Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Association between muscular tissue desaturation and acute kidney injury in older patients undergoing major abdominal surgery: a prospective cohort study.

PURPOSE: Present study was designed to investigate the association between muscular tissue desaturation and acute kidney injury (AKI) in older patients undergoing major abdominal surgery. METHOD: A total of 253 patients (≥ 65 years old) who underwent abdominal surgery with expected duration ≥ 2 h were enrolled. Muscular tissue oxygen saturation (SmtO2) was monitored at quadriceps and bilateral flanks during surgery. Muscular desaturation was defined as SmtO2 < 90% baseline lasting for > 60 s. The primary outcome was the incidence of AKI within postoperative 7 days. The association between muscular desaturation and AKI was analyzed by multivariable logistic regression model. The secondary outcomes indicated the other complications within postoperative 30 days. RESULTS: Among 236 patients, 44 (18.6%) of them developed AKI. The incidence of muscular desaturation at quadriceps was 28.8% (68/236). Patients with muscular desaturation had higher incidence of AKI than those without desaturation (27.9% [19/68], vs. 14.9% [25/168], P = 0.020). After adjustment of confounders, multivariable analysis showed that muscular desaturation at quadriceps was significantly associated with an increased risk of AKI (OR = 2.84, 95% CI 1.21-6.67, P = 0.016). Muscular desaturations at left and right flank were also associated with an increased risk of AKI (OR = 6.38, 95% CI 1.78-22.89, P = 0.004; OR = 8.90, 95% CI 1.42-45.63; P = 0.019, respectively). Furthermore, patients with muscular desaturation may have a higher risk of pulmonary complications, sepsis and stroke at 30-day follow-up. CONCLUSION: Muscular desaturation was associated with postoperative AKI in older patients undergoing major abdominal surgery which may serve as a predictor of AKI.

25-hydroxyvitamin D concentrations and risk of incident dementia, mild cognitive impairment, and delirium in 443,427 UK Biobank participants.

This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and dementia, mild cognitive impairment (MCI), and delirium. Participants from the United Kingdom (UK) Biobank with complete information on serum 25(OH)D concentrations were enrolled. Dementia, MCI and delirium were defined using the UK Biobank algorithm. 443,427 participants with a mean (standard deviation) age of 56.8 (8.0) years were included in this study. Based on Cox regression models, serum 25(OH)D concentrations were inversely associated with the risk of dementia, MCI, and delirium in a dose-dependent manner after adjusting for demographics (P-trend <0.001). In comparison with 25(OH)D levels less than 32.4 nmol/L, participants with the highest 25(OH)D levels (i.e., >64.4 nmol/L) had the lowest risk of dementia (hazards ratio [HR]: 0.58, 95% confidence interval [CI] 0.49-0.69, P<0.001), MCI (HR: 0.55, 95% CI 0.37-0.84, P=0.005), and delirium (HR: 0.63, 95% CI 0.51-0.79, P<0.001). These results were consistent with the sensitivity analysis, in which participants with events occurring within the first two years of follow-up were excluded. This study found that a lower serum 25(OH)D concentration was significantly associated with a higher risk of dementia (including Alzheimer's disease and vascular dementia), MCI, and delirium.

SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.

BACKGROUND: Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS). METHODS: Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice. RESULTS: Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1ß, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1ß, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein. CONCLUSIONS: Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

Effect of intraoperative remimazolam on postoperative sleep quality in elderly patients after total joint arthroplasty: a randomized control trial.

