Optimal Positioning of Nasopharyngeal Temperature Probes in Infants and Children: A Prospective Cohort Study.

BACKGROUND: The nasopharynx is an easily accessible core-temperature monitoring site, but insufficient or excessive nasopharyngeal probe insertion can underestimate core temperature. Our goal was to estimate optimal nasopharyngeal probe insertion depth as a function of age. METHODS: We enrolled 157 pediatric patients who had noncardiac surgery with endotracheal intubation in 5 groups: (1) newborn to 6 months old, (2) infants 7 months to 1 year old, (3) children 13 to 23 months old, (4) children 2 to 5 years old, and (5) children 6 to 12 years old. A reference esophageal temperature probe was inserted at an appropriate depth based on each patient's height. A nasopharyngeal temperature probe was inserted from the naris at 10 cm in newborn and infants, 15 cm in children aged 1 to 5 years old, and 20 cm in children who were 6 years or older. The study nasopharyngeal probes were withdrawn 1, 2.5, or 2 cm (depending on age) 10 times at 5-minute intervals. Optimal probe insertion distances were defined by limits of agreement (LOAs) between nasopharyngeal and esophageal temperatures <0.5 °C. RESULTS: Optimal nasopharyngeal temperature probe position ranged from 6 to 10 cm in infants up to 6 months old, 7 to 8 cm in infants 7 to 12 months old, 7.5 to 12 cm in children 13 to 23 months old, and 10 to 12 cm in children aged 6 years and older. The 95% LOAs were <0.5 °C for all age categories except the 2- to 5-year-old group where the limits extended from -0.67 °C to 0.52 °C at 9 cm. At the optimal position within each age range, the bias (average nasopharyngeal-to-esophageal temperature difference) was ≤0.1 °C. CONCLUSIONS: Nasopharyngeal thermometers accurately measure core temperature, but only when probes are inserted a proper distance, which varies with age. As with much in pediatrics, nasopharyngeal thermometer insertion depths should be age appropriate.

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.

The effect of intraoperative positive end expiratory pressure and tidal volume on postoperative acute kidney injury after orthopedic surgery.

BACKGROUND: To test whether higher intraoperative PEEP levels and/or higher TV levels are associated with higher incidence of postoperative AKI within the first postoperative week, in adult patients having orthopedic surgeries under general anesthesia. METHODS: We conducted a sub analysis of a non-randomized alternating intervention cross over study performed in patients undergoing orthopedic surgery under general anesthesia at Cleveland Clinic, Cleveland, OH. We included four different combinations of PEEP (5 or 8 cm H2 O) and TV (6 or 10 mL/kg of PBW) that alternated each week in the six orthopedic operating rooms. Our primary outcome was postoperative AKI defined by the KDIGO criteria with baseline creatinine as the closest preoperative value to the time of surgery obtained within 30 days and postoperative value as the highest creatinine value within 7 days after surgery. Secondary outcome was the maximum postoperative in-hospital creatinine level within seven postoperative days. MAIN RESULTS: A total of 1933 patients were included in the analysis. The incidence of AKI was 6.8% in the study population and similar in high TV versus low TV group and high PEEP versus low PEEP group. Neither TV nor PEEP significantly impacted AKI incidence. The estimated odds ratio of AKI comparing TV = 6 mL/kg to TV = 10 mL/kg was 0.96 (97.5% CI: 0.63, 1.46; p = .811); while the estimated odds ratio of AKI comparing PEEP = 5cm H2 O to PEEP = 8cm H2 O was 0.92 (97.5% CI: 0.60, 1.39; p = .623). No interaction was found between TV and PEEP on AKI. Additionally, neither TV nor PEEP had a significant effect on the seven postoperative day creatinine levels. CONCLUSION: Higher levels of PEEP or TV during mechanical ventilation in adult patients undergoing orthopedic surgeries under general anesthesia do not increase the odds of developing postoperative AKI within the narrow limits studied.

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.

Tidal Volume and Positive End-expiratory Pressure and Postoperative Hypoxemia during General Anesthesia: A Single-center Multiple Crossover Factorial Cluster Trial.

