Michele Dambrosio

Effects of Positive End-expiratory Pressure and Different Tidal Volumes on Alveolar Recruitment and Hyperinflation

BackgroundThe morphologic effect of positive end-expiratory pressure (PEEP) and of two tidal volumes were studied by computed tomography to determine whether setting the tidal volume (Vt) at the upper inflection point (UIP) of the pressure-volume (P-V) curve of the respiratory system or 10 ml/kg hav

Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease.

Objective: 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. Design: Prospective observational cohort study. Setting: A 14‐bed general intensive care unit in a university hospital. Patients: Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean. Interventions: None. Measurements and Main Results: 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). Conclusions: 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.

Physiological effects of a lung‐recruiting strategy applied during one‐lung ventilation

Background: One‐lung ventilation (OLV) affects respiratory mechanics and ventilation/perfusion matching, reducing functional residual capacity of the ventilated lung. While the application of a lung‐recruiting manoeuvre (RM) on the ventilated lung has been shown to improve oxygenation, data regarding the impact of RM on respiratory mechanics are not available.

Right ventricular myocardial function in ARF patients. PEEP as a challenge for the right heart.

ObjectiveTo examine the hemodynamic effects of external positive end-expiratory pressure (PEEP) on right ventricular (RV) function in acute respiratory failure (ARF) patients.DesignProspective, with retrospective analysis on the basis of RV volume response to PEEP.SettingGeneral intensive care unit in a university teaching hospital.Patients20 mechanically ventilated ARF patients (mean lung injury score=2.6±0.45 SD).InterventionIncremental levels of PEEP (0–5–10–15 cmH2O) were applied and RV hemodynamics were studied by means of a Swan-Ganz catheter with a fast-response thermistor for right ventricular ejection fraction (RVEF) measurement. According to their response to PEEP 15, two groups of patients were defined: group A (9 patients) with unchanged or increased RV end-diastolic volume index (RVED-VI) and group B (11 patients) with decreased RVEDVI.Measurements and resultsAt zero PEEP (ZEEP) the hemodynamic parameters of the two groups did not differ. In group A, cardiac index (CI) and stroke volume index (SI) decreased at all PEEP levels (5, 10, and 15 cmH2O), while RVEF started to decrease only at a PEEP of 10 cmH2O (−10.8%), and RVES(systolic)VI increased only at PEEP 15 cmH2O (+21.5%). RVED-VI was not affected by PEEP. In group B, CI and SI decreased at all PEEP levels (5, 10, and 15 cmH2O). Similarly, RVEDVI started to decrease at PEEP 5 cmH2O, while RVESVI decreased only at PEEP 15 cmH2O (−21.4%). RVEF was not affected by PEEP in this group. In each patient the slope of the relationship between RVEDVI and right ventricular stroke work index (RVSWI), expressing RV myocardial performance, was studied. This relationship was significant (no change in RV contractility) in 8 of 11 patients in group B and in only 2 patients in group A. In 4 patients in group A, PEEP shifted the RVSWI/RVEDVI ratio rightward in the plot, indicating a decrease in RV myocardial performance in these patients.ConclusionsPEEP affects RV function in ARF patients. The decrease in cardiac output is more often associated with a preload decrease and no change in RV contractility. On the other hand, the finding of increased RV volumes with PEEP may be associated with a reduction in RV myocardial performance. Thus, these results suggest that assessment of RV function by PEEP and preload recruitable stroke work may disclose otherwise unpredictable alterations in RV function.

Bupivacaine uncouples the mitochondrial oxidative phosphorylation, inhibits respiratory chain complexes I and III and enhances ROS production: results of a study on cell cultures.

This study aimed to validate, in situ, proposed mechanisms of bupivacaine cytotoxicity pointing to impairment of the mitochondrial oxidative metabolism. High resolution oxymetry, carried out on a panel of cell cultures, revealed a dual dose- and time-dependent effect of bupivacaine consisting of uncoupling of the mt Delta mu(H+)-controlled respiratory rates in a cyclosporine A-insensitive manner and further inhibition of the respiratory rates. Intriguingly, a relatively small decrease on the mt Delta Psi (about 20 mV) was sufficient to account for both the bupivacaine- and the FCCP-mediated impairment of the oxidative phosphorylation coupling thereby supporting a common protonophoric mechanism of action. The bupivacaine-induced depression of the cell respiration related to specific inhibition of complexes I and III and accompanied with production of reactive oxygen species. Importantly, inhibition of the respiratory chain complexes was prevented by antioxidant treatment and reversed following removal of the anaesthetic thereby suggesting an oxidant-mediated feed-back mechanism reinforcing the primary inhibitory action of the anaesthetic.

