Dexamethasone and dexmedetomidine as adjuvants to ropivacaine do not prolong analgesia in wound infiltration for lumbar spinal fusion: a prospective randomized controlled study.

BACKGROUND AND OBJECTIVES: Local anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when added to LA agents, could improve and prolong analgesia. The aim of this trial was to evaluate the analgesic efficacy and opioid-sparing properties of dexamethasone and dexmedetomidine when added to ropivacaine for wound infiltration in transforaminal lumbar interbody fusion (TLIF). METHODS: We conducted a controlled study among 68 adult patients undergoing TLIF, which was prospective, randomized and double-blind in nature. The participants were divided into four equal groups at random. Group R was given 150 mg of 1% ropivacaine (15 mL) and 15 mL of normal saline. Group R + DXM received 150 mg of 1% ropivacaine (15 mL) and 10 mg of dexamethasone (15 mL). Group R + DEX received 150 mg of 1% ropivacaine (15 mL) and 1 µg/kg of dexmedetomidine (15 mL). Lastly, group R + DXM + DEX was given 150 mg of 1% ropivacaine (15 mL), 10 mg of dexamethasone and 1 µg/kg of dexmedetomidine (15 mL). The primary focus was on the length of pain relief provided. Additionally, secondary evaluations included the amount of hydromorphone taken after surgery, the numerical rating scale and safety assessments within 48 h after the operation. RESULTS: Based on the p value (P > 0.05), there was no significant variance in the duration of pain relief or the total usage of hydromorphone after surgery across the four groups. Similarly, the numerical rating scale scores at rest and during activity at 6-, 12-, 24- and 48-h post-surgery for all four groups showed no difference (P > 0.05). However, the incidence of delayed anesthesia recovery was slightly higher in group R + DEX and group R + DXM + DEX when compared to group R or group R + DXM. Furthermore, there were no significant differences between the four groups in terms of vomiting, nausea, dizziness or delayed anesthesia recovery. CONCLUSION: For wound infiltration in TLIF, the addition of dexamethasone and dexmedetomidine to ropivacaine did not result in any clinically significant reduction in pain or opioid consumption and could prompt some side effects.

A Comprehensive Review of the Use of Alpha 2 Agonists in Spinal Anesthetics.

BACKGROUND: Spinal Anesthesia was the first regional anesthetic technique to be performed. It was performed by Dr. August Bier, known for the Bier block, and his colleagues on August 16, 1898. Dr. Bier opted for, what he referred to at the time as "cocainization of the spinal cord" by introducing 15 mg of cocaine intrathecally prior to the operation. The surgery was largely uneventful and painless. The patient only experienced some vomiting and a headache postoperatively. Dr. Bier's use of neuraxial anesthesia aimed to directly inject local anesthetics in and around the central nervous system (CNS) for more direct control of pain and anesthesia. Local anesthetics were an important discovery in anesthesiology. However, since the advent of local anesthetics and spinal anesthesia as an alternative technique to general anesthesia, much has been learned about both the benefits and adverse effects of local anesthetics. It was quickly learned that use of local anesthetics would be limited by their potential for life-threatening toxic effects. For this reason, there was a push towards development of novel local anesthetics that had a larger therapeutic window with less likelihood of serious side effects. In addition to developing newer local anesthetics, the idea of adding adjuvants provided an opportunity to potentially limit the life-threatening events. These adjuvants would include medications such as epinephrine and alpha-2 agonists, such as clonidine and dexmedetomidine. Other adjuvants include opioids, glucocorticoids, and mineralocorticoids. OBJECTIVES: In this review, we will delve further into the indications, contraindications, uses, mechanisms, and future of spinal anesthesia and its adjuvants. STUDY DESIGN: A literature review of recent publications in the field of alpha 2 agonists used in spinal anesthetics was carried out from 2015 to present day. Consensus opinions were formulated in various areas. SETTING: This literature review was carried out at various medical universities throughout the nation and Europe. LIMITATIONS: As research has only just begun in this field data is limited at this time. CONCLUSIONS: The use of spinal anesthesia provides a reliable dermatome blockade to facilitate many different surgical procedures. The combination of local anesthetics with opioid medications within the subarachnoid space has been the standard of care. Adjuvant medications like alpha 2 agonists may play a significant role in prolonging spinal blockade as well as limiting cardiovascular complications such as hypotension and bradycardia. The use of alpha 2 agonists instead of opioid medications intrathecally decreases pruritus and delayed respiratory depression. Animal models have demonstrated the synergistic effects of utilizing alpha 2 agonists with opioids in the subarachnoid space. The addition of clonidine to fentanyl and local anesthetic demonstrated a shorter time to neural blockade, but no significant change in duration of the spinal. Interestingly alpha 2 agonists with local anesthetics showed increase block duration compared to opioid with local anesthetics. Further human trials need to be undertaken to analyze the effectiveness of alpha 2 agonists in the intrathecal space, but preliminary data does indicate it is an exemplary alternative to opioids.

