Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight.

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A. heterophyllum. Chemical profiling of the most effective fraction obtained via bioassay-guided fractionation was done using LC-MS (Liquid chromatography-mass spectrometry, a technique utilized in the identification, separation, and quantification of known and unknown compounds). Molecular docking analysis of characterized constituents was performed to recognize the binding receptors, followed by an evaluation of the tracheal relaxation ability of active fraction. An acute oral toxicity study of the most effective fraction was done using OECD guidelines 423. Further, the therapeutic efficacy of the fraction was validated in asthma using a guinea pig model of ovalbumin (OVA) induced allergic asthma. The bio-guided activity revealed that hydro-methanolic extract of A. heterophyllum roots (F-1) was the most active fraction. LC-MS analysis of F-1 showed the presence of six major bioactive compounds in F-1. Molecular docking studies revealed strong binding affinities of identified constituents with histaminic receptor (H1) and muscarinic receptor (M3). The ex vivo study demonstrated smooth muscle relaxant activity of F-1 via dysregulating diverse signal transduction pathways viz. histaminic and muscarinic receptors antagonism (non-competitive), stimulation of ß2-adrenergic receptor pathway, and soluble guanylyl cyclase activation. The findings of acute oral toxicity studies revealed that F-1 had no toxicity up to the dose of 2000 mg/Kg. The anti-asthmatic therapeutic efficacy of F-1 was further confirmed by the amelioration of respiratory hyperresponsiveness in asthmatic guinea pigs. This is the first evidence-based study showing the antiasthmatic therapeutic potential of the traditionally used herb A. heterophyllum through, computational and animal studies.

In vivo analgesic, anti-inflammatory, sedative, muscle relaxant activities, and docking studies of 3',4',7,8-tetrahydroxy-3-methoxyflavone isolated from Pistacia chinensis.

Background: Pistacia chinensis is extensively employed in traditional medicine. This study aimed to isolate and evaluate the therapeutic effects of 3'4'78-tetrahydroxy-3-methoxyflavone from P. chinensis crude extract. Materials and Methods: The study utilized column chromatography for isolation. The plant extract and its isolated compound were assessed for in vivo analgesic (hot plate model), anti-inflammatory (carrageenan-induced paw edema), sedative (open field model), and muscle relaxing properties (inclined plane and traction test). Results: In the thermal-induced analgesic model, a significant analgesic effect was observed for the extract (25, 50, and 100 mg/kg) and the isolated compound (2.5, 5, 10, and 15 mg/kg) at higher doses. The extract (100 mg/kg) significantly prolonged latency time (21.98 seconds) after 120 minutes of administration. The isolated compound elevated the latency time (20.03 seconds) after 30 minutes, remaining significant up to 120 minutes with a latency time of 24.11 seconds. The anti-inflammatory effect showed a reduction in inflammatory reactions by 50.23% (extract) and 67.09% (compound) after the fifth hour of treatment. Both samples demonstrated significant sedative effects, with the extract hindering movement by 54.11 lines crossed compared to the negative control (180.99 lines). The isolated compound reduced the number of lines crossed to 15.23±SEM compared to the negative control. Both samples were also significant muscle relaxants. Docking studies indicated that the compound's therapeutic effect is due to inhibiting COX and nociceptive pathways. Conclusion: The isolated compound from Pistacia chinensis exhibits significant analgesic, anti-inflammatory, sedative, and muscle relaxing properties, with potential therapeutic applications by inhibiting COX and nociceptive pathways.

Association of Opioid and Concurrent Benzodiazepine, Skeletal Muscle Relaxant, and Gabapentinoid Usage on Healthcare Expenditure and Resource Utilization: A Serial Cross-Sectional Study, 2009 to 2019.

