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The pupillary dilation reflex (PDR), the change in pupil size after a nociceptive stimulus, has been used to assess antinociception during anesthesia. The aim of this study was to compare the antinociceptive properties of sevoflurane and desflurane by measuring the PDR amplitude.Seventy patients between 20 and 55 years of age were randomly allocated to receive either sevoflurane or desflurane. The PDR amplitude after an electrical standardized noxious stimulation (SNT) was measured using an infrared pupillometer under 1.0 minimum alveolar concentration (MAC). The pupil diameter was measured from 5 seconds before to 5 minutes after the SNT. The mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were also measured immediately before and after SNT as well as 1 minute and 5 minutes after SNT. The primary outcome was the maximum percent increase from the prestimulation value of the pupil diameter, and the secondary outcomes were the maximum percent increase from the prestimulation value of the MAP, HR, and BIS after SNT.The maximum percent increase of the pupil diameter after SNT was not different between the 2 groups (median [first quartile to third quartile], 45.1 [29.3-80.3] vs 43.4 [27.0-103.1]; median difference, -0.3 [95% confidence interval, -16.0 to 16.5]; P = .986). Before SNT, the MAP was higher under 1.0 MAC of sevoflurane than desflurane; however, the maximum percent increase of MAP, HR, and BIS was not different between the 2 groups.The amount of change in the PDR amplitude, MAP, and HR after SNT was not different between sevoflurane and desflurane anesthesia. This result might suggest that sevoflurane and desflurane may not have different antinociceptive properties at equivalent MAC.

Background The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. Objective Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. Design Randomised controlled study. Setting Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. Patients Fifty-one patients. Interventions After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. Main outcome measures Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. Results The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. Conclusion Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. Trial registration Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

Background An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed. Objectives The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery. Design A systematic review and meta-analysis of randomised controlled trials (RCTs). Data sources A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019. Eligibility criteria RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia. Results Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = -3.32 min (95% CI -4.02 to -2.61)) with a substantial heterogeneity (I = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = -0.45 min (95% CI -5.89 to 4.99)). Conclusion Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account. Trial registration PROSPERO (CRD42019147939).

Background Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. Objective To investigate the effect of THC on the MAC of sevoflurane in rats. Methods Observer-blinded, randomised controlled trial. Setting Centre for Biomedical Research of the Medical University of Vienna, 2019. Individuals Thirty-eight adult Wistar rats. Interventions The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. Main outcome measures The primary outcome was the MAC of sevoflurane in Groups A and B. Results The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. Conclusion Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. Trial registration Not applicable.

Sevoflurane and desflurane are commonly used inhalation anesthetics in clinical practice. This study compared the synergistic effects of sevoflurane and desflurane on the muscarinic agent vecuronium in laparoscopic colon cancer surgery. The aim of this study was to compare sevoflurane and desflurane in a synergistic effect on the muscle relaxant vecuronium in laparoscopic colon cancer surgery. Sixty patients undergoing elective laparoscopic radical resection of colon cancer were randomly divided into sevoflurane (n = 30) and desflurane (n = 30) groups. After anesthesia and successful tracheal intubation, patients in both groups were maintained with combined remifentanil. Muscle relaxant effects were monitored in both groups using a muscle relaxant monitor (train of stimuli-Watch), the onset time, T1 and T2 recovery time, and muscle relaxant dosage of vecuronium were observed. Hemodynamic changes were observed in both groups, and the dosage of vasoactive drugs was recorded. The quality of recovery of the patients was evaluated using the Mini-Mental State Examination (MMSE) and the discharge from the Aldrete score criteria. There was no significant difference in the onset time of vecuronium between the two groups (P .05). The desflurane group's T1 and T2 recovery times were later than that of the sevoflurane group. The dosage of vecuronium was statistically significantly less than that in the sevoflurane group (P .05); the extubation time in the desflurane group was statistically significantly longer than that in the sevoflurane group (P .05). There were no significant differences in preoperative and intraoperative mean arterial pressure, heart rate, ephedrine and atropine dosage, MMSE score, and Aldrete score between the 2 groups (P .05). Compared with sevoflurane, desflurane has a stronger synergistic effect on the muscle relaxant of vecuronium without increasing the incidence of cardiovascular adverse reactions and affecting patient recovery.

Thyroidectomy is performed under general anesthesia using inhaled anesthetics such as sevoflurane or desflurane in many cases. The objective of this study was to investigate whether the incidence of postoperative pain and discomfort after thyroidectomy differed with the type of inhaled anesthetic.Eighty-one female patients who underwent thyroidectomy were randomly assigned to the Sevo group (n = 42) or the Des group (n = 39). On the day of surgery and on the first, third, and seventh days after surgery, one registered nurse in charge of the entire questionnaire survey conducted the questionnaire assessment through face-to-face interviews or phone calls with the patients. The questionnaire evaluated the severity scores for seven items (sore throat, wound pain, nausea and vomiting, dizziness, occipital headache, posterior neck pain, and shoulder pain) regarding postoperative pain and discomfort experienced by patients and assessed which of these seven items caused the greatest discomfort to the patient on each day.Except for the severity score for dizziness on the day of surgery, the severity scores of postoperative pain and discomfort experienced by patients on the day of surgery and on the first, third, and seventh days after surgery showed no statistically significant differences between the two groups. In addition, on the day of surgery and on the first, third, and seventh days after surgery, patients reported that sore throat caused the greatest discomfort.In patients undergoing thyroidectomy under general anesthesia using sevoflurane or desflurane, except for dizziness on the day of surgery, no other manifestation of postoperative pain and discomfort was influenced by the type of inhaled anesthetic. Moreover, after thyroidectomy, postoperative sore throat caused the greatest discomfort to patients from the day of surgery to the seventh day after surgery.

BACKGROUND General anesthesia has been associated with neuronal apoptosis and activation of caspases. Apoptosis is a crucial factor in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). We conducted a double-blind, prospective, randomized pilot study to evaluate the effect of 4 anesthetic agents on cerebrospinal fluid (CSF) and serum caspase-3 levels in aSAH patients. MATERIALS AND METHODS A total of 44 good-grade aSAH patients with preoperative lumbar drain scheduled for surgical clipping or endovascular coiling were randomized to receive maintenance of anesthesia with propofol, isoflurane, sevoflurane, or desflurane. Caspase-3 levels were measured in CSF and serum samples collected at baseline, 1 hour after induction, and 1 hour after cessation of anesthesia. RESULTS Compared with baseline, there was a decrease in CSF caspase-3 levels and an increase in serum caspase-3 levels 1 hour after exposure to all 4 anesthetic agents; levels returned to baseline values after cessation of anesthesia. Median CSF caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1 hour after cessation of anesthesia were 0.0679, 0.0004, and 0.0689 ng/mL, respectively (P

Anesthesia neurotoxicity in developing brain has gained increasing attention. However, knowledge regarding its mitigating strategies remains scant. Sevoflurane, a commonly used anesthetic, is responsible for learning and memory deficits in neonates. Molecular hydrogen is reported to be a potential neuroprotective agent because of its antioxidative and anti-inflammatory activities. This study aimed to investigate the effect of hydrogen gas on sevoflurane neurotoxicity. The newborn rats were treated with sevoflurane and/or hydrogen gas for 2 h. Spatial recognition memory and fear memory were determined by Y-maze and fear conditioning tests at 10 weeks of age. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and proinflammatory cytokine levels were detected using western blot analysis. The data showed that the spatial recognition memory and fear memory of the rats treated with sevoflurane decreased compared with the control, and the cognitive function of the rats treated with sevoflurane and hydrogen gas significantly increased in comparison with treatment with sevoflurane alone. Moreover, hydrogen gas suppressed NF-κB phosphorylation and nuclear translocation and reduced the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α following sevoflurane administration. Thus, the results proposed that hydrogen gas might protect against sevoflurane neurotoxicity by inhibiting NF-κB activation and proinflammatory cytokine release, providing a novel therapeutic strategy for anesthesia neurotoxicity.

