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.

Effect of an Individualized Lung Protective Ventilation on Lung Strain and Stress in Children Undergoing Laparoscopy: An Observational Cohort Study.

BACKGROUND: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children. METHODS: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure. RESULTS: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum. CONCLUSIONS: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits.

Capnodynamic end-expiratory lung volume assessment in anesthetized healthy children.

BACKGROUND: Capnodynamic lung function monitoring generates variables that may be useful for pediatric perioperative ventilation. AIMS: Establish normal values for end-expiratory lung volume CO2 in healthy children undergoing anesthesia and to compare these values to previously published values obtained with alternative end-expiratory lung volume methods. The secondary aim was to investigate the ability of end-expiratory lung volume CO2 to react to positive end-expiratory pressure-induced changes in end-expiratory lung volume. In addition, normal values for associated volumetric capnography lung function variables were examined. METHODS: Fifteen pediatric patients with healthy lungs (median age 8 months, range 1-36 months) undergoing general anesthesia were examined before start of surgery. Tested variables were recorded at baseline positive end-expiratory pressure 3 cmH2 O, 1 and 3 min after positive end-expiratory pressure 10 cmH2 O and 3 min after returning to baseline positive end-expiratory pressure 3 cmH2 O. RESULTS: Baseline end-expiratory lung volume CO2 was 32 mL kg-1 (95% CI 29-34 mL kg-1 ) which increased to 39 mL kg-1 (95% CI 35-43 mL kg-1 , p < .0001) and 37 mL kg-1 (95% CI 34-41 mL kg-1 , p = .0003) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively. End-expiratory lung volume CO2 returned to baseline, 33 mL kg-1 (95% CI 29-37 mL kg-1 , p = .72) 3 min after re-establishing positive end-expiratory pressure 3 cmH2 O. Airway dead space increased from 1.1 mL kg-1 (95% CI 0.9-1.4 mL kg-1 ) to 1.4 (95% CI 1.1-1.8 mL kg-1 , p = .003) and 1.5 (95% CI 1.1-1.8 mL kg-1 , p < .0001) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively, and 1.2 mL kg-1 (95% CI 0.9-1.4 mL kg-1 , p = .08) after 3 min of positive end-expiratory pressure 3 cmH2 O. Additional volumetric capnography and lung function variables showed no major changes in response to positive end-expiratory pressure variations. CONCLUSIONS: Capnodynamic noninvasive and continuous end-expiratory lung volume CO2 values assessed during anesthesia in children were in close agreement with previously reported end-expiratory lung volume values generated by alternative methods. Furthermore, positive end-expiratory pressure changes resulted in physiologically expected end-expiratory lung volume CO2 responses in a timely manner, suggesting that it can be used to trend end-expiratory lung volume changes during 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.

Capnodynamic monitoring of lung volume and blood flow in response to increased positive end-expiratory pressure in moderate to severe COVID-19 pneumonia: an observational study.

BACKGROUND: The optimal level of positive end-expiratory pressure (PEEP) during mechanical ventilation for COVID-19 pneumonia remains debated and should ideally be guided by responses in both lung volume and perfusion. Capnodynamic monitoring allows both end-expiratory lung volume ([Formula: see text]) and effective pulmonary blood flow (EPBF) to be determined at the bedside with ongoing ventilation. METHODS: Patients with COVID-19-related moderate to severe respiratory failure underwent capnodynamic monitoring of [Formula: see text] and EPBF during a step increase in PEEP by 50% above the baseline (PEEPlow to PEEPhigh). The primary outcome was a > 20 mm Hg increase in arterial oxygen tension to inspired fraction of oxygen (P/F) ratio to define responders versus non-responders. Secondary outcomes included changes in physiological dead space and correlations with independently determined recruited lung volume and the recruitment-to-inflation ratio at an instantaneous, single breath decrease in PEEP. Mixed factor ANOVA for group mean differences and correlations by Pearson's correlation coefficient are reported including their 95% confidence intervals. RESULTS: Of 27 patients studied, 15 responders increased the P/F ratio by 55 [24-86] mm Hg compared to 12 non-responders (p < 0.01) as PEEPlow (11 ± 2.7 cm H2O) was increased to PEEPhigh (18 ± 3.0 cm H2O). The [Formula: see text] was 461 [82-839] ml less in responders at PEEPlow (p = 0.02) but not statistically different between groups at PEEPhigh. Responders increased both [Formula: see text] and EPBF at PEEPhigh (r = 0.56 [0.18-0.83], p = 0.03). In contrast, non-responders demonstrated a negative correlation (r = - 0.65 [- 0.12 to - 0.89], p = 0.02) with increased lung volume associated with decreased pulmonary perfusion. Decreased (- 0.06 [- 0.02 to - 0.09] %, p < 0.01) dead space was observed in responders. The change in [Formula: see text] correlated with both the recruited lung volume (r = 0.85 [0.69-0.93], p < 0.01) and the recruitment-to-inflation ratio (r = 0.87 [0.74-0.94], p < 0.01). CONCLUSIONS: In mechanically ventilated patients with moderate to severe COVID-19 respiratory failure, improved oxygenation in response to increased PEEP was associated with increased end-expiratory lung volume and pulmonary perfusion. The change in end-expiratory lung volume was positively correlated with the lung volume recruited and the recruitment-to-inflation ratio. This study demonstrates the feasibility of capnodynamic monitoring to assess physiological responses to PEEP at the bedside to facilitate an individualised setting of PEEP. TRIAL REGISTRATION: NCT05082168 (18th October 2021).

