Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients.

BACKGROUND: Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release. METHODS: Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling. RESULTS: The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 h-1, respectively. CONCLUSIONS: Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight.

Intracardiac echocardiography guided transeptal catheter injection of microspheres for assessment of cerebral microcirculation in experimental models.

The use of microspheres for the determination of regional microvascular blood flow (RMBF) has previously used different approaches. This study presents for the first time the intracardiac injection of microspheres using transeptal puncture under intracardiac echocardiography guidance. Five Merino sheep were instrumented and cardiovascularly supported according to local guidelines. Two catheter sheaths into the internal jugular vein facilitated the introduction of an intracardiac probe and transeptal catheter, respectively. Five million colour coded microspheres were injected into the left atrium via this catheter. After euthanasia the brain was used as proof of principle and the endpoint for determination of microcirculation at different time points. Homogeneous allocation of microspheres to different regions of the brain was found over time. Alternate slices from both hemispheres showed the following flow ranges: for slice 02; 0.57-1.02 mL/min/g, slice 04; 0.45-1.42 mL/min/g, slice 06; 0.35-1.87 mL/min/g, slice 08; 0.46-1.77 mL/min/g, slice 10; 0.34-1.28 mL/min/g. A mixed effect regression model demonstrated that the confidence interval did include zero suggesting that the apparent variability intra- and intersubject was not statistically significant, supporting the stability and reproducibility of the injection technique. This study demonstrates the feasibility of the transeptal injection of microspheres, showing a homogeneous distribution of blood flow through the brain unchanged over time and has established a new interventional model for the measurement of RMBF in ovine models.

Remote care by telemedicine in the ICU: many models of care can be effective.

PURPOSE OF REVIEW: Telemedicine, by the use of audiovisual technologies, is increasingly being used to assist in patient care by ICUs unable to be staffed by consultant intensivists. This review discusses the recent evaluation of these services and their potential role in managing intensive care patients. RECENT FINDINGS: Models of care range from complete remote 24 h surveillance requiring direct video observation to a consultation liaison service only requiring conventional telephone links. There has been a rapid adoption of such services especially in North America where access to on-site intensive care specialists is limited for the volume of intensive care being undertaken. Early work suggests savings in terms of cost and length of stay with an improvement in compliance with care protocols. However, later work is not as supportive of such services, possibly related to differing care infrastructures and the organization of individual units. The key task is to ascertain the most appropriate service requirements that would assist in care for a given patient circumstance. SUMMARY: Clear benefits of ICU-telemedicine systems remain unclear but at least the systems appear safe. Formal reviews of the impacts and contribution of ICU telemedicine to processes of care, the effects on unit staffing, hospital organization, and the healthcare region are needed. However, ICU-telemedicine is available and being embraced by some, especially to deal with the tyranny of distance.