PURPOSE: To investigate the effect of intraoperative remimazolam sedation on postoperative sleep quality in elderly patients after total joint arthroplasty. METHODS: Between May 15, 2021 and March 26, 2022, 108 elderly patients (age ≥ 65 years) who received total joint arthroplasty under neuraxial anesthesia were randomized into remimazolam group (a loading dose of 0.025-0.1 mg/kg and followed by an infusion rate of 0.1-1.0 mg/kg/h till end of surgery) or routine group (sedation was given on patient's requirement by dexmedetomidine 0.2-0.7 µg/kg/h). Primary outcome was the subjective sleep quality at surgery night which was evaluated by Richards Campbell Sleep Questionnaire (RCSQ). Secondary outcomes included RCSQ scores at postoperative first and second nights and numeric rating scale pain intensity within first 3 days after surgery. RESULTS: RCSQ score at surgery night was 59 (28, 75) in remimazolam group which was comparable with 53 (28, 67) in routine group (median difference 6, 95% CI - 6 to 16, P = 0.315). After adjustment of confounders, preoperative high Pittsburg sleep quality index was associated worse RCSQ score (P = 0.032), but not remimazolam (P = 0.754). RCSQ score at postoperative first night [69 (56, 85) vs. 70 (54, 80), P = 0.472] and second night [80 (68, 87) vs. 76 (64, 84), P = 0.066] were equivalent between two groups. Safety outcomes were comparable between the two groups. CONCLUSIONS: Intraoperative remimazolam did not significantly improve postoperative sleep quality in elderly patients undergoing total joint arthroplasty. But it is proved to be effective and safe for moderate sedation in these patients. CLINICAL TRIAL NUMBER AND REGISTRY URL: ChiCTR2000041286 ( www.chictr.org.cn ).

A comprehensive overview of clinical research on dexmedetomidine in the past 2 decades: A bibliometric analysis.

Introduction: Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist with sedative, analgesic, anxiolytic, and opioid-sparing properties. A large number of dexmedetomidine-related publications have sprung out in the last 2 decades. However, no bibliometric analysis for clinical research on dexmedetomidine has been published to analyze hot spots, trends, and frontiers in this field. Methods: The clinical articles and reviews related to dexmedetomidine, published from 2002 to 2021 in the Web of Science Core Collection, were retrieved on 19 May 2022, using relevant search terms. VOSviewer and CiteSpace were used to conduct this bibliometric study. Results: The results showed that a total of 2,299 publications were retrieved from 656 academic journals with 48,549 co-cited references by 2,335 institutions from 65 countries/regions. The United States had the most publications among all the countries (n = 870, 37.8%) and the Harvard University contributed the most among all institutions (n = 57, 2.48%). The most productive academic journal on dexmedetomidine was Pediatric Anesthesia and the first co-cited journal was Anesthesiology. Mika Scheinin is the most productive author and Pratik P Pandharipande is the most co-cited author. Co-cited reference analysis and keyword analysis illustrated hot spots in the dexmedetomidine field including pharmacokinetics and pharmacodynamics, intensive care unit sedation and outcome, pain management and nerve block, and premedication and use in children. The effect of dexmedetomidine sedation on the outcomes of critically ill patients, the analgesic effect of dexmedetomidine, and its organ protective property are the frontiers in future research. Conclusion: This bibliometric analysis provided us with concise information about the development trend and provided an important reference for researchers to guide future research.

Intraoperative body temperature and emergence delirium in elderly patients after non-cardiac surgery: A secondary analysis of a prospective observational study.

BACKGROUND: Emergence delirium (ED) is a kind of delirium that occured in the immediate post-anesthesia period. Lower body temperature on post-anesthesia care unit (PACU) admission was an independent risk factor of ED. The present study was designed to investigate the association between intraoperative body temperature and ED in elderly patients undergoing non-cardiac surgery. METHODS: This study was a secondary analysis of a prospective observational study. Taking baseline body temperature as a reference, intraoperative absolute and relative temperature changes were calculated. The relative change was defined as the amplitude between intraoperative lowest/highest temperature and baseline reference. ED was assessed with the confusion assessment method for intensive care unit at 10 and 30 min after PACU admission and before PACU discharge. RESULTS: A total of 874 patients were analyzed with a mean age of 71.8 ±â€Š5.3 years. The incidence of ED was 38.4% (336/874). When taking 36.0°C, 35.5°C, and 35.0°C as thresholds, the incidences of absolute hypothermia were 76.7% (670/874), 38.4% (336/874), and 17.5% (153/874), respectively. In multivariable logistic regression analysis, absolute hypothermia (lowest value <35.5°C) and its cumulative duration were respectively associated with an increased risk of ED after adjusting for confounders including age, education, preoperative mild cognitive impairment, American Society of Anesthesiologists grade, duration of surgery, site of surgery, and pain intensity. Relative hypothermia (decrement >1.0°C from baseline) and its cumulative duration were also associated with an increased risk of ED, respectively. When taking the relative increment >0.5°C as a threshold, the incidence of relative hyperthermia was 21.7% (190/874) and it was associated with a decreased risk of ED after adjusting above confounders. CONCLUSIONS: In the present study, we found that intraoperative hypothermia, defined as either absolute or relative hypothermia, was associated with an increased risk of ED in elderly patients after non-cardiac surgery. Relative hyperthermia, but not absolute hyperthermia, was associated with a decreased risk of ED. REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-OOC-17012734).

