Comparison Between Preoperative and Intraoperative Administration of Nefopam for Acute and Chronic Postoperative Pain in Colon Cancer Patients: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: The present study was designed as a prospective, randomized, double-blind clinical trial to evaluate the effects of preoperatively administered nefopam on postoperative acute hyperalgesia and the long-term painful sequelae compared to intraoperative administration. METHODS: One hundred and fifty patients undergoing elective laparoscopic colectomy were enrolled. Group 1 (post-incisional nefopam) patients received saline at 30 min before skin incision followed by intraoperative administration of 20 mg nefopam at 1 h after incision. Group 2 (pre-incisional nefopam) patients were administered 20 mg nefopam before skin incision and received saline after skin incision. At postoperative 2, 6, 24, 48, and 72 h, fentanyl consumption and pain intensities at rest and during deep breathing were evaluated by visual analog scale (VAS). The incidence of the long-term painful sequelae after surgery was evaluated more than one year after surgery. RESULTS: Cumulative fentanyl consumption during postoperative 72 h was similar between Group 1 and Group 2 (1534 ± 698 µg, 95% CI 1367-1702 µg vs. 1442 ± 721 µg, 95% CI 1266-1618 µg, P = 0.197). VAS pain scores at rest were comparable between the two groups, but VAS scores during deep breathing were significantly lower in Group 2 than in Group 1. Six and five patients complained of mild pain (pain rating 1) at the surgical site in Group 1 and 2, respectively. CONCLUSIONS: Preoperatively administered nefopam reduced exertional pain compared to intraoperative administration although postoperative analgesic consumption was similar between two groups. It may be helpful to conduct early ambulation and deep breathing during the acute postoperative period in patients undergoing intestinal surgery. Trial registration No: KCT0001656.

High-dose intraoperative remifentanil infusion increases early postoperative analgesic consumption: a prospective, randomized, double-blind controlled study.

PURPOSE: The purpose of this study was to determine whether intraoperative infusion of remifentanil induces acute tolerance to opioids, and compare the postoperative pain and opioid consumption by the effect site concentrations of remifentanil. METHODS: One hundred and ninety-eight patients undergoing gastrectomy were randomly assigned to maintain target effect site concentrations of remifentanil at 0 (Group 1, n = 39), 2 (Group 2, n = 40), 4 (Group 3, n = 39), 8 (Group 4, n = 40), or 12 ng/ml (Group 5, n = 40) during operation. Postoperative pain intensities and fentanyl requirement were recorded at postoperative 2, 6, 24, and 48 h. RESULTS: Fentanyl requirement for postoperative 2 h was significantly greater in Group 5 compared to Group 1 (376 ± 116 vs. 283 ± 129 µg, P = 0.03). However, there were no differences in fentanyl requirements among the groups after postoperative 2 h. Also, total fentanyl consumption for 48 h was similar in all groups (Group 1; 3106 ± 629, Group 2; 2970 ± 705, Group 3; 3017 ± 555, Group 4; 3151 ± 606, and Group 5; 2984 ± 443 µg, P = 0.717). Pain scores at rest and during deep breathing were comparable in all groups at the time of each examination. CONCLUSION: Intraoperative infusion of remifentanil with 12 ng/ml of effect site concentration in patients undergoing gastrectomy increases early postoperative fentanyl requirement. Acute opioid tolerance would be developed by higher concentration of remifentanil than dosage of common anesthetic practice.

Effects of hypercapnia on postoperative nausea and vomiting after laparoscopic surgery: a double-blind randomized controlled study.

