Rationale and study design for an individualised perioperative open-lung ventilatory strategy with a high versus conventional inspiratory oxygen fraction (iPROVE-O2) and its effects on surgical site infection: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is a serious postoperative complication that increases morbidity and healthcare costs. SSIs tend to increase as the partial pressure of tissue oxygen decreases: previous trials have focused on trying to reduce them by comparing high versus conventional inspiratory oxygen fractions (FIO2) in the perioperative period but did not use a protocolised ventilatory strategy. The open-lung ventilatory approach restores functional lung volume and improves gas exchange, and therefore it may increase the partial pressure of tissue oxygen for a given FIO2. The trial presented here aims to compare the efficacy of high versus conventional FIO2 in reducing the overall incidence of SSIs in patients by implementing a protocolised and individualised global approach to perioperative open-lung ventilation. METHODS AND ANALYSIS: This is a comparative, prospective, multicentre, randomised and controlled two-arm trial that will include 756 patients scheduled for abdominal surgery. The patients will be randomised into two groups: (1) a high FIO2 group (80% oxygen; FIO2 of 0.80) and (2) a conventional FIO2 group (30% oxygen; FIO2 of 0.30). Each group will be assessed intra- and postoperatively. The primary outcome is the appearance of postoperative SSI complications. Secondary outcomes are the appearance of systemic and pulmonary complications. ETHICS AND DISSEMINATION: The iPROVE-O2 trial has been approved by the Ethics Review Board at the reference centre (the Hospital Clínico Universitario in Valencia). Informed consent will be obtained from all patients before their participation. If the approach using high FIO2 during individualised open-lung ventilation decreases SSIs, use of this method will become standard practice for patients scheduled for future abdominal surgery. Publication of the results is anticipated in early 2019. TRIAL REGISTRATION NUMBER: NCT02776046; Pre-results.

Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

BACKGROUND: During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. METHODS: We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). RESULTS: Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10-146), 66 (14-118), and 58 (12-104), respectively. CONCLUSIONS: Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.

The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study.

OBJECTIVE: To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO2) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. DESIGN: Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. SETTING: Postanaesthetic care unit in a tertiary hospital in Spain. PARTICIPANTS: Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. INTERVENTION: The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO2 was ≤96% and negative when SpO2 was ≥97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. MAIN OUTCOME MEASURES: The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. RESULTS: The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). CONCLUSION: The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis. TRIAL REGISTRATION: NCT02650037.

Expression of aquaporins 1 and 5 in a model of ventilator-induced lung injury and its relation to tidal volume.

NEW FINDINGS: What is the central question of this study? Although different studies have attempted to find factors that influence the expression of aquaporins (AQPs) in the lung in different situations, to date no research group has explored the expression of AQP1 and AQP5 jointly in rats mechanically ventilated with different tidal volumes in a model of ventilator-induced lung injury. What is the main finding? Mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases. We analysed the expression of aquaporins 1 and 5 and its relation with tidal volume in a model of ventilator-induced lung injury. Forty-two rats were used. Six non-ventilated animals were killed (control group). The remaining rats were ventilated for 2 h with different tidal volumes (group 7ML with 7 ml kg-1 and group 20ML with 20 ml kg-1 ) and a respiratory rate of 90 breaths min-1 . Lung oedema was measured, and the expression of AQP1 and AQP5 was determined by Western immunoblotting and measurement of mRNA. Lung oedema and alveolar-capillary membrane permeability were significantly increased in the animals of group 20ML compared with the control group. Expression of AQP1 was decreased in groups 7ML and 20ML compared with the control group. In conclusion, mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases.

The effects of advanced monitoring on hemodynamic management in critically ill patients: a pre and post questionnaire study.

