Intraoperative Ventilation/Perfusion Mismatch and Postoperative Pulmonary Complications after Major non-cardiac surgery: a prospective cohort study.

BACKGROUND: Postoperative pulmonary complications (PPCs) can increase hospital length of stay, postoperative morbidity and mortality. Despite many factors can increase the risk of PPCs, it is not known whether intraoperative ventilation/perfusion (V/Q) mismatch can be associated with an increased risk of PPCs after major non-cardiac surgery. METHODS: We enrolled patients undergoing general anesthesia for non-cardiac surgery and evaluated intraoperative V/Q distribution using the Automatic Lung Parameter Estimator technique. The assessment was done after anesthesia induction (T1), after 1 hour from surgery start (T2) and at the end of surgery (T3). We collected demographic and procedural information and measured intraoperative ventilatory and hemodynamic parameters at each time-point. Patients were followed up for 7 days after surgery and assessed daily for PPCs occurrence. RESULTS: We enrolled 101 patients with a median age of 71 [62-77] years, a BMI of 25 [22.4-27.9] kg/m 2 and a preoperative ARISCAT score of 41 [34-47]. Of them, 29 (29%) developed PPCs, mainly acute respiratory failure (23%) and pleural effusion (11%). Patients with and without PPCs did not differ in levels of shunt at T1 (PPCs:22.4[10.4-35.9] % vs No PPCs:19.3[9.4-24.1] %, p=0.18) or during the protocol, while significantly different levels of high V/Q were found during surgery (PPCs:13[11-15] mmHg vs No PPCs:10[8-13.5] mmHg, p=0.007) and before extubation (PPCs:13[11-14]mmHg vs No PPCs:10[8-12] mmHg, p=0.006). After adjusting for age, ARISCAT, BMI, smoking, fluid balance, anesthesia type, laparoscopic procedure and surgery duration, high V/Q before extubation was independently associated with the development of PPCs (OR 1.147, CI 95% [1.021-1.289], p=0.02). The sensitivity analysis showed an E-value of 1.35 (CI=1.11). CONCLUSIONS: In patients with intermediate/high risk of PPCs undergoing major non-cardiac surgery, intraoperative V/Q mismatch is associated with the development of PPCs. Increased high V/Q before extubation is independently associated with the occurrence of PPCs in the first 7 days after surgery.

Clinical practice, decision-making, and use of clinical decision support systems in invasive mechanical ventilation: a narrative review.

Invasive mechanical ventilation is a key supportive therapy for patients on intensive care. There is increasing emphasis on personalised ventilation strategies. Clinical decision support systems (CDSS) have been developed to support this. We conducted a narrative review to assess evidence that could inform device implementation. A search was conducted in MEDLINE (Ovid) and EMBASE. Twenty-nine studies met the inclusion criteria. Role allocation is well described, with interprofessional collaboration dependent on culture, nurse:patient ratio, the use of protocols, and perception of responsibility. There were no descriptions of process measures, quality metrics, or clinical workflow. Nurse-led weaning is well-described, with factors grouped by patient, nurse, and system. Physician-led weaning is heterogenous, guided by subjective and objective information, and 'gestalt'. No studies explored decision-making with CDSS. Several explored facilitators and barriers to implementation, grouped by clinician (facilitators: confidence using CDSS, retaining decision-making ownership; barriers: undermining clinician's role, ambiguity moving off protocol), intervention (facilitators: user-friendly interface, ease of workflow integration, minimal training requirement; barriers: increased documentation time), and organisation (facilitators: system-level mandate; barriers: poor communication, inconsistent training, lack of technical support). One study described factors that support CDSS implementation. There are gaps in our understanding of ventilation practice. A coordinated approach grounded in implementation science is required to support CDSS implementation. Future research should describe factors that guide clinical decision-making throughout mechanical ventilation, with and without CDSS, map clinical workflow, and devise implementation toolkits. Novel research design analogous to a learning organisation, that considers the commercial aspects of device design, is required.