BACKGROUND: Intraoperative mechanical ventilation is a major component of general anesthesia. The extent to which various intraoperative tidal volumes and positive end-expiratory pressures (PEEP) effect on postoperative hypoxia and lung injury remains unclear. We hypothesized that adults having orthopedic surgery, ventilation using different tidal volumes and PEEP levels affect the oxygenation within first hour in the postoperative care unit. METHODS: We conducted a two-by-two factorial crossover cluster trial at the Cleveland Clinic Main Campus. We enrolled patients having orthopedic surgery with general anesthesia who were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. The primary outcome was the effect of tidal volume or PEEP on time-weighted average peripheral oxygen saturation measured by pulse oximetry divided by the fraction of inspired oxygen (Spo2/Fio2 ratio) during the initial postoperative hour. RESULTS: We enrolled 2,860 patients who had general anesthesia for orthopedic surgery from September 2018 through October 2020. The interaction between tidal volume and PEEP was not significant (P = 0.565). The mean ± SD time-weighted average of Spo2/Fio2 ratio was 353 ± 47 and not different in patients assigned to high and low tidal volume (estimated effect, 3.5%; 97.5% CI, -0.4% to 7.3%; P = 0.042), for those assigned to high and low PEEP (estimated effect, -0.2%; 97.5% CI, -4.0% to 3.6%; P = 0.906). We did not find significant difference in ward Spo2/Fio2 ratio, pulmonary complications, and duration of hospitalization among patients assigned to various tidal volumes and PEEP levels. CONCLUSIONS: Among adults having major orthopedic surgery, postoperative oxygenation is similar, with tidal volumes between 6 and 10 ml/kg and PEEP between 5 and 8 cm H2O. Our results suggest that any combination of tidal volumes between 6 and 10 ml/kg and PEEP between 5 versus 8 ml cm H2O can be used safely for orthopedic surgery.

Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial.

BACKGROUND: Atrial fibrillation and delirium are common consequences of cardiac surgery. Dexmedetomidine has unique properties as sedative agent and might reduce the risk of each complication. This study coprimarily aimed to establish whether dexmedetomidine reduces the incidence of new-onset atrial fibrillation and the incidence of delirium. METHODS: A randomised, placebo-controlled trial was done at six academic hospitals in the USA. Patients who had had cardiac surgery with cardiopulmonary bypass were enrolled. Patients were randomly assigned 1:1, stratified by site, to dexmedetomidine or normal saline placebo. Randomisation was computer generated with random permuted block size 2 and 4, and allocation was concealed by a web-based system. Patients, caregivers, and evaluators were all masked to treatment. The study drug was prepared by the pharmacy or an otherwise uninvolved research associate so that investigators and clinicians were fully masked to allocation. Participants were given either dexmedetomidine infusion or saline placebo started before the surgical incision at a rate of 0·1 µg/kg per h then increased to 0·2 µg/kg per h at the end of bypass, and postoperatively increased to 0·4 µg/kg per h, which was maintained until 24 h. The coprimary outcomes were atrial fibrillation and delirium occurring between intensive care unit admission and the earlier of postoperative day 5 or hospital discharge. All analyses were intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT02004613 and is closed. FINDINGS: 798 patients of 3357 screened were enrolled from April 17, 2013, to Dec 6, 2018. The trial was stopped per protocol after the last designated interim analysis. Among 798 patients randomly assigned, 794 were analysed, with 400 assigned to dexmedetomidine and 398 assigned to placebo. The incidence of atrial fibrillation was 121 (30%) in 397 patients given dexmedetomidine and 134 (34%) in 395 patients given placebo, a difference that was not significant: relative risk 0·90 (97·8% CI 0·72, 1·15; p=0·34). The incidence of delirium was non-significantly increased from 12% in patients given placebo to 17% in those given dexmedetomidine: 1·48 (97·8% CI 0·99-2·23). Safety outcomes were clinically important bradycardia (requiring treatment) and hypotension, myocardial infarction, stroke, surgical site infection, pulmonary embolism, deep venous thrombosis, and death. 21 (5%) of 394 patients given dexmedetomidine and 8 (2%) of 396 patients given placebo, had a serious adverse event as determined by clinicians. 1 (<1%) of 391 patients given dexmedetomidine and 1 (<1%) of 387 patients given placebo died. INTERPRETATION: Dexmedetomidine infusion, initiated at anaesthetic induction and continued for 24 h, did not decrease postoperative atrial arrhythmias or delirium in patients recovering from cardiac surgery. Dexmedetomidine should not be infused to reduce atrial fibrillation or delirium in patients having cardiac surgery. FUNDING: Hospira Pharmaceuticals.

