Therapeutic hypercapnia has been proposed as a potential strategy to enhance cerebral perfusion and improve outcomes in patients after cardiac arrest. However, the effects of targeted hypercapnia remain unclear. We conducted a systematic review and meta-analysis to evaluate the impact of hypercapnia compared to normocapnia on mortality and length of stay in post-cardiac arrest patients. We searched major databases for randomized controlled trials and observational studies comparing outcomes between hypercapnia and normocapnia in adult post-cardiac arrest patients. Data on in-hospital mortality and the ICU and hospital length of stay were extracted and pooled using random-effects meta-analysis. Five studies (two randomized controlled trials (RCTs) and three observational studies) with a total of 1,837 patients were included. Pooled analysis showed hypercapnia was associated with significantly higher in-hospital mortality compared to normocapnia (56.2% vs. 50.5%, OR 1.24, 95% CI 1.12-1.37, p<0.001). There was no significant heterogeneity (I2 = 25%, p = 0.26). No statistically significant differences were found for ICU length of stay (mean difference 0.72 days, 95% CI -0.51 to 1.95) or hospital length of stay (mean difference 1.13 days, 95% CI -0.67 to 2.93) between the groups. Sensitivity analysis restricted to mild hypercapnia studies did not alter the mortality findings. This meta-analysis did not find a mortality benefit with targeted hypercapnia compared to normocapnia in post-cardiac arrest patients. The results align with current guidelines recommending a normal partial pressure of arterial carbon dioxide (PaCO2) target range and do not support routinely targeting higher carbon dioxide levels in this setting.

OBJECTIVE: Review changes in neonatal ventilation practice within our regional transport service, Embrace, identifying interventions with greatest impact on improved rates of normocapnia during transfer.
METHODS: Using internal transport databases and UK Neonatal Transport Group data submissions, we tracked local and national rates of ventilation and normocapnia. We correlated this with internal changes in practice, including introduction of new equipment, staffing changes, educational interventions and quality improvement projects.
RESULTS: Data demonstrated improvement in normocapnia rates benchmarked against national figures, which was not explained by changes in ventilation methods or rates, or by changes in availability of post-transfer gases. Greatest improvement was identified following introduction of transcutaneous CO2 monitoring and ventilators enabling volume-guided ventilation strategies. Additionally, although less quantifiable, educational and quality improvement interventions, and case review mechanisms were felt to be influential.
CONCLUSIONS: Volume guided ventilation and transcutaneous CO2 monitoring have had a positive influence on the maintenance of normocapnia during transfer at Embrace Transport Service, although introduction of new equipment still presents challenges which must be overcome. Recognising the significant impact of these technologies allows for ongoing financial, time and educational investment to emphasise their importance and ensure appropriate awareness of limitations and troubleshooting options, maximising their positive impact.

The effect of mild changes in CO2 levels to organ perfusion and tissue inflammation are well known, whereas an influence of hypercapnia under general anesthesia on adverse events as nausea and vomiting, or length of hospital stay is barely examined. The goal of our meta-analysis was to identify possibly positive effects of hypercapnia versus normocapnia in general anesthesia in adult patients.
We conducted a systematic review of parallel-arm randomised controlled trials comparing hypercapnia versus normocapnia in adult patients undergoing general anesthesia. In July 2018 and September 2019 we searched \"CENTRAL‿, \"MEDLINE‿, and \"Embase‿, checked reference lists of all included studies and relevant systematic reviews for additional references to trials. Two review authors independently assessed trials for inclusion, extracted data, and completed a \"Risk of bias‿ assessment for all included studies.
Our search identified 297 records after abstract screening 30 full-text papers remained for further examination. Ten publications met our inclusion criteria and were used for narrative description of this systematic review. Three studies were eligible for the meta-analysis normocapnia versus hypercapnia with the outcomes: time to extubation and adverse events. On average, time to extubation was significantly reduced in the hypercapnia group with a mean difference 3.78 (95% CI 0.85 to 6.71). No difference was found regarding adverse events.
The findings of our study do not enable us to produce evidence of a positive influence of increased CO2 partial pressure levels during general anesthesia. A well-planned, adequately powered randomized controlled trial would be desirable in the future.

