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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.

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 p 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.

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 reestimated 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.

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.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.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, Por = 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, Por = 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, P0.05; 10 (9.6 to 10.4) minutes in group P versus 8 (7 to 9) in group S, P0.05. 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.Sevoflurane/remifentanil neuroanesthesia is not superior to propofol/remifentanil in time to reach an ASor = 9.

SUMMARY 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 (mitoKATP) channels. 2. Mechanically ventilated rats were exposed to normoxia (Fio2 = 0.3) or hyperoxia (Fio2 = 1.0) for 30 min and pH, Pco2, 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 Pco2, 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 KATP 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.

A systematic review, including a meta-analysis, on the timing effects of neuraxial analgesia (NA) on cesarean and instrumental vaginal deliveries in nulliparous women was conducted. Of 20 articles identified, 9 met the inclusion quality criteria (3,320 participants). Cesarean delivery (odds ratio, 1.00; 95% confidence interval, 0.82-1.23) and instrumental vaginal delivery (odds ratio, 1.00; 95% confidence interval, 0.83-1.21) rates were similar in the early NA and control groups. Neonates of women with early NA had a higher umbilical artery pH and received less naloxone. In the early NA group, fewer women were not compliant with assigned treatment and crossed over to the control group. Women receiving early NA for pain relief are not at increased risk of operative delivery, whereas those receiving early parenteral opioid and late epidural analgesia present a higher risk of instrumental vaginal delivery for nonreassuring fetal status, worse indices of neonatal wellness, and a lower quality of maternal analgesia.

To evaluate the utility of serial measurements of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect acute cardiac dysfunction during weaning failure in difficult to wean patients with chronic obstructive pulmonary disease.Prospective observational cohort study.A 14-bed general intensive care unit in a university hospital.Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean.None.Cardiac and hemodynamic variables, arterial and central venous blood gas, breathing pattern, respiratory mechanics, indexes of oxygen cost of breathing, and plasma levels of NT-proBNP were measured and analyzed immediately before (baseline) and at the end of a spontaneous breathing trial. Eight of 19 patients (42%) were identified with acute cardiac dysfunction at the end of the weaning trial. Baseline NT-proBNP levels were significantly higher (median 5000, interquartile range 4218 pg/mL) in these patients than in patients without evidence of acute cardiac dysfunction (median 1705, interquartile range 3491 pg/mL). Plasma levels of NT-proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median 12,733, interquartile range 16,456 pg/mL, p.05). The elevation in NT-proBNP at the end of the weaning trial had a good diagnostic performance in detecting acute cardiac dysfunction, as estimated by area under the receiver operating characteristic curve analysis (area under the curve 0.909, se 0.077, 95% confidence interval 0.69-0.98; p.0001, cutoff = 184.7 pg/mL).Serial measurements of NT-proBNP plasma levels provided a noninvasive manner to detect acute cardiac dysfunction during an unsuccessful weaning trial in difficult to wean patients with chronic obstructive pulmonary disease. The utility of this test as a complement of the standard clinical monitoring of the weaning trial deserves further investigation.

