Impact of positive end-expiratory pressure on renal resistive index in mechanical ventilated patients.

PURPOSE: Growing evidence shows the complex interaction between lung and kidney in critically ill patients. The renal resistive index (RRI) is a bedside measurement of the resistance of the renal blood flow and it is correlated with kidney injury. The positive end-expiratory pressure (PEEP) level could affect the resistance of renal blood flow, so we assumed that RRI could help to monitoring the changes in renal hemodynamics at different PEEP levels. Our hypothesis was that the RRI at ICU admission could predict the risk of acute kidney injury in mechanical ventilated critically ill patients. METHODS: We performed a prospective study including 92 patients requiring mechanical ventilation for ≥ 48 h. A RRI ≥ 0.70, was deemed as pathological. RRI was measured within 24 h from ICU admission while applying 5,10 and 15 cmH2O of PEEP in random order (PEEP trial). RESULTS: Overall, RRI increased from 0.62 ± 0.09 at PEEP 5 to 0.66 ± 0.09 at PEEP 15 (p < 0.001). The mean RRI value during the PEEP trial was able to predict the occurrence of AKI with AUROC = 0.834 [95%CI 0.742-0.927]. Patients exhibiting a RRI ≥ 0.70 were 17/92(18%) at PEEP 5, 28/92(30%) at PEEP 10, 38/92(41%) at PEEP 15, respectively. Thirty-eight patients (41%) exhibited RRI ≥ 0.70 at least once during the PEEP trial. In these patients, AKI occurred in 55% of the cases, versus 13% remaining patients, p < 0.001. CONCLUSIONS: RRI seems able to predict the risk of AKI in mechanical ventilated patients; further, RRI values are influenced by the PEEP level applied. TRIAL REGISTRATION: Clinical gov NCT03969914 Registered 31 May 2019.

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial.

BACKGROUND: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). METHODS: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. DISCUSSION: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

Case Report: Inferior Bilobectomy for Lung Cancer to Allow Weaning From Veno-Venous Extracorporeal Membrane Oxygenation.

In recent years, veno-venous extracorporeal membrane oxygenation (V-V ECMO) has allowed complex lung and airways resections in patients with a compromised perioperative respiratory function. In the following report, we present a case of successful weaning from V-V ECMO in a patient who underwent an inferior bilobectomy for lung cancer.

Circulating Skeletal Troponin During Weaning From Mechanical Ventilation and Their Association to Diaphragmatic Function: A Pilot Study.

Background: Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers. We aimed therefore at describing the trend of skeletal troponin in mixed population of ICU patients undergoing weaning from mechanical ventilation and compared the value of fsTnI and ssTnI with diaphragmatic ultrasound derived parameters. Methods: In this prospective observational study we enrolled consecutive patients recovering from acute hypoxemic respiratory failure (AHRF) within 24 h from the start of weaning. Every day an arterial blood sample was collected to measure fsTnI, ssTnI, and global markers of muscle damage, such as ALT, AST, and CPK. Moreover, thickening fraction (TF) and diaphragmatic displacement (DE) were assessed by diaphragmatic ultrasound. The trend of fsTnI and ssTnI was evaluated during the first 3 days of weaning. Results: We enrolled 62 consecutive patients in the study, with a mean age of 67 ± 13 years and 43 of them (69%) were male. We did not find significant variations in the ssTnI trend (p = 0.623), but fsTnI significantly decreased over time by 30% from Day 1 to Day 2 and by 20% from Day 2 to Day 3 (p < 0.05). There was a significant interaction effect between baseline ssTnI and DE [F (2) = 4.396, p = 0.015], with high basal levels of ssTnI being associated to a higher decrease in DE. On the contrary, the high basal levels of fsTnI at day 1 were characterized by significant higher DE at each time point. Conclusions: Skeletal muscle proteins have a distinctive pattern of variation during weaning from mechanical ventilation. At day 1, a high basal value of ssTnI were associated to a higher decrease over time of diaphragmatic function while high values of fsTnI were associated to a higher displacement at each time point.

Can visual inspection of the electrical activity of the diaphragm improve the detection of patient-ventilator asynchronies by pediatric critical care physicians?

BACKGROUND: Patient-ventilator asynchronies are challenging during pediatric mechanical ventilation. We hypothesized that monitoring the electrical activity of the diaphragm (EAdi) together with the "standard" airway opening pressure (Pao) and flow-time waveforms during pressure support ventilation would improve the ability of a cohort of critical care physicians to detect asynchronies in ventilated children. METHODS: We recorded the flow, Pao and EAdi waveforms in ten consecutive patients. The recordings were split in periods of 15 s, each reproducing a ventilator screenshot. From this pool, a team of four experts selected the most representative screenshots including at least one of the three most common asynchronies (missed efforts, auto-triggering and double triggering) and split them into two versions, respectively showing or not the EAdi waveforms. The screenshots were shown in random order in a questionnaire to sixty experienced pediatric intensivists that were asked to identify any episode of patient-ventilator asynchrony. RESULTS: Among the ten patients included in the study, only eight had EAdi tracings without artifacts and were analyzed. When the Eadi waveform was shown, the auto-triggering detection improved from 13% to 67% (P<0.0001) and the missed efforts detection improved from 43% to 95% (P<0.0001). The detection of double triggering, instead, did not improve (85% with the EAdi vs. 78% without the EAdi waveform; P=0.52). CONCLUSIONS: This single center study suggests that the EAdi waveform may improve the ability of pediatric intensivists to detect missed efforts and auto-triggering asynchronies. Further studies are required to determine the clinical implications of these findings.

