Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

BACKGROUND: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine. METHODS: We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. RESULTS: Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). CONCLUSIONS: Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Metformin Use in Type 2 Diabetics and Delirium After Noncardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive. METHODS: We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables. RESULTS: No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13). CONCLUSIONS: Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.

Serratus anterior and pectoralis plane blocks for robotically assisted mitral valve repair: a randomised clinical trial.

BACKGROUND: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. METHODS: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1-3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. RESULTS: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1-3 with a median difference of 0.08 (95% confidence interval [CI]: -0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85-1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. CONCLUSIONS: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. CLINICAL TRIAL REGISTRATION: NCT03743194.

Postoperative Risk of Transfusion After Reversal of Residual Neuromuscular Block With Sugammadex Versus Neostigmine: A Retrospective Cohort Study.

BACKGROUND: Sugammadex and neostigmine are routinely used to reverse residual neuromuscular blocks at the end of surgery. Sugammadex has been linked with prolongation of laboratory coagulation markers, but clinical relevance on postoperative blood loss and transfusions remains unclear. METHODS: In this retrospective, single-center, cohort study, we analyzed medical records of adult patients having noncardiac surgery who were given sugammadex or neostigmine from May 2016 to December 2020. Our primary outcome was the incidence of any postoperative transfusion of red blood cells, and/or fresh-frozen plasma, and/or platelets. Secondary outcomes were duration of hospitalization, need for resurgery, and postoperative intensive care unit (ICU) admission. After propensity score weighting, the odds ratio (OR) for postoperative transfusion was assessed in both groups (sugammadex versus neostigmine) using a generalized estimation equation to count within-subject correlation weighted by the inverse propensity score. RESULTS: Out of 39,325 eligible surgeries, 33,903 surgeries in 29,062 patients were included in the analysis; with 4581 patients receiving sugammadex and 29,322 patients receiving neostigmine. The raw incidence of postoperative transfusion was 7.40% in sugammadex and 7.45% in the neostigmine group. After weighting by propensity score, the incidence of postoperative transfusion was 8.01% in the sugammadex and 7.38% in the neostigmine group (OR, 1.11 [95% confidence interval [CI], 0.97-1.26; P = .118]). There was no difference in duration of hospitalization and need for resurgery, but odds of postoperative ICU admission were significantly higher for patients receiving sugammadex than those receiving neostigmine (OR, 1.33 [98.33% CI, 1.17-1.52; P < .0001]). Our a priori planned analysis of coagulation laboratory parameters could not be completed because of a high amount of missing laboratory data. CONCLUSIONS: There is no statistically significant nor clinically important difference in the risk of postoperative transfusion in patients receiving sugammadex or neostigmine.

Association between postoperative hypotension and acute kidney injury after noncardiac surgery: a historical cohort analysis.

PURPOSE: The extent to which postoperative hypotension contributes to renal injury remains unclear, much less what the harm thresholds might be. We therefore tested the primary hypothesis that there is an absolute hypotensive arterial pressure threshold for acute kidney injury during the initial seven days after noncardiac surgery. METHODS: We conducted a single-centre historical cohort analysis of adults who had noncardiac surgery and had creatinine recorded preoperatively and postoperatively. Our exposure was the lowest postoperative mean arterial pressure, defined as the average of the three lowest postoperative pressure measurements. Our primary analysis was the association between the lowest mean arterial pressure and acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes initiative criteria. Our analysis was adjusted for potentially relevant confounding factors including intraoperative hypotension. RESULTS: Among 64,349 patients analyzed, 2,812 (4.4%) patients had postoperative acute kidney injury. Each 5-mm Hg decrease in the lowest mean arterial pressure was associated with a 28% (97.5% confidence interval [CI], 23 to 32; P < 0.001) increase in the odds of acute kidney injury for lowest mean arterial pressures < 80 mm Hg. Higher lowest pressures were not associated with acute kidney injury (odds ratio, 1.08; 97.5% CI, 0.99 to 1.17; P = 0.04) for each 5-mm Hg decrease in the lowest mean arterial pressure. CONCLUSION: Postoperative hypotension, defined as the lowest postoperative mean arterial pressure < 80 mm Hg, was associated with acute kidney injury after noncardiac surgery. A prospective trial will be required to determine whether the observed association is causal and thus amenable to modification.