BACKGROUND: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified. We sought to characterize healthcare costs and expenditures associated with a population reporting concurrent CNS depressants and opioid use compared with nonopioid analgesics in the United States from 2009 to 2019. METHODS: A serial cross-sectional design was used to compare the healthcare expenditures of adult Medical Expenditure Panel Survey respondents who were prescribed nonopioid analgesics, opioids only, opioids/benzodiazepines (BZD), opioids/BZD/skeletal muscle relaxants (SMR), or opioids/gabapentin (gaba) using pooled data from 2009 to 2019. Expenditure (cost and resource utilization) categories included inpatient, outpatient, office-based, and prescription medicine. Average marginal effects were used to compare survey-weighted annual costs and resource utilizations across the groups as compared to nonopioid analgesic respondents, adjusted for covariates. RESULTS: A weighted total of 34 241 838 individuals were identified. Most were opioid-only respondents (46.5%), followed by nonopioid analgesic (43.4%), opioid/BZD (5.3%), opioid-gaba (3.5%), and opioid/BZD/SMR respondents (1.3%). In comparison to the study groups with nonopioid analgesics, opioid-gaba users had the highest significant incremental cost difference among the different pairings (+$11 684, P < .001). Opioid-gaba, opioid/BZD, and opioid/BZD/SMR respondents had significantly higher inpatient, emergency department, and prescription drug costs and use compared to nonopioid analgesic respondents. Opioid-only respondents had higher outpatient and office-based costs and visits compared to nonopioid analgesic respondents. CONCLUSIONS: As healthcare providers seek to utilize fewer opioids for pain management, attention must be paid to ensuring safe and effective use of concurrent CNS depressants to mitigate high healthcare costs and burden.

Muscle relaxant and antipyretic effects of pentacyclic triterpenes isolated from the roots of Diospyros lotus L.

The present article describes the muscle relaxant and antipyretic effects of pentacyclic triterpenes, oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) isolated from roots of Diospyros lotus in animal models. The muscle relaxant effects of isolated pentacyclic triterpenes were determined by chimney and inclined plane tests. In the chimney test, pretreatment of pentacyclic triterpenes evoked significant dose dependent influence on muscle coordination. When administered intraperitoneally (i.p.) to mice at 10 mg/kg for 90 min, OA, UA, and BA exhibited muscle relaxant effects of 66.72 %, 60.21 %, and 50.77 %, respectively. Similarly, OA, UA, and BA (at 10 mg/kg) illustrated 65.74 %, 59.84 % and 51.40 % muscle relaxant effects in the inclined plane test. In the antipyretic test, significant amelioration was caused by pretreatment of all compounds in dose dependent manner. OA, UA, and BA (at 5 mg/kg) showed 39.32 %, 34.32 % and 29.99 % anti-hyperthermic effects, respectively 4 h post-treatment, while at 10 mg/kg, OA, UA, and BA exhibited 71.59 %, 60.99 % and 52.44 % impact, respectively. The muscle relaxant effect of benzodiazepines is well known for enhancement of GABA receptors. There may exist a similar mechanism for muscle relaxant effect of pentacyclic triterpenes. The in-silico predicted binding pattern of all the compounds reflects good affinity of compounds with GABAA receptor and COX-2. These results indicate that the muscle relaxant and antipyretic activities of these molecules can be further improved by structural optimization.

The Use of Muscle Relaxants After Chemotherapy and Radiotherapy.

Introduction: Patients after chemotherapy and radiotherapy while being operated can suffer from different systemic problems, which may complicate the anesthetic management. Some interactions between muscle relaxants and chemotherapeutics can occur. Aim: This article aims to present the use of muscle relaxants in cancer patients who have undergone chemotherapy and radiotherapy. Material and Methods: Our work is based on the available literature and the authors' experience. Conclusion: Based on our observations and a thorough examination of the medical literature, it is advisable to exercise significant caution when employing muscle relaxants in individuals undergoing chemotherapy and radiotherapy. All muscle relaxants can behave differently after chemotherapy and radiotherapy, and for this reason, practitioners should familiarize themselves with the pharmacodynamics and pharmacokinetics of their chosen muscle relaxant.

Comparison of Magnesium Pre-treatment With Two Different Doses of Rocuronium in Rapid Sequence Intubation: A Randomized Controlled Trial.

