Rationale and study design for an Individualized PeriopeRative Open lung VEntilatory approach in Emergency Abdominal Laparotomy/scopy: study protocol for a prospective international randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequent postoperative complications, with an estimated prevalence in elective surgery ranging from 20% in observational cohort studies to 40% in randomized clinical trials. However, the prevalence of PPCs in patients undergoing emergency abdominal surgery is not well defined. Lung-protective ventilation aims to minimize ventilator-induced lung injury and reduce PPCs. The open lung approach (OLA), which combines recruitment manoeuvres (RM) and positive end-expiratory pressure (PEEP) titration, aims to minimize areas of atelectasis and the development of PPCs; however, there is no conclusive evidence in the literature that OLA can prevent PPCs. The purpose of this study is to compare an individualized perioperative OLA with conventional standardized lung-protective ventilation in patients undergoing emergency abdominal surgery with clinical signs of intraoperative lung collapse. METHODS: Randomized international clinical trial to compare an individualized perioperative OLA (RM plus individualized PEEP and individualized postoperative respiratory support) with conventional lung-protective ventilation (standard PEEP of 5 cmH2O and conventional postoperative oxygen therapy) in patients undergoing emergency abdominal surgery with clinical signs of lung collapse. Patients will be randomised to open-label parallel groups. The primary outcome is any severe PPC during the first 7 postoperative days, including: acute respiratory failure, pneumothorax, weaning failure, acute respiratory distress syndrome, and pulmonary infection. The estimated sample size is 732 patients (366 per group). The final sample size will be readjusted during the interim analysis. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy in emergency abdominal laparotomy (iPROVE-EAL) is the first multicentre, randomized, controlled trial to investigate whether an individualized perioperative approach prevents PPCs in patients undergoing emergency surgery.

Análisis de la fotopletismografía para determinación de variaciones en el tono vascular y la presión arterial: Estudio basado en redes neuronales / Photoplethys mography waveform analysis for classification of vascular tone and arterial blood pressure: Study based on neural networks

Antecedentes y objetivo: El propósito del presente estudio fue evaluar si una red neuronal superficial (RN-S) puede detectar y clasificar los cambios en la presión arterial (PA), dependientes del tono vascular mediante un análisis del contorno de la onda de fotopletismografía (FPG). Material y métodos: Las señales de FPG y PA invasivas fueron simultáneamente registradas en 26 pacientes programados para cirugía general. Se estudió la aparición de episodios de hipertensión (presión arterial sistólica (PAS) > 140 mmHg), normotensión e hipotensión (PAS < 90 mmHg). El tono vascular fue clasificado según la FPG en dos formas: 1) Mediante inspección visual de los cambios en la amplitud de la onda de FPG y en la posición de la incisura dícrota; donde las clases I-II representan vasoconstricción (incisura dícrota ubicada a > 50% de la amplitud de FPG en ondas de pequeña amplitud), tono vascular normal de clase III (incisura dícrota ubicada entre 20-50% de la amplitud de FPG en ondas normales) y vasodilatación de clases IV-V-VI (incisura dícrota a < 20% de la amplitud FPG en ondas grandes). 2) Mediante un análisis automatizado basado en RN-S que combina siete parámetros derivados de la onda de FPG. Resultados: La evaluación visual fue precisa en la detección de hipotensión (sensibilidad 91%, especificidad 86% y precisión 88%) e hipertensión (sensibilidad 93%, especificidad 88% y precisión 90%). La normotensión se presentó como clase visual III (III-III) (mediana y 1°- 3° cuartiles), hipotensión como clase V (IV-VI) e hipertensión como clase II (I-III); todos con significancia estadística (p < 0,0001). La RN-S funcionó bien en la clasificación de las condiciones de PA. El porcentaje de datos con clasificación correcta por la RN-S fue del 83% para normotensión, 94% para hipotensión y 90% para hipertensión. Conclusiones: Los cambios en la PA inducidos por alteraciones en el tono vascular fueron clasificados correctamente de forma automática con una RN-S con base en...(AU)

