Lung-protective Ventilation Strategies Research Articles

The Potential Dangers of Recruitment Maneuvers During One Lung Ventilation Surgery

BackgroundExisting evidence regarding lung-protective ventilation (LPV) during one-lung ventilation (OLV) focuses on surrogate outcomes. Our objective was to assess whether an LPV protocol during OLV surgery is associated with reduced respiratory complications. Materials and methodsThis was a matched control retrospective cohort study of patients undergoing pulmonary resection at a tertiary Canadian hospital. The experimental group (n = 50) was derived from primary data of two crossover RCTs, which utilized protocolized LPV strategies with varying levels of positive end-expiratory pressure and recruitment maneuvers. The control group was drawn from a prospectively maintained database; these patients received conventional nonprotocolized ventilation (2000-2010). Each experimental group patient was matched 1:1 with a control group patient with respect to clinically relevant variables (age, sex, diagnosis, smoking status, cardiovascular disease status, comorbidity, BMI, preoperative forced expiratory volume in 1 s, surgery type). Major respiratory complications were defined as composite of acute respiratory distress syndrome, need for new positive-pressure ventilation, and atelectasis requiring bronchoscopy. Paired and unpaired statistical tests were used. ResultsPatients appeared well matched. Major respiratory complications occurred in 8% (n = 4) and 2% (n = 1) of patients in experimental and control groups, respectively (P = 0.50). There was a trend toward increased mortality (4 versus 0, P = 0.06) with protocolized LPV. The patients who died had respiratory complications; one had acute respiratory distress syndrome and two had profound hypoxemia. ConclusionsThere was a nonsignificant trend toward increased mortality with LPV during OLV. Although limited by a small sample size, our findings identify a potential danger to excessive recruitment maneuvers. Larger studies, with clinically important outcomes are needed to better define the risk/benefit trade-offs for LPV during OLV.

DIFFERENCES IN LUNG PROTECTIVE VENTILATION USE IN FEMALE VS MALE ORGAN DONORS

SESSION TITLE: Transplantation SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Given that 15% of patients on the lung transplant list die waiting for a transplant, it is imperative that potential donors be managed optimally to preserve suitable organs. At present, the proportion of potential lungs judged suitable for transplant is only 15-25%. Lung protective ventilation strategies, largely focused on the use of lower tidal volumes (TVs), have been shown to improve outcomes in both ARDS and non-ARDS ICU patients, leading to the recommendation for TVs <=8ml/kg PBW for patients without lung injury, and <=6ml/kg PBW in ARDS. However, adherence to lung protective ventilation remains poor, with women and shorter patients receiving excessive TVs more frequently. With increasing evidence supporting the use of lung protective strategies in potential organ donors, we examined our institutions adherence to lung protective ventilation and whether similar sex disparities exist in this population. METHODS: We analyzed every patient accepted for organ donation at our institution from 2009-2016 (n=112) and a 2:1 randomly matched group of patients referred for donation but who were medically ruled out. We extracted ventilator data, demographic information and arterial blood gas data in 4-hour intervals for the 48 hours preceding the time of death. Data were analyzed to determine patient factors associated with receiving excessive TVs (>8cc/kg PBW). RESULTS: 65% of all subjects received excessive TVs during the 48 hours prior to death, and subjects received excessive TVs during 40% of all measured time points. Frequency of receiving excessive TVs did not differ between donors and rule-outs. 76% of women received excessive TVs at some point, compared to 57% of men (p<0.001). Women were also 50% more likely to receive excessive TVs of greater than 10ml/kg (12% vs 8%, p<0.001). Women received excessive TVs 46% of the time vs. 32% for men (p<0.001). Women also spent more time receiving excessive TVs (11h vs 7h, p<.001) than men. The association between female sex and excessive TVs remained significant after multiple regression analysis adjusting for height, BMI, trauma death and donation outcome (p=0.01). Other independent predictors of excessive TVs were morbid obesity, shorter height, and trauma as a cause of death (all p<0.001). CONCLUSIONS: We show that potential organ donors frequently did not receive appropriate low TV ventilation in the transplant evaluation period. Furthermore, women were less likely to receive lung protective tidal volumes. This association remains even after adjusting for other factors associated with receiving large TVs, including obesity and shorter height. CLINICAL IMPLICATIONS: While this is a single-center retrospective review, it suggests the possibility of an important disparity. Our findings suggest the need for larger, multi-center studies to determine the impact of excessive tidal volumes on organ suitability and outcomes. DISCLOSURES: No relevant relationships by Joaquin Chapa, source=Web Response No relevant relationships by Stephanie Nonas, source=Web Response

