Mixed Venous Oxygen Content Research Articles

Beyond VO2: the complex cardiopulmonary exercise test.

Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for 'complex' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin-1ꞏkg-1. The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (β=0.46, P<0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (β=0.72, P<0.001), peak arterial mixed venous oxygen content difference (β=0.56, P<0.001), and resting mean pulmonary arterial pressure (β=-0.25, P=0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (β=0.35, P=0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, P<0.001; peak oxygen consumption: ρ=0.56, P<0.001) and weakly correlated with ventilatory efficiency (ρ=-0.32, P=0.007). Conclusions Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

Metabolic, ventilatory and cardiovascular responses to FES-cycling: A comparison to NMES and passive cycling.

Cyclergometry with functional electrical stimulation (FES-cycling) is a feasible method for rehabilitation. The concept is to promote exercise induced by depolarization of the motoneuron and muscular contraction. To measure acute physiological responses to FES-cycling. Retrospective study of data from ten healthy volunteers who performed FES-cycling, passive cycling and neuromuscular electrical stimulation (NMES) alone. Metabolic, ventilatory and cardiovascular parameters were analyzed. Oxygen uptake enhanced 97 ± 15% during FES-cycling, with medium effect size compared to NMES and large effect size compared to passive cycling. Energy expenditure enhanced 102 ± 15% during FES-cycling, with medium effect size compared to NMES and large effect size compared to passive cycling. Minute ventilation enhanced 115 ± 26% during FES-cycling, with small effect size compared to NMES and medium effect size compared to passive cycling. Cardiac output enhanced 21 ± 4% during FES-cycling, with medium effect size compared to NMES and passive cycling. Arterial - mixed venous oxygen content difference enhanced 60 ± 8% during FES-cycling, with a medium effect size compared to NMES and large effect size compared to passive cycling. FES-cycling enhances metabolic, ventilatory and cardiovascular demands and the physiological responses are higher than NMES and passive cycling.

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses.

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10min of dobutamine infusion (2µgkg-1 min-1 ). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.

Comparison of different methods to calculate venous admixture in anaesthetized horses

ObjectiveThe aim of this study was to compare different methods to determine venous admixture (Q˙s/Q˙t) in anaesthetized horses. The first objective was to estimate Q˙s/Q˙t using jugular venous blood oxygen content (Q˙s/Q˙t jugular), and a fixed value for the oxygen extraction (F-shunt). The second objective was to assess the influence of blood pressure and positioning on oxygen extraction. The third objective was to perform regression analysis between jugular and mixed venous blood oxygen tensions. Study designProspective, experimental trial. AnimalsThe study was performed with seven warmblood horses that were anaesthetized with detomidine, butorphanol, ketamine, diazepam and isoflurane in oxygen. MethodsMultiple simultaneous arterial, jugular venous and pulmonary arterial blood samples were taken under normotensive and hypotensive conditions in lateral and dorsal recumbency. Arterial, mixed venous, and end-capillary oxygen content were calculated. ResultsA significant correlation between Q˙s/Q˙t and Q˙s/Q˙t jugular was found [intraclass correlation coefficient (ICC) = 0.68, p < 0.001], and Bland–Altman analysis showed a bias of –11.5% and wide limits of agreement (–27.7% to 4.6%). F-shunt significantly correlated with Q˙s/Q˙t (ICC = 0.88, p < 0.001), and Bland–Altman analysis showed a lower bias (–1.97) and narrower limits of agreement (–13.8% to 9.9%). Positioning and blood pressure significantly influenced oxygen extraction. The regression formula was Y = 0.80X + 2.61 (where Y is the calculated mixed venous oxygen tension and X is the jugular venous oxygen tension) when outliers were excluded (ICC=0.82, p < 0.001). Conclusions and clinical relevanceThis study shows that F-shunt provides reasonable estimates of Q˙s/Q˙t but can possibly be improved by using simple algorithms without the need for pulmonary arterial catheterization. These algorithms use blood pressure- and positioning-dependent oxygen extraction and regression analysis between jugular venous and pulmonary arterial oxygen tension. Although promising, the validity of these algorithms needs to be determined in future studies.

