Background: Preoperative sedation is critical to alleviate anxiety in children undergoing neurosurgery, but the role of remimazolam is still uncertain such as its unestablished dosing and safety. This study was aimed to determine the 90% effective dose (ED90) of remimazolam for moderate sedation in this pediatric population. Methods: This dose-finding study enrolled children aged 3 months to 6 years scheduled for neurosurgery. The up-and-down method (k-in-a-row, k= 6) was employed to investigate the ED90 of remimazolam for moderate sedation. According to the k-in-a-row rule, one patient received a predefined dose of remimazolam and the dosing assignment of the next patient depended on whether the former patient reached moderate sedation or not. Moderate sedation was assessed using the modified Observer's Assessment of Alertness/ Sedation (MOAA/S). Remimazolam doses ranged from 0.05mg/kg to 0.35mg/kg with a step gradient of 0.05mg/kg. The ED90 and 95% confidence interval (CI) were calculated by centered isotonic regression. Secondary outcomes included drug-related adverse events, the incidence of emergence delirium (ED), and changes in brain network connectivity which were monitored by functional near-infrared spectroscopy (fNIRS). Results: Forty-eight children were enrolled with a median age of 20.5 (9.0, 35.0) months. The ED90 of remimazolam for moderate sedation was 0.28 (95% CI 0.24-0.42) mg/kg. The incidence of drug-related adverse events was about 12.5%, including respiratory depression and hiccup. The incidence of ED was 62.2%. fNIRS showed increased connectivity in right frontal lobe-right occipital lobe, right frontal lobe-left occipital lobe, and right frontal lobe-left parietal lobe (all P values < 0.05 after correction by false discovery rate). Conclusion: This study reported the ED90 of remimazolam for moderate sedation in neurosurgical children. These results provided important information for the use of remimazolam in children with neurologic disease.

Objective To evaluate the relationship between preoperative COVID-19 infection and major postoperative pulmonary complications (PPC) risk after major elective surgeries during the Omicron wave.Design A multicentre, prospective, observational cohort study.Setting Four tertiary medical centres in Beijing, China.Participants All adult patients who underwent major elective surgeries under general anaesthesia from 30 December 2022 to 18 May 2023 were screened for eligibility. A total of 3211 patients were included.Primary and secondary measures The primary outcome was 30-day major PPC, defined as pneumonia, acute respiratory distress syndrome or unexpected postoperative ventilation. The secondary outcomes included length of hospital stay (LOS), reoperation and mortality.Results Major PPC occurred in 3.5% of patients with preoperative COVID-19 and 3.3% of those without. Inverse probability of treatment weighting-adjusted analysis showed no significant association between preoperative COVID-19 within 12 weeks and PPC risk (adjusted OR, 0.89; 95% CI 0.69 to 1.13). However, multivariable analysis revealed that COVID-19 infection within 3 weeks was independently associated with an increased PPC risk (OR, 3.44; 95% CI 1.37 to 8.68). Cardiothoracic surgery (OR, 12.47; 95% CI 8.11 to 19.17) and longer duration of surgery (OR, 1.24 per hour; 95% CI 1.13 to 1.37) were significant risk factors. In the cardiothoracic subgroup, PPC risk was significantly elevated within 7 weeks of infection. No significant differences were observed in LOS, reoperation rates or mortality between patients with and without preoperative COVID-19 infection.Conclusions Preoperative COVID-19 infection within 12 weeks was not associated with an increased overall risk of major PPC during the Omicron wave. Although very short infection-to-surgery intervals and cardiothoracic surgery showed exploratory signals of higher risk, these findings should be interpreted cautiously and support an individualised approach to perioperative risk assessment.Trial registration number ChiCTR2200067250.

