Global Initiative for chronic obstructive lung disease, revised 2011.
H Gong
Air travel and oxygen therapy in cardiopulmonary patients.
Chest. 1992 Apr;101(4):1104-13.
Abstract/Text
Rika Suda, Nobuhiro Tanabe, Jiro Terada, Akira Naito, Hajime Kasai, Rintaro Nishimura, Takayuki Jujo Sanada, Toshihiko Sugiura, Seiichiro Sakao, Koichiro Tatsumi
Pulmonary hypertension with a low cardiac index requires a higher PaO2 level to avoid tissue hypoxia.
Respirology. 2020 Jan;25(1):97-103. doi: 10.1111/resp.13574. Epub 2019 May 16.
Abstract/Text
BACKGROUND AND OBJECTIVE: The optimal oxygen supplementation needed to avoid tissue hypoxia in patients with pulmonary hypertension (PH) remains unclear. This study aimed to identify the arterial oxygen tension (PaO2 ) level needed to avoid tissue hypoxia which results in a poor prognosis in patients with PH.
METHODS: We retrospectively analysed the data for 1571 right heart catheterizations in patients suspected of having PH between 1983 and 2017 at our institution. Examinations were classified according to mean pulmonary arterial pressure (mPAP), cardiac index (CI) and the presence of lung disease, pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH). The PaO2 levels needed to avoid tissue hypoxia were compared in each subgroup.
RESULTS: The estimated PaO2 equivalent to a mixed venous oxygen tension (PvO2 ) of 35 mm Hg (tissue hypoxia) was 63.2 mm Hg in all patients, 77.0 mm Hg in those with decreased CI (<2.5 L/min/m2 ) and 57.0 mm Hg in those with preserved CI. Multivariate regression analysis identified mPAP, CI and PaO2 to be independent predictors of extremely low PvO2 . Similar results were observed regardless of the severity of PH or the presence of lung disease, PAH or CTEPH. The PaO2 level needed to avoid tissue hypoxia was higher in patients with mild PH and decreased CI than in those with severe PH and preserved CI (70.2 vs 61.5 mm Hg).
CONCLUSION: These findings indicate that a decreased CI rather than increased mPAP induces tissue hypoxia in PH. Patients with PH and decreased CI may need adjustment of oxygen therapy at higher PaO2 levels compared with patients with preserved CI.
© 2019 Asian Pacific Society of Respirology.
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group.
Ann Intern Med. 1980 Sep;93(3):391-8.
Abstract/Text
At six centers, 203 patients with hypoxemic chronic obstructive lung disease were randomly allocated to either continuous oxygen (O2) therapy or 12-hour nocturnal O2 therapy and followed for at least 12 months (mean, 19.3 months). The two groups were initially well matched in terms of physiological and neuropsychological function. Compliance with each oxygen regimen was good. Overall mortality in the nocturnal O2 therapy group was 1.94 times that in the continuous O2 therapy group (P = 0.01). This trend was striking in patients with carbon dioxide retention and also present in patients with relatively poor lung function, low mean nocturnal oxygen saturation, more severe brain dysfunction, and prominent mood disturbances. Continuous O2 therapy also appeared to benefit patients with low mean pulmonary artery pressure and pulmonary vascular resistance and those with relatively well-preserved exercise capacity. We conclude that in hypoxemic chronic obstructive lung disease, continuous O2 therapy is associated with a lower mortality than is nocturnal O2 therapy. The reason for this difference is not clear.
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party.
Lancet. 1981 Mar 28;1(8222):681-6.
Abstract/Text
A controlled trial of long term domiciliary oxygen therapy has been carried out in three centres in the U.K. The 87 patients, all under 70 years of age, who took part had chronic bronchitis or emphysema with irreversible airways obstruction, severe arterial hypoxaemia, carbon dioxide retention, and a history of congestive heart failure. The patients were randomised to oxygen therapy (treated) or no oxygen (controls). Oxygen was given by nasal prongs for at least 15 h daily, usually at 2 1/min. The two groups were well matched, both clinically and in terms of lung function and other laboratory findings. 19 of the 42 oxygen treated patients died in the five years of survival follow-up compared with 30 out of 45 controls: in the 66 men in this trial the survival advantage of oxygen did not emerge until 500 days had elapsed. Survival for the 12 female controls was surprisingly poor, 8 of them being dead at 3 years. Mortality was not easy to predict, though a summation of arterial carbon dioxide tension and red cell mass was helpful. Neither time spent in hospital because of exacerbations of respiratory failure nor work attendance were affected by oxygen therapy, but these patients were very ill at the start of the trial and many had already retired on grounds of age or ill-health. Physiological measurements suggested that oxygen did not slow the progress of respiratory failure in those who died early. However, in longer term survivors on oxygen, arterial oxygenation did seem to stop deterioration.
