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Fluid therapy to restore and/or maintain tissue perfusion may affect patient outcomes in perioperative, emergency, and intensive care. Kinetic analyses and outcome-oriented studies have provided more insight into fluid management. Crystalloids are slowly distributed to the interstitial space, and the efficiency (proportion of infused fluid retained in the bloodstream) is 50%-75% as long as infusion continues and may increase up to 100% when the arterial pressure has decreased. Elimination of the infused fluid during general anesthesia and surgery is very slow, amounting to only 10%-20% compared with that in conscious patients. When the endothelial glycocalyx layer is degraded in sepsis or trauma-induced systemic inflammation, turnover of colloids and crystalloids is accelerated and the efficiency is reduced, which may lead to tissue edema, inflammation, poor wound healing, and organ dysfunction. Balanced crystalloids are pragmatic initial resuscitation fluids and improve patient outcomes compared to saline (0.9% sodium chloride). Albumin may be beneficial, but other synthetic colloids appear to increase the risk of acute kidney injury and death among patients in the intensive care unit. Fluid kinetics is likely to change based on patient physiological conditions (e.g., general anesthesia, surgery, stress, dehydration, blood pressure, or inflammation) and fluid types. To maximize efficacy and minimize iatrogenic side effects, fluids should be prescribed based on individual patient factors, disease states, and other treatment remedies.

BackgroundArytenoid dislocation is a rare laryngeal injury that may follow endotracheal intubation. We aimed to determine the incidence and risk factors for arytenoid dislocation after surgery under general anaesthesia.MethodsWe reviewed the medical records of patients who underwent operation under general anaesthesia with endotracheal intubation from January 2014 to December 2018. Patients were divided into the non-dislocation and dislocation groups depending on the presence or absence of arytenoid dislocation. Patient, anaesthetic, and surgical factors associated with arytenoid dislocation were determined using Poisson regression analysis.ResultsAmong the 25,538 patients enrolled, 33 (0.13%) had arytenoid dislocation, with higher incidence after anterior neck and brain surgery. Patients in the dislocation group were younger (52.6 ± 14.4vs58.2 ± 14.2 yrs,P = 0.025), more likely to be female (78.8vs56.5%,P = 0.014), and more likely to be intubated by a first-year anaesthesia resident (33.3vs18.5%,P = 0.048) compared to those in the non-dislocation group. Patient positions during surgery were significantly different between the groups (P = 0.000). Multivariable Poisson regression identified head-neck positioning (incidence rate ratio [IRR], 3.10; 95% confidence interval [CI], 1.50–6.25,P = 0.002), endotracheal intubation by a first-year anaesthesia resident (IRR, 2.30; 95% CI, 1.07–4.64,P = 0.024), and female (IRR, 3.05; 95% CI, 1.38–7.73,P = 0.010) as risk factors for arytenoid dislocation.ConclusionThis study showed that the incidence of arytenoid dislocation was 0.13%, and that head-neck positioning during surgery, less anaesthetist experience, and female were significantly associated with arytenoid dislocation in patients who underwent surgeries under general anaesthesia with endotracheal intubation.

Background The monitoring of regional cerebral oxygen saturation (SrO2) using near-infrared spectroscopy is useful method to detect cerebral ischemia during. Sevoflurane and propofol decrease cerebral metabolic rate (CMRO2) in a similar manner, but the effects on the cerebral blood flow (CBF) are different. We hypothesized that the effects of sevoflurane and propofol on SrO2 were different in patients with deficits of CBF. This study compared the effect of sevoflurane and propofol on SrO2 of patients undergoing cerebral endarterectomy (CEA). Method Patients undergoing CEA were randomly assigned to the sevoflurane or propofol group (n = 74). The experiment was preceded in 2 stages based on carotid artery clamping. The first stage was from induction of anaesthesia to immediately before clamping of the carotid artery, and the second stage was until the end of the operation after clamping of the carotid artery. Oxygen saturation (SrO2, SpO2), haemodynamic variables (blood pressure, heart rate), respiratory parameters (end-tidal carbon dioxide tension, inspired oxygen tension), concentration of anesthetics, and anesthesia depth (bispectral index score) were recorded. Results During stage 1 period (before carotid artery clamping), the mean value of the relative changes in SrO2 was higher (P = 0.033) and the maximal decrease in SrO2 was lower in the sevoflurane group compared with the propofol group (P = 0.019) in the contralateral (normal) site. However, there is no difference in ipsilateral site (affected site). SrO2 decreased after carotid artery clamping and increased after declamping, but the difference was not significant between two groups. Changes in mean arterial blood pressure was lower in sevoflurane group than propofol group after the carotid artery declamping (P = 0.048). Conclusion Propofol-remifentanil anesthesia was comparable with sevoflurane-remifentanil anesthesia in an aspect of preserving the SrO2 in patients undergoing carotid endarterectomy. Trial registration Clinical Trials.gov identifier: NCT02609087, retrospectively registered on November 18, 2015.

Background Sugammadex is associated with few postoperative complications. Postoperative pulmonary complications (PPC) are related to prolonged hospitalizations. Present study explored whether the use of sugammadex could reduce PPCs and thereby reduce hospital length of stay (LOS) after lung surgery. Methods We reviewed the medical records of patients who underwent elective open lobectomy for lung cancer from January 2010 to December 2015. Patients were divided into the sugammadex group and pyridostigmine group. The primary outcome was hospital LOS and secondary outcomes were postoperative complications and overall survival at 1 year. The cohort was subdivided into patients with and without prolonged LOS to explore the effects of sugammadex on outcomes in each group. Risk factors for LOS were determined via multivariate analyses. After propensity score matching, 127 patients were assigned to each group. Results Median hospital LOS was shorter (10.0 vs. 12.0 days) and the incidence of postoperative atelectasis was lower (18.1 vs. 29.9%) in the sugammadex group. However, no significant difference in overall survival between the groups was seen over 1 year (hazard ratio, 0.967; 95% confidence interval, 0.363 to 2.577). Sugammadex was a predictor related to LOS (exponential coefficient 0.88; 95% CI 0.82–0.95). Conclusions Our data suggest that sugammadex is a preferable agent for neuromuscular blockade (NMB) reversal than cholinesterase inhibitors in this patient population. Trial registration This study registered in the Clinical Research Information Service of the Korea National Institute of Health (approval number: KCT0004735, Date of registration: 21 January 2020, Retrospectively registered).