RATIONALE:Amyotrophic lateral sclerosis (ALS) confers heightened and unpredictable sensitivity to nondepolarizing neuromuscular blocking agents and a high risk of postoperative respiratory failure. Although sugammadex reliably reverses rocuronium, recurarization may occur and is likely under-recognized in ALS. We report 2 ALS patients undergoing percutaneous endoscopic gastrostomy, one of whom developed delayed recurarization after apparent reversal. PATIENT CONCERNS:Both women (67 and 68 years) presented with progressive dysphagia requiring percutaneous endoscopic gastrostomy. Case 1 had dyspnea, dysarthria, and long-standing noninvasive positive-pressure ventilation; Case 2 had bulbar signs without preoperative ventilatory support. The key perioperative concern in both cases was ventilatory failure from residual neuromuscular block. DIAGNOSES:ALS had been established clinically. In Case 2, recurarization was diagnosed shortly after extubation when acute hypercapnic respiratory failure and clinical weakness followed an earlier recovery to a train-of-four (TOF) ratio of 92%. INTERVENTIONS:Intravenous anesthesia with propofol and remifentanil was used. Case 1 received rocuronium 10 mg (0.2 mg/kg) and was reversed with sugammadex 90 mg (2 mg/kg) at TOF count 0, achieving a TOF ratio of 98% within 3 minutes before extubation and postoperative noninvasive ventilation. Case 2 received rocuronium 30 mg (0.6 mg/kg) and sugammadex 200 mg (3.8 mg/kg) at TOF count 1, recovered to a TOF ratio of 92% at 4 minutes, but developed respiratory failure 3 minutes after extubation; mask ventilation and neostigmine 2 mg with atropine 0.25 mg were given. OUTCOMES:Case 1 recovered uneventfully and was discharged on postoperative day (POD) 6. Case 2 required intensive care unit admission, re-intubation on POD 1, and re-extubation on POD 3; she was discharged on POD 23 without new neurologic deficits. LESSONS:In ALS, recurarization can occur despite seemingly adequate sugammadex reversal. When rocuronium is used, sugammadex is recommended for reversal, with vigilant quantitative neuromuscular monitoring and extended post-extubation observation to detect delayed weakness.

Introduction Deep brain stimulation (DBS) has increasingly become an accepted therapy for pediatric patients with medically refractory dystonia. Most pediatric dystonia patients are unable to tolerate the DBS procedure under local anesthesia or awake anesthesia. Therefore, general anesthesia is a potentially feasible choice. However, the negative impacts of general anesthetics may impair the quality of intraoperative microelectrode recording (MER). Additionally, pediatric dystonia patients frequently present with comorbidities including difficult airway, cardiovascular dysfunction, respiratory impairment, and metabolic disorders, which collectively posing challenges to perioperative management. Methods In this study, we retrospectively reviewed the anesthetic managements for 32 pediatric dystonia patients who received DBS surgery in our center, and analyzed the safety profile and adverse effects. Results and Conclusions We found that general anesthesia with endotracheal intubation might be a feasible anesthetic regimen for this pediatric dystonia patient population. Challenges regarding the anesthetic management of these patients mainly come from the potential impacts of general anesthetics on MER quality, patients' fragility secondary to severe dystonia, and the pathophysiological disorders associated with comorbid conditions. Therefore, meticulous perioperative monitors are required and special concerns should be paid to preventing perioperative complications caused by anesthetic procedure and some rare but serious hereditary metabolic disorders.

Patients with morbid obesity are at a high risk of comorbid depressive and anxiety symptoms. While bariatric surgery is an effective treatment, conventional opioid-based anesthesia carries significant perioperative risks. Opioid-free anesthesia (OFA) presents a safer alternative. Esketamine, known for its dual analgesic and rapid antidepressant effects, is a promising component of OFA. However, clinical evidence supporting its simultaneous benefits for both physical and psychological recovery in bariatric patients remains limited. In this double-blind, randomized clinical trial, patients scheduled for laparoscopic sleeve gastrectomy were randomly assigned (1:1) to receive either esketamine-based anaesthesia or opioid-based anaesthesia with remifentanil during surgery. The co-primary outcomes were postoperative pain intensity within the first 24 h and mental health status at three months after surgery. Secondary outcomes included pharmacokinetics of esketamine and adverse events. A total of 84 patients were randomized, with 42 allocated to each group. Seventy-four participants (88.1%) completed the 3-month follow-up. Patients in the esketamine group experienced significantly lower postoperative pain intensity (P < 0.01) and a reduced incidence of moderate-to-severe pain (P < 0.05) within 24 h after surgery. Mental health outcomes at 3 months were also significantly better in the esketamine group, and adverse events rate did not differ significantly. Pharmacokinetic analysis showed that plasma esketamine concentrations increased rapidly during infusion, with early formation of the active metabolite (S)-norketamine. Compared to opioid-based anaesthesia, esketamine-based opioid-free anaesthesia was associated with improved postoperative analgesia and better mental health outcomes in morbidly obese patients undergoing bariatric surgery, without increasing adverse events.

