The Pharmacokinetics of Atomized Lidocaine Administered via the Trachea: A Randomized Trial.

BACKGROUND: Under emergent conditions, endotracheal drug administration may be an effective method of delivering emergency drugs. A common technique is to administer these drugs using a nonatomized spray. Atomized drug delivery may be an attractive alternative to nonatomized delivery because atomized particles are small, cover a large surface area, and may better adhere to endotracheal membrane resulting in more effective drug absorption. In this study, we compared the pharmacokinetic profile of lidocaine administered into the trachea using an atomized or a nonatomized technique. METHODS: Twenty patients were anesthetized using propofol and remifentanil. Ten minutes after rocuronium was administered, patients received 4% lidocaine (2 mg/kg) intratracheally over 2 seconds before tracheal intubation. Ten patients received atomized lidocaine using a mucosal atomization device, and the other 10 patients received nonatomized lidocaine using a traditional spray tube. Arterial lidocaine plasma concentrations were measured before; at 1, 3, 5, 7, 10, 15, 20, 30, 45, and 60 minutes; and then every 60 minutes after the administration of lidocaine until the end of the operation. We developed a pharmacokinetic model to examine whether bioavailability or absorption rate was different between atomized versus nonatomized lidocaine administration. The total body clearance was fixed at a published value to determine the bioavailability. RESULTS: Peak plasma concentrations were larger using the mucosal atomization device (median [range]: 1.9 [1.4-3.2] µg/mL) than the spray tube (1.1 [0.6-2.0] µg/mL; P = 0.0021). Our pharmacokinetic model estimated a difference of bioavailability between the atomized and the nonatomized lidocaine (0.801 and 0.559 respectively, P = 0.0005), whereas our model estimated no difference in the absorption rate constant (0.00688/min). CONCLUSIONS: Our results suggest that when using atomized delivery of lidocaine, less drug is required to achieve a near equivalent plasma lidocaine concentration. Atomized drug administration may be a more efficient method for endotracheal drug administration.

[Anesthetic Management of a Patient with Langerhans Cell Histiocytosis during Cesarean section].

Langerhans cell histiocytosis is a rare disease, associated with histiocyte increases, and granuloma, in various organs. About 160 patients are reported in Japan. A pregnant patient with a pulmonary Langerhans cell histiocytosis underwent cesarean section under spinal anesthesia. She had repeated pneumothorax with bilateral pulmonary cysts rapidly becoming worse during pregnancy. She was treated with continuous oxygen after 28 weeks of the pregnancy. On 34 weeks of the pregnancy, spinal anesthesia with 0.5% hyperbaric bupivacaine (2 ml) and fentanyl (25 µg) for cesarean section was performed, and provided excellent analgesia without any side-effects.

Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic Phenotypes as an Adult in Mice.

The critical period is a distinct time-window during the neonatal stage when animals display elevated sensitivity to certain environmental stimuli, and particular experiences can have profound and long-lasting effects on behaviors. Increasing evidence suggests that disruption of neuronal activity during the critical period contributes to autistic phenotype, although the pathogenic mechanism is largely unknown. Herein we show that extracellular signal-regulated protein kinases (ERKs) play important roles in proper formation of neural circuits during the critical period. Transient blockade of ERKs phosphorylation at postnatal day 6 (P6) by intraperitoneal injection of blood-brain barrier-penetrating MEK inhibitor, α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327) caused significant increase of apoptosis in the forebrain. Furthermore, this induced long-term deleterious effects on brain functioning later in adulthood, resulting in social deficits, impaired memory and reduced long-term potentiation (LTP). Conversely, blockade of ERK phosphorylation at P14 no longer induced apoptosis, nor behavioral deficits, nor the reduced LTP. Thus, surprisingly, these effects of ERKs are strongly age-dependent, indicating that phosphorylation of ERKs during the critical period is absolutely required for proper development of brain functioning. This study provides novel insight into the mechanistic basis for neurodevelopment disorders: various neurodevelopment disorders might be generally linked to defects in ERKs signaling during the critical period.

Neonatal exposure to sevoflurane in mice causes deficits in maternal behavior later in adulthood.

BACKGROUND: In animal models, exposure to general anesthetics induces widespread increases in neuronal apoptosis in the developing brain. Subsequently, abnormalities in brain functioning are found in adulthood, long after the anesthetic exposure. These abnormalities include not only reduced learning abilities but also impaired social behaviors, suggesting pervasive deficits in brain functioning. But the underlying features of these deficits are still largely unknown. METHODS: Six-day-old C57BL/6 female mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (1.3%) as part of the carrier gas mixture. At 7-9 weeks of age, they were mated with healthy males. The first day after parturition, the maternal behaviors of dams were evaluated. The survival rate of newborn pups was recorded for 6 days after birth. RESULTS: Female mice that received neonatal exposure to sevoflurane could mate normally and deliver healthy pups similar to controls. But these dams often left the pups scattered in the cage and nurtured them very little, so that about half of the pups died within a couple of days. Yet, these dams did not show any deficits in olfactory or exploratory behaviors. Notably, pups born to sevoflurane-treated dams were successfully fostered when nursed by control dams. Mice coadministered of hydrogen gas with sevoflurane did not exhibit the deficits of maternal behaviors. CONCLUSION: In an animal model, sevoflurane exposure in the developing brain caused serious impairment of maternal behaviors when fostering their pups, suggesting pervasive impairment of brain functions including innate behavior essential to species survival.