Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study.

BACKGROUND: Early identification of patients at high-risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. The authors also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76 457 patients in the discovery cohort and 11 910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees. The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 years), and 1179 patients (1.5%) developed AKI after surgery. The gradient boosting decision trees algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI: 0.835-0.863) and 0.828 (95% CI: 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine, and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, the authors observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models the authors developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Furthermore, the authors found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

Activation of mitochondrial DNA-mediated cGAS-STING pathway contributes to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

Chronic postsurgical pain (CPSP) is increasingly recognized as a public health issue. Recent studies indicated the innate immune pathway of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) was involved in pain regulation. However, the detailed mechanisms remain unclear. Previous studies found A1 reactive astrocytes in the spinal cord contributed to CPSP. This study aimed to investigate the roles and mechanisms of the cGAS-STING pathway in regulating the generation of A1 reactive astrocytes during CPSP. First, CPSP model was established using skin/muscle incision and retraction (SMIR) in rats. We found that cGAS-STING pathway was activated accompanied with an increase in mitochondrial DNA in the cytosol in the spinal cord following SMIR. Second, a STING inhibitor C-176 was intrathecally administrated. We found that C-176 decreased the expression of type I interferons and A1 reactive astrocytes in the spinal cord, and alleviated mechanical allodynia in SMIR rats. Third, cyclosporin A as a mitochondrial permeability transition pore blocker was intrathecally administrated. We found that cyclosporin A decreased the leakage of mitochondrial DNA and inhibited the activation of cGAS-STING pathway. Compared with C-176, cyclosporin A exhibits similar analgesic effects. The expression of type I interferons and A1 reactive astrocytes in the spinal cord were also down-regulated after intervention with cyclosporin A. Moreover, simultaneous administration of cyclosporin A and C-176 did not show synergistic effects in SMIR rats. Therefore, our study demonstrated that the cGAS-STING pathway activated by the leakage of mitochondrial DNA contributed to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

Predictive value of the geriatric nutrition risk index for postoperative delirium in elderly patients undergoing cardiac surgery.

AIMS: The aims of the study were to determine the relationship between preoperative geriatric nutritional risk index (GNRI) and the occurrence of postoperative delirium (POD) in elderly patients after cardiac surgery and to evaluate the additive value of GNRI for predicting POD. METHODS: The data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database. Patients who underwent cardiac surgery and were aged 65 or older were included. The relationship between preoperative GNRI and POD was investigated using logistic regression. We determined the added predictive value of preoperative GNRI for POD by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 4286 patients were included in the study, and 659 (16.1%) developed POD. Patients with POD had significantly lower GNRI scores than patients without POD (median 111.1 vs. 113.4, p < 0.001). Malnourished patients (GNRI ≤ 98) had a significantly higher risk of POD (odds ratio, 1.83, 90% CI, 1.42-2.34, p < 0.001) than those without malnutrition (GNRI > 98). This correlation remains after adjusting for confounding variables. The addition of GNRI to the multivariable models slightly but not significantly increases the AUCs (all p > 0.05). Incorporating GNRI increases NRIs in some models and IDIs in all models (all p < 0.05). CONCLUSIONS: Our results showed a negative association between preoperative GNRI and POD in elderly patients undergoing cardiac surgery. The addition of GNRI to POD prediction models may improve their predictive accuracy. However, these findings were based on a single-center cohort and will need to be validated in future studies involving multiple centers.

Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study.

BACKGROUND: The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, the authors examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI. MATERIALS AND METHODS: The authors retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using three objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. The authors performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI. RESULTS: A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification. CONCLUSIONS: Poor preoperative nutritional status, as assessed by GNRI, PNI, and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.

Postoperative short-term mortality between insulin-treated and non-insulin-treated patients with diabetes after non-cardiac surgery: a systematic review and meta-analysis.

