Publications by authors named "Robert M Kacmarek"

216 Publications

Stratification for Identification of Prognostic Categories In the Acute RESpiratory Distress Syndrome (SPIRES) Score.

Crit Care Med 2021 Jul 2. Epub 2021 Jul 2.

1 CIBER de Enfermedades Respiratorias, Instituto Salud Carlos III, Madrid, Spain. 2 Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain. 3 Division of Biostatistics, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain. 4 Intensive Care Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. 5 Intensive Care Unit, Hospital Universitario A Coruña, La Coruña, Spain. 6 Intensive Care Unit, Hospital Universitario Virgen de Arrixaca, Murcia, Spain. 7 Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain. 8 Intensive Care Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 9 Intensive Care Unit, Hospital Virgen de la Luz, Cuenca, Spain. 10 Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain. 11 Intensive Care Unit, Complejo Asistencial Universitario de León, León, Spain. 12 Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 13 Intensive Care Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain. 14 Intensive Care Unit, Fundación Hospital Universitario Jiménez Díaz, Madrid, Spain. 15 Department of Anesthesiology and Critical Care, Hospital Clinic, Institut D'investigació August Pi i Sunyer, Barcelona, Spain. 16 Intensive Care Unit, Hospital Regional Universitario de Málaga Carlos Haya, Málaga, Spain. 17 Intensive Care Unit, Hospital Universitario Mutua Terrassa, Terrassa, Barcelona, Spain. 18 Department of Thoracic Surgery, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain. 19 Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. 20 Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. 21 Department of Respiratory Care, Massachusetts General Hospital, Boston, MA. 22 Department of Anesthesiology, Harvard University, Boston, MA.

Objectives: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death.

Design: A development and validation study using clinical data from four prospective, multicenter, observational cohorts.

Setting: A network of multidisciplinary ICUs.

Patients: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation.

Interventions: None.

Measurements And Main Results: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of PaO2 to FIO2 assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of PaO2 to FIO2 at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale.

Conclusions: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials.
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http://dx.doi.org/10.1097/CCM.0000000000005142DOI Listing
July 2021

Longitudinal Changes in Patient-Ventilator Asynchronies and Respiratory System Mechanics Before and After Tracheostomy. A Pilot Study.

Respir Care 2021 Jul 6. Epub 2021 Jul 6.

Critical Care Center, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí I3PT. Sabadell, Spain.

Background: This was a pilot study to analyze the effects of tracheostomy on patient-ventilator asynchronies and respiratory system mechanics. Data were extracted from an ongoing prospective, real-world database that stores continuous output from ventilators and bedside monitors. Twenty adult subjects were on mechanical ventilation and were tracheostomized during an ICU stay: 55% were admitted to the ICU for respiratory failure and 35% for neurologic conditions; the median duration of mechanical ventilation before tracheostomy was 12 d; and the median duration of mechanical ventilation was 16 d.

Methods: We compared patient-ventilator asynchronies (the overall asynchrony index and the rates of specific asynchronies) and respiratory system mechanics (respiratory-system compliance and airway resistance) during the 24 h before tracheostomy versus the 24 h after tracheostomy. We analyzed possible differences in these variables among the subjects who underwent surgical versus percutaneous tracheostomy. To compare longitudinal changes in the variables, we used linear mixed-effects models for repeated measures along time in different observation periods. A total of 920 h of mechanical ventilation were analyzed.

Results: Respiratory mechanics and asynchronies did not differ significantly between the 24-h periods before and after tracheostomy: compliance of the respiratory system median (IQR) (47.9 [41.3 - 54.6] mL/cm HO vs 47.6 [40.9 - 54.3] mL/cm HO; = .94), airway resistance (9.3 [7.5 - 11.1] cm HO/L/s vs 7.0 [5.2 - 8.8] cm HO/L/s; = .07), asynchrony index (2.0% [1.1 - 3.6%] vs 4.1% [2.3 - 7.6%]; = .09), ineffective expiratory efforts (0.9% [0.4 - 1.8%] vs 2.2% [1.0 - 4.4%]; = .08), double cycling (0.5% [0.3 - 1.0%] vs 0.9% [0.5 - 1.9%]; = .24), and percentage of air trapping (7.6% [4.2 - 13.8%] vs 10.6% [5.9 - 19.2%]; = .43). No differences in respiratory mechanics or patient-ventilator asynchronies were observed between percutaneous and surgical procedures.

Conclusions: Tracheostomy did not affect patient-ventilator asynchronies or respiratory mechanics within 24 h before and after the procedure.
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http://dx.doi.org/10.4187/respcare.08824DOI Listing
July 2021

Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity.

Chest 2021 Jun 8;159(6):2373-2383. Epub 2021 May 8.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Department of Respiratory Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA. Electronic address:

Background: Increased pleural pressure affects the mechanics of breathing of people with class III obesity (BMI > 40 kg/m).

Research Question: What are the acute effects of CPAP titrated to match pleural pressure on cardiopulmonary function in spontaneously breathing patients with class III obesity?

