World Health Organization Analgesic Research Articles

Efficacy of the World Health Organization analgesic ladder in the paclitaxel-induced pain syndrome in rats.

Paclitaxel use in cancer treatment is limited by a painful syndrome that has no effective treatment. Despite new therapies, drugs of the World Health Organization (WHO) analgesic ladder remain a useful therapeutic tool for cancer pain relief. Since cancer pain is caused by both tumor and chemotherapy, we assessed the efficacy of drugs from the WHO analgesic ladder for cancer pain relief in a paclitaxel-induced pain syndrome (P-IPS) model. P-IPS was induced in rats by one or four injections of paclitaxel on alternate days. The acute and chronic phases were assessed 24h and 15days after the first paclitaxelinjection, respectively. The mechanical allodynia was evaluated after (step 1 of the ladder) paracetamol, (step 2) codeine alone or plus paracetamol and (step 3) morphine treatment in the acute or chronic phase of P-IPS. Paracetamol, codeine and morphine were equally efficacious in reducing the acute phase of the P-IPS. Codeine plus paracetamol had similar efficacy and potency when administered together in the acute phase of the P-IPS, but produced a longer-lasting effect than when separately managed. Moreover, paracetamol, codeine and morphine partially reduced the chronic phase of P-IPS, losing their efficacy and, in the case of codeine, potency when compared to the acute phase. However, paracetamol plus codeine increased the potency and efficacy of the codeine when compared to codeine administered alone in the chronic phase of P-IPS, producing a long-lasting anti-allodynic effect. Together, analgesics of WHO analgesic ladder reduce both acute and chronic phases of P-IPS, with codeine plus paracetamol presenting more potent, efficacious and long-lasting effect. Thus, in addition to tumor pain, drugs of WHO analgesics ladder could also be useful to treat P-IPS.

Assessing Analgesic Use in Patients with Advanced Cancer: Development of a New Scale-The Analgesic Quantification Algorithm

Many patients with advanced cancer frequently use analgesic medications for their pain. Systematically assessing and quantifying changes in analgesic use remains challenging in the clinical trials setting. Currently, there is no sensitive scale for categorizing the intensity of analgesic medications to understand the reasons for changes in patient-reported pain. We assessed whether the Analgesic Quantification Algorithm (AQA) is more sensitive than the World Health Organization Analgesic Treatment Ladder (WHO-AL) for quantifying analgesic medication use among patients with advanced cancer. An expanded equianalgesic potency conversion table was developed to establish oral morphine equivalents for use in the AQA. Categories of opioid use were selected to increase sensitivity within the higher dose range of opioids and to better capture increases in analgesic dose intensity. The resulting 8-point AQA scale corresponds to no analgesic use, non-opioid analgesics, weak opioids only, ≤75 mg, >75-150 mg, >150-300 mg, >300-600 mg, and >600 mg oral morphine equivalents per day. Baseline and 6-month analgesic data from a clinical trial of cancer patients were compared for each instrument. At both time points, the 4-point WHO-AL demonstrated a ceiling effect with a clustering of patients in the strong opioid category, whereas the AQA resulted in a distribution of scores throughout the eight categories, including the five strong opioid categories. The AQA represents a more sensitive measure of analgesic use than the WHO-AL, and may better determine whether changes in pain assessments in clinical trials are due to the intervention or changes in analgesic use.

Incidence and Management of Noncancer Pain in Cancer Patients Referred to a Radiotherapy Center

The incidence of noncancer pain (NCP) in cancer patients is unknown. An analysis of incidence, severity, impact on quality of life (QoL), and appropriateness of NCP treatment in a cohort of cancer patients referred to a radiotherapy center is reported. Pain was scored from 0 (absence) to 3 (severe) and the adequacy of analgesic therapy was evaluated according to International Guidelines. Correlation between Pain Management Index and World Health Organization Analgesic Ladder was used to analyze the appropriateness of NCP treatment. In addition, pain was differentiated according to its origin and types and a comparison was performed between cancer pain (CP) and NCP. A total of 903 patients were eligible and 865 (95.8%) were considered evaluable. Three hundred ninety-eight patients (46.0%) had pain. CP and NCP pain incidence was 11.2% and 34.8%, respectively. Pain intensity was higher in patients with CP versus NCP (P=0.021). A neuropathic pain lower incidence (P=0.024) in NCP versus CP was recorded. Moreover, NCP was more inadequately treated than CP (P<0.001). QoL was significantly lower in patients with NCP when compared with patients without pain (P<0.001). In addition, QoL of patients with CP was significantly lower than QoL of patients with NCP (P<0.001). In a cancer patients' population referred to a radiotherapy center, the NCP incidence was higher than the CP incidence and NCP intensity was only slightly lower than CP. NCP was significantly pharmacologically undertreated and it was related to a decline in QoL.