RéSUMé: OBJECTIF: Nous ne savons pas dans quelle mesure l'hypotension postopératoire contribue aux lésions rénales, et nous connaissons encore moins les seuils de lésion. Nous avons donc testé l'hypothèse primaire selon laquelle il existerait un seuil absolu de tension artérielle hypotensive pour l'insuffisance rénale aiguë au cours des sept premiers jours suivant une chirurgie non cardiaque. MéTHODE: Nous avons mené une analyse de cohorte historique monocentrique auprès d'adultes ayant bénéficié d'une chirurgie non cardiaque et pour lesquel·les les taux de créatinine avant et après l'opération avaient été enregistrés. Notre exposition était la tension artérielle moyenne postopératoire la plus basse, définie comme la moyenne des trois mesures de tension postopératoire les plus basses. Notre analyse principale a porté sur l'association entre la tension artérielle moyenne la plus basse et l'insuffisance rénale aiguë, définies selon les critères de l'initiative KDIGO (Kidney Disease: Improving Global Outcomes). Notre analyse a été ajustée pour tenir compte des facteurs de confusion potentiellement pertinents, notamment de l'hypotension peropératoire. RéSULTATS: Parmi les 64 349 patient·es analysé·es, 2812 (4,4 %) ont présenté une insuffisance rénale aiguë postopératoire. Chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible était associée à une augmentation de 28 % (intervalle de confiance [IC] de 97,5 %, 23 à 32; P < 0,001) des risques d'insuffisance rénale aiguë pour les tensions artérielles moyennes les plus faibles < 80 mm Hg. Des tensions les plus faibles plus hautes n'ont pas été associées à une insuffisance rénale aiguë (rapport de cotes, 1,08; IC 97,5 %, 0,99 à 1,17; P = 0,04) pour chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible. CONCLUSION: L'hypotension postopératoire, définie comme la tension artérielle moyenne postopératoire < 80 mm Hg la plus basse, a été associée à une insuffisance rénale aiguë après une chirurgie non cardiaque. Une étude prospective sera nécessaire pour déterminer si l'association observée est causale et donc susceptible d'être modifiée.

Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial.

BACKGROUND: Hypotension and postoperative anaemia are associated with myocardial and renal injury after noncardiac surgery, but the interaction between them remains unknown. OBJECTIVES: To test the hypothesis that a double-hit of postoperative anaemia and hypotension synergistically worsens a 30-day composite of myocardial infarction (MI) and mortality and acute kidney injury (AKI). Characterising the interaction when hypotension and anaemia occur at same time on myocardial infarction and acute kidney injury. DESIGN: Post hoc analysis of the POISE-2 trial. SETTING: Patients were enrolled between July 2010 and December 2013 at 135 hospitals in 23 countries. PATIENTS: Adults at least 45 years old with known or suspected cardiovascular disease. We excluded patients without available postoperative haemoglobin measurements or hypotension duration records. Exposures were the lowest haemoglobin concentration and the average daily duration of SBP less than 90 mmHg within the first four postoperative days. MAIN OUTCOME MEASURES: The primary outcome was a collapsed composite of nonfatal MI and all-cause mortality during the initial 30 postoperative days; our secondary outcome was AKI. RESULTS: We included 7940 patients. The mean ±â€ŠSD lowest postoperative haemoglobin was 10 ±â€Š2 g dl -1 , and 24% of the patients had SBP less than 90 mmHg with daily duration ranging from 0 to 15 h. Four hundred and nine (5.2%) patients had an infarction or died within 30 postoperative days, and 417 (6.4%) patients developed AKI. Lowest haemoglobin concentrations less than 11 g dl -1 , and duration of SBP less than 90 mmHg was associated with greater hazard of composite outcome of nonfatal MI and all-cause mortality, as well as with AKI. However, we did not find significant multiplicative interactions between haemoglobin splines and hypotension duration on the primary composite or on AKI. CONCLUSION: Postoperative anaemia and hypotension were meaningfully associated with both our primary composite and AKI. However, lack of significant interaction suggests that the effects of hypotension and anaemia are additive rather than multiplicative. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01082874.

Intraoperative Hypotension and Acute Kidney Injury after Noncardiac Surgery in Infants and Children: A Retrospective Cohort Analysis.