Study Design And Methods: We enrolled six participants with BMI within normal range (control participants, group I) and 12 patients with class III obesity (group II) divided into subgroups: IIa, BMI of 40 to 50 kg/m; and IIb, BMI of ≥ 50 kg/m. The study was performed in two phases: in phase 1, participants were supine and breathing spontaneously at atmospheric pressure, and in phase 2, participants were supine and breathing with CPAP titrated to match their end-expiratory esophageal pressure in the absence of CPAP. Respiratory mechanics, esophageal pressure, and hemodynamic data were collected, and right heart function was evaluated by transthoracic echocardiography.

Results: The levels of CPAP titrated to match pleural pressure in group I, subgroup IIa, and subgroup IIb were 6 ± 2 cmHO, 12 ± 3 cmHO, and 18 ± 4 cmHO, respectively. In both subgroups IIa and IIb, CPAP titrated to match pleural pressure decreased minute ventilation (IIa, P = .03; IIb, P = .03), improved peripheral oxygen saturation (IIa, P = .04; IIb, P = .02), improved homogeneity of tidal volume distribution between ventral and dorsal lung regions (IIa, P = .22; IIb, P = .03), and decreased work of breathing (IIa, P < .001; IIb, P = .003) with a reduction in both the work spent to initiate inspiratory flow as well as tidal ventilation. In five hypertensive participants with obesity, BP decreased to normal range, without impairment of right heart function.

Interpretation: In ambulatory patients with class III obesity, CPAP titrated to match pleural pressure decreased work of breathing and improved respiratory mechanics while maintaining hemodynamic stability, without impairing right heart function.

Trial Registry: ClinicalTrials.gov; No.: NCT02523352; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.01.055DOI Listing
June 2021

Inhaled Nitric Oxide Delivery Systems for Mechanically Ventilated and Nonintubated Patients: A Review.

Respir Care 2021 Jun;66(6):1021-1028

Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Nitric oxide (NO) is a biologically active molecule approved for the treatment of pulmonary hypertension in newborn patients. Commercially available NO delivery systems use pressurized cylinders as the source of NO and a sensor to control the concentrations of NO and nitrogen dioxide (NO) delivered. Cylinder-based delivery systems are safe and widely used around the world, but they are bulky, expensive, and reliant on a robust supply chain. In the past few years, novel NO generators and delivery systems have been developed to overcome these limitations. Electric NO generators produce NO from ambient air using high-voltage electrical discharge to ionize air, which leads to the formation of NO, NO, and ozone (O). A scavenging system is incorporated to reduce the concentration of the toxic byproducts generated in this type of system. NO can also be generated by the reduction of NO by ascorbic acid or released from liquid solutions or solid nanoparticles. The development of easy-to-use, safe, and portable NO delivery systems may enable the delivery of NO in the out-patient setting or at home. Furthermore, non-cylinder-based NO generators reduce the cost of NO production and storage and may therefore make NO delivery feasible in low-resource settings. Here we review commercially available systems that can generate and administer inhalable NO.
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http://dx.doi.org/10.4187/respcare.08856DOI Listing
June 2021

Clusters of Double Triggering Impact Clinical Outcomes: Insights From the EPIdemiology of Patient-Ventilator aSYNChrony (EPISYNC) Cohort Study.

Crit Care Med 2021 Apr 21. Epub 2021 Apr 21.

Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina Universidade de São Paulo, São Paulo, Brazil. Serviço de Fisioterapia, Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina Universidade de São Paulo, Faculdade de Medicina Universidade de São Paulo, São Paulo, Brazil. Critical Care Center, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. Department of Respiratory Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Department of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Objectives: To measure the impact of clusters of double triggering on clinical outcomes.

Design: Prospective cohort study.

Setting: Respiratory ICU in Brazil.

Patients: Adult patients under recent mechanical ventilation and with expectation of mechanical ventilation for more than 24 hours after enrollment.

Interventions: None.

Measurements And Main Results: We used a dedicated software to analyze ventilator waveforms throughout the entire period of mechanical ventilation and detect double triggering. We defined a cluster of double triggering as a period of time containing at least six double triggering events in a 3-minute period. Patients were followed until hospital discharge. We addressed the association between the presence and the duration of clusters with clinical outcomes. A total of 103 patients were enrolled in the study and 90 (87%) had at least one cluster of double triggering. The median number of clusters per patient was 19 (interquartile range, 6-41), with a median duration of 8 minutes (6-12 min). Compared with patients who had no clusters, patients with at least one cluster had longer duration of mechanical ventilation (7 d [4-11 d] vs 2 d [2-3 d]) and ICU length of stay (9 d [7-16 d] vs 13 d [2-8 d]). Thirty-three patients had high cumulative duration of clusters of double triggering (≥ 12 hr), and it was associated with longer duration of mechanical ventilation, fewer ventilator-free days, and longer ICU length of stay. Adjusted by duration of mechanical ventilation and severity of illness, high cumulative duration of clusters was associated with shorter survival at 28 days (hazard ratio, 2.09 d; 95% CI, 1.04-4.19 d).