Background: We compared the effects of different remifentanil effect-site concentrations on intubating conditions, and cardiovascular and bispectral index score (BIS) responses to intubation at a fixed effect-site concentration of propofol without muscle relaxants. Methods: Sixty-four patients were randomly assigned to one of three groups: remifentanil 2 (group R2, n = 22), 4 (group R4, n = 21), or 6 ng/ml (group R6, n = 21). Anesthesia was induced using target-controlled infusion of propofol 5 μ g/ml and each concentration of remifentanil. Laryngoscopy and intubation was attempted at 2.5 min following induction. Intubating conditions were assessed as excellent, good or poor using a standard scoring sy stem. Mean arterial pressure (MAP), heart rate (HR), and BIS values were assessed. Results: Excellent or good intubating conditions were obtained in 91% of group R4 and 95% of R6, both of which are higher compared with 32% of R2 (P ＜ 0.01). MAP and HR decreased significantly after induction in all groups. After intubation, they recovered to baseline value in group R2 and R4 but were significantly less than baseline values in R6. BIS response to intubation was attenuated in group R4 and R6 but not R2. Hypotension was more frequent in group R6 than R2. Conclusions: Remifentanil target concentrations of 4 or 6 ng/ml combined with 5 μg/ml propofol provided good or excellent conditions for tracheal intubation and prevented cardiovascular and BIS response during induction without muscle relaxants. However, the use of 6 ng/ml dose was associated with frequent occurrence of hypotension and bradycardia requiring treatment. (Korean J Anesthesiol 2009; 57 13∼9)

Objective To determine the correlation between anatomical features of the upper airway (evaluated via computed tomography imaging) and the ease of light wand-assisted endotracheal intubation in patients undergoing ear, nose and throat surgery under general anaesthesia. Methods Mallampati class, laryngoscopic grade, thyromental distance, neck circumference, body mass index, mouth opening and upper lip bite class were assessed. Epiglottis length and angle, tongue size and narrowest pharyngeal distance were determined using computed tomography imaging. Intubation success rate, time to successful intubation (intubating time) and postoperative throat symptoms were documented. Results Of 152 patients, 148 (97.4%) were successfully intubated on the first attempt (mean intubating time 11.5 ± 6.7 s). Intubating time was positively correlated with laryngoscopic grade and body mass index in both male and female patients, and Mallampati class and neck circumference in male patients. Epiglottis length was positively correlated with intubating time. Conclusions Ease of intubation was influenced by epiglottis length. Radiological evaluation may be useful for preoperative assessment of patients undergoing endotracheal intubation with light wand.

Background The beach chair position (BCP) is associated with hypotension that may lead to cerebral ischemia. Arginine vasopressin (AVP), a potent vasoconstrictor, has been shown to prevent hypotension in BCP. It also improves cerebral oxygenation in different animal models. The present study examined the effect of escalating doses of AVP on systemic hemodynamics and cerebral oxygenation during surgery in BCP under general anesthesia. Methods Sixty patients undergoing arthroscopic shoulder surgery in BCP under general anesthesia were randomly allocated to receive either saline (control, n = 15) or three different doses of AVP (0.025, 0.05, or 0.075 U/kg; n = 15 each) 2 minutes before BCP. Mean arterial pressure (MAP), heart rate (HR), regional cerebral oxygen saturation (SctO2), and jugular venous oxygen saturation (SjvO2) were measured after induction of anesthesia and before (presitting in supine position) and after BCP. Results AVP per se given before BCP increased MAP, and decreased SjvO2, SctO2, and HR in all patients (P < 0.05 for all). BCP decreased MAP, the magnitude of which and hence the incidence of hypotension was decreased by AVP in a dose-dependent manner. While in BCP, every dose of AVP reduced the HR and SctO2. Accordingly, it increased the incidence of cerebral desaturation (> 20% SctO2 decrease from the baseline value) with no differences in SjvO2 and the incidence of SjvO2 < 50% or SjvO2 < 40% among the groups. Conclusions AVP ameliorates hypotension associated with BCP in a dose-dependent manner in patients undergoing shoulder surgery under general anesthesia. However, AVP may have negative effects on SctO2 before and after BCP and on SjvO2 before BCP.

BACKGROUND Near-infrared spectroscopy assesses cerebral tissue oxygen saturation (Scto2) based on the absorption spectra of oxygenated and deoxygenated hemoglobin. It has been reported that IV-administered dyes including methylene blue, indigo carmine, and indocyanine green (ICG) may cause falsely low-pulse oximetry readings (Spo2). Although methylene blue and indigo carmine may also decrease Scto2, the effect of ICG has not been documented. METHODS Simultaneous changes in the heart rate, arterial blood pressure, Scto2, and Spo2 were measured after IV administration of ICG (12.5 mg diluted in 5.0 mL 0.9% NaCl) in 15 patients undergoing carotid endarterectomy under sevoflurane-remifentanil anesthesia. RESULTS After the dye administration, no change in heart rate or arterial blood pressure was observed in any patient. Scto2 increased by 13.3±4.0 percentage points, reaching the peak at 42.0±28.4 seconds after the administration, whereas Spo2 decreased by 1.9±1.2 percentage points, reaching the peak at 64.0±42.5 seconds (P