Background: Diabetes mellitus is an independent risk factor for postoperative complications. It has been reported that insulin-treated diabetes is associated with increased postoperative mortality compared to non-insulin-treated diabetes after cardiac surgery; however, it is unclear whether this finding is applicable to non-cardiac surgery. Objective: We aimed to assess the effects of insulin-treated and non-insulin-treated diabetes on short-term mortality after non-cardiac surgery. Methods: Our study was a systematic review and meta-analysis of observational studies. PubMed, CENTRAL, EMBASE, and ISI Web of Science databases were searched from inception to February 22, 2021. Cohort or case-control studies that provided information on postoperative short-term mortality in insulin-treated diabetic and non-insulin-treated diabetic patients were included. We pooled the data with a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to rate the quality of evidence. Results: Twenty-two cohort studies involving 208,214 participants were included. Our study suggested that insulin-treated diabetic patients was associated with a higher risk of 30-day mortality than non-insulin-treated diabetic patients [19 studies with 197,704 patients, risk ratio (RR) 1.305; 95% confidence interval (CI), 1.127 to 1.511; p < 0.001]. The studies were rated as very low quality. The new pooled result only slightly changed after seven simulated missing studies were added using the trim-and-fill method (RR, 1.260; 95% CI, 1.076-1.476; p = 0.004). Our results also showed no significant difference between insulin-treated diabetes and non-insulin-treated diabetes regarding in-hospital mortality (two studies with 9,032 patients, RR, 0.970; 95% CI, 0.584-1.611; p = 0.905). Conclusion: Very-low-quality evidence suggests that insulin-treated diabetes was associated with increased 30-day mortality after non-cardiac surgery. However, this finding is non-definitive because of the influence of confounding factors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246752, identifier: CRD42021246752.

Farnesol Exerts Protective Effects against Chronic Sleep Deprivation-Induced Cognitive Impairment via Activation SIRT1/Nrf2 Pathway in the Hippocampi of Adult Mice.

SCOPE: Sleep deprivation (SD) negatively affects all aspects of health, with one serious consequence being impaired cognition. Farnesol (FOL) is a sesquiterpene synthesized by plants and mammals that has antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the mechanism underlying the neuroprotective effect of FOL on SD-induced cognitive impairment. METHODS AND RESULTS: Administration of FOL dramatically ameliorates chronic sleep deprivation (CSD)-induced cognitive impairment. In addition, FOL notably attenuates oxidative stress damage, pro-inflammatory cytokines activation, and microglial activation in the hippocampi of the CSD-exposed mice. Further examination indicates that administration of FOL after the CSD significantly increases the protein expressions of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (Gpx4) in the hippocampi. Sirt1 agonist resveratrol (RES) has a similar neuroprotective effect, indicating that FOL could exert neuroprotective effects through the activation of the Sirt1/Nrf2 signaling pathway. CONCLUSION: The results reveal that FOL could protect against CSD-induced cognitive impairment by activating the Sirt1/Nrf2 signaling pathway.

Analgesic Efficacy of Quadratus Lumborum Block in Patients Undergoing Nephrectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the analgesic efficacy of quadratus lumborum block (QLB) in adults undergoing nephrectomy. DESIGN: Systematic review and meta-analysis. PATIENTS: Adult patients (≥18 years of age) received nephrectomy under general anesthesia. METHODS: We searched PubMed, Embase, the Cochrane Library, and Web of Science on January 10, 2022, including randomized controlled trials that evaluated the analgesic efficacy of QLB for patients undergoing nephrectomy. RESULTS: A total of 12 randomized controlled trials (N = 821 patients) were included in the study. Compared with the non-block, single-shot QLB reduced postoperative opioid consumption (mean difference [MD], -8.37 mg intravenous morphine equivalent; 95% confidence interval [CI], -12.19 to -4.54 mg) and pain scores at 2 hours, 6 hours, 12 hours, and 24 hours at rest and during movement after nephrectomy. Single-shot QLB also prolonged the time to first analgesic request (MD, 6.44 hours; 95% CI, 2.23 to 10.65 hours), shortened the length of hospital stay (MD, -0.32 day; 95% CI, -0.55 to -0.09 day), and decreased the incidence of postoperative nausea and vomiting (risk ratio, 0.48; 95% CI, 0.36 to 0.65). Compared with continuous epidural anesthesia, repeated QLB could provide comparable postoperative analgesic benefits. CONCLUSIONS: Single-shot QLB provided a statistically significant but clinically small improvement in postoperative analgesia and recovery for patients undergoing nephrectomy. The QLB would be beneficial as part of multimodal analgesia. Future research might need to determine which approach of QLB is superior for postoperative analgesia after nephrectomy.

