Inhomogeneity of lung parenchyma during the open lung strategy: a computed tomography scan study.

RATIONALE: The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung). OBJECTIVES: We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung. METHODS: Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol. MEASUREMENTS AND MAIN RESULTS: During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75-117%) and 48% (41-63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1-28% of total lung volume; P < 0.01) and open lung protocol ventilation at end-inspiration (by 1-15% of total lung volume; P < 0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P < 0.01). CONCLUSIONS: Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.

Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening. Isolated perfused rat hearts were subjected to global ischemia and reperfusion in the presence or absence of melatonin in a Langerdoff apparatus. Melatonin treatment significantly improves the functional recovery of Langerdoff hearts on reperfusion, reduces the infarct size, and decreases necrotic damage as shown by the reduced release of lactate dehydrogenase. Mitochondria isolated from melatonin-treated hearts are less sensitive than mitochondria from reperfused hearts to MPTP opening as demonstrated by their higher resistance to Ca(2+). Similar results were obtained following treatment of ischemic-reperfused rat heart with cyclosporine A, a known inhibitor of MPTP opening. In addition, melatonin prevents mitochondrial NAD(+) release and mitochondrial cytochrome c release and, as previously shown, cardiolipin oxidation associated with ischemia-reperfusion. Together, these results demonstrate that melatonin protects heart from reperfusion injury by inhibiting MPTP opening, probably via prevention of cardiolipin peroxidation.

Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study.

OBJECTIVE: Postoperative acute deterioration in renal function, producing oliguria and/or increase in serum creatinine, is one of the most serious complication in surgical patients. Most cases are due to renal hypoperfusion as a consequence of systemic hypotension, hypovolemia, and cardiac dysfunction. Although some evidence suggests that perioperative monitoring and manipulation of oxygen delivery by volume expansion and inotropic drugs may decrease mortality in surgical patients, no study analyzed this approach on postoperative renal dysfunction. The objective of this investigation is to perform a meta-analysis on the effects of perioperative hemodynamic optimization on postoperative renal dysfunction. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION: A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through January 2008 was conducted and 20 studies met the inclusion criteria (4220 participants). Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by random-effects model. DATA SYNTHESIS: Postoperative acute renal injury was significantly reduced by perioperative hemodynamic optimization when compared with control group (OR 0.64; CI 0.50-0.83; p = 0.0007). Perioperative optimization was effective in reducing renal injury defined consistently with risk, injury, failure, and loss and end-stage kidney disease and Acute Kidney Injury Network classifications, and in studies defining renal dysfunction by serum creatinine and/or need of renal replacement therapy only (OR 0.66; CI 0.50-0.88; p = 0.004). The occurrence of renal dysfunction was reduced when treatment started both preoperatively and intraoperatively or postoperatively, was performed in high-risk patients, and was obtained by fluids and inotropes. Mortality was significantly reduced in treatment group (OR 0.50; CI 0.31-0.80; p = 0.004), but statistical heterogeneity was observed. CONCLUSIONS: Surgical patients receiving perioperative hemodynamic optimization are at decreased risk of renal impairment. Because of the impact of postoperative renal complications on adverse outcome, efforts should be aimed to identify patients and surgery that would most benefit from perioperative optimization.

Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy.

OBJECTIVE: Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs. DESIGN: Prospective randomized study. SETTING: University animal laboratory. SUBJECTS: Adult male 129/Sv mice. INTERVENTIONS: Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8-10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14-16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index. MEASUREMENT AND MAIN RESULT: Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001). CONCLUSION: Low stretch strategies provide similar attenuation of VILI. However, low stretch/lung rest strategy is associated to less apoptosis and more ultrastructural evidence of cell damage possibly through MAPKs-mediated pathway.

Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels.