Physiological effects of two driving pressure-based methods to set positive end-expiratory pressure during one lung ventilation.

During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEPINCREMENTAL) or by stepwise decrease after a lung recruiting manoeuvre (PEEPDECREMENTAL). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEPINCREMENTAL or PEEPDECREMENTAL strategy to match the lowest ∆P. In the PEEPINCREMENTAL group, PEEP was stepwise titrated from ZEEP up to 16 cm H2O, whereas in the PEEPDECREMENTAL group PEEP was decrementally titrated, starting from 16 cm H2O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39-55]% to 35 [28-42]% in the PEEPINCREMENTAL and from 45 [37-58]% to 33 [25-45]% in the PEEPDECREMENTAL group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEPDECREMENTAL than in the PEEPINCREMENTAL group (8 [7-11] vs 10 [9-11] cm H2O; p = 0.03). In the PEEPDECREMENTAL group the PaO2/ FIO2 ratio increased significantly after intervention (from 140 [99-176] to 186 [152-243], p < 0.001). Both the PEEPINCREMENTAL and the PEEPDECREMENTAL strategies were able to decrease intraoperative shunt, but only PEEPDECREMENTAL improved oxygenation and lowered intraoperative ΔP.Clinical trial number NCT03635281; August 2018; "retrospectively registered".

Continuous assessment of neuro-ventilatory drive during 12 h of pressure support ventilation in critically ill patients.

INTRODUCTION: Pressure support ventilation (PSV) should allow spontaneous breathing with a "normal" neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of "Low" and/or "High" neuro-ventilatory drive during clinical application of PSV. METHOD: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with "Normal" (EAdiPEAK 5-15 µV), "Low" (EAdiPEAK < 5 µV) and "High" (EAdiPEAK > 15 µV) neuro-ventilatory drive. RESULTS: Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdiPEAK, was "Low" in 50.116 breath (28%), "Normal" in 88.419 breaths (50%) and "High" in 38.582 breaths (22%). The average times spent in "Low", "Normal" and "High" class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the "Low" neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9-8.5] h and 6 in the "High" neuro-ventilatory drive class, median 3.4 [2.2-7.8] h. The asynchrony index was significantly higher in the "Low" neuro-ventilatory class, mainly because of a higher number of missed efforts. CONCLUSIONS: We observed wide variations in EAdi amplitude and unevenly distributed "Low" and "High" neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

High-flow oxygen therapy in tracheostomized patients at high risk of weaning failure.

PURPOSE: High-flow oxygen therapy delivered through nasal cannulae improves oxygenation and decreases work of breathing in critically ill patients. Little is known of the physiological effects of high-flow oxygen therapy applied to the tracheostomy cannula (T-HF). In this study, we compared the effects of T-HF or conventional low-flow oxygen therapy (conventional O2) on neuro-ventilatory drive, work of breathing, respiratory rate (RR) and gas exchange, in a mixed population of tracheostomized patients at high risk of weaning failure. METHODS: This was a single-center, unblinded, cross-over study on fourteen patients. After disconnection from the ventilator, each patient received two 1-h periods of T-HF (T-HF1 and T-HF2) alternated with 1 h of conventional O2. The inspiratory oxygen fraction was titrated to achieve an arterial O2 saturation target of 94-98% (88-92% in COPD patients). We recorded neuro-ventilatory drive (electrical diaphragmatic activity, EAdi), work of breathing (inspiratory muscular pressure-time product per breath and per minute, PTPmusc/b and PTPmusc/min, respectively) respiratory rate and arterial blood gases. RESULTS: The EAdipeak remained unchanged (mean ± SD) in the T-HF1, conventional O2 and T-HF2 study periods (8.8 ± 4.3 µV vs 8.9 ± 4.8 µV vs 9.0 ± 4.1 µV, respectively, p = 0.99). Similarly, PTPmusc/b and PTPmusc/min, RR and gas exchange remained unchanged. CONCLUSIONS: In tracheostomized patients at high risk of weaning failure from mechanical ventilation, T-HF did not improve neuro-ventilatory drive, work of breathing, respiratory rate and gas exchange compared with conventional O2 after disconnection from the ventilator. The present findings might suggest that physiological effects of high-flow therapy through tracheostomy substantially differ from nasal high flow.

High-flow nasal cannula oxygen therapy decreases postextubation neuroventilatory drive and work of breathing in patients with chronic obstructive pulmonary disease.

BACKGROUND: The physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure. METHODS: This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88-92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded. RESULTS: EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 µV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 µV during HFNC2 (conventional O2: p < 0.05 versus HFNC1 and HFNC2). Similarly, the PTPDI/min increased from 135 ± 60 to 211 ± 70 cmH2O/s/min, and then decreased again during HFNC2 to 132 ± 56 (conventional O2: p < 0.05 versus HFNC1 and HFNC2). CONCLUSIONS: In patients with COPD, the application of HFNC postextubation significantly decreased the neuroventilatory drive and work of breathing compared with conventional O2 therapy.

Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV.

BACKGROUND: Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency. METHOD: Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours. RESULTS: In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/µV at baseline to 62 ± 30 ml/µV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH2O/µV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38- 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78- 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04). CONCLUSION: After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not. TRIAL REGISTRATION: ClinicalTrials.gov study registration: NCT02473172, 06/11/2015.