A Prospective, Longitudinal Study Evaluating the Efficacy of an Automated Secretion Removal Technology.

BACKGROUND: Endotracheal suctioning causes discomfort, is associated with adverse effects, and is resource-demanding. An artificial secretion removal method, known as an automated cough, has been developed, which applies rapid, automated deflation, and inflation of the endotracheal tube cuff during the inspiratory phase of mechanical ventilation. This method has been evaluated in the hands of researchers but not when used by attending nurses. The aim of this study was to explore the efficacy of the method over the course of patient management as part of routine care. METHODS: This prospective, longitudinal, interventional study recruited 28 subjects who were intubated and mechanically ventilated. For a maximum of 7 d and on clinical need for endotracheal suctioning, the automatic cough procedure was applied. The subjects were placed in a pressure-regulated ventilation mode with elevated inspiratory pressure, and automated cuff deflation and inflation were performed 3 times, with this repeated if deemed necessary. Success was determined by resolution of the clinical need for suctioning as determined by the attending nurse. Adverse effects were recorded. RESULTS: A total of 84 procedures were performed. In 54% of the subjects, the artificial cough procedure was successful on > 70% of occasions, with 56% of all procedures considered successful. Ninety percent of all the procedures were performed in subjects who were spontaneously breathing and on pressure-support ventilation with peak inspiratory pressures of 20 cm H2O. Rates of adverse events were similar to those seen in the application of endotracheal suctioning. CONCLUSIONS: This study solely evaluated the efficacy of an automated artificial cough procedure, which illustrated the potential for reducing the need for endotracheal suctioning when applied by attending nurses in routine care.

The effects of respiratory rate and tidal volume on pulse pressure variation in healthy lungs-a generalized additive model approach may help overcome limitations.

Pulse pressure variation (PPV) is a well-established method for predicting fluid responsiveness in mechanically ventilated patients. The predictive accuracy is, however, disputed for ventilation with low tidal volume (VT) or low heart-rate-to-respiratory-rate ratio (HR/RR). We investigated the effects of VT and RR on PPV and on PPV's ability to predict fluid responsiveness. We included patients scheduled for open abdominal surgery. Prior to a 250 ml fluid bolus, we ventilated patients with combinations of VT from 4 to 10 ml kg-1 and RR from 10 to 31 min-1. For each of 10 RR-VT combinations, PPV was derived using both a classic approach and a generalized additive model (GAM) approach. The stroke volume (SV) response to fluid was evaluated using uncalibrated pulse contour analysis. An SV increase > 10% defined fluid responsiveness. Fifty of 52 included patients received a fluid bolus. Ten were fluid responders. For all ventilator settings, fluid responsiveness prediction with PPV was inconclusive with point estimates for the area under the receiver operating characteristics curve between 0.62 and 0.82. Both PPV measures were nearly proportional to VT. Higher RR was associated with lower PPV. Classically derived PPV was affected more by RR than GAM-derived PPV. Correcting PPV for VT could improve PPV's predictive utility. Low HR/RR has limited effect on GAM-derived PPV, indicating that the low HR/RR limitation is related to how PPV is calculated. We did not demonstrate any benefit of GAM-derived PPV in predicting fluid responsiveness.Trial registration: ClinicalTrials.gov, reg. March 6, 2020, NCT04298931.

The metabolic cost of inspiratory muscle training in mechanically ventilated patients in critical care.

