Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice.

Background: The effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action. Methods: By repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4+ T cells and CD8+ T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered. Results: Repeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4+ T cells, with little effect on CD8+ T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees. Conclusion: Repeated intraperitoneal injection of oxycodone induces immunosuppression in mice.

In Situ Array Microextraction and Metabolic Profiling of Small Extracellular Vesicles to Guide and Monitor Maternal Delivery.

The advantages of small extracellular vesicles (sEV) in disease management have become increasingly prominent, with the main challenge lying in meeting the demands of large-scale extraction and high-throughput analysis, a crucial aspect in the realm of precision medicine. To overcome this challenge, an engineered on-plate aptamer array (16×24 spots) is developed for continuous scale-up microextraction of plasma sEV and their in situ metabolic analysis using mass spectrometry. With this integrated array strategy, metabolic profiles of sEV are acquired from the plasma of 274 antenatal or postpartum women, reducing analysis time by half (7.5 h) and sample volume by 95% (only 0.125 µL usage) compared to the traditional suspension method. Moreover, using machine learning algorithms on sEV metabolic profiles, a risk score system is constructed that accurately assesses the need for epidural analgesia during childbirth and the likelihood of post-administration fever. The system, based on admission samples, achieves an impressive 94% accuracy. Furthermore, post-administration fever can be identified from delivery samples, reaching an overall accuracy rate of 88%. This work offers real-time monitoring of the childbirth process that can provide timely guidance for maternal delivery, underscoring the significance of sEV detection in large-scale clinical samples for medicine innovation and advancement.

Using part of the initial analgesic dose as the epidural test dose did not delay the onset of labor analgesia: a randomized controlled clinical trial.

BACKGROUND: Epidural test dose for labor analgesia is controversial and varies widely in clinical practice. It is currently unclear whether using a portion of the initial dose for analgesia as the test dose delays the onset time of analgesia, compared to the traditional test dose. METHODS: One hundred and twenty-six parturients who chose epidural analgesia during labor were randomly assigned to two groups. The first dose in group L was 3 ml 1.5% lidocaine, and in the RF group was 10 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. After 3 min of observation, both groups received 8 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. The onset time of analgesia, motor and sensory blockade level, numerical pain rating scale, patient satisfaction score, and side effects were recorded. RESULTS: The onset time of analgesia in group RF was similar to that in group L (group RF vs group L, 7.0 [5.0-9.0] minutes vs 8.0 [5.0-11.0] minutes, p = 0.197). The incidence of foot numbness (group RF vs group L, 34.9% vs 57.1%, p = 0.020) and foot warming (group RF vs group L, 15.9% vs 47.6%, p < 0.001) in group RF was significantly lower than that in group L. There was no difference between the two groups on other outcomes. CONCLUSIONS: Compared with 1.5% lidocaine 3 ml, 0.1% ropivacaine 10 ml combined with 2 µg/ml fentanyl as an epidural test dose did not delay the onset of labor analgesia, and the side effects were slightly reduced. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2100043071).

The Median Effective Dose of Intrathecal Hyperbaric Bupivacaine for Cesarean Section at Moderately High-Altitude.

Objective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude. Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded. Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52-9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48-9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed. Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.

Comparison of the bispectral indices of patients receiving remimazolam and propofol for general anesthesia: a randomized crossover trial.

BACKGROUND: Remimazolam is a safe and effective new benzodiazepine sedative that has unique advantages in anesthesia induction and maintenance. The differences in the electroencephalogram bispectral index (BIS) during general anesthesia between propofol and remimazolam deserve further exploration. METHODS: Single-center randomized crossover study. Patients who required multiple hysteroscopic surgery were randomly assigned to use remimazolam (0.27 mg/kg for induction and 1 mg/kg/h for maintenance) first and then propofol (2.0 mg/kg for induction and 6 mg/kg/h for maintenance) during hysteroscopic surgery again 3 months later, or in the opposite order. Both drugs were used at the latest ED95 for unconsciousness. The BIS values (primary endpoint), intraoperative conditions, and incidence of adverse reactions (secondary endpoints) were compared at each time point. BIS values were analyzed with a mixed model of repeated measurements (MMRM). RESULTS: Seventeen patients completed the study. The lowest BIS value in the remimazolam regimen was significantly higher than that in the propofol regimen (p = 0.001). The MMRM analysis of the BIS values revealed significant differences between the regimens at each time point (p < 0.001). The intraoperative diastolic blood pressure and heart rate changes were smaller, the recovery was faster, and there were fewer adverse reactions and less injection pain, but a greater incidence of intraoperative body movement and hiccups, in the remimazolam regimen. CONCLUSION: The trial indicated that remimazolam maintained a higher BIS level than propofol. The correlation between the BIS and the depth of anesthesia induced by remimazolam needs to be further studied. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov: ChiCTR2200064551.