In critically ill patients, many decisions depend on accurate assessment of the hemodynamic status. We evaluated the accuracy of physicians' conventional hemodynamic assessment and the impact that additional advanced monitoring had on therapeutic decisions. Physicians from seven European countries filled in a questionnaire in patients in whom advanced hemodynamic monitoring using transpulmonary thermodilution (PiCCO system; Pulsion Medical Systems SE, Feldkirchen, Germany) was going to be initialized as part of routine care. The collected information included the currently proposed therapeutic intervention(s) and a prediction of the expected transpulmonary thermodilution-derived variables. After transpulmonary thermodilution measurements, physicians recorded any changes that were eventually made in the original therapeutic plan. A total of 315 questionnaires pertaining to 206 patients were completed. The mean difference (±standard deviation; 95 % limits of agreement) between estimated and measured hemodynamic variables was -1.54 (±2.16; -5.77 to 2.69) L/min for the cardiac output (CO), -74 (±235; -536 to 387) mL/m(2) for the global end-diastolic volume index (GEDVI), and -0.5 (±5.2; -10.6 to 9.7) mL/kg for the extravascular lung water index (EVLWI). The percentage error for the CO, GEDVI, and EVLWI was 66, 64, and 95 %, respectively. In 54 % of cases physicians underestimated the actual CO by more than 20 %. The information provided by the additional advanced monitoring led 33, 22, 22, and 13 % of physicians to change their decisions about fluids, inotropes, vasoconstrictors, and diuretics, respectively. The limited clinical ability of physicians to correctly assess the hemodynamic status, and the significant impact that more physiological information has on major therapeutic decisions, support the use of advanced hemodynamic monitoring in critically ill patients.

La elevación del índice de agua pulmonar extravascular como factor predictivo del fracaso de la presión continua en la vía aérea con casco (CPAP-Helmet) en pacientes con insuficiencia respiratoria aguda tras intervención quirúrgica mayor / Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery

Introducción: La ventilación no invasiva (VNI) se utiliza cada vez más para la prevención y el tratamiento de las complicaciones y la insuficiencia respiratorias. Algunos pacientes ingresan en las unidades de reanimación postanestésica portando monitores hemodinámicos avanzados que permiten cuantificar el agua pulmonar extravascular (EVLW) mediante la técnica de termodilución transpulmonar y la permeabilidad vascular pulmonar (PVP), parámetros que permiten obtener información sobre el edema pulmonar. Objetivo: El objetivo de este estudio fue determinar si el índice de EVLW y el índice de la PVP pueden pronosticar el fracaso (intubación) o el éxito (no intubación) en pacientes que desarrollan insuficiencia respiratoria aguda (IRA) durante el período postoperatorio de una intervención quirúrgica mayor abdominal y cuyo tratamiento de primera línea es la presión positiva continua en la vía aérea (CPAP) administrada mediante casco (CPAP-Helmet). Métodos: Se monitorizaron las variables hemodinámicas, el índice de agua pulmonar extravascular (EVLWI) y el índice de permeabilidad vascular pulmonar (PVPI) mediante un dispositivo de monitorización hemodinámica de termodilución transpulmonar (PiCCO(TM)), antes y después de la aplicación de la CPAP. Resultados: En un 66% de los pacientes con CPAP-Helmet se evitó la intubación. En dichos pacientes, el cociente PaO2/FiO2 aumentó de forma significativa (303,33 ± 65,2 vs. 141,6 ± 14,6, p < 0,01) tras la primera hora de aplicación de la CPAP. Antes de iniciar la CPAP-Helmet los valores de EVLWI y PVPI eran significativamente inferiores en los pacientes no intubados (EVLWI 8,6 ± 1,08 vs. 11,8 ± 0,99 ml/kg de peso corporal ideal (PCI), p < 0,01 y PVPI 1,7 ± 0,56 vs. 3,0 ± 0,88, p < 0,01). Se establecieron unos valores de corte óptimos de 9,5 para el EVLWI y de 2,45 para el PVPI (sensibilidad de 0,7; especificidad de 0,9, p < 0,01). Conclusión: En este tipo de pacientes, los parámetros fisiológicos que pronosticaron el fracaso de la CPAP-Helmet con mayor precisión fueron el EVLWI y el PVPI previos al inicio de la CPAP-Helmet, el cociente PaO2/FiO2 y la frecuencia respiratoria tras una hora de CPAP

Introduction: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. Aim: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. Methods: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO(TM)) before and after the application of CPAP. Results: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33 ± 65.2 vs. 141.6 ± 14.6, P < .01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6 ± 1.08 vs. 11.8 ± 0.99 ml/kg IBW, P < .01 and PVPI 1.7 ± 0.56 vs. 3.0 ± 0.88, P < .01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P < .01). Conclusion: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. METHODS: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. TRIAL REGISTRATION: Registered on 5 June 2014 with identification no. NCT02158923 .