Effect of one-lung ventilation on the correlation between left and right cerebral saturation.

BACKGROUND: To investigate if the correlation between left and right cerebral tissue oxygen saturation (SctO2) was affected by one-lung ventilation (OLV) in patients undergoing lung cancer surgery. METHODS: Patients who underwent surgery for lung cancer were enrolled. Left and right SctO2 were collected during anesthesia. The primary outcome was the correlation between left and right SctO2 at 30 min after OLV which was analysed by Pearson correlation and linear regression model. Secondary outcomes included the trend of left-right SctO2 change over the first 30 min after OLV, correlation of left-right SctO2 during OLV for each patient; maximal difference between left-right SctO2 and its relationship with postoperative delirium. RESULTS: Left-right SctO2 was moderately correlated at baseline (r = 0.690, P < 0.001) and poorly correlated at 30 min after OLV (r = 0.383, P < 0.001) in the Pearson correlation analysis. Linear regression analysis showed a poor correlation between left and right SctO2 at 30 min after OLV (r = 0.323, P < 0.001) after adjusting for confounders. The linear mixed model showed a change in left-right SctO2 over the first 30 min after OLV that was statistically significant (coefficient, -0.042; 95% CI, -0.070--0.014; P = 0.004). For the left-right SctO2 correlation during OLV in each patient, 62.9% (78/124) patients showed a strong correlation, 19.4% (24/124) a medium correlation, and the rest a poor correlation. The maximal difference between the left and right SctO2 was 13.5 (9.0, 20.0). Multivariate analysis showed that it was not associated with delirium (odds ratio [OR], 1.023; 95% CI, 0.963-1.087; P = 0.463). CONCLUSIONS: The correlation between left and right SctO2 was affected by one-lung ventilation in patients undergoing lung cancer surgery. This result indicates the requirement of bilateral SctO2 monitoring to reflect brain oxygenation. TRIAL REGISTRATION: This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017-1378) and was registered in the Chinese Clinical Trial Registry on 10/09/2017 ( http://www.chictr.org.cn , ChiCTR-ROC-17012627).

Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial.

STUDY OBJECTIVE: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer. DESIGN: A long-term follow-up of patients enrolled in a randomized trial. SETTING: The initial trial was performed in a tertiary care hospital in Beijing, China. PARTICIPANTS: Patients aged 60 years or older who were scheduled for major noncardiac surgery. INTERVENTION: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 µg/kg over 10 min, followed by a continuous infusion of 0.5 µg/kg/h until 1 h before end of surgery) or placebo during anesthesia. MEASUREMENTS: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis. RESULTS: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients. CONCLUSIONS: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

Muscular tissue desaturation and pneumonia in patients receiving lung cancer surgery: a cohort study.

