Mixed Venous Oxygen Tension Research Articles

Mixed venous oxygen tension is a crucial prognostic factor in pulmonary hypertension: a retrospective cohort study

BackgroundThe prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH.MethodsWe retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2 < 35 mmHg) and identified their prognostic factors based on the pulmonary hypertension risk stratification guidelines.ResultsSurvival was significantly poorer in patients with tissue hypoxia than in those without it for PAH (P = 0.001) and CTEPH (P = 0.017) treated with selective pulmonary vasodilators. In patients with PAH, PvO2 more strongly correlated with prognosis than other hemodynamic prognostic factors regardless of selective pulmonary vasodilators usage. PvO2 was the only significant prognostic factor in patients with CTEPH treated with pulmonary hypertension medication. Patients with CTEPH experiencing tissue hypoxia exhibited significantly poorer survival than those in the intervention group (P < 0.001). PvO2 more strongly correlated with the cardiac index (CI) than the alveolar-arterial oxygen gradient (A-aDO2) in PAH; whereas in CTEPH, PvO2 was more strongly correlated with A-aDO2 than with CI.ConclusionsPvO2 may represent a crucial prognostic factor for pulmonary hypertension. The prognostic impact of tissue hypoxia affects different aspects of PAH and CTEPH, thereby reflecting their distinct pathogenesis.

The physiological basis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right ventricular (RV) failure. In spite of extensive pulmonary vascular remodelling, lung function in PAH is generally well preserved, with hyperventilation and increased physiological dead space, but minimal changes in lung mechanics and only mild to moderate hypoxaemia and hypocapnia. Hypoxaemia is mainly caused by a low mixed venous oxygen tension from a decreased cardiac output. Hypocapnia is mainly caused by an increased chemosensitivity. Exercise limitation in PAH is cardiovascular rather than ventilatory or muscular. The extent of pulmonary vascular disease in PAH is defined by multipoint pulmonary vascular pressure–flow relationships with a correction for haematocrit. Pulsatile pulmonary vascular pressure–flow relationships in PAH allow for the assessment of RV hydraulic load. This analysis is possible either in the frequency domain or in the time domain. The RV in PAH adapts to increased afterload by an increased contractility to preserve its coupling to the pulmonary circulation. When this homeometric mechanism is exhausted, the RV dilates to preserve flow output by an additional heterometric mechanism. Right heart failure is then diagnosed by imaging of increased right heart dimensions and clinical systemic congestion signs and symptoms. The coupling of the RV to the pulmonary circulation is assessed by the ratio of end-systolic to arterial elastances, but these measurements are difficult. Simplified estimates of RV–pulmonary artery coupling can be obtained by magnetic resonance or echocardiographic imaging of ejection fraction.

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and a target range of 91–95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial PaO2, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO2, and SpO2 in the management of PPHN. Translational and clinical studies suggest maintaining a PaO2 of 50–80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO2 or PO2. Also, most critically ill patients have umbilical arterial catheters and postductal PaO2 may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 target ranges for the management of PPHN and compare outcomes.

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Validity of Peripheral Capillary Oxygen Saturation and Normal Mixed Venous Oxygen Tension in Measurement of O2 Content

Background The change in venous oxygen saturation occurs earlier, and even its reduction is faster than arterial oxygen saturation. The aim of this study was to validate SvO2 and PvO2 for O2 content measurement in children hospitalized with respiratory distress. Materials and Methods In this cross-sectional study, 80 children who were admitted with respiratory distress were included in the study according to the study inclusion and exclusion criteria. Baseline characteristics such as age and gender were recorded in the data collection form, designed by the researcher. In order to determine the amount of SaO2 and PaO2 the arterial blood sample was prepared, venous blood sample was prepared to determine the amount of hemoglobin, SvO2 and PvO2. The gold standard for the determination of O2 content was the arterial blood sample. All samples were examined by a blood gas analyzer and then calculated using the formula of O2 content values. For SvO2 and PvO2 validation, we used diagnostic analysis methods including sensitivity, specificity, positive and negative predictive values. Cut-point value for SvO2 and PvO2 were 76.50 and 44.30, respectively. Results In this study, the patients’ mean age was 5.15 ± 4.20 years. 62.5% (n=50) were male and 38.5% (n=30) were female. The values ​​of arterial and venous O2 content were 14.13 ± 3.05 and 11.95 ± 3.04 from a total of 80 patients. SvO2 and PvO2 for measuring O2 content had a sensitivity of 80.5 and 71.80%, respectively, and specificity of 80.5 and 78%, respectively. Conclusion SvO2 and PvO2 have good validity for evaluating O2 content in patients admitted to PICU. So that SvO2 had a sensitivity and specificity of over 80%, and PvO2 had a sensitivity and specificity of over 70%.

