An educational intervention to reduce the incidence of postoperative residual curarisation: a cluster randomised crossover trial in patients undergoing general anaesthesia.

BACKGROUND: The incidence of postoperative residual curarisation remains unacceptably high. We assessed whether an educational intervention on perioperative neuromuscular block management can reduce it. METHODS: In this multicentre, cluster randomised crossover trial, centres were allocated to receive an educational intervention either in a first or a second period. The educational intervention consisted of a lecture about neuromuscular management key points, including quantitative neuromuscular monitoring and use of reversal agents. The lecture was streamed to allow repetition. Additionally, memory cards were distributed in each operating theatre. The primary outcome was postoperative residual curarisation in the PACU. Secondary outcomes were frequency of quantitative neuromuscular monitoring, use of reversal agents, and incidence of postoperative pulmonary complications during hospital stay. Measurements were performed before randomisation and after the first and the second period. The effect of the educational intervention was estimated using multivariable mixed effects logistic regression models. RESULTS: We included 2314 subjects in 34 Spanish centres. Postoperative residual curarisation incidence was not affected by the educational intervention (odds ratio [OR] 0.90 [95% confidence interval {CI}: 0.51-1.58]; P=0.717 and 1.30 [0.73-2.30]; P=0.371] for first and second time-period interaction). The educational intervention increased the quantitative neuromuscular monitor usage (OR 2.04 [95% CI: 1.31-3.19]; P=0.002), the use of reversal agents was unchanged (OR 0.79 [95% CI: 0.50-1.26]; P=0.322), and the incidence of postoperative pulmonary complications decreased (OR 0.19 [95% CI: 0.10-0.35]; P<0.001). CONCLUSIONS: An educational intervention on perioperative neuromuscular block management did not reduce the incidence of postoperative residual curarisation nor increase reversal, despite increased quantitative neuromuscular monitoring. Sugammadex reversal was associated with reduced postoperative residual curarisation. The educational intervention was associated with a decrease in postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03128151.

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p < 0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p < 0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p < 0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Introducción: Nuestro trabajo describe la frecuencia de sobreinfecciones en pacientes con COVID-19 en UCI e identifica factores de riesgo asociados con su aparición. Secundariamente, evaluamos la estancia en UCI, mortalidad intrahospitalaria y analizamos un subgrupo de infecciones causadas por microorganismos multirresistentes (MDR). Métodos: Estudio realizado entre marzo y junio de 2020. Definimos como sobreinfección a aquellas que aparecieron ≥48 h del ingreso. Incluimos las causadas por bacterias y hongos y evaluamos la infección respiratoria asociada a la ventilación mecánica (IRAVM), bacteriemia primaria, bacteriemia secundaria e infección del tracto urinario. Se realizó un análisis multivariante de los factores de riesgo. Resultados: Incluimos 213 pacientes, documentándose 174 episodios de sobreinfección en 95 casos (44,6%): IRAVM 78 episodios, bacteriemia primaria 66, bacteriemia secundaria 9 e ITU 21. Los MDR causaron el 29,3% de los episodios. La mediana de tiempo hasta el primer episodio fue de 18 días, siendo mayor en las causadas por MDR vs. no MDR (28 vs. 16, p < 0,01). El análisis multivariante identificó la administración de corticoides (OR 4,9 IC 95% 1,4-16,9), tocilizumab (OR 2,4 IC 95% 1,1-5,9) y antibióticos de amplio espectro (OR 2,5 IC 95% 1,2-5,1) como factores de riesgo asociados. Los pacientes con sobreinfección presentaron una estancia en UCI más prolongada (35 vs. 12 días, p < 0,01) pero no mayor mortalidad intrahospitalaria (45,3% vs. 39,7%, p 0,13). Conclusiones: Las sobreinfecciones en los pacientes con COVID-19 aparecen tardíamente. La administración de corticoides, tocilizumab y antibióticos de amplio espectro se asocia con su aparición.

