Massimo Borelli

Mean airway pressure vs. positive end-expiratory pressure during mechanical ventilation

To investigate the effects of both positive end-expiratory pressure (PEEP) and mean airway pressure (Paw) on gas exchange, we used lung lavage to induce severe respiratory insufficiency in six lambs. The animals were then mechanically ventilated at constant tidal volume, respiratory rate, and inspired O2 fraction. PEEP levels were varied −5, +5 and +10 cm H2O around the pressure (Pflex) corresponding to a major change in slope of the inspiratory limb of the respiratory volume-pressure curve. In each animal the effects of the three PEEP levels were studied at two Paw levels, differing by 5 cm H2O.Increasing Paw significantly improved PaO2 and reduced venous admixture. A 5-cm H2O PEEP increase from +5 to +10 did not affect oxygenation; however, oxygenation was significantly better when PEEP was greater than Pflex. Both PaCO2 and anatomic dead space were higher at higher PEEP, and decreased with increasing Paw. Hence, Paw was a major determinant of oxygenation, although a PEEP greater than Pflex appeared necessary to optimize oxygenation at a constant Paw.

Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit.

Objective: To test the effects of positive expiratory pressure on the leakage of fluid around cuffs of different tracheal tubes, in mechanically ventilated patients and in a benchtop model. Design: Randomized clinical trial and experimental in vitro study. Setting: Intensive care unit of a university hospital. Patients: Forty patients recovering in the intensive care unit were ventilated in volume-controlled mode. Twenty patients were randomly intubated with Hi-Lo tubes (HL group), whereas the remaining 20 subjects were intubated with SealGuard tubes (SG group). Interventions: Immediately after intubation and cuff inflation with 30 cm H2O, Evans blue was applied onto the cephalic surface of the tracheal tube cuff. A 5-cm H2O positive expiratory pressure was used during the first 5 hrs of stay, and thereafter it was removed. Bronchoscopy verified whether the dye leaked around the cuff. The experiment lasted 12 hrs. Leakage was also tested in vitro with the same tracheal tubes with incremental level of positive expiratory pressure. Measurements and Main Results: At 1 hr, 5 hrs, and thereafter hourly until 12 hrs, bronchoscopy was used to test the presence of dye on the trachea caudal to the cuff. At the fifth hour, two patients of the HL group failed the test. One hour after positive expiratory pressure removal, all subjects in group HL exhibited a dyed lower trachea. On the other hand, one patient in group SG presented a leak at the eighth hour, and at the 12th hour three of them were still sealed. In vitro, the same level of positive expiratory pressure delayed the passage of dye around the cuff; after 30 mins positive expiratory pressure was removed, and in 10 mins all dye leaked only in the Hi-Lo tube. Conclusions: We found that 5 cm H2O positive expiratory pressure was effective in delaying the passage of fluid around the cuffs of tracheal tubes both in vivo and in vitro. The SealGuard tube proved to be more resistant to leakage than Hi-Lo.

Relationship between the timing of administration of IgM and IgA enriched immunoglobulins in patients with severe sepsis and septic shock and the outcome: a retrospective analysis.

PURPOSE Because the use of IgM and IgA enriched polyclonal intravenous immunoglobulins (eIg) is a standard of care in critically ill patients admitted to our intensive care unit (ICU) with the diagnosis of severe sepsis or septic shock, we investigated if the delay from the onset of severe sepsis and septic shock and their administration could influence the outcome. MATERIALS AND METHODS The medical records of all patients with severe sepsis or septic shock admitted to our ICU from July 2004 through October 2009 and treated with eIg (Pentaglobin®; Biotest, Dreieich, Germany) were retrospectively examined. RESULTS A total of 129 adult patients with severe sepsis or septic shock were considered eligible. Thirty-two percent of patients died during the ICU stay. Survivors were given eIg significantly earlier than nonsurvivors (23 vs 63 hours, P < .05). The delay in the administration of eIg and the Simplified Acute Physiology Score II were the only variables that entered stepwise a propensity score-adjusted logistic model. The delay in the administration of eIg was a significant predictor of the odds of dying during the ICU stay (odds ratio for 1 hour of delay, 1.007; P < .01; 99% confidence interval from 1.001 to 1.010) and proved to be independent from the Simplified Acute Physiology Score II and other variables. CONCLUSIONS The efficacy of eIg, being maximal in early phases of severe sepsis and/or septic shock, is probably time dependent.

Hemodynamic and gas exchange response to inhaled nitric oxide and prone positioning in acute respiratory distress syndrome patients

ObjectiveTo analyze the single effect and the interaction of prone position and inhaled nitric oxide (iNO) on lung function and hemodynamic variables. Design2 × 2 factorial trial. SettingDepartment of intensive care medicine at a university hospital. PatientsFourteen patients on volume-controlled mechanical ventilation for acute respiratory distress syndrome (ARDS). InterventionFour experimental conditions, each one characterized by the patient’s position (supine or prone) with iNO or without iNO. Measurements and ResultsHemodynamic and gas exchange data were collected for each experimental condition. Pao2 was increased both by positioning (p < .01) and iNO (p < .01); iNO caused also a reduction in venous admixture (p < .01), pulmonary artery pressure (p < .01), and pulmonary vascular resistance index (p < .05). We could not demonstrate any significant interaction between the two treatments. The average effect of prone positioning was the same both with and without iNO, whereas the average effect of iNO was the same in both the prone and the supine position. ConclusionIn the studied acute respiratory distress syndrome patients the average effects of iNO and positioning on oxygenation were additive and no interaction could be shown. A strategy including both treatments could warrant the best improvement in oxygenation, and should take into account the individual response to each treatment and the possible combination of the two.

Effects of continuous negative extrathoracic pressure versus positive end-expiratory pressure in acute lung injury patients

OBJECTIVE To compare the effects of continuous negative extrathoracic pressure (CNEP) and positive end-expiratory pressure (PEEP) at the same level of transpulmonary pressure. DESIGN Prospective analysis. SETTING Medical intensive care unit of a university hospital. PATIENTS Nine consecutive acute lung injury patients. Patients with cardiac failure and patients with chronic lung disease were excluded from the investigation. INTERVENTIONS The patients were sedated and paralyzed while receiving mechanical ventilation and were studied in three different conditions: a) using a PEEP of 0 cm H2O (zero end-expiratory pressure); b) using a PEEP of 15 cm H2O; c) using CNEP. CNEP was applied to the thorax and the upper abdomen and its level was chosen to obtain a transpulmonary pressure similar to the one observed at a PEEP of 15 cm H2O. All patients had an arterial catheter, a pulmonary artery catheter, and a thermistor-tip fiberoptic catheter for thermo-dye-dilution in the femoral artery. These catheters were connected to an integrated monitoring system. We also placed an esophageal catheter in each patient to detect esophageal pressure. MEASUREMENTS AND MAIN RESULTS For each step, we assessed the hemodynamic variations by measuring intravascular pressures (via a pulmonary artery catheter), transmural pressures (computed by subtracting esophageal pressure from intravascular pressure), and blood volumes (derived from the technique of double indicator). The application of CNEP of -20+/-0.7 cm H2O produced a venous admixture and PaO2/FO2 improvement similar to that obtained with a PEEP of 15 cm H2O. This procedure is associated with a higher cardiac index (5.5+/-1.5 vs. 4.6+/-1.2 L/min/m2; p < .05) coupled with lower central venous pressure, pulmonary artery occlusion pressure, and higher transmural pressures and blood volume parameters. CONCLUSIONS In acute lung injury patients, a CNEP of -20 cm H2O has the capability to obtain transpulmonary pressure and lung function improvement similar to a PEEP of 15 cm H2O. CNEP differs from the positive pressure by increasing the venous return and the preload of the heart, and has no negative effects on cardiac performance.

High-frequency percussive ventilation improves perioperatively clinical evolution in pulmonary resection.

Objective:During thoracotomy, positive end-expiratory pressure is applied to the dependent lung and continuous positive airway pressure (CPAP) inflates the nondependent lung to avoid hypoxemia. These methods do not allow the removal of produced secretions. We hypothesized that high-frequency percussive ventilation (HFPV) can improve both conditions and reduce hospital length of stay in these patients. Design:Randomized prospective study. Setting:University Hospital. Patients:Fifty-three consecutive patients undergoing elective pulmonary partial resection were enrolled. Nine were excluded because of surgical reasons. Interventions:The nondependent lung was ventilated with HFPV in 22 patients and other 22 received CPAP. In both groups, the dependent lung was ventilated with continuous mechanical ventilation. Measurement and Main Results:Cardiocirculatory variables and blood gas analysis were measured during surgery. Postoperatively, all patients underwent chest physiotherapy, and Spo2, body temperature, the amount of sputum produced, and chest radiography were recorded. Before nondependent lung re-expansion, HFPV patients presented higher Pao2 than CPAP group (p = 0.020). The amount of secretions was higher in chronic obstructive pulmonary disease patients treated with HFPV than in those who received CPAP (199 and 64 mL, respectively, p = 0.028). HFPV increased by 5.28 times the chance of sputum production by chronic obstructive pulmonary disease patients (&khgr;2 = 46.66, p < 0.0001; odds ratio = 5.28). A patient treated with HFPV had a 3.14-fold larger chance of being discharged earlier than a CPAP-treated subject (likelihood ratio = 11.5, p = 0.0007). Conclusions:Under the present settings, HFPV improved oxygenation in one-lung ventilation during pulmonary resection. Postoperatively, it decreased the length of stay and increased the removal of secretions in comparison with CPAP.

Temporal Logic Based Monitoring of Assisted Ventilation in Intensive Care Patients

We introduce a novel approach to automatically detect ineffective breathing efforts in patients in intensive care subject to assisted ventilation. The method is based on synthesising from data temporal logic formulae which are able to discriminate between normal and ineffective breaths. The learning procedure consists in first constructing statistical models of normal and abnormal breath signals, and then in looking for an optimally discriminating formula. The space of formula structures, and the space of parameters of each formula, are searched with an evolutionary algorithm and with a Bayesian optimisation scheme, respectively. We present here our preliminary results and we discuss our future research directions.

Motor excitability evaluation in developmental stuttering: a transcranial magnetic stimulation study.

INTRODUCTION Developmental stuttering (DS) is viewed as a motor speech-specific disorder, although several lines of research suggest that DS is a symptom of a broader motor disorder. We investigated corticospinal excitability in adult DS and normal speakers. METHODS Transcranial magnetic stimulation (TMS) was administered over left/right hand representation of the motor cortex while recording motor evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI) muscle. Resting, active motor thresholds, silent period threshold and duration were measured. A stimulus-response curve at resting was also obtained to evaluate MEP amplitudes. RESULTS Lower corticospinal responses in the left hemisphere of DS were found, as indicated by a reduction of peak-to-peak MEP amplitudes compared to normal speakers. CONCLUSIONS This provides further evidence that DS may be a general motor deficit that also involves motor non-speech-related structures. Moreover, our results confirm that DS may be related to left hemisphere hypoactivation and/or lower left hemisphere dominance. The present data and protocol may be useful for diagnosis of subtypes of DS that may benefit from pharmacological treatment by targeting the general level of cortical excitability.

Early short-term application of high-frequency percussive ventilation improves gas exchange in hypoxemic patients.

Background: Hypoxemia in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients represents a common finding in the intensive care unit (ICU) and frequently does not respond to standard ventilatory techniques. Objective: To study whether the early short-term application of high-frequency percussive ventilation (HFPV) can improve gas exchange in hypoxemic patients with ALI/ARDS or many other conditions in comparison to conventional ventilation (CV) using the same mean airway pressure (P_aw), representing the main determinant of oxygenation and hemodynamics, irrespective of the mode of ventilation. Methods: Thirty-five patients not responding to CV were studied. During the first 12 h after admission to the ICU the patients underwent CV. Thereafter HFPV was applied for 12 h with P_aw kept constant. They were then returned to CV. Gas exchange was measured at: 12 h after admission, every 4 h during the HFPV trial, 1 h after the end of HFPV, and 12 h after HFPV. Thirty-five matched patients ventilated with CV served as the control group (CTRL). Results: Pa<smlcap>o</smlcap>₂/Fi<smlcap>o</smlcap>₂ and the arterial alveolar ratio (a/A P<smlcap>o</smlcap>₂) increased during HFPV treatment and a Pa<smlcap>o</smlcap>₂/Fi<smlcap>o</smlcap>₂ steady state was reached during the last 12 h of CV, whereas both did not change in CTRL. Pa<smlcap>c</smlcap><smlcap>o</smlcap>₂ decreased during the first 4 h of HFPV, but thereafter it remained unaltered; Pa<smlcap>c</smlcap><smlcap>o</smlcap>₂ did not vary in CTRL. Respiratory system compliance increased after HFPV. Conclusions: HFPV improved gas exchange in patients who did not respond to conventional treatment. This improvement remained unaltered until 12 h after the end of HFPV.

Investigating the efficacy of paroxetine in developmental stuttering.

Objectives:Paroxetine has been reported to be useful for management of stuttering symptoms, but only a few reports have examined its effects. We have investigated the efficacy of paroxetine in a randomized, placebo-controlled study. Methods:Five stuttering subjects received paroxetine at 20 mg once daily at night for 12 weeks, and 5 received placebo. The percentages of stuttered words and stuttering-associated movements during speech were measured at baseline and after 6 and 12 weeks of treatment. Moreover, left primary motor cortex excitability was measured using transcranial magnetic stimulation. Specifically, resting and active motor thresholds and the cortical silent period (CSP) were obtained at the same periods in both groups. Results:Paroxetine did not affect the percentage of stuttered words between groups. Stuttering-associated movements, however, during speech in facial muscular districts were significantly reduced in subjects treated with paroxetine. Finally, paroxetine administration shortened the CSP with no effect on motor thresholds. Conclusion:Paroxetine may be useful in qualitative management of stuttering symptoms and may act on the stuttering brain by diminution of intracortical inhibition, as revealed by the shortening of the CSP after paroxetine administration.