BACKGROUND: Post-operative pneumonia (POP) is a common complication of lung cancer surgery, and muscular tissue oxygenation is a root cause of post-operative complications. However, the association between muscular tissue desaturation and POP in patients receiving lung cancer surgery has not been specifically studied. This study aimed to investigate the potential use of intra-operative muscular tissue desaturation as a predictor of POP in patients undergoing lung cancer surgery. METHODS: This cohort study enrolled patients (≥55 years) who had undergone lobectomy with one-lung ventilation. Muscular tissue oxygen saturation (SmtO 2 ) was monitored in the forearm (over the brachioradialis muscle) and upper thigh (over the quadriceps) using a tissue oximeter. The minimum SmtO 2 was the lowest intra-operative measurement at any time point. Muscular tissue desaturation was defined as a minimum baseline SmtO 2 of <80% for >15 s. The area under or above the threshold was the product of the magnitude and time of desaturation. The primary outcome was the association between intra-operative muscular tissue desaturation and POP within seven post-operative days using multivariable logistic regression. The secondary outcome was the correlation between SmtO 2 in the forearm and that in the thigh. RESULTS: We enrolled 174 patients. The overall incidence of muscular desaturation (defined as SmtO 2 < 80% in the forearm at baseline) was approximately 47.1% (82/174). The patients with muscular desaturation had a higher incidence of pneumonia than those without desaturation (28.0% [23/82] vs. 12.0% [11/92]; P  = 0.008). The multivariable analysis revealed that muscular desaturation was associated with an increased risk of pneumonia (odds ratio: 2.995, 95% confidence interval: 1.080-8.310, P  = 0.035) after adjusting for age, American Society of Anesthesiologists status, Assess Respiratory Risk in Surgical Patients in Catalonia score, smoking, use of peripheral nerve block, propofol, and study center. CONCLUSION: Muscular tissue desaturation, defined as a baseline SmtO 2 < 80% in the forearm, may be associated with an increased risk of POP. TRIAL REGISTRATION: No. ChiCTR-ROC-17012627.

Effect of acute pain on the association between preoperative cognitive impairment and postoperative delirium: a secondary analysis of three trials.

BACKGROUND: The association between preoperative cognitive impairment, postoperative pain, and postoperative delirium in older patients after noncardiac surgery is not known. METHODS: This was a secondary analysis of datasets from three previous studies. Patients aged ≥55 yr who underwent elective noncardiac surgery were enrolled. Preoperative cognitive impairment was defined as Mini-Mental State Examination <27. Pain intensity with movement was assessed using an 11-point numeric rating scale at 12-h intervals during the first 72 h after surgery; time-weighted average (TWA) pain score was calculated. Primary outcome was the occurrence of delirium within the first 5 postoperative days. Mediation analysis was used to investigate the relationships between cognitive impairment, pain score, and delirium. RESULTS: A total of 1497 patients were included. Prevalence of preoperative cognitive impairment was 40.3% (603/1497). Patients with cognitive impairment suffered higher TWA pain score within 72 h (4 [3-5] vs 3 [2-5], P=0.004) and more delirium within 5 days (12.9% [78/603] vs 4.9% [44/894], P<0.001) when compared with those without. Total and direct associations between cognitive impairment and delirium were (adjusted ß) 8.3% (95% confidence interval [CI], 4.8-12.0%; P<0.001) and 7.8% (95% CI, 4.4-12.0%; P<0.001), respectively. A significant indirect association with acute pain was observed between cognitive impairment and delirium (adjusted ß=0.4%; 95% CI, 0.1-1.0%; P=0.006), accounting for 4.9% of the total effect. CONCLUSIONS: The association between preoperative cognitive impairment and delirium is significantly mediated by acute pain in patients after noncardiac surgery. Considering the small effect size, clinical significance of this mediation effect requires further investigation.

Sedation efficacy of different dose of remimazolam with sufentanil for nerve block in young and elderly patients: a randomized, controlled study.

PURPOSE: Anxiety and pain commonly occur during nerve block, we aimed to investigate the sedation efficacy of different doses of remimazolam with sufentanil in young and elderly patients. METHODS: In this randomized trial, patients aged 18-85 years who underwent nerve block was enrolled. All patients received sufentanil 0.08 µg/kg for analgesia. Young patients (age < 65 years) were randomized into the control group (Group C, 0.9% saline), medium-dose remimazolam (Group M, 0.06 mg/kg) and high-dose remimazolam group (Group H, 0.08 mg/kg). Elderly patients (age ≥ 65 years) were randomized into the Group C, low-dose remimazolam group (Group L, 0.04 mg/kg) and Group M. Primary outcome was the success rate of procedure sedation. Respiratory depression and hypoxia were the interested safety outcomes. RESULTS: Ninety young and 114 elderly patients were enrolled, respectively. In comparison with Groups C and M, young patients in Group H had the highest success rate of procedure sedation (80.0 vs. 73.3 vs. 43.3%, P = 0.006). Elderly patients in Groups M and L had similar success rates of procedure sedation, which were significantly higher than that in Group C (78.9 vs. 78.9 vs. 50.0%, P = 0.007). In elderly patients, the incidence of respiratory depression and hypoxia tended to be higher in Group M than those in Groups L and C (both P < 0.001). CONCLUSION: Remimazolam 0.08 mg/kg provided the best sedation efficacy in young patients while remimazolam 0.04 mg/kg with the trend of less respiratory adverse events was more optimal for elderly patients. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=122016 .