Persistent Incisional Pain after Noncardiac Surgery: An International Prospective Cohort Study.

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.

The effect of immediate postoperative Boussignac CPAP on adverse pulmonary events after thoracic surgery: A multicentre, randomised controlled trial.

BACKGROUND: The effectiveness of prophylactic continuous positive pressure ventilation (CPAP) after thoracic surgery is not clearly established. OBJECTIVE: The aim of this study was to assess the effectiveness of CPAP immediately after lung resection either by thoracotomy or thoracoscopy in preventing atelectasis and pneumonia. DESIGN: A multicentre, randomised, controlled, open-label trial. SETTINGS: Four large University hospitals at Madrid (Spain) from March 2014 to December 2016. PATIENTS: Immunocompetent patients scheduled for lung resection, without previous diagnosis of sleep-apnoea syndrome or severe bullous emphysema. Four hundred and sixty-four patients were assessed, 426 were randomised and 422 were finally analysed. INTERVENTION: Six hours of continuous CPAP through a Boussignac system versus standard care. MAIN OUTCOME MEASURES: Primary outcome: incidence of the composite endpoint 'atelectasis + pneumonia'. Secondary outcome: incidence of the composite endpoint 'persistent air leak + pneumothorax'. RESULTS: The primary outcome occurred in 35 patients (17%) of the CPAP group and in 58 (27%) of the control group [adjusted relative risk (ARR) 0.53, 95% CI 0.30 to 0.93]. The secondary outcome occurred in 33 patients (16%) of the CPAP group and in 29 (14%) of the control group [ARR 0.92, 95% CI 0.51 to 1.65]. CONCLUSION: Prophylactic CPAP decreased the incidence of the composite endpoint 'postoperative atelectasis + pneumonia' without increasing the incidence of the endpoint 'postoperative persistent air leaks + pneumothorax'.

Intraoperative Troponin Elevation in Liver Transplantation Is Independently Associated With Mortality: A Prospective Observational Study.

Intraoperative factors implicated in postoperative mortality after liver transplantation (LT) are poorly understood. Because LT is a particularly demanding procedure, we hypothesized that intraoperative myocardial injury may be frequent and independently associated with early postoperative outcomes. We aimed to determine the association between intraoperative high-sensitivity troponin (hsTn) elevation during LT and 30-day postoperative mortality. A total of 203 adult patients undergoing LT were prospectively included in the cohort and followed during 1 year. Advanced hemodynamic parameters and serial high-sensitivity troponin T (hsTnT) measurements were assessed at 6 intraoperative time points. The optimal hsTnT cutoff level for intraoperative troponin elevation (ITE) was identified. Patients were classified into 2 groups according to the presence of ITE. Independent impact of ITE on survival was assessed through survival curves and multivariate Cox regression analysis. Intraoperative cardiac function was compared between groups. Troponin levels increased early during surgery in the ITE group. Troponin values at abdominal closure were associated with 30-day mortality (area under the receiver operating caracteristic curve, [AUROC], 0.73; P = 0.005). Patients with ITE showing values of hsTnT ≥61 ng/L at abdominal closure presented higher 30-day mortality (29.6% versus 3.4%; P < 0.001). ITE was independently associated with 30-day mortality (hazard ratio, 3.8; 95% confidence interval, 1.1-13.8; P = 0.04) and with worse overall intraoperative cardiac function. The hsTnT upper reference limit showed no discriminant capacity during LT. Intraoperative myocardial injury identified by hsTn elevation is frequently observed during LT, and it is associated with myocardial dysfunction and short-term mortality. Determinations of hsTn may serve as a valuable intraoperative monitoring tool during LT.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Spontaneous recovery of neuromuscular blockade is an independent risk factor for postoperative pulmonary complications after abdominal surgery: A secondary analysis.