Conclusions: Clusters of double triggering are common and were associated with worse clinical outcomes. Patients who had a high cumulative duration of clusters had fewer ventilator-free days, longer duration of mechanical ventilation, longer ICU length of stay, and shorter survival than patients with low cumulative duration of cluster.
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http://dx.doi.org/10.1097/CCM.0000000000005029DOI Listing
April 2021

Weaning patients with obesity from ventilatory support.

Curr Opin Crit Care 2021 06;27(3):311-319

Harvard Medical School.

Purpose Of Review: Obesity prevalence is increasing in most countries in the world. In the United States, 42% of the population is obese (body mass index (BMI) > 30) and 9.2% is obese class III (BMI > 40). One of the greatest challenges in critically ill patients with obesity is the optimization of mechanical ventilation. The goal of this review is to describe respiratory physiologic changes in patients with obesity and discuss possible mechanical ventilation strategies to improve respiratory function.

Recent Findings: Individualized mechanical ventilation based on respiratory physiology after a decremental positive end-expiratory pressure (PEEP) trial improves oxygenation and respiratory mechanics. In a recent study, mortality of patients with respiratory failure and obesity was reduced by about 50% when mechanical ventilation was associated with the use of esophageal manometry and electrical impedance tomography (EIT).

Summary: Obesity greatly alters the respiratory system mechanics causing atelectasis and prolonged duration of mechanical ventilation. At present, novel strategies to ventilate patients with obesity based on individual respiratory physiology showed to be superior to those based on standard universal tables of mechanical ventilation. Esophageal manometry and EIT are essential tools to systematically assess respiratory system mechanics, safely adjust relatively high levels of PEEP, and improve chances for successful weaning.
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http://dx.doi.org/10.1097/MCC.0000000000000823DOI Listing
June 2021

An algorithm for the sedation of patients with obstructive sleep apnea by non-anesthesiologists.

Curr Med Res Opin 2021 Apr 24;37(4):531-534. Epub 2021 Feb 24.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Objective: Patients with obstructive sleep apnea (OSA) are at risk for adverse events when moderate sedation is administered by nurse protocols (NAMS) under the guidance of non-anesthesiologists. An algorithm was applied for the appropriate section of patients to receive NAMS and the application of continuous positive airway pressure (CPAP).

Methods: An algorithm was developed for patients with OSA who were scheduled for gastroenterology, radiology, and cardiology procedures using NAMS. Those with normal airways and without contraindications for NAMS were classified as CPAP-independent (CPAP-I; not routinely used) or CPAP-dependent (CPAP-D; always used). CPAP machines were brought in by CPAP-D patients or supplied by the hospital and set at a patient's routine setting or 10 cm HO if not known. CPAP-D patients for procedures for which CPAP could not be applied were done under anesthesia care. We retrospectively examined this program for the 2008-2018 period.

Results: Since the inception of this protocol in 2008, 803 patients with OSA safely underwent procedures using either personal CPAP or CPAP provided by the hospital.

Conclusions: Patients with OSA can safely have NAMS for procedures when CPAP is applied based on a protocol that considers airway evaluation, the procedure, and whether there is dependence upon CPAP.
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http://dx.doi.org/10.1080/03007995.2021.1888706DOI Listing
April 2021

Consequences to the Lungs When Gas Swings Between Lung Units During Patient Triggered Mechanical Ventilation.

Respir Care 2021 01;66(1):170-172

CIBER de Enfermedades Respiratorias Instituto de Salud Carlos III Madrid, Spain.

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http://dx.doi.org/10.4187/respcare.08764DOI Listing
January 2021

Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019.

Crit Care Explor 2020 Nov 16;2(11):e0277. Epub 2020 Nov 16.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Treatment options are limited for patients with respiratory failure due to coronavirus disease 2019. Conventional oxygen therapy and awake proning are options, but the use of high-flow nasal cannula and continuous positive airway pressure are controversial. There is an urgent need for effective rescue therapies. Our aim is to evaluate the role of inhaled nitric oxide 160 ppm as a possible rescue therapy in nonintubated coronavirus disease 2019 patients.

Design: Retrospective evaluation of coronavirus disease 2019 patients in respiratory distress receiving nitric oxide gas as rescue therapy.

Setting: Massachusetts General Hospital, between March 18, 2020, and May 20, 2020, during the local coronavirus disease 2019 surge.

Patients: Coronavirus disease 2019 patients at high risk for acute hypoxemic respiratory failure with worsening symptoms despite use of supplemental oxygen and/or awake proning.

Interventions: Patients received nitric oxide at concentrations of 160 ppm for 30 minutes twice per day via a face mask until resolution of symptoms, discharge, intubation, or the transition to comfort measures only.

Measurements And Main Results: Between March 18, 2020, and May 20, 2020, five patients received nitric oxide inhalation as a rescue therapy for coronavirus disease 2019 at Massachusetts General Hospital. All received at least one dosage. The three patients that received multiple treatments (ranging from five to nine) survived and were discharged home. Maximum methemoglobin concentration after 30 minutes of breathing nitric oxide was 2.0% (1.7-2.3%). Nitrogen dioxide was below 2 ppm. No changes in mean arterial pressure or heart rate were observed during or after nitric oxide treatment. Oxygenation and the respiratory rate remained stable during and after nitric oxide treatments. For two patients, inflammatory marker data were available and demonstrate a reduction or a cessation of escalation after nitric oxide treatment.

