RESUMEN
BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.
Asunto(s)
Fibrilación Atrial , Sepsis , Cirugía Torácica , Humanos , Masculino , Anciano , Femenino , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Colchicina/efectos adversos , Sepsis/epidemiología , Sepsis/etiología , Sepsis/prevención & control , Diarrea/inducido químicamente , Ontario , Resultado del Tratamiento , Método Doble CiegoRESUMEN
BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.
Asunto(s)
Alta del Paciente , Sepsis , Humanos , Estudios Prospectivos , Cuidados Posteriores , Hemorragia , Complicaciones Posoperatorias/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.
Asunto(s)
Fibrilación Atrial , Cirugía Torácica , Humanos , Fibrilación Atrial/prevención & control , Fibrilación Atrial/complicaciones , Colchicina/uso terapéutico , Incidencia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológicoRESUMEN
Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.
Asunto(s)
Pulmón , Insuficiencia Respiratoria , Humanos , Estudios de Casos y Controles , Estudios Prospectivos , Pulmón/cirugía , Pulmón/metabolismo , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/metabolismo , Inflamación/etiología , Inflamación/metabolismo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Respiración ArtificialRESUMEN
BACKGROUND: The purpose of this study was to determine the incidence, characteristics, impact, and risk factors associated with persistent incisional pain. The hypothesis was that patient demographics and perioperative interventions are associated with persistent pain. METHODS: This was a secondary analysis of an international prospective cohort study from 2012 to 2014. This study included patients who were 45 yr of age or older who underwent major inpatient noncardiac surgery. Data were collected perioperatively and at 1 yr after surgery to assess for the development of persistent incisional pain (pain present around incision at 1 yr after surgery). RESULTS: Among 14,831 patients, 495 (3.3%; 95% CI, 3.1 to 3.6) reported persistent incisional pain at 1 yr, with an average pain intensity of 3.6 ± 2.5 (0 to 10 numeric rating scale), with 35% and 14% reporting moderate and severe pain intensities, respectively. More than half of patients with persistent pain reported needing analgesic medications, and 85% reported interference with daily activities (denominator = 495 in the above proportions). Risk factors for persistent pain included female sex (P = 0.007), Asian ethnicity (P < 0.001), surgery for fracture (P < 0.001), history of chronic pain (P < 0.001), coronary artery disease (P < 0.001), history of tobacco use (P = 0.048), postoperative patient-controlled analgesia (P < 0.001), postoperative continuous nerve block (P = 0.010), insulin initiation within 24 h of surgery (P < 0.001), and withholding nonsteroidal anti-inflammatory medication or cyclooxygenase-2 inhibitors on the day of surgery (P = 0.029 and P < 0.001, respectively). Older age (P < 0.001), endoscopic surgery (P = 0.005), and South Asian (P < 0.001), Native American/Australian (P = 0.004), and Latin/Hispanic ethnicities (P < 0.001) were associated with a lower risk of persistent pain. CONCLUSIONS: Persistent incisional pain is a common complication of inpatient noncardiac surgery, occurring in approximately 1 in 30 adults. It results in significant morbidity, interferes with daily living, and is associated with persistent analgesic consumption. Certain demographics, ethnicities, and perioperative practices are associated with increased risk of persistent pain.
Asunto(s)
Dolor Crónico/epidemiología , Dolor Crónico/etiología , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Herida Quirúrgica/complicaciones , Herida Quirúrgica/epidemiología , Anciano , Dolor Crónico/diagnóstico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Estudios Prospectivos , Herida Quirúrgica/diagnósticoRESUMEN
AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.
Asunto(s)
Fibrilación Atrial , Infarto del Miocardio , Accidente Cerebrovascular , Anciano , Fibrilación Atrial/epidemiología , Femenino , Humanos , Masculino , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. METHODS: In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. FINDINGS: Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76). INTERPRETATION: Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication [corrected]. FUNDING: Boehringer Ingelheim and Canadian Institutes of Health Research.
Asunto(s)
Dabigatrán/farmacología , Hemorragia/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Enfermedad Arterial Periférica/complicaciones , Accidente Cerebrovascular/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antitrombinas/farmacología , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Femenino , Hemorragia/tratamiento farmacológico , Hemorragia/prevención & control , Humanos , Masculino , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Periodo Perioperatorio/mortalidad , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/prevención & control , Efecto Placebo , Inhibidores de la Bomba de Protones/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Trombosis/patología , Resultado del Tratamiento , Troponina/efectos de los fármacos , Troponina/metabolismo , Tromboembolia Venosa/prevención & controlRESUMEN
BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.
Asunto(s)
Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Operativos/mortalidad , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/mortalidad , Estudios Prospectivos , Sepsis/mortalidadRESUMEN
OBJECTIVE: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described. METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03âng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring. RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4). CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.