BACKGROUND: Diaphragmatic dysfunction is well documented in patients receiving mechanical ventilation. Inspiratory muscle training (IMT) has been used to facilitate weaning by strengthening the inspiratory muscles, yet the optimal approach remains uncertain. Whilst some data on the metabolic response to whole body exercise in critical care exist, the metabolic response to IMT in critical care is yet to be investigated. This study aimed to quantify the metabolic response to IMT in critical care and its relationship to physiological variables. METHODS: We conducted a prospective observational study on mechanically ventilated patients ventilated for ≥ 72 h and able to participate in IMT in a medical, surgical, and cardiothoracic intensive care unit. 76 measurements were taken on 26 patients performing IMT using an inspiratory threshold loading device at 4 cmH2O, and at 30, 50 and 80% of their negative inspiratory force (NIF). Oxygen consumption (VO2) was measured continuously using indirect calorimetry. RESULTS: First session mean (SD) VO2 was 276 (86) ml/min at baseline, significantly increasing to 321 (93) ml/min, 333 (92) ml/min, 351(101) ml/min and 388 (98) ml/min after IMT at 4 cmH2O and 30, 50 and 80% NIF, respectively (p = 0.003). Post hoc comparisons revealed significant differences in VO2 between baseline and 50% NIF and baseline and 80% NIF (p = 0.048 and p = 0.001, respectively). VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Every increase in P/F ratio of 1 decreased the intercept VO2 by 0.41 ml/min (CI - 0.58 to - 0.24 p < 0.001). NIF had a significant effect on the intercept and slope, with every 1 cmH2O increase in NIF increasing intercept VO2 by 3.28 ml/min (CI 1.98-4.59 p < 0.001) and decreasing the dose-response slope by 0.15 ml/min/cmH2O (CI - 0.24 to - 0.05 p = 0.002). CONCLUSIONS: IMT causes a significant load-dependent increase in VO2. P/F ratio and NIF impact baseline VO2. The dose-response relationship of the applied respiratory load during IMT is modulated by respiratory strength. These data may offer a novel approach to prescription of IMT. TAKE HOME MESSAGE: The optimal approach to IMT in ICU is uncertain; we measured VO2 at different applied respiratory loads to assess whether VO2 increased proportionally with load and found VO2 increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Baseline NIF has a significant effect on the intercept and slope, participants with a higher baseline NIF have a higher resting VO2 but a less pronounced increase in VO2 as the inspiratory load increases; this may offer a novel approach to IMT prescription. Trial registration ClinicalTrials.gov, registration number: NCT05101850. Registered on 28 September 2021, https://clinicaltrials.gov/ct2/show/NCT05101850.

Comparison of mathematically arterialised venous blood gas sampling with arterial, capillary, and venous sampling in adult patients with hypercapnic respiratory failure: a single-centre longitudinal cohort study.

BACKGROUND: Accurate arterial blood gas (ABG) analysis is essential in the management of patients with hypercapnic respiratory failure, but repeated sampling requires technical expertise and is painful. Missed sampling is common and has a negative impact on patient care. A newer venous to arterial conversion method (v-TAC, Roche) uses mathematical models of acid-base chemistry, a venous blood gas sample and peripheral blood oxygen saturation to calculate arterial acid-base status. It has the potential to replace routine ABG sampling for selected patient cohorts. The aim of this study was to compare v-TAC with ABG, capillary and venous sampling in a patient cohort referred to start non-invasive ventilation (NIV). METHODS: Recruited patients underwent near simultaneous ABG, capillary blood gas (CBG) and venous blood gas (VBG) sampling at day 0, and up to two further occasions (day 1 NIV and discharge). The primary outcome was the reliability of v-TAC sampling compared with ABG, via Bland-Altman analysis, to identify respiratory failure (via PaCO2) and to detect changes in PaCO2 in response to NIV. Secondary outcomes included agreements with pH, sampling success rates and pain. RESULTS: The agreement between ABG and v-TAC/venous PaCO2 was assessed for 119 matched sampling episodes and 105 between ABG and CBG. Close agreement was shown for v-TAC (mean difference (SD) 0.01 (0.5) kPa), but not for CBG (-0.75 (0.69) kPa) or VBG (+1.00 (0.90) kPa). Longitudinal data for 32 patients started on NIV showed the closest agreement for ABG and v-TAC (R2=0.61). v-TAC sampling had the highest first-time success rate (88%) and was less painful than arterial (p<0.0001). CONCLUSION: Mathematical arterialisation of venous samples was easier to obtain and less painful than ABG sampling. Results showed close agreement for PaCO2 and pH and tracked well longitudinally such that the v-TAC method could replace routine ABG testing to recognise and monitor patients with hypercapnic respiratory failure. TRIAL REGISTRATION NUMBER: NCT04072848; www. CLINICALTRIALS: gov.

