Anaesthetic depth and delirium after major surgery: a randomised clinical trial.

BACKGROUND: Postoperative delirium is a serious complication of surgery associated with prolonged hospitalisation, long-term cognitive decline, and mortality. This study aimed to determine whether targeting bispectral index (BIS) readings of 50 (light anaesthesia) was associated with a lower incidence of POD than targeting BIS readings of 35 (deep anaesthesia). METHODS: This multicentre randomised clinical trial of 655 at-risk patients undergoing major surgery from eight centres in three countries assessed delirium for 5 days postoperatively using the 3 min confusion assessment method (3D-CAM) or CAM-ICU, and cognitive screening using the Mini-Mental State Examination at baseline and discharge and the Abbreviated Mental Test score (AMTS) at 30 days and 1 yr. Patients were assigned to light or deep anaesthesia. The primary outcome was the presence of postoperative delirium on any of the first 5 postoperative days. Secondary outcomes included mortality at 1 yr, cognitive decline at discharge, cognitive impairment at 30 days and 1 yr, unplanned ICU admission, length of stay, and time in electroencephalographic burst suppression. RESULTS: The incidence of postoperative delirium in the BIS 50 group was 19% and in the BIS 35 group was 28% (odds ratio 0.58 [95% confidence interval: 0.38-0.88]; P=0.010). At 1 yr, those in the BIS 50 group demonstrated significantly better cognitive function than those in the BIS 35 group (9% with AMTS ≤6 vs 20%; P<0.001). CONCLUSIONS: Among patients undergoing major surgery, targeting light anaesthesia reduced the risk of postoperative delirium and cognitive impairment at 1 yr. CLINICAL TRIAL REGISTRATION: ACTRN12612000632897.

Association of Obstructive Sleep Apnea With Difficult Intubation: Prospective Multicenter Observational Cohort Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been found to be associated with difficult airway, although there is a paucity of prospective studies investigating thresholds of OSA severity with difficult airway outcomes. The aim of this study was to examine the association between OSA and difficult intubation or difficult mask ventilation. We also explored the utility of the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender (STOP-Bang) score for difficult airway prediction. METHODS: The Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) trial was an international prospective cohort study of surgical patients 45 years or older with one or more cardiac risk factor presenting for noncardiac surgery, with planned secondary analyses of difficult airway outcomes. Multivariable logistic regression analyses tested associations between OSA severity and predictors of difficult airway with difficult intubation or difficult mask ventilation. Overall, 869 patients without prior diagnosis of OSA were screened for OSA risk with the STOP-Bang tool, underwent preoperative sleep study, and had routine perioperative care, including general anesthesia with tracheal intubation. The primary outcome analyzed was difficult intubation, and the secondary outcome was difficult mask ventilation. RESULTS: Based on the sleep studies, 287 (33%), 324 (37%), 169 (20%), and 89 (10%) of the 869 patients had no, mild, moderate, and severe OSA, respectively. One hundred and seventy-two (20%) had a STOP-Bang score of 0-2 (low risk), 483 (55%) had a STOP-Bang score of 3-4 (intermediate risk), and 214 (25%) had a STOP-Bang score 5-8 (high risk). The incidence of difficult intubation was 6.7% (58 of 869), and difficult mask ventilation was 3.7% (32 of 869). Multivariable logistic regression demonstrated that moderate OSA (odds ratio [OR] = 3.26 [95% confidence interval {CI}, 1.37-8.38], adjusted P = .010) and severe OSA (OR = 4.05 [95% CI, 1.51-11.36], adjusted P = .006) but not mild OSA were independently associated with difficult intubation compared to patients without OSA. Relative to scores of 0-2, STOP-Bang scores of 3-4 and 5-8 were associated with increased odds of difficult intubation (OR = 3.01 [95% CI, 1.13-10.40, adjusted P = .046] and 4.38 [95% CI, 1.46-16.36, adjusted P = .014]), respectively. OSA was not associated with difficult mask ventilation, and only increasing neck circumference was found to be associated (adjusted P = .002). CONCLUSIONS: Moderate and severe OSA were associated with difficult intubation, and increasing neck circumference was associated with difficult mask ventilation. A higher STOP-Bang score of 3 or more may be associated with difficult intubation versus STOP-Bang score of 0-2. Anesthesiologists should be vigilant for difficult intubation when managing patients suspected or diagnosed with OSA.

