Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Predicting Postoperative Emergence Delirium From the Heart Rate Variability of Patients Undergoing Elective Cardiac Surgery.

Background and objective The complication of postoperative delirium is directly linked to prognosis, leading to prolonged hospital stays and an increase in mortality. Since there is no magic medicine that cures delirium, the prevention of its onset is important, and the development of simple tools that enable the early assessment of the risk is valuable. In the previous study, we hypothesized that postoperative delirium could be predicted from heart rate variability (HRV) measured by using an electrocardiogram (ECG) on the day before elective esophageal cancer surgery. HRV is calculated based on the fluctuation of RR intervals on ECG. The preoperative high-frequency (HF) power in delirium patients was significantly lower than that in non-delirium patients. The HF component is considered a reflection of parasympathetic function. In the current study, we evaluated the hypothesis that parasympathetic nerve activity is low in the resting HRV on the night before surgery in patients who go on to develop postoperative delirium. To that end, we recorded resting HRV in patients scheduled for cardiac surgery on the night before surgery. We then compared the HRV between patients with and without delirium in the postoperative intensive care unit (ICU). The Confusion Assessment Method for the ICU (CAM-ICU) was used to diagnose delirium. Methods This was a prospective observational study involving patients undergoing elective cardiac surgery. After obtaining approval from the institutional review board, patients aged 65 years and older were enrolled in the study. The day before surgery, a Mini-Mental State Examination (MMSE) was performed. The ECG was used in patients for five minutes. All patients were transferred to the ICU after surgery, and CAM-ICU was measured every eight hours until discharge from the ICU, and positive patients were diagnosed with delirium. Results In this study, 14 patients who developed delirium and 22 patients who did not were included in the analysis. The average MMSE score was 27.4, with no patients diagnosed with preoperative dementia. In the analysis of HRV, the HF component was significantly lower in the group with delirium compared to the group without delirium (Mann-Whitney U test, p<0.05). Conclusion Based on our findings, in patients with postoperative delirium, the activity of parasympathetic nerves was lower than before surgery, and we concluded that it is possible to predict the onset of postoperative delirium based on preoperative ECG measurement.

Preoperative heart rate variability analysis is as a potential simple and easy measure for predicting perioperative delirium in esophageal surgery.

BACKGROUND: Delirium is one of the most common but severe perioperative complications. Autonomic activity evaluated by heart rate variability (HRV) has been recently reported as a useful tool for prediction and for early detection of delirium in acute care medicine, especially in postoperative intensive care unit (ICU) patients. We hypothesized that HRV, by 3-lead electrocardiogram (ECG), one day prior to surgery might correlate with the presence of postoperative delirium. MATERIALS AND METHODS: This study was cohort prospective pilot study. We measured preoperative HRV and postoperative delirium in patients who underwent surgery for elective esophageal cancer. ECG of the participants was performed for 10 min 6-12 h preceding surgery. Postoperatively, patients were admitted to the ICU or critical care unit and stayed for at least 3 days. Delirium was diagnosed by psychiatrist rounds twice a day. RESULTS: Delirium was assessed for 3 days after surgery and 30 patients performed the study. Seven patients developed delirium during their ICU stay, while the remaining twenty-three did not. After HRV analysis, the preoperative high frequency power in delirium patients was significantly lower than that in non-delirium patient. Other parameters of HRV, including lower frequency power, total power and the ratio showed no statistically significant difference between the groups. CONCLUSION: The results of current study demonstrated that preoperative measurement of HRV may be a useful predictor of delirium. Further investigation could pave the way to a non-invasive, minimally stressful method of predicting postoperative delirium.

JM-1232(-) and propofol, a new combination of hypnotics with short-acting and non-cumulative preferable properties.

