Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure. METHODS: We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios. RESULTS: A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. "Higher extraction" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R. CONCLUSIONS: ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. "Higher extraction" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R's effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model.

Whole blood analysis can evaluate numerous parameters, including pH, pCO2, pO2, HCO3 - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO2, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

Venous-to-arterial carbon-dioxide tension difference as a useful predictor of patient prognosis after major surgery.

PURPOSE: Change in venous-to-arterial carbon dioxide partial pressure difference[P(v-a)CO2] could be a useful marker to assess tissue perfusion status. Herein, we assessed the predictive values of postoperative P(v-a)CO2 measurements for mortality in critically ill patients after major surgery. The correlation between P(v-a)CO2 values and other conventional parameters of patient prognosis was also evaluated. METHODS: Patients admitted to the intensive care unit(ICU) after abdominal surgery were enrolled. Arterial and venous blood gas analyses were performed within 1 h(T0) and after 24 h(T1) of admission to the ICU, respectively. The relationship between P(v-a)CO2 levels at T1 and other conventional parameters were assessed using a Bland-Altman plot. Logistic regression analysis was performed to examine the predisposing factors of mortality after surgery. RESULTS: A total of 231 patients were finally analyzed. We divided the participants into the high PvaCO2 group[P(v-a)CO2 ≥ 8.6] and the low PvaCO2 group[P(v-a)CO2 < 8.6]. Seven-day-, 28-day, and in-hospital mortality were significantly higher in the high PvaCO2 group than in the low PvaCO2 group. There was significant agreement between P(v-a)CO2 values at T1 and APACHE II scores, lactate levels at T1 and total SOFA scores at T1. In multivariate logistic analysis, an increased P(v-a)CO2 value at T1 was the only significant risk factor of 7-day mortality after surgery. [odds ratio:1.341, 95%confidence interval: 1.050-1.714, p=0.019]. CONCLUSION: P(v-a)CO2 measurements could be not only a significant predictor of postoperative prognosis, but also a useful surveillance parameter to maintain tissue perfusion after abdominal surgery in patients with a potential risk of fatal complication-related tissue hypoperfusion.

The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study.

BACKGROUND: Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. METHODS: We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. RESULTS: 59 trauma patients were included in the study. Median ISS was 26 (22-32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. CONCLUSION: In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.

Papel del Delta de PCO2 en la evaluación pronóstica de morbimortalidad en una cohorte de pacientes de un hospital latinoamericano / Role of PCO2 Delta in the Prognostic Evaluation of Morbidity and Mortality in a Cohort of Patients from a Latin American Hospital

Introducción. El shock séptico es la manifestación más grave de sepsis con tasas de letalidad que pueden llegar hasta el 80%. En los últimos años, ha cobrado relevancia la diferencia arteriovenosa de dióxido de carbono, por su implicación teórica en el metabolismo anaerobio y su significado respecto del normal funcionamiento celular. Por lo antes mencionado, creemos necesario realizar un estudio que nos permita establecer la utilidad de la diferencia arteriovenosa de dióxido de carbono en el paciente con shock séptico de la unidad de cuidados intensivos, como medida indirecta de la perfusión tisular y de la utilización de oxígeno por los tejidos, que nos permita establecer un diagnóstico precoz y el pronóstico de los pacientes críticamente enfermos. Métodos. Estudio observacional, descriptivo y transversal. Muestra de veintiocho pacientes adultos. Resultados. Como se ha registrado en otras series, la mayor parte de los pacientes afectados por shock séptico, en nuestro estudio, fueron hombres mayores de 65 años, con al menos una comorbilidad, siendo el principal sitio de infección el respiratorio (67,9%), asociado a una alta tasa de mortalidad (67%). Conclusiones. Los pacientes con diferencia arteriovenosa de PCO2 mayor a 6 mmHg tienen un riesgo aumentado de muerte de 3,2 veces. (AU)

