Short-Term Effects of Early Postoperative Celecoxib Administration for Pain, Sleep Quality, and Range of Motion After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: We hypothesized that early postoperative administration of celecoxib would reduce pain scores and improve sleep quality and active range of motion after total knee arthroplasty (TKA) under general anesthesia. METHODS: Patients in the celecoxib group received 400 mg of celecoxib 2 hours after TKA, followed 6 hours later by 200 mg of celecoxib. Patients in the control group received 400 mg of celecoxib the second day after surgery. Patients in both group had access to patient-controlled analgesia fentanyl. The primary outcome measure was the patient-reported visual analog scale (VAS) pain score the second day after TKA. The secondary outcome measure was sleep quality (days 1, 2, and 7 postoperatively). Active knee joint range of motion was assessed on days 2 and 7 postoperatively, and VAS pain scores were evaluated on postoperative days 1 to 7. Total fentanyl consumption was also assessed. RESULTS: Compared to the control group, the celecoxib group had significantly lower median VAS pain scores on postoperative days 1 and 2, significantly less nocturnal awakening (in minutes) and frequency of body motion, and better sleep efficacy on postoperative day 1. The celecoxib group also had a significantly better median flexion angle (°) on postoperative days 2 and 7, and lower cumulative fentanyl consumption. CONCLUSION: Early administration of celecoxib after TKA was associated with significantly reduced early VAS pain scores and improved sleep quality and active knee flexion angles. Thus, the early administration of celecoxib after TKA under general anesthesia may reduce pain and improve sleep quality and functional recovery. LEVELS OF EVIDENCE: Level II, therapeutic study. TRIAL REGISTRATION: UMIN-CTR 000014624 (July 23, 2014).

Combined Treatment with Hydrophilic and Lipophilic Statins Improves Neurological Outcomes Following Experimental Cardiac Arrest in Mice.

BACKGROUND: Global ischemia due to cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) causes significant neuronal damage in vulnerable areas in the brain. Currently, a majority of patients eventually die after successful CPR due to neurological injury. Statins have pleiotropic effects including anti-inflammatory and/or antioxidant responses. These pleiotropic effects can have a beneficial role in the post-CPR phase. We tested whether two different types of statins, hydrophilic pravastatin and lipophilic simvastatin, attenuated neurological injury following CA/CPR. The efficacy of pravastatin and simvastatin combination treatment was also assessed. METHODS: Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 8-min CA/CPR were randomized into four groups: control, 2 mg/kg pravastatin, 20 mg/kg simvastatin, or a combination of 3 mg/kg pravastatin and 10 mg/kg simvastatin. Neurobehavioral assessment and histological analyses were performed to assess overall general health condition and neuronal injury, respectively. RESULTS: Combination treatment with pravastatin and simvastatin significantly reduced neuronal injury in the striatum and hippocampus, reduced cerebral edema, and improved general health at 4 days after CA/CPR. Combination statin treatment upregulated endothelial nitric oxide synthase mRNA in the brain. Pravastatin alone, but not simvastatin alone, improved general health after CA/CPR. Pravastatin was less potent than simvastatin at reducing neuronal injury in the brain. CONCLUSION: Combination treatment with two different types of statins at the correct dose may be a promising approach to neuroprotection following CA/CPR.

Glibenclamide and Therapeutic Hypothermia Have Comparable Effect on Attenuating Global Cerebral Edema Following Experimental Cardiac Arrest.

BACKGROUND: Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia. METHODS: Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 7-min CA/CPR were randomized into five groups: sham operation, control with normothermia, GBC with normothermia, control with hypothermia, and GBC with hypothermia. The primary outcome was to evaluate regional brain water content; the secondary outcome was to measure blood glucose level, Sur1-TRPM4 expression, and pro-inflammatory factor expression. RESULTS: Compared with normothermia, GBC treatment or hypothermia significantly attenuated brain water content in mice subjected to CA/CPR. GBC combined with hypothermia had no additional effects on attenuating cerebral edema. Pro-inflammatory factor messenger RNA expression (TNF-α and IL-6), NFκß activation, and SUR1-TRPM4 levels were upregulated after CA/CPR. Compared with normothermia, hypothermia, but not GBC, partly suppressed these factors' expression. CONCLUSIONS: GBC attenuated cerebral edema following CA/CPR by blocking Sur1-TRPM4 channels upregulated by CA insult. The effect of GBC was comparable with that of therapeutic hypothermia alone. These results suggest that GBC is an alternative approach for treating CA-evoked cerebral edema.

