Continuing Education Activity

Opioids have had 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. This activity covers opioid anesthesia, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the role of the interprofessional team in the management of opioid anesthesia in light of the opioid crisis.

Objectives:

• Identify the indications for opioid anesthesia.
• Summarize the mechanism of action of opioid anesthetic agents.
• Review the potential adverse effects of opioid anesthetics.
• Outline the importance of collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from therapy with opioid anesthetics, especially in light of the ongoing opioid crisis.

Indications

Opioids have had 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 vital 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 received approval 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 demonstrated to reduce the incidence as well as the severity of the adverse effects that can commonly accompany opioid use.[1] Studies investigating the utilization of the addition of opioids to the local anesthetic used during spinal blocks have shown them to be very effective, resulting in a reduction in additional intraoperative analgesia need or use and better postoperative pain control.[2][3]

Mechanism of Action

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 the greatest receptor activity to no activity at all.[4] 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 three main opioid receptors. These receptors are known as the mu-opioid receptor, delta-opioid receptor, and gamma-opioid receptor.[5] The 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 couple with G-proteins.[6] 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 critical 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.[6] The G beta-gamma subunit appears to contribute to this alteration in membrane potential further by reducing calcium conductance.

While these receptors are present in both neural and non-neural tissue, they tend to cluster in the periaqueductal grey, rostral ventral medulla, locus coeruleus, and substantia gelatinosa. Activation of opioid receptors at these structures appears to lead to the descending inhibitory signaling that interferes with the transmission of nociceptive signals from the peripheral nervous system to the cortex.[6]

Administration

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 useful for select cases.[2]

Adverse Effects

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 the 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 is reducible through dose reduction, opioid-sparing, or multimodal analgesia.[1]

Contraindications

Avoidance of opioid use is the recommendation in patients who have taken an MAO inhibitor within 14 days due to the increased risk of serotonin toxicity.[7] Recommendations also include caution in patients currently taking SSRIs or SNRIs.[8] 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.[9][9] Caution is also necessary for renal or hepatic impairment.[10] Avoidance of opioids is also a suggestion 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 that occurred with opioid use.

Monitoring

The 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 monitored under the standard of care.

Toxicity

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 the stimulation is insufficient, positive pressure ventilation or titration of IV naloxone can support the patient until recovery is sufficient for adequate spontaneous ventilation. Careful titration of naloxone is a necessity to allow for adequate analgesia as well as the prevention of a sympathetic surge.

Enhancing Healthcare Team Outcomes

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 challenging with multiple institutes, pharmacies, and physicians handling the same patient care. Many pharmacists and physicians have found direct communication ineffective.[11]

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.[12][13][14][15]