Conclusions: Nitric oxide at 160 ppm may be an effective adjuvant rescue therapy for patients with coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671879PMC
November 2020

Prevalence and Outcomes of Acute Hypoxaemic Respiratory Failure in Wales: The PANDORA-WALES Study.

J Clin Med 2020 Oct 31;9(11). Epub 2020 Oct 31.

Department of Anaesthesia, Intensive Care and Pain Medicine, Division of Population Medicine, Heath Park Campus, Cardiff University, Cardiff CF14 4XN, UK.

Background: We aimed to identify the prevalence of acute hypoxaemic respiratory failure (AHRF) in the intensive care unit (ICU) and its associated mortality. The secondary aim was to describe ventilatory management as well as the use of rescue therapies.

Methods: Multi-centre prospective study in nine hospitals in Wales, UK, over 2-month periods. All patients admitted to an ICU were screened for AHRF and followed-up until discharge from the ICU. Data were collected from patient charts on patient demographics, clinical characteristics, management and outcomes.

Results: Out of 2215 critical care admissions, 886 patients received mechanical ventilation. A total of 197 patients met inclusion criteria and were recruited. Seventy (35.5%) were non-survivors. Non-survivors were significantly older, had higher SOFA scores and received more vasopressor support than survivors. Twenty-five (12.7%) patients who fulfilled the Berlin definition of acute respiratory distress syndrome (ARDS) during the ICU stay without impact on overall survival. Rescue therapies were rarely used. Analysis of ventilation showed that median Vt was 7.1 mL/kg PBW (IQR 5.9-9.1) and 21.3% of patients had optimal ventilation during their ICU stay.

Conclusions: One in four mechanically ventilated patients have AHRF. Despite advances of care and better, but not optimal, utilisation of low tidal volume ventilation, mortality remains high.
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http://dx.doi.org/10.3390/jcm9113521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692809PMC
October 2020

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis.

Mediators Inflamm 2020 15;2020:5101834. Epub 2020 Oct 15.

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic ( = 39), sham-septic ( = 16), and healthy ( = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy.
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http://dx.doi.org/10.1155/2020/5101834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585649PMC
October 2020

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.

Crit Care 2020 10 6;24(1):597. Epub 2020 Oct 6.

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

Background: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone.

Methods: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP.

Results: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92].

Conclusion: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.
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http://dx.doi.org/10.1186/s13054-020-03314-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537953PMC
October 2020

Neurally adjusted ventilatory assist in acute respiratory failure: a randomized controlled trial.

Intensive Care Med 2020 12 6;46(12):2327-2337. Epub 2020 Sep 6.

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

Purpose: We hypothesized that neurally adjusted ventilatory assist (NAVA) compared to conventional lung-protective mechanical ventilation (MV) decreases duration of MV and mortality in patients with acute respiratory failure (ARF).

Methods: We carried out a multicenter, randomized, controlled trial in patients with ARF from several etiologies. Intubated patients ventilated for ≤ 5 days expected to require MV for ≥ 72 h and able to breathe spontaneously were eligible for enrollment. Eligible patients were randomly assigned based on balanced treatment assignments with a computerized randomization allocation sequence to two ventilatory strategies: (1) lung-protective MV (control group), and (2) lung-protective MV with NAVA (NAVA group). Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days (VFDs) at 28 days. Secondary outcome was all-cause hospital mortality. All analyses were done according to the intention-to-treat principle.

Results: Between March 2014 and October 2019, we enrolled 306 patients and randomly assigned 153 patients to the NAVA group and 153 to the control group. Median VFDs were higher in the NAVA than in the control group (22 vs. 18 days; between-group difference 4 days; 95% confidence interval [CI] 0 to 8 days; p = 0.016). At hospital discharge, 39 (25.5%) patients in the NAVA group and 47 (30.7%) patients in the control group had died (between-group difference - 5.2%, 95% CI - 15.2 to 4.8, p = 0.31). Other clinical, physiological or safety outcomes did not differ significantly between the trial groups.

Conclusion: NAVA decreased duration of MV although it did not improve survival in ventilated patients with ARF.
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http://dx.doi.org/10.1007/s00134-020-06181-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474954PMC
December 2020

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in ARDS with Class III Obesity.

Am J Respir Crit Care Med 2020 Sep 2. Epub 2020 Sep 2.

Massachusetts General Hospital, 2348, Boston, Massachusetts, United States.