Administration of arginine vasopressin (AVP) is associated with reducing jugular venous (SjvO2) and regional cerebral (rScO2) oxygen saturation under propofol-remifentanil (P/R) anaesthesia. We determined whether background anaesthetics modulate the effect of AVP on cerebral oxygenation and haemodynamics. We randomly allocated 60 adult patients scheduled for shoulder surgery in the beach chair position (BCP) into 4 groups, to receive either an intravenous bolus of saline (groups PR-S and SN-S) or 0.05 U/kg AVP (groups PR-AVP and SN-AVP) under P/R or sevoflurane-nitrous oxide (S/N) anaesthesia (n = 15 each). Haemodynamic variables, SjvO2 and rScO2 were measured. AVP significantly increased mean arterial blood pressure (MAP) and decreased rScO2 in either anaesthetic group. AVP also decreased SjvO2 in the P/R groups but not in the S/N groups. The AVP-treated groups showed higher MAP and cerebral desaturation (>20% rScO2 decrease from baseline), along with lower HR and rScO2 in the BCP than those in the saline-treated groups. In contrast, AVP did not affect SjvO2 values or the incidence of SjvO 2

Background Opioid agonists have been implicated in neuroprotection from hypoxic injury through regulating mitogen-activated protein kinases and cytokines. We determined the effects of remifentanil in focal brain ischemia and reperfusion (I/R) injury. Mechanisms linked to mitogen-activated protein kinases, including extracellular signaling-regulated kinase (ERK) 1/2, p38 kinases, and c-Jun N-terminal kinase (JNK), and various cytokines were also examined. Methods Male Sprague-Dawley rats were subjected to an I/R insult consisting of 90 minutes' middle cerebral artery occlusion (MCAO) followed by reperfusion under general anesthesia. Neurological deficit scores and infarct volume were determined after 24 hours of reperfusion. Remifentanil (5 μg/kg/min) was given alone or combined with naltrindole (δ-opioid receptor antagonist; 1 mg/kg), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (μ-opioid receptor antagonist; 1 mg/kg), or 5'-guanidinonaltrindole (κ-opioid receptor antagonist; 1 mg/kg). Opioid antagonists were administered 20 minutes before MCAO. Remifentanil infusion was started 10 minutes before MCAO and continued throughout. The control group was without drugs. The expression levels of ERK1/2, p38, and JNK, and also those of tumor necrosis factor-α (TNF-α) and interleukin-6, were determined after 1, 3, and 24 hours of reperfusion. Results Remifentanil significantly improved the functional outcome and reduced the infarct volumes (69.0±24.3 mm(3) vs. 108.9±24.8 mm(3)), which were not affected by D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) or 5'-guanidinonaltrindole, but were abolished by naltrindole. The I/R insult enhanced the phosphorylation of ERK 1/2 and the expression of TNF-α, which were significantly reduced by remifentanil. Neither the phosphorylation of p38 and JNK nor the production of interleukin-6 was altered throughout the experiment. Conclusions Remifentanil may be neuroprotective against focal I/R injury, possibly through the activation of δ-opioid receptors and attenuation of ERK 1/2 activity and TNF-α production, in the rat brain.

BACKGROUND: An inhaled anesthetic concentration required to block autonomic hyperreflexia (AHR) is high enough to cause severe hypotension in patients with high spinal cord injury (SCI). We determined the effects of remifentanil on the sevoflurane requirement to block AHR in SCI. METHODS: The study involved 96 patients with chronic, complete SCI scheduled to undergo transurethral litholapaxy during general anesthesia. Anesthesia was induced with thiopental, and sevoflurane concentrations in 50% nitrous oxide were adjusted to maintain a bispectral index of 40 to 50. Whether the patient develops an AHR [an increase of systolic blood pressure (SBP) >20 to 40 mm Hg] was first examined by distending the bladder with glycine solution (the first trial). Patients who developed AHR were then allocated to receive no remifentanil infusion (control, n = 31), a target-controlled plasma concentration of 1 ng/mL (n = 25), or 3 ng/mL remifentanil (n = 24). After baseline hemodynamics had recovered, the target sevoflurane and remifentanil concentrations were maintained for at least 20 minutes and the procedure was resumed (the second trial). Each target sevoflurane concentration was determined by the up-and-down method based on changes (15% increase or more) of SBP in response to the bladder distension. SBP, heart rate, and bispectral index were measured before and during the bladder distension during the trials, and plasma concentrations of catecholamines during the first trial. RESULTS: Eighty-two (85.4%) of 96 patients developed AHR during the first trial, in which 2 were excluded because of hypotension (mean arterial blood pressure

A 22-year-old woman with no history of asthma developed an acute recurrent attack of severe bronchoconstriction and right upper lobe atelectasis immediately after laryngoscopy and endotracheal intubation. The first attack had taken place 2 months earlier under identical circumstances. Induction of anesthesia for tracheal intubation was achieved using propofol, fentanyl, and rocuronium. Bronchial obstruction and bronchial intubation were excluded by bronchoscopy. The atelectasis was quickly resolved with mechanical ventilation and spasmolytic treatment on both occasions. The surgical procedure could proceed soon after resolution of the atelectasis.

