ABSTRACT
BACKGROUND: Precise fluid balance monitoring is essential for patient treatment, as incorrect fluid balance can lead to disorders. OBJECTIVE: This study aimed to assess the accuracy of the digital technology LICENSE (LIquid balanCE moNitoring SystEm) for fluid balance charting and compare it to the standard method (SM) to determine its usability in clinical practice. METHODS: This prospective study included 20 patients. The results from LICENSE were compared to those from SM and a reference measurement (manual weight of fluids, RM). Three LICENSE devices were used for urine output, intravenous fluids, and oral fluid intake. The accuracy of methods was evaluated using Bland Altman plots. RESULTS: The mean difference between LICENSE and RM was less than 2 millilitres (p= 0.031 and p= 0.047), whereas the mean difference between SM and RM was 6.6 ml and 10.8 ml (p< 0.0001). The range between the upper and lower limits of agreement was between 16.4 and 27.8 ml for LICENSE measurements and 25.2 and 52 ml for SM. CONCLUSION: LICENSE is comparable to or more accurate than the standard method for fluid balance monitoring. The use of LICENSE may improve the accuracy of fluid balance measurements. Further research is needed to evaluate its feasibility in daily clinical practice.
Subject(s)
Patient Care , Water-Electrolyte Balance , Humans , Prospective Studies , Monitoring, Physiologic/methodsABSTRACT
Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.
Subject(s)
Benzylamines/metabolism , Brain/metabolism , Phenethylamines/metabolism , Positron-Emission Tomography , Receptor, Serotonin, 5-HT2A/metabolism , Serotonin 5-HT2 Receptor Agonists/metabolism , Serotonin/metabolism , Animals , Benzylamines/analysis , Brain/diagnostic imaging , Brain/drug effects , Carbon Radioisotopes/analysis , Carbon Radioisotopes/metabolism , Female , Fenfluramine/pharmacology , Phenethylamines/analysis , Positron-Emission Tomography/methods , Receptor, Serotonin, 5-HT2A/analysis , Serotonin 5-HT2 Receptor Agonists/analysis , Serotonin Agents/pharmacology , SwineABSTRACT
[(11)C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT(2A)) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [(11)C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT(2A) receptors with [(11)C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [(11)C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [(11)C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT(2A) receptor antagonist ketanserin before a second PET scan significantly decreased [(11)C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [(11)C]Cimbi-36 binding is selective for 5-HT(2A) receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT(2A) receptors in the human brain. Thus, we here describe [(11)C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT(2A) receptors in the human brain.
