Management of posterior reversible syndrome in preeclamptic women.

Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome associated with a number of conditions including preeclampsia. It is characterized by seizures, alteration of consciousness, visual disturbances, and symmetric white matter abnormalities, typically in the posterior parietooccipital regions of the cerebral hemispheres, at computed tomography (CT) and magnetic resonance (MRI). We report three new cases of PRES in preeclamptic patients and describe the management of these patients. We present a brief review of other cases in the literature, with particular attention to the anesthetic management.

Hospital survival and long term quality of life after emergency institution of venoarterial ECMO for refractory circulatory collapse.

BACKGROUND: Thanks to significant technical improvements, VA-ECMO is increasingly used to reverse circulatory collapse refractory to standard treatments. METHODS: We studied patients who underwent VA-ECMO due to primary cardiogenic shock or cardiac arrest between January 2008 and June 2011 at our institution. Variables related to hospital survival were analyzed. Long-term survival and health-related quality of life were checked. RESULTS: VA-ECMO was instituted in 23 patients: 17 outpatients and 6 inpatients. Seven of the outpatients were admitted to hospital under ongoing CPR. In these pts, time to CPR was 7 min (6-8) and time to ECMO 93 min (74-107); after 20 hours (16-22), all these pts died. Among remaining 16 pts, 6 were bridged to heart transplant and 4 to heart recovery, 8 survived to hospital discharge and 7 were alive with high health-related quality of life after 46 months (36-54). Ongoing CPR, inotropic score and lactates at cannulation did not differ between survivors and non-survivors; duration of shock, SOFA score and serum creatinine at ECMO institution, and lactates and fluid balance after 36 hours were higher in non-survivors. Patients could be kept on spontaneous breathing for >30% of time while on VA-ECMO. CONCLUSION: Emergency VA-ECMO institution can reverse refractory acute cardiovascular collapse, provided it is carried out before significant organ dysfunction occurs. Light sedation and spontaneous breathing while on VA-ECMO can be well tolerated by patients, but related clinical benefits should be proved. Patients successfully bridged to heart recovery or transplant are candidates for long-term good quality of life.

Intraoperative intravenous administration of rFVIIa and hematoma volume after early surgery for spontaneous intracerebral hemorrhage: a randomized prospective phase II study.

BACKGROUND: Surgery of spontaneous supratentorial intracerebral hemorrhage (ICH), especially if performed early, can be complicated by rebleeding, a condition that can worsen the outcome. We evaluated the effect of recombinant activated factor VII (rFVIIa) on postoperative rebleeding. METHODS: In this randomized, open-label, single-blinded study, 21 patients with spontaneous supratentorial ICH diagnosed by computed tomography (CT) scan were treated with intravenous rFVIIa (100 mcg/Kg b.w., N=13) or placebo (N=8). Hematoma volume was assessed using CT scan immediately, 18-30 hours, and 5-7 days after hematoma evacuation. The primary endpoint was a hematoma volume at 18-30 hours after surgery. All CT scans were evaluated at one center by the same investigator who was unaware of the treatment. Hematoma volume was measured using dedicated software. RESULTS: At baseline, the hematoma volume was 59.2±27.4 and 71.5±32.1 mL in the rFVIIa and placebo group, respectively. Hematoma evacuation resulted in significantly smaller ICH volumes that were similar in the rFVIIa and placebo group at 18-30 hours after surgery (15.9±14.2 mL and 18±15.1 mL, respectively; mean difference 2.1 mL, 95% confidence interval -12.1 to 16.2, P=0.76 (0.03 mL after adjustment for baseline value)). The frequencies of deep venous thrombosis, myocardial infarction, troponin I elevation and cerebral ischemia were similar in both groups. CONCLUSION: In this pilot study, intraoperative, intravenous rFVIIa administration did not modify hematoma volume after early ICH surgery. However, the 95% CI was wide, which indicates considerable uncertainty. Therefore, our results do not disprove the potential benefit of rFVIIa administration, which could be shown in a larger study.

Severe outcome of influenza A/H1N1/09v infection associated with 222G/N polymorphisms in the haemagglutinin: a multicentre study.