Validating the Physiologic Model HumMod as a Substitute for Clinical Trials Involving Acute Normovolemic Hemodilution.

Blood conservation strategies and transfusion guidelines remain a heavily debated clinical topic. Previous investigational trials have shown that acute isovolemic hemodilution does not limit adequate oxygen delivery; however, a true critical hemoglobin level has never been investigated or defined due to safety concerns for human volunteers. Validated physiologic modeling may be useful to investigate hemodilution at critical hemoglobin levels without the ethical or safety hazards of clinical trials. Our hypothesis is that HumMod, an integrative physiological model, can replicate the cardiovascular and metabolic findings of previous clinical studies of acute isovolemic hemodilution and use coronary blood flow and coronary oxygen delivery in extreme hemodilution to predict a safety threshold. By varying cardiovascular and sizing parameters, unique individuals were generated to simulate a population using HumMod, an integrative mathematical model of human physiology. Hemodilution was performed by simultaneously hemorrhaging 500 mL aliquots of blood while infusing equal volumes of hetastarch, 5% albumin balanced salt solution, or triple volumes of lactated Ringer's solution over 10 minutes. Five hemodilution protocols reported over 3 studies were directly replicated with HumMod to compare and validate essential cardiovascular and metabolic responses to hemodilution in moderately healthy, awake adults. Cardiovascular parameters, mental status, arterial and mixed venous oxygen content, and oxyhemoglobin saturation were recorded after the removal of each aliquot. The outputs of this simulation were considered independent variables and were stratified by hemoglobin concentration at the time of measurement to assess hemoglobin as an independent predictor of hemodynamic and metabolic behavior. The published reports exhibited discrepancies: Weiskopf saw increased heart rate and cardiac index, while Jones and Ickx saw no change in these variables. In HumMod, arterial pressure was maintained during moderate hemodilution due to decreases in peripheral resistance opposing increases in cardiac index. HumMod showed preserved ventilation through moderate hemodilution, compensated for by an increased oxygen extraction similar to the studies of Jones and Ickx. The simulation results qualitatively followed the clinical studies, but there were statistical differences. In more extreme hemodilution, HumMod had a lesser increase in cardiac index, which led to deficiencies in oxygen delivery and low venous saturation. In the simulations, coronary blood flow and oxygen delivery increase up to a critical hemoglobin threshold of 55-75 g/L in HumMod. In this range, coronary blood flow and oxygen delivery fell, leading to cardiac injury. The allowable amount of hemodilution before reaching the critical point is most closely correlated with nonmuscle mass (r = 0.69) and resting cardiac output (r = 0.67). There were significant statistical differences in the model population and the clinical populations, but overall, the model responses lay within the clinical findings. This suggests our model is an effective replication of hemodilution in conscious, healthy adults. A critical hemoglobin range of 5.5-7.5 g/L was predicted and found to be highly correlated with nonmuscle mass and resting cardiac output.

Exercise Facilitates Early Detection of Cardiac and Vascular Remodelling During Development of Chronic Thrombo‐Embolic Pulmonary Hypertension in a Novel Swine Model