Elevated Extravascular Lung Water Index (ELWI) as a Predictor of Failure of Continuous Positive Airway Pressure Via Helmet (Helmet-CPAP) in Patients With Acute Respiratory Failure After Major Surgery.

INTRODUCTION: NIV is increasingly used for prevention and treatment of respiratory complications and failure. Some of them are admitted to the PACU with advanced hemodynamic monitors which allow quantification of Extravascular Lung Water (EVLW) by transpulmonary thermodilution technique (TPTD) and Pulmonary Vascular Permeability (PVP) providing information on lung edema. AIM: The objective of this study was to ascertain if EVLW Index and PVP Index may predict failure (intubation) or success (non-intubation) in patients developing acute respiratory failure (ARF) in the postoperative period following major abdominal surgery, where the first line of treatment was non-invasive continuous positive airway pressure via a helmet. METHODS: Hemodynamic variables, EVLWI and PVPI were monitored with a transpulmonary thermodilution hemodynamic monitor device (PiCCO™) before and after the application of CPAP. RESULTS: Avoidance of intubation was observed in 66% of patients with Helmet-CPAP. In these patients after the first hour of application of CPAP, PaO2/FiO2 ratio significantly increased (303.33±65.2 vs. 141.6±14.6, P<.01). Before starting Helmet-CPAP values of EVLWI and PVPI were significantly lower in non-intubated patients (EVLWI 8.6±1.08 vs. 11.8±0.99ml/kg IBW, P<.01 and PVPI 1.7±0.56 vs. 3.0±0.88, P<.01). An optimal cut-off value for EVLWI was established at 9.5, and at 2.45 for PVPI (sensitivity of 0.7; specificity of 0.9, P<.01). CONCLUSION: In this type of patient the physiological parameters that predict the failure of Helmet-CPAP with the greatest accuracy were the value of the EVLWI and PVPI before Helmet-CPAP institution and the PaO2/FiO2 ratio and the respiratory rate after one hour of CPAP.

Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance.

INTRODUCTION: The stress index (SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). METHODS: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. RESULTS: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg(-1), P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat- and SI-groups respectively, without differences in overinflated lung areas at end- inspiration in both groups. Cytokines and histopathology showed no differences. CONCLUSIONS: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

Insulin infusion therapy in critical care patients: regular insulin vs short-acting insulin. A prospective, crossover, randomized, multicenter blind study.

INTRODUCTION: The aim of this multicenter, prospective, randomized, crossover trial is to compare, in critical care patients receiving insulin infusion therapy (IIT), the pharmacodynamic of Humulin insulin (Hlin), currently used as "standard of care," and Humalog insulin (Hlog), a shorter acting insulin formulation. This was measured as extent and duration of the carryover effect of insulin treatment, with the latter calculated as ratio between blood glucose concentration (BGC) reduction during and after IIT. MATERIALS AND METHODS: Twenty-eight patients treated in an intensive care unit and receiving full nutritional support were randomly assigned to Hlin or Hlog as first treatment. Insulin was infused at a constant rate in patients presenting with BGC greater than or equal to 180 mg/dL (0.04 U/kg per hour) and was discontinued when BGC was less than or equal to 140 mg/dL (therapeutic BGC drop). Further reductions in BGC after discontinuation of insulin infusion were recorded (postinfusional BGC drop). During the study period, whole blood BGC was measured every 30 minutes. A minimal 6-hour washout interval was maintained between treatments with the 2 types of insulin. The primary end point was the extent (calculated as ratio between the therapeutic BGC drop and the postinfusional BGC drop) and duration of the carryover effect. RESULTS: Treatment with Hlog, as compared with Hlin, was associated with a less profound carryover effect as well as a briefer duration of carryover (median, 0.40 vs 0.62; P < .001; median, 1 vs 1.5 hours; P < .001). CONCLUSIONS: The use of constant Hlog infusion for IIT, when compared with Hlin at the same dose, is associated with a less profound carryover effect on BGC after discontinuation of IIT, a briefer duration of carryover, a faster BGC drop during infusion, and a quicker BGC rise after discontinuation. These characteristics suggest that Hlog IIT may be preferable for use in critically ill patients.

