Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

High-flow nasal cannula oxygenation reduces postoperative hypoxemia in morbidly obese patients: a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are common in high-risk surgical patients. Postoperative ventilatory management may improve their outcome. Supplemental oxygen through a high-flow nasal cannula (HFNC) has become an alternative to classical oxygenation techniques, although the results published for postoperative patients are contradictory. We examined the efficacy of HFNC in postoperative morbidly obese patients who were ventilated intraoperatively with an open-lung approach (OLA). METHODS: We performed an open, two-arm, randomized controlled trial in 64 patients undergoing bariatric surgery (N.=32 in each arm) from May to November 2017 at the Hospital Clínico of Valencia. Patients were randomly assigned to receive HFNC oxygen therapy at the time of extubation or to receive conventional oxygen therapy, both applied during the first three postoperative hours. Intraoperatively, a recruitment maneuver and individualized positive end-expiratory pressure was applied in all patients. The primary outcome was postoperative hypoxemia. RESULTS: All patients were included in the final analysis. There were no significant differences between the baseline characteristics. Postoperative hypoxemia was less frequent in the HFNC group compared to those who received standard care (28.6% vs. 80.0%, relative risk [RR]: 0.35; 95%CI: 0.150-0.849, P=0.009). Prevalence of atelectasis was lower in the HFNC group (31% vs. 77%, RR: 0.39; 95%CI: 0.166-0.925, P=0.013). No severe PPCs were reported in any patient. CONCLUSIONS: Early application of HFNC in the operating room before extubation and during the immediate postoperative period decreases postoperative hypoxemia in obese patients after bariatric surgery who were intraoperatively ventilated using an OLA approach.

Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

BACKGROUND: Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. METHODS: Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. RESULTS: OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). CONCLUSIONS: Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02798133.

Neurosurgery planning in rodents using a magnetic resonance imaging assisted framework to target experimentally defined networks.

BACKGROUND AND OBJECTIVE: Meaningful targeting of brain structures is required in a number of experimental designs in neuroscience. Current technological developments as high density electrode arrays for parallel electrophysiological recordings and optogenetic tools that allow fine control of activity in specific cell populations provide powerful tools to investigate brain physio-pathology. However, to extract the maximum yield from these fine developments, increased precision, reproducibility and cost-efficiency in experimental procedures is also required. METHODS: We introduce here a framework based on magnetic resonance imaging (MRI) and digitized brain atlases to produce customizable 3D-environments for brain navigation. It allows the use of individualized anatomical and/or functional information from multiple MRI modalities to assist experimental neurosurgery planning and in vivo tissue processing. RESULTS: As a proof of concept we show three examples of experimental designs facilitated by the presented framework, with extraordinary applicability in neuroscience. CONCLUSIONS: The obtained results illustrate its feasibility for identifying and selecting functionally and/or anatomically connected neuronal population in vivo and directing electrode implantations to targeted nodes in the intricate system of brain networks.

Late evaluation of upper limb arterial flow in patients after long radial (PiCCO™) catheter placement.

BACKGROUND: The purpose of the study was to assess blood flow in the upper limb arteries after prolonged catheterization with long radial artery catheters (LRC) which reach the subclavian artery compared to catheterization with standard short radial artery catheters (SRC) and a group of upper limb flow without any catheter placement (NOCATH), with both SRC and NOCATH as control groups. METHODS: Prospective observational study with 20 patients admitted to ICU (40 upper limbs) with LRC and/or SRC inserted >48 h for hemodynamic monitoring. More than 45 days after catheter withdrawal, patients underwent a Doppler ultrasound study of both upper limbs. Arterial flows of arms with LRC (FlowLRC) were compared with arterial flows of arms with SRC (FlowSRC) and those without any catheter (FlowNOCATH). RESULTS: Flow in the ulnar, brachial, and subclavian arteries did not show any significant difference between the two types of catheters. The only significant difference was in the radial arteries, showing a lower mean flow in the arms with LRC than in the arms with SRC (2.2 vs. 8.5 cc/min; p = 0.041). Flow reduction in the radial artery (74%) in the arms with LRC compared to the SRC arms showed a tendency to increase ulnar flow as a compensatory mechanism. None of the patients with LRC included in our study had any ischemic events, in spite of observing complete flow occlusion in three radial arteries (18%) from the Doppler study. CONCLUSIONS: In this sample, the use of PiCCO long radial catheters reaching the subclavian artery did not produce chronic significant changes in brachial or subclavian flows. However, LRC produces a significant reduction in radial flow and a tendency to increase ulnar flow. When comparing these blood flow changes with those produced by SRC use, only the radial flow reduction was significantly lower, whereas the other arterial flow changes did not significantly differ.