Ramosetron is a selective serotonergic 5-hydroxy-tryptamine receptor 3 antagonist that is used to prevent and treat postoperative nausea and vomiting. This study aimed to characterize the population pharmacokinetics of ramosetron in patients undergoing surgery with general anesthesia. Patients aged 19-80 years received a single intravenous bolus of ramosetron (0.3, 0.45, or 0.6 mg) 30 min before the end of surgery. Blood samples were collected, and plasma concentrations of ramosetron were measured by high performance liquid chromatography-tandem mass spectrometry. Pooled data from 50 patients and 479 pharmacokinetic samples were used for population pharmacokinetic analysis using the nonlinear mixed effect modeling program (NONMEM(®)). The pharmacokinetics of ramosetron was best described by a three-compartment mammillary model with first-order elimination. Based on allometric principles, body weight was incorporated in the base model, along with fixed allometric exponents. The typical value of clearance was 0.19 L/h in a 60-kg subject, and it decreased approximately 3% for every year of age, starting at age of 57. The bootstrap method and visual predictive check showed that the final pharmacokinetic model was appropriate. A population pharmacokinetic model of ramosetron was constructed in adult surgical patients, providing a foundation for further defining the relationship between ramosetron dose and postoperative nausea and vomiting.

Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.

STUDY DESIGN A case of acute respiratory distress syndrome following percutaneous vertebroplasty is described. OBJECTIVE To alert clinicians to the potential occurrence of acute respiratory distress syndrome following use of polymethylmethacrylate bone cement. SUMMARY OF BACKGROUND DATA Noncardiogenic pulmonary edema has not been reported following intravertebral injection of polymethylmethacrylate. METHODS A 68-year-old woman underwent percutaneous vertebroplasty for a painful L5 compression fracture under local anesthesia. A contralateral transpedicular approach was made to inject polymethylmethacrylate. RESULTS On the third postoperative day, she developed arthralgia, myalgia, fever, and frequent coughing. Chest radiography revealed bilateral, multifocal, patchy consolidations, suggestive of acute respiratory distress syndrome, and a 5-cm-long tubular radiopacity in the right pulmonary artery. She died 20 days after the vertebroplasty. CONCLUSION This case illustrates that clinicians must be aware of the potential occurrence of acute respiratory distress syndrome in patients who received percutaneous vertebroplasty.

Endotracheal intubation usually causes transient hypertension and tachycardia. We investigated whether the cardiovascular responses to intubation change as a function of the time elapsed in patients with spinal cord injury. One-hundred-six patients with traumatic complete spinal cord injury were grouped into acute and chronic groups according to the time elapsed (less than and more than 4 wk after injury) and into those with quadriplegia and paraplegia according to the level of injury (above C7 and below T5): acute quadriplegia, n = 26; chronic quadriplegia, n = 27; acute paraplegia, n = 24; and chronic paraplegia, n = 29. Twenty-five patients with no spinal cord injury served as controls. Systolic arterial blood pressure (SAP), heart rate, and plasma concentrations of catecholamines were measured. The intubation did not affect SAP in either the acute or chronic quadriplegics, but it significantly increased SAP in both acute and chronic paraplegics. Heart rate was significantly increased in all groups; however, the magnitude of change was less in acute quadriplegics than in the other groups. Plasma concentrations of norepinephrine increased in every group but the acute quadriplegics. The magnitude of increase was attenuated in chronic quadriplegics, accentuated in acute paraplegics, and similar in chronic paraplegics when compared with controls. The incidence of arrhythmias did not differ among groups. We conclude that the cardiovascular and catecholamine responses to endotracheal intubation may change as a function of the time elapsed and the level of spinal cord injury.Cardiovascular and catecholamine responses to endotracheal intubation may differ according to the time elapsed and the level of injury in patients with complete spinal cord injury.

UNLABELLED Nitrous oxide (N(2)O) exerts a sympathomimetic action. We investigated whether N(2)O modifies the cardiovascular responses to tracheal intubation during general anesthesia. One-hundred healthy patients were assigned randomly to receive one of four concentrations (0%, 25%, 50%, or 75%; n = 25 each) of N(2)O in oxygen throughout the study beginning 3 min before tracheal intubation. Anesthesia was induced with IV thiopental (5-7 mg/kg) whereas patients were ventilated with designated concentrations of N(2)O. Tracheal intubation was facilitated with IV vecuronium (0.12 mg/kg). After intubation, all received 2% sevoflurane in oxygen via a semiclosed anesthesia circuit. Systolic arterial blood pressure, heart rate and rhythm, and plasma catecholamine concentrations were measured. The intubation significantly increased arterial blood pressure and heart rate. The maximum pressure changes were 46 +/- 21 and 65 +/- 24 mm Hg in 75% N(2)O and control groups, respectively (P < 0.05), being attenuated by N(2)O without affecting the tachycardiac response. Norepinephrine concentrations were increased at 1 min after the intubation, the magnitude of which was augmented by N(2)O. N(2)O did not affect the incidence of arrhythmias. It was shown that N(2)O suppressed the pressor response to endotracheal intubation, despite the augmented increase of norepinephrine concentrations. IMPLICATIONS We examined whether nitrous oxide modifies the cardiovascular response to endotracheal intubation because it activates the sympathetic nervous system. Nitrous oxide attenuated the pressor response, whereas it augmented the norepinephrine response to laryngoscopy and endotracheal intubation.

We investigated whether sildenafil citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate that sildenafil may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented accumulation of cGMP.Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.

UNLABELLED: We determined the effects of fentanyl, sufentanil, morphine, and meperidine on the spontaneous contractility of isolated human pregnant uterine muscle strips. Uterine specimens were obtained from normal full-term parturients undergoing elective lower-segment cesarean delivery. Longitudinal muscle strips were prepared and mounted vertically in tissue chambers to record their isometric tension. Opioid concentration-response curves were constructed after rhythmic contractions were established. The responses were also examined in the presence of opioid receptor blocker, nitric oxide synthase inhibitor, beta-adrenoceptor blocker, or cyclooxygenase inhibitor. Fentanyl and meperidine inhibited uterine contractility in a concentration-dependent manner, their concentration that inhibited 50% being 2.3 x 10(-6) and 1.0 x 10(-3)M, respectively. Sufentanil and morphine had no significant effects on uterine contractility. Pretreatment with either naloxone, N(G)-nitro-L-arginine methyl ester, atenolol, or indomethacin did not affect the uterine responses to opioids. These results demonstrate that fentanyl and meperidine may have direct inhibitory effects on the contractility of the human uterus, though at supraclinical concentrations. IMPLICATIONS: Opioids do not have a significant effect on spontaneous contractions of gravid human uterine muscle at their clinically relevant concentrations.

