Effect of Immature Rubus occidentalis on Postoperative Pain in a Rat Model.

Background and Objectives: This study aimed to identify the analgesic properties of immature Rubus occidentalis extract (iROE) using a postoperative-pain rat model. We also aimed to compare the analgesic effects of iROE to those of mature R. occidentalis extract (mROE) and examine the proinflammatory cytokine response and associated underlying mechanisms. Materials and Methods: In adult male Sprague Dawley rats, acute postoperative pain was induced through plantar hind-paw incisions. After the plantar incisions were made, the rats were intraperitoneally administered with normal saline or various doses of iROE and mROE to investigate and compare the analgesic effects of iROE and mROE. The mechanisms underlying iROE-induced analgesia were investigated via post-incisional administration of yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine, followed by iROE. Mechanical withdrawal threshold (MWT) evaluations with von Frey filaments were carried out at different time points. Serum levels of tumor necrosis factor α, interleukin (IL)-1ß, and IL-6 were measured to assess inflammatory responses. Multivariate analysis of variance (MANOVA) and linear mixed-effects model (LMEM) analysis were used to analyze the analgesic effect data. Results: The MWTs demonstrated significant increases in iROE in a dose-dependent manner up to 2 h after the plantar incisions were made. An LMEM analysis demonstrated that iROE yielded a significantly greater analgesic effect than mROE, but there was no significant difference between the two according to MANOVA. Dexmedetomidine enhanced the MWT-confirmed iROE response, while yohimbine and naloxone diminished it. Administration of iROE significantly attenuated the post-incisional increases in serum IL-1ß and IL-6 levels. Conclusions: The iROE demonstrated analgesic and anti-inflammatory effects in a rat model of incisional pain, which were more pronounced than those associated with mROE. The analgesic activity of iROE may be associated with α2-adrenergic and opioid receptors.

Effects of ramosetron orally disintegrating tablets on the prophylaxis of post-discharge nausea and/or vomiting in female patients undergoing day surgery under general anesthesia: a randomized controlled trial.

BACKGROUND: This study was performed to evaluate the effectiveness of ramosetron orally disintegrating tablets (ODTs) in preventing post-discharge nausea and/or vomiting (PDNV) in female patients following outpatient surgery under general anesthesia. METHODS: This multicenter randomized study included three South Korean tertiary hospitals. Before surgery, 138 patients were randomly allocated into two groups. In the ramosetron group, ramosetron ODT 0.1 mg was administered after discharge in the morning of postoperative days 1 and 2. Metoclopramide 10 mg was administered as a rescue antiemetic (capped at 30 mg per day). In the control group, patients were administered only metoclopramide 10 mg when nausea and/or vomiting occurred. The primary outcome was the incidence of nausea during 24 h after discharge. RESULTS: We found significant differences in the incidence (13% vs. 33%, P = 0.008) and severity (P = 0.011) of nausea between the ramosetron and the control groups during 24 h after discharge. In addition, the rate of rescue antiemetic (metoclopramide) administration during 24 h after discharge was lower in the ramosetron group (6%) than in the control group (18%) (P = 0.033). Patient satisfaction score was higher in the ramosetron group than in the control group (P < 0.001). CONCLUSION: Ramosetron ODT reduces the incidence and severity of postoperative nausea after discharge during the first 24 h and may be a valuable option for the prevention of PDNV in female patients after day surgery under general anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04297293 . Registered on 05 March 2020.

Effect of methylene blue on experimental postoperative adhesion: A systematic review and meta-analysis.

Adhesion is a primary challenge following surgery, and the anti-adhesive effect of methylene blue (MB) has been investigated. This systematic review and meta-analysis aimed to evaluate the effect of MB on postoperative adhesions in experimental studies. We initially searched OVID-MEDLINE, EMBASE, and Google Scholar in February 2021, and then in May 2021. The anti-adhesive efficacy of MB was compared with that of the control (either placebo or nothing) after the surgical procedure. The primary and secondary outcomes were the macroscopic and microscopic adhesion scores, respectively. Traditional meta-analysis, meta-regression, and trial sequential analysis (TSA) were performed to analyze the retrieved outcomes. We included 13 experimental studies of 367 rats (200 rats received MB and 167 rats received placebo or nothing). The macroscopic adhesion scores were significantly lower in the MB-administered group than in the control group (standardized mean difference, 2.313; 95% confidence interval, 1.104 to3.523; I2 = 94.0%, Tau = 2.059). Meta-regression analysis showed that macroscopic adhesion tended to decrease with an increase in MB dose. TSA demonstrated that the cumulative Z curve crossed both the conventional test and trial sequential monitoring boundary for the macroscopic adhesion score. MB had a beneficial effect on intraperitoneal adhesion following laparotomy, and adhesions decreased with increase in dose.

