: We carried out a retrospective investigation on the effect of obesity on dexmedetomidine (DEX) requirements when administered with fentanyl (FEN) during mechanical ventilation after major surgeries. After Institutional Review Board approval, 14 obese patients with a body mass index (BMI) ≥ 30 kg/m 2 and the same number of non -obese patients with similar backgrounds to the obese patients were selected from medical records. Doses of DEX in the first 48 h or until the end of sedation or extubation were calculated for comparison. In addition to comparison of dosing between the groups, associations between total body weight (TBW), BMI, and lean body mass (LBM) values and doses of DEX (mcg/h), between BMI and various indices (i.e., amount per TBW per hour and amount per LBM per hour) of DEX doses, and between above indices of DEX and FEN doses were also examined. There were no significant differences in DEX dose indices between the groups. However, DEX requirements (mcg/h) were significantly increased with TBW (kg) (r = 0.51, P = 0.003), BMI (r = 0.49, P = 0.006) and LBM (kg) (r = 0.42, P = 0.02), which might have enhanced the DEX metabolism with physiological changes with obesity. These findings will be beneficial for future clinical pharmacological analysis of DEX.

BACKGROUND The pathophysiology of Fabry disease (FD)-induced progressive vital organ damage is irreversible. Disease progression can be delayed using enzyme replacement therapy (ERT). In patients with classic FD, sporadic accumulation of globotriaosylceramide (GL-3) in the heart and kidney begins in utero ; however, until childhood, GL-3 accumulation is mild and reversible and can be restored by ERT. The current consensus is that ERT initiation during early childhood is paramount. Nonetheless, complete recovery of organs in patients with advanced FD is challenging. CASE SUMMARY Two related male patients, an uncle (patient 1) and nephew (patient 2), presented with classic FD. Both patients were treated by us. Patient 1 was in his 50s, and ERT was initiated following end-organ damage; this was subsequently ineffective. He developed cerebral infarction and died of sudden cardiac arrest. Patient 2 was in his mid-30s, and ERT was initiated when the patient was diagnosed with FD, during which the damage to vital organs was not overtly apparent. Although he had left ventricular hypertrophy at the beginning of this treatment, the degree of hypertrophy progression was limited to a minimal range after > 18 years of ERT. CONCLUSION We obtained discouraging ERT outcomes for older patients but encouraging outcomes for younger adults with classic FD.

To confirm that an increase in blood pressure induced by ketamine is mediated through the central nervous system, we examined the effect of ketamine, applied directly to the amygdala, on blood pressure. Six male Sprague-Dawley rats were used in the study. Under head-restrained and unanesthetized condition, 0.2 μl (5 mg/ml) of ketamine was injected in and around the amygdala at a flow rate of 0.2 μl/min through a glass pipette, and the blood pressure was recorded while monitoring the state of the animals by electroencephalogram and electromyogram. After ketamine injection, the injection site was marked by Pontamine Sky Blue infusion. Blood pressure was increased by ketamine injection into the basolateral and central nuclei of the amygdala, endopiriform nucleus and piriform cortex. In a total of 11 responses, an increase in blood pressure started with a mean latency of 193.5 ± 43.0 sec, reached its peak 180.2 ± 23.3 sec after the response onset, then gradually returned to the baseline with mean duration of 706.7 ± 113.5 sec. The mean fluctuation was 17.1 ± 2.5 mmHg. We revealed that blood pressure fluctuations induced by ketamine are associated with the amygdala. Elucidation of the mechanism of ketamine-induced blood pressure increase will lead to understanding of the mechanism of side effects of ketamine, and will contribute to its appropriate use.