Drug interactions are significant in anesthesiology because drug combinations can potentially possess novel properties. The pharmacological advantages of a new combination of the benzodiazepine receptor agonist JM-1232(-) and propofol were investigated in mice. Male adult mice were administered JM-1232(-) or propofol or combinations of the two drugs intravenously. Loss of the righting reflex was evaluated as achieving hypnosis, and the time until recovery of the reflex was measured as hypnosis time. After determining the ED50, doses double and triple the ED50 of propofol were injected with JM-1232(-) to compare hypnosis time. The injections were repeated four times, and the hypnosis times were compared. Flumazenil was administered separately immediately after the last dose was injected. The ED50 values ([95% confidence interval]) for hypnosis were 3.76 [3.36-4.10] for JM-1232(-) and 9.88 [8.03-11.58] mg kg-1 for propofol. Co-administration of 0.5 and 1 mg kg-1 JM-1232(-) reduced the ED50 values of propofol to 1.76 [1.21-2.51] and 1.00 [0.46-1.86] mg kg-1, respectively. The drug combination for hypnosis produced a supra-additive interaction. Hypnosis time was significantly shorter in the groups given the mixtures compared to each hypnotic administered alone. After repeated injections, hypnosis time with the mixtures showed smaller prolongation than that with the hypnotic alone. Flumazenil completely restored the recovery time after anesthesia. The combination of JM-1232(-) and propofol showed a supra-additive interaction, and the reduced hypnotic dose contributed to a faster recovery even after multiple injections.

Aspiration of massive free air from a large bore intravenous catheter sheath: A case report.

We firstly experienced a rare case demonstrating that massive volume of free air was aspirated from a large bore intravenous catheter sheath of the pulmonary arterial catheter during placement. A 44-year-old male patient underwent the emergency induction of anesthesia for transplantation of liver donated by the brain death subject. After the induction, the central venous and pulmonary artery catheter placement was conducted. The aspiration of venous blood confirmed the intravascular insertion, but massive free air was aspirated when we advanced the sheath proximally. A perforation of subclavian vein and subsequent pneumothorax was strongly suspected. The emergency computed tomography revealed no sign of pneumothorax, pneumomediastinum nor extravasation. The operation was undergone with intensive monitoring and no further adverse complication was observed. The postoperative medical inquiry concluded that the massive free air was not aspirated from extravascular space, for example, thorax or mediastinum through the tip of the sheath, but from the proximal main port of the sheath. When the tip of sheath is occluded by the migration into small vessels, the large negative pressure through side port might easily aspirate the air through the 1-way valve of the main proximal port. Physicians should keep in mind of the structure of the catheter sheath.

Smaller effect of propofol than sevoflurane anesthesia on dopamine turnover induced by methamphetamine and nomifensine in the rat striatum: an in vivo microdialysis study.

Volatile anesthetics accelerate dopamine turnover in the brain, especially when used in conjunction with psychotropic agents such as methamphetamine and nomifensine. The effect of intravenous propofol anesthesia on the extracellular dopamine concentrations is unclear. The aim of this study was to compare the effect of two anesthetics on the extracellular concentrations of dopamine and metabolites using an in vivo microdialysis model. Male Sprague Dawley rats were implanted with a microdialysis probe into the right striatum. The probe was perfused with modified Ringer's solution, and the dialysate was directly injected into a high-performance liquid chromatography system every 20 min. The rats were intraperitoneally administered saline, methamphetamine at 2 mg/kg, or nomifensine at 10 mg/kg. After treatment, the rats were anesthetized with intravenous propofol (20 mg/kg followed by 25 or 50 mg/kg/h) or inhalational sevoflurane (2.5%) for 1 h. Propofol showed no effect on the extracellular concentration of dopamine during anesthesia; however, propofol decreased the dopamine concentration after anesthesia in the high-dose group. Sevoflurane anesthesia increased the concentration of metabolites. Systemic administration of methamphetamine and nomifensine increased the extracellular concentration of dopamine. Sevoflurane anesthesia significantly enhanced the increase in the dopamine concentration induced by both methamphetamine and nomifensine, whereas propofol anesthesia showed no effect on the methamphetamine- and nomifensine-induced dopamine increase during anesthesia. The enhancing effect of psychotropic agent-induced acceleration of dopamine turnover was smaller for propofol anesthesia than for sevoflurane anesthesia.

Neonatal Sevoflurane Exposure Induces Adulthood Fear-induced Learning Disability and Decreases Glutamatergic Neurons in the Basolateral Amygdala.

