Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] = 0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

Veno-Venous Extracorporeal Lung Support as a Bridge to or Through Lung Volume Reduction Surgery in Patients with Severe Hypercapnia.

Extracorporeal lung support (ECLS) represents an essential support tool especially for critically ill patients undergoing thoracic surgical procedures. Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we report the efficacy of veno-venous ECLS (VV ECLS) as a bridge to or through LVRS in patients with end-stage lung emphysema and severe hypercapnia. Between January 2016 and May 2017, 125 patients with end-stage lung emphysema undergoing LVRS were prospectively enrolled into this study. Patients with severe hypercapnia caused by chronic respiratory failure were bridged to or through LVRS with low-flow VV ECLS (65 patients, group 1). Patients with preoperative normocapnia served as a control group (60 patients, group 2). In group 1, VV ECLS was implemented preoperatively in five patients and in 60 patients intraoperatively. Extracorporeal lung support was continued postoperatively in all 65 patients. Mean length of postoperative VV ECLS support was 3 ± 1 day. The 90 day mortality rate was 7.8% in group 1 compared with 5% in group 2 (p = 0.5). Postoperatively, a significant improvement was observed in quality of life, exercise capacity, and dyspnea symptoms in both groups. VV ECLS in patients with severe hypercapnia undergoing LVRS is an effective and well-tolerated treatment option. In particular, it increases the intraoperative safety, supports de-escalation of ventilatory strategies, and reduces the rate of postoperative complications in a cohort of patients considered "high risk" for LVRS in the current literature.

Patterns and Impact of Arterial CO2 Management in Patients With Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study.

BACKGROUND: Considerable variability exists regarding CO2 management in early ARDS, with the impact of arterial CO2 tension on management and outcomes poorly understood. RESEARCH QUESTION: To determine the prevalence and impact of hypocapnia and hypercapnia on the management and outcomes of patients with early ARDS enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study, an international multicenter observational study. STUDY DESIGN AND METHODS: Our primary objective was to examine the prevalence of day 1 and sustained (day 1 and 2) hypocapnia (Paco2 < 35 mm Hg), normocapnia (Paco2 35-45 mm Hg), and hypercapnia (Paco2 > 45 mm Hg) in patients with ARDS. Secondary objectives included elucidating the effect of CO2 tension on ventilatory management and examining the relationship with ARDS outcome. RESULTS: Of 2,813 patients analyzed, 551 (19.6%; 95%CI, 18.1-21.1) were hypocapnic, 1,018 (36.2%; 95% CI, 34.4-38.0) were normocapnic, and 1,214 (43.2%; 95% CI, 41.3-45.0) were hypercapnic, on day 1. Sustained hypocapnia was seen in 252 (9.3%; 95% CI, 8.2-10.4), sustained normocapnia in 544 (19.3%; 95% CI, 17.9-20.8), and sustained hypercapnia in 654 (24.1%; 95% CI, 22.5-25.7) patients. Hypocapnia was more frequent and severe in patients receiving noninvasive ventilation but also was observed in patients on controlled mechanical ventilation. Sustained hypocapnia was more frequent in middle-income countries, whereas sustained hypercapnia was more frequent in Europe. ARDS severity profile was highest in sustained hypercapnia, and these patients received more protective ventilation. No independent association was seen between arterial CO2 and outcome. In propensity-matched analyses, the hospital mortality rate was 36% in both sustained normocapnic and hypercapnic patients (P = 1.0). ICU mortality was higher in patients with mild to moderate ARDS receiving sustained hypocapnia (38.1%) compared with normocapnia (27.1%). INTERPRETATION: No evidence was found for benefit or harm with hypercapnia. Of concern, ICU mortality was higher with sustained hypocapnia in mild to moderate ARDS.

Gait speed is associated with death or readmission among patients surviving acute hypercapnic respiratory failure.

