Adjuvant Drugs for Peripheral Nerve Blocks: The Role of NMDA Antagonists, Neostigmine, Epinephrine, and Sodium Bicarbonate

Abstract

: The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes.

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

“…Sensory neurons residing in the dorsal root ganglia convey pain signals from nociceptors in the periphery to the synaptic contacts in the dorsal horn of the spinal cord. Glutamate is the primary transmitter involved in pain signaling at the spinal level, and the role of ionotropic glutamate receptors in this process is well described [99,100]. The role of mGluRs, on the other hand, is only partly understood.…”

Nuts and Bolts of Peripheral Nerve Blocks for Pain After Hip Fracture for Everyday Anesthetist

“…Furthermore, the duration of sensory and motor blocks is limited without an adjuvant drug. The use of adjuvant drugs prolongs the duration of analgesia and reduces the dose-dependent side effects of local anesthetics (12,13).…”

Supraclavicular vs. Infraclavicular Brachial Plexus Nerve Blocks: Clinical, Pharmacological, and Anatomical Considerations

“…Furthermore, some peripheral nerve entrapments and surgical conditions can be successfully treated by peripheral nerve blocks (9)(10)(11)(12). The use of adjuvant agents for pain relief and peripheral nerve blocks (by single injection, and continuous infusion) are a popular practice to reduce the reliance on opioids during perioperative pain management (13)(14)(15)(16)(17).…”