BACKGROUND: In intermediate-to-high-risk patients, major abdominal surgery is associated with a high incidence of postoperative complications, mainly pulmonary. Neuromuscular blocking drugs have been suggested as a contributing factor, but this remains unproven. OBJECTIVE: To define the relationship of neuromuscular blockade management (reversal) with postoperative pulmonary complications (PPCs). DESIGN: The individualised PeRioperative Open-lung approach Versus standard protectivE ventilation in abdominal surgery study was a prospective, multicentre, four-arm, randomised controlled trial. This is a secondary analysis of the data. SETTING: Twenty-one teaching hospitals in Spain. The study was conducted between 2 January 2015, and 18 May 2016. PATIENTS: Age more than 18 years with an intermediate-to-high risk for PPCs, scheduled for major abdominal surgery lasting more than 2 h. Exclusion criteria included pregnancy or breastfeeding, and moderate-to-severe organ diseases. INTERVENTIONS: The mode of reversal of neuromuscular blockade determined two patient groups: pharmacological reversal versus spontaneous recovery. MAIN OUTCOME MEASURES: The primary outcome was a composite of PPCs during the first 30 postoperative days. The association between categorical variables and PPCs within 30 days was studied. Univariate and multivariable logistic regression modelling and propensity score analyses were performed. RESULTS: From the 923 patients included, 596 (64.6%) presented with PPCs within 30 days after surgery. Patients who developed these complications were older with a higher BMI, a lower pre-operative SpO2, a higher ASA physical status score and a higher incidence of arterial hypertension, diabetes mellitus or chronic obstructive pulmonary disease. Pharmacological neuromuscular blockade reversal was associated with a lower incidence of PPCs (odds ratio 0.62, 95% CI 0.47 to 0.82). CONCLUSION: Spontaneous recovery of neuromuscular blockade was an independent risk factor for PPCs in patients with intermediate-to-high risk, undergoing abdominal surgery. We suggest this factor should be included in future studies on PPCs. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02158923.

Association between complications and death within 30 days after noncardiac surgery.

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.

Effects of Intraoperative Infusion of Esmolol on Systemic and Pulmonary Inflammation in a Porcine Experimental Model of Lung Resection Surgery.

BACKGROUND: Lung resection surgery (LRS) is associated with systemic and pulmonary inflammation, which can affect postoperative outcomes. Activation of ß-adrenergic receptors increases the expression of proinflammatory and anti-inflammatory mediators, and their blockade may attenuate the systemic inflammatory response. The aim of this study was to analyze the effect of a continuous perioperative intravenous perfusion of esmolol on postoperative pulmonary edema in an experimental model of LRS requiring periods of one-lung ventilation (OLV). METHODS: Twenty-four large white pigs were randomly assigned to 3 groups: control (CON), esmolol (ESM), and sham. The ESM group received an intravenous esmolol bolus (0.5 mg/kg) and then an esmolol infusion (0.05 mg·kg·minute) throughout the procedure. The CON group received the same volume of 0.9% saline solution as the ESM group plus a continual infusion of saline. The sham group underwent a left thoracotomy without LRS or OLV. At the end of the LRS, the animals were awakened, and after 24 hours, they underwent general anesthesia again. Lung biopsies and plasma samples were obtained to analyze the levels and expression of inflammatory mediators, and the animals also received a bronchoalveolar lavage. RESULTS: At 24 hours after the operation, the ESM group had less lung edema and lower expression of the proinflammatory biomarkers tumor necrosis factor (TNF) and interleukin (IL)-1 compared to the CON group for both lung lobes. For the mediastinal lobe biopsies, the mean difference and 95% confidence interval (CI) between the groups for edema, TNF, and IL-1 were 14.3 (95% CI, 5.6-23.1), P = .002; 0.19 (95% CI, 0.07-0.32), P = .002; and 0.13 (95% CI, 0.04-0.22), P = .006, respectively. In the left upper lobe, the mean differences for edema, TNF, and IL-1 were 12.4 (95% CI, 4.2-20.6), P = .003; 0.25 (95% CI, 0.12-0.37), P < .001; and 0.3 (95% CI, 0.08-0.53), P = .009. CONCLUSIONS: Our results suggest that esmolol reduces lung edema and inflammatory responses in the intraoperative and postoperative periods in animals that underwent LRS with OLV.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

Usefulness of combining clinical and biochemical parameters for prediction of postoperative pulmonary complications after lung resection surgery.

