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PurposeTo describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design.MethodsUsing data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland–Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population.ResultsChanges in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9 cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate.ConclusionsThe lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R.

PurposeNoninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure.MethodsHighly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality.ResultsWe enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0–7.0) vs. 5.5 (4.0–9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0–12.0) vs. 9.0 (6.5–12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13–32) vs. 27(18–39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies.ConclusionsIn highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Objective Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent. Methods Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO 2 ) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO 2 , maximum PaO 2 difference, and gradually increasing PaO 2 levels (13.3–53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO 2 and a biomarker of brain injury, peak serum Tau levels. Results Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO 2 exposure or maximum PaO 2 difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p  = 0.146–0.847). We were not able to define a PaO 2 level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO 2 . Conclusion Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC.

When hemoglobin (Hb) is fully saturated with oxygen, the additional gain in oxygen delivery (DO 2 ) achieved by increasing the fraction of inspired oxygen (FiO 2 ) is often considered clinically insignificant. In this study, we evaluated the change in DO 2 , interrogated by mixed venous oxygen saturation (SvO 2 ), in response to a change in FiO 2 of 0.5 during cardiac surgery. When patients were hemodynamically stable, FiO 2 was alternated between 0.5 and 1.0 in on-pump cardiac surgery patients (pilot study), and between 0.3 and 0.8 in off-pump coronary artery bypass grafting patients (substudy of the CARROT trial). After the patient had stabilized, a blood gas analysis was performed to measure SvO 2 . The observed change in SvO 2 (ΔSvO 2 ) was compared to the expected ΔSvO 2 calculated using Fick’s equation. A total 106 changes in FiO 2 (two changes per patient; total 53 patients; on-pump, n = 36; off-pump, n = 17) were finally analyzed. While Hb saturation remained near 100% (on-pump, 100%; off-pump, mean [SD] = 98.1% [1.5] when FiO 2 was 0.3 and 99.9% [0.2] when FiO 2 was 0.8), SvO 2 changed significantly as FiO 2 was changed (the first and second changes in on-pump, 7.7%p [3.8] and 7.6%p [3.5], respectively; off-pump, 7.9%p [4.9] and 6.2%p [3.9]; all P < 0.001). As a total, regardless of the surgery type, the observed ΔSvO 2 after the FiO 2 change of 0.5 was ≥ 5%p in 82 (77.4%) changes and ≥ 10%p in 31 (29.2%) changes (mean [SD], 7.5%p [3.9]). Hb concentration was not correlated with the observed ΔSvO 2 (the first changes, r  =  − 0.06, P = 0.677; the second changes, r  =  − 0.21, P = 0.138). The mean (SD) residual ΔSvO 2 (observed − expected ΔSvO 2 ) was 0%p (4). Residual ΔSvO 2 was more than 5%p in 14 (13.2%) changes and exceeded 10%p in 2 (1.9%) changes. Residual ΔSvO 2 was greater in patients with chronic kidney disease than in those without (median [IQR], 5%p [0 to 7] vs. 0%p [− 3 to 2]; P = 0.049). DO 2 , interrogated by SvO 2 , may increase to a clinically significant degree as FiO 2 is increased during cardiac surgery, and the increase of SvO 2 is not related to Hb concentration. SvO 2 increases more than expected in patients with chronic kidney disease. Increasing FiO 2 can be used to increase DO 2 during cardiac surgery.

ObjectivesThe effects of hypercapnia on regional cerebral oxygen saturation (rSO2) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO2. We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO2.DesignA prospective, randomised, controlled trial in adult participants undergoing elective major surgery.SettingA single tertiary centre in Heidelberg, Victoria, Australia.Participants40 participants were randomised to either a TMH or TN group (20 to each).InterventionsTMH (partial pressure of carbon dioxide in arterial blood, PaCO2, 45–55 mm Hg) or TN (PaCO2 35–40 mm Hg) was delivered via controlled ventilation throughout surgery.Primary and secondary outcome measuresThe primary endpoint was the absolute difference between the two groups in percentage change in rSO2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital.ResultsThe absolute difference between the two groups in percentage change in rSO2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p<0.001). On both sides, the percentage change in rSO2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99).ConclusionTMH was associated with a stable increase in rSO2 from the baseline, while TN was associated with a decrease in rSO2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery.Trial registration numberThe Australian New Zealand Clinical Trials Registry (ACTRN12616000320459).