Inspiratory pressure waveform influences time to failure, respiratory muscle fatigue, and metabolism during resistive breathing.

Increased ventilatory work beyond working capacity of the respiratory muscles can induce fatigue, resulting in limited respiratory muscle endurance (Tlim ). Previous resistive breathing investigations all applied square wave inspiratory pressure as fatigue-inducing pattern. Spontaneous breathing pressure pattern more closely approximate a triangle waveform. This study aimed at comparing Tlim , maximal inspiratory pressure (PImax ), and metabolism between square and triangle wave breathing. Eight healthy subjects (Wei = 76 ± 10 kg, H = 181 ± 7.9 cm, age = 33.5 ± 4.8 years, sex [F/M] = 1/7) completed the study, comprising two randomized matched load resistive breathing trials with square and triangle wave inspiratory pressure waveform. Tlim decreased with a mean difference of 8 ± 7.2 min (p = 0.01) between square and triangle wave breathing. PImax was reduced following square wave (p = 0.04) but not for triangle wave breathing (p = 0.88). Higher VO2 was observed in the beginning and end for the triangle wave breathing compared with the square wave breathing (p = 0.036 and p = 0.048). Despite higher metabolism, Tlim was significantly longer in triangle wave breathing compared with square wave breathing, showing that the pressure waveform has an impact on the function and endurance of the respiratory muscles.

Efficacy of an Automated Secretion Removal Technology at Different Inspiratory Pressures.

BACKGROUND: Endotracheal suctioning is resource demanding, causes patient discomfort, and is associated with adverse effects. A new artificial cough method has been developed for automated secretion removal by using rapid deflation and inflation of the endotracheal tube cuff during the inspiratory phase of mechanical ventilation. This method has been evaluated in a bench model and in animals but not in human subjects. The aim of this study was to investigate whether this method can remove the need for endotracheal suctioning in subjects and whether this is dependent on ventilator settings. METHODS: This prospective, non-controlled study recruited 20 subjects on invasive mechanical ventilation. On the clinical need for endotracheal suctioning, the automatic cough procedure was applied 3 times over 30 s, with this repeated at higher ventilatory pressure and lower respiratory frequency if considered unsuccessful. Success was determined by removal of the clinical need for suctioning. Subject safety and comfort was measured by using the Critical-Care Pain Observation Tool before and after the procedure, and negative effects were recorded. To assess intra-subject variability, the procedure was performed on 3 different occasions for each subject. RESULTS: The procedure was successful in 18 of 20 subjects (90%), with mean subject success rates of 53% at low settings (peak inspiratory pressure 21.8 ± 3.8 cm H2O) and 83% at high settings (peak inspiratory pressure 25.6 ± 3.6 cm H2O). The Critical-Care Pain Observation Tool category remained unchanged in 30 procedures (77%), improved in 7 (18%), and deteriorated in 2 (5%). CONCLUSIONS: This study illustrated the potential for significant reduction in the clinical need for endotracheal suctioning after the use of an automated artificial cough procedure at both low and high peak inspiratory pressures, and that was well tolerated.

Sulfate and acid-base balance.