Postoperative pulmonary complications are common and associated with worse long-term outcomes. In our previous trial, prophylactic penehyclidine inhalation reduced pulmonary complications in high-risk patients. Herein, we tested the hypothesis that penehyclidine inhalation might also improve long-term survival after surgery. This was a long-term follow-up of a randomized trial. We enrolled 864 patients aged more than 50 years who were scheduled for major upper-abdominal or non-cardiac thoracic surgery and judged to be at high risk of pulmonary complications. Participants were randomized to receive either penehyclidine or placebo inhalation during the perioperative period. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survivals. Among patients included in the underlying trial, 826 (mean age 64 years, 63.0

Effects of preoperative continuous regional block on perioperative analgesia and postoperative recovery in hip fracture patients remain to be determined. This randomized trial was designed to investigate the impact of preoperative continuous supra-inguinal fascia iliaca block (FIB) or anterior quadratus lumborum block (QLB) on quality of recovery after hip fracture surgery. Eligible patients were randomized to receive preoperative continuous supra-inguinal FIB, continuous anterior QLB, or conventional analgesia (no block; control group). Preoperative continuous regional blocks were initiated at hospital admission and induced with 40 ml of 0.375

Background: Dexmedetomidine, in combination with opioids, improves postoperative analgesia and sleep quality. Some previous trials also report reduced delirium, although others do not. We therefore tested the primary hypothesis that dexmedetomidine supplemented analgesia reduces delirium in older patients during the initial 5 days after major cancer surgery. Methods: We enrolled patients 65-90 years old who were scheduled for major cancer surgery expected to last ≥2 hours with general anesthesia. All were given patient-controlled morphine (0·5 mg/ml) analgesia after surgery, supplemented with either dexmedetomidine (1·25 μg/ml) or placebo which was randomly assigned and fully blinded. Our primary endpoint was the incidence of delirium which was assessed twice daily during the initial 5 postoperative days. Pain intensity and subjective sleep quality were assessed with 11-point scales with 10 being worst. Results: A total of 1500 patients (mean age 72 years; 492 [33%] women) were enrolled and randomized; all were included in the intent-to-treat analysis. Patients in the dexmedetomidine group had a median infusion rate of 0·021 μg/kg/h (interquartile range, 0·018 to 0·025). Delirium occurred in 10·4% (78/750) of patients with dexmedetomidine vs. 15·7% (118/750) of patients with placebo (relative risk, 0·66; 95% CI, 0·51 to 0·86; P=0·002). Dexmedetomidine reduced the proportion of patients with moderate-to-severe pain with movement (relative risk, 0·90; 95% CI, 0·84 to 0·97; P=0·004) within 5 postoperative days. The fraction of patients who reported moderate-to-severe sleep disturbances within 5 days was also lower in patients assigned to dexmedetomidine (relative risk, 0·94; 95% CI, 0·89 to 1·00; P=0·035). Adverse events were comparable in each group. Conclusions: In older patients after major cancer surgery, dexmedetomidine-supplemented opioid analgesia reduced delirium by a third without provoking complications. Low-dose dexmedetomidine should be considered as an adjuvant to opioid analgesia for prevention of postoperative delirium.

Complex spinal surgery is associated with significant trauma and pain. Herein we tested the hypothesis that increasing the dose of esketamine, as a supplement to patient-controlled analgesia, might improve pain relief after extensive spinal surgery. In this randomized, double-blind, and controlled trial, we enrolled adults who were scheduled to undergo extensive posterior spinal fusion. Participants were randomized in a 1:1:1 ratio to receive patient-controlled sufentanil-dexmedetomidine analgesia supplemented with esketamine at 0.25 (Esk25), 0.5 (Esk50), or 0.75 (Esk75) mg/ml. Our primary endpoint was an integrated index of pain intensity and opioid consumption (ranging from − 200

