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.

Use of arterialized venous blood sampling during incremental exercise tests.

Close agreement between arterialized venous and arterial pH, PCO2, and lactate has previously been demonstrated during steady-state exercise. The purpose of the present study was to compare arterialized venous and arterial pH, PCO2, K+, lactate, pyruvate, and epinephrine during the constantly changing circumstances of an incremental exercise test. Eight normal subjects undertook an incremental exercise test (increasing by 20 W/min) to exhaustion on a cycle ergometer during which simultaneous arterial and arterialized venous samples were drawn over the last 20 s of each work load. Linear regression of arterialized venous on arterial values showed that r varied from 0.97 to 0.99 for the variables examined and, therefore, showed that accurate estimates of arterial values could be made from the arterialized venous results during incremental testing. For many purposes it could be assumed that arterialized venous values equaled arterial values without serious error.

The effect of potassium and venous CO2 loading on chemoreceptor firing in anaesthetized cats.

The CO2 production of 5 anaesthetized cats, ventilated to a constant PaCO2 and PaO2 by appropriate alteration of tidal volume and FIO2, was altered by means of an extracorporeal gas exchanger. Afferent chemoreceptor discharge was recorded from a single fibre preparation of the right carotid sinus nerve and the respiratory oscillations in firing were derived over 50 breath (2.5 min) periods. In response to an approximate doubling of CO2 production the discharge oscillation showed an increase in amplitude (P less than 0.05) but no change in mean level. When KCl was infused to produce a mean arterial [K+] of 5.9 mmol/L, while maintaining the same level of CO2 loading, the amplitude of the oscillation increased from 2.9 +/- 0.5 impulses/sec to 5.2 +/- 1.0 impulses/sec (P less than 0.05) and the mean increased from 2.6 +/- 0.4 impulses/sec to 3.9 +/- 0.2 impulses/sec (P less than 0.01). The implications of these findings are discussed.