Pulmonary hypertension with a low cardiac index requires a higher PaO2 level to avoid tissue hypoxia.

The optimal oxygen supplementation needed to avoid tissue hypoxia in patients with pulmonary hypertension (PH) remains unclear. This study aimed to identify the arterial oxygen tension (PaO2 ) level needed to avoid tissue hypoxia which results in a poor prognosis in patients with PH. We retrospectively analysed the data for 1571 right heart catheterizations in patients suspected of having PH between 1983 and 2017 at our institution. Examinations were classified according to mean pulmonary arterial pressure (mPAP), cardiac index (CI) and the presence of lung disease, pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH). The PaO2 levels needed to avoid tissue hypoxia were compared in each subgroup. The estimated PaO2 equivalent to a mixed venous oxygen tension (PvO2 ) of 35 mm Hg (tissue hypoxia) was 63.2 mm Hg in all patients, 77.0 mm Hg in those with decreased CI (<2.5 L/min/m2 ) and 57.0 mm Hg in those with preserved CI. Multivariate regression analysis identified mPAP, CI and PaO2 to be independent predictors of extremely low PvO2 . Similar results were observed regardless of the severity of PH or the presence of lung disease, PAH or CTEPH. The PaO2 level needed to avoid tissue hypoxia was higher in patients with mild PH and decreased CI than in those with severe PH and preserved CI (70.2 vs 61.5 mm Hg). These findings indicate that a decreased CI rather than increased mPAP induces tissue hypoxia in PH. Patients with PH and decreased CI may need adjustment of oxygen therapy at higher PaO2 levels compared with patients with preserved CI.

Dobutamine and Nitroglycerin Versus Milrinone for Perioperative Management of Pulmonary Hypertension in Mitral Valve Surgery. A Randomized Controlled Study

To compare the effects of dobutamine and nitroglycerin to milrinone in young patients with severe pulmonary hypertension undergoing mitral valve replacement. A prospective randomized, double-blinded, controlled study. Single university hospital. Forty patients had systolic pulmonary arterial pressure ≥60 mmHg and were scheduled for elective mitral valve replacement. The patients were divided randomly into 2 equal groups according to the drugs given during the study. The patients in group I received 5 to 20 µg/kg/min of dobutamine and 0.5 to 3 µg/kg/min of nitroglycerin, and patients in group II received a loading dose of milrinone, 50 µg/kg over 10 minutes, followed by a maintenance dose of 0.25 to 0.75 µg/kg/min. The primary outcome was the effects of interventional drugs on mean pulmonary artery pressure. The secondary outcomes were the effects of interventional drugs on systemic and pulmonary hemodynamic parameters measured from induction of anesthesia until the first 12 hours in the intensive care unit stay. There was a more significant decrease in mean pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure in group II than group I at all time points after cardiopulmonary bypass. There were more significant increases in heart rate, mean arterial pressure, cardiac output, and mixed venous oxygen tension in group I than group II, which became more obvious in time. In both groups, there was a significant decrease in systemic vascular resistance and pulmonary vascular resistance at all times. Milrinone provides adequate cardiac performance, causing a greater reduction in pulmonary artery pressure and pulmonary capillary wedge pressure.

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.

Effects of Changes in Arterial Carbon Dioxide and Oxygen Partial Pressures on Cerebral Oximeter Performance.

