Stephen Edward Rees

Using physiological models and decision theory for selecting appropriate ventilator settings.

ObjectiveTo present a decision support system for optimising mechanical ventilation in patients residing in the intensive care unit.MethodsMathematical models of oxygen transport, carbon dioxide transport and lung mechanics are combined with penalty functions describing clinical preference toward the goals and side-effects of mechanical ventilation in a decision theoretic approach. Penalties are quantified for risk of lung barotrauma, acidosis or alkalosis, oxygen toxicity or absorption atelectasis, and hypoxaemia.ResultsThe system is presented with an example of its use in a post-surgical patient. The mathematical models describe the patient’s data, and the system suggests an optimal ventilator strategy in line with clinical practice.ConclusionsThe system illustrates how mathematical models combined with decision theory can aid in the difficult compromises necessary when deciding on ventilator settings.

The automatic lung parameter estimator (ALPE) system: non-invasive estimation of pulmonary gas exchange parameters in 10-15 minutes.

Objective.Clinical measurements of pulmonary gas exchangeabnormalities might help prevent hypoxaemia and be useful in monitoringthe effects of therapy. In clinical practice single parameters are oftenused to describe the abnormality e.g., the “effectiveshunt.” A single parameter description is often insufficient,lumping the effects of several abnormalities. A more detailed picturecan be obtained from experiments where FIO2 is varied and twoparameters estimated. These experiments have previously taken30–40 minutes to complete, making them inappropriate for routineclinical use. However with automation of data collection and parameterestimation, the experimental time can be reduced to 10–15 minutes.Methods.A system has been built for non-invasive, Automatic,Lung Parameter Estimation (ALPE). This system consists of a ventilator,a gas analyser with pulse oximeter, and a computer. Computer programscontrol the experimental procedure, collect data from the ventilator andgas analyser, and estimate pulmonary gas exchange parameters. Use of theALPE system, i.e. in estimating gas exchange parameters and reducingexperimental time, has been tested on five normal subjects, two patientsbefore and during diuretic therapy, and on 50 occasions in patientsbefore and after surgical intervention. Results.The ALPE systemprovides estimation of pulmonary gas exchange parameters from a simple,clinical, non-invasive procedure, automatically and quickly. For normalsubjects and in patients receiving diuretic therapy, data collection byclinicians familiar with ALPE took (mean ± SD) 13 min 40 sec± 1 min 23 sec. For studies on patients before and after surgery,data collection by an intensive care nurse took (mean ± SD) 10min 47 sec ± 2 min 14 sec. Parameter estimates were: for normalsubjects, shunt = 4.95% ± 2.64% and fA2 = 0.89± 0.01; for patients with heart failure prior to diuretictherapy, patient 1, shunt = 11.50% fA2 = 0.41, patient 2 shunt =11.61% fA2 = 0.55; and during therapy: patient 1, shunt =11.51% fA2 = 0.71, patient 2, shunt = 11.22% fA2 = 0.49.Conclusions.The ALPE system provides quick, non-invasiveestimation of pulmonary gas exchange parameters and may have severalclinical applications. These include, monitoring pulmonary gas exchangeabnormalities in the ICU, assessing post-operative gas exchangeabnormalities, and titrating diuretic therapy in patients with heartfailure.

Non-invasive estimation of shunt and ventilation-perfusion mismatch.

ObjectiveTo investigate whether parameters describing pulmonary gas exchange (shunt and ventilation-perfusion mismatch) can be estimated consistently by the use of non-invasive data as input to a mathematical model of oxygen transport.DesignProspective study.SettingInvestigations were carried out in the post-anaesthesia care unit, coronary care unit, and intensive care unit.PatientsData from ninety-five patients and six normal subjects were included for the comparison. The clinical situations differed, ranging from healthy subjects to patients with acute respiratory failure in the intensive care unit.MeasurementsThe experimental procedure involved changing the inspired oxygen fraction (FIO2) in 4–6 steps in order to obtain arterial oxygen saturations (SaO2) in the range from 90–100%. This procedure allows plotting a FIO2/SaO2 or FEO2/SaO2 curve, the shape and position of which was quantified using the mathematical model estimating pulmonary shunt and a measure of ventilation-perfusion mismatch (ΔPO2). This procedure was performed using either arterial blood samples at each FIO2 level (invasive approach) or using values from the pulse oximeter (non-invasive approach).Main resultsThe model provided good fit to data using both the invasive and non-invasive experimental approach. The parameter estimates were linearly correlated with highly significant correlation coefficients; shuntinvasive vs shuntnon-invasive, r2 = 0.74, P <0.01, and ΔPO2invasive vs ΔPO2non-invasive, r2 = 0.97, P <0.001.ConclusionsPulmonary gas exchange can be described equally well using non-invasive data. The simplicity of the non-invasive approach makes the method suitable for large-scale clinical use.

