ABSTRACT
BACKGROUND: Droperidol (DHB) reportedly reduces the dose of propofol needed to achieve hypnosis when anesthesia is induced and decreases the bispectral index (BIS) in propofol-sedated patients during spinal anesthesia. We reported previously that supplemental DHB decreased the BIS after the administration of sevoflurane and remifentanil. This study investigated the effect of DHB on desflurane (DES) consumption in a clinical setting. METHODS: We conducted a prospective, randomized double-blinded study of 35 women with American Society of Anesthesiologist physical status I or II who underwent a mastectomy. Either DHB (20 µg/kg) or a saline placebo was administered to patients 30 min after the induction of anesthesia. A blinded anesthesiologist maintained a BIS value of 50 during anesthesia by modulating inhaled DES concentrations that changed 0.5% at 2.5 min intervals and maintained analgesia via the constant administration of remifentanil by referring to vital signs. The primary endpoint was the effect of DHB on DES consumption. The secondary endpoints included blood circulatory parameters, the time from the end of surgery to extubation, and discharge time between the groups. RESULTS: The characteristics of the patients did not differ between the groups. The DHB group used a mean of 27.2 ± 6.0 ml of DES compared with 41.4 ± 9.5 ml by the placebo group (P < 0.05). CONCLUSIONS: A small dose of DHB reduced the DES concentration needed to maintain a BIS of 50. Our results show that DHB reduced the consumption of DES without adverse effects.
Subject(s)
Female , Humans , Analgesia , Anesthesia , Anesthesia, General , Anesthesia, Spinal , Breast Neoplasms , Breast , Droperidol , Hypnosis , Mastectomy , Propofol , Prospective Studies , Vital SignsABSTRACT
BACKGROUND: Neonatal exposure to anesthetics induces neuronal apoptosis and long-term cognitive dysfunction in rodents. We showed that the nicotinamide adenine dinucleotide phosphate-oxidase inhibitor apocynin not only reduces neurotoxicity by decreasing superoxide levels and preventing mitochondrial dysfunction but also improves long-term memory impairment in neonatal mice exposed to sevoflurane. We also found that after the contextual fear conditioning test, glutamatergic neurons expressed c-Fos (neural activation) regardless of previous exposure to sevoflurane. Moreover, there were fewer c-Fos-expressing glutamatergic neurons in the basolateral amygdala (BLA) after exposure to sevoflurane than after exposure to carrier gas. In this study, we investigated whether the administration of apocynin prior to sevoflurane exposure would preserve glutamatergic neurons in the BLA. METHODS: Apocynin (50 mg/kg) was injected intraperitoneally into six-day-old male mice 30 min before 6 h of exposure to 3% sevoflurane or carrier gas only. The mice were allowed to mature and then were subjected to the contextual fear conditioning test. The neural activation and neuron population in the BLA were investigated 2 h later. RESULTS: Administration of apocynin prior to neonatal sevoflurane exposure not only prevented learning deficits but also preserved c-Fos-expressing glutamatergic neurons in the BLA. CONCLUSIONS: Apocynin mitigates the cognitive impairment induced by neonatal sevoflurane exposure and preserves c-Fos-expressing glutamatergic neurons in the basolateral amygdala.
Subject(s)
Animals , Humans , Male , Mice , Anesthesia , Anesthetics , Apoptosis , Basolateral Nuclear Complex , Brain , Cognition Disorders , Learning , Memory, Long-Term , NAD , Neurons , Pediatrics , Rodentia , SuperoxidesABSTRACT
BACKGROUND: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats. METHODS: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia. RESULTS: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group). CONCLUSIONS: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.
Subject(s)
Animals , Rats , Administration, Intravenous , Anesthesia , Apoptosis , Bone Marrow , Brain , Caspase 3 , Central Nervous System , Interleukin-6 , Mesenchymal Stem Cells , Neurons , Rats, Sprague-Dawley , Rodentia , StrokeABSTRACT
BACKGROUND: The required dose of anesthetics is generally smaller in patients with low cardiac output (CO). A high CO decreases the blood concentration of anesthetics during induction and maintenance of anesthesia. However, a high CO may also shorten the delivery time of anesthetics to the effect site, e.g. the brain. We assessed the time required for induction of anesthesia with propofol administered by target-controlled infusion (TCI), and investigated factors that modify the pharmacodynamics of propofol. METHODS: After measuring CO and blood volume (BV) by dye densitometry, propofol was infused using TCI to simulate a plasma concentration of 3 microg/ml. After infusion, the time taken to achieve bispectral index (BIS) values of 80 and 60 was determined. Age, sex, lean body mass (LBM), and cardiovascular parameters were analyzed as independent variables. The dependent variables were the time taken to achieve each BIS value and the plasma concentration of propofol (Cp) 10 min after the commencement of infusion. RESULTS: Multiple regression analysis revealed that a high CO significantly reduced the time taken to reach the first end point (P = 0.020, R2 = 0.076). Age and LBM significantly prolonged the time taken to reach the second end point (P = 0.001). Cp was negatively correlated with BV (P = 0.020, R2 = 0.073). CONCLUSIONS: Cardiac output was a statistically significant factor for predicting the time required for induction of anesthesia in the initial phase, whereas, age and LBM were significant variables in the late phase. The pharmacodynamics of propofol was intricately altered by CO, age, and LBM.