BACKGROUND: Laparoscopic surgery is associated with a high incidence of postoperative nausea and vomiting (PONV). The use of CO2 pneumoperitoneum has been proposed as a potential cause of high PONV incidence. However, intraoperative hypercarbia may be related to enhanced perfusion to the main effector sites for PONV, including the brain and gastrointestinal tract. In this study, we investigated whether an increase in intraoperative CO2 partial pressure in arterial blood (PaCO2) reduces the incidence of PONV. METHODS: This study enrolled 400 female patients aged 20-60 years who were undergoing laparoscopic gynecologic surgery. The patients were allocated randomly to one of three groups with the following intraoperative PaCO2 levels: 36-40 mmHg (Group 1), 41-45 mmHg (Group 2), or 46-50 mmHg (Group 3). The anesthetic regimen used a standardized total intravenous anesthesia consisting of propofol and remifentanil for all patients. The arterial blood gas analysis was performed to identify the difference in CO2 partial pressure between arterial blood and end-tidal gas. The PONV incidence was evaluated for the periods of 0-2, 2-6, and 6-24 h after anesthesia. The incidence and severity of PONV and the administration of rescue antiemetics were recorded. RESULTS: The three groups were comparable for the patient, anesthesia, and surgical characteristics. The average PaCO2 level during surgery was 38-39, 43-44, and 47-48 mmHg in Groups 1, 2, and 3, respectively. The incidence and severity of PONV and use of rescue antiemetics were not significantly different among the groups. The overall incidence of nausea during the first 24-h postoperative period was 54, 48, and 50% in Groups 1, 2, and 3, respectively (P = 0.593). CONCLUSION: Our data suggest that mild to moderate intraoperative hypercapnia did not decrease the incidence and severity of PONV or the requirement for rescue antiemetics after gynecologic laparoscopic surgery.

Hypertensive crisis caused by electrocauterization of the adrenal gland during hepatectomy.

BACKGROUND: Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is very rare during operation except pheochromocytoma, but it can be a fatal and embarrassing to surgeons and anesthesiologists. The right adrenal gland can be electrocauterized during a right hemi-hepatectomy. We report a case of hypertensive crisis during right hemi-hepatectomy in which the right adrenal gland was stimulated by monopolar electrocautery in a patient with normal neuroendocrine function. CASE PRESENTATION: A 73-year-old man with hepatocellular carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the surgery, the patient's blood pressure increased abruptly from 100/40 to over 350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The surgeon had cauterized the right adrenal gland using monopolar electrocautery to separate the liver from the adrenal gland immediately prior to the event. Approximately 3 minutes after suspending the operation, blood pressure returned to baseline levels. After the event, the operation was successfully completed without any complication. Hormonal studies and iodine-123 meta-iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a pheochromocytoma. CONCLUSION: Operations such as hepatectomy that stimulate the adrenal gland may lead to an unexpected catecholamine surge and result in hypertensive crisis, even if neuroendocrine function of the adrenal gland is normal.

The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery.

BACKGROUND: In clinical practice, pregnant women have lower anesthetic requirements for general anesthesia than nonpregnant women. Although the hormonal changes such as progesterone associated with pregnancy may affect the minimum alveolar concentration of volatile anesthetics, the relationship between the anesthetic or analgesic requirements and progesterone level in full-term women has not been studied. In this study, we attempted to identify relationships between anesthetic or analgesic requirements and maternal serum concentrations of progesterone. METHODS: We studied 100 parturients >36 weeks' gestation who were scheduled for planned cesarean delivery under general anesthesia. Venous blood was collected to measure the maternal progesterone concentration. Anesthesia was induced with 4 to 5 mg/kg thiopental and 0.8 mg/kg rocuronium. During anesthetic maintenance, sevoflurane 0.5% to 2.0% and nitrous oxide 50% in oxygen were titrated based on arterial blood pressure, heart rate, and bispectral index value. Vital signs, bispectral index, end-tidal sevoflurane concentration, and sevoflurane consumption per hour were recorded. Visual analog scale pain scores and cumulative analgesic consumption were recorded at 2, 24, and 48 hours postoperatively. RESULTS: The mean serum progesterone concentration was 128.2 ± 83.0 ng/mL. There was a significant negative correlation between sevoflurane consumption per hour and serum progesterone concentration (Pearson correlation r = -0.26; 95% confidence interval, -0.44 to -0.05, P = 0.01). Cumulative analgesic consumption at postoperative hours 2 (r = -0.20, P = 0.05), 24 (r = -0.25, P = 0.02), and 48 (r = -0.28, P = 0.01) were correlated inversely with serum progesterone concentration. Women with high progesterone levels (higher than the median value) had lower sevoflurane consumption per hour (P = 0.02) and 48-hour postoperative cumulative analgesic consumption (P = 0.02) than women with low (below the median value) levels. CONCLUSIONS: The decreased anesthetic and analgesic requirements of near full-term parturients might partially depend on serum progesterone concentration.