BACKGROUND: High-intensity noninvasive positive pressure ventilation (NPPV) is a novel ventilatory approach to maximally decreasing elevated arterial carbon dioxide tension (PaCO2) toward normocapnia with stepwise up-titration of pressure support. We tested whether high-intensity NPPV is more effective than low-intensity NPPV at decreasing PaCO2, reducing inspiratory effort, alleviating dyspnoea, improving consciousness, and improving NPPV tolerance in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
METHODS: In this physiological, randomised controlled trial, we assigned 24 AECOPD patients to undergo either high-intensity NPPV (n = 12) or low-intensity NPPV (n = 12). The primary outcome was PaCO2 24 h after randomisation. Secondary outcomes included gas exchange other than PaCO2 24 h after randomisation, inspiratory effort, dyspnoea, consciousness, NPPV tolerance, patient-ventilator asynchrony, cardiac function, ventilator-induced lung injury (VILI), and NPPV-related adverse events.
RESULTS: Inspiratory positive airway pressure 24 h after randomisation was significantly higher (28.0 [26.0-28.0] vs. 15.5 [15.0-17.5] cmH2O; p = 0.000) and NPPV duration within the first 24 h was significantly longer (21.8 ± 2.1 vs. 15.3 ± 4.7 h; p = 0.001) in the high-intensity NPPV group. PaCO2 24 h after randomisation decreased to 54.0 ± 11.6 mmHg in the high-intensity NPPV group but only decreased to 67.4 ± 10.6 mmHg in the low-intensity NPPV group (p = 0.008). Inspiratory oesophageal pressure swing, oesophageal pressure-time product (PTPes)/breath, PTPes/min, and PTPes/L were significantly lower in the high-intensity group. Accessory muscle use and dyspnoea score 24 h after randomisation were also significantly lower in that group. No significant between-groups differences were observed in consciousness, NPPV tolerance, patient-ventilator asynchrony, cardiac function, VILI, or NPPV-related adverse events.
CONCLUSIONS: High-intensity NPPV is more effective than low-intensity NPPV at decreasing elevated PaCO2, reducing inspiratory effort, and alleviating dyspnoea in AECOPD patients.
BACKGROUND: ClinicalTrials.gov (NCT04044625; registered 5 August 2019).

OBJECTIVE: To test whether targeted therapeutic mild hypercapnia (TTMH) would attenuate cerebral oxygen desaturation detected using near-infrared spectroscopy during cardiac surgery requiring cardiopulmonary bypass (CPB).
METHODS: Randomized controlled trials.
METHODS: Operating rooms and intensive care unit of tertiary hospital.
METHODS: The study comprised 30 patients undergoing cardiac surgery with CPB.
METHODS: Patients were randomly assigned to receive either standard carbon dioxide management (normocapnia) or TTMH (target arterial carbon dioxide partial pressure between 50 and 55 mmHg) throughout the intraoperative period and postoperatively until the onset of spontaneous ventilation.
RESULTS: Relevant biochemical and hemodynamic variables were measured, and cerebral tissue oxygen saturation (SctO2) was monitored with near-infrared spectroscopy. Patients were followed-up with neuropsychological testing. Patient demographics between groups were compared using the Fisher exact and Mann-Whitney tests, and SctO2 between groups was compared using repeated measures analysis of variance. The median patient age was 67 years (interquartile range [IQR] 62-72 y), and the median EuroSCORE II was 1.1. The median CPB time was 106 minutes. The mean intraoperative arterial carbon dioxide partial pressure for each patient was significantly higher with TTMH (52.1 mmHg [IQR 49.9-53.9 mmHg] v 40.8 mmHg [IQR 38.7-41.7 mmHg]; p < 0.001) as was pulmonary artery pressure (23.9 mmHg [IQR 22.4-25.3 mmHg] v 18.5 mmHg [IQR 14.8-20.7 mmHg]; p = 0.004). There was no difference in mean percentage change in SctO2 during CPB in the control group for both hemispheres (left: -6.7% v -2.3%; p = 0.110; right: -7.9% v -1.0%; p = 0.120). Compliance with neuropsychological test protocols was poor. However, the proportion of patients with drops in test score >20% was similar between groups in all tests.
CONCLUSIONS: TTMH did not increase SctO2 appreciably during CPB but increased pulmonary artery pressures before and after CPB. These findings do not support further investigation of TTMH as a means of improving SctO2 during and after cardiac surgery requiring CPB.