Cholesterol and triglyceride concentrations in lipoproteins as related to carotid intima-media thickness.

Since distinct cholesterol and triglyceride concentrations in major lipoproteins and their subclasses may be related to atherosclerosis, we investigated the relationship of cholesterol and triglyceride concentrations in lipoprotein subclasses and the severity of carotid intima-media thickness (IMT), a surrogate marker of subclinical atherosclerosis. We studied 116 apparently healthy Japanese men (53 ± 9 years) without a history of cardiovascular diseases who were not taking any medication. Carotid IMT was measured by means of high-resolution vascular ultrasound. Plasma cholesterol and triglyceride concentrations in major lipoproteins and their subclasses were determined by HPLC with gel permeation columns. By univariate analyses, carotid IMT was the most closely related to age (r = 0.528, P < 0.001), followed by smoking habit expressed as pack-year cigarette consumption (r = 0.409, P < 0.001). In addition to total cholesterol and LDL cholesterol, carotid IMT was significantly associated with cholesterol and triglyceride concentrations in several LDL and VLDL subclasses. Stepwise multiple linear regression analysis revealed that age (ß = 0.436, P < 0.001), smoking (pack-years) (ß = 0.225, P = 0.007), and large LDL cholesterol (ß = 0.175, P = 0.023) were independent predictors of determining carotid IMT (adjusted R(2) = 0.347, P < 0.001). These results indicate that large LDL cholesterol is an important, independent determinant of carotid IMT in healthy men.

Contact dermatitis associated with the Bispectral index™ sensor: a case report.

BACKGROUND: Contact dermatitis caused by electroencephalography electrodes is rare and insufficiently studied. We described a case of contact dermatitis caused by Bispectral Index (BIS) monitor electrodes. CASE PRESENTATION: A 38-year-old woman underwent tooth extraction under general anesthesia with BIS monitoring. She noticed erythema on her forehead 3 days after surgery, which peaked on the fifth postoperative day. Slight pigmentation was observed at 42 days after surgery. We performed patch testing and confirmed positive reactions to the sensor and some allergens. CONCLUSIONS: Many reports have attributed contact dermatitis to an allergen present in electrocardiogram electrodes. It is important to recognize that complications similar to those caused by electrocardiogram electrodes can occur with this sensor.

Ischemic insult to cerebellar Purkinje cells causes diminished GABAA receptor function and allopregnanolone neuroprotection is associated with GABAA receptor stabilization.

Cerebellar Purkinje cells (PC) are particularly vulnerable to ischemic injury and excitotoxicity, although the molecular basis of this sensitivity remains unclear. We tested the hypothesis that ischemia causes rapid down-regulation of GABA(A) receptors in cerebellar PC, thereby increasing susceptibility to excitotoxicity. Oxygen-glucose deprivation (OGD) caused a decline in functional GABA(A) receptors, within the first hour of re-oxygenation. Decreased amplitude of miniature inhibitory post-synaptic potentials confirmed that OGD caused a significant decrease in functional synaptic GABA(A) receptors and quantitative Western blot analysis demonstrated the loss of GABA(A) receptor current was associated with a decline in total receptor protein. Interestingly, the potent neuroprotectant allopregnanolone (ALLO) prevented the decline in GABA(A) receptor current and protein. Consistent with our in vitro data, global ischemia in mice caused a significant decline in total cerebellar GABA(A) receptor protein and PC specific immunoreactivity. Moreover, ALLO provided strong protection of PC and prevented ischemia-induced decline in GABA(A) receptor protein. Our findings indicate that ischemia causes a rapid and sustained loss of GABA(A) receptors in PC, whereas ALLO prevents the decline in GABA(A) receptors and protects against ischemia-induced damage. Thus, interventions which prevent ischemia-induced decline in GABA(A) receptors may represent a novel neuroprotective strategy.