In a multicentre study, influenza A/H1N1/09v 222G/N variants were more frequently detected in patients admitted to the intensive-care unit for invasive mechanical ventilation or extracorporeal membrane oxygenation (10/23; 43.5%) than in patients hospitalized in other units (2/27; 7.4%) and community patients (0/81; 0.0%) (p <0.01). A significantly higher virus load (p 0.02) in the lower vs the upper respiratory tract was observed. Predominance of 222G/N variants in the lower respiratory tract (40% of total virus population) vs the upper respiratory tract (10%) was shown by clonal analysis of haemagglutinin sequences in paired nasal swab and bronchoalveolar lavage samples. The time from illness onset to sampling was significantly longer in patients with severe infection vs community patients (p <0.001). It was concluded that the 222G/N variants showed increased virulence; mutant variants were probably selected in individual patients; and the longer duration of illness might have favoured the emergence of adaptive mutations through multiple replication cycles.

Increased levothyroxine requirements in critically ill patients with hypothyroidism.

AIM: An increased thyroxine requirement has been described in hypothyroid patients who have chronic gastritis as well as in patients who are treated with drugs that modify the acidic environment of the stomach. Patients with acute critical illnesses are generally treated with calorically dense enteral solutions and antacids, both of which influence the gastric acidic environment. In this study, we evaluated levothyroxine (L-thyroxine) requirements in hypothyroid patients admitted to our ICU. METHODS: The medical records of nine patients with pre-existing hypothyroidism who did not have gastrointestinal diseases and who were admitted to our ICU between 2003 and 2008 were retrospectively reviewed. Serum TSH, FT4, and FT3 levels were measured at the time of admission and every four to eight days thereafter. After the second measurement of these parameters, patients' L-thyroxine doses were adjusted to maintain their TSH concentrations at baseline levels. RESULTS: At the time of ICU admission, the median [interquartile range] TSH, FT4, and FT3 values of the included patients were 1.52 [0.79-3.8] mU/L, 6.5 [4.9-9.3] pg/mL, and 1.0 [<1.0-1.25] pg/mL, respectively. After the first 4-8 days of their ICU stay, while their L-thyroxine doses were unchanged, the TSH levels of all included patients increased (5.69 [3.87-6.83] mU/L, P=0.012). Over the same period, their FT4 levels decreased significantly. To restore patients' TSH levels to those at the time of admission, the L-thyroxine dose was increased in 8/9 patients by an average of 54.4+/-31.6% (P=0.001). At the time of ICU discharge, patients' TSH and FT4 levels had returned to near their levels at the time of admission. All patients' serum FT3 levels remained low throughout the entire duration of their ICU stay. CONCLUSION: To maintain TSH levels in the normal range, it may be necessary to increase the L-thyroxine dose of critically ill patients with hypothyroidism. Our findings also suggest that during the first several days of a critical illness, the hypothalamic-pituitary-thyroid axis is not suppressed in hypothyroid patients.

Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: a tumor suppressor role for Prep1.

The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphomas and carcinomas). In addition, transplantation of E14.5 fetal liver (FL) Prep1(i/i) cells into lethally irradiated mice induces lymphomas. In agreement with the above data, haploinsufficiency of a different Prep1-deficient (null) allele accelerates EmuMyc lymphoma growth. Therefore Prep1 has a tumor suppressor function in mice. Immunohistochemistry on tissue micrroarrays (TMA) generated from three distinct human cohorts comprising a total of some 1000 human tumors revealed that 70% of the tumors express no or extremely low levels of Prep1, unlike normal tissues. Our data in mice are thus potentially relevant to human cancer.

Expression of CCL9/MIP-1gamma is repressed by BCR/ABL and its restoration suppresses in vivo leukemogenesis of 32D-BCR/ABL cells.

