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Acute pain in chronic opiate users 

Acute pain in chronic opiate users
Acute pain in chronic opiate users

Sanjay Bajaj

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date: 14 November 2019

Key points

  • The main goals in treating perioperative pain are effective analgesia and prevention of withdrawal.

  • An acute pain management plan should be formulated and agreed with the patient.

  • Discharge planning is only successful if the psychosocial background of the patient is considered.

17.1 Introduction

The management of acute pain in opioid-dependent patients can be challenging as it is well recognized that opioid-dependent patients report higher pain scores. Patients with underlying chronic pain often find themselves in a vicious circle resulting in repeated hospital admission and even surgery. Opioid use for non-malignant pain is socially acceptable within the recommendations of the British Pain Society (2004) for the appropriate use of opioids for persistent non-cancer pain; however, patients who have been addicted to opioids and related drugs are exposed to a higher risk of relapse. Addiction to opioids is rare in patients with chronic pain; however, there are currently an estimated 327 000 people addicted to opiate and or crack cocaine in the United Kingdom. The National Institute for Clinical Excellence (NICE) has issued guidelines on maintenance and abstinence therapy, which is an integral part of acute pain treatment.

In severe acute pain, opioid therapy remains a cornerstone, however exploring non-opioid options to treat pain can reduce escalating opioid requirements. Following the World Health Organization (WHO) Pain Ladder, adjuvants such as antidepressants and anti-epileptics may be incorporated depending on the nature of pain. Non-pharmacological option should be encouraged such as TENS, acupuncture, and hypnosis. Psychological support can help to reduce stress and anxiety.

A clear understanding of the differences with regard to physical dependence, tolerance, abuse, addiction, and pseudoaddiction are crucial to set up appropriate treatment plans.

17.2 The elements of drug misuse

17.2.1 Addiction

Addiction is a compulsive drug-seeking behaviour that results from recurring drug intoxication. Physical dependence and the emergence of withdrawal symptoms were once believed to be the key features of addiction, but craving and relapse can occur weeks and months after withdrawal symptoms are long gone.

17.2.2 Physical dependence

Physical dependence may develop within days and is an expected consequence of drug use and is not addiction. It is characterized by the compulsion to take the drug in order to experience its physical effects. On cessation of the drug or administration of an antagonist intense withdrawal symptoms occur. Patients who use opioids for pain relief may be physically dependent on them although few may be psychologically dependent.

17.2.3 Tolerance

Tolerance is a progressively decreasing response to repeated dosage of a drug. This has been demonstrated in animals and volunteer studies. It classically occurs with morphine. The adaptive changes can be explained by a right shift of the opioid response curve though progressive loss of receptor site action, functional uncoupling of opioid receptors from GTP subunit decrease agonist-binding affinity and loss of receptors from cell surface. In chronic pain, once a dose has been established tolerance is seldom a problem. Acute opioid tolerance is a new concept described in animal models. It is more likely to occur with large doses of short-acting drugs.

17.2.4 Pseudoaddiction

This is described as a drug-seeking behaviour in patients in severe pain and is due to the pharmacokinetics of a short-acting opioid such as pethidine with a short onset and offset of action.

17.2.5 Maladaptation

Care needs to be taken once the patient shows loss of control over use, craving, preoccupation despite adequate pain relief, and continued use despite ill effect. Behaviours such as earlier prescription seeking, unsanctioned escalation, requesting specific drugs, various sources, and coexistence of illicit drug use should prompt concern.

17.2.6 Cross-tolerance

Tolerance implying an intake of larger doses to obtain the initial effect occurs also with other opioid agonists and is called cross-tolerance. This can also be incomplete, when the initial opioid can be replaced with another one that produces a milder abstinence syndrome.

17.3 Opioid rotation

There are numerous reports describing improvement or adverse effects from opioids after switching to an alternative opioid. Switching the opioid opioid rotation allows the metabolites to be eliminated while maintaining analgesia with a strong opioid. This strategy can be particularly useful when the toxicity is severe and/or pain is not well controlled. Switching the opioid requires the use of equianalgesic dose tables. Given the interindividual variability in response to various opioids, these should be viewed as guidelines and close monitoring of patient is essential. There is no sound evidence to suggest superiority of one opioid over another, but some theoretical support of methadone as a useful second-line opioid.

17.4 Treatment plan

The main goal for treating acute pain in opioid-dependent patients is satisfactory pain relief, preventing withdrawal, and psychological support. Patients on chronic opioid therapy have often a background of chronic illness or malignancy. It is important to get familiar with the medical background. The general practitioner, palliative care practitioner, or pain management consultant will be able to confirm opioid medication. In dealing with the addicted patient, it is essential to be familiar with common treatments for addiction.