Effect of early oral carbohydrate intake after elective Cesarean delivery on maternal body temperature and satisfaction: a randomized controlled trial.

PURPOSE: Although the Enhanced Recovery After Cesarean Delivery (ERAC) consensus statement provides recommendations for early postoperative drinking and eating, evidence from high-quality clinical research directly addressing parturients is sparse. Our objective was to assess if early oral carbohydrate intake after elective Cesarean delivery improves maternal recovery. METHODS: In this randomized controlled trial, we enrolled parturients undergoing elective Cesarean delivery under spinal anesthesia with tympanic membrane temperatures ≤ 36.5 °C immediately upon arrival at the postanesthesia care unit. Parturients were randomized to either 100 mL of oral complex carbohydrate intake (group CC) or 10 mL of water (group C). The primary outcome was maternal tympanic membrane temperature. Other outcomes included maternal thermal comfort score, degree of shivering, satisfaction, degree of thirst and hunger, and gastric emptying assessed by ultrasonography. RESULTS: We included 90 participants in the final analysis. The mean (standard deviation [SD]) maternal body temperature at 120 min after ingestion was 36.7 (0.3) °C in group CC and 36.6 (0.3) °C in group C (difference in means, 0.14 °C; 95% confidence interval, 0.02 to 0.26; P = 0.02). Furthermore, using repeated measure models, the linear trends of temperature changes over time between groups CC and C were significantly different (P = 0.04). The thermal comfort scores at 120 min after ingestion were higher in group CC than in group C (P = 0.02), and the linear trends of shivering score changes over time between groups CC and C also were different (P = 0.003). The mean (SD) visual analogue scale scores for maternal satisfaction were 84 (13) mm in group CC and 47 (20) mm in group C (P < 0.001). Nevertheless, at 90 and 120 min after ingestion, there were no differences between the two groups in the number of participants with a gastric antrum cross-sectional area > 10.3 cm2. CONCLUSIONS: Early oral carbohydrate intake after Cesarean delivery helped to restore maternal body temperature postoperatively and improve maternal satisfaction. Nevertheless, the clinical importance of these finding is unclear, given that most of the differences were small. In addition, there was no delay in maternal gastric emptying after consumption of a complex carbohydrate beverage in the early post-Cesarean period. STUDY REGISTRATION: www.chictr.org.cn (ChiCTR2000031085); first submitted 13 November 2022.