OBJECTIVES: Death or hospital readmission are frequent among patients surviving acute hypercapnic respiratory failure (AHRF). Severity scores are not valid to predict death or readmission after AHRF. Gait speed, a simple functional parameter, has been associated with hospital admission and death in the general population. The purpose of this study is to highlight an association between gait speed at hospital discharge and death or readmission among AHRF survivors. DESIGN: Secondary analysis of a prospective cohort study. SETTINGS: Single Swiss tertiary hospital, pulmonary division. PARTICIPANTS: Patients were prospectively recruited to form a cohort of patients surviving AHRF in the intensive care unit between January 2012 and May 2015. OUTCOME MEASURE: Gait speed was derived from a 6 min walking test (6MWT) before hospital discharge. All predictive variables were prospectively collected. Death or hospital readmission were recorded for 6 months. Univariate and multivariate analyses were performed to evaluate the association between predictive variables and death or hospital readmission. RESULTS: 71 patients performed a 6MWT. 34/71 (48%) patients died or were readmitted to the hospital during the observation period. Median gait speed was 0.7 (IQR 0.3-1.0) m/s. At 6 months, 66% (25/38) of slow walkers (gait speed <0.7 m/s) and 27% (9/33) of non-slow walkers died or were readmitted to the hospital (p=0.002). In univariate analysis, gait speed was associated with death or readmission (HR 0.41; 95% CI 0.19 to 0.90, p=0.025). In a multivariate model adjusted for age, gender, body mass index, forced expired volume, heart failure and home mechanical ventilation, gait speed remained the only variable associated with death or readmission (multivariate HR: 0.35; 95% CI 0.14 to 0.88, p=0.025). CONCLUSION: This study suggests that a simple functional parameter such as gait speed is associated with death or hospital readmission in patients surviving AHRF. TRIAL REGISTRATION NUMBER: NCT02111876.

ST2 Predicts Mortality In Patients With Acute Hypercapnic Respiratory Failure Treated With Noninvasive Positive Pressure Ventilation.

Background: Patients with Acute Hypercapnic Respiratory Failure (AHRF) are often treated with Noninvasive Positive Pressure Ventilation (NPPV). In this heterogeneous patient group, there is a lack of clinical tools for predicting mortality and outcome. Aims: In order to facilitate the choice of treatment in patients with AHRF we evaluated the protein ST2, an established biomarker for cardiac stress, and its role in predicting mortality in patients with AHRF treated with NPPV. We also examined if ST2 baseline levels and changes during the first 12 hrs of treatment were predictive of treatment outcome. Methods: The study population consisted of 46 patients treated with NPPV for AHRF. Background data and clinical parameters were obtained and blood samples taken at various time points during the treatment. During the follow-up period of 18 months, the prognostic value of ST2 with regards to mortality was evaluated using Cox proportional hazard model. Results: Of the 46 patients, there were 3 subgroups in regards to primary diagnosis: Acute Exacerbation of COPD (n=34), Acute Heart Failure (n=8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (n=4). We found that ST2 was an independent predictor of both short-term and long-term mortality during the follow-up period. The Hazard Ratio (HR) per 1-SD increment of ST2 for 28-day mortality was 11.00 (95% CI 1.8-67.2, p 0.009) and for 18-month mortality 2.11 (95% CI 1.4-3.2, p 0.001). The results seem to be driven by the largest subgroup of patients, with Acute Exacerbation of COPD, and deaths within the first 28 days. Furthermore, changes in ST2 values during the first 12 hrs of treatment were not predictive of treatment outcome. Conclusion: Our results show that ST2 is a target to explore further as a predictor of short-term mortality in patients with AHRF treated with NPPV.

High flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: an observational cohort study.

Background: High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular. However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited. Methods: Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25-7.35, PaCO2>50 mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively. The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality. Results: Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study. The mean age was 71.8±8.2 and 54 patients (65.9%) were male. The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268). No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824). During the first 24 hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P<0.05). Skin breakdown was significantly more common in the NIV group (20.9% vs 5.1%, P<0.05). Conclusion: Among COPD patients with moderate hypercarbic ARF, the use of HFNC compared with NIV did not result in increased rates of treatment failure, while there were fewer nursing interventions and skin breakdown episodes reported in the HFNC group.