Increased expression of AQP 1 and AQP 5 in rat lungs ventilated with low tidal volume is time dependent.

BACKGROUND AND GOALS: Mechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats. METHODS: 25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups. RESULTS: Lung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples. CONCLUSION: In lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV.

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation.

BACKGROUND: We investigated whether individualized positive end-expiratory pressure (PEEP) improves oxygenation, ventilation, and lung mechanics during one-lung ventilation compared with standardized PEEP. METHODS: Thirty patients undergoing thoracic surgery were randomly allocated to the study or control group. Both groups received an alveolar recruitment maneuver at the beginning and end of one-lung ventilation. After the alveolar recruitment maneuver, the control group had their lungs ventilated with a 5 cm·H2O PEEP, while the study group had their lungs ventilated with an individualized PEEP level determined by a PEEP decrement trial. Arterial blood samples, lung mechanics, and volumetric capnography were recorded at multiple timepoints throughout the procedure. RESULTS: The individualized PEEP values in study group were higher than the standardized PEEP values (10 ± 2 vs 5 cm·H2O; P < 0.001). In both groups, arterial oxygenation decreased when bilateral-lung ventilation was switched to one-lung ventilation and increased after the alveolar recruitment maneuver. During one-lung ventilation, oxygenation was maintained in the study group but decreased in the control group. After one-lung ventilation, arterial oxygenation was significantly higher in the study group (306 vs 231 mm·Hg, P = 0.007). Static compliance decreased in both groups when bilateral-lung ventilation was switched to one-lung ventilation. Static compliance increased significantly only in the study group (P < 0.001) after the alveolar recruitment maneuver and optimal PEEP adjustment. The alveolar recruitment maneuver did not decrease cardiac index in any patient. CONCLUSIONS: During one-lung ventilation, the improvements in oxygenation and lung mechanics after an alveolar recruitment maneuver were better preserved by ventilation by using individualized PEEP with a PEEP decrement trial than with a standardized 5 cm·H2O of PEEP.

Oxidative stress injury after on-pump cardiac surgery: effects of aortic cross clamp time and type of surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) in on-pump cardiac surgery can have harmful systemic effects, triggered in part by radical oxygen species (ROS) produced by ischemia-reperfusion in the heart and the lung. We determined the relationship between levels of oxidative stress markers (8-isoprostane and nitrites/nitrates) in plasma with aortic cross clamp duration in patients undergoing cardiac surgery with CPB. METHODS: Thirty patients with CPB were studied: 14 with coronary artery bypass graft surgery and 16 with valve surgery. Plasma levels of 8-isoprostane, and nitrites/nitrates were measured over a 24-hour time course: before (T0) and after CPB: 5 minutes (T1), 1 hour (T2), 12 hours (T3), and 24 hours (T4). RESULTS: Plasma levels of 8-isoprostane and nitrites/nitrates increased early after CPB, with a subsequent and progressive decline. Levels of oxidative stress markers in T1-T2 were positively correlated with the aortic cross clamp duration. Aortic cross clamp duration times greater than 50 minutes were correlated with higher oxidative stress levels. There were no significant differences in the levels of oxidative stress markers between surgery types. CONCLUSION: Cardiac surgery with CPB is associated with an early increase of oxidative stress markers in systemic blood. Aortic cross clamp duration is positively correlated with oxidative stress injury.

Different oxidative stress marker levels in blood from the operated knee or the antecubital vein in patients undergoing knee surgery: a tourniquet-induced ischemia-reperfusion model.