Inhalation Injury and Toxic Industrial Chemical Exposure.

Toxic industrial chemicals include chlorine, phosgene, hydrogen sulfide, and ammonia have variable effects on the respiratory tract, and maybe seen alone or in combination, secondary to inhalation injury. Other considerations include the effects of cyanide, carbon monoxide, and fire suppressants. This Clinical Practice Guideline (CPG) will provide the reader with a brief overview of these important topics and general management strategies for each as well as for inhalation injury. Chlorine, phosgene, hydrogen sulfide, and ammonia are either of intermediate or high water solubility leading to immediate reactions with mucous membranes of the face, throat, and lungs and rapid symptoms onset after exposure. The exception to rapid symptom onset is phosgene which may take up to a day to develop severe acute respiratory distress syndrome. Management of these patients includes early airway management, lung-protective ventilator strategies, aggressive pulmonary toilet, and avoidance of volume overload.

A virtual patient model for mechanical ventilation

Background and ObjectivesMechanical ventilation (MV) is a primary therapy for patients with acute respiratory failure. However, poorly selected ventilator settings can cause further lung damage due to heterogeneity of healthy and damaged alveoli. Varying positive-end-expiratory-pressure (PEEP) to a point of minimum elastance is a lung protective ventilator strategy. However, even low levels of PEEP can lead to ventilator induced lung injury for individuals with highly inflamed pulmonary tissue. Hence, models that could accurately predict peak inspiratory pressures after changes to PEEP could improve clinician confidence in attempting potentially beneficial treatment strategies. MethodsThis study develops and validates a physiologically relevant respiratory model that captures elastance and resistance via basis functions within a well-validated single compartment lung model. The model can be personalised using information available at a low PEEP to predict lung mechanics at a higher PEEP. Proof of concept validation is undertaken with data from four patients and eight recruitment manoeuvre arms. ResultsResults show low error when predicting upwards over the clinically relevant pressure range, with the model able to predict peak inspiratory pressure with less than 10% error over 90% of the range of PEEP changes up to 12 cmH2O. ConclusionsThe results provide an in-silico model-based means of predicting clinically relevant responses to changes in MV therapy, which is the foundation of a first virtual patient for MV.

Extrapleural pneumonectomy- perioperative anaesthetic conduct

Malignant mesothelioma is a rare tumour arising from mesothelial lining that mostly occurs in the pleura with survival of around 12 months. 1 Extrapleural pneumonectomy, which is the mainstay of treatment for locally advanced malignant pleural mesothelioma, presents a great challenge to anaesthesiologists as it can be associated with high perioperative morbidity and mortality. We present a case report on anaesthetic management for extrapleural pneumonectomy in a 64-year-old patient with advanced malignant pleura mesothelioma. Our case report highlights: crucial role of anaesthetic management in reducing perioperative complications by better knowledge of physiology and technical aspects of the surgery; issues and challenges related to the anaesthetic management such as invasive monitoring, lung isolation, protective lung ventilation strategy, appropriate fluid management and adequate analgesia to enable extubation post-surgery in the operating room; high vigilance for diagnosing life-threatening complications such as cardiac herniation; team working and collaboration with surgeon to improve patient outcome and post-operative monitoring and management.

Monitoring Lung Mechanics during Mechanical Ventilation using Machine Learning Algorithms.