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.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

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.

Subcostal Anterior Quadratus Lumborum Block Versus Epidural Block for Analgesia in Open Nephrectomy: A Randomized Clinical Trial.

BACKGROUND: Epidural block are often used for analgesia after open nephrectomy surgery. Subcostal anterior quadratus lumborum block may be an alternative. We therefore tested the hypothesis that the continuous subcostal anterior quadratus lumborum block is noninferior to epidural block for analgesia in patients having open partial nephrectomies. METHODS: Adults having open partial nephrectomies were randomly allocated to epidural or unilateral subcostal anterior quadratus lumborum block. The joint primary outcomes were opioid consumption measured in morphine equivalents and pain measured on a numeric rating scale (0-10) from postanesthesia care unit (PACU) until 72 hours after surgery. The noninferiority deltas were 30% for opioid consumption and 1 point on a 0-10 scale for pain. Secondary outcomes included patient global assessment of pain management on the third postoperative day, the number of antiemetic medication doses through the third postoperative day, duration of PACU stay, and postoperative duration of hospitalization. RESULTS: Twenty-six patients were randomized to anterior quadratus lumborum block and 29 to epidural analgesia. Neither pain scores nor opioid consumption in the quadratus lumborum patients were noninferior to epidural analgesia. At 72 hours, mean ± standard deviation pain scores in subcoastal anterior quadratus lumborum block and epidural group were 4.7 ± 1.8 and 4.1 ± 1.7, with an estimated difference in pain scores of 0.62 (95% confidence interval [CI], 0.74-1.99; noninferiority P = .21). The median [Q1, Q3] opioid consumption was more than doubled in quadratus lumborum patients at 70 mg [43, 125] versus 30 mg [18, 75] in the epidural group with an estimated ratio of geometric means of 1.69 (95% CI, 0.66-4.33; noninferiority P = .80). Patient global assessment and duration of PACU and hospital stays did not differ significantly in the 2 groups. CONCLUSIONS: We were unable to show that subcostal anterior quadratus lumborum block are noninferior to epidural analgesia in terms of pain scores and opioid consumption for open partial nephrectomies. Effectiveness of novel blocks should be rigorously tested in specific surgical setting before widespread adoption.

Association of Pain With Atrial Fibrillation and Delirium After Cardiac Surgery: A DECADE Sub-Study.

OBJECTIVE: The authors aimed to evaluate the effects of postoperative pain on the incidence of atrial fibrillation and delirium in patients having surgery with cardiopulmonary bypass (CPB). DESIGN: Post hoc analysis of the (An investigator-initiated, multicentre, double-blind trial (ClinicalTrials NCT02004613) (DECADE)), a randomized, placebo-controlled trial. SETTING: Tertiary, academic hospital. PARTICIPANTS: Six hundred five adults from the DECADE enrolled at Cleveland Clinic Main Campus, who had had surgery with CPB. INTERVENTIONS: Dexmedetomidine versus placebo started before surgical incision and postoperatively was maintained until 24 hours. MEASUREMENTS: Primary outcomes were atrial fibrillation, diagnosed by clinicians in the intensive care unit (ICU), presence of delirium assessed with the Confusion Assessment Method for the ICU, data on pain scores, and opioid consumption, occurring between ICU admission and the earlier of postoperative day five or hospital discharge. RESULTS: Postoperative pain levels were similar among patients with or without atrial fibrillation. Two hundred six (34%) patients had atrial fibrillation and ninety-two (15%) had delirium before hospital discharge within the first five postoperative days. The risk of atrial fibrillation was not significantly different between groups (hazard ratio: 1.09; 97.5% confidence interval [CI]: 0.99, 1.20, p = 0.039); there were no associations between postoperative pain and the risk of postoperative delirium (hazard ratio: 0.96; 97.5% CI: 0.84-1.11; p = 0.57). Postoperative opioid consumption was neither significantly associated with postoperative atrial fibrillation nor delirium. CONCLUSIONS: Atrial fibrillation and delirium was not associated with pain after cardiac surgery. Opioid use was not associated with atrial fibrillation and delirium. Because both atrial fibrillation and delirium have a multifactorial nature, further studies should be focused on other plausible mechanisms.