Optimal nasopharyngeal temperature probe placement.

BACKGROUND: Although the nasopharynx is a commonly used temperature-monitoring site during general anesthesia, it is unknown whether the position of nasopharyngeal temperature probes placed blindly by anesthesia practitioners is optimal. The purposes of this study were (1) to determine where the nasopharyngeal mucosa is in closest proximity to the internal carotid artery (ICA) and (2) to evaluate the tip position of nasopharyngeal temperature probes that were placed by anesthesiology residents and nurse anesthetists. METHODS: In the first phase of the study, we reviewed enhanced axial computed tomography images of 100 patients to determine where the nasopharyngeal mucosa was in closest proximity to the left or the right ICA. The distance from this point to the nares was then measured in the sagittal image. In the second phase of the study, nasendoscopy was used to evaluate the positioning of nasopharyngeal temperature probes placed by anesthesiology residents (244 patients) or nurse anesthetists (116 patients). Malpositioned probes were repositioned to an optimal location, and the temperature differences were recorded. RESULTS: In the computed tomography images, the mucosa in closest proximity to the ICA was in the upper, mid-, and lower nasopharynx in 60%, 38%, and 2% of patients, respectively. The average distances between the ICA and the nasopharyngeal mucosa in the upper portion were significantly shorter than those in the lower portion (female: 9.4 vs 16.8 mm, P < 0.001; male: 12.4 vs 18.8 mm, P < 0.001). The average distances (95% prediction interval) from the nares to the upper portion of the nasopharynx through the inferior meatus were 9.1 (8.1-10.2) cm in females and 9.7 (8.6-10.8) cm in males. Temperature probes were correctly positioned in the upper or mid-nasopharynx by residents and nurses in 43% (95% confidence interval [CI], 37%-49%) and 41% (95% CI, 36%-50%), respectively. When the probe was inadvertently placed in the nasal cavity, the median (95% CI) temperature difference from the upper nasopharynx was 0.2°C (0.15°C-0.25°C). CONCLUSIONS: The closest portion of the nasopharyngeal mucosa to the ICA is within the upper or mid-nasopharynx. The depth from the nares to the upper one-third of the nasopharynx is approximately 10 cm. Less than half of nasopharyngeal temperature probes placed blindly by practitioners were optimally positioned.

Measurements of the length and diameter of main bronchi on three-dimensional images in Asian adult patients in comparison with the height of patients.

OBJECTIVE: To measure the length and diameter of the main bronchus using the three-dimensional reconstruction images from the spiral chest computerized tomography scans in Asian adult patients, and to evaluate the relationship between the height of patients and the length and diameter of main bronchi. DESIGN: Prospective observational study. SETTING: Academic, tertiary care hospital. PARTICIPANTS: Two hundred Asian adults undergoing a chest spiral computerized tomography scan. INTERVENTION: No intervention. MEASUREMENTS AND MAIN RESULTS: The authors measured the anteroposterior and transverse diameters of the mid-portion of the right main bronchus and 2 cm below the carina of the left main bronchus. In addition, the length of both main bronchi was also measured. The length of the left main bronchus was about 3-4 times greater than its right counterpart. The main bronchus of women was oval-shape, with a large anteroposterior diameter, but the main bronchus of men was round-shape. There was no significant correlation between the measurements of main bronchi and the height of patients. CONCLUSIONS: The results showed that there is no direct relationship between the length and diameter of main bronchi and the height of patients. The height is not the criterion for choosing DLT size. Therefore, the authors proposed that 3-D images be used to determine the size of the main bronchi. The diameter of main bronchus using the 3-D images can be used to determine the optimal size of the DLT in a clinical setting, although further studies are needed.