1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. 2. Mechanically ventilated rats were exposed to normoxia (Fi O2 = 0.3) or hyperoxia (Fi O2 = 1.0) for 30 min and pH, P CO2, PO2, heart rate, airway and blood pressure were measured at baseline and after 30 min mechanical ventilation. Isolated hearts were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct size and left ventricular end-diastolic pressure (LVEDP), developed pressure (LVDP) and coronary flow (CF) were measured. In order to investigate the role of ROS and KATP channels within the mechanism leading to cardioprotection, the free radical scavenger N-acetylcysteine (NAC; 150 mg/kg) was infused in mechanically ventilated rats and the KATP channel blockers glibenclamide (200 mmol/L) or 5-hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before ischaemia. 3. No differences were detected in P CO2, pH, heart rate, airway and blood pressure between the groups. However, the PO2 in hyperoxic groups was significantly higher compared with that in normoxic groups (P < 0.01). After 30 min ischaemia, we found that hyperoxic preconditioning significantly improved CF (P < 0.01), LVDP (P < 0.01) and LVEDP (P < 0.01) and reduced the extent of infarct size in the reperfused heart compared with the normoxic group (P < 0.01). When rats were pretreated either with NAC before hyperoxic ventilation or with K(ATP) channel blockers before ischaemia, myocardial protection was abolished. 4. Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial reperfusion injury. This is likely to occur through the induction of oxidative stress, which leads to myocyte mitoKATP channel opening.

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion.

Several recent works have shown that a brief ischemia applied during the onset of reperfusion (postconditioning) is cardioprotective in different animal models and that the early minutes of reperfusion are critical to its cardioprotection. This effect has been related to prevention of oxidative stress, but mechanisms have not been clearly demonstrated. The present study tested the hypothesis that mitochondria play a central role in peroxide production and oxidative stress during reperfusion and are responsible for the protective effect of postconditioning. Isolated perfused rat hearts were subjected to complete global ischemia for 45 min and reperfused for 40 min. Normoxic group was reperfused with a Krebs-Henseleit solution with the preischemic pO2 level (600 mmHg); in the "hypoxic group," normoxic reperfusion was preceded by 3 min with 150 mmHg pO2. Reperfusion was stopped at 3 and 40 min. The rate of hydroperoxide production, GSH, GSSG, and carbonyl protein levels were measured in mitochondria at 3 min and at the end of reperfusion. GSH and GSSG were also measured in tissue. Hemodinamic function was monitored during the experiment. LVEDp increased and LVDp decreased in the normoxic group but not in the hypoxic group. The rate of mitochondrial peroxide production was higher in normoxic than in the hypoxic group 3 min after reperfusion and at its conclusion. Accordingly, GSH was oxidized in normoxic but not in hypoxic hearts. Mitochondria carbonyl proteins were significantly higher in normoxic than in the hypoxic group at the end of reperfusion. In this model, 1) hypoxic reperfusion at the onset of reperfusion reduces myocardial injury; 2) the major rate of mitochondrial peroxide production is 3 min after the onset of reperfusion; 3) cardioprotection of postconditioning correlates with reduced mitochondria peroxide production and prevention of GSH oxidation.

Jaundice in critical illness: promoting factors of a concealed reality.

OBJECTIVE: In critical illness, liver dysfunction (LD) is associated with a poor outcome independently of other organ dysfunctions. Since strategies to support liver function are not available, a timely and accurate identification of factors promoting LD may lead to prevention or attenuation of its consequences. The aim of this study was to assess risk factors for LD in critically ill patients. DESIGN: Prospective, observational study. SETTING: A multidisciplinary intensive care unit (ICU) of a university hospital. PATIENTS: All patients consecutively admitted over a 6-month period. INTERVENTION: None. MEASUREMENTS AND RESULTS: LD was defined as serum bilirubin levels >or=2 mg/dl and lasting for at least 48 h. Out of 283 patients, 141 matched inclusion criteria. Forty-four patients (31.2%) showed LD (LD group), while 97 (68.8%) were included in control group (C group). A binomial analysis showed that LD occurrence was associated with moderate (odds ratio [OR] 3.11; p=0.04) and severe shock (OR 3.46; p= 0.05), sepsis (OR 3.03; p=0.04), PEEP ventilation (OR 4.25; p=0.006), major surgery (OR 4.03; p=0.03), and gram-negative infections (OR 3.94; p=0.002). In stepwise multivariate analysis, the single independent predictive factors of LD resulted in severe shock (p=0.002), sepsis (p=0.03), PEEP ventilation (p=0.04), and major surgery (p=0.05). CONCLUSIONS: In critically ill patients jaundice is common, and severe shock states, sepsis, mechanical ventilation with PEEP and major surgery are critical risk factors for its onset. Since there is no specific treatment, prompt resuscitation, treatment of sepsis and meticulous supportive care will likely reduce its incidence and severity.