Background: To test whether a Shallow Neural Network (S-NN) can detect and classify vascular tone dependent changes in arterial blood pressure (ABP) by advanced photopletysmographic (PPG) waveform analysis. Methods: PPG and invasive ABP signals were recorded in 26 patients undergoing scheduled general surgery. We studied the occurrence of episodes of hypertension (systolic arterial pressure (SAP) > 140 mmHg), normotension and hypotension (SAP < 90 mmHg). Vascular tone according to PPG was classified in two ways: 1) By visual inspection of changes in PPG waveform amplitude and dichrotic notch position; where Classes I-II represent vasoconstriction (notch placed > 50% of PPG amplitude in small amplitude waves), Class III normal vascular tone (notch placed between 20-50% of PPG amplitude in normal waves) and Classes IV-V-VI vasodilation (notch < 20% of PPG amplitude in large waves). 2) By an automated analysis, using S-NN trained and validated system that combines seven PPG derived parameters. Results: The visual assessment was precise in detecting hypotension (sensitivity 91%, specificity 86% and accuracy 88%) and hypertension (sensitivity 93%, specificity 88% and accuracy 90%). Normotension presented as a visual Class III (III-III) (median and 1st-3rd quartiles), hypotension as a Class V (IV-VI) and hypertension as a Class II (I-III); all p < 0.0001. The automated S-NN performed well in classifying ABP conditions. The percentage of data with correct classification by S-ANN was 83% for normotension, 94% for hypotension, and 90% for hypertension. Conclusions: Changes in ABP were correctly classified automatically by S-NN analysis of the PPG waveform contour.(AU)

Photoplethysmography waveform analysis for classification of vascular tone and arterial blood pressure: Study based on neural networks.

BACKGROUND: To test whether a Shallow Neural Network (S-NN) can detect and classify vascular tone dependent changes in arterial blood pressure (ABP) by advanced photopletysmographic (PPG) waveform analysis. METHODS: PPG and invasive ABP signals were recorded in 26 patients undergoing scheduled general surgery. We studied the occurrence of episodes of hypertension (systolic arterial pressure (SAP) >140 mmHg), normotension and hypotension (SAP < 90 mmHg). Vascular tone according to PPG was classified in two ways: 1) By visual inspection of changes in PPG waveform amplitude and dichrotic notch position; where Classes I-II represent vasoconstriction (notch placed >50% of PPG amplitude in small amplitude waves), Class III normal vascular tone (notch placed between 20-50% of PPG amplitude in normal waves) and Classes IV-V-VI vasodilation (notch <20% of PPG amplitude in large waves). 2) By an automated analysis, using S-NN trained and validated system that combines seven PPG derived parameters. RESULTS: The visual assessment was precise in detecting hypotension (sensitivity 91%, specificity 86% and accuracy 88%) and hypertension (sensitivity 93%, specificity 88% and accuracy 90%). Normotension presented as a visual Class III (III-III) (median and 1st-3rd quartiles), hypotension as a Class V (IV-VI) and hypertension as a Class II (I-III); all p < .0001. The automated S-NN performed well in classifying ABP conditions. The percentage of data with correct classification by S-ANN was 83% for normotension, 94% for hypotension, and 90% for hypertension. CONCLUSIONS: Changes in ABP were correctly classified automatically by S-NN analysis of the PPG waveform contour.

Individualized lung recruitment maneuver guided by pulse-oximetry in anesthetized patients undergoing laparoscopy: a feasibility study.

