Influence of Different Sevoflurane Concentrations on Postoperative Cognitive Function in Aged Rats.

BACKGROUND: Postoperative cognitive dysfunction may be associated with neuroinflammation, and sevoflurane suppresses surgery-induced inflammation. We hypothesized that low concentrations of sevoflurane would result in more impaired postoperative cognitive function compared to high concentrations. METHODS: Aged male Sprague-Dawley rats (n = 21, 17-22 months) were randomly assigned to 1 of 3 groups: control (C), sevoflurane 2% (S2), and sevoflurane 4% (S4). Rats in the S2 and S4 groups underwent open femoral fracture and intramedullary fixation of the left hind limb under 2 hours of sevoflurane anesthesia. Neurological outcomes were evaluated using the Morris water maze (MWM) test, and histopathological outcomes were assessed 28 days after surgery. RESULTS: The S2 group showed prolonged swimming latency compared to S4 on day 7 (difference of means, 34.4; 95% confidence interval [CI], 2.57-66.3; P = .031) and compared to the C group on day 9 (difference of means, -33.4; 95% CI, -65.3 to -1.55; P = .037). The intact CA1 cells in the S2 group were significantly less than those in the C and S4 groups (H statistic, 10.87; P = .006 versus C; P = .033 versus S4). CONCLUSIONS: We found that low concentrations of sevoflurane prolonged the swimming latency of the MWM compared to high concentrations and reduced intact CA1 hippocampal neurons in aged rats. These results suggest that low-concentration sevoflurane anesthesia may be more detrimental than high concentration for spatial cognitive function and postoperative impairment of hippocampal CA1 cells in aged rats.

Esophageal achalasia detected by vomiting during induction of general anesthesia: a case report.

BACKGROUND: Esophageal achalasia is a rare disease with a high risk of aspiration during anesthesia induction. Here, we describe our experience involving a case of undiagnosed esophageal achalasia with profuse vomiting during anesthesia induction. CASE PRESENTATION: A 58-year-old woman was scheduled for orthopedic surgery under general anesthesia. She vomited a large amount of watery contents during anesthesia induction, and planned surgery was postponed. After recovery from anesthesia, she informed us that she usually had to drink a large amount of water to get food into her stomach and purged watery vomit every night before sleep. However, she attributed it to her constitutional problem, not to a specific disease. She was subsequently diagnosed with esophageal achalasia and underwent Heller myotomy with Dor fundoplication before her re-scheduled orthopedic surgery. CONCLUSIONS: A detailed history of dysphagia and regurgitation should be taken in preoperative examinations to prevent unexpected aspiration due to undiagnosed achalasia.

Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury.

Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.

Nicorandil, a KATP Channel Opener, Attenuates Ischemia-Reperfusion Injury in Isolated Rat Lungs.

PURPOSE: Nicorandil is a hybrid between nitrates and KATP channel opener activators. The aim of this study was to evaluate the nicorandil's effects on ischemia-reperfusion (IR) lung injury and examine the mechanism of its effects. METHODS: Isolated rat lungs were divided into 6 groups. In the sham group, the lungs were perfused and ventilated for 150 min. In the IR group, after perfusion and ventilation for 30 min, they were interrupted (ischemia) for 60 min, and then resumed for 60 min. In the nicorandil (N) + IR group, nicorandil 6 mg was added before ischemia (nicorandil concentration was 75 µg ml-1). In the glibenclamide + N + IR group, the L-NAME (Nω-Nitro-L-arginine methyl ester) + N + IR group and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) + N + IR group, glibenclamide 3 µM, L-NAME 100 µM, and ODQ 30 µM were added 5 min before nicorandil administration, respectively. We measured the coefficient of filtration (Kfc) of the lungs, total pulmonary vascular resistance, and the wet-to-dry lung weight ratio (WW/DW ratio). RESULTS: Kfc was significantly increased after 60 min reperfusion compared with baseline in the IR group, but no change in the sham group. An increase in Kfc was inhibited in the N + IR group compared with the IR group (0.92 ± 0.28 vs. 2.82 ± 0.68 ml min-1 mmHg-1 100 g-1; P < 0.01). Also, nicorandil attenuated WW/DW ratio was compared with IR group (8.3 ± 0.41 vs. 10.9 ± 2.5; P < 0.05). Nicorandil's inhibitory effect was blocked by glibenclamide and ODQ (P < 0.01), but not by L-NAME. CONCLUSIONS: Nicorandil attenuated IR injury in isolated rat lungs. This protective effect appears to involve its activation as KATP channel opener as well as that of the sGC-cGMP pathway.