Perioperative Continuous Noninvasive Cardiac Output Monitoring in Cardiac Surgery Patients by a Novel Capnodynamic Method.

OBJECTIVES: To test the clinical performance of a novel continuous noninvasive cardiac output (CO) monitoring based on expired carbon dioxide kinetics in cardiac surgery patients. DESIGN: A prospective feasibility pragmatic clinical study. SETTING: A single-center, large community hospital. PARTICIPANTS: Thirty-two patients undergoing cardiac surgery were studied during the intraoperative (before cardiopulmonary bypass) and postoperative (in the intensive care unit before extubation) periods. INTERVENTIONS: CO was measured simultaneously by the continuous capnodynamic method and by transpulmonary thermodilution during changes in the patient's hemodynamic and/or respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The current recommended comparative statistics for CO measurement methods were analyzed, including bias, precision, and percentage error obtained from Bland-Altman analysis, and concordance between methods obtained from the four-quadrant plot analysis to evaluate the trending ability. Bias ± limits of agreement and percentage error were -0.6 (-1.9 to +0.8; 95% CI of 3.73-5.25) L/min and 31% (n = 147 measurements) for the intraoperative period, -0.8 (-2.4 to +0.9; 95% CI of 3.03-5.21) L/min and 41% (n = 66) for the postoperative period, and -0.6 (-2.1 to +0.8; 95% CI of 3.74-5.00) L/min and 34% (n = 213) for the pooled data. The trending analysis obtained a concordance of 82% (n = 65) for the intraoperative and 71% (n = 24) for the early postoperative periods. Aggregation of both data sets gave a concordance of 79% (n = 89). CONCLUSIONS: The continuous capnodynamic method was reliable and in good agreement with the reference method, and had an accuracy and trending ability good enough to make it a possible future alternative for hemodynamic monitoring in the studied population of elective adult cardiac surgery patients.

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.

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.

Effects of an open lung ventilatory strategy on lung gas exchange during laparoscopic surgery.

In general anaesthesia, early collapse of poorly ventilated lung segments with low alveolar ventilation-perfusion ratios occurs and may lead to postoperative pulmonary complications after abdominal surgery. An 'open lung' ventilation strategy involves lung recruitment followed by 'individualised' positive end-expiratory pressure titrated to maintain recruitment of low alveolar ventilation-perfusion ratio lung segments. There are limited data in laparoscopic surgery on the effects of this on pulmonary gas exchange. Forty laparoscopic bowel surgery patients were randomly assigned to standard ventilation or an 'open lung' ventilation intervention, with end-tidal target sevoflurane of 1% supplemented by propofol infusion. After peritoneal insufflation, stepped lung recruitment was performed in the intervention group followed by maintenance positive end-expiratory pressure of 12-15 cmH2O adjusted to maintain dynamic lung compliance at post-recruitment levels. Baseline gas and blood samples were taken and repeated after a minimum of 30 minutes for oxygen and carbon dioxide and for sevoflurane partial pressures using headspace equilibration. The sevoflurane arterial/alveolar partial pressure ratio and alveolar deadspace fraction were unchanged from baseline and remained similar between groups (mean (standard deviation) control group = 0.754 (0.086) versus intervention group = 0.785 (0.099), P = 0.319), while the arterial oxygen partial pressure/fractional inspired oxygen concentration ratio was significantly higher in the intervention group at the second timepoint (control group median (interquartile range) 288 (234-372) versus 376 (297-470) mmHg in the intervention group, P = 0.011). There was no difference between groups in the sevoflurane consumption rate. The efficiency of sevoflurane uptake is not improved by open lung ventilation in laparoscopy, despite improved arterial oxygenation associated with effective and sustained recruitment of low alveolar ventilation-perfusion ratio lung segments.