Evaluation of lung mechanics is the primary component for designing lung protective optimal ventilation strategies. This paper presents a machine learning approach for bedside assessment of respiratory resistance (R) and compliance (C). We develop machine learning algorithms to track flow rate and airway pressure and estimate R and C continuously and in real-time. An experimental study is conducted, by connecting a pressure control ventilator to a test lung that simulates various R and C values, to gather sensor data for validation of the devised algorithms. We develop supervised learning algorithms based on decision tree, decision table, and Support Vector Machine (SVM) techniques to predict R and C values. Our experimental results demonstrate that the proposed algorithms achieve 90.3%, 93.1%, and 63.9% accuracy in assessing respiratory R and C using decision table, decision tree, and SVM, respectively. These results along with our ability to estimate R and C with 99.4% accuracy using a linear regression model demonstrate the potential of the proposed approach for constructing a new generation of ventilation technologies that leverage novel computational models to control their underlying parameters for personalized healthcare and context-aware interventions.

Adoption of Lung Protective ventilation IN patients undergoing Emergency laparotomy: the ALPINE study. A prospective multicentre observational study

Emergency abdominal surgery is associated with a high risk of postoperative pulmonary complications (PPCs). The primary aim of this study was to determine whether patients undergoing emergency laparotomy are ventilated using a lung-protective ventilation strategy employing tidal volume ≤8 ml kg-1 ideal body weight-1, PEEP >5 cm H2O, and recruitment manoeuvres. The secondary aim was to investigate the association between ventilation factors (lung-protective ventilation strategy, intraoperative FiO2, and peak inspiratory pressure) and the occurrence of PPCs. Data were collected prospectively in 28 hospitals across London as part of routine National Emergency Laparotomy Audit (NELA). Patients were followed for 7 days. Complications were defined according to the European Perioperative Clinical Outcome definition. Data were collected from 568 patients. The median [inter-quartile range (IQR)] tidal volume observed was 500 ml (450-540 ml), corresponding to a median tidal volume of 8 ml kg-1 ideal body weight-1 (IQR: 7.2-9.1 ml). A lung-protectiveventilation strategy was employed in 4.9% (28/568) of patients, and was not protective against the occurrence of PPCs in the multivariable analysis (hazard ratio=1.06; P=0.69). Peak inspiratory pressure of <30 cm H2O was protective against development of PPCs (hazard ratio=0.46; confidence interval: 0.30-0.72; P=0.001). Median FiO2 was 0.5 (IQR: 0.44-0.53), and an increase in FiO2 by 5% increased the risk of developing a PPC by 8% (2.6-14.1%; P=0.008). Both intraoperative peak inspiratory pressure and FiO2 are independent factors significantly associated with development of a postoperative pulmonary complication in emergency laparotomy patients. Further studies are required to identify causality and to demonstrate if their manipulation could lead to better clinical outcomes.

Recruitment maneuver does not provide any mortality benefit over lung protective strategy ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis and systematic review of the randomized controlled trials

BackgroundClinical benefits of recruitment maneuver in ARDS patients are controversial. A number of previous studies showed possible benefits; a large recent study reported that recruitment maneuver and PEEP titration may even be harmful. This meta-analysis was designed to compare the clinical utility of recruitment maneuver with low tidal volume ventilation in adult patients with ARDS.MethodsRandomized controlled trials comparing recruitment maneuver and lung protective ventilation strategy with lung protective strategy ventilation protocol alone in adult patients with ARDS has been included in this meta-analysis. PubMed and Cochrane Central Register of Controlled Trials were searched from inception to 10 November 2017 to identify potentially eligible trials. Pooled risk ratio (RR) and standardized mean difference (SMD) were calculated for binary and continuous variables respectively.ResultsData of 2480 patients from 7 randomized controlled trials have been included in this meta-analysis and systemic review. Reported mortality at the longest available follow-up [RR (95% CI) 0.93 (0.80, 1.08); p = 0.33], ICU mortality [RR (95% CI) 0.91 (0.76, 1.10); p = 0.33] and in-hospital mortality [RR (95% CI) 0.95 (0.83, 1.08); p = 0.45] were similar between recruitment maneuver group and standard lung protective ventilation group. Duration of hospital stay [SMD (95% CI) 0.00 (− 0.09, 0.10); p = 0.92] and duration of ICU stays [SMD (95% CI) 0.05 (− 0.09, 0.19); p = 0.49] were also similar between recruitment maneuver group and standard lung protective ventilation group. Risk of barotrauma was also similar.ConclusionUse of recruitment maneuver along with co-interventions such as PEEP titration does not provide any benefit in terms of mortality, length of ICU, and hospital stay in ARDS patients.