Asunto(s)
Isquemia Miocárdica/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Troponina T/sangre , Procedimientos Quirúrgicos Vasculares , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/etiología , Oportunidad Relativa , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
AIMS: The aim of this study was to assess the effects of pre-operative statin therapy on cardiovascular events in the first 30-days after non-cardiac surgery. METHODS AND RESULTS: We conducted an international, prospective, cohort study of patients who were ≥45 years having in-patient non-cardiac surgery. We estimated the probability of receiving statins pre-operatively using a multivariable logistic model and conducted a propensity score analysis to correct for confounding. A total of 15 478 patients were recruited at 12 centres in eight countries from August 2007 to January 2011. The matched population consisted of 2845 patients (18.4%) treated with a statin and 4492 (29.0%) controls. The pre-operative use of statins was associated with lower risk of the primary outcome, a composite of all-cause mortality, myocardial injury after non-cardiac surgery (MINS), or stroke at 30 days [relative risk (RR), 0.83; 95% confidence interval (CI), 0.73-0.95; P = 0.007]. Statins were also associated with a significant lower risk of all-cause mortality (RR, 0.58; 95% CI, 0.40-0.83; P = 0.003), cardiovascular mortality (RR, 0.42; 95% CI, 0.23-0.76; P = 0.004), and MINS (RR, 0.86; 95% CI, 0.73-0.98; P = 0.02). There were no statistically significant differences in the risk of myocardial infarction or stroke. CONCLUSION: Among patients undergoing non-cardiac surgery, pre-operative statin therapy was independently associated with a lower risk of cardiovascular outcomes at 30 days. These results require confirmation in a large randomized trial. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov NCT00512109.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Adulto , Anciano , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Cuidados Preoperatorios/mortalidad , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21â¯842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. CONCLUSIONS AND RELEVANCE: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.
Asunto(s)
Infarto del Miocardio/mortalidad , Isquemia Miocárdica/mortalidad , Troponina T/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Periodo Posoperatorio , Estudios Prospectivos , Medición de RiesgoRESUMEN
OBJECTIVES: Patients undergoing thoracic surgery experience high complication rates. It is uncertain whether preoperative health-related quality of life (HRQOL) measurements can predict patients at higher risk for postoperative complications. The objective of this study was to determine the association between preoperative HRQOL and postoperative complications among patients undergoing thoracic surgery. METHODS: This was a retrospective cohort study of prospectively collected data. Consecutive patients undergoing elective thoracic surgery at a Canadian tertiary care centre between January 2018 and January 2019 were included. Patient HRQOL was measured using the Euroqol-5 Dimension (EQ-5D) survey. Complications were recorded using the Ottawa Thoracic Morbidity and Mortality system. Uni- and multivariable analysis were performed. RESULTS: Of 515 surgeries performed, 133 (25.8%) patients experienced at least 1 postoperative complication; 345 (67.0%) patients underwent surgery for malignancy. A range of 271 (52.7%) to 310 (60.2%) patients experienced pain/discomfort at each timepoint. On multivariable analysis, lower preoperative EQ-5D visual analogue scale scores were significantly associated with postoperative complications (adjusted odds ratio 0.97, 95% confidence interval 0.95-0.99; P = 0.01). Presence of malignancy was not independently associated with complications (P = 0.68). CONCLUSIONS: Self-reported preoperative HRQOL can predict incidence of postoperative complications among patients undergoing thoracic surgery. Assessments of preoperative HRQOL may help identify patients at higher risk for developing complications. These findings could be used to direct preoperative risk-mitigation strategies in areas of HRQOL where patients suffer most, such as pain. The full perioperative trajectory of patient HRQOL should be discerned to identify subsets of patients who share common risk factors.
Asunto(s)
Complicaciones Posoperatorias , Calidad de Vida , Procedimientos Quirúrgicos Torácicos , Humanos , Estudios Retrospectivos , Femenino , Masculino , Procedimientos Quirúrgicos Torácicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/psicología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Anciano , Periodo Preoperatorio , Factores de RiesgoRESUMEN
INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their shortterm mortality. Prospective reports describing the incidence of longterm complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1year followup. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3fold increase in 1year mortality.
Asunto(s)
Lesiones Cardíacas , Infarto del Miocardio , Humanos , Masculino , Femenino , Estudios Prospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Infarto del Miocardio/etiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Troponina TRESUMEN
BACKGROUND: Surgical jejunostomy tubes are a routine part of elective esophagectomies in patients with carcinomas and provide a route for nutritional support in those who experience complications. We wished to determine how frequently oral intake is delayed and the amount of nutrition delivered via the jejunostomy tube. METHODS: We reviewed the charts of all adults undergoing esophagectomy for carcinoma between January 2000 and June 2008. We determined the proportion of patients unable to resume oral nutrition after 8 days and the amount of nutrition delivered in each of the 8 days. RESULTS: In all, 111 patients underwent elective esophagectomy for carcinoma, and 103 had a jejunostomy tube placed. The mean age was 67 ± 10.8 years. The median time to oral intake was 7 (interquartile range 7-11) days. Seventy-four (67%) patients resumed oral intake within 8 days. The mean nutrition delivered by jejunostomy within the first 8 days as a percentage of the target was 45.6% (95% confidence interval 41.2%-49.9%). Six (5.4%) patients experienced complications attributable solely to the jejunostomy tube; 3 (2.9%) required surgery. Forty (38.8%) patients had abdominal issues serious enough to warrant delaying the progression of feeding. CONCLUSION: Two-thirds of patients undergoing elective esophagectomy were tolerating oral intake by the end of the eighth postoperative day, and less than half of the target nutrition was delivered over the first 8 days. We now selectively place surgical jejunostomy tubes in patients undergoing elective esophagectomies.