BACKGROUND: Swyer-James-Macleod Syndrome (SJMS) is a rare respiratory disease usually caused by obliterative bronchiolitis since childhood and characterized by expiratory air trapping, hypoxia-induced parenchymal destruction, pulmonary hypoperfusion, and impaired gas exchange. Anesthetic management for bronchoscopy in patients with SJMS is challenging due to compromised cardiopulmonary function and shared airway paradigm during the procedure. Herein, we report the use of dexmedetomidine-esketamine combination during anesthesia induction and maintenance for bronchoscopy in a patient with severe SJMS. CASE PRESENTATION: A 39-year-old man with Swyer-James-Macleod Syndrome and severely compromised cardiopulmonary function was scheduled for endoscopic lung volume reduction under a standby extracorporeal membrane oxygenation support. To maintain hemodynamic stability and facilitate withdrawing from mechanical ventilation, we explored the use of dexmedetomidine-esketamine combination as a supplement during induction and maintenance of general anesthesia in this specific critically ill patient. Upon procedure completion, the patient was extubated in the operating room and transferred to the respiratory intensive care unit. Extracorporeal membrane oxygenation support was not required. CONCLUSIONS: We found that supplemental use of the dexmedetomidine-esketamine combination during general anesthesia for bronchoscopy helped maintain a stable hemodynamic state and facilitate early extubation in this patient with severe SJMS. Our findings provided initial evidence for future clinical investigations.

BACKGROUND:Heterogeneity of postoperative pain trajectories and their impact on clinical outcomes in older orthopedic patients remain insufficiently characterized. This study aimed to identify distinct postoperative pain trajectories, determine their potential predictors, and evaluate their impacts on postoperative outcomes. METHODS:This secondary analysis included 710 patients age 65 to 90 yr who underwent orthopedic surgery and received self-controlled analgesia. After surgery, pain intensity was assessed twice daily for 5 days using an 11-point numeric rating scale; occurrence of complications was followed up until 30 days; quality of life was evaluated at 30 days. Growth mixture modeling was used to identify pain trajectories according to pain intensity with movement. Multinomial logistic regression analysis was used to identify predictors of trajectory membership. Multivariable regression was used to evaluate associations between trajectory membership and postoperative outcomes. RESULTS:Four distinct pain trajectories were identified: the slow decrease pattern (57.9%), the rapid decrease pattern (23.4%), the increase-decrease pattern (10.8%), and the slow increase pattern (7.9%). Taking the slow decrease pattern as a reference, preoperative analgesic use was associated with higher risks of increase-decrease (adjusted odds ratio [OR], 3.76; 95% CI, 1.53 to 9.23; P = 0.004) and slow increase trajectories (adjusted OR, 3.89; 95% CI, 1.52 to 9.98; P = 0.005), whereas using dexmedetomidine in self-controlled analgesia was associated with lower risks of rapid decrease (adjusted OR, 0.47; 95% CI, 0.32 to 0.70; P < 0.001) and increase-decrease trajectories (adjusted OR, 0.15; 95% CI, 0.08 to 0.28; P < 0.001). When compared with the slow decrease pattern, patients with a rapid decrease trajectory required more opioids and developed more complications; patients with an increase-decrease trajectory required more opioids and had a lower physical domain quality of life score at 30 days; patients with a slow increase trajectory stayed longer in the hospital after surgery. CONCLUSIONS:Postoperative pain in older orthopedic patients followed four distinct trajectories that were influenced by baseline and perioperative factors. Specific pain trajectories were associated with adverse postoperative outcomes.

Objective: To test the hypothesis that peripheral nerve block (PNB) use might be associated with improved perioperative outcomes following major surgery. Summary Background Data: PNB has been used to improve postoperative analgesia. Methods: This was a retrospective cohort study with propensity score matching. We included patients aged ≥65 years who underwent major (≥2 h) non-cardiac thoracic and abdominal surgery under general anesthesia. Data were analyzed according to whether patients received PNB or not during anesthesia. Our primary outcome was the length of hospital stay; secondary outcomes included occurrence of major complications in hospital after surgery. Results: A total of 1,915 patients were included in the full cohort, of whom 1,316 received PNB and 599 did not; 1,174 patients remained in the cohort after matching, with 587 in each group. Length of hospital stay after surgery was shorter in patients who received PNB than in those who did not (7 days [5 to 9] with PNB vs. 7 days [5 to 11] without PNB: HR 1.15, 95% CI 1.02 to 1.29, P =0.012). When compared with patients who did not receive PNB, those who received PNB developed fewer major complications during hospital stay (RR 0.41, 95% CI 0.30 to 0.58, P <0.001). Patients with PNB required less supplemental analgesia within 72 h (RR 0.70, 95% CI 0.59 to 0.84, P <0.001). Conclusions: Use of PNB was associated with shortened length of hospital stay and reduced major complications in older patients after major non-cardiac thoracic and abdominal surgery, possibly due to improved analgesia.