BACKGROUND: In knee surgery a tourniquet is usually applied in order to provide a bloodless surgical field. This study aims to compare, in a tourniquet-induced ischemia-reperfusion model, the glutathione oxidation and lipid peroxidation in two different blood sources: an operated knee drainage tube or the antecubital vein. METHODS: Thirty-two patients undergoing total knee replacement were studied. We measured reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and other metabolic parameters in the blood from the operated knee (17 patients), or from the antecubital vein (15 patients) before tourniquet inflation (T(0)) and after tourniquet release at different times: 3, 10, and 60 minutes (T(1), T(2), and T(3), respectively). RESULTS: We have found an early increase of approximately 100% in GSSG and MDA blood levels coinciding with a decrease in GSH levels at T(1)-T(3) in blood from the operated knee. These changes were also observed in blood from the antecubital vein at T(1) and T(2), but at lower levels than in blood from the operated knee. CONCLUSIONS: There is an intense glutathione oxidation and lipid peroxidation in the operated knee after tourniquet deflation. The surgical drainage is a good source of blood for the determination of biomarkers in a tourniquet-induced ischemia-reperfusion model, because changes are observed more early and it is more direct than another source of systemic blood.

Tratamiento con equinocandinas en un paciente crítico sometido a técnica continua de reemplazo renal / Echinocandins in a critically ill patient during continuous venovenous renal replacement

Los pacientes críticos con candidiasis invasiva (CI) suelen presentar con frecuencia insuficiencia renal, por lo que en ocasiones requieren técnicas continuas de reemplazo renal (TCRR). Las equinocandinas son la primera opción en el tratamiento de la CI en el paciente crítico con enfermedad moderada o grave. Debido a su perfil farmacocinético y farmacodinámico (FC/FD), su eliminación durante las TCRR debe ser despreciable, sin que sea necesario ajustar sus dosis, como así lo indican los escasos estudios clínicos que hay al respecto. Caso clínico. Varón de 66 años intervenido por peritonitis secundaria a dehiscencia de sutura intestinal, que ingresa en la unidad de cuidados intensivos con cuadro clínico compatible con shock séptico y síndrome de disfunción multiorgánica (SDMO), por lo que se inicia TCRR. Al presentar factores de riesgo de CI, y al haberse observado levaduras en el líquido peritoneal, se pauta anidulafungina a dosis habituales. Se opta por anidulafungina debido a la insuficiencia hepática del paciente. En los cultivos del líquido peritoneal y exudado anal, se aísla Candida albicans sensible a fluconazol. No obstante, se decide mantener la anidulafungina debido al SDMO y al aclaramiento que presenta el fluconazol durante las TCRR. La evolución del paciente es favorable, y es trasladado a sala de hospitalización a los 20 días de la cirugía. Conclusiones. Dado su perfil FC/FD, las equinocandinas podrían administrarse con seguridad a dosis habituales en el paciente crítico con CI sometido a TCRR. No obstante, se requieren nuevos estudios que aporten más información para reforzar esta recomendación. El metabolismo extrahepático de la anidulafungina la hace especialmente interesante frente al resto de equinocandinas y otros antifúngicos en pacientes con diferentes grados de insuficiencia hepática(AU)

Background. Critically ill patients with invasive candidiasis (IC) often suffer renal failure, which sometimes requires continuous renal replacement techniques (CRRT). Echinocandins are the first line treatment for IC in critically ill patients with mild or severe illness. Their elimination during CRRT should be negligible due to their pharmacokinetic and pharmacodynamic (PK/PD) profile, and dose adjustment are not needed, as suggested by the few reported clinical studies. Clinical case. This is the case of a 66 year old male who underwent surgery due to peritonitis secondary to intestinal suture dehiscence. The patient was admitted to ICU with septic shock symptoms and multiple organ dysfunction syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual dosage due to the IC risk factors present, and the observation of yeasts in the peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered by the patient. An isolate of Candida albicans susceptible to fluconazole was cultured from peritoneal fluid and rectal exudates. However, anidulafungin was maintained due to the MODS and observing the clearance of fluconazole during CRRT. The patient's condition improved favourably, being moved to the surgical ward 20 days after the surgery. Conclusions. Echinocandins, due to their PK/PD profile, could be safely given at usual doses to critically ill patients undergoing CRRT. However, new studies are required to strengthen this recommendation. Its extrahepatic metabolism makes anidulafungin a more attractive option among echinocandins and other antifungals when used in patients with different degrees of hepatic failure(AU)

[Echinocandins in a critically ill patient during continuous venovenous renal replacement]. / Tratamiento con equinocandinas en un paciente crítico sometido a técnica continua de reemplazo renal.