BackgroundPulmonary hypertension (PH) is a chronic disease of the pulmonary vasculature characterized by impaired pulmonary hemodynamics and vascular remodeling which often progresses to right heart failure with high mortality. One subform of PH is chronic thrombo‐embolic pulmonary hypertension (CTEPH) which develops in 4% of patients after a pulmonary embolism and is characterized by remodeling of the distal, unobstructed pulmonary vasculature.PurposeHere we studied the progression of pulmonary vascular disease as well as the adaptation of the right ventricle to the increased after load, by repeated measurement of hemodynamics at rest and during graded treadmill exercise in a novel swine model of CTEPH.MethodsSwine (n=16) of either sex (23±1kg) were chronically instrumented with catheters (right ventricle (RV), pulmonary artery, left atrium and aorta) for hemodynamic measurements and blood sampling. Additionally, a flow probe was placed around the ascending aorta to measure cardiac output. CTEPH was induced in 8 swine by up to 4 weekly infusions of microspheres (Ø700μm, total ~40,000.‐spheres) into the pulmonary circulation, followed by 4–6 weeks of follow‐up without embolisations. In addition, the CTEPH animals received daily L‐NG‐Nitroarginine methyl ester (L‐NAME) i.v. (30mg·kg−1·day−1, week 1–7), During total follow‐up (7–10 weeks), hemodynamics at rest and during exercise were obtained. RV dimensions were weekly assessed using echocardiography.ResultsRepeated embolisation of the pulmonary vasculature resulted in a progressive increase in mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance index (tPVRi, Table). tPVRi did not change during exercise in either the control or CTEPH swine. At the end of the embolisation period at 4 weeks, the increase in MPAP during exercise was maintained in CTEPH swine while the increase in cardiac index (CI) was attenuated. Despite a lower arterial oxygen content (CaO2) in CTEPH swine, body oxygen consumption (BVO2) was maintained at rest and during exercise by an increase in oxygen extraction resulting in a decreased mixed venous oxygen content (CVO2). After 8 weeks of follow‐up, the increase of MPAP and tPVRi and decrease of CI were sustained at rest, while oxygen extraction in CTEPH swine had returned towards control levels. However, although CI did increase during exercise, the exercise‐induced increase in BVO2 was attenuated due to arterial desaturation.The sustained increase in after load resulted in RV dilation (RV end‐diastolic area index increased from 27±2mm2·kg−1 to 35±3mm2·kg−1 in control vs CTEPH, week 8, P=0.03) and RV hypertrophy (Fulton index increased from 0.44±0.01 to 0.52±0.03, P=0.02).ConclusionsRepeated embolization results in CTEPH in swine, with a progressive increase in tPVRi. The early phase of CTEPH is characterized by RV dilation and dysfunction, as evidenced by the inability of the RV to increase CI commensurate with the increase in body oxygen consumption. When PH is sustained, RV hypertrophy occurs, which, together with an increase in heart rate is able to increase CI during exercise.Support or Funding InformationCVON2012‐08‐PHAEDRA Effect of exercise and time on hemodynamic and oxygenation status in CTEPH development. Variable Follow‐up (wk) CON rest CON ex CTEPH rest CTEPH ex MPAP (mmHg) 0 19 ± 1 33 ± 2* 22 ± 1# 33 ± 3* 4 19 ± 1 34 ± 2* 32 ± 4^# 56 ± 8*# 8 21 ± 1 38 ± 5* 41 ± 8^# 68 ± 10*# tPVRi (mmHg·L−1·kg−1) 0 106 ± 7 121 ± 11 92 ± 6 97 ± 11 4 118 ± 8 124 ± 9 151 ± 29^ 216 ± 39# 8 120 ± 10 159 ± 20 374 ± 147^# 323 ± 51# Cl (L·kg−1) 0 0.18 ± 0.01 0.28 ± 0.03* 0.25 ± 0.03# 0.35 ± 0.03* 4 0.17 ± 0.01 0.28 ± 0.02* 0.21 ± 0.06^ 0.27 ± 0.03 8 0.16 ± 0.01 0.25 ± 0.02* 0.14 ± 0.02^$ 0.22 ± 0.02* BVO2i (mmol·min−1·kg−1) 0 0.45 ± 0.02 1.09 ± 0.08* 0.58 ± 0.08^ 1.36 ± 0.16*# 4 0.43 ± 0.03 1.18 ± 0.10* 0.64 ± 0.16 1.05 ± 0.12* 8 0.45 ± 0.03 1.25 ± 0.09* 0.31 ± 0.06$ 0.85 ± 0.08*# CaO2 (mL O2·dL−1) 0 5.75 ± 0.22 5.53 ± 0.23 5.53 ± 0.22 5.69 ± 0.12 4 5.89 ± 0.21 6.52 ± 0.31* 5.45 ± 0.18$ 5.99 ± 0.29*# 8 6.03 ± 0.25 6.90 ± 0.25* 5.86 ± 0.26 6.14 ± 0.21$ CvO2 (mL O2·dL−1) 0 3.34 ± 0.20 1.87 ± 0.16* 3.40 ± 0.10 2.03 ± 0.17* 4 3.32 ± 0.16 2.41 ± 0.23* 2.90 ± 0.29$ 1.99 ± 0.38*$ 8 3.32 ± 0.18 2.06 ± 0.30* 3.16 ± 0.21 1.58 ± 0.39* p&lt;0.05 effect of exercise; p&lt;0.05 compared to week 0 all at rest; p&lt;0.05, p&lt;0.1 CTEPH vs Control same week and exercise level; con, control animals; ex, exercise.