Spinal alpha-2 adrenoceptors and cholinergic receptors are involved in the regulation of acute nociception and the facilitated processing. The aim of this study was to examine the pharmacological effect of an intrathecal alpha-2 agonist and a cholinesterase inhibitor on the facilitated pain model induced by formalin injection and to determine the nature of drug interaction using an isobolographic analysis. Both intrathecal clonidine and neostigmine dose-dependently suppressed the flinching during phase 1 and phase 2. Intrathecal pretreatment with atropine reversed the antinociceptive effects of clonidine and neostigmine in both phases. Pretreatment with intrathecal yohimbine attenuated the effect of clonidine. The antinociception of clonidine and neostigmine was not reversed by mecamylamine. Isobolographic analysis showed that intrathecal clonidine and neostigmine acted synergistically in both phase 1 and 2. Intrathecal pretreatment with atropine and yohimbine antagonized the effect of the mixture of clonidine and neostigmine in both phases, but no antagonism was observed with mecamylamine pretreatment. These data indicate that spinal clonidine and neostigmine are effective to counteract the facilitated state evoked formalin stimulus, and these two drugs interact in a synergistic fashion. In addition, the analgesic action of intrathecal clonidine is mediated by spinal muscarinic receptors as well as alpha-2 adrenoceptors.

Patients undergoing surgery in the beach chair position (BCP) are at a risk of cerebral ischemia. We evaluated the effect of arginine vasopressin (AVP) on hemodynamics and cerebral oxygenation during surgery in the BCP.Thirty patients undergoing shoulder surgery in BCP under propofol-remifentanil anesthesia were randomly allocated either to receive IV AVP 0.07 U/kg (AVP group, N = 15) or an equal volume of saline (control group, N = 15) 2 minutes before taking BCP. Mean arterial blood pressure (MAP), heart rate (HR), jugular venous bulb oxygen saturation (SjvO2), and regional cerebral tissue oxygen saturation (SctO2) were measured after induction of anesthesia and before (presitting in supine position) and after patients took BCP.AVP itself given before the positioning increased MAP and decreased SjvO2 and SctO2 (P0.0001), with HR unaffected. Although MAP was decreased by BCP in both groups, it was higher in the AVP group (P0.0001). While in BCP, HR remained unaltered in the control and decreased in the AVP group. SjvO2 in BCP did not differ between the groups. SctO2 was decreased by BCP in both groups, which was more pronounced in the AVP group until the end of study. The incidence of hypotension (13% vs 67%; P = 0.003) was less frequent, and that of cerebral desaturation (20% SctO2 decrease from presitting value) (80% vs 13%; P = 0.0003) was higher in the AVP group. The incidence of jugular desaturation (SjvO250%) was comparable between the groups.A prophylactic bolus administration of AVP prevents hypotension associated with BCP in patients undergoing shoulder surgery under general anesthesia. However, it was associated with regional cerebral but not jugular venous oxygen desaturation on upright positioning.

Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3β or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3β, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3β but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.

Background: Nitrous oxide (N2O) and remifentanil both have anesthetic-reducing and antinociceptive effects. We aimed to determine the anesthetic requirements and stress hormone responses in spinal cord-injured (SCI) patients undergoing surgery under sevoflurane anesthesia with or without pharmacodynamically equivalent doses of N 2O or remifentanil. Methods: Forty-five chronic, complete SCI patients undergoing surgery below the level of injury were randomly allocated to receive sevoflurane alone (control, n = 15), or in combination with 67% N 2O (n = 15) or target-controlled infusion of 1.37 ng/ml remifentanil (n = 15). Sevoflurane concentrations were titrated to maintain a Bispectral Index (BIS) value between 40 and 50. Measurements included end-tidal sevoflurane concentrations, mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine and cortisol concentrations. Results: During surgery, MAP, HR, and BIS did not differ among the groups. Sevoflurane concentrations were lower in the N2O group (0.94 ± 0.30%) and the remifentanil group (1.06 ± 0.29%) than in the control group (1.55 ± 0.34%) (P < 0.001, both). Plasma concentrations of norepinephrine remained unchanged compared to baseline values in each group, with no significant differences among groups throughout the study. Cortisol levels decreased during surgery as compared to baseline values, and returned to levels higher than baseline at 1 h after surgery (P < 0.05) without intergroup differences. Conclusions: Remifentanil (1.37 ng/ml) and N2O (67%) reduced the sevoflurane requirements similarly by 31 -39%, with no significant differences in hemodynamic and neuroendocrine responses. Either remifentanil or N 2O can be used as an anesthetic adjuvant during sevoflurane anesthesia in SCI patients undergoing surgery below the level of injury. (Korean J Anesthesiol 2013; 65: 531-538)

Background We examined the effects of different anesthetics on cerebral oxygenation and systemic hemodynamics in patients undergoing surgery in beach chair position (BCP). Jugular venous bulb oxygen saturation (SjvO2) and regional cerebral tissue oxygen saturation (SctO2) were determined while patients were placed from the supine to BCP. Whether SctO2 and SjvO2 are interchangeable in assessing the cerebral oxygenation was also examined. Methods Forty patients undergoing shoulder surgery in BCP were randomly assigned to receive sevoflurane-nitrous oxide (S/N) or propofol-remifentanil (P/R) anesthesia. Four patients taking angiotensin II receptor antagonists were excluded post hoc. Mean arterial pressure and heart rate, as well as SjvO2 and SctO2, were measured before (postinduction baseline in supine position) and after BCP. Results Mean arterial pressure decreased by BCP in both groups. It was, however, significantly higher in S/N (n = 19) than in P/R group (n = 17) at 7 to 8 min after the positioning. SjvO2 also significantly decreased after BCP in both groups, the magnitude of which was lower in S/N than in P/R group (11 ± 10% vs. 23 ± 9%, P = 0.0006). The incidences of SjvO2 Conclusions The margin of safety against impaired cerebral oxygenation is greater and SjvO2 is more preserved with S/N than with P/R anesthesia. SctO2 may not be reliable in detecting a low SjvO2 during the surgery in BCP.