Efficacy of Nalbuphine as a Local Anesthetic Adjuvant for Brachial Plexus Block: A Systematic Review and Meta-analysis.

BACKGROUND: Nalbuphine has been increasingly used as a local anesthetic adjuvant to extend the duration of analgesia in brachial plexus block (BPB). OBJECTIVES: To systematically and firstly evaluate the available evidence on the efficacy of nalbuphine as an adjuvant to local anesthetics in BPB. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, Medline, Embase, Scopus, Web of Science, EBSCO, PubMed, and additional databases were searched. Randomized controlled trials comparing combination of perineural nalbuphine with local anesthetics to local anesthetics alone in BPB for upper extremity surgical procedures were eligible for inclusion. RESULTS: Nineteen randomized controlled trials involving 1,355 patients met the inclusion criteria. Perineural use of nalbuphine prolonged the duration of analgesia in BPB (mean difference [MD], 162.5; 95% confidence interval [CI], 119.0 to 205.9; P < 0.00001; very low quality of evidence). The duration of sensory block was also extended (MD, 141.6; 95% CI, 100.3 to 182.9; P < 0.00001; very low quality of evidence). Furthermore, nalbuphine shortened the onset time of sensory block (MD, -2.6; 95% CI, -3.6 to -1.5; P < 0.00001; very low quality of evidence). There were no significant differences in side effect-related outcomes, including nausea (risk radio [RR], 1.56; 95% CI, 0.82 to 2.59; P = 0.17; moderate quality of evidence) and vomiting (RR, 1.41; 95%  CI, 0.66 to 3.02; P = 0.38; moderate quality of evidence). LIMITATIONS: The study was limited by substantial heterogeneity, a relatively small sample size and difference-in-differences in how outcomes of interest were described and assessed. CONCLUSIONS: Perineural use of nalbuphine in BPB is an effective strategy for analgesia in adult patients undergoing upper extremity surgery.

Comparing the effects of dexmedetomidine and dexamethasone as perineural adjuvants on peripheral nerve block: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB). METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796. RESULTS: After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05). CONCLUSIONS: This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.

Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone.

BACKGROUND: Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABAA) currents. However, we previously demonstrated that an endogenous neuroactive steroid epipregnanolone [(3ß,5ß)-3-hydroxypregnan-20-one] (EpiP) exerts potent peripheral analgesia and blocks T-type calcium currents while sparing GABAA currents in rat sensory neurons. This study seeks to investigate the behavioral effects elicited by systemic administration of EpiP and to characterize its use as an adjuvant agent to commonly used general anesthetics (GAs). METHODS: Here, we utilized electroencephalographic (EEG) recordings to characterize thalamocortical oscillations, as well as behavioral assessment and mouse genetics with wild-type (WT) and different knockout (KO) models of T-channel isoforms to investigate potential sedative/hypnotic and immobilizing properties of EpiP. RESULTS: Consistent with increased oscillations in slower EEG frequencies, EpiP induced an hypnotic state in WT mice when injected alone intra-peritoneally (i.p.) and effectively facilitated anesthetic effects of isoflurane (ISO) and sevoflurane (SEVO). The CaV3.1 (Cacna1g) KO mice demonstrated decreased sensitivity to EpiP-induced hypnosis when compared to WT mice, whereas no significant difference was noted between CaV3.2 (Cacna1h), CaV3.3 (Cacna1i) and WT mice. Finally, when compared to WT mice, onset of EpiP-induced hypnosis was delayed in CaV3.2 KO mice but not in CaV3.1 and CaV3.3 KO mice. CONCLUSION: We posit that EpiP may have an important role as novel hypnotic and/or adjuvant to volatile anesthetic agents. We speculate that distinct hypnotic effects of EpiP across all three T-channel isoforms is due to their differential expression in thalamocortical circuitry.

Use of hyaluronidase in plastic surgery: A review.

Hyaluronidase is a family of enzymes that degrade hyaluronic acid (HA). It is found to increase vascular permeability and temporarily disrupt the extracellular matrix, promoting diffusion of substances through tissues. Alongside its applications in ophthalmology, obstetrics and gynaecology, musculoskeletal medicine, radiology and drug and fluid administration, hyaluronidase has a number of roles in the field of plastic surgery. The popularity of HA fillers in recent years has led to an increase in the usage of hyaluronidase in the treatment of filler-related complications. The purpose of this article is to review the current and future uses of hyaluronidase within the field of plastic surgery. Hyaluronidase is used as an adjunct to local anaesthetics in skin infiltration, skin graft harvesting, tumescent analgesia, managing complications of dermal fillers, treatment of extravasation injury, prevention and management of oedema, treatment of ganglion and management of scars. However, it has some limitations. Hyaluronidase is known to interact with a number of common medications. Several case reports also highlight the risk of allergic reaction to the substance. Although rare and usually mild, hyaluronidase has the potential to cause anaphylaxis. Other adverse effects include bruising and swelling. Overall, hyaluronidase appears to be a very safe, cheap and effective medication for a variety of uses in the field of plastic surgery and beyond.

Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting.

BACKGROUND: Anesthesia in lactating women is frequently indicated for time-sensitive procedures such as postpartum tubal ligation. Ketamine and diazepam are two of the most commonly used anesthetic agents in low resource settings, but their safety profile in lactating women has not been established. METHODS: Medical records of post-partum tubal ligations between 2013 and 2018 at clinics of the Shoklo Malaria Research Unit were reviewed for completeness of key outcome variables. Logistic regression identified presence or absence of associations between drug doses and adverse neonatal outcomes: clinically significant weight loss (≥95th percentile) and neonatal hyperbilirubinemia requiring phototherapy. RESULTS: Of 358 records reviewed, 298 were lactating women with singleton, term neonates. There were no severe outcomes in mothers or neonates. On the first postoperative day 98.0% (290/296) of neonates were reported to be breastfeeding well and 6.4% (19/298) had clinically significant weight loss. Phototherapy was required for 13.8% (41/298) of neonates. There was no association between either of the outcomes and increasing ketamine doses (up to 3.8 mg/kg), preoperative oral diazepam (5 mg), or increasing lidocaine doses (up to 200 mg). Preoperative oral diazepam resulted in lower doses of intraoperative anesthetics. Doses of intravenous diazepam above 0.1 mg/kg were associated with increased risk (adjusted odds ratio per 0.1 mg/kg increase, 95%CI) of weight loss (1.95, 95%CI 1.13-3.35, p = 0.016) and jaundice requiring phototherapy (1.87, 95%CI 1.11-3.13, p = 0.017). CONCLUSIONS: In resource-limited settings ketamine use appears safe in lactating women and uninterrupted breastfeeding should be encouraged and supported. Preoperative oral diazepam may help reduce intraoperative anesthetic doses, but intravenous diazepam should be used with caution and avoided in high doses in lactating women.

Local Anesthesia Thoracoscopy with versus without Midazolam: A Randomized Controlled Trial.

BACKGROUND: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. OBJECTIVE: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. METHODS: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients' quality of life (QoL) as assessed by a visual analog scale (VAS). RESULTS: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. CONCLUSION: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients' QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

Transient lower cranial nerve palsies following spinal anesthesia with bupivacaine-fentanyl combination for transurethral resection of the prostate.

Spinal anesthesia is a widely used regional anesthesia for many infra-umbilical surgical procedures with proven efficacy and safety. However, although rare, some neurologic complications can occur with potentially life threatening consequences. Among them, lower cranial nerve palsies have been rarely reported in the literature. We report such a case in a 75-year-old man with transient dysphagia, dysphonia and spinal accessory nerve palsy occurring four days after spinal anesthesia for transurethral resection of the prostate. His symptoms completely resolved spontaneously within 2 weeks. The possibility of lower cranial nerve palsies should be added to the potential complications during or following spinal anesthesia with bupivacaine-fentanyl combination. Although transitional, this complication may occur few days after the procedure and need to be promptly recognized, carefully evaluated and treated by conservative measures.

GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats.