Obesity is characterized by elevated pleural pressure (P) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). To determine the effects of lung recruitment maneuver (LRM) in the presence of elevated P on hemodynamics, left and right ventricular pressures and pulmonary vascular resistance. We hypothesized that elevated P protects the cardiovascular system against high airway pressures and prevents lung overdistension. First, an interventional crossover trial in adult subjects with ARDS and BMI ≥35 kg/m (n=21) was performed to explore the hemodynamic consequences of LRM. Second, cardiovascular function was studied during low/high PEEPs in a model of swine with ARDS and high P (n=9) versus healthy swine with normal P (n=6). Subjects with ARDS and obesity (BMI=57±12 kg/m), following LRM, required an increase in PEEP of 8[7, 10] cmHO above traditional ARDSnet settings to improve lung function, oxygenation and ventilation/perfusion matching, without impairment of hemodynamics or right heart function. ARDS swine with high P demonstrated unchanged transmural left ventricle pressure and systemic blood pressure after LRM protocol. Pulmonary artery hypertension decreased 8[13, 4] mmHg, as did vascular resistance 1.5[2.2, 0.9] WU, and transmural right ventricle pressure 10[15, 6] mmHg during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized ventilation/perfusion ratio. High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. Additionally, patients with ARDS and class III obesity tolerate hemodynamically LRM with high airway pressure.
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http://dx.doi.org/10.1164/rccm.201909-1687OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924574PMC
September 2020

Bedside monitoring of lung perfusion by electrical impedance tomography in the time of COVID-19.

Br J Anaesth 2020 11 7;125(5):e434-e436. Epub 2020 Aug 7.

Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Respiratory Care Department, Massachusetts General Hospital, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413127PMC
November 2020

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19).

Obstet Gynecol 2020 12;136(6):1109-1113

Department of Anesthesia, the Department of Pediatrics, the Respiratory Care Department, the Department of Obstetrics and Gynecology, and the Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking.

Method: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response.

Experience: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission.

Conclusion: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.
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http://dx.doi.org/10.1097/AOG.0000000000004128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673637PMC
December 2020

Response to the letter: Esophageal pressure and potential confounders for evaluating patient-ventilator asynchrony.

J Crit Care 2020 12 8;60:345-346. Epub 2020 Jul 8.

Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo, SP, Brazil.

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http://dx.doi.org/10.1016/j.jcrc.2020.07.006DOI Listing
December 2020

Measured CPAP in a Noninvasive Pediatric Airway and Lung Model.

Respir Care 2021 Jan 23;66(1):87-94. Epub 2020 Jun 23.

Massachusetts General Hospital, Boston, Massachusetts.

Background: Bronchiolitis is the most common cause of admission in children < 2 y of age in the United States. The standard of care involves supportive measures, including noninvasive interventions such as CPAP. CPAP is traditionally delivered through a full face mask; however, pediatric ICUs have been exploring the use of the RAM cannula by Neotech as a mode of CPAP delivery. The level of CPAP delivered via the RAM cannula is uncertain. We performed an in vitro study to determine the level of CPAP delivered via the RAM cannula utilizing a pediatric lung model.

Methods: Models of 7 sizes of pediatric upper airways, produced with a 3-dimensional printer, were connected to a breathing simulator. We applied each size of RAM cannula to weight-appropriate airway and lung compliance parameters, delivering pressures of 5, 7, and 10 cm HO using a ventilator in the CPAP mode. Leaks of 0%, 20%, 40%, and 60% were generated to emulate a complete seal, a poor fit, and open-mouth breathing. The outcome measure was the difference in CPAP, referred to as "%leak effect," measured by the lung simulator relative to the CPAP set on the ventilator.

Results: We found that set CPAP of 5-10 cm HO generated measured CPAP ranging from 2.6 to 9.7 cm HO. For the set CPAP levels of 5, 7, and 10 cm HO, the mean %leak effect values of measured CPAP from the set CPAP were -25%, -26%, and -25.7%, respectively. For each specific cannula-airway combination, increasing the set pressure and decreasing the air leak resulted in higher levels of CPAP delivered.

Conclusions: The RAM cannula delivered varying amounts of CPAP, with a percent loss of approximately -25% depending on the level of leak in the system. With minimal leak, it is conceivable that the RAM cannula can be used to deliver clinically meaningful CPAP.
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http://dx.doi.org/10.4187/respcare.07864DOI Listing
January 2021

Predictors of asynchronies during assisted ventilation and its impact on clinical outcomes: The EPISYNC cohort study.

J Crit Care 2020 06 21;57:30-35. Epub 2020 Jan 21.

Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo, SP, Brazil.

Purpose: To investigate if respiratory mechanics and other baseline characteristics are predictors of patient-ventilator asynchrony and to evaluate the relationship between asynchrony during assisted ventilation and clinical outcomes.

Methods: We performed a prospective cohort study in patients under mechanical ventilation (MV). Baseline measurements included severity of illness and respiratory mechanics. The primary outcome was the Asynchrony Index (AI), defined as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. We recorded ventilator waveforms throughout the entire period of MV.

