Ventilatory Equivalents For Carbon Dioxide Research Articles

Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboembolic disease.

Symptomatic patients with chronic thromboembolic disease (CTED) without pulmonary hypertension often show an excessive increase in mean pulmonary arterial pressure (MPAP) during exercise.We report on the impact of pulmonary endarterectomy (PEA) on pulmonary haemodynamics in a prospective series of 32 consecutive CTED patients who underwent PEA. All patients had a comprehensive diagnostic work-up including right heart catheterisation at baseline and 12 months after PEA. Furthermore, in 12 patients exercise right heart catheterisation was performed before and after PEA.After PEA, MPAP was lower at rest (20±3 versus 17±3 mmHg; p=0.008) and during maximal exercise (39±8 versus 31±6 mmHg; p=0.016). The mean total pulmonary resistance (TPR) decreased from 3.6±0.8 Wood Units (WU) pre-operatively to 2.7±0.7 WU 1 year after PEA (p=0.004) and the mean slope of the MPAP/cardiac output (CO) relationship decreased from 3.6±1.0 to 2.3±0.8 WU (p=0.002). Peak oxygen uptake increased from 1.2±0.4 to 1.5±0.3 L·min-1 (p=0.014) and ventilatory equivalents of carbon dioxide decreased from 39±2 to 30±2 (p=0.002). There was a significant improvement in quality of life assessed by the Cambridge Pulmonary Hypertension Outcome Review questionnaire.In CTED patients, PEA resulted in haemodynamic and clinical improvements. The means of TPR and MPAP/CO slopes decreased to <3.0 WU.

Pre-operative variables including fitness associated with complications after oesophagectomy.

Oesophagectomy is a technically-demanding operation associated with a high level of morbidity. We analysed the association of pre-operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02-1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre-operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37-0.80), p = 0.002 and 0.89 (0.82-0.96), p = 0.004, respectively. Survival was associated with the ratio of expected-to-observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03-0.91), p = 0.039 and 0.96 (0.90-1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17-1.63), p < 0.0001.

Cardiopulmonary Exercise Testing and Surgery.

The surgical patient population is increasingly elderly and comorbid and poses challenges to perioperative physicians. Accurate preoperative risk stratification is important to direct perioperative care. Reduced aerobic fitness is associated with increased postoperative morbidity and mortality. Cardiopulmonary exercise testing is an integrated and dynamic test that gives an objective measure of aerobic fitness or functional capacity and identifies the cause of exercise intolerance. Cardiopulmonary exercise testing provides an individualized estimate of patient risk that can be used to predict postoperative morbidity and mortality. This technology can therefore be used to inform collaborative decision-making and patient consent, to triage the patient to an appropriate perioperative care environment, to diagnose unexpected comorbidity, to optimize medical comorbidities preoperatively, and to direct individualized preoperative exercise programs. Functional capacity, evaluated as the anaerobic threshold and peak oxygen uptake ([Formula: see text]o2peak) predicts postoperative morbidity and mortality in the majority of surgical cohort studies. The ventilatory equivalents for carbon dioxide (an index of gas exchange efficiency), is predictive of surgical outcome in some cohorts. Prospective cohort studies are needed to improve the precision of risk estimates for different patient groups and to clarify the best combination of variables to predict outcome. Early data suggest that preoperative exercise training improves fitness, reduces the debilitating effects of neoadjuvant chemotherapy, and may improve clinical outcomes. Further research is required to identify the most effective type of training and the minimum duration required for a positive effect.

The impact of neoadjuvant chemotherapy on cardiopulmonary physical fitness in gastro-oesophageal adenocarcinoma.