Effect of lidocaine cream analgesia for chest drain tube removal after video-assisted thoracoscopic surgery for lung cancer: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Pain management makes an important contribution to good respiratory care and early recovery after thoracic surgery. Although the development of video-assisted thoracoscopic surgery (VATS) has led to improved patient outcomes, chest tube removal could be distressful experience for many patients. The aim of this trial was to test whether the addition of lidocaine cream would have a significant impact on the pain treatment during chest tube removal from patients who had undergone VATS for lung cancer. METHODS: This clinical trial was a double-blind randomized study. Forty patients with histologically confirmed lung cancer amenable to lobectomy/segmentectomy were enrolled. All patients had standard perioperative care. Patients were randomly assigned to receive either epidural anesthesia plus placebo cream (placebo, Group P) or epidural anesthesia plus 7% lidocaine cream cutaneously around the chest tube insertion site and on the skin over the tube's course 20 min (Group L) before chest drain removal. RESULTS: Visual analog scale (VAS) scores were higher in Group P (median 5, IQR, 3.25-8) than in Group L (median 2, IQR, 1-3). Pain intensities measured using a PainVision system were also higher in Group P (median 296.7, IQR, 216.9-563.5) than Group L (median 41.2, IQR, 11.8-97.0). VAS scores and the pain intensity associated with chest drain removal were significantly lower in Group L than Group P (p=0.0002 vs p<0.0001). CONCLUSION: Analgesia using lidocaine cream is a very simple way to reduce the pain of chest tube removal after VATS. TRIAL REGISTRATION NUMBER: UMIN000013824.

Neuroprotective Effects of Fasudil, a Rho-Kinase Inhibitor, After Spinal Cord Ischemia and Reperfusion in Rats.

BACKGROUND: Excessive Rho/Rho-kinase pathway activation occurs subsequent to stroke. We examined the neuroprotective effects of pre- and posttreatment with fasudil (a Rho-kinase inhibitor) in a rat transient spinal cord ischemia-reperfusion model under normothermic conditions. METHODS: After approval by our animal research committee, male Sprague-Dawley rats were assigned to 1 of 6 groups: pre- and postcontrol (C); pre- and postfasudil (F); and pre- and postsham (S). Fasudil (10 mg/kg) or normal saline was administered intravenously over 30 minutes before ischemia in the pre-F or pre-C groups, and over 30 minutes after reperfusion in the post-F or post-C groups. Sham groups were not subjected to ischemia. Ischemia was induced by aortic occlusion using a balloon catheter combined with hypotension for 10 minutes. Neurologic deficit scores (NDS; 0-8 points) were assessed 1, 7, and 14 days after ischemia, and then histopathologic outcomes were assessed. RESULTS: NDS 7 and 14 days after ischemia in the pre-F group (median [range]; 3.5 [2-6] and 2.5 [0-6]) were lower than those in the pre-C group (5.5 [4-7] and 4.5 [4-6]; P = .046 and P = .049), whereas NDS in the post-F group and in the post-C group were not different. The numbers of intact neurons in the gray matter in the pre- and post-F groups (mean ± standard deviation [95% confidence interval]: 25 ± 7 [20-30] and 16 ± 5 [12-19]) were greater than those in the pre- and post-C groups (11 ± 5 [7-14] and 9 ± 3 [7-11]; P < .001 and P = .002). The number of intact neurons in the post-F group (16 ± 5 [12-19]) was lower than the number in the post-S group (26 ± 2 [24-29]; P < .001). The percentages of vacuolation in the white matter in the pre- and post-F groups (21.5 ± 8.4 [15.5-27.5] and 13.6 ± 7.4 [8.3-18.9]) were lower than those in the pre- and post-C groups (43.7 ± 10.4 [36.3-51.1] and 40.6 ± 12.3 [31.8-49.4]; P < .001 and P < .001). CONCLUSIONS: Our results demonstrated that intravenous fasudil administered before ischemia improved both neurologic and histopathologic outcomes even 14 days after ischemia, while fasudil administered postinsult improved histopathologic outcomes only in normothermic rats. Fasudil may be a relevant pretreatment paradigm for planned procedures at risk for spinal cord ischemia.