Purpose We evaluated the effects of a single loading dose of remifentanil (1 μg/kg) administered as an adjunct to sevoflurane, on the duration of seizure activity, recovery times, and hemodynamic profiles, during electroconvulsive therapy. Methods The patients were randomly allocated to receive sevoflurane-saline (Group SS) or sevoflurane-remifentanil (Group SR). Sevoflurane (8%) was initiated for anesthesia induction in both groups until loss of consciousness was achieved. Remifentanil was then administered to Group SR via a 1-μg/kg intravenous bolus. Patients in Group SS received saline in the same manner. Mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthetic induction (T1), at the loss of consciousness (T2), and at 0, 1, 3, and 10 minutes after the electrical stimuli were completed (T3, T4, T5, and T6, respectively). Results Compared with the baseline values, HR increased significantly in Group SS at times T2 and T4 to T6 and decreased significantly in Group SR at time T2. When the groups were compared, we found that HR decreased significantly in Group SR at T2 and T4 to T6. Compared with baseline, MAP increased in Group SS between T3 and T6, and MAP decreased in Group SR at T2 and increased at T3 to T4. Mean arterial pressure decreased to a greater extent in Group SR than in Group SS during the T2 to T6 period. There were no group differences in seizure duration or recovery time. Conclusions The addition of 1-μg/kg remifentanil to anesthetic induction with sevoflurane attenuated the acute hemodynamic response to electroconvulsive therapy under sevoflurane anesthesia without adversely affecting the duration of seizure activity or the recovery profile.

Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics.We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes.Laboratory rat study.Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016.A total of 32 adult male Wistar rats.After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg h) or sevoflurane (2 vol%) continuously for 12 h.Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined.Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P 0.001). There was no significant difference in microglia or astrocyte activation or apoptosis in the brain between sevoflurane and propofol.We have shown that systemic attenuation of inflammation by the volatile anaesthetic sevoflurane did not translate into attenuated neuro-inflammation in this LPS-induced inflammation model.Animal approval No. 134/2014, Veterinäramt Zürich.

To evaluate the feasibility and safety of the MIRUS system (Pall International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for postsurgical ICU patients and to evaluate atmospheric pollution during sedation.Prospective interventional study.Surgical ICU. February 2016 to December 2016.Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation.Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration.Data collected included Richmond Agitation Sedation Scale, minimum alveolar concentration, inspired and expired sevoflurane fraction, wake-up times, duration of sedation, sevoflurane consumption, respiratory and hemodynamic data, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment, and laboratory data and biomarkers of organ injury. Atmospheric pollution was monitored at different sites: before sevoflurane delivery (baseline) and during sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5 (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD, 0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19 hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained stable over the study period, and no laboratory data indicated liver or kidney injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts per million (interquartile range, 0.07-0.15), 0.17 parts per million (interquartile range, 0.14-0.27), and 0.15 parts per million (interquartile range, 0.07-0.19) at baseline, S1, and S2, respectively.The MIRUS system is a promising and safe alternative for short-term sedation with sevoflurane of ICU patients. Atmospheric pollution is largely below the recommended thresholds (5 parts per million). Studies extended to more heterogeneous population of patients undergoing longer duration of sedation are needed to confirm these observations.

BACKGROUND Sevoflurane is a volatile anesthetic commonly used to maintain anesthesia in patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT). Growing evidence suggests that patients with ESLD have decreased anesthetic requirements compared to patients with preserved liver function. The potency of volatile anesthetics is expressed as the minimum alveolar concentration (MAC). In this prospective, blinded study, we compared the MAC of sevoflurane among patients with ESLD undergoing OLT and patients with normal liver function undergoing major abdominal surgery. METHODS After propofol-induced anesthesia, the MAC of sevoflurane was assessed by evaluating motor response to initial skin incision in patients undergoing OLT and in patients with normal liver function undergoing major abdominal surgery. The MAC was determined using Dixon "up-and-down" method and compared between groups. In addition, the bispectral index was documented immediately before and after skin incision. RESULTS Twenty patients undergoing OLT and 20 control patients were included in the study. The MAC of sevoflurane in patients undergoing OLT was 1.3% (95% confidence interval [CI], 1.1-1.4). In comparison, the MAC of sevoflurane in patients with normal liver function was 1.7% (95% CI, 1.6-1.9), equal to a relative reduction of the MAC in patients with ESLD of 26% (95% CI, 14-39). The bispectral index was higher in patients with ESLD than in control patients at 3 minutes before (47 [95% CI, 40-53] vs 35 [95% CI, 31-40], P = .011), 1 minute before (48 [95% CI, 42-54] vs 37 [95% CI, 33-43], P = .03), and 1 minute after skin incision (57 [95% CI, 50-64] vs 41 [95% CI, 36-47], P < .001). CONCLUSIONS Our results suggest that the MAC of sevoflurane is lower in patients with ESLD than in patients with normal liver function after propofol-induced anesthesia. However, as we did not measure propofol concentrations at the time of skin incision, the difference in MAC should be interpreted with caution given that residual propofol may have been present at the time of skin incision.

The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France) is a proposed noninvasive guide to analgesia derived from an electrocardiogram trace. ANI is scaled from 0 to 100; with previous studies suggesting that values ≥50 can indicate adequate analgesia. This clinical trial was designed to investigate the effect of intraoperative ANI-guided fentanyl administration on postoperative pain, under anesthetic conditions optimized for ANI functioning.Fifty patients aged 18 to 75 years undergoing lumbar discectomy or laminectomy were studied. Participants were randomly allocated to receive intraoperative fentanyl guided either by the anesthesiologist's standard clinical practice (control group) or by maintaining ANI ≥50 with boluses of fentanyl at 5-minute intervals (ANI group). A standardized anesthetic regimen (sevoflurane, rocuronium, and nonopioid analgesia) was utilized for both groups. The primary outcome was Numerical Rating Scale pain scores recorded from 0 to 90 minutes of recovery room stay. Secondary outcomes included those in the recovery room period (total fentanyl administration, nausea, vomiting, shivering, airway obstruction, respiratory depression, sedation, emergence time, and time spent in the recovery room) and in the intraoperative period (total fentanyl administration, intraoperative-predicted fentanyl effect-site concentrations over time [CeFent], the correlation between ANI and predicted CeFent and the incidence of movement). Statistical analysis was performed with 2-tailed Student t tests, χ tests, ordinal logistic generalized estimating equation models, and linear mixed-effects models. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes.Over the recovery room period (0-90 minutes) Numerical Rating Scale pain scores were on average 1.3 units lower in ANI group compared to the control group (95% confidence interval [CI], -0.4 to 2.4; P= .01). Patients in the ANI group additionally had 64% lower recovery room total fentanyl administration (95% CI, -12% to 85%; P= .44, unadjusted P= .026), 82% lower nausea scores (95% CI, -19% to 96%; P= .43, unadjusted P= .03), and a reduced incidence of shivering (ANI 4%, control 27%, P= .80, unadjusted P= .047) compared to the control group. Intraoperatively, ANI group patients had on average 27% higher predicted CeFent levels during the highly nociceptive periods of intubation and first incision (5-30 minutes) compared with control group patients (95% CI, 3%-57%; P= .51, unadjusted P= .03). For a 1-unit decrease in ANI scores, predicted CeFent on average increased by an estimated 1.98% in the ANI group (95% CI, 1.7%-2.26%; P.0001) and 1.08% in the control group (95% CI, 0.76%-1.39%; P.0001). This correlation was significantly different between groups (0.9%, 95% CI, 0.5%-1.3%; P.0001). Recovery room vomiting, airway obstruction, respiratory depression, sedation, emergence time, time spent in the recovery room as well as total intraoperative fentanyl administration, hypnotic parameters, and incidence of intraoperative movement were not different between groups.Patients receiving intraoperative ANI-guided fentanyl administration during sevoflurane anesthesia for lumbar discectomy and laminectomy demonstrated decreased pain in the recovery room, likely as a result of more objective intraoperative fentanyl administration.

This study aimed to investigate the effect of subchronic exposure to morphine on the 50% effective dose (EC50) (median effective concentration/EC50) values of intravenous (propofol and ketamine) and inhalation (sevoflurane) anaesthetics in mice. Eight to 12-week-old male mice were administered morphine subcutaneously for 5 days to create a subchronic morphine exposure model. Control mice were injected with saline. The EC50 for righting reflex loss and tail clip reflex of general anaesthetics on the first (D1), third (D3) and seventh days (D7), after establishing a subchronic morphine exposure model, were determined. Sevoflurane: No change in the minimum alveolar concentration for righting reflex loss or tail clip reflex loss was observed between the treated and the control values (P>0.05). Propofol: the EC50 for righting reflex loss of D7 was significantly lower than the control and D1 (P

Background: Volatile anesthetics are known to limit myocardial ischemia-reperfusion injuries. Mitochondria were shown to be major contributors to cardioprotection. Cyclophilin D (CypD) is one of the main regulators of mitochondria-induced cell death. We compared the effect of isoflurane, sevoflurane, and desflurane in the presence or absence of CypD, to clarify its role in the mechanism of cardioprotection induced by these anesthetics.Methods: Oxidative phosphorylation, mitochondrial membrane potential, and H2O2 production were measured in isolated mitochondria from wild-type (WT) or CypD knockout mice in basal conditions and after hypoxia-reoxygenation in the presence or absence of volatile anesthetics.Results: All volatile anesthetics inhibited mitochondrial state 3 of complex I, decreased membrane potential, and increased adenosine diphosphate consumption duration in both WT and CypD knockout mice. However, they differently modified H2O2 production after stimulation by succinate: CypD ablation reduced H2O2 production, isoflurane decreased H2O2 level in WT but not in CypD knockout mice, sevoflurane affected both lines whereas desflurane increased H2O2 production in CypD knockout and had no effect on WT mice.Conclusions: This study showed different effects of isoflurane, sevoflurane, and desflurane on mitochondrial functions and highlighted the implication of CypD in the regulation of adenosine diphosphate consumption and complex I-induced radical oxygen species production.