Nociception monitors vs. standard practice for titration of opioid administration in general anesthesia: A meta-analysis of randomized controlled trials.

Background: Nociception monitors are being increasingly used during surgery, but their effectiveness in guiding intraoperative opioid administration is still uncertain. This meta-analysis of randomized controlled trials (RCTs) aimed to compare the effectiveness of nociception monitors vs. standard practice for opioid administration titration during general anesthesia. Methods: We searched the electronic databases of PubMed, EMBASE, Cochrane Library, Clinical Trial, and Web of Science from inception up to August 1, 2021, to identify relevant articles, and extracted the relevant data. Intraoperative opioid administration, extubation time, postoperative pain score, postoperative opioid consumption and postoperative nausea and vomiting (PONV) were compared between patients receiving nociception monitoring guidance and patients receiving standard management. The standardized mean difference (SMD), with 95% confidence interval (CI), was used to assess the significance of differences. The risk ratio (RR), with 95% CI, was used to assess the difference in incidence of PONV. Heterogeneity among the included trials was evaluated by the I 2 test. RevMan 5.3 software was used for statistical analysis. Results: A total of 21 RCTs (with 1957 patients) were included in the meta-analysis. Intraoperative opioid administration was significantly lower in patients receiving nociception monitor-guided analgesia than in patients receiving standard management (SMD, -0.71; 95% CI, -1.07 to -0.36; P < 0.001). However, pain scores and postoperative opioid consumption were not significantly higher in the former group. Considerable heterogeneity was found among the studies (92%). Extubation time was significantly shorter (SMD, -0.22; 95% CI, -0.41 to -0.03; P = 0.02) and the incidence of PONV significantly lower (RR, 0.78; 95% CI, 0.61 to 1.00; P = 0.05) in patients receiving nociception monitoring guidance. Conclusions: Intraoperative nociception monitoring guidance may reduce intraoperative opioid administration and appears to be a viable strategy for intraoperative titration of opioids. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273619, identifier: CRD42019129776.

Acute Kidney Injury and 3-Year Mortality in Elderly Patients After Non-cardiac Surgery.

Objective: The present study aimed to investigate whether acute kidney injury (AKI) was associated with 3-year mortality in elderly patients after non-cardiac surgery. Methods: The present study was a 3-year follow-up study of two randomized controlled trials. A total of 1,319 elderly patients who received non-cardiac surgery under general anesthesia were screened. AKI was diagnosed by the elevation of serum creatinine within a 7-day postoperative period according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. A long-term telephonic follow-up was undertaken by investigators who were not involved in the previous two trials and had no access to the study group assignment. The date of death was taken from the official medical death certificate. The primary outcome was to investigate the association between AKI and postoperative 3-year mortality using the multivariable Cox regression risk model. Results: Of the 1,297 elderly patients (mean age 71.8 ± 7.2 years old) who were included in the study, the incidence of AKI was 15.5% (201/1297). Of the patients with AKI, 85% (170/201) were at stage 1, 10% (20/201) at stage 2, and 5% (11/201) at stage 3. The 3-year all-cause mortality was 28.9% (58/201) in patients with AKI and 24.0% (263/1,096) in patients without AKI (hazard ratio 1.247, 95% confidence interval 0.939-1.657, P = 0.128). The multivariable Cox regression showed that AKI was not associated with 3-year mortality after adjustment of confounding factors (adjusted hazard ratio 1.045, 95% confidence interval 0.780-1.401, P = 0.766). Conclusions: AKI was a common postoperative complication, but it was not associated with 3-year mortality in elderly patients who underwent non-cardiac surgery. The low incidence of severe AKI might underestimate its underlying association with long-term mortality.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Comparison of Two Malnutrition Assessment Scales in Predicting Postoperative Complications in Elderly Patients Undergoing Noncardiac Surgery.