Recovery From Ropivacaine-Induced or Levobupivacaine-Induced Cardiac Arrest in Rats: Comparison of Lipid Emulsion Effects.

BACKGROUND: Lipid emulsion treatment appears to have application in the treatment of local anesthetic-induced cardiac arrest. To examine whether the efficacy of lipid resuscitation in the treatment of local anesthetic-induced cardiac arrest is affected by lipophilicity, the effects of lipid infusions were compared between levobupivacaine-induced (high lipophilicity) and ropivacaine-induced (lower lipophilicity) rat cardiac arrest model. METHODS: A total of 28 female Sprague-Dawley rats were anesthetized using sevoflurane, which subsequently underwent tracheostomy, followed by femoral artery and vein cannulation. Two hours after the discontinuation of sevoflurane, either levobupivacaine 0.2% (n = 14) or ropivacaine 0.2% (n = 14) was administered at a rate of 2 mg/kg/min to the awake rats. When the pulse pressure decreased to 0, the infusion of local anesthetic was discontinued, and treatment with chest compressions and ventilation with 100% oxygen were immediately initiated. The total doses of local anesthetics needed to trigger the first seizure and pulse pressure of 0 mm Hg were calculated. The 2 groups were each subdivided into a lipid emulsion group (n = 7) and a control group (n = 7). In the lipid emulsion group, 20% lipid emulsion was administered intravenously (5 mL/kg bolus plus continuous infusion of 0.5 mL/kg/min), while in the control group, the same volume of normal saline was administered. Chest compressions were discontinued when the rate-pressure product had increased by more than 20% of baseline. RESULTS: The cumulative doses of levobupivacaine and ropivacaine that produced seizures and 0 pulse pressure showed no significant difference. Mean arterial blood pressure (MAP) values were higher in the levobupivacaine group than in the ropivacaine group after resuscitation was initiated (P < .05). In levobupivacaine-induced cardiac arrest, heart rate and MAP values were higher in the lipid group than in the control group after starting resuscitation (P < .05); all rats in the lipid group achieved spontaneous circulation (rate-pressure product >20% baseline), while only 2 of 7 rats in the control group achieved spontaneous circulation at 10 minutes. In ropivacaine-induced cardiac arrest, there were no significant differences in heart rate and MAP between the lipid and control groups from the start of resuscitation to 10 minutes; spontaneous circulation returned in 6 of 7 lipid group rats, but in only 2 of 7 control group rats at 10 minutes. CONCLUSIONS: Lipid emulsion treatment was more effective for levobupivacaine-induced cardiac arrest than for ropivacaine-induced cardiac arrest. Although lipid therapy is also effective for ropivacaine-induced cardiac arrest, it takes more time than in levobupivacaine-induced cardiac arrest. This suggests that the lipophilicity of local anesthetics influences the efficacy of lipid infusion when treating cardiac arrest caused by these drugs.

Evaluation of postoperative pregabalin for attenuation of postoperative shoulder pain after thoracotomy in patients with lung cancer, a preliminary result.

