Haemodynamic response to a small intravenous bolus injection of epinephrine in cardiac surgical patients.

BACKGROUND AND OBJECTIVE: The aim was to study the rapid changes in cardiac output and systemic vascular resistance produced by intravenous epinephrine (5 microg) on a beat-by-beat basis. METHODS: Ten patients were studied during cardiac surgery. Radial or brachial arterial pressure was recorded continuously during intravenous administration of epinephrine (5 microg). Cardiac output and systemic vascular resistance were derived for each beat using arterial pulse contour analysis calibrated by lithium indicator dilution. In each patient a further dose of epinephrine (5 microg) was administered during cardiopulmonary bypass with the blood flow kept constant so that changes in arterial pressure corresponded to changes in systemic vascular resistance. RESULTS: When the patients were not on cardiopulmonary bypass, the epinephrine produced an initial increase in systemic vascular resistance to 129 +/- 15% (mean +/- SD) of control, followed by a more prolonged reduction to 57 +/- 13% of control. Cardiac output showed a small initial reduction coincident with the increase in systemic vascular resistance, followed by an increase to 152 +/- 24% of control. During cardiopulmonary bypass, the changes produced by epinephrine on systemic vascular resistance were qualitatively similar but smaller in amplitude, probably because of a greater volume of dilution in the bypass circuit. CONCLUSIONS: Small bolus doses of epinephrine produce an initial increase in systemic vascular resistance followed by a much greater reduction that may cause hypotension.

Estimation of changes in cardiac output from the arterial blood pressure waveform in the upper limb.

We have developed a new pulse contour cardiac output (PulseCO) algorithm based on frequency analysis studies of the arterial system. PulseCO was compared with thermodilution cardiac output (TDCO) in 10 patients undergoing cardiac surgery. Results from one patient were unsuitable for analysis. In the remaining nine patients, 142 TDCO determinations were compared with PulseCO after logarithmic transformation and after being normalized by the initial cardiac output in each patient. Each determination was usually the average of three measurements. Least squares regression gave y = 0.77 x (r2 = 0.81) and the limits of agreement were from -26% to +21%. The accuracy of PulseCO in determining short-term changes in cardiac output was assessed by comparing the ratios of consecutive PulseCO determinations with the ratios of the corresponding, consecutive TDCO determinations. Least squares regression gave y = 0.71 x (r2 = 0.70) and the limits of agreement were from -21% to +25%. After phenylephrine had been given to five patients, PulseCO showed an increase in systemic vascular resistance consistent with the known pharmacological actions of the drug. The PulseCO algorithm was incorporated into a computer program that acquires arterial pressure data from an analogue-to-digital converter and displays beat-to-beat trend values.

Cardiac output measured by lithium dilution and transpulmonary thermodilution in patients in a paediatric intensive care unit.

OBJECTIVE: To compare the results of cardiac output measurements obtained by lithium dilution and transpulmonary thermodilution in paediatric patients. DESIGN: A prospective study. SETTING: Paediatric intensive care unit in a university teaching hospital. PATIENTS: Twenty patients (age 5 days-9 years; weight 2.6-28.2 kg) were studied. INTERVENTIONS: Between two and four comparisons of lithium dilution cardiac output (LiDCO) and transpulmonary thermodilution (TPCO) were made in each patient. MEASUREMENTS AND RESULTS: Results from three patients were excluded: in one patient there was an unsuspected right-to-left shunt, in two patients there was a problem with blood sampling through the lithium sensor. There were 48 comparisons of LiDCO and TPCO in the remaining 17 patients over a range of 0.4-6 l/min. The mean of the differences (LiDCO-TPCO) was -0.1 +/- 0.3 (SD) l/min. Linear regression analysis gave LiDCO = 0.11 + 0.90 x TPCO l/min (r2 = 0.96). There were no adverse effects in any patient. CONCLUSIONS: These results suggest that the LiDCO method can be used to provide safe and accurate measurement of cardiac output in paediatric patients. The method is simple and quick to perform, requiring only arterial and venous catheters, which will already have been inserted for other reasons in these patients.

Cardiac output measured by lithium dilution, thermodilution, and transesophageal Doppler echocardiography in anesthetized horses.