Hereditary Haemorrhagic Teleangiectasia (HHT) is a vascular disorder of angiogenesis transmitted in an autosomal dominant pattern, characterised by heterogeneity in clinical manifestations. One of the most important organ involved is lung, including pulmonary arteriovenous malformations (PAVM). PAVM occur in 20 to 30% of the HHT population and recently are considered a marker of disease. PAVM are direct artery-to-vein connections with low pressure and without an interveining capillary bed. PAVM are classified as simple (supplied by one feeding artery) or complex (receiving blood supply from two or more feeding artery). According to the international reports, treatment it's recommendable for all PAVM with feeding vessels 3mm or larger, in order to reduce the risk of cerebral ischaemia and neurologic manifestations frequently attributed to paradoxical embolisation. Transcatheter embolotherapy of PAVM is a form of treatment based on occlusion of the feeding artery to a PAVM by using platinum coils or detachable balloons. The technique of coil embolisation involves the exact localisation of PAVM by pulmonary angiography followed by superselective percutaneous caheterisation of feeding artery obtained by using a dedicated 7F guiding catheter, which coaxially allocates a 5F hydrophilic catheter advanced in order to perform both superselective angiography of feeding artery and embolisation itself. Inside the 5F catheter the platinum coils are advanced using a .035'' guide-wire and released until an optimal occlusion of feeding artery is achieved. At the end of the procedure angiographic control is performed in order to verify the occlusion of feeding artery. The use of platinum coils is preferable over detachable balloons when feeding artery are greater than 7 mm in diameter and have irregular anatomical configuration. On the other hand, the principal advantage of using detachable balloons is that the balloon itself can be deflated and repositioned if necessary. Transcatheter embolotherapy is technically safe and clinically effective and may represent the primary choice of treatment in HHT patients. On the other hand the most common complications of this treatment (pleurisy and air embolism) can be prevented by using some tips during the embolisation procedure like "anchor technique," "scaffold technique" and "balloon assisted technique." Cerebral arteriovenous malformations (CAVM) are present in 10-20% of patients with HHT and multiple in 50% of cases. Cortical surface is the most frequent localisation. Angiography is needed to diagnose all CAVM and to clarify the angioarchitecture of the lesion. In HHT CAVM are usually either micro-AVM, with a nidus not bigger than 1 cm, or small AVM, with a nidus between 1 and 3 cm. Quite frequently there are lesions characterised by arteriovenous fistulas. In the three patterns of CAVM usually found in HHT, small AVM are the most risky for bleeding although the risk is lower than that associated with sporadic ones. It is estimated from 0.38 to 0.69% per year in spite of the general incidence of bleeding in sporadic CAVM that ranges from 2 to 4% per year. In HHT patients, at present, the precise indications and timing of treatment are not established. Trend is to treat small AVM and AVF and to follow-up micro-AVM with MRI and angiography. As for sporadic CAVM, treatment of small AVM is usually referred to stereotactic radiosurgery. Endovascular embolisation is proposable if the lesion is easily reachable by microcatheterism and the position of the microcatheter is safe. Glue is used for embolisation and the technique is briefly discussed.

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. Prospective, observational study. A multidisciplinary intensive care unit (ICU) of a university hospital. All patients consecutively admitted over a 6-month period. None. LD was defined as serum bilirubin levels ≥ 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). 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.

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocites. Mitochondrial respiration is an important source of ROS generation and hence a potential contributor to cardiac reperfusion injury. Appropriate treatment strategy could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. In the present study, we examined the effect of lowering the oxygen tension, at the onset of the reperfusion, on various parameters of mitochondrial bioenergetics in rat heart tissue. After isolation of mitochondria from control, ischemic, normoxic and hypoxic reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production and in addition, the degree of lipid peroxidation, cardiolipin content and cardiolipin oxidation. We found that normoxic reperfusion significantly altered all these mitochondrial parameters, while hypoxic reperfusion had a protective effect attenuating these alterations. This effect appears to be due, at least in part, to a reduction of mitochondrial ROS generation with subsequent preservation of cardiolipin integrity, protection of mitochondrial function and improvement of post-ischemic hemodynamic function of the heart.

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 +/- 2 cm H2O) and higher (16 +/- 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 +/- 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 +/- 36 to 396 +/- 138), and reduction in static lung elastance (from 23 +/- 3 to 20 +/- 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 +/- 5 to 28 +/- 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume-pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.

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: Twentyeight 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 (EFO30%; NZ16), group B (EF%30%; NZ12). 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. q 2004 Published by Elsevier B.V.

Backgrounds: An overview of the validity of transesophageal echocardiography (TEE) in patients suspected to have traumatic aortic injury (TAI). Methods: Computerized bibliographic search of trials from 1994 to 2002 evaluating the use of TEE to confirm the diagnosis of TAI. Seven relevant studies out of 204 were identified, involving 758 patients. The accuracy of TEE was analyzed by constructing summary receiver-operating characteristic (sROC) curves and computing areas under the sROC curve. Results: No prospective randomized trial was found. Although accuracy varied greatly, summary ROC curve found that TEE enjoyed a high diagnostic performance. Some study characteristics can affect accuracy. Conclusions: Our findings seems to indicate that TEE is a valuable tool for diagnosing TAI, and its use as first-line evaluation of such patients can be supported; however, given the lack of randomized trials, no standard of care can be drawn from the present overview: future studies should look at this problem more carefully, and should be methodologically rigorous.