Late presentation of acute hypercapnic respiratory failure carries a high mortality risk in COPD patients treated with ward-based NIV.

INTRODUCTION: Non-invasive ventilation (NIV) is recommended for treatment of acute hypercapnic respiratory failure (AHRF) refractory to medical management in patients with COPD. This study investigated the relationship between time from hospital presentation to diagnosis of AHRF and in-hospital mortality. METHODS: Retrospective analysis of hospitalised COPD patients treated with a first episode of ward-based NIV for AHRF at a large UK teaching hospital between 2004 and 2017. Data collected prospectively as part of NIV service evaluation. Multivariable logistic regression performed to identify predictors of in-hospital mortality. RESULTS: In total, 547 unique patients were studied comprising 245 males (44.8%), median age 70.6 years, median FEV1% predicted 34%. Overall in-hospital mortality was 19% (n = 104); median survival was 1.7 years. In univariate analysis, a longer time between hospital presentation to diagnosis of AHRF was associated with in-hospital mortality (median [IQR]: 8.7 [0.7-75.8] hours vs. 1.9 [0.3-13.6] hours, p < 0.0001). In multivariable logistic regression, significant predictors of in-hospital mortality were AHRF >24 h after hospital presentation (odds ratio [95% CI]: 2.29 [1.33-3.95], p = 0.003), pneumonia on admission (1.81 [1.07-3.08], p = 0.027), increased age (1.10 [1.07-1.14], p < 0.001) and NIV as ceiling of treatment (5.86 [2.87-11.94], p < 0.001). CONCLUSIONS: Hospitalised COPD patients with late presentation of AHRF, requiring acute ward-based NIV, may have increased in-hospital mortality. These patients may benefit from closer monitoring and earlier specialist respiratory review.

Temporal trends in survival following ward-based NIV for acute hypercapnic respiratory failure in patients with COPD.

INTRODUCTION: Non-invasive ventilation (NIV) is recommended for treatment of acute hypercapnic respiratory failure (AHRF) in acute exacerbations of COPD. National UK audit data suggests that mortality rates are rising in COPD patients treated with NIV. OBJECTIVE: To investigate temporal trends in in-hospital mortality in COPD patients undergoing a first episode of ward-based NIV for AHRF. METHODS: Retrospective study of hospitalised COPD patients treated with a first episode of ward-based NIV at a large UK teaching hospital between 2004 and 2017. Patients were split into two cohorts based on year of admission, 2004-2010 (Cohort 1) and 2013-2017 (Cohort 2), to facilitate comparison of patient characteristics. RESULTS: In total, 547 unique patients were studied. There was no difference in in-hospital mortality rate between the time periods studied (17.6% vs 20.5%, P = .378). In Cohort 2 there were more females, a higher rate of co-morbid bronchiectasis and pneumonia on admission and more severe acidosis, hypercapnia and hypoxia. More patients in Cohort 2 had NIV as the ceiling of treatment. Patients in Cohort 2 experienced a longer time from AHRF diagnosis to application of NIV, higher maximum inspiratory positive airway pressure, lower maximum oxygen and shorter duration of NIV. Finally, patients in Cohort 2 experienced a shorter hospital length of stay (LOS), with no differences observed in rate of transfer to critical care or intubation. CONCLUSION: In-hospital mortality remained stable and LOS decreased over time, despite greater comorbidity and more severe AHRF in COPD patients treated for the first time with ward-based NIV.

High-intensity versus low-intensity noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (HAPPEN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival. METHODS/DESIGN: The HAPPEN study is a multicenter, two-arm, single-blind, prospective, randomized controlled trial. In total, 600 AECOPD patients with low to moderate hypercapnic respiratory failure will be included and randomized to receive high-intensity or low-intensity NPPV, with randomization stratified by study center. The primary endpoint is NPPV failure rate, defined as the need for endotracheal intubation and invasive ventilation. Secondary endpoints include the decrement of arterial carbon dioxide tension from baseline to 2 h after randomization, in-hospital and 28-day mortality, and 90-day survival. Patients will be followed up for 90 days after randomization. DISCUSSION: The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02985918 . Registered on 7 December 2016.

