Influence Of Cardiac Output Research Articles

The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery

Cardiac output (CO) is expected to affect elimination and distribution of highly extracted and perfusion rate-limited drugs. This work was undertaken to quantify the effect of CO measured by the pulse pressure method on pharmacokinetics and pharmacodynamics of propofol and fentanyl administrated during total intravenous anesthesia (TIVA). The data were obtained from 22 ASA III patients undergoing abdominal aortic surgery. Propofol was administered via target-controlled infusion system (Diprifusor) and fentanyl was administered at a dose of 2–3 µg/kg each time analgesia appeared to be inadequate. Hemodynamic measurements as well as bispectral index were monitored and recorded throughout the surgery. Data analysis was performed by using a non-linear mixed-effect population modeling (NONMEM 7.4 software). Three compartment models that incorporated blood flows as parameters were used to describe propofol and fentanyl pharmacokinetics. The delay of the anesthetic effect, with respect to plasma concentrations, was described using a biophase (effect) compartment. The bispectral index was linked to the propofol and fentanyl effect site concentrations through a synergistic Emax model. An empirical linear model was used to describe CO changes observed during the surgery. Cardiac output was identified as an important predictor of propofol and fentanyl pharmacokinetics. Consequently, it affected the depth of anesthesia and the recovery time after propofol-fentanyl TIVA infusion cessation. The model predicted (not observed) CO values correlated best with measured responses. Patients‘ age was identified as a covariate affecting the rate of CO changes during the anesthesia leading to age-related difference in individual patient’s responses to both drugs.

Influence of Cardiac Output on the Pharmacokinetics of Sufentanil in Anesthetized Pigs.

Sufentanil is used for general anesthesia and analgesia. The study aim was to determine the effect of pharmacologically induced changes in cardiac output on the pharmacokinetics of sufentanil in anesthetized pigs. Twenty-four pigs were randomly assigned to low, high, and control cardiac output groups. Cardiac output was decreased or increased from baseline by at least 40%, or maintained within ± 10% of baseline, respectively. Sufentanil was administered as a bolus followed by a continuous infusion for 120 min. Timed arterial samples were drawn for sufentanil concentration measurements. Data from 20 animals were analyzed. The cardiac outputs (means ± SD) were 2.9 ± 0.7, 5.4 ± 0.7, and 9.6 ± 1.6 l/min in the low, control, and high cardiac output groups, respectively. The parameters of the two-compartment pharmacokinetic model for these cardiac outputs were: CL1: 0.9, 1.2, and 1.7 l/min; CL2: 0.9, 3.1, and 6.9 l/min; V1: 1.6, 2.9, and 5.2 l; and V2: 27.5, 47.0, and 79.8 l, respectively. Simulated sufentanil doses to maintain a target plasma concentration of 0.5 ng/ml for 3 h were 99.5, 128.6, and 157.6 μg for cardiac outputs of 3, 5, and 7 l/min, respectively. The context-sensitive half-times for these cardiac outputs increased from 3.1 to 19.9 and 25.9 min, respectively. Cardiac output influences the pharmacokinetics of sufentanil. Simulations suggest that in the case of increased cardiac output, the dose should be increased to avoid inadequate drug effect at the expense of prolonged recovery, whereas for low cardiac output the dose should be reduced, and a faster recovery may be expected.

Aortic Stenosis in Dialysis Patients.

Aortic valve stenosis occurs 10-20 years earlier in patients on dialysis compared with the general population. This is likely related to the exposure of the valve to a milieu that predisposes to calcification as well as increased shear stress across the valve. Objective assessment of stenosis severity is largely made using echocardiography though accurate interpretation requires an understanding of the potential pitfalls of the technique and the influence of cardiac output upon the gradient measured across the valve. Timing of valve replacement in severe aortic stenosis is predominantly guided by exercise-induced symptoms (breathlessness, chest pain and [pre] syncope), which are often difficult to assess in the dialysis population who may have limited exercise capacity and symptoms due to renal failure and other comorbidities. Finally, treatment of aortic stenosis remains a constantly evolving area with advances in both conventional surgery and percutaneous techniques.