Introduction. Septic shock is the most serious manifestation of sepsis with mortality rates that can reach up to 80%. In recent years, the arteriovenous carbon dioxide difference has gained relevance, due to its theoretical implication in anaerobic metabolism and its significance with respect to normal cell function. Due to the aforementioned, we believe it is necessary to carry out a study that allows us to establish the usefulness of the arteriovenous carbon dioxide difference in the patient with septic shock in the intensive care unit as an indirect measure of tissue perfusion and utilization. of oxygen through the tissues, which allows us to establish an early diagnosis and prognosis of critically ill patients. Methods. Observational, descriptive and cross-sectional study. Sample of 28 adult patients. Results. As has been reported in other series, most of the patients affected by septic shock in our study were men over 65 years of age, with at least one comorbidity, the main site of infection being respiratory (67.9%), associated with a high mortality rate (67%) Conclusions. Patients with an arteriovenous PCO2 difference greater than 6 mmHg have a 3.2-fold increased risk of death. (AU)

A randomised controlled trial of 7.5-mm and 7.0-mm tracheal tubes vs. 6.5-mm and 6.0-mm tracheal tubes for men and women during laparoscopic surgery.

Sore throat after tracheal intubation impairs postoperative recovery. We randomly allocated 172 ASA physical status 1-2 participants, scheduled for laparoscopic lower abdominal surgery, to tracheal intubation with larger tubes (n = 88) or smaller tubes (n = 84), with internal diameters 7.5-mm vs. 6.5-mm for men and 7.0-mm vs. 6.0-mm for women. Primary outcome was the rates of no, mild, moderate or severe sore throat 1 h after surgery, which were 60, 10, 17 and 1 with larger tracheal tubes and 79, 5, 0 and 0 with smaller tubes, p < 0.001. The equivalent rates 24 h after surgery were 64, 16, 8 and 0 vs. 74, 6, 3 and 1, p = 0.037. Intra-operative ventilatory variables were unaffected by tube diameter, including peak inspiratory pressure, plateau pressure and end-tidal carbon dioxide partial pressure. In summary, smaller tracheal tubes benefitted patients having laparoscopic operations.

Fisiología respiratoria: transporte de gases en sangre / Respiratory physiology: transport of oxygen and carbon dioxide in the blood

La sangre normalmente transporta pequeñas cantidades de oxígeno (O2) disuelto en el plasma y altas cantidades combinadas en forma química con la hemoglobina. La presión parcial depende solo del oxígeno disuelto físicamente, lo que determina cuánto oxígeno se combinará con hemoglobina. La curva de disociación de la hemoglobina describe la reversibilidad de la reacción entre oxígeno y hemoglobina. Los factores habituales que aumentan o disminuyen la afinidad de la hemoglobina por el oxígeno son el pH, presión parcial de CO2, temperatura y 2,3 difosfoglicerato. La sangre también transporta grandes cantidades en forma de bicarbonato y bajas cantidades de CO2 disuelto en plasma y combinado con proteínas como compuestos carbamino. La desoxihemoglobina favorece la formación de compuestos carbamínicos y promueve el transporte del CO2 como bicarbonato uniéndose al hidrógeno proveniente de la disociación del ácido carbónico. A continuación se describe en forma detallada los mecanismos fisiológicos del transporte de gases en sangre.

Blood normally carries small amounts of oxygen dissolved in plasma and large amounts chemically combined with hemoglobin. Partial pressure of oxygen depends only on physically dissolved oxygen which determines how much oxygen will combine with hemoglobin. The oxygen-hemoglobin dissociation curve (or oxyhemoglobin dissociation curve) describes the reversibility of the reaction between oxygen and hemoglobin. The usual factors that increase or decrease the affinity of hemoglobin for oxygen are pH, CO2 partial pressure, temperature, and 2,3 diphosphoglycerate. Blood also carries large amounts of CO2 as bicarbonate and low amounts dissolved in plasma and combined with proteins as carbamino compounds. Deoxyhemoglobin favors the formation of carbamino compounds and promotes the transport of CO2 as bicarbonate by joining the hydrogen from the dissociation of carbonic acid. The physiological mechanisms of gas transport in blood are described in detail below.

Laparoscopic appendicectomy in a postpneumonectomy patient.

