Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients: A Multicenter, Randomized Clinical Trial (PROLABI).

BACKGROUND: Lung protective strategies using low tidal volumes and moderate positive end expiratory pressures (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in acutely brain-injured patients due to concerns about carbon dioxide control and effect of PEEP on cerebral hemodynamic. METHODS: In this multicenter, open-label, controlled clinical trial 190 adult acute brain injured patients were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency and ARDS at day 28. Neurological outcome was assessed at intensive care unit discharge by Oxford Handicap Scale and at six months by Glasgow Outcome Scale. FINDINGS: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (RR 1.35; 95%CI 1.03-1.79; p=0.025). Mortality was 28.9% and 15.1% (RR 1.91; 95%CI 1.06-3.42; p=0.02), ventilator dependency was 42.3% and 27.9% (RR 1.52; 95%CI 1.01-2.28; p=0.039), and incidence of ARDS was 30.8% and 22.1% (RR 1.39; 95%CI 0.85-2.27; p=0.179) respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. INTERPRETATION: In acutely brain-injured patients without ARDS a lung-protective ventilatory strategy as compared to a conventional strategy did not reduce mortality, percentage of patients weaned from mechanical ventilation, incidence of ARDS and was not beneficial in terms of neurological outcomes. Due to the early termination, these preliminary results require confirmation in larger trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01690819.

Positive end-expiratory pressure management in patients with severe ARDS: implications of prone positioning and extracorporeal membrane oxygenation.

The optimal strategy for positive end-expiratory pressure (PEEP) titration in the management of severe acute respiratory distress syndrome (ARDS) patients remains unclear. Current guidelines emphasize the importance of a careful risk-benefit assessment for PEEP titration in terms of cardiopulmonary function in these patients. Over the last few decades, the primary goal of PEEP usage has shifted from merely improving oxygenation to emphasizing lung protection, with a growing focus on the individual pattern of lung injury, lung and chest wall mechanics, and the hemodynamic consequences of PEEP. In moderate-to-severe ARDS patients, prone positioning (PP) is recommended as part of a lung protective ventilation strategy to reduce mortality. However, the physiologic changes in respiratory mechanics and hemodynamics during PP may require careful re-assessment of the ventilation strategy, including PEEP. For the most severe ARDS patients with refractory gas exchange impairment, where lung protective ventilation is not possible, veno-venous extracorporeal membrane oxygenation (V-V ECMO) facilitates gas exchange and allows for a "lung rest" strategy using "ultraprotective" ventilation. Consequently, the importance of lung recruitment to improve oxygenation and homogenize ventilation with adequate PEEP may differ in severe ARDS patients treated with V-V ECMO compared to those managed conservatively. This review discusses PEEP management in severe ARDS patients and the implications of management with PP or V-V ECMO with respect to respiratory mechanics and hemodynamic function.

Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study.

BACKGROUND: Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV). METHODS: This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters. RESULTS: Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP. CONCLUSIONS: In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

Association between inspired oxygen fraction and development of postoperative pulmonary complications in thoracic surgery: a multicentre retrospective cohort study.

BACKGROUND: Limited data exist to guide oxygen administration during one-lung ventilation for thoracic surgery. We hypothesised that high intraoperative inspired oxygen fraction during lung resection surgery requiring one-lung ventilation is independently associated with postoperative pulmonary complications (PPCs). METHODS: We performed this retrospective multicentre study using two integrated perioperative databases (Multicenter Perioperative Outcomes Group and Society of Thoracic Surgeons General Thoracic Surgery Database) to study adult thoracic surgical procedures using one-lung ventilation. The primary outcome was a composite of PPCs (atelectasis, acute respiratory distress syndrome, pneumonia, respiratory failure, reintubation, and prolonged ventilation >48 h). The exposure of interest was high inspired oxygen fraction (FiO2), defined by area under the curve of a FiO2 threshold > 80%. Univariate analysis and logistic regression modelling assessed the association between intraoperative FiO2 and PPCs. RESULTS: Across four US medical centres, 141/2733 (5.2%) procedures conducted in 2716 patients (55% female; mean age 66 yr) resulted in PPCs. FiO2 was univariately associated with PPCs (adjusted OR [aOR]: 1.17, 95% confidence interval [CI]: 1.04-1.33, P=0.012). Logistic regression modelling showed that duration of one-lung ventilation (aOR: 1.20, 95% CI: 1.03-1.41, P=0.022), but not the time-weighted average FiO2 (aOR: 1.01, 95% CI: 1.00-1.02, P=0.165), was associated with PPCs. CONCLUSIONS: Our results do not support limiting the inspired oxygen fraction for the purpose of reducing postoperative pulmonary complications in thoracic surgery involving one-lung ventilation.