Influence of cardiac output on the pseudo‐steady state remifentanil and propofol concentrations in swine

The propofol concentration during constant infusion is affected by a change in cardiac output, but the effect of this change on remifentanil, which is frequently used in combination with propofol, is unclear. Ten swine were anaesthetised through inhalation of isoflurane and maintained with 1.5% isoflurane. After infusion of remifentanil (0.5 μg/kg/min) and propofol (6 mg/kg/h after 2 mg/kg bolus infusion) for 60 min (baseline 1), cardiac output was increased by continuous infusion of dobutamine and termination of isoflurane (high cardiac output state). Dobutamine infusion was then stopped, 1.5% isoflurane was restarted, and cardiac output was allowed to return to baseline (baseline 2). Finally, cardiac output was decreased by administration of 3% isoflurane (low cardiac output state). Blood samples were collected from the femoral artery at 10, 30, and 60 min after the change to each haemodynamic state. An inverse relationship was found between cardiac output and the plasma remifentanil and propofol concentrations. The plasma drug concentrations were given by the following equations: [remifentanil] (ng/ml) = 17.5/cardiac output (l/min) + 4.52; and [propofol] (μg/ml) = 3.34/cardiac output + 1.17. The influence of changes in cardiac output on remifentanil were similar to those for coadministered propofol and the influence on the concentration of each drug was greater with decreasing cardiac output. The plasma remifentanil concentration is influenced by cardiac output in a similar manner to that of propofol during remifentanil and propofol anaesthesia, although the metabolic sites are different.

Variability in measures of exhaled breath Na+ and K+, influence of cardiac output and saliva

The assessment of inflammatory markers, ions, and cations in exhaled breath condensate (EBC) is being used more frequently in diseases such as asthma and cystic fibrosis. Previous work has demonstrated significant variability in the measures of exhaled Na+ and K+ in healthy subjects and in patients with cystic fibrosis. We sought to determine if the previously‐described variability in exhaled Na+ and K+ was due to differences in cardiac output (Q) or saliva Na+. To determine this, we collected EBC three times over 1.5hrs with the simultaneous sampling of saliva Na+ and assessment of Q (using acetylene rebreathing) in 7 healthy subjects (age=25±4yrs., ht.=177±7cm, wt.=70±25kg, BMI=22±7kg/m2). Exhaled Na+ averaged 2.1±0.8mmol/l and exhaled K+ averaged 0.14±0.04mmol/l. The coefficients of variation for exhaled ions across three measures averaged 30% for exhaled Na+ and 32% for exhaled K+. Within subjects, the relationship (Pearson correlation) between exhaled Na+ and K+ with Q averaged 0.61 and 0.45, respectively, and the relationship between exhaled Na+ with saliva values averaged 0.85 (p<0.05). Between subjects, the relationship between exhaled Na+ and K+ with Q averaged 0.52 and 0.38 (p<0.05 for both), respectively, and that between exhaled Na+ with saliva values averaged 0.72 (p<0.05). These results suggest that both cardiac output and saliva may contribute to the variability in exhaled ion measurement.

Hypoxemia due to increased venous admixture: influence of cardiac output on oxygenation

In the hypoxemic patient under mechanical ventilation, changes in cardiac output may influence the level of arterial oxygenation, with several and sometimes opposite effects. The purpose of this Physiological Note is to give the reader the physiological background to understand these effects, which are often highly relevant for the bedside management of patients with acute lung injury.

Influence of cardiac output on plasma propofol concentrations during constant infusion in swine.