Pneumoperitoneum for laparoscopic surgeries has anesthetic implications due to increase in the intra-abdominal pressure and end-tidal carbon dioxide. The effects are more pronounced if the patient has only one lung. However, the advantages of laparoscopy include reduced postoperative pain and early recovery. We present a case of 30-year-old patient who had undergone pneumonectomy and was posted for laparoscopic appendicectomy. General anesthesia was instituted, and with some modifications in ventilation, the procedure was uneventful and we were able to extubate the patient on the table. Understanding of the physiological consequences of pneumonectomy facilitated the provision of safe anesthesia.

Résumé Le pneumopéritoine pour les chirurgies laparoscopiques a des implications anesthésiques en raison de l'augmentation de la pression intra-abdominale et du dioxyde de carbone en fin d'expiration. Les effets sont plus prononcés si le patient n'a qu'un seul poumon. Cependant, les avantages de la laparoscopie comprennent une réduction de la douleur postopératoire et une récupération précoce. Nous présentons un cas de patient de 30 ans ayant subi une pneumonectomie et posté pour une appendicectomie laparoscopique. Une anesthésie générale a été instituée, et avec quelques modifications de ventilation, la procédure s'est déroulée sans incident et nous avons pu extuber le patient sur la table. La compréhension des conséquences physiologiques de la pneumonectomie a facilité la fourniture d'une anesthésie sûre. Mots-clés: Appendicectomie, laparoscopie, pression maximale des voies respiratoires, pneumonectomie.

The effect of selective cerebral perfusion on cerebral versus somatic tissue oxygenation during aortic coarctation repair in neonates and infants.

BACKGROUND: Suboptimal tissue perfusion and oxygenation may be the root cause of certain perioperative complications in neonates and infants having complicated aortic coarctation repair. Practical, effective, and real-time monitoring of organ perfusion and/or tissue oxygenation may provide early warning of end-organ mal-perfusion. METHODS: Neonates/infants who were scheduled for aortic coarctation repair with cardiopulmonary bypass (CPB) and selective cerebral perfusion (SCP) from January 2015 to February 2017 in Children's Hospital of Nanjing Medical University participated in this prospective observational study. Cerebral and somatic tissue oxygen saturation (SctO2 and SstO2) were monitored on the forehead and at the thoracolumbar paraspinal region, respectively. SctO2 and SstO2 were recorded at different time points (baseline, skin incision, CPB start, SCP start, SCP end, aortic opening, CPB end, and surgery end). SctO2 and SstO2 were correlated with mean arterial pressure (MAP) and partial pressure of arterial blood carbon dioxide (PaCO2). RESULTS: Data of 21 patients were analyzed (age=75±67 days, body weight=4.4±1.0 kg). SstO2 was significantly lower than SctO2 before aortic opening and significantly higher than SctO2 after aortic opening. SstO2 correlated with leg MAP when the measurements during SCP were (r=0.67, p<0.0001) and were not included (r=0.46, p<0.0001); in contrast, SctO2 correlated with arm MAP only when the measurements during SCP were excluded (r=0.14, p=0.08 vs. r=0.66, p<0.0001). SCP also confounded SctO2/SstO2's correlation with PaCO2; when the measurements during SCP were excluded, SctO2 positively correlated with PaCO2 (r=0.65, p<0.0001), while SstO2 negatively correlated with PaCO2 (r=-0.53, p<0.0001). CONCLUSIONS: SctO2 and SstO2 have distinct patterns of changes before and after aortic opening during neonate/infant aortic coarctation repair. SctO2/SstO2's correlations with MAP and PaCO2 are confounded by SCP. The outcome impact of combined SctO2/SstO2 monitoring remains to be studied.

Changes in hemoglobin function and isoform expression during embryonic development in the American alligator, Alligator mississippiensis.