Early detection of patients with a high risk of postoperative pulmonary complications (PPCs) could improve postoperative strategies. We investigated the role of monitoring systemic and lung inflammatory biomarkers during surgery and the early postoperative period to detect patients at high risk of PPCs after lung resection surgery (LRS). This is a substudy of a randomized control trial on the inflammatory effects of anaesthetic drugs during LRS. We classified patients into two groups, depending on whether or not they developed PPCs. We constructed three multivariate logistic regression models to analyse the power of the biomarkers to predict PPCs. Model 1 only included the usual clinical variables; Model 2 included lung and systemic inflammatory biomarkers; and Model 3 combined Models 1 and 2. Comparisons between mathematical models were based on the area under the receiver operating characteristic curve (AUROC) and tests of integrated discrimination improvement (IDI). Statistical significance was set at p < 0.05. PPCs were detected in 37 (21.3%) patients during admission. The AUROC for Models 1, 2, and 3 was 0.79 (95% CI 0.71-0.87), 0.80 (95% CI 0.72-0.88), and 0.93 (95% CI 0.88-0.97), respectively. Comparison of the AUROC between Models 1 and 2 did not reveal statistically significant values (p = 0.79). However, Model 3 was superior to Model 1 (p < 0.001). Model 3 had had an IDI of 0.29 (p < 0.001) and a net reclassification index of 0.28 (p = 0.007). A mathematical model combining inflammation biomarkers with clinical variables predicts PPCs after LRS better than a model that includes only clinical data. Clinical registration number Clinical Trial Registration NCT02168751; EudraCT 2011-002294-29.

The Effects of an Open-Lung Approach During One-Lung Ventilation on Postoperative Pulmonary Complications and Driving Pressure: A Descriptive, Multicenter National Study.

OBJECTIVE: Thoracic surgical procedures are associated with an increased risk of postoperative pulmonary complications (PPCs), which seem to be related directly to intraoperative driving pressure. The authors conducted this study to describe the incidence of PPCs in patients in whom an individualized open-lung approach was applied during one-lung ventilation. DESIGN: This was a prospective, multicenter, national descriptive study. SETTING: Thoracic surgery patients undergoing one-lung ventilation. PARTICIPANTS: Eligible participants were included consecutively from October 1, 2016, to September 30, 2017. A total of 690 patients were included. INTERVENTIONS: An individualized open-lung approach that consisted of an alveolar recruitment maneuver followed by a positive end-expiratory pressure adjusted to best respiratory system compliance was performed in all patients. MEASUREMENTS AND MAIN RESULTS: Preoperative and intraoperative data were recorded; the primary outcome was a description of the incidence of PPCs in these patients during the first 7 postoperative days. The patients were mainly male, and half of them had a high risk of PPCs (ARISCAT score exceeding 44). Eleven percent of participants developed a PPC within the first postoperative week. The mean open lung positive end-expiratory pressure was 8 ± 3 cmH2O. When compared with pre-open lung approach values, the open-lung approach significantly decreased the driving pressure (14 ± 4 cmH2O v 11 ± 3 cmH2O; p < 0.001) and increased dynamic compliance (30 ± 10 mL/cmH2O v 43 ±15 mL/cmH2O; p < 0.001). CONCLUSIONS: The low incidence of PPCs in patients who underwent an open-lung approach during one-lung ventilation compared with that reported for other thoracic surgery series and the decrease in the driving pressure in these patients justify an additional randomized controlled trial to compare the open-lung approach with the standard protective strategy of low tidal volume and low positive end-expiratory pressure.

Glycocalyx Degradation after Pulmonary Transplantation Surgery.