Consider Palliative Care Options for Patients With ESRD

Kerri Wachter is a senior writer with Elsevier Global Medical News. TAMPA — Patients with end-stage renal disease are good candidates for palliative care and hospice, but many are not referred, according to Dr. Alvin H. Moss. “Nephrologists, by nature, are not inclined toward talking about end-of-life care” and are not trained to deal with it, said Dr. Moss, director of the palliative care service in the nephrology section of West Virginia University, Morgantown. Patients with end-stage renal disease tend to be old with short life expectancies, and they typically have multiple comorbidities and a high symptom burden, Dr. Moss said at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association. Most patients on hemodialysis are older than age 65. Of the estimated 85,000 patients on dialysis who die each year, 20%–25% die after choosing to stop dialysis. The 1-year survival rate for dialysis patients is 78%; the 5-year rate is 32%,” he said. Patients on dialysis have an average of nine symptoms, which may include dry skin, fatigue, itching, bone and joint pain, and muscle cramps. Also, half of dialysis patients report pain (J. Am. Soc. Nephrol. 2005;16:2487–94). “The symptom burden is similar for dialysis patients as for cancer patients,” Dr. Moss said. Predictors of poor prognosis for patients with end-stage renal disease include greater age, reduced functional ability, poor nutritional status, and the presence of comorbid illness, Dr. Moss said. “If a patient has severely impaired functional status, it confers a 3.5-fold greater risk of early mortality,” Dr. Moss said. “If the patient is not independent in activities of daily living … we're talking about a significantly increased risk of early death.” Nephrologists are often unsure about which patients to refer for palliative care. “I teach them to ask themselves on rounds, ‘Would I be surprised if this patient died in the next month?’ It takes about 10 seconds,” Dr. Moss said. If the answer is no, the patient is a good candidate for palliative care. “That question turns out to predict those patients who have greater comorbidities, greater pain scores, lower functional status, lower serum albumin levels, and a greatly increased risk of being dead within a year.” In one study, Dr. Moss asked nephrology nurse practitioners to answer this question with regard to their patients. The nurse practitioners indicated that they would not be surprised regarding 22% of patients. One year later, those in the “no” group had a 2.74-fold increased risk of death, compared with those in the “yes” group. “Pain is a very common and severe symptom. … Usually it's the most severe symptom that dialysis patients report,” Dr. Moss said. In one study, pain was undertreated in about three-quarters of dialysis patients (Am. J. Kidney Dis. 2003;42:1239–47). In his own study of 143 dialysis patients, 54% reported pain. Of those who reported pain, 16 were already being treated for pain and 17 refused treatment. Those remaining were treated for pain using the World Health Organization Analgesic ladder (J. Am. Soc. Nephrol. 2006;17:3198–203). Of the 45 patients who completed pre- and posttreatment evaluations, 31% had neuropathic pain, 40% had nociceptive pain, and 29% had both types. Treatment using the analgesic ladder worked equally well for neuropathic and nociceptive pain. Many opioids are renally excreted, so a few precautions are needed when choosing a pain medication for patients with end-stage renal disease, Dr. Moss said. “Because of problems with renal excretion, we have to look at which ones are safe, which ones you might want to use with caution … and which drugs not to use.” Pain medications that are considered safe and effective in this population include fentanyl, methadone, hydromorphone, acetaminophen, gabapentin, and pregabalin. Avoid codeine, meperidine, morphine, and propoxyphene, because the renally excreted active metabolites can accumulate and cause opioid neurotoxicity. “If we're teaching evidence-based medicine, we know there's a higher risk for complications using these pain medications in dialysis patients. … We should use medications that are safer,” he said. Caution should be used in prescribing hydrocodone, oxycodone, tramadol, desipramine, and nortriptyline. These drugs have been reported to be safely used in dialysis patients, but the data on pharmacokinetics are insufficient to conclude that these drugs are safe in this population. AMDA has two resources that could help long-term care medical directors and staff care for residents near death with renal disease: ▸ “Palliative Care in the Long-Term Care Setting” is available at www.amda.com/resources/whatsnew.cfm#palliativecare. ▸ “Clinical Corner: Chronic Kidney Disease” can be found at www.amda.com/tools/clinical/ckd.cfm.