In this study we evaluated whether a technology based on artificial neural networks (ANN) could estimate the static compliance (C(RS)) of the respiratory system, even in the absence of an end-inspiratory pause, during continuous mechanical ventilation. A porcine model of acute lung injury was used to provide recordings of different respiratory mechanics conditions. Each recording consisted of 10 or more consecutive breaths in volume-controlled mechanical ventilation, followed by a breath having an end-inspiratory pause used to calculate C(RS) according to the interrupter technique (IT). The volume-pressure loop of the breath immediately preceding the one with pause was given to the ANN for the training, together with the C(RS) separately calculated by the IT. The prospective phase consisted of giving only the loops to the trained ANN and comparing the results yielded by it to the compliance separately calculated by the investigators. Determination of measurement agreement between ANN and IT methods showed an error of -0.67 +/- 1.52 mL/cm H(2)O (bias +/- SD). We could conclude that ANN, during volume-controlled mechanical ventilation, can extract C(RS) without needing to stop inspiratory flow.We studied the application of artificial neural networks (ANN) to the estimation of respiratory compliance during mechanical ventilation. The study was performed on an animal model of acute lung injury, testing the performance of ANN in both healthy and diseased conditions of the lung.

Spontaneous breathing during mechanical ventilation is still controversial. It is well known that incongruous patterns of mechanical ventilation can trigger or exacerbate lung injury. NAVA is a mode of mechanical ventilation that delivers ventilatory assist in proportion to the Electrical activity of the Diaphragm (EDi), which mirrors the performance of the whole respiratory system. However during NAVA, the effects of PEEP on the EDi signal, respiratory rate and breathing heterogeneity are unknown.

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.

Variation in respiratory impedance may occur in mechanically ventilated patients. During pressure-targeted ventilatory support, this may lead to patient-ventilator asynchrony. We assessed the hypothesis that during pressure-support ventilation (PSV), preservation of minute ventilation (V E) consequent to added mechanical loads would result in an increase in respiratory rate (RR) due to the large reduction in tidal volume (VT). WITH proportional-assist ventilation (PAV), preservation of V E would occur through the preservation of VT, with a smaller effect on RR. We anticipated that this compensatory strategy would result in greater patient comfort and a reduce work of breathing. An increase in respiratory impedance was obtained by chest and abdominal binding in 10 patients during weaning from mechanical ventilation. V E remained constant in both ventilatory modes after chest and abdominal compression. During PSV, this maintenance of VE was obtained through a 58 +/- 3% increase in RR that compensated for a 29 +/- 2% reduction in VT. The magnitudes of the reduction in VT (10 +/- 3%) and of the increase in RR (14 +/- 2%) were smaller (p0. 001) during PAV. During both PSV and PAV, chest and abdominal compression caused increases in both the pressure-time product (PTP) of the diaphragm per minute (142.9 +/- 26.9 cm H(2)O. s/min, PSV, and 117.6 +/- 16.4 cm H(2)O. s/min, PAV) and per liter (13.4 +/- 2.5 cm H(2)O. s/L, PSV, and 9.6 +/- 0.7 cm H(2)O. s/L, PAV). These increments were greater (p0.001) during PSV than during PAV. The capability of keeping VT and V E constant through increases in inspiratory effort after increases in mechanical loads is relatively preserved only during PAV. The ventilatory response to an added respiratory load during PSV required greater muscle effort than during PAV.

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.

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 Ca2+. 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.

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).We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung.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.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; P0.01) and open lung protocol ventilation at end-inspiration (by 1-15% of total lung volume; P0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P0.01).Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

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.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.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.

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. Comment in The role of positive end-expiratory pressure in modulating the apoptosis response during atelectasis-induced lung injury. [Crit Care Med. 2009]

Backgrounds 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 ≥ 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.