BACKGROUND: Age- and sex-specific reference nomograms for intraoperative blood pressure have been published, but they do not identify harm thresholds. The authors therefore assessed the relationship between various absolute and relative characterizations of hypotension and acute kidney injury in children having noncardiac surgery. METHODS: The authors conducted a retrospective cohort study using electronic data from two tertiary care centers. They included inpatients 18 yr or younger who had noncardiac surgery with general anesthesia. Postoperative renal injury was defined using the Kidney Disease Improving Global Outcomes definitions, based on serum creatinine concentrations. The authors evaluated potential renal harm thresholds for absolute lowest intraoperative mean arterial pressure (MAP) or largest MAP reduction from baseline maintained for a cumulative period of 5 min. Separate analyses were performed in children aged 2 yr or younger, 2 to 6 yr, 6 to 12 yr, and 12 to 18 yr. RESULTS: Among 64,412 children who had noncardiac surgery, 4,506 had creatinine assessed preoperatively and postoperatively. The incidence of acute kidney injury in this population was 11% (499 of 4,506): 17% in children under 6 yr old, 11% in children 6 to 12 yr old, and 6% in adolescents, which is similar to the incidence reported in adults. There was no association between lowest cumulative MAP sustained for 5 min and postoperative kidney injury. Similarly, there was no association between largest cumulative percentage MAP reduction and postoperative kidney injury. The adjusted estimated odds for kidney injury was 0.99 (95% CI, 0.94 to 1.05) for each 5-mmHg decrease in lowest MAP and 1.00 (95% CI, 0.97 to 1.03) for each 5% decrease in largest MAP reduction from baseline. CONCLUSIONS: In distinct contrast to adults, the authors did not find any association between intraoperative hypotension and postoperative renal injury. Avoiding short periods of hypotension should not be the clinician's primary concern when trying to prevent intraoperative renal injury in pediatric patients.

Pain and Opioid Consumption and Mobilization after Surgery: Post Hoc Analysis of Two Randomized Trials.

BACKGROUND: Early mobilization is incorporated into many enhanced recovery pathways. Inadequate analgesia or excessive opioids may restrict postoperative mobilization. The authors tested the hypotheses that in adults recovering from abdominal surgery, postoperative pain and opioid consumption are inversely related to postoperative mobilization, and that postoperative mobilization is associated with fewer potentially related complications. METHODS: The authors conducted a subanalysis of two trials that enrolled adults recovering from abdominal surgery. Posture and movement were continuously monitored for 48 postoperative hours using noninvasive untethered monitors. Mobilization was defined as the fraction of monitored time spent sitting or standing. RESULTS: A total of 673 patients spent a median [interquartile range] of 7% [3 to 13%] of monitored time sitting or standing. Mobilization time was 1.9 [1.0 to 3.6] h/day for patients with average pain scores 3 or lower, but only 1.2 [0.5 to 2.6] h/day in those with average scores 6 or greater. Each unit increase in average pain score was associated with a decrease in mobilization time of 0.12 (97.5% CI, 0.02 to 0.24; P = 0.009) h/day. In contrast, there was no association between postoperative opioid consumption and mobilization time. The incidence of the composite of postoperative complications was 6.0% (10 of 168) in the lower mobilization quartile, 4.2% (7 of 168) in the second quartile, and 0% among 337 patients in the highest two quartiles (P = 0.009). CONCLUSIONS: Patients recovering from abdominal surgery spent only 7% of their time mobilized, which is considerably less than recommended. Lower pain scores are associated with increased mobility, independently of opioid consumption. Complications were more common in patients who mobilized poorly.

Association between postoperative haemoglobin concentrations and composite of non-fatal myocardial infarction and all-cause mortality in noncardiac surgical patients: post hoc analysis of the POISE-2 trial.

BACKGROUND: Myocardial infarction is the most common postoperative major vascular complication. Perioperative anaemia may contribute to cardiac supply-demand mismatch, and therefore myocardial injury. We therefore tested the hypothesis that the lowest in-hospital postoperative haemoglobin concentration is associated with a composite of non-fatal myocardial infarction and all-cause mortality within the first 30 days after noncardiac surgery. METHODS: We conducted a retrospective analysis of patients enrolled in the PeriOperative Ischemic Evaluation-2 (POISE-2) trial. We assessed the association between the lowest postoperative haemoglobin concentration during the initial hospitalisation and a composite of non-fatal myocardial infarction (Third Universal Definition) and all-cause mortality within 30 postoperative days, using a multivariable logistic regression model. RESULTS: We analysed 7227 patients from POISE-2, of whom 7.8% developed myocardial infarction; 1.5% died within 30 days. The composite primary outcome of non-fatal myocardial infarction and all-cause mortality occurred in 8.9% patients overall, ranging from 16% in patients with postoperative haemoglobin concentrations <88 g L-1 to 4.1% in patients with postoperative haemoglobin >113 g L-1. After adjusting for baseline factors, in patients with a lowest postoperative haemoglobin concentration <110 g L-1, each 10 g L-1 reduction in the lowest postoperative haemoglobin concentration was associated with a 1.46 (95% confidence interval: 1.37-1.56; P<0.001) fold increase in the odds of the composite outcome. In contrast, there was no significant relationship amongst patients with lowest postoperative haemoglobin concentration >110 g L-1. CONCLUSIONS: Postoperative anaemia may be a modifiable risk factor for non-fatal myocardial infarction and all-cause mortality.