Gravity of injury and analgesia in patients who suffered traffic accidents

OBJECTIVE: Identifying the frequency and gravity of injuries in patients who suffered accidents in traffic and the analgesic drugs utilized. METHODS: Retrospective study, with a sample of 200 medical records of patients admitted to the emergency services of a reference hospital for trauma care. The gravity of the injuries was characterized by anatomic gravity rates and the analgesic therapy was based on the World Health Organization's Analgesic Ladder. RESULTS: The main findings pointed to injuries in limbs, head, face and outer surface as the most frequent, and, in 85% of the cases, gravity was equal or lower than 3; As for analgesia, it was verified that 46;6% of the patients received dipyrone and paracetamol. Among the opioids, meperidine was used in 10.4% of the cases. CONCLUSION: The gravity of most injuries was equal or lower to 3, indicating injuries of light, moderate and serious gravity, located especially in four body regions; regarding analgesia, dipyrone was shown to be the most commonly-used drug and a low use of opioids was verified.

Proposed 5-step World Health Organization analgesic and side effect ladder

The WHO analgesic ladder has, up to now, been the “gold standard” for pain management. The ladder focuses on the presence or absence of pain relief but, at present, does not take into account the intolerable side effects of opioids. We believe that debilitating side effects are an equally valid reason for changing analgesia, particularly in light of new evidence supporting 'opioid switching'. Opioid switching involves changing a patient's strong opioid to an alternative strong opioid with the aim of improving analgesic response and/or reducing adverse side effects. We propose adding two additional steps to the WHO analgesic ladder to build an alternative five step ladder. The proposed fourth step involves 'opioid switching' and includes both pain and side effects as criteria for switching analgesics. The evidence for Step IV uses an algorithm derived from analysis of intervention patterns based on our recent trial data to identify the point at which a change in management is indicated. In our prospective study we identified four main factors which predict the need to switch. Three out of the four factors are opioid-induced side effects. Thus, once a strong opioid has been commenced (Step 3) and a patient has had an adequate trial of titration on their first-line strong opioid, the need for opioid switching (Step 4) is identified in the clinical setting once side effect scores fall within a critical range, triggering a change of treatment. If switching opioids fails, we propose that the fifth and final step of the WHO analgesic ladder should involve anaesthetic intervention.

Incidence and Management of Phantom Limb Pain According to World Health Organization Analgesic Ladder in Amputees of Malignant Origin

Antidepressants and anticonvulsants are currently considered to be the drug treatment of choice for neuropathic pain. Opioids are effective in relieving neuropathic pain, including phantom pain in the early postoperative course. The present study of 42 cancer patients with limb amputation was conducted to determine the incidence of phantom limb pain and phantom sensation and to test the utility of the World Health Organization 3-step analgesic ladder in phantom limb pain management. Patients were monitored monthly for the first 2 months postoperatively and every 2 months thereafter for 2 years. The World Health Organization analgesic ladder was followed for pain management. The patients complaining of phantom sensation, phantom pain, and stump pain decreased from 69%, 60%, and 31%, respectively, at 1 month to 32%, 32%, and 5%, at the end of 2 years with the addition of opioids. The World Health Organization analgesic ladder played significant role in phantom limb pain management.

Efficacy of the World Health Organization Analgesic Ladder to Treat Pain in End-Stage Renal Disease

Pain is the one of the most common symptoms experienced by patients with ESRD; it impairs their quality of life and is undertreated. Most pain clinicians believe that the pain management approach of the World Health Organization (WHO) three-step analgesic ladder is applicable to the treatment of patients with ESRD, but this approach has not been validated for them. A cohort of 45 hemodialysis patients were assessed for type and severity of pain using the Short-Form McGill Pain Questionnaire and then treated during a 4-wk period according to the WHO analgesic ladder. Mean age was 65 +/- 12.5 yr, and 22 (49%) patients had diabetic nephropathy as the cause of ESRD. Initial pain was rated severe by 34 (76%) patients. There was no difference in initial pain rating by gender, age, race, or type of pain. Forty percent of patients reported nociceptive pain, 31% neuropathic, and 29% both. Adequate analgesia was achieved in 43 (96%) of 45 patients. The mean pain score decreased from 7.8 +/- 1.2 to 1.6 +/- 1.3 (P < 0.001). Patients who were 65 yr and older had higher posttreatment scores than those who were younger than 65 (2.1 +/- 1.4 versus 0.94 +/- 0.93; P = 0.002) and more medication adverse effects. It is concluded that the use of the WHO three-step analgesic ladder leads to effective pain relief in hemodialysis patients. Older patients will need more careful pain management to achieve the same results as younger patients. Further studies are needed to confirm these results in a larger, more diverse dialysis population.

