Association of dead space fraction to mortality in patients with COVID-19-related ARDS: A historical cohort observational study.

OBJECTIVE: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DESIGN: Observational study of a historical cohort. SETTING: University hospital in Medellin, Colombia. PARTICIPANTS: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. INTERVENTIONS: Measurement of VD/VT, CMV, and VR in COVID-19 patients. MAIN VARIABLES OF INTEREST: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. RESULTS: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017). CONCLUSIONS: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Increased Dead Space Ventilation as a Contributing Factor to Persistent Exercise Limitation in Patients with a Left Ventricular Assist Device.

(1) Background: The exercise capacity of patients with a left ventricular assist device (LVAD) remains limited despite mechanical support. Higher dead space ventilation (VD/VT) may be a surrogate for right ventricular to pulmonary artery uncoupling (RV-PA) during cardiopulmonary exercise testing (CPET) to explain persistent exercise limitations. (2) Methods: We investigated 197 patients with heart failure and reduced ejection fraction with (n = 89) and without (HFrEF, n = 108) LVAD. As a primary outcome NTproBNP, CPET, and echocardiographic variables were analyzed for their potential to discriminate between HFrEF and LVAD. As a secondary outcome CPET variables were evaluated for a composite of hospitalization due to worsening heart failure and overall mortality over 22 months. (3) Results: NTproBNP (OR 0.6315, 0.5037-0.7647) and RV function (OR 0.45, 0.34-0.56) discriminated between LVAD and HFrEF. The rise of endtidal CO2 (OR 4.25, 1.31-15.81) and VD/VT (OR 1.23, 1.10-1.40) were higher in LVAD patients. Group (OR 2.01, 1.07-3.85), VE/VCO2 (OR 1.04, 1.00-1.08), and ventilatory power (OR 0.74, 0.55-0.98) were best associated with rehospitalization and mortality. (4) Conclusions: LVAD patients displayed higher VD/VT compared to HFrEF. Higher VD/VT as a surrogate for RV-PA uncoupling could be another marker of persistent exercise limitations in LVAD patients.

Comparison between PtCO2 and PaCO2 and Derived Parameters in Heart Failure Patients during Exercise: A Preliminary Study.

Evaluation of arterial carbon dioxide pressure (PaCO2) and dead space to tidal volume ratio (VD/VT) during exercise is important for the identification of exercise limitation causes in heart failure (HF). However, repeated sampling of arterial or arterialized ear lobe capillary blood may be clumsy. The aim of our study was to estimate PaCO2 by means of a non-invasive technique, transcutaneous PCO2 (PtCO2), and to verify the correlation between PtCO2 and PaCO2 and between their derived parameters, such as VD/VT, during exercise in HF patients. 29 cardiopulmonary exercise tests (CPET) performed on a bike with a ramp protocol aimed at achieving maximal effort in ≈10 min were analyzed. PaCO2 and PtCO2 values were collected at rest and every 2 min during active pedaling. The uncertainty of PCO2 and VD/VT measurements were determined by analyzing the error between the two methods. The accuracy of PtCO2 measurements vs. PaCO2 decreases towards the end of exercise. Therefore, a correction to PtCO2 that keeps into account the time of the measurement was implemented with a multiple regression model. PtCO2 and VD/VT changes at 6, 8 and 10 min vs. 2 min data were evaluated before and after PtCO2 correction. PtCO2 overestimates PaCO2 for high timestamps (median error 2.45, IQR -0.635-5.405, at 10 min vs. 2 min, p-value = 0.011), while the error is negligible after correction (median error 0.50, IQR = -2.21-3.19, p-value > 0.05). The correction allows removing differences also in PCO2 and VD/VT changes. In HF patients PtCO2 is a reliable PaCO2 estimation at rest and at low exercise intensity. At high exercise intensity the overall response appears delayed but reproducible and the error can be overcome by mathematical modeling allowing an accurate estimation by PtCO2 of PaCO2 and VD/VT.