RéSUMé: OBJECTIF: Bien que la déclaration de consensus sur la Récupération améliorée après un accouchement par césarienne (ERAC/RAAC) fournisse des recommandations pour l'ingestion postopératoire précoce de liquides et d'aliments, les données probantes issues de recherches cliniques de haute qualité portant directement sur les personnes parturientes sont rares. Notre objectif était d'évaluer si l'ingestion précoce de glucides par voie orale après une césarienne programmée améliorait la récupération maternelle. MéTHODE: Dans cette étude randomisée contrôlée, nous avons recruté des personnes parturientes bénéficiant d'une césarienne programmée sous rachianesthésie avec une température tympanique ≤ 36,5 °C immédiatement après leur arrivée en salle de réveil. Les personnes parturientes ont été randomisées à recevoir soit 100 mL de glucides complexes par voie orale (groupe GC) ou 10 mL d'eau (groupe C). Le critère d'évaluation principal était la température tympanique maternelle. Les autres critères d'évaluation comprenaient, chez la mère, le score de confort thermique, le degré de frissons, la satisfaction, le degré de soif et de faim, et la vidange gastrique évaluée par échographie. RéSULTATS: Nous avons inclus 90 personnes dans l'analyse finale. La température corporelle maternelle moyenne (écart type [ET]) à 120 minutes après l'ingestion était de 36,7 (0,3) °C dans le groupe GC et de 36,6 (0,3) °C dans le groupe C (différence dans les moyennes, 0,14 °C; intervalle de confiance à 95 %, 0,02 à 0,26; P = 0,02). De plus, à l'aide de modèles à mesures répétées, les tendances linéaires des changements de température au fil du temps entre les groupes GC et C étaient significativement différentes (P = 0,04). Les scores de confort thermique à 120 minutes après l'ingestion étaient plus élevés dans le groupe GC que dans le groupe C (P = 0,02), et les tendances linéaires des changements de score de frissons au fil du temps entre les groupes GC et C étaient également différentes (P = 0,003). Les scores moyens (ET) de l'échelle visuelle analogique concernant la satisfaction maternelle étaient de 84 (13) mm dans le groupe GC et de 47 (20) mm dans le groupe C (P < 0,001). Néanmoins, à 90 et 120 minutes après l'ingestion, il n'y avait aucune différence entre les deux groupes dans le nombre de personnes présentant une section transversale de l'antre gastrique > 10,3 cm2. CONCLUSION: L'ingestion précoce de glucides par voie orale après un accouchement par césarienne a aidé à rétablir la température corporelle maternelle postopératoire et à améliorer la satisfaction maternelle. Néanmoins, l'importance clinique de ces résultats n'est pas claire, étant donné que la plupart des différences étaient faibles. De plus, il n'y avait pas de retard dans la vidange gastrique maternelle après la consommation d'une boisson glucidique complexe au début de la période post-césarienne. ENREGISTREMENT DE L'éTUDE: www.chictr.org.cn (ChiCTR2000031085); soumis pour la première fois le 13 novembre 2022.

Impact of Bilateral Quadratus Lumborum Block Using Different Doses of Dexmedetomidine for Postoperative Analgesia in Laparoscopic Myomectomy: A Randomized Controlled Trial.

OBJECTIVES: The optimal dosage of dexmedetomidine (DEX) for postoperative analgesia of quadratus lumborum block (QLB) after laparoscopic myomectomy is not clear. Our study evaluated the analgesic and adverse effects of different doses of locally administered DEX. MATERIALS AND METHODS: Patients underwent laparoscopic myomectomy were enrolled in this randomized controlled trial. Transmuscular bilateral QLB was conducted postoperatively using local anesthetic plus different doses of DEX, as an adjuvant, per side. Numeric rating scales (NRS) of pain score and heart rate (HR) were assessed after performing QLB. Additional analgesics through patient-controlled analgesia pump, recovery time to first flatus, hospital stay, and other outcomes were also compared. RESULTS: A total of 150 participants were randomly divided into 3 groups (DEX1 group: 0.1 µg/kg; DEX2 group: 0.3 µg/kg; DEX3 group: 0.5 µg/kg), 50 for each group. Compared with the DEX1 group, NRS pain scores were lower in groups DEX2 and DEX3 ( P <0.017) 20 minutes after QLB and the significance lasted for 24 hours. Patients in groups DEX2 and DEX3 needed fewer additional analgesics than the group DEX1 ( P <0.017). HR in groups DEX2 and DEX3 was lower than the group DEX1 10 minutes and 20 minutes after QLB, respectively ( P <0.017). Sixty minutes after QLB, HR in the DEX3 group was still lower than the other groups. More patients in the DEX3 group were found bradycardia. Satisfaction score of postoperative analgesia was higher in groups DEX2 and DEX3 than the DEX1 group ( P <0.017). DISCUSSION: The results suggest that solution of DEX 0.3 µg/kg in ropivacaine 0.25% for QLB is recommended to relieve postoperative pain after laparoscopic myomectomy effectively and safely.