Association between postoperative haemoglobin and myocardial injury after noncardiac surgery: a retrospective cohort analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply-demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. METHODS: We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml-1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. RESULTS: Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl-1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was <8 g dl-1. The confounder-adjusted hazard ratio [95% confidence interval] for having MINS was 1.29 [1.16-1.42] for every 1 g dl-1 decrease in postoperative haemoglobin in a time-varying covariate analysis. Similar associations were identified in sensitivity analyses. CONCLUSION: Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of anaemia remains to be determined.

Effect of Intravenous Acetaminophen on Mean Arterial Blood Pressure: A Post Hoc Analysis of the EFfect of Intravenous ACetaminophen on PosToperative HypOxemia After Abdominal SurgeRy Trial.

BACKGROUND: Acetaminophen is commonly used as part of multimodal analgesia for acute pain. The intravenous formulation offers a more predictable bioavailability compared to oral and rectal acetaminophen. There have been reports of hypotension with intravenous acetaminophen attributable to centrally mediated and vasodilatory effects. We tested the hypothesis that in adults having abdominal surgery the use of intravenous acetaminophen versus placebo for postoperative pain management is associated with a decrease in mean arterial pressure (MAP) after its administration. METHODS: This is a substudy of eFfect of intravenous ACetaminophen on posToperative hypOxemia after abdominal surgeRy (FACTOR) trial (NCT02156154). FACTOR trial randomly assigned adults undergoing abdominal surgery to either 1 g of acetaminophen or placebo every 6 hours during the first postoperative 48 hours. Continuous monitoring of blood pressure was obtained by noninvasive ViSi Mobile device (Sotera Wireless, Inc, San Diego, CA) at 15-second intervals during initial 48 hours postoperatively. We excluded patients without continuous monitoring data available. The primary outcome was the MAP difference between MAP 5 minutes before study drug administration (baseline) and MAP 30 minutes poststudy drug administration initiation. We used a linear mixed effects model to assess the treatment effect on MAP change. The secondary outcome was MAP area under baseline (AUB) during the 30 minutes after treatment. In a sensitivity analysis of change in MAP from predrug to postdrug administration, we instead used postdrug MAP as the outcome adjusting for the baseline MAP in the model. RESULTS: Among 358 patients analyzed, 182 received acetaminophen and 176 placebo. The mean (standard deviation [SD]) of average MAP change was -0.75 (5.9) mm Hg for the treatment and 0.32 (6.3) mm Hg for the placebo. Acetaminophen was found to decrease the MAP from baseline more than placebo after drug administration. The estimated difference in mean change of MAP was -1.03 (95% confidence interval [CI] -1.60 to -0.47) mm Hg; P < .001. The sensitivity analysis showed postoperative MAP in the acetaminophen group was 1.33 (95% CI, 0.76-1.90) mm Hg lower than in the placebo group (P < .001). The median of MAP AUB was 33 [Q1 = 3.3, Q3 = 109] mm Hg × minutes for the treatment and 23 [1.6, 79] mm Hg × minutes for the placebo. Acetaminophen was found to increase the AUB with an estimated median difference of 15 (95% CI, 5-25) mm Hg × minutes (P = .003). CONCLUSIONS: Intravenous acetaminophen decreases MAP after its administration. However, this decrease does not appear to be clinically meaningful. Clinicians should not refrain to use intravenous acetaminophen for acute pain management because of worries of hypotension.

Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular Block in Patients Having Catheter-Based Neurointerventional Procedures: A Randomized Trial.

