organ dysfunction is integral to the practice of anaesthesia. Although intraoperative hypotension is associated with postoperative end organ dysfunction, there remains ambiguity with regards to its definition, targets, thresholds for initiating treatment, and ideal treatment modalities.

Intraoperative blood pressure: could less be more?

Retrospective observational studies have reported a significant association between intraoperative hypotension and postoperative morbidity. However, association does not imply causation, and whether preventing intraoperative hypotension can improve patient outcome remains to be demonstrated. In this issue of the British Journal of Anaesthesia, D'Amico and colleagues meta-analysed 10 prospective randomised trials comparing low (≤60 mm Hg) and higher mean arterial pressure targets during anaesthesia and surgery. They did not observe an increase in postoperative morbidity and mortality in the low target group. In contrast, they reported a statistically significant (but not clinically relevant) reduction in postoperative cardiac arrhythmia and hospital length of stay when targeting mean arterial pressure ≤60 mm Hg. These findings suggest that during most surgical cases, intraoperative hypotension is a marker of the severity, frailty, or both rather than a mediator of postoperative complications.

Application Value of Limb Ischemic Preconditioning in Preventing Intradialytic Hypotension during Maintenance Hemodialysis.

INTRODUCTION: The aim of this study was to investigate the efficacy and safety of limb ischemia preconditioning (LIPC) in the treatment of intradialytic hypotension (IDH) in patients with maintenance hemodialysis (MHD). METHODS: This was a single-center, prospective, and randomized controlled case study. A total of 38 patients with MHD who met the inclusion criteria from September 2021 to August 2022 were selected from the Blood Purification Center of our hospital. They were randomly divided into the LIPC group (n = 19) and the control group (n = 19). For patients in the LIPC group, the femoral artery blood flow was blocked with an LIPC instrument for 5 min (pressurized to 200 mm Hg) before each dialysis, and they were reperfused for 5 min. The cycle was repeated five times, with a total of 50 min for 12 weeks. The control group was pressurized to 20 mm Hg with an LIPC instrument, and the rest was the same as the LIPC group. The blood pressure of 0 h, 1 h, 2 h, 3 h, 4 h, and body weight before and after hemodialysis were measured in the two groups during hemodialysis, the incidence of IDH and the changes of serum troponin I (TNI) and creatine kinase isoenzyme MB (CK-MB) levels before and after the intervention were observed, and the ultrafiltration volume and ultrafiltration rate were recorded. RESULTS: At the 8th and 12th week after intervention, the MAP in the LIPC group was higher than that in the control group (103.28 ± 12.19 mm Hg vs. 93.18 ± 11.11 mm Hg, p = 0.04; 101.81 ± 11.36 mm Hg vs. 91.81 ± 11.92 mm Hg, p = 0.047). The incidence of IDH in the LIPC group was lower than that in the control group (36.5% vs. 43.1%, p = 0.01). The incidence of clinical treatment in IDH patients in the LIPC group was lower than that in the control group (6.3% vs. 12.4%, p = 0.00). The incidence of early termination of hemodialysis in the LIPC group was lower than that in the control group (1.6% vs. 3.8%, p = 0.01). The levels of TNI and CK-MB in the LIPC group after the intervention were lower than those in the control group (322.30 ± 13.72 ng/dL vs. 438.50 ± 24.72 ng/dL, p = 0.00; 159.78 ± 8.48 U/dL vs. 207.00 ± 8.70 U/dL, p = 0.00). The changes of MAP before and after the intervention were negatively correlated with the changes of TNI and CK-MB before and after the intervention (r = -0.473, p = 0.04; r = -0.469, p = 0.04). There were no differences in dry body mass and ultrafiltration rate between the two groups before and after the LIPC intervention (p > 0.05). Multiple linear regression analysis shows that TNI is the main influencing factor of ΔMAP. No LIPC-related adverse events were found during the study period. CONCLUSION: LIPC can effectively reduce the incidence of IDH in patients with MHD and may be associated with the alleviation of myocardial damage.

Oxytocin infusion for maintenance of uterine tone under prophylactic phenylephrine infusion for prevention of post-spinal hypotension in cesarean delivery: a prospective randomised double-blinded dose-finding study.

BACKGROUND: Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery. METHODS: In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored. RESULTS: The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3-16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes. CONCLUSION: Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).

Hemodynamic effects of a low versus a high dose of propofol during induction of anesthesia. A randomized trial.