Background: Curcumin, the active ingredient of turmeric ( Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases. Methods: Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3β]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3β, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion. Results: Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3β, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3β induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3β compared with the control. Conclusions: Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3β, and attenuation of p38 and JNK.

Dear Editor, Safavi et al. (1) examined whether hydralazine, nitroglycerin or nifedipine effectively attenuates the hemodynamic response to laryngoscopy and tracheal intubation in severe preeclamptic women undergoing cesarean delivery under general anesthesia. They found that continuous intravenous (IV) infusion of nitroglycerin was more effective in attenuating the pressor response than IV hydralazine 5-10 mg or sublingual nifedipine 10 mg without significant adverse effects on the newborn. While their study provides some important informations, we would like to point out some methodological concerns and the choice of drugs. First, they administered drugs 3 minutes before laryngoscopy and tracheal intubation despite their different onset of action. The relatively slow onset and long duration of action of hydralazine may prevent rapid adjustment of blood pressure. Moreover, after a single sublingual administration of nifedipine 10 mg, an antihypertensive action is obvious within 5 to 8 minutes with peak effects at 20 to 30 minutes (2). Therefore, to maximize the effect, it should have been better to administer nifedipine at time point when it would exhibit its peak effect during the tracheal intubation. Indeed, Kumar et al. (3) have demonstrated that sublingual nifedipine given 20 minutes before induction of anesthesia effectively attenuates the hypertensive response to tracheal intubation in pregnancy-induced hypertension. On the other hand, nitroglycerin has rapid onset and short duration of action (4). However, mean systolic blood pressure just before the onset of tracheal intubation was similar to their baseline values in the nitroglycerin group (1), suggesting that the effect of nitroglycerin was not apparent at the time point. In contrast, in a previous study, nitroglycerin lowered mean arterial blood pressure by 20% just before tracheal intubation, and effectively attenuated the pressor response to intubation in preeclamptic women undergoing cesarean delivery (4). Nitroglycerin should have been started earlier in their study. Second, the hypertensive response to intubation is transient, so that the duration of action of drugs should be short. With a prolonged duration of action, they may result in hypotension, as shown by a higher incidence of hypotension in those given hydralazine or nifedipine in their study (1). Moreover, opioids have been demonstrated to increase the risk of neonatal respiratory depression after cesarean delivery owing to their long duration of action (5). Remifentanil, a potent, synthetic μ-receptor agonist, has an extremely short duration of action (6). It may thus afford advantages at the induction, without subsequent neonatal depression. It has been indeed shown to attenuate the cardiovascular response to intubation with minimal neonatal respiratory depression (7). Several pharmacologic agents, including opioids (5, 7), hydralazine, nifedipine (3), calcium channel blockers, or nitrates (4), have been tried to prevent or to control hemodynamic responses to intubation while undergoing cesarean delivery. Nevertheless, they are not always safe, convenient, or predictable. Nitroglycerin dilates cerebral vasculature (8) and may increase intracranial pressure especially in severe pre-eclamptics with cerebral edema, and crosses the placenta (4). In addition, nitroglycerin and nifedipine attenuate the pressor but not the tachycardia responses (3, 4). Owing to its high potency and ultra-short duration of action, remifentanil appears to be most reliable thus far in attenuating the cardiovascular response to intubation while undergoing cesarean delivery in both the maternal and fetal perspectives. Nevertheless, in many countries, neuraxial anaesthesia has become a preferred technique to provide anaesthesia for cesarean delivery even among women with severe pre-eclampsia (9).

Background: Endotracheal intubation usually causes transient hypertension and tachycardia. The cardiovascular and arousal responses to endotracheal and endobronchial intubation were determined during rapid­sequence induction of anesthesia in normotensive and hypertensive elderly patients. Methods: Patients requiring endotracheal intubation with (HT, n = 30) or without hypertension (NT, n = 30) and those requiring endobronchial intubation with (HB, n = 30) or without hypertension (NB, n = 30) were included in the study. Anesthesia was induced with intravenous thiopental 5 mg/kg followed by succinylcholine 1.5 mg/kg. After intubation, all subjects received 2% sevoflurane in 50% nitrous oxide and oxygen. Mean arterial pressure (MAP), heart rate (HR), plasma catecholamine concentration, and Bispectral Index (BIS) values, were measured before and after intubation. Results: The intubation significantly increased MAP, HR, BIS values and plasma catecholamine concentrations in all groups, the peak value of increases was comparable between endotracheal and endobronchial intubation. However, pressor response persisted longer in the HB group than in the HT group (5.1 ± 1.6 vs. 3.2 ± 0.9 min, P < 0.05). The magnitude of increases in MAP and norepinephrine from pre­intubation values was greater in the hypertensive than in the normotensive group (P < 0.05), while there were no differences in those of HR and BIS between the hypertensive and normotensive groups. Conclusions: Cardiovascular response and arousal response, as measured by BIS, were similar in endobronchial and endotracheal intubation groups regardless of the presence or absence of hypertension except for prolonged pressor response in the HB group. However, the hypertensive patients showed enhanced cardiovascular responses than the normotensive patients. (Korean J Anesthesiol 2011; 60: 90­97)

