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1.
Anesth Analg ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31166234

RESUMO

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.

2.
Anesth Analg ; 128(6): 1160-1166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31094783

RESUMO

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.

3.
Crit Care Med ; 47(7): 910-917, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30985388

RESUMO

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.

4.
Eur J Anaesthesiol ; 36(5): 320-326, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30865003

RESUMO

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.

5.
Anesth Analg ; 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30896595

RESUMO

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.

6.
PLoS One ; 14(2): e0212704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30811470

RESUMO

BACKGROUND: High-quality chest compressions are imperative for Cardio-Pulmonary-Resuscitation (CPR). International CPR guidelines advocate, that chest compressions should not be interrupted for ventilation once a patient's trachea is intubated or a supraglottic-airway-device positioned. Supraglottic-airway-devices offer limited protection against pulmonary aspiration. Simultaneous chest compressions and positive pressure ventilation both increase intrathoracic pressure and potentially enhances the risk of pulmonary aspiration. The hypothesis was, that regurgitation and pulmonary aspiration is more common during continuous versus interrupted chest compressions in human cadavers ventilated with a laryngeal tube airway. METHODS: Twenty suitable cadavers were included, and were positioned supine, the stomach was emptied, 500 ml of methylene-blue-solution instilled and laryngeal tube inserted. Cadavers were randomly assigned to: 1) continuous chest compressions; or, 2) interrupted chest compressions for ventilation breaths. After 14 minutes of the initial designated CPR strategy, pulmonary aspiration was assessed with a flexible bronchoscope. The methylene-blue-solution was replaced by 500 ml barium-sulfate radiopaque suspension. 14 minutes of CPR with the second designated ventilation strategy was performed. Pulmonary aspiration was then assessed with a conventional chest X-ray. RESULTS: Two cadavers were excluded for technical reasons, leaving 18 cadavers for statistical analysis. Pulmonary aspiration was observed in 9 (50%) cadavers with continuous chest compressions, and 7 (39%) with interrupted chest compressions (P = 0.75). CONCLUSION: Our pilot study indicate, that incidence of pulmonary aspiration is generally high in patients undergoing CPR when a laryngeal tube is used for ventilation. Our study was not powered to identify potentially important differences in regurgitation or aspiration between ongoing vs. interrupted chest compression. Our results nonetheless suggest that interrupted chest compressions might better protect against pulmonary aspiration when a laryngeal tube is used for ventilation.

7.
Eur J Anaesthesiol ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30507620

RESUMO

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a major contributor to peri-operative morbidity and mortality with a reported incidence of about 8%. Tachycardia increases myocardial oxygen demand, and decreases oxygen supply, and is therefore a potential cause of MINS. OBJECTIVE: We tested the hypothesis that there is an association between intra-operative area above a heart rate (HR) of 90 bpm and a composite of MINS and in-hospital all-cause mortality. DESIGN: Retrospective analyses. SETTING: Major tertiary care hospital, Cleveland, USA. PATIENTS: Adults having elective or nonelective noncardiac surgery and scheduled troponin monitoring during the first 3 postoperative days between 2010 and 2015. MAIN OUTCOME MEASURES: All-or-none composite of myocardial injury (MINS), defined by a peak postoperative generation 4 troponin T concentration at least 0.03 ng ml, and in-hospital all-cause mortality. RESULTS: Among 2652 eligible patients, 123 (4.6%) experienced MINS within 7 days after surgery and 6 (0.2%) died before discharge. Intra-operative area above HR more than 90 bpm was not associated with the all-or-none composite of MINS and in-hospital mortality, with an estimated odds ratio (95% confidence interval) of 0.99 (0.97 to 1.01) per 1 h bpm increase in area above HR more than 90 bpm. Secondary outcomes were also unrelated to the composite, with estimated odds ratios (98.3% confidence interval) of 0.99 (0.98 to 1.00) for area above HR more than 80, 0.98 (0.92 to 1.04) for area above HR more than 100 bpm, and 0.96 (0.88 to 1.05) for maximum HR. CONCLUSION: There was no apparent association between various measures of tachycardia and a composite of MINS and death, a result that contradicts previously reported associations between other measures of intra-operative tachycardia and MINS/mortality.