Cerebral oximetry (cerebral oxygen saturation; ScO2) is used to noninvasively monitor cerebral oxygenation. ScO2 readings are based on the fraction of reduced and oxidized hemoglobin as an indirect estimate of brain tissue oxygenation and assume a static ratio of arterial to venous intracranial blood. Conditions that alter cerebral blood flow, such as acute changes in PaCO2, may decrease accuracy. We assessed the performance of two commercial cerebral oximeters across a range of oxygen concentrations during normocapnia and hypocapnia. Casmed FORE-SIGHT Elite (CAS Medical Systems, Inc., USA) and Covidien INVOS 5100C (Covidien, USA) oximeter sensors were placed on 12 healthy volunteers. The fractional inspired oxygen tension was varied to achieve seven steady-state levels including hypoxic and hyperoxic PaO2 values. ScO2 and simultaneous arterial and jugular venous blood gas measurements were obtained with both normocapnia and hypocapnia. Oximeter bias was calculated as the difference between the ScO2 and reference saturation using manufacturer-specified weighting ratios from the arterial and venous samples. FORE-SIGHT Elite bias was greater during hypocapnia as compared with normocapnia (4 ± 9% vs. 0 ± 6%; P < 0.001). The INVOS 5100C bias was also lower during normocapnia (5 ± 15% vs. 3 ± 12%; P = 0.01). Hypocapnia resulted in a significant decrease in mixed venous oxygen saturation and mixed venous oxygen tension, as well as increased oxygen extraction across fractional inspired oxygen tension levels (P < 0.0001). Bias increased significantly with increasing oxygen extraction (P < 0.0001). Changes in PaCO2 affect cerebral oximeter accuracy, and increased bias occurs with hypocapnia. Decreased accuracy may represent an incorrect assumption of a static arterial-venous blood fraction. Understanding cerebral oximetry limitations is especially important in patients at risk for hypoxia-induced brain injury, where PaCO2 may be purposefully altered.

Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery

To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

Pulmonary Shunt Is Independent of Decrease in Cardiac Output during Unsupported Spontaneous Breathing in the Pig

During mechanical ventilation (MV), pulmonary shunt is cardiac output (CO) dependent; however, whether this relationship is valid during unsupported spontaneous breathing (SB) is unknown. The CO dependency of the calculated venous admixture was investigated, with both minor and major shunt, during unsupported SB, MV, and SB with continuous positive airway pressure (CPAP). In seven anesthetized supine piglets breathing 100% oxygen, unsupported SB, MV (with tidal volume and respiratory rate corresponding to SB), and 8 cm H2O CPAP (airway pressure corresponding to MV) were applied at random. Venous return and CO were reduced by partial balloon occlusion of the inferior vena cava. Measurements were repeated with the left main bronchus blocked, creating a nonrecruitable pulmonary shunt. CO decreased from 4.2 l/min (95% CI, 3.9-4.5) to 2.5 l/min (95% CI, 2.2-2.7) with partially occluded venous return. Irrespective of whether shunt was minor or major, during unsupported SB, venous admixture was independent of CO (slope: minor shunt, 0.5; major shunt, 1.1% · min(-1) · l(-1)) and mixed venous oxygen tension. During both MV and CPAP, venous admixture was dependent on CO (slope MV: minor shunt, 1.9; major shunt, 3.5; CPAP: minor shunt, 1.3; major shunt, 2.9% · min(-1) · l(-1)) and mixed-venous oxygen tension (coefficient of determination 0.61-0.86 for all regressions). In contrast to MV and CPAP, venous admixture was independent of CO during unsupported SB, and was unaffected by mixed-venous oxygen tension, casting doubt on the role of hypoxic pulmonary vasoconstriction in pulmonary blood flow redistribution during unsupported SB.