Bedside perspectives on the use of opioids: transferring results of clinical research into practice.

1. Transference of research findings to clinical practice has been a challenge for those managing chronic pain. Generally, pain is not well controlled in hospitals and steps need to be taken to make pain control more effective. 2. Clinical trials of opioids have shown that pain can be controlled in the great majority of patients. Apart from the use of the World Health Organization Analgesic Ladder, a 'pain diagnosis' should be made and a comprehensive view of pain needs to be considered by the clinician. This would include pain and other physical symptoms, psychological issues and social and spiritual stresses. 3. Respiratory depression and tolerance for opioids are often seen as negative aspects of opioids and, therefore, may lead to inadequate control of pain. The evidence cited suggests that, in the long-term treatment of cancer pain, respiratory depression almost never occurs. The only situation that warrants caution is when an anaesthetic block or similar procedure relieves pain treated by opioids, when that patient has been receiving large doses of opioids. Long-term studies with opioids show that tolerance may occur, but is not a clinical problem and should not impair their use in adequate doses to relieve the patient's pain. 4. The active morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) do need to be considered when administering morphine. There seems to be considerable interindividual variation in the production and elimination of metabolites. In cases of renal failure or in the elderly, the ratios of M3G and M6G to morphine accumulate exponentially, making opioid toxicity more likely. Even different routes of administration seem to be associated with different ratios of metabolites. A knowledge of these sources of pharmacokinetic variability may lead to more effective use of the opioids in clinical practice.

Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder?

For most patients with cancer pain, the World Health Organization's three-step analgesic ladder provides adequate management with oral or transdermal options. However, some cancer patients are not well palliated with these approaches. The author reviews interventional options that include nerve blocks, spinal administration of local anesthetics, opioids, alpha-2 agonists, spinal cord stimulation, and surgical interventions. Numerous interventional options are readily accessible and most can be performed on an outpatient basis. They can be used as sole agents for the control of cancer pain or as useful adjuncts to supplement analgesia provided by opioids, thus decreasing opioid dose requirements and side effects. Cancer-related pain can be controlled with several interventions when oral or transdermal opioids are inadequate. A risk:benefit ratio should be considered before implementing invasive analgesic methods.

Pain Control and the World Health Organization Analgesic Ladder

<h3>To the Editor.</h3> —We would like to congratulate you on the attention devoted by<i>JAMA</i>on the treatment of cancer pain, a much neglected topic. But we cannot fail to be somewhat concerned by the article by Drs Jadad and Browman¹regarding the WHO analgesic ladder for cancer pain control. We do not need a meta-analysis of randomized controlled studies to know whether aspirin and morphine are effective against pain. Common sense is not always common, obviously. Furthermore, everything measurable is not necessarily relevant. Moreover, in their article, Jadad and Browman do not give enough consideration to the fact that these analgesic guidelines have also been produced to disseminate important therapeutic and caring principles, indispensable for correct treatment of cancer pain, in both developed and developing countries.²Thanks to the principles of the WHO analgesic ladder for cancer pain and the development of concordant policies, education of the

Pain Control and the World Health Organization Analgesic Ladder

Pain Control and the World Health Organization Analgesic Ladder

Pain Control and the World Health Organization Analgesic Ladder

To the Editor. —Like many others, we welcome the increasingly systematic approach to therapeutic review articles. We wonder, however, whether there is need for a code of practice to govern the publication of systematic reviews. Thus, while we cannot argue with the presentation of data from eight studies in the article by Drs Jadad and Browman, 1 we are disturbed by the tone and content of the commentary. In our opinion, the authors have made a fundamental error in calling for a randomized controlled trial of a concept (the WHO three-step analgesic ladder). Indeed, it has already been demonstrated in Canada that it is difficult to evaluate the broader concept of palliative care. 1 Thus, to say that randomized controlled trials of the three-step analgesic ladder are necessary before we can say that it has improved the management of cancer pain is naive and irrelevant. In all areas of clinical