Effectiveness of maturity of Rubus occidentalis on hyperalgesia induced by acidic saline injection in rats.

BACKGROUND: Rubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs. METHODS: In adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 µg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction. RESULTS: The iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups. CONCLUSIONS: Immature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α2-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.

Effects of a BMI1008 mixture on postoperative pain in a rat model of incisional pain.

BACKGROUND: The purpose of this study was to evaluate the analgesic effect of BMI1008 (a new drug containing lidocaine, methylene blue, dexamethasone and vitamin B complex) and to investigate the analgesic effect of lidocaine and BMI-L (other components of BMI1008 except lidocaine) at different concentrations in a rat model of incisional pain. METHODS: Male Sprague-Dawley rats (250-300 g) were used for the incisional pain model simulating postoperative pain. After the operation, normal saline, various concentrations of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine were injected at the incision site. The preventive analgesic effect was evaluated using BMI1008 administered 30 min before and immediately after the operation. In addition, BMI1008 was compared with positive controls using intraperitoneal ketorolac 30 mg/kg and fentanyl 0.5 µg/kg. The mechanical withdrawal threshold was measured with a von Frey filament. RESULTS: The analgesic effect according to the concentration of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine showed a concentration-dependent response and statistically significant difference among the groups (P <0.001, P <0.001, and P <0.001, respectively). The analgesic effect according to the time point of administration (before and after the operation) showed no evidence of a statistically significant difference between the groups (P = 0.170). Compared with the positive control groups, the results showed a statistically significant difference between the groups (P = 0.024). CONCLUSION: BMI1008 showed its analgesic effect in a rat model of incisional pain in a concentration-dependent manner. Moreover, BMI-L showed an additive effect on the analgesic effect of lidocaine.

Moderate versus deep sedation in adults undergoing colonoscopy: systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis comparing effectiveness and safety of moderate and deep sedation during colonoscopy. RESEARCH DESIGN AND METHODS: We searched Medline, Embase, Central and Google scholar in May 2017 and updated in March 2018 to identify all randomized controlled trials that compared the effectiveness and safety of moderate and deep sedation during colonoscopy. The quality of studies was assessed using the "Risk of bias" tool. The primary endpoints were defined as patient satisfaction, physician satisfaction, incidence of recall and incidence of desaturation. Recovery time was also evaluated. Review Manager and Comprehensive Meta-Analysis software were used for statistical analysis. RESULTS: A total of 919 patients from three studies were included in the final analysis. The combined analysis did not reveal any differences in patient satisfaction between moderate and deep sedation (RR = 0.94; 95% CI: 0.86 to 1.04; Pchi2 = 0.06; I2 = 65%; number needed to treat to harm [NNTH] = 15.6; 95% CI: NNTH 7.8 to ∞ to number needed to treat to benefit [NNTB] = 3078.0), physician satisfaction (RR = 0.35; 95% CI: 0.02 to 6.95; Pchi2 < 0.001; I2 = 100%; NNTB = 1.6; 95% CI: 1.5 to 1.8), incidence of recall (RR = 5.82; 95% CI: 0.51 to 66.48; Pchi2 = 0.11; I2 = 60%; NNTH = 11.0; 95% CI: 7.5 to 20.5) or recovery time (mean difference = -6.77; 95% CI: -16.21 to 2.67; Pchi2 < 0.001; I2 = 99%). However, incidence of desaturation was higher in the deep group than in the moderate group (RR = 0.18; 95% CI: 0.01 to 0.99; Pchi2 = 0.48; I2 = 0%; NNTB = 56.7; 95% CI: 31.6 to 273.1). CONCLUSIONS: Moderate sedation showed comparable safety and effectiveness to deep sedation with respect to patient satisfaction, physician satisfaction, incidence of recall and recovery time.