In patients with acute respiratory distress syndrome (ARDS), a focal distribution of loss of aeration in lung computed tomography predicts low potential for alveolar recruitment and susceptibility to alveolar hyperinflation with high levels of positive end-expiratory pressure (PEEP).We tested the hypothesis that, in this cohort of patients, the table-based PEEP setting criteria of the National Heart, Lung, and Blood Institute's ARDS Network (ARDSnet) low tidal volume ventilatory protocol could induce tidal alveolar hyperinflation.In 15 patients, physiologic parameters and plasma inflammatory mediators were measured during two ventilatory strategies, applied randomly: the ARDSnet and the stress index strategy. The latter used the same ARDSnet ventilatory pattern except for the PEEP level, which was adjusted based on the stress index, a monitoring tool intended to quantify tidal alveolar hyperinflation and/or recruiting/derecruiting that occurs during constant-flow ventilation, on a breath-by-breath basis.In all patients, the stress index revealed alveolar hyperinflation during application of the ARDSnet strategy, and consequently, PEEP was significantly decreased (P0.01) to normalize the stress index value. Static lung elastance (P = 0.01), plasma concentrations of interleukin-6 (P0.01), interleukin-8 (P = 0.031), and soluble tumor necrosis factor receptor I (P = 0.013) were significantly lower during the stress index as compared with the ARDSnet strategy-guided ventilation.Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.

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 PEEPor=10 cm H(2)O (P0.05). 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 (P0.05) and with changes in compliance of the respiratory system (P0.05), 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 levelsor=10 cm H(2)O and frequencies between 75 and 600 Hz for PEEP levelsor=15 cm H(2)O. The application of increasing levels of PEEP reduced the amplitude and changed the spectral characteristics of normal lung sounds.

Patients undergoing cardiac surgery are at increased risk of gut hypoperfusion. During off-pump surgery, hemodynamic derangements at the time of heart displacement could reduce splanchnic perfusion, outweighing the beneficial effects of avoiding cardiopulmonary bypass. The purpose of this study is to assess, prospectively, blood flow modifications in the superior mesenteric artery during off-pump surgery using transesophageal echocardiography.In 19 patients undergoing multivessel elective off-pump coronary revascularization, systemic hemodynamics and superior mesenteric flow were assessed. Blood flow in the superior mesenteric artery was evaluated with duplex ultrasound using a transesophageal echo probe. Measurements were made four times: T0 (baseline), T1 (left anterior descendent anastomosis), T2 (heart displacement to expose the inferolateral and inferior walls), and T3 (closed chest, at the end of surgery).Superior mesenteric blood flow significantly decreased at T2 (from 426.4 +/- 83.1 mL to 212.9 +/- 48.6 mL, p0.001), when also cardiac output was reduced. The percentage of the cardiac output directed toward the mesenteric arterial bed was also decreased at this time. At the end of surgery (T3), whereas cardiac output returned to the initial values, mesenteric flow was significantly increased compared with baseline, with a higher percentage of the systemic output flowing through the superior mesenteric artery.Hemodynamic changes during off-pump coronary surgery induce a significant mesenteric hypoperfusion followed by a hyperemic response at the end of surgery. Transesophageal echo-Doppler allows the intraoperative measurement of blood flow distribution to splanchnic viscera.

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.

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.

We evaluated 1) the performance of an artificial neural network (ANN)-based technology in assessing the respiratory system resistance (Rrs) and compliance (Crs) in a porcine model of acute lung injury and 2) the possibility of using, for ANN training, signals coming from an electrical analog (EA) of the lung. Two differently experienced ANNs were compared. One ANN (ANNBIO) was trained on tracings recorded at different time points after the administration of oleic acid in 10 anesthetized and paralyzed pigs during constant-flow mechanical ventilation. A second ANN (ANNMOD) was trained on EA simulations. Both ANNs were evaluated prospectively on data coming from four different pigs. Linear regression between ANN output and manually computed mechanics showed a regression coefficient ( R) of 0.98 for both ANNs in assessing Crs. On Rrs, ANNBIO showed a performance expressed by R= 0.40 and ANNMOD by R = 0.61. These results suggest that ANNs can learn to assess the respiratory system mechanics during mechanical ventilation but that the assessment of resistance and compliance by ANNs may require different approaches.

Objective: Cardiopulmonary bypass (CPB) is associated with abnormalities of lung function characterized by an increase in static elastance of the respiratory system. We examined the following: a) the effects of CPB on the total inspiratory volume-pressure (V-P) relationship of the respiratory system; b) the relative contribution of the chest wall and lung to the impairment of respiratory system mechanics; and c) the time-course of such impairment. Design: Prospective, interventional study. Setting: Surgical and medical intensive care units in a teaching hospital. Patients: Eight adult patients scheduled for elective open heart surgery to correct valvular dysfunction. Interventations: V-P curves (interrupter technique) of the respiratory system were partitioned between the chest wall and lung by measurements of esophageal pressure. Measurements were obtained before stemotomy (control), immediately after, 4 hrs after, and 7 hrs after separation from CPB. Measurements and Main Results : Control V-P relationships of the respiratory system and lung showed lower inflection points (P flex ) at pressure values of 5.9 ± 2.3 and 4.3 ± 2.5 cm H 2 O, respectively. Immediately after and 4 hrs after separation from CPB, both curves had sigmoid shapes because of lower P flex and formation of upper inflection (UIP) points. The pressures corresponding to the P flex increased significantly (p