Anesthesia or sedation is needed when intraocular pressure (IOP) measurement is required in certain circumstances. The effect of different anesthetic regimens on the IOP is still debatable. We aimed to evaluate alterations in the IOP under anesthesia with either propofol or different end-tidal concentrations of sevoflurane, when compared with the awake state.The IOP was measured in both eyes of 20 adult patients undergoing extraocular ophthalmic surgeries at 5 timepoints: before the induction of general anesthesia (under topical anesthesia), after the induction using propofol target-controlled infusion, and under 3 end-tidal concentrations of sevoflurane (0.5%, 2%, and 5%), either in a decreasing (group A) or an increasing (group B) concentration order.With either propofol or sevoflurane anesthesia, the IOP did not differ significantly from the measurement performed during the awake state (no anesthesia), regardless of the concentration of sevoflurane used (in the range of 0.5% to 5%) or the order of sevoflurane administration (from low to high concentration or vice versa).These data suggest that propofol and sevoflurane are valid anesthetic agents for the evaluation of IOP in adults when anesthesia is needed.

BackgroundThe authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2–related factor 2 through multiple pathways. However, whether nuclear factor-E2–related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown.MethodsSevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2–related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2–related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH–associated protein 1-nuclear factor-E2–related factor 2 signal was modulated by nuclear factor-E2–related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed.ResultsSevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2–related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2–related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch-like ECH-associated protein 1 overexpression reversed nuclear factor-E2–related factor 2 up-regulation and abolished the neuroprotection induced by sevoflurane preconditioning. Kelch-like ECH-associated protein 1 small interfering RNA administration improved nuclear factor-E2–related factor 2 expression and the outcome of mice subjected to ischemia/reperfusion injury.ConclusionsKelch-like ECH-associated protein 1 down-regulation–dependent nuclear factor-E2–related factor 2 activation underlies the ability of sevoflurane preconditioning to activate the endogenous antioxidant response, which elicits its neuroprotection.

OBJECTIVE To describe a case of partial nephrogenic diabetes insipidus in a burned patient after prolonged delivery of low inspired concentrations of sevoflurane via an Anesthetic Conserving Device. DATA SOURCES Clinical observation. STUDY SELECTION Case report. DATA EXTRACTION Relevant clinical information. DATA SYNTHESIS A 34-year-old man was admitted with burns covering 52% of his total body surface area. Mechanical ventilation was provided during sedation with continuous infusions of sufentanil and midazolam. Sedation became increasingly difficult, and in order to limit administration of IV agents, sevoflurane was added to the inspiratory gas flow. This was provided using an Anesthetic Conserving Device and continued for 8 days. The patient rapidly developed polyuria and hypernatremia with an inappropriate decrease in urinary osmolality. Administration of desmopressin resulted in only a modest effect on renal concentrating ability. After cessation of sevoflurane, all variables returned to normal within 5 days. The results of further investigations (cerebral computed tomographic scan, cerebral magnetic resonance imaging, and serum arginine vasopressin concentration) were compatible with a diagnosis of partial nephrogenic diabetes insipidus. The temporal sequence of clinical findings in relation to sevoflurane administration suggests that the sevoflurane was the probable underlying cause. CONCLUSIONS Clinicians should be aware of the possibility of sevoflurane-induced diabetes insipidus not only during general anesthesia but also in the intensive care setting of sedation in critically ill patients. This is especially important in patients, such as those with severe burns, in whom preserved renal concentrating ability is important to ensure compensation for extrarenal fluid losses.

Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37°C without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 ± 6 versus 162 ± 86 U/L; P = 0.01), 2 hours (43 ± 5 versus 191 ± 111 U/L; P = 0.008), and 3 hours (24 ± 16 versus 218 ± 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor α, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 ± 653 versus 2097 ± 1071 versus 1747 ± 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 ± 1.5 versus 6.60 ± 1.5 μmol/L; P = 0.02) and 3 (2 ± 1.1 versus 9.7 ± 7.6 μmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti-inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573-1583 2016 AASLD.

Early postnatal exposure to general anesthetic agents causes a lasting impairment in learning and memory in animal models. One hypothesis to explain this finding is that exposure to anesthetic agents during critical points in neural development disrupts the formation of brain circuitry. Here, we explore the effects of sevoflurane on the neuronal growth cone, a specialization at the growing end of axons and dendrites that is responsible for the targeted growth that underlies connectivity between neurons.Dissociated neuronal cultures were prepared from embryonic mouse neocortex. Time-lapse images of live growth cones exposed to anesthetics were taken using differential interference contrast microscopy, and the rate of change of the area of the lamellipodia and the speed of the filopodial tip were quantified as measures of motility. The involvement of the p75 neurotropin receptor (p75NTR) was tested using inhibitors applied to the media and by a coimmunoprecipitation assay.The rate of lamellipodial area change and filopodial tip velocity in both axonal and dendritic growth cones was significantly reduced with sevoflurane exposure between 2% and 6%. Motility could be substantially restored by treatment with Y27632 and TAT-peptide 5, which are inhibitors of Rho Kinase and p75NTR, respectively. Sevoflurane results in reduced coimmunoprecipitation of Rho-Guanosine-5'-diphosphate dissociation inhibitor after pulldown with p75NTR.Sevoflurane interferes with growth cone motility, which is a critical process in brain circuitry formation. Our data suggest that this may occur through an action on the p75NTR, which promotes growth inhibitory signaling by the Rho pathway.

A harmful effect of stress hormone secretion during surgery is lipolysis and proteolysis to maintain normal blood glucose levels. A well-titrated general anesthetic improves blood glucose control by suppressing secretion of these stress hormones. The aim of this study was to explore the effect of intraoperative glucose infusion on lipolysis and proteolysis in patients undergoing a general anesthetic consisting of sevoflurane and remifentanil during long (6 hours) major surgery.In this prospective, single-blinded, randomized, multicenter trial, 80 patients with an expected duration of anesthesia of6 hours were allocated to either the glucose group, consisting of 40 patients who were infused with acetated Ringer's solution with glucose (2 mg/kg/min), or the no glucose group, consisting of 40 patients who were infused with the same solution, but without glucose. After oxygenation, general anesthesia was induced with propofol, fentanyl, and rocuronium and was maintained with sevoflurane, oxygen, rocuronium, and remifentanil infusions. The rates of remifentanil infusion were titrated based on systolic arterial blood pressure, maintaining this parameter within 10% of its postanesthesia values. Seventy-four patients completed the study. Urinary 3-methylhistidine/creatinine (3-MH/Cre) ratio, acetoacetic acid, 3-hydroxybutyric acid, blood glucose, insulin, and cortisol were measured 3 times: at anesthesia induction (0 hour) and at 3 and 6 hours after anesthesia induction. Urinary 3-MH/Cre ratio was the primary study outcome.In the no glucose group, the urinary 3-MH/Cre ratio at 6 hours was increased compared with that at 0 hour (213 [range, 42-1903] vs 124 [18-672] nmol/μmol; the difference in medians, 89; the 95% confidence interval [CI] of the difference, 82-252; P = .0002). Acetoacetic acid and 3-hydroxybutyric acid levels in the no glucose group were greater than those in the glucose group at 6 hours (110 [8-1036] vs 11 [2-238] μmol/L; the difference in medians, 99; the 95% CI of the difference, 92-196; P.0001 and 481 [15-2783] vs 19 [4-555] μmol/L; the difference in medians, 462; the 95% CI of the difference, 367-675; P0.0001, respectively). Blood glucose and insulin levels in the glucose group were greater than those in the no glucose group at 3 hours (146 [103-190] vs 93 [72-124] mg/dL; the difference in medians, 53; the 95% CI of the difference, 47-55; P.0001 and 9.8 [1.2-25.4] vs 3.2 [0.4-15.0] μU/mL; the difference in medians, 6.5; the 95% CI of the difference, 4.8-6.8; P.0001) and 6 hours (139 [92-189] vs 87 [68-126] mg/dL; the difference in medians, 52; the 95% CI of the difference, 44-58; P.0001 and 8.1 [1.2-22.3] vs 3.2 [0.4-10.1] μU/mL; the difference in medians, 4.9; the 95% CI of the difference, 4.0-5.9; P.0001). Cortisol levels in both groups were similarly within normal levels at 0, 3, and 6 hours.The study showed that intraoperative glucose infusion suppressed lipolysis and proteolysis in patients anesthetized with remifentanil in combination with sevoflurane during surgery of6 hours in length.