Association of Intraoperative Tidal Volumes and Acute Kidney Injury After Noncardiac Surgery.

BACKGROUND: Patients with acute lung injury who received lower tidal volume (VT) ventilation had significantly fewer days with acute kidney injury (AKI) when compared to those receiving higher VTs. There is a paucity of studies on the relationship between intraoperative VTs and postoperative AKI in patients undergoing noncardiac surgery. We therefore sought to assess the association of mean delivered intraoperative VT per kilogram based on predicted body weight (PBW) and postoperative AKI. METHODS: This retrospective cohort study was conducted in a large tertiary multispecialty academic medical center. Adult patients who underwent noncardiac surgery between January 2005 and July 2016 under general anesthesia with endotracheal intubation and mechanical ventilation were included. A total of 41,224 patients were included in the study.The relationship between mean intraoperative VT per PBW and AKI was assessed using logistic regression, adjusting for prespecified potential confounding variables. The secondary outcomes were postoperative major pulmonary complications, myocardial injury after noncardiac surgery (MINS), and in-hospital mortality. RESULTS: The incidence of AKI was 10.9% in the study population. Postoperative renal replacement therapy was required in 0.1% of patients. Higher delivered mean intraoperative VT per PBW was significantly associated with increased odds of AKI. The estimated odds ratio for each 1 mL increase in VT per kilogram of PBW (1 unit) was 1.05 (95% confidence interval [CI], 1.02-1.08; P = .001), after adjusting for potential confounding variables. A higher delivered mean intraoperative VT per PBW was significantly associated with increased odds of postoperative myocardial injury and was not significantly associated with major postoperative pulmonary complications or in-hospital mortality after noncardiac surgery. CONCLUSIONS: In adult patients undergoing noncardiac surgery, higher delivered mean intraoperative VTs per PBW are associated with an increased odds of developing AKI.

Association of Testosterone Replacement Therapy and the Incidence of a Composite of Postoperative In-Hospital Mortality and Cardiovascular Events in Men Undergoing Cardiac Surgery.

BACKGROUND: Data on testosterone replacement therapy and cardiovascular outcomes are conflicting, with the Food and Drug Administration requiring prescription testosterone preparations to indicate a possible increased cardiovascular risk. Whether patients on testosterone replacement therapy undergoing cardiac surgery have an increased risk of postoperative in-hospital mortality and cardiovascular events remains unknown. We therefore sought to identify the impact of testosterone replacement on the incidence of a composite of postoperative in-hospital mortality and cardiovascular events in men undergoing cardiac surgery. METHODS: After institutional review board approval, data from male American Society of Anesthesiologists III/IV patients ≥40 years of age who underwent cardiac surgery between May 2005 and March 2017 at the Cleveland Clinic (Cleveland, OH) main campus were included. The primary exposure was preoperative testosterone use. The primary outcome was a collapsed composite of postoperative in-hospital mortality and cardiovascular events, including myocardial infarction, stroke, and pulmonary embolism. The secondary outcome was a collapsed composite of minor cardiovascular events, including postoperative rhythm disturbance requiring permanent device, atrial fibrillation, and deep venous thrombosis. We compared patients who received testosterone and those who did not, using propensity score matching within surgical procedure matches. Moreover, as a sensitivity analysis, we used a multivariable logistic regression model to assess the association between testosterone replacement therapy and major or minor cardiovascular events adjusted for potential baseline and intraoperative confounders by including all eligible patients. RESULTS: Among 20,604 patients who met inclusion and exclusion criteria, 301 patients who used testosterone routinely within 1 month before the surgery were matched to 1505 of 20,303 patients who did not use testosterone. Among the matched cohort, 8 (2.7%) patients in the testosterone group and 45 (3.0%) in the nontestosterone group had ≥1 major cardiovascular adverse event after surgery. The adjusted odds ratio was 0.89 (95% CI, 0.41-1.90; P = .756), comparing testosterone to nontestosterone patients. As for the secondary outcomes, 89 (30%) patients in the testosterone group and 525 (35%) patients in the nontestosterone group had ≥1 minor cardiovascular event. The odds of minor events were not significantly different, with an odds ratio of 0.78 (95% CI, 0.60-1.02; P = .074) comparing testosterone to nontestosterone patients. CONCLUSIONS: Preoperative testosterone is not associated with a statistically significant increased incidence of a composite of postoperative in-hospital mortality and cardiovascular events after cardiac surgery.