OBJECTIVE: To assess the suitability of lithium dilution as a method for measuring cardiac output in anesthetized horses, compared with thermodilution and transesophageal Doppler echocardiography. ANIMALS: 6 horses (3 Thoroughbreds, 3 crossbreeds). PROCEDURE: Cardiac output was measured in 6 anesthetized horses as lithium dilution cardiac output (LiDCO), thermodilution cardiac output (TDCO), and transesophageal Doppler echocardiographic cardiac output (DopplerCO). For the LiDCO measurements, lithium chloride was administered i.v., and cardiac output was derived from the arterial lithium dilution curve. Sodium nitroprusside, phenylephrine hydrochloride, and dobutamine hydrochloride were used to alter cardiac output. Experiments were divided into 4 periods. During each period, 3 LiDCO measurements, 3 DopplerCO measurements, and 3 sets of 3 TDCO measurements were obtained. RESULTS: 70 comparisons were made between LiDCO, DopplerCO, and triplicate TDCO measurements over a range of 10 to 43 L/min. The mean (+/- SD) of the differences of LiDCO - TDCO was -0.86 +/- 2.80 L/min; LiDCO = -1.90 + 1.05 TDCO (r = 0.94). The mean of the differences of DopplerCO - TDCO was 1.82 +/- 2.67 L/min; DopplerCO = 2.36 + 0.98 TDCO (r = 0.94). The mean of the differences of LiDCO - DopplerCO was -2.68 +/- 3.01 L/min; LiDCO = -2.53 + 0.99 DopplerCO (r = 0.93). CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that lithium dilution is a suitable method for measuring cardiac output in horses. As well as being accurate, it avoids the need for pulmonary artery catheterization and is quick and safe to use. Monitoring cardiac output during anesthesia in horses may help reduce the high anesthetic mortality in this species.

A new technique for measuring cardiac output and shunt fraction during venovenous extracorporeal membrane oxygenation.

A new indicator dilution technique is described for measuring cardiac output and shunt fraction in patients undergoing venovenous extracorporeal membrane oxygenation (ECMO). Shunt fraction is the proportion of the ECMO pump flow which recirculates through the ECMO circuit (passing directly from the inflow cannula to the outflow cannula) instead of flowing through the pulmonary and systemic circulations. The indicator is an isotonic (150 mmol/l) solution of lithium chloride which is injected into the ECMO flow returning to the patient. Two lithium sensors are used simultaneously to record the resulting lithium dilution curves in arterial blood and in the blood in the ECMO circuit. Cardiac output and shunt fraction are derived from these curves. The techniques, which is simple and safe, provides measurements that allow optimal adjustment of ECMO flow and cardiovascular support.

A comparison of lithium dilution cardiac output measurements made using central and antecubital venous injection of lithium chloride.

OBJECTIVE: We have previously described an indicator dilution technique of measuring cardiac output in which lithium chloride is injected as a bolus via a central venous catheter and cardiac output derived from the arterial lithium dilution curve recorded from a lithium-selective electrode, which we have developed for this purpose. It would be an advantage if the lithium could be injected via the basilic vein (in the antecubital fossa) in those patients who do not need central venous catheterisation for other reasons. We have therefore compared cardiac output measurements made using these two routes of lithium chloride administration. METHODS: Lithium dilution cardiac output was measured 10 times in each of 10 patients, injecting the lithium chloride alternately via the basilic or central venous catheter. RESULTS: The mean difference was 0.8 +/- 5.2% (SD) (range -8.5 to +7.0%) over a range of cardiac output of 4.5-13 l/min. CONCLUSIONS: Injection of lithium chloride via the basilic vein in the antecubital fossa allows accurate lithium dilution cardiac output measurements to be made in patients who do not have central venous catheters in place.

The shape of indicator dilution curves used for cardiac output measurement in man.

1. In six patients arterial plasma lithium concentration-time curves were recorded following injection of lithium chloride into the right or left atrium. 2. Lognormal curve fitting was used to derive the areas under the first pass dilution curves. 3. Subjecting the curves produced by left atrial injection to a delay and sequential filtering produced curves that closely approximated those produced by right atrial injection. 4. We conclude that the transfer function of the right heart and lungs is equivalent to a delay and sequential filtering, that the primary indicator dilution curve is closely approximated by a lognormal curve and that loss of lithium in the lungs following right atrial injection is clinically insignificant.