Perioperative neurocognitive disorder (PND) is a significant neurological complication in aging perioperative patients that impacts post-operative cognition. PND is currently diagnosed through cognitive function testing, which is limited by its subjectivity and time requirements. Thus, the identification of biomarkers to assess PND onset is a priority to identify at-risk individuals and enable interventions and treatments to patient outcomes. This article synthesizes expert perspectives on brain aging and PND, presents the latest clinical evidence on PND biomarkers (imaging, electroencephalography, and molecular biomarkers), and delves into the relationship between PND and other age-related cognitive disorders. Thorough review of PND research identified several biomarkers with high sensitivity and specificity, offering a solid scientific foundation to predict and diagnose PND. These biomarkers not only enhance diagnostic accuracy for clinicians but also provide opportunities for earlier intervention and more effective treatment, potentially enhancing patient outcomes and quality of life.

BackgroundThis phase 2 trial comprised dose exploration (stage 1) and dose confirmation stages (stage 2) to determine the safety and efficacy of HSK21542 in patients undergoing laparoscopic abdominal surgery.MethodsIn stage 1, patients were randomly allocated at a ratio of 4:1 (12 to receive HSK21542, 3 to receive placebo) to 4 ascending dose groups in a sequential manner (group 1: preoperative HSK21542-0.4 μg/kg (or placebo) + HSK21542-0.2 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; group 2: preoperative HSK21542-1.0 μg/kg (or placebo) + HSK21542-0.5 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h; groups 3 and 4: HSK21542-0.5 μg/kg or HSK21542-1.0 μg/kg (or placebo) at postoperative 0 h, 8 h and 16 h). In stage 2, patients received HSK21542-0.5 μg/kg, HSK21542-1.0 μg/kg or placebo postoperatively at 0 h, 8 h and 16 h in a 1:1:1 ratio. The primary endpoints in stage 1 were the safety outcomes including the incidence and severity of treatment-emergent adverse events (TEAEs) while the primary endpoint of stage 2 was the time-weighted summed pain intensity differences over 24 h (SPID0–24h).ResultsStage 1 enrolled 63 patients and 57 completed the trial, while 61 patients were enrolled in stage 2, and 60 completed the trial. The most common TEAEs were fever (22.9% vs. 41.7%), nausea (25.0% vs. 33.3%) and vomiting (22.9% vs. 25.0%) in the HSK21542 and placebo groups in stage 1. HSK21542 doses of 0.5 μg/kg and 1.0 μg/kg administered postoperatively were recommended for the subsequent stage 2. The pooled results revealed a slightly lower SPID0–24h in HSK21542-1.0 μg/kg group (−1,679.8 ± 2,284.3 scores × min) than those in HSK21542-0.5 μg/kg (−1,499.4 ± 2,487.2 scores × min) and placebo groups (−435.2 ± 2,852.9 scores × min; P = 0.114). A significantly higher least squares mean difference of pain intensity differences (PID) was found in HSK21542-1.0 μg/kg group compared to the placebo (P = 0.020).ConclusionHSK21542 at all dose regimens demonstrated well tolerability and safety comparable to that of the placebo among patients undergoing laparoscopic abdominal surgery in the phase 2 trial. The dosing regimen of HSK21542-1.0 μg/kg administered postoperatively at 0 h, 8 h and 16 h exhibited an acceptable efficacy, warranting its recommendation for further phase 3 trial.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04424251.

