Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. Keywords: opioids, postoperative pain, addiction, abusers, buprenorphine, methadone.
Perioperative management of patients who have been exposed to long-term opioids, whether of therapeutic or recreational origin, is a challenging issue for anesthesiologists. This population is increasing, because in most developed countries, the number of patients for whom opioids are prescribed on a long-term basis has grown rapidly over the last decade.
In the USA, sales of prescription opioids have quadrupled in the last 15 years, leading to one out of five patients with chronic nonmalignant pain being under treatment with opioids. Over 90 Americans die every day from an opioid overdose. The opiates commonly abused include prescription opioids, being oxycodone and hydrocodone, which are most commonly involved in overdose death; illicit drugs like heroin; and de-addiction opioids like methadone and buprenorphine.
Conversely, European countries are still far away from the prescription opioid market that is observed in the USA. A decline in the estimated number of high-risk opioid users that was noted from onwards stopped in , when a noticeable increase was seen. These epidemiological data explain why anesthesiologists, surgeons, and all health care professionals HCPs involved in perioperative management are likely to encounter with increasing probability in their clinical practice opioid users and abusers who require surgical treatment and adequate perioperative analgesia.
Opioids are the mainstay of an effective analgesia after surgery, for the management of moderate to severe pain, along with regional techniques. The aim of this narrative review was to give a clinical perspective of the perioperative management of opioid-tolerant patients. Our first suggestion for HCPs is to be familiar with some pharmacological phenomena that are typical of the opioid treatment.
Tolerance and physical dependence can happen after chronic exposure to many drugs, including opiates. Tolerance is the decrease of the pharmacological effect occurring after repeated administration of opioid receptor agonists, that is, the body adapts to the drug and requires increased doses to achieve a certain effect. These changes in body homeostasis lead to physical dependence, a state of neuro-adaption to a specific opioid, characterized by the withdrawal crisis if the agonist administration is abruptly discontinued.
These two phenomena are therefore related to each other and independent from the psychic dependence, also named addiction, but often accompany it. It is now believed that neuronal adaptation phenomena to the chronic effects of opiates occur, involving a complex series of molecular and cellular events, including receptor desensitization, downregulation, and internalization.
Conversely, drug addiction is defined as a chronic, relapsing brain disease, characterized by compulsive illegal drug seeking and use, despite harmful consequences.
Perioperative Management of Patients with Addiction to Opioid and Non-opioid Medications.
A therapeutically appropriate use of opiates for the treatment of chronic pain has been hindered to date by the incorrect belief that their use will inevitably lead to the psychic dependence. The actual prevailing hypothesis suggests that the therapeutic use of opiates does not affect the conditioning environmental stimuli, which are so important in determining the positive reinforcement that leads to the compulsive use. The condition in which the drug is taken, and especially the underlying painful disease, do not provide the substrate and the context in which the patient seeks for the drug; clinical findings in the field of pain confirm that the phenomenon of abuse is observed very rarely.
Opiates produce strong analgesia, but sometimes their use is limited by an increased paradoxical hypersensitivity, known as opioid-induced hyperalgesia OIH , in some cases associated with tolerance. Recently, it has been proposed that epigenetic mechanisms, such as DNA hyper-methylation and histone deacetylases, might be responsible for OIH, leading to a novel approach in pain therapy by means of drugs acting on epigenetic targets, such as L -acetylcarnitine. During preoperative evaluation, anesthesiologists, in their practice, are likely to encounter an increasing number of opioid users and abusers, which presents a wide array of challenges.
Table 1 Clinical differentiation between opioid users for chronic pain and opioid abusers. Table 2 Signs and symptoms of opioid abuse and opioid withdrawal.
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Prejudice and misconceptions that limit postoperative pain treatment in opioid-tolerant patients. Recent warning on the risk of abuse among opioid users in chronic non-cancer pain, including the Center for Disease Control and individual state guidelines, have generated a sort of opiophobia. Addiction is commonly perceived as a crime rather than a disease; therefore, these patients are stigmatized for their opioid use. Consequently, when asked for more opioids to relieve pain, they are seen under suspicion and perceived as drug-seeking. These patients are more demanding than others because of fear that their pain will be under-treated or their opioid therapy be discontinued causing a withdrawal syndrome.
A careful clinical assessment for objective evidence of pain can decrease the risk of being manipulated. Four common misconceptions of HCPs may result in under-treatment of postoperative pain: Perioperative management of patients taking opioid therapy for chronic pain is very challenging for anesthesiologists. This population is at a very high risk of suffering severe postoperative pain.
Limited application of guidelines in real life can be one of the reasons for the high incidence of uncontrolled postoperative pain. Inadequate postoperative pain management may increase pulmonary and cardiovascular complications as well as hospital length of stay. Nowadays, evidence on perioperative management of opioid users is lacking. Therefore, most information comes from expert opinions, more than from clinical trials. In patients taking opioids, when significant pain can be anticipated, such as after elective surgery, it is helpful planning in advance a pain treatment and documenting this plan in the medical record, as resumed in the IDEAL five steps Table 3.