Acoustic effects of positive end-expiratory pressure on normal lung sounds in mechanically ventilated pigs.

Computerized lung sounds analysis offers a new technique to monitor regional ventilation during spontaneous breathing. The purpose of the present study was to assess the acoustic behaviour of the respiratory system in healthy pigs during mechanical ventilation when a positive end-expiratory pressure (PEEP) is applied. Lung sounds were recorded during mechanical ventilation and different PEEP levels of 0, 5, 10, 15 and 20 cm H(2)O were applied. The increase in end-expiratory lung volume (EELV) related to the PEEP application was also measured and the correlation between changes in EELV (DeltaEELV) and sound amplitude (DeltaA) was examined. The amplitude of normal lung sounds was reduced by application of PEEP >or=10 cm H(2)O (P<0.05). The increase in PEEP from 0 to 20 cm H(2)O reduced the acoustic energy of lung sounds recorded at ZEEP by 0.3 dB (PEEP 5), 2 dB (PEEP 10), 5 dB (PEEP 15) and 7 dB (PEEP 20), which corresponds to 1%, 6%, 14% and 21% in acoustic attenuation, respectively. The variations in DeltaA correlated with changes in lung volume (P<0.05) and with changes in compliance of the respiratory system (P<0.05), but were not correlated with changes of the resistance of respiratory system. The frequency analysis showed a downward shifting of the spectra at frequencies between 150 and 600 Hz for PEEP levels >or=10 cm H(2)O and frequencies between 75 and 600 Hz for PEEP levels >or=15 cm H(2)O. The application of increasing levels of PEEP reduced the amplitude and changed the spectral characteristics of normal lung sounds.

Effects of superimposed tissue weight on regional compliance of injured lungs.

Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (VREG) and local transpulmonary pressure (PTP,REG) maps of the lung. Purpose of this study is to assess the distribution of VREG vs PTP,REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPs) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level VREG vs PTP,REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that VREG vs PTP,REG curves derived from different anatomical planes (p-values<1.4E-3), exposed to different PEEPs (p-values<1.5E-5) or subtending different lung status (p-values<3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.

Immediate versus delayed endovascular treatment of post-traumatic aortic pseudoaneurysms and type B dissections: retrospective analysis and premises to the upcoming European trial.

BACKGROUND: Stent grafting has been reported as a viable therapeutic option for the delayed treatment of traumatic rupture of the aortic isthmus as well as reconstruction of thoracic aortic dissections. We tested the hypothesis of whether immediate endovascular management offers clinical and pathological advantages over a delayed approach in patients with post-traumatic aortic pseudoaneurysms (PAPs) and Stanford type-B dissections (TBDs). METHODS: Thirty-one consecutive patients who were admitted with diagnosis of either PAP (n=10; 33.4+/-8.7 years) or TBD (n=21; 58.2+/-8.4 years) were respectively divided into 2 groups according to the timing of diagnosis and endovascular treatment after the traumatic or pathologic event: immediate ([lteq]2 weeks; PAP=6 and TBD=7) and delayed (>2 weeks; PAP=4 and TBD=14). Excluder-Gore (11 in PAP and 8 in TBD) and Talent-Medtronic (1 in PAP and 7 in TBD) endovascular stent grafts were deployed. Follow-up was performed at 3 months, 6 months, and 1 year and based on laboratory tests; chest angio-computed tomography scans of chest, abdomen, and pelvis; and transesophageal echocardiography. RESULTS: The endovascular procedure proved uneventful in all PAP patients who underwent either immediate or delayed treatment. In 1 PAP patient with delayed treatment, surgical removal of the pseudoaneurysm was still necessary because of further compression of the airway stem. All immediately treated TBD patients were also successful. However, in 8 of 13 TBD patients with delayed treatment (61.5%), a stent graft deployment was not possible because of complicated progression of the false lumen and multiple intimal entry tears: 1 patient benefited by fenestrations of the false lumen and 7 patients underwent medical therapy. One patient (8.3%) died because of retrograde dissection involving the aortic arch. All patients treated with endovascular stent grafts were discharged within 5 days. CONCLUSIONS: An immediate endovascular management of PAP and TBD patients offers important advantages such as avoidance of high-risk surgical procedures and postoperative complications with short hospital stay. Moreover, it has been observed that an immediate endovascular treatment allows a safe management of all patients with complete healing of the aortic wall and regression of the pseudoaneurysm in the PAP group and thrombosis of the false lumen in TBD patients.

Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure.

OBJECTIVE: In patients with severe brain injury and acute lung injury the use of positive end-expiratory pressure (PEEP) is limited by conflicting results on its effect on intracranial pressure. We hypothesised that the occurrence of alveolar hyperinflation during the application of PEEP would lead to an increase in PaCO(2) responsible for a rise in intracranial pressure. DESIGN: Prospective interventional study. SETTING: Intensive Care Unit of University Hospitals. PATIENTS AND PARTICIPANTS: Twelve severely brain-injured patients with acute lung injury and intracranial pressure higher than applied PEEP. INTERVENTIONS: 5 and 10 cmH(2)O of PEEP was randomly applied. MEASUREMENTS AND RESULTS: In all patients intracranial pressure, flow velocity by transcranial Doppler of middle cerebral artery, and jugular oxygen saturation were recorded. Static volume-pressure curves of the respiratory system were obtained, recruited volume and elastance calculated to classify patients as recruiters and non-recruiters. In recruiters (= 6 patients), elastance decreased (P<0.01) and PaO(2) increased (P<0.005), while in non-recruiters (= 6 patients) elastance and PaCO(2) significantly increased (P<0.001). Intracranial pressure, Doppler flow velocity, and jugular saturation remained constant in recruiters but significantly increased (P<0.0001) in non-recruiters. A significant correlation was found between changes in intracranial pressure and elastance (r(2) = 0.8 P<0.0001) and between changes in PaCO(2) and intracranial pressure (P<0.001, r(2) = 0.4) and elastance (P<0.001, r(2) = 0.4), respectively. CONCLUSIONS: When PEEP induced alveolar hyperinflation leading to a significant increase in PaCO(2), intracranial pressure significantly increased, whereas when PEEP caused alveolar recruitment intracranial pressure did not change.

Hemodynamics in off-pump surgery: normal versus compromised preoperative left ventricular function.

OBJECTIVE: Off-pump coronary surgery (OPCABG), avoiding cardiopulmonary bypass and cardioplegic arrest, seems to be a better choice in patients with poor baseline cardiac function. Since cardiocirculatory collapse could be induced by heart displacement in this group of patients at high risk, a greater pathophysiologic understanding of the hemodynamic derangements occurring in such patients is needed. METHODS: Twenty-eight elective OPCABG patients were evaluated for hemodynamic changes induced by heart displacement, using arterial thermodilution to measure cardiac output and global end-diastolic volume. Hemodynamic parameters were recorded: at baseline; during proper exposure and stabilization of each vessel; and at the end of surgery. Patients were divided into two groups, according to baseline ejection fraction (EF): group A (EF>30%; N=16), group B (EF< or =30%; N=12). RESULTS: Heart displacement induced a significant drop in the cardiac and stroke index, with a lesser decrease of mean arterial pressure because of raised systemic vascular resistance. Preload, measured as global end diastolic volume, significantly decreased in group A, while it remained unchanged or increased in group B. Linear regression between the preload index and left ventricular stroke work was significant only in group A. CONCLUSIONS: Patients with poor baseline cardiac function can well tolerate OPCABG. However, the pathophysiologic modifications underlying the hemodynamic changes are different compared to those in patients with good preoperative cardiac performance.