Predictors for Dexmedetomidine Requirement for Sedation under Regional Anesthesia.

(1) Background: This prospective observational study aimed to investigate the predictors affecting DMT requirements for sedation during regional anesthesia. (2) Method: A total of 108 patients who received regional anesthesia with intravenous DMT administration for orthopedic upper- or lower-extremity surgery were enrolled. Following successful regional anesthesia, DMT was administered at a rate of 4 µg/kg/h until reaching loss of consciousness (LOC). The administered dose of DMT per body weight until LOC (DMTLOC; µg/kg) was evaluated. The infusion was maintained at a rate of 0.2-0.7 µg/kg/h during the surgery. At the end of surgery, the elapsed time to a BIS value of 90 (TBIS90; s) was recorded. Linear regression models were used to identify potential predictors of DMTLOC and TBIS90. (3) Results: One hundred patients were analyzed. There were negative relationships between DMTLOC and age (r = -0.297, p = 0.003) and DMTLOC and body mass index (BMI) (r = -0.425, p < 0.001), respectively. Multiple linear regression models revealed that both increasing age and BMI were significantly related to DMTLOC (r2 = 0.259, p < 0.001), but those variables showed no association with TBIS90. (4) Conclusions: The results of this study suggest that initial loading of DMT should be carefully titrated to minimize risk in elderly and obese surgical populations.

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

BACKGROUND: This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. METHODS: The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. RESULTS: Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). CONCLUSIONS: The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

Cartoon distraction alleviates anxiety in children during induction of anesthesia.

BACKGROUND: We performed this study to determine the beneficial effects of viewing an animated cartoon and playing with a favorite toy on preoperative anxiety in children aged 3 to 7 years in the operating room before anesthesia induction. METHODS: One hundred thirty children aged 3 to 7 years with ASA physical status I or II were enrolled. Subjects were randomly assigned to 1 of 3 groups: group 1 (control), group 2 (toy), and group 3 (animated cartoon). The children in group 2 were asked to bring their favorite toy and were allowed to play with it until anesthesia induction. The children in group 3 watched their selected animated cartoon until anesthesia induction. Children's preoperative anxiety was determined by the modified Yale Preoperative Anxiety Scale (mYPAS) and parent-recorded anxiety Visual Analog Scale (VAS) the night before surgery, in the preanesthetic holding room, and just before anesthesia induction. RESULTS: In the preanesthetic holding room, the group 2 mYPAS and parent-recorded anxiety VAS scores were significantly lower than those of groups 1 and 3 (mYPAS: P = 0.007; parent-recorded anxiety VAS: P = 0.02). In the operating room, the children in group 3 had the lowest mYPAS and parent-recorded anxiety VAS scores among the 3 groups (mYPAS: P < 0.001; parent-recorded anxiety VAS: P < 0.001). In group 3, the mYPAS and parent-recorded anxiety VAS scores of only 3 and 5 children were increased in the operating room compared with their scores in the preanesthetic holding room, whereas the anxiety scores of 32 and 34 children in group 1 and 25 and 32 children in group 2 had increased (P < 0.001). The number of children whose scores indicated no anxiety (mYPAS score <30) in the operating room was 3 (7%), 9 (23%), and 18 (43%) in groups 1, 2, and 3, respectively (P < 0.001). CONCLUSIONS: Allowing the viewing of animated cartoons by pediatric surgical patients is a very effective method to alleviate preoperative anxiety. Our study suggests that this intervention is an inexpensive, easy to administer, and comprehensive method for anxiety reduction in the pediatric surgical population.

Influence of the amount of skeletal muscle mass on rocuronium-induced neuromuscular block.

OBJECTIVE: To evaluate the effects of skeletal muscle mass on the rocuronium-induced neuromuscular block. DESIGN: A prospective, double-blinded, observational study. SETTING: A tertiary care university hospital. POPULATION: One hundred one patients aged 18-65 years who were scheduled to undergo major surgery lasting more than 1 h under general anaesthesia. METHODS: All participants underwent body composition analysis before anaesthesia and were allocated into two groups; the muscular and non-muscular group, according to skeletal muscle mass. During anaesthesia induction, rocuronium 1.0 mg kg-1 of total body weight was injected followed by neuromuscular monitoring using train-of-four stimulation every 15 s. MAIN OUTCOME MEASURES: The onset time of rocuronium included the elapsed time from the rocuronium injection until 95% depression of first twitch (T1) and the time to no response to TOF stimulation. The duration was evaluated as the elapsed time from the rocuronium injection to 25% recovery of the final T1 (TDUR25), and the time to the reappearance of T1 (TTOF1) and T4 (TTOF4). These pharmacologic data were compared between two groups. RESULTS: There was no significant difference in the onset time of rocuronium between the two groups. However, TDUR25 (min) was significantly shorter in the muscular group than in the non-muscular group (p = 0.035 and p = 0.014 in males and females, respectively). TTOF1 and TTOF4 were also shorter in the muscular group than in the non-muscular group. CONCLUSIONS: Total body weight-based dosing of rocuronium might prolong the neuromuscular relaxation effect in patients with a small amount of skeletal muscle.

Influence of body fatness on propofol requirements for loss of consciousness in target-controlled infusion: A STROBE-compliant study.

This prospective observational study evaluated the effects of body fat on the pharmacologic effect of propofol. Hundred patients aged 18 to 75 years who were scheduled to undergo orthopedic surgery under regional block were enrolled. All participants underwent bioelectrical impedance analysis and were allocated into 2 groups: the high and normal adiposity group, according to percent body fat. Following successful regional block, propofol was incrementally infused until loss of consciousness (LOC) with a target-controlled infusion pump. The effect-site concentration of propofol at LOC and the total infused dose of propofol per total body weight until LOC were recorded. At the end of the surgery, the infusion of propofol was stopped. The elapsed time to recovery of consciousness (ROC) and the effect-site concentration at ROC were recorded. These pharmacologic data were compared between 2 groups. The effect-site concentration of propofol at LOC (µg/mL) was significantly lower in the high adiposity group than in the normal group in both sexes (3.5 ± 0.4 vs 3.9 ± 0.6; P = .020 in males, and 3.4 [interquartile range: 2.9-3.5] vs 3.8 [interquartile range: 3.3-3.9]; P = .006 in females). Total dose per total body weight until LOC (mg/kg) were also significantly lower in the high adiposity group than in the normal group. There was no significant difference in the data related to ROC. The pharmacologic effects of propofol may be affected by the composition of body components. The concentration of propofol using a target-controlled infusion system may be diminished in patients with a high proportion of body fat.

Aqueous extract of Chrysanthemum morifolium Ramat. inhibits RANKL-induced osteoclast differentiation by suppressing the c-fos/NFATc1 pathway.

OBJECTIVE: The flower of chrysanthemum, used worldwide as a medicinal and edible product, has shown various bioactivities, such as anti-inflammatory, antioxidant, anti-tumorigenic, and hepatoprotective activities, as well as cardiovascular protection. However, the effect of Chrysanthemum morifolium Ramat. on the regulation of osteoclast differentiation has not yet been reported. In this study, we aimed to investigate the inhibitory effect of Chrysanthemum morifolium Ramat. water extract (CME) on RANKL-induced osteoclast differentiation in mouse bone marrow-derived macrophages (BMMs). STUDY DESIGN: Bone marrow-derived macrophages (BMMs) isolated from the C57BL/6 J mice. The viability of BMMs was detected with MTT assays. Inhibitory effects of CME on osteoclast differentiation and bone resorption was measured by TRAP staining and Pit assay. Osteoclast differentiation-associated gene expression were assessed by Real-time quantitative polymerase chain reaction. Intracellular signaling molecules was assessed by western blot. RESULTS: CME significantly inhibited osteoclast differentiation in BMMs without cytotoxicity, besides inhibiting MAPK/c-fos and PLCγ2/CREB activation. The inhibitory effects of CME on differentiation-related signaling molecules resulted in significant repression of NFATc1 expression, which is a key transcription factor in osteoclast differentiation, fusion, and activation. CONCLUSION: Our results confirmed the inhibition of RANKL-induced PLCγ2/CREB/c-fos/NFATc1 activation by CME during osteoclast differentiation. The findings collectively suggested CME as a traditional therapeutic agent for osteoporosis, RA, and periodontitis.

Effects of hypercarbia on arterial oxygenation during one-lung ventilation: prospective randomized crossover study.

Background: This study aimed to evaluate the effects of hypercarbia on arterial oxygenation during one-lung ventilation (OLV). Methods: Fifty adult patients undergoing elective video-assisted thoracoscopic lobectomy or pneumonectomy were enrolled. Group I patients (n = 25) were first maintained at normocarbia (PaCO2: 38‒42 mmHg) for 30 min and then at hypercarbia (45‒50 mmHg). In Group II patients (n = 25), PaCO2 was maintained in the reverse order. Arterial oxygen partial pressure (PaO2), respiratory variables, hemodynamic variables, and hemoglobin concentration were compared during normocarbia and hypercarbia. Arterial O2 content and O2 delivery were calculated. Results: PaO2 values during normocarbia and hypercarbia were 66.5 ± 10.6 and 79.7 ± 17.3 mmHg, respectively (mean difference: 13.2 mmHg, 95% CI for difference of means: 17.0 to 9.3, P < 0.001). SaO2 values during normocarbia and hypercarbia were 92.5 ± 4.8% and 94.3 ± 3.1% (P = 0.009), respectively. Static compliance of the lung (33.0 ± 5.4 vs. 30.4 ± 5.3 ml/cmH2O, P < 0.001), arterial O2 content (15.4 ± 1.4 vs. 14.9 ± 1.5 ml/dl, P < 0.001) and O2 delivery (69.9 ± 18.4 vs. 65.1 ± 18.1 ml/min, P < 0.001) were significantly higher during hypercarbia than during normocarbia. Conclusions: Hypercarbia increases PaO2 and O2 carrying capacity and improves pulmonary mechanics during OLV, suggesting that it may help manage oxygenation during OLV. Therefore, permissive hypercarbia may be a simple and valuable modality to manage arterial oxygenation during OLV.

Hemodynamic effects of different types of pneumatic compression of the lower extremities during anesthesia induction: a prospective randomized controlled trial.

BACKGROUND: The current study evaluated the hemodynamic effects of different types of pneumatic compressions of the lower extremities during anesthesia induction. In addition, the hemodynamic effects were compared between patients older than 65 age years and those aged 65 years or younger. METHODS: One hundred and eighty patients (90: > 65 years and 90: ≤ 65 years) were enrolled. Each age group of patients was randomly assigned to one of three groups; Group 1 (no compression), Group 2 (sequential pneumatic compression), and Group 3 (sustained pneumatic compression without decompression). Invasive blood pressure, cardiac index (CI), and stroke volume variation (SVV) were measured. RESULTS: In patients aged ≤ 65 years, mean arterial pressure (MAP) and CI were significantly higher and SVV was lower in Group 3 compared to Group 1 before tracheal intubation, but there were no differences between Groups 1 and 2. However, there were no differences in MAP, CI, and SVV among the three groups in patients aged > 65 years. The number of patients who showed a MAP < 60 mmHg was less in Group 3 than Group 1 in patients aged ≤ 65 years, but not in patients aged > 65 years. CONCLUSIONS: Sustained pneumatic compression of the lower extremities has more hemodynamic stabilizing effects compared to sequential compression during anesthesia induction in patients aged 65 years or younger. However, no difference between methods of compression was observed in patients older than 65 years.