Activated AMPK mitigates diabetes-related cognitive dysfunction by inhibiting hippocampal ferroptosis.

Clinical and preclinical interest in Type 2 diabetes (T2D)-associated cognitive dysfunction (TDACD) has grown in recent years. However, the precise mechanisms underlying TDACD need to be further elucidated. Ferroptosis was reportedly involved in neurodegenerative diseases and diabetes-related organ injuries; however, its role in TDACD remains elusive. In this study, mice fed with a high-fat-diet combined with streptozotocin (HFD-STZ) were used as a T2D model to assess the role of ferroptosis in cognitive dysfunction. We found that ferroptosis was mainly activated in hippocampal neurons but not in microglia or astrocytes. Accordingly, increased levels of transferrin receptor and decreased levels of ferritin, GPX4, and SLC7A11 were observed in hippocampal neurons. In addition, pre-treatment with liproxstatin-1, a ferroptosis inhibitor, attenuated iron accumulation and oxidative stress response, which resulted in improved cognitive function in the HFD-STZ group. Furthermore, we found that p-AMP-activated protein kinase (AMPK) was decreased in the HFD-STZ group. Pre-treatment with AMPK agonist increased the expression of AMPK and GPX4, but decreased lipocalin 2 (LCN2) in the hippocampus that resulted in improved spatial learning ability in the HFD-STZ group. Taken together, we found that activation of neuronal ferroptosis in the hippocampus contributed to cognitive impairment of HFD-STZ mice. Furthermore, AMPK activation may reduce hippocampal ferroptosis, and consequently improve cognitive performance in diabetic mice.

Pharmacological inhibition of the cGAS-STING signaling pathway suppresses microglial M1-polarization in the spinal cord and attenuates neuropathic pain.

Neuroinflammation plays a vital role in the development of neuropathic pain and is mediated mainly by microglia. Suppressing microglial M1-polarization attenuates neuropathic pain. Recently, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a key mediator of inflammation and shows potential in modulating microglial polarization. In this study, we evaluated whether cGAS-STING is a potential therapeutic target. Spared nerve injury (SNI) surgery was conducted in adult male rats to establish a neuropathic pain model. We showed that SNI promoted microglial M1-polarization and induced cGAS-STING pathway activation in the spinal cord. Double-label immunofluorescence assays showed that cGAS-STING activation mainly occurred in neurons and microglia but not astrocytes. We further conducted in vitro experiments using BV-2 microglial cells. The results showed that LPS-induced microglial M1-polarization was accompanied by cGAS-STING pathway activation, but cGAS-STING inhibition by antagonists suppressed LPS-induced microglial M1-polarization. In vivo, we also showed that a cGAS antagonist and a STING antagonist suppressed the microglial M1-polarization and ameliorated the mechanical allodynia induced by SNI. These findings suggested that the cGAS-STING pathway might be a potential therapeutic target for treating neuropathic pain. However, further research is warranted to verify our findings in female rodents.

Preoperative screening of patients at high risk of obstructive sleep apnea and postoperative complications: A systematic review and meta-analysis.