The effect of long-acting dual bronchodilator therapy on exercise tolerance, dynamic hyperinflation, and dead space during constant work rate exercise in COPD.

We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (VD/VT) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in chronic obstructive pulmonary disease (COPD). In all, 48 patients with COPD (62.9 ± 7.6 yrs; 33 male; GOLD spirometry stage 1/2/3/4, n = 2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two-period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak work rate. Transcutaneous [Formula: see text] (Tc[Formula: see text]) measurement was used for VD/VT estimation. Baseline postalbuterol forced expiratory volume in 1 s (FEV1) was 1.86 ± 0.58 L (63.6% ± 13.9 predicted). GFF increased FEV1 by 0.18 ± 0.21 L relative to placebo (PL; P < 0.001). CWRET endurance time was greater after GFF vs. PL (383 ± 184 s vs. 328 ± 115 s; difference 55 ± 125 s; P = 0.013; confidence interval: 20-90 s), a 17% increase. IC on GFF was above placebo IC at all time points and fell less with GFF vs. PL (P ≤ 0.0001). Isotime tidal volume (1.54 ± 0.50 vs. 1.47 ± 0.45 L; P = 0.022) and ventilation (52.9 ± 19.9 vs. 51.0 ± 18.9 L/min; P = 0.011) were greater, and respiratory rate was unchanged (34.9 ± 9.2 vs. 35.1 ± 8.0 br/min, P = 0.865). Isotime VD/VT did not differ between groups (GFF 0.28 ± 0.08 vs. PL 0.27 ± 0.09; P = 0.926). GFF increased exercise tolerance in patients with COPD, and the increase was accompanied by attenuated dynamic hyperinflation without altering VD/VT.NEW & NOTEWORTHY This study was a randomized clinical trial (NCT03081156) that collected detailed physiology data to investigate the effect of dual bronchodilator therapy on exercise tolerance in COPD, and additionally to determine the relative contributions of changes in dead space ventilation (VD/VT) and dynamic hyperinflation to alterations in exercise limitation. We utilized a unique noninvasive method to assess VD/VT (transcutaneous carbon dioxide, Tc[Formula: see text]) and found that dual bronchodilators yielded a moderate improvement in exercise tolerance. Importantly, attenuation of dynamic hyperinflation rather than change in dead space ventilation was the most important contributor to exercise tolerance improvement.

Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study.

BACKGROUND: Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS. METHODS: Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after. RESULTS: Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001). CONCLUSION: Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.

Exploring the intraoperative lung protective ventilation of different positive end-expiratory pressure levels during abdominal laparoscopic surgery with Trendelenburg position.

BACKGROUND: The intraoperative lung protective effect of mechanical ventilation of different positive end-expiratory pressure (PEEP) levels on patients undergoing abdominal laparoscopic surgery with the steep Trendelenburg position remains undefined. The purpose of the study was to explore the optimal PEEP. METHODS: Sixty patients scheduled for abdominal laparoscopic surgery were randomized to four groups including: PEEP 0, 4, 8 and 12 cmH2O. The pulmonary dynamic compliance (Cdyn), dead space to tidal volume ratio (VD/VT), and intrapulmonary shunt ratio (QS/QT) were measured after anesthesia induction (T0), 5 min after pneumoperitoneum (PNP) with position change (T1), 30 (T2) and 60 min (T3) after PEEP, and end of surgery (T4). RESULTS: Cdyn increased when different levels of PEEP (including the 4, 8, and 12 cmH2O) were used vs. no PEEP (P<0.05). The VD/VT in PEEP 8 and 12 cmH2O were significantly improved than no PEEP (P<0.05). Meanwhile, the QS/QT in PEEP 12 cmH2O was higher than others during the procedures. CONCLUSIONS: A moderate PEEP level (8 cmH2O) with low tidal volume was sufficient to improve Cdyn and to decrease VD/VT without increasing QS/QT, which was suggested to be a good choice of intraoperative lung protective ventilation during abdominal laparoscopic surgery with Trendelenburg position.