BackgroundAnimals exposed to sevoflurane during development sustain neuronal cell death in their developing brains. In vivo micro-positron emission tomography (PET)/computed tomography imaging has been utilized as a minimally invasive method to detect anesthetic-induced neuronal adverse effects in animal studies.MethodsNeonatal rhesus monkeys (postnatal day 5 or 6, 3 to 6 per group) were exposed for 8 h to 2.5% sevoflurane with or without acetyl-l-carnitine (ALC). Control monkeys were exposed to room air with or without ALC. Physiologic status was monitored throughout exposures. Depth of anesthesia was monitored using quantitative electroencephalography. After the exposure, microPET/computed tomography scans using 18F-labeled fluoroethoxybenzyl-N-(4-phenoxypyridin-3-yl) acetamide (FEPPA) were performed repeatedly on day 1, 1 and 3 weeks, and 2 and 6 months after exposure.ResultsCritical physiologic metrics in neonatal monkeys remained within the normal range during anesthetic exposures. The uptake of [18F]-FEPPA in the frontal and temporal lobes was increased significantly 1 day or 1 week after exposure, respectively. Analyses of microPET images recorded 1 day after exposure showed that sevoflurane exposure increased [18F]-FEPPA uptake in the frontal lobe from 0.927 ± 0.04 to 1.146 ± 0.04, and in the temporal lobe from 0.859 ± 0.05 to 1.046 ± 0.04 (mean ± SE, P < 0.05). Coadministration of ALC effectively blocked the increase in FEPPA uptake. Sevoflurane-induced adverse effects were confirmed by histopathologic evidence as well.ConclusionsSevoflurane-induced general anesthesia during development increases glial activation, which may serve as a surrogate for neurotoxicity in the nonhuman primate brain. ALC is a potential protective agent against some of the adverse effects associated with such exposures.

Remifentanil target-controlled infusion and dexmedetomidine single-dose administration are known to reduce airway response and hemodynamic stimulation during anesthetic recovery. We compared the effects of 2 drugs on the prevention of cough during emergence. We enrolled 70 female patients aged 20-60 years with American Society of Anesthesiologists (ASA) I-II who underwent general anesthesia for elective thyroidectomy. The patients were randomly assigned to remifentanil (group R) or dexmedetomidine (group D). Anesthesia was maintained with sevoflurane and effect-site target-controlled infusion of remifentanil. In group D, remifentanil was discontinued, and dexmedetomidine 0.5 μg/kg was given 10 minutes before the end of surgery. In group R, remifentanil target-controlled infusion at an effective-site concentration of 2.0 ng/mL was maintained during emergence until extubation. The cough grade, hemodynamic values, respiration, and other recovery profiles were evaluated during the periextubation period. The proportion of patients with no cough or just a single cough during extubation was significantly higher in group R than in group D (96.8% vs. 55.9%). The change of mean arterial pressure and heart rate were not significantly different during extubation in both groups. Respiratory rate and the incidence of residual sedation after extubation were lower in group R. There were no desaturation events and no differences in time to extubation or duration of postanesthesia care unit stay in both groups. Remifentanil target-controlled infusion reduces emergence cough from general anesthesia more effectively than single-dose dexmedetomidine. However, a single-dose of dexmedetomidine has the effect with respect to respiratory and hemodynamic stability during emergence.

BACKGROUND Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C). RESULTS A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.

The cause of emergence agitation (EA) in children is unknown. Rapid emergence from inhaled anesthesia has been implicated because EA is more common with sevoflurane than with halothane. A dose-dependent effect of sevoflurane, which increases seizure-like electroencephalogram activity, has also been proposed.To determine whether depth of anesthesia as measured by bispectral index (BIS) affects EA, 40 ASA physical status I to II children aged 2 to 8 years undergoing ophthalmic surgery were enrolled in a blinded randomized controlled trial of low-normal (40-45, deep) versus high-normal (55-60, light) anesthesia. To distinguish transient irritability from severe EA, the primary outcome was first-stage postanesthesia care unit (PACU I) peak Pediatric Assessment of Emergence Delirium (PAED) score, with secondary outcomes of PAED and Face, Legs, Activity, Cry, and Consolability scores at emergence, postoperative fentanyl dose, emergence time, and discharge time. Subjects received a standard anesthesia protocol with oral midazolam followed by mask induction with sevoflurane 8%, fentanyl 1 to 1.5 μg/kg IV (then as needed), neuromuscular blockade, and endotracheal intubation. Providers titrated expired sevoflurane (in N2O 67%) from 0.5% to 3% to maintain BIS range. PAED, Richmond Agitation Sedation Scale, and Face, Legs, Activity, Cry, and Consolability scores were measured at emergence, at PACU I arrival, and during PACU I stay.There was little difference between the groups in the primary outcome, peak PACU I PAED score (light: 7.7 ± 4.6; deep: 8.6 ± 5.3; mean difference, 0.9; 95% confidence interval, 4.1 to -2.3; effect size, 0.18). Discharge times were similar between groups. Treatment for severe EA was rare.There was no significant effect of BIS-guided deep versus light anesthesia on severe EA.

Reducing fresh gas flow (FGF) during general anesthesia reduces costs by decreasing the consumption of volatile anesthetics and attenuates their contribution to greenhouse gas pollution of the environment. The sevoflurane FGF recommendations in the Food and Drug Administration package insert relate to concern over potential toxicity from accumulation in the breathing circuit of compound A, a by-product of the reaction of the volatile agent with legacy carbon dioxide absorbents containing strong alkali such as sodium or potassium hydroxide. Newer, nonreactive absorbents do not produce compound A, making such restrictions moot. We evaluated 4 hypotheses for sevoflurane comparing intervals before and after converting from a legacy absorbent (soda lime) to a nonreactive absorbent (Litholyme): (1) intraoperative FGF would be reduced; (2) sevoflurane consumption per minute of volatile agent administration would be reduced; (3) cost savings due to reduced sevoflurane consumption would (modestly) exceed the incremental cost of the premium absorbent; and (4) residual wastage in discarded sevoflurane bottles would be1%.Inspired carbon dioxide (PICO2), expired carbon dioxide, oxygen, air, and nitrous oxide FGF, inspired volatile agent concentrations (FiAgent), and liquid volatile agent consumption were extracted from our anesthesia information management system for 8 4 week intervals before and after the absorbent conversion. Anesthesia providers were notified by e-mail and announcements at Grand Rounds about the impending change and were encouraged to reduce their average intraoperative sevoflurane FGF to 1.25 L/min. Personalized e-mail reports were sent every 4 weeks throughout the study period regarding the average intraoperative FGF (i.e., from surgery begin to surgery end) for each agent. Batch means methods were used to compare FGF, volatile agent consumption, net cost savings, and residual sevoflurane left in bottles to be discarded in the trash after filling vaporizers. The time from reaching a PICO2 = 3 mm Hg for 3 minutes until agent exhaustion (PICO2 = 5 mm Hg for 5 minutes) was evaluated.A total of N = 20,235 cases were analyzed (80.2% sevoflurane, 15.1% desflurane, and 4.7% isoflurane). Intraoperative FGF was reduced for cases in which sevoflurane was administered by 435 mL/min (95% confidence interval [CI], 391 to 479 mL/min; P10). Hypothesis 1 was accepted. Sevoflurane consumption per minute of administration decreased by 0.039 mL/min (95% CI, 0.029 to 0.049 mL/min; P10) after the change to the nonreactive absorbent. Hypothesis 2 was accepted. The difference in mean cost for the sum of the sevoflurane and absorbent purchases for each of the 10 4-week intervals before and after the absorbent switch was -$293 per 4-week interval (95% CI, -$2853 to $2266; P = 0.81). Hypothesis 3 was rejected. The average amount of residual sevoflurane per bottle was 0.67 ± 0.06 mL (95% CI, 0.54 to 0.81 mL per bottle; P10 vs 2.5 mL). Hypothesis 4 was accepted. Once the PICO2 reached 3 mm Hg for at least 3 consecutive minutes, the absorbent became exhausted within 95 minutes in most (i.e.,50%) canisters.We showed that an anesthesia department can transition to a premium, nonreactive carbon dioxide absorbent in a manner that is at least cost neutral by reducing FGF below the lower flow limits recommended in the sevoflurane package insert. This was achieved, in part, by electronically monitoring PICO2, automatically notifying the anesthesia technicians when to change the absorbent, and by providing personalized feedback via e-mail to the anesthesia providers.