PURPOSE: Ischaemia-reperfusion injury (IRI) is a main cause of morbidity after pulmonary resection surgery. The degradation of glycocalyx, a dynamic layer of macromolecules at the luminal surface of the endothelium, seems to participate in tissue dysfunction after IRI. Lidocaine has a proven anti-inflammatory activity in several tissues but its modulation of glycocalyx has not been investigated. This work aimed to investigate the potential involvement of glycocalyx in lung IRI in a lung auto-transplantation model and the possible effect of lidocaine in modulating IRI. METHODS: Three groups (sham-operated, control, and lidocaine), each consisting of 6 Large White pigs, were subjected to lung auto-transplantation. All groups received the same anaesthesia. In addition, the lidocaine group received a continuous IV administration of lidocaine (1.5 mg/kg/h). Lung tissue and plasma samples were taken before pulmonary artery clamp, before reperfusion, and 30 and 60 min post-reperfusion in order to analyse pulmonary oedema, glycocalyx components, adhesion molecules, and myeloperoxidase level. RESULTS: Ischaemia caused pulmonary oedema, which was greater after reperfusion. This effect was accompanied by decreased levels of syndecan-1 and heparan sulphate in the lung samples, together with increased levels of both glycocalyx components in the plasma samples. After reperfusion, neutrophil activation and the expression of adhesion molecules were increased. All these alterations were significantly lower or absent in the lidocaine group. CONCLUSION: Lung IRI caused glycocalyx degradation that contributed to neutrophil activation and adhesion. The administration of lidocaine was able to protect the lung from glycocalyx degradation.

Troponin T monitoring to detect myocardial injury after noncardiac surgery: a cost-consequence analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a mostly asymptomatic condition that is strongly associated with 30-day mortality; however, it remains mostly undetected without systematic troponin T monitoring. We evaluated the cost and consequences of postoperative troponin T monitoring to detect MINS. METHODS: We conducted a model-based cost-consequence analysis to compare the impact of routine troponin T monitoring versus standard care (troponin T measurement triggered by ischemic symptoms) on the incidence of MINS detection. Model inputs were based on Canadian patients enrolled in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, which enrolled patients aged 45 years or older undergoing inpatient noncardiac surgery. We conducted probability analyses with 10 000 iterations and extensive sensitivity analyses. RESULTS: The data were based on 6021 patients (48% men, mean age 65 [standard deviation 12] yr). The 30-day mortality rate for MINS was 9.6%. We determined the incremental cost to avoid missing a MINS event as $1632 (2015 Canadian dollars). The cost-effectiveness of troponin monitoring was higher in patient subgroups at higher risk for MINS, e.g., those aged 65 years or more, or with a history of atherosclerosis or diabetes ($1309). CONCLUSION: The costs associated with a troponin T monitoring program to detect MINS were moderate. Based on the estimated incremental cost per health gain, implementation of postoperative troponin T monitoring seems appealing, particularly in patients at high risk for MINS.

CONTEXTE: Les lésions myocardiques après chirurgie non cardiaque (CNC) sont majoritairement asymptomatiques et fortement associées au risque de mortalité dans les 30 jours; toutefois, dans la plupart des cas, elles ne sont pas détectées en l'absence d'une surveillance systématique de la troponine T. Nous avons évalué les coûts et les conséquences d'une telle surveillance pour détecter les lésions myocardiques après CNC. MÉTHODES: Nous avons mené une analyse coût-conséquence modélisée pour comparer la surveillance systématique de la troponine T aux soins habituels seuls (mesure de la troponine T seulement s'il y a présence de symptômes d'ischémie) sur la fréquence de détection de lésions myocardiques après CNC. Les données ayant servi à l'analyse provenaient des patients canadiens ayant participé à l'étude de cohorte VISION, qui visait à évaluer les complications vasculaires chez les patients de 45 ans et plus ayant subi une CNC. Nous avons mené des analyses de probabilité avec 10  000 itérations et des analyses de sensibilité approfondies. RÉSULTATS: Les données portaient sur 6021 patients (48 % du sexe masculin; âge moyen de 65 ans [écart-type de 12 ans]). Le taux de mortalité dans les 30 jours associé à une lésion myocardique après CNC était de 9,6 %. Nous avons déterminé que le coût marginal de la détection de la présence d'une lésion par surveillance de la troponine T était de 1632 $ (dollars canadiens en 2015). Le rapport coût-efficacité était plus bas pour les sous-groupes de patients à risque élevé de lésion myocardique après CNC, comme les patients de 65 ans et plus ou ceux ayant des antécédents d'athérosclérose ou de diabète (1309 $), que pour leurs pairs. CONCLUSION: Les coûts associés à un programme de surveillance de la troponine T pour détecter les lésions myocardiques après CNC étaient modérés. Le coût marginal estimé par gain de santé indique que la mise en œuvre de ce type de programme pourrait être une option intéressante, surtout pour les patients à risque élevé de lésion myocardique après CNC.

Chemokine Involvement in Lung Injury Secondary to Ischaemia/Reperfusion.

INTRODUCTION: During transplant surgeries, the lung experiences an ischaemia-reperfusion (I/R)-induced damage identified as a significant cause of morbidity and mortality. However, the mechanisms by which I/R induces leucocyte accumulation and subsequent tissue damage in lung surgeries remain unknown. Therefore, the present study aims to assess the role of monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in leucocyte chemotaxis related to lung injury secondary to I/R. METHODS: Six pigs were subjected to an orthotopic left caudal lobe lung transplantation with a subsequent 60-min graft reperfusion (Transplant group). In addition, six animals underwent to sham surgery (Sham Group). Plasma samples and lung biopsies were collected before the beginning of pneumonectomy, before starting the reperfusion, and 30 min and 60 min after the beginning of the reperfusion. Plasma levels of intercellular adhesion molecule 1 (ICAM-1) and lung expressions of MCP-1, MIP-2, myeloperoxidase (MPO), and lung oedema were measured. RESULTS: Lung I/R caused substantial damage observed as pulmonary oedema. The oedema was evident after the ischemic insult and increased after reperfusion. After reperfusion, increased levels of MPO were observed which suggests an activation and infiltration of neutrophils into the lung tissue. After 30 min of reperfusion, MCP-1, MIP-2, and ICAM-1 levels were significantly increased compared to prepneumonectomy levels (p < 0.05) and a further increase was observed after 60 min of reperfusion (p < 0.05). CONCLUSION: The present study demonstrates that activated neutrophils, as well as MCP-1, MIP-2, and ICAM-1, are involved in inflammatory response induced by ischaemia-reperfusion-induced lung injury.

Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) is associated with morbidity and mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are involved in the pathogenesis of organ rejection. Lidocaine has proven anti-inflammatory activity in several tissues but its modulation of miRNAs has not been investigated. This work aims to investigate the involvement of miRNAs in lung IRI in a lung auto-transplantation model and to investigate the effect of lidocaine. METHODS: Three groups (sham, control, and Lidocaine), each comprising 6 pigs, underwent a lung autotransplantation. All groups received the same anesthesia. In addition, animals of lidocaine group received a continuous intravenous administration of lidocaine (1.5 mg/kg/h) during surgery. Lung biopsies were taken before pulmonary artery clamp, before reperfusion, 30 minutes postreperfusion (Rp-30), and 60 minutes postreperfusion (Rp-60). Samples were analyzed for different miRNAs (miR-122, miR-145, miR-146a, miR-182, miR-107, miR-192, miR-16, miR-21, miR-126, miR-127, miR142-5p, miR152, miR155, miR-223, and let7) via the use of reverse-transcription quantitative polymerase chain reaction. Results were normalized with miR-103. RESULTS: The expression of miR-127 and miR-16 did not increase after IRI. Let-7d, miR-21, miR-107, miR-126, miR-145, miR-146a, miR-182, and miR-192 significantly increased at the Rp-60 (control versus sham P < .001). miR-142-5p, miR-152, miR-155, and miR 223 significantly increased at the Rp-30 (control versus sham P < .001) and at the Rp-60 (control versus. sham P < .001). The administration of lidocaine was able to attenuate these alterations in a significant way (control versus Lidocaine P < .001). CONCLUSIONS: Lung IRI caused dysregulation miRNA. The administration of lidocaine reduced significantly miRNAs alterations.

Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model.

PURPOSE: The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. METHODS: Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). CONCLUSION: Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.

Extravascular Lung Water and Pulmonary Vascular Permeability Index Measured at the End of Surgery Are Independent Predictors of Prolonged Mechanical Ventilation in Patients Undergoing Liver Transplantation.

BACKGROUND: Pulmonary edema (PE) after orthotopic liver transplantation (OLT) may compromise the postoperative course and prolong the duration of mechanical ventilation (MV) and intensive care unit length of stay. Hemodynamic monitoring with transpulmonary thermodilution permits quantification of extravascular lung water index (ELWI) and calculation of the pulmonary vascular permeability index (PVPI), which is the ratio between the ELWI and the pulmonary blood volume. This ratio can discriminate between PE hydrostatic and nonhydrostatic PE. We investigated the relationship between ELWI and PVPI values, measured at the end of surgery, and prolonged MV (PMV) in patients after OLT. METHODS: We retrospectively studied 93 consecutive patients who underwent OLT. We recorded preoperative data including spirometry, echocardiography, severity liver disease with the Model for End-Stage Liver Disease score, and the Child-Pugh classification scores. Intraoperatively, we performed hemodynamic measurements with transpulmonary thermodilution and pulmonary arterial catheters after the induction of anesthesia, 10 minutes before reperfusion, and at the end of surgery. Moreover, we recorded the length of surgery, the amount of IV volume infused, the results of blood coagulation analyses, and blood transfusion. Postoperatively, we recorded the duration of MV and intensive care unit length of stay, mortality, and graft function. Patients were then classified as requiring PMV (>48 hours after surgery) or not. Statistical analyses, preoperative and intraoperative variables between patients with and without PMV, were compared using Mann-Whitney U tests. Receiver-operating characteristic curves were used to evaluate the ability of preoperative and intraoperative variables to predict PMV. RESULTS: Twelve patients required PMV after surgery. Patients who required PMV exhibited increased ELWI (11.6 ± 3 mL/kg vs 9.3 ± 2 mL/kg, P = 0.0099) and PVPI values (2.94 ± 1 vs 1.8 ± 0.6, P = 0.000015) at the end of surgery. The areas under the receiver-operating characteristic curve were 0.890 ± 0.04 for PVPI with a 99% confidence interval of 0.782 to 0.958 and 0.730 ± 0.08 for ELWI with a 99% confidence interval of 0.594 to 0.839. Using a cutoff of 2.3 for PVPI allowed a sensitivity = 91.7%, a specificity = 83.8, a positive predictive value = 45.8%, and a negative predictive value = 98.5% for predicting PMV. A cutoff of 12 for ELWI allowed a sensitivity of 50%, specificity of 85%, positive predictive value of 33.3%, and negative predictive value of 91.9% for PMV. CONCLUSIONS: PVPI and ELWI values obtained at the end of OLT are useful for predicting the need for postoperative PMV.

Systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery: A prospective observational study.