The impact of a lung-protective ventilation mode using transpulmonary driving pressure titrated positive end-expiratory pressure on the prognosis of patients with acute respiratory distress syndrome.

OBJECTIVE: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS). METHODS: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients. RESULTS: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999). CONCLUSION: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

Effects of Intra-operative Cardiopulmonary Variability On Post-operative Pulmonary Complications in Major Non-cardiac Surgery: A Retrospective Cohort Study.

Intraoperative cardiopulmonary variables are well-known predictors of postoperative pulmonary complications (PPC), traditionally quantified by median values over the duration of surgery. However, it is unknown whether cardiopulmonary instability, or wider intra-operative variability of the same metrics, is distinctly associated with PPC risk and severity. We leveraged a retrospective cohort of adults (n = 1202) undergoing major non-cardiothoracic surgery. We used multivariable logistic regression to evaluate the association of two outcomes (1)moderate-or-severe PPC and (2)any PPC with two sets of exposure variables- (a)variability of cardiopulmonary metrics (inter-quartile range, IQR) and (b)median intraoperative cardiopulmonary metrics. We compared predictive ability (receiver operating curve analysis, ROC) and parsimony (information criteria) of three models evaluating different aspects of the intra-operative cardiopulmonary metrics: Median-based: Median cardiopulmonary metrics alone, Variability-based: IQR of cardiopulmonary metrics alone, and Combined: Medians and IQR. Models controlled for peri-operative/surgical factors, demographics, and comorbidities. PPC occurred in 400(33%) of patients, and 91(8%) experienced moderate-or-severe PPC. Variability in multiple intra-operative cardiopulmonary metrics was independently associated with risk of moderate-or-severe, but not any, PPC. For moderate-or-severe PPC, the best-fit predictive model was the Variability-based model by both information criteria and ROC analysis (area under the curve, AUCVariability-based = 0.74 vs AUCMedian-based = 0.65, p = 0.0015; AUCVariability-based = 0.74 vs AUCCombined = 0.68, p = 0.012). For any PPC, the Median-based model yielded the best fit by information criteria. Predictive accuracy was marginally but not significantly higher for the Combined model (AUCCombined = 0.661) than for the Median-based (AUCMedian-based = 0.657, p = 0.60) or Variability-based (AUCVariability-based = 0.649, p = 0.29) models. Variability of cardiopulmonary metrics, distinct from median intra-operative values, is an important predictor of moderate-or-severe PPC.

A novel method for assessment of airway opening pressure without the need for low-flow insufflation.

BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.

Respiratory challenges and ventilatory management in different types of acute brain-injured patients.

Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.

Neurological and respiratory effects of lung protective ventilation in acute brain injury patients without lung injury: brain vent, a single centre randomized interventional study.

INTRODUCTION: Lung protective ventilation (LPV) comprising low tidal volume (VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation. METHODS: In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 cmH2O) or high PEEP (12 cmH2O). Between each intervention, baseline ventilation (VT 9 ml/kg/pbw and PEEP 5 cmH2O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis. RESULTS: We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to "low VT/low PEEP" and "low VT/high PEEP" were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p < 0.001), low brain compensatory reserve (p < 0.01) and mechanical power (p < 0.05). The transpulmonary driving pressure was 5 ± 2 cmH2O in both interventions. Partial arterial pressure of carbon dioxide was kept in the range 34-36 mmHg by adjusting the respiratory rate, hence, changes in carbon dioxide were not associated with the increase in ICP. CONCLUSIONS: The present study found that most patients did not experience any adverse effects of LPV, neither on ICP nor CA. However, in almost a quarter of patients, the ICP rose above the safety limit for interrupting the interventions. Baseline ICP, brain compensatory reserve, and mechanical power can predict a potentially deleterious effect of LPV and can be used to personalize ventilator settings. Trial registration NCT03278769 . Registered September 12, 2017.

