Giorgio Antonio Iotti

Respiratory response and inspiratory effort during pressure support ventilation in COPD patients

ObjectivePressure Support Ventilation (PSV) is now widely used in the process of weaning patients from mechanical ventilation. The aim of this study was to evaluate the effects of various levels of PS on respiratory pattern and diaphragmatic efforts in patients affected by chronic obstructive pulmonary disease (COPD).SettingIntermediate intensive care unit.PatientsWe studied ten patients undergoing PSV and recovering from an episode of acute respiratory failure due to exacerbation of COPD.MethodsThree levels of PSV were studied, starting from the lowest (PSb) one at which it was possible to obtain an adequate Vt with a pH≥7.32 and an SaO2>93%. Then, PS was set at 5 cmH2O above (PSb+5) and below (PSb-5) this starting level. Ventilatory pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm (PTPdi), the integrated EMG of the diaphragm, static PEEP (PEEPi, stat), dynamic PEEP (PEEPi, dyn), and the static compliance and resistance of the total respiratory system were recorded.ResultsMinute ventilation did not significantly change with variations in the level of PS, while Vt significantly increased with PS (PS−5=6.3±0.5 ml/kg vs. PSb=10.1±0.9 [p<0.01] and vs. PS+5=11.7±0.6 [p<0.01]), producing a reduction in respiratory frequency with longer expiratory time. The best values of blood gases were obtained at PSb, while at PSb−5, PaCO2 markedly increased. During PSb and PSb+5 and to a lesser extent during PSb−5, most of the patients made several inspiratory efforts that were not efficient enough to trigger the ventilator to inspire; thus, the PTPdi “wasted” during these inefficient efforts was increased, especially during PS+5. The application of an external PEEP (PEEPe) of 75% of the static intrinsic PEEP during PSb caused a significant reduction in the occurrence of these inefficient efforts (p<0.05). Minute ventilation remained constant, but Vt decreased, together with Te, leaving the blood gases unaltered. The PTPdi per breath and the dynamic PEEPi were also significantly reduced (by 59% and 31% of control, respectively,p<0.001) with the application of PEEPe.ConclusionWe conclude that in COPD patients, different levels of PSV may induce different respiratory patterns and gas exchange. PS levels capable of obtaining a satisfactory equilibrium in blood gases may result in ineffective respiratory efforts if external PEEP is not applied. The addition of PEEPe, not exceeding dynamic intrinsic PEEP, may also reduce the metabolic work of the diaphragm without altering gas exchange.

Steady-State Pharmacokinetics and BAL Concentration of Colistin in Critically Ill Patients After IV Colistin Methanesulfonate Administration

BACKGROUND Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. METHODS In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 μg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8)), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 μg × h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC(0-24)/MIC ratio (MIC = 2 μg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. CONCLUSIONS Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen.

Respiratory mechanics by least squares fitting in mechanically ventilated patients: Applications during paralysis and during pressure support ventilation

ObjectiveTo evaluate a least squares fitting technique for the purpose of measuring total respiratory compliance (Crs) and resistance (Rrs) in patients submitted to partial ventilatory support, without the need for esophageal pressure measurement.DesignProspective, randomized study.SettingA general ICU of a University Hospital.Patients11 patients in acute respiratory failure, intubated and assisted by pressure support ventilation (PSV).InterventionsPatients were ventilated at 4 different levels of pressure support. At the end of the study, they were paralyzed for diagnostic reasons and submitted to volume controlled ventilation (CMV).Measurements and resultsA least squares fitting (LSF) method was applied to measure Crs and Rrs at different levels of pressure support as well as in CMV. Crs and Rrs calculated by the LSF method were compared to reference values which were obtained in PSV by measurement of esophageal pressure, and in CMV by the application of the constant flow, end-inspiratory occlusion method. Inspiratory activity was measured by P0.1. In CMV, Crs and Rrs measured by the LSF method are close to quasistatic compliance (−1.5±1.5 ml/cmH2O) and to the mean value of minimum and maximum end-inspiratory resistance (+0.9±2.5 cmH2O/(l/s)). Applied during PSV, the LSF method leads to gross underestimation of Rrs (−10.4±2.3 cmH2O/(l/s)) and overestimation of Crs (+35.2±33 ml/cmH2O) whenever the set pressure support level is low and the activity of the respiratory muscles is high (P0.1 was 4.6±3.1 cmH2O). However, satisfactory estimations of Crs and Rrs by the LSF method were obtained at increased pressure support levels, resulting in a mean error of −0.4±6 ml/cmH2O and −2.8±1.5 cmH2O/(l/s), respectively. This condition was coincident with a P0.1 of 1.6±0.7 cmH2O.ConclusionThe LSF method allows non-invasive evaluation of respiratory mechanics during PSV, provided that a near-relaxation condition is obtained by means of an adequately increased pressure support level. The measurement of P0.1 may be helpful for titrating the pressure support in order to obtain the condition of near-relaxation.