As propofol is a high-clearance drug, plasma propofol concentrations can be influenced by cardiac output (CO), which can easily change in response to several factors. If propofol is metabolized in the lungs, the difference between pulmonary and arterial propofol concentrations might also be affected by CO. The objective of the current study was to assess how much plasma propofol concentrations are affected by CO and to determine how much the lungs take part in propofol elimination and in concentration changes affected by CO in anesthetized swine. Thirteen swine were studied. Propofol was administered via a peripheral vein at a rate of 6 mg x kg(-1) x h(- 1), and blood samples were simultaneously collected from pulmonary and femoral arteries at 0, 2, 3.5, 5, 7, 10, 20, and 30 min and at 20-min intervals up to 270 min. After 90 min of sampling (baseline 1), CO increased in response to a continuous infusion of dobutamine (20 microg x kg(-1) x min(- 1); high-CO state); the infusion was then stopped, and CO was allowed to return to baseline (baseline 2). Finally, CO decreased with the administration of propranolol (2.0-4.0 mg administered intravenously; low-CO state). Each hemodynamic status was maintained for 1 h. As CO increased 36% from baseline 1, plasma propofol concentrations decreased by 18% from baseline 1, and as CO decreased 42% from baseline 1, plasma propofol concentrations increased by 70% from baseline 1. Plasma propofol concentrations can be expressed by the following equation: plasma propofol concentration (micrograms per milliliter) = 6.51/CO (l/min) + 1.11 (r = 0.78, P < 0.0001). No significant differences were observed between plasma propofol concentrations in pulmonary and femoral arteries in any state, and CO caused no apparent differences between pulmonary and arterial propofol concentrations. An inverse relation was observed between CO and propofol concentrations. The lungs appear to have a minor effect on plasma propofol concentrations during constant infusion in anesthetized swine.

Relation between pulmonary venous flow and pulmonary wedge pressure: Influence of cardiac output

Multiple factors affect the systolic and diastolic components of pulmonary venous flow. It has been suggested that left ventricular function might influence the effects of filling pressures on indexes of pulmonary venous flow. The present study was designed to evaluate the effect of the pulmonary wedge pressures, left ventricular function, and cardiac output on the pulmonary vein flow pattern. Forty-five patients undergoing cardiac surgery were included in this study. Pulmonary venous flow and mitral flow variables were obtained by transesophageal echocardiography with hemodynamic variables obtained simultaneously. In the total group, there was no consistent relation between the pulmonary venous flow or the mitral flow parameters and the capillary wedge pressures. When patients were grouped according to normal (>2.2 L/min/m 2) or low (<2.2 L/min/m 2) cardiac index, a significant and positive relation was found between the systolic component of the pulmonary venous flow and the pulmonary wedge pressure in patients with normal cardiac index ( r = 0.69; p = 0.003). Conversely, in patients with low cardiac index there was also a significant although negative correlation between the systolic velocity integral and the pulmonary wedge pressure ( r = −0.58; p < 0.001). In conclusion, the systolic component of the pulmonary venous flow correlates closely and significantly with the capillary wedge pressures. The direction of this relation depends to a large extent on the total cardiac output and to a lesser extent on the left ventricular systolic function as assessed by the ejection fraction.

Influence of Cardiac Output on Peak t-PA Plasma Levels in Patients Receiving Thrombolytic Therapy with Recombinant Tissue-Type Plasminogen Activator – Correlation with Patency Rate

We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

INFLUENCE OF CARDIAC OUTPUT ON THE CORRELATION BETWEEN MIXED VENOUS AND CENTRAL VENOUS OXYGEN SATURATION

The influence of cardiac output on the correlation between central venous oxygen saturation and mixed venous oxygen saturation was assessed in 51 patients who had both a pulmonary artery catheter and separate central venous catheter in situ. Seventy-six paired samples were taken from the catheters and oxygen saturation measured immediately in a Ciba Corning 2500 Co-oximeter. Cardiac output was measured using a standard thermodilution technique. The data were separated into groups with low cardiac index (< 2.5 litre min-1 m-2; n = 20), medium cardiac index (2.5-4.0 litre min-1 m-2; n = 36) and high cardiac index (> 4.0 litre min-1 m-2; n = 20). The correlation coefficients of the three groups were: low cardiac index 0.95, medium cardiac index 0.88 and high cardiac index 0.95 (P < .001 for all three groups). All measurements were made before any x-ray and necessary repositioning of the central venous catheter. These results suggest that central venous oxygen saturation is a useful estimate of mixed venous oxygen saturation and that the influence of cardiac output on that estimate is minimal.

