General principles of management

Breakthrough pain is not a single entity, but a spectrum of very different entities. In most cases, the underlying cause of the pain is a direct effect of the cancer. There is emerging evidence to suggest certain oncological treatments may be effective in managing certain types of breakthrough pain. Optimal treatment of breakthrough pain depends on a variety of pain-related factors. Optimal treatment of breakthrough pain depends on a variety of patient-related factors. Avoidance or treatment of precipitating factors should be considered in patients with incident-type breakthrough pain. Movement-related/incident pain, secondary to metastatic bone disease, is a common phenomenon. Modification of the background analgesic regimen has been shown to be a useful approach in managing breakthrough pain. Multimodal approaches are often required. The cornerstone of the management of breakthrough pain episodes is the use of so-called rescue medication. The management of end-of-dose failure involves modification of the background analgesic regimen. The use of rescue medication depends on the type of breakthrough pain and acceptance depends on factors such as the route of administration of medication.

Clinical features

Breakthrough pain is a heterogeneous condition that can have several causes and several pathophysiologies. Breakthrough pain can present with numerous clinical features and numerous complications. Breakthrough pain is a cause of significant morbidity. The clinical features of the breakthrough pain are often related to the clinical features of the background pain. The diagnosis of breakthrough pain depends on the presence of well-controlled background pain, and so the initial presentation of the breakthrough pain often coincides with the successful management of the background pain. It appears that there is also a circadian variation in the occurrence of breakthrough pain in patients with cancer, with a much greater incidence reported during the day. Breakthrough pain can result in a number of physical, psychological, and social sequelae.

Oral transmucosal opioids

The oral transmucosal routes are buccal and sublingual. The absorption of drugs across the oral mucosa involves a process of passive absorption, and may involve either the transcellular route or the paracellular route. A number of drug factors affect the absorption of drugs across the oral mucosa. Oral transmucosal drug delivery does not require expertise, preparation, or technical equipment. Oral transmucosal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. A variety of other opioids have been subject to oral transmucosal administration. However, many of these opioids are not very lipophilic and, therefore, not suited for buccal or sublingual administration. Some of the more successful ones are alfentanil and sufentanil.

Introduction

Breakthrough pain is a transient exacerbation of pain that occurs despite relatively stable and adequately controlled background pain. Breakthrough pain is a common and heterogeneous condition. It is a significant cause of morbidity. The focus of this book is on cancer-related breakthrough pain in adults. Background pain refers to ‘constant or continuous pain of long duration’. However, breakthrough pain has been described as: ‘a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain’. It can be spontaneous or incident related and is common in cancer patients, with around 60% being affected. Breakthrough pain is a major challenge to healthcare professionals (as well as to their patients).

Intranasal and intrapulmonary opioids

The intranasal and intrapulmonary routes are simple, do not necessarily require any specialized equipment, and can be used by both patients and their non-professional caregivers. Intranasal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. Intranasal opioids can be delivered by traditional spray bottles, and also by syringes fitted with atomisers. The intrapulmonary route has the potential for rapid onset of analgesia. and can be delivered by traditional nebulizers, and other inhalation devices (e.g. metered dose inhalers, dry powder inhalers). The transdermal route has less potential for rapid onset of analgesia. However, new patch technology (iontophoretic technology) may alter the current position.

Non-opioid analgesics

Breakthrough pain is a heterogeneous condition. Non-opioid analgesics are a diverse group of drugs. Non-opioid analgesics may have a role in the management of breakthrough pain. Data on the use of most non-opioid analgesics is limited. Paracetamol and non-steroidal anti-inflammatory drugs are generally used as around-the-clock medication, although they may also be used as rescue medication. Systematic reviews of oral NSAIDs have confirmed benefits in cancer pain. Midazolam has been used in the treatment of refractory incident pain secondary to bone metastases and there is the potential for its use in the management of breakthrough pain secondary to muscle spasm. Ketamine is employed in anaesthetic doses in the management of procedural pain and in the management of predominantly non-malignant breakthrough pain. There is conflicting evidence for the use of nitrous oxide in the management of breakthrough pain.

Assessment

Successful management of breakthrough pain depends on adequate assessment and adequate re-assessment. The assessment of pain primarily depends on basic clinical skills, that is, taking a detailed history and performing a thorough examination. Inadequate assessment may lead to ineffective or even inappropriate treatment. The objectives of assessment are to determine the aetiology and pathophysiology of the pain, and factors that indicate or contraindicate particular treatments. It is important to differentiate patients with uncontrolled background pain experiencing transient exacerbations of that pain, from patients with controlled background pain experiencing episodes of breakthrough pain. Inadequate reassessment may lead to the continuance of ineffective or inappropriate treatment. A number of different tools have been developed for the assessment of cancer-related pain. Those focusing on breakthrough pain include: the Breakthrough Pain Questionnaire, the Alberta Breakthrough Pain Assessment Tool, and the Breakthrough Pain Assessment Tool.

Other therapeutic interventions

Breakthrough pain is a heterogeneous condition. Non-pharmacological interventions include: rubbing/massage, application of heat, application of cold, distraction techniques, relaxation techniques, hypnotherapy/hypnosis, transcutaneous electrical nerve stimulation (TENS), and acupuncture. But most of these have not been subject to rigorous study. Anaesthetic interventions are usually utilized in patients with uncontrolled background pain, but they are sometimes used in patients with uncontrolled breakthrough pain. A variety of different techniques are available. Peripheral (local anaesthetic) nerve blockade and neuraxial analgesia delivery may be used. Non-surgical stabilization, surgical stabilization, corticosteroid instillation, alcohol instillation, phenol instillation, cryoablation, radiofrequency ablation, laser ablation, cementoplasty/vertebroplasty, balloon kyphoplasty, and MR-guided focused ultrasound surgery are other strategies, most of which have not been subject to rigorous scientific investigation. Non-opioid analgesics are a diverse group of drugs. Non-opioid analgesics may have a role in the management of breakthrough pain. Data on the use of most non-opioid analgesics is limited.

Oral and parenteral opioids

Rescue medication is taken as required, rather than on a regular basis. Oral opioids have a defined role in the management of breakthrough pain, but will only be effective if it is an opioid-responsive pain. Although the oral route is generally effective in the management of background pain, it is often less effective in the management of breakthrough pain. The ‘correct’ dose of rescue medication is the dose that provides maximal analgesia with minimal side effects. The pharmacokinetic profile of many orally delivered drugs does not mirror the temporal characteristics of many breakthrough pain episodes. The rectal administration of opioids is well established, although is now uncommon in day-to-day clinical practice. The intravenous route of administration is primarily used in secondary care settings. Intravenous/subcutaneous opioids provide rapid onset of analgesia, but are generally not practical in outpatient settings.