Anesthetics are used to produce hypnosis and analgesic effects during surgery, but anesthesia for a long time after the operation is not conducive to the recovery of animals or patients. Therefore, finding appropriate treatments to counter the effects of anesthetics could enhance postoperative recovery. In the current study, we discovered the novel role of a GluN2A-selective positive allosteric modulator (PAM) in ketamine-induced anesthesia and investigated the effects of the PAM combined with nalmefene and flumazenil (PNF) in reversing the actions of an anesthetic combination (ketamine-fentanyl-dexmedetomidine, KFD). PAM treatment dose-dependently decreased the duration of the ketamine-induced loss of righting reflex (LORR). Compared with those in the KFD group, the duration of LORR and the analgesic effect of the KFD + PNF group were obviously decreased. Meanwhile, successive administration of PNF and KFD had no adverse effects on the cardiovascular and respiratory systems. Both the KFD group and the KFD + PNF group showed no changes in hepatic and renal function or cognitive function in rats. Moreover, the recovery of motor coordination of the KFD + PNF group was faster than that of the KFD group. In summary, our results suggest the potential application of the PNF combination as an antagonistic treatment strategy for anesthesia.

Efficacy of midazolam addition to local anesthetic in peribulbar block : Randomized controlled trial.

BACKGROUND: Peribulbar block is considered a safe option for patients undergoing cataract surgery. The limited duration of regional eye blocks was shown to be the main problem. The objective of this study was to evaluate the effects of adjuvant midazolam (in two concentrations) to lidocaine in the peribulbar block. MATERIAL AND METHODS: This study included 90 adult patients aged 40-70 years undergoing cataract surgery. Each patient was appointed to one of three groups. Group C received a single injection of a peribulbar block using a combination of lidocaine 2% and hyaluronidase 15 IU/ml, group M1 received a combination of lidocaine 2%, hyaluronidase 15 IU/ml plus midazolam 50 µg/ml and group M2 received lidocaine 2%, hyaluronidase 15 IU/ml plus midazolam 100 µg/ml. RESULTS: The quality of the peribulbar block showed significant improvement among groups by one-way ANOVA (p = 0.002). The mean onset time of the sensory block was significantly shorter in the M2 and M1 groups (1.66 min and 2.17 min, respectively) compared to the control group C (2.52 min), while the onset of lid and globe akinesia lacked significance between the three groups (p = 0.23 and 0.06, respectively). Significance in mean values was found between the control (C) and M2 groups regarding orbicularis oculi function, digital spear pressure, topical anesthetic sting and the total score (P-values = 0.004, 0.016, 0.033 and 0.001, respectively). The duration of lid akinesia and sensory anesthesia were significantly different between the three groups (P = 0.048 and P<0.001, respectively) whereas the duration of globe akinesia was insignificant (P = 0.432). CONCLUSION: Addition of midazolam to local anesthetic significantly improved the quality of peribulbar block, hastened the onset of sensory anesthesia, lid and globe akinesia and increased the duration of analgesia without notable side effects.

[Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment]. / Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie : Aus der Forschung in die evidenzbasierte Patientenversorgung.

The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.

Effectiveness and safety of local anesthetic, semi-flexible pleuroscopy - experience from a peripheral hospital.

If the seemingly less invasive semi-flexible pleuroscopes are combined with strategies of conscious sedation and local anesthesia the pleuroscopy has the potential to reach an increasing number of hospital settings. Local experiences can provide valuable information pertaining to the reproducibility of this technique in different scenarios. We performed a retrospective analysis of the clinical records of all patients that had undergone local anesthetic semi-flexible pleuroscopy in our unit between February 2015 and July 2017. Data on demographics, previous biochemical, cytological and histopathological analysis, procedure details, diagnostic and therapeutic results, complications and mortality were collected from all patients. Statistical analysis was performed using SPSS v23. A total of 30 patients were included. They were mainly male (66.7%), with a median age of 72 years (minimum 19 years, maximum 87 years). All presented with exudative pleural effusions and the exam was performed for diagnostic reasons. Pleural tissue was obtained in all patients and the overall diagnostic accuracy was 93.3%. Malignancy was the chief group of diagnosis (66.7%), followed by pleural tuberculosis (13.3%). The procedure was well tolerated and self-limited subcutaneous emphysema was the only complication registered (13.3%). No deaths were associated with the procedure. Our results globally overlap those of wider series and reinforce the perception that local anesthetic semi-flexible pleuroscopy is a well-tolerated, safe and highly accurate diagnostic and therapeutic tool which has proved to be both feasible and effective in our experience.