PurposeThe Nova StatStrip® Glucose Hospital Meter System (Nova Biomedical, Waltham, MA, USA) is United States Food and Drug Administration approved for point-of-care use in critically ill patients, but its use during cardiac surgery has not been evaluated. In this study, we compare glucose values obtained during cardiac surgery by StatStrip® with values obtained by a blood gas analyzer.MethodsBlood glucose concentrations were analyzed in 121 patients by the StatStrip point- of-care test (POCT) glucose monitor and the GEM® Premier™ 3000 blood gas analyzer (Instrumentation Laboratory Company, Bedford MA, USA). Arterial blood samples were taken at baseline (before surgery), before cardiopulmonary bypass (CPB), during early and late CPB, and 30 min after CPB. Accuracy of the StatStrip glucometer was analyzed using the Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 criteria (criterion 1; 95% of samples should be ± 0.66 mMol·L−1 of reference glucose values < 5.5 mMol·L−1 and ± 12.5% for reference glucose values > 5.5 mMol·L−1, criterion 2; 98% of samples should be ± 0.83 mMol·L−1 of reference glucose values < 4.1 mMol·L−1 or 20% of the reference glucose for values > 4.1 mMol·L−1).ResultsThe accuracy of StatStrip glucose measurements at baseline (99%, 100%) and before CPB (95%, 98%), but not during (early: 84%, 97%; late: 83%, 96%) and after (92%, 100%) CPB, satisfied the CLSI POCT12-A3 criteria.ConclusionArterial blood glucose measurement by StatStrip was accurate before CPB, but lacked accuracy during and after CPB. Glucose values should be interpreted with caution when intensive glucose control protocols are being used during cardiac surgery.Trial registrationClinicalTrials.gov (NCT02729064); registered 5 April, 2016.

Introduction The purpose of this study was to evaluate the clinical relevance of high values of central venous-to-arterial carbon dioxide difference (PCO 2 gap) in high-risk surgical patients admitted to a postoperative ICU. We hypothesized that PCO 2 gap could serve as a useful tool to identify patients still requiring hemodynamic optimization at ICU admission. Methods One hundred and fifteen patients were included in this prospective single-center observational study during a 1-year period. High-risk surgical inclusion criteria were adapted from Schoemaker and colleagues. Demographic and biological data, PCO 2 gap, central venous oxygen saturation, lactate level and postoperative complications were recorded for all patients at ICU admission, and 6 hours and 12 hours after admission. Results A total of 78 (68%) patients developed postoperative complications, of whom 54 (47%) developed organ failure. From admission to 12 hours after admission, there was a significant difference in mean PCO 2 gap (8.7 ± 2.8 mmHg versus 5.1 ± 2.6 mmHg; P  = 0.001) and median lactate values (1.54 (1.1-3.2) mmol/l versus 1.06 (0.8-1.8) mmol/l; P  = 0.003) between patients who developed postoperative complications and those who did not. These differences were maximal at admission to the ICU. At ICU admission, the area under the receiver operating characteristic curve for occurrence of postoperative complications was 0.86 for the PCO 2 gap compared to Sequential Organ Failure Assessment score (0.82), Simplified Acute Physiology Score II score (0.67), and lactate level (0.67). The threshold value for PCO 2 gap was 5.8 mmHg. Multivariate analysis showed that only a high PCO 2 gap and a high Sequential Organ Failure Assessment score were independently associated with the occurrence of postoperative complications. A high PCO 2 gap (≥6 mmHg) was associated with more organ failure, an increase in duration of mechanical ventilation and length of hospital stay. Conclusion A high PCO 2 gap at admission in the postoperative ICU was significantly associated with increased postoperative complications in high-risk surgical patients. If the increase in PCO 2 gap is secondary to tissue hypoperfusion then the PCO 2 gap might be a useful tool complementary to central venous oxygen saturation as a therapeutic target.