BACKGROUND: Catheter-based endovascular neurointerventions require deep neuromuscular blocks during the procedure and rapid subsequent recovery of strength to facilitate neurological evaluation. We tested the primary hypothesis that sugammadex reverses deep neuromuscular blocks faster than neostigmine reverses moderate neuromuscular blocks. METHODS: Patients having catheter-based cerebral neurointerventional procedures were randomized to: (1) deep rocuronium neuromuscular block with posttetanic count 1 to 2 and 4-mg/kg sugammadex as the reversal agent or (2) moderate rocuronium neuromuscular block with train-of-four (TOF) count 1 during the procedure and neuromuscular reversal with 0.07-mg/kg neostigmine to a maximum of 5 mg. Recovery of diaphragmatic function was assessed by ultrasound at baseline before the procedure and 90 minutes thereafter. The primary outcome-time to reach a TOF ratio ≥0.9 after administration of the designated reversal agent-was analyzed with a log-rank test. Secondary outcomes included time to successful tracheal extubation and the difference between postoperative and preoperative diaphragmatic contraction speed and distance. RESULTS: Thirty-five patients were randomized to sugammadex and 33 to neostigmine. Baseline characteristics and surgical factors were well balanced. The median time to reach TOF ratio ≥0.9 was 3 minutes (95% confidence interval [CI], 2-3 minutes) in patients given sugammadex versus 8 minutes (95% CI, 6-10 minutes) in patients given neostigmine. Sugammadex was significantly faster by a median of 5 minutes (95% CI, 3-6 minutes; P < .001). However, times to tracheal extubation and diaphragmatic function at 90 minutes did not differ significantly. CONCLUSIONS: Sugammadex reversed deep rocuronium neuromuscular blocks considerably faster than neostigmine reversed moderate neuromuscular blocks. However, times to extubation did not differ significantly, apparently because extubation was largely determined by the time required for awaking from general anesthesia and because clinicians were willing to extubate before full neuromuscular recovery. Sugammadex may nonetheless be preferable to procedures that require a deep neuromuscular block and rapid recovery.

Utilization of apnea-hypopnea index as a novel predictive factor for difficult mask ventilation in the Chinese population under general anesthesia.

PURPOSE: Difficult mask ventilation (DMV) is a potentially life-threatening situation that can arise during anesthesia. However, most clinical predictors of DMV are based on European and US populations. On the other hand, most predictive models consist of multiple factors and complicated assessments. Since obstructive sleep apnea (OSA) is among the most important risk factors associated with DMV, the apnea-hypopnea index (AHI) may play an important role in determining patient risk.The purpose of this study was to investigate the relationship between DMV and AHI, and to determine preoperative risk factors for DMV in Chinese patients. METHODS: A prospective cohort trial enrolled patients scheduled for elective surgery. After obtaining informed consent, patient demographic information was collected, and patients were tested with pre-operative polysomnography. The anesthesiologist who managed the airway graded the mask ventilation. The difficult mask ventilation was defined as the mask ventilation provided by an unassisted anesthesiologist without oral airway or other adjuvant. A logistic regression model was used to analyze the association between AHI and DMV. RESULTS: A total of 159 patients were analyzed. For both primary and secondary outcomes, the unadjusted and adjusted odds ratio for DMV showed significant increases by 5 AHI units. AHI, age, and the Mallampati classification were found to be independent predictive factors for DMV. CONCLUSIONS: AHI is associated with DMV as a novel independent risk factor in Chinese patients. Along with age and Mallampati classification, AHI should be included in establishing a superior predictive strategy for DMV screening. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-DDD-17013076.

Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery.

OBJECTIVES: Kidney Disease: Improving Global Outcomes (KDIGO) guidelines include assessment of creatinine and urine output to identify acute kidney injury (AKI). Whether urine output is an accurate indicator of AKI after cardiac surgery, however, is unclear. The authors' goal was to examine whether cardiac surgery patients who fulfilled criteria for AKI by KDIGO urine output criteria also demonstrated kidney injury by elevated creatinine, other kidney biomarkers, or had worse clinical outcomes. DESIGN: Secondary analysis of prospectively collected data from a clinical trial, "6% Hydroxyethyl starch 130/0.4 in Cardiac Surgery (NCT02192502)." SETTING: Academic, quaternary care hospital. PARTICIPANTS: Patients undergoing elective aortic valve replacement INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: One hundred forty-one patients were classified into AKI stage by KDIGO urine output criteria within 24 hours after surgery. Kidney biomarkers (serum creatinine, urinary neutrophil gelatinase-associated lipocalin [NGAL], urinary interleukin-18 [IL-18]) and hospital and intensive care unit length of stay were analyzed across AKI stages. Urine output criteria classified four times as many patients with AKI than creatinine criteria (95 [67%] v 21 [15%]). Most patients meeting KDIGO urine output criteria for AKI postoperatively did not satisfy KDIGO creatinine criteria for AKI within one week (77 of 95 [81%]) or six-to-12 months (27 of 29 [93%]). Higher AKI stage assessed by urine output was not associated with higher NGAL, IL-18, or longer hospital or intensive care unit stays. CONCLUSIONS: Acute kidney injury classified by KDIGO urine output criteria was not associated with other biomarkers of kidney injury or worse patient outcomes. These data suggested that KDIGO urine output criteria after cardiac surgery may overclassify AKI stage; further research is needed.