BACKGROUND: Neonatal mice exposed to sevoflurane show certain cognitive and behavioral impairments in adulthood. However, the mechanisms underlying long-term cognitive deficits induced by sevoflurane exposure remain unknown. The present study was performed to investigate whether there is differential neuronal activation between naive mice and sevoflurane-exposed neonates in fear-conditioning tests based on immediate early gene (c-Fos) expression. METHODS: Male mice were exposed to 3% sevoflurane (SEVO group) or carrier gas alone (no anesthesia, NA group) for 6 hours on postnatal day 6. The mice were allowed to mature before performing the contextual fear-conditioning test. A reduced freezing response was confirmed in the SEVO group. Neural activation in the regions of the medial prefrontal cortex, hippocampus, and amygdala was investigated using c-Fos immunostaining 2 hours after the test. The types of neurons activated were also identified. RESULTS: The number of c-Fos-positive cells decreased by 27% in the basolateral amygdala in the SEVO group, while no significant changes were observed in other regions. Furthermore, glutamatergic, but not γ-aminobutyric acid (GABA)ergic, neurons expressed c-Fos after the contextual fear-conditioning test in both groups. The number of glutamatergic neurons in the basolateral amygdala in the SEVO group was reduced by 27%. CONCLUSIONS: Decreased neural activation in the basolateral amygdala may be associated with reduced freezing time in neonatal sevoflurane-exposed mice. Fewer glutamatergic neurons responding to fear stimuli in the basolateral amygdala may contribute to decreased neural activation and learning deficits in mice exposed to sevoflurane as neonates.

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice.

Systemic inflammation induces brain neuronal inflammation, in turn causing acute cognitive disorders. Furthermore, neuronal inflammation is one cause of postoperative cognitive disorder (POCD) and delirium. However, no sufficiently established pharmacological treatment is available for neurocognitive inflammation. This study evaluated the possible neuroprotective effects of preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory changes in an animal model of lipopolysaccharide (LPS)-induced systemic inflammation. Adult mice were randomly divided into (1) control, (2) 2% sevoflurane preconditioning for 1 h, (3) intraperitoneal 5 mg/kg LPS injection, and (4) 2% sevoflurane preconditioning for 1 h + LPS injection groups. At 24 h after 5 mg/kg LPS injection, microglial activation based on ionized calcium-binding adapter molecule 1 (Iba-1) expression in the hippocampus was determined using immunostaining and immunoblotting. IL-1ß and IL-6 immunoblotting were used as inflammation markers, and ß-site of amyloid precursor protein cleaving enzyme 1 (BACE1) immunoblotting was performed to evaluate amyloid ß-protein (Aß) accumulation. Long-term cognitive impairment was evaluated using fear conditioning tests. Intraperitoneal LPS increased levels of Iba-1 (150%), inflammation markers (160%), and Aß accumulation (350%), and sevoflurane preconditioning suppressed these increases. Systemic LPS caused learning deficits. Sevoflurane also maintained long-term memory in mice receiving LPS injection. Sevoflurane preconditioning prevented long-term memory impairment in the mouse model administered systemic LPS by decreasing excessive microglial activation, inflammation, and Aß accumulation. This study supports the hypothesis that sevoflurane preconditioning might also be beneficial for neuronal inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

Corrigendum to "Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice".

[This corrects the article DOI: 10.1155/2016/9682703.].

Perioperative airway management of a 16-year-old boy with progressive airway obstruction due to juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma (JNA) involves difficult anesthetic management because of the risk of massive bleeding, while airway management is rarely a problem in JNA. This report presents an unusual case of JNA causing airway obstruction.

Apocynin preserves glutamatergic neurons in the basolateral amygdala in mice with neonatal sevoflurane exposure.

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.

A low dose of droperidol decreases the desflurane concentration needed during breast cancer surgery: a randomized double-blinded study.

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.

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice.

In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150%) in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence.

Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory consolidation via the increased cytoskeleton constitution in the hippocampus of animals in early adolescence.