The Effects of Over- and Under-Specified Linguistic Input on L2 Online Processing of Referring Expressions.

Via two reading experiments, this exploratory study examined the effects of over-and under-specified linguistic input on L2 online processing of Chinese referring expressions (REs). In each experiment, a group of advanced L2 Chinese speakers (all with Uyghurs as L1) and a control group of native Chinese speakers read 48 sets of 4 sentence pairs with each set including one sentence pair containing referential underspecification (ambiguity) and one pair containing overspecification (redundancy). An analysis of the two groups' reaction time (RT) using mixed-effects linear modelling reveals that underspecification had no effect on native Chinese speakers in both experiments, and overspecification also had no effect in the form of a redundant size noun modifier in Experiment 1 but showed a facilitating effect in the form of a color noun modifier in Experiment 2. In contrast, L2 Chinese speakers were significantly disrupted by underspecification in both experiments but not by overspecification. The results seem to support the hypothesis that L2 processing is constraint-based. Tentative research and pedagogical implications of the findings are discussed.

The effect of first trimester body mass index on the changes in the upper lip bite test classification before and after delivery: A prospective observational study.

Background: The difficult airway (DA) assessment and management of pregnant woman has always brought specific challenges. The aim of this study was to investigate the effect of labor on the airway by assessing changes in the upper lip bite test (ULBT) classes and to explore its correlation with the first trimester's body mass index (BMI). Methods: According to the BMI of the first trimester, 354 full-term women were divided into low BMI group, normal BMI group and high BMI group. The ULBT class and pregnancy outcome were recorded and compared at early labor, after delivery, and 48 h after delivery. Results: The ULBT class was increased in 75(21.1%) patients after delivery. Compared to the normal BMI group, the high BMI group had a higher probability of increasing (34.8 vs. 17.5%; P = 0.002). The number of women with ULBT class 2-3 increased to 157, which was 1.48 times that of early labor. The number of women with ULBT class 3 increased from 4 to 16, of which 7 (53.8%) were from the high BMI group. Binary logistic regression analysis showed that first trimester's BMI was associated with a significant increase in ULBT class after delivery (adjusted odds ratio [aOR] = 2.13 [0.91-4.98], P = 0.02). The ULBT classes of the three groups tended to return to their initial level 48 h after delivery (P > 0.05). Conclusion: Labor results in an approximately one-fifth increase in ULBT class. Being overweight or obese in the first trimester is associated with an increased risk of DA during labor. Trial registration: This study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn) on September 26, 2020. Registration number ChiCTR2000038643.

Role of modified nasopharyngeal oxygen therapy in apnoeic oxygenation under general anaesthesia: a single-centre, randomized controlled clinical study.

Apnoeic oxygenation is not only important for patients who cannot be intubated/ventilated, but also can be routinely employed when planning to secure the airway.We aimed to compare safe apnoea times between patients receiving modified nasopharyngeal oxygen therapy and those receiving high-flow nasal oxygen therapy (HFNO) following the induction of general anaesthesia.This was a single-centre, randomized controlled clinical study. Eighty-four female patients undergoing elective laparoscopic gynaecological surgery under general anaesthesia were randomly assigned to the high-flow nasal oxygen therapy group (Group HFNO) or the modified nasopharyngeal oxygen therapy group (Group Naso). A Kaplan-Meier survival curve was used to describe the apnoeic oxygenation time.The safe apnoea time of the patients in the Group Naso was higher than that of the patients in the Group HFNO (20 (19.3 to 20.0) vs. 16.5 (12.9 to 20) minutes, P < 0.05). The incidence of SpO2 < 95% in the Group Naso was lower than that in the Group HFNO; hazard ratio 0.3 (95% confidence interval 0.2 to 0.6, P < 0.0001). Modified nasopharyngeal oxygen therapy which uses far less oxygen than HFNO is a convenient and effective method of apnoeic oxygenation in normal female patients.Trial registration: https://www.chictr.org.cn , ChiCTR2000039433; date of registration: 28/10/2020.

The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus.