BackgroundIntensive care unit (ICU) admission after surgery is an important part of perioperative care but was found not effective in reducing perioperative mortality. This study was designed to test our hypothesis that ICU admission in older patients after elective major noncardiac surgery was not associated with improved long-term survival.MethodsThis was a secondary analysis of database from a previous trial and long-term follow-up. Patients were analyzed according to whether they were admitted to ICU after surgery or not. We used propensity score-matching to balance baseline, perioperative, and long-term variables and multivariable Cox proportional hazard regression to adjust confounding factors. Our primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival.ResultsA total of 1712 patients (mean age 69.5 years, 65.3% male, 91.9% cancer surgery) completed long-term follow-up (median 74 months) and were included in this secondary analysis. After propensity score matching, 464 patients remained in the matched cohort, with 232 patients in each group. At the end of follow-up, there were 112 deaths of 232 patients (48.3%) who were admitted to the ICU, compared with 111 deaths of 232 patients (47.8%) who were not: adjusted HR 1.08, 95% CI 0.83-1.41, P = 0.573. Secondary endpoints, including recurrence-free survival and event-free survival, also did not differ significantly between groups.ConclusionsFor older patients after elective major noncardiac surgery mainly for cancer, ICU admission was not associated with improved long-term survival. Studies are required to identify patients who would benefit from postoperative ICU admission regarding long-term outcomes.

BACKGROUND:The Qnox index is a novel monitor to quantify intraoperative nociception based on an electroencephalographic algorithm. We evaluated the ability of the Qnox index to discriminate noxious from non-noxious stimuli, respond to stimuli, and discriminate different levels of analgesia in patients under propofol anaesthesia with neuromuscular block. METHODS:Qnox was compared with heart rate and mean arterial pressure with five designated stimuli: tetanic stimulations without (tetanic 1) and with sufentanil (tetanic 2), skin incision, tracheal intubation, and a non-noxious period. The response around the skin incision was also evaluated at two target remifentanil concentrations. RESULTS:In 83 adult patients scheduled for elective surgery, Qnox performed worse than heart rate and mean arterial pressure in discriminating tetanic 2, tetanic 1, skin incision, and tracheal intubation noxious stimuli from the non-noxious period, with an area under curve of 0.52 (95% confidence interval 0.43-0.61), 0.54 (0.45-0.62), 0.67 (0.58-0.75), and 0.65 (0.57-0.73), respectively. The post-stimulus values of Qnox increased significantly after tracheal intubation and skin incision, but not after tetanic 1 or tetanic 2. Qnox values after skin incision were similar between the low- and high-remifentanil-concentration groups. CONCLUSIONS:Qnox had a poor ability to discriminate noxious stimuli from non-noxious stimuli. Although Qnox responded to tracheal intubation and skin incision, it did not respond to tetanic stimulations and failed to discriminate different levels of analgesia. The Qnox index was not superior to heart rate or mean arterial pressure in assessing nociception during general anaesthesia. CLINICAL TRIAL REGISTRATION:Chinese Clinical Trial Registry (ChiCTR2100046063).

Postoperative pulmonary complications (PPCs) after major upper abdominal surgery are an important cause of morbidity and mortality. However, existing preoperative risk models inadequately address perioperative factors. Although diaphragmatic ultrasonography offers real-time assessment of respiratory muscle function, its predictive utility for PPCs remains underexplored. This study aimed to evaluate the predictive value of diaphragmatic ultrasound parameters for PPCs and to identify the optimal index among them. This prospective observational cohort study included patients aged ≥ 50 years who underwent elective upper abdominal surgery under general anesthesia. Right-sided diaphragmatic ultrasound evaluations were performed on preoperative day 1 (PreD1) and on postoperative day 1 (POD1), and measured diaphragm thickening fraction (DTF) and diaphragmatic excursion (DE) during quiet, deep, and sniff breathing. Patients were followed up for 14 days after surgery to assess the incidence of PPCs. Receiver operating characteristic (ROC) analysis and multivariate logistic regression were used to evaluate predictive performance and adjust for confounders. Among the 223 patients enrolled, 37 (16.6

Background Intraoperative hypotension is associated with cardiovascular complications after major noncardiac surgery, but randomized trials assessing whether intensive blood pressure management during surgery can reduce these complications have shown inconsistent results. Objectives The purpose of this study was to determine whether intensive intraoperative blood pressure management reduces the incidence of a composite of cardiovascular complications within 30 days after major abdominal surgery. Methods In this investigator-initiated parallel-group trial, patients at 3 Chinese sites were randomly assigned (1:1) to intensive blood pressure management targeting intraoperative MAP ≥80 mm Hg (intensive strategy group) or conventional management targeting intraoperative MAP ≥ the higher of 65 mm Hg or 60% of preoperative baseline pressure (conventional strategy group). We included patients aged ≥45 years who had known cardiovascular disease or cardiovascular risk factors and were scheduled for inpatient abdominal surgery expected to last at least 2 hours. The primary outcome was a composite of myocardial injury or infarction, new-onset clinically important arrhythmias, acute heart failure, stroke, cardiac arrest, and all-cause death within 30 days of surgery. Results Between June 30, 2020, and September 23, 2022, 1,500 patients were enrolled, of whom 1,477 were included in the modified intention-to-treat population (739 in the intensive strategy group and 738 in the conventional strategy group). Patients assigned to intensive intraoperative blood pressure management experienced a lower burden of hypotension exposure, as assessed by several measures. For example, the median cumulative duration of MAP <65 mm Hg was 1 minute (Q1-Q3: 0-7 minutes) in the intensive strategy group, compared with 8 minutes (Q1-Q3: 0-20 minutes) in the conventional strategy group. The primary composite outcome occurred in 107 of 739 patients (14.5%) in the intensive strategy group and 100 of 738 patients (13.6%) in the conventional strategy group (relative risk: 1.07; 95% CI: 0.83-1.38; P = 0.61). Conclusions In high-risk patients having major abdominal inpatient surgery, intensive intraoperative blood pressure management targeting a mean arterial pressure ≥80 mm Hg did not reduce the incidence of cardiovascular events compared with the conventional target of ≥65 mm Hg and 60% of the preoperative baseline.

BACKGROUND:Dexmedetomidine may suppress the surgery-induced inflammatory response, which is considered the underlying mechanism of postoperative complications. This study was designed to investigate whether perioperative dexmedetomidine could decrease the risk of postoperative complications among high-risk patients. METHODS:This multicenter randomized controlled trial is a superiority trial. Central randomization was used. Elderly patients (age ≥60 years) with revised cardiac risk index (RCRI) ≥3 and scheduled for major non-cardiac surgery were enrolled. Patients in dexmedetomidine group received intraoperative dexmedetomidine (a loading dose of 0.5 μg/kg followed by 0.3 μg·kg-1·h-1) as adjuvant to general anesthesia and postoperative dexmedetomidine (2 μg/h for 72 h) as supplementation to patient-controlled analgesia with sufentanil. Patients in the control group received an equivalent dose of normal saline as placebo during anesthesia and sufentanil only for postoperative analgesia. The primary outcome was the incidence of major postoperative complications including neurologic, cardiovascular, acute kidney injury pulmonary, coagulation, infectious, and gastrointestinal systems within postoperative 30 days. Secondary outcomes included pain intensity, sleep quality, postoperative length of in-hospital stay, and medical expenses during hospitalization. Neutrophil-to-lymphocyte ratio (NLR) was used to monitor inflammatory response. RESULTS:This study included 272 patients, with similar median age (70 years vs. 69 years) and median RCRI (both 3) between dexmedetomidine and control groups. The incidence of major postoperative complications in the dexmedetomidine group was significantly lower than that in the control group (38.2% [52/136] vs. 52.9% [72/136], relative risk [RR] = 0.722, 95% confidence interval (CI) 0.554-0.942, P = 0.015). Postoperative in-hospital stay was shorter in the dexmedetomidine group than that in the control group (mean difference [MD] = -1 day, 95% CI: -2 to 0 days, P = 0.013). Other secondary outcomes were comparable between the two groups. The highest NLR within postoperative first 3 days in the dexmedetomidine group was lower than that in the control group (MD = -2.1, 95% CI: -4.1 to -0.3, P = 0.037). The proportion of all drug-related adverse events were comparable between the two groups. CONCLUSION:Dexmedetomidine, infused from the beginning of anesthesia to postoperative 72 h, decreased the risk of postoperative complications in high-risk elderly patients undergoing non-cardiac surgery. TRIAL REGISTRATION:No. ChiCTR2000030566 at www.chictr.org.cn.