Protection strategies during cardiopulmonary bypass: ventilation, anesthetics and oxygen.

PURPOSE OF REVIEW: To provide an update of research findings regarding the protection strategies utilized for patients undergoing cardiopulmonary bypass (CPB), including perioperative ventilatory strategies, different anesthetic regimens, and inspiratory oxygen fraction. The article will review and comment on some of the most important findings in this field to provide a global view of strategies that may improve patient outcomes by reducing inflammation. RECENT FINDINGS: Postoperative complications are directly related to ischemia and inflammation. The application of lung-protective ventilation with lower tidal volumes and higher positive end-expiratory pressure reduces inflammation, thereby reducing postoperative pulmonary complications. Although inhalation anesthesia has clear cardioprotective effects compared with intravenous anesthesia, several factors can interfere to reduce cardioprotection. Hyperoxia up to 0.8 FiO(2) may confer benefits without increasing oxidative stress or postoperative pulmonary complications. During the early postoperative period, inhalation anesthesia prior to extubation and the application of preventive noninvasive ventilation may reduce cardiac and pulmonary complications, improving patients' outcomes. SUMMARY: Lung-protective mechanical ventilation, inhalation anesthesia, and high FiO(2) have the potential to reduce postoperative complications in patients undergoing CPB; however, larger, well powered, randomized control trials are still needed.

Effects of different flow patterns and end-inspiratory pause on oxygenation and ventilation in newborn piglets: an experimental study.

BACKGROUND: Historically, the elective ventilatory flow pattern for neonates has been decelerating flow (DF). Decelerating flow waveform has been suggested to improve gas exchange in the neonate when compared with square flow (SF) waveform by improving the ventilation perfusion. However, the superiority of DF compared with SF has not yet been demonstrated during ventilation in small infants. The aim of this study was to compare SF vs. DF, with or without end-inspiratory pause (EIP), in terms of oxygenation and ventilation in an experimental model of newborn piglets. METHODS: The lungs of 12 newborn Landrace/LargeWhite crossbred piglets were ventilated with SF, DF, SF-EIP and DF-EIP. Tidal volume (VT), inspiratory to expiratory ratio (I/E), respiratory rate (RR), and FiO2 were keep constant during the study. In order to assure an open lung during the study while preventing alveolar collapse, a positive end-expiratory pressure (PEEP) of 6 cmH2O was applied after a single recruitment maneuver. Gas exchange, lung mechanics and hemodynamics were measured. RESULTS: The inspiratory flow waveform had no effect on arterial oxygenation pressure (PaO2) (276 vs. 278 mmHg, p = 0.77), alveolar dead space to alveolar tidal volume (VDalv/VTalv) (0.21 vs. 0.19 ml, p = 0.33), mean airway pressure (Pawm) (13.1 vs. 14.0 cmH2O, p = 0.69) and compliance (Crs) (3.5 vs. 3.5 ml cmH2O(-1), p = 0.73) when comparing SF and DF. A short EIP (10%) did not produce changes in the results. CONCLUSION: The present study showed that there are no differences between SF, DF, SF-EIP and DF-EIP in oxygenation, ventilation, lung mechanics, or hemodynamics in this experimental model of newborn piglets with healthy lungs.