BACKGROUND AND OBJECTIVE Neuraxial anaesthesia has been shown to produce a sedative and anaesthetic-sparing effect. The purpose of the present study was to determine the effects of acute spinal cord injury on sevoflurane requirement and stress hormone responses during spinal surgery at the level of the injury. METHODS Thirty-five patients with traumatic complete spinal cord injury undergoing spinal surgery at the level of the injury were studied. They were grouped into quadriplegics (above C7, n = 20) and paraplegics (below T1, n = 15) according to the level of injury. Patients (n = 35) with spine trauma without neurological impairment undergoing spinal surgery at the respective level served as controls. The bispectral index score was maintained at 40-50 throughout the surgery. Measurements included end-tidal sevoflurane concentrations, mean arterial pressure, heart rate, and plasma concentrations of catecholamines and arginine vasopressin. RESULTS During the surgery, the mean arterial pressure was significantly lower in both quadriplegics and paraplegics (P < 0.05). The heart rate did not differ significantly in the quadriplegics, but was higher in the paraplegics, compared with their controls. However, end-tidal sevoflurane concentrations and bispectral index score were comparable with controls in both quadriplegics and paraplegics. Throughout the study, the plasma arginine vasopressin concentrations were not altered, although norepinephrine and epinephrine concentrations were lower in the quadriplegics. There were no significant differences in stress hormones between the groups having thoraco-lumbar surgery. CONCLUSION Spinal cord injury neither alters the anaesthetic requirement regardless of the level of injury during spinal surgery at the level of the injury, nor enhances arginine vasopressin release. However, it blunts catecholamine responses in quadriplegics.

Background: We determined the effect of urinary trypsin inhibitors (UTI) in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases such as phosphatidylinositol-3-OH kinases (PI3K)-Akt and extracellular signal-regulated kinases (ERK 1/2) and apoptotic kinases such as p38 and JNK. Methods: The rats were anesthetized and subjected to an I/R insult consisting of 30-min left anterior descending coronary artery (LAD) occlusion followed by reperfusion. Infarct size was measured after 120 min of reperfusion. UTI was given alone or along with wortmannin (inhibitor of PI3K) or PD098059 (inhibitor of ERK1/2) before LAD occlusion. The phosphorylation of Akt, ERK1/2, p38 and JNK was determined by immunoblotting after 5 min of reperfusion. UTI was administered 10 min before LAD occlusion, and wortmannin and PD098059 were administered 20 min before LAD occlusion. Results: UTI significantly reduced the infarct size compared with the control. Wortmannin or PD098059 alone did not affect the infarct size, but they abolished the UTI-induced cardioprotective effect. UTI significantly reduced the phosphorylation of p38 and JNK, while it enhanced that of Akt and ERK1/2. Conclusions: UTI has a protective effect against regional myocardial I/R injury through activation of survival kinases PI3K-Akt and ERK1/2 and attenuation of p38 and JNK.

An end-tidal concentration of 1% sevoflurane (1% ET(SEVO)) in 50% nitrous oxide (N(2)O) during elective cesarean delivery has been associated with bispectral index (BIS) values60, which are associated with an increased risk of awareness. We hypothesized that BIS values during sevoflurane-N(2)O general anesthesia for cesarean delivery would be lower in women with prior labor compared with women without prior labor.Forty patients undergoing cesarean delivery were enrolled in this observational study. One group had urgent surgery after labor (labor group, n = 20) and the other had elective surgery without labor (control group, n = 20). General anesthesia was induced with thiopental 4 mg/kg, followed by succinylcholine 1.5 mg/kg, and maintained with 1% ET(SEVO) and 50% N(2)O in oxygen. BIS values, systolic arterial blood pressure, heart rate, plasma stress hormone concentrations, Apgar scores, and postoperative analgesia variables were assessed and compared between groups.BIS values during the period between intubation and delivery were lower in the labor group than in the control group (P0.001). Plasma norepinephrine concentrations increased at delivery compared with baseline in both groups. They were higher in the labor group than in the control group both at baseline and at delivery. Systolic arterial blood pressure, heart rate, Apgar scores, surgical characteristics, and plasma concentrations of vasopressin and cortisol were not different between groups. Postoperative visual analog scale pain scores were similar between groups, while the labor group consumed less analgesics (P0.01) during the first 24 h after the operation.Prior labor was associated with lower intraoperative BIS values during sevoflurane/N(2)O general anesthesia and reduced postoperative analgesic consumption in women undergoing cesarean delivery compared with women without prior labor.

We examined the effects of equianesthetic concentrations of sevoflurane, desflurane, isoflurane, and halothane on the spontaneous contractility of isolated human pregnant uterine muscles. We also determined if their action was related to potassium channels. Uterine specimens were obtained from normal full-term pregnant women undergoing elective lower-segment cesarean delivery. Longitudinal muscle strips were mounted vertically in tissue chambers. Their isometric tension was recorded while they were exposed to 0.5-3 minimum alveolar concentration (MAC) of volatile anesthetics in the absence and presence of the high conductance calcium-activated potassium channel blocker, tetraethylammonium, or the adenosine triphosphate-sensitive potassium channel (K(ATP))-blocker, glibenclamide. The anesthetics examined produced a dose-dependent depression of contractility. The inhibitory potency of sevoflurane and desflurane was comparable to, whereas that of isoflurane was smaller than, that of halothane: concentrations causing 50% inhibition of the contractile amplitude (ED(50)) were 1.72, 1.44, 2.35, and 1.66 MAC (P < 0.05), respectively. Tetraethylammonium and glibenclamide did not affect the uterine response to the anesthetics, except for glibenclamide, which attenuated the response to isoflurane. These results indicate that the volatile anesthetics have inhibitory effects on the contractility of the human uterus. The inhibitory effect of isoflurane may in part be mediated through activation of K(ATP) channels.