Associations between changes in oxygenation, dead space and driving pressure induced by the first prone position session and mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Outcome prediction in acute respiratory distress syndrome (ARDS) is challenging, especially in patients with severe hypoxemia. The aim of the current study was to determine the prognostic capacity of changes in PaO2/FiO2, dead space fraction (VD/VT) and respiratory system driving pressure (ΔPRS) induced by the first prone position (PP) session in patients with ARDS. METHODS: This was a post hoc analysis of the conveniently-sized 'Molecular Diagnosis and Risk Stratification of Sepsis' study (MARS). The current analysis included ARDS patients who were placed in the PP. The primary endpoint was the prognostic capacity of the PP-induced changes in PaO2/FiO2, VD/VT, and ΔPRS for 28-day mortality. PaO2/FiO2, VD/VT, and ΔPRS was calculated using variables obtained in the supine position before and after completion of the first PP session. Receiving operator characteristic curves (ROC) were constructed, and sensitivity, specificity positive and negative predictive value were calculated based on the best cutoffs. RESULTS: Ninety patients were included; 28-day mortality was 46%. PP-induced changes in PaO2/FiO2 and VD/VT were similar between survivors vs. non-survivors [+83 (+24 to +137) vs. +58 (+21 to +113) mmHg, and -0.06 (-0.17 to +0.05) vs. -0.08 (-0.16 to +0.08), respectively]. PP-induced changes in ΔPRS were different between survivors vs. non-survivors [-3 (-7 to 2) vs. 0 (-3 to +3) cmH2O; P=0.03]. The area under the ROC of PP-induced changes in ΔPRS for mortality, however, was low [0.63 (95% confidence interval (CI), 0.50 to 0.75]; PP-induced changes in ΔPRS had a sensitivity and specificity of 76% and 56%, and a positive and negative predictive value of 60% and 73%. CONCLUSIONS: Changes in PaO2/FiO2, VD/VT, and ΔPRS induced by the first PP session have poor prognostic capacities for 28-day mortality in ARDS patients.

Effects of neurally adjusted ventilatory assist on air distribution and dead space in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) could improve patient-ventilator interaction; its effects on ventilation distribution and dead space are still unknown. The aim of this study was to evaluate the effects of varying levels of assist during NAVA and pressure support ventilation (PSV) on ventilation distribution and dead space in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Fifteen mechanically ventilated patients with AECOPD were included in the study. The initial PSV levels were set to 10 cmH2O for 10 min. Thereafter, the ventilator mode was changed to NAVA for another 10 min with the same electrical activity of the diaphragm as during PSV. Furthermore, the ventilation mode was switched between PSV and NAVA every 10 min in the following order: PSV 5 cmH2O; NAVA 50%; PSV 15 cmH2O; and NAVA 150% (relative to the initial NAVA support level). Ventilation distribution in the lung was evaluated in percentages in regions of interest (ROI) of four anteroposterior segments of equal height (ROI1 to ROI4 represents ventral, mid-ventral, mid-dorsal, and dorsal, respectively). Blood gases, ventilation distribution (electrical impedance tomography), diaphragm activity (B-mode ultrasonography), and dead space fraction (PeCO2 and PaCO2) were measured. RESULTS: The trigger and cycle delays were lower during NAVA than during PSV. The work of trigger was significantly lower during NAVA compared to PSV. The diaphragm activities based on ultrasonography were higher during NAVA compared to the same support level during PSV. The ventilation distribution in ROI4 increased significantly (P < 0.05) during NAVA compared to PSV (except for a support level of 50%). Similar results were found in ROI3 + 4. NAVA reduced dead space fraction compared to the corresponding support level of PSV. CONCLUSIONS: NAVA was superior to PSV in AECOPD for increasing ventilation distribution in ROI4 and reducing dead space. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02289573 . Registered on 12 November 2014.