Effect of Ca-antagonists on pulmonary blood flow during single-lung ventilation in the dog

Experiments were conducted in 21 adult mongrel dogs to clarify the effects of Ca-antagonist (nifedipine sublingual administration 2.5 mg or 5 mg, or nicardipine intravenous administration 30 micrograms/kg or 60 micrograms/kg) on pulmonary blood flow under the condition of collapsed lung on the side of thoracotomy. Under anesthesia, an endotracheal tube with a movable blocker was used to intubate the trachea and the thoracotomized lung was collapsed. Subsequently, a Ca-antagonist was given and the ratio of the left main pulmonary artery/ascending thoracic aorta blood flow was used as an index of hypoxic pulmonary vasoconstriction (HPV). The following results were obtained. 1. Ca-antagonist administration under lung-collapse on the thoracotomy side resulted in inhibition of HPV of the collapsed lung, whereas, arterial blood oxygen tension (PaO2) remained in the acceptable range. 2. The maintenance of the lowered PaO2 within the acceptable range may have been due to the increase in cardiac output and the elevation of mixed venous blood oxygen tension resulting from Ca-antagonist administration, as well as the residual HPV even after administration of the Ca-antagonist.

Effects of Arginine Vasopressin on Oxygenation and Haemodynamics during One-Lung Ventilation in an Animal Model

In a case of arterial hypotension during one-lung ventilation, haemodynamic support may be required to maintain adequate mean arterial pressure. Arginine vasopressin, a potent systemic vasoconstrictor with limited effects on the pulmonary artery pressure, has not been studied in this setting. Twelve female pigs were anaesthetised and ventilated and arterial, central venous and pulmonary artery catheters were inserted. A left-sided double lumen tube was placed via tracheostomy and one-lung ventilation was initiated. The animals were in the left lateral position, with the left lung ventilated and right lung collapsed. Respiratory and haemodynamic values were recorded before and during a continuous infusion of arginine vasopressin sufficient to double the mean arterial pressure. The arginine vasopressin caused a decrease in cardiac output (3.8+/-1.1 vs. 2.7+/-0.7 l/min, P <0.001) and mixed-venous oxygen tension (39.1+/-5.8 vs. 34.4+/-5 mmHg, P=0.003). Pulmonary artery pressure was unchanged (24+/-2 vs. 24+/-3 mmHg, P=0.682). There was no effect of the arginine vasopressin on arterial oxygen tension (226+/-106 vs. 231+/-118 mmHg, P=0.745). However, there was a significant decrease in shunt fraction (28.3+/-6.2 vs. 24.3+/-7.8%, P=0.043) and a significant proportional increase in perfusion of the ventilated lung (78.8+/-9.5 vs. 85.5+/-7.9%, P=0.036). In our animal model of one-lung ventilation, doubling mean arterial pressure by infusion of arginine vasopressin significantly affected global haemodynamics, but had no influence on systemic arterial oxygen tension.

The degree of exercise hypoxemia reflects pulmonary artery pressure during early exercise in chronic obstructive pulmonary disease patients

The causes of both exertional pulmonary hypertension and pulmonary hypertension in general in chronic obstructive pulmonary disease (COPD) remain to be elucidated. To further understand the pathophysiology in COPD patients, it may be important to recognize the existence of exertional pulmonary hypertension and to determine the severity of exertional hypoxemia. However, little is known about their relationship. To investigate whether the severity of exertional hypoxemia, as evaluated by the Deltaartery oxygen tension/Deltaoxygen consumption (PaO(2)-slope) correlates with the mean pulmonary artery pressure (Ppa), cardiopulmonary exercise testing with haemodynamics was done in 10 patients with moderate to very severe COPD. The PaO(2)-slope was significantly correlated with the mean Ppa from 25% to 40% of the maximum Watts (Wmax), and was most significant at 30% Wmax (r = -0.904, P<0.0001). In this phase, all parameters, except for the mean Ppa and the mixed venous oxygen tension, were not markedly changed from resting levels. At 30% Wmax, the mean Ppa (mean, 27 mmHg) with no or mild hypoxemia was also significantly correlated with the Deltaartery oxygen saturation/Deltaoxygen consumption (SpO(2)-slope) (r = -0.789, P = 0.004). On stepwise multiple regression analysis, the PaO(2)-slope was the most significant predictor of mean Ppa at 30% Wmax. In conclusion, the PaO(2)-slope and the SpO(2)-slope reflect Ppa during the early exercise phase. Thus, assessment of these parameters could be useful to evaluate the cardiopulmonary haemodynamic pathophysiology of COPD patients.