Introduction Magnesium is recognized for its ability to reduce the onset time of rocuronium while simultaneously extending its duration of action. This study aims to assess the efficacy of magnesium pre-treatment in decreasing the onset time with two different doses of rocuronium in patients undergoing rapid sequence intubation. Materials and methods This randomized prospective double-blind clinical study involved 50 patients classified as American Society Of Anesthesiologists (ASA) I/II, with no preoperative indications of difficult intubation, undergoing elective surgery under general anesthesia. The patients were divided into two groups: group A received 60 mg/kg of magnesium 15 minutes before intubation with 1.2 mg/kg of rocuronium, and group B received 60 mg/kg of magnesium before 0.6 mg/kg of rocuronium. Intubating conditions were assessed and graded at loss of last twitch after administration in both groups, considering ease of intubation, vocal cord position, and response to the insertion of the tracheal tube. Simultaneously, hemodynamic variations were recorded just before intubation, at one minute and five minutes post-intubation. Results Intubating conditions with 0.6 mg/kg of rocuronium were comparable or equally good compared to 1.2 mg/kg of rocuronium with magnesium pre-treatment. Conclusions Magnesium pre-treatment enhances the neuromuscular blocking effect of rocuronium, reducing its onset time without clinically significant prolongation of the duration of the block.

Comparison of diclofenac with tramadol, tizanidine or placebo in the treatment of acute low back pain and sciatica: multi-center randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

Effects of a single dose of rocuronium in patients with different body fat percentages: A randomised controlled trial.

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.

Impact of the combination of abdominal peripheral nerve block and neuromuscular blockade on the surgical space during robot-assisted laparoscopic surgery: a prospective randomized controlled study.

PURPOSE: The impact of the combination of abdominal peripheral nerve block (PNB) and the depth of neuromuscular blockade on the surgical field were assessed. METHODS: Thirty-eight patients undergoing elective robot-assisted laparoscopic radical prostatectomy (RARP) were randomized into two groups: a PNB group (moderate neuromuscular block [train-of-four 1-3 twitches] with abdominal PNB) and a non-PNB group (deep neuromuscular block [post-tetanic count 0-2 twitches] without abdominal PNB). The primary outcome was the change in the depth of the abdominal cavity relaxation assessed by the change in the distance (Δdistance) between the umbilicus port and peritoneum upon pneumoperitoneal pressure increase from 8 to 12 mmHg. The secondary outcomes were the CO2 usage for the pneumoperitoneal pressure increase and the subjective differences in the Surgical Rating Score (SRS) during surgery. RESULTS: The Δdistance and the CO2 usage from 8 to 12 mmHg did not differ significantly between the non-PNB and PNB groups (1.34 ± 0.65 vs. 1.28 ± 0.61 cm, p = 0.763 and 3.64 ± 1.68 vs. 4.34 ± 1.44 L, p = 0.180, respectively). There was also no significant difference in SRS. Comparisons of the Δdistance values for pressure increases from 6 to 8 mmHg, 6 to 10 mmHg and 6 to 12 mmHg between the non-PNB and PNB groups also showed no between-group differences, despite significant intra-group differences (p < 0.001) by pressure increment. CONCLUSIONS: Our findings indicate that moderate neuromuscular block with abdominal PNB maintained an adequate surgical space for RARP, with no significant difference from the space achieved by deep neuromuscular block.

Case report: Treatment of cyclobenzaprine ingestion in two dogs with intravenous intralipid therapy.

Introduction: The objective of this case series is to describe the clinical signs and outcome of cyclobenzaprine ingestion in two dogs treated with intralipid emulsion (ILE) and supportive care. Case or series summary: Two dogs presented for evaluation of cyclobenzaprine ingestion. A 4-year-old female spayed Rat Terrier (dog 1) presented within 4 h of ingestion of cyclobenzaprine (between 9.7 and 25.9 mg/kg). The dog experienced abnormal behavior, agitation, tremors, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. The dog was treated with ILE, cyproheptadine, and activated charcoal. All clinical signs resolved after treatment. A 5-month-old female intact mixed-breed dog (dog 2) presented after ingestion of an unknown amount of cyclobenzaprine 2-3 h prior to presentation. The dog experienced dull mentation, tremors, loss of gag reflex, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. Orogastric decontamination was performed via gastric lavage, and activated charcoal was given via orogastric tube, followed by ILE. All clinical signs resolved after therapeutic intervention. Discussion: This is the first report documenting clinical signs of cyclobenzaprine toxicity in two dogs followed by successful treatment with gastric emptying, ILE, and supportive care.

