Opioid Anesthesia


Article Author:
Nicolas Ferry


Article Editor:
Sandeep Dhanjal


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
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Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/17/2019 4:01:12 PM

Indications

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.[1] 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.[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 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 3 main opioid receptors. These receptors are known as the mu-opioid receptor, delta-opioid receptor, and gamma-opioid receptor [5] 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.[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 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.[6] 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.[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 utilized 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 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.[1]

Contraindications

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.[7] Caution in patients currently taking SSRIs or SNRIs is also recommended.[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,[9] although the cause of delirium is controversial.[10] Caution should also be utilized in renal or hepatic impairment.[11] 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.

Monitoring

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.

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 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.

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 very difficult with multiple institutes, pharmacies, and physicians handling the same patient care. Many pharmacists and physicians have found direct communication ineffective.[12]

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.[13][14][15][16]


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Opioid Anesthesia - Questions

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Which adverse effect is not commonly associated with opioid use in anesthesia?



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For chronic, non-cancer pain, which of the following is not recommended?



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Which of the following shows increased incidence with opioid anesthesia use in patients with concurrent risks?



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An anesthesiology provider is considering the anesthetic plan for a patient set to undergo a total knee replacement. The plan includes the use of a volatile anesthetic agent combined with a spinal anesthetic. To avoid profound hypotension the anesthesiology provider decides to include an opioid agent in the spinal anesthetic. What would be an appropriate measure when using an opioid adjunct for this case?



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In what stage(s) of anesthesia are opioids most commonly used?



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Opioid Anesthesia - References

References

Dahl JB,Jeppesen IS,Jørgensen H,Wetterslev J,Møiniche S, Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology. 1999 Dec     [PubMed]
Schwenk ES,Mariano ER, Designing the ideal perioperative pain management plan starts with multimodal analgesia. Korean journal of anesthesiology. 2018 Aug 24     [PubMed]
Fléron MH,Weiskopf RB,Bertrand M,Mouren S,Eyraud D,Godet G,Riou B,Kieffer E,Coriat P, A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery. Anesthesia and analgesia. 2003 Jul     [PubMed]
Gillman PK, Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British journal of anaesthesia. 2005 Oct     [PubMed]
Gnanadesigan N,Espinoza RT,Smith R,Israel M,Reuben DB, Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected? Journal of the American Medical Directors Association. 2005 Jul-Aug     [PubMed]
Swart LM,van der Zanden V,Spies PE,de Rooij SE,van Munster BC, The Comparative Risk of Delirium with Different Opioids: A Systematic Review. Drugs     [PubMed]
Chau DL,Walker V,Pai L,Cho LM, Opiates and elderly: use and side effects. Clinical interventions in aging. 2008     [PubMed]
Mallappallil M,Sabu J,Friedman EA,Salifu M, What Do We Know about Opioids and the Kidney? International journal of molecular sciences. 2017 Jan 22     [PubMed]
Pathan H,Williams J, Basic opioid pharmacology: an update. British journal of pain. 2012 Feb     [PubMed]
Feng Y,He X,Yang Y,Chao D,Lazarus LH,Xia Y, Current research on opioid receptor function. Current drug targets. 2012 Feb     [PubMed]
Al-Hasani R,Bruchas MR, Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 2011 Dec     [PubMed]
Hagemeier NE,Tudiver F,Brewster S,Hagy EJ,Ratliff B,Hagaman A,Pack RP, Interprofessional prescription opioid abuse communication among prescribers and pharmacists: A qualitative analysis. Substance abuse. 2018 Jan 2     [PubMed]
Walker PW,Palla S,Pei BL,Kaur G,Zhang K,Hanohano J,Munsell M,Bruera E, Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Journal of palliative medicine. 2008 Oct     [PubMed]
Oviedo-Joekes E,Marsh DC,Guh D,Brissette S,Schechter MT, Potency ratio of hydromorphone and diacetylmorphine in substitution treatment for long-term opioid dependency. Journal of opioid management. 2011 Sep-Oct     [PubMed]
Natusch D, Equianalgesic doses of opioids - their use in clinical practice. British journal of pain. 2012 Feb     [PubMed]
Vieweg WV,Lipps WF,Fernandez A, Opioids and methadone equivalents for clinicians. Primary care companion to the Journal of clinical psychiatry. 2005     [PubMed]

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