Role of Cranial Temperature in Neuroprotection by Sodium Hydrogen Sulfide After Cardiac Arrest in Mice.

The hydrogen sulfide donor sodium hydrogen sulfide (NaHS) is recognized as a neuroprotective agent, which induces a hibernation-like metabolic state and hypothermia. However, it remains unclear whether it is the sulfide itself or the hypothermia induced by the sulfide that mediates treatment outcomes following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). We therefore tested whether NaHS improved outcomes following CA/CPR in mice maintained at 35.0°C by active warming during recovery. Adult male mice were subjected to 8 minutes CA/CPR and randomly treated intraperitoneally with either implantation of miniosmotic pump with NaHS (50 µmol/kg/day) for 3 days or vehicle 30 minutes after CPR. A normothermia group had cranial temperatures kept >35.0°C for 6 hours with a heat pad, and a hypothermia group was allowed to spontaneous hypothermia at room temperature (26.0°C). Behavioral testing and histological evaluation of neurons in the CA1 hippocampal region and striatum were performed on days 4 and 12 after CA/CPR. Both cranial and body temperature decreased following CA/CPR in the hypothermia group, and this was enhanced by NaHS treatment. In the active warming (normothermia) group, NaHS protected striatal neurons and improved long-term survival, which was comparable to the hypothermia groups. No differences were found in the CA1 region. Following CA/CPR, NaHS treatment decreased the heart rate, but not the mean arterial pressure. Our study demonstrated that post-CPR treatment with NaHS exerted neuroprotection in mice while maintaining a normal cranial temperature, indicating that NaHS-related neuroprotection is independent of the known protective effect of spontaneous hypothermia.

Single administration of soluble epoxide hydrolase inhibitor suppresses neuroinflammation and improves neuronal damage after cardiac arrest in mice.

Cardiac arrest (CA) causes ischemia-reperfusion injury in the whole body among victims. Especially in the brain, inflammation and neuronal cell death can lead to irreversible dysfunction. Our goal was to determine whether a single administration of soluble epoxide hydrolase inhibitor (AS2586144-CL) has a neuroprotective effect and decreases the inflammatory response after CA and cardiopulmonary resuscitation (CPR). Global cerebral ischemia was induced in male C57BL/6 mice with 8min of CA. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned to three groups and administered AS2586144-CL: 1mg/kg (n=25), 10mg/kg (n=25), or 0mg/kg (vehicle, n=25). At 6 and 7 days after CA/CPR, behavioral tests were conducted and brains were removed for histological evaluation. Analysis of histological damage 7 days after CA/CPR revealed that 10mg/kg of AS2586144-CL protected neurons, and suppressed cytokine production and microglial migration into the hippocampus. Two hours after CA/CPR, 10mg/kg of AS2586144-CL suppressed serum tumor necrosis factor-α and hippocampal nuclear factor κB expression. Our data show that 10mg/kg of AS2586144-CL administered following CA/CPR suppresses inflammation and decreases neuronal damage.

Effects of postoperative administration of celecoxib on pain management in patients after total knee arthroplasty: study protocol for an open-label randomized controlled trial.

BACKGROUND: Multimodal analgesia is achieved by combining different analgesics and different methods of analgesic administration, synergistically providing superior pain relief when compared with conventional analgesia. Multimodal analgesia can also result in reductions in the side effects and complications of analgesia, thereby improving patient safety. Preventive analgesia, treatment before initiation of the surgical procedure, has a potential to be more effective in reducing pain sensitization than treatment initiated after surgery. Multimodal analgesia that includes prophylactic administration of selective cyclooxygenase-2 (COX-2) inhibitors can improve postoperative pain and reduce opioid analgesic consumption after total knee arthroplasty (TKA). However COX-2 inhibitors are not approved for use as preventive analgesia in Japan. Thus, assessing the effectiveness of COX-2 inhibitors during the early postoperative period is important to establish clinical practice guidelines in Japan. This study was designed to examine the effects of celecoxib administration immediately after surgery, in addition to multimodal analgesia, on postoperative pain management after TKA. METHODS/DESIGN: This randomized, prospective, open-label controlled study will include 120 patients undergoing unilateral TKA. All patients will routinely receive single injections of femoral and sciatic nerve blocks, along with postoperative patient-controlled analgesia (PCA) with fentanyl. Patients will be randomly assigned to receive or not receive immediate postoperative administration of celecoxib. The primary outcome is a visual analog scale (VAS) pain score the second day after surgery. Secondary outcomes include opioid consumption, VAS pain score for 7 days after surgery, range of knee motion, evaluation of sleep quality, overall evaluations by patients and physicians, rates of postoperative nausea and vomiting, and consumption of rescue analgesics. DISCUSSION: The objective of this study is to evaluate the effects of celecoxib administration immediately after surgery on pain after TKA surgery. A randomized controlled trial design will address the hypothesis that administration of oral celecoxib immediately after surgery, along with multimodal analgesia that includes peripheral nerve block and PCA, could reduce VAS pain score after TKA surgery. TRIAL REGISTRATION: UMIN-CTR 000014624 (23 July 2014).