In the developing embryos of egg-laying vertebrates, O2 flux takes place across a fixed surface area of the eggshell and the chorioallantoic membrane. In the case of crocodilians, the developing embryo may experience a decrease in O2 flux when the nest becomes hypoxic, which may cause compensatory adjustments in blood O2 transport. However, whether the switch from embryonic to adult hemoglobin isoforms (isoHbs) plays some role in these adjustments is unknown. Here, we provide a detailed characterization of the developmental switch of isoHb synthesis in the American alligator, Alligator mississippiensis. We examined the in vitro functional properties and subunit composition of purified alligator isoHbs expressed during embryonic developmental stages in normoxia and hypoxia (10% O2). We found distinct patterns of isoHb expression in alligator embryos at different stages of development, but these patterns were not affected by hypoxia. Specifically, alligator embryos expressed two main isoHbs: HbI, prevalent at early developmental stages, with a high O2 affinity and high ATP sensitivity, and HbII, prevalent at later stages and identical to the adult protein, with a low O2 affinity and high CO2 sensitivity. These results indicate that whole blood O2 affinity is mainly regulated by ATP in the early embryo and by CO2 and bicarbonate from the late embryo until adult life, but the developmental regulation of isoHb expression is not affected by hypoxia exposure.

Relationship between end-tidal carbon dioxide and arterial carbon dioxide in critically ill patients on mechanical ventilation: A cross-sectional study.

ABSTRACT: So far, only a few studies have examined and confirmed the correlation between end-expiratory carbon dioxide partial pressure (PETCO2) and arterial carbon dioxide tension (PaCO2) during invasive mechanical ventilation in critically ill patients. This study aimed to observe the correlation between PaCO2 and PETCO2 in patients on invasive mechanical ventilation.This was a cross-sectional study of adult patients on invasive mechanical ventilation enrolled between June 2018 and March 2019. Patients requiring invasive mechanical ventilation underwent one of the following mechanical ventilation modes: assisted/controlled ventilation, synchronized intermittent mandatory ventilation, and spontaneous breathing. Subsequently, the difference and correlation between PETCO2 and PaCO2 were analyzed.A total of 184 patients with 298 pairs of PETCO2-PaCO2 data were included in the analysis. Without distinguishing the ventilator mode, there was significant positive correlation between PETCO2 and PaCO2. In different ventilator modes, the correlation coefficient was 0.81 for synchronized intermittent mandatory ventilation, 0.47 for assisted/controlled ventilation, and 0.55 for spontaneous breathing, respectively. In patients with chronic obstructive pulmonary disease (r = 0.80), multiple trauma (r = 0.64), severe pneumonia (r = 0.60), gastrointestinal surgery (r = 0.57), and cerebrovascular diseases (r = 0.53), PETCO2 and PaCO2 were positively correlated. For oxygenation index <200 mm Hg, correlation coefficient r = 0.69, P < .001; oxygenation index ≥200, r = 0.73, P < .001. Under different oxygenation indexes, there was no statistically significant difference between the 2 correlation coefficients. Among 116 pairs of data with oxygenation index <200 mm Hg, the difference of PaCO2-PETCO2 ≥10 mm Hg was found in 25 pairs (21.55%); in 182 pairs of data with oxygenation index ≥200 mm Hg, the difference of PaCO2-PETCO2 ≥10 mm Hg was found in 26 pairsIn patients on invasive mechanical ventilation, there was a good correlation between PETCO2 and PaCO2 in different ventilator modes, different disease types, and different oxygenation indexes, especially in synchronized intermittent mandatory ventilation mode and chronic obstructive pulmonary disease patients.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

An Initiative to Decrease Laboratory Testing in a NICU.

