BACKGROUND: Dexmedetomidine is a highly selective central α₂-agonist used as a sedative in pediatric intensive care unit (PICU). However, little is known about the relationship between dexmedetomidine dose and its plasma concentration during long-term infusion. We have previously demonstrated that the sedative plasma dexmedetomidine concentration is moderately correlated with the administered dose in adults (r = 0.653, P = 0.001). We hypothesized that there would be a similar relationship between the sedative dexmedetomidine concentration and administered dose in infants. METHODS: All patients admitted to the PICU at Nagoya City University Hospital, Japan, between November 2012 and March 2013 were eligible for inclusion in the study. Plasma dexmedetomidine concentration was measured by ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: We measured the plasma dexmedetomidine concentration in 203 samples from 45 patients. Of these, 96 samples collected from 27 patients < 2 years old were included in this study. All patients received dexmedetomidine at 0.12–1.40 µg/kg/h. The median administration duration was 87.6 hours (range: 6–540 hours). Plasma dexmedetomidine concentration ranged from 0.07 to 3.17 ng/ml. Plasma dexmedetomidine concentration was not correlated with the administered dose (r = 0.273, P = 0.007). The approximate linear equation was y = 0.690x + 0.423. CONCLUSIONS: In infants, plasma dexmedetomidine concentration did not exhibit any correlation with administered dose, which is not a reliable means of obtaining optimal plasma concentration.
Adult ; Chromatography, Liquid ; Cohort Studies* ; Critical Illness* ; Dexmedetomidine* ; Humans ; Infant* ; Intensive Care Units ; Japan ; Plasma* ; Prospective Studies* ; Tandem Mass Spectrometry

BACKGROUND: The requisite anesthetic concentration of sevoflurane required to obtain adequate sedation when sufficient analgesics are supplied has not been determined. The purpose of this study was to determine the requisite age-associated concentration of sevoflurane to obtain an adequate level of anesthesia during combined epidural-general anesthesia by bispectral index (BIS) monitoring. METHODS: Twenty-seven elective abdominal surgery patients (American Society of Anesthesiologists physical status I-II) were enrolled. The patients were divided into two groups of more or less than 60 years of age. We investigated the concentration of sevoflurane required to obtain an adequate sedation level during combined epidural-general anesthesia, maintaining the BIS value between 40 and 60. RESULTS: The requisite sevoflurane concentration required to keep the BIS value at 40-60 was not stable during surgery. In the younger group, the maximum concentration of sevoflurane needed during surgery was 1.95 +/- 0.14 (95% confidence interval: 1.87-2.10) vol%, while it was 1.54 +/- 0.44 (95% confidence interval: 1.27-1.80) vol% in the older group (P < 0.01). CONCLUSIONS: The requisite concentration of sevoflurane required with combined epidural-general anesthesia was 2.5 vol% for the younger group and 2.0 vol% for the older group as determined by BIS monitoring. We believe that these percentages are sufficient to avoid awareness during surgery with adequate analgesia.
Analgesia ; Analgesics ; Anesthesia ; Anesthesia, Epidural ; Anesthetics, Inhalation ; Humans ; Methyl Ethers

No abstract available.
Stroke Volume* ; Stroke*

Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. Patients with MSA show various phenotypes during the course of their illness, including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. Patients with MSA sometimes present with isolated autonomic failure or motor symptoms/signs. The median duration from onset to the concomitant appearance of motor and autonomic symptoms is approximately 2 years but can range up to 14 years. As the presence of both motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. In contrast, patients with MSA may show severe autonomic failure and die before the presentation of motor symptoms/signs, which are currently required for the diagnosis of MSA. Recent studies have also revealed that patients with MSA may show nonsupporting features of MSA such as dementia, hallucinations, and vertical gaze palsy. To establish early diagnostic criteria and clinically definitive categorization for the successful development of disease-modifying therapy or symptomatic interventions for MSA, research should focus on the isolated phase and atypical symptoms to develop specific clinical, imaging, and fluid biomarkers that satisfy the requirements for objectivity, for semi- or quantitative measurements, and for uncomplicated, worldwide availability. Several novel techniques, such as automated compartmentalization of the brain into multiple parcels for the quantification of gray and white matter volumes on an individual basis and the visualization of α-synuclein and other candidate serum and cerebrospinal fluid biomarkers, may be promising for the early and clinically definitive diagnosis of MSA.
Biomarkers ; Brain ; Cerebellar Ataxia ; Cerebrospinal Fluid ; Dementia ; Diagnosis ; Early Diagnosis ; Hallucinations ; Humans ; Multiple System Atrophy ; Neurodegenerative Diseases ; Paralysis ; Parkinsonian Disorders ; Phenotype ; White Matter