The conventional method for the analysis of myocardial cell transplantation depends on postmortem histology. Here, we have sought to demonstrate the feasibility of a longitudinal monitoring of transplanted cell survival in living animals, accomplished with optical imaging techniques and pharmacological interventions.Human cord blood (50 ml) was donated with parental consent. After getting cord blood derived mesenchymal stem cells (CBMSCs), cells were transfected (MOI = 100) overnight with adenovirus encoding firefly luciferase gene (Ad-CMV-Fluc). Our experimental Sprague-Dawley rats (n = 12) were given intramyocardial injections containing 1 x 10(6) CBMSCs, which had been made to express the firefly luciferase (Fluc) reporter gene. Optical bioluminescence imaging was then conducted using a cooled charged-coupled device (CCD) camera (Xenogen), beginning on the day after the transplantation (day 1). Groups of mice were intraperitoneally injected with cyclosporine (5 mg/kg) or tacrolimus (1 mg/kg), in an attempt to determine the degree to which cell survival had been prolonged, and these values were then compared with the cell survival values of the negative control group. The presence of transplanted CBMSCs on in vivo images confirmed by in situ hybridization for human specific Alu in the myocardium.Cardiac bioluminescence signals were determined to be present for 6 days after transplantation: day 1 (97000 +/- 9100 x 10(5) p/s/cm2/sr), day 3 (9600 +/- 1110 p/s/cm2/sr), and day 5 (3200 +/- 550 p/s/cm2/sr). The six mice that received either cyclosporine or tacrolimus displayed cardiac bioluminescence signals for a period of 8 days after transplantation. We observed significant differences between the treated group and the non-treated group, beginning on day 3 (tacrolimus; 26500 +/- 4340 p/s/cm2/sr, cyclosporine; 27200 +/- 3340 p/s/cm2/sr, non-treated; 9630 +/- 1180 p/s/cm2/sr, p0.01), and persisting until day 7 (tacrolimus; 12500 +/- 2946 p/s/cm2/sr, cyclosporine; 7310 +/- 1258 p/s/cm2/sr, non-treated; 2460 +/- 160 p/s/cm2/sr, p0.01). The human-derived CBMSCs were detected in the myocardium 3 days after transplantation by in situ hybridization.The locations, magnitude, and survival duration of the CBMSCs were noninvasively monitored with a bioluminescence optical imaging system. We determined that optical molecular imaging expedites the fast throughput screening of pharmaceutical agents, allowing for the noninvasive tracking of cell survival within animals. In rat cardiac CBMSC transplant models, transient immunosuppressive treatment with tacrolimus or cyclosporine was shown to improve donor cell survival.

Brief ischemic episodes that induce myocardial and coronary endothelial dysfunction may alter the responses to inotropic drugs. To determine the effects of inotropic drugs in stunned myocardium, the coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to intracoronary dobutamine, epinephrine, amrinone, and calcium chloride (CaCl2) were measured before (normal) and 30 min after a 15-min-period occlusion of the left anterior descending artery (stunned) in an open-chest canine model. Percent segment shortening (%SS) and post-systolic shortening (%PSS) were determined. Myocardial extraction of oxygen (EO2) and lactate (E(lac)) was calculated. The inotropic drugs increased %SS, CBF, and MVO2 in normal myocardium. Epinephrine and amrinone decreased, while dobutamine and CaCl2 did not affect EO2. The ischemia and reperfusion itself significantly reduced %SS and E(lac), and increased %PSS. In stunned myocardium, the responses to inotropic drugs were not significantly altered, except that they progressively reduced %PSS and epinephrine did not affect EO2. These findings indicate that a brief episode of ischemia does not affect the mechanical and metabolic coronary flow responses to inotropic drugs, although it abolishes direct vasodilator responses to epinephrine.

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.

It was interesting to read the paper by Ko et al. [1] regarding cerebral oxygen saturation monitoring in patients undergoing an arthroscopic shoulder surgery in beach chair position (BCP). While mostly agreeing with their conclusion, one may also raise a few concerns, such as the timely determination of baseline values and the proper use of vasopressors. As to whether blood pressure should be corrected to account for the level difference between the site of measurement (most commonly a non-invasive cuff on the non-operative arm) and the brain in BCP is under debate [2]. They indeed evaluated whether MAP measured at the level of the brain or at the level of the heart correlated with regional cerebral oxygen saturation (rSO2) in patients undergoing BCP surgery, and found that MAP measured at the brain, but not at the heart level, correlated with rSO2. Nevertheless, they stated in the conclusion that "Monitoring cerebral rSO2 and MAP at the level of brain can be helpful to detect the possibility of cerebral deoxygenation earlier" [1]. To admit their observation, it would be proper to state that "MAP measured at the brain but not at the heart level reflects rSO2 in patients undergoing surgery in BCP". They also mentioned that "Baseline mean arterial pressure, ---, BIS, and left and right rSO2 were recorded while the patient's condition was stable over 5 minutes before induction." However, the induction of anesthesia and the use of high inspired oxygen fraction per se may significantly decrease BIS and increase rSO2 values [3]. As such, we believe that these parameters measured after (i.e., immediately before patients were raised into BCP) the induction of anesthesia better represents the baseline values. Phenylephrine, an α-agonist, and ephedrine, an α- and β-agonist, are both commonly used to maintain MAP and thus, cerebral perfusion pressure in neurosurgical patients who develop hypotension. However, in healthy anesthetized subjects with intact cerebral autoregulation, a bolus administration of phenylephrine reduced the rSO2 measured by a near-infrared spectroscopy device under intravenous anesthesia with propofol/remifentanil, whereas ephedrine maintained it [4,5]. In this context, phenylephrine and ephedrine may have differentially affected rSO2 in their study. Moreover, they did not use equipotent dosages of the two vasopressors. Would it not be better for them to have included it as one of the limitations of the study?