Adaptation of carotid chemoreceptors to step increases in PaCO2 in anesthetized cats.

1. The rate of change sensitivity of some carotid chemoreceptors to within-breath changes in PaCO2 would suggest that the half-life of adaptation of these receptors to a step increase is shorter than the 5-10 s previously reported. 2. In six anesthetized cats, step increases in PaCO2 (10 in each cat) were produced by injection of CO2 into the inspired gas during high-frequency jet ventilation. Chemoreceptor discharge was recorded from single-fiber preparations of the divided carotid sinus nerve, and the changes in PaCO2 were followed with the use of an in vivo pH electrode. 3. The adaptation half-lives were 0.3, 0.8, 1.2, 1.3, 1.6, and 8.6 s. The physiological significance of these findings in terms of respiratory control and the mechanism of chemotransduction are discussed. The receptors with the shortest and longest half-lives showed corresponding differences in response to sine-wave oscillations in PaCO2. 4. In a further group of five cats, chemoreceptor responses to step increases in PaCO2 were tested before and during infusion of KCl to produce a mean arterial [K-] of 6.8 +/- 0.2 (SE) mM. Under these conditions the hyperkalemia caused no further increase in discharge. 5. We conclude that adaptation of the chemoreceptor response to increases in PaCO2 is much faster than previously reported and that this finding is consistent with observations of chemoreceptor responses to respiratory PaCO2 oscillations.

A new method of analysing indicator dilution curves.

OBJECTIVE: We are currently developing a new indicator dilution method of measuring cardiac output using lithium chloride as the indicator. The aim of the present study was to develop a simple and accurate method of deriving the area under the primary indicator dilution curve: that is, the area which would have been inscribed had there been no recirculation of the indicator. METHOD: A model based upon the representation of the mixing in the circulation as similar to that of the passage of an impulse through a series of filter elements was studied. This was represented physically by a model which consisted of a series of mixing chambers. The model was analysed theoretically using Laplace transforms and was used to test the new method of deriving the area of primary indicator dilution curves. RESULTS: Theoretical analysis showed that such a filter model produces curves which closely approximate the shape of a lognormal distribution over a range of skewness greater than that of human indicator dilution curves. The single pass curves from the physical model were shown to be similar in shape to lognormal distributions, as were the curves obtained from patients to the point when recirculation occurred. A method of estimating the area under the primary curve based upon the lognormal distribution was developed and equations derived. The use of these equations to calculate flows from lithium dilution curves in the mixing chamber model was validated by comparing the results with simultaneous timed collection. CONCLUSIONS: Theoretical justification for treating primary indicator dilution curves as lognormal is presented. A simple method of deriving the integral of the primary indicator dilution curve is described. It uses the whole of the curve up to a point short of recirculation, avoiding the problem which can occur with the classical Hamilton extrapolation method when the cardiac output is low and recirculation distorts the primary curve in the early part of the washout.

Effects of potassium and lactic acid on chemoreceptor discharge in anaesthetized cats.

Both increasing [K+]a and falling pHa stimulate ventilation through an action on the peripheral chemoreceptors. We have examined the effect on afferent carotid chemoreceptor discharge, of intravenous infusion of lactic acid alone, KCl alone, and both combined at constant PETCO2 in anaesthetized, artificially ventilated cats. Infusions of lactic acid alone and KCl alone caused similar increases in both the mean and amplitude of oscillation of chemoreceptor discharge. In the case of the lactic acid alone infusion the increase in the amplitude of oscillation could be accounted for by the resultant increase in carbon dioxide production. Simultaneous infusion of KCl and lactic acid caused an increase in the mean and amplitude of the discharge which was greater than either given alone, although the combined effect was less than additive. The alterations in mean and amplitude of oscillation of discharge during infusion of both agents together may be completely accounted for by a combined effect of increased carbon dioxide production and elevated [K+]a.

Exercise-induced changes in plasma potassium and the ventilatory threshold in man.