Interferon-alpha (IFN-α)-conditioned DC Preferentially Stimulate Type-1 and Limit Treg-type In Vitro T-cell Responses From RCC Patients

Dendritic cells (DCs) are potent antigen presenting cells and represent attractive candidates for use in novel immunotherapies for patients with renal cell carcinoma (RCC), a disease that has proven refractory to conventional treatment modalities, such as chemotherapy and radiotherapy. Given the perceived need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end point, and the known functional plasticity of DC populations that may display heterogeneous capacity to promote T-cell responses, we sought to identify a preferred DC preparation with this capacity. We compared 2 different preparations of monocyte-derived DC using interferon-alpha (IFN-α) (IFN-DC and αDC1) with classic DCs “matured” (mDCs) using interleukin-1β/interleukin-6/tumor necrosis factor-α/prostaglandin E2, for their ability to promote autologous TC1 antitumor responses from RCC patients in vitro. IFN-α–conditioned DC promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs. Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among CD4+ T-cell responder populations versus IVS using conventional mDC-based vaccines. These data emphasize an important role for IFN-α in modulating the immunologic functions of DCs toward a polarized DC1-type capable of coordinately promoting TH1-type and TC1-type T-cell mediated immunity and supports the translational development of patient-derived IFN-α–conditioned DC for use in novel immunotherapies for patients with RCC, and in whom, endogenous tumor-specific TC1 effector cells may be dysfunctional, anergic, or prone to undergo apoptosis.

Effects of Recruitment Maneuver and Positive End-expiratory Pressure on Respiratory Mechanics and Transpulmonary Pressure during Laparoscopic Surgery

Background:The authors tested the hypothesis that during laparoscopic surgery, Trendelenburg position and pneumoperitoneum may worsen chest wall elastance, concomitantly decreasing transpulmonary pressure, and that a protective ventilator strategy applied after pneumoperitoneum induction, by increasing transpulmonary pressure, would result in alveolar recruitment and improvement in respiratory mechanics and gas exchange. Methods:In 29 consecutive patients, a recruiting maneuver followed by positive end-expiratory pressure 5 cm H2O maintained until the end of surgery was applied after pneumoperitoneum induction. Respiratory mechanics, gas exchange, blood pressure, and cardiac index were measured before (TBSL) and after pneumoperitoneum with zero positive end-expiratory pressure (TpreOLS), after recruitment with positive end-expiratory pressure (TpostOLS), and after peritoneum desufflation with positive end-expiratory pressure (Tend). Results:Esophageal pressure was used for partitioning respiratory mechanics between lung and chest wall (data are mean ± SD): on TpreOLS, chest wall elastance (Ecw) and elastance of the lung (EL) increased (8.2 ± 0.9 vs. 6.2 ± 1.2 cm H2O/L, respectively, on TBSL; P = 0.00016; and 11.69 ± 1.68 vs. 9.61 ± 1.52 cm H2O/L on TBSL; P = 0.0007). On TpostOLS, both chest wall elastance and EL decreased (5.2 ± 1.2 and 8.62 ± 1.03 cm H2O/L, respectively; P = 0.00015 vs. TpreOLS), and PaO2/inspiratory oxygen fraction improved (491 ± 107 vs. 425 ± 97 on TpreOLS; P = 0.008) remaining stable thereafter. Recruited volume (the difference in lung volume for the same static airway pressure) was 194 ± 80 ml. PplatRS remained stable while inspiratory transpulmonary pressure increased (11.65 + 1.37 cm H2O vs. 9.21 + 2.03 on TpreOLS; P = 0.007). All respiratory mechanics parameters remained stable after abdominal desufflation. Hemodynamic parameters remained stable throughout the study. Conclusions:In patients submitted to laparoscopic surgery in Trendelenburg position, an open lung strategy applied after pneumoperitoneum induction increased transpulmonary pressure and led to alveolar recruitment and improvement of Ecw and gas exchange.