It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to sulfate, and therefore the mEq sulfate excreted in the urine is counted as acid retained in the body. In this study we show that pH in fluids with constant [Na] and [HEPES] declines as sulfate ions are added, and we show that titratable acidity increases exactly with the equivalents of sulfate. Therefore, sulfate excretion in urine is also acid excretion per se. This is in accordance with the down-regulation of proximal sulfate reabsorption under acidosis and the observation that children with distal renal tubular acidosis may be sulfate depleted. These results are well explained using charge-balance modeling, which is based only on the three fundamental principles of electroneutrality, conservation of mass, and rules of dissociation as devised from physical chemistry. In contrast, the findings are in contrast to expectations from conventional narratives. These are unable to understand the decreasing pH as sulfate is added since no conventional acid is present. The results may undermine the traditional notion of endogenous acid production since in the case of sulfur balance, S oxidation and its excretion as sulfate exactly balance each other. Possible clinical correlates with these findings are discussed.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

BACKGROUND: Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. METHODS: This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). RESULTS: Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). CONCLUSIONS: Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V̇/Q̇) matching. PEEP can increase end-expiratory lung volume, but its effect on V̇/Q̇ mismatch in COVID-19-related ARDS is not clear. METHODS: We enrolled intubated and mechanically ventilated subjects with COVID-19 ARDS and used the automatic lung parameter estimator (ALPE) to measure V̇/Q̇. Respiratory mechanics measurements, shunt, and V̇/Q̇ mismatch (low V̇/Q̇ and high V̇/Q̇) were collected at 3 PEEP levels (clinical PEEP = intermediate PEEP, low PEEP [clinical - 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V̇/Q̇. We also investigated if PEEP might have a different effect on V̇/Q̇ mismatch in 2 different respiratory mechanics phenotypes, that is, high elastance/low compliance (phenotype H) and low elastance/high compliance (phenotype L). RESULTS: Seventeen subjects with COVID-related ARDS age 66 [60-71] y with a PaO2 /FIO2 of 141 ± 74 mm Hg were studied at low PEEP = 5.6 ± 2.2 cm H2O, intermediate PEEP = 10.6 ± 3.8 cm H2O, and high PEEP = 15 ± 5 cm H2O. Shunt, low V̇/Q̇, high V̇/Q̇, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of PaO2 /FIO2 (P = .26). In the 2 phenotypes, PEEP had opposite effects on shunt, with a decrease in the phenotype L and an increase in phenotype H (P = .048). CONCLUSIONS: In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V̇/Q̇ mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V̇/Q̇ mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance.

Acid content and buffer-capacity: a charge-balance perspective.

Rational treatment and thorough diagnostic classification of acid-base disorders requires quantitative understanding of the mechanisms that generate and dissipate loads of acid and base. A natural precondition for this tallying is the ability to quantify the acid content in any specified fluid. Physical chemistry defines the pH-dependent charge on any buffer species, and also on strong ions on which, by definition, the charge is pH-invariant. Based, then, on the requirement of electroneutrality and conservation of mass, it was shown in 1914 that pH can be calculated and understood on the basis of the chemical composition of any fluid. Herein we first show that this specification for [H+] of the charge-balance model directly delivers the pH-dependent buffer-capacity as defined in the literature. Next, we show how the notion of acid transport as proposed in experimental physiology can be understood as a change in strong ion difference, ΔSID. Finally, based on Brønsted-Lowry theory we demonstrate that by defining the acid content as titratable acidity, this is equal to SIDref - SID, where SIDref is SID at pH 7.4. Thereby, any chemical situation is represented as a curve in a novel diagram with titratable acidity = SIDref - SID as a function of pH. For any specification of buffer chemistry, therefore, the change in acid content in the fluid is path invariant. Since constituents of SID and titratable acidity are additive, we thereby, based on first principles, have defined a new framework for modeling acid balance across a cell, a whole organ, or the whole-body.

Transparent decision support for mechanical ventilation using visualization of clinical preferences.