Unfavorable mechanical effects of heat and moisture exchangers in ventilated patients

Objective: To investigate the mechanical effects of artificial noses. Setting: A general intensive care unit of a university hospital. Patients: 10 patients in pressure support ventilation for acute respir

Whole lung lavage: a unique model for ultrasound assessment of lung aeration changes

PurposeWhole lung lavage (WLL) pathophysiologically represents a human model of controlled lung de-aeration, resembling various pathological conditions encountered in the critically ill. Through one-lung ventilation and progressive alveolar flooding, it mimics, respectively, re-absorption atelectasis formation and lung consolidation. With re-ventilation of the treated lung, PEEP application and diuretics administration, it then creates a model of pulmonary edema and its progressive resolution. No studies have so far described lung aeration changes during WLL with ultrasound: objectives of the study were to describe ultrasound findings during WLL with validated semiotics in the critically ill and to investigate their relation with the lung’s state of relative aeration.MethodsIn seven patients, 12 lung areas/patient were prospectively studied with ultrasound during six procedural steps of WLL. A three-tiered pattern classification was assigned (1, normal/nearly normal; 2, alveolar-interstitial syndrome; 3, alveolar consolidation) consistently with their previously described meaning in terms of relative air content. The distribution was compared throughout different WLL maneuvers as it was for arterial oxygen measurement distribution.ResultsDuring one-lung ventilation and saline flooding, ultrasound findings shifted from artifact patterns (normal/nearly normal and alveolar-interstitial syndrome) to alveolar consolidation. Saline removal, re-ventilation and negative water balance were associated with a gradual return to alveolar-interstitial syndrome, then to a normal/nearly normal pattern. Arterial oxygen tension variations were not always consistent with these changes.ConclusionsIn a controlled human model of lung air content variation, the different states of aeration determined by WLL procedure were reliably described with lung ultrasound.

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

ABSTRACT Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

Organ Allocation Waiting Time During Extracorporeal Bridge to Lung Transplant Affects Outcomes

BACKGROUND The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated. METHODS We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group). We also analyzed the impact of the ventilation strategy during ECMO bridging (ie, spontaneous breathing and noninvasive ventilation [NIV] or intubation and invasive mechanical ventilation [IMV]). RESULTS Seventeen of 25 patients underwent a transplant (with a 76% 1-year survival), whereas eight patients died during bridging. In the 17 patients who underwent a transplant, mortality was positively related to waiting days until LTX (hazard ratio [HR], 1.12 per day; 95% CI, 1.02-1.23; P = .02), and the Early group showed better Kaplan-Meier curves (P = .02), higher 1-year survival rates (100% vs 50%, P = .03), and lower morbidity (days on IMV and length of stay in ICU and hospital). During the bridge to transplant, mortality increased steadily with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR, 1.06 per day; 95% CI, 1.01-1.11; P = .015) and 1-year survival (Early, 82% vs Late, 29%; P = .015). Morbidity indexes were lower in patients treated with NIV during the bridge. CONCLUSIONS The duration of the ECMO bridge is a relevant cofactor in the mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

Closed-loop control of airway occlusion pressure at 0.1 second (P0.1) applied to pressure-support ventilation: algorithm and application in intubated patients.

OBJECTIVE Airway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome. DESIGN Prospective, randomized trial. SETTING A general intensive care unit of a university hospital in Italy. PATIENTS Eight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure. INTERVENTIONS Patients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1, and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each. MEASUREMENTS AND MAIN RESULTS The closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 +/- 0.27 (SD) cm H2O. CONCLUSIONS The study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.

Equipment review: Mechanical effects of heat-moisture exchangers in ventilated patients

Although they represent a valuable alternative to heated humidifiers, artificial noses have unfavourable mechanical effects. Most important of these is the increase in dead space, with consequent increase in the ventilation requirement. Also, artificial noses increase the inspiratory and expiratory resistance of the apparatus, and may mildly increase intrinsic positive end-expiratory pressure. The significance of these effects depends on the design and function of the artificial nose. The pure humidifying function results in just a moderate increase in dead space and resistance of the apparatus, whereas the combination of a filtering function with the humidifying function may critically increase the volume and the resistance of the artificial nose, especially when a mechanical filter is used. The increase in the inspiratory load of ventilation that is imposed by artificial noses, which is particularly significant for the combined heat-moisture exchanger filters, should be compensated for by an increase either in ventilator output or in patients work of breathing. Although both approaches can be tolerated by most patients, some exceptions should be considered. The increased pressure and volume that are required to compensate for the artificial nose application increase the risk of barotrauma and volutrauma in those patients who have the most severe alterations in respiratory mechanics. Moreover, those patients who have very limited respiratory reserve may not be able to compensate for the inspiratory work imposed by an artificial nose. When we choose an artificial nose, we should take into account the volume and resistance of the available devices. We should also consider the mechanical effects of the artificial noses when setting mechanical ventilation and when assessing a patients ability to breathe spontaneously.

Segregation of virulent influenza A(H1N1) variants in the lower respiratory tract of critically ill patients during the 2010-2011 seasonal epidemic

Background Since its appearance in 2009, the pandemic influenza A(H1N1) virus circulated worldwide causing several severe infections. Methods Respiratory samples from patients with 2009 influenza A(H1N1) and acute respiratory distress attending 24 intensive care units (ICUs) as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants) of Italy during the 2010–2011 winter-spring season, were analyzed. Results In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL) with respect to nasal swab (NS), (p<0.001) suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D) circulated simultaneously. Most (72.7%, n = 48) of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26) or moderate ILI (n = 22). Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D) were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples. Conclusions Multiple virus clusters co-circulated during the 2010–2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1) variants, which replicated preferentially in the lower respiratory tract.