Positive end-expiratory pressure individualization guided by continuous end-expiratory lung volume monitoring during laparoscopic surgery.

To determine whether end-expiratory lung volume measured with volumetric capnography (EELVCO2) can individualize positive end-expiratory pressure (PEEP) setting during laparoscopic surgery. We studied patients undergoing laparoscopic surgery subjected to Fowler (F-group; n = 20) or Trendelenburg (T-group; n = 20) positions. EELVCO2 was measured at 0° supine (baseline), during capnoperitoneum (CP) at 0° supine, during CP with Fowler (head up + 20°) or Trendelenburg (head down - 30°) positions and after CP back to 0° supine. PEEP was adjusted to preserve baseline EELVCO2 during and after CP. Baseline EELVCO2 was statistically similar to predicted FRC in both groups. At supine and CP, EELVCO2 decreased from baseline values in F-group [median and IQR 2079 (768) to 1545 (725) mL; p = 0.0001] and in T-group [2164 (789) to 1870 (940) mL; p = 0.0001]. Change in body position maintained EELVCO2 unchanged in both groups. PEEP adjustments from 5.6 (1.1) to 10.0 (2.5) cmH2O in the F-group (p = 0.0001) and from 5.6 (0.9) to 10.0 (2.6) cmH2O in T-group (p = 0.0001) were necessary to reach baseline EELVCO2 values. EELVCO2 increased close to baseline with PEEP in the F-group [1984 (600) mL; p = 0.073] and in the T-group [2175 (703) mL; p = 0.167]. After capnoperitoneum and back to 0° supine, PEEP needed to maintain EELVCO2 was similar to baseline PEEP in F-group [5.9 (1.8) cmH2O; p = 0.179] but slightly higher in the T-group [6.5 (2.2) cmH2O; p = 0.006]. Those new PEEP values gave EELVCO2 similar to baseline in the F-group [2039 (980) mL; p = 0.370] and in the T-group [2150 (715) mL; p = 0.881]. Breath-by-breath noninvasive EELVCO2 detected changes in lung volume induced by capnoperitoneum and body position and was useful to individualize the level of PEEP during laparoscopy.Trial registry: Clinicaltrials.gov NCT03693352. Protocol started 1st October 2018.

Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study.

BACKGROUND: Cardiac output (CO) monitoring is the basis of goal-directed treatment for major abdominal surgery. A capnodynamic method estimating cardiac output (COEPBF) by continuously calculating nonshunted pulmonary blood flow has previously shown good agreement and trending ability when evaluated in mechanically ventilated pigs. OBJECTIVES: To compare the performance of the capnodynamic method of CO monitoring with transpulmonary thermodilution (COTPTD) in patients undergoing major abdominal surgery. DESIGN: Prospective, observational, method comparison study. Simultaneous measurements of COEPBF and COTPTD were performed before incision at baseline and before and after increased (+10 cmH2O) positive end-expiratory pressure (PEEP), activation of epidural anaesthesia and intra-operative events of hypovolemia and low CO. The first 25 patients were ventilated with PEEP 5 cmH2O (PEEP5), while in the last 10 patients, lung recruitment followed by individual PEEP adjustment (PEEPadj) was performed before protocol start. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: In total, 35 patients (>18 years) scheduled for major abdominal surgery with advanced hemodynamic monitoring were included in the study. MAIN OUTCOME MEASURES AND ANALYSIS: Agreement and trending ability between COEPBF and COTPTD at different clinical moments were analysed with Bland--Altman and four quadrant plots. RESULTS: In total, 322 paired values, 227 in PEEP5 and 95 in PEEPadj were analysed. Respectively, the mean COEPBF and COTPTD were 4.5 ±â€Š1.0 and 4.8 ±â€Š1.1 in the PEEP5 group and 4.9 ±â€Š1.2 and 5.0 ±â€Š1.0 l min-1 in the PEEPadj group. Mean bias (levels of agreement) and percentage error (PE) were -0.2 (-2.2 to 1.7) l min-1 and 41% for the PEEP5 group and -0.1 (-1.7 to 1.5) l min-1 and 31% in the PEEPadj group. Concordance rates during changes in COEPBF and COTPTD were 92% in the PEEP5 group and 90% in the PEEPadj group. CONCLUSION: COEPBF provides continuous noninvasive CO estimation with acceptable performance, which improved after lung recruitment and PEEP adjustment, although not interchangeable with COTPTD. This method may become a tool for continuous intra-operative CO monitoring during general anaesthesia in the future. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03444545.