Regional distribution of lung compliance by image analysis of computed tomograms.

Computed tomography (CT) can yield quantitative information about volume distribution in the lung. By combining information provided by CT and respiratory mechanics, this study aims at quantifying regional lung compliance (CL) and its distribution and homogeneity in mechanically ventilated pigs. The animals underwent inspiratory hold maneuvers at 12 lung volumes with simultaneous CT exposure at two end-expiratory pressure levels and before and after acute lung injury (ALI) by oleic acid administration. CL and the sum of positive voxel compliances from CT were linearly correlated; negative compliance areas were found. A remarkably heterogeneous distribution of voxel compliance was found in the injured lungs. As the lung inflation increased, the homogeneity increased in healthy lungs but decreased in injured lungs. Image analysis brought novel findings regarding spatial homogeneity of compliance, which increases in ALI but not in healthy lungs by applying PEEP after a recruitment maneuver.

Antithrombin administration in patients with low antithrombin values after cardiac surgery: a randomized controlled trial.

BACKGROUND: Antithrombin (AT) concentrations are reduced after cardiac surgery with cardiopulmonary bypass compared with the preoperative levels. Low postoperative AT is associated with worse short- and mid-term clinical outcomes. The aim of the study is to evaluate the effects of AT administration on activation of the coagulation and fibrinolytic systems, platelet function, and the inflammatory response in patients with low postoperative AT levels. METHODS: Sixty patients with postoperative AT levels of less than 65% were randomly assigned to receive purified AT (5000 IU in three administrations) or placebo in the postoperative intensive care unit. Thirty patients with postoperative AT levels greater than 65% were observed as controls. Interleukin 6 (a marker of inflammation), prothrombin fragment 1-2 (a marker of thrombin generation), plasmin-antiplasmin complex (a marker of fibrinolysis), and platelet factor 4 (a marker of platelet activation) were measured at six different times. RESULTS: Compared with the no AT group and control patients, patients receiving AT showed significantly higher AT values until 48 hours after the last administration. Analysis of variance for repeated measures showed a significant effect of study treatment in reducing prothrombin fragment 1-2 (p=0.009; interaction with time sample, p=0.006) and plasmin-antiplasmin complex (p<0.001; interaction with time sample, p<0.001) values but not interleukin 6 (p=0.877; interaction with time sample, p=0.521) and platelet factor 4 (p=0.913; interaction with time sample, p=0.543). No difference in chest tube drainage, reopening for bleeding, and blood transfusion was observed. CONCLUSIONS: Antithrombin administration in patients with low AT activity after surgery with cardiopulmonary bypass reduces postoperative thrombin generation and fibrinolysis with no effects on platelet activation and inflammatory response.

Risk stratification for in-hospital mortality after cardiac surgery: external validation of EuroSCORE II in a prospective regional registry.