Mechanisms with clinical implications for atrial fibrillation-associated remodeling: cathepsin K expression, regulation, and therapeutic target and biomarker.

BACKGROUND: The cysteine protease cathepsin K (CatK) has been implicated in the pathogenesis of cardiovascular disease. We sought to determine the link between atrial fibrillation (AF) and plasma CatK levels and to investigate the expression of and therapeutic target for CatK in vivo and in vitro. METHODS AND RESULTS: Plasma CatK and extracellular matrix protein peptides (intact procollagen type I of N-terminal propeptide; carboxyl-terminal telopeptide of type I collagen [ICTP]) were measured in 209 consecutive patients with AF (paroxysmal AF, 146; persistent AF, 63) and 112 control subjects. In addition, the regulation of CatK expression was investigated in vivo and vitro. Patients with AF had higher plasma CatK and ICTP levels than did control subjects. Patients with persistent AF had higher levels of plasma CatK and ICTP than did patients with paroxysmal AF. CatK was correlated with ICTP concentration and left atrial diameter in all subjects. In rabbits, superoxide production, CatK activity, fibrosis, and the levels of atrial tissue angiotensin II, angiotensin type 1 receptor, gp91phox, phospho-p38 mitogen-activated protein kinase, and CatK were greater in those with tachypacing-induced AF than in controls, and these changes were reversed with angiotensin type 1 receptor antagonist. Olmesartan and mitogen-activated protein kinase inhibitor decreased the CatK expression induced by angiotensin II in rat neonatal myocytes. CONCLUSIONS: These data indicated that increased plasma CatK levels are linked with the presence of AF. Angiotensin type 1 receptor antagonist appears to be effective in alleviating atrial fibrosis in a rabbit AF model, partly reducing angiotensin type 1 receptor-p38mitogen-activated protein kinase-dependent and -independent CatK activation, thus preventing AF.

Fluoxetine has neuroprotective effects after cardiac arrest and cardiopulmonary resuscitation in mouse.

AIMS: Fluoxetine, a selective serotonin reuptake inhibitor, is protective in a rat focal ischaemia model via anti-inflammatory mechanisms. Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) were performed in mice to test the hypothesis that fluoxetine protects the brain following global cerebral ischaemia, even when administered after an insult. METHODS: Global cerebral ischaemia was induced with 8 min CA/CPR in C57BL/6 male mice. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned into 3 groups and administered fluoxetine; fluoxetine (5 mg/kg: n=15, 10 mg/kg: n=15) or vehicle (NaCl: n=15). Three days after CA/CPR, sensorimotor evaluations were conducted and brains were removed for histological evaluation of the hippocampus and caudate putamen. RESULTS: Analysis of histological damage 72 h after resuscitation revealed that low dose fluoxetine (5 mg/kg) did not protect, while high dose (10 mg/kg) fluoxetine protected neurons in the caudate putamen. In contrast, there were no protective effects in the hippocampus at either dose. In agreement with histological observations of neuronal damage in the caudate putamen, high dose fluoxetine decreased sensorimotor deficits following CA/CPR compared to vehicle-treated animals. CONCLUSIONS: Our data showed that 10mg/kg fluoxetine administered following global cerebral ischaemia decreases neuronal damage. Although long-term neuroprotection needs further study, the results of our study suggest that fluoxetine may have therapeutic potential when administered after global cerebral ischaemia, cardiac arrest and cardiopulmonary resuscitation.