Baclofen and the risk of fall and fracture in older adults: A real-world cohort study.

BACKGROUND: The growth of oral muscle relaxant prescriptions among older adults in the United States is concerning due to the drugs' adverse sedative effects. Baclofen is a gamma-aminobutyric acid agonist muscle relaxant that is associated with encephalopathy. We characterized the risk of fall and fracture associated with oral baclofen against other muscle relaxants (tizanidine or cyclobenzaprine) in older adults. METHODS: We designed a new-user, active-comparator study using tertiary health system data from Geisinger Health, Pennsylvania (January 2005 through December 2018). Older adults (aged ≥65 years) newly treated with baclofen, tizanidine, or cyclobenzaprine were included. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the treatment groups on 58 baseline characteristics. Fine-Gray competing risk regression was used to estimate the risk of fall and fracture. RESULTS: The study cohort comprised of 2205 new baclofen users, 1103 new tizanidine users, and 9708 new cyclobenzaprine users. During a median follow-up of 100 days, baclofen was associated with a higher risk of fall compared to tizanidine (IPTW incidence rate, 108.4 vs. 61.9 per 1000 person-years; subdistribution hazard ratio [SHR], 1.68 [95% CI, 1.20-2.36]). The risk of fall associated with baclofen was comparable to cyclobenzaprine (SHR, 1.17 [95% CI, 0.93-1.47]) with a median follow-up of 106 days. The risk of fracture was similar among patients treated with baclofen versus tizanidine (SHR, 0.85 [95% CI, 0.63-1.14]) or cyclobenzaprine (SHR, 0.85 [95% CI, 0.67-1.07]). CONCLUSIONS: The risk of fall associated with baclofen was greater than tizanidine, but not compared to cyclobenzaprine in older adults. The risk of fracture was comparable among the older users of baclofen, tizanidine, and cyclobenzaprine. Our findings may inform risk-benefit considerations in the increasingly common clinical encounters where oral muscle relaxants are prescribed.

Does adding muscle relaxant make post-operative pain better? a narrative review of the literature from US and European studies.

Centrally acting skeletal muscle relaxants (CASMR) are widely prescribed as adjuncts for acute and chronic pain. Given the recent interest in multimodal analgesia and reducing opioid consumption, there has been an increase in its use for perioperative/postoperative pain control. The mechanism of action, pharmacodynamics, and pharmacokinetics of these drugs vary. Their use has been studied in a wide range of operative and non-operative settings. The best evidence for the efficacy of CASMRs is in acute, nonoperative musculoskeletal pain and, in the operative setting, in patients undergoing total knee arthroplasty and abdominal surgery, including inguinal herniorrhaphy and hemorrhoidectomy. The risk of complications and side effects, coupled with the limited evidence of efficacy, should prompt careful consideration of individual patient circumstances when prescribing CASMRs as part of perioperative pain management strategies.

Bilateral tonic seizures probably induced by eperisone hydrochloride: a case report.

Eperisone hydrochloride is a central muscle relaxant used to treat osteoporosis. Seizures are rare side effects of eperisone hydrochloride and have been previously reported in the medical literature in overdose situations but not at regular doses. This case report describes a 42-year-old male painter who developed severe bilateral tonic seizures after the initiation of eperisone hydrochloride at regular doses for low back pain. Symptoms gradually eased in the days following the discontinuation of eperisone hydrochloride and antiepileptic treatment, with no recurrence. This rare adverse drug reaction warrants clinical awareness; however, the mechanisms underlying these adverse reactions remain to be clarified.

Electrocardiogram Cream Reduces Skin-Electrode Impedance Upon Neuromuscular Monitoring Using TOF-Cuff®.