Improvement in hypercapnia does not predict survival in COPD patients on chronic noninvasive ventilation.

PURPOSE: It has recently been shown that chronic noninvasive ventilation (NIV) improves a number of outcomes including survival, in patients with stable hypercapnic COPD. However, the mechanisms responsible for these improved outcomes are still unknown. The aim of the present study was to identify parameters associated with: 1) an improved arterial partial pressure of carbon dioxide (PaCO2) and 2) survival, in a cohort of hypercapnic COPD patients treated with chronic NIV. PATIENTS AND METHODS: Data from 240 COPD patients treated with chronic NIV were analyzed. Predictors for the change in PaCO2 and survival were investigated using multivariate linear and Cox regression models, respectively. RESULTS: A higher level of bicarbonate before NIV initiation, the use of higher inspiratory ventilator pressures, the presence of anxiety symptoms, and NIV initiated following an exacerbation compared to NIV initiated in stable disease were associated with a larger reduction in PaCO2. A higher body mass index, a higher FEV1, a lower bicarbonate before NIV initiation, and younger age and NIV initiation in stable condition were independently associated with better survival. The change in PaCO2 was not associated with survival, neither in a subgroup of patients with a PaCO2 >7.0 kPa before the initiation of NIV. CONCLUSION: Patients with anxiety symptoms and a high bicarbonate level at NIV initiation are potentially good responders in terms of an improvement in hypercapnia. Also, higher inspiratory ventilator pressures are associated with a larger reduction in PaCO2. However, the improvement in hypercapnia does not seem to be associated with an improved survival and emphasizes the need to look beyond PaCO2 when considering NIV initiation.

Pressure support ventilation vs Continuous positive airway pressure for treating of acute cardiogenic pulmonary edema: A pilot study.

Non-invasive ventilation is usually adopted as a support to medical therapy in patients with acute pulmonary edema, but which modality between Pressure Support Ventilation (PSV) and Continuous Positive Airway Pressure (CPAP) has better favourable effects is not been yet well known. Aim of this observational study was to provide data on these different non-invasive ventilation modalities in the management of acute cardiogenic pulmonary edema. One-hundred-fifty-three patients consecutively admitted to the Emergency Room of two different Center were enrolled and randomly assigned to CPAP or PSV. Data relative to mortality, need of endotracheal intubation, sequential blood gas analysis were compared. Furthermore, there were no significant differences regarding mortality in the two groups, but patients treated with PSV had a significant lower rate of endotracheal intubation and a higher improvement of blood gas analyses parameters. In conclusion, our data support only a slight advantage in favour to PSV versus CPAP.

Respiratory parameters predict poor outcome in COPD patients, category GOLD 2017 B.

Background: Respiratory parameters are important predictors of prognosis in the COPD population. Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous. The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients. Methods: The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients. Kaplan-Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]). Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD. Results: All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%. Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ≤60% for the overall cohort and for GOLD B category patients. Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects. Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality. Conclusion: Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects. More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients. In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort.

High flow nasal cannulae oxygen therapy in acute-moderate hypercapnic respiratory failure.