BACKGROUND: Measurement of inflammatory mediators in bronchoalveolar lavage (BAL) during lung resection surgery with periods of one-lung ventilation (OLV) has revealed an intense local pulmonary response. The role of each lung in the inflammation that occurs during this procedure has never been investigated. OBJECTIVE(S): The primary objective of our study was to compare the inflammatory response in the dependent lung with that of the nondependent lung by measuring inflammatory markers in BAL. Our secondary objective was to assess the behaviour of these inflammatory mediators in patients with and without postoperative pulmonary complications (PPCs). DESIGN: A prospective, observational study. SETTING: Department of Anaesthesiology in a university hospital. PATIENTS: Forty-six consecutive patients undergoing lung resection surgery. INTERVENTION(S): BAL samples were taken from dependent and nondependent lung 10 min before initiating OLV and at the end of OLV (once two-lung ventilation was established). All patients were followed up until 30 days after surgery. MAIN OUTCOME MEASURES: The concentration of cytokines [interleukin (IL)-1, IL-2, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α)], nitric oxide, carbon monoxide and matrix metalloproteinase 2 (MMP-2) was analysed in both lungs before and after OLV. PPCs were recorded. RESULTS: In BAL fluid, all measured biomarkers, apart from IL-10, were significantly greater (P < 0.05) at the end of OLV than those obtained before OLV, both for the dependent and nondependent lung. The increase in measured biomarkers was similar in both lungs. Eight patients developed PPC. Patients who developed PPC had higher levels of TNF-α (P < 0.05) in BAL from the nondependent lung before and after OLV than patients who did not have PPC. Patients who developed PPC had a smaller increase in MMP-2 levels (P < 0.05) in the dependent lung than patients who did not have PPC. CONCLUSION: In lung resection surgery, the inflammatory response is similar in both lungs. However, the greater increase in TNF-α levels in the nondependent lung and the smaller increase of MMP-2 concentration in the dependent lung may increase the susceptibility to develop PPC.

Intravenous lidocaine decreases tumor necrosis factor alpha expression both locally and systemically in pigs undergoing lung resection surgery.

BACKGROUND: Lung resection surgery is associated with an inflammatory reaction. The use of 1-lung ventilation (OLV) seems to increase the likelihood of this reaction. Different prophylactic and therapeutic measures have been investigated to prevent lung injury secondary to OLV. Lidocaine, a commonly used local anesthetic drug, has antiinflammatory activity. Our main goal in this study was to investigate the effect of IV lidocaine on tumor necrosis factor α (TNF-α) lung expression during lung resection surgery with OLV. METHODS: Eighteen pigs underwent left caudal lobectomy. The animals were divided into 3 groups: control, lidocaine, and sham. All animals received general anesthesia. In addition, animals in the lidocaine group received a continuous IV infusion of lidocaine during surgery (1.5 mg/kg/h). Animals in the sham group only underwent thoracotomy. Samples of bronchoalveolar lavage (BAL) fluid and plasma were collected before initiation of OLV, at the end of OLV, at the end of surgery, and 24 hours after surgery. Lung biopsy specimens were collected from the left caudal lobe (baseline) before surgery and from the mediastinal lobe and the left cranial lobe 24 hours after surgery. Samples were flash-frozen and stored to measure levels of the following inflammatory markers: interleukin (IL) 1ß, IL-2, IL-10, TNF-α, nuclear factor κB, monocyte chemoattractant protein-1, inducible nitric oxide synthase, and endothelial nitric oxide synthase. Markers of apoptosis (caspase 3, caspase 9, Bad, Bax, and Bcl-2) were also measured. In addition, levels of metalloproteinases and nitric oxide metabolites were determined in BAL fluid and in plasma samples. A nonparametric test was used to examine statistical significance. RESULTS: OLV caused lung damage with increased TNF-α expression in BAL, plasma, and lung samples. Other inflammatory (IL-1ß, nuclear factor κB, monocyte chemoattractant protein-1) and apoptosis (caspase 3, caspase 9, and BAX) markers were also increased. With the use of IV lidocaine there was a significant decrease in the levels of TNF-α in the same samples compared with the control group. Lidocaine administration also reduced the inflammatory and apoptotic changes observed in the control group. Hemodynamic values, blood gas values, and airway pressure were similar in all groups. CONCLUSIONS: Our results suggest that lidocaine can prevent OLV-induced lung injury through reduced expression of proinflammatory cytokines and lung apoptosis. Administration of lidocaine may help to prevent lung injury during lung surgery with OLV.