Respiratory dynamics and dead space to tidal volume ratio of volume-controlled versus pressure-controlled ventilation during prolonged gynecological laparoscopic surgery.

BACKGROUND: Laparoscopic operations have become longer and more complex and applied to a broader patient population in the last decades. Prolonged gynecological laparoscopic surgeries require prolonged pneumoperitoneum and Trendelenburg position, which can influence respiratory dynamics and other measurements of pulmonary function. We investigated the differences between volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) and tried to determine the more efficient ventilation mode during prolonged pneumoperitoneum in gynecological laparoscopy. METHODS: Twenty-six patients scheduled for laparoscopic radical hysterectomy combined with or without laparoscopic pelvic lymphadenectomy were randomly allocated to be ventilated by either VCV or PCV. Standard anesthesic management and laparoscopic procedures were performed. Measurements of respiratory and hemodynamic dynamics were obtained after induction of anesthesia, at 10, 30, 60, and 120 min after establishing pneumoperitoneum, and at 10 min after return to supine lithotomy position and removal of carbon dioxide. The logistic regression model was applied to predict the corresponding critical value of duration of pneumoperitoneum when the Ppeak was higher than 40 cmH2O. RESULTS: Prolonged pneumoperitoneum and Trendelenburg position produced significant and clinically relevant changes in dynamic compliance and respiratory mechanics in anesthetized patients under PCV and VCV ventilation. Patients under PCV ventilation had a similar increase of dead space/tidal volume ratio, but had a lower Ppeak increase compared with those under VCV ventilation. The critical value of duration of pneumoperitoneum was predicted to be 355 min under VCV ventilation, corresponding to the risk of Ppeak higher than 40 cmH2O. CONCLUSIONS: Both VCV and PCV can be safely applied to prolonged gynecological laparoscopic surgery. However, PCV may become the better choice of ventilation after ruling out of other reasons for Ppeak increasing.

Non invasive monitoring in mechanically ventilated pediatric patients.

Cardiopulmonary monitoring is a key component in the evaluation and management of critically ill patients. Clinicians typically rely on a combination of invasive and non-invasive monitoring to assess cardiac output and adequacy of ventilation. Recent technological advances have led to the introduction: of continuous non-invasive monitors that allow for data to be obtained at the bedside of critically ill patients. These advances help to identify hemodynamic changes and allow for interventions before complications occur. In this manuscript, we highlight several important methods of non-invasive cardiopulmonary monitoring, including capnography, transcutaneous monitoring, pulse oximetry, and near infrared spectroscopy.

Corrections of Enghoff's dead space formula for shunt effects still overestimate Bohr's dead space.

Dead space ratio is determined using Enghoff's modification (VD(B-E)/VT) of Bohr's formula (VD(Bohr)/VT) in which arterial is used as a surrogate of alveolar PCO2. In presence of intrapulmonary shunt Enghoff's approach overestimates dead space. In 40 lung-lavaged pigs we evaluated the Kuwabara's and Niklason's algorithms to correct for shunt effects and hypothesized that corrected VD(B-E)/VT should provide similar values as VD(Bohr)/VT. We analyzed 396 volumetric capnograms and arterial and mixed-venous blood samples to calculate VD(Bohr)/VT and VD(B-E)/VT. Thereafter, we corrected the latter for shunt effects using Kuwabara's (K) VD(B-E)/VT and Niklason's (N) VD(B-E)/VT algorithms. Uncorrected VD(B-E)/VT (mean ± SD of 0.70 ± 0.10) overestimated VD(Bohr)/VT (0.59 ± 0.12) (p < 0.05), over the entire range of shunts. Mean (K) VD(B-E)/VT was significantly higher than VD(Bohr)/VT (0.67 ± 0.08, bias -0.085, limits of agreement -0.232 to 0.085; p < 0.05) whereas (N)VD(B-E)/VT showed a better correction for shunt effects (0.64 ± 0.09, bias 0.048, limits of agreement -0.168 to 0.072; p < 0.05). Neither Kuwabara's nor Niklason's algorithms were able to correct Enghoff's dead space formula for shunt effects.