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial.

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.

SOLVe: a closed-loop system focused on protective mechanical ventilation.

BACKGROUND: Mechanical ventilation is an essential component in the treatment of patients with acute respiratory distress syndrome. Prompt adaptation of the settings of a ventilator to the variable needs of patients is essential to ensure personalised and protective ventilation. Still, it is challenging and time-consuming for the therapist at the bedside. In addition, general implementation barriers hinder the timely incorporation of new evidence from clinical studies into routine clinical practice. RESULTS: We present a system combing clinical evidence and expert knowledge within a physiological closed-loop control structure for mechanical ventilation. The system includes multiple controllers to support adequate gas exchange while adhering to multiple evidence-based components of lung protective ventilation. We performed a pilot study on three animals with an induced ARDS. The system achieved a time-in-target of over 75 % for all targets and avoided any critical phases of low oxygen saturation, despite provoked disturbances such as disconnections from the ventilator and positional changes of the subject. CONCLUSIONS: The presented system can provide personalised and lung-protective ventilation and reduce clinician workload in clinical practice.

Increased Longevity of a Novel Gas Exchanger System for Low-Flow Veno-Venous Extracorporeal CO2 Removal in Acute Hypercapnic Respiratory Failure.

INTRODUCTION: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. METHODS: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. RESULTS: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). CONCLUSION: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure.

Risks and Benefits of Ultra-Lung-Protective Invasive Mechanical Ventilation Strategies with a Focus on Extracorporeal Support.

Lung-protective ventilation strategies are the current standard of care for patients with acute respiratory distress syndrome in an effort to provide adequate ventilatory requirements while minimizing ventilator-induced lung injury. Some patients may benefit from ultra-lung-protective ventilation, a strategy that achieves lower airway pressures and Vt than the current standard. Specific physiological parameters beyond severity of hypoxemia, such as driving pressure and respiratory system elastance, may be predictive of those most likely to benefit. Because application of ultra-lung-protective ventilation is often limited by respiratory acidosis, extracorporeal membrane oxygenation or extracorporeal carbon dioxide removal, which remove carbon dioxide from blood, is an attractive option. These strategies are associated with hematological complications, especially when applied at low blood-flow rates with devices designed for higher blood flows, and a recent large randomized controlled trial failed to show a benefit from an extracorporeal carbon dioxide removal-facilitated ultra-lung-protective ventilation strategy. Only in patients with very severe forms of acute respiratory distress syndrome has the use of an ultra-lung-protective ventilation strategy-accomplished with extracorporeal membrane oxygenation-been suggested to have a favorable risk-to-benefit profile. In this critical care perspective, we address key areas of controversy related to ultra-lung-protective ventilation, including the trade-offs between minimizing ventilator-induced lung injury and the risks from strategies to achieve this added protection. In addition, we suggest which patients might benefit most from an ultra-lung-protective strategy and propose areas of future research.

The association of intraoperative low driving pressure ventilation and nonhome discharge: a historical cohort study.