BACKGROUND: Critically ill patients with invasive candidiasis (IC) often suffer renal failure, which sometimes requires continuous renal replacement techniques (CRRT). Echinocandins are the first line treatment for IC in critically ill patients with mild or severe illness. Their elimination during CRRT should be negligible due to their pharmacokinetic and pharmacodynamic (PK/PD) profile, and dose adjustment are not needed, as suggested by the few reported clinical studies. CLINICAL CASE: This is the case of a 66 year old male who underwent surgery due to peritonitis secondary to intestinal suture dehiscence. The patient was admitted to ICU with septic shock symptoms and multiple organ dysfunction syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual dosage due to the IC risk factors present, and the observation of yeasts in the peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered by the patient. An isolate of Candida albicans susceptible to fluconazole was cultured from peritoneal fluid and rectal exudates. However, anidulafungin was maintained due to the MODS and observing the clearance of fluconazole during CRRT. The patient's condition improved favourably, being moved to the surgical ward 20 days after the surgery. CONCLUSIONS: Echinocandins, due to their PK/PD profile, could be safely given at usual doses to critically ill patients undergoing CRRT. However, new studies are required to strengthen this recommendation. Its extrahepatic metabolism makes anidulafungin a more attractive option among echinocandins and other antifungals when used in patients with different degrees of hepatic failure.

Hyperoxia during colon surgery is associated with a reduction of xanthine oxidase activity and oxidative stress in colonic mucosa.

BACKGROUND: Gut manipulation during surgery may induce local oxidative stress. Supplemental inspired oxygen increases arterial and tissue oxygen partial pressures. This study examined whether a 0.80 fraction of inspired oxygen (FiO(2)) attenuates the oxidative stress, reducing xanthine oxidase (XO) activity in colonic mucosa as a possible mechanism during colon surgery. METHODS: Twenty-four cancer patients who underwent elective colon resection were randomly assigned to either 0.30 FiO(2) or 0.80 FiO(2) during surgery. Malondialdehyde (MDA) and oxidized glutathione (GSSG) levels were measured in blood plasma. We also determined the enzymatic activities of XO and xanthine dehydrogenase (XDH) in the colonic mucosa after resection of the piece of colon. RESULTS: Oxygen partial pressure in arterial blood was higher in the 0.80 FiO(2) group than in the 0.30 FiO(2) group (P<0.001). MDA and GSSG levels measured in blood plasma as well as MDA measured in colonic mucosa were lower in the 0.80 FiO(2) group than in the 0.30 FiO(2) group. Otherwise, XO enzymatic activity and XO/(XO+XDH) ratio in colonic mucosa were lower in the 0.80 FiO(2) group than in the 0.30 FiO(2) group. CONCLUSIONS: XO may be a major source of reactive oxygen species in patients during colon surgery. Inspiring 0.80 oxygen during colon surgery increases arterial partial pressure and this treatment was associated with reduced XO activity and levels of oxidative stress in colonic mucosa.

Epidural anesthesia for laminectomy lead placement in spinal cord stimulation.

BACKGROUND: Spinal cord stimulation (SCS) is used to treat chronic pain and requires an awake patient for optimized lead positioning to locate paresthesias. Epidural anesthesia may be a suitable anesthetic but has not been evaluated. METHODS: We performed an open-label, prospective, observational, single-center study to evaluate the safety and efficacy of laminectomy lead placement under epidural anesthesia for the treatment of neuropathic chronic pain. RESULTS: The results in our study demonstrate that epidural anesthesia is a suitable technique for SCS lead implant. CONCLUSIONS: This is the first study using epidural anesthesia for SCS lead implants by laminectomy. The technique seems to be safe and effective.