Background Mechanistic insight into the high failure rate of TOF-Cuff® (RGB Medical Devices, Madrid, Spain) measurements on the lower leg is unclear. Aims We aimed to determine whether materials applied to pseudo-skin can reduce the impedance between a model arm and TOF-Cuff® electrodes and whether a material between TOF-Cuff® electrodes and the patient's skin surface decreases the skin-TOF-Cuff® electrode impedance within the appropriate range. Methods This was a combination of an in vitro study using non-living materials and a prospective observational clinical study. Eight patients aged > 70 years who had undergone elective surgery were eligible. One of the primary outcomes was whether water, electrocardiogram (ECG) cream, or ECG gel applied on the pseudo-skin could reduce the impedance between the model arm and the TOF-Cuff® electrodes in the in vitro study. Another was whether a material between the TOF-Cuff® electrodes and the patient's skin surface decreased the skin-TOF-Cuff® electrode impedance to an appropriate level of less than 5,000 Ω in the clinical study. Results The application of water, ECG cream, and ECG gel similarly reduced the impedance values within the electrical circuit in the in vitro study. ECG cream application between the patient's skin surface and the TOF-Cuff® electrodes decreased the skin-TOF-Cuff® electrode impedance (median (interquartile range (IQR)) Ω) from 8,600 (6,450 to 9,775) to 2,000 (1,600 to 2,600) (P = 0.012) in surgical patients. Conclusion ECG cream application between the patient's skin surface and the TOF-Cuff® electrodes decreased the skin-TOF-Cuff® electrode impedance appropriately, and thus, the application can facilitate precise TOF-Cuff® measurements in patients.

Propofol TCI or sevoflurane anesthesia without muscle relaxant for thoracoscopic thymectomy in myasthenia gravis patients: a prospective, observational study.

BACKGROUND: Myasthenia gravis (MG) patients interact unpredictably with anesthetic agents, including neuromuscular blocking agents. Here, we investigate the effectiveness of general anesthesia without muscle relaxants using either propofol via target-controlled infusion systems (TCI) or sevoflurane in MG patients undergoing thoracoscopic thymectomy. METHODS: This prospective, open-label, observational study was conducted in a university hospital. We included 90 myasthenic patients undergoing thoracoscopic thymectomy with general anesthesia. Patients received induction and maintenance anesthesia with propofol TCI (group P, n = 45) or induction with propofol 2-3 mg.kg-1 and maintenance anesthesia with sevoflurane (group S, n = 45). In both groups, the procedure was performed under the guidance of entropy with sufentanil but not a muscle relaxant. Intubation conditions, hemodynamic changes, respiratory function, neuromuscular transmission, arterial blood gas, and complications were evaluated. RESULTS: All patients achieved good intubation conditions. Hemodynamic instability was more frequent in group S than in group P, mostly in the induction stage, and was controllable. The reduction in the intraoperative train-of-four ratio from baseline at 30 min, 60 min, and 90 min in group S was 10.3%, 14.2%, and 14.3%, respectively, significantly higher than that in group P (6.8%, 7.2%, and 8.4%, respectively), which completely recovered at the end of the surgery. All patients were extubated in the operating room without complications. No other significant differences between the groups were observed. CONCLUSIONS: Anesthesia with propofol TCI or sevoflurane without muscle relaxants in MG patients offered safe and effective conditions for thoracoscopic thymectomy. Sevoflurane achieved higher levels of intraoperative muscular relaxation than propofol TCI. Postoperative neuromuscular function was not affected by these anesthetics.

Baclofen Toxicity in a Dialysis-Dependent Patient: A Case Report.

Baclofen toxicity is a significant concern, particularly in patients with advanced chronic kidney disease. We present a case of a 74-year-old female who developed depressed consciousness after receiving 20 mg of baclofen for back pain control. A presumptive diagnosis of baclofen toxicity was made, and the patient underwent continuous hemodialysis sessions, leading to neurological recovery within two days. This case highlights the risk of baclofen toxicity in dialysis-dependent patients with advanced chronic kidney disease, emphasizing the importance of vigilance and alternative treatment options in this population.

Tonic down-rolling and eccentric down-positioning of eyes under sevoflurane anesthesia without non-depolarizing muscle relaxant and its relationship with depth of anesthesia.