Results: We analyzed 11,881 h of MV from 103 subjects. Median AI during the entire period of MV was 5.1% (IQR:2.6-8.7). Intrinsic PEEP was associated with AI (OR:1.72, 95%CI:1.1-2.68), but static compliance and airway resistance were not. Simplified Acute Physiology Score 3 (OR:1.03, 95%CI:1-1.06) was also associated with AI. Median AI was higher during assisted (5.4%, IQR:2.9-9.1) than controlled (2%, IQR:0.6-4.9) ventilation, and 22% of subjects had high incidence of asynchrony (AI≥10%). Subjects with AI≥10% had more extubation failure (33%) than patients with AI<10% (6%), p = .01.

Conclusions: Predictors of high incidence of asynchrony were severity of illness and intrinsic PEEP. High incidence of asynchrony was associated with extubation failure, but not mortality.

Trial Registration: ClinicalTrials.gov, NCT02687802.
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June 2020

Development of a Lung Rescue Team to Improve Care of Subjects With Refractory Acute Respiratory Failure.

Respir Care 2020 Apr 4;65(4):420-426. Epub 2020 Feb 4.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: A lung-protective mechanical ventilation strategy has become the hallmark of ventilation management for patients with acute respiratory failure. However, some patients progress to more severe forms of acute respiratory failure with refractory hypoxemia. In such circumstances, individualized titration of mechanical ventilation according to the patient's specific respiratory and cardiovascular pathophysiology is desirable. A lung rescue team (LRT) was recently established at our institution to improve the medical care of patients with acute respiratory failure when conventional treatment fails. The aim of this report is to describe the consultation processes, the cardiopulmonary assessment, and the procedures of the LRT.

Methods: This was a retrospective review of the LRT management of patients with acute respiratory failure and refractory hypoxemia at Massachusetts General Hospital in Boston, Massachusetts. The LRT is composed of a critical care physician, the ICU respiratory therapist on duty, the ICU nurse on duty, and 2 critical care fellows. In the LRT approach, respiratory mechanics are evaluated through lung recruitment maneuvers and decremental PEEP trials by means of 3 tools: esophageal manometry, echocardiography, and electrical impedance tomography lung imaging.

Results: The LRT was consulted 89 times from 2014 to 2019 for evaluation and management of severely critically ill patients with acute respiratory failure and refractory hypoxemia on mechanical ventilation. The LRT was requested a median of 2 (interquartile range 1-6) d after intubation to optimize mechanical ventilation and to titrate PEEP in 77 (86%) subjects, to manage ventilation in 8 (9%) subjects on extracorporeal membrane oxygenation (ECMO), and to manage weaning strategy from mechanical ventilation in 4 (5%) subjects. The LRT found consolidations with atelectasis responsive to recruitment maneuvers in 79% ( = 70) of consultations. The LRT findings translated into a change of care in 81% ( = 72) of subjects.

Conclusions: The LRT individualized the management of severe acute respiratory failure. The LRT consultations were shown to be effective, safe, and efficient, with an impact on decision-making in the ICU.
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http://dx.doi.org/10.4187/respcare.07350DOI Listing
April 2020

A lung rescue team improves survival in obesity with acute respiratory distress syndrome.

Crit Care 2020 01 15;24(1). Epub 2020 Jan 15.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02141, USA.

Background: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS.

Methods: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring.

Results: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74).

Conclusion: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.
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http://dx.doi.org/10.1186/s13054-019-2709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961369PMC
January 2020

Independent lung ventilation: Implementation strategies and review of literature.

World J Crit Care Med 2019 Jul 31;8(4):49-58. Epub 2019 Jul 31.

Division of Critical Care, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, United

Independent lung ventilation, though infrequently used in the critical care setting, has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology. This involves isolating and ventilating the right and left lung differently, using separate ventilators. Here, we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage, who presented with severe hypoxemic respiratory failure despite maximal ventilatory support. Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the non-diseased lung causing over distension and inadvertent volume trauma. Since each lung has a different compliance and respiratory mechanics, instituting separate ventilation strategies to each lung could potentially minimize lung injury. Based on review of literature, we provide a detailed description of indications and procedures for establishing independent lung ventilation, and also provide an algorithm for management and weaning a patient from independent lung ventilation.
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http://dx.doi.org/10.5492/wjccm.v8.i4.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817931PMC
July 2019

Endotracheal tube management during mechanical ventilation: less is more!

Intensive Care Med 2019 11 17;45(11):1632-1634. Epub 2019 Sep 17.

Division of Animal Experimentation, Critical Care Research Group, The Prince Charles Hospital, Chermside, Australia.

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http://dx.doi.org/10.1007/s00134-019-05777-wDOI Listing
November 2019

Protocol of a randomised controlled trial in cardiac surgical patients with endothelial dysfunction aimed to prevent postoperative acute kidney injury by administering nitric oxide gas.