Research progress about effects of lung protective ventilation strategy on respiratory function in the elderly with laparoscopic surgery

With the further study of the ventilation model, pulmonary protective ventilation has been paid increasing attention by more and more scholars. Recent studies have shown that lung protective ventilation strategy has been proved to improve oxygenation and reduce postoperative pulmonary complications. Due to the special physiological function of the elderly, they are more likely to have postoperative pulmonary complications after mechanical ventilation. The article discusses which ventilation mode is more suitable for elderly patients undergoing laparoscopic surgery. This article reviews some theories about the physiological function of the elderly, and the effect of laparoscopy on the respiratory function of the elderly. It also reviews the related progress and controversy of low tidal volume, positive end expiratory pressure, recruitment maneuvers and other pulmonary protective strategies. Key words: Pulmonary ventilation; Laparoscopy; Aged; Review

Application of intraoperative lung-protective ventilation varies in accordance with the knowledge of anaesthesiologists: a single-Centre questionnaire study and a retrospective observational study

BackgroundThe benefits of lung-protective ventilation (LPV) with a low tidal volume (6 mL/kg of ideal body weight [IBW]), limited plateau pressure (< 28–30 cm H2O), and appropriate positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome have become apparent and it is now widely adopted in intensive care units. Recently evidence for LPV in general anaesthesia has been accumulated, but it is not yet generally applied by anaesthesiologists in the operating room.MethodsThis study investigated the perception about intraoperative LPV among 82 anaesthesiologists through a questionnaire survey and identified the differences in ventilator settings according to recognition of lung-protective ventilation. Furthermore, we investigated the changes in the trend for using this form of ventilation during general anaesthesia in the past 10 years.ResultsAnaesthesiologists who had received training in LPV were more knowledgeable about this approach. Anaesthesiologists with knowledge of the concept behind LPV strategies applied a lower tidal volume (median (IQR [range]), 8.2 (8.0–9.2 [7.1–10.3]) vs. 9.2 (9.1–10.1 [7.6–10.1]) mL/kg; p = 0.033) and used PEEP more frequently (69/72 [95.8%] vs. 5/8 [62.5%]; p = 0.012; odds ratio, 13.8 [2.19–86.9]) for laparoscopic surgery than did those without such knowledge. Anaesthesiologists who were able to answer a question related to LPV correctly (respondents who chose ‘height’ to a multiple choice question asking what variables should be considered most important in the initial setting of tidal volume) applied a lower tidal volume in cases of laparoscopic surgery and obese patients. There was an increase in the number of patients receiving LPV (VT < 10 mL/kgIBW and PEEP ≥5 cm H2O) between 2004 and 2014 (0/818 [0.0%] vs. 280/818 [34.2%]; p < 0.001).ConclusionsOur study suggests that the knowledge of LPV is directly related to its implementation, and can explain the increase in LPV use in general anaesthesia. Further studies should assess the impact of using intraoperative LPV on clinical outcomes and should determine the efficacy of education on intraoperative LPV implementation.