Background: The present study was designed to investigate the relationship between two malnutrition assessment scales, perioperative nutrition screen (PONS) and Nutritional Risk Screening 2002 (NRS2002), with postoperative complications in elderly patients after noncardiac surgery. Methods: This was a secondary analysis of a prospective cohort study. Elderly patients (65-90 years) undergoing noncardiac surgery were enrolled in Peking University First Hospital. Malnutrition was screened by PONS and NRS2002 at the day before surgery. Multivariable analysis was employed to analyze the relationship between PONS and NRS2002 and postoperative 30-day complications. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive value of PONS and NRS2002 in predicting postoperative complications. Results: A total of 915 patients with mean age of 71.6 ± 5.2 years were consecutively enrolled from September 21, 2017, to April 10, 2019. The incidence of malnutrition was 27.3% (250/915) by PONS ≥ 1 and 53.6% (490/915) by NRS2002 ≥ 3. The overall incidence of complications within postoperative 30 days was 45.8% (419/915). After confounders were adjusted, malnutrition by PONS ≥ 1 (OR 2.308, 95% CI 1.676-3.178, P < 0.001), but not NRS2002 ≥ 3 (OR 1.313, 95% CI 0.973-1.771, P = 0.075), was related with an increased risk of postoperative complications. ROC curve analysis showed that the performances of PONS [area under the ROC curve (AUC) 0.595, 95% CI 0.558-0.633] showed very weak improvement in predicting postoperative complications than NRS2002 score (AUC 0.577, 95% CI 0.540-0.614). Conclusion: The present study found that malnutrition diagnosed by PONS was related with an increased risk of postoperative complications. The performances of PONS and NRS2002 were poor in predicting overall postoperative complications. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR-OOC-17012734.

Long-term Survival after Combined Epidural-General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial.

BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.

The effect of dexmedetomidine on intraoperative blood glucose homeostasis: secondary analysis of a randomized controlled trial.

PURPOSE: To investigate the effect of dexmedetomidine on intraoperative blood glucose hemostasis in elderly patients undergoing non-cardiac major surgery. METHODS: This was secondary analysis of a randomized controlled trial. Patients in dexmedetomidine group received a loading dose dexmedetomidine (0.6 µg/kg in 10 min before anaesthesia induction) followed by a continuous infusion (0.5 µg/kg/hr) till 1 h before the end of surgery. Patients in control group received volume-matched normal saline at the same time interval. Primary outcome was the incidence of intraoperative hyperglycemia (blood glucose higher than 10 mmol/L). RESULTS: 303 patients in dexmedetomidine group and 306 patients in control group were analysed. The incidence of intraoperative hyperglycemia showed no statistical significance between dexmedetomidine group and control group (27.4% vs. 22.5%, RR = 1.22, 95%CI 0.92-1.60, P = 0.167). Median value of glycemic variation in dexmedetomidine group (2.5, IQR 1.4-3.7, mmol) was slightly lower than that in control group (2.6, IQR 1.5-4.0, mmol), P = 0.034. In multivariable logistic analysis, history of diabetes (OR 3.007, 95%CI 1.826-4.950, P < 0.001), higher baseline blood glucose (OR 1.353, 95%CI 1.174-1.560, P < 0.001) and prolonged surgery time (OR 1.197, 95%CI 1.083-1.324, P < 0.001) were independent risk factors of hyperglycaemia. CONCLUSIONS: Dexmedetomidine presented no effect on intraoperative hyperglycemia in elderly patients undergoing major non-cardiac surgery. TRIAL REGISTRATION: Present study was registered at Chinese Clinical Trial Registry on December 1, 2015 ( www.chictr.org.cn , registration number ChiCTR-IPR-15007654).