Background: Postoperative delirium (POD) might be associated with anesthetic management, but research has focused on choice or dosage of anesthetic drugs. We examined potential contributions of intraoperative ventilatory and hemodynamic management to POD. Methods: This was a sub-study of the ENGAGES-Canada trial (NCT02692300) involving non-cardiac surgery patients enrolled in Winnipeg, Canada. Patients received preoperative psychiatric and cognitive assessments, and intraoperatively underwent high-fidelity data collection of blood pressure, end-tidal respiratory gases and anesthetic agent concentration. POD was assessed by peak and mean POD scores using the Confusion Assessment Method-Severity (CAM-S) tool. Bivariate and multiple linear regression models were constructed controlling for age, psychiatric illness, and cognitive dysfunction in the examination of deviations in intraoperative end-tidal carbon dioxide (areas over (AOC) and under the curve (AUC)) on POD severity scores. Results: A total of 101 subjects [69 (6) years of age] were studied; 89 had comprehensive intraoperative hemodynamic and end-tidal gas measurements (data recorded at 1 Hz). The incidence of POD was 11.9% (12/101). Age, cognitive dysfunction, anxiety, depression, and intraoperative end-tidal CO2 (AUC) were significant correlates of POD severity. In the multiple regression model, cognitive dysfunction and AUC end-tidal CO2 (0.67 kPa below median intra-operative value) were the only independent significant predictors across both POD severity (mean and peak) scores. There was no association between cumulative anesthetic agent exposure and POD. Conclusions: POD was associated with intraoperative ventilatory management, reflected by low end-tidal CO2 concentrations, but not with cumulative anesthetic drug exposure. These findings suggest that maintenance of intraoperative normocapnia might benefit patients at risk of POD.

Ventilatory after-discharge (sustained elevation of ventilation following stimulus removal) occurs during sleep but not when hypocapnia is present. Genioglossus after-discharge also occurs during sleep, but CO2 effects have not been assessed. The relevance is that postarousal after-discharge may protect against upper airway collapse. This study aimed to determine whether arousal elicits genioglossus after-discharge that persists into sleep, and whether it is influenced by CO2.
Twenty-four healthy individuals (6 female) slept with a nasal mask and ventilator. Sleep (EEG, EOG, EMG), ventilation (pneumotachograph), end-tidal CO2 (PETCO2), and intramuscular genioglossus EMG were monitored. NREM eucapnia was determined during 5 minutes on continuous positive airway pressure (4 cmH2O). Inspiratory pressure support was increased until PETCO2 was ≥2 mm Hg below NREM eucapnia. Supplemental CO2 was added to reproduce normocapnia, without changing ventilator settings. Arousals were induced by auditory tones and genioglossus EMG compared during steady-state hypocapnia and normocapnia.
Eleven participants (4 female) provided data. Prearousal PETCO2 was less (p < .05) during hypocapnia (40.74 ± 2.37) than normocapnia (43.82 ± 2.89), with differences maintained postarousal. After-discharge, defined as an increase in genioglossus activity above prearousal levels, occurred following the return to sleep. For tonic activity, after-discharge lasted four breaths irrespective of CO2 condition. For peak activity, after-discharge lasted one breath during hypocapnia and 6 breaths during normocapnia. However, when peak activity following the return to sleep was compared between CO2 conditions no individual breath differences were observed.
Postarousal genioglossal after-discharge may protect against upper airway collapse during sleep. Steady-state CO2 levels minimally influence postarousal genioglossus after-discharge.

OBJECTIVE: The aim of this study was to determine the association between PaCO2 and patient outcome in patients admitted to the intensive care unit (ICU) after coronary artery bypass grafting (CABG).
METHODS: A retrospective cohort study.
METHODS: Single-institutional, university hospital.
METHODS: All patients admitted to the ICU after CABG between January 2009 and December 2012.
METHODS: None.
RESULTS: Based on PaCO2 status during the first 24 hours after CABG, 1,011 patients were classified into 4 groups: normocapnia, hypocapnia, hypercapnia, and dual hyper/hypocapnia. The 30-day mortality rate was 0.7% (n = 4) for normocapnia, 1.5% (n = 4) for hypocapnia, 2.2% (n = 3) for hypercapnia, and 7.5% (n = 4) for the dual-exposure group. The extubation times were 13.3±21.7 hours, 15.8±21.37 hours, 21.79±39.70 hours, and 42.29±75.35 hours, respectively. After adjusting for confounding variables, the dual hypocapnia and hypercapnia exposure group was associated with increased 30-day mortality (odds ratio [OR] = 8.08; 95% confidence interval [CI], 1.82-35.86; p = 0.006) and delayed extubation (OR = 2.40; 95% CI, 1.24-4.64; p = 0.010).
CONCLUSIONS: Exposure to both hypocapnia and hypercapnia within 24 hours after CABG was associated independently with increased risk of 30-day mortality and delayed extubation. Exposure to either hypocapnia or hypercapnia alone was not associated with patient outcome.

BACKGROUND: Optimal cerebral oxygenation is considered fundamental to cerebral protection in cardiac arrest (CA) patients. Hypercapnia increases cerebral blood flow and may also improve cerebral oxygenation. It is uncertain, however, whether this effect occurs in mechanically ventilated early survivors of CA.
METHODS: We enrolled mechanically ventilated resuscitated patients within 36h of their cardiac arrest. We performed a prospective double cross-over physiological study comparing the impact of normocapnia (PaCO2 35-45mmHg) vs. mild hypercapnia (PaCO2 45-55mmHg) on regional cerebral tissue oxygen saturation (SctO2) assessed by near infrared spectroscopy (NIRS).
RESULTS: We studied seven adult CA patients with a median time to return of spontaneous circulation of 28min at a median of 26h and 30min after CA. During normocapnia (median EtCO2 of 32mmHg [30-41mmHg] and PaCO2 of 37mmHg [32-45mmHg]) the median NIRS-derived left frontal SctO2 was 61% [52-65%] and the right frontal SctO2 was 61% [54-68%]. However, during mild hypercapnia (median EtCO2 of 49mmHg [40-57mmHg] and PaCO2 of 52mmHg [43-55mmHg) the median left frontal SctO2 increased to 69% [59-78%] and the right frontal SctO2 increased to 73% [61-76%])(p=0.001, for all comparisons).
CONCLUSIONS: During the early post-resuscitation period, in mechanically ventilated CA patients, mild hypercapnia increases cerebral oxygenation as assessed by NIRS. Further investigations of the effect of prolonged mild hypercapnia on cerebral oxygenation and patient outcomes appear justified.

BACKGROUND: The use of domiciliary noninvasive positive pressure ventilation (NPPV) in stable chronic obstructive pulmonary disease (COPD) with chronic hypercapnic respiratory failure has yielded variable effects on survival, quality of life, and dyspnea. We hypothesized that use of NPPV in stable COPD and partial pressure of carbon dioxide (PaCO2) <52 mmHg might result in improvement in quality of life and dyspnea.
METHODS: Thirty patients with stable COPD (forced expiratory volume in the first second <50% predicted and PaCO2 <52 mmHg) were prospectively randomized to receive domiciliary NPPV (bilevel positive airway pressure, 15/5 cm H2O) or usual therapy for 6 months. Measurements were made at baseline, 6 weeks, 3 months, and 6 months. Primary outcomes were quality of life as assessed by the Chronic Respiratory Disease Questionnaire (CRQ), and dyspnea as measured by the Transitional Dyspnea Index (TDI).
RESULTS: Fifteen subjects in the NPPV arm and 12 controls completed all the study visits. At 6 weeks and 3 months, the NPPV arm showed significant improvement in TDI total score. However, this effect persisted only in the TDI-Task at 6 months (P=0.03). NPPV use was associated with a small improvement in the CRQ-Mastery domain (0.6 versus -0.1, P=0.04). The arterial partial pressure of oxygen (PaO2) in the control arm worsened over the period of the study, whereas it remained stable in the NPPV arm (change -7.2 mmHg versus +2.1 mmHg, respectively, P=0.02).
CONCLUSIONS: NPPV resulted in a small improvement in quality of life indices in stable COPD patients with PaCO2 <52 mmHg. Future larger studies will clarify the role of NPPV in this stable subgroup of patients with COPD.