Fatal Acute Respiratory Distress Syndrome Due to Influenza A (H1N1) Infection in Patients After Kidney Transplantation: A Report of Five Cases

BackgroundIn the general population, swine influenza is a self-limited infection. Patients after kidney transplantation, however, are at increased risk for complications and mortality from influenza A (H1N1). Acute respiratory distress syndrome (ARDS) complicates up to 55% of influenza-related pneumonia in hospitalized patients and carries a mortality of 40–46%. We describe our experience in intensive care of kidney transplant patients with ARDS complicating influenza A (H1N1) pneumonia during a flu outbreak.Case ReportFive adult post kidney transplantation patients with progressive respiratory failure admitted to the ICU between February 2016 and April 2016 were included in this retrospectively analysis.All patients had influenza A (H1N1) viral pneumonia (confirmed with RT-PCR) complicated by ARDS and septic shock with multiple organ dysfunction syndrome. None of the patients received seasonal influenza vaccines. All patients had negative rapid influenza bedside tests, which resulted in delay of administration of antiviral therapy prior to admission to the ICU. All patients were managed with a lung protective ventilation strategy (average days of mechanical ventilation, 17.6±15.3). Three patients required additional therapies for refractory hypoxemia, including high positive end-expiratory pressure and prone positioning. Extracorporeal membrane oxygenation was not implemented. Treatment with oseltamivir was added to a broad-spectrum antibiotic on the first to the fifth day of intensive care. Despite these measures, all patients eventually died.ConclusionsDespite great progress in the management of ARDS, based mostly on advanced mechanical ventilation, early antiviral treatment of pneumonia caused by influenza A (H1N1) and annual vaccinations seem essential in prevention and management of influenza A (H1N1) infection among kidney transplant recipients.

Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of continuing education programmes on mechanical ventilation involving nurses in improving patient outcomes exists. Comprehensive continuing education is required. Well-designed trials are required to confirm that comprehensive continuing education involving intensive care nurses about mechanical ventilation improves patient outcomes.

Management of severe respiratory failure in complex trauma patients

Acute respiratory failure represents a major challenge in the management of complex trauma patients. Both direct thoracic injury and extrathoracic injury can lead to respiratory failure. The pathophysiologic mechanisms underlying respiratory failure in this setting can vary. Successful management of severe respiratory failure in complex trauma patients requires an understanding of these pathophysiologic processes and careful attention to multiple treatment priorities. Lung-protective ventilation strategies, judicious fluid management, and the use of rescue modalities are discussed in this review.

Safety and Effectiveness of Alveolar Recruitment Maneuvers and Positive End-expiratory Pressure During General Anesthesia for Cesarean Section: A Prospective, Randomized Trial

(Int J Obstet Anesth. 2017;30:30–38) General anesthesia (GA) is sometimes associated with impaired oxygenation. Changes in respiratory mechanics and lung function under anesthesia contribute to this, with atelectasis being one of the most common etiologies of decreased oxygenation during GA. The supine position required during cesarean delivery results in decreased functional residual capacity and impaired lung compliance, as does the gravid uterus. Therefore, this patient population may be more likely to develop clinically significant atelectasis during general anesthesia. Alveolar recruitment maneuvers (ARM) with positive end-expiratory pressure (PEEP) along with low tidal volumes, considered a lung-protective ventilation strategy, can improve lung function and oxygenation and are frequently used for critically ill patients with respiratory distress syndrome. ARM with PEEP has also been shown to improve oxygenation and lung compliance in patients during general anesthesia. The current study was undertaken to test the hypothesis that ARM with PEEP and low tidal volume could improve intraoperative lung dynamic compliance during GA for cesarean delivery.

The effect of an intraoperative, lung-protective ventilation strategy in neurosurgical patients undergoing craniotomy: study protocol for a randomized controlled trial