Small low-density lipoprotein cholesterol concentration is a determinant of endothelial dysfunction by peripheral artery tonometry in men.

AIM: Endothelial dysfunction is an initial step in the progression of atherosclerosis. Precise measurements of lipoprotein subclass distribution by high-performance liquid chromatography (HPLC) have been established. Here, we investigated the potential associations between lipoprotein subclass cholesterol concentrations and endothelial dysfunction evaluated by digital reactive hyperemia peripheral arterial tonometry (PAT). METHODS: We recruited 120 apparently healthy Japanese men. Endothelial function was assessed by digital reactive hyperemia PAT, expressed as the logarithmic-scaled reactive hyperemia index (RHI). Plasma cholesterol concentrations in lipoproteins and their subclasses were determined by HPLC with gel permeation columns. RESULTS: RHI was inversely correlated with age (r=-0.258, p=0.004), followed by LDL cholesterol (r=-0.236, p=0.010) and small LDL cholesterol (r=-0.223, p=0.014). In addition, RHI was significantly inversely associated with heart rate, hemoglobin A1c, total cholesterol, medium LDL cholesterol, apolipoprotein B100, and non-HDL cholesterol. In stepwise multiple regression analysis, age (ß=-0.266, p=0.024), small LDL cholesterol (ß=-0.213, p=0.015), and heart rate (ß=-0.183, p=0.036) were found to be independent determinants of RHI (adjusted R(2) =0.132, p<0.001). CONCLUSIONS: Small LDL cholesterol concentration was an important, independent determinant of endothelial dysfunction in men.

Sex difference in sensitivity to allopregnanolone neuroprotection in mice correlates with effect on spontaneous inhibitory post synaptic currents.

Allopregnanolone (ALLO) is a neurosteroid that has many functions in the brain, most notably neuroprotection and modulation of gamma-amino butyric acid (GABA) neurotransmission. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we have previously demonstrated that ALLO protects cerebellar Purkinje cells (PCs) from ischemia in a GABA(A) receptor-dependent manner. In this study we examined the effect of sex on ALLO neuroprotection, observing that low dose ALLO (2 mg/kg) provided greater neuroprotection in females compared to males. At a higher dose of ALLO (8 mg/kg), both sexes were significantly protected from ischemic damage. Using an acute cerebellar slice preparation, whole cell voltage clamp recordings were made from PCs. Spontaneous inhibitory post synaptic currents (IPSCs) were analyzed and the response to physiological ALLO (10 nM) was significantly greater in female PCs compared to male. In contrast, recordings of miniature IPSCs, did not exhibit a sex difference in response to ALLO, suggesting that ALLO affects males and females differentially through a mechanism other than binding postsynaptic GABA(A) receptors. We conclude that the female brain has greater sensitivity to ALLO mediated potentiation of GABAergic neurotransmission, contributing to increased neuroprotection.

The StyletScope is a better intubation tool than a conventional stylet during simulated cervical spine immobilization.

PURPOSE: We compare the StyletScope fibreoptic stylet (FOS) and the Satin Slip conventional metal stylet (CMS), during simulated difficult airway management with manual-in-line stabilization in terms of ease of intubation and esophageal intubation. METHODS: 193 patients (ASA I-II, 18-80 yr) were studied in a non-crossover, randomized fashion. Manual-in-line stabilization was applied and the best laryngoscopic view obtained. For the CMS, the primed tracheal tube was advanced under direct vision if Cormack-Lehane grade 1/2, placed behind the epiglottis and advanced blindly if grade 3, and intubation was not attempted if grade 4. For the FOS, the primed tracheal tube was advanced under the direct vision if grade 1/2 and under fibreoptic vision if grade 3/4. RESULTS: Intubation was successful more frequently (P = 0.02) and required fewer attempts (P = 0.003) with the FOS than the CMS. Intubation with the FOS was successful more frequently (P = 0.02) and required fewer attempts (P = 0.007) than the CMS if grade 3/4. For both stylets, intubation required fewer attempts (P < 0.007) and was quicker (P

A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces nasal morbidity for nasotracheal intubation.