OBJECTIVES: To evaluate performance of the European System for Cardiac Operation Risk Evaluation (EuroSCORE II), to assess the influence of model updating and to derive a hierarchical tree for modelling the relationship between EuroSCORE II risk factors and hospital mortality after cardiac surgery in a large prospective contemporary cohort of consecutive adult patients. METHODS: Data on consecutive patients, who underwent on-pump cardiac surgery or off-pump coronary artery bypass graft intervention, were retrieved from Puglia Adult Cardiac Surgery Registry. Discrimination, calibration, re-estimation of EuroSCORE II coefficients and hierarchical tree analysis of risk factors were assessed. RESULTS: Out 6293 procedures, 6191 (98.4%) had complete data for EuroSCORE II assessment with a hospital mortality rate of 4.85% and EuroSCORE II of 4.40 ± 7.04%. The area under the receiver operator characteristic curve (0.830) showed good discriminative ability of EuroSCORE II in distinguishing patients who died and those who survived. Calibration of EuroSCORE II was preserved with lower predicted than observed risk in the highest EuroSCORE II deciles. At logistic regression analysis, the complete revision of the model had most of re-estimated regression coefficients not statistically different from those in the original EuroSCORE II model. When missing values were replaced with the mean EuroSCORE II value according to urgency and weight of intervention, the risk score confirmed discrimination and calibration obtained over the entire sample. A recursive tree-building algorithm of EuroSCORE II variables identified three large groups (55.1, 17.1 and 18.1% of procedures) with low-to-moderate risk (observed mortality of 1.5, 3.2 and 6.4%) and two groups (3.8 and 5.9% of procedures) at high risk (mortality of 14.6 and 32.2%). Patients with low-to-moderate risk had good agreement between observed events and predicted frequencies by EuroSCORE II, whereas those at greater risk showed an underestimation of expected mortality. CONCLUSIONS: This study demonstrates that EuroSCORE II is a good predictor of hospital mortality after cardiac surgery in an external validation cohort of contemporary patients from a multicentre prospective regional registry. The EuroSCORE II predicts hospital mortality with a slight underestimation in high-risk patients that should be further and better evaluated. The EuroSCORE II variables as a risk tree provides clinicians and surgeons a practical bedside tool for mortality risk stratification of patients at low, intermediate and high risk for hospital mortality after cardiac surgery.

Development and results of Puglia adult cardiac surgery registry.

AIMS: To evaluate the feasibility of a cardiac surgery registry and to describe patients' characteristics, type of procedures performed, incidence of postoperative complications with short and middle-term mortality. METHODS: A database with clinical information and details on cardiac surgical operations was implemented by Puglia Health Regional Agency to collect data of each cardiac surgery procedure performed in the seven adult cardiac surgery centres of the region. Health regional agency personnel guaranteed data accuracy and quality control procedures. Mortality after the discharge was evaluated for residents in Puglia by linking clinical data to the Health Information System. RESULTS: From January 2011 to December 2012, 6429 operations were performed. All operations were included in the registry with very high completeness of collected data (95.3% per patient). The majority of the operations performed were coronary artery bypass graft alone (41.1%), valve surgery alone (26.2%), coronary artery bypass graft and valve surgery (11.4%), or valve with other surgery (11.8%). During a median follow-up of 12 months (interquartile range 6-18 months), 211 deaths were detected after the discharge. Overall, cumulative mortality from the operation was 8.2% at 6 months and 9.5% at 12 months. CONCLUSION: Implementation of a regional clinical registry of cardiac surgery is feasible with a great level of accuracy and the evaluation of mid-term mortality overcomes the limited value of hospital mortality. An accurate cardiac surgery registry elicits epidemiologic evaluations, comparisons between expected and observed mortality, incidence of postoperative complications and encourages a reliable public reporting.

Lung regional stress and strain as a function of posture and ventilatory mode.

During positive-pressure ventilation parenchymal deformation can be assessed as strain (volume increase above functional residual capacity) in response to stress (transpulmonary pressure). The aim of this study was to explore the relationship between stress and strain on the regional level using computed tomography in anesthetized healthy pigs in two postures and two patterns of breathing. Airway opening and esophageal pressures were used to calculate stress; change of gas content as assessed from computed tomography was used to calculate strain. Static stress-strain curves and dynamic strain-time curves were constructed, the latter during the inspiratory phase of volume and pressure-controlled ventilation, both in supine and prone position. The lung was divided into nondependent, intermediate, dependent, and central regions: their curves were modeled by exponential regression and examined for statistically significant differences. In all the examined regions, there were strong but different exponential relations between stress and strain. During mechanical ventilation, the end-inspiratory strain was higher in the dependent than in the nondependent regions. No differences between volume- and pressure-controlled ventilation were found. However, during volume control ventilation, prone positioning decreased the end-inspiratory strain of dependent regions and increased it in nondependent regions, resulting in reduced strain gradient. Strain is inhomogeneously distributed within the healthy lung. Prone positioning attenuates differences between dependent and nondependent regions. The regional effects of ventilatory mode and body positioning should be further explored in patients with acute lung injury.