BMJ Open 2019 07 4;9(7):e026848. Epub 2019 Jul 4.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Postoperative acute kidney injury (AKI) is a common complication in cardiac surgery. Levels of intravascular haemolysis are strongly associated with postoperative AKI and with prolonged (>90 min) use of cardiopulmonary bypass (CPB). Ferrous plasma haemoglobin released into the circulation acts as a scavenger of nitric oxide (NO) produced by endothelial cells. Consequently, the vascular bioavailability of NO is reduced, leading to vasoconstriction and impaired renal function. In patients with cardiovascular risk factors, the endothelium is dysfunctional and cannot replenish the NO deficit. A previous clinical study in young cardiac surgical patients with rheumatic fever, without evidence of endothelial dysfunction, showed that supplementation of NO gas decreases AKI by converting ferrous plasma haemoglobin to ferric methaemoglobin, thus preserving vascular NO. In this current trial, we hypothesised that 24 hours administration of NO gas will reduce AKI following CPB in patients with endothelial dysfunction.

Methods: This is a single-centre, randomised (1:1) controlled, parallel-arm superiority trial that includes patients with endothelial dysfunction, stable kidney function and who are undergoing cardiac surgery procedures with an expected CPB duration >90 min. After randomisation, 80 parts per million (ppm) NO (intervention group) or 80 ppm nitrogen (N, control group) are added to the gas mixture. Test gases (N or NO) are delivered during CPB and for 24 hours after surgery. The primary study outcome is the occurrence of AKI among study groups. Key secondary outcomes include AKI severity, occurrence of renal replacement therapy, major adverse kidney events at 6 weeks after surgery and mortality. We are recruiting 250 patients, allowing detection of a 35% AKI relative risk reduction, assuming a two-sided error of 0.05.

Ethics And Dissemination: The Partners Human Research Committee approved this trial. Recruitment began in February 2017. Dissemination plans include presentations at scientific conferences, scientific publications and advertising flyers and posters at Massachusetts General Hospital.

Trial Registration Number: NCT02836899.
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http://dx.doi.org/10.1136/bmjopen-2018-026848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615910PMC
July 2019

Effects of sedatives and opioids on trigger and cycling asynchronies throughout mechanical ventilation: an observational study in a large dataset from critically ill patients.

Crit Care 2019 Jul 5;23(1):245. Epub 2019 Jul 5.

Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.

Background: In critically ill patients, poor patient-ventilator interaction may worsen outcomes. Although sedatives are often administered to improve comfort and facilitate ventilation, they can be deleterious. Whether opioids improve asynchronies with fewer negative effects is unknown. We hypothesized that opioids alone would improve asynchronies and result in more wakeful patients than sedatives alone or sedatives-plus-opioids.

Methods: This prospective multicenter observational trial enrolled critically ill adults mechanically ventilated (MV) > 24 h. We compared asynchronies and sedation depth in patients receiving sedatives, opioids, or both. We recorded sedation level and doses of sedatives and opioids. BetterCare™ software continuously registered ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI) as well as MV modes. All variables were averaged per day. We used linear mixed-effects models to analyze the relationships between asynchronies, sedation level, and sedative and opioid doses.

Results: In 79 patients, 14,166,469 breaths were recorded during 579 days of MV. Overall asynchronies were not significantly different in days classified as sedatives-only, opioids-only, and sedatives-plus-opioids and were more prevalent in days classified as no-drugs than in those classified as sedatives-plus-opioids, irrespective of the ventilatory mode. Sedative doses were associated with sedation level and with reduced DC (p < 0.0001) in sedatives-only days. However, on days classified as sedatives-plus-opioids, higher sedative doses and deeper sedation had more IEE (p < 0.0001) and higher AI (p = 0.0004). Opioid dosing was inversely associated with overall asynchronies (p < 0.001) without worsening sedation levels into morbid ranges.

Conclusions: Sedatives, whether alone or combined with opioids, do not result in better patient-ventilator interaction than opioids alone, in any ventilatory mode. Higher opioid dose (alone or with sedatives) was associated with lower AI without depressing consciousness. Higher sedative doses administered alone were associated only with less DC.

Trial Registration: ClinicalTrial.gov, NCT03451461.
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http://dx.doi.org/10.1186/s13054-019-2531-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612107PMC
July 2019

Noninvasive Respiratory Support for Postextubation Respiratory Failure.

Respir Care 2019 Jun;64(6):658-678

Respiratory Care, Massachusetts General Hospital, Boston, Massachusetts.

The rate of re-intubation after endotracheal extubation for all indications is estimated at ∼20%. This high rate is related, in part, to the development of postoperative complications that leads to acute respiratory failure that requires re-intubation. In general, 5-10% of all surgical patients develop postoperative respiratory failure, and, in patients who require abdominal surgery, up to 40% develop respiratory failure. The forms of respiratory support that have been shown to be most effective in managing postextubation respiratory failure and preventing re-intubation are noninvasive ventilation, CPAP, and high-flow nasal cannula. From an analysis of the data, it is clear that patients at high risk of re-intubation require CPAP, noninvasive ventilation, or high-flow nasal cannula after extubation to allow for a smooth transition to spontaneous breathing and to minimize the need for re-intubation. CPAP is most indicated in patients with atelectasis in which high levels of PEEP are needed, noninvasive ventilation is indicated in the patient unable to maintain an adequate minute ventilation without excessive work of breathing, and high-flow nasal cannula is indicated in the patient with severe hypoxemia that was not a result of marked atelectasis or severe ARDS. It is also clear that there are insufficient data to support the use of any of these therapies in patients at low risk for re-intubation or the development of postoperative pulmonary complications.
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http://dx.doi.org/10.4187/respcare.06671DOI Listing
June 2019

PEEP Generated by High-Flow Nasal Cannula in a Pediatric Model.