Transesophageal echocardiography for diagnosis of traumatic aortic injury: An appraisal of the evidence

BACKGROUND 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.

Physiological Effects of the Open Lung Approach in Patients with Early, Mild, Diffuse Acute Respiratory Distress Syndrome: An Electrical Impedance Tomography Study.

Background: To test the hypothesis that in early, mild, acute respiratory distress syndrome (ARDS) patients with diffuse loss of aeration, the application of the open lung approach (OLA) would improve homogeneity in lung aeration and lung mechanics, without affecting hemodynamics. Methods: Patients were ventilated according to the ARDS Network protocol at baseline (pre-OLA). OLA consisted in a recruitment maneuver followed by a decremental positive end-expiratory pressure trial. Respiratory mechanics, gas exchange, electrical impedance tomography (EIT), cardiac index, and stroke volume variation were measured at baseline and 20 min after OLA implementation (post-OLA). Esophageal pressure was used for lung and chest wall elastance partitioning. The tomographic lung image obtained at the fifth intercostal space by EIT was divided in two ventral and two dorsal regions of interest (ROIventral and ROIDorsal). Results: Fifteen consecutive patients were studied. The OLA increased arterial oxygen partial pressure/inspired oxygen fraction from 216 ± 13 to 311 ± 19 mmHg (P < 0.001) and decreased elastance of the respiratory system from 29.4 ± 3 cm H2O/l to 23.6 ± 1.7 cm H2O/l (P < 0.01). The driving pressure (airway opening plateau pressure − total positive end-expiratory pressure) decreased from 17.9 ± 1.5 cm H2O pre-OLA to 15.4 ± 2.1 post-OLA (P < 0.05). The tidal volume fraction reaching the dorsal ROIs increased, and consequently the ROIVentral/Dorsal impedance tidal variation decreased from 2.01 ± 0.36 to 1.19 ± 0.1 (P < 0.01). Conclusions: The OLA decreases the driving pressure and improves the oxygenation and lung mechanics in patients with early, mild, diffuse ARDS. EIT is useful to assess the impact of OLA on regional tidal volume distribution.

Counseling, quality of life, and acute postoperative pain in elderly patients with hip fracture

Introduction Hip fractures represent one of the most important causes of morbidity and mortality in elderly people. Anxiety and depression affect their quality of life and increase pain severity, and have adverse effects on functional recovery. Recent World Health Organization guidelines emphasize that therapeutic regimes need to be individualized and combined with psychological support. This study was launched with the primary endpoint of assessing if and to what extent client-centered therapy affects the perception of pain, reduces anxiety and depression, and increases the quality of life of elderly patients with hip fracture. Materials and methods Forty patients were admitted to the Orthopedic and Trauma Surgery ward for hip fracture. Patients were randomly divided into two subgroups: (1) case (group C), had to receive patient-centered counseling throughout the hospitalization; and (2) control (group NC), receiving the analgesic treatment without receiving counseling. Short Form-36-item Health Survey Questionnaire, State–Trait Anxiety Inventory, and Hamilton Rating Scale for Depression scores were recorded before any treatment, at discharge, and after 30 days. Pain levels were evaluated by means of Visual Analog Scale every 12 hours during the hospitalization from the day of surgery until day 5. Results The hierarchical clustering analysis identified before any treatment were two clusters based on different physical functioning perceptions and role limitations, which were due to physical and emotional problems. Counseling did have a positive impact on quality of life on all patients, but in a more relevant way if patients were low functioning upon admittance to the ward. Anxiety and depression decreased in patients undergoing counseling, and their pain levels were lower than among patients not receiving it. Conclusion This study reveals that hip fracture patients can be clustered on the basis of Short Form-36 baseline scores. Counseling affects the evolution of mental and physical status in these patients, and the major benefit is reported in patients whose quality of life perception is worse after the trauma. Decreasing anxiety and depression levels, as well as more satisfying pain management, assessed by means of specific tests, confirm the effectiveness of counseling in elderly patients with hip fracture.