Introduction Operable oesophagogastric adenocarcinoma management in the UK includes three cycles of neoadjuvant chemotherapy (NAC) followed by resection. Determination of oxygen uptake at the anaerobic threshold (AT) with cardiopulmonary exercise testing (CPET) is used to objectively measure cardiorespiratory reserve. Oxygen uptake at AT predicts perioperative risk, with low values associated with increased morbidity. Previous studies indicate NAC may have a detrimental impact on cardiorespiratory reserve. Methods CPET was completed by 30 patients before and after a standardised NAC protocol. The ventilatory AT was determined using the V-slope method, and the peak oxygen uptake and ventilatory equivalents for carbon dioxide measured. Median AT before and after chemotherapy was compared using a paired Student's t-test. Results Median oxygen uptake at AT pre- and post-NAC was 13.9±3.1 ml/kg/min and 11.5±2.0 ml/kg/min, respectively. The mean decrease was 2.4 ml/kg/min (95% confidence interval [CI] 1.3-3.85; p<0.001). Median peak oxygen delivery also decreased by 2.17 ml/kg/min (95% CI 1.02-3.84; p=0.001) after NAC. Ventilatory equivalents were unchanged. Conclusions This reduction in AT objectively quantifies a decrease in cardiorespiratory reserve after NAC. Patients with lower cardiorespiratory reserve have increased postoperative morbidity and mortality. Preventing this decrease in cardiorespiratory reserve during chemotherapy, or optimising the timing of surgical resection after recovery of AT, may allow perioperative risk-reduction.

Oxygen Uptake Efficiency Slope Predicts Major Cardiac Events in Patients With End-Stage Heart Failure

IntroductionOxygen uptake efficiency slope (OUES) has been shown as a predictor of stable heart failure (HF) survival. However, there is a lack of evidence for end-stage HF. ObjectivesWe aimed to investigate the prognostic value of OUES in end-stage HF patients. MethodsThe study design was a retrospective cohort. End-staged HF patients who had cardiopulmonary exercise testing (CPET) for evaluation between 2004 and 2009 were included. The primary outcomes were cardiac death and heart transplantation. The independent survival predictors were determined using Cox regression hazard model adjusted for demographics, New York Heart Association (NYHA) classification, medication, and left ventricular ejection fraction (LVEF). The Kaplan-Meier survival curves and log-rank test were used. Probability values less than .05 were considered significant. ResultsMean age of the 128 patients was 50 ± 12 years and 93 were male. Mean LVEF was 23% ± 9%. Forty-three subjects suffered cardiac events (5 cardiac deaths and 38 urgent heart transplantations) during the 2-year follow-up period. Cox regression indicated that OUES and diuretics were significant predictors of 2-year survival, although peak oxygen uptake and ventilatory equivalent of carbon dioxide were not. Patients with high OUES (≥1.6) had a higher survival rate (P < .001; odds ratio [OR], 13.10; 95% confidence interval [CI], 3.30–58.63). The Kaplan-Meier curves show survival was significantly higher in those with OUES ≥1.6. ConclusionsOUES might be an aid in prognosis of patients with end-stage HF and useful in the assessment of patients unable to perform maximal exercise testing.

Exercise-related risk at anaerobic threshold in patients with chronic obstructive pulmonary disease

To investigate the exercise-related risk at anaerobic threshold(AT) in patients with chronic obstructive pulmonary disease(COPD). Sixty two patients [men 56, women 6, aged (66±8) yr] with stable COPD in Beijing Friendship Hospital during 2013-2014, participated in this study. Incremental symptom-limited cardiopulmonary exercise test was performed on cycle ergometer. The AT was determined using the V-Slope technique and ventilatory equivalents for carbon dioxide and oxygen. Symptoms, 10-lead electrocardiogram, oxygen saturation by pulse oximetry(SpO(2)) were monitored during exercise. The AT, detectable in 53 patients, occurred at (68±10)% of peak oxygen uptake(peak VO(2)). The SpO(2) was in the safe range (94±2) % and the respiratory reserve was relatively high at AT (i.e. 48%). High-intensity exercise training can be performed in patients with moderate-to- severe COPD without resting oxygen desaturation.