Table 3 Perioperative treatment plan for opioid-tolerant patients. It is well recognized that patients should take their usual dose of oral opioid on the morning of surgery, with preoperative administration of their daily maintenance or baseline opioid dose before induction of general, spinal, or regional anesthesia. If the patient cannot receive oral intake preoperative fasting , the oral opioid dose can be converted to the corresponding intravenous IV dose of morphine:. PKs refer to once daily hydromorphone formulation. Also in these patients, the usual oral dose can be perioperatively administered if possible.
This formulation has also been used as postoperative pain treatment in orthopedic surgery. There are no data suggesting the preference for a specific intraoperative opioid over another in patients chronically treated with opioids or addicted. The anesthesiologist responsible for the patient may select the opioid and titrate the doses following the usual method. Usually a parenteral infusion is used. The use of remifentanil is controversial because of possible acute development of tolerance and hyperalgesia.
Also wound infiltration with local anesthetics should be considered. Low dose of ketamine subanesthetic dose can lead to improved pain scores and reduced opioid consumption. Chronic opioid users for malignant pain have been reported to use three times more epidural morphine and five times more IV morphine for breakthrough pain in the postoperative period to experience full pain control. Multimodal analgesia is mandatory to reduce opioid consumption.
Regional analgesia may be useful; however, anesthesiologists should consider baseline opioid requirements to avoid withdrawal symptoms. PCA may be helpful to minimize the risk of under-medication and breakthrough pain and to provide equivalent baseline preoperative opioid dose. Opioid antagonists, including naloxone and naltrexone, in opioid users should be avoided. Their use, as well as the use of mixed agonist-antagonist-type opioids such as nalbuphine, butorphanol, and pentazocine could precipitate withdrawal symptoms.
These drugs may precipitate acute opioid withdrawal in these individuals. The efficacy of full opioid agonists used for surgical pain could be reduced by the presence of buprenorphine. Therefore, if the acute pain episode is anticipated ie, postoperative pain after elective surgery , buprenorphine should be discontinued 72 hours prior to surgery and conversion to a full agonist can be achieved preoperatively.
If the acute pain is unanticipated eg, from trauma and it is not possible to discontinue the buprenorphine, we suggest using an intravenous opioid agonist that binds strongly to MOR, such as fentanyl and sufentanil. Higher doses of opioids may be necessary to overcome the buprenorphine occupation of receptors; hence, very close perioperative monitoring is required. The patient will then be discharged on full opioid agonist for the control of pain. Reconversion to buprenorphine therapy will be done after discharge by the pain specialist. Conversely, transdermal fentanyl patch should be maintained during the surgery.
In case this preparation is removed, a new patch may then be applied intraoperatively. Hypothermia or rewarming may affect the kinetics of transdermal fentanyl. Therefore, in the case of major surgery, it is preferable to remove the fentanyl patch and to administer an equipotent dose of morphine as a substitute. Presence of invasive pain treatment devices eg, intrathecal pumps, spinal cord stimulators should be investigated as additional information in patients with chronic cancer or non-cancer pain. Continuous epidural and intrathecal opioid infusions, delivered by internally implanted devices, can be maintained during the surgery as a baseline requirement, compatible with the kind of surgery.
Caution should be taken if undertaking a central block or a surgical procedure near the neuroaxial device. Obviously, in the case of spine surgery, it is reasonable to prescribe the patient with an equivalent dose of IV morphine, to guarantee background analgesia for chronic pain management. In , the American Pain Society APS released new guidelines for postsurgical pain management, which encourage an interdisciplinary approach with routine use of nonpharmacological therapies and nonopioid medications into multimodal analgesia regimens.
When a patient has opioid tolerance, or a history of substance abuse or addiction, APS guidelines recommend to consult a pain management specialist. Adequate pain treatment should not be withheld from patients with active or previous opioid addiction because of fears of worsening addiction or precipitation of relapse. It is important to distinguish clinically between abusers, former abusers, and abusers in pharmacological treatment with methadone, buprenorphine, or naltrexone. For abusers, the major problem is related in identifying the exact street dose of the abused drugs or other adjuvants, to convert these doses to morphine or methadone basal daily dose for maintenance during the perioperative phase.
Stromer et al suggest a basal equivalence between 1 g of heroin and 40—80 mg of methadone. For former abusers under maintenance treatment programs, anesthesiologists should be aware of the drug therapy and the timing of the last dose, in order to plan adequate perioperative management.
Theoretically, any long-acting oral opioid could be used in the opioid maintenance approach, as the goals are to reduce the infective risks of IV injections, to decrease craving and rewarding effects, and to reduce crimes related to the use of illicit drugs. Methadone is a synthetic opioid agonist and N-metyl-D-aspartate receptor antagonist, which has been used to treat opioid dependence since the s. Methadone is dosed daily in methadone maintenance treatment MMT because after oral administration, the elimination half-life averages 15—40 hours and its activity is significantly longer than most other opioids.