Low-dose triptolide enhances antitumor effect of JQ1 on acute myeloid leukemia through inhibiting RNA polymerase II in vitro and in vivo.

The bromodomain and extra-terminal (BET) domain inhibitor JQ1 exerts potent anticancer activity in various cancer cells. However, the resistance to BET inhibitors in leukemia stem cells limits its implication in acute myeloid leukemia (AML). High concentration of triptolide (TPL) presents anticancer activities but with adverse effects. Here, we investigated whether the combination of low-dose TPL with JQ1 could help to circumvent the dilemma of drug resistance and side effect in treating AML. AML cell lines, primary cells from 10 AML patients with different status, as well as AML mice model were subjected to different treatments and apoptotic related protein expression were evaluated. Data showed that low-dose TPL combined with JQ1 effectively killed AML cell lines and primary cells from AML patients without exerting significantly greater lethal activity against normal cells. Mechanism study revealed that low-dose TPL combined with JQ1 triggered reactive oxygen species production and induced mitochondrial-mediated apoptosis in AML cells, in which the inhibition of RNA polymerase II to downregulate c-Myc was mainly responsible for the enhanced activity of TPL in combination with JQ1. In vivo study presented that cotreatment with low-dose TPL and JQ1 significantly reduced tumor burden of the NOD/SCID mice engrafted with MOLM-13 cells. In conclusion, low-dose TPL enhanced the antitumor effect of JQ1 on AML without increasing the side effects, supporting a potential option for AML treatment.

Dependence of intravoxel incoherent motion diffusion MR threshold b-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance.

BACKGROUND: Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value. PURPOSE: To explore how threshold b-value impacts PF ( f), Dslow ( D), and Dfast ( D*) values and their performance for liver fibrosis detection. MATERIAL AND METHODS: Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm2. Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm2 were compared. PF, Dslow, and Dfast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients. RESULTS: Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher Dslow and Dfast measurements. The dependence of PF, Dslow, and Dfast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), Dslow (Dslow < 1.239 × 10-3 mm2/s), and Dfast (Dfast < 20.85 × 10-3 mm2/s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1. CONCLUSION: For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm2 improves IVIM differentiation between healthy livers and fibrotic livers.

Correlation between 18F-FDG PET CT SUV and symptomatic or asymptomatic pulmonary tuberculosis.

OBJECTIVE: To explore the difference of 18F-FDG PET/CT images between the symptomatic and asymptomatic pulmonary tuberculosis, as well as the correlation between the standard uptake value (SUV) and the symptomatic/asymptomatic pulmonary tuberculosis. METHODS: A study dataset of 57 pulmonary tuberculosis cases was retrospectively assembled and analyzed. Among these cases, 30 were diagnosed having symptomatic pulmonary tuberculosis and 27 were asymptomatic pulmonary tuberculosis. PET/CT was performed in all 57 cases. The clinical data, CT images and PET/CT radioactive uptake data were analyzed using statistical data analysis software. RESULTS: All 57 cases showed radioactively high uptake, with the maximum standard uptake value (SUVmax) of the lesion ranging from 1.60 to 27.30 and a mean value of 6.63±4.82. The symptomatic cases had an SUVmax of 8.76±4.97 and the asymptomatic cases had an SUVmax of 4.27±3.39. The SUVmax as well as singular or multiple lesions showed statistical differences between symptomatic and asymptomatic cases. CONCLUSION: The symptomatic pulmonary tuberculosis cases show significantly higher SUVmax than the asymptomatic cases. Based on the criteria of SUVmax greater than 2.0 to define active lesions, 100% of symptomatic cases might have active lesions while 70.4% of asymptomatic cases might have active lesions. Therefore, focused attention should be clinically paid on the asymptomatic cases of pulmonary tuberculosis to avoid miss diagnosis and delayed treatment.

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival.

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086-1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan-Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts.