Opioid Anesthesia

Mechanism of Action

Opioids characteristically exert their effects by interacting with various types of opioid receptors. These interactions may result in a range of receptor responses, from inducing the most significant receptor activity to no activity.[6] Those medications that cause the most profound positive receptor response are referred to as agonists. Medications inducing a partial positive response are known as partial agonists, and those that inhibit or block receptor response activity are described as antagonists.

Although numerous subgroups exist, there are 3 main opioid receptors: mu, delta, and kappa.[7] The nociceptin/orphanin FQ receptor (NOP), also known as the opioid receptor-like (ORL1) receptor, is considered another opioid receptor system. Opioid receptors are G protein-coupled receptors comprised of 7 transmembrane domains that interact with G-proteins.[8] 

After the receptor and ligand interaction activates the G-protein, G alpha and G beta-gamma subunits separate and 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, producing cell hyperpolarization and reduced neuronal excitability.[8] The G beta-gamma subunit appears to further contribute to this alteration in membrane potential 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.[8]

Administration

The routes of administration available in opioid use are diverse. Administration routes include buccal, enteral, transdermal, subcutaneous, epidural, intrathecal, aerosolized, and intravenous. The primary route of administration for an opioid anesthetic is intravenous with either repeat injections or a continuous infusion. Mixtures of local anesthetic and opioid medication in an intrathecal or epidural approach are also useful for select cases.[2]

Opioid agents for perioperative anesthesia include the more commonly known drugs such as fentanyl, morphine, and hydromorphone. Less well-known and much more potent opioid medications include continuous intravenous administration of sufentanil, remifentanil, and alfentanil, mainly reserved for use during the intraoperative period.[9] Fentanyl has a rapid onset, is very potent, and is straightforward for anesthesiologists to dose; it has been the favored intraoperative opioid agent for years.

Adverse Effects

Adverse effects from opioid anesthesia are consistent with the general adverse effects of opioid use. Common adverse effects of intravenous opioid anesthetic include hypotension exacerbation, respiratory depression or apnea, bradycardia, somnolence, confusion, 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 the comorbidities of the patient increase. The risk of adverse effects of opioid use is reducible through dose reduction, opioid-sparing, or newer multimodal analgesia approaches.[1][5][10]

Contraindications

Avoidance of opioid use is recommended in patients who have taken a monoamine oxidase inhibitor (MAOI) within 14 days due to the increased risk of serotonin toxicity.[11] Recommendations also include caution in patients currently taking selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs).[12] Other contraindications/cautions include patients older than 65 due to an increased likelihood of polypharmacy with accompanying drug interactions and greater potential for cognitive impairment. Opioids increase the risk of delirium, confusion, and increased sedation, although the cause of delirium is controversial.[13] Caution is also necessary for patients with renal or hepatic impairment.[14] 

For patients with renal or hepatic disease, consideration should be taken in choosing the appropriate opioid based on the drug's rate of metabolism and excretion. Avoiding opioids is also suggested in patients with pulmonary impairment, eg, chronic obstructive pulmonary disease, due to the decreased respiratory drive caused by opioid administration. Similarly, caution is warranted in patients with increased intracranial pressure, bradyarrhythmias, or gastrointestinal obstruction due to the previously listed common adverse reactions of opioid use.

Patients with substance use disorder may also pose a contraindication to intraoperative and perioperative opioid anesthesia and analgesia. Clinicians must carefully weigh the benefit-to-risk ratio in these patients when deciding how to best proceed with anesthesia for a given procedure.[15][10]

Monitoring

The standard of care of anesthesia monitoring is employed when using opioid anesthetics for general anesthesia or monitored anesthesia care sedation. These monitors include electrocardiogram, pulse oximetry, end-tidal CO₂, respiratory rate, ventilation volume and pressures, and blood pressure measurement. The possible adverse effects that necessitate monitoring include bradycardia, hypotension, and depressed respiratory drive. Monitoring also involves assessing intraoperative nociception to surgical stimulation to optimize opioid dosing, using the lowest possible dose to achieve the needed effect.[16] 

Blood pressure, respiration rate, and heart rate all provide useful information when titrating optimal intraoperative dosing of opioid medications. When correlated with surgical stimulation, high heart rate, blood pressure, and respiratory rate may indicate the need for more opioid pain medication. Conversely, low or normal values in the same vital signs likely indicate no need for further opioid administration at that time.

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 necessary for adequate analgesia and the prevention of a sympathetic surge. This is why patients receiving intraoperative opioid anesthesia require constant vital sign monitoring, as outlined above, to help prevent potential toxicity.

Enhancing Healthcare Team Outcomes

As the opioid epidemic continues, interprofessional communication and care coordination among healthcare team members are imperative to appropriately and safely use 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 clinicians involved in the ongoing care of the same patient. Many clinicians and pharmacists have found direct communication less than 100% effective.[17]

It remains unclear how to proceed with anesthesia for patients that addresses all patient anesthesia needs, particularly intraprocedural and immediately postoperative, while not relying excessively on opioid drugs, which can lead to long-term misuse and addiction.

Opioids have become a leading cause of unintentional death in the United States. Many patients are opioid naive, and their initial exposure to opioid drugs may be in the perioperative setting when anesthesiologists play a significant role in pain management. This is where multimodal analgesia, enhanced recovery pathways, and regional anesthesia can be essential tools in helping anesthesiologists achieve optimal opioid stewardship while providing adequate analgesia without undesirable sequelae.[18]

Clinicians must also pay special attention to opioid conversions. Due to the recurring medical shortages, many clinicians are forced to be flexible with preferred pharmaceuticals. If unfamiliar with the conversion ratios, reviewing proper dose adjustments is imperative to prevent accidental opioid toxicity. Many sources are available for this conversion based on preference and other available agents.[19][20][21][22]

Knowing how to manage opioid anesthesia is essential. Management, treatment, and prevention of perioperative adverse events associated with opioid anesthesia is an important strategy. Opioid anesthesia management is a critical skill set for those in patient care throughout the perioperative environment. Therefore, opioid anesthesia management crosses the breadth and depth of healthcare situations and settings in the perioperative environment.  

It is most appropriate to maintain continuous closed-loop communication between all members of the perioperative care team regarding the need, technique, and potential management issues associated with opioid anesthesia. Collaboration, interdisciplinary and interprofessional teamwork, and a culture of integrity and quality improvement are essential to a successful strategy. Monitoring must be diligent and consistent between and among team members. Maintaining clear and closed-loop professional communication between interdisciplinary team members and among all team members is crucial to successful treatment.

The interprofessional team approach is critical to providing effective opioid therapy and preventing the misuse of these agents. The interprofessional team must work together to ensure the effective use of opioid anesthesia while decreasing the morbidity of opioids.