Exercise capacity in adult patients after Fontan procedure. (RCD code: IV-5B.1)

Background: The aim of Fontan procedure is to restore a balance between pulmonary and systemic circulation and improve or nearly normalize arterial saturation in patients with functionally univentricular heart. Nevertheless, due to the lack of subpulmonary pump, the circulatory system becomes haemodynamically less efficient, what can lead to the impairment of exercise capacity. Aim: The aim of the study was to investigate exercise capacity by means of cardiopulmonary exercise test and pulmonary function tests, of 37 adult Fontan patients with regard to the time passed from the index procedure. The patients were divided into 3 groups: group I – up to 15 years post procedure; group II – 16–20 years, group III – more than 20 years after Fontan procedure). Results: 37 Fontan patients (mean age was 24.4 ±5.7 years, 40% of women) were enrolled in the study. The mean postoperative time was 19.4 ±5.1 (13–30) years. Mean, peak oxygen consumption (VO2peak) was 22.7 ±7.1 ml/kg/min (64.2 ±18.5% of predicted value). According to postoperative time a significant increase of ventilatory equivalent of carbon dioxide (VE/VCO2) (p = 0.033) and significant decrease of forced expiratory volume in 1 s/ vital capacity (FEV1%VC) between group 2 and 3 (p = 0.026) were observed. Additionally, the age of the patients correlated negatively with and heart rate (HR) (r = -0.360, p <0.05) and peak oxygen consumption (VO2peak) (r = -0,337, p < 0.05). Moreover, age at Fontan operation and time after Fontan procedure was related to ventilator equivalent of oxygen (VE/VO2) (r = -0,343, p <0.05, and r = 0.393, p <0.05). Single ventricle ejection fraction (SVEF) and atrioventricular regurgitation degree did not corresponded with cardiopulmonary exercise test (CPET) values. Conclusions: Results highlight the complex problem of diminished exercise capacity of Fontan patients depending on the time passed from the procedure. Exercise tolerance deteriorates in time: VE/VCO2 increases, FEV1/VC markedly lowers in a group of Fontan patients at 20 years follow-up. JRCD 2016; 2 (8): 254–258

Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks.

Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO2 and VE/VCO2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO2), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI>25kg/m2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure.

Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO2) are elevated in moderate HF patients and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, sex, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress, and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Furthermore, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.

Diagnostic and Prognostic Value of Lactate Threshold and pH - Threshold Determination during Cardiopulmonary Testing in Patients with Chronic Heart Failure

Objective: lactate threshold and pH-threshold determination during cardiopulmonary testing (CPET) and evaluate their diagnostic and prognostic value in patients with chronic heart failure. Methods: The study included 58 HF patients with NYHA class II-IV, who have performed CPET on treadmill using equipment «Oxycon PRO», Jaeger, Germany. Individual exercise test protocol (ramp protocol) was created for every participant. The cubital venous catheter was installed in all subjects before exercise test. Blood samples were taken at baseline and at 1-minute intervals during test. PH, lactate and HCO3concentration were estimated using analyzer i-STAT, cartridge CG4 (Abbot, USA). Lactate threshold (LT) and pH-threshold (pH-T) were determined by changes in pH and lactate levels in correlation with dynamics of oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), ventilatory equivalent of carbon dioxide (VE/VCO2), respiratory exchange ratio (RER). Respiratory compensation point (RCP) was determined, when ventilation Original Research Article Lelyavina et al.; BJMMR, 5(3): 289-296, 2015; Article no. BJMMR.2015.031 290 dramatically increase relative VE/VCO2. Results: In HF patients with NYHA class II level of physical performance was significantly higher than in patients NYHA class III and IV. However, during exercise in all HF patients were observed similar physiological stages and compensatory mechanisms of regulation of homeostasis, but with varying of exercise intensity. In HF patient with NYHA class IV, exercise was stopped before reaching of RCP in connection with the development shortness of breath, weakness, tiredness, fatigue in the legs 8-9/10 Borg scale. Among HF patients with NYHA class III RCP reached 12 (36%) of people, among patients with class II 14 (82%). The 95% confidence intervals (CI) for the VO2 peak, RCP, pH-T and LT in II, III and IV NYHA class are follows: in HF patients with NYHA class II 17.4 to 18.2, 16.3 to 17.2, 14.7 to 15.3 and 9.7 to 10.1; NYHA class III 13.5 to 14.3, 12.2 to 12.8, 11.4 to 11.8 and 8.2 to 8.6; NYHA class IV 8.6 to 10.6 for VO2 peak, 8.1 to 9.7 for VO2 pHT, 5.7 to 7.5 for VO2 LT. HF NYHA class correlated with VO2 LT, VO2 pH-T and VO2 RCP, r=-0.7, p<0.01, r=-0.5, p<0.01 and r=-0.4, p<0.01, respectively. Patients were observed in the average 21.4 of +/ 1.5 months (6-48). For the specified period in the study group died 15 HF patients (25%) with III-IV FC. We observed the following correlations: the survival and VO2 LT r=0.8, p<0.05; survival and VO2 рН-T r=0.5, p<0.05; survival and VO2 RCP r=0.2, p<0.07. Conclusion: In HF patients with NYHA class II-IV significant diagnostic and prognostic markers are content VO2 at lactate threshold and pH-threshold, especially at the lactate threshold.