"Sodium bicarbonate": an adjunct to painless palatal anesthesia.

PURPOSE: It is believed that whenever we inject local anesthesia into the palate it is a painful experience for the patients. The aim of this study was to make palatal anesthesia painless by adding 7.4% sodium bicarbonate as an adjunct in local anesthesia. METHODS: Fifty subjects requiring extraction of maxillary bilateral premolar teeth for orthodontic purpose free from periapical infections. These extractions were divided in such a way that all right-sided extractions were done under 2% lignocaine with 1:80,000 adrenaline; and all left-sided extractions were done under 2% lignocaine with 1:80,000 adrenaline with 7.4% sodium bicarbonate added. All extractions were performed using a consistent intra-alveolar technique by a single operator. Both the patient and the operator were blinded to the contents of the local anesthetic solution. Data records of these patients were procured on the basis of VAS and VRS, requirement of repeated injection, and onset and duration of anesthesia. RESULTS: Clinical and statistical data confirmed that the addition of sodium bicarbonate in local anesthetics reduces pain and decreased the onset and increased duration of local anesthesia in the palatal site, as compared to injection of local anesthetic without sodium bicarbonate. CONCLUSION: Effect of sodium bicarbonate on reducing pain while injecting into the palatal aspect was noted in this study.

Role of Music for Conscious Sedation During Invasive Cardiac Catheterization.

Patients undergoing invasive cardiac catheterization (ICC) can experience anxiety and pain. A common practice in the United States is to administer benzodiazepines and opioids for conscious sedation to relieve these symptoms. Music may reduce anxiety and pain perception. We sought to evaluate the role of music in lieu of pharmacotherapy for conscious sedation during elective ICC. A retrospective data analysis was performed on patients who underwent ICC and received music therapy ± intravenous sedation/analgesics based on patient's preference compared with control patients who were offered and received intravenous sedation/analgesics based on patient's preference. A total of 161 patients were analyzed, 49 in the music arm, and 112 in the control arm. Baseline characteristics were similar in the 2 groups except that the rate of drug addiction, back pain, post-traumatic stress disorder, and hearing loss were higher in the control group when compared with the music arm. 42 (86%) of the patients in the music group and 29 (26%) of the control group received no sedation or analgesia in the periprocedural period. The average dose of midazolam (0.7 mg vs 0.1 mg, p <0.0001) and fentanyl (39.5 mcg vs 3 mcg, p <0.0001) was higher in the control than the music arm, respectively. 42 (86%) of patients receiving music therapy believed music was helpful in reducing their stress/anxiety levels. In conclusion, music may serve as adjunctive/alternative intervention to pharmacotherapy in relieving anxiety and stress for patients undergoing elective ICC.

Profiling of hepatic metabolizing enzymes and nuclear receptors in rats with adjuvant arthritis by targeted proteomics.

Inflammatory conditions alter the expression and activity of factors influencing pharmacokinetics, such as metabolizing enzymes. The study examined alterations of hepatic protein levels of cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and nuclear receptors in rats with adjuvant-induced arthritis (AA rats), an inflammatory animal model, by liquid chromatography-tandem mass spectrometry-based targeted proteomics. The protein levels of CYP1A1, CYP1A2, CYP2A1, CYP2A3, CYP2C6, CYP2C12, CYP2D3, CYP2E1, CYP3A9, UGT1A1 and UGT1A2/3 in liver microsomes of AA rats were significantly lower than those in control rats. The protein levels of constitutive androstane receptor (CAR) and retinoid X receptor α (RXRα) in the cytoplasm and nucleus were also significantly decreased, to approximately 60% of the control levels. The decreased protein levels of CYP1A2, CYP2C6, CYP2D3, CYP2E1 and UGT1A1 were potentially associated with downregulation of CAR or RXRα expression in the nucleus.

Effect of magnesium sulfate on anesthesia depth, awareness incidence, and postoperative pain scores in obstetric patients. A double-blind randomized controlled trial.