8.
Anesth Analg ; 127(6): 1335-1341, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30300173

RESUMO

BACKGROUND: We tested the primary hypothesis that final intraoperative esophageal temperature is associated with increased odds of a composite of in-hospital all-cause mortality and myocardial injury within 7 days after noncardiac surgery. Secondary exposures were time-weighted average intraoperative temperature and area <37°C threshold. METHODS: Myocardial injury was defined by postoperative fourth-generation troponin T ≥0.03 ng/mL apparently due to cardiac ischemia. Data were extracted for inpatients who had noncardiac surgery with general anesthesia at the Cleveland Clinic between 2012 and 2015. All had esophageal temperature monitoring and routine postoperative troponin monitoring. We estimated the confounder-adjusted association between final intraoperative esophageal temperature and the collapsed composite with multivariable logistic regression. We similarly estimated associations with time-weighted average intraoperative temperature and area <37°C. RESULTS: Two thousand two hundred ten patients were included. Nearly all final esophageal temperatures were 36°C-37°C. Ninety-seven patients (4.4%) had myocardial injury, and 7 (0.3%) died before discharge. Final intraoperative core temperature was not associated with the collapsed composite: odds ratio, 0.91 (95% confidence interval, 0.68-1.24) per 1°C decrease. Similarly, neither of the secondary exposures was associated with the composite outcome. CONCLUSIONS: We did not observe an association between mild perioperative hypothermia and mortality or myocardial injury in adults having noncardiac surgery. However, the range of final intraoperative temperatures was small and largely restricted to the normothermic range (36°C-37°C). Trials are needed to further assess the effect of temperature on myocardial injury.

9.
Reg Anesth Pain Med ; 43(7): 768-775, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30192304

RESUMO

BACKGROUND AND OBJECTIVES: Despite the observation that select nicotine receptor agonists have analgesic effects, smokers report higher pain scores and more functional impairments than lifelong nonsmokers, attributable to exaggerated stress responses, receptor desensitization, and altered pharmacokinetics compounded by accelerated structural damage resulting from impaired bone healing, osteoporosis, and advancement of disk disease. We hypothesized that smoking diminishes the analgesic response to spinal cord stimulation (SCS) in patients with chronic spine-related pain conditions. METHODS: A retrospective cohort study was performed at Cleveland Clinic by collecting and assessing data of 213 patients who had been implanted with SCS for spine-pain indications. History of tobacco smoking was subcategorized into 3 categories: past (former smoker), present (current smoker), or those who had never previously smoked (lifelong nonsmokers), and a multivariable linear regression was run to measure the correlation, if any, between smoking status and numerical rating scale pain score. In addition, opioid consumption at baseline and 12-month follow-up, expressed in milligram oral morphine equivalents, was collected and compared. RESULTS: Adjusted for differences, at 1-year follow-up, current smokers (n = 62) reported numerical rating scale pain score of 7.0, which is 1.93 (P < 0.001) and 1.32 (P = 0.001) points higher than those of lifelong nonsmokers (n = 77) and former smokers (n = 74), respectively. Opioid intake was 2.4 times higher (P = 0.004) in smokers than in lifelong nonsmokers. CONCLUSIONS: Among our SCS-implanted sample, a positive correlation was observed between tobacco use and degree of pain reduction as early as 12 months postimplant; this was evident by the reported higher pain scores and opioid use in current smokers in comparison with former smokers and lifelong nonsmokers.

10.
Anesth Analg ; 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29697506

RESUMO

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.

11.
J Am Heart Assoc ; 7(3)2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382665

RESUMO

BACKGROUND: As a monoamine neurotransmitter, 5-hydroxytryptamine (5-HT) or serotonin modulates mood, appetite, and sleep. Besides, 5-HT also has important peripheral functions. 5-HT receptor 2B (5-HT2BR) plays a key role in cardiovascular diseases, such as pulmonary arterial hypertension and cardiac valve disease. Percutaneous intervention has been used to restore blood flow in occlusive vascular disease. However, restenosis remains a significant problem. Herein, we investigated the role of 5-HT2BR in neointimal hyperplasia, a key pathological process in restenosis. METHODS AND RESULTS: The expression of 5-HT2BR was upregulated in wire-injured mouse femoral arteries. In addition, BW723C86, a selective 5-HT2BR agonist, promoted the injury response during restenosis. 5-HT and BW723C86 stimulated migration and proliferation of rat aortic smooth muscle cells. Conversely, LY272015, a selective antagonist, attenuated the 5-HT-induced smooth muscle cell migration and proliferation. In vitro study showed that the promigratory effects of 5-HT2BR were mediated through the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling in a ß-arrestin2-dependent manner. Inhibition of mammalian target of rapamycin or p70S6K mitigated 5-HT2BR-mediated smooth muscle cell migration. Mice with deficiency of 5-HT2BR showed significantly reduced neointimal formation in wire-injured arteries. CONCLUSIONS: These results demonstrated that activation of 5-HT2BR and ß-arrestin2-biased downstream signaling are key pathological processes in neointimal formation, and 5-HT2BR may be a potential target for the therapeutic intervention of vascular restenosis.