Influence of Cardiac Output on Oxygen Exchange in Acute Pulmonary Embolism

We investigated interactions between cardiac output, VA/Q distribution pattern, pulmonary gas exchange, O2 transport, and tissue oxygenation in 16 patients during the acute phase of pulmonary embolism (PE). The effects of breathing room air, O2 therapy (FIO2 = 0.40) (11 patients), and dobutamine (four patients) were studied after right catheterization using the multiple inert gas elimination technique. The pattern of VA/Q ratio distributions was found to depend essentially on cardiac output level. The individual blood flow perfusing ventilated areas was found to be inversely related to the mean VA/Q ratio of blood flow distribution. PVO2 was directly related to cardiac index (p less than 0.02), and negatively related to the mean VA/Q of blood flow distribution. In view of the influence of low VA/Q ratios and PVO2 on arterial hypoxemia, our results showed that the heart's response to PE conditioned the strategy of pulmonary gas exchange and O2 transport. Oxygen breathing led to a slight but consistent fall in cardiac output (-0.6 +/- 0.5 L/min, p less than 0.01). However, although PaO2 remained normal and PVO2 was slightly improved, we found no evidence for a role of hypoxic pulmonary vasoconstriction in the pulmonary hypertension observed during the acute phase of PE. Administration of dobutamine improved O2 transport and tissue oxygenation, although PaO2 remained constant or even fell in some cases because of increased VA/Q mismatch.

Influence of cardiac output on thermal-dye extravascular lung water (EVLW) in cardiac patients.

The influence of varying cardiac output (CO) on thermal-dye extravascular lung water (EVLW) was investigated in a total of 40 cardiac surgery patients before the onset of the operation. EVLW was measured by means of the double indicator dilution technique with indocyanine green as the non-diffusible indicator and a microprocessed lung water computer 15 min and 30 min after change of CO. CO was varied from -45% to +70% of the baseline value by nifedipine infusion (CO increases, n = 20) or halothane application (CO decreases, n = 20), respectively. CO was measured from the femoral artery instream thermistor tipped lung water catheter and, simultaneously, from the pulmonary artery. In spite of a highly significant decrease (-45%) and increase (+70%) in CO no change in EVLW could be observed. CO estimation was comparable for both methods used. Regression analysis revealed no relationship between CO and EVLW as well as between EVLW and various hemodynamic parameters. We conclude that thermal-dye technique for estimation of EVLW may be accurate in spite of changing cardiac output over a wide range.

Continuous positive pressure ventilation in children with bronchopneumonia

The application of a small end-expiratory pressure of 5 cmH2O to the assisted ventilation of nineteen children (mean age 19 months) with bronchopneumonia was compared with intermittent positive pressure ventilation. Within 1 h of introducing continuous positive pressure ventilation the alveolar-to-arterial oxygen gradient was reduced in most patients, with an increase in functional residual capacity and a decrease in total pulmonary blood shunt. Physiological dead space was also reduced, a feature not observed in other studies, and the significance of this finding is discussed. The use of continuous positive pressure ventilation in broncho-pulmonary infection was shown to be effective even at small pressures, and can be recommended especially for patients requiring long-term ventilation.

Effects of physiotherapy during intermittent positive pressure ventilation. Changes in arterial blood gas tensions.