James K Stoller, Ralph J Panos, Samuel Krachman, Dennis E Doherty, Barry Make, Long-term Oxygen Treatment Trial Research Group
Oxygen therapy for patients with COPD: current evidence and the long-term oxygen treatment trial.
Chest. 2010 Jul;138(1):179-87. doi: 10.1378/chest.09-2555.
Abstract/Text
Long-term use of supplemental oxygen improves survival in patients with COPD and severe resting hypoxemia. However, the role of oxygen in symptomatic patients with COPD and more moderate hypoxemia at rest and desaturation with activity is unclear. The few long-term reports of supplemental oxygen in this group have been of small size and insufficient to demonstrate a survival benefit. Short-term trials have suggested beneficial effects other than survival in patients with COPD and moderate hypoxemia at rest. In addition, supplemental oxygen appeared to improve exercise performance in small short-term investigations of patients with COPD and moderate hypoxemia at rest and desaturation with exercise, but long-term trials evaluating patient-reported outcomes are lacking. This article reviews the evidence for long-term use of supplemental oxygen therapy and provides a rationale for the National Heart, Lung, and Blood Institute Long-term Oxygen Treatment Trial. The trial plans to enroll subjects with COPD with moderate hypoxemia at rest or desaturation with exercise and compare tailored oxygen therapy to no oxygen therapy.
Rosemary P Moore, David J Berlowitz, Linda Denehy, Jeffrey J Pretto, Danny J Brazzale, Ken Sharpe, Bruce Jackson, Christine F McDonald
A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia.
Thorax. 2011 Jan;66(1):32-7. doi: 10.1136/thx.2009.132522. Epub 2010 Sep 29.
Abstract/Text
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who are not severely hypoxaemic at rest may experience significant breathlessness on exertion, and ambulatory oxygen is often prescribed in this circumstance despite a lack of conclusive evidence for benefit. This study aimed to determine whether such patients benefit from domiciliary ambulatory oxygen and, if so, which factors may be associated with benefit.
METHODS: This was a 12 week, parallel, double-blinded, randomised, placebo-controlled trial of cylinder air versus cylinder oxygen, provided at 6 l/min intranasally, for use during any activity provoking breathlessness. Patients underwent baseline measurements of arterial blood gases and lung function. Outcome measures assessed dyspnoea, health-related quality of life, mood disturbance, functional status and cylinder utilisation. Data were analysed on an intention-to-treat basis, p≤0.05.
RESULTS: 143 subjects (44 female), mean±SD age 71.8±9.8 years, forced expiratory volume in 1 s (FEV(1))1.16±0.51 litres, Pao(2) 9.5±1.1 kPa (71.4±8.5 mm Hg) were randomised, including 50 patients with exertional desaturation to ≤88%. No significant differences in any outcome were found between groups receiving air or oxygen. Statistically significant but clinically small improvements in dyspnoea and depression were observed in the whole study group over the 12 weeks of the study.
CONCLUSION: In breathless patients with COPD who do not have severe resting hypoxaemia, domiciliary ambulatory oxygen confers no benefits in terms of dyspnoea, quality of life or function. Exertional desaturation is not predictive of outcome. Intranasal gas (either air or oxygen) may provide a placebo benefit.
CLINICAL TRIAL NUMBER: ACTRN12605000457640.
Stanley I Ejiofor, Susan Bayliss, Abubacarr Gassamma, Alice M Turner
Ambulatory Oxygen for Exercise-Induced Desaturation and Dyspnea in Chronic Obstructive Pulmonary Disease (COPD): Systematic Review and Meta-Analysis.
Chronic Obstr Pulm Dis. 2016 Jan 6;3(1):419-434. doi: 10.15326/jcopdf.3.1.2015.0146. Epub 2016 Jan 6.