Association Between Perioperative Hypotension and Delirium in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis.

BACKGROUND: Postoperative delirium is common in critically ill patients, with a reported incidence of 11%-43%, and is associated with significant morbidity and cost. Perioperative hypotension and consequent brain hypoperfusion may contribute. We, therefore, tested the hypotheses that intraoperative and postoperative hypotension are associated with critical care delirium. METHODS: We included 1083 postoperative patients who were admitted directly from an operating room to the surgical intensive care unit. Delirium was assessed with the Confusion Assessment Method for Intensive Care Unit patients at 12-hour intervals. We used a confounder-adjusted Cox proportional hazard survival model to assess the association between the amount of intraoperative hypotension, which was measured as the time-weighted average of mean arterial pressure <65 mm Hg, and delirium while in critical care. Thereafter, we used a Cox model with the lowest mean arterial pressure on each intensive care day as a time-varying covariate to assess the relationship between critical care hypotension and delirium, adjusted for confounders and amount of intraoperative hypotension. RESULTS: Three hundred seventy-seven (35%) patients had delirium within the first 5 postoperative days in the surgical intensive care unit. Intraoperative hypotension was moderately associated with higher odds of postoperative delirium. The adjusted hazard ratio associated with 1 mm Hg increase in time-weighted average of mean arterial pressure <65 mm Hg was 1.11 (95% confidence interval [CI], 1.03-1.20; P = .008). Postoperatively, a 10 mm Hg reduction in the lowest mean pressure on each day in the critical care unit was significantly associated with a higher hazard of delirium, with an adjusted hazard ratio 1.12 (95% CI, 1.04-1.20; P = .003). CONCLUSIONS: Both intraoperative and postoperative hypotension are associated with delirium in postoperative critical care patients. The extent to which these relationships are causal remains unknown, but to the extent that they are, hypotension prevention may help reduce delirium and should be studied in prospective clinical trials.

Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Uncontrolled pain after noncardiac surgery activates the sympathetic nervous system, which causes tachycardia, hypertension, and increased cardiac contractility-all of which may increase myocardial oxygen demand. We therefore determined whether time-weighted average pain scores over the initial 72 postoperative hours are associated with myocardial injury after noncardiac surgery (MINS). METHODS: We conducted a retrospective cohort analysis of adults with routine postoperative troponin monitoring after noncardiac surgery under general, regional, or combined anesthesia at tertiary level centers in Cleveland from January 2012 to December 2015. Time-weighted average pain scores were calculated from all the available pain scores, typically at 4-hour intervals, until a troponin elevation was detected. MINS was defined as peak troponin T concentrations exceeding 0.03 ng/mL within 72 hours after surgery. We used a generalized linear mixed model to assess the association between pain and MINS with 3 hospitals as clusters, adjusting for potential confounders. RESULTS: Among 2892 eligible patients, 4.5% had myocardial injury within 72 hours after surgery. Higher time-weighted average pain scores were associated with increased hazard of myocardial injury. The estimated hazard ratio for a 1-unit increase in pain score was 1.12 (95% confidence interval [CI], 1.02-1.22; P = .013), adjusting for confounding variables. CONCLUSIONS: Among patients undergoing noncardiac surgery, time-weighted average pain scores within 72 hours after surgery were significantly associated with myocardial injury.

Association Between Mean Arterial Pressure and Acute Kidney Injury and a Composite of Myocardial Injury and Mortality in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis.

