Validation of an alternative technique for RQ estimation in anesthetized pigs.

BACKGROUND: Respiratory quotient (RQ) is an important variable when assessing metabolic status in intensive care patients. However, analysis of RQ requires cumbersome technical equipment. The aim of the current study was to examine a simplified blood gas-based method of RQ assessment, using Douglas bag measurement of RQ (Douglas-RQ) as reference in a laboratory porcine model under metabolic steady state. In addition, we aimed at establishing reference values for RQ in the same population, thereby generating data to facilitate further research. METHODS: RQ was measured in 11 mechanically ventilated pigs under metabolic steady state using Douglas-RQ and CO-oximetry blood gas analysis of pulmonary artery and systemic carbon dioxide and oxygen content. The CO-oximetry data were used to calculate RQ (blood gas RQ). Paired recordings with both methods were made once in the morning and once in the afternoon and values obtained were analyzed for potential significant differences. RESULTS: The average Douglas-RQ, for all data points over the whole day, was 0.97 (95%CI 0.95-0.99). The corresponding blood gas RQ was 0.95 (95%CI 0.87-1.02). There was no statistically significant difference in RQ values obtained using Douglas-RQ or blood gas RQ for all data over the whole day (P = 0.43). Bias was - 0.02 (95% limits of agreement ± 0.3). Douglas-RQ decreased during the day 1.00 (95%CI 0.97-1.03) vs 0.95 (95%CI 0.92-0.98) P < 0.001, whereas the decrease was not significant for blood gas RQ 1.02 (95%CI 0.89-1.16 vs 0.87 (0.80-0.94) P = 0.11. CONCLUSION: RQ values obtained with blood gas analysis did not differ statistically, compared to gold standard Douglas bag RQ measurement, showing low bias but relatively large limits of agreement, when analyzed for the whole day. This indicates that a simplified blood gas-based method for RQ estimations may be used as an alternative to gold standard expired gas analysis on a group level, even if individual values may differ. In addition, RQ estimated with Douglas bag analysis of exhaled air, was 0.97 in anesthetized non-fasted pigs and decreased during prolonged anesthesia.

Standardized blood volume changes monitored by capnodynamic hemodynamic variables: An experimental comparative study in pigs.

BACKGROUND: The capnodynamic method, based on Volumetric capnography and differential Fick mathematics, assess cardiac output in mechanically ventilated subjects. Capnodynamic and established hemodynamic monitoring parameters' capability to depict alterations in blood volume were investigated in a model of standardized hemorrhage, followed by crystalloid and blood transfusion. METHODS: Ten anesthetized piglets were subjected to controlled hemorrhage (450 mL), followed by isovolemic crystalloid bolus and blood re-transfusion. Intravascular blood volume, and all hemodynamic variables, were determined twice after each intervention. The investigated hemodynamic variables were: cardiac output and stroke volume for capnodynamics and pulse contour analysis, respectively, pulse pressure and stroke volume variability and mean arterial pressure. One-way ANOVA and Tukey's test for multiple comparisons were used to identify significant changes. Trending was assessed by correlation and concordance. RESULT: Concordance against intravascular volume changes for capnodynamic cardiac output and stroke volume were 96 and 94%, with correlations r = .78 and .68, (p < .0001) with significant changes for 6 and 5 of the 6 measuring points, respectively. Mean arterial pressure and pulse pressure variation had a concordance of 85% and 87%, r = .67 (p < .0001) and r = -.45 (p < .0001), respectively, and both changed significantly for 3 of 6 measuring points. Pulse contour stroke volume variation, stroke volume and cardiac output, showed concordance and correlation of 76%, r = -.18 (p = .11), 63%, r = .28 (p = .01) and 50%, r = .31 (p = .007), respectively and significant change for 1, 1 and 0 of the measuring points, respectively. CONCLUSION: Capnodynamic cardiac output and stroke volume did best depict the changes in intravascular blood volume. Pulse contour parameters did not follow volume changes in a reliable way.

Interactions of the protease inhibitor, ritonavir, with common anesthesia drugs.

The protease inhibitor, ritonavir, is a strong inhibitor of CYP 3A. The drug is used for management of the human immunovirus and is currently part of an oral antiviral drug combination (nirmatrelvir-ritonavir) for the early treatment of SARS-2 COVID-19-positive patients aged 12 years and over who have recognized comorbidities. The CYP 3A enzyme system is responsible for clearance of numerous drugs used in anesthesia (e.g., alfentanil, fentanyl, methadone, rocuronium, bupivacaine, midazolam, ketamine). Ritonavir will have an impact on drug clearances that are dependent on ritonavir concentration, anesthesia drug intrinsic hepatic clearance, metabolic pathways, concentration-response relationship, and route of administration. Drugs with a steep concentration-response relationship (ketamine, midazolam, rocuronium) are mostly affected because small changes in concentration have major changes in effect response. An increase in midazolam concentration is observed after oral administration because CYP 3A in the gastrointestinal wall is inhibited, causing a large increase in relative bioavailability. Fentanyl infusion may be associated with a modest increase in plasma concentration and effect, but the large between subject variability of pharmacokinetic and pharmacodynamic concentration changes suggests it will have little impact on an individual patient, especially when used with adverse effect monitoring. It has been proposed that drugs that have no or only a small metabolic pathway involving the CYP 3A enzyme be used during anesthesia, for example, propofol, atracurium, remifentanil, and the volatile agents. That anesthesia approach denies children of drugs with considerable value. It is better that the inhibitory changes in clearance of these drugs are understood so that rational drug choices can be made to tailor drug use to the individual patient. Altered drug dose, anticipation of duration of effect, timing of administration, use of reversal agents and perioperative monitoring would better behoove children undergoing anesthesia.