Noninvasive estimation of mixed venous oxygen content [J Phys Fitness Sports Med, 3 (1): 27-33 (2014)

Noninvasive estimation of mixed venous oxygen content [J Phys Fitness Sports Med, 3 (1): 27-33 (2014)

Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia

The aim of this study was to evaluate the correlation of commonly used oxygenation indices with venous admixture (Qs/Qt) in anaesthetised horses under different infusion rates of dobutamine. Six female horses were anaesthetised with acepromazine, xylazine, diazepam, ketamine, and isoflurane, and then intubated and mechanically ventilated with 100% O2. A Swan–Ganz catheter was introduced into the left jugular vein and its tip advanced into the pulmonary artery. Horses received different standardised rates of dobutamine.For each horse, eight samples of arterial and mixed venous blood were simultaneously obtained at fixed times. Arterial and venous haemoglobin (Hb) concentration and O2 saturation, arterial oxygen partial pressure (PaO2), venous oxygen partial pressure (PvO2), and barometric pressure were measured. Arterial (CaO2), mixed venous (CvO2), and capillary (Cc′O2) oxygen contents were calculated using standard formulae. The correlations between F-shunt, arterial oxygen tension to fraction of inspired oxygen ratio (PaO2/FiO2), arterial to alveolar oxygen tension ratio (PaO2/PAO2), alveolar to arterial oxygen tension difference (P[A − a]O2), and respiratory index (P[A − a]O2/PaO2) were tested with linear regression analysis. The goodness-of-fit for each calculated formula was evaluated by means of the coefficient of determination (r2). The agreement between Qs/Qt and F-shunt was analysed with the Bland–Altman test.All tested oxygen tension-based indices were weakly correlated (r2 < 0.2) with the Qs/Qt, whereas F-shunt showed a stronger correlation (r2 = 0.73). F-shunt also showed substantial agreement with Qs/Qt independent of the dobutamine infusion rate. F-shunt better correlated with Qs/Qt than other oxygen indices in isoflurane-anaesthetised horses under different infusion rates of dobutamine.

A practical method of measuring oxygen consumption in children with complex mixing circulations by the use of thermodilution cardiac output studies

We describe a method to measure oxygen consumption (VO2) and pulmonary vascular resistive index (PVRI) based on thermodilution cardiac output in patients with complex mixing circulations. We apply this method to patients with a bidirectional cavopulmonary anastomosis (BDCPA). We compare our measured VO2 with a predicted VO2 based on a formula using height and weight. We reviewed data based on cardiac catheterization and thermodilution cardiac output in a series of 25 catheterizations in patients with BDCPA. We used this data to measure VO2 and PVRI, and looked for a correlation between the predicted and measured VO2. We also assessed whether any other hemodynamic parameter correlated with measured VO2. There was no significant correlation between the predicted and the measured VO2 (correlation coefficient=-0.258, P=.21). We did find a significant correlation in the difference between the measured and predicted VO2 against the measured VO2 such that at a lower measured VO2 the predictive formula tended to overestimate VO2 and at a higher VO2 the formula underestimated VO2 (correlation coefficient=0.963, P<.0001). Body surface area did not correlate with measured VO2 (correlation coefficient=0.28, P<.16). Mixed venous oxygen content showed a weak negative correlation with VO2 (correlation coefficient=-0.54, P=.005). An assessment of PVRI that is based on a predicted VO2 is unreliable in this patient population. No hemodynamic parameter correlated well with VO2. The use of a measured VO2 is necessary in determining PVRI in these patients.