New Approaches to Marking Stages of Incremental Physical Work by Example of Cardiopulmonary Exercise Testing

The present study aims to divide physiological stages of involving physiological compensatory reactions in organs and systems which provide transport and consumption of O2 during incremental physical exercise in healthy adults. Twenty seven untrained healthy volunteers, 19 men, mean age 25.0 ± 8.7 (18-28 years), BMI (body mass index) 26 ±2.8 (19.0-27.3 kg/height, m 2 ) and 18 triathletes, 10 men, mean age 22.3 ± 3.2 (17-25 years), BMI 21.4 ± 2.1 (19.8-23.4 kg/height, m 2 ) were evaluated during progressive treadmill exercise test. CPET (cardiopulmonary exercise testing) was performed on treadmill with gas exchange system Oxycon Pro (Jaeger, Germany). Individual incremental exercise test protocol (ramp protocol) was created for every participant. All persons reached peak exercise in 12-15 minutes. Everybody was instructed to perform maximal exercise. Maximal exercise has been defined by a plateau of VO2 (absence of increase VO2 during incremental work rate), achievement RER 1.2 or maximal predicted HR (heart rate). The cubital venous catheter was installed in all subjects before exercise test. Blood samples were taken at baseline and at 1-minute intervals during test. PH, lactate and HCO3 - concentration were estimated using analyzer i-STAT, cartridge CG4 (Abbot, USA). Physiological stages of involving compensatory reactions were determined by changes in pH, lactate and HCO3 - levels in correlation with dynamics of VO2 (oxygen uptake), VCO2 (carbon dioxide output), VE (minute ventilation), VE/VCO2 (ventilatory equivalent of carbon dioxide), RER (respiratory exchange ratio). RCP (respiratory compensation point) was determined, when ventilation dramatically increase relative to carbon dioxide output. Maximal work rate of athletes was reliably higher than of untrained healthy volunteers due to high level of training. Through first 3-5 min lactate concentration in blood was 2.1 ± 0.2 (1.9-2.5) Mm/L. It starts to increase when intensity of physical exercise reaches 12%-30% VO2 peak and comes up to 12 ± 3.2 Mm/L (8-19 Mm/L) on exercise peak. Significant inflection of lactate concentration curve can be fixed on this stage and after this lactate concentration increases gradually. pH and HCO3 - values were in normal limits at baseline: pH 7.32 ± 0.05, HCO3 - 27.3 ± 2.1 Mm/L. pH does not change significantly till the intensity of exercise ≥ 45% of VO2 peak and after this begins to diminish, that marks start of metabolic acidosis development. In all examined persons, this phenomenon appears significantly later than the increase of lactate concentration. Plateau of VO2 appears at exercise intensity 93 ± 2.5% VO2 peak. Entry of exercise in stage of plateau means that either cardiovascular and pulmonary systems, provide delivery of O2 as utilization O2 in muscles achieve its maximal capacities and increase of aerobic energy production is impossible further. Thus, we have marked four physiological stages during incremental physical exercise: lactate threshold, pH-threshold, respiratory compensation point and aerobic limit.