Respir Care 2019 Oct 14;64(10):1240-1249. Epub 2019 May 14.

Massachusetts General Hospital, Boston, Massachusetts.

Background: High-flow nasal cannulas (HFNC) have been increasingly used in the pediatric critical care patient population. There are different theories about the mechanism by which HFNC reduces work of breathing, including diminishing upper airway dead space by the washout of carbon dioxide. However, one of the likely primary mechanisms by which HFNC reduces work of breathing is by generating PEEP. There are limited data assessing the PEEP delivered by moderate flows (8-50 L/min) of HFNC, which are used most commonly in pediatric patients.

Methods: Pediatric upper-airway models were created with 5 different nares produced by a 3-dimensional printer and connected to a lung simulator. Age-specific flows were delivered via the 5 different setups. Pressure throughout the simulated airway was measured at HFNC flows of 6-60 L/min with 25%, 50%, and 75% air leak to simulate open-mouth breathing.

Results: PEEPs of 1.2-36 cm HO were generated with HFNC flows of 6-60 L/min. In general, for each specific cannula, increasing the flow and decreasing the air leak resulted in higher levels of PEEP delivered ( < .001 and > 10% difference). Changes in lung mechanics as generated by the lung simulator to simulate different patient ages resulted in the establishment of different levels of PEEP.

Conclusions: HFNCs deliver varying amounts of PEEP at the alveolar level with flows of 6-60 L/min. Increasing flow and decreasing leak resulted in the generation of greater PEEP. PEEP levels differed across cannulas and model weights at the same leak level, likely due to differences in the nasal interface between the HFNC device and the model nares.
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http://dx.doi.org/10.4187/respcare.06470DOI Listing
October 2019

Lung Recruitment in Obese Patients with Acute Respiratory Distress Syndrome.

Anesthesiology 2019 05;130(5):791-803

From the Department of Anesthesia, Critical Care and Pain Medicine (J.F., R.R.S.S., M.T.D., C.Z., L.B.) the Respiratory Care Department (R.M.K.) the Department of Radiology (F.J.F., F,M.T.), Massachusetts General Hospital, Boston, Massachusetts the Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (Incor), Hospital Das Clínicas, Faculty of Medicine, University of Sao Paulo, São Paulo, Brazil (C.C.A.M., M.B.P.A.). Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Respiratory Care Department, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Background: Obese patients are characterized by normal chest-wall elastance and high pleural pressure and have been excluded from trials assessing best strategies to set positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). The authors hypothesized that severely obese patients with ARDS present with a high degree of lung collapse, reversible by titrated PEEP preceded by a lung recruitment maneuver.

Methods: Severely obese ARDS patients were enrolled in a physiologic crossover study evaluating the effects of three PEEP titration strategies applied in the following order: (1) PEEPARDSNET: the low PEEP/FIO2 ARDSnet table; (2) PEEPINCREMENTAL: PEEP levels set to determine a positive end-expiratory transpulmonary pressure; and (3) PEEPDECREMENTAL: PEEP levels set to determine the lowest respiratory system elastance during a decremental PEEP trial following a recruitment maneuver on respiratory mechanics, regional lung collapse, and overdistension according to electrical impedance tomography and gas exchange.

Results: Fourteen patients underwent the study procedures. At PEEPARDSNET (13 ± 1 cm H2O) end-expiratory transpulmonary pressure was negative (-5 ± 5 cm H2O), lung elastance was 27 ± 12 cm H2O/L, and PaO2/FIO2 was 194 ± 111 mmHg. Compared to PEEPARDSNET, at PEEPINCREMENTAL level (22 ± 3 cm H2O) lung volume increased (977 ± 708 ml), lung elastance decreased (23 ± 7 cm H2O/l), lung collapse decreased (18 ± 10%), and ventilation homogeneity increased thus rising oxygenation (251 ± 105 mmHg), despite higher overdistension levels (16 ± 12%), all values P < 0.05 versus PEEPARDSnet. Setting PEEP according to a PEEPDECREMENTAL trial after a recruitment maneuver (21 ± 4 cm H2O, P = 0.99 vs. PEEPINCREMENTAL) further lowered lung elastance (19 ± 6 cm H2O/l) and increased oxygenation (329 ± 82 mmHg) while reducing lung collapse (9 ± 2%) and overdistension (11 ± 2%), all values P < 0.05 versus PEEPARDSnet and PEEPINCREMENTAL. All patients were maintained on titrated PEEP levels up to 24 h without hemodynamic or ventilation related complications.

Conclusions: Among the PEEP titration strategies tested, setting PEEP according to a PEEPDECREMENTAL trial preceded by a recruitment maneuver obtained the best lung function by decreasing lung overdistension and collapse, restoring lung elastance, and oxygenation suggesting lung tissue recruitment.
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May 2019
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