Emergence times are similar with sevoflurane and total intravenous anesthesia: results of a multicenter RCT of patients scheduled for elective supratentorial craniotomy.

BACKGROUND: Nearly every anesthetic agent has been used for craniotomy, yet the choice between intravenous or volatile agents has been considered an area of significant debate in neuroanesthesia. We designed a Randomized Clinical Trial to test the hypothesis that inhalation anesthesia (sevoflurane/remifentanil--group S) reduces emergence time by 5 minutes compared with intravenous anesthesia (propofol/remifentanil--group P) in patients undergoing neurosurgery for supratentorial neoplasms. METHODS: Adult ASA I-III elective patients were randomly assigned to group S or P. The primary outcome was time to reach an Aldrete test score (AS) of more than equal to 9; secondary outcomes were times to eyes opening (TEO) and extubation (ET), adverse events, intraoperative hemodynamics, brain relaxation score (BRS), opioid consumption, and diuresis. RESULTS: No significant differences were found between S (n=149) and P (n=153) treatments in primary outcomes: median time to reach AS=9 was 5 minutes (25th to 75th percentile 5 to 10 minutes in both groups, P > or = 0.05); and 15 minutes to reach AS=10 (P group 95% CI=10.3-19.7 min; S group 95% CI=11.4-18.5 min, P > or = 0.05) in both groups. TEO and ET expressed as median values (95% CI) were, respectively: 8 (6.8 to 9.2) minutes in group P versus 6 (4.6 to 7.4) in group S, P < 0.05; 10 (9.6 to 10.4) minutes in group P versus 8 (7 to 9) in group S, P < 0.05. Shivering, postoperative nausea and vomiting, pain, and seizure during the first 3 postoperative hours were not significantly different between the 2 groups, nor was BRS. Hypotension was more frequent in group S. Intraoperative diuresis and opioid consumption were greater in group P. CONCLUSIONS: Sevoflurane/remifentanil neuroanesthesia is not superior to propofol/remifentanil in time to reach an AS > or = 9.

Antithrombin after cardiac surgery: implications on short and mid-term outcome.

BACKGROUND: Antithrombin (AT) drop during cardiac surgery has been described. The causes and the effects of this phenomenon are not clear. The objective of the study is to evaluate the relationship of AT postoperative values on short and mid-term outcome after cardiac surgery. METHODS: Between January and June 2005, 405 patients, who underwent cardiac operations at our Institution had AT values available preoperatively and postoperatively. Using Receiver Operating Characteristic curves, a cut-off equal to 63.7% for ICU-arrival AT was chosen in order to divide the entire population in two groups (117 patients with ICU-arrival AT < 63.7%, Low AT group, and 288 patients with ICU-arrival AT > or = 63.7%, High AT group). Objective of the study was to evaluate the predictive role of ICU-arrival AT < 63.7% on in-hospital mortality and morbidity and on 18 months follow-up after cardiac surgery. RESULTS: ICU-arrival AT was significantly lower than preoperative AT (90.7 +/- 16.3% vs. 71.2 +/- 15.1%, P < 0.0001). Patients in the Low AT group were older, more often female, had a worse Euroscore and required longer CPB duration and cross clamp time. They had significantly higher preoperative and postoperative D-dimer levels. ICU arrival AT < 63.7% was not associated with increased in-hospital mortality but it was an independent risk factor for longer mechanical ventilation, need of inotropic support, excessive bleeding and blood products transfusion. ICU arrival-AT < 63.7% was associated with worse survival during 18 months follow up (92.3% vs. 85.4% in the High AT and Low AT group, respectively, P = 0.05). CONCLUSIONS: Low AT after cardiac surgery is associated with higher incidences of peri-operative complications and worse survival in the mid-term. Future studies should clarify the pathophysiologic mechanism of this findings and possible therapeutic directions.