Performance of a closed-loop glucose control system, comprising a continuous glucose monitoring system and an AI-based controller in swine during severe hypo- and hyperglycemic provocations.

Intensive care unit (ICU) patients develop stress induced insulin resistance causing hyperglycemia, large glucose variability and hypoglycemia. These glucose metrics have all been associated with increased rates of morbidity and mortality. The only way to achieve safe glucose control at a lower glucose range (e.g., 4.4-6.6 mmol/L) will be through use of an autonomous closed loop glucose control system (artificial pancreas). Our goal with the present study was to assess the safety and performance of an artificial pancreas system, composed of the EIRUS (Maquet Critical Care AB) continuous glucose monitor (CGM) and novel artificial intelligence-based glucose control software, in a swine model using unannounced hypo- and hyperglycemia challenges. Fourteen piglets (6 control, 8 treated) underwent sequential unannounced hypoglycemic and hyperglycemic challenges with 3 IU of NovoRapid and a glucose infusion at 17 mg/kg/min over the course of 5 h. In the Control animals an experienced ICU physician used every 30-min blood glucose values to maintain control to a range of 4.4-9 mmol/L. In the Treated group the artificial pancreas system attempted to maintain blood glucose control to a range of 4.4-6.6 mmol/L. Five of six Control animals and none of eight Treated animals experienced severe hypoglycemia (< 2.22 mmol/L). The area under the curve 3.5 mmol/L was 28.9 (21.1-54.2) for Control and 4.8 (3.1-5.2) for the Treated animals. The total percent time within tight glucose control range, 4.4-6.6 mmol/L, was 32.8% (32.4-47.1) for Controls and 55.4% (52.9-59.4) for Treated (p < 0.034). Data are median and quartiles. The artificial pancreas system abolished severe hypoglycemia and outperformed the experienced ICU physician in avoiding clinically significant hypoglycemic excursions.

A Continuous Noninvasive Method to Assess Mixed Venous Oxygen Saturation: A Proof-of-Concept Study in Pigs.

BACKGROUND: Mixed venous oxygen saturation (Svo2) is important when evaluating the balance between oxygen delivery and whole-body oxygen consumption. Monitoring Svo2 has so far required blood samples from a pulmonary artery catheter. By combining volumetric capnography, for measurement of effective pulmonary blood flow, with the Fick principle for oxygen consumption, we have developed a continuous noninvasive method, capnodynamic Svo2, for assessment of Svo2. The objective of this study was to validate this new technique against the gold standard cardiac output (CO)-oximetry Svo2 measurement of blood samples obtained from a pulmonary artery catheter and to assess the potential influence of intrapulmonary shunting. METHODS: Eight anesthetized mechanically ventilated domestic-breed piglets of both sexes (median weight 23.9 kg) were exposed to a series of interventions intended to reduce as well as increase Svo2. Simultaneous recordings of capnodynamic and CO-oximetry Svo2 as well as shunt fraction, using the Berggren formula, were performed throughout the protocol. Agreement of absolute values for capnodynamic and CO-oximetry Svo2 and the ability for capnodynamic Svo2 to detect change were assessed using Bland-Altman plot and concordance analysis. RESULTS: Overall bias for capnodynamic versus CO-oximetry Svo2 was -1 percentage point (limits of agreement -13 to +11 percentage points), a mean percentage error of 22%, and a concordance rate of 100%. Shunt fraction varied between 13% at baseline and 22% at the end of the study and was associated with only minor alterations in agreement between the tested methods. CONCLUSIONS: In the current experimental setting, capnodynamic assessment of Svo2 generates absolute values very close to the reference method CO-oximetry and is associated with 100% trending ability.

Determination of adequate positive end-expiratory pressure level required for carbon dioxide homeostasis in an animal model of infant laparoscopy.