Background Various interventions to reduce postreperfusion syndrome during liver transplantation have been explored, but the effect of volatile anesthetics used during liver transplantation on the incidence of postreperfusion syndrome has not been evaluated. A randomized controlled trial was performed to compare the incidence of postreperfusion syndrome between 2 commonly used volatile anesthetics, sevoflurane and desflurane. Methods Sixty-two adult liver recipients scheduled for living-donor liver transplantation were randomized to receive either sevoflurane or desflurane for general anesthesia. The incidence of postreperfusion syndrome, use of vasoactive drugs, and postoperative course were compared. The risk factors associated with postreperfusion syndrome were also analyzed. Results There was significantly less postreperfusion syndrome in the sevoflurane group compared to the desflurane group (38.7% vs 77.4%, P = 0.004) and less epinephrine was required in the sevoflurane group than the desflurane group (19.4% vs 45.2%, P = 0.030). Postoperative intensive care unit and hospital length of stay and postoperative course were similar between the groups. Multivariate analysis identified desflurane (compared to sevoflurane) as the only risk factor (odds ratio 7.314, P = 0.001) for reperfusion syndrome. Conclusions When using volatile anesthetics for elective living donor liver transplantation, sevoflurane seems to be a better option than desflurane for reducing the incidence of postreperfusion syndrome.

Background Inhaled induction with spontaneous respiration is a technique used for difficult airways. One of the proposed advantages is if airway patency is lost, the anesthetic agent will spontaneously redistribute until anesthetic depth is reduced and airway patency can be recovered. There are little and conflicting clinical or experimental data regarding the kinetics of this anesthetic technique. We used computer simulation to investigate this situation. Methods We used GasMan, a computer simulation of inhaled anesthetic kinetics. For each simulation, alveolar ventilation was initiated with a set anesthetic induction concentration. When the vessel-rich group level reached the simulation specified airway obstruction threshold, alveolar ventilation was set at 0 to simulate complete airway obstruction. The time until the vessel-rich group anesthetic level decreased below the airway obstruction threshold was designated time to spontaneous recovery. We varied the parameters for each simulation, exploring the use of sevoflurane and halothane, airway obstruction threshold from 0.5 to 2 minimum alveolar concentration (MAC), anesthetic induction concentration 2 to 4 MAC sevoflurane and 4 to 6 MAC halothane, cardiac output 2.5 to 10 L/min, functional residual capacity 1.5 to 3.5 L, and relative vessel-rich group perfusion 67% to 85%. Results In each simulation, there were 3 general phases: anesthetic wash-in, obstruction and overshoot, and then slow redistribution. During the first 2 phases, there was a large gradient between the alveolar and vessel-rich group. Alveolar do not reflect vessel-rich group anesthetic levels until the late third phase. Time to spontaneous recovery varied between 35 and 749 seconds for sevoflurane and 13 and 222 seconds for halothane depending on the simulation parameters. Halothane had a faster time to spontaneous recovery because of the lower alveolar gradient and less overshoot of the vessel-rich group, not faster redistribution. Higher airway obstruction thresholds, decreased anesthetic induction, and higher cardiac output reduced time to spontaneous recovery. To a lesser effect, decreased functional residual capacity and the decreased relative vessel-rich groups' perfusion also reduced the time to spontaneous recovery. Conclusions Spontaneous recovery after complete airway obstruction during inhaled induction is plausible, but the recovery time is highly variable and depends on the clinical and physiologic situation. These results emphasize that induction is a non-steady-state situation, thus effect-site anesthetic levels should be modeled in future research, not alveolar concentration. Finally, this study provides an example of using computer simulation to explore situations that are difficult to investigate clinically.

Background It is widely known that blood pressure (BP) in the lower extremity is higher than in the upper extremity. However, whether this phenomenon remains the same during general anesthesia is still unclear. This study aims to investigate the difference between invasive dorsalis pedis artery (DPA) pressure and the most commonly used noninvasive arm pressure during sevoflurane anesthesia. Methods A total of 50 normotensive Chinese patients were enrolled in this observational study. Invasive DPA pressure, noninvasive arm pressure, and systemic vascular resistance index were assessed simultaneously. BP data during the entire surgery were analyzed through a Bland-Altman plot for repeated measures. The concordance of BP variation in the DPA and the arm was analyzed using four-quadrant plots and linear regression. The time-dependent changes in BP and the systemic vascular resistance index were also evaluated. Results Data from 46 effective cases were analyzed. Bias (95% limits of agreement) was -7.40 mmHg (-20.36 to +5.57 mmHg) for mean blood pressure, +3.54 mmHg (-20.32 to +27.41 mmHg) for systolic blood pressure, and -10.20 mmHg (-23.66 to +3.26 mmHg) for diastolic blood pressure, respectively. The concordance of BP variation at the two measurement sites was clinically acceptable. DPA pressure and vascular resistance in the lower limb decreased gradually during surgery. Conclusion DPA pressure tends to be lower than arm pressure under sevoflurane anesthesia, especially the mean blood pressure and the diastolic blood pressure. Hence, noninvasive arm BP monitoring is recommend to be retained when invasive BP is measured at the DPA, so as to allow clinicians to comprehensively evaluate the BP condition of the patients and make appropriate therapeutic decisions.

Background The dorsalis pedis artery (DPA) is a good alternative to the radial artery (RA) for invasive blood pressure monitoring when the upper limb is burned or injured, or if the RA is not available. Understanding the pattern of pressure difference between DPA and the commonly used RA during inhalational anaesthesia is helpful for haemodynamic management and therapeutic decisions. Objectives The objective of this study was to investigate the time-dependent variation of DPA-to-RA pressure gradient during sevoflurane anaesthesia and the overall difference between the two pressures during neurosurgery, together with the causes of the pressure gradient change. Design A prospective, self-control, single-centre study. Setting The operating room of a teaching hospital from 1 January 2013 to 1 September 2013. Patients Thirty-seven patients between 18 and 60 years of age, American Society of Anesthesiologists' physical status 1-3, scheduled for neurosurgery in the supine position and requiring invasive arterial pressure monitoring. Main outcome measures The time-dependent change of DPA-to-RA pressure gradient and skin temperature gradient, the difference between absolute values and average values of SBP, DBP and mean blood pressure (MBP) between RA and DPA during surgery, and the internal cross-sections and systolic blood flow velocities of RA and DPA at the baseline and at the end of surgery. Results Data from 30 patients were analysed. The mean ± standard deviation DPA-to-RA pressure gradient gradually decreased with time from 9.7 ± 8.8 to -1.8 ± 7.6 mmHg for systolic pressure, -2.3 ± 2.7 to -3.7 ± 2.8 mmHg for diastolic pressure and -2.1 ± 3.2 to -5.4 ± 3.4 mmHg for MBP. Biases during the entire procedure were 2.2 ± 10.1, -3.1 ± 3.4 and -4.3 ± 4.2 mmHg for SBP, DBP and MBP, respectively. The DPA-to-RA skin temperature gradient gradually reduced from -3.6 ± 2.4 to -1.1 ± 1.3°C. A greater increase in the inner cross-sectional area and blood flow from the baseline was observed at DPA compared with RA. Conclusion The blood pressure, temperature and inner cross-sectional area differences between DPA and RA reduced gradually during sevoflurane anaesthesia in patients undergoing neurosurgery. Therapeutic decisions may rely on DPA pressure as long as the anaesthetists are aware of the pattern of change in DPA pressure during surgery. Trial registration www.chictr.org with registry number ChiCTR-RNRC-13003853.

BOLD activation studies discussed vary in the anesthetic agent studied (propofol, sevoflurane, and isoflurane), the concentration of the anesthetic (mostly under 0.5MAC or equivalent doses), and the activation paradigm/functional activation. The data analysis technique also differs between the studies. Notwithstanding these variations, the results can be summarized as follows: Higher order association cortices are more sensitive to anesthesia. Higher order regions processing language and semantics (regions in the frontal cortex) are affected at a lower concentration of anesthetic as compared with regions processing auditory stimuli. Whereas primary visual activation regions in the visual cortex and the thalamus are less sensitive, higher order visual spatial attention regions in the parietal cortex are more sensitive to anesthesia. In most studies, the loss of consciousness (no response to call) is achieved at or below 0.5MAC of anesthesia.