OBJECTIVES: Hypotension thresholds that provoke renal injury, myocardial injury, and mortality in critical care patients remain unknown. We primarily sought to determine the relationship between hypotension and a composite of myocardial injury (troponin T ≥ 0.03 ng/mL without nonischemic cause) and death up to 7 postoperative days. Secondarily, we considered acute kidney injury (creatinine concentration ≥ 0.3 mg/dL or 1.5 times baseline). DESIGN: Retrospective cohort. SETTING: Surgical ICU at an academic medical center. PATIENTS: Two-thousand eight-hundred thirty-three postoperative patients admitted to the surgical ICU. INTERVENTIONS: A Cox proportional hazard survival model was used to assess the association between lowest mean arterial pressure on each intensive care day, considered as a time-varying covariate, and outcomes. In sensitivity analyses hypotension defined as pressures less than 80 mm Hg and 70 mm Hg were also considered. MEASUREMENTS AND MAIN RESULTS: There was a strong nonlinear (quadratic) association between the lowest mean arterial pressure and the primary outcome of myocardial injury after noncardiac surgery or mortality, with estimated risk increasing at lower pressures. The risk of myocardial injury after noncardiac surgery or mortality was an estimated 23% higher at the 25th percentile (78 mm Hg) of lowest mean arterial pressure compared with at the median of 87 mm Hg, with adjusted hazard ratio (95% CI) of 1.23 (1.12-1.355; p < 0.001). Overall results were generally similar in sensitivity analyses based on every hour of mean arterial pressure less than 80 mm Hg and any mean arterial pressure less than 70 mm Hg. Post hoc analyses showed that the relationship between ICU hypotension and outcomes depended on the amount of intraoperative hypotension. The risk of acute kidney injury increased over a range of minimum daily pressures from 110 mm Hg to 50 mm Hg, with an adjusted hazard ratio of 1.27 (95% CI, 1.18-1.37; p < 0.001). CONCLUSIONS: Increasing amounts of hypotension (defined by lowest mean arterial pressures per day) were strongly associated with myocardial injury, mortality, and renal injury in postoperative critical care patients.

Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1/Th17 and Th2 in Multiple Sclerosis Patients.

Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4-6 and 18-26 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry. The absolute numbers of CD4 and CD8 T cells were significantly decreased and the CD4/CD8 ratio was increased with DMF treatment. The proportions of both effector memory T cells and central memory T cells were reduced, whereas naive T cells increased in treated patients. T cell activation was reduced with DMF treatment, especially among effector memory T cells and effector memory RA T cells. Th subsets Th1 (CXCR3+), Th17 (CCR6+), and particularly those expressing both CXCR3 and CD161 were reduced most significantly, whereas the anti-inflammatory Th2 subset (CCR3+) was increased after DMF treatment. A corresponding increase in IL-4 and decrease in IFN-γ and IL-17-expressing CD4+ T cells were observed in DMF-treated patients. DMF in vitro treatment also led to increased T cell apoptosis and decreased activation, proliferation, reactive oxygen species, and CCR7 expression. Our results suggest that DMF acts on specific memory and effector T cell subsets by limiting their survival, proliferation, activation, and cytokine production. Monitoring these subsets could help to evaluate the efficacy and safety of DMF treatment.

Association of Neuraxial Anesthesia With Postoperative Venous Thromboembolism After Noncardiac Surgery: A Propensity-Matched Analysis of ACS-NSQIP Database.

BACKGROUND: Neuraxial anesthesia improves components of the Virchow's triad (hypercoagulability, venous stasis, and endothelial injury) which are key pathogenic contributors to venous thrombosis in surgical patients. However, whether neuraxial anesthesia reduces the incidence of venous thromboembolism (VTE) remain unclear. We therefore tested the primary hypothesis that neuraxial anesthesia reduces the incidence of 30-day VTE in adults recovering from orthopedic surgery. Secondarily, we tested the hypotheses that neuraxial anesthesia reduces 30-day readmission, 30-day mortality, and the duration of postoperative hospitalization. METHODS: Inpatient orthopedic surgeries from American College of Surgeons National Surgical Quality Improvement Program database (2011-2015) in adults lasting more than 1 hour with either neuraxial or general anesthesia were included. Groups were matched 1:1 by propensity score matching for appropriate confounders. Logistic regression model was used to assess the effect of neuraxial anesthesia on 30-day VTE, 30-day mortality, and readmission, while Cox proportional hazard regression model was used to assess its effect on length of stay. RESULTS: Neuraxial anesthesia decreased odds of 30-day VTE (odds ratio 0.85, 95% confidence interval, 0.78-0.95; P = .002) corresponding to number-needed-to-treat of 500. Although there was no difference in 30-day mortality, neuraxial anesthesia reduced 30-day readmission (odds ratio 0.90, 98.3% confidence interval, 0.85-0.95; P < .001) corresponding to number-needed-to-treat of 250 and had a shortened hospitalization (2.87 vs 3.11; P < .001). CONCLUSIONS: Neuraxial anesthesia appears to provide only weak VTE prophylaxis, but can be offered as an adjuvant to current thromboprophylaxis in high-risk patients.