OBJECTIVES: To assess the effects of magnesium on the depth of anesthesia and to determine the effects of magnesium on incidence of awareness and postoperative pain after caesarean section.  Methods: The study was designed as a double-blind, controlled, randomized study and conducted in Hacettepe University Hospital, Ankara, Turkey  between January 2015 and March 2016. A total of 100 pregnant healthy women who were between 17 and 41 years old, ASA II, and scheduled for an elective cesarean section with general anesthesia were included in the study. After induction, sevoflurane was used for maintenance in Group S and desflurane in Group D (control groups). At Group S-M and Group D-M (study groups), magnesium infusion was started with sevoflurane and desflurane anesthesia respectively. Minimum alveolar concentration of sevoflurane and desflurane were kept constant. Bispectral index scores (BIS), fentanyl consumption and postoperative visual analogue scale (VAS) values were recorded. All of the patients had been followed-up for awareness until the postoperative first year. Results: Demographic variables of the patients were similar. BIS values were significantly higher in control groups throughout the operation (p less than 0.001). No significant difference was detected for intraoperative fentanyl consumption and awareness incidence. VAS values were significantly lower in study groups (p less than 0.05). Conclusion: Magnesium infusion provided significantly lower intraoperative BIS values and lower postoperative VAS scores. We believe that magnesium can be useful as an adjuvant to general anesthesia.

A comparative study of the effect of two dosages of submucosal injection of dexamethasone on postoperative discomfort after third molar surgery: a prospective randomized study.

INTRODUCTION: The aim of this clinical study was to evaluate and compare the relative efficacy of two different dosages of dexamethasone, i.e., 4 and 8 mg injected submucosally to reduce postoperative discomfort after mandibular third molar surgery. METHODOLOGY: A prospective randomized study was conducted on 45 patients requiring surgical removal of an impacted third molar. Selected patients were divided randomly into three groups of 15 patients each: group I patients received one regimen single dose of 4 mg dexamethasone submucosally, group II received one regimen single dose of 8 mg dexamethasone submucosally, and group III (control group), no dexamethasone was given but only received injection of normal saline submucosally after establishing local anesthesia. The postoperative sequelae were assessed on the second and seventh postoperative day. RESULT: As compared to group III, groups I and II showed statistically significant reduction in pain and swelling whereas no statistically significant difference was found between the test groups. CONCLUSION: It can be concluded that corticosteroids are effective in curtailing the postoperative edema of lower third molar surgery but have negligible analgesic effect. As no statistically significant difference is found between both the regimes of dexamethasone, i.e., 4 and 8 mg so within the confines of our study, it may be concluded that 4 mg dexamethasone can be given safely to reduce the postoperative edema after the third molar surgery.

Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.

PURPOSE: Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. METHODS: Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . RESULTS: Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. CONCLUSIONS: Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.

Prolonged Duration Local Anesthesia Using Liposomal Bupivacaine Combined With Liposomal Dexamethasone and Dexmedetomidine.

BACKGROUND: The relatively short duration of effect of local anesthetics has been addressed by encapsulation in drug delivery systems. Codelivery with a single compound that produces an adjuvant effect on nerve block but without intrinsic local anesthetic properties can further prolong the nerve block effect. Here, we investigated whether codelivery of more than 1 encapsulated adjuvant compound can further enhance nerve blockade. METHODS: Liposomes loaded with bupivacaine (Bup), dexamethasone phosphate (DexP), or dexmedetomidine (DMED) were synthesized and its in vitro drug release profiles were determined. Animals (Sprague-Dawley rats) were injected with liposomal Bup (Lipo-Bup) and adjuvants at the sciatic nerve and underwent a modified hot plate test to assess the degree of nerve block. The duration of block was monitored and the tissue reaction was assessed. RESULTS: Coinjection of Lipo-Bup with liposomal DexP (Lipo-DexP) and liposomal DMED (Lipo-DMED) prolonged the duration of sciatic nerve block 2.9-fold compared to Lipo-Bup alone (95% confidence interval, 1.9- to 3.9-fold). The duration of the block using this combination was significantly increased to 16.2 ± 3.5 hours compared to Lipo-Bup with a single liposomal adjuvant (8.7 ± 2.4 hours with Lipo-DMED, P = .006 and 9.9 ± 5.9 hours with Lipo-DexP, P = .008). The coinjection of Lipo-Bup with liposomal adjuvants decreased tissue inflammation (P = .014) but did not have a significant effect on myotoxicity when compared to Lipo-Bup alone. Coinjection of Lipo-Bup with unencapsulated adjuvants prolonged the duration of nerve block as well (25.0 ± 6.3 hours; P < .001) however was accompanied by systemic side effects. CONCLUSIONS: Codelivery of Lipo-DexP and Lipo-DMED enhanced the efficacy of Lipo-Bup. This benefit was also seen with codelivery of both adjuvant molecules in the unencapsulated state, but with marked systemic toxicity.