Cardiopulmonary Exercise Testing for Preoperative Risk Assessment before Pancreaticoduodenectomy for Cancer

Pancreaticoduodenectomy is the standard of care for tumors confined to the head of pancreas and can be undertaken with low operative mortality. The procedure has a high morbidity, particularly in older patient populations with preexisting comorbidities. This study evaluated the role of cardiopulmonary exercise testing to predict postoperative morbidity and outcome in high-risk patients undergoing pancreaticoduodenectomy. In a prospective cohort of consecutive patients undergoing pancreaticoduodenectomy, those aged over 65years (or younger with comorbidity) were categorized as high risk and underwent preoperative assessment by cardiopulmonary exercise testing (CPET) according to a predefined protocol. Data were collected on functional status, postoperative complications, and survival. A total of 143 patients underwent preoperative assessment, 50 of whom were deemed to be at low risk for surgery per study protocol. Of 93 high-risk patients, 64 proceeded to surgery after preoperative CPET. Neither anaerobic threshold (AT) nor maximal oxygen consumption ([Formula: see text] O 2 MAX) predicted patient mortality or morbidity. However, ventilatory equivalent of carbon dioxide ([Formula: see text] E/[Formula: see text] CO 2) at AT was a predictive marker of postoperative mortality, with an area under the curve (AUC) of 0.84 (95% confidence interval [CI] 0.63-1.00, p=0.020); a threshold of 41 was 75% sensitive and 95% specific (positive predictive value 50%, negative predictive value 98%). Above this threshold, raised [Formula: see text] E/[Formula: see text] CO 2 predicted poor long-term survival (hazard ratio 2.05, 95% CI 1.09-3.86, p=0.026). CPET is a useful adjunctive test for predicting postoperative outcome in patients being assessed for pancreaticoduodenectomy. Raised CPET-derived [Formula: see text] E/[Formula: see text] CO 2 predicts early postoperative death and poor long-term survival.

Use of cardiopulmonary exercise testing (CPET) to identify patients at high risk for adverse outcome after pancreaticoduodenectomy.

e15072 Background: Pancreaticoduodenectomy is the standard of care for tumours confined to the head of pancreas and can be undertaken with low operative mortality. However, the procedure has a high morbidity, particularly in older patient populations with pre-existing co-morbidities. Many of the currently available methods for assessment of pre-operative risk rely on either scoring systems or indirect measures of cardiopulmonary function. In contrast, pre-operative cardiopulmonary exercise testing (CPET) provides a direct functional assessment of integrated cardiac and respiratory performance. This study evaluates the role of pre-operative cardiopulmonary exercise testing (CPET) for prediction of post-operative morbidity and outcome after pancreaticoduodenectomy. Methods: In a prospective cohort undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with co-morbidity) were categorized as high-risk and underwent preoperative assessment by CPET according to pre-defined protocol. Data were collected on functional status, postoperative complications and survival. The predictive potential of CPET-derived markers was assessed. Results: 143 patients underwent preoperative assessment of whom 50 were deemed low-risk for surgery per protocol. Of 93 high-risk patients 64 proceeded to surgery after preoperative CPET. CPET-derived ventilatory equivalent of carbon dioxide (VE/VCO2) at anaerobic threshold (AT) was a predictive marker of postoperative mortality with an AUC of 0.85 (95% CI 0.63 to 1.07, p = 0.020); a threshold of 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). Above this threshold, raised VE/VCO2 was a predictor of poor long-term survival (HR 1.90, 95%CI: 1.02 to 3.57, p = 0.045). Conclusions: CPET is a useful adjunctive test for predicting post-operative outcome in patients being assessed for pancreaticoduodenectomy. CPET-derived VE/VCO2 above a threshold of 41 predicts early post-operative death and poor long-term survival. CPET should be considered in the pre-operative work-up prior to pancreaticoduodenectomy.