BACKGROUND AND OBJECTIVES: Laboratory testing is performed frequently in the NICU. Unnecessary tests can result in increased costs, blood loss, and pain, which can increase the risk of long-term growth and neurodevelopmental impairment. Our aim was to decrease routine screening laboratory testing in all infants admitted to our NICU by 20% over a 24-month period. METHODS: We designed and implemented a multifaceted quality improvement project using the Institute for Healthcare Improvement's Model for Improvement. Baseline data were reviewed and analyzed to prioritize order of interventions. The primary outcome measure was number of laboratory tests performed per 1000 patient days. Secondary outcome measures included number of blood glucose and serum bilirubin tests per 1000 patient days, blood volume removed per 1000 patient days, and cost. Extreme laboratory values were tracked and reviewed as balancing measures. Statistical process control charts were used to track measures over time. RESULTS: Over a 24-month period, we achieved a 26.8% decrease in laboratory tests performed per 1000 patient days (∽51 000 fewer tests). We observed significant decreases in all secondary measures, including a decrease of almost 8 L of blood drawn and a savings of $258 000. No extreme laboratory values were deemed attributable to the interventions. Improvement was sustained for an additional 7 months. CONCLUSIONS: Targeted interventions, including guideline development, dashboard creation and distribution, electronic medical record optimization, and expansion of noninvasive and point-of-care testing resulted in a significant and sustained reduction in laboratory testing without notable adverse effects.

Estimating cardiac output based on gas exchange during veno-arterial extracorporeal membrane oxygenation in a simulation study using paediatric oxygenators.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy is a rescue strategy for severe cardiopulmonary failure. The estimation of cardiac output during VA-ECMO is challenging. A lung circuit ([Formula: see text]Lung) and an ECMO circuit ([Formula: see text]ECMO) with oxygenators for CO2 removal ([Formula: see text]CO2) and O2 uptake ([Formula: see text]O2) simulated the setting of VA-ECMO with varying ventilation/perfusion ([Formula: see text]/[Formula: see text]) ratios and shunt. A metabolic chamber with a CO2/N2 blend simulated [Formula: see text]CO2 and [Formula: see text]O2. [Formula: see text] Lung was estimated with a modified Fick principle: [Formula: see text]Lung = [Formula: see text]ECMO × ([Formula: see text] CO2 or [Formula: see text]O2Lung)/([Formula: see text]CO2 or [Formula: see text]O2ECMO). A normalization procedure corrected [Formula: see text]CO2 values for a [Formula: see text]/[Formula: see text] of 1. Method agreement was evaluated by Bland-Altman analysis. Calculated [Formula: see text]Lung using gaseous [Formula: see text]CO2 and [Formula: see text]O2 correlated well with measured [Formula: see text]Lung with a bias of 103 ml/min [- 268 to 185] ml/min; Limits of Agreement: - 306 ml/min [- 241 to - 877 ml/min] to 512 ml/min [447 to 610 ml/min], r2 0.85 [0.79-0.88]). Blood measurements of [Formula: see text]CO2 showed an increased bias (- 260 ml/min [- 1503 to 982] ml/min), clinically not applicable. Shunt and [Formula: see text]/[Formula: see text] mismatch decreased the agreement of methods significantly. This in-vitro simulation shows that [Formula: see text]CO2 and [Formula: see text]O2 in steady-state conditions allow for clinically applicable calculations of [Formula: see text]Lung during VA-ECMO therapy.

D-Cystine di(m)ethyl ester reverses the deleterious effects of morphine on ventilation and arterial blood gas chemistry while promoting antinociception.

We have identified thiolesters that reverse the negative effects of opioids on breathing without compromising antinociception. Here we report the effects of D-cystine diethyl ester (D-cystine diEE) or D-cystine dimethyl ester (D-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and antinociception in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of D-cystine diEE (500 µmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO2 and sO2 accompanied by pronounced increases in pCO2 (all indicative of a decrease in ventilatory drive) and A-a gradient (mismatch in ventilation-perfusion in the lungs). These effects of morphine were reversed in an immediate and sustained fashion by D-cystine diME (500 µmol/kg, IV). Finally, the duration of morphine (5 and 10 mg/kg, IV) antinociception was augmented by D-cystine diEE. D-cystine diEE and D-cystine diME may be clinically useful agents that can effectively reverse the negative effects of morphine on breathing and gas-exchange in the lungs while promoting antinociception. Our study suggests that the D-cystine thiolesters are able to differentially modulate the intracellular signaling cascades that mediate morphine-induced ventilatory depression as opposed to those that mediate morphine-induced antinociception and sedation.