STUDY OBJECTIVE: To determine the association between postoperative complications and a high versus low risk of obstructive sleep apnea (OSA) as determined via screening tools. DESIGN: Systematic review and meta-analysis of cohort studies. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to January 5, 2021. SETTING: Operating room, postoperative recovery area, and ward. PATIENTS: Adult patients scheduled for surgery. INTERVENTIONS: We used Review Manager 5.4 to pool the data. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MEASUREMENTS: The primary outcome was the composite endpoint of postoperative respiratory complications. The secondary outcomes were postoperative cardiac and neurological complications, intensive care unit (ICU) admission, and mortality. MAIN RESULTS: Twenty-six studies with 50,592 patients were included. A STOP-Bang score ≥ 3 (versus <3) was associated with higher incidences of postoperative respiratory (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.66-2.68) and neurological complications (OR, 3.60; 95% CI, 1.56-8.31). A STOP-Bang score ≥ 5 (versus <5) was associated with higher incidences of postoperative respiratory (OR, 2.37; 95% CI, 1.11-5.04) and cardiac complications (OR, 4.95; 95% CI, 1.22-20.00) and higher in-hospital mortality (OR, 26.39; 95% CI, 2.89-241.30). A Berlin score ≥ 2 (versus <2) was not associated with the incidence of postoperative complications, ICU admission, or mortality. The quality of evidence for all outcomes was very low. CONCLUSIONS: Very low-quality evidence suggested that a high risk of OSA, as assessed using the STOP-Bang questionnaire, was associated with a higher incidence of postoperative respiratory complications, and may also be associated with higher incidences of postoperative cardiac and neurological complications than a low risk of OSA. Since most of the included studies did not adjust for confounding factors, our findings need to be interpreted with caution. PROSPERO registration number: CRD42021220236.

Intensive glucose control during the perioperative period for diabetic patients undergoing surgery: An updated systematic review and meta-analysis.

STUDY OBJECTIVE: To evaluate the impact of intensive glucose control on diabetic patients undergoing surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. PubMed, CENTRAL, EMBASE, ISI Web of Science, and CINAHL databases were searched from inception to 13 December 2020. SETTING: Operating room, postoperative recovery area and ward, up to 30 days after surgery. PATIENTS: Diabetic patients undergoing surgery. INTERVENTIONS: We used Review Manager 5.4 to pool the data with a random-effects model. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MEASUREMENTS: The primary outcomes were infectious complications, postoperative mortality, and hypoglycaemia. The secondary outcomes included atrial fibrillation, myocardial infarction, stroke, delirium, renal failure, postoperative mechanical ventilation time, length of intensive care unit (ICU) stay, and hospital stay. MAIN RESULTS: Thirteen studies involving 1582 participants were included. Compared with conventional glucose control, intensive glucose control was associated with a lower risk of infectious complications (risk ratio [RR], 0.35; 95% confidence interval [CI], 0.19-0.63; low-quality evidence), atrial fibrillation (RR, 0.55; 95% CI, 0.42-0.71; high-quality evidence), and renal failure (RR, 0.38; 95% CI, 0.15-0.95; moderate-quality evidence), as well as a shorter length of stay in the ICU (mean difference (MD), -0.55 day; 95% CI, -1.05 to -0.05 days; very-low-quality evidence) and hospital (MD, -1.61 days; 95% CI, -2.78 to -0.44 days; very-low-quality evidence). However, intensive glucose control was associated with a higher risk of hypoglycaemia (RR, 3.00; 95% CI, 1.97-4.55; high-quality evidence). There were no significant differences in postoperative mortality, myocardial infarction, stroke, delirium, or postoperative mechanical ventilation time. CONCLUSIONS: Intensive glucose control in diabetic patients is associated with a reduction in some adverse postoperative outcomes including infectious complications, but also appears to increase the risk of hypoglycaemia. Further well-designed studies may be needed to determine appropriate regimens to reduce hypoglycaemia incidence. PROSPERO REGISTRATION NUMBER: CRD42021226138.