BACKGROUND: Systems aiding in selecting the correct settings for mechanical ventilation should visualize patient information at an appropriate level of complexity, so as to reduce information overload and to make reasoning behind advice transparent. Metaphor graphics have been applied to this effect, but these have largely been used to display diagnostic and physiologic information, rather than the clinical decision at hand. This paper describes how the conflicting goals of mechanical ventilation can be visualized and applied in making decisions. Data from previous studies are analyzed to assess whether visual patterns exist which may be of use to the clinical decision maker. MATERIALS AND METHODS: The structure and screen visualizations of a commercial clinical decision support system (CDSS) are described, including the visualization of the conflicting goals of mechanical ventilation represented as a hexagon. Retrospective analysis is performed on 95 patients from 2 previous clinical studies applying the CDSS, to identify repeated patterns of hexagon symbols. RESULTS: Visual patterns were identified describing optimal ventilation, over and under ventilation and pressure support, and over oxygenation, with these patterns identified for both control and support modes of mechanical ventilation. Numerous clinical examples are presented for these patterns illustrating their potential interpretation at the bedside. CONCLUSIONS: Visual patterns can be identified which describe the trade-offs required in mechanical ventilation. These may have potential to reduce information overload and help in simple and rapid identification of sub-optimal settings.

Decision support system to evaluate ventilation in the acute respiratory distress syndrome (DeVENT study)-trial protocol.

BACKGROUND: The acute respiratory distress syndrome (ARDS) occurs in response to a variety of insults, and mechanical ventilation is life-saving in this setting, but ventilator-induced lung injury can also contribute to the morbidity and mortality in the condition. The Beacon Caresystem is a model-based bedside decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean, in particular ARDS. METHODS: We will conduct a multi-centre international randomised, controlled, allocation concealed, open, pragmatic clinical trial to compare mechanical ventilation in ARDS patients following application of the Beacon Caresystem to that of standard routine care to investigate whether use of the system results in a reduction in driving pressure across all severities and phases of ARDS. DISCUSSION: Despite 20 years of clinical trial data showing significant improvements in ARDS mortality through mitigation of ventilator-induced lung injury, there remains a gap in its personalised application at the bedside. Importantly, the protective effects of higher positive end-expiratory pressure (PEEP) were noted only when there were associated decreases in driving pressure. Hence, the pressures set on the ventilator should be determined by the diseased lungs' pressure-volume relationship which is often unknown or difficult to determine. Knowledge of extent of recruitable lung could improve the ventilator driving pressure. Hence, personalised management demands the application of mechanical ventilation according to the physiological state of the diseased lung at that time. Hence, there is significant rationale for the development of point-of-care clinical decision support systems which help personalise ventilatory strategy according to the current physiology. Furthermore, the potential for the application of the Beacon Caresystem to facilitate local and remote management of large numbers of ventilated patients (as seen during this COVID-19 pandemic) could change the outcome of mechanically ventilated patients during the course of this and future pandemics. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04115709. Registered on 4 October 2019, version 4.0.

Mathematically arterialised venous blood is a stable representation of patient acid-base status at steady state following acute transient changes in ventilation.

Hyper- or hypoventilation are commonly occurring stress responses to arterial puncture around the time of blood sampling and have been shown to rapidly alter arterial blood acid-base parameters. This study aimed to evaluate a physiology-based mathematical method to transform peripheral venous blood acid-base values into mathematically arterialised equivalents following acute, transient changes in ventilation. Data from thirty patients scheduled for elective surgery were analysed using the physiology-based method. These data described ventilator changes simulating 'hyper-' or 'hypoventilation' at arterial puncture and included acid-base status from simultaneously drawn blood samples from arterial and peripheral venous catheters at baseline and following ventilatory change. Venous blood was used to calculate mathematically arterialised equivalents using the physiology-based method; baseline values were analysed using Bland-Altman plots. When compared to baseline, measured arterial and calculated arterialised values at each time point within limits of pH: ± 0.03 and PCO2: ± 0.5 kPa, were considered 'not different from baseline'. Percentage of values considered not different from baseline were calculated at each sampling timepoint following hyper- and hypoventilation. For the physiological method, bias and limits of agreement for pH and PCO2 were -0.001 (-0.022 to 0.020) and -0.02 (-0.37 to 0.33) kPa at baseline, respectively. 60 s following a change in ventilation, 100% of the mathematically arterialised values of pH and PCO2 were not different from baseline, compared to less than 40% of the measured arterial values at the same timepoint. In clinical situations where transient breath-holding or hyperventilation may compromise the accuracy of arterial blood samples, arterialised venous blood is a stable representative of steady state arterial blood.