Preoperative cardiopulmonary exercise testing and risk of early mortality following abdominal aortic aneurysm repair8

Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity. The aim of this study was to assess whether preoperative CPET identifies patients at risk of early death following elective open and endovascular abdominal aortic aneurysm (AAA) repair. Prospective data were collected from a pilot study between September 2005 and February 2007, and from all patients who underwent CPET before elective AAA repair at two vascular centres between February 2007 and November 2011. Symptom-limited, maximal CPET was performed on each patient. Univariable and multivariable analyses were used to identify risk factors for 30- and 90-day mortality. Some 415 patients underwent CPET before elective AAA repair. Anaerobic threshold (AT), peak oxygen consumption (peak V.O(2) ) and ventilatory equivalents for carbon dioxide were associated with 30- and 90-day mortality on univariable analysis. On multivariable analysis, open repair (odds ratio (OR) 4·92, 95 per cent confidence interval 1·55 to 17·00; P = 0·008), AT below 10·2 ml per kg per min (OR 6·35, 1·84 to 29·80; P = 0·007), anaemia (OR 3·27, 1·04 to 10·50; P = 0·041) and inducible cardiac ischaemia (OR 6·16, 1·48 to 23·07; P = 0·008) were associated with 30-day mortality. Anaemia, inducible cardiac ischaemia and peak V.O(2) less than 15 ml per kg per min (OR 8·59, 2·33 to 55·75; P = 0·005) were associated with 90-day mortality on multivariable analysis. Patients with two or more subthreshold CPET values were at increased risk of both 30- and 90-day mortality. An AT below 10·2 ml per kg per min, peak V.O(2) less than 15 ml per kg per min and at least two subthreshold CPET values identify patients at increased risk of early death following AAA repair.

Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension

In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organisation of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area over-perfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant, i.e. resistance × compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy. Structure and function of the right ventricle show a similar pattern to right ventricular hypertrophy, namely dilatation and wall thickening, as well as loss of function in CTEPH and PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial carbon dioxide tension, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal carbon dioxide tension gradient in CTEPH shows a contribution of increased dead space ventilation.

Relationship between cardioventilatory coupling and pulmonary gas exchange

Cardioventilatory coupling (CVC) is a temporal alignment between the heartbeat and inspiratory activity caused by pulsatile baroreceptor afferent activity. However, although first described over a century ago, the functional significance of CVC has yet to be established. One hypothesis is that baroreceptor triggering of inspiration positions heartbeats into phases of the respiratory cycle that may optimize pulmonary gas exchange efficiency. To test this hypothesis, we recruited ten patients with permanently implanted fixed-rate cardiac pacemakers and instructed them to pace breathe at heart rate-to-respiratory rate (HR/f) ratios of 3·8, 4·0 and 4·2. This breathing protocol enabled us to simulate heartbeat distributions similar to those seen in the presence (4·0) and complete absence (3·8, 4·2) of CVC. Results showed that heart rate, mean arterial pressure, end-tidal carbon dioxide and tidal volume remained unchanged across the three conditions (P> 0·05). Pulmonary gas exchange efficiency, as determined by the ventilatory equivalents of carbon dioxide (V·E/V·CO2) and oxygen (V·E/V·O2) did not differ significantly by HR/f ratio (P = 0·29 and P = 0·70, respectively). These data suggest that CVC does not play a significant role in optimizing pulmonary gas exchange efficiency in humans.