Purpose: To analyze the relationship between eccentric downward eye movement/eccentric downward eye-positioning (EDEM/EDEP) encountered in patients undergoing ophthalmic surgeries and its return to a centralized position under general anesthesia (GA) with the depth of anesthesia (DOA). Methods: Patients undergoing ophthalmic surgeries (6 months-12 years) under sevoflurane anesthesia without non-depolarizing muscle relaxant (NDMR) who witnessed a sudden tonic EDEM/EDEP were both retrospectively (R-group) and prospectively (P-group) enrolled (ambispective study). R-group included data-points after induction (AI) till the time surgery lasted while P-group compiled data both during induction (DI) and AI. DOA in terms of MAC (minimum alveolar concentration) at the time of EDEM/EDEP and centralization of eyeball and their timings were noted and compared for both AI and DI data-points. Also, vertical eccentric eye positions were scored and correlated with MAC. Results: AI data included 22 (14R+8P) events and their mean MAC of EDEM/EDEP and centralization were 1.60 ± 0.25 and 1.18 ± 0.17 respectively (p = 0.000). DI data included 62 (P) cases and its mean MAC of EDEM/EDEP and centralization was 2.19 ± 0.43 and 1.39 ± 0.26 respectively (p = 0.000). Median (IQR) eye positions during down-positioning in 84 events was -3 (-3.9 to -2.5). It was preceded by an eccentric upward drift of eyes in 10/22 (6R+4P) AI cases. A strong negative correlation was seen between DOA and eccentric eye positions (r = -0.77, p = 0.000). Conclusions: Tonic down-rolling of eyes is not uncommon in children seen without NDMR with higher depths of sevoflurane anesthesia compared to point of centralization and fluctuations in DOA should be avoided to circumvent inadvertent complications during ocular surgery.

The evolution of anesthesia management of patients with anterior mediastinal mass.

Anesthesia management of patients with mediastinal mass compressing the central airway is considered challenging. It is widely believed that general anesthesia induction in patients with mediastinal mass is associated with airway collapse, difficulty in ventilation and hemodynamic compromise. Additionally, several case reports and case series described patients demise after induction of general anesthesia. This has led to the strong recommendations to use inhalation induction, avoid the use of muscle relaxant and maintenance of spontaneous ventilation. Recent studies shed new light on our understanding of airway changes associated with mediastinal mass by directly visualizing and measuring the actual changes of the airway caliber and the variation in the peak inspiratory flow (PIF) and peak expiratory flow (PEF) in patients with mediastinal mass. These studies describe the changes in airway mechanics in different states e.g., awake and anesthetized, spontaneous and positive pressure ventilated with or without muscle relaxation. Interesting new findings in these recent publications show that general anesthesia with and without muscle relaxation does not worsen a pre-existing narrowing of the airway compressed by mediastinal mass. Moreover, it was discovered that the addition of positive pressure ventilation, positive end-expiratory pressure (PEEP) and muscle relaxation in an anesthetized patient were associated with improvement in the airway caliber and airflow in these patient's population. This new understanding of the mechanics of airway obstruction and the effects of anesthesia and mechanical ventilation on patients with mediastinal mass challenges our current anesthesia practices and leads us to consider a new approach to anesthetize and ventilate these patients. This article will review the past literature that led to the widely practiced current anesthesia techniques and how it is challenged with the new research. The author will also provide a new perspective and anesthesia technique that align with the new research findings for safe induction and maintenance of general anesthesia in patients with mediastinal mass.

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

BACKGROUND: Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential. OBJECTIVES: The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T. indica. METHODS: The most active fraction of T. indica leaves selected through bio-guided activity was subjected to liquid chromatography-mass spectrometry (LC-MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F-2 (chloroform fraction prepared from methanolic extract of T. indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea-pig. Further, F-2 was evaluated through in vivo studies employing ovalbumin-induced asthma model in guinea-pigs. RESULTS: F-2 was found most effective in bioassay-guided fractionation. Characterization by LC-MS analysis revealed presence of five major bioactive compounds in F-2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F-2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, ß2-adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F-2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE). CONCLUSION: These results confirm the traditional use of T. indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.