BACKGROUND: We conducted this study to test whether pulse-oximetry hemoglobin saturation (SpO2 ) can personalize the implementation of an open-lung approach during laparoscopy. Thirty patients with SpO2  ≥ 97% on room-air before anesthesia were studied. After anesthesia and capnoperitoneum the FIO2 was reduced to 0.21. Those patients whose SpO2 decreased below 97% - an indication of shunt related to atelectasis - completed the following phases: (1) First recruitment maneuver (RM), until reaching lung's opening pressure, defined as the inspiratory pressure level yielding a SpO2 ≥ 97%; (2) decremental positive end-expiratory (PEEP) titration trial until reaching lung's closing pressure defined as the PEEP level yielding a SpO2  < 97%; (3) second RM and, (4) ongoing ventilation with PEEP adjusted above the detected closing pressure. RESULTS: When breathing air, in 24 of 30 patients SpO2 was < 97%, PaO2 /FIO2  Ë‚ 53.3 kPa and negative end-expiratory transpulmonary pressure (PTP-EE ). The mean (SD) opening pressures were found at 40 (5) and 33 (4) cmH2 O during the first and second RM, respectively (P < 0.001; 95% CI: 3.2-7.7). The closing pressure was found at 11 (5) cmH2 O. This SpO2 -guided approach increased PTP-EE (from -6.4 to 1.2 cmH2 O, P < 0.001) and PaO2 /FIO2 (from 30.3 to 58.1 kPa, P < 0.001) while decreased driving pressure (from 18 to 10 cmH2 O, P < 0.001). SpO2 discriminated the lung's opening and closing pressures with accuracy taking the reference parameter PTP-EE (area under the receiver-operating-curve of 0.89, 95% CI: 0.80-0.99). CONCLUSION: The non-invasive SpO2 monitoring can help to individualize an open-lung approach, including all involved steps, from the identification of those patients who can benefit from recruitment, the identification of opening and closing pressures to the subsequent monitoring of an open-lung condition.

Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury.

BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy. METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated. RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups. CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.

High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS.

BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-ß) in the lung epithelium. METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-ß pathway markers, regional histology, and cytokines were evaluated. RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-ß pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR. CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-ß pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage.

BACKGROUND: We have evaluated a new method for continuous monitoring of effective pulmonary blood flow (COEPBF ), i.e. cardiac output (CO) minus intra-pulmonary shunt, during mechanical ventilation. The method has shown good trending ability during severe hemodynamic challenges in a porcine model with intact lungs. In this study, we further evaluate the COEPBF method in a model of lung lavage. METHODS: COEPBF was compared to a reference method for CO during hemodynamic and PEEP alterations, 5 and 12 cmH2 O, before and after repeated lung lavages in 10 anaesthetised pigs. Bland-Altman, four-quadrant and polar plot methodologies were used to determine agreement and trending ability. RESULTS: After lung lavage at PEEP 5 cmH2 O, the ratio of arterial oxygen partial pressure related to inspired fraction of oxygen significantly decreased. The mean difference (limits of agreement) between methods changed from 0.2 (-1.1 to 1.5) to -0.9 (-3.6 to 1.9) l/min and percentage error increased from 34% to 70%. Trending ability remained good according to the four-quadrant plot (concordance rate 94%), whereas mean angular bias increased from 4° to -16° when using the polar plot methodology. CONCLUSION: Both agreement and precision of COEPBF were impaired in relation to CO when the shunt fraction was increased after lavage at PEEP 5 cmH2 O. However, trending ability remained good as assessed by the four-quadrant plot, whereas the mean polar angle, calculated by the polar plot, was wide.

New modes of assisted mechanical ventilation.