Use of the oxygen content–based index, Fshunt, as an indicator of pulmonary venous admixture at various inspired oxygen fractions in anesthetized sheep

To evaluate the use of the oxygen content-based index, Fshunt, as an indicator of venous admixture (Qs/Qt) at various fractions of inspired oxygen (FIO(2)s) in anesthetized sheep undergoing Flung or 2-lung ventilation. Animals-6 healthy adult female sheep. Sheep were anesthetized and administered 5 different FIO(2)s (0.21, 0.40, 0.60, 0.80, and 1.00) in random order during 2-lung mechanical ventilation. Arterial and mixed venous blood samples were obtained at each FIO(2) after a 15-minute stabilization period. Vital capacity alveolar recruitment maneuvers were performed after blood collection. The previously used FIO(2) sequence was reversed for sample collection during Flung ventilation. Blood samples were analyzed for arterial, pulmonary end-capillary, and mixed venous oxygen content and partial pressure and for hemoglobin concentration. Oxygen hemoglobin saturation, Qs/Qt, Fshunt, and oxygen tension-based indices (OTIs; including PAO(2):FIO(2), alveolar-arterial difference in partial pressure of oxygen [PAO(2) - PAO(2)], [PAO(2) - Pao(2)]:FIO(2), [PAO(2) - PAO(2)]:PAO(2), and PAO(2):PAO(2)) were calculated at each FIO(2); associations were evaluated with linear regression analysis, concordance, and correlation tests. Intermethod agreement between Qs/Qt and Fshunt was tested via Bland-Altman analysis. Strong and significant associations and substantial agreement were detected between Fshunt and Qs/Qt. Relationships between OTIs and Qs/Qt varied, but overall correlations were weak. Conclusions and Clinical Relevance-Whereas OTIs were generally poor indicators of Qs/Qt, Fshunt was a good indicator of Qs/Qt at various FIO(2)s, regardless of the magnitude of Qs/Qt, and could be potentially used as a surrogate for Qs/Qt measurements in healthy sheep.

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Update COPD 2011 – Was ist neu?

Im letzten Jahr waren im Bereich der COPD (chronisch obstruktive Lungenerkrankung) eine ganze Reihe interessanter Entwicklungen zu verzeichnen. Durch Weiterentwicklung von Klassifikationssystemen (BODE-Index) ist es gelungen, die Mortalität von COPD-Patienten wesentlich besser vorherzusagen als bisher. In der medikamentösen Therapie hat sich bei häufigen Exazerbationen, die oft zu Krankenhausaufenthalten führen, der erste 2010 zugelassene Vertreter der Substanzgruppe der Phosphodiesterase-4-Inhibitoren Roflumilast als interessant gezeigt. Das erste über 24 Stunden wirksame inhalierbare Beta-2-Mimetikum Indacaterol erweitert die medikamentösen Therapiemöglichkeiten zusätzlich. Zu den nicht-medikamentösen Therapieoptionen zählen die Lungenvolumenreduktion sowie moderne endoskopische Techniken zur Therapie des Lungenemphysems, ebenso wie die wichtige chronische nicht-invasive Beatmungstherapie. Eine weitere nicht-medikamentöse COPD-Therapie, die einen etwas ungewöhnlichen Ansatz verfolgt, ist die Implantation einer peripheren AV-Fistel, die letztlich wie ein Dialyse-Shunt funktioniert. Die Therapie ist in Deutschland bereits zugelassen, wird momentan jedoch ausschließlich im Rahmen von Studien angewendet.