The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders.

Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk of long-term cognitive impairment. Perioperative sleep disturbance is prevalent and commonly ignored and may increase the risk of PND. However, the role of perioperative sleep disturbances in PND remains unclear. Nocturnal sleep plays an indispensable role in learning, memory, and maintenance of cerebral microenvironmental homeostasis. Hospitalized sleep disturbances also increase the incidence of postoperative delirium and cognitive dysfunction. This review summarizes the role of perioperative sleep disturbances in PND and elucidates the potential mechanisms underlying sleep-deprivation-mediated PND. Activated neuroinflammation and oxidative stress; impaired function of the blood-brain barrier and glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, and sirtuin1 expression; and accumulated amyloid-beta proteins are associated with PND in individuals with perioperative sleep disorders. These findings suggest that the improvement of perioperative sleep might reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Future studies should further investigate the role of perioperative sleep disturbance in PND.

Angiotensin II type 1 receptor blockade attenuates posttraumatic stress disorder-related chronic pain by inhibiting glial activation in the spinal cord.

Clinically, posttraumatic stress disorder (PTSD) and chronic pain are highly comorbid conditions, but the underlying mechanisms of and therapeutic strategies against PTSD-related pain remain unclear. Our previous studies suggested that dysregulation of neuroinflammation contributes to the development of stress-induced hyperalgesia. Recent studies reported that angiotensin II was a 'stress-related hormone', and could induce glial activation by stimulating the type 1 receptor (AT1R). In the present study, we aimed to investigate whether AT1R blockade could attenuate mechanical allodynia induced by PTSD-like stress. Adult male rats were exposed to single prolonged stress (SPS) to establish a model of PTSD-pain comorbidity. Our results showed that SPS exposure increased the levels of angiotensin II in the hippocampus, prefrontal cortex (PFC) and spinal cord; intraperitoneal injection of losartan attenuated SPS-induced mechanical allodynia, and suppressed SPS-induced glial activation (both microglia and astrocytes) and proinflammatory cytokine expression in the PFC and spinal cord, but not in the hippocampus. We further showed that intrathecal injection of losartan also exerted anti-hyperalgesic effect and suppressed SPS-induced glial activation and proinflammatory cytokine expression in the spinal cord. These results indicated that AT1R blockade by losartan attenuated mechanical allodynia induced by PTSD-like stress, and this may be attributed to the suppression of glial activation and proinflammatory cytokine expression in the spinal cord. Although further research is warranted to verify our findings in female rodents and to assess pharmacological effects of AT1R blockade in PFC and hippocampus, our study suggested the therapeutic potential of targeting AT1R in the treatment of PTSD-related chronic pain.

Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice.

Sevoflurane, the most commonly used inhaled anesthetic in pediatric anesthesia, has been reported to induce cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated. Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in neurological disorders and aging models through anti-inflammatory activity. However, its effect on sevoflurane-induced cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of resveratrol on sevoflurane-induced cognitive impairment. Six-day-old mice received anesthesia with 3% sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before anesthesia. Sevoflurane exposure significantly suppressed the expression of Sirtuin 1 (SIRT1) and activated microglia in hippocampi. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly increased after sevoflurane exposure. Strikingly, resveratrol pretreatment ameliorated sevoflurane-induced SIRT1 inhibition and microglial activation. Of note, resveratrol reversed sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing mRNA level of clusters of differentiation 206 (CD206) and decreasing mRNA levels of clusters of differentiation 86 (CD86) and suppressor of cytokine signaling 3 (SOCS3). Consequently, sevoflurane-induced cognitive impairment in developing mice was ameliorated by resveratrol pretreatment. Taken together, repeated sevoflurane exposure to the developing brain resulted in SIRT1 inhibition, NF-κB acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1-NF-κB pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane.

Effect of dexmedetomidine on delirium during sedation in adult patients in intensive care units: A systematic review and meta-analysis.

