Background
The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants.

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Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review.

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).

Adjuvants to local anesthetics: Current understanding and future trends

In recent anesthetic practice, peripheral nerve blocks (PNBs) are used extensively for surgical anesthesia and nonsurgical analgesia. PNBs offer many benefits over other anesthetic techniques in a certain population of patients, and in some specific clinical setting, that may contribute to faster and safer pain relief, increased patient satisfaction, reduced hospital stay, and decreased overall healthcare cost. The technique involves the injection of the anesthetic in the vicinity of a specific nerve or bundle of nerves to block the sensation of pain transmitting to a specific portion of the body. However, the length of analgesia when a single anesthetic is used for PNB may not last long. Therefore, the practice of adding an additional agent called adjuvant has been evolved to prolong the analgesic effect. There are many such adjuvants available that are clinically being used for this purpose imparting great efficacy and safety to the anesthetic process. The adjuvants molecules are generally classified as opioids, alpha-2 agonist, steroids, etc. Most of them are safe to use and show little or no adverse event related to neurotoxicity and tissue damage. Although there is extensive use of such adjuvants in the clinical field, none of the molecules is approved by the FDA and is used as an off-label drug. The risk to benefit ratio must be assessed while using such an agent. This review will try to delineate the basic need of adjuvant in peripheral nerve block and will discuss the advantages and limitations of using different adjuvants and will discuss the future prospect of such application.

Review of adjuvants to local anesthetics in peripheral nerve blocks: Current and future trends

Even after a vast safety record, the role of spinal anesthesia (SA) as a primary anesthetic technique in children remains contentious and is mainly limited to specialized pediatric centers. It is usually practiced on moribund former preterm infants (<60 weeks post-conception) to reduce the incidence of post-operative apnea when compared to general anesthesia (GA). However, there is ample literature to suggest its safety and efficacy for suitable procedures in older children as well. SA in children has many advantages as in adults with an added advantage of minimal cardio-respiratory disturbance. Recently, several reports from animal studies have raised serious concerns regarding the harmful effects of GA on young developing brain. This may further increase the utility of SA in children as it provides all components of balanced anesthesia technique. Also, SA can be an economical option for countries with finite resources. Limited duration of surgical anesthesia in children is one of the major deterrents for its widespread use in them. To overcome this, several additives like epinephrine, clonidine, fentanyl, morphine, neostigmine etc. have been used and found to be effective even in neonates. But, the developing spinal cord may also be vulnerable to drug-related toxicity, though this has not been systematically evaluated in children. So, adjuvants and drugs with widest therapeutic index should be preferred in children. Despite its widespread use, incidence of side-effects is low and permanent neurological sequalae have not been reported with SA. Literature yields encouraging results regarding its safety and efficacy. Technical skills and constant vigilance of experienced anesthesia providers is indispensable to achieve good results with this technique.

Spinal anesthesia in children: A review.

Surgery-induced acute postoperative pain and stress response can lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia and recovery following abdominal hysterectomy surgeries. Sixty-four patients scheduled for abdominal hysterectomy under general anesthesia were divided into two groups that were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score immediately after extubation than patients in the PRS group. During the first 24 hours post-surgery, PRD patients consumed less morphine with patient-controlled analgesia (PCA) and had lower scores on a visual analogue scale (VAS) than their controls from the PRS group. The global 40-item quality of recovery questionnaire and 9-question fatigue severity score both showed higher recovery scores from day 3 after surgery in the PRD group. with the data are considered together, intraoperative administration of dexmedetomidine appeared to promote the analgesic properties of morphine-based PCA and to expedite recovery following surgery in patients undergoing abdominal hysterectomy.

/pdf/intraoperative-dexmedetomidine-promotes-postoperative-q0k7dy9tyz.pdf

Intraoperative Dexmedetomidine Promotes Postoperative Analgesia and Recovery in Patients after Abdominal Hysterectomy: a Double-Blind, Randomized Clinical Trial

Background
Dexmedetomidine (DEX) has been used under perioperative settings as an adjuvant to enhance the analgesic property of local anesthetics by some anesthesiologists. However, the analgesic mechanisms and neurotoxicity of DEX were poorly understood. This study examined the effect of DEX alone on inflammatory pain, and it also examined the underlying molecular mechanisms of DEX in the spinal cord. Furthermore, in vivo and in vitro experiments were performed to investigate the neurotoxicity of DEX on the spinal cord and cortical neurons.

/pdf/molecular-mechanisms-underlying-the-analgesic-property-of-gb272pzu9f.pdf

Molecular Mechanisms Underlying the Analgesic Property of Intrathecal Dexmedetomidine and Its Neurotoxicity Evaluation: An In Vivo and In Vitro Experimental Study

BACKGROUND
Traditional Chinese medicine (TCM) is a type of alternative medicine that has been widely utilized in the prevention and treatment of mental diseases such as schizophrenia, ADHD, Alzheimer's disease, and Tourette's syndrome (TS) in many countries. However, the evidence regarding TCM's effectiveness and safety in treating TS are conflicting. Therefore, the goal of the present study is to analyze and summarize the available literature related to the efficacy of TCM in the treatment of TIC disorders especially, TS.


MATERIALS AND METHODS
Relevant articles for the meta-analysis were searched using appropriate keywords from PubMed, MEDLINE, and CENTRAL databases. Event data for TCM for the treatment of TS in the control and intervention arms were determined from the RCTs, and Diagnostic odds ratio and risk of bias analysis were performed. Meta-analysis was performed using MedCalc software, and suitable parameters to assess heterogeneity were computed.


RESULTS
Twelve randomized clinical trials with a total of 1681 Tourette syndrome patients were included as per the inclusion criteria. The patient's clinical symptoms were improved to a greater extent, and the pooled diagnostic odds ratio (DOR) of 1.311 with a 95% confidence interval (CI) value ranging from 0.804 to 2.139 I2 value of 72.04 % was obtained. The pooled relative risk was 1.09, with a 95%CI value ranging from 0.97 to 1.268. The data heterogeneity was assessed, and we achieved the Q value of 33.54, p-value 0.0004, and I2 value of 67.21% with a 95% CI value of 32.91 to 82.10. All these values are statistically significant, with p <0.005, and confirmed the effectiveness of TCM for TICS patients Conclusion: The present meta-analysis on account of these statistically significant results highly recommends using traditional Chinese medicine (TCM) to treat Tourette syndrome.

Is Traditional Chinese Medicine Effective in Treating TIC Disorders (Tourette's Syndrome)? A Meta-Analysis of RCT's.

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Molecular Mechanisms Underlying the Analgesic Property of Intrathecal Dexmedetomidine and Its Neurotoxicity Evaluation: An In Vivo and In Vitro Experimental Study

Is Traditional Chinese Medicine Effective in Treating TIC Disorders (Tourette's Syndrome)? A Meta-Analysis of RCT's.