Valor preditivo da razão entre espaço morto e volume corrente fisiológicos no processo de desmame da ventilação mecânica em crianças / Predictive value of the physiological deadspace/tidal volume ratio in the weaning process of mechanical ventilation in children

OBJETIVO: Avaliar a razão entre espaço morto e volume corrente fisiológicos (V D/V T) como preditor do fracasso na extubação em 42 crianças ventiladas (idade média: 4,75 anos). MÉTODO: Prontidão para extubação foi determinada usando os critérios propostos pela 6ª Conferência Internacional de Consenso em Medicina Intensiva adaptados a crianças. RESULTADOS: A ventilação não invasiva (VNI) foi usada em quatro pacientes que desenvolveram insuficiência respiratória após a extubação; nenhum foi reintubado. Crianças que precisaram de VNI para evitar a reintubação tiveram razão V D/V T significativamente maior do que as que foram extubadas sem VNI (p < 0,001). O valor de corte da razão V D/V T foi 0,55, e a área sob a curva ROC foi 0,86. CONCLUSÃO: Nossos achados confirmam o bom valor preditivo do sucesso/fracasso do desmame pela razão V D/V T e sugere seu papel como preditor da necessidade de VNI após extubação.

OBJECTIVE: To evaluate the physiological deadspace/tidal volume ratio (V D/V T) as a predictor of extubation failure in 42 ventilated children (median age: 4.75 years). METHOD: Extubation readiness was determined using the criteria proposed by the 6th International Consensus Conference on Intensive Care Medicine adapted to children. RESULTS: Non-invasive ventilation (NIV) was used in four patients who developed respiratory failure after extubation; none was reintubated. Children who needed NIV to avoid reintubation had a significantly higher V D/V T ratio than those who were extubated without NIV (p < 0.001). The cut-off value of V D/V T ratio was 0.55 and the area under the receiver operating characteristic curve was 0.86. CONCLUSION: Our findings confirm the good predictive value of weaning success/failure of the V D/V T ratio and suggest its role for predicting the need for NIV after extubation.

VD/VT and Arterial Blood Gas Changes during Gynecologic Laparoscopic Surgery under Enflurane or Propofol Anesthesia / 대한마취과학회지

BACKGROUND: Laparoscopic gynecologic surgery is a standard procedure today for its small skin incision and short hospital admission stay. However pneumoperitoneum (PP) and Trendelenberg position induce adverse effects in hemodynamics and pulmonary gas exchange. The purpose of this study is to evaluate the effects of propofol compared with enflurane for pulmonary gas exchange in the Trendelenberg position and pneumoperitoneum. METHODS: Twenty women were randomly allocated to either the enflurane (n = 10) or propofol (n = 10) with fentanyl-N2O/O2 anesthesia. PaCO2, PaO2, PETCO2 were checked at pre-PP, 10 min after PP, 30 min after PP, and 10 min after CO2 deflation. In addition the Vd/Vt ratio was calculated according to the Bohr equation. Vital sign and peak airway pressure were checked at each stage. RESULTS: PaCO2 and PETCO2 increased and PaO2 decreased significantly during PP in both groups. Vd/Vt increased significantly in the enflurane group at 30 min after PP. Peak airway pressure increased significantly in both groups. Blood preassure and heart rate were not changed significantly. All of the parameters were not significantly different between groups. CONCLSIONS: Propofol compared with enflurane did not show any advantage in gas exchange during gynecologic laparoscopic surgery under Trendelenberg position and PP.