The long-term effect of average volume-assured pressure support (AVAPS) on health-related quality of life (HRQOL) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure (CHRF) remains unclear. The objective of this study is to identify the long-term effect of AVAPS in COPD patients with CHRF through assessment of HRQOL, exercise tolerance after six months duration. Methods In this randomized, controlled, parallel-group study, 40 stable hypercapnic COPD patients were randomized in a 1:1 ratio to receive either spontaneous timed AVAPS (ST/AVAPS) (intervention) or Bilevel positive airway pressure (ST/BiPAP) (control). HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12). Exercise tolerance assessed by 6 min walking distance. Analyses were done between groups from baseline to the average of six months measurements. Results AVAPS led to significant 6 months improvements in several domains of (SF-12) compared to the control group, with the greatest improvement seen in general health [treatment effect of 8.2 points (95% confidence interval [95% CI 3.2 to 11.7; p  = 0.001)], vitality (treatment effect 5.4 points [95% CI 1.4 to 9.3]; p  = 0.001), physical functioning 5.5 points [95% CI 1.1 to 9.8]; p  = 0.001) and bodily pain 5.1 points [95% CI 3.4 to 8.8]; p  = 0.002). The physical health summary score improved by 3.7 points (95% CI 1.2 to 5.8; p  = 0.001), but no significant improvement in the emotional or social role functioning, mental health subscale was noted. AVAPS also resulted in improvement 6 min walking distance 9.2 points (95% CI − 1 to − 15]; p  = 0.001). A significant reduction in the daytime (PaCO2) was observed after 6 months in those treated with AVAPS. Conclusions In COPD patients with hypercapnic respiratory failure, AVAPS improved exercise tolerance and multiple domains of HRQOL over six months of follow-up, with the significant improvement observed in general health.

Background and Objectives: Percutaneous liver radiofrequency ablation (RFA) under monitored anesthesia care (MAC) carries a risk of hypoxia due to respiratory depression. Ensuring adequate oxygenation during such procedures is essential for patient safety. This study aimed to evaluate whether a high-flow nasal cannula (HFNC) improves oxygenation compared to a simple facemask during RFA. Materials and Methods: In this prospective, randomized controlled trial, 51 patients undergoing ultrasound-guided RFA under MAC were allocated to receive oxygen via an HFNC (30 L/min) or a facemask (6 L/min). Arterial blood gases were collected at the baseline and 5 min after oxygenation. The primary outcome was the arterial partial pressure of oxygen (PaO2). Secondary outcomes included hypoxia incidence (SpO2 < 95%), the difference in the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen concentration (ΔP/F ratio), the difference in the arterial partial pressure of carbon dioxide (ΔPaCO2), respiratory rate (RR) changes, and patient satisfaction. Results: After adjustment for the baseline PaO2, the HFNC group showed significantly higher intra-procedural PaO2 compared to the facemask group (299 ± 18.6 vs. 194 ± 19.0 mmHg, p < 0.001). No significant differences were found in the ΔP/F ratio, ΔPaCO2, or patient satisfaction. Among the secondary outcomes, RR was more stable in the HFNC group throughout the procedure (Group × Time interaction, p = 0.003). Conclusions: The HFNC significantly improved intra-procedural PaO2 during RFA under MAC but did not reduce hypoxia incidence or improve other clinical outcomes compared to facemask oxygenation. The stability of RR observed with the HFNC may reflect a physiological advantage, though further studies are needed to determine its clinical relevance.

Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude. To determine the therapeutic efficacy of acetazolamide on central sleep apnea associated with heart failure. Twelve male patients with stable systolic heart failure whose initial polysomnograms showed more than 15 episodes per hour of apnea and hypopnea participated in the study. The patients were randomized to a double-blind cross-over protocol with acetazolamide or placebo, taken 1 h before bedtime for six nights with 2 wk of washout. Polysomnography, pulmonary function tests, arterial blood gases, and left ventricular ejection fraction were obtained initially along with a sleep questionnaire, history, and physical examination. Baseline measurements were repeated at the end of each arm. There were no significant differences between parameters at baseline and placebo. In comparing placebo with acetazolamide, the hourly number of episodes of central apnea (49 +/- 28 vs. 23 +/- 21 [mean +/- SD]; p = 0.004) and the percentage of total sleep time spent below an arterial oxyhemoglobin saturation of 90% (19 +/- 32 vs. 6 +/- 13%; p = 0.01) decreased significantly. Acetazolamide improved subjective perception of overall sleep quality (p = 0.003), feeling rested on awakening (p = 0.007), daytime fatigue (p = 0.02), and falling asleep unintentionally during daytime (p = 0.002). In patients with heart failure, administration of a single dose of acetazolamide before sleep improves central sleep apnea and related daytime symptoms.