Abstract/Text
Introduction: Ambulatory oxygen therapy is indicated in patients that use long term oxygen therapy (LTOT) and current guidelines suggest its use in patients who exhibit exertional desaturation if there is a demonstrable improvement in exercise capacity. Evidence for this is largely derived from single assessment studies which have shown clear benefit in this setting when oxygen versus air is used. The long term effects, however, of ambulatory oxygen therapy in this particular group of patients is controversial. Methods: We conducted a systematic review of published literature from 1980 to June 2014 for trials in which ambulatory oxygen was compared to placebo in chronic obstructive pulmonary disease (COPD) patients not on LTOT. We also reviewed the effectiveness of devices delivering ambulatory oxygen. Outcome measures were focused towards exercise capacity, Borg scores and the ability of the delivery devices to maintain oxygen saturations on exercise. Results: Twenty three studies (620 patients) were included in the review. Nine studies evaluated the clinical effectiveness of ambulatory oxygen and 14 studies evaluated the impact of the delivery devices. Ambulatory oxygen had no statistical effect on improving exercise capacity when assessed by the 6-minute walk test (6MWT) or the endurance shuttle walk test (ESWT);p=0.44 and p=0.29 respectively. End of test Borg scores showed no statistical improvement with ambulatory oxygen therapy during 6MWT (p=0.68). Oxygen conserving devices significantly improved oxygen saturations on exercise compared with continuous flow nasal cannulae (p=0.04). Conclusion: Ambulatory oxygen therapy has limited long term benefit in improving functional exercise capacity or Borg dyspnea scores.
Faisal Ameer, Kristin V Carson, Zafar A Usmani, Brian J Smith
Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest.
Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238. doi: 10.1002/14651858.CD000238.pub2. Epub 2014 Jun 24.
Abstract/Text
BACKGROUND: People with chronic obstructive pulmonary disease (COPD) often become transiently hypoxaemic (low oxygen levels in blood) on exercise, necessitating oxygen therapy to improve breathlessness and exercise capacity and to reduce disability. Ambulatory oxygen therapy refers to provision of oxygen therapy during exercise and activities of daily living. Ambulatory oxygen therapy is often used by patients on long-term oxygen therapy (LTOT) during exercise or by non-LTOT users with or without resting hypoxaemia when they show evidence of exercise de-saturation and demonstrate improvement in exercise capacity with supplemental oxygen.
OBJECTIVES: To determine the longer-term efficacy of ambulatory oxygen therapy only in patients with COPD who do not meet the criteria for LTOT, with respect to improvement in exercise capacity, mortality, quality of life and other relevant measures of improvement.
SEARCH METHODS: The Cochrane Airways Group Specialised Register, including MEDLINE, EMBASE and CINAHL, was searched. Online clinical trial registers, including Controlled Clinical Trials (www.controlled-trials.com), government registries (clinicaltrials.gov) and World Health Organization (WHO) registries (www.who.int/trialsearch), were screened for ongoing and recently completed studies. Bibliographies of included studies were searched for additional trials that may meet the inclusion criteria and were not retrieved by the above search strategy. Authors of identified trials were contacted to provide other published and unpublished studies. Searches were current as of November 2012.
SELECTION CRITERIA: Randomised controlled trials (RCTs) that compare ambulatory oxygen therapy provided through portable oxygen cylinders/battery-powered devices or liquid oxygen canisters versus placebo air cylinders, usual medical care or co-intervention in study participants with COPD who did not meet criteria for LTOT.
DATA COLLECTION AND ANALYSIS: We used standard methods as expected by The Cochrane Collaboration.
MAIN RESULTS: Four studies met the inclusion criteria (331 participants), with two studies producing a statistically and clinically significant benefit in favour of the intervention for dyspnoea post exercise.The quality of life domain for all four included studies produced a statistically significant benefit for the subcategories of dyspnoea and fatigue, in favour of the oxygen group (dyspnoea mean difference (MD) 0.28, 95% confidence interval (CI) 0.10 to 0.45; P value 0.002; fatigue MD 0.17, 95% CI 0.04 to 0.31; P value 0.009). No evidence of any effect was reported for survival, and limited benefits were observed for exercise capacity (as measured by step test and distance walk test), with one study showing a statistically significant improvement in the number of steps taken in the oxygen group for group N-of-1 studies only. No other statistically significant benefits were observed for exercise capacity among the other trials or individual N-of-1 studies.