Comparison of propofol monotherapy and propofol combination therapy for sedation during gastrointestinal endoscopy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Previous randomized controlled trials have reported conflicting findings comparing propofol combination therapy (PCT) with propofol monotherapy (PMT) for sedation of patients undergoing gastrointestinal endoscopy. Therefore, a systematic review was carried out to compare the efficacy and safety of PCT and PMT in such patients. METHODS: We searched MEDLINE, EMBASE and CENTRAL databases to identify all randomized controlled trials that compared the efficacy and safety of PCT and PMT for sedation of patients undergoing gastrointestinal endoscopy. Primary endpoints were incidence of respiratory complications, hypotension and arrhythmia, dose of propofol used, and recovery time. Procedure duration and the satisfaction of patients and doctors were also evaluated. RESULTS: A total of 2250 patients from 22 studies were included in the final analysis. The combined analysis did not show any difference between PCT and PMT in the incidence of respiratory complications (risk ratio [RR], 0.80; 95% CI, 0.52 to 1.23; I2 = 58.34%), hypotension (RR, 1.06; 95% CI, 0.63 to 1.78; I2 = 72.13%), arrhythmia (RR,1.40; 95% CI, 0.74 to 2.64; I2 = 43.71%), recovery time (standardized mean difference [SMD], 0.16; 95% CI, -0.49 to 0.81; I2 = 95.9%), procedure duration (SMD, 0.04; 95% CI, -0.05 to 0.14; I2 = 0.0%), patient satisfaction (SMD, 0.13; 95% CI, -0.26 to 0.52; I2 = 89.63%) or doctor satisfaction (SMD, 0.01; 95% CI, -0.15 to 0.17; I2 = 0.00%). However, the dose of propofol used was significantly lower in PCT than in PMT (SMD, -1.38; 95% CI, -1.99 to -0.77; I2 = 97.70%). CONCLUSION: PCT showed comparable efficacy and safety to PMT with respect to respiratory complications, hypotension and arrhythmia, recovery time, procedure duration, patient satisfaction, and doctor satisfaction. However, the average dose of propofol used was higher in PMT.

Optimal dose of intravenous oxycodone for attenuating hemodynamic changes after endotracheal intubation in healthy patients: A randomized controlled trial.

BACKGROUND: Intravenous oxycodone has been used as an adjunct to anesthetic agents. This study aimed to assess the optimal dose of intravenous oxycodone for the attenuation of the hemodynamic responses to laryngoscopy and endotracheal intubation. METHODS: A prospective, randomized, double-blind study was conducted. Ninety-five patients were randomly divided into 5 groups based on the oxycodone dose: 0, 0.05, 0.1, 0.15, 0.2 mg/kg. After administering the assigned dose of intravenous oxycodone, anesthesia was induced with thiopental. Heart rate (HR) and blood pressure (BP) were measured at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The percentage increase of BP was calculated as (highest BP after intubation - baseline BP)/baseline BP × 100 (%). The percentage increase of HR was calculated in same formula as above. Hypertension was defined as a 15% increase of systolic BP from baseline, and probit analysis was conducted. RESULTS: Hemodynamic data from 86 patients were analyzed. The percentage increase of mean arterial pressure after intubation in groups 0.05, 0.1, 0.15, and 0.2 was significantly different from that in the control (P < 0.001). For HR, the percentage increase was lower than control group when oxycodone was same or more than 0.1 mg/kg (P < 0.05). Using probit analysis, the 95% effective dose (ED95) for preventing hypertension was 0.159 mg/kg (95% confidence interval [CI], 0.122-0.243). In addition, ED50 was 0.020 mg/kg (95% CI, -0.037 to 0.049). However, oxycodone was not effective for maintaining the HR in our study dosage. There were no significant differences in the incidence of hypotension during induction between groups. CONCLUSIONS: Using 0.1 mg/kg of intravenous oxycodone is sufficient to attenuate the increase of BP and HR during induction period in healthy patients. The ED95, which was 0.159 mg/kg, can be useful to adjust the dosage of IV oxycodone for maintain stable BP during induction of general anesthesia.

The changes of non-invasive hemoglobin and perfusion index of Pulse CO-Oximetry during induction of general anesthesia.

BACKGROUND: We hypothesized that induction of general anesthesia using sevoflurane improves the accuracy of non-invasive hemoglobin (SpHb) measurement of Masimo Radical-7® Pulse CO-Oximetry by inducing peripheral vasodilation and increasing the perfusion index (PI). The aim of this study is to investigate the change in the SpHb and the PI measured by Rad7 during induction of general anesthesia using sevoflurane. METHODS: The laboratory hemoglobin (Hblab) was measured before surgery by venous blood sampling. The SpHb and the PI was measured twice; before and after the induction of general anesthesia using sevoflurane. The changes of SpHb, Hbbias (Hbbias = SpHb - Hblab), and PI before and after the induction of general anesthesia were analyzed using a paired t-test. Also, a Pearson correlation coefficient analysis was used to analyze the correlation between the Hbbias and the PI. RESULTS: The SpHb and the PI were increased after the induction of general anesthesia using sevoflurane. There was a statistically significant change in the Hbbias from -2.8 to -0.7 after the induction of general anesthesia. However, the limit of agreement (2 SD) of the Hbbias did not change after the induction of general anesthesia. The Pearson correlation coefficient between the Hbbias and the PI was not statistically significant. CONCLUSIONS: During induction of general anesthesia using sevoflurane, the accuracy of SpHb measurement was improved and precision was not changed. The correlation between Hbbias and PI was not significant.