Intraoperative Hyperoxia Does Not Reduce Postoperative Pain: Subanalysis of an Alternating Cohort Trial.

BACKGROUND: Postoperative pain is common and promotes opioid use. Surgical wounds are hypoxic because normal perfusion is impaired. Local wound ischemia and acidosis promote incisional pain. Some evidence suggests that improving oxygen supply to surgical wounds might reduce pain. We therefore tested the hypothesis that supplemental (80% inspired) intraoperative oxygen reduces postoperative pain and opioid consumption. METHODS: We conducted a post hoc analysis of a large, single-center alternating cohort trial allocating surgical patients having general anesthesia for colorectal surgery to either 30% or 80% intraoperative oxygen concentration in 2-week blocks for a total of 39 months. Irrespective of allocation, patients were given sufficient oxygen to maintain saturation ≥95%. Patients who had regional anesthesia or nerve blocks were excluded. The primary outcome was pain and opioid consumption during the initial 2 postoperative hours, analyzed jointly. The secondary outcome was pain and opioid consumption over the subsequent 24 postoperative hours. Subgroup analyses of the primary outcome were conducted for open versus laparoscopic procedures and for patients with versus without chronic pain. RESULTS: A total of 4702 cases were eligible for analysis: 2415 were assigned to 80% oxygen and 2287 to 30% oxygen. The groups were well balanced on potential confounding factors. Average pain scores and opioid consumption were similar between the groups (mean difference in pain scores, -0.01 [97.5% CI, -0.16 to 0.14; P = .45], median difference in opioid consumption, 0.0 [97.5% CI, 0 to 0] mg morphine equivalents; P = .82). There were also no significant differences in the secondary outcome or subgroup analyses. CONCLUSIONS: Supplemental intraoperative oxygen does not reduce acute postoperative pain or reduce opioid consumption.

Intra-operative high inspired oxygen fraction does not increase the risk of postoperative respiratory complications: Alternating intervention clinical trial.

BACKGROUND: The WHO recommends routine intra-operative and early postoperative use of high inspired oxygen concentrations (hyperoxia). However, a high intra-operative inspired oxygen fraction (FiO2) might result in an increased risk of postoperative respiratory complications. AIM: To test the hypothesis that intra-operative FiO2 of 80% compared with 30% inspired oxygen decreases the postoperative ratio of arterial saturation to fraction of inspired oxygen (SpO2/FiO2). Secondarily, to evaluate whether an intra-operative inspired FiO2 of 80% increases the incidence of pulmonary complications. DESIGN: Posthoc subanalysis of a large alternating cohort trial. SETTING: Cleveland Clinic, Cleveland, United States, from 2013 to 2016. PATIENTS: Adults having colorectal surgery. Cases lasting less than 2 h, re-operations on the same hospitalisation, and cases with missing intra-operative or postoperative data were excluded. INTERVENTION: Maintaining intra-operative FiO2 at 30 or 80% and alternating this management every 2 weeks for a study period of 39 months. MAIN OUTCOME: Minimal SpO2/FiO2 ratio value in the postanaesthesia care unit. Secondary outcome was a composite of postoperative pulmonary complications throughout hospitalisation. RESULTS: A total of 5056 patients were included. Groups were well balanced on all demographic, baseline and procedural variables. Median time-weighted averages of intra-operative FiO2 in the 30 and 80% groups were 43% (IQR 38 to 54%, N=2486) and 81% (IQR 78 to 82%, N=2570), respectively. No difference was found in the lowest SpO2/FiO2 ratio (estimated median difference 0 [95% confidence interval: 0, 0], P = 0.91). The incidence of postoperative pulmonary complications was 16.3 and 17.6% in the 30 and 80% FiO2 groups, respectively (relative risk 1.07 [95% confidence interval: 0.95, 1.21], P = 0.25). CONCLUSION: Intra-operative hyperoxia did not change the postoperative SpO2/FiO2 ratio or the risk for pulmonary complications. Clinicians should not refrain from using hyperoxia for fear of provoking respiratory complications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01777568.