BACKGROUND: Capnoperitoneum provides a ventilatory challenge due to reduction in end-expiratory lung volume and peritoneal carbon dioxide absorption in both children and adults. The primary aim of this controlled interventional trial was to determine the positive end-expiratory pressure (PEEP) level needed to ensure for adequate carbon dioxide clearance and preservation of carbon dioxide homeostasis in an experimental model of infant laparoscopy. The secondary aim was to evaluate potential effects on cardiac output of PEEP and abdominal pressure level variations in the same setting. METHODS: Eight chinchilla bastard rabbits were anesthetized and mechanically ventilated. Intra-abdominal pressures were randomly set to 0, 6, and 12 mm Hg by carbon dioxide insufflation. Carbon dioxide clearance using volumetric capnography, arterial blood gas data, and cardiac output was recorded, while PEEP 3, 6, and 9 cmH2 O were applied in a random order. RESULTS: A PEEP of 9 cmH2 O showed restoration of carbon dioxide clearance without causing changes in arterial partial pressure of carbon dioxide and bicarbonate and with no associated deterioration in cardiac output. CONCLUSION: The results promote a PEEP level of 9 cmH2 O in this model of infant capnoperitoneum to allow for adequate carbon dioxide removal with subsequent preservation of carbon dioxide homeostasis. The use of high PEEP was not associated with any decrease in cardiac output.

End-expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum.

BACKGROUND: Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELV CO 2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS: Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELV CO 2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS: Significant correlations were found between EELV CO 2 and EELVHe before capnoperitoneum (r = .85, P < .001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between EELV CO 2 and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20 mL kg-1 , determined with a receiver operating characteristic curve, was associated with near-normal LCI values. CONCLUSION: In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on EELV CO 2 requires an open lung strategy, defined as EELV above approximately 20 mL kg-1 .

Clinical and experimental validation of a capnodynamic method for end-expiratory lung volume assessment.

INTRODUCTION: Lung protective ventilation can decrease post-operative pulmonary complications. The aim of this study was to evaluate a capnodynamic method estimating effective lung volume (ELV) as a proxy for end-expiratory lung volume in response to PEEP changes in patients, healthy subjects and a porcine model. METHODS: Agreement and trending ability for ELV in anaesthetized patients and agreement in awake subjects were evaluated using nitrogen multiple breath wash-out/in and plethysmography as a reference respectively. Agreement and trending ability were evaluated in pigs during PEEP elevations with inert gas wash-out as reference. RESULTS: In anaesthetized patients bias (95% limits of agreement [LoA]) and percentage error (PE) at PEEP 0 cm H2 O were 133 mL (-1049 to 1315) and 71%, at PEEP 5 cm H2 O 161 mL (-1291 to 1613 mL) and 66%. In healthy subjects: 21 mL (-755 to 796 mL) and 26%. In porcines, at PEEP 5-20 cm H2 O bias decreased from 223 mL to 136 mL LoA (34-412) to (-30 to 902) and PE 29%-49%. Trending abilities in anaesthetized patients and porcines were 100% concordant. CONCLUSION: The ELV-method showed low bias but high PE in anaesthetized patients. Agreement was good in awake subjects. In porcines, agreement was good at lower PEEP levels. Concordance related to PEEP changes reached 100% in all settings. This method may become a useful trending tool for monitoring lung function during mechanical ventilation, if findings are confirmed in other clinical contexts.

Performance of a capnodynamic method estimating cardiac output during respiratory failure - before and after lung recruitment.

Respiratory failure may cause hemodynamic instability with strain on the right ventricle. The capnodynamic method continuously calculates cardiac output (CO) based on effective pulmonary blood flow (COEPBF) and could provide CO monitoring complementary to mechanical ventilation during surgery and intensive care. The aim of the current study was to evaluate the ability of a revised capnodynamic method, based on short expiratory holds (COEPBFexp), to estimate CO during acute respiratory failure (LI) with high shunt fractions before and after compliance-based lung recruitment. Ten pigs were submitted to lung lavage and subsequent ventilator-induced lung injury. COEPBFexp, without any shunt correction, was compared to a reference method for CO, an ultrasonic flow probe placed around the pulmonary artery trunk (COTS) at (1) baseline in healthy lungs with PEEP 5 cmH2O (HLP5), (2) LI with PEEP 5 cmH2O (LIP5) and (3) LI after lung recruitment and PEEP adjustment (LIPadj). CO changes were enforced during LIP5 and LIPadj to estimate trending. LI resulted in changes in shunt fraction from 0.1 (0.03) to 0.36 (0.1) and restored to 0.09 (0.04) after recruitment manoeuvre. Bias (levels of agreement) and percentage error between COEPBFexp and COTS changed from 0.5 (- 0.5 to 1.5) L/min and 30% at HLP5 to - 0.6 (- 2.3 to 1.1) L/min and 39% during LIP5 and finally 1.1 (- 0.3 to 2.5) L/min and 38% at LIPadj. Concordance during CO changes improved from 87 to 100% after lung recruitment and PEEP adjustment. COEPBFexp could possibly be used for continuous CO monitoring and trending in hemodynamically unstable patients with increased shunt and after recruitment manoeuvre.