INTRODUCTION: Severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a significant event that results in substantial mortality. OBJECTIVES: We evaluated the effectiveness of the high flow nasal cannulae (HFNC) therapy in severe AECOPD with moderate hypercapnic acute respiratory failure (ARF) compared to non-invasive ventilation (NIV). METHODS: The prospective observational trial was performed to compare the effectiveness between the HFNC and NIV in severe AECOPD with moderate hypercapnic ARF. The end point was the intubation rate and 30-day mortality. RESULTS: Ninety-two AECOPD patients enrolled during study periods. The median age was 73 (66.5-79) years, and 57 patients (64.8%) were male. Forty-four patients were assigned to HFNC, and 44 patients were assigned to NIV. The intubation rate at day 30 was 25.0% in the HFNC group and 27.3% in the NIV group (P = .857), and the 30-day mortality was 15.9% in the HFNC group and 18.2% in the NIV group (P = .845). The pH (7.38 ± 0.59 vs 7.36 ± 0.10, P = .295), PaO2 (82.2 ± 24.9 vs 81.6 ± 21.7 mm Hg, P = .899) and PaCO2 (46.8 ± 15.2 vs 51.7 ± 17.2 mm Hg, P = .160) after 6 hours and the pH (7.39 ± 0.07 vs 7.39 ± 0.08, P = .743), PaO2 (84.3 ± 18.5 vs 84.7 ± 23.2 mm Hg, P = .934) and PaCO2 (47.0 ± 16.0 vs 49.6 ± 13.7 mm Hg, P = .422) after 24 hours were not significantly different. CONCLUSION: There was no difference of the 30-day mortality and intubation rate between HFNC and NIV groups.

Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest.

OBJECTIVE: To determine if arterial oxygen and carbon dioxide abnormalities in the first 24h after return of spontaneous circulation (ROSC) are associated with increased mortality in adult out-of-hospital cardiac arrest (OHCA). METHODS: We used data from the Resuscitation Outcomes Consortium (ROC), including adult OHCA with sustained ROSC ≥1h after Emergency Department arrival and at least one arterial blood gas (ABG) measurement. Among ABGs measured during the first 24h of hospitalization, we identified the presence of hyperoxemia (PaO2≥300mmHg), hypoxemia (PaO2<60mmHg), hypercarbia (PaCO2>50mmHg) and hypocarbia (PaCO2<30mmHg). We evaluated the associations between oxygen and carbon dioxide abnormalities and hospital mortality, adjusting for confounders. RESULTS: Among 9186 OHCA included in the analysis, hospital mortality was 67.3%. Hyperoxemia, hypoxemia, hypercarbia, and hypocarbia occurred in 26.5%, 19.0%, 51.0% and 30.6%, respectively. Initial hyperoxemia only was not associated with hospital mortality (adjusted OR 1.10; 95% CI: 0.97-1.26). However, final and any hyperoxemia (1.25; 1.11-1.41) were associated with increased hospital mortality. Initial (1.58; 1.30-1.92), final (3.06; 2.42-3.86) and any (1.76; 1.54-2.02) hypoxemia (PaO2<60mmHg) were associated with increased hospital mortality. Initial (1.89; 1.70-2.10); final (2.57; 2.18-3.04) and any (1.85; 1.67-2.05) hypercarbia (PaCO2>50mmHg) were associated with increased hospital mortality. Initial (1.13; 0.90-1.41), final (1.19; 1.04-1.37) and any (1.01; 0.91-1.12) hypocarbia (PaCO2<30mmHg) were not associated with hospital mortality. CONCLUSIONS: In the first 24h after ROSC, abnormal post-arrest oxygen and carbon dioxide tensions are associated with increased out of-hospital cardiac arrest mortality.

Delayed but successful response to noninvasive ventilation in COPD patients with acute hypercapnic respiratory failure.

BACKGROUND: We evaluated a new noninvasive ventilation (NIV) protocol that allows the pursuit of NIV in the case of persistent severe respiratory acidosis despite a first NIV challenge in COPD patients with acute hypercapnic respiratory failure (AHRF). PATIENTS AND METHODS: A prospective observational multicentric pilot study was conducted in three tertiary hospitals over a 12-month study period. A total of 155 consecutive COPD patients who were admitted for AHRF and treated by NIV were enrolled. Delayed response to NIV was defined as a significant clinical improvement in the first 48 h following NIV initiation despite a persistent severe respiratory acidosis (pH <7.30) after the first 2 h of NIV trial. RESULTS: NIV failed in only 10 patients (6.5%). Delayed responders to NIV (n=83, 53%) exhibited similar nutritional status, comorbidities, functional status, frailty score, dyspnea score, and severity score at admission, compared with early responders (n=62, 40%). Only age (66 vs 70 years in early responders; P=0.03) and encephalopathy score (3 [2-4] vs 3 [2-4] in early responders; P=0.015) were different among the responders. Inhospital mortality did not differ between responders to NIV (n=10, 12% for delayed responders vs n=10, 16% for early responders, P=0.49). A second episode of AHRF occurred in 20 responders (14%), equally distributed among early and delayed responders to NIV (n=9, 14.5% in early responders vs n=11, 13% in delayed responders; P=0.83), with a poor survival rate (n=1, 5%). CONCLUSION: Most of the COPD patients with AHRF have a successful outcome when NIV is pursued despite a persistent severe respiratory acidosis after the first NIV trial. The outcome of delayed responders is similar to the one of the early responders. On the contrary, the second episode of AHRF during the hospital stay carries a poor prognosis.