1. It has been reported that, during incremental exercise testing, the patterns of change in ventilation (VE) and arterial K+ (Ka+) are similar, suggesting that changing Ka+ may lead to the phenomenon of the ventilatory threshold through its action on the peripheral chemoreceptors. 2. Expiratory ventilation, oxygen consumption, CO2 production (VE, VO2, VCO2), arterialized venous PCO2 (Pav, CO2; see Methods), pH (pHav), K+ (Kav+) and lactate were measured during incremental exercise tests undertaken by six normal male subjects under control conditions and during lactic acidosis following severe exercise (experimental trial). 3. A ventilatory threshold, associated with a period of isocapnic buffering, was observed under both control and experimental conditions. During the control trial, plots of Kav+ against VO2 showed an inflexion close to the ventilatory threshold. Throughout the experimental trial Kav+ rose linearly relative to VO2. In both control and experimental trials Kav+ concentrations were similar at the ventilatory threshold. 4. These results suggest that the pattern of change of Ka+ cannot account for the phenomenon of the ventilatory threshold. The possibility that the peripheral chemoreceptor response is non-linear above a critical value of Ka+ requires further investigation.

Effects of potassium and lactic acid on ventilation in anaesthetized cats.

Intravenous infusions of lactic acid alone, KCl alone and both together were administered to anaesthetized, spontaneously breathing cats. Ventilation (VI), end-tidal PO2 (PETO2), end-tidal PCO2 (PETCO2), arterial blood pressure and heart rate were recorded continuously. [K+]a and pHa were monitored using intravascular ion selective catheter electrodes. The increase in VI during infusion of KCl and lactic acid together was greater than that observed during infusion of lactic acid alone. The increment in VI produced by the addition of an infusion of KCl to the lactic acid infusion was greater than the increment produced by the addition of KCl to a control infusion of normal saline. The reduction in PaCO2 which occurred when KCl was added to the lactic acid infusion was similar to that when KCl was infused with NaCl. Thus the inhibition of respiration secondary to reduced PaCO2 was similar in both circumstances. These results suggest that the combined respiratory stimulant effect of elevation of [K+]a and acute lactic acidosis is more than additive.

A new method of measuring cardiac output in man using lithium dilution.

We describe a new indicator dilution method of measuring cardiac output in man. A bolus injection of lithium chloride 0.6 mmol was given via a central venous catheter and arterial plasma [Li+] recorded using a specially developed sensor incorporating an Li(+)-selective electrode. Cardiac output was derived from the lithium dilution curve, with a correction for packed cell volume. Lithium dilution cardiac output (LiDCO) was compared with thermodilution cardiac output (TD) using 22 lithium sensors in nine patients. For each sensor, one LiDCO was measured immediately before and one immediately after three TD estimations and mean values of LiDCO and TD derived. The correlation coefficient, r, was 0.89; slope of the regression 0.84; y intercept 0.72; bias 0.3 (0.5) litre min-1 (mean (TD-LiDCO) (1 SD). LiDCO appeared to be a safe, simple and accurate technique which does not require insertion of a pulmonary artery catheter.

Carotid chemoreceptor discharge during epinephrine infusion in anesthetized cats.

It is known that during exercise there is an increase in plasma epinephrine. The purpose of the present investigation was to determine whether stimulation of carotid chemoreceptors by epinephrine is a direct effect or secondary to epinephrine-induced increases in arterial plasma [K+] and whole body CO2 production (VCO2). Chemoreceptor discharge was recorded from single fiber preparations of the carotid sinus nerves in anesthetized cats ventilated to a constant arterial PCO2 (PaCO2). Infusion of epinephrine (1 microgram.kg-1 x min-1) caused arterial [K+] to increase from a mean of 2.7 to 3.8 mM. VCO2 increased so that ventilation had to be increased by 60% to maintain PaCO2 constant. Mean chemoreceptor discharge increased by 50%, but this was no greater than would be predicted on the basis of the increases in arterial [K+] and VCO2. In a further group of experiments epinephrine was infused at 0.1 microgram.kg-1 x min-1 and produced no significant increase in chemoreceptor firing. These experiments provide no evidence for epinephrine having a direct effect on the carotid chemoreceptor.