OBJECTIVE: Thirty-one to 97% of patients who undergo thoracotomy for lung cancer experience ipsilateral shoulder pain, marring the otherwise excellent relief provided by thoracic epidural analgesia. The aim of this study was to test whether the addition of pregabalin to the treatment for shoulder pain would provide a significant benefit. METHODS: Twenty patients undergoing thoracic surgery for lung cancer were enrolled in the control group between May 2012 and December 2012, and 20 patients were enrolled in the pregabalin group between January 2013 and July 2013, consecutively. All patients had standard pre- and intraoperative care. Patients received pregabalin 150 mg po POD 1 and then non-steroidal anti-inflammatory drugs (NSAIDs) po 2 h later (pregabalin group), or they received only NSAIDs po at exactly the same times (control group). Pain severity was then measured using a 100-mm visual analog scale (VAS) scoring system. RESULTS: The VAS scores indicated that patients in the pregabalin group had significantly less shoulder pain on postoperative day (POD) 2 than those in the control group (control: 27.9 ± 28.1 vs. pregabalin: 11.8 ± 14.4; p = 0.030). No differences in pain were observed between the two groups on other POD. There were significant differences on only POD 2 in the patients with shoulder pain immediately after surgery. Three of the pregabalin-treated patients showed mild somnolence. CONCLUSIONS: Postoperative administration of pregabalin provided significant relief of postoperative shoulder pain during earlier POD after thoracic surgery for lung cancer when received multimodal analgesia in combination with NSAIDs.

[Successful epidural anesthesia using 120 mm epidural needle for cesarean section in a morbidly obese parturient with body mass index 50.2 kg x m(-2)].

In a morbidly obese parturient, epidural anesthesia is occasionally difficult because of great distance from the skin to the epidural space, and difficulty in identification of appropriate landmarks. We successfully managed cesarean section in a morbidly obese parturient with body mass index of 50.2 kg x m(-2) under epidural anesthesia. We used a 17 G custom-made epidural needle 120 mm long (Hakko, Tokyo, Japan), and the depth from the skin to the epidural space was 95 mm. We conclude that an extremely long epidural needle was useful in a morbidly obese parturient for overcoming the difficulties in epidural puncture and avoiding general anesthesia-related complications.

Beta-adrenoreceptor antagonists attenuate brain injury after transient focal ischemia in rats.

Beta-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, beta-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several beta-adrenoreceptor antagonists in rat transient focal cerebral ischemia. Halothane-anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received an IV infusion of saline 0.5 mL/h, propranolol 100 microg x kg(-1) x min(-1), carvedilol 4 microg x kg(-1) x min(-1), esmolol 200 microg x kg(-1) x min(-1), or landiolol 50 microg x kg(-1) x min(-1) (n = 6 in each group). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. Additional rats received esmolol 50 microg x kg(-1) x min(-1) or landiolol 10 microg x kg(-1) x min(-1) intrathecally (IT) via the cisterna magna (n = 5 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 22 h after reperfusion, and the brains were removed and stained with triphenyltetrazolium chloride for evaluation of infarct volume. Additional rats that received saline, esmolol, and landiolol IV (n = 6 in each group) were allowed to survive for 7 days followed by measurement of infarct size. Neurological deficit scores were smaller in rats treated with propranolol-IV, carvedilol-IV, esmolol-IV, landiolol-IV, esmolol-IT, and landiolol-IT compared with saline-treated rats (P < 0.05). Cortical and striatum infarct volumes were less in the rats receiving beta-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that beta-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.

The effects of cervical and lumbar epidural anesthesia on heart rate variability and spontaneous sequence baroreflex sensitivity.

A high level of neuroaxial block may produce profound bradycardia and hypotension, possibly as a result of an imbalance between sympathetic and parasympathetic control of heart rate. We designed this study to test the hypothesis that cervical epidural anesthesia would increase the high-frequency (HF) component of heart rate variability (HRV) as a result of cardiac sympathectomy, whereas lumbar epidural anesthesia would cause sympathetic predominance. HRV and spontaneous baroreflex (SBR) sensitivity were assessed before and after cervical and lumbar epidural anesthesia by using plain 1.5% lidocaine (median upper/lower sensory block: C3/T8 for cervical and T11/L5 for lumbar) in healthy patients (n = 10 each). Electrocardiogram and noninvasive beat-to-beat arterial blood pressure were monitored. HRV was analyzed by using fast Fourier transformation. Least-square regression analysis relating R-R interval and systolic blood pressure during spontaneous fluctuation was performed to obtain SBR sensitivities. Cervical epidural group patients were significantly older (P < 0.01) and taller (P < 0.01). Cervical epidural anesthesia attenuated HF (0.15-0.4 Hz) and low-frequency (0.04-0.15 Hz) power of HRV with concomitant reductions in up- and down-sequence SBR sensitivities, suggesting decreased vagal modulation of heart rate. Lumbar epidural anesthesia resulted in a significant increase in the low-frequency/HF ratio of HRV and unchanged SBR indices, suggesting sympathetic predominance. HF power correlated well with SBR sensitivities under most of our study conditions. Respiratory rates and Paco(2) were unchanged by either epidural technique. Our results indicate that cervical, but not lumbar, epidural anesthesia depresses phasic and tonic dynamic modulation of the cardiac cycle by the vagal nerve in conscious humans.