PURPOSE: To evaluate whether intraoperative ventilation using lower driving pressure decreases the risk of nonhome discharge. METHODS: We conducted a historical cohort study of patients aged ≥ 60 yr who were living at home before undergoing elective, noncardiothoracic surgery at two tertiary healthcare networks in Massachusetts between 2007 and 2018. We assessed the association of the median driving pressure during intraoperative mechanical ventilation with nonhome discharge using multivariable logistic regression analysis, adjusted for patient and procedural factors. Contingent on the primary association, we assessed effect modification by patients' baseline risk and mediation by postoperative respiratory failure. RESULTS: Of 87,407 included patients, 12,584 (14.4%) experienced nonhome discharge. In adjusted analyses, a lower driving pressure was associated with a lower risk of nonhome discharge (adjusted odds ratio [aOR], 0.88; 95% confidence interval [CI], 0.83 to 0.93, per 10 cm H2O decrease; P < 0.001). This association was magnified in patients with a high baseline risk (aOR, 0.77; 95% CI, 0.73 to 0.81, per 10 cm H2O decrease, P-for-interaction < 0.001). The findings were confirmed in 19,518 patients matched for their baseline respiratory system compliance (aOR, 0.90; 95% CI, 0.81 to 1.00; P = 0.04 for low [< 15 cm H2O] vs high [≥ 15 cm H2O] driving pressures). A lower risk of respiratory failure mediated the association of a low driving pressure with nonhome discharge (20.8%; 95% CI, 15.0 to 56.8; P < 0.001). CONCLUSIONS: Intraoperative ventilation maintaining lower driving pressure was associated with a lower risk of nonhome discharge, which can be partially explained by lowered rates of postoperative respiratory failure. Future randomized controlled trials should target driving pressure as a potential intervention to decrease nonhome discharge.

RéSUMé: OBJECTIF: Évaluer si la ventilation peropératoire utilisant une pression motrice plus faible diminue le risque de congé hors domicile. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients âgés de ≥ 60 ans vivant à la maison avant de bénéficier d'une chirurgie non cardiothoracique non urgente dans deux réseaux de soins de santé tertiaires du Massachusetts entre 2007 et 2018. Nous avons évalué l'association entre la pression motrice médiane pendant la ventilation mécanique peropératoire et le congé ailleurs qu'au domicile à l'aide d'une analyse de régression logistique multivariable, ajustée pour tenir compte des facteurs liés aux patients et à l'intervention. En fonction de l'association primaire, nous avons évalué la modification de l'effet par le risque initial des patients et la médiation par l'insuffisance respiratoire postopératoire. RéSULTATS: Sur les 87 407 patients inclus, 12 584 (14,4 %) ont reçu leur congé ailleurs qu'au domicile. Dans les analyses ajustées, une pression motrice plus faible était associée à un risque réduit de congé hors domicile (rapport de cotes ajusté [RCa], 0,88; intervalle de confiance [IC] à 95 %, 0,83 à 0,93, par diminution de 10 cm H2O; P < 0,001). Cette association a été amplifiée chez les patients présentant un risque initial élevé (RCa, 0,77; IC 95 %, 0,73 à 0,81, par diminution de 10 cm H2O, P-pour-interaction < 0,001). Les résultats ont été confirmés chez 19 518 patients appariés pour la compliance initiale de leur système respiratoire (RCa, 0,90; IC 95 %, 0,81 à 1,00; P = 0,04 pour des pressions motrices faibles [< 15 cm H2O] vs élevées [≥ 15 cm H2O]). Un risque plus faible d'insuffisance respiratoire a entraîné une association entre une faible pression motrice et un congé à l'extérieur du domicile (20,8 %; IC 95 %, 15,0 à 56,8 ; P < 0,001). CONCLUSION: La ventilation peropératoire maintenant une pression motrice plus faible a été associée à un risque plus faible de congé hors domicile, ce qui peut s'expliquer en partie par des taux réduits d'insuffisance respiratoire postopératoire. Les futures études randomisées contrôlées devraient cibler la pression motrice comme intervention potentielle pour réduire les congés hors domicile.