Glutathione ethyl ester reverses the deleterious effects of fentanyl on ventilation and arterial blood-gas chemistry while prolonging fentanyl-induced analgesia.

There is an urgent need to develop novel compounds that prevent the deleterious effects of opioids such as fentanyl on minute ventilation while, if possible, preserving the analgesic actions of the opioids. We report that L-glutathione ethyl ester (GSHee) may be such a novel compound. In this study, we measured tail flick latency (TFL), arterial blood gas (ABG) chemistry, Alveolar-arterial gradient, and ventilatory parameters by whole body plethysmography to determine the responses elicited by bolus injections of fentanyl (75 µg/kg, IV) in male adult Sprague-Dawley rats that had received a bolus injection of GSHee (100 µmol/kg, IV) 15 min previously. GSHee given alone had minimal effects on TFL, ABG chemistry and A-a gradient whereas it elicited changes in some ventilatory parameters such as an increase in breathing frequency. In vehicle-treated rats, fentanyl elicited (1) an increase in TFL, (2) decreases in pH, pO2 and sO2 and increases in pCO2 (all indicative of ventilatory depression), (3) an increase in Alveolar-arterial gradient (indicative of a mismatch in ventilation-perfusion in the lungs), and (4) changes in ventilatory parameters such as a reduction in tidal volume, that were indicative of pronounced ventilatory depression. In GSHee-pretreated rats, fentanyl elicited a more prolonged analgesia, relatively minor changes in ABG chemistry and Alveolar-arterial gradient, and a substantially milder depression of ventilation. GSHee may represent an effective member of a novel class of thiolester drugs that are able to prevent the ventilatory depressant effects elicited by powerful opioids such as fentanyl and their deleterious effects on gas-exchange in the lungs without compromising opioid analgesia.

Comparing Central Venous Blood Gas to Arterial Blood Gas and Determining Its Utility in Critically Ill Patients: Narrative Review.

Arterial blood gas (ABG) analysis is used in critical care units to determine the degree of oxygenation, adequacy of ventilation, and the presence and severity of acid-base disturbances in the body. However, arterial puncture may result in complications, and the difficulty in acquiring arterial blood may delay care. Central venous blood gas (VBG) is a potentially more accessible alternative to ABG sampling. Current evidence suggests that pH and Pco2 obtained via peripheral VBG correlate well with ABG measurement. Nevertheless, the value of using central VBG to guide clinical decisions or as a surrogate for ABG is unclear. The purpose of this review is to explore the relationship between ABGs and central VBGs in critically ill patients. We performed a MEDLINE search using the following search terms: venous blood gas, arterial blood gas, and central venous blood gas. We excluded studies that did not involve human subjects, and only pH and Pco2 values were reviewed and examined from the studies included. All cited references from included studies were also reviewed to identify relevant literature. We identified 7 studies that met our criteria. In studies of hemodynamically stable patients, the mean difference between arterial and central venous pH and Pco2 was 0.03 units and 4-6.5 mm Hg, respectively. However, in patients with circulatory failure, the difference between central venous and arterial pH/Pco2 was 4-fold greater. We concluded that central VBG parameters of pH and Pco2 are potentially good surrogates for determining arterial pH and Pco2 in a stable patient without severe acid-base disturbances. Furthermore, central VBG can be used as a useful screening tool for arterial hypercapnia. In addition, we derived an adjustment formula for ABG conversion from central VBG: (1) arterial pH = venous pH + 0.05 units and (2) arterial Pco2 = venous Pco2 - 5 mm Hg.

