• adjuvants
• local anesthetics
• prolongation of action
• regional anesthesia

• admixtures
• compatibility
• local anaesthetics
• pharmacodynamics
• pharmacokinetics

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.

• Additive
• alpha-2 agonists
• analgesia
• opioids
• peripheral nerve block
• steroid

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).

• Local anesthetics
• Adjuvants
• Neurotoxicity
• Opioids
• Ketamine
• Midazolam
• Alpha-2 adrenoreceptor antagonists

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.

To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks.

Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded.

Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks.

Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist.

• acute pain
• adjuvant medication
• balanced anesthesia
• chronic postoperative pain
• multimodal perioperative analgesia
• persistent postoperative pain
• postoperative pain
• regional anesthesia