Impact of a positive end-expiratory pressure strategy on oxygenation, respiratory compliance, and hemodynamics during laparoscopic surgery in non-obese patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Higher positive end-expiratory pressure (PEEP) during laparoscopic surgery may increase oxygenation and respiratory compliance. This meta-analysis aimed to compare the impact of different intraoperative PEEP strategies on arterial oxygenation, compliance, and hemodynamics during laparoscopic surgery in non-obese patients. METHODS: We searched RCTs in PubMed, Cochrane Library, Web of Science, and Google Scholar from January 2012 to April 2022 comparing the different intraoperative PEEP (Low PEEP (LPEEP): 0-4 mbar; Moderate PEEP (MPEEP): 5-8 mbar; high PEEP (HPEEP): >8 mbar; individualized PEEP - iPEEP) on arterial oxygenation, respiratory compliance (Cdyn), mean arterial pressure (MAP), and heart rate (HR). We calculated mean differences (MD) with 95% confidence intervals (CI), and predictive intervals (PI) using random-effects models. The Cochrane Bias Risk Assessment Tool was applied. RESULTS: 21 RCTs (n = 1554) met the inclusion criteria. HPEEP vs. LPEEP increased PaO2 (+ 29.38 [16.20; 42.56] mmHg, p < 0.0001) or PaO2/FiO2 (+ 36.7 [+ 2.23; +71.70] mmHg, p = 0.04). HPEEP vs. MPEEP increased PaO2 (+ 22.00 [+ 1.11; +42.88] mmHg, p = 0.04) or PaO2/FiO2 (+ 42.7 [+ 2.74; +82.67] mmHg, p = 0.04). iPEEP vs. MPEEP increased PaO2/FiO2 (+ 115.2 [+ 87.21; +143.20] mmHg, p < 0.001). MPEEP vs. LPEP, and HPEEP vs. MPEEP increased PaO2 or PaO2/FiO2 significantly with different heterogeneity. HPEEP vs. LPEEP increased Cdyn (+ 7.87 [+ 1.49; +14.25] ml/mbar, p = 0.02). MPEEP vs. LPEEP, and HPEEP vs. MPEEP did not impact Cdyn (p = 0.14 and 0.38, respectively). iPEEP vs. LPEEP decreased driving pressure (-4.13 [-2.63; -5.63] mbar, p < 0.001). No significant differences in MAP or HR were found between any subgroups. CONCLUSION: HPEEP and iPEEP during PNP in non-obese patients could promote oxygenation and increase Cdyn without clinically significant changes in MAP and HR. MPEEP could be insufficient to increase respiratory compliance and improve oxygenation. LPEEP may lead to decreased respiratory compliance and worsened oxygenation. PROSPERO REGISTRATION: CRD42022362379; registered October 09, 2022.

Exploring phenotype-based ventilator parameter optimization to mitigate postoperative pulmonary complications: a retrospective observational cohort study.

PURPOSE: To identify tidal volume (VT) and positive end-expiratory pressure (PEEP) associated with the lowest incidence and severity of postoperative pulmonary complications (PPCs) for each phenotype based on preoperative characteristics. METHODS: The subjects of this retrospective observational cohort study were 34,910 adults who underwent surgery, using general anesthesia with mechanical ventilation. Initially, the least absolute shrinkage and selection operator regression was employed to select relevant preoperative characteristics. Then, the classification and regression tree (CART) was built to identify phenotypes. Finally, we computed the area under the receiver operating characteristic curves from logistic regressions to identify VT and PEEP associated with the lowest incidence and severity of PPCs for each phenotype. RESULTS: CARTs classified seven phenotypes for each outcome. A probability of the development of PPCs ranged from the lowest (3.51%) to the highest (68.57%), whereas the probability of the development of the highest level of PPC severity ranged from 3.3% to 91.0%. Across all phenotypes, the VT and PEEP associated with the most desirable outcomes were within a small range of VT 7-8 ml/kg predicted body weight with PEEP of between 6 and 8 cmH2O. CONCLUSIONS: The ranges of optimal VT and PEEP were small, regardless of the phenotypes, which had a wide range of risk profiles.

A NOVEL EQUATION SUCCESSFULLY CALCULATES TIDAL VOLUMES FOR LUNG PROTECTIVE VENTILATION.

BACKGROUND: Early application of low-tidal-volume ventilation (LTVV) has been associated with improved outcomes in the emergency department (ED) and intensive care unit (ICU), but is not consistently applied. The perceived complexity of calculating an ideal body weight (IBW)-based tidal volume (Vt) may contribute to this disparity. We hypothesized that a simplified equation could successfully predict LTVV. OBJECTIVE: To create a memorable, single-step, sex-independent equation to estimate LTVV based on height. METHODS: We conducted a retrospective observational cohort study of patients who received mechanical ventilation (MV) at 2 EDs from January 2016 to June 2019. Data were abstracted by automatic query. Patients < 18 years old, < 60 inches in height, and with implausible or incomplete data were excluded. LTVV was defined as ≤ 8 mL/kg IBW. We created a formula predicting a 6-8-mL/kg IBW Vt. We applied this formula to a population of ICU patients in the same health care system who received MV from January 2017 to December 2019 using the same exclusion criteria. The outcome was whether the equation predicted a 6-8-mL/kg IBW Vt. RESULTS: A total of 982 ED patients were included; 753 (76.7%) had an initial Vt < 8 mL/kg IBW. The equation Vt = 20*(Ht-60) + 300 was derived. A total of 3720 ICU patients were included. The Vt equation successfully predicted a Vt of 6-8 mL/kg IBW in 3720 (100%) of ICU patients. CONCLUSIONS: A novel equation successfully predicted a 6-8-mL/kg IBW Vt in a cohort of patients with height ≥ 60 inches.