Impact of Locally Adopted Simulation-Based Crew Resource Management Training on Patient Safety Culture: Comparison Between Operating Room Personnel and General Health Care Populations Pre and Post Course.

Crew resource management (CRM) was introduced to enhance patient safety and reduce medical errors through multidisciplinary learning experience. This study investigates the impact of locally adopted simulation-based CRM training on participants' perceptions and knowledge. A 32-item web-based questionnaire was administered pre course, 1 month, and 1 year post course to assess changes in perceptions and knowledge. Another 12-item paper-based questionnaire was administered immediately post course to assess reactions. Among 712 participants analyzed, 165 were operating room staff. The majority agreed that the training is useful and relevant in daily practice. All participants showed significant improvements in perception and knowledge 1 month post course; however, these improvements declined 1 year post course. The CRM course is associated with satisfactory reaction (Kirkpatrick level 1) and improvement in attitude and knowledge (level 2) toward patient safety. However, the effect may be short-lived and regular refresher courses should be mandatory to sustain momentum of ongoing change.

Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery.

Importance: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. Objectives: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. Design, Setting, and Participants: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. Exposures: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. Main Outcomes and Measures: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. Results: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy. Conclusions and Relevance: Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain.

BACKGROUND: The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. METHODS: Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1,152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. RESULTS: At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNF mice compared with BDNF group after plantar incision. CONCLUSIONS: This study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain.

BIS-guided anesthesia decreases postoperative delirium and cognitive decline.

BACKGROUND: Previous clinical trials and animal experiments have suggested that long-lasting neurotoxicity of general anesthetics may lead to postoperative cognitive dysfunction (POCD). Brain function monitoring such as the bispectral index (BIS) facilitates anesthetic titration and has been shown to reduce anesthetic exposure. In a randomized controlled trial, we tested the effect of BIS monitoring on POCD in 921 elderly patients undergoing major noncardiac surgery. METHODS: Patients were randomly assigned to receive either BIS-guided anesthesia or routine care. The BIS group had anesthesia adjusted to maintain a BIS value between 40 and 60 during maintenance of anesthesia. Routine care group had BIS measured but not revealed to attending anesthesiologists. Anesthesia was adjusted according to traditional clinical signs and hemodynamic parameters. A neuropsychology battery of tests was administered before and at 1 week and 3 months after surgery. Results were compared with matched control patients who did not have surgery during the same period. Delirium was measured using the confusion assessment method criteria. RESULTS: The median (interquartile range) BIS values during the maintenance period of anesthesia were significantly lower in the control group, 36 (31 to 49), compared with the BIS-guided group, 53 (48 to 57), P<0.001. BIS-guided anesthesia reduced propofol delivery by 21% and that for volatile anesthetics by 30%. There were fewer patients with delirium in the BIS group compared with routine care (15.6% vs. 24.1%, P=0.01). Although cognitive performance was similar between groups at 1 week after surgery, patients in the BIS group had a lower rate of POCD at 3 months compared with routine care (10.2% vs. 14.7%; adjusted odds ratio 0.67; 95% confidence interval, 0.32-0.98; P=0.025). CONCLUSIONS: BIS-guided anesthesia reduced anesthetic exposure and decreased the risk of POCD at 3 months after surgery. For every 1000 elderly patients undergoing major surgery, anesthetic delivery titrated to a range of BIS between 40 and 60 would prevent 23 patients from POCD and 83 patients from delirium.