Malnutrition is not related with emergence delirium in older patients after noncardiac surgery.

BACKGROUND: Delirium is one of the most common complications in older surgical patients. Although previous studies reported that preoperative malnutrition was related with postoperative delirium (POD), there was lack of evidence to illustrate the relationship between malnutrition and emergency delirium (ED). The objective of this study was to investigate the relationship between preoperative malnutrition and ED in older patients undergoing noncardiac surgery. METHODS: The study was carried out in accordance with STROBE guidelines. This was a secondary analysis of a prospective cohort study. Older patients (65-90 years) who underwent noncardiac surgery under general anesthesia were enrolled in Peking University First Hospital. RESULTS: 915 patients were enrolled. The incidence of malnutrition was 53.6 % (490/915). The incidence of emergency delirium was 41.8 % (205/490) in malnutrition group and 31.5 % (134/425) in control group, P < 0.001. After adjusting confounding factors (i.e., age, cognitive impairment, American Society of Anesthesiologists classification (ASA), duration of surgery, pain score, low body temperature and allogeneic blood transfusion), malnutrition was not associated with increased risk of emergency delirium (OR = 1.055, 95 % CI 0.767-1.452, P = 0.742). CONCLUSIONS: Malnutrition was common in older patients undergoing non-cardiac surgery, but it's not related with emergence delirium after adjusted for confounders. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ( ChiCTR-OOC-17,012,734 ).

Association Between Cerebral Desaturation and Postoperative Delirium in Thoracotomy With One-Lung Ventilation: A Prospective Cohort Study.

BACKGROUND: The association between cerebral desaturation and postoperative delirium in thoracotomy with one-lung ventilation (OLV) has not been specifically studied. METHODS: A prospective observational study performed in thoracic surgical patients. Cerebral tissue oxygen saturation (Scto2) was monitored on the left and right foreheads using a near-infrared spectroscopy oximeter. Baseline Scto2 was measured with patients awake and breathing room air. The minimum Scto2 was the lowest measurement at any time during surgery. Cerebral desaturation and hypersaturation were an episode of Scto2 below and above a given threshold for ≥15 seconds during surgery, respectively. The thresholds based on relative changes by referring to the baseline measurement were <80%, <85%, <90%, <95%, and <100% baseline for desaturation and >105%, >110%, >115%, and >120% baseline for hypersaturation. The thresholds based on absolute values were <50%, <55%, <60%, <65%, and <70% for desaturation and >75%, >80%, >85%, and >90% for hypersaturation. The given area under the threshold (AUT)/area above the threshold (AAT) was analyzed. Delirium was assessed until postoperative day 5. The primary analysis was the association between the minimum Scto2 and delirium using multivariable logistic regression controlled for confounders (age, OLV time, use of midazolam, occurrence of hypotension, and severity of pain). The secondary analysis was the association between cerebral desaturation/hypersaturation and delirium, and between the AUT/AAT and delirium using multivariable logistic regression controlled for the same confounders. Multiple testing was corrected using the Holm-Bonferroni method. We additionally monitored somatic tissue oxygen saturation on the forearm and upper thigh. RESULTS: Delirium occurred in 35 (20%) of 175 patients (65 ± 6 years old). The minimum left or right Scto2 was not associated with delirium. Cerebral desaturation defined by <90% baseline for left Scto2 (odds ratio [OR], 5.82; 95% confidence interval [CI], 2.12-19.2; corrected P =.008) and <85% baseline for right Scto2 (OR, 4.27; 95% CI, 1.77-11.0; corrected P =.01) was associated with an increased risk of delirium. Cerebral desaturation defined by other thresholds, cerebral hypersaturation, the AUT/AAT, and somatic desaturation and hypersaturation were all not associated with delirium. CONCLUSIONS: Cerebral desaturation defined by <90% baseline for left Scto2 and <85% baseline for right Scto2, but not the minimum Scto2, may be associated with an increased risk of postthoracotomy delirium. The validity of these thresholds needs to be tested by randomized controlled trials.