Norepinephrine causes a pressure‐dependent plasma volume decrease in clinical vasodilatory shock

Recent experimental studies have shown that a norepinephrine-induced increase in blood pressure induces a loss of plasma volume, particularly under increased microvascular permeability. We studied the effects of norepinephrine-induced variations in the mean arterial pressure (MAP) on plasma volume changes and systemic haemodynamics in patients with vasodilatory shock. Twenty-one mechanically ventilated patients who required norepinephrine to maintain MAP > or =70 mmHg because of septic/postcardiotomy vasodilatory shock were included. The norepinephrine dose was randomly titrated to target MAPs of 60, 75 and 90 mmHg. At each target MAP, data on systemic haemodynamics, haematocrit, arterial and mixed venous oxygen content and urine flow urine were measured. Changes in the plasma volume were calculated as 100 x (Hct(pre)/Hct(post)-1)/ (1-Hct(pre)), where Hct(pre) and Hct(post) are haematocrits before and after intervention. Norepinephrine doses to obtain target MAPs of 60, 75 and 90 mmHg were 0.20+/-0.18, 0.29+/-0.18 and 0.42+/-0.31 microg/kg/min, respectively. From 60 to 90 mmHg, increases in the cardiac index (15%), systemic oxygen delivery index (25%), central venous pressure (CVP) (20%) and pulmonary artery occlusion pressure (33%) were seen, while the intrapulmonary shunt fraction was unaffected by norepinehrine. Plasma volume decreased by 6.5% and 9.4% (P<0.0001) when blood pressure was increased from 60 to 75 and 90 mmHg, respectively. MAP (P<0.02) independently predicted the decrease in plasma volume with norepinephrine but not CVP (P=0.19), cardiac index (P=0.73), norepinephrine dose (P=0.58) or urine flow (P=0.64). Norepinephrine causes a pressure-dependent decrease in the plasma volume in patients with vasodilatory shock most likely caused by transcapillary fluid extravasation.

An Arteriovenous Fistula Increases Exercise Capacity in Patients With COPD

Supplemental oxygen usually increases exercise capacity in hypoxemic COPD, but some patients are refractory because of venous admixture. An arteriovenous fistula (AVF) with left-to-right shunt increases mixed venous oxygen content and cardiac output; therefore, this might improve arterial oxygen delivery. We hypothesized that creation of an AVF would therefore increase exercise capacity in severe COPD. We created an AVF in 12 patients with severe hypoxemic COPD: mean (SD) age, 66 (6) years; Pao(2), 57.5 (3.0) mm Hg, and FEV(1), 19% (8%) predicted. We measured 6-min walk distance (6MWD) while the subjects were breathing room air and again while they were breathing portable supplemental oxygen at baseline, 6 weeks, and 12 weeks after creation of an AVF in the iliofemoral region. After surgery, the mean (SEM) 6MWD increased from 217 (63) m at baseline to 272 (18) m and 276 (25) m, 6 weeks and 12 weeks after surgery, respectively. Patients who walked > 54 m further while breathing supplemental oxygen at baseline (n = 5) increased 6MWD while breathing room air by 129 (34) m after 6 weeks (P = .02) and by 124 (29) m after 12 weeks (P = .004). Walking distance did not change in patients who did not have a clinically meaningful response to oxygen at baseline. An iliofemoral AVF increased 6MWD patients with severe COPD, matching the improvement seen with supplemental oxygen. An initial response to supplemental oxygen predicted a therapeutic response to the AVF.