Recent major advances in mechanical ventilation have resulted in new exciting modes of assisted ventilation. Compared to traditional ventilation modes such as assisted-controlled ventilation or pressure support ventilation, these new modes offer a number of physiological advantages derived from the improved patient control over the ventilator. By implementing advanced closed-loop control systems and using information on lung mechanics, respiratory muscle function and respiratory drive, these modes are specifically designed to improve patient-ventilator synchrony and reduce the work of breathing. Depending on their specific operational characteristics, these modes can assist spontaneous breathing efforts synchronically in time and magnitude, adapt to changing patient demands, implement automated weaning protocols, and introduce a more physiological variability in the breathing pattern. Clinicians have now the possibility to individualize and optimize ventilatory assistance during the complex transition from fully controlled to spontaneous assisted ventilation. The growing evidence of the physiological and clinical benefits of these new modes is favoring their progressive introduction into clinical practice. Future clinical trials should improve our understanding of these modes and help determine whether the claimed benefits result in better outcomes.

Alveolar recruitment improves ventilation during thoracic surgery: a randomized controlled trial.

BACKGROUND: This study was conducted to determine whether an alveolar recruitment strategy (ARS) applied during two-lung ventilation (TLV) just before starting one-lung ventilation (OLV) improves ventilatory efficiency. METHODS: Subjects were randomly allocated to two groups: (i) control group: ventilation with tidal volume (VT) of 8 or 6 ml kg(-1) for TLV and OLV, respectively, and (ii) ARS group: same ventilatory pattern with ARS consisting of 10 consecutive breaths at a plateau pressure of 40 and 20 cm H(2)O PEEP applied immediately before and after OLV. Volumetric capnography and arterial blood samples were recorded 5 min (baseline) and 20 min into TLV, at 20 and 40 min during OLV, and finally 10 min after re-establishing TLV. RESULTS: Twenty subjects were included in each group. In all subjects, the airway component of dead space remained constant during the study. Compared with baseline, the alveolar dead space ratio (VD(alv)/VT(alv)) increased throughout the protocol in the control but decreased in the ARS group. Differences in VD(alv)/VT(alv) between groups were significant (P<0.001). Except for baseline, all values in kPa (sd) were higher in the ARS than in the control group (P<0.001), respectively [70 (7) and 55 (9); 33 (9) and 24 (10); 33 (8) and 22 (10); 70 (7) and 55 (10)]. CONCLUSIONS: Recruitment of both lungs before instituting OLV not only decreased alveolar dead space but also improved arterial oxygenation and the efficiency of ventilation.

Capnography reflects ventilation/perfusion distribution in a model of acute lung injury.

BACKGROUND: Changes in the shape of the capnogram may reflect changes in lung physiology. We studied the effect of different ventilation/perfusion ratios (V/Q) induced by positive end-expiratory pressures (PEEP) and lung recruitment on phase III slope (S(III)) of volumetric capnograms. METHODS: Seven lung-lavaged pigs received volume control ventilation at tidal volumes of 6 ml/kg. After a lung recruitment maneuver, open-lung PEEP (OL-PEEP) was defined at 2 cmH(2)O above the PEEP at the onset of lung collapse as identified by the maximum respiratory compliance during a decremental PEEP trial. Thereafter, six distinct PEEP levels either at OL-PEEP, 4 cmH(2)O above or below this level were applied in a random order, either with or without a prior lung recruitment maneuver. Ventilation-perfusion distribution (using multiple inert gas elimination technique), hemodynamics, blood gases and volumetric capnography data were recorded at the end of each condition (minute 40). RESULTS: S (III) showed the lowest value whenever lung recruitment and OL-PEEP were jointly applied and was associated with the lowest dispersion of ventilation and perfusion (Disp(R-E)), the lowest ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) and the lowest difference between arterial and end-tidal pCO(2) (Pa-ETCO(2)). Spearman's rank correlations between S(III) and Disp(R-E) showed a ρ=0.85 with 95% CI for ρ (Fisher's Z-transformation) of 0.74-0.91, P<0.0001. CONCLUSION: In this experimental model of lung injury, changes in the phase III slope of the capnograms were directly correlated with the degree of ventilation/perfusion dispersion.

[Utility of recruitment maneuvers (pro)]. / Utilidad de las maniobras de reclutamiento (PRO).