Permissive hypercapnia for severe acute respiratory distress syndrome in immunocompromised children: A single center experience.

BACKGROUND: Controlled hypoventilation while accepting hypercapnia has been advocated to reduce ventilator-induced lung injury. The aim of the study was to analyze outcomes of a cohort of immunocompromised children with acute respiratory distress syndrome (ARDS) ventilated with a strategy of stepwise increasing PCO2 targets up to 140 mm Hg. METHODS: Retrospective analysis of outcomes of a cohort of children with oncologic disease or after stem cell transplantation and severe respiratory failure in comparison with a historical control cohort. RESULTS: Out of 150 episodes of admission to the PICU 88 children underwent invasive mechanical ventilation for >24h (overall survival 75%). In a subgroup of 38 children with high ventilator requirements the PCO2 target ranges were increased stepwise. Fifteen children survived and were discharged from the PICU. Severe pulmonary hypertension was seen in two patients and no case of cerebral edema was observed. Long term outcome was available in 15 patients and 10 of these patients survived without adverse neurological sequelae. With introduction of this strategy survival of immunocompromised children undergoing mechanical ventilation for >24h increased to 48% compared to 32% prior to introduction (historical cohort). CONCLUSIONS: A ventilation strategy incorporating very high carbon dioxide levels to allow for low tidal volumes and limited inspiratory pressures is feasible in children. Even severe hypercapnia may be well tolerated. No severe side effects associated with hypercapnia were observed. This strategy could potentially increase survival in immunocompromised children with severe ARDS.

Partial pressure of arterial carbon dioxide and survival to hospital discharge among patients requiring acute mechanical ventilation: A cohort study.

PURPOSE: To describe the prevalence of hypocapnia and hypercapnia during the earliest period of mechanical ventilation, and determine the association between PaCO2 and mortality. MATERIALS AND METHODS: A cohort study using an emergency department registry of mechanically ventilated patients. PaCO2 was categorized: hypocapnia (<35mmHg), normocapnia (35-45mmHg), and hypercapnia (>45mmHg). The primary outcome was survival to hospital discharge. RESULTS: A total of 1,491 patients were included. Hypocapnia occurred in 375 (25%) patients and hypercapnia in 569 (38%). Hypercapnia (85%) had higher survival rate compared to normocapnia (74%) and hypocapnia (66%), P<0.001. PaCO2 was an independent predictor of survival to hospital discharge [hypocapnia (aOR 0.65 (95% confidence interval [CI] 0.48-0.89), normocapnia (reference category), hypercapnia (aOR 1.83 (95% CI 1.32-2.54)]. Over ascending ranges of PaCO2, there was a linear trend of increasing survival up to a PaCO2 range of 66-75mmHg, which had the strongest survival association, aOR 3.18 (95% CI 1.35-7.50). CONCLUSIONS: Hypocapnia and hypercapnia occurred frequently after initiation of mechanical ventilation. Higher PaCO2 levels were associated with increased survival. These data provide rationale for a trial examining the optimal PaCO2 in the critically ill.

Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER).

PURPOSE: Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders. METHODS: A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852). RESULTS: Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2-6) versus 4 days (IQR 2-7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59-14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07-13.31); p = 0.04]. CONCLUSIONS: Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.

Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in Mechanically Ventilated Patients.