AUTHORS' CONCLUSIONS: In patients with COPD with moderate hypoxia, current evidence on ambulatory oxygen therapy reveals improvements in dyspnoea post exercise and in the dyspnoea and fatigue domain of quality of life. However, evidence for the clinical utility and effectiveness of ambulatory oxygen in improving mortality and exercise capacity was not evident in this review. Methodologically rigorous RCTs with sufficient power to detect a difference are required to investigate the role of ambulatory oxygen in the management of COPD.
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.
N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
Abstract/Text
BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.
METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28.
RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively.
CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
Peter Q Eichacker, Eric P Gerstenberger, Steven M Banks, Xizhong Cui, Charles Natanson
Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes.
Am J Respir Crit Care Med. 2002 Dec 1;166(11):1510-4. doi: 10.1164/rccm.200208-956OC. Epub 2002 Aug 28.
Abstract/Text
M B Amato, C S Barbas, D M Medeiros, G de P Schettino, G Lorenzi Filho, R A Kairalla, D Deheinzelin, C Morais, E de O Fernandes, T Y Takagaki
Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation.
Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1835-46. doi: 10.1164/ajrccm.152.6.8520744.
Abstract/Text
Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes) or a conventional approach (C = conventional volume-cycled ventilation, VT = 12 ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels). Fifteen patients were selected to receive NA, exhibiting a better evolution of the PaO2/FIO2 ratio (p < 0.0001) and of compliance (p = 0.0018), requiring shorter periods under FIO2 > 50% (p = 0.001) and a lower FIO2 at the day of death (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed a higher weaning rate in NA (p = 0.014) but not a significantly improved survival (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.
Jesús Villar, Robert M Kacmarek, Lina Pérez-Méndez, Armando Aguirre-Jaime
A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.
Crit Care Med. 2006 May;34(5):1311-8. doi: 10.1097/01.CCM.0000215598.84885.01.
Abstract/Text
OBJECTIVE: It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS).
DESIGN: Randomized, controlled clinical trial.
SETTING: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study).
PATIENTS: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV.
INTERVENTIONS: In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg.
MEASUREMENTS AND MAIN RESULTS: The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001).
CONCLUSIONS: A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.
Roy G Brower, Paul N Lanken, Neil MacIntyre, Michael A Matthay, Alan Morris, Marek Ancukiewicz, David Schoenfeld, B Taylor Thompson, National Heart, Lung, and Blood Institute ARDS Clinical Trials Network
Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.
N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.
Abstract/Text
BACKGROUND: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients.
METHODS: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen.
RESULTS: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50).
CONCLUSIONS: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.
Copyright 2004 Massachusetts Medical Society
Matthias Briel, Maureen Meade, Alain Mercat, Roy G Brower, Daniel Talmor, Stephen D Walter, Arthur S Slutsky, Eleanor Pullenayegum, Qi Zhou, Deborah Cook, Laurent Brochard, Jean-Christophe M Richard, Francois Lamontagne, Neera Bhatnagar, Thomas E Stewart, Gordon Guyatt
Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis.
JAMA. 2010 Mar 3;303(9):865-73. doi: 10.1001/jama.2010.218.
Abstract/Text
CONTEXT: Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences.
OBJECTIVES: To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups.
DATA SOURCES: Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010).
STUDY SELECTION: Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality.
DATA EXTRACTION: Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.
RESULTS: There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar.
CONCLUSIONS: Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS.
A Esteban, I Alía, F Gordo, R de Pablo, J Suarez, G González, J Blanco
Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure Collaborative Group.
Chest. 2000 Jun;117(6):1690-6.
Abstract/Text
STUDY OBJECTIVES: To compare in-hospital mortality of patients with ARDS ventilated with either pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV) with a square-wave inspiratory flow.
DESIGN: : Multicenter and randomized trial.
SETTING: Twelve medical-surgical ICUs located in tertiary-care hospitals.
PATIENTS: Seventy-nine patients having ARDS, as defined by the American-European Consensus Conference.
INTERVENTIONS: Patients were randomly assigned to be ventilated with either PCV (n = 37) or VCV (n = 42). In both instances, inspiratory plateau pressure was limited to < or = 35 cm H(2)O.
