Opioids in pain management of blood-related malignancies

Opioids are basic analgesics used in the treatment of moderate to severe pain in patients affected by blood-related malignancies. They should be sequentially administered according to the World Health Organisation scale for cancer pain. Initial treatment and titration with opioids should be based on immediate-release preparations, to be administered at appropriate intervals in order to relieve pain and to satisfy the individual opioid requirement. Once a relatively good pain control has been achieved, a slow release formulation at equivalent doses can be given. Most patients can be adequately managed using oral formulation opioids. However, a small group, such as those presenting severe mucositis or requiring a rapid pain relief, should be managed by intravenous continuous infusion and/or by a patient-controlled analgesia system; while for patients in the community, there are distinct advantages to using the subcutaneous route. Other available routes of administration for opioids, can be used in selected circumstances, including rectal, transdermal, epidural, intrathecal and intramuscular. The invasive neuraxial route has a very limited role in patients with haematological malignancies, given the high risk of infection and bleeding. Through a close observation and a careful management, opioid-related side effects can be effectively prevented and treated. This article reviews the principles of opioid therapy and how opioids can be adapted for patients with pain due to haematological malignancies.     

Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians

RECOMMENDATION 1: In patients with serious illness at the end of life, clinicians should regularly assess patients for pain, dyspnea, and depression. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 2: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage pain. For patients with cancer, this includes nonsteroidal anti-inflammatory drugs, opioids, and bisphosphonates. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 3: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage dyspnea, which include opioids in patients with unrelieved dyspnea and oxygen for short-term relief of hypoxemia. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 4: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage depression. For patients with cancer, this includes tricyclic antidepressants, selective serotonin reuptake inhibitors, or psychosocial intervention. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 5: Clinicians should ensure that advance care planning, including completion of advance directives, occurs for all patients with serious illness. (Grade: strong recommendation, low quality of evidence.).     

The use of rapid onset opioids for breakthrough cancer pain: the challenge of its dosing

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on analgesic treatment regularly administered. This review provides updated information about the use of opioids for the treatment of BTcP, with special emphasis on the use of new rapid onset opioids (ROOs). Due to its slow onset to effect oral opioids cannot be considered an efficacious treatment for BTcP. Parenteral opioids may provide rapid onset of analgesia, but not always available particularly at home. Different technologies have been developed to provide fast pain relief with potent opioid drugs such fentanyl, delivered by non-invasive routes. Transmucosal administration of lipophilic substances has gained a growing popularity in the last years, due to the rapid effect clinically observable 10-15 min after drug administration, obtainable in non-invasive forms. Fentanyl is a potent and strongly lipophilic drug, which matches the characteristics to favour the passage through the mucosa and then across the blood-brain barrier to provide fast analgesia. Transmucosal, buccal, sublingual, and intranasal fentanyl showed their efficacy in comparison with oral morphine or placebo and are available for clinical use in most countries. All the studies performed with ROOs have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. The choice of the dose of ROO to be prescribed as needed remains controversial. The need of titrating opioid doses for BTcP has been commonly recommended in all the controlled studies, but has never been substantiated in appropriate studies.     

Opioids for nonmalignant pain

Pain is the most common symptom in the world for which patients seek professional help. Opioids offer an appropriate and safe treatment for some but not all patients with nonmalignant chronic pain. Potential risks, including drug abuse and intolerable side effects, appear to be manageable or even preventable in most cases. Patients with persistent rheumatic pain who have failed traditional treatments should be considered for long-acting opioids. Opioids are best administered in the framework of weighing the good against the bad in each patient, recognizing the potential morbidity and sometimes mortality in untreated patients who have severe and disabling pain daily.     