Modelling of hypoxaemia after gynaecological laparotomy

Background: Late postoperative arterial hypoxaemia is common after major surgery, and may contribute to cardiovascular, cerebral or wound complications. This study investigates the time course of hypoxaemia following gynaecological laparotomy, and estimates parameters of mathematical models of pulmonary gas exchange to describe hypoxaemia.

Correlation between acid-base parameters measured in arterial blood and venous blood sampled peripherally, from vena cavae superior, and from the pulmonary artery.

Objective In intensive care units arterial blood sampling is routine for analysing acid–base and oxygenation status. In nonintensive departments arterial blood sampling is seldom performed. Venous blood sampling is routine but not usually analysed for acid–base and oxygenation status. This study describes the correlation between arterial and peripheral, central and mixed venous pH, PCO2 and PO2 in a wide range of adult patients. Methods Arterial and venous blood samples were taken anaerobically and simultaneously. The values of pH, PCO2 and PO2 were compared using Bland–Altman plots. Results A total of 103 patients were included. The arteriovenous difference (bias±SD) for pH was 0.026±0.023 and for PCO2 −0.60±0.57 kPa (peripheral venous blood), 0.036±0.014 and −0.79±0.26 kPa (central venous blood) and 0.026±0.010 and −0.67±0.22 kPa (mixed venous blood). The arteriovenous difference for PO2 for peripheral, central and mixed venous blood was 6.27±4.36, 8.33±3.94 and 11.00±4.87 kPa, respectively. Conclusion The venous values of pH, corrected for bias, can give arterial values which are within reasonable laboratory and clinical acceptance criteria. For PCO2 this is also true, except for peripheral blood, where the standard deviation is outside laboratory acceptance criteria but within clinical acceptance criteria. For PO2 the arteriovenous differences are not randomly distributed and even for PO2≤12 kPa the value of the mean difference is clearly outside both laboratory and reasonable clinical acceptance criteria.

Evaluation of a method for converting venous values of acid-base and oxygenation status to arterial values

Objective: This paper evaluates a method in which arterial values of pH, carbon dioxide tension (Pco2) and oxygen tension (Po2) calculated from venous values and pulse oximetry are compared with simultaneously measured arterial values. Methods: 103 adult patients from three departments (pulmonary medicine, thoracic intensive care and multidisciplinary intensive care) were studied. The patients belonged to three groups: (1) 31 haemodynamically stable patients with a diagnosis of chronic obstructive lung disease (COLD); (2) 49 haemodynamically stable patients without COLD; and (3) 23 haemodynamically unstable patients without COLD. Arterial and venous (peripheral and, where possible, central and mixed) blood samples were taken simultaneously and anaerobically. Peripheral arterial oxygen saturation was measured with a pulse oximeter. The principle of the method is to simulate the transport of venous blood back through the tissues using the respiratory quotient (adding oxygen and removing carbon dioxide) until simulated arterial oxygenation matches that measured by pulse oximetry. Results: Calculated values of arterial pH and Pco2 had very small bias and standard deviations regardless of the venous sampling site. In all cases these errors were within those considered acceptable for the performance of laboratory equipment, and well within the limits of error acceptable in clinical practice. In addition, the standard deviation (SD) of calculated values of pH and Pco2 was similar to the variability between consecutive arterial samples. For peripheral oxygen saturation values ⩽96%, the method can calculate Po2 with an SD of 0.93, which may be useful in clinical practice. Calculations made from peripheral venous blood were significantly more accurate than those from central venous blood. Conclusion: Arterial pH and Pco2 can be calculated precisely from peripheral venous blood in a broad patient population. The method has potential for use as a screening tool in emergency medical departments and in medical and surgical wards to assess a patient’s acid-base and oxygenation status prior to sampling arterial blood or to help in the decision to refer the patient to the ICU. In departments where arterial blood gas values are used to monitor patients (eg, pulmonary medicine), the method might reduce the number of arterial samples taken by replacing them with peripheral venous blood samples, thus reducing the need for painful arterial punctures.

Simulation of cardiovascular system diseases by including the autonomic nervous system into a minimal model

Diagnosing cardiovascular system (CVS) diseases from clinically measured data is difficult, due to the complexity of the hemodynamic and autonomic nervous system (ANS) interactions. Physiological models could describe these interactions to enable simulation of a variety of diseases, and could be combined with parameter estimation algorithms to help clinicians diagnose CVS dysfunctions. This paper presents modifications to an existing CVS model to include a minimal physiological model of ANS activation. A minimal model is used so as to minimise the number of parameters required to specify ANS activation, enabling the effects of each parameter on hemodynamics to be easily understood. The combined CVS and ANS model is verified by simulating a variety of CVS diseases, and comparing simulation results with common physiological understanding of ANS function and the characteristic hemodynamics seen in these diseases. The model of ANS activation is required to simulate hemodynamic effects such as increased cardiac output in septic shock, elevated pulmonary artery pressure in left ventricular infarction, and elevated filling pressures in pericardial tamponade. This is the first known example of a minimal CVS model that includes a generic model of ANS activation and is shown to simulate diseases from throughout the CVS.