AnaesthesiaVolume 27, Issue 3 p. 258-264 Free Access Effects of physiotherapy during intermittent positive pressure ventilation Changes in arterial blood gas tensions J. Gormezano, J. Gormezano J. Gormezano, FFARCS, Research Assistant in Anaesthetics and M. A. Branthwaite, MRCP, FFARCS, Consultant Anaesthetist, Brompton Hospital, Fulham Road, London S W5 6HP.Search for more papers by this authorM. A. Branthwaite, M. A. Branthwaite J. Gormezano, FFARCS, Research Assistant in Anaesthetics and M. A. Branthwaite, MRCP, FFARCS, Consultant Anaesthetist, Brompton Hospital, Fulham Road, London S W5 6HP.Search for more papers by this author J. Gormezano, J. Gormezano J. Gormezano, FFARCS, Research Assistant in Anaesthetics and M. A. Branthwaite, MRCP, FFARCS, Consultant Anaesthetist, Brompton Hospital, Fulham Road, London S W5 6HP.Search for more papers by this authorM. A. Branthwaite, M. A. Branthwaite J. Gormezano, FFARCS, Research Assistant in Anaesthetics and M. A. Branthwaite, MRCP, FFARCS, Consultant Anaesthetist, Brompton Hospital, Fulham Road, London S W5 6HP.Search for more papers by this author First published: July 1972 https://doi.org/10.1111/j.1365-2044.1972.tb08218.xCitations: 36AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Spencer, G.T. (1966). In W.D. Wylie, H.C. Churchill-Davidson A Practice of Anaesthesia, 2nd edn, p. 405. London : Lloyd-Luke Ltd. 2 Gilston, A. & Resnekov, L. (1971). Cardio-Respiratory Resuscitation, 1st edn., p. 157. London : William Heinemann Medical Books Ltd. 3 Clement, A.J. & Hübsch, S.K. (1968). Chest physiotherapy by the “Bag-Squeezing” method: A guide to technique. Physiotherapy, 54, 355. 4 Rosen, M. & Hillard, E.K. (1962). The effects of negative pressure during tracheal suction. Anesthesia and Analgesia, Current Researches, 41, 50. 5 Berman, I.R. & Stah, J.W.M. (1968). Prevention of hypoxic complications during endotracheal suctioning. Surgery, 63, 586. 6 Boutros, A.R. (1970). Arterial blood oxygenation during and after endotracheal suctioning in the apnoeic patient. Anesthesiology, 32, 114. 7 Taylor, P.A. & Waters, H.R. (1971). Arterial oxygen tensions following endotracheal suction on IPPV. Anaesthesia, 26, 289. 8 Holloway, R., Adams, E.B., Desai, S.D. & Thambiran, A.K. (1969). Effect of chest physiotherapy on blood gases of neonates treated by intermittent positive pressure respiration. Thorax, 24, 421. 9 English, I.C.W. & Manley, R.E.W. (1970). The Brompton system of artificial ventilation. Anaesthesia, 25, 541. 10 Kelman, G.R., Nunn, J.F. Prys-Roberts, C. & Greenbaum, R. (1967). The influence of cardiac output on arterial oxygenation: a theoretical study. British Journal of Anaesthesia, 39, 450. 11 Ross, J.Jr. & Braunwald, E. (1964). Studies on Starling's law of the heart, IX. The effects of impeding venous return on performance of the normal and failing human left ventricle. Circulation, 30, 719. 12 Watson, W.E., Smith, A.C. & Spalding, J.M.K. (1962). Transmural central venous pressure during intermittent positive pressure respiration. British Journal of Anaesthesia, 34, 278. 13 Nunn, J.F. & Freeman, J. (1964). Problems of oxygenation and oxygen transport during haemorrhage. Anaesthesia, 19, 206. 14 Sykes, M.K., Adams, A.P. McCormick, P.W. Bird, B., Greenburgh, S. (1970). The effect of mechanical ventilation after open-heart surgery. Anaesthesia, 25, 525. 15 Dammann, J.F., Thung, N. Christlieb, I., Littlefield, J.B., Muller, W.H. (1963). The management of the severely ill patient after open-heart surgery. Journal of Thoracic and Cardiovascular Surgery, 45, 80. 16 Sykes, M.K. (1969). Post-operative respiratory insufficiency. In W. Cleland, J. Goodwin, J. McDonald & D. Ross. Medical and Surgical Cardiology, 1st edn. p. 392. Oxford : Blackwell Scientific Publications. 17 Björk, V.O., Grenvik, A. Holmdahl, M.H. & Westerholm, C.J. (1964). Cardiac output and oxygen consumption during respirator treatment. Acta anaesthesiologica Scandinavica, Suppl., 15, 158. 18 Thung, N., Herzog, P. Christlieb, I.I. Thompson, W.M., Jr, Dammann, J.F., Jr. (1963). The cost of respiratory effort in post-operative cardiac patients. Circulation, 28, 552. 19 Gilston, A. & Resnekov, L. (1971). Cardio-Respiratory Resuscitation, 1st edn, p. 163– 191. London : William Heinemann Medical Books Limited. Citing Literature Volume27, Issue3July 1972Pages 258-264 ReferencesRelatedInformation