Breakthrough pain in cancer patients.

Breakthrough pain is 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. A typical episode of breakthrough pain has a fast onset and short duration, yet despite the self-limiting nature of each breakthrough pain, the repeated episodes can have a significant effect on patients' quality of life. Normal-release oral opioids have been the mainstay pharmacological approach for patients who are receiving an around the clock opioid regimen, but the onset and duration of action of oral opioids such as morphine may not be suitable for treating many breakthrough pains. Efforts to provide non-parenteral opioid formulations that could provide more rapid, and more effective, relief of breakthrough pain have led to the development of transmucosal opioid formulations.

Dynamics of breakthrough pain vs. pharmacokinetics of oral morphine: implications for management.

Dynamics of breakthrough pain vs. pharmacokinetics of oral morphine: implications for managementBreakthrough pain is 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. The onset of breakthrough pain is typically fast and the duration is usually relatively short, but despite the self-limiting nature of each breakthrough pain, the repeated episodes can have a significant impact on patients' quality of life. Effective management is therefore imperative and often involves the use of supplemental doses of medication known as 'rescue medication'. The ideal rescue medication should be efficacious, have a rapid onset of action, a relatively short duration of effect and minimal adverse effects. Normal-release oral opioids have been the mainstay approach for patients who are receiving around the clock opioid regimen, but the onset and duration of action of oral opioids such as morphine may not be suitable for treating many breakthrough pains.

Radiofrequency ablation of bone metastases induces long-lasting palliation in patients with untreatable cancer.

INTRODUCTION: In oncological patients, life quality can be greatly impaired by the presence of painful bone metastases, as standard forms of treatment often achieve inadequate palliation. The aim of our study was to evaluate the clinical efficacy of radiofrequency ablation (RFA) with respect to pain relief in patients with refractory bone metastases or who are ineligible to conventional treatments. METHODS: 12 patients with 13 painful osteolytic skeletal metastases, and who were unresponsive to analgesic drug therapy, underwent one (seven lesions) or two (five lesions) RFA sessions under computed tomography (CT) guidance. The RFA procedure was completed in all patients without complications. One patient also received cementoplasty after the RFA procedure. To obtain semiquantitative pain scores, the brief pain inventory (BPI) was administered before treatment and during follow-up. The local effects of RFA were monitored for at least one year in eight of 12 patients with CT and/or magnetic resonance imaging. RESULTS: Immediate pain relief after treatment was experienced by nine of 12 patients, but in two cases, pain recurred within the first week. Long-lasting palliation was obtained in seven of 12 patients. BPI mean scores for worst and average daily pain decreased from 7.7 and 5.0, respectively, at baseline, to 3.1 and 1.8, respectively, at one year. Imaging follow-up showed large areas of necrosis in nine of 12 lesions. CONCLUSION: In our preliminary experience, RFA showed good and long-lasting efficacy for pain control in bone metastases. A possible role of RFA as a coadjuvant palliative treatment in these cases is suggested.

The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE).

Current management of bone metastases involves a multimodal approach. Aminobisphosphonates (BPs) are a valid weapon in the treatment of skeletal localization of tumour disease. Patients with bone metastases from breast and lung cancer were enrolled in order to evaluate the impact of the addition of bisphosphonates therapy to standard treatments in terms of (i) pain control, (ii) quality of life (QoL) and (iii) toxicity and to evaluate (iv) any relations between clinical activity and the occurrence of SREs. A total of 60 patients were included in the study. Median age was 76 years (range 40-83). The majority of patients were treated with chemotherapy or hormonal therapy. All patients received zoledronic acid (ZOL) (4 mg) every 3-4 weeks for at least 3 cycles. No significant improvement in Performance Status of patients after 12 cycles of ZOL (p = 0.1672) was recorded. A statistically significant early and long-lasting amelioration of both pain, narcotic scores and QoL was found. Twenty-one patients (48%) experienced at least one SRE during the study. The most common SRE was radiation to bone (30% of patients). An inverse correlation between bone tumour response and SREs was also found (p = 0.019). ZOL addition induces a clinical benefit and improves QoL of patients with bone metastases. Moreover, the occurrence of bone clinical response is related to a reduced risk of SREs.

Opioids for the management of breakthrough (episodic) pain in cancer patients.