BACKGROUND Anesthesia and sedation are associated with paradoxical breathing. Respiratory inductance plethysmography (RIP) permits measurement of respiratory motion in clinical settings not conducive to spirometry, but correlation of RIP volume changes and spirometer flow in the time domain is degraded by the development of paradoxical breathing. The Hilbert-Huang transform (HHT) is a nonlinear signal analysis method that permits the instantaneous magnitude and phase of nonstationary signals to be estimated in the frequency domain. We hypothesized that these frequency domain estimates would provide higher correlation between RIP and spirometer signals than time domain signals during the transition between normal and paradoxical breathing. METHODS From 51 patients undergoing sevoflurane anesthesia for minor procedures, a 5-minute epoch containing transitions between pressure support ventilation and spontaneous ventilation was selected for analysis. Pearson correlation for models based on HHT magnitude and phase was compared with models based on time domain signals. Bland-Altman analysis was performed to assess deviation from linearity in the models. RESULTS For the 51 patients analyzed, the modulation of tidal volume over the epoch ranged from 30% to 215% of epoch mean. The coefficient of determination for time domain analysis was 0.62 ± 0.2 compared with 0.93 ± 0.07 for the HHT model incorporating phase. This improvement of 0.31 (99% confidence interval, 0.24-0.37) was significant (P < 0.0001). No trend was observed in prediction residuals. CONCLUSIONS Under conditions of changing ventilation, HHT-derived magnitude and phase measures provide higher correlation with spirometry than those obtained with traditional time domain methods.

Background Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. Objectives The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. Design A randomised, experimental study. Setting Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. Animals Thirty-nine adult male Wistar rats. Interventions Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. Main outcome measures The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. Results Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P 0.05). Conclusion Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.

Background: A wealth of data shows neuronal demise after general anesthesia in the very young rodent brain. Herein, the authors apply proton magnetic resonance spectroscopy (1HMRS), testing the hypothesis that neurotoxic exposure during peak synaptogenesis can be tracked via changes in neuronal metabolites. Methods: 1HMRS spectra were acquired in the brain (thalamus) of neonatal rat pups 24 and 48 h after sevoflurane exposure on postnatal day (PND) 7 and 15 and in unexposed, sham controls. A repeated measure ANOVA was performed to examine whether changes in metabolites were different between exposed and unexposed groups. Sevoflurane-induced neurotoxicity on PND7 was confirmed by immunohistochemistry. Results: In unexposed PND7 pups (N = 21), concentration of N-acetylaspartate (NAA; [NAA]) increased by 16% from PND8 to PND9, whereas in exposed PND7 pups (N = 19), [NAA] did not change and concentration of glycerophosphorylcholine and phosphorylcholine ([GPC + PCh]) decreased by 25%. In PND15 rats, [NAA] increased from PND16 to PND17 for both the exposed (N = 14) and the unexposed (N = 16) groups. Two-way ANOVA for PND7 pups demonstrated that changes over time observed in [NAA] (P = 0.031) and [GPC + PCh] (P = 0.024) were different between those two groups. Conclusions: The authors demonstrated that normal [NAA] increase from PND8 to PND9 was impeded in sevoflurane-exposed rats when exposed at PND7; however, not impeded when exposed on PND15. Furthermore, the authors showed that noninvasive 1HMRS is sufficiently sensitive to detect subtle differences in developmental time trajectory of [NAA]. This is potentially clinically relevant because 1HMRS can be applied across species and may be useful in providing evidence of neurotoxicity in the human neonatal brain.

Background: Myocardial infarction is an important cause of mortality after carotid endarterectomy (CEA). Sevoflurane provides myocardial protection to patients undergoing coronary surgery, but whether it also reduces the incidence of myocardial injury in CEA patients is unclear. In this study, we evaluated the cardioprotective effect of low-dose sevoflurane with propofol in patients undergoing CEA. Methods: This was a single-center, prospective, randomized study conducted between November 2011 and December 2013. The study population of 122 patients who underwent CEA were randomly assigned to two groups. Group A ( n = 62) received propofol for anesthetic maintenance, and Group B ( n = 60) additionally received 0.8% end-tidal sevoflurane. The bispectral index was kept at 40-60. Myocardial injury, defined as cardiac troponin I (cTnI) levels >0.04 ng/ml, was the primary end-point. Levels of cTnI were measured before anesthesia, and at 4, 24, and 72 h after surgery. Perioperative hemodynamic parameters and adverse cardiovascular events after surgery were also recorded. Results: Myocardial injury was detected in 18 patients in Group A and 7 in Group B. The difference was statistically significant (29.0% vs. 11.7%, P = 0.018). The hemodynamic parameters were comparable between the groups, as were adverse cardiovascular events ( P = 0.619). Conclusions: Low-dose sevoflurane inhalation along with propofol reduces the incidence of myocardial injury in symptomatic patients after CEA.

We previously showed that preischemic administration of high-dose isoflurane worsened the outcome from severe forebrain ischemia in rats. Conversely, high doses of sevoflurane have been reported to improve the outcome from forebrain ischemia when the insult is moderate. To clarify the dose-dependent effects of sevoflurane on severe forebrain ischemia, we performed an outcome study using an identical protocol to that in our previous study with isoflurane. Fasting male Sprague-Dawley rats underwent surgical preparation for forebrain ischemia under halothane anesthesia. Anesthesia was changed to fentanyl/nitrous oxide to eliminate the halothane, after which 30 minutes of 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration sevoflurane was administered. Ten minutes of ischemia was induced by bilateral carotid occlusion plus systemic hypotension, in which cessation of electroencephalographic activity was confirmed. Sevoflurane was discontinued and anesthesia continued with fentanyl/nitrous oxide for an additional 100 minutes. Outcome evaluation at 5 days postischemia included seizure incidence, mortality rate, neuromotor score, and histologic injuries to the cerebral cortex and hippocampal CA1 and CA3. Different doses of sevoflurane did not statistically affect seizure incidence (10.0% to 18.2%), mortality rate (20.0% to 46.7%), cortical damage (mild to moderate degree), or hippocampal CA1 damage (93.7% to 96.7% neuronal necrosis) or CA3 damage (36.3% to 41.7%). Dose-dependent effects of sevoflurane were not observed for any of the outcome variables assessed in this rat model of severe forebrain ischemia.

BACKGROUND The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane minimum alveolar concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN A randomised, laboratory study. SETTING Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS One hundred and fourteen adult male Wistar rats. INTERVENTIONS Intraperitoneal administration of amitriptyline (10 and 50 mg kg-1), minocycline (30 and 100 mg kg-1), maropitant (10 and 30 mg kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg-1 h-1) or saline. MAIN OUTCOME MEASURES Sevoflurane minimum alveolar concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the minimum alveolar concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS Amitriptyline, minocycline and maropitant reduced minimum alveolar concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P

The importance of anesthetic technique is often underappreciated in face-lift procedures and is sparsely written about in the literature. Appropriate control of blood pressure, anxiety, pain, and nausea is essential for reducing the complications of face lift, primarily, hematoma risk. This study discusses the standard anesthetic protocol provided at the authors' institution and describes the preoperative, intraoperative, and postoperative management of face-lift patients resulting in low hematoma and complication rates.One thousand eighty-nine patients who underwent face-lift procedures performed by a single surgeon (R.J.R) were included in a retrospective chart review following institutional review board approval. Patient demographics, operative data including additional ancillary procedures, and the anesthesia regimen were recorded. In addition, postoperative complications and reoperation rates were documented.Between 1990 and 2013, 1089 face-lift procedures were performed. Of these, 10 patients developed postoperative hematomas. Benzodiazepines were commonly administered preoperatively to reduce anxiety level. Intraoperatively, a specific regimen and combination of inhalation agents, neuromuscular blockers, antiemetics, antihypertensives, and narcotics was given to control the ease of induction and emergence from anesthesia. Postoperatively, nausea, vomiting, anxiety, pain, and hypertension were treated as needed.The described protocol is safe and has been instituted at the authors' facility for approximately 20 years. The benefit of this regimen is related to the synergy of combination therapy. It is successful in reducing patient anxiety and pain, controlling blood pressure and postoperative emesis, and subsequently results in a reduced risk of hematoma.Therapeutic, IV.