A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile.

Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy against partial and generalized seizures. We have developed a novel hydantoin compound (HA) using comparative molecular field analysis (CoMFA) and evaluated its effects on hNa(v)1.2 channels. Both DPH and HA demonstrated affinity for resting (K(r)=13.9microM for HA, K(r)=464microM for DPH) and slow inactivated channels (K(I)=975nM for HA, K(I)=20.6microM for DPH). However, HA also exhibited an affinity for fast inactivated channels (K(I)=2.5microM) and shifted the V(1/2) for activation in the depolarizing direction. Furthermore, HA exhibited profound use dependent block at both 5 and 10Hz stimulation frequencies. In the 6Hz seizure model (32mA) HA had an ED(50) of 47.1mg/kg and a TD(50) of 131mg/kg (protective index (PI)=2.8). In comparison, the ED(50) for DPH was approximately 27.5mg/kg with a TD(50) of 35.6mg/kg (PI approximately 1.3). These findings provide evidence for the utility of CoMFA in the design of novel anticonvulsants and support the hypothesis that states selectivity plays an important role in achieving optimal protection with minimal side effects.

A comparison between ketorolac and nefopam as adjuvant analgesics for postoperative patient-controlled analgesia: a randomized, double-blind, prospective study.

BACKGROUND: We compared the analgesic efficacy and side effects of ketorolac and nefopam that were co-administered with fentanyl via intravenous patient-controlled analgesia. METHODS: One hundred and sixty patients scheduled for laparoscopic cholecystectomy were randomly assigned to ketorolac (Group K) or nefopam (Group N) groups. The anesthetic regimen was standardized for all patients. The analgesic solution contained fentanyl 600 µg and ketorolac 180 mg in Group K, and fentanyl 600 µg and nefopam 120 mg in Group N. The total volume of analgesic solution was 120 ml. Postoperative analgesic consumption, recovery of pulmonary function, and pain intensities at rest and during the forced expiration were evaluated at postoperative 2, 6, 24, and 48 h. The postoperative side effects of analgesics were recorded. RESULTS: Cumulative postoperative analgesic consumptions at postoperative 48 h were comparable (Group K: 93.4 ± 24.0 ml vs. Group N: 92.9 ± 26.1 ml, P = 0.906) between the groups. Pain scores at rest and during deep breathing were similar at the time of each examination. The recovery of pulmonary function showed no significant differences between the groups. Overall, postoperative nausea and vomiting incidence was higher in Group N compared with Group K (59% vs. 34%, P = 0.015). The other side effects were comparable between both groups. CONCLUSIONS: Analgesic efficacies of ketorolac and nefopam that were co-administered with fentanyl for postoperative pain management as adjuvant analgesics were similar. However, postoperative nausea and vomiting incidence was higher in the nefopam-fentanyl combination compared with the ketorolac-fentanyl combination.

Reversal of neuropathic pain by alpha-hydroxyphenylamide: a novel sodium channel antagonist.