12.
Anesth Analg ; 126(3): 833-838, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29293176

RESUMO

BACKGROUND: Core temperature can be accurately measured from the esophagus or nasopharynx during general anesthesia, but neither site is suitable for neuraxial anesthesia. We therefore determined the precision and accuracy of a novel wireless axillary thermometer, the iThermonitor, to determine its suitability for use during neuraxial anesthesia and in other patients who are not intubated. METHODS: We enrolled 80 adults having upper abdominal surgery with endotracheal intubation. Intraoperative core temperature was measured in distal esophagus and was estimated at the axilla with a wireless iThermonitor WT701 (Raiing Medical, Boston MA) at 5-minute intervals. Pairs of axillary and reference distal esophageal temperatures were compared and summarized using linear regression and repeated-measured Bland-Altman methods. We a priori determined that the iThermonitor would have clinically acceptable accuracy if most estimates were within ±0.5°C of the esophageal reference, and suitable precision if the limits of agreement were within ±0.5°C. RESULTS: There were 3339 sets of paired temperatures. Axillary and esophageal temperatures were similar, with a mean difference (esophageal minus axillary) of only 0.14°C ± 0.26°C (standard deviation). The Bland-Altman 95% limits of agreement were reasonably narrow, with the estimated upper limit at 0.66°C and the lower limit at -0.38°C, thus ±0.52°C, indicating good agreement across the range of mean temperatures from 34.9°C to 38.1°C. The absolute difference was within 0.5°C in 91% of the measurements (95% confidence interval, 88%-93%). CONCLUSIONS: Axillary temperature, as recorded by the iThermonitor WT701, well represents core temperature in adults having noncardiac surgery and thus appears suitable for clinical use.

13.
Anesthesiology ; 128(5): 903-911, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29369893

RESUMO

BACKGROUND: The effect of ambient temperature, with and without active warming, on intraoperative core temperature remains poorly characterized. The authors determined the effect of ambient temperature on core temperature changes with and without forced-air warming. METHODS: In this unblinded three-by-two factorial trial, 292 adults were randomized to ambient temperatures 19°, 21°, or 23°C, and to passive insulation or forced-air warming. The primary outcome was core temperature change between 1 and 3 h after induction. Linear mixed-effects models assessed the effects of ambient temperature, warming method, and their interaction. RESULTS: A 1°C increase in ambient temperature attenuated the negative slope of core temperature change 1 to 3 h after anesthesia induction by 0.03 (98.3% CI, 0.01 to 0.06) °Ccore/(h°Cambient) (P < 0.001), for patients who received passive insulation, but not for those warmed with forced-air (-0.01 [98.3% CI, -0.03 to 0.01] °Ccore/[h°Cambient]; P = 0.40). Final core temperature at the end of surgery increased 0.13°C (98.3% CI, 0.07 to 0.20; P < 0.01) per degree increase in ambient temperature with passive insulation, but was unaffected by ambient temperature during forced-air warming (0.02 [98.3% CI, -0.04 to 0.09] °Ccore/°Cambient; P = 0.40). After an average of 3.4 h of surgery, core temperature was 36.3° ± 0.5°C in each of the forced-air groups, and ranged from 35.6° to 36.1°C in passively insulated patients. CONCLUSIONS: Ambient intraoperative temperature has a negligible effect on core temperature when patients are warmed with forced air. The effect is larger when patients are passively insulated, but the magnitude remains small. Ambient temperature can thus be set to comfortable levels for staff in patients who are actively warmed.

14.
Anesthesiology ; 128(2): 317-327, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29189290

RESUMO

BACKGROUND: The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days. METHODS: This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction. Clinically important hypotension was defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes of hypotension was the exposure variable intraoperatively and for the remaining day of surgery, whereas hypotension status was treated as binary variable for postoperative days 1 to 4. We estimated the average relative effect of hypotension across components of the composite using a distinct effect generalized estimating model, adjusting for hypotension during earlier periods. RESULTS: Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the estimated average relative effect across myocardial infarction and mortality was 1.08 (98.3% CI, 1.03, 1.12; P < 0.001) per 10-min increase in hypotension duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI, 1.01, 1.05; P < 0.001) per 10-min increase in hypotension duration. The average relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients with hypotension during the subsequent four days of hospitalization. CONCLUSIONS: Clinically important hypotension-a potentially modifiable exposure-was significantly associated with a composite of myocardial infarction and death during each of three perioperative periods, even after adjustment for previous hypotension.


