Opioid Anesthesia

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Opioids have had a wide range of uses in medicine throughout history. However, they have recently fallen under scrutiny due to the opioid crisis/epidemic currently plaguing the world, particularly in the USA. Opioids are still a crucial tool in many fields and aspects of medicine but are especially important in treating pain and anesthesia adjuncts or primary anesthetic agents during surgery and post-operatively. Opioids remain an essential tool in many aspects of anesthesia and surgical pain management. This activity covers opioid anesthesia, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the interprofessional team's role in managing opioid anesthesia in light of the opioid crisis.


  • 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.


Opioids have had a wide range of uses in medicine throughout history. However, their use has recently fallen under increasing scrutiny due to the opioid crisis/epidemic currently plaguing the world, particularly in the USA. Opioids are still a crucial tool in many fields and aspects of medicine. They are especially vital in treating pain and as anesthesia adjuncts or primary anesthetic agents during surgery and post-operatively.

Intravenous opioids are frequently utilized to provide analgesia and supplemental sedation during procedures requiring general anesthesia or monitored anesthesia care. 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; these agents are the most widely utilized agents for postoperative acute pain control. 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 been demonstrated to reduce the incidence and 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]

The opioid epidemic has created a movement away from using opioids as frequently as has been the case in the recent past; ongoing opioid use following surgery has been a component of the opioid epidemic, creating a significant concern for perioperative clinicians. While the movement away from perioperative opioid use has cogent reasoning, it remains unclear whether limiting intraoperative opioids and other changes as surgeons and anesthesiologists/nurse anesthetists move toward a multimodal anesthesia paradigm will improve anesthesia outcomes (including persistent opioid use following surgery).[4][5] This article will not address these topics but instead focuses on the clinical use of opioids in anesthesia apart from these issues.

Mechanism of Action

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

Although numerous subgroups exist, there are only three main opioid receptors. These receptors are the mu-opioid receptor, delta-opioid receptor, and gamma-opioid receptor.[7] The opioid receptor-like (ORL1) receptor is also considered an opioid receptor system. Each of these receptors is made up of 7 transmembrane proteins that couple with G-proteins.[8] 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.[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]


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]

Opioid agents chosen for anesthesia include more commonly known drugs like fentanyl, morphine, and hydromorphone, as well as drugs that are only used intraoperatively by anesthesiologists, like sufentanil, remifentanil, and alfentanil, which are significantly more potent than morphine.[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 correlate with the adverse events of opioids in general. 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 of opioid use is reducible through dose reduction, opioid-sparing, or newer multimodal analgesia approaches.[1][5][10]


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.[11] Recommendations also include caution in patients currently taking SSRIs or SNRIs.[12] Other contraindications/cautions include elderly patients due to an increased likelihood of polypharmacy/drug interactions. It also increases the risk of delirium, confusion, and increased sedation, although the cause of delirium is controversial.[13] Caution is also necessary for renal or hepatic impairment.[14] 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 occur with opioid use.

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


The standard of care of anesthesia monitoring is employed when using 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. Monitoring can also involve assessing intraoperative nociception to optimize opioid dosing, using the lowest possible dose to achieve the needed effect.[16]


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 to allow 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 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 clinicians involved in the ongoing care of the same patient. Many clinicians, nurses, and pharmacists have found direct communication ineffective.[17]

It remains unclear how to proceed with anesthesia for patients that addresses all patient anesthesia needs, particularly intraprocedural and immediately post-operative, while not relying excessively on opioids 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 important tools helping anesthesiologists achieve optimal opioid stewardship while also providing effective analgesia without undesirable sequelae.[18]

The interprofessional healthcare team, especially anesthesiologists, nurses, and pharmacists, must also pay special attention to opioid conversions. Due to the recurring shortages that plague medicine, many clinicians 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.[19][20][21][22]

Nursing staff can be a valuable resource in this area by establishing working relationships with multiple pharmacies and liaising between the prescriber, the patient, and the pharmacist. The interprofessional team approach is critical to provide effective opioid therapy and prevent misuse of these agents. [Level 5]

Article Details

Article Author

Nicolas Ferry

Article Author

Laura E. Hancock

Article Editor:

Sandeep Dhanjal


8/10/2022 7:23:38 PM

PubMed Link:

Opioid Anesthesia



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