Opioids have been used in a wide range of uses in medicine throughout history. However, they have fallen under scrutiny in recent history due to the opioid crisis/epidemic that currently plagues the medicinal world. Opioids still prove to be a crucial tool in many fields and aspects of medicine but are especially crucial in the treatment of pain as well as anesthesia adjuncts or primary anesthetic agents during surgery and post-operatively.
Common anesthetic specific uses for opioids that have been FDA approved include use during almost every phase of surgery, including use during pre-induction for chronic pain conditions, induction of anesthesia, maintenance, as well as to reduce immediate postoperative pain and decrease agitation. Long-term, postoperative pain control utilizing opioids is also an FDA-approved use. As the popularity of regional blocks increases, it is important to note that opioid anesthetics have also been approved for analgesic supplementation in general and regional anesthesia techniques.
As multimodal anesthetic approaches increase in popularity, opioids have become one of the more common adjuncts utilized during surgical procedures for induction and maintenance of anesthesia. The multimodal approach has been shown to reduce the incidence as well as the severity of the adverse effects that can commonly be seen from opioid use. Studies investigating the utilization of the addition of opioids to the local anesthetic used during spinal blocks has been shown to be very effective, resulting in a reduction in additional intraoperative analgesia need or use and better postoperative pain control.
Opioids characteristically exert their effects by interacting with the few types of opioid receptors in the body. These interactions may result in a range of receptor responses from inducing greatest receptor activity to no activity at all . Those medications that induce the most profound receptor response are referred to as agonists, while those inducing a partial response are known as partial agonists, and those which induce no activity are described as antagonists.
Although numerous subgroups exist, there are only 3 main opioid receptors. These receptors are known as the mu-opioid receptor, delta-opioid receptor, and gamma-opioid receptor  Opioid receptor-like (ORL1) receptor is also considered to be an opioid receptor system. Each of these receptors is made up of 7 transmembrane proteins that are coupled with G-proteins. After the receptor and ligand interaction results in activation of the G-protein, G alpha and G beta-gamma subunits separate and move to impact various intracellular pathways, including kinase cascades and various proteins. Although this receptor activation leads to many downstream effects, ion channel modulation seems to be one of the most important immediate consequences. For instance, after receptor activation, the G alpha subunit directly alters potassium channel conductance, resulting in hyperpolarization of the cell and reduced neuronal excitability. The G beta-gamma subunit is thought to further contribute to this alteration in membrane potential by reducing calcium conductance.
While these receptors are found in both neural and non-neural tissue, they tend to be clustered in the periaqueductal grey, rostral ventral medulla, locus coeruleus, and substantia gelatinosa. Activation of opioid receptors at these structures is believed to lead to the descending inhibitory signaling that interferes with the transmission of nociceptive signals from the peripheral nervous system to the cortex.
The route of administration available in opioid use is diverse and includes oral, enteral, transdermal, subcutaneous, epidural, intrathecal, aerosolized, and intravenous. The primary route of administration for an opioid anesthetic is intravenous in either repeat injections or continuous infusion. Mixtures of local anesthetic and opioids in an intrathecal approach are also utilized for select cases.
The most frequently experienced adverse effects of intravenous opioid anesthetic include hypotension exacerbation, respiratory depression/apnea, bradycardia, somnolence, urinary retention, and constipation. Other potential adverse effects include increased intracranial pressure secondary to hypercapnia, rigidity, delayed emergence, delirium, postoperative nausea and vomiting, pruritis, ileus, and the potential for development of opioid-induced hyperalgesia or development of abuse/misuse habits. The risk of adverse effects increases as the population age increases or comorbidities of the patient increases. The risk of adverse effects seen with opioid use can be reduced through dose reduction, opioid-sparing, or multimodal analgesia.
Avoidance of opioid use is recommended in patients who have taken an MAO inhibitor within 14 days due to the increased risk of serotonin toxicity. Caution in patients currently taking SSRIs or SNRIs is also recommended. Other contraindications/cautions include elderly patients due to an increased likelihood of polypharmacy/drug interactions as well as the increased risk of delirium, confusion, and increased sedation, although the cause of delirium is controversial. Caution should also be utilized in renal or hepatic impairment. Avoidance of opioids is also suggested in patients with pulmonary impairment (e.g., chronic obstructive pulmonary disease [COPD]) due to the decreased respiratory drive. Similarly, caution is warranted in patients with increased intracranial pressure, bradyarrhythmias, or gastrointestinal (GI) obstruction due to the common adverse reactions were seen with opioid use.
Standard of care of anesthesia monitoring is employed in the use of opioid anesthetics, including ECG, pulse oximetry, end-tidal CO2, respiratory rate, ventilation volume and pressures, and blood pressure. The more severe adverse effects that require monitoring include bradycardia, hypotension, and depressed respiratory drive. All of these are already to be monitored utilizing the standard of care.
In the cases of significant hypoventilation induced by opioid anesthesia, or excessive levels at the end of a case, frequent stimulation may be initially necessary to maintain and encourage adequate ventilation. If stimulation is insufficient, positive pressure ventilation or titration of IV naloxone can maintain the patient until emergence is sufficient for adequate spontaneous ventilation. Careful titration of naloxone must be ensured to allow for adequate analgesia as well as the prevention of a sympathetic surge.
As the opioid epidemic continues, interprofessional communication and care coordination are imperative in the appropriate and safe use of opioids for patient care. With proper interprofessional communication, excess quantities, as well as duplicate prescriptions, will be reduced. Unfortunately, such communication can be very difficult with multiple institutes, pharmacies, and physicians handling the same patient care. Many pharmacists and physicians have found direct communication ineffective.
Healthcare professionals must also pay special attention to opioid conversions. Due to the recurring shortages that plague medicine, many physicians are forced to be flexible with preferred pharmaceuticals. If unfamiliar with the conversion ratios, it is imperative to review proper dose adjustments to prevent accidental opioid toxicity, and many sources are available for this conversion based on preference and other available agents.
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