Comparison of two methods for converting central venous values of acid-base status to arterial values in critically ill patients.

BACKGROUND: Assessment of the critically ill patient requires arterial acid-base status. Venous blood could provide a surrogate, with methods transforming venous values to arterial, improving their utility. This manuscript compares two of these methods, a statistical and a physiological method. Where these methods are inadequate to describe critically ill patients, physiological mechanisms are explored to explain discrepancies. METHODS: 1109 paired arterial and central-venous blood samples, from patients diagnosed with acute circulatory failure, were available for retrospective analysis. Of these, 386 samples were used previously to validate the statistical model. The statistical method of Boulain et al. 2016 and the physiological method of Rees et al. 2006 were applied to the 386 sample pairs, and compared using Bland-Altman analysis. A subset of the 1109 samples, where the physiological method could not accurately calculate arterial values, were analysed further to assess the necessary addition of CO2 or strong acid at the tissues to account for arterio-venous differences. RESULTS: Bias (LoA) for comparison of calculated and measured arterial values (n = 386) were similar for the statistical method (pH: -0.003 (-0.051 to 0.045), PCO2: -0.02 (-1.33 to 1.29 kPa)) and physiological method (pH: 0.009 (-0.033 to 0.052), PCO2: -0.08 (-1.20 to 1.03 kPa)). In the 381 cases (of the 1109 sample pairs) defined as not accurately described, addition of a median CO2 concentration of 0.72 mmol/l in excess of aerobic metabolism, explained this for 333 cases, with the remainder requiring simultaneous strong acid transport. CONCLUSION: Both methods appear equal in their ability to transform central-venous values to arterial, albeit warranting caution when using either in a critically ill population. The physiological approach was able to describe arterio-venous differences not explained by aerobic metabolism alone.

Changes in central venous to arterial carbon dioxide gap (PCO2 gap) in response to acute changes in ventilation.

BACKGROUND: Early diagnosis of shock is a predetermining factor for a good prognosis in intensive care. An elevated central venous to arterial PCO2 difference (∆PCO2) over 0.8 kPa (6 mm Hg) is indicative of low blood flow states. Disturbances around the time of blood sampling could result in inaccurate calculations of ∆PCO2, thereby misrepresenting the patient status. This study aimed to determine the influences of acute changes in ventilation on ∆PCO2 and understand its clinical implications. METHODS: To investigate the isolated effects of changes in ventilation on ∆PCO2, eight pigs were studied in a prospective observational cohort. Arterial and central venous catheters were inserted following anaesthetisation. Baseline ventilator settings were titrated to achieve an EtCO2 of 5±0.5 kPa (VT = 8 mL/kg, Freq = 14 ± 2/min). Blood was sampled simultaneously from both catheters at baseline and 30, 60, 90, 120, 180 and 240 s after a change in ventilation. Pigs were subjected to both hyperventilation and hypoventilation, wherein the respiratory frequency was doubled or halved from baseline. ∆PCO2 changes from baseline were analysed using repeated measures ANOVA with post-hoc analysis using Bonferroni's correction. RESULTS: ∆PCO2 at baseline for all pigs was 0.76±0.29 kPa (5.7±2.2 mm Hg). Following hyperventilation, there was a rapid increase in the ∆PCO2, increasing maximally to 1.35±0.29 kPa (10.1±2.2 mm Hg). A corresponding decrease in the ∆PCO2 was seen following hypoventilation, decreasing maximally to 0.23±0.31 kPa (1.7±2.3 mm Hg). These changes were statistically significant from baseline 30 s after the change in ventilation. CONCLUSION: Disturbances around the time of blood sampling can rapidly affect the PCO2, leading to inaccurate calculations of the ∆PCO2, resulting in misinterpretation of patient status. Care should be taken when interpreting blood gases, if there is doubt as to the presence of acute and transient changes in ventilation.

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

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.