Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain

Objective: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α₂ adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.

Methods: Systemic saline, ketamine 20?mg/kg, or dexmedetomidine at 30 or 45?μg/kg were given six times to postnatal day 7 rats (n = 6/group) every 90?min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry.

Results: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions.

Conclusions: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.     

Apnea during induction of anesthesia with sevoflurane is related to its mode of administration

PURPOSE: The incidence and duration of apnea during sevoflurane anesthesia have not been fully characterized. We hypothesized that sevoflurane at slowly increasing concentrations reduces incidence and shortens the duration of apnea compared to administration of a highly concentrated anesthetic mixture. METHODS: 131 women were randomly assigned to receive 35% oxygen in air and sevoflurane at: incremental concentrations of 1%, from 1% to 8% (group 1-8%, n = 42); decremental-incremental concentrations of 2%, from 8% to 4% and then from 4% to 8% (group 8-4-8%, n = 36); or fixed concentrations of 8% for induction of anesthesia (group 8%, n = 53). A blinded investigator observed whether and for how long patients stopped breathing. RESULTS: All groups reached 2.5 minimum alveolar concentration of end-tidal sevoflurane. Although apnea was observed in all groups, it was more frequent in the 8% group than in 1 to 8% (68% vs 21%, P < 0.05) or 8 to 4 to 8% groups (68% vs 20%, P < 0.05). Duration of apnea was also more pronounced in the 8% group than in 1 to 8% and 8 to 4 to 8% groups ( 58 +/- 25 s vs 32 +/- 18 sec, P < 0.05 and vs 35 +/- 16 sec, P < 0.05, respectively). CONCLUSIONS: Sevoflurane induces apnea more frequently and for longer duration at a fixed high concentration compared to incremental or decremental-incremental concentrations. Decremental-incremental concentrations offer the additional advantage of a speed of induction similar to that elicited by the 8% concentration.     

Sevoflurane analgesia in obstetrics: a pilot study

Continuous and intermittent administration of inhalational anesthetics has been successfully employed for treating pain during labor. We conjectured that intermittent sevoflurane administration would be effective for pain relief during labor without side effects to the mother or fetus. Fifty parturients breathed a mixture of 2-3% sevoflurane, oxygen and air before each uterine contraction began. The patients assessed the quality of analgesia by using a visual analogue scale (0-10) before the administration of sevoflurane and after each uterine contraction. All parturients but one were satisfied, demonstrating a mean visual analogue score before and after sevoflurane administration of 8.7 +/- 1.1 and 3.3 +/- 1.5, respectively. Apgar scores at 1 and 5 min were 9 (range 5-9) and 10 (range 8-10), respectively. Our findings suggest that sevoflurane could be effective for the treatment of labor pain.     

Scopolamine Prevents Dreams during General Anesthesia

Background: Dreaming during anesthesia is not a well-understood phenomenon. Anticholinergic drugs are used in anesthesia as premedication, but their use to decrease the incidence of dreams and psychological adverse reactions after anesthesia is not well established. The authors therefore studied the efficacy of intramuscular atropine and scopolamine for the prevention of dreams during general anesthesia with propofol and nitrous oxide.

Methods: Healthy women undergoing minor gynecologic surgery were randomly assigned to receive 2.5 [mu]g/kg scopolamine or 10 [mu]g/kg atropine intramuscularly (n = 50/group). In both groups, anesthesia was induced and maintained with propofol as a 2.5-mg/kg bolus, followed by 12 mg [middle dot] kg-1 [middle dot] h-1 as a continuous infusion and 70% nitrous oxide in oxygen. Two interviews regarding dreaming activity and characteristics were conducted at 20 min and 6 h after surgery.

Results: None of the patients in the scopolamine group and 47% of the patients in the atropine group reported the occurrence of dreams 20 min after recovery. The results were similar at 6 h: 6% of the scopolamine group and 43% of the atropine group reported dream activity. No differences in sedation or anesthetic requirements were found.     

Clonidine-induced neuronal activation in the spinal cord is altered after peripheral nerve injury

BACKGROUND: Alpha 2 adrenoceptor agonists produce antinociception in normal animals and alleviate mechanical allodynia in animals with nerve injury, although their mechanism of action may differ in these situations. The purpose of this study was to examine the location and number of cells in the spinal cord activated by intrathecal clonidine in these two circumstances and to test whether one class of interneurons, cholinergic, express alpha 2 adrenoceptors. METHODS: Intrathecal saline or clonidine, 10 and 30 microg, was injected in normal rats or those with mechanical allodynia following partial sciatic nerve section. Two hours later, animals were anesthetized and pericardially perfused. The number of cells in superficial and deep dorsal horn laminae at the L4-L5 level immunostained for phosphorylated cAMP response element binding protein (pCREB) were quantified. In separate studies, the authors colocalized alpha2C adrenoceptors with cholinergic neurons. RESULTS: Intrathecal clonidine increased pCREB immunoreactive cells in both superficial and deep laminae by 50-100% in normal animals. The number of pCREB immunoreactive cells increased in nerve-injured compared to normal rats. Intrathecal clonidine decreased pCREB immunoreactive cells in the deep dorsal horn of injured animals. Alpha2C adrenoceptors colocalized with cholinergic neurons in both superficial and deep dorsal horn. DISCUSSION: Previous studies suggest a shift in alpha 2 adrenoceptor subtype and the involvement of cholinergic interneurons in antinociception in the spinal cord after nerve injury. The current results suggest that intrathecal clonidine, by direct or indirect methods, increases neuronal activation in normal animals, presumably leading to net inhibition of pain signaling, whereas it reduces the increase in neuronal activity induced by nerve injury.