Sodium (Na) channel blockers are known to possess antihyperalgesic properties. We have designed and synthesized a novel Na channel antagonist, alpha-hydroxyphenylamide, and determined its ability to inhibit both TTX-sensitive (TTX-s) and TTX-resistant (TTX-r) Na currents from small dorsal root ganglion (DRG) neurons. alpha-Hydroxyphenylamide tonically inhibited both TTX-s and TTX-r Na currents yielding an IC(50) of 8.2+/-2.2 microM (n=7) and 28.9+/-1.8 microM (n=8), respectively. In comparison, phenytoin was less potent inhibiting TTX-s and TTX-r currents by 26.2+/-4.0% (n=8) and 25.5+/-2.0%, respectively, at 100 microM. alpha-Hydroxyphenylamide (10 microM) also shifted equilibrium gating parameters of TTX-s Na channels to greater hyperpolarized potentials, slowed recovery from inactivation, accelerated the development of inactivation and exhibited use-dependent block. In the chronic constriction injury (CCI) rat model of neuropathic pain, intraperitoneal administration of alpha-hydroxyphenylamide attenuated the hyperalgesia by 53% at 100mg/kg, without affecting motor coordination in the Rotorod test. By contrast, the reduction in pain behavior produced by phenytoin (73%; 100mg/kg) was associated with significant motor impairment. In summary, we report that alpha-hydroxyphenylamide, a sodium channel antagonist, exhibits antihyperalgesic properties in a rat model of neuropathic pain, with favorable sedative and ataxic side effects compared with phenytoin.

Distinct domains of the sodium channel beta3-subunit modulate channel-gating kinetics and subcellular location.

Electrical excitability in neurons depends on the expression and activity of voltage-gated sodium channels in the neuronal plasma membrane. The ion-conducting alpha-subunit of the channel is associated with auxiliary beta-subunits of which there are four known types. In the present study, we describe the first detailed structure/function analysis of the beta3-subunit. We correlate the effect of point mutations and deletions in beta3 with the functional properties of the sodium channel and its membrane-targeting behaviour. We show that the extracellular domain influences sodium channel gating properties, but is not required for the delivery of beta3 to the plasma membrane when expressed with the alpha-subunit. In contrast, the intracellular domain is essential for correct subunit targeting. Our results reveal the crucial importance of the Cys21-Cys96 disulphide bond in maintaining the functionally correct beta3 structure and establish a role for a second putative disulphide bond (Cys2-Cys24) in modulating channel inactivation kinetics. Surprisingly, our results imply that the wild-type beta3 molecule can traverse the secretory pathway independently of the alpha-subunit.

A comparison of the temperature difference according to the placement of a nasopharyngeal temperature probe.

BACKGROUND: The purpose of this study was to compare temperatures measured at three different sites where a nasopharyngeal temperature probe is commonly placed. METHODS: Eighty elective abdominal surgical patients were enrolled. After anesthesia induction, four temperature probes were placed at the nasal cavity, upper portion of the nasopharynx, oropharynx, and the esophagus. The placement of the nasopharyngeal temperature probes was evaluated using a flexible nasendoscope, and the depth from the nares was measured. The four temperatures were simultaneously recorded at 10-minute intervals for 60 minutes. RESULTS: The average depths of the probes that were placed in the nasal cavity, upper nasopharynx, and the oropharynx were respectively 5.7 ± 0.9 cm, 9.9 ± 0.7 cm, and 13.6 ± 1.7 cm from the nares. In the baseline temperatures, the temperature differences were significantly greater in the nasal cavity 0.32 (95% CI; 0.27-0.37)℃ than in the nasopharynx 0.02 (0.01-0.04)℃, and oropharynx 0.02 (-0.01 to 0.05)℃ compared with the esophagus (P < 0.001). These differences were maintained for 60 minutes. Twenty patients showed a 0.5℃ or greater temperature difference between the nasal cavity and the esophagus, but no patient showed such a difference at the nasopharynx and oropharynx. CONCLUSIONS: During general anesthesia, the temperatures measured at the upper nasopharynx and the oropharynx, but not the nasal cavity, reflected the core temperature. Therefore, the authors recommend that a probe should be placed at the nasopharynx (≈ 10 cm) or oropharynx (≈ 14 cm) with mucosal attachment for accurate core temperature measurement.