Background: Neonatal exposure to general anesthetics may pose significant neurocognitive risk. Human epidemiological studies demonstrate higher rates of learning disability among children with multiple, but not single, exposures to anesthesia. The authors employ a rat model to provide a histological correlate for these population-based observations. The authors examined long-term differences in hippocampal synaptic density, mitochondrial density, and dendritic spine morphology. Methods: Twenty male rat pups (n = 5/condition) were exposed to 2.5% sevoflurane under one of four conditions: single 2-h exposure on postnatal day 7 (P7); single 6-h exposure on P7; repeated 2-h exposures on P7, P10, and P13 for a cumulative 6 h of general anesthetics; or control exposure to 30% oxygen on P7, P10, and P13. Results: Repeated exposure to general anesthetics resulted in greater synaptic loss relative to a single 2-h exposure (P < 0.001). The magnitude of synaptic loss induced by three 2-h exposures (1.977 ± 0.040 μm3 [mean ± SEM]) was more profound than that of a single 6-h exposure (2.280 ± 0.045 μm3, P = 0.022). Repeated exposures did not alter the distribution of postsynaptic density length, indicating a uniform pattern of loss across spine types. In contrast, mitochondrial toxicity was best predicted by the cumulative duration of exposure. Relative to control (0.595 ± 0.017), both repeated 2-h exposures (0.479 ± 0.015) and a single 6-h exposure (0.488 ± 0.013) were associated with equivalent reductions in the fraction of presynaptic terminals containing mitochondria (P < 0.001). Conclusion: This suggests a “threshold effect” for general anesthetic–induced neurotoxicity, whereby even brief exposures induce long-lasting alterations in neuronal circuitry and sensitize surviving synapses to subsequent loss.

Background The aim of this prospective, comparative, randomized study was to compare the inhalational anesthetics isoflurane, sevoflurane, and desflurane in pediatric patients undergoing craniotomy for excision of supratentorial tumors. We assessed early postoperative recovery outcome, intraoperative hemodynamics, and degree of brain swelling, as well as postoperative vomiting and shivering. Methods Sixty patients scheduled for supratentorial brain tumor excision, were randomly allocated into 1 of 3 groups (20 patients each); isoflurane, sevoflurane, and desflurane group. After IV induction of anesthesia, maintenance was achieved using the inhalational anesthetic according to the allocated group. Tracheal extubation time was the primary endpoint. The secondary endpoints included: emergence time and the interval time needed to reach Aldrete score ≥9, intraoperative degree of brain swelling, intraoperative heart rate and mean arterial blood pressure, as well as postoperative vomiting and shivering. Results The mean emergence time, extubation time, and the interval required to reach Aldrete score 9 were significantly shorter in the desflurane and sevoflurane groups than the isoflurane group. No statistically significant changes in the 3 groups regarding intraoperative brain swelling, hemodynamics, and postoperative shivering or vomiting were noted. Conclusions Desflurane and sevoflurane can be used to facilitate early emergence from anesthesia in neurosurgical pediatric patients. Emergence times are shorter with desflurane or sevoflurane than with isoflurane. The patients who received desflurane or sevoflurane have similar intraoperative and postoperative incidence of adverse effects compared with those who received isoflurane. Thus, desflurane and sevoflurane can be considered as suitable for emergence in pediatric neurosurgical anesthesia.

Background: The effects of inhaled anesthetics on the developing brain are studied using neonatal rodents exposed to fractions of minimum alveolar concentration (to avoid cardiorespiratory compromise). However, these fractions cannot be assumed to be equipotent. Xenon’s anesthetic and neuroprotective properties warrant investigation in these models. Therefore, equipotent, subanesthetic concentrations of inhaled anesthetics are needed. Methods: Forty-eight Wistar rats (Charles River Laboratories, Kent, United Kingdom) on postnatal day 9 were randomized to eight concentrations of inhaled anesthetics: isoflurane, sevoflurane, or xenon. Exposure was closely monitored in individual metal-based chambers resting on a 35°C mat to maintain normothermia. A 25°C mat was used to stimulate vocalization and a sound recording made (1 min, 1 to 100 kHz). Rectal temperature or partial pressure of carbon dioxide and pH of mixed arteriovenous blood were measured immediately after the exposure. Concentration–response models were constructed using logistic regression (dependent variable: vocalization and explanatory variable: concentration). The effects of all other explanatory variables were assessed by inserting them individually into the model. Results: The effective inhaled concentrations preventing cold-stimulated vocalization in 50 and 95% of neonatal rats (EiC50 and EiC95) on postnatal day 9 were 0.46 and 0.89% sevoflurane and 20.15 and 34.81% xenon, respectively. The effect on the EiC50 of all other explanatory variables, including duration, was minimal. Stability of EiC50 isoflurane was not achieved over three durations (40, 80, and 120 min exposure). Partial pressure of carbon dioxide and pH in mixed arteriovenous blood appeared normal. Conclusions: The authors report equipotent subanesthetic concentrations of sevoflurane and xenon in neonatal rats with preserved cardiopulmonary function. This may be useful in designing neonatal rodent models of anesthesia.

BACKGROUND: General anesthesia in patients with or at risk for neuronal injury remains challenging due to the controversial influence of volatile anesthetics on neuronal damage. We hypothesized that isoflurane, sevoflurane, and desflurane would exert variable degrees of neurotoxicity in vitro and in vivo via activation of the p75 neurotrophin receptor (p75 NTR ). METHODS: SH-SY5Y cells were exposed to oxygen–glucose deprivation (OGD, 16 hours), preceded or followed by incubation with isoflurane, sevoflurane, or desflurane (1.2 minimal alveolar concentration, 2 hours). Neuronal cell death was analyzed by flow cytometry (mitochondrial membrane potential, Annexin V/propidium iodide [AV/Pi]) and quantification of lactate dehydrogenase release. We analyzed NF-κB activity by DNA-binding ELISA and luciferase assay. The role of p75 NTR was studied using the p75 NTR -blocking peptide TAT-pep5 and siRNA knockdown. The effect of isoflurane ±p75 NTR inhibition on retinal ischemia-reperfusion injury (IRI) in adult Sprague-Dawley rats was assessed by analyzing retinal ganglion cell (RGC) density. RESULTS: Isoflurane but not sevoflurane or desflurane postexposure aggravated OGD-induced neuronal cell death (AV/Pi positive cells: OGD 41.1% [39.0/43.3] versus OGD + isoflurane 48.5% [46.4/63.4], P = 0.001). Isoflurane significantly increased NF-κB DNA-binding and transcriptional activity of NF-κB (relative Luminescence Units: OGD 500 [499/637] versus OGD + isoflurane 1478 [1363/1643], P = 0.001). Pharmacological inhibition or siRNA knockdown of p75 NTR counteracted the aggravating effects of isoflurane. Isoflurane increased RGC damage in vivo (IRI 1479 RGC/mm 2 [1311/1697] versus IRI + isoflurane 1170 [1093/1211], P = 0.03), which was counteracted by p75 NTR -inhibition via TAT-pep5 (P = 0.02). CONCLUSIONS: Isoflurane but not sevoflurane or desflurane postexposure aggravates neurotoxicity in preinjured neurons via activation of p75 NTR and NF-κB. These findings may have implications for the choice of volatile anesthetic being used in patients with or at risk for neuronal injury, specifically in patients with a stroke or history of stroke and in surgical procedures in which neuronal injury is likely to occur, such as cardiac surgery and neurovascular interventions. (Anesth Analg 2014;119:1429–41)

Infant brain injury from hypoxia-ischemia (HI) can lead to life-long impairment, but protective strategies are lacking. Short-term but not long-term protection has been demonstrated in the Rice-Vannucci neonatal brain ischemia model (RVM) by volatile anesthetic administration before HI, while exposure during HI has not been tested. In the current study, we evaluated a combination of sevoflurane and mild hypothermia as a protective approach during HI, both short- and long-term, by introducing intubation and mechanical ventilation to the RVM.The right common carotid artery was ligated in 10-day-old mice during brief sevoflurane anesthesia, followed by a 2-hour recovery with the dam. Littermates were then randomized to either: HI spontaneously breathing 10% oxygen for 60 minutes (the classical RVM); HI-Protect mild hypothermia and orotracheal intubation and mechanical ventilation with 3.5% sevoflurane in 10% oxygen for 60 minutes; or Room Air spontaneously breathing room air for 60 minutes. In a nonsurviving cohort, cerebral oxygenation was monitored in the area at risk and the contralateral hemisphere during HI or HI-Protect using visible-light spectroscopy (Spectros Corp). Mean arterial blood pressure and heart rate were measured. Arterial blood gases were obtained. Right/left brain hemispheric weight ratios and brain damage scores were determined 1 week after HI. In another group, learning and behavior were assessed in young adulthood (9 weeks) using spontaneous locomotion, Morris water maze, and apomorphine injection.During HI, ipsilateral and contralateral brain oxygenation, arterial blood pressures, blood gases, and glucose levels were similar in both ischemic groups, while heart rate was slower in the HI-Protect group. One week after ischemia, brain hemispheric weight ratios and injury scores in several brain regions were significantly worse after HI, compared with HI-Protect. Nine weeks after HI, Morris water maze hidden platform and reversal platform escape latencies, measures of spatial memory function, were superior after HI-Protect, compared with HI (P0.0001). HI-Protect animals demonstrated significantly less circling behavior after an apomorphine challenge (P0.0001), a measure of striatal integrity.To test the neuroprotective effects of volatile anesthetics during neonatal brain ischemia, we developed a modification of the RVM. By using mechanical ventilation and endotracheal intubation, sevoflurane administration during HI was survivable. The combination of sevoflurane administration and mild hypothermia during HI conferred not only short-term structural, but also long-term functional protection, compared with littermates treated according to the RVM. These findings warrant further studies to improve neurological outcome in critically ill infants.