Neurological recovery by EEG bursting after resuscitation from cardiac arrest in rats.

INTRODUCTION: The return of neurological function during the early period after resuscitation from cardiac arrest (CA) has not been evaluated systematically. We report the temporal analysis of EEG bursting pattern during the very early periods after resuscitation. DESIGN/METHOD: A balanced group of good and poor outcome animals was selected from a population of rats subjected to either 5 or 7 min of asphyxial cardiac arrest (ACA) on the basis of a single criteria: 24 h neurobehavioral function based on the neurodeficit score (NDS). The EEGs of six consecutive good outcome rats (NDS > or = 60) and six consecutive poor outcome rats (NDS < 60) were selected for the study. The EEGs of these animals were given to two EEG examiners who were blinded to the selection process, the experimental conditions and the neurobehavioral recovery. The EEG bursting characteristics, such as rate, peak and duration of bursting were studied. RESULTS: There was significantly higher EEG bursting in the good outcome animals (P < 0.05) and the burst complexes evolved into continuous activity by 90 min. Lower frequency bursting that persisted and failed to evolve into continuous activity was observed in the poor outcome group. CONCLUSION: Increased EEG bursting during first 30-40 min after resuscitation from moderate to severe ACA was observed in rats with good neurological outcome at 24 h. Early EEG bursting patterns may provide additional prognostication after resuscitation from CA.

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-N2O anesthesia.

PURPOSE: Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. METHODS: Thirty-six adult patients were randomly assigned to two groups ( n = 18 each): the propofol group patients were anesthetized with propofol (5-10 mg.kg(-1).h(-1))-(2)O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%-1.0%)-(2)O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg.kg(-1) and atropine 0.02 mg.kg(-1) was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. RESULTS: At the completion of the surgery, the average infusion rate of propofol was 6.2 +/- 1.7 mg.kg(-1).h(-1), and the average inspired concentration of isoflurane was 0.73 +/- 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 +/- 9 and 34 +/- 6 beats.min(-1), respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (-9 +/- 4 and -5 +/- 4 beats.min(-1), respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats.min(-1)) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). CONCLUSION: We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia.

Hemodynamic effects of oral clonidine premedication in lumbar epidural anesthesia.

Clonidine, an α2-adrenergic agonist, has a potent sympatholytic effect and augments the pressor effect of ephedrine during general anesthesia. We evaluated whether oral clonidine premedication would alter the hemodynamic changes and enhance the pressor response to intravenous ephedrine during epidural anesthesia in 35 adult patients. They were randomly administered either premedication with clonidine approximately 5 µg·kg-1 po (n=17) or no clonidine medication (n=18). After establishment of epidural anesthesia, the hemodynamic response to ephedrine iv was measured in the awake state at 1-min intervals for 10 min. Then, the same hemodynamic measurement was repeated in the asleep state induced with midazolam iv. There were no differences in blood pressure (BP) and heart rate values between groups during the onset of epidural anesthesia, except that BP before epidural anesthesia was lower in the clonidine group than the control group (P<0.05). The magnitude and duration of pressor responses to ephedrine were comparable between groups in awake and asleep states. In conclusion oral clonidine premedication 5 µg·kg-1 alters neither the hemodynamic changes nor the pressor response to intravenous ephedrine during epidural anesthesia.