In recent years lung recruitment maneuvers (RM) have awakened an increasing interest due to their potential beneficial effects in lung protection so that they have been progressively introduced into clinical practice. Many clinical and experimental studies have described the physiological benefits obtained after lung re-expansion although these benefits are not uniform, partly because of the wide heterogeneity of the RMs applied and lack of criteria defining their goal. Therefore, to date it has been difficult to establish the role of recruitment in the ventilatory management of ARDS patients. However, the information obtained from recent studies has improved our understanding regarding the mechanisms governing lung recruitment, interpretation of its response and its side effects and this has strongly contributed to its improved practical application. Lung recruitment must be applied in a protocolized and individualized way, establishing the pressure necessary to obtain the reasonably possible maximum lung re-expansion in each patient. Post RM PEEP adjustment is an essential aspect which, if ignored, renders RM useless and possibly without indication. Taking these essential aspects into account we are getting closer to, as the author believes, finally demonstrating the benefit of RM in lung protection and ARDS patients' outcome.

Utilidad de las maniobras de reclutamiento (PRO) / Utility of recruitment maneuvers (PRO)

En los últimos años las maniobras de reclutamiento (MR) han despertado un interés creciente por su potencial efecto beneficioso en la protección pulmonar y se han ido introduciendo en la práctica clínica de forma progresiva. Numerosos estudios clínicos y experimentales han descrito los beneficios fisiológicos obtenidos tras la reexpansión pulmonar, si bien éstos no son uniformes debido en parte a la gran heterogeneidad de las MR aplicadas y a la falta de criterios que definan sus objetivos. Por ello hasta la fecha ha sido difícil establecer cuál es el papel que el reclutamiento tiene en el manejo ventilatorio de los pacientes con SDRA. La información obtenida de los estudios recientes ha permitido entender mejor los mecanismos por los que actúa el reclutamiento, la interpretación de su respuesta y sus efectos secundarios, lo que ha contribuido a la mejora en su aplicación práctica. Las MR deben aplicarse de forma protocolizada e individualizada, determinando la presión necesaria para obtener la mayor reexpansión pulmonar razonablemente posible en cada paciente. El ajuste de la PEEP tras el reclutamiento es un aspecto esencial sin el cual las MR no tienen utilidad ni posiblemente justificación. Teniendo en cuenta estos aspectos fundamentales, estamos más cerca de, como cree el autor, demostrar el beneficio de las MR en la protección pulmonar y con ello mejorar el pronóstico de los pacientes con SDRA (AU)

In recent years lung recruitment maneuvers (RM) have awakened an increasing interest due to their potential beneficial effects in lung protection so that they have been progressively introduced into clinical practice. Many clinical and experimental studies have described the physiological benefits obtained after lung re-expansion although these benefits are not uniform, partly because of the wide heterogeneity of the RMs applied and lack of criteria defining their goal. Therefore, to date it has been difficult to establish the role of recruitment in the ventilatory management of ARDS patients. However, the information obtained from recent studies has improved our understanding regarding the mechanisms governing lung recruitment, interpretation of its response and its side effects and this has strongly contributed to its improved practical application. Lung recruitment must be applied in a protocolized and individualized way, establishing the pressure necessary to obtain the reasonably possible maximum lung re-expansion in each patient. Post RM PEEP adjustment is an essential aspect which, if ignored, renders RM useless and possibly without indication. Taking these essential aspects into account we are getting closer to, as the author believes, finally demonstrating the benefit of RM in lung protection and ARDS patient's; outcome (AU)

[New modes of ventilation: NAVA]. / Nuevos modos de ventilación: NAVA.

