Breakthrough Pain: The Final Frontier

AUGUST 07, 2014
Virginia Bartok, RPh

Each patient’s breakthrough pain has a unique mix of clinical features, just as each patient’s clinical experience of chronic pain differs.
The health care profession has made tremendous strides in pain management in the past 20 years. Patients today are more likely to receive counseling, have access to physical therapy, and be prescribed analgesics when they have chronic pain. However, 1 type of pain remains seriously undertreated: breakthrough pain (BTP). Between 64% and 90% of cancer patients experience intermittent flares of pain,1 as do a majority of patients with chronic nonmalignant pain.2 This article explores BTP, with an emphasis on ways to treat it successfully.

Pain occurs in many forms. To have BTP, patients must, by definition, have background pain—chronic pain that occurs fairly constantly and predictably for more than 12 hours a day for at least a week. BTP is a transient pain exacerbation lasting 30 minutes or less that occurs despite relatively stable and adequately controlled background pain. BTP tends to occur more often during the day. Table 13-5 describes 3 types of BTP. In general, BTP is acute in onset, short in duration, and moderate to severe in intensity. Each patient’s BTP has a unique mix of clinical features, just as each patient’s clinical experience of chronic pain differs.3

Putting the Brakes on BTP
Before creating a BTP management plan, clinicians should use the PQRSTU (precipitating, palliating, previous treatment, quality, region/radiation, severity, temporal, you [U] effect on the patient) assessment technique.6 Once the patient’s pain is clearly profiled, several effective strategies can manage BTP. Some of them are obvious (eg, identify and treat the underlying cause, avoid precipitating factors, use nonpharmacologic methods and interventions). Other strategies require attention to the patient’s medication regimen. Clinicians may need to modify the around-the-clock background analgesic regimen, and if the BTP continues, prescribe rescue medication as needed.3

Ideal pain rescue agents work quickly and have short durations of action. That is, they must mirror a BTP episode’s temporal characteristics. Nonopioid and adjuvant analgesics usually lack these characteristics, and even immediate-release opioids act too slowly to provide ideal relief because they require 20 to 30 minutes to take effect, may have a duration of effect of 3 to 6 hours, and exacerbate side effects. The drug should have an analgesic potency sufficient to relieve severe pain.3,7 Fortunately, a number of options are available to provide relief.

Transmucosal Opioids
Transmucosal opioid products include intranasal and oral fentanyl formulations, also called rapid-onset opioids (ROOs). A recent metaanalysis found that intranasal fentanyl products (Instanyl, PecFent) and oral transmucosal fentanyl products (Effentora, Actiq, Abstral, Onsolis) yield lower pain intensity scores and higher pain relief scores than placebo and morphine at all time points. Oral immediate-release morphine took effect 45 minutes after administration.8,9 The new oral transmucosal/sublingual fentanyl (Subsys) was not included, as it had not been approved when the study was conducted.

ROOs should only be administered to opioid-tolerant patients receiving oral morphine equivalents of at least 60 mg. Different fentanyl formulations vary in pharmacokinetic properties and ease of use. All of these systems theoretically deliver analgesia within 5 to 15 minutes.10 With oral opioids, rescue doses are calculated as a percentage of the maintenance dose. Clinicians should titrate patients’ transmucosal opioid doses, however, using each product’s complete prescribing information as a guide because the dose of opioid background medication and the optimal dose of transmucosal opioid formulations (the dose that is most effective with an acceptable side effect profile) correlate poorly, so the rescue dose is unpredictable.11

Some clinicians continue to use immediate- release opioid formulations to preempt predictable BTP episodes. In these situations, patients are dosed 20 to 30 minutes before the anticipated trigger, whether it is movement, physical manipulation, or a procedure.12 The usual starting dose is 1/10 to 1/6 of a patient’s total daily opioid dose.13

Some patients find adequate relief from nonopioid analgesics such as acetaminophen and nonsteroidal antiinflammatory drugs. Few studies have investigated nonopioid drugs.14

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