Clinical Studies


These are presented chronologically. Ethical approval for the studies in patients was obtained from the St. Thomas' Hospital Research Ethics Committee.


1. Initial description of the lithium dilution method and clinical trial comparing it with thermodilution [Linton RAF, Band DM, Haire KM: A new method of measuring cardiac output in man using lithium dilution. British Journal of Anaesthesia 1993; 71:262-266.]

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2. Unpublished study in which flows in a cardiopulmonary bypass circuit were measured by lithium dilution and with an electromagnetic flow probe.

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3. Clinical investigation of lithium dilution curves produced by right and left atrial injection of lithium chloride. [Band DM, Linton RAF, O'Brien TK, Jonas MM , Linton NWF. The shape of indicator dilution curves used for cardiac output measurement in man. Journal of Physiology 1997; 498:225-229].

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4. A further clinical trial of the lithium dilution method, comparing it with thermodilution. [Linton RAF, Band DM, O'Brien TK, Jonas MM, Leach R. Lithium dilution cardiac output measurement: a comparison with thermodilution. Critical Care Medicine 1997; 25:1796-1800].

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5. A new technique for measuring cardiac output and shunt fraction during venovenous extracorporeal membrane oxygenation. Linton RAF, Turtle M, Band DM, O'Brien TK, Jonas MM, Linton NWF. Perfusion 1999; 14: 43-48.

During venovenous extracorporeal oxygenation (ECMO) some of the blood flowing from the oxygenator to the right atrium may pass directly back into the ECMO circuit instead of going into the right ventricle and from there to the pulmonary and systemic circulations. By using a single injection of lithium and measuring its dilution curves simultaneously in the arterial blood and in the ECMO circuit it is possible to calculate this shunt flow as well as the cardiac output. These measurements have not been made before during this type of ECMO but would be valuable in terms of improved patient management.

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6. Cardiac output measured by lithium dilution, thermodilution and echocardiography in anesthetized horses. Linton RA, Young LE, Marlin DJ, Blissitt KJ, Brearley JC Jonas MM, O'Brien TK, Linton NW, Band DM, Hollingworth C, Jones RS. American Journal of Veterinary Research 2000; 61: 731-737.

This study was carried out at the Animal Health Trust, Newmarket.


Objective – To assess the suitability of a new lithium dilution method for measuring cardiac output in anesthetized horses.

Animals – 3 thoroughbred and 3 crossbred horses.

Procedure - Cardiac output was measured in 6 anesthetized horses using a new lithium dilution (LDCO) method, conventional bolus thermodilution (TDCO) and transesophageal Doppler echocardiography (DopplerCO). For the LDCO measurements, lithium chloride was injected intravenously and cardiac output derived from the arterial lithium dilution curve. Sodium nitroprusside, phenylephrine and dobutamine were used to alter cardiac output.

Results - There were 70 comparisons between LDCO, DopplerCO and triplicate TDCO over a range of 10 - 43 l/min. The mean of the differences (LDCO - TDCO) was - 0.86 ± 2.80 (SD) l/min; linear regression analysis gave LDCO = - 1.90 + 1.05TDCO (r = 0.94). The mean of the differences (DopplerCO - TDCO) was 1.82 ± 2.67 (SD) l/min; DopplerCO = 2.36 + 0.98TDCO (r = 0.94). The mean of the differences (LDCO - DopplerCO) was - 2.68 ± 3.01 (SD); linear regression analysis gave LDCO = -2.53 + 0.99DopplerCO (r = 0.93).

Conclusion - These results show that the LDCO method is suitable for measuring cardiac output in horses. As well as being accurate, it avoids the need for pulmonary artery catheteristion and so is quick to use and safe.

Clinical Relevance – Monitoring cardiac output during anesthesia in horses may help reduce the high anesthetic mortality in this species.

7. Cardiac output measurement in an anaesthetized giraffe using lithium dilution. Linton, R.A.F., Taylor, P.M., Linton, N.W.F., Flach, E.J., O'Brien, T.K. and Band, D.M. The Veterinary Record 1999; 145: 498-499.

Giraffes have a high anaesthetic mortality and we wondered if a reduction in cardiac output, produced by the anaesthetic, might play a part in this. A giraffe at Whipsnade zoo needed a general anaesthetic for trimming of her hooves. The expected cardiac output on a weight basis was about 56 l/min (the estimated weight was 800 kg). During halothane anaesthesia the cardiac output was only 20 l/min.

8. A comparison of lithium dilution cardiac output measurements made using central and antecubital venous injection of lithium chloride. Jonas, M.M., Kelly, F.E., Linton, R.A.F., Band, D.M., O'Brien, T.K. and Linton, N.W.F. Journal of Clinical Monitoring and Computing 1999; 15: 525-528.


We have previously described an indicator dilution technique of measuring cardiac output in which lithium chloride is injected via a central venous catheter and cardiac output derived from the arterial lithium dilution curve recorded from a lithium-selective electrode. 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.

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.

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.

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.

9. Cardiac output measured by lithium dilution and transpulmonary thermodilution in patients in a pediatric intensive care unit. Linton RAF, Jonas MM, Tibby SM, Murdoch IA, O'Brien TK, Linton NWF, Band DM. Intensive Care Medicine 2000; 26: 1507-1511.


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 2 and 4 comparisons of lithium dilution cardiac output (LDCO) and transpulmonary thermodilution (TPCO) were made in each patient.

Measurements and results: Results from 3 patients were excluded: in one patient there was an unsuspected right-to-left shunt, in 2 patients there was a problem with blood sampling through the lithium sensor. There were 48 comparisons of LDCO and TPCO in the remaining 17 patients over a range of 0.4 – 6 l/min. The mean of the differences (LDCO – TPCO) was – 0.1 ± 0.3 (SD) l/min. Linear regression analysis gave LDCO = 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 LDCO 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.

10. The pharmacokinetics of intravenous lithium chloride in patients and normal volunteers. Jonas MM, Linton RAF, O'Brien TK, Band DM, Linton NWF, Kelly F, Burden TJ, Chevalier SFA, Thompson RPH, Birch NJ, Powell JJ. Journal of Trace and Microprobe Techniques 2001; 19: 313-320.


Objectives To study the pharmacokinetics of lithium chloride administered intravenously to patients who had undergone cardiac surgery within the previous 12 hours and to normal volunteers, since lithium is used in a new indicator dilution method for measuring cardiac output.

Methods A prospective study was carried out in a London teaching hospital. Lithium chloride was administered intravenously and blood samples taken at intervals for up to one hour. Plasma lithium levels were measured by inductively coupled plasma optical emission spectrometry and standard pharmacokinetic parameters were calculated.

Results Two groups of patients were investigated; the first (n=10) received five doses of 0.6 mmol LiCl at 2 min intervals, the second (n=10) a single dose of 0.6 mmol LiCl. A further group of six normal volunteers also received a single dose of 0.6 mmol LiCl. Biexponential curves were fitted to the data. For the three groups the half-lives of the first exponentials (T1/2alpha) were 3.3, 4.2 and 3.9 min, respectively; the half-lives of the second exponentials (T1/2beta) were 100, 83 and 102 min, respectively; the volume of distribution at steady state in all three groups was 0.2 l kg-1.

Conclusion Since lithium chloride is used diagnostically for measurement of cardiac output, knowledge of the rate constants for disappearance of lithium from the vascular compartment allows recommendations for the safe maximum frequency of lithium dilution cardiac output determinations to be made.