Robustness of nanofiltration for increasing the viral safety margin of biological products.

In this study, the virus-removal capacity of nanofiltration was assessed using validated laboratory scale models on a wide range of viruses (pseudorabies virus; human immunodeficiency virus; bovine viral diarrhea virus; West Nile virus; hepatitis A virus; murine encephalomyocarditis virus; and porcine parvovirus) with sizes from 18 nm to 200 nm and applying the different process conditions existing in a number of Grifols' plasma-derived manufacturing processes (thrombin, α1-proteinase inhibitor, Factor IX, antithrombin, plasmin, intravenous immunoglobulin, and fibrinogen). Spiking experiments (n = 133) were performed in process intermediate products, and removal was subsequently determined by infectivity titration. Reduction Factor (RF) was calculated by comparing the virus load before and after nanofiltration under each product purification condition. In all experiments, the RFs were close to or greater than 4 log10 (>99.99% of virus elimination). RF values were not significantly affected by the process conditions within the limits assayed (pH, ionic strength, temperature, filtration ratio, and protein concentration). The virus-removal capacity of nanofiltration correlated only with the size of the removed agent. In conclusion, nanofiltration, as used in the manufacturing of several Grifols' products, is consistent, robust, and not significantly affected by process conditions.

Sevoflurane, but not propofol, reduces the lung inflammatory response and improves oxygenation in an acute respiratory distress syndrome model: a randomised laboratory study.

CONTEXT: Acute respiratory distress syndrome is characterised by activation of the inflammatory cascade. The only treatment that reduces the mortality rate associated with this syndrome is lung protective ventilation, which requires sedation of patients. Sedation in critical care units is usually induced intravenously, although there is reason to believe that inhaled anaesthetics are a suitable alternative. Sevoflurane has recently been shown to modulate the lung inflammatory response in a model of lung injury more favourably than propofol. OBJECTIVE: The goal of this study was to confirm whether or not sevoflurane is more effective than propofol in ameliorating the inflammatory response in an animal model of acute respiratory distress syndrome. DESIGN: A prospective, randomised, controlled study. SETTING: Research foundation laboratory at the Hospital Clínico Universitario, Valencia, Spain. EXPERIMENTAL ANIMALS: Sixteen Landrace/large white crossbred pigs weighing 30 to 45 kg. INTERVENTIONS: Animals were allocated randomly to one of two groups: one sedated with intravenous propofol 5 to 7 mg kg h (group P) and the other with sevoflurane, administered using an AnaConDa device to obtain an end-tidal concentration of 1.5% (group S). Monitoring, lung protective ventilation and anaesthetic management were identical in both groups. MAIN OUTCOME MEASURES: The PaO2/FiO2 ratio and cytokine concentrations in bronchoalveolar lavage specimens were determined at 10, 150 and 240 min after confirmation of acute respiratory distress syndrome (PaO2/FiO2 <26.7 kPa). RESULTS: At 240 min, median and interquartile range (IQR) concentrations of cytokines in bronchial lavage specimens in group S were lower than those in group P [interleukin-1ß (IL-1ß) 53, IQR 16-140 vs. 311, IQR 183-637 pg ml, P = 0.04; tumour necrosis factor-α 347, IQR 161-433 vs. 552, IQR 475-649 pg ml, P = 0.04; and IL-6 101, IQR 76-282 vs. 580, IQR 369-701 pg ml, P = 0.03]. The polymorphonuclear neutrophil count was also lower in group S (P = 0.007), which also had a higher PaO2/FiO2 ratio. TRIAL REGISTRATION: GE-015/09. CONCLUSION: In an animal model of acute respiratory distress syndrome, sevoflurane ameliorates the lung inflammatory response and improves oxygenation to a greater extent than propofol.