Sevoflurane or halothane with target-controlled sufentanil infusions for coronary artery bypass surgery

Objectives Comparison of hemodynamics, circulatory efficiency, myocardial ischemia and recall during and after sevoflurane or halothane (0.6 MAC {Minimum Alveolar Concentration} inspired) combined with a target-controlled sufentanil infusion (2 ng.ml 1 ) for coronary artery bypass grafting. Methods Prospective randomised non-blinded study in a university teaching hospital of 45 patients undergoing on-pump surgery. Inhalation anesthetic agent was delivered before, during and after cardiopulmonary bypass. Results Intraoperative hemodynamics were maintained within predetermined limits using vasoactive and cardioactive drugs. Heart rate was unchanged from baseline, however the sevoflurane-sufentanil group required more glycopyrrollate, indicating a tendency towards a slower heart rate. In both groups, similar low incidences of myocardial ischemia were detected. After induction of anesthesia, as well as intraoperatively, oxygen consumption decreased by up to 36.6% compared with the awake values in both groups. Oxygen delivery remained unchanged during all measuring periods. Mixed venous oxygen tensions rose after induction, even in patients with cardiac indices below 2.2 L.min 1 .m 2 , indicating maintenance of an effective circulation when utilising these techniques. Twelve hours postoperatively, oxygen consumption exceeded awake values by 31%. No explicit recall was reported by any patient on enquiry on the third postoperative day. Conclusions Low concentrations of sevoflurane or halothane, supplementing target-controlled sufentanil infusions, were both suitable for providing anesthesia for coronary bypass surgery.

Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: A pilot study*

Acute respiratory distress syndrome (ARDS) is frequently associated with increased pulmonary vascular resistance and thus with systolic load of the right ventricle. We hypothesized that levosimendan, a new calcium sensitizer with potential pulmonary vasodilator properties, improves hemodynamics by unloading the right ventricle in patients with ARDS. Prospective, randomized, placebo-controlled, pilot study. Twenty-two-bed multidisciplinary intensive care unit of a university hospital. Thirty-five patients with ARDS in association with septic shock. Patients were randomly allocated to receive a 24-hr infusion of either levosimendan 0.2 microg/kg/min (n = 18) or placebo (n = 17). Data from right heart catheterization, cardiac magnetic resonance, arterial and mixed venous oxygen tensions and saturations, and carbon dioxide tensions were obtained before and 24 hrs after drug infusion. At a mean arterial pressure between 70 and 80 mm Hg (sustained with norepinephrine infusion), levosimendan increased cardiac index (from 3.8 +/- 1.1 to 4.2 +/- 1.0 L/min/m) and decreased mean pulmonary artery pressure (from 29 +/- 3 to 25 +/- 3 mm Hg) and pulmonary vascular resistance index (from 290 +/- 77 to 213 +/- 50 dynes/s/cm(5)/m(2); each p < .05). Levosimendan also decreased right ventricular end-systolic volume and increased right ventricular ejection fraction (p < .05). In addition, levosimendan increased mixed venous oxygen saturation (from 63 +/- 8 to 70 +/- 8%; p < .01). This study provides evidence that levosimendan improves right ventricular performance through pulmonary vasodilator effects in septic patients with ARDS. A large multiple-center trial is needed to investigate whether levosimendan is able to improve the overall prognosis of patients with sepsis and ARDS.

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock

To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. Prospective study. A total of 12 patients with septic shock in a tertiary medical intensive care unit. A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.