Transformation of hematopoietic cells by the BCR/ABL oncogene is caused by perturbation of signal transduction pathways leading to altered patterns of gene expression and activity. By oligonucleotide microarray hybridization of polysomal RNA of untreated and STI571-treated 32D-BCR/ABL cells, we identified the beta-chemokine CCL9 as a gene regulated by BCR/ABL in a tyrosine kinase-dependent manner. BCR/ABL repressed CCL9 expression at the transcriptional level by mechanisms involving suppression of p38 MAP kinase, and modulation of the activity of CDP/cut and C/EBPalpha, two transcription regulators of myeloid differentiation. However, repression of C/EBP-dependent transcription did not prevent the induction of CCL9 expression by STI571, suggesting that C/EBPalpha is involved in maintaining rather than in inducing CCL9 expression. Restoration of CCL9 expression in 32D-BCR/ABL cells had no effect on the in vitro proliferation of these cells, but reduced their leukemogenic potential in vivo, possibly by recruitment of CD3-positive immune cells. Together, these findings suggest that downregulation of chemokine expression may be involved in BCR/ABL-dependent leukemogenesis by altering the relationship between transformed cells and the microenvironment.

Evaluation of adaptive support ventilation in paralysed patients and in a physical lung model.

OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure and normal lungs and in a physical lung model. DESIGN: We tested ASV both on patients and in a physical lung model, with a normal level of minute ventilation and with minute ventilation increased by 30%. In each patient, respiratory pattern, mechanics and blood gases were recorded. SETTING: General ICU of a University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min, Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/-SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one, mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR 16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt 883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt 545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients ASV selected a ventilatory pattern close to the physiological one, in COPD almost a high expiratory time pattern and in restrictive ones a reduced tidal volume pattern. In the model the selection was similar. In the hyperventilation test, ASV chose a balanced increase in both Vt and RR.

Adaptive Support Ventilation (ASV).

Adaptive Support Ventilation is a novel ventilation mode, a closed-loop control mode that may switch automatically from a PCV-like behaviour to an SIMV-like or PSV-like behaviour, according to the patient status. The operating principles are based on pressure-controlled SIMV with pressure levels and SIMV rate automatically adjusted according to measured lung mechanics at each breath. ASV provided a safe and effective ventilation in patients with normal lungs, restrective or obstructive diseases. In cardiac surgery tracheal extrubation was faster in ASV patients then in controls. In the early weaning phase of acute ventilatory insufficiency the need of resetting ventilator parameters was decreased, suggesting potential benefit for patient care.

Closed-loop support of ventilatory workload: the P0.1 controller.

Conventional mechanical ventilation modes fail to provide a setting for direct control of a patient's ventilatory effort; however, with all modes clinicians may manipulate conventional controls to modulate the spontaneous respiratory activity of the patient. For instance, during pressure support ventilation the spontaneous respiratory activity can be decreased by increasing the pressure support level to achieve an adequate residual load for the respiratory muscles of the patient, neither too high nor too low. This choice is based on the clinical observation. A closed-loop controller can be envisaged to accomplish automatically, precisely, and on a breath-by-breath basis, this difficult task. The closed-loop controller should be based on the continuous and possibly noninvasive monitoring of a parameter that quantitatively reflects the patient's effort for ventilation. Occlusion pressure at 0.1 second (P0.1) can be the ideal parameter for that purpose. The authors have designed a noninvasive method for breath-by-breath monitoring of P0.1, and then a closed-loop control mode that automatically adapts the pressure support level to reach and maintain a user-set P0.1 and alveolar volume. This article discusses features and performance of this P0.1 control mode, fields of application, known limits, and possible future improvements.

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 patient's 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 patient's ability to breathe spontaneously.

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome.

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.

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 respiratory failure. INTERVENTIONS: The following three conditions were randomly tested on each patient: the use of a heated humidifier (control condition), the use of a heat and moisture exchanger without filtering function (HME), and the use of a combined heat and moisture exchanger and mechanical filter (HMEF). The pressure support level was automatically adapted by means of a closed-loop control in order to obtain constancy, throughout the study, of patient inspiratory effort as evaluated from airway occlusion pressure at 0.1 s (P0.1). Patient's ventilatory pattern, P0.1, work of breathing, and blood gases were recorded. MEASUREMENTS AND MAIN RESULTS: The artificial noses increased different components of the inspiratory load: inspiratory resistance, ventilation requirements (due to increased dead space ventilation), and dynamic intrinsic positive end-expiratory pressure (PEEP). The additional load imposed by the artificial noses was entirely undertaken by the ventilator, being the closed-loop control of P0.1 effective to maintain constancy of patient inspiratory work by means of adequate increases in pressure support level. CONCLUSIONS: The artificial noses cause unfavorable mechanical effects by increasing inspiratory resistance, ventilation requirements, and dynamic intrinsic PEEP. Clinicians should consider these effects when setting mechanical ventilation and when assessing patients' ability to breathe spontaneously.