Assuntos
Hipotensão/epidemiologia , Complicações Intraoperatórias/mortalidade , Infarto do Miocárdio/epidemiologia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Idoso , Comorbidade , Feminino , Humanos , Masculino
15.
Anesthesiology ; 127(3): 457-465, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28816783

RESUMO

BACKGROUND: Whether patients on testosterone replacement therapy undergoing noncardiac 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 noncardiac surgery. METHODS: Data from male American Society of Anesthesiologists I through IV patients 40 yr or older who underwent noncardiac surgery between May 2005 and December 2015 at the Cleveland Clinic (Cleveland, Ohio) main campus were included. The primary exposure was preoperative testosterone use. The primary outcome was a composite of postoperative in-hospital mortality and cardiovascular events. We compared patients who received testosterone and those who did not using propensity score matching within surgical procedure matches. RESULTS: Among 49,273 patients who met inclusion and exclusion criteria, 947 patients on testosterone were matched to 4,598 nontestosterone patients. The incidence of in-hospital mortality was 1.3% in the testosterone group and 1.1% in the nontestosterone group, giving an odds ratio of 1.17 (99% CI, 0.51 to 2.68; P = 0.63). The incidence of myocardial infarction was 0.2% in the testosterone group and 0.6% in the nontestosterone group (odds ratio = 0.34; 99% CI, 0.05 to 2.28; P = 0.15). Similarly, no significant difference was found in stroke (testosterone vs. nontestosterone: 2.0% vs. 2.1%), pulmonary embolism (0.5% vs. 0.7%), or deep venous thrombosis (2.0% vs. 1.7%). CONCLUSIONS: Preoperative testosterone is not associated with an increased incidence of a composite of postoperative in-hospital mortality and cardiovascular events.


Assuntos
Doenças Cardiovasculares/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Mortalidade Hospitalar , Procedimentos Cirúrgicos Operatórios , Testosterona/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Pontuação de Propensão
16.
Mol Pharmacol ; 92(3): 256-264, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28546421

RESUMO

Excessive activation of the NLRP3 inflammasome is implicated in cardiovascular diseases. Statins exert an anti-inflammatory effect independent of their cholesterol-lowering effect. This study investigated the potential role of statins in the activation of the NLRP3 inflammasome in endothelial cells (ECs). Western blotting and quantitative reverse-transcription polymerase chain reaction showed that oxidized low-density lipoprotein (ox-LDL) or tumor necrosis factor α (TNFα) activated the NLRP3 inflammasome in ECs. Simvastatin or mevastatin significantly suppressed the effects of ox-LDL or TNFα Promoter reporter assays and small interfering RNA knockdown revealed that statins inhibit ox-LDL-mediated NLRP3 inflammasome activation via the pregnane X receptor (PXR). In addition, PXR agonists (rifampicin and SR12813) or overexpression of a constitutively active PXR markedly suppressed the NLRP3 inflammasome activation. Conversely, PXR knockdown abrogated the suppressive effect of rifampicin on NLRP3 inflammasome activation. Knockdown of lectin-like ox-LDL receptor or overexpression of IκBα-attenuated ox-LDL- or TNFα-triggered activation of the NLRP3 inflammasome. Chromatin immunoprecipitation assays indicated that mevastatin inhibited nuclear factor-κB binding to the promoter regions of the human NLRP3 gene. Collectively, these results demonstrate that the statin activation of PXR inhibits the activation of NLRP3 inflammasome in response to atherogenic stimuli such as ox-LDL and TNFα in ECs, providing a new mechanism for the cardiovascular benefit of statins.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipoproteínas LDL/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Receptores de Esteroides/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Células Cultivadas , Células Endoteliais/metabolismo , Humanos , Lipoproteínas LDL/farmacologia , NF-kappa B/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Receptor de Pregnano X , Regiões Promotoras Genéticas , Receptores de Esteroides/agonistas , Receptores Depuradores Classe E/fisiologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
17.
J Immunol ; 198(8): 3069-3080, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28258191

RESUMO

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.