Use of an implantable drug delivery system for refractory chronic sickle cell pain

An increasing number of chronic sickle cell patients are being treated with sustained-release opioids in the same manner as cancer patients. In a randomized clinical trial of patients with refractory cancer pain, implantable intrathecal drug delivery systems (IDDS) improved clinical success compared to comprehensive medical management alone. We implanted IDDS pumps in two sickle cell patients with refractory bone pain. Both patients achieved rapid and sustained relief of pain, with dramatic reduction in the use of as-needed opioids, crises, and admissions. IDDS may offer relief for sickle cell patients with refractory pain. A prospective trial with more participants is planned.     

Pain therapy of urologic tumors -- prophylaxis and therapy of side effects

Pain is a cardinal symptom in 70 % of cancer patients. Even in developed countries, 30 to 80 % of these patients are inadequately treated. The main cause for this lack of care is not pain refractory to treatment but inadequate or incorrect use of analgesic drugs. A sufficient treatment of pain requires knowledge of the pathomechanism of pain and of the basics of pain management in cancer patients. The choice of analgesic drugs follows the WHO-recommended increase based on need. As long as possible, analgesic drugs should be given orally following a strict schedule and pre-emptively prior to renewed pain. The non-opioids are a heterogeneous group of drugs with different actions and side effects. Maximum doses exist for this group and weak opioids. A change to strong opioids is indicated when weak opioids fail to achieve sufficient pain control despite titration to the maximum dose. No upper limit exists for strong opioids and their use is limited by the side effects. The most frequent side effects are initial emesis and vomiting as well as long-lasting constipation. For this reason, most patients should be prescribed a temporary antiemetic and a laxative on a permanent basis.     

Opioids for cancer pain: the challenge of optimizing treatment

During 2007, 11.7 million US men and women of all ages suffered from some form of invasive cancer. During their illness, at least 70% (8.2 million) will experience pain sufficiently severe to require chronic opioid treatment. Cancer-induced pain is usually described under 3 headings: acute pain, chronic pain, and breakthrough pain. Among patients with chronic, persistent cancer pain controlled by around-the-clock analgesics, there is a high prevalence of breakthrough pain—often precipitated by some form of physical activity. Breakthrough pain seems best treated by a powerful, fast-acting opioid such as intravenous morphine or transmucosal fentanyl. At present, opioids are virtually the only analgesics capable of controlling moderate and severe cancer pain. In recent years, a veritable arsenal of opioids with a wide range of pharmacologic properties has become available for use in different pain situations. The World Health Organization has developed a 3-step “analgesic ladder” to guide management of cancer pain, based on the pain's severity, estimated by means of a 1 to 10 numeric rating scale. As the severity of the pain escalates, more potent (World Health Organization Step III) opioids are used. When faced with a difficult case of cancer pain, the physician must choose—from an array of options—the safest and most effective opioid analgesic and the most appropriate delivery system. Such decisions require an adequate understanding of the available opioids and experience with their use. The pharmacodynamic response to a given opioid depends on the nature of the receptor to which the opioid binds and its affinity for the receptor. Morphine activates the μ-opioid receptors, resulting in not only analgesia and sedation, but also euphoria, respiratory depression, constipation, and pruritus. The existence of a number of opioid receptor subtypes, each with its own repertoire of responses, has given rise to the hope (as yet unrealized) that an opioid can be found (or engineered) that will selectively produce adequate analgesia and sedation without, at the same time, causing unwanted adverse effects. Furthermore, suitable neurostimulatory or neuroinhibitive methods involving the central nervous system are being sought that can amplify the analgesic action of opioids. In the search for antinociceptive agents as efficacious as currently available opioids, but without their troublesome adverse effects, the endogenous opioids, such as the endomorphins, are being examined as offering possible solutions to the adverse effect problem.     

Treatment of chronic pain in pediatric rheumatic disease

Pain in children with rheumatic disease is common, and is most often caused by arthritis. Despite the widespread use of effective new biologic agents, pain continues to be a problem in these patients, and it greatly impairs their daily functioning and quality of life. The pathogenesis of pain in children with rheumatic diseases is multifactorial, and disease treatment alone is often not enough to alleviate it. No standard of care or detailed algorithm for managing pain in these patients exists. Specific pain treatments often include acetaminophen, NSAIDs and medications that treat arthritis, such as methotrexate and etanercept. Other approaches should include nonpharmacologic interventions, for example exercise and cognitive-behavioral therapy, as well as the use of analgesics such as opioids in patients whose pain is refractory to standard therapies. The use of systemic corticosteroids to treat pain in children with arthritis should be avoided.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized,placebo‐controlled trial

Objective

Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.

Methods

The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.

Conclusion

TDF can reduce pain and improve function in patients with knee or hip OA.

     

Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial

Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; p<0.0001); mean change in pain intensity was a reduction of greater than 2 (p<0.0001); almost 50% were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (p<0.0001). Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score, individual pain, stiffness and physical function sub-scores (p<0.0001). AEs causing discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life in these patients. The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub-population of patients with OA pain.     

Use of nonopioid analgesics and adjunctive agents in the management of pain in rheumatic diseases.

Antirheumatic analgesic medications generally fall into one of the following categories: acetaminophen, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, traditional opioids, or adjunctive analgesics. This article does not discuss corticosteroids, opioids, or topical analgesics. Acetaminophen, usually indicated early for mild pain, is often used in combination with other drugs. It has established safety. Traditional NSAIDs are effective in relieving moderate pain in certain inflammatory and noninflammatory conditions. There are many effective choices, but as a class it is fraught with the risk of serious peptic ulcer disease and its complications. Cyclooxygenase-2 specific inhibitors are NSAIDS that reduce the gastrointestinal risk and platelet-mediated bleeding. All NSAIDs may produce peripheral edema, hypertension, and potentiate warfarin. The evidence that coxibs cause thrombotic heart disease is weak. Tramadol is an alternative to musculoskeletal pain management, particularly in patients with moderate to moderately severe pain who do not respond to or who cannot tolerate acetaminophen, NSAIDs, or opioids. The role of analgesic adjuvants is discussed.     

Palliative Schmerztherapie

Palliative care patients do not only suffer from cancer pain but also from painful muscle spasticity due to multiple sclerosis, amyotrophic lateral sclerosis, after stroke or due to dementia if damage of the pyramidal motor system is present. Centrally active muscle relaxants can be helpful also when used as coanalgesics for cancer pain. In addition to opioids other coanalgesics, such as tricyclic antidepressants or serotonin/noradrenalin reuptake inhibitors as well as anticonvulsants (sodium channel and calcium channel blockers) can be helpful if neuropathic cancer pain is present. Idiopathic Parkinsonism or multiple system atrophy leads more to a painful rigor and pain control should be supported here by optimal adjustment of L-DOPA or DOPA agonist therapy. However, pain treatment should always address the psychological, social and spiritual demands of the patient.     

Pain in children with rheumatic diseases

Pain is common in rheumatic diseases in children. Despite recent advances in arthritis treatment, pain continues to be a problem impacting daily functioning and quality of life, and no standard of care for pain management exists. The pathogenesis of pain in children with rheumatic diseases is multifactorial, and treatment of the disease alone may not be enough. Current pain treatment often includes acetaminophen, nonsteroidal anti-inflammatory drugs, and medications that treat arthritis such as methotrexate and etanercept. Nonpharmacologic interventions, such as exercise and cognitive-behavioral therapy as well as the use of analgesics such as opioids in patients whose pain is refractory to standard therapies, should also be considered. The use of systemic corticosteroids to treat pain in children with arthritis should be avoided. Idiopathic pain may coexist in children with rheumatic disease, but treatment of idiopathic pain is different than that of pain due to inflammatory disorders.     

Regulatory issues in pain management.

Patients commonly are left to suffer from pain that affects their daily lives. The prevalence of undertreated, moderate to severe pain is a public health problem in many countries, including the United States. In many cases, opioids should be the mainstay for the treatment of this level of pain, but they often are not used or are underdosed. One of the reasons for this underuse most cited by health care professionals is their fear of sanctions by their governing boards, law enforcement, or their misunderstanding of the laws and regulations governing the use of these controlled substances. This article reviews some of the relevant issues of the regulation of controlled substances, updates the reader about the laws, and provides guidance to practitioners about the appropriate use of controlled substances, especially opioids, to manage pain.     

Spinal analgesia for advanced cancer patients: an update

In the nineties, spinal analgesia has been described as an useful means to control pain in advanced cancer patients. The aim of this review was to update this information with a systematic analysis of studies performed in the last 10 years. 27 papers pertinent with the topic selected for review were collected according to selection criteria. Few studies added further information on spinal analgesia in last decade. Despite a lack of a clinical evidence, spinal analgesia with a combination of opioids, principally morphine, and local anesthetics may allow to achieve analgesia in patients who had been intensively treated unsuccessfully with different trials of opioids. Some adjuvant drugs such as clonidine, ketamine, betamethasone, meperidine, and ziconotide may be promising agents, but several problems have to be solved before they can be used in the daily practice. In complex pain situations, spinal analgesia should not be negated to cancer patients, and oncologists should address this group of patients to other specialists.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial

OBJECTIVE: Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study. METHODS: The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group. CONCLUSION: TDF can reduce pain and improve function in patients with knee or hip OA.     

Chronic pain management in older adults: with coxibs under fire, what now?

Chronic non-cancer pain is notoriously undertreated, especially when the source cannot be identified by objective testing. Effective treatment often requires a combination of pharmacologic and non-pharmacologic approaches. This article describes current medication management of chronic pain, with particular attention to opioids. Acetaminophen and anti-inflammatories are first-line drugs for mild to moderate pain. For neuropathic pain, anticonvulsants are finding an increasing role, as are topical agents. Antidepressants are often advisable. Regarding opioids, the article addresses concerns about addiction potential; distinguishes between addiction and physical dependency; details the role of tolerance to different effects of opioids; and discusses their safety. With appropriate dosing, vigilant management, and careful tapering, opioids are a safe and effective choice for pain management in older adults. Appropriate follow-up guidelines are presented.     

Opioid use in osteoarthritis: From guidelines to clinical care

Three treatment guidelines for the treatment of knee and hip osteoarthritis (OA) which pick up the aspects of treatment supported by evidence have been published. Opioid drugs have an important role in symptomatic treatment. The guidelines, the effectiveness, and the safety of opioid analgesics in osteoarthritis, as well as its implications in clinical practice are reviewed. Tramadol is the opioid with the biggest evidence of effectiveness and safety, besides being the most used in clinical practice. Strong opioids (transdermic brupenorphine or fentanyl, oxycodone, and morphine) can be used in severe pain that does not respond to other treatments. Opioids can be used in patients that have moderate or severe pain or in those with inadequate response or intolerance to NSAID's. The opioids also have a sedative effect that facilitates sleep and can improve functional limitations and anxiety. The side effects are frequent; they usually appear at the beginning of treatment and are rarely severe, but frequently force to stop treatment.     

Pancreatic Pain: A Mini Review

Pain management is one of the corner stones in the treatment of pancreatitis. There are a variety of pharmacological and non-pharmacological strategies to manage the symptoms. Recognizing the type of pain, nociceptive or neuropathic, is essential for appropriate treatment. The pharmacological armamentarium currently available is substantial and includes adjuvant analgesics, non-steroidal anti-inflammatories, and opioids that are customized to the etiology of the pain. When pain relief is suboptimal with pharmacological interventions, celiac block and other interventions should be considered. In acute pancreatitis the use of opioids is widely accepted while its use in chronic states is more controversial. When opioids are utilized, special care has to be taken for the assessment of indicators of misuse or abuse. A multidisciplinary approach to manage these complex patients will result in a high yield of success in controlling this and Other Symptoms.