BACKGROUND: Hypotension is common after anesthesia induction with propofol and is associated with increased morbidity. It is important to examine the effects of the proposed interventions to limit preventable hypotension, as suggested by the reduction in the dose of propofol. Our objective was to investigate whether a high dose of propofol is inferior to a low dose with respect to changes in systolic arterial blood pressure (SAP). METHODS: This randomized, double-blind, dose-controlled, non-inferiority study included 68 healthy women scheduled for gynecological surgery at the Day Surgery Unit, Haugesund Hospital, Norway. The patients were randomly allocated 1:1 to a low or high dose (1.4 mg/kg total body weight (TBW) versus 2.7 mg/kg TBW of propofol corresponding to maximal effect site concentrations (Ce) of 2.0 µg/mL versus 4.0 µg/mL. The dose of remifentanil was 1.9-2.0 µg/kg TBW, with maximal Ce of 5.0 ng/mL. The patients were observed for 450 s from the start of the infusions. The first 150 s was the sedation period, after which a bolus of propofol and remifentanil was administered. Baseline was defined as 55-5 s before the bolus doses. LiDCOplus was used for invasive beat-to-beat hemodynamic monitoring of changes in SAP, heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). A difference of 10 mmHg in the change in SAP was considered to be clinically important. RESULTS: The SAP change difference for low versus high dose was -2.9 mmHg (95% CI -9.0-3.1). The relative changes for low versus high dose were SAP -31% versus -36%, (p < .01); HR -24% versus -20%, (p = .09); SVR -20% versus -31%, (p < .001); SV -16% versus -20%, (p = .04); and CO -35% versus -32%, (p = .33). CONCLUSION: A high dose of propofol was not inferior to a low dose, and a reduction in the dose of propofol did not result in clinically important attenuation of major hemodynamic changes during induction in healthy women. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03861364, January 3, 2019.

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial.

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.

Bradykinin B2 receptor blockade and intradialytic hypotension.

INTRODUCTION: Intradialytic hypotension (IDH) is a common clinical complication and is associated with increased morbidity and mortality in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of IDH has been attributed to the rapid reduction of plasma volume during hemodialysis and the inadequate compensatory mechanisms in response to hypovolemia, such as the lack of vasoconstriction. This may be due to the increased production of vasodilators, such as bradykinin. In this study we test the hypothesis that bradykinin B2 receptor blockade prevents intradialytic hypotension. METHODS: We performed a post-hoc analysis of a double-blind, placebo-controlled, randomized, 2 × 2 crossover clinical trial comparing the continuous infusion of icatibant, a bradykinin B2 receptor blocker, and placebo during hemodialysis. Icatibant or placebo was infused for 30 min before and during hemodialysis in 11 patients on MHD. RESULTS: Seven of the patients had IDH, defined as a reduction of systolic blood pressure equal to or greater than 20 mmHg during hemodialysis. Stratified analysis, based on the presence of IDH, revealed that icatibant prevented the decrease in blood pressure compared to placebo in patients with IDH [blood pressure at average nadir (2.5 h after hemodialysis): Placebo,114.3 ± 8.9 vs. icatibant, 125.6 ± 9.1 mmHg, mean ± S.E.M]. Icatibant did not affect blood pressure in the group of patients without IDH. CONCLUSION: Bradykinin B2 receptor blocker may prevent the occurrence of IDH. Further studies should evaluate the hemodynamic effects of icatibant during hemodialysis and the symptomatology associated with IDH.

Hypotension prediction index guided versus conventional goal directed therapy to reduce intraoperative hypotension during thoracic surgery: a randomized trial.

PURPOSE: Intraoperative hypotension is linked to increased incidence of perioperative adverse events such as myocardial and cerebrovascular infarction and acute kidney injury. Hypotension prediction index (HPI) is a novel machine learning guided algorithm which can predict hypotensive events using high fidelity analysis of pulse-wave contour. Goal of this trial is to determine whether use of HPI can reduce the number and duration of hypotensive events in patients undergoing major thoracic procedures. METHODS: Thirty four patients undergoing esophageal or lung resection were randomized into 2 groups -"machine learning algorithm" (AcumenIQ) and "conventional pulse contour analysis" (Flotrac). Analyzed variables were occurrence, severity and duration of hypotensive events (defined as a period of at least one minute of MAP below 65 mmHg), hemodynamic parameters at 9 different timepoints interesting from a hemodynamics viewpoint and laboratory (serum lactate levels, arterial blood gas) and clinical outcomes (duration of mechanical ventilation, ICU and hospital stay, occurrence of adverse events and in-hospital and 28-day mortality). RESULTS: Patients in the AcumenIQ group had significantly lower area below the hypotensive threshold (AUT, 2 vs 16.7 mmHg x minutes) and time-weighted AUT (TWA, 0.01 vs 0.08 mmHg). Also, there were less patients with hypotensive events and cumulative duration of hypotension in the AcumenIQ group. No significant difference between groups was found in terms of laboratory and clinical outcomes. CONCLUSIONS: Hemodynamic optimization guided by machine learning algorithm leads to a significant decrease in number and duration of hypotensive events compared to traditional goal directed therapy using pulse-contour analysis hemodynamic monitoring in patients undergoing major thoracic procedures. Further, larger studies are needed to determine true clinical utility of HPI guided hemodynamic monitoring. TRIAL REGISTRATION: Date of first registration: 14/11/2022 Registration number: 04729481-3a96-4763-a9d5-23fc45fb722d.

Subclavian vein ultrasound-guided fluid management to prevent post-spinal anesthetic hypotension during cesarean delivery: a randomized controlled trial.