High inspired oxygen concentrations increase intrapulmonary shunt in anaesthetized horses

ObjectivesTo compare pulmonary function and gas exchange in anaesthetized horses during and after breathing either O2-rich gas mixtures or air. AnimalsSix healthy standard bred trotters (age range 3–12 years; mass range 423–520 kg), four geldings and two mares. Study designRandomized, cross-over experimental study. MethodsHorses were anaesthetized on two occasions with tiletamine-zolazepam after pre-anaesthetic medication with acepromazine, romifidine and butorphanol. After endotracheal intubation and positioning in left lateral recumbency, animals were allowed to breathe spontaneously. One of two, randomly allocated inspired gas treatments was provided: either i) room air (fractional concentration of inspired O2 [FiO2] = 0.21) provided throughout anaesthesia; or ii) an O2-rich gas mixture (FiO2 = >0.95) for 15 minutes, followed by room air. The alternative treatment was delivered at the second anaesthetic. Respiratory and haemodynamic variables and the distribution of ventilation-perfusion (VA/Q) ratios (using the multiple inert gas elimination technique) were determined in the standing conscious horse (baseline) after sedation and during anaesthesia. ResultsBreathing O2-rich gas was associated with a decreased respiratory rate (p = 0.015) increased PaCO2 (p < 0.001) and increased PaO2 (p = 0.004) compared with breathing air. All horses developed intrapulmonary shunt during anaesthesia, but shunt was significantly greater (13 ± 5%) when O2-rich gas was delivered compared with air breathing (5 ± 2%; p = 0.013). Ten minutes after O2-rich gas was replaced by air, shunt remained larger in horses that had initially received oxygen compared with those breathing air (p = 0.042). Mixed venous oxygen tensions were significantly lower during sedation than at baseline (p < 0.001) and during anaesthesia (p < 0.001). ConclusionsDuring dissociative anaesthesia, arterial oxygenation was greater when horses breathed gas containing more than 95% oxygen, compared with when they breathed air. However, breathing O2-rich gas increased intrapulmonary shunt and caused hypoventilation. The intrapulmonary shunt created during anaesthesia by high inspired O2 concentrations remained larger when FiO2 was reduced to 0.21, indicating that absorption atelectasis produced during O2-rich gas breathing persisted throughout anaesthesia. Clinical relevanceIn healthy horses undergoing short-term dissociative anaesthesia, air breathing ensures a level of oxygen delivery that meets tissue demand. There is no benefit to horses in breathing O2-rich gas after the gas supply is discontinued. On the contrary, the degree of shunt induced by breathing O2-rich gas persists. The clinical relevance of this during recovery requires investigation.

Association of clinical features with HLA in chronic pulmonary thromboembolism

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.

Bedside exclusion of clinically significant recirculation volume during venovenous ECMO using conventional blood gas analyses

Study objectiveTo investigate prospectively whether blood gas samples drawn from extracorporeal membrane oxygenation (ECMO) cannulae help to exclude at least clinically significant recirculation volumes in patients with acute respiratory failure. DesignFeasibility study. SettingIntensive care unit at a university-affiliated hospital. PatientsTen consecutive adult patients suffering from severe respiratory failure and undergoing ECMO. InterventionsThe drawing (venous) ECMO cannula was placed into the inferior vena cava via a femoral vein, and the oxygenated blood was returned via the right subclavian vein by supraclavicular access directly into the right atrium. Blood gas samples were obtained from both cannulae. Measurements and main resultsThe median arterial oxygen tension (PaO2) obtained from the arterial cannula was 537 mmHg (range, 366 to 625 mmHg), the median mixed venous oxygen tension (PvO2) drawn from the venous cannula was 42 mmHg (range, 25 to 54 mmHg), which was less than 10% of that observed in the arterial cannula, and also within the physiologic range of PvO2. The ECMO flow necessary to maintain patients′ oxygen saturation above 90% (4.1 L/min; range, 1.95 to 5.8 L/min) was significantly lower than the patients′ cardiac output (CO; 6.2 L/min; range, 4.1 to 7.9 L/min; p < 0.001). ConclusionsWe recommend obtaining blood gas samples—immediately after initiation of ECMO—from both cannulae. A PvO2 within physiologic range and below 10% of PaO2 rules out any clinically relevant recirculation volume.