The maintenance dose of oral methadone begins with initial oral doses of 15—30 mg, usually increased to the most effective dose between 80 and mg daily. Long-term use of MMT dramatically reduces opiate abuse patterns. Perioperative recommendations for patients in MMT include: Unfortunately, methadone conversion is challenging for prescribers, because conversion calculations may not be bidirectional ie, the morphine-to-methadone conversion ratio may not be the same as the methadone-to morphine ratio.
Moreover, because methadone is metabolized by CYP, PK parameters and polymorphism of CYP may result in large interpatient variability in the equianalgesic conversion ratio and huge half-life variation up to hours. Conversely, other drugs such as antiepileptics carbamazepine, phenobarbital, phenytoin , antipsychotics risperidone , antiretrovirals nevirapine, ritonavir , anitubercular rifampin may decrease methadone concentrations. When converting from high doses of opiates to methadone, less methadone will be required. Conversely, changing from methadone to other opioids is still an area of limited research but of increasing importance.
The estimated dose ratio for oral methadone to oral MED is 4. When oral methadone is converted to IV morphine sulfate, the estimated dose ratio is However, this ratio may hugely vary depending on patient metabolism. Carefully titrate the new opioid, after rotation. Usually 2—3 days are required to achieve a stable dose.
Reassess patients at appropriate intervals. Further doses of morphine are required for analgesia. The initial daily dose of 2—8 mg is increased up to 4 mg each week, up to a daily dose as high as 32 mg. There are several possible approaches for treating severe acute pain that requires opioid analgesia in patients under buprenorphine maintenance treatment BMT : 26 , Therefore, if the risk for relapse is too high, we could suggest replacing buprenorphine with methadone a few days beforehand, with a ratio of about titrate methadone dose by increasing daily methadone doses of 10 to 20 mg increments every 1—2 hours up to an adequate pain relief.
If time does not permit this conversion, due to unexpected events requiring opioid therapy eg, accidents , titration of mu opioids agonist must be aggressive to provide sufficiently high doses to overcome the buprenorphine blockade. For example: In a patient taking buprenorphine at 32 mg daily, the dose of oral methadone would be — mg daily starting dose 40 mg or intramuscular IM methadone 70—80 mg.
Naltrexone is an opioid antagonist, used in alcohol-dependent and opioid-dependent patients. Its efficacy is mediated through interactions between dopamine and the endogenous opioid neuropeptide systems, also involved in the expression of reinforcing effects of alcohol.
The new once-monthly extended-release formulation of injectable naltrexone prevents the relapse to opioid dependence following detoxification. Few data are available on perioperative management of patients under maintenance naltrexone treatment. These patients represent a real challenge for anesthesiologists, because naltrexone may cause reduced sensitivity to opioids or precipitate withdrawal symptoms, when re-dosing naltrexone soon after opioid use.
Within the first 2 weeks, they may continue to be refractory to opioid induced analgesia, whereas by the fourth week, the opioid receptor antagonism may be overcome by using larger doses of opioid agonist than in a typical patient. Sometimes, these patients may be more sensitive to opioids, because chronic opioid antagonism may result in an increased density of opioid receptors in the brain, and therefore, they may be more likely to develop the side effects and be at risk for significant respiratory depression.
Therefore, we suggest to mainly use nonopioid analgesics, such as NSAIDs and acetaminophen, corticosteroids, ketamine, and regional analgesic techniques, when indicated. Oral naltrexone should be discontinued at least 24—72 hours prior, if opioid-based anesthesia is planned. The number of opioid-tolerant patients requiring acute pain treatment is increasing. The management of these patients in the perioperative period may be truly a challenge. This narrative review describes the view of a panel of experts on what the practicing clinicians anesthesiologist, surgeon, or other HCPs should know about the perioperative pain management of opioid-tolerant patients.
Universal agreement on the management of these patients, particularly those under maintenance treatment, is lacking. A short list of key messages is reported as a Decalogue in the following box. The effective pain management of patients with an addictive disorder requires a comprehensive multidisciplinary approach that encompasses biological, pharmacological, social, and psychiatric aspects of a complex CNS disorder.
Decalogue of good practice for perioperative pain management of opioid users and abusers:. Center for Disease Control. Prescription Opioid Overdose Data. Accessed April Allegri M, Fanelli G. Opioids and chronic pain. Minerva Anestesiol. The prevention of analgesic opioids abuse: expert opinion. Eur Rev Med Pharmacol Sci. Thanki D, Vicente J. Available from: www. Accessed February Statistical bulletin ; J Pain. Romualdi P, Candeletti S. The opioid system. In: Clementi F, Fumagalli G, editors.
The development and maintenance of drug addiction. Squeglia LM, Cservenka A. Adolescence and drug use vulnerability: findings from neuroimaging. Curr Opin Behav Sci. Pain control in the presence of drug addiction. Curr Pain Headache Rep.
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