Ventilatory equivalents for carbon dioxide and oxygen are measures of ventilatory efficiency and not of pulmonary gas exchange efficiency

Sin et al. (2010) have compared ventilatory equivalents for carbon dioxide and oxygen ( and , respectively) at two different breathing rates in healthy control subjects and patients with permanent cardiac pacemakers. In the healthy control group, reduction of breathing frequency from 15 to 6 breaths min−1 resulted not only in a 2.5-fold increase in respiratory sinus arrhythmia (RSA), but also in a significant reduction of and . In subjects with permanent cardiac pacemakers and therefore fixed-rate pacing, while there was no RSA, the reduction in and with reduction in breathing rate was similar to that in the healthy control subjects. The conclusion, therefore, is that there is improvement in gas exchange efficiency at the lower breathing rate, and this improvement is not contingent upon an enhancement of RSA. Our opinion is that and reflect ventilatory performance and not gas exchange efficiency. It is evident that these ratios will decrease with slow breathing (compared with a higher breathing rate) in any individual, irrespective of RSA, if the individual is asked to maintain end-tidal CO2 at a given value at both breathing rates (normocapnic range of 5–6% in this study), owing to an improved ratio of alveolar-to-dead space ventilation, resulting in lower minute ventilation. The effect of ventilation to perfusion ratio ( ratio) mismatch on gas exchange in a subject without RSA can be appreciated only by measuring the alveolar–arterial difference (A–a difference) and not by the parameters mentioned in the study. The authors themselves have stated that they chose not to study the three standard parameters for measuring gas exchange efficiency, including A–a difference, because these involve invasive procedures such as arterial or mixed venous blood sampling. It is clear, therefore, that the mechanism they refer to as pulmonary gas exchange is indeed the one assessed by A–a difference. However, cannot serve as a measure of gas exchange efficiency, in the sense conveyed in the paper, because carbon dioxide elimination will not be affected by temporal changes in ratios, as long as total ventilation and perfusion remain unchanged. Ventilation ( ) is a function of the arterial , and arterial is equal to end-tidal CO2. If the subjects are allowed to breathe voluntarily so as to maintain end-tidal CO2, as has been done in this study, reduction in breathing rate will not change , but will lead to lowering of because of less dead space ventilation at the lower breathing rate (Ganong, 2005), irrespective of the presence or absence of RSA. When decreases, the ventilatory equivalents estimated in this study will decrease. A decrease in A–a difference may occur in control subjects as a result of improved RSA when breathing rate is reduced, which may not be seen in the paced subjects. A reduction in A–a difference will lead to an increase in arterial and probably an increase in arterial and venous oxygen saturation in the control subjects. The lack of such an increase in oxygen saturation with slow breathing in paced subjects without RSA will not translate into any reduction in because oxygen consumption is a function of metabolic rate, and tissues can extract the required oxygen even from less saturated arterial blood.