Neurally adjusted ventilatory assist (NAVA) is a new mode of assisted mechanical ventilation that uses the signal obtained from diaphragmatic electrical activity (Edi) to control the mechanical ventilator. Edi directly represents the central respiratory drive and reflects the length and intensity of the patient's neural effort. During NAVA, mechanical inspiratory assist starts when the respiratory center initiates the breath and is therefore independent of any pneumatic component. During inspiration, the pressure delivered is proportional to the Edi and the inspiratory pressure assist ceases when the neural activation of the diaphragm starts to decline after reaching the inspiratory maximum value. NAVA is a new conceptual approach to mechanical ventilation that can significantly improve patient-ventilator interaction and optimize the level of effective respiratory muscle unloading during assisted mechanical ventilation.

Nuevos modos de ventilación: NAVA / New modes of ventilation: NAVA

La ventilación asistida ajustada neuronalmente (NAVA) es un nuevo modo de ventilación mecánica asistida basado en la utilización de la señal obtenida de actividad eléctrica diafragmática (Edi) para el control del ventilador. La Edi representa directamente el impulso ventilatorio central y refleja la duración y la intensidad con que el paciente desea ventilar. Durante la NAVA la asistencia inspiratoria mecánica se inicia en el momento en que el centro respiratorio lo demanda, y el disparo es independiente de cualquier componente neumático. Durante la inspiración, la presión suministrada es proporcional a la Edi y la presurización inspiratoria cesa cuando la activación neural del diafragma comienza a disminuir tras alcanzar un valor máximo. Por sus características, el modo NAVA ofrece un nuevo enfoque conceptual a la ventilación mecánica que puede mejorar significativamente la interacción entre paciente y ventilador y puede optimizar la descarga muscular efectiva durante la ventilación asistida

Neurally adjusted ventilatory assist (NAVA) is anew mode of assisted mechanical ventilation thatuses the signal obtained from diaphragmaticelectrical activity (Edi) to control the mechanicalventilator. Edi directly represents the central respiratory drive and reflects the length and intensityof the patient’s neural effort. During NAVA, mechanicalinspiratory assist starts when the respiratorycenter initiates the breath and is thereforeindependent of any pneumatic component.During inspiration, the pressure delivered is proportional to the Edi and the inspiratory pressureassist ceases when the neural activation of the diaphragmstarts to decline after reaching the inspiratorymaximum value. NAVA is a new conceptualapproach to mechanical ventilation that cansignificantly improve patient-ventilator interactionand optimize the level of effective respiratorymuscle unloading during assisted mechanicalventilation

Effect of pulmonary perfusion on the slopes of single-breath test of CO2.

The objective of this study was to evaluate the effects of lung perfusion on the slopes of phases II (S(II)) and III (S(III)) of a single-breath test of CO(2) (SBT-CO(2)). Fourteen patients submitted to cardiac surgery were studied during weaning from cardiopulmonary bypass (CPB). Pump flow was decreased in 20% steps, from 100% (total CPB = 2.5 l.min(-1).m(-2)) to 0%. This maneuver resulted in a progressive and opposite increase in pulmonary blood flow (PBF) while maintaining ventilator settings constant. SBT-CO(2), respiratory, and hemodynamic variables remained unchanged before and after CPB, reflecting a constant condition at those stages. S(III) was similar before and after CPB (19.6 +/- 2.8 and 18.7 +/- 2.1 mmHg/l, respectively). S(III) was lowest during 20% PBF (8.6 +/- 1.9 mmHg/l) and increased in proportion to PBF until exit from CPB (15.6 +/- 2.2 mmHg/l; P < 0.05). Similarly, S(II) and the CO(2) area under the curve increased from 163 +/- 41 mmHg/l and 4.7 +/- 0.6 ml, respectively, at 20% PBF to 313 +/- 32 mmHg/l and 7.9 +/- 0.6 ml (P < 0.05) at CPB end. When S(II) and S(III) were normalized by the mean percent expired CO(2), they remained unchanged during the protocol. In summary, the changes in PBF affect the slopes of the SBT-CO(2). Normalizing S(II) and S(III) eliminated the effect of changes in the magnitude of PBF on the shape of the SBT-CO(2) curve.