OBJECTIVES: Lung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of hypercapnia and hypercapnic acidosis in patients requiring mechanical ventilation. DESIGN: Multicenter, binational, retrospective study aimed to assess the impact of compensated hypercapnia and hypercapnic acidosis in patients receiving mechanical ventilation. SETTINGS: Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database over a 14-year period where 171 ICUs contributed deidentified data. PATIENTS: Patients were classified into three groups based on a combination of pH and carbon dioxide levels (normocapnia and normal pH, compensated hypercapnia [normal pH with elevated carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay. Logistic regression analysis was used to identify the independent association of hypercapnia and hypercapnic acidosis with hospital mortality. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: A total of 252,812 patients (normocapnia and normal pH, 110,104; compensated hypercapnia, 20,463; and hypercapnic acidosis, 122,245) were included in analysis. Patients with compensated hypercapnia and hypercapnic acidosis had higher Acute Physiology and Chronic Health Evaluation III scores (49.2 vs 53.2 vs 68.6; p < 0.01). The mortality was higher in hypercapnic acidosis patients when compared with other groups, with the lowest mortality in patients with normocapnia and normal pH. After adjusting for severity of illness, the adjusted odds ratio for hospital mortality was higher in hypercapnic acidosis patients (odds ratio, 1.74; 95% CI, 1.62-1.88) and compensated hypercapnia (odds ratio, 1.18; 95% CI, 1.10-1.26) when compared with patients with normocapnia and normal pH (p < 0.001). In patients with hypercapnic acidosis, the mortality increased with increasing PCO2 until 65 mm Hg after which the mortality plateaued. CONCLUSIONS: Hypercapnic acidosis during the first 24 hours of intensive care admission is more strongly associated with increased hospital mortality than compensated hypercapnia or normocapnia.

Early use of noninvasive techniques for clearing respiratory secretions during noninvasive positive-pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease and hypercapnic encephalopathy: A prospective cohort study.

Noninvasive positive-pressure ventilation (NPPV) might be superior to conventional mechanical ventilation (CMV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Inefficient clearance of respiratory secretions provokes NPPV failure in patients with hypercapnic encephalopathy (HE). This study compared CMV and NPPV combined with a noninvasive strategy for clearing secretions in HE and AECOPD patients.The present study is a prospective cohort study of AECOPD and HE patients enrolled between October 2013 and August 2015 in a critical care unit of a major university teaching hospital in China.A total of 74 patients received NPPV and 90 patients received CMV. Inclusion criteria included the following: physician-diagnosed AECOPD, spontaneous airway clearance of excessive secretions, arterial blood gas analysis requiring intensive care, moderate-to-severe dyspnea, and a Kelly-Matthay scale score of 3 to 5. Exclusion criteria included the following: preexisting psychiatric/neurological disorders unrelated to HE, upper gastrointestinal bleeding, upper airway obstruction, acute coronary syndromes, preadmission tracheostomy or endotracheal intubation, and urgent endotracheal intubation for cardiovascular, psychomotor agitation, or severe hemodynamic conditions.Intensive care unit participants were managed by NPPV. Participants received standard treatment consisting of controlled oxygen therapy during NPPV-free periods; antibiotics, intravenous doxofylline, corticosteroids (e.g., salbutamol and ambroxol), and subcutaneous low-molecular-weight heparin; and therapy for comorbidities if necessary. Nasogastric tubes were inserted only in participants who developed gastric distension. No pharmacological sedation was administered.The primary and secondary outcome measures included comparative complication rates, durations of ventilation and hospitalization, number of invasive devices/patient, and in-hospital and 1-year mortality rates.Arterial blood gases and sensorium levels improved significantly within 2 hours in the NPPV group with lower hospital mortality, fewer complications and invasive devices/patient, and superior weaning off mechanical ventilation. Mechanical ventilation duration, hospital stay, or 1-year mortality was similar between groups.NPPV combined with a noninvasive strategy to clear secretions during the first 2 hours may offer advantages over CMV in treating AECOPD patients complicated by HE.