STUDY OBJECTIVE: To compare the effect of sedation protocols with and without dexmedetomidine on delirium risk and duration in adult patients in intensive care units (ICUs). DESIGN: A meta-analysis of randomized controlled trials. REVIEW METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and ISI Web of Science from inception to September 3, 2020. We included studies comparing the effect of dexmedetomidine-based sedation on delirium risk with non-dexmedetomidine-based sedation in adult patients in ICUs. We pooled the data using a random-effects model using Review Manager 5.2, and assessed publication bias using Stata 11.0. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MAIN RESULTS: We included 36 studies involving 9623 participants. The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54-0.75; very low-quality evidence), but higher incidences of hypotension and bradycardia during hospital stay. Dexmedetomidine was also associated with shorter durations of ICU stay, hospital stay and mechanical ventilation. Dexmedetomidine did not affect ICU mortality (RR, 1.01; 95% CI, 0.89-1.14; low-quality evidence), hospital mortality (RR, 1.01; 95% CI, 0.91-1.12; very low-quality evidence), or 30-day mortality (RR, 0.77; 95% CI, 0.58-1.01; moderate-quality evidence), or duration of delirium (mean difference, -0.74 days; 95% CI, -1.83 to 0.36 days; very low-quality evidence). We identified publication bias for risk and duration of delirium, length of ICU stay, and hospital stay. CONCLUSIONS: Low- or very low-quality evidence suggests that dexmedetomidine was associated with a clinically-small reduction of delirium risk, ICU/hospital stay and mechanical ventilation duration, but were not associated with improved mortality or shorter delirium duration in ICU patients. These findings were inconclusive because of publication bias, heterogeneity, and limited sample size. Significant adverse effects of dexmedetomidine include hypotension and bradycardia. PROSPERO registration number: CRD42018095358.

Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery.

Postoperative cognitive dysfunction (POCD) is a sever postsurgical neurological complication in the elderly population. As the global acceleration of population ageing, POCD is proved to be a great challenge to the present labor market and healthcare system. In the present study, our findings showed that tau acetylation mediated by SIRT1 deficiency resulted in tau hyperphosphorylation in the hippocampus of the aged POCD model and consequently contributed to cognitive impairment. Interestingly, pretreatment with resveratrol almost restored the expression of SIRT1, reduced the levels of acetylated tau and hyperphosphorylated tau in the hippocampus, and improved the cognitive performance in the behavioral tests. What is more, we observed that microglia-derived neuroinflammation resulting from SIRT1 inhibition in microglia probably aggravated the tau acetylation in cultured neurons in vitro. Our findings supported the notion that activation SIRT1 provided dually beneficial effect in the aged POCD model. Taken together, our findings provided the initial evidence that tau acetylation was associated with cognitive impairment in the aged POCD model and paved a promising avenue to prevent POCD by inhibiting tau acetylation in a SIRT1-dependent manner.

Clinical experience with emergency endotracheal intubation in COVID-19 patients in the intensive care units: a single-centered, retrospective, descriptive study.

Few studies have reported the implications of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units (ICUs). Therefore, this study aimed to summarize the outcomes of COVID-19 patients in the ICU following endotracheal intubation and provide a clinical reference for the high-risk procedure. From February 1 to February 18, 2020, we enrolled 59 critically ill COVID-19 patients who received emergency endotracheal intubation in the ICUs of Tongji Hospital. We recorded demographic information, laboratory parameters, comorbidities, changes in vital signs pre- and post-intubation, the airway grade, intubation success rate using three types of laryngoscopes, and the experience of intubators. Follow-up evaluations were performed for all proceduralists to monitor nosocomial infections. The majority of the patients requiring intubation were elderly and had at least one comorbidity. Of the patients, 86.4% developed hypoxia before intubation. The first and second attempts of successful endotracheal intubation with the Macintosh laryngoscope (70.0% and 83.3%), Airtraq videolaryngoscope (93.5% and 80%), and UE videolaryngoscope (88.9% and 100%) were performed. Notably, SpO2 <93% and hypotension were observed 3 min after intubation in 32.2% and 39% patients, respectively. With the proper use of personal protective equipment (PPE), no nosocomial infections were observed among proceduralists. Full PPE increased the occurrence of fogging on goggles and myopia glasses. Overall, a higher success rate of intubation was achieved by senior intubators using a videolaryngoscope. Although inconvenient, appropriate ensembles of PPE could prevent nosocomial infections.