Cardiopulmonary Exercise Testing in Combined Pulmonary Fibrosis and Emphysema.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct entity among fibrosing lung diseases with a high risk for lung cancer and pulmonary hypertension (PH). Notably, concomitant PH was identified as a negative prognostic indicator that could help with early diagnosis to provide important information regarding prognosis. OBJECTIVES: The current study aimed to determine whether cardiopulmonary exercise testing (CPET) can be helpful in differentiating patients having CPFE with and without PH. METHODS: Patients diagnosed with CPFE in 2 German cities (Hemer and Greifswald) over a period of 10 years were included herein. CPET parameters, such as peak oxygen uptake (peak VO2), functional dead space ventilation (VDf/VT), alveolar-arterial oxygen difference (AaDO2), arterial-end-tidal CO2 difference [P(a-ET)CO2] at peak exercise, and the minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), were compared between patients with and without PH. RESULTS: A total of 41 patients with CPET (22 with PH, 19 without PH) were analyzed. Right heart catheterization was performed in 15 of 41 patients without clinically relevant complications. Significant differences in peak VO2 (861 ± 190 vs. 1,397 ± 439 mL), VO2/kg body weight/min (10.8 ± 2.6 vs. 17.4 ± 5.2 mL), peak AaDO2 (72.3 ± 7.3 vs. 46.3 ± 14.2 mm Hg), VE/VCO2 slope (70.1 ± 31.5 vs. 39.6 ± 9.6), and peak P(a-ET)tCO2 (13.9 ± 3.5 vs. 8.1 ± 3.6 mm Hg) were observed between patients with and without PH (p < 0.001). Patients with PH had significantly higher VDf/VT at rest, VT1, and at peak exercise (65.6 ± 16.8% vs. 47.2 ± 11.6%; p < 0.001) than those without PH. A cutoff value of 44 for VE/VCO2 slope had a sensitivity and specificity of 94.7 and 72.7%, while a cutoff value of 11 mm Hg for P(a-ET)CO2 in combination with peak AaDO2 >60 mm Hg had a specificity and sensitivity of 95.5 and 84.2%, respectively. Combining peak AaDO2 >60 mm Hg with peak VO2/body weight/min <16.5 mL/kg/min provided a sensitivity and specificity of 100 and 95.5%, respectively. CONCLUSION: This study provided initial data on CPET among patients having CPFE with and without PH. CPET can help noninvasively detect PH and identify patients at risk. AaDO2 at peak exercise, VE/VCO2 slope, peak P(a-ET)CO2, and peak VO2 were parameters that had high sensitivity and, when combined, high specificity.

Is venous blood a more reliable description of acid-base state following simulated hypo- and hyperventilation?

BACKGROUND: ABGs are performed in acute conditions as the reference method for assessing the acid-base status of blood. Hyperventilation and breath-holding are common ventilatory changes that occur around the time of sampling, rapidly altering the 'true' status of the blood. This is particularly relevant in emergency medicine patients without permanent arterial catheters, where the pain and anxiety of arterial punctures can cause ventilatory changes. This study aimed to determine whether peripheral venous values could be a more reliable measure of blood gases following acute changes in ventilation. METHODS: To allow for characterisation of ventilatory changes typical of acutely ill patients, but without the confounding influence of perfusion or metabolic disturbances, 30 patients scheduled for elective surgery were studied in a prospective observational study. Following anaesthesia, and before the start of the surgery, ventilator settings were altered to achieve a + 100% or - 60% change in alveolar ventilation ('hyper-' or 'hypoventilation'), changes consistent with the anticipation of a painful arterial puncture commonly encountered in the emergency room. Blood samples were drawn simultaneously from indwelling arterial and peripheral venous catheters at baseline, and at 15, 30, 45, 60, 90 and 120 s following the ventilatory change. Comparisons between the timed arterial (or venous) samples were done using repeated-measures ANOVA, with post-hoc analysis using Bonferroni's correction. RESULTS: Arterial blood pH and PCO2 changed rapidly within the first 15-30s after both hyper- and hypoventilation, plateauing at around 60s (∆pH = ±0.036 and ∆PCO2 = ±0.64 kPa (4.7 mmHg), respectively), with peripheral venous values remaining relatively constant until 60s, and changing minimally thereafter. Mean arterial changes were significantly different at 30s (P < 0.001) when compared to baseline, in response to both hyper- and hypoventilation. CONCLUSION: This study has shown that substantial differences in arterial and peripheral venous acid-base status can be due to acute changes in ventilation, commonly seen in the ER over the 30s necessary to sample arterial blood. If changes are transient, peripheral venous blood may provide a more reliable description of acid-base status.