Reply

We appreciate and welcome the comments from Drs Tharion and Subramani on our paper (Sin et al. 2010), which we summarize as follows: (1) ventilatory equivalents of carbon dioxide ( ) and oxygen ( ) are imperfect measures of pulmonary gas exchange efficiency; and therefore (2) our study does not allow conclusions to be drawn regarding the role of respiratory sinus arrhythmia (RSA) in pulmonary gas exchange optimization. At first glance it may seem that our measurement choice compromises our study conclusions. Closer examination of our stated hypothesis, however, shows that the conclusions are in fact well justified. To date, evidence in favour of Hayano's hypothesis that ‘RSA improves pulmonary gas exchange efficiency by matching alveolar ventilation and capillary perfusion throughout respiratory cycle…by suppressing unnecessary heartbeats during expiration and ineffective ventilation during waning phases of perfusion’ is largely based on animal experiments (Hayano & Yasuma, 2003). In an attempt to establish the relevance of this hypothesis in humans, Giardino et al. (2003) showed that and were significantly reduced during slow breathing and attributed this ‘pulmonary gas exchange’ improvement to the concomitant rise in RSA amplitude. We were sceptical of this interpretation given we had already shown that physiological levels of RSA do not give rise to significant heartbeat redistribution (Tzeng et al. 2009). Consequently, the study was conducted to test our hypothesis that a previously described association between RSA amplitude, and is unrelated to the presence of RSA itself; the study was not an attempt to re-examine Hayano's hypothesis, which we had already shown to be physiologically improbable (Tzeng et al. 2009). Although ventilatory equivalents have been previously applied as indices of pulmonary gas exchange efficiency (e.g. Giardino et al. 2003), we are in full agreement with Drs Tharion and Subramani that they are not gold standard and never alluded to this being the case. Nevertheless, as discussed in the Viewpoint article that accompanied our work, ‘opinions based upon faulty logic can have a long duration, unless being meticulously challenged’ (Buchheit, 2010). Knowing that the fundamental premise of Hayano's hypothesis is not met, we simply took one further step to demonstrate unequivocally the faulty logic that underpins current evidence. Thus, for the benefit of the general readership, we reiterate again that the use of ventilatory equivalents, whatever they reflect, does not compromise our position that the concurrent rise in RSA and reduction in and during slow breathing cannot be taken as evidence that RSA optimizes human pulmonary gas exchange efficiency. The commentary from Drs Tharion and Subramani further reinforces our core message that a teleological role of human RSA, if it has one, remains to be determined.

Cardiopulmonary exercise testing and length of stay in patients undergoing major surgery

We read with interest the review published in Anaesthesia analysing studies that assessed the value of cardiopulmonary exercise testing (CPET) in evaluating risk in patients undergoing non-cardiopulmonary surgery [1]. Cardiopulmonary exercise testing is increasingly used in the pre-operative assessment of patients undergoing major surgery. Studies have shown a relationship between pre-operative CPET values and mortality [2], postoperative complications and length of hospital stay [3]. Our aim was to determine whether CPET measures might predict postoperative length of stay in both the critical care unit and hospital, in patients undergoing major surgery. We hoped CPET might then assist in better planning and organisation of peri-operative care. We retrospectively analysed data of all 325 patients who had undergone CPET at a large tertiary centre over a 26-month period (January 2008 to March 2010). To achieve some homogeneity in our sample, we selected a subgroup of patients undergoing major vascular or upper gastro-intestinal surgery for further analysis (n = 112). We acquired length of stay data from critical care admission records, hospital notes and discharge letters. We then estimated Spearman correlation coefficients for typical pre-operative CPET measures (anaerobic threshold, peak oxygen consumption and ventilatory equivalents for carbon dioxide (VE/VCO2)) and postoperative length of stay for critical care and hospital. A value of p < 0.05 was considered significant (two-sided). Two out of the 112 patients (1.8%) undergoing major vascular or upper gastro-intestinal surgery died. Median (IQR [range]) length of stay in critical care was 70 (46–110 [18–928]) h and in hospital was 10 (7–15 [3–51]) days. There were no significant correlations between any of the CPET measures and length of stay in either critical care or hospital (Table 1). Therefore, in our series, pre-operative CPET data were not useful in predicting lengths of stay in critical care or hospital. Our negative results may be explained by two reasons. Firstly, the factors influencing a patient’s length of stay are numerous and complex, for example a lack of beds, day of the week, social circumstances and the patient’s surgical team. Secondly, although efforts were made to correct for patients’ heterogeneity, this could have been improved further by comparing patients undergoing more similar procedures, for example, upper gastro-intestinal surgery only, as previous authors have suggested that different types of surgery may differ in sensitivity to CPET values [1]. We look forward to the results of further studies looking in more detail at the outcomes of surgical patients who have undergone pre-operative CPET testing. No external funding and no competing interests declared. Previously posted at the Anaesthesia Correspondence website: http://www.anaesthesiacorrespondence.com. Published with the permission of the Trust's Caldicott guardian.

Impact of Oral Sildenafil on Exercise Performance in Children and Young Adults After the Fontan Operation

Background— Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity. Methods and Results— This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL. Conclusions— In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00507819.