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11 Articles in Volume 14, Issue #5
DEA and Doctors Working Together
Working With Law Enforcement and DEA
Demystifying CRPS: What Clinicians Need to Know
Glial Cell Activation and Neuroinflammation: How They Cause Centralized Pain
History of Pain: The Treatment of Pain
Spirituality Assessments and Interventions In Pain Medicine
The Stanford Opioid Management Model
We Need More “Tolerance” in Medical Pain Management
Treating Rebound or Chronic Daily Headaches
Buprenorphine With Naloxone for Chronic Pain
More on Nitrous Oxide and Meperidine in Pain Care

We Need More “Tolerance” in Medical Pain Management

Editor's Memo from June, 2014

From what I can ascertain, therapeutic tolerance is the most misunderstood aspect of the medical management of pain. What’s worse, everyone including physicians and non-physicians either seems to think they’re an expert on tolerance or feel tolerance is irrelevant. Every time I hear a clamor for dosage restrictions of opioids or hear such statements as “no one could possibly take that much medication,” I suspect the person uttering the statement is pretty ignorant about therapeutic tolerance and the legitimate need for opioid dosage escalation in selected patients.

What is Tolerance?

Let’s review. According to the American Pain Society, therapeutic tolerance is defined as “a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the opioid effects over time.”1 This is not to be confused with physical dependence or addiction, which are defined in the Table.

Another confounding phenomenon is that of opioid-induced hyperalgesia (OIH).2-4 This is the phenomenon by which opioids actually increase a patient’s sensitivity to noxious stimuli and previously non-noxious stimuli (allodynia). The clinical reality of OIH is a topic of some controversy, with supporters and opponents on both sides. Although the mechanism of action is still being debated, OIH should be ruled out when diagnosing therapeutic tolerance, since both present as “medication tolerance,” but treatments differ considerably. The treatment of OIH involves reducing the opioid dosage, tapering off opioids, or supplementation with N-methyl-D-aspartate (NMDA) receptor modulator, such as ketamine.4

However, there is much more to these definitions in pain practice. I simply define therapeutic tolerance as “good pain control while maintaining normal physiologic functions.” A practitioner must fully understand and be able to articulate to all concerned parties that the basic goal of medical management is good pain control, while simultaneously maintaining normal physiologic functions such as blood pressure, pulse rate, reflexes, and mentation. This is done by starting pain patients on all medications, be it an opioid, antidepressant, antianxiety, or neuropathic agent, at a low dosage and titrating the drug upward, over time. Patients on long-term opioids must become tolerant to the sedating and depressant effect on the autonomic nervous system (blood pressure, pulse rate, pupil size, speech, and ambulation). To do so otherwise, is dangerous and the patient is not safe. Some, but not all patients, may not become tolerant to the constipating effects of opioids. Those that don’t become tolerant to these complications will have to be appropriately treated.

Document, Document, Document!

My main message is that physicians who medically manage pain patients must not only fully understand tolerance as applied to pain management, but also document that therapeutic tolerance has been achieved. What’s more, therapeutic tolerance must be continually documented and recorded. Why? Good patient care and legal protection.

A pain practitioner must document that he/she has achieved therapeutic tolerance and is safely prescribing opioids. Too many parties are more than eager to besmirch, denigrate, humiliate, and/or charge a pain practitioner who prescribes medicine to a pain patient. For example, if a pain patient has an automobile accident or unexpectedly dies and an opioid, benzodiazepine, or antidepressant is found in the patient’s blood, the prescribing physician may be erroneously and maliciously blamed.

In fact, there are many parties who zealously claim opioid over-prescribing and report such complaints to a state medical board or other government agency. The complainer of “over-prescribing” may be an insurance company, local pharmacist, fellow physician, hospital, or family member. In the end, your only defense may be that your patient has achieved therapeutic tolerance and that you have documented this fact in the patient’s chart. Dosage or which drugs were prescribed aren’t very relevant, but therapeutic tolerance is.

How to Document

A pain practitioner can easily and routinely document the presence of therapeutic tolerance at each clinic visit so that the patient can safely take his or her medications. After conducting your usual physical examination, taking a medication and pain history and documenting medication compliance, also make note in the chart that the patient has normal speech, clear mentation, and ambulation. I also take and record the patient’s vital signs, such as blood pressure and pulse rate, at each visit.

If you ever have a legal inquiry or one of those heavenly calls from an insurance company, remind your critic that “too much medicine” lowers the blood pressure, pulse rate, and slurs the speech, but your patient was perfectly normal at the last clinic visit.

To be extra cautious and to legally protect you, I have two other recommendations that I personally follow:

  • Stamp or paste a sticker on each chart that reads, “Therapeutic Tolerance is Present”
  • Take a quantitative blood level of patients who are prescribed high-doses of opioids, benzodiazepines, or carisoprodol (Soma).

Take special note of my second recommendation. If your patient has an auto accident, enters a hospital, or dies, a blood sample will likely be taken. Be prepared to defend yourself because the blood test taken by the outside party may show opioids, benzodiazepines, stimulants, seizure agents, antidepressants, or all of the above. I clearly recall a patient of mine who had porphyria and required about 2,000 mg equivalent of morphine a day just to swallow, eat, and get out of bed. She died of her disease in her late 50’s, as most porphyria patients are prone to do. A few days after her death, I received a threatening phone call from the coroner and district attorney in a semi-rural county claiming she had 550 ng/mL of morphine in her blood. The call, of course, was to inform me that I was responsible for her death. They gulped and faded away forever when I told them her blood level was low as she usually ran about 800 ng/mL.

The best way to document the presence of therapeutic tolerance is by obtaining a blood level for opioids when the patient has normal physiologic parameters, such as blood pressure, speech and ambulation, and simultaneously claims good pain control. The dosage and time and date of last dose should be clearly recorded on all clinical records and any laboratory work. Although urine drug testing is commonly performed, having drugs, including opioids, in the urine has no relationship to tolerance. Only identifying drug levels in blood that directly interact with tissue receptors indicate a degree of tolerance.


Last updated on: May 19, 2015
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