BackgroundVentilator-induced lung injury is a major cause of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgery after general anesthesia. However, there is no study on the effect of a lung-protective ventilation strategy in patients undergoing neurosurgery.MethodsThis is a single-center, randomized, parallel-group controlled trial which will be carried out at Beijing Tiantan Hospital, Capital Medical University. Three hundred and thirty-four patients undergoing intracranial tumor surgery will be randomly allocated to the control group and the protective-ventilation strategy group. In the control group, tidal volume (VT) will be set at 10–12 ml/kg of predicted body weight but PEEP and recruitment maneuvers will not be used. In the protective group, VT will be set at 6–8 ml/kg of predicted body weight, PEEP at 6–8 cmH2O, and a recruitment maneuver will be used intermittently. The primary outcome is pulmonary complications within 7 days postoperatively. Secondary outcomes include intraoperative brain relaxation, the postoperative complications within 30 days and the cost analysis.DiscussionThis study aims to determine if the protective, pulmonary-ventilation strategy decreases the incidence of PPCs in patients undergoing neurosurgical anesthesia. If our results are positive, the study will indicate whether the protective, pulmonary-ventilation strategy is efficiently and safely used in neurosurgical patients undergoing the craniotomy.Trial registrationClinicalTrials.gov, ID: NCT02386683. Registered on 18 October 2014.

Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial

The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m2. Patients were randomly assigned (1:1:1:1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0·89 [95% CI 0·74-1·07; p=0·25]), OLA-CPAP (111 [47%] of 238, 0·91 [0·76-1·09; p=0·35]), or STD-CPAP groups (118 [48%] of 244, 0·95 [0·80-1·14; p=0·65]) when compared with patients in the STD-O2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation. Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness, and Grants Programme of the European Society of Anaesthesiology.

Hypercapnia induces IL-1\u03b2 overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats

BackgroundCognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1β) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1β secretion outside the central nervous system (CNS). However, the underlying mechanism of hypercapnia aggravating cognitive impairment under hypoxia has remained uncertain. This study was aimed to explore whether hypercapnia would partake in increasing IL-1β secretion via activating the NLRP3 (NLR family, pyrin domain-containing 3) inflammasome in the hypoxic CNS and in aggravating cognitive impairment.MethodsThe Sprague-Dawley (SD) rats that underwent hypercapnia/hypoxemia were used for assessment of NLRP3, caspase-1, IL-1β, Bcl-2, Bax, and caspase-3 expression by Western blotting or double immunofluorescence, and the model was also used for Morris water maze test. In addition, Z-YVAD-FMK, a caspase-1 inhibitor, was used to treat BV-2 microglia to determine whether activation of NLRP3 inflammasome was required for the enhancing effect of hypercapnia on expressing IL-1β by Western blotting or double immunofluorescence. The interaction effects were analyzed by factorial ANOVA. Simple effects analyses were performed when an interaction was observed.ResultsThere were interaction effects on cognitive impairment, apoptosis of hippocampal neurons, activation of NLRP3 inflammasome, and upregulation of IL-1β between hypercapnia treatment and hypoxia treatment. Hypercapnia + hypoxia treatment caused more serious damage to the learning and memory of rats than those subjected to hypoxia treatment alone. Expression levels of Bcl-2 were reduced, while that of Bax and caspase-3 were increased by hypercapnia in hypoxic hippocampus. Hypercapnia markedly increased the expression of NLRP3, caspase-1, and IL-1β in hypoxia-activated microglia both in vivo and in vitro. Pharmacological inhibition of NLRP3 inflammasome activation and release of IL-1β might ameliorate apoptosis of neurons.ConclusionsThe present results suggest that hypercapnia-induced IL-1β overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.

Is There a Relationship Between Optimal Cerebral Perfusion Pressure-Guided Management and PaO2/FiO2 Ratio After Severe Traumatic Brain Injury?