UNLABELLED: We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved tube with a conventional diagonal bevel for nasotracheal intubation. Eighty anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal intubation for tonsillectomy were randomly allocated into two equal-sized groups for airway management with the silicone tracheal tube or PVC tracheal tube. Intubation was subdivided into three phases: 1). passage through the nose into the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3). laryngoscope-guided passage into the trachea. A specific sequence of airway maneuvers was followed at each stage if it was unsuccessful. The number of attempts and intubation time were documented by an unblinded observer. The frequency of epistaxis and postoperative nasal complications was documented by blinded observers. There were no intubation failures. The number of attempts at pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005) placement was smaller for the silicone tracheal tube, but the number of attempts at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis were less for the silicone tracheal tube. The total number of postoperative nasal symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We conclude that the pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with the silicone tracheal tube than the PVC tracheal tube but that the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical bevel than with a polyvinyl chloride-based precurved tracheal tube with a conventional diagonal bevel, but the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube.

A comparison of sex- and weight-based ProSeal laryngeal mask size selection criteria: a randomized study of healthy anesthetized, paralyzed adult patients.

BACKGROUND: The authors compared the manufacturer's weight-based formula (size 3 for weight < 50 kg, size 4 for weight 50-70 kg, and size 5 for weight > 70 kg) with a sex-based formula (size 4 for women and size 5 for men) for selecting the appropriate size of ProSeal laryngeal mask airway. METHODS: Two hundred thirty-seven healthy, anesthetized, paralyzed adult patients (American Society of Anesthesiologists physical status I or II; age, 18-80 yr) were randomly allocated for weight- or sex-based size selection. An experienced user inserted the ProSeal laryngeal mask airway with the digital technique. The following were compared: ease of insertion, oropharyngeal leak pressure, ease of ventilation, gas exchange, location of gas leak, anatomic position, mucosal injury, and postoperative pharyngolaryngeal problems. Intraoperative and postoperative data collection were unblinded and blinded, respectively. RESULTS: Ease of insertion, anatomic position, gas exchange, mucosal injury, and postoperative pharyngolaryngeal problems were similar between groups. For the sex-based group, larger ProSeal laryngeal mask airways were selected more frequently (P < 0.0001), oropharyngeal leak pressure (P = 0.02) was higher, leak volume (P = 0.004) and leak fraction (P = 0.007) were lower, and oropharyngeal leaks (P = 0.03) were detected less frequently. CONCLUSION: Size selection for the ProSeal laryngeal mask airway is equally effective using the manufacturer's weight-based formula or the sex-based formula in healthy, anesthetized, paralyzed adult patients, but leakage of small volumes of air from the mouth occurs less frequently with the sex-based formula.

Influence of nitrous oxide on minimum alveolar concentration of sevoflurane for laryngeal mask insertion in children.

BACKGROUND: Inhalational induction with sevoflurane and nitrous oxide is frequently used for Laryngeal Mask Airway (LMA; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) insertion in children. The authors determined the influence of nitrous oxide on the minimum alveolar concentration (MAC) of sevoflurane for LMA insertion. METHODS: One hundred twenty unpremedicated children (age, 1-9 yr; American Society of Anesthesiologists physical status I) were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0, 1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or 1.2% sevoflurane. The LMA was inserted after steady state end-tidal anesthetic concentrations had been maintained for 15 min. The response to insertion was recorded by three independent blinded observers. The interaction between nitrous oxide and sevoflurane was determined using logistic regression analysis. RESULTS: The MAC of sevoflurane for LMA insertion (95% confidence limit) was 1.57% (1.42-1.72%), and the concentration of sevoflurane required to prevent movement in 95% of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide linearly decreased the MAC of sevoflurane for LMA insertion by 22% and 49%, respectively (P < 0.001). The interaction coefficient between nitrous oxide and sevoflurane did not differ from zero (P = 0.7843), indicating that the relation was additive. CONCLUSIONS: Nitrous oxide and sevoflurane suppress the responses to LMA insertion in a linear and additive fashion in children.