Introduction: Women with Gestational diabetes mellitus (GDM) had a higher need and consumption of analgesics than women without GDM. The preoperative level of HbA1c was associated with the postoperative consumption for analgesics in diabetic patients. This prospective observational study go further to investigate the relationship between the pre-operative HbA1c and the post-operative consumption for analgesics in women with GDM. Methods: Women with GDM and a singleton pregnancy undergoing elective cesarean section under combined spinal-epidural anaesthesia were divided into two groups based on pre-operative HbA1c: group HbA1c < 6% and group HbA1c ≥ 6%. Analgesics consumption, number of patient-controlled analgesia (PCA) compression, and pain scores in 6 hours and 24 hours post-operation were compared between the two groups. Then Pearson's correlation coefficient and a stepwise multivariate linear regression were performed to investigate possible independentpredictors of post-operative 24-hour sufentanil consumption. Results: Analgesics consumption was significantly lower (18.8 ± 0.4 vs 23.2 ± 4.3; 82.7 ± 2.4 vs 115.8 ± 17.4, P < 0.001), and number of PCA compressions was significantly less frequent (1 [1-2] vs 3 [1-5]; 5 [3-7] vs 7 [3-15], P < 0.001), and in group HbA1c < 6% than in group HbA1c ≥ 6% in 6 hours and 24 hours post-operation.The univariate analysis showed that sufentanil consumption at 24 hours post-operation was significantly related to pre-operative HbA1c (r = 0.338, P < 0.001) and parity (r = 0.184, P = 0.03) and was related to blood glucose management methods (r = 0.172, P = 0.043). Multivariate linear regression analysis showed that HbA1c was the independent factor related to post-operative 24-hour sufentanil consumption (adjusted r2 = 0.246, P < 0.001). Conclusions: This study demonstrated that in pregnant women with GDM, the pre-operative HbA1c is independently related to the need for and consumption of analgesics in 24 hours after CS.

The effectiveness of different education methods conducted at different times for decreasing the time required for a parturient to position herself for epidural placement.

BACKGROUND: Decreasing the anaesthesia preparation time for primiparas experiencing painful uterine contractions is clinically relevant. This prospective intervention study investigated the effect of various educational methods conducted at different times on body positioning for primiparas undergoing labour analgesia. METHODS: Ninety primiparas who were about to receive labour analgesia were randomly divided into a verbal instruction group, a photo instructions group, and an educational video group for immediate education, and 60 primiparas who were willing to receive labour analgesia but were not in labour were randomly divided into a photo instruction group and an educational video group for advance education. The times required for body positioning were compared. RESULTS: In the immediate education cohort, the body positioning time in the verbal group (50.48 ± 28.97 s) was significantly longer than those in the photo group (30.47 ± 6.94 s) and the video group (23.14 ± 9.74 s) (P = 0.00). In the advance education cohort, the time in the photo group (17.47 ± 6.48 s) was longer than that in the video group (13.71 ± 7.01 s) (P = 0.042). Whether photos or videos are used, advance education can significantly decrease body positioning time. CONCLUSIONS: Video or photo education for primiparas who are about to receive labour analgesia can decrease the body positioning time and is more effective when provided in advance.

Ropivacaine with intraspinal administration alleviates preeclampsia-induced kidney injury via glycocalyx /alpha 7 nicotinic acetylcholine receptor pathway.

Preeclampsia is characterized by hypertension and proteinuria, which is associated with kidney injury. Glycocalyx (GCX) degradation mediated endothelial injury can result in proteinuria and kidney damage. alpha 7 nicotinic acetylcholine receptor (α7nAChR) connects nervous and immune systems to respond to stress or injury. We aimed to explore the protective effect and mechanism of intraspinal analgesia on maternal kidney injury in preeclampsia. Endotoxin-induced preeclampsia rats treated with ropivacaine via intraspinal administration. Renal histopathological examination was performed, cell apoptosis in the kidney, the levels of Glycocalyx markers of Syndecan-1 and heparin sulfate (HS) in maternal serum, Syndecan-1 along with α7nAChR in the kidney were measured. Our results showed that kidney injury was obviously in preeclampsia rats with proteinuria, endothelial damage, higher apoptosis rate, increasing levels of Syndecan-1 and HS in serum, upregulated Syndecan-1 expression but downregulated α7nAChR expression in kidney. Preeclampsia rats treated with intraspinal injected ropivacaine attenuated preeclampsia-induced kidney injury as Syndecan-1 and HS were decreased in serum, Syndecan-1 expression was suppressed as well as α7nAChR was activated in the kidney. Our results suggested that Ropivacaine administered through the spinal canal may protect preeclampsia-induced renal injury by decreasing GCX and α7nAChR activation.

Effects of nalbuphine on the cardiotoxicity of ropivacaine in rats.

When combined with nalbuphine, local anesthetics show a longer duration of nerve block without increasing complications. However, no evidence is available concerning the effect of nalbuphine on the cardiotoxicity of local anesthetics. The objective of this work is to investigate whether nalbuphine pretreatment can increase the lethal dose threshold of ropivacaine in rats. Anesthetized Sprague Dawley rats were pretreated with different doses of nalbuphine (0.4, 0.8, 1.5, 3.0, 5.0 mg/kg) or NS (normal saline, negative control) or 30% LE (lipid emulsion, positive control) 2 ml/kg/min for 5 min (n = 6). Then 0.5% ropivacaine was infused at a rate of 2.5 mg/kg/min until asystole occurs. Time of arrhythmia, 50% mean arterial pressure- and 50% heart rate-reduction, and asystole were recorded, and ropivacaine doses were calculated. Nalbuphine (0.4-5.0 mg/kg) did not affect ropivacaine-induced arrhythmia, 50% mean arterial pressure-reduction and 50% heart rate-reduction, and asystole in rats compared with NS pre-treatment. The asystole dose threshold (in milligrams per kilogram) of group LE was higher than that of group NS (NS 28.25(6.32) vs. LE, 41.58(10.65); P = 0.04; 95% confidence interval 0.23 to 26.45), while thresholds of arrhythmia, 50% mean arterial pressure-reduction, and 50% heart rate-reduction were not affected by LE. Nalbuphine doses of 0.4-5.0 mg/kg pretreatment did not increase the threshold of ropivacaine cardiotoxicity compared with NS control; 30% LE increases the lethal dose threshold of ropivacaine in rats.

Effect of maternal body mass index on the prophylactic dose of phenylephrine for preventing hypotension in parturients after spinal anaesthesia.

BACKGROUND: To compare the median effective dose (ED50) of phenylephrine for prophylactic continuous infusion in parturients with different body mass indices (BMIs) during combined spinal-epidural anaesthesia for caesarean section and to investigate the impact of maternal BMI on the prophylactic dose of phenylephrine. METHODS: Parturients receiving combined spinal-epidural anaesthesia for elective caesarean section were divided into a standard group (Group S, BMI < 30 kg/m2) and an obesity group (Group O, BMI > 30 kg/m2), each with 30 patients. A sequential allocation design was used to administer the prophylactic infusion of phenylephrine after the completion of a spinal anaesthetic injection to prevent hypotension (defined as a reduction of systolic blood pressure ≥ 20% of the baseline value or systolic blood pressure < 90 mmHg), with an initial infusion rate of 50 µg/min for the first parturient subsequent adjusted up or down by 10 µg/min depending on whether the previous parturient developed hypotension or not during the study period. The Dixon and Massey method and the isotonic regression method were used to calculate and compare the ED50 and 95% confidence interval (CI) of phenylephrine between the two groups. RESULTS: The results were 21.92 µg/min (95% CI, 14.90-28.94 µg/min) for Group S and 42.14 µg/min (95% CI, 24.58-59.70 µg/min) for Group O. The ratio of relative potency of Group O to Group S is 1.92 (95% CI 1.09-3.14), P = 0.034. CONCLUSIONS: The dose of phenylephrine for the prevention of hypotension after spinal anaesthesia for caesarean section is dependent on maternal BMI. Therefore, a weight-based phenylephrine dose is reasonable.

Effect of opioid-free anesthesia on postoperative analgesia after laparoscopic gynecologic surgery.