Cardiac Output Assessments in Anesthetized Children: Dynamic Capnography Versus Esophageal Doppler.

BACKGROUND: The objective of this study was to compare esophageal Doppler cardiac output (COEDM) against the reference method effective pulmonary blood flow cardiac output (COEPBF), for agreement of absolute values and ability to detect change in cardiac output (CO) in pediatric surgical patients. Furthermore, the relationship between these 2 methods and noninvasive blood pressure (NIBP) parameters was evaluated. METHODS: Fifteen children American Society of Anesthesiology (ASA) I and II (median age, 8 months; median weight, 9 kg) scheduled for surgery were investigated in this prospective observational cohort study. Baseline COEPBF/COEDM/NIBP measurements were made at positive end-expiratory pressure (PEEP) 3 cm H2O. PEEP was increased to 10 cm H2O and COEPBF/COEDM/NIBP was recorded after 1 and 3 minutes. PEEP was then lowered to 3 cm H2O, and all measurements were repeated after 3 minutes. Finally, 20-µg kg-1 intravenous atropine was given with the intent to increase CO, and all measurements were recorded again after 5 minutes. Paired recordings of COEDM and COEPBF were examined for agreement and trending ability, and all parameters were analyzed for their responses to the hemodynamic challenges. RESULTS: Bias between COEDM and COEPBF (COEDM - COEPBF) was -17 mL kg-1 min-1 (limits of agreement, -67 to +33 mL kg-1 min-1) with a mean percentage error of 32% (95% confidence interval [CI], 25-37) and a concordance rate of 71% (95% CI, 63-80). The hemodynamic interventions caused by PEEP manipulations resulted in significant decrease in COEPBF absolute numbers (155 mL kg-1 min-1 [95% CI, 151-159] to 127 mL kg-1 min-1 [95% CI, 113-141]) and a corresponding relative decrease of 18% (95% CI, 14-22) 3 minutes after application of PEEP 10. No corresponding decreases were detected by COEDM. Mean arterial pressure showed a relative decrease with 5 (95% CI, 2-8) and 6% (95% CI, 2-10) 1 and 3 minutes after the application of PEEP 10, respectively. Systolic arterial pressure showed a relative decrease of 5% (95% CI, 2-10) 3 minutes after application of PEEP 10. None of the recorded parameters responded to atropine administration except for heart rate that showed a 4% relative increase (95% CI, 1-7, P = .02) 5 minutes after atropine. CONCLUSIONS: COEDM was unable to detect the reduction of CO cause by increased PEEP, whereas COEPBF and to a minimal extent NIBP detected these changes in CO. The ability of COEPBF to react to minor reductions in CO, before noticeable changes in NIBP are seen, suggests that COEPBF may be a potentially useful tool for hemodynamic monitoring in mechanically ventilated children.

Non-invasive capnodynamic mixed venous oxygen saturation during major changes in oxygen delivery.

Mixed venous oxygen saturation (SvO2) is an important variable in anesthesia and intensive care but currently requires pulmonary artery catheterization. Recently, non-invasive determination of SvO2 (Capno-SvO2) using capnodynamics has shown good agreement against CO-oximetry in an animal model of modest hemodynamic changes. The purpose of the current study was to validate Capno-SvO2 against CO-oximetry during major alterations in oxygen delivery. Furthermore, evaluating fiberoptic SvO2 for its response to the same challenges. Eleven mechanically ventilated pigs were exposed to oxygen delivery changes: increased inhaled oxygen concentration, hemorrhage, crystalloid and blood transfusion, preload reduction and dobutamine infusion. Capno-SvO2 and fiberoptic SvO2 recordings were made in parallel with CO-oximetry. Respiratory quotient, needed for capnodynamic SvO2, was measured by analysis of mixed expired gases. Agreement of absolute values between CO-oximetry and Capno-SvO2 and fiberoptic SvO2 respectively, was assessed using Bland-Altman plots. Ability of Capno- SvO2 and fiberoptic SvO2 to detect change compared to CO-oximetry was assessed using concordance analysis. The interventions caused significant hemodynamic variations. Bias between Capno-SvO2 and CO-oximetry was + 3% points (95% limits of agreements - 7 to + 13). Bias between fiberoptic SvO2 and CO-oximetry was + 1% point, (95% limits of agreements - 7 to + 9). Concordance rate for Capno-SvO2 and fiberoptic SvO2 vs. CO-oximetry was 98% and 93%, respectively. Capno-SvO2 generates absolute values close to CO-oximetry. The performance of Capno-SvO2 vs. CO-oximetry was comparable to the performance of fiberoptic SvO2 vs. CO-oximetry. Capno-SvO2 appears to be a promising tool for non-invasive SvO2 monitoring.