BACKGROUND: Hypotension frequently occurs after spinal anesthesia during cesarean delivery, and fluid loading is recommended for its prevention. We evaluated the efficacy of subclavian vein (SCV) ultrasound (US)-guided volume optimization in preventing hypotension after spinal anesthesia during cesarean delivery. METHODS: This randomized controlled study included 80 consecutive full-term parturients scheduled for cesarean delivery under spinal anesthesia. The women were randomly divided into the SCVUS group, with SCVUS analysis before spinal anesthesia with SCVUS-guided volume management, and the control group without SCVUS assessment. The SCVUS group received 3 mL/kg crystalloid fluid challenges repeatedly within 3 min with a 1-min interval based on the SCV collapsibility index (SCVCI), while the control group received a fixed dose (10 mL/kg). Incidence of post-spinal anesthetic hypotension was the primary outcome. Total fluid volume, vasopressor dosage, changes in hemodynamic parameters, maternal adverse effects, and neonatal status were secondary outcomes. RESULTS: The total fluid volume was significantly higher in the control group than in the SCVUS group (690 [650-757.5] vs. 160 [80-360] mL, p < 0.001), while the phenylephrine dose (0 [0-40] vs. 0 [0-30] µg, p = 0.276) and incidence of post-spinal anesthetic hypotension (65% vs. 60%, p = 0.950) were comparable between both the groups. The incidence of maternal adverse effects, including nausea/vomiting and bradycardia (12.5% vs. 17.5%, p = 0.531 and 7.5% vs. 5%, p = 1.00, respectively), and neonatal outcomes (Apgar scores) were comparable between the groups. SCVCI correlated with the amount of fluid administered (R = 0.885, p < 0.001). CONCLUSIONS: SCVUS-guided volume management did not ameliorate post-spinal anesthetic hypotension but reduced the volume of the preload required before spinal anesthesia. Reducing preload volume did not increase the incidence of maternal and neonatal adverse effects nor did it increase the total vasopressor dose. Moreover, reducing preload volume could relieve the heart burden of parturients, which has high clinical significance. CLINICAL TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry at chictr.org.cn (registration number, ChiCTR2100055050) on December 31, 2021.

Prevention of spinal hypotension during cesarean section: A systematic review and Bayesian network meta-analysis based on ephedrine, phenylephrine, and norepinephrine.

AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.

Intraoperative Hypotension Prediction-A Proactive Perioperative Hemodynamic Management-A Literature Review.

Intraoperative hypotension (IH) is a frequent phenomenon affecting a substantial number of patients undergoing general anesthesia. The occurrence of IH is related to significant perioperative complications, including kidney failure, myocardial injury, and even increased mortality. Despite advanced hemodynamic monitoring and protocols utilizing goal directed therapy, our management is still reactive; we intervene when the episode of hypotension has already occurred. This literature review evaluated the Hypotension Prediction Index (HPI), which is designed to predict and reduce the incidence of IH. The HPI algorithm is based on a machine learning algorithm that analyzes the arterial pressure waveform as an input and the occurrence of hypotension with MAP <65 mmHg for at least 1 min as an output. There are several studies, both retrospective and prospective, showing a significant reduction in IH episodes with the use of the HPI algorithm. However, the level of evidence on the use of HPI remains very low, and further studies are needed to show the benefits of this algorithm on perioperative outcomes.

A randomized controlled trial of two dialysate sodium concentrations in hospitalized hemodialysis patients.

BACKGROUND: Several large dialysis organizations have lowered the dialysate sodium concentration (DNa) in an effort to ameliorate hypervolemia. The implications of lower DNa on intra-dialytic hypotension (IDH) during hospitalizations of hemodialysis (HD) patients is unclear. METHODS: In this double-blind, single center, randomized controlled trial (RCT), hospitalized maintenance HD patients were randomized to receive higher (142 mmol/L) or lower (138 mmol/L) DNa for up to six sessions. Blood pressure (BP) was measured in a standardized fashion pre-HD, post-HD and every 15 min during HD. The endpoints were: (i) the average decline in systolic BP (pre-HD minus lowest intra-HD, primary endpoint) and (ii) the proportion of total sessions complicated by IDH (drop of ≥20 mmHg from the pre-HD systolic BP, secondary endpoint). RESULTS: A total of 139 patients completed the trial, contributing 311 study visits. There were no significant differences in the average systolic blood pressure (SBP) decline between the higher and lower DNa groups (23 ± 16 versus 26 ± 16 mmHg; P = 0.57). The proportion of total sessions complicated by IDH was similar in the higher DNa group, compared with the lower DNa group [54% versus 59%; odds ratio 0.72; 95% confidence interval (95% CI) 0.36-1.44; P = 0.35]. In post hoc analyses adjusting for imbalances in baseline characteristics, higher DNa was associated with 8 mmHg (95% CI 2-13 mmHg) less decline in SBP, compared with lower DNa. Patient symptoms and adverse events were similar between the groups. CONCLUSIONS: In this RCT for hospitalized maintenance of HD patients, we found no difference in the absolute SBP decline between those who received higher versus lower DNa in intention-to-treat analyses. Post hoc adjusted analyses suggested a lower risk of IDH with higher DNa; thus, larger, multi-center studies to confirm these findings are warranted.