Oxygenation and release of inflammatory mediators after off‐pump compared with after on‐pump coronary artery bypass surgery

Background:  In a previous study, we showed that oxygenation was impaired for up to 5 day after conventional coronary artery bypass grafting (CABG). As cardiopulmonary bypass (CPB) may have a detrimental effect on pulmonary function, we hypothesized that coronary revascularization grafting without the use of CPB (OPCAB) would affect post‐operative oxygenation and release of inflammatory mediators less compared with CABG.

Effect of growth hormone treatment on postprandial protein metabolism in growth hormone-deficient adults.

Growth hormone (GH) treatment of GH-deficient adults increases lean body mass. To investigate this anabolic effect of GH, body composition and postabsorptive and postprandial protein metabolism were measured in 12 GH-deficient adults randomized to placebo or GH treatment. Protein metabolism was measured after an infusion of [1-13C]leucine before and after a standard meal at 0 and 2 mo. After 2 mo, there was an increase in lean body mass in the GH group (P < 0. 05) but no change in the placebo group. In the postabsorptive state, there was increased nonoxidative leucine disappearance (NOLD; a measure of protein synthesis) and leucine metabolic clearance rate and decreased leucine oxidation in the GH group (P < 0.05) but no change in the placebo group. After the meal, there was an increase in NOLD and oxidation in all studies (P < 0.05), but the increase in NOLD, measured as area under the curve, was greater in the GH group (P < 0.05). This study clearly demonstrates for the first time that the increase in protein synthesis in the postabsorptive state after GH treatment of GH-deficient adults is maintained in the postprandial state.Growth hormone (GH) treatment of GH-deficient adults increases lean body mass. To investigate this anabolic effect of GH, body composition and postabsorptive and postprandial protein metabolism were measured in 12 GH-deficient adults randomized to placebo or GH treatment. Protein metabolism was measured after an infusion of [1-13C]leucine before and after a standard meal at 0 and 2 mo. After 2 mo, there was an increase in lean body mass in the GH group ( P < 0.05) but no change in the placebo group. In the postabsorptive state, there was increased nonoxidative leucine disappearance (NOLD; a measure of protein synthesis) and leucine metabolic clearance rate and decreased leucine oxidation in the GH group ( P < 0.05) but no change in the placebo group. After the meal, there was an increase in NOLD and oxidation in all studies ( P < 0.05), but the increase in NOLD, measured as area under the curve, was greater in the GH group ( P < 0.05). This study clearly demonstrates for the first time that the increase in protein synthesis in the postabsorptive state after GH treatment of GH-deficient adults is maintained in the postprandial state.

Hypoxaemia after cardiac surgery : clinical application of a model of pulmonary gas exchange

Background and objective: To investigate the clinical application of a mathematical model of pulmonary gas exchange, which ascribes hypoxaemia to shunt and ventilation/perfusion mismatch. Ventilation/perfusion mismatch is quantified by ΔPO2, which is the drop in oxygen pressure from alveoli to lung capillaries. Shunt and ΔPO2 were used to describe changes in oxygenation after coronary artery bypass grafting. Methods: Fourteen patients were studied 2-4 h after surgery and on postoperative days 2, 3 and 7. On each occasion inspired oxygen fraction was changed in four to six steps to obtain arterial oxygen saturation (SaO2) in the range of 90-100%, enabling construction of FEO2/SaO2 curves. Measurements of ventilation, circulation and oxygenation were entered in a previously described mathematical model of pulmonary gas exchange. Results: We found that oxygenation was most impaired 3 days after surgery. By fitting the mathematical model to the FEO2/SaO2 curve, we found that shunt remained constant throughout the study period. However, ΔPO2 increased from 0.5 kPa (median, range 0-3.8) 2-4 h after surgery, to 3.2 kPa (range 1.2-6.4, P < 0.05) on day 2, and to 4.0 kPa (range 1.2-8.3) on day 3. On day 7, ΔPO2 decreased to 2.2 kPa (range 0-3.5, P < 0.05). Conclusions: Ventilation/perfusion mismatch (ΔPO2), rather than shunt, explains the changes in postoperative oxygenation. The model of pulmonary gas exchange may serve as a useful and potentially non-invasive clinical tool for monitoring patients at risk of postoperative hypoxaemia.