Opioid Blood Levels in Chronic Pain Management

Determination of opioid levels in the blood is emerging as an important tool for ensuring the safety, effectiveness, and integrity of opioid analgesic therapy in the treatment of chronic pain.
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In an ideal world, measurement of opioid levels rarely would be necessary. The ideal chronic pain patient always would follow treatment instructions exactly and never use more medicine than prescribed. Pharmacies would maintain ample inventories of all opioids and never make dispensing errors. Addiction and pseuodoaddiction would be rare, non-existent, or someone else’s problem. No patients would have personality disorders or create angry and unpleasant situations with office staff and clinicians. The fear of lawsuits over any possible adverse event would not cast a shadow over daily practice, and defensive medicine would not be necessary. Patients would have textbook pharmacokinetics without problems of swallowing, absorption, digestion, drug-drug interactions, enzyme inhibition or induction. Allergic reactions to medications would be rare. Insurance companies would approve of first-choice and brand-name medication without prior authorizations. Since these conditions do not exist, clinicians should take advantage of opioid blood levels to complement other forms of monitoring in our “real-world” patients.

Safety of Treatment

Safety at the start of treatment relies principally on clinical evaluation and patient selection, and measurement of blood opioid levels is not a routine need when starting opioid therapy. However, in the elderly, the young, the debilitated, and those at higher risk for misuse, abuse and diversion of drugs, opioid blood level monitoring early in treatment might be indicated.

The most immediate safety concerns with opioids are ventilatory depression and hypotension, which primarily are acute risks upon initiating the drugs or raising the dose. They are managed by careful evaluation of the patient before starting the opioids, education of the patient and family about the side effects and risks of treatment, and clinical monitoring.

When evaluating a patient with chronic pain for opioid therapy, it is important to consider cardiopulmonary functioning and any disorders that might increase the risk of ventilatory suppression. Patients with diagnosed or suspected sleep apnea might require evaluation in a sleep disorders clinic and/or overnight polysomnography, and — if indicated — treatment with continuous positive airway pressure (CPAP) or other interventions. One approach is to prescribe lower doses of short-acting drugs for use only during the daytime when the patient is awake and active. This reduces the risk of a long-acting drug suppressing respiration and ventilation during sleep at night, when the risks are greater. Around-the-clock opioid therapy and treatment with controlled-release and long-acting opioids can be delayed until the patient is evaluated more completely and any indicated treatment started. Patients with chronic obstructive pulmonary disease (COPD) and asthma may require consultation with a pulmonologist to optimize respiratory management prior to initiating chronic opioids.

Fortunately, tolerance to most of the undesired effects of opioids develops rapidly after reaching a stable dose, including effects on respiration and blood pressure — which usually return to normal levels. The only two effects to which tolerance does not develop routinely are constipation and analgesia itself. Most patients on chronic opioids require bowel management plans. True tolerance to analgesia in long-term therapy is uncommon, and a much more likely explanation for loss of analgesia is pseudotolerance: increased pain caused by disease progression or pharmacokinetic factors of ingestion, absorption and metabolism that lower blood levels.

In order to minimize the risk of hypotension, patients should be advised to maintain good hydration, eat regular meals and carefully manage treatment for diabetes, hypertension and other problems. In patients at increased risk for hypotension, the prescribing physician should consider additional cardiovascular evaluation (electrocardiogram, cardiology consultation).

Sedation may occur with opioids both acutely and during chronic administration. All patients should be cautioned about drowsiness, cognitive dulling and motor slowing, and they should be instructed not to drive, operate machinery, or engage in any other potentially hazardous activities if they do not feel fully alert and awake. Considering the prevalence of medical disorders (especially sleep apnea) and social situations (sleep deprivation, shift work sleep disorder) that cause excessive daytime sleepiness (EDS), all patients — even those not taking opioids or other sedating drugs — should be evaluated for possible disorders of arousal.

Opioids have a narrow therapeutic index upon acute administration... However, upon chronic administration, the therapeutic range widens, so that some patients require levels two to four times greater than patients treated for acute trauma or postoperative pain.

Opioids have a narrow therapeutic index upon acute administration, which means that blood levels progress from safe and therapeutic to potentially intoxicating and dangerous over a relatively narrow range. However, upon chronic administration, the therapeutic range widens, so that some patients require levels two to four times greater than patients treated for acute trauma or postoperative pain. Individuals with chronic chemical dependence disorders may have blood levels of various drugs five times greater or more than the laboratory reference range and yet show minimal or no clinical evidence of sedation or intoxication.

The terms “toxic” and “detoxification” often are applied incorrectly in the context of chronic pain management. A more useful term is “intoxication.” When opioids reach a dose that is too high or when the blood levels are rising very quickly upon acute administration, the most reliable signs of excessive medication are the behaviors of intoxication. Signs of intoxication due to alcohol, sedative-hypnotics and opiates are familiar to clinicians and the public alike and include slurred speech (dysarthria), unsteady gait with staggering or swaying (ataxia), rambling speech, decreased coordination, and drowsiness (appearing sleepy or actually falling asleep).

Intoxication cannot be implied by a particular blood level. It is a clinical term based on clinical criteria that may be observed and described objectively. There are legal definitions of intoxication, such as a certain blood alcohol level, but for clinical purposes these are not very useful. It is possible for a person to be intoxicated and grossly impaired with relatively low blood levels of an opioid after acute administration. Likewise, patients who take opioids chronically may have blood levels well above what the laboratory reports as a “toxic” level and yet show no signs of intoxication or impairment. Unfortunately, pain patients — experiencing opioid withdrawal after being unable to obtain their medication — are sometimes sent to a recovery program for “detox,” when in fact they show no signs of intoxication whatsoever. These patients need totally excellent pain and psychiatric treatment, possibly in a doctor’s office or perhaps in a pain program or inpatient psychiatric dual-diagnosis unit.

It is important at each office visit to document the overall behavior and mental status of opioid patients. Consider this excerpt from an office progress note:

First published on: April 1, 2005