BACKGROUND: We performed this randomized controlled trial to evaluate the effect of opioid-free anesthesia (OFA) on postoperative analgesia after laparoscopic gynecologic surgery. METHODS: Seventy-eight patients undergoing laparoscopic gynecologic surgery were randomized to receive either OFA (group OF) or opioid-inclusive anesthesia (group C). Postoperative sufentanil consumption within the first 24 h, Visual Analogue Scale (VAS) for pain, postoperative equivalent milligrams of morphine (EMM), severity of postoperative nausea (PN) and vomiting (PV), prevalence of postoperative nausea and vomiting (PONV), use of antiemetics, time to first passage of flatus were compared by a two-tailed Student's t-test, Wilcoxon rank-sum tests or Fisher's exact tests. Repeated measures ANOVA was used to assess the effect of allocation of groups over time. RESULTS: The median [IQR] sufentanil consumption within 24 h was lower in group OF (4[4.5]) than in group C (6[8], mean difference [MD]=-2, 95% confidence interval [CI] [-4 to 0], P=0.029). The VAS scores at rest and during coughing at 6 h (P=0.009 at rest; P=0.002 during coughing), VAS scores during coughing at 2 h (P=0.013) and 4 h (P=0.008), EMM (P=0.026), severities of PN (P=0.003) and PV (P=0.003), and the mean time to first passage of flatus (P=0.017) was significantly less in group OF than that in group C. The prevalence of PONV (26.3% [group OF], 68.4% [group C], OR=0.31, 95% CI [0.158 to 0.589], P<0.001), use of antiemetics (5.3% [group OF], 28.9% [group C], OR=0.136, 95% CI [0.028 to 0.667], P=0.012) was also significantly different between groups. CONCLUSIONS: Compared to opioid-inclusive anesthesia during laparoscopic gynecologic surgery, OFA was associated with significant improvement in postoperative analgesia, reduced PONV incidence prevalence and severity, and faster first passage of flatus.

Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats.

BACKGROUND: Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics. METHODS: Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg-1·min-1 normal saline, group LE received 2 ml·kg-1·min-1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg-1·min-1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated. RESULTS: All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4-20.7] versus 7.2 [5.9-8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0-29.1] versus 11.3 [10.7-13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9-11.7] versus 5.6 [4.5-7.0], p = 0.060). CONCLUSIONS: Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

A Prospective Randomized Trial of Ropivacaine 5 mg with Sufentanil 2.5 µg as a Test Dose for Detecting Epidural and Intrathecal Injection in Obstetric Patients.

Objectives: Traditional epidural test dose is somewhat unsuited in obstetrics because of potential risk of severe adverse effects when it is accidentally injected into the subarachnoid space. Some hospitals use a proportion of the total dose of epidural labor analgesia as a test dose. The aim of our study was to assess the effectiveness and safety of ropivacaine 5 mg with sufentanil 2.5 µg to detect intrathecal injection. Methods: This prospective randomized study enrolled parturients who had the demand for epidural labor analgesia and randomly divided them into two groups. Then, 5 mL of 0.1% ropivacaine with sufentanil 2.5 µg was injected into the epidural space or the subarachnoid space in the epidural (EP) group and the intrathecal (IT) group, respectively. The ability to detect intrathecal injection and side effects were assessed to work out the effectiveness and safety. Results: For spinal injection, the sensitivity and the specificity of the symptoms of either warmth or numbness or both assessed at 3 min were both 100%, and the observed negative predictive value (NPV) and positive predictive value (PPV) were 100%. All parturients in the IT group and 2.33% of parturients in the EP group had sensory blockade to cold or pinprick (p < 0.0001). A total of 77.55% (38 of 49) of parturients in the IT group were found to have a motor block. A 10 min assessment showed the median cephalad cold and pin levels were T8 and T10, respectively, and the median Bromage score was 4 in the IT group. Incidences of adverse effects in both groups were low. Conclusions: Ropivacaine 5 mg with sufentanil 2.5 µg is effective and safe to detect intrathecal injection as an epidural test dose in obstetric patients.

Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy.

BACKGROUND: Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation. METHODS: Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed. RESULTS: The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels. CONCLUSIONS: In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus.