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To investigate the association between labor epidural analgesia exposure and the risk of autism spectrum disorder in offspring, this meta-analysis reviewed relevant literature from Medline, Cochrane Library, Google Scholar, and EMBASE databases from inception to May 2022 to evaluate the overall adjusted risk of autism spectrum disorder in offspring (primary outcome) and adjusted risks of autism spectrum disorder focusing on sibling-matched data, children who were delivered vaginally, and duration of labor epidural analgesia exposure (secondary outcomes). Pooled results of seven eligible observational studies involving 4,021,406 children revealed slightly higher risks of autism spectrum disorder in children with labor epidural analgesia exposure than those without (hazard ratio = 1.11, 95% confidence interval: 1.06–1.16, I2 = 67%, seven studies, level of evidence: very low). Consistent findings were found in subgroup analysis focusing on sibling data (hazard ratio: 1.10, 95% confidence interval: 1.02–1.18, I2 = 0%, five studies) and children delivered vaginally (hazard ratio: 1.11, 95% confidence interval: 1.06–1.17, I2 = 64%, seven studies). The tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia 8 h (two studies). Although our results demonstrated a slightly increased risk of autism spectrum disorder in offspring with previous labor epidural analgesia exposure, the small effect size and lack of cumulative dose–response effect precluded tangible evidence supporting the association. Lay abstract A previous meta-analysis has demonstrated a superior analgesic efficacy of epidural analgesia (e.g. labor epidural analgesia) in comparison with non-epidural approaches. The widely accepted safety of labor epidural analgesia also endorses its current popularity in obstetric practice. However, the results of a recent large-scale longitudinal study that demonstrated a significant increase in risk of autism spectrum disorder in offspring from mothers with labor epidural analgesia exposure have raised some concerns over the safety of its use. The current meta-analysis aimed at examining the strength of evidence regarding this issue based on updated clinical data. Through systematically reviewing seven eligible observational studies involving 4,021,406 children from electronic databases, our results showed a slight but statistically significant increase in risk of autism spectrum disorder in children with exposure to labor epidural analgesia compared with those without. The finding was consistent in subgroup analysis focusing on siblings and children delivered vaginally. Nevertheless, despite the tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia 8 h (data from two studies). In conclusion, the level of evidence linking labor epidural analgesia to autism spectrum disorder development in offspring was very low based on the latest data because of the small effect size and the finding of a lack of cumulative dose–response effect in the current analysis. Further studies are warranted to provide an insight into this issue.

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund’s Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.

Airway management in patients with giant neck masses is usually a challenge to anesthesiologists. A giant neck mass could compress the airway and thus impede endotracheal intubation. We encountered a situation where the giant neck masses of a patient pushed the epiglottis posteriorly toward the posterior pharyngeal wall and compressed the laryngeal aperture narrowing after anesthetic induction, causing direct laryngoscopic intubation and sequential fiber-optic intubation failed. The neck masses twisted the aryepiglottic fold tortuously and clogged the laryngeal aperture tightly, making a flexible fiber-optic bronchoscope unable to pass through the laryngeal aperture. Later, we utilized a McCoy laryngoscope alternately to lift the compressed larynx up and away from the posterior pharyngeal wall, creating a passage and completing endotracheal intubation successfully with the aid of a gum elastic bougie. Our case suggested that the tilting tip blade of the McCoy laryngoscope could lever the tongue base up against the tumor mass compression to improve laryngeal views and facilitate endotracheal intubation when a difficult fiber-optic intubation was encountered on a compressed laryngeal aperture.

We hypothesized that optimal laryngeal mask airway (LMA) insertion conditions might be achieved with topical lidocaine and a smaller dose of propofol. In this study, insertion conditions after topical lidocaine 40 mg followed by propofol 2 mg.kg(-1) were compared with propofol 2 mg.kg(-1) or propofol 3 mg.kg(-1) alone.Ninety patients were recruited for this randomized prospective double-blind study. One group received four sprays of topical lidocaine (40 mg) over the posterior pharyngeal wall followed by propofol 2 mg.kg(-1) (Group 2PL; n = 30). The other two groups received four sprays of 0.9% normal saline followed by propofol 2 mg.kg(-1) (Group 2P; n = 30) or by propofol 3 mg.kg(-1) (Group 3P; n = 30). The frequency of optimal insertion conditions (successful insertion at the first attempt without adverse responses) and side effects were recorded.The frequency of optimal insertion conditions was greater in Group 2PL (20/30, 67%) and Group 3P (22/30, 73%) than in Group 2P (11/20, 37%) (P = 0.009). In Group 3P, the mean blood pressure was lower than in the other groups prior to LMA-Classic insertion (P = 0.003) but was similar after insertion. The incidence of apnea was greater in Group 3P patients (17/30, 57%) than in Group 2P (2/30, 7%) or Group 2PL patients (1/30, 3%) (P0.001).Topical lidocaine 40 mg followed by propofol 2 mg.kg(-1) can provide optimal insertion conditions of the LMA-Classic comparable to those of propofol 3 mg.kg(-1), with fewer hemodynamic changes and a lower incidence of apnea.

From the Department of Anesthesiology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan. Address reprint requests to: Kuo-Chuan Hung, MD, 1, E-Da Road, Jiau-shu Tsuen, Yan-Chau Shiang, Kaohsiung, Taiwan, 824. E-mail: ed102605@gmail.com © 2016 Elsevier Inc. All rights reserved. 1053-0770/2602-0033$36.00/0 http://dx.doi.org/10.1053/j.jvca.2015.06.016

Background: Animal and human studies indicate that genetics may contribute to the variability of morphine efficacy. A recent report suggested that cancer patients homozygous for the 118G allele caused by the single nucleotide polymorphism at nucleotide position 118 in the -opioid receptor gene require higher doses of morphine to relieve pain. The purpose of the current study was to investigate whether this polymorphism contributes to the variability of morphine efficacy in women who undergo abdominal total hysterectomy. Methods: After informed consent was obtained, 80 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective total hysterectomy surgery were enrolled in this study. All patients received general anesthesia and were screened for A118G polymorphism by blood sample. Intravenous morphine patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The authors recorded the morphine consumption doses and demand times. Pain at rest and side effects were measured with rating scales. Results: Forty-three women were A118 homozygous, 19 were heterozygous, and 18 were G118 homozygous. Patients homozygous for G118 required more morphine doses (33 10 mg) to achieve adequate pain relief compared with patients homozygous for A118 (27 10 mg) in the first 24 h (P 0.02). However, there was no statistically significant difference for morphine consumption at 48 h. Conclusion: Genetic variation of the -opioid receptor may contribute to interindividual differences in postoperative morphine consumption. In the future, identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control. IT has been known for a long time that the effects of morphine as an agent for pain control vary in different individuals. Morphine produces its clinical effects mainly through -opioid receptors. Polymorphisms in the -opioid receptor gene may be associated with the clinical effects of opioid analgesics, 1–3 which encourages research into human genetic polymorphisms and their clinical consequences. Several single nucleotide polymorphisms (SNPs) have been identified in the human -opioid receptor gene. The A118G mutation is the most common one leading to a change in the gene product in the human -opioid receptors, which is an A to G substitution in exon 1 and results in an amino acid exchange at position 40 from asparagine to aspartate (N40D). 4 Functional effects of the A118G polymorphism have been demonstrated both in vitro and in vivo. In vitro, -endorphin has been shown to bind three times more tightly at the receptor of homozygous G allele than at that of homozygous A allele. 4 A recent report also suggested that cancer patients who were homozygous for the G118 variant required higher doses of oral morphine for long-term treatment of their pain. 2 Romberg et al. 5,6 studied the pharmacokinetics and pharmacodynamics of morphine-6-glucuronide (M6G), a -opioid agonist, and also found that A118G mutation of the human -opioid receptor gene reduced analgesic responses to M6G. The effect of -opioid receptor genotype on acute postoperative morphine requirements has not been reported; therefore, we decided to determine morphine consumption with intravenous patient-controlled analgesia in women undergoing total abdominal hysterectomy according to A118G polymorphism.

The ProSeal™ laryngeal mask airway (PLMA) offers a more effective seal and is easier for gastric tube placement to prevent aspiration than the classical laryngeal mask airway. However, it is more difficult to insert with the digital and introducer tooling techniques. The Rusch Flexi-Slip stylet (RFSS) is an accessory intubation tool that consists of a malleable coated wire and a soft atraumatic tip. It has been reported that it can facilitate easier insertion of the PLMA. Here, we report two cases in which the PLMA could not be inserted correctly on the initial attempts, and with successful placement of the PLMA after using an RFSS. In the first case, three attempts to insert the PLMA with the digital and introducer tooling techniques were unsuccessful. The second case was known to be difficult for PLMA placement because, in a previous operation, PLMA insertion for general anesthesia was unsuccessful, and in that instance required endotracheal intubation for general anesthesia. In both cases, the PLMA was successfully inserted using the RFSS technique, without difficulty. The RFSS technique offers several advantages for PLMA insertion, including the provision of effective support and a soft tip for the PLMA insertion. Other techniques to facilitate the insertion of the PLMA, including priming the drain tube with a guide are discussed. We recommend that the RFSS technique offers an effective method for cases with difficult insertion of the PLMA.

The delayed and incomplete sensory block of the sacral roots in epidural anesthesia often results from too huge the size of the first sacral nerve root. To overcome the problem, the enhancement of anesthetic effect on the sacral segment by injecting the local anesthetic toward the caudal direction has been reported. Thus, in this study, we compared the anesthetic effects of epidural anesthesia by catheterization toward caudal direction with that toward cephalic direction on the areas innervated by the sacral nerve roots.The study enrolled 45 ASA physical status I or II patients scheduled for ankle surgery or hemorrhoidectomy who were randomly and evenly divided into two groups. The epidural catheter was placed either cephalad (EU group) or caudad (ED group) and confirmed by C-arm fluoroscopy after catheter insertion. Each group finally consisted of 10 patients for ankle surgery and 10 for hemorrhoidectomy after exclusion of the ineligibles. The onset time, duration of, and recovery time from epidural anesthesia, as well as demand of intra-operative analgesic in the two groups were recorded and compared.No significant differences were noted in the patients' characteristics between the two groups. There were also no statistically significant differences in onset, duration, recovery time, and anesthetic level attained between the two groups. More patients in the EU group demanded analgesics during surgery than did patients in the ED group. However, there were no statistically significant differences in the rate of analgesic demand between the two groups.Epidural injection of local anesthetic via catheter oriented caudad or cephalad did not change the characteristics of epidural anesthesia including onset time, duration, anesthetic level, and analgesic effect on the surgical areas innervated by the sacral roots.

To investigate whether the incidence of hiccups in patients undergoing esophagogastroduodenoscopy (EGD) or same-day bidirectional endoscopy (EGD and colonoscopy; BDE) with sedation is different from those without sedation in terms of quantity, duration and typical onset time.Consecutive patients scheduled for elective EGD or same-day BDE at the gastrointestinal endoscopy unit or the health examination center were allocated to two groups: EGD without sedation (Group A) and BDE with sedation (Group B). The use of sedation was based on the patients' request. Anesthesiologists participated in this study by administrating sedative drugs as usual. A single experienced gastroenterologist performed both the EGD and the colonoscopic examinations for all the patients. The incidence, duration and onset time of hiccups were measured in both groups. In addition, the association between clinical variables and hiccups were analyzed.A total of 435 patients were enrolled in the study. The incidences of hiccups in the patients with and without sedation were significantly different (20.5% and 5.1%, respectively). The use of sedation for patients undergoing endoscopy was still significantly associated with an increased risk of hiccups (adjusted odds ratio: 8.79, P0.001) after adjustment. The incidence of hiccups in males under sedation was high (67.4%). The sedated patients who received 2 mg midazolam developed hiccups more frequently compared to those receiving 1 mg midazolam (P = 0.0028). The patients with the diagnosis of gastroesophageal reflux disease (GERD) were prone to develop hiccups (P = 0.018).Male patients undergoing EGD or BDE with sedation are significantly more likely to suffer from hiccups compared to those without sedation. Midazolam was significantly associated with an increased risk of hiccups. Furthermore, patients with GERD are prone to develop hiccups.