[Inhaled nitrous oxide (NO) for the treatment of ARDS]. / Ossido nitrico (NO) per via inalatoria nel trattamento dell'ARDS.

OBJECTIVE: To investigate the initial longterm effect of inhaled NO on hypoxemia in ARDS patients. DESIGN: Retrospective study. PATIENTS: Nine hypoxemic patients with ARDS (Murray Lung Injury Score, LIS, 2.8 +/- 0.3), treated with conventional mechanical ventilation. INTERVENTIONS: Continuous NO inhalation was started after a test of inhaled NO efficacy on gas exchange and hemodynamics. Long term effects of inhaled NO were evaluated daily in terms of arterial oxygenation and methemoglobin formation. RESULTS: The initial NO inhalation increased the PaO2/FiO2 from 141 +/- 64 mmHg to 216 +/- 70 mmHg (p < 0.0001) and decreased the mean pulmonary pressure from 38 +/- 7 mmHg to 32 +/- 5 mmHg (p < 0.01), the pulmonary venous admixture from 29 +/- 10% to 20 +/- 8% (p < 0.01) and the pulmonary vascular resistance from 325 +/- 97 dyne.s.cm-5 to 238 +/- 48 dyne.s.cm-5 (p < 0.01). Daily withdrawal of inhaled NO, which was administered for 14 +/- 16 days at 8 +/- 2 ppm, was associated with a decrease in PaO2/FiO2 by 61 +/- 32 mmHg (p < 0.0001). During prolonged NO inhalation the FiO2 was decreased, on average, by 0.34 +/- 0.19 (p < 0.01), the positive end-expiratory pressure by 4 +/- 2 cmH2O (p < 0.01) and the peak inspiratory pressure by 7 +/- 4 cmH2O (p < 0.01). Three patients died during the ICU stay. CONCLUSIONS: Our results confirm the interest for inhaled NO as an additional approach for the treatment of hypoxemia in ARDS. Inhaled NO seems to allow for a better control of gas exchange, rather than for a rapid reduction of the ventilatory support.

Bronchoalveolar lavage fluid composition in alveolar proteinosis. Early changes after therapeutic lavage.

In patients with idiopathic alveolar proteinosis, the alveoli are filled with materials rich in surfactant components, especially surfactant protein A (SP-A). The anomaly could be caused by either increased secretion, decreased clearance, or both. To clarify this point, we studied five patients who underwent therapeutic lavage and then were ventilated mechanically for 24 h. During the first 8 h of mechanical ventilation, a surfactant-depleted lung was lavaged at selected intervals, and the bronchoalveolar lavage fluid was analyzed. We observed that, after lavage, various surfactant components accumulated in the airways with different time courses. We also observed that SP-A increased until the second hour and then dropped rapidly, suggesting the existence of an efficient mechanism of removal. These findings suggest that idiopathic alveolar proteinosis might be caused by a primary defect in a slow mechanism of removal or by the presence of factor(s) that interfere with the clearance of surfactant and that can be removed by lavage. It seems clear, however, that an increased secretion rate is unlikely to be the major cause of idiopathic alveolar proteinosis.

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.

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

OBJECTIVE: Pressure 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). SETTING: Intermediate intensive care unit. PATIENTS: We studied ten patients undergoing PSV and recovering from an episode of acute respiratory failure due to exacerbation of COPD. METHODS: Three levels of PSV were studied, starting from the lowest (PSb) one at which it was possible to obtain an adequate Vt with a pH > or = 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. RESULTS: Minute 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. CONCLUSION: We 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.