Severe traumatic brain injury (TBI) management has been associated with adult respiratory distress syndrome (ARDS) in previous literature. We aimed to investigate the relationships between optimal CPP-guided management, ventilation parameters over time and outcome after severe TBI. We performed retrospective analysis of recorded data from 38 patients admitted to the NCCU after severe TBI, managed with optimal cerebral perfusion pressure (CPPopt)-guided therapy, calculated using pressure reactivity index (PRx). All patients were sedated and ventilated with lung protective criteria (Peep > 5, tidal volume 6-8 ml/kg and airway pressure < 30 cmH2O). Daily mean CPPopt varied between a minimum of 84 mmHg and a maximum of 91 mmHg with an all period mean value of 88 mmHg. The mean value for the difference between CPP and CPPopt was -1.9 mmHg. Daily mean P/F ratio decreased and varied between 253 and 387 with an all-period mean of 294 mmHg. During the 10 days of recording data, five patients (13%) developed criteria of severe ARDS, but only two patients died due to severe ARDS (5%). PaO2/FiO2 (P/F) ratio did not correlate with CPPopt, but showed a strong correlation with tidal volume (p = 0.000) and driving pressure (p = 0.000). Although CPPopt-guided therapy may induce a decrease in P/F ratio over time during the first 10 days, we could not find an association with worst outcome, which may be influenced by lung protective ventilation strategies and preservation of cerebral autoregulation.

Comparison of Hemodynamic Monitoring between Transesophageal Doppler and Ultrasonography-Guided Inferior Vena Cava Distensibility in Supine versus Prone Position: A Pilot Study.

Introduction:Lung-protective ventilation strategy and prone positioning are the strategies practiced to manage patients suffering from acute respiratory distress syndrome (ARDS). Inferior Vena Cava Distensibility (dIVC) Index has been used for predicting fluid responsiveness (FR) in supine position. We conducted this study to observe the utility of dIVC in prone position in ARDS patients and compare it with esophageal Doppler (ED) parameters.Materials and Methods:After ethical clearance, a prospective observational pilot study was conducted in a 12-bedded tertiary care hospital. Adult ARDS patients who were treated with prone ventilation were included. Informed consent was taken from the relatives. IVC was visualized through right lateral approach both in supine and prone positions. We compared IVC distensibility and ED parameters, first in 45° head up and then in prone. FR was defined as an increase in the stroke volume of ≥15% as measured by ED. The patients with dIVC >18% were assumed to be fluid responsive. Statistical analysis was done using SPSS software version 20.Results:Twenty-five patients met the inclusion criteria. ARDS was (mean P/F ratio 116.64 ± 44.76) mostly due to pulmonary etiology. Out of 25 patients, 10 patients were fluid responsive based on dIVC (cutoff >18%) in supine position. When compared to ED values after passive leg raising, dIVC had a sensitivity and specificity of 77.78% and 81.25%, respectively, in predicting FR with a moderate-to-absolute agreement between the two methods. IVC distensibility showed statistically significant negative correlation with corrected flow time (FTc) values both in supine and in prone positions.Conclusion:IVC variability can be observed in acute respiratory distress syndrome patients in prone position. Inferior Vena Cava Distensibility correlates with flow time in both the positions.

Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies.

Acute respiratory distress syndrome (ARDS) is the most severe form of acute respiratory failure characterized by diffuse alveolar and endothelial damage. The severe pathophysiological changes in lung parenchyma and pulmonary circulation together with the effects of positive pressure ventilation profoundly affect heart lung interactions in ARDS. The term pulmonary vascular dysfunction (PVD) refers to the specific involvement of the vascular compartment in ARDS and is expressed clinically by an increase in pulmonary arterial (PA) pressure and pulmonary vascular resistance both affecting right ventricular (RV) afterload. When severe, PVD can lead to RV failure which is associated to an increased mortality. The effect of PVD on RV function is not only a consequence of increased pulmonary vascular resistance as afterload is a much more complex phenomenon that includes all factors that oppose efficient ventricular ejection. Impaired pulmonary vascular mechanics including increased arterial elastance and augmented wave-reflection phenomena are commonly seen in ARDS and can additionally affect RV afterload. The use of selective pulmonary vasodilators and lung protective mechanical ventilation strategies are therapeutic interventions that can ameliorate PVD. Prone positioning and the open lung approach (OLA) are especially attractive strategies to improve PVD due to their effects on increasing functional lung volume. In this review we will describe some pathophysiological aspects of heart-lung interactions during the ventilatory support of ARDS, its clinical assessment and discuss therapeutic interventions to prevent the occurrence and progression of PVD and RV failure.