The incorporation of microprocessors into the design of ventilators has produced a confounding array of products, each with its own peculiar features and modes of operation. This confusion has been compounded in the medical literature with unproved statements favouring one new device or mode of ventilation over another. We believe that physicians concerned with the ventilatory management of patients with respiratory failure must base their approach on physiologic principles and an understanding of patient-ventilator interactions [1].

Background Acute respiratory failure may develop in patients with chronic obstructive pulmonary disease because of intrinsic positive end-expiratory pressure (PEEPi) and increased resistive and elastic loads. Proportional assist ventilation is an experimental mode of partial ventilatory support in which the ventilator generates flow to unload the resistive burden (flow assistance: FA) and volume to unload the elastic burden (volume assistance: VA) proportionally to inspiratory muscle effort, and PEEPi can be counterbalanced by application of external PEEP. The authors assessed effects of proportional assist ventilation and optimal ventilatory settings in patients with chronic obstructive pulmonary disease and acute respiratory failure. Methods Inspiratory muscles and diaphragmatic efforts were evaluated by measurements of esophageal, gastric, and transdiaphragmatic pressures. Minute ventilation and breathing patterns were evaluated by measuring airway pressure and flow. Measurements were performed during spontaneous breathing, continuous positive airway pressure, FA, FA+PEEP, VA, VA+PEEP, FA+VA, and FA+VA+PEEP. Results FA+PEEP provided the greatest improvement in minute ventilation (89 +/- 3%) and dyspnea (62 +/- 2%). The largest reduction in pressure time product per breath of the respiratory muscles and diaphragm (44 +/- 3% and 33 +/- 2%, respectively) also was observed during FA+PEEP condition. When VA was added to this setting, a reduction in respiratory rate (50 +/- 3%), an increase in inspiratory time (102 +/- 6%), and a further reduction in pressure time product per minute (65 +/- 2% and 64% for the respiratory muscles and diaphragm, respectively) was observed. However, values of pressure time product per liter of minute ventilation during FA+VA+PEEP did not differ with those observed during FA+PEEP condition. Worsening of patient-ventilator interaction and breathing asynchrony occurred when VA was implemented. Conclusions Application of PEEP to counterbalance PEEPi and FA to unload the resistive burden provided the optimal conditions in such patients. Ventilator over-assistance and patient-ventilator asynchrony was observed when VA was added to this setting. The clinical use of proportional assist ventilation should be based on continuous measurements of respiratory mechanics.

The objective of this study was to compare patient-ventilator interaction during pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) in the course of increased ventilatory requirement obtained by adding a dead space in 12 patients on weaning from mechanical ventilation. With PSV, the level of unloading was provided by setting the inspiratory pressure at 20 and 10 cmH2O, whereas with PAV the level of unloading was at 80 and 40% of the elastic and resistive load. Hypercapnia increased (P < 0.001) tidal swing of esophageal pressure and pressure-time product per breath at both levels of PSV and PAV. During PSV, application of dead space increased ventilation (VE) during PSV (67 +/- 4 and 145 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001). This was due to a relevant increase in respiratory rate (48 +/- 4 and 103 +/- 5% during 20 and 10 cmH2O PSV, respectively, P < 0.001), whereas the increase in tidal volume (VT) played a small role (13 +/- 1 and 21 +/- 2% during 20 and 10 cmH2O PSV, respectively, P < 0.001). With PAV, the increase in VE consequent to hypercapnia (27 +/- 3 and 64 +/- 4% during 80 and 40% PAV, respectively, P < 0.001) was related to the increase in VT (32 +/- 1 and 66 +/- 2% during 80 and 40% PAV, respectively, P < 0.001), respiratory rate remaining unchanged. The increase in pressure-time product per minute and per liter consequent to acute hypercapnia and the sense of breathlessness were significantly (P < 0.001) higher during PSV than during PAV. Our data show that, after hypercapnic stimulation of the respiratory drive, the capability to increase VE through changes in VT modulated by variations in inspiratory muscle effort is preserved only during PAV; the compensatory strategy used to increase VE during PSV requires greater muscle effort and causes more pronounced patient discomfort than during PAV.

Conflicting data are available on the relative contribution of the chest wall (cw) to the intrinsic positive end-expiratory pressure of the total respiratory system (PEEPi,rs) in patients with chronic obstructive pulmonary disease (COPD). In order to assess the chest wall and lung contribution to the elastic properties of the respiratory system in COPD patients during acute ventilatory failure, using the "interrupter technique", static inflation volume-pressure (V-P) curves of the total respiratory system (rs), lung (L) and cw were obtained in seven mechanically-ventilated COPD patients during application of zero end-expiratory pressure (ZEEP) and different levels (0-15 cmH2O) of PEEP. On ZEEP, PEEPi,rs was present in all patients (range 10.5-13.1 cmH2O), to which PEEPi,cw and PEEPi,L contributed 17 +/- 2 and 83 +/- 1%, respectively. The static V-P curves of the rs, L, and cw on ZEEP were concave toward the horizontal axis, indicating that elastance increased with inflating volume. Application of PEEP did not affect lung and chest wall mechanics until PEEP levels exceeding 90% of PEEPi,cw on ZEEP (critical value of PEEP (Pcrit)). At PEEP levels higher than Pcrit, and relative to the V-P curves on ZEEP, we observed that: 1) the V-P curve of the rs showed an initial shift along the curve on ZEEP followed by a downward displacement with inflating volume; 2) the V-P curve of the L was shifted along the curve on ZEEP throughout inflating volume; and 3) the V-P curve of the cw was initially displaced along the curve on ZEEP, whilst a downward displacement appeared at higher lung volume. In conclusion, our data show that, in chronic obstructive pulmonary disease patients with flow limitation, the increase in pleural pressure does not make a significant contribution to the intrinsic positive end-expiratory pressure of the total respiratory system. However, during tidal ventilation, a substantial increase in elastance of the chest wall is present. The critical values of positive end-expiratory pressure below which there are no changes in chest wall and lung mechanics amount to 90% of the total PEEPi,rs on ZEEP. Positive end-expiratory pressure levels higher than such critical value cause important alterations of the elastic properties of the lung and chest wall.

To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi).Prospective study.General intensive care unit in a university teaching hospital.Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure.Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O).Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur.In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.

Background In patients with acute respiratory distress syndrome (ARDS), the ventilatory approach is based on tidal volume (VT) of 10-15 ml/kg and positive end-expiratory pressure (PEEP). To avoid further pulmonary injury, decreasing VT and allowing PaCO2 to increase (permissive hypercapnia) has been suggested. Effects of 10 cmH2O of PEEP on respiratory mechanics, hemodynamics, and gas exchange were compared during mechanical ventilation with conventional (10-15 ml/kg) and low (5-8 ml/kg) VT. Methods Nine sedated and paralyzed patients were studied. VT was decreased gradually (50 ml every 20-30 min). Static volume-pressure (V-P) curves, hemodynamics, and gas exchange were measured. Results During mechanical ventilation with conventional VT, V-P curves on PEEP 0 (ZEEP) exhibited an upward convexity in six patients reflecting a progressive reduction in compliance with inflating volume, whereas PEEP resulted in a volume displacement along the flat part of this curve. After VT reduction, V-P curves in the same patients showed an upward concavity, reflecting progressive alveolar recruitment with inflating volume, and application of PEEP resulted in alveolar recruitment. The other three patients showed a V-P curve with an upward concavity; VT reduction increased this concavity, and application of PEEP induced greater alveolar recruitment than during conventional VT. With PEEP, cardiac index decreased by, respectively, 31% during conventional VT and 11% during low VT (P < 0.01); PaO2 increased by 32% and 71% (P < 0.01), respectively, whereas right-to-left venous admixture (Qs/Qt) decreased by 11% and 40%, respectively (P < 0.01). The greatest values of PaO2, static compliance, and oxygen delivery and the lowest values of Qs/Qt (best PEEP) were obtained during application of PEEP with low VT (P < 0.01). Conclusions Although PEEP induced alveolar hyperinflation in most patients during mechanical ventilation with conventional VT, at low VT, there appeared to be a significant alveolar collapse, and PEEP was able to expand these units, improving gas exchange and hemodynamics.

Synchronized intermittent mandatory ventilation (SIMV) intermixes assisted and spontaneous breaths. Its ability as a weaning technique has been questioned on the basis that patients show little adaptation to ventilator assistance. We studied inspiratory effort and patient-ventilator interaction at different levels (SIMV, 100, 50, and 0%) of flow-triggered SIMV versus pressure-triggered SIMV in patients during the weaning period. The two triggering systems were evaluated during constant flow and constant pressure mandatory SIMV breaths. Inspiratory effort was estimated as the esophageal pressure time product (PTP) per breath (PTP/b) and per minute (PTP/min). The PTP/b and PTP/min of both mandatory and spontaneous breaths were significantly lower during flow triggering than during pressure triggering SIMV, irrespective of the ventilatory mode. During pressure-triggered SIMV PTP/b and PTP/min were identical for mandatory and spontaneous breaths, whereas during flow-triggered SIMV PTP/b and PTP/min were significantly lower for mandatory than for spontaneous breaths. This difference was greatest when flow triggering and constant pressure ventilation were associated. These data show that flow triggering reduces inspiratory effort during both mandatory and spontaneous SIMV breaths and obtains a better patient-ventilator interaction.

The effects of positive end-expiratory pressure (PEEP) on static ("rapid airway occlusion" technique) and dynamic ("constant flow" technique) volume-pressure (V-P) curves were studied in 19 patients with adult respiratory distress syndrome (ARDS). To describe the shape of both curves, the nonlinear coefficient of a second-order polynomial equation fitted to the static (static nonlinear coefficient) and dynamic (dynamic nonlinear coefficient) V-P curves on zero end-expiratory pressure (ZEEP) was used. Two distinct patterns were observed: (1) in ten patients, the static and dynamic V-P curves on ZEEP exhibited a convex shape with a progressive decrease in slope with increasing inflation volume (nonlinear coefficients: negative). In these patients PEEP induced a volume displacement along the static and dynamic V-P curves on ZEEP (hyperinflation). (2) In nine patients, the static and dynamic V-P curves on ZEEP showed a concave shape with a progressive increase in slope with increasing volume (nonlinear coefficients: positive) and PEEP shifted both curves upward along the volume axis (alveolar recruitment). A correlation (p < 0.0001) between static and dynamic nonlinear coefficients was found at all levels of PEEP. Both static and dynamic nonlinear coefficients on ZEEP were correlated (p < 0.0001) with the amount of lung volume recruited with PEEP, and the variations of cardiac index (CI), O2 delivery (DO2), right-to-left venous admixture (Qs/Qt), and PaO2 with PEEP. Besides, the effects of PEEP on Cl, DO2, Qs/Qt, and PaO2 were less pronounced (p < 0.001) in patients with convex V-P curves than in patients with concave V-P curves.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi) are observed in patients with chronic obstructive pulmonary disease (COPD) and flow limitation. Several reports suggest that PEEP levels approaching PEEPi reduce inspiratory load due to PEEPi, without further hyperinflation. Hence PEEP should not increase intrathoracic pressure or affect hemodynamics and gas exchange. To verify this hypothesis, the effects of PEEP (0 to 15 cm H2O) on respiratory mechanics, hemodynamics, and gas exchange were studied in nine COPD patients during controlled mechanical ventilation. PEEP levels approaching PEEPi (9.8 +/- 0.5 cm H2O) did not affect the expiratory flow/volume relationship, confirming the presence of flow limitation. PEEP levels of 5 and 10 cm H2O did not change lung volume and PEEPi in the respiratory system (PEEPtot,rs) and chest wall (PEEPtot,cw) or affect hemodynamics and gas exchange. When applied PEEP overcame PEEPi, changes in lung volume and the expiratory flow/volume relationship were observed. PEEPtot,rs and PEEPtot,cw also increased. Under these circumstances, PEEP increased static elastance in both the respiratory system and the chest wall, reducing cardiac index and affecting hemodynamics and gas exchange. Our data show that in mechanically ventilated COPD patients with PEEPi due to flow limitation, PEEP levels exceeding the 85% of PEEPi (Pcrit) caused further hyperinflation and compromised hemodynamics and gas exchange.