CONTEXTE: Des cathéters de jéjunostomie chirurgicale sont d'emblée posés lors des oesophagectomies non urgentes chez les patients atteints de cancer et procurent une voie d'administration du soutien nutritionnel chez les patients qui présentent des complications. Nous avons voulu déterminer la fréquence à laquelle la prise orale est retardée et la quantité de solution pour nutrition parentérale administrée par le cathéter de jéjunostomie. MÉTHODES: Nous avons analysé les dossiers de tous les adultes soumis à une oesophagectomie pour un cancer entre janvier 2000 et juin 2008. Nous avons calculé la proportion de patients incapables de recommencer à se nourrir par la bouche après 8 jours et la quantité de solution administrée à chacun des 8 jours. RÉSULTATS: En tout, 111 patients ont subi une oesophagectomie non urgente pour un cancer et on a posé un cathéter de jéjunostomie à 103 d'entre eux. L'âge moyen était de 67 ± 10,8 ans. L'intervalle médian avant le début des prises orales a été de 7 jours (fourchette interquartile de 711). Soixante-quatorze patients (67 %) ont recommencé à s'alimenter par la bouche en l'espace de 8 jours. La quantité moyenne de solution pour nutrition parentérale administrée par jéjunostomie au cours des 8 premiers jours en pourcentage de l'objectif cible a été de 45,6 % (intervalle de confiance [IC] de 95 %, 41,2 %49,9 %). Six patients (5,4 %) ont présenté des complications attribuables uniquement au cathéter de jéjunostomie; 3 (2,9 %) ont eu besoin d'une chirurgie. Quarante patients (38,8 %) ont présenté des symptômes abdominaux suffi - samment graves pour retarder la progression de l'alimentation. CONCLUSION: Les deux tiers des patients soumis à une oesophagectomie non urgente toléraient la prise orale à la fin du huitième jour postopératoire et moins de la moitié de la nutrition cible a été administrée au cours des 8 premiers jours. Nous plaçons maintenant des cathéters de jéjunostomie chirurgicale de façon sélective chez les patients qui subissent des oesophagectomies non urgentes.
Asunto(s)
Nutrición Enteral/estadística & datos numéricos , Esofagectomía , Yeyunostomía , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Background: Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV. Methods: A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included. Results: After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6. Conclusions: A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.
RESUMEN
BACKGROUND: The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications. METHODS: Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted. RESULTS: The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of - $97 (95% confidence interval [CI] - $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI -$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered. CONCLUSION: Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT01661101.
Asunto(s)
Dabigatrán , Lesiones Cardíacas , Complicaciones Posoperatorias , Canadá , Costos y Análisis de Costo , Dabigatrán/economía , Dabigatrán/uso terapéutico , Lesiones Cardíacas/tratamiento farmacológico , Lesiones Cardíacas/etiología , Humanos , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the same population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.
RESUMEN
Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non-small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
RESUMEN
Herpes simplex virus is an uncommon cause of esophagitis and particularly so in immunocompetent individuals. Although the common presentation tends to be odynophagia and/or dysphagia, fever, and retrosternal chest pain, there are variations and rarely it can present more ominously as esophageal rupture. We report a rare case of esophageal perforation with penetration into the vertebral space secondary to chronic herpes simplex virus esophagitis in a 71-year-old immunocompetent woman. This is the second known such occurrence. The patient had a long stay in the hospital but recovered from the condition and was followed up for 1 year after initial presentation.
Asunto(s)
Perforación del Esófago/etiología , Perforación del Esófago/cirugía , Esofagitis/complicaciones , Esofagitis/cirugía , Herpes Simple/complicaciones , Herpes Simple/cirugía , Anciano , Fístula Bronquial/diagnóstico por imagen , Fístula Bronquial/etiología , Fístula Bronquial/cirugía , Enfermedad Crónica , Endoscopía del Sistema Digestivo , Fístula Esofágica/diagnóstico por imagen , Fístula Esofágica/etiología , Fístula Esofágica/cirugía , Perforación del Esófago/diagnóstico por imagen , Esofagitis/diagnóstico por imagen , Extravasación de Materiales Terapéuticos y Diagnósticos/diagnóstico por imagen , Extravasación de Materiales Terapéuticos y Diagnósticos/etiología , Extravasación de Materiales Terapéuticos y Diagnósticos/cirugía , Femenino , Estudios de Seguimiento , Herpes Simple/diagnóstico por imagen , Humanos , Tiempo de Internación , Stents , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin. METHODS: Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored. RESULTS: After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients. CONCLUSIONS: Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance. TRIAL REGISTRATION: ClinicalTrials.govNCT02546648.