Effects of driving pressure-guided ventilation by individualized positive end-expiratory pressure on oxygenation undergoing robot-assisted laparoscopic radical prostatectomy: a randomized controlled clinical trial.

PURPOSE: Patients with robot-assisted laparoscopic radical prostatectomy (RALP) need to be placed in Trendelenburg position, which results in cranial displacement of the diaphragm and decreases functional residual capacity and pulmonary compliance. Positive end-expiratory pressure (PEEP) can increase ventilation in the dorsal area, reduce the occurrence of atelectasis and improve oxygenation. However, due to individual differences, inappropriate PEEP will cause lung injury and even hemodynamic instability. Therefore, our study is to evaluate the efficacy of individualized PEEP in RALP. METHODS: We randomly recruited 48 patients and divided them into driving pressure-guided individualized PEEP group (P group, individualized PEEP) or traditional lung-protective ventilation strategy group (C group, tidal volume 8 mL/kg combined with PEEP of 5cmH2O). The primary outcome was the PaO2/FiO2 before extubation. The secondary outcomes included individualized PEEP values in the P group, the results of arterial blood gas analysis, respiratory mechanics parameters and vital sign parameters. Other measurements included intraoperative vasoactive drug dosage, length of stay, postoperative SpO2, leukocyte count, temperature, serum inflammatory factors and soluble receptor for advanced glycation end products (sRAGE). RESULTS: Individualized PEEP improved the PaO2/FiO2 before extubation (P = 0.034) and decreased driving pressure (P = 0.011). The PEEP valued in the P group was 14 [10-14] cmH2O. The lung compliance of the P group was significantly higher than that in the C group (P = 0.013). There was no significant difference in other measurements. CONCLUSIONS: Individualized PEEP could improve PaO2/FiO2 in patients who underwent RALP and do not increase the dosage of intraoperative vasoactive drug and the release of inflammatory factors. TRIAL REGISTRATION: www.chictr.org.cn (registration no. ChiCTR2100047271).

Improving Certified Registered Nurse Anesthetists' Adherence to a Standardized Intraoperative Lung Protective Ventilation Protocol.

PURPOSE: The use of lung protective ventilation (LPV) during general anesthesia is an effective strategy among certified registered nurse anesthetists (CRNAs) to reduce and prevent the incidence of postoperative pulmonary complications. The purpose of this project was to implement a LPV protocol, assess CRNA provider adherence, and investigate differences in ventilation parameters and postoperative oxygen requirements. DESIGN: This quality improvement project was conducted using a pre- and postimplementation design. METHODS: Sixty patients undergoing robotic laparoscopic abdominal surgery and 35 CRNAs at a community hospital participated. An evidence-based intraoperative LPV protocol was developed, CRNA education was provided, and the protocol was implemented. Pre- and postimplementation, CRNA knowledge, and confidence were assessed. Ventilation data were collected at 1-minute intervals intraoperatively and oxygen requirements were recorded in the postanesthesia care unit (PACU). FINDINGS: Use of intraoperative LPV strategies increased 2.4%. Overall CRNA knowledge (P = .588), confidence (P = .031), and practice (P < .001) improved from pre- to postimplementation. Driving pressures decreased from pre- to postimplementation (P < .001). Supplemental oxygen use on admission to the PACU decreased from 93.3% to 70.0%. CONCLUSIONS: Educational interventions and implementation of a standardized protocol can improve the use of intraoperative LPV strategies and patient outcomes.