Dexmedetomidine facilitates induction of noninvasive positive pressure ventilation for acute respiratory failure in patients with severe asthma.

Noninvasive positive pressure ventilation (NPPV) has been reported to be effective for acute respiratory failure in patients with severe asthma. Although NPPV requires less sedative than invasive mechanical ventilation, agitated patients with severe asthma should be given the minimum sedation necessary to facilitate the induction of NPPV. Two asthmatic patients (a 65-year-old man and a 32-year-old woman) separately presented to the intensive care unit with exacerbating respiratory failure. We initiated NPPV using bilevel positive airway pressure (PAP) ventilation. The ventilation was initially set as an inspiratory PAP of 15 cmH(2)O and an expiratory PAP of 4 cmH2O. Because they seemed too agitated to tolerate the mask ventilation, dexmedetomidine was administered intravenously, at 3 microg x kg(-1) x h(-1) [DOSAGE ERROR CORRECTED] for 10 min, followed by a continuous infusion at 0.2-0.6 mircog x kg(-1) x h(-1) [DOSAGE ERROR CORRECTED]. One hour after the institution of NPPV, the patients were well cooperative with the mask ventilation and the respiratory symptoms had markedly improved. While the Ramsay sedation scale was maintained at 2 or 3 during the continuous dexmedetomidine infusion, we successfully weaned the patients from NPPV by reducing the inspiratory PAP. Dexmedetomidine helped the agitated patients cooperate with mask ventilation without inducing respiratory depression. We conclude that dexmedetomidine may be a valuable sedative to facilitate the induction of NPPV.

A comparison of protective effects between L-histidine and hypothermia against ischemia-induced neuronal damage in gerbil hippocampus.

An increase in the histamine concentration in the brain has been demonstrated to provide protective effects against ischemia/reperfusion brain injury. Since hypothermia and barbiturates are also regarded to protect ischemic brains, effects of postischemic treatments were compared in gerbils between mild hypothermia and intraperitoneal administration of L-histidine, a precursor of histamine. Furthermore, effects of thioperamide, a histamine H(3) receptor antagonist, were evaluated in histidine-treated gerbils after 60 days. Transient forebrain ischemia for 4 min at 37 degrees C provoked severe neuronal damage in the hippocampal CA1 pyramidal cells after 7 days. Postischemic hypothermia (33 degrees C) for 3 h under pentobarbital anesthesia alleviated neuronal death, and the number of preserved neurons was 77+/-56/mm (mean+/-S.D., n=14). The effect of L-histidine injected three times, immediately, 6 h, and 24 h after reperfusion (1,000 mg/kg, i.p., each), was more prominent than that of hypothermia, and the number of preserved neurons was 142+/-55/mm (n=14). When the histologic outcome was evaluated after 60 days, most neurons were damaged in both the hypothermic and histidine groups. The improvement of the histologic outcome was observed even after 60 days in animals injected with thioperamide, immediately and 6 h after reperfusion (5 mg/kg, s.c., each), with three injections of l-histidine. The number of preserved neurons was 133+/-88/mm (n=10), while that in the hypothermic group was 7+/-15 (n=10). Activation of the central histaminergic system provides beneficial effects against cerebral ischemia.

Reduction in brain infarction by augmentation of central histaminergic activity in rats.

Inflammation is a factor in the aggravation of reperfusion injury after cerebral ischemia. Since histamine H(2) receptor stimulation suppresses inflammatory reactions, effects of the central histaminergic activation on brain infarction were examined in rats. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery, and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride stain after 24 h. Effects of postischemic administration of thioperamide, an H(3) antagonist, and metoprine, an inhibitor of histamine-N-methyltransferase, were evaluated in rats treated with l-histidine, a precursor of histamine. Furthermore, effects of these agents on changes in the striatal histamine level were examined by a microdialysis procedure. Focal ischemia provoked marked damage in rats treated with l-histidine (1000 mg/kg) alone. Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction. The size of brain infarction was 27% and 10% of that in animals treated solely with l-histidine, respectively. The combination treatment with thioperamide and metoprine decreased the size of brain infarction in rats given l-histidine (500 mg/kg), although protective effects were not clear without l-histidine. A marked increase in the histamine concentration was observed in the histidine plus metoprine group, the value being 363% of that in the saline-injected group after 2-3 h. The histamine concentrations in the histidine group and histidine plus thioperamide group were 188% and 248%, respectively. These findings indicate that facilitation of central histaminergic activity reduced the brain infarction.

Facilitation of serotonergic activity and amnesia in rats caused by intravenous anesthetics.

BACKGROUND: Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory. METHODS: Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test. RESULTS: Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 microg), a 5-hydroxytryptamine 1A antagonist, 30 min before training. CONCLUSIONS: Midazolam and propofol increased central serotonergic activity and provoked retrograde amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine antagonist, facilitation of the serotonergic system may be involved in retrograde amnesia caused by these agents.