Venous Admixture in COPD: Pathophysiology and Therapeutic Approaches

Chronic obstructive and interstitial lung diseases impair pulmonary gas exchange leading to wasted ventilation (alveolar dead space) and wasted perfusion (venous admixture). These two fundamental types of abnormality represent opposite ends of the spectrum of ventilation-perfusion mismatch with V˙/Q˙ ratios of infinity and zero. Treatment approaches that improve airway function, reduce air trapping and hyperinflation have received much attention and might be successful at ameliorating the problems associated with high V˙/Q˙. However, in patients with low V˙/Q˙ abnormality in whom venous admixture leads to hypoxemia, there are few therapeutic options. Indeed, some patients are refractory to treatment with supplemental oxygen particularly during exercise. Theoretically these patients could benefit from an intervention that increased mixed venous oxygen content thereby ameliorating the deleterious effects of venous admixture. In this perspective article we discuss the mechanisms whereby venous admixture contributes to hypoxemia and reduced oxygen delivery to tissues. We explore methods which could potentially increase mixed venous oxygen content thus ameliorating the deleterious effects of venous admixture. One such intervention that warrants further investigation is the therapeutic creation of an arterio-venous fistula. Such an approach would be novel, simple and minimally invasive. There is reason to believe that complications would be minor leading to a favorable risk-benefit analysis. This approach to treatment could have significant impact for patients with COPD but should also benefit any patient with chronic hypoxemia that impairs exercise performance.

IMPROVED EXERCISE PERFORMANCE WITH SUPPLEMENTAL OXYGEN PREDICTS A BENEFICIAL RESPONSE TO THERAPEUTIC ARTERIOVENOUS FISTULA IN PATIENTS WITH SEVERE COPD

PURPOSE: An arterio-venous fistula (AVF) raises mixed venous oxygen content and might thereby lessen the adverse consequences of venous admixture (physiological shunt) in patients with chronic lung disease. We hypothesized that therapeutic creation of an AVF in patients with severe COPD would thereby enhance oxygen delivery and improve exercise performance.

The Effects on Arterial Haemoglobin Oxygen Saturation and on Shunt of Increasing Cardiac Output with Dopamine or Dobutamine during One-lung Ventilation

Theoretically, if the cardiac output were increased in the presence of a given intrapulmonary shunt, the arterial saturation should improve as the venous oxygen extraction per ml of blood decreases if the total oxygen consumption remains constant. Previous work demonstrated that this was not achieved with adrenaline or isoprenaline as increased shunting negated any benefit from improved cardiac output and mixed venous oxygen content. However pharmacological stimulation of cardiac output and venous oxygen without any increase in shunt should achieve the goal of improved arterial oxygenation. To test this hypothesis, seven pigs were subjected to one-lung ventilation and infused on separate occasions, with dopamine and with dobutamine in random order to increase the cardiac output. The mixed venous oxygen content, shunt fraction, oxygen consumption and arterial oxygen saturation were measured. With both dopamine and dobutamine there was a consistent rise in venous oxygen content. However, with dopamine, the mean shunt rose from 28% to 42% and with dobutamine, the mean shunt rose from 45% to 59% (both changes P<0.01). With dopamine, the mean arterial oxygen saturation fell by 4.7%, and with dobutamine by 2.9%, but neither fall was statistically significant. It is concluded that any benefit to arterial saturation which might occur from a dopamine- or dobutamine-induced increase in mixed venous oxygen content during one-lung ventilation is offset by increased shunting. During one-lung anaesthesia, there would appear to be no benefit to arterial saturation in increasing cardiac output with an infusion of either dopamine or dobutamine.

Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia.

Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 microg. kg(-1). min(-1); each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 +/- 13 dynes. cm(-5). m(-2) versus 202 +/- 16 dynes. cm(-5). m(-2)) and a decrease in oxygen delivery index (health: 842 +/- 66 mL. min(-2). m(-2) versus 475 +/- 38 mL. min(-2). m(-2); endotoxemia: 1073 +/- 49 mL. min(-2). m(-2) versus 613 +/- 44 mL. min(-2). m(-2)) and mixed venous oxygen content (health: 63% +/- 2% versus 47% +/- 2%; endotoxemia: 68% +/- 2% versus 51% +/- 3%; P < 0.001 each). Small doses of DPX (1 and 5 microg. kg(-1). min(-1)) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 microg. kg(-1). min(-1)) also reduced mean pulmonary arterial pressure in endotoxemia (27 +/- 1 mm Hg versus 23 +/- 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 +/- 4 mm Hg versus 80 +/- 3 mm Hg) and heart rate increased (84 +/- 4 bpm versus 136 +/- 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.