MEASUREMENTS AND RESULTS: There were no significant differences among the studied groups at the moment of randomization, although there was a trend toward greater renal failure in patients assigned to VCV. Ventilatory settings and blood gases did not significantly differ over time between the two groups. Patients in the VCV group had both a significantly higher in-hospital mortality rate than those in the PCV group (78% vs 51%, respectively) and a higher number of extrapulmonary organ failures (median, 4 vs 2, respectively). The development of renal failure during the study period was also significantly more frequent among VCV patients (64% vs 32%, respectively). Multivariate analysis showed that factors independently associated with an increased mortality rate were the presence of two or more extrapulmonary organ failures (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.38 to 15.40) and acute renal failure (OR, 3.96; 95% CI, 1.10 to 14.28) but not the ventilatory mode used.
CONCLUSIONS: The increased number of extrapulmonary organ failures developed in patients of the VCV group was strongly associated with a higher mortality rate. The development of organ failures was probably not related to the ventilatory mode.
K G Hickling, J Walsh, S Henderson, R Jackson
Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study.
Crit Care Med. 1994 Oct;22(10):1568-78.
Abstract/Text
OBJECTIVES: To evaluate the outcome in patients with severe adult respiratory distress syndrome (ARDS) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O, low tidal volumes (4 to 7 mL/kg), spontaneous breathing using synchronized intermittent mandatory ventilation from the start of ventilation, and permissive hypercapnia without the use of bicarbonate to buffer acidosis. Also, to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system and the "ventilator score."
SETTING: A ten-bed general intensive care unit in a university hospital.
DESIGN: Prospective, descriptive study.
PATIENTS: Fifty-three patients with severe ARDS having a lung injury score of > or = 2.5.
INTERVENTIONS: Data recording.
RESULTS: The hospital mortality rate was significantly lower than that predicted by the APACHE II scores (26.4% vs. 53.3%, p = .004), even after correcting the latter for the effect of hypercapnic acidosis (26.4% vs. 51.1%, p = .008). The mortality rate increased with increasing number of organ failures, but was only 43% in patients with > or = 4 organ failures, 20.5% with < or = 3 organ failures, and 6.6% with only respiratory failure. The mean maximum PaCO2 was 66.5 torr (range 38 to 158 torr [8.87 kPa, range 5.07 to 21.07]), and the mean arterial pH at the same time was 7.23 (range 6.79 to 7.45). There was no correlation between the maximum PaCO2 or the corresponding pH and the total respiratory rate at the same time. No pneumothoraces developed during mechanical ventilation.
CONCLUSIONS: These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator-induced lung injury and improve outcome in severe ARDS. This hypothesis is supported by a large body of experimental evidence, which also suggests that ventilator-induced lung injury may result in the release of inflammatory mediators, and thus may have the potential to augment the development of multiple organ dysfunction. However, the hypothesis requires testing in a randomized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects.
R D McEvoy, R J Pierce, D Hillman, A Esterman, E E Ellis, P G Catcheside, F J O'Donoghue, D J Barnes, R R Grunstein, Australian trial of non-invasive Ventilation in Chronic Airflow Limitation (AVCAL) Study Group
Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial.
Thorax. 2009 Jul;64(7):561-6. doi: 10.1136/thx.2008.108274. Epub 2009 Feb 12.
Abstract/Text
BACKGROUND: Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease (COPD). A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation (NIV) on survival, lung function and quality of life in patients with severe hypercapnic COPD.
METHOD: A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV1.0) <1.5 litres or <50% predicted and ratio of FEV1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (PaCO2) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood.
RESULTS: 144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01-5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV1.0 and PaCO2 measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour.
CONCLUSIONS: Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life.
TRIAL REGISTRATION NUMBER: ACTRN12605000205639.
Long-Term Oxygen Treatment Trial Research Group, Richard K Albert, David H Au, Amanda L Blackford, Richard Casaburi, J Allen Cooper, Gerard J Criner, Philip Diaz, Anne L Fuhlbrigge, Steven E Gay, Richard E Kanner, Neil MacIntyre, Fernando J Martinez, Ralph J Panos, Steven Piantadosi, Frank Sciurba, David Shade, Thomas Stibolt, James K Stoller, Robert Wise, Roger D Yusen, James Tonascia, Alice L Sternberg, William Bailey
A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.
N Engl J Med. 2016 Oct 27;375(17):1617-1627. doi: 10.1056/NEJMoa1604344.
Abstract/Text
BACKGROUND: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation.
METHODS: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked.
RESULTS: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes.
CONCLUSIONS: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .).