Assuntos
Fumarato de Dimetilo/uso terapêutico , Memória Imunológica/efeitos dos fármacos , Imunossupressores/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Memória Imunológica/imunologia , Imunofenotipagem , Estudos Longitudinais , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Subpopulações de Linfócitos T/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
18.
Neurol Neuroimmunol Neuroinflamm ; 3(2): e211, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27006972

RESUMO

OBJECTIVE: To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4-6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)-10 by RRMS patient B cells was also analyzed. RESULTS: Total numbers of peripheral blood B lymphocytes declined after 4-6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27(neg) B-cell subsets. Some interpatient variability was observed. In contrast, circulating CD24(high)CD38(high) (T2-MZP) B cells increased in percentage in the majority of patients with RRMS after 4-6 months and were present in higher numbers in all of the patients after 12 months of treatment. The CD43+CD27+ B-1 B cells also increased at the later time point in most patients but were unchanged at 4-6 months compared to pretreatment levels. Purified B cells from 7 of the 9 patients with RRMS tested after 4-6 months of treatment were able to produce IL-10 following CD40 ligand stimulation, and the amount corresponded with the combined levels of T2-MZP and B-1 B cells in the sample. None of the patients with RRMS in this study have had a relapse while taking BG-12. CONCLUSIONS: These data suggest that BG-12 differentially affects B-cell subsets in patients with RRMS, resulting in increased numbers of circulating B lymphocytes with regulatory capacity.

19.
Angiogenesis ; 18(3): 373-82, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26040900

RESUMO

Angiogenesis, a crucial step in tumor growth and metastasis, is regulated by various pro- or anti-angiogenic factors. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, roles of tumor-derived microRNAs in regulating tumor vascularization remain to be elucidated. In this study, we found that delivery of miR-494 into human vascular endothelial cells (ECs) enhanced the EC migration and promoted angiogenesis. The angiogenic effect of miR-494 was mediated by the targeting of PTEN and the subsequent activation of Akt/eNOS pathway. Importantly, co-culture experiments demonstrated that a lung cancer cell line, A549, secreted and delivered miR-494 into ECs via a microvesicle-mediated route. In addition, we found that the expression of miR-494 was induced in the tumor cells in response to hypoxia, likely via a HIF-1α-mediated mechanism. Furthermore, a specific miR-494 antagomiR effectively inhibited angiogenesis and attenuated the growth of tumor xenografts in nude mice. Taken together, these results demonstrated that miR-494 is a novel tumor-derived paracrine signal to promote angiogenesis and tumor growth under hypoxic condition.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Técnicas de Cocultura , Células Endoteliais/metabolismo , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Microcirculação , Transplante de Neoplasias , Neovascularização Patológica , PTEN Fosfo-Hidrolase/metabolismo , Cicatrização
20.
BMC Med Genomics ; 8: 21, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25958224

RESUMO

BACKGROUND: Recent genome-wide association studies (GWAS) have shown that single nucleotide polymorphisms (SNPs) in the Chr9p21 region are associated with coronary artery disease (CAD). Most of the SNPs identified in this region are non-coding SNPs, suggesting that they may influence gene expression by cis or trans mechanisms to affect disease susceptibility. Since all cells from an individual have the same DNA sequence variations, levels of gene expression in immortalized cell lines can reflect the functional effects of DNA sequence variations that influence or regulate gene expression. The objective of this study is to evaluate the functional consequences of the risk variants in the Chr9p21 region on gene expression. METHODS: We examined the association between the variants in the Chr9p21 region and the transcript-level mRNA expression of the adjacent genes (cis) as well as all other genes across the whole genome (trans) from transformed beta-lymphocytes in 801 non-Hispanic white participants from The Genetic Epidemiology Network of Arteriopathy (GENOA) study. RESULTS: We found that the CAD risk variants in the Chr9p21 region were significantly associated with the mRNA expression of the ANRIL transcript ENST00000428597 (p = 8.58e-06). Importantly, a few distant transcripts were also found to be associated with the variants in this region, including the well-known CAD risk gene ABCA1 (p = 1.01e-05). Gene enrichment testing suggests that retinol metabolism, N-Glycan biosynthesis, and TGF signaling pathways may be involved. CONCLUSION: These results suggest that the effect of risk variants in the Chr9p21 region on susceptibility to CAD is likely to be mediated through both cis and trans mechanisms.


Assuntos
Cromossomos Humanos Par 9/ultraestrutura , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Idoso , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Variação Genética , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Controle de Qualidade , RNA Mensageiro/metabolismo , Análise de Sequência de DNA
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