17.4.1 Methadone maintenance

Methadone is a synthetic opioid agonist with a long half-life of 12100hr; it has slow onset and no rush. Opioid tolerance does not eliminate the possibility of methadone overdose, iatrogenic, or otherwise. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during the initiation of methadone treatment of addiction in subjects previously abusing high doses of other agonists. Methadone is an effective analgesic in acute and chronic pain. It is a racemic mixture, which includes an NMDA antagonist and can therefore have an unexpected high potency. Its analgesic effect lasts 48hr and a steady-state plateau is reached in days to weeks.

Methadone for maintenance therapy (MMT) is typically dosed between 60 and 120mg/day, fixed or flexible dosing. The success of therapy is dependent on correct dosing and psychosocial support.

17.4.2 Buprenorphine

Buprenorphine is a thebaine derivative used for maintenance therapy, usually given by the sublingual route in opiate dependence. It is prescribed 0.8 to 4mg sublingually as a single daily dose. Its analgesic effect is due to partial agonist activity at -opioid receptors. An overdose cannot be easily reversed although overdose is unlikely in substance misusers or people with tolerance to opioids. This therapy has a higher relapse rate than high MMT (NICE 2007 Level I). People who are less opioid dependent are more likely to achieve successful abstinence with this therapy. However, for the pain clinician buprenorphine poses a problem due to the unpredictability in its interaction with other opioid therapies and with a elimination half-life of 2037hr.

17.4.3 Naltrexone

Naltrexone, an opioid receptor antagonist, is used for abstinence therapy for alcohol and opioids. When given orally its action is between 24 and 48hr and as a depot injection 34 monthly. In the United Kingdom, there is little experience in treating patients on this therapy who require acute pain management. In emergencies such as cases of acute severe pain, higher doses of opioid analgesics may be used with extreme caution to override the blockade produced by naltrexone. The narcotic dose needs to be carefully titrated to achieve adequate pain relief without oversedation or respiratory suppression. If a patient is taken off naltrexone and put on an opioid analgesic, he or she should be abstinent from the narcotic for at least 35 days before resuming naltrexone treatment.

17.4.4 Providing satisfactory pain relief

Patients can have unrealistic expectation about the outcome of a new treatment or surgery and it is crucial to state that complete pain relief may not be achieved. The patient should be made aware of the nature of their exaggerated pain response and also be informed on the available techniques before surgery, such as in a preassessment clinic. This reduces anxieties and fear and will improve coping. Physiologically, the thermal and nociceptive thresholds are lowered due to central sensitization, the depletion of endogenous opioids with downregulation of secondary messenger systems increases the requirement for opioids.

As pain is one of the most important factors to trigger the stress response it is essential to treat pain promptly. Even after long-term abstinence, the stress response is impaired.

A treatment plan for acute pain in drug-dependent patients guides the health carers involved. Patients are identified as early as possible and are referred to the specialist Acute Pain Team to form an individualized plan, which is discussed with the patient, agreed, and then liaise with all care workers involved. This can be a difficult task in the addicted patient, who is admitted frequently after trauma and infection manifesting in endocarditis and abscesses. Inadvertent intra-arterial injection causing severe ischaemic pain may lead to amputation of the affected limb. Phantom limb pain is not uncommon as preamputation pain is often severe.

Patients who are on maintenance therapy under the care of the drug dependency services or general practitioner have to have their doses confirmed. To prevent withdrawal before dose confirmation, a dose as low as 10mg of methadone is effective; however, positive urine toxicology is mandatory.

17.4.5 Assessment

Patients with underlying history of chronic pain or addiction require a thorough assessment after life-threatening conditions have been controlled. The initial consultation in the addicted patient should include physical (human immunodeficiency virus, hepatitis B and C) and mental health such as anxiety, depression, and personality disorders are common. Previous and current records have to be attained. Establishing the social circumstances with current health care providers will facilitate discharge. Particular attention has to be paid to the drug history, and urine toxicology is mandatory in the addicted patient. Current maintenance therapy has to be confirmed with the provider either the general practitioner or the drug dependency unit.

17.5 Suitable techniques of pain management

All regular pain medication has to be continued as long as possible orally, as inadvertent discontinuation can lead to severe exacerbation and withdrawal. There is occasionally a misconception that all opioids should be withdrawn before surgery. Clinical experience shows that it is often best to use a single full opioid receptor agonist with little euphoric effect such as morphine. In the addicted patient, drugs, such as codeine, tramadol, oxycodone, pethidine, and diamorphine, that have the potential to be abused are best avoided.