During spinal surgery, intraoperative monitoring of motor-evoked potentials (MEPs) is a useful means of assessing the intraoperative integrity of corticospinal pathways. However, MEPs are known to be particularly sensitive to the suppressive effects of inhalational halogenated anesthetic agents.To investigate the effects of increasing end-tidal concentrations of desflurane and sevoflurane anesthesia in a background of propofol and remifentanil with multipulse cortical stimulation on intraoperative monitoring of MEPs.In this randomized crossover trial, 14 consecutive patients (7 in each arm) undergoing major spine surgery, under a background anesthetic of propofol (75 to 125 mcg/kg/min) and remifentanil (0.1 to 0.2 mcg/kg/min), were randomly assigned to receive the sequence of inhalational agents studied: either DES-SEVO (desflurane followed by sevoflurane); or SEVO-DES (sevoflurane followed by desflurane). Multiples (0.3, 0.5, and 0.7) of minimum alveolar concentration (MAC) of desflurane and sevoflurane were administered. After a washout period of 15 minutes using high fresh oxygen/air flows, each of the patients then received the other gas as the second agent. Cortical stimulation was achieved with a train of 5 equivalent square pulses, each 0.05 ms in duration, delivered at 2 ms intervals. MEP recordings were made in the upper limb (UL) from first dorsal interosseus and lower limb (LL) from tibialis anterior with subdermal needle electrodes.At 0.3 MAC desflurane, there was no statistical significant difference in transcranial-evoked MEP amplitudes from the baseline in both UL and LL stimulation. However, this was not the case for sevoflurane for which even a low concentration at 0.3 MAC significantly depressed MEP amplitudes of LL (but not UL) from baseline value. Desflurane at 0.5 and 0.7 MAC depresses LL MEP to 58.4% and 59.9% of baseline, respectively (P0.05), whereas sevoflurane at 0.3, 0.5, and 0.7 MAC depresses LL MEP to 66.2%, 41.3%, and 25.3% of baseline, respectively (P0.05). There was no difference in latency of the responses at any MAC.Inhalational anesthetic agents (sevofluranedesflurane) suppress MEP amplitudes in a dose-dependent manner. The use of 0.3 MAC of desflurane (but not sevoflurane) provided good MEP recordings acceptable for clinical interpretation for both upper and LLs. The LL appears to be more sensitive to anesthetic-induced depression compared with the UL. All patients studied had normal neurological examination hence, these results may not be applicable to those with preexisting deficits.

BACKGROUND During emergence from volatile anesthesia, hypoventilation may result from many causes. In this study, we examined the effect of hypoventilation after initial emergence from volatile anesthesia and the potential for reanesthetization. METHODS The uptake and excretion of desflurane (Des), sevoflurane, and isoflurane were studied using the Gas Man® computer simulation program for a 70-kg simulated patient. The vaporizer setting was adjusted so that a VRG (vessel-rich tissue group, including brain) level of 0.75 minimum alveolar concentration (MAC), 1.0 MAC, and 1.5 MAC was rapidly achieved and maintained within tight limits for a 1-, 2-, 4-, and 6-hour period of anesthesia.At the end of the simulated period of anesthesia, the vaporizer was set to 0 and fresh gas flow was set to 8 L/min. Ventilation (VA) was continued at 4 L/min until the anesthetic level in the VRG reached MAC awake, equal to 0.33 MAC for each drug. Then, the VA was adjusted to 0.1 L/min to simulate near-apnea and 0.0 L/min to simulate true apnea. Severe reanesthetization was said to occur if the VRG level increased to or above 0.5 MAC. Mild reanesthetization was said to occur if VRG increased from its value of 0.33 MAC but did not reach 0.5 MAC. The minimum VA required to avoid severe reanesthetization was studied by trials of decreased VA beginning at the time the VRG reached 0.33 MAC. RESULTS After emergence from 1 hour of anesthesia, all simulated patients were protected against mild and severe reanesthetization if anesthesia was at 0.75 or 1.0 MAC. After 4 or 6 hours of anesthesia, severe reanesthetization occurred with all drugs with near or true apnea if anesthesia was at 1.0 or 1.5 MAC. The minimum alveolar VA to protect against severe reanesthetization after 6 hours of anesthesia was no more than 0.5 L/min for all drugs at 0.75 MAC, no more than 0.5 L/min at 1.0 MAC, and no more than 1.2 L/min at 1.5 MAC. In all simulated cases, the source of anesthetic drug that allowed reanesthetization was muscle (MUS), which reached a value of 0.8 MAC within 4 hours with all drugs and reached a value of 0.75 MAC with desflurane after 2 hours. Fat levels of anesthetic remained less than 0.15 MAC for all drugs up to the 6 hours tested. CONCLUSIONS Reanesthetization from hypoventilation after inhaled anesthesia is possible. After initial emergence, muscle is a source of anesthetic and predisposes to reanesthetization while fat is a sink for anesthetic and fosters continued emergence. Severe hypoventilation will cause some degree of reanesthetization from anesthetic released from muscle after 4 hours of 1 MAC inhaled anesthesia with desflurane, sevoflurane, or isoflurane.

Background:Sevoflurane sedation in the intensive care unit is possible with a special heat and moisture exchanger called the Anesthetic Conserving Device (ACD) (AnaConDa®; Sedana Medical AB, Uppsala, Sweden). The ACD, however, may corrupt ventilatory mechanics when used during the weaning process of intensive care unit patients. The authors compared the ventilatory effects of light-sedation with sevoflurane administered with the ACD and those of classic management, consisting of a heated humidifier and intravenous sedation, in intensive care unit patients receiving pressure-support ventilation.Methods:Fifteen intensive care unit patients without chronic pulmonary disease were included. A target Richmond Agitation Sedation Scale level of −1/−2 was obtained with intravenous remifentanil (baseline 1-condition). Two successive interventions were tested: replacement of the heated humidifier by the ACD without sedation change (ACD-condition) and sevoflurane with the ACD with an identical target level (ACD-sevoflurane-condition). Patients finally returned to baseline (baseline 2-condition). Work of breathing, ventilatory patterns, blood gases, and tolerance were recorded. A steady state of 30 min was achieved for each experimental condition.Results:ACD alone worsened ventilatory parameters, with significant increases in work of breathing (from 1.7 ± 1.1 to 2.3 ± 1.2 J/l), minute ventilation, P0,1, intrinsic positive end-expiratory pressure (from 1.3 ± 2.6 to 4.7 ± 4.2 cm H2O), inspiratory pressure swings, and decreased patient comfort. Sevoflurane normalized work of breathing (from 2.3 ± 1.2 to 1.8 ± 1 J/l), intrinsic positive end-expiratory pressure (from 4.7 ± 4.2 to 1.8 ± 2 cm H2O), inspiratory pressure swings, other ventilatory parameters, and patient tolerance.Conclusions:ACD increases work of breathing and worsens ventilatory parameters. Sevoflurane use via the ACD (for a light-sedation target) normalizes respiratory parameters. In this patient’s population, light-sedation with sevoflurane and the ACD may be possible during the weaning process.

Mastocytosis includes a spectrum of diseases characterized by abnormal mast cell infiltration in various organs, which can lead to mast cell mediator release and immediate hypersensitivity. We review anesthetic challenges presented by a 6-year-old girl with a history of mast cell mediator release because of the urticaria pigmentosa variant of cutaneous mastocytosis, factor VII deficiency, increasing episodes of urinary tract infections, and pyelonephritis. She underwent spine magnetic resonance imaging, subsequent lumbar laminectomy for fatty filum release, and a cystourethroscopy. Perioperative management included factor VII desensitization, avoidance of triggers, minimizing histamine-releasing medications, mast cell stabilization, and preparation for potential immediate hypersensitivity.