Topical application of ketamine to prevent postoperative sore throat in adults: A systematic review and meta-analysis.

BACKGROUND: Postoperative sore throat is a leading undesirable postoperative outcome. Ketamine is an N-methyl-d-aspartate receptor antagonist and its topical application is used for chronic pain and oral/throat indications. We conducted a systematic review to assess the efficacy of preoperative, topical ketamine application for preventing postoperative sore throat. METHODS: We searched MEDLINE, EMBASE, and CENTRAL through September 23, 2019 for randomized controlled trials in which at least one intervention was topical ketamine to prevent postoperative sore throat in adults undergoing endotracheal intubation. The primary outcome was the incidence of sore throat at 24 hours postoperatively. The comparators were non-analgesic controls (placebo, no treatment, or usual care) or active agents. We pooled the data using a random-effects model. RESULTS: We included 41 randomized controlled trials involving 3784 participants. Topical ketamine was associated with reduced incidence of sore throat at 24 hours postoperatively compared to non-analgesic methods (risk ratio, 0.45; 95% CI, 0.37-0.54; P < .001). We found significant publication bias, but the results remained unchanged with a trim-and-fill analysis. Trial sequential analysis (TSA) suggested that the efficacy of topical ketamine was adequate (TSA-adjusted 95% CI, 0.33-0.56). The GRADE quality for this evidence was moderate. Topical ketamine was inferior to a combination of nebulized ketamine and clonidine in preventing postoperative sore throat. CONCLUSIONS: Preoperative, topical ketamine application may be more effective than non-analgesic methods in preventing postoperative sore throat. The number of studies did not suffice to determine the place of topical ketamine among agents to prevent postoperative sore throat.

Topical application of magnesium to prevent intubation-related sore throat in adult surgical patients: a systematic review and meta-analysis.

BACKGROUND: Postoperative sore throat negatively affects patient satisfaction and recovery. We conducted a systematic review and meta-analysis to examine the efficacy of preoperative topical administration of magnesium sulfate in preventing postoperative sore throat in adult patients. METHODS: We searched Medline, EMBASE, China National Knowledge Infrastructure, and the Cochrane Central Register of Controlled Trials from inception to 6 October, 2018. We included randomized-controlled trials that assessed the efficacy and safety of topical application of magnesium preoperatively in adult patients who underwent endotracheal intubation for general anesthesia. We then pooled the data using a random-effects model and conducted a trial sequential analysis on the incidence of sore throat. Our primary outcome was the incidence of sore throat at 24 hr after surgery/extubation. Our secondary outcomes included the severity of sore throat at 24 hr after surgery/extubation and adverse events. RESULTS: Eleven randomized-controlled trials involving 1,096 patients were included in this study. Topical application of magnesium was associated with reduced incidence of postoperative sore throat (risk ratio, 0.31; 95% confidence interval [CI], 0.21 to 0.45) as well as reduced severity of postoperative sore throat (standardized mean difference, - 2.66; 95% CI, - 3.89 to - 1.43). Three studies reported that significant adverse events were not associated with topical magnesium. The trial sequential analysis suggested that there is adequate evidence supporting the efficacy of topical magnesium in preventing postoperative sore throat. CONCLUSION: Our study suggests that preoperative topical magnesium can effectively prevent postoperative sore throat. TRIAL REGISTRATION: PROSPERO (CRD42018110019); registered 26 September, 2018.