If only the parenteral route is available, then all opioids should be converted into a parenteral dose (Table 17.1) with morphine as the reference drug. Patient-controlled analgesia is a safe method of delivering opioids. Morphine is often first-line opioid used in conjunction with non-opioid medication. Patients who are opioid tolerant require manyfold higher doses and are less likely to suffer from side effects such as respiratory depression. A background infusion can address the underlying requirement with an altered bolus setting. Ultrashort-acting opioids such as remifentanil may lead to acute tolerance and worsen pain in the opioid-dependent patient. The conversion of methadone to morphine can be difficult.

Table 17.1 Equianalgesic doses


Equivalent dose (30 mg codeine)

Potency (vs morphine)


30 mg



30 mg



5 mg



3 mg



1.52 mg


Morphine IV/IM

0.75 mg



0.6 mg



0.075 mg



0.030.06 mg


Figure 17.1 Conversion for parenteral opioids

Figure 17.1
Conversion for parenteral opioids

If regional blockade or local anaesthetic limb blocks are used, then the underlying dependency has to be addressed to avoid withdrawal.

As soon as oral intake is possible, the patient should be converted to all oral medication. The discharge planning will be in conjunction with the general practitioner, and possibly in follow-up clinic as an escalation in opioid requirement from preoperative levels is of serious concern.

Some patients will suffer from excruciating pain despite high opioid use. Alternative agents such as sedatives, antipsychotic agents, or NMDA antagonists can be prescribed. The response can be unpredictable and respiratory depression is likely and the patient should transferred to a high dependency unit for monitoring. This structured approach has led to good patient satisfaction and raised the awareness within clinicians involved.

17.5.1 Withdrawal

The clinical syndrome is produced by the withdrawal of an opioid drug from a opioid-dependent individual either by cessation of the drug or by the administration of an antagonist, such as naloxone or naltrexone. Initial symptoms and signs may develop immediately after the administration of an opioid antagonist or up to 48hr after cessation or reduction in dosage of the opioid, depending upon the half-life of the drug concerned. These include restlessness, mydriasis, lacrimation, rhinorrhea, sneezing, piloerection, yawning, perspiration, restless sleep, and aggressive behaviour. Severe manifestations include muscle spasms, backaches, abdominal cramps, hot and cold flashes, insomnia, nausea, vomiting, diarrhoea, tachypnoea, hypertension, hypotension, tachycardia, bradycardia, and cardiac dysrhythmias. Seizures may be observed in neonates.

The management of withdrawal in the acute pain setting is mainly pharmacological either with substitution of the drug or with a long-acting opioid such as methadone. Agents such as clonidine and sedatives mitigate symptoms and signs of withdrawal. Withdrawal of longer-acting opioids such as methadone produced a withdrawal syndrome with a more delayed onset, milder severity, and prolonged duration. Withdrawal is rarely fatal.

The withdrawal syndrome produced by the administration of naloxone is intense, occurs within 5min, peaks at approximately 30min, and subsides within 2hr.

17.5.2 Conversion to intravenous opioids

It requires clinical experience to convert opioids safely as patients. There is no hard evidence that one opioid is better than another; however some patients seem to tolerate one better than another. Oral opioids need to be converted to parenteral administration according to their bioavailability, that is, 10mg oral morphine equates to 5mg intravenous morphine. Conversion of methadone can be difficult as the morphine:methadone ratio does not correlate linear. Transdermal fentanyl (fentanyl patch) can be converted to parenteral morphine, for example, a 50mcg/hr patch equivalent to oral morphine 100mg in 24hr or 50mg intravenous morphine.

17.5.3 Psychological support

There is little in the literature on the needed support for this patient group. However, depression and anxiety with a background of uncontrolled pain can be very distressing. Liaison psychiatric input can be very helpful particularly in the suicidal patient. Integrating psychological support into the inpatient setting is rare; however, in paediatric and adolescent ward more common and their use in this situation is to be evaluated.

17.5.4 Planning discharge

It is essential to establish a therapeutic trustful relationship with the patient in order to address the issue of opioid reduction. However, once the acute pain has settled, the patients are often more motivated to return home. This is dependent on social factors. In complex patients, a multidisciplinary meeting with nurses, medical team, Acute Pain Team, DDU key worker, physiotherapist, occupational therapist, and social worker, occasionally psychiatrist can be useful.

In practice, intravenous opioids are converted to a slow release opioid preparation such as slow release morphine, as this has less euphoric effects. The reduction of the oral opioids is negotiated with the patient according to their pain. The amount of methadone can be increased temporarily for its analgesic effects, this is liaised with the DDU.


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