BACKGROUND: Breakthrough pain is a transient increase in pain intensity over background pain. It is a common and distinct component of cancer pain that can have a negative impact for both the patient and carers' quality of life. Breakthrough pain is usually related to background pain and is typically of rapid onset, severe in intensity, and generally self-limiting with an average duration of 30 minutes. At present the current approach to managing breakthrough pain is using supplemental analgesia (also known as rescue medication) at a dose proportional to the total around-the-clock (ATC) opioid dose. OBJECTIVES: This review explores and assesses the evidence for the use of opioids in the management of breakthrough pain in patients with cancer. SEARCH STRATEGY: MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CancerLit (1993 to 2005), CINAHL (1982 to 2005) and Cochrane databases were searched. Handsearching of medical journals and reference from key textbooks was undertaken and drug companies contacted for unpublished data. There was no language restriction. Date of most recent search: January 2005. SELECTION CRITERIA: Randomized controlled trials of opioids used as rescue medication against active or placebo comparator in patients with cancer pain were included. Outcome measures sought were reduction in pain intensity measured by an appropriate scale, adverse effects, attrition, patient satisfaction and quality of life. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Eligible studies were selected and examined independently by the two reviewers. Full text was retrieved if any uncertainty about eligibility remained. Non-English texts were screened. Quality assessment and data extraction were conducted using standardised data forms. Drug and placebo dose, titration, route and formulation were compared and detail of all outcome measures (if available) recorded. MAIN RESULTS: Four studies (393 participants) met the inclusion criteria, all were concerned with the use of oral transmucosal fentanyl citrate (OTFC) in the management of breakthrough pain. Two studies examined the titration of OTFC, one study compared OTFC to normal release morphine and one study compared OTFC to placebo.OTFC was shown to be an effective treatment for breakthrough pain. When compared to placebo and morphine, participants gave lower pain intensity scores and higher pain relief scores for OTFC at all time points. Global assessment scores also favoured OTFC. AUTHORS' CONCLUSIONS: There is evidence that OTFC is an effective treatment in the management of breakthrough pain. The randomised trial literature for the management of breakthrough pain is small and no trials were found for other opioids. Given the importance of this subject, more trials need to be undertaken.

A prospective, within-patient comparison between metal butterfly needles and Teflon cannulae in subcutaneous infusion of drugs to terminally ill hospice patients.

We performed a prospective study of hospice in-patients requiring a syringe driver (SD), to determine the site duration and tolerability of metal butterfly needles compared to Teflon cannulae. Using patients as their own control, prescribed medications were divided equally between two SDs (Graseby MS16a), for delivery over 24 h. A butterfly infusion (Flosafer, 25 gauge) was connected to one SD and a Teflon cannula (Abbocath-T, 24 gauge), to the second. These were inserted subcutaneously (s.c.) on opposite sides of the body at comparable sites; oedematous, broken or painful sites were excluded. SD sites were examined at 4-hourly intervals. The study was terminated when both devices had required resiting. Needle and cannula times were compared using the Wilcoxon signed rank test. Thirty patients entered the study, 13 males and 17 females, mean age (standard deviation): 70 (11) years. Thirteen patients completed the study. Nine patients died and eight patients discontinued the study before both needle and cannula had been resited. All 30 patients are included in the analysis. The time from insertion to resiting of the cannula was significantly longer than the needle: P < 0.0002, median (range) 93.5 (22.8-263.5) h versus 42.8 (7.5-162.3) h, respectively. The cost of the needle versus cannula is 1.93 Pounds versus 2.51 Pounds, respectively. Teflon cannulae have a median life span twice that of metal butterfly needles and are a cost-effective alternative for administration of medications by s.c. infusion in terminally ill patients.

Prevalence and characteristics of breakthrough pain in patients with non-malignant terminal disease admitted to a hospice.

A prospective survey was undertaken to determine the prevalence and characteristics of breakthrough pain in patients with non-malignant terminal disease admitted to a hospice. Of the 78 admissions surveyed, 10 patients were confused or too unwell to take part and 25 were pain-free. The remaining 43 reported 86 pains (range 1-6 per patient); of these patients, 27 (63%) had breakthrough pain and identified 52 pains (range 1-5 per patient). Breakthrough pain was classified as somatic (46%) visceral (14%), neuropathic (25%) or mixed aetiology (15%); 60% of pains were severe or excruciating. The mean number of daily breakthrough pain episodes was five (range 1-13), 54% of which occurred suddenly. Most pains (56%) were unpredictable; 75% lasted less than 30 min. These findings suggest that breakthrough pain is common in patients with non-malignant terminal disease; it is frequent, short lasting and often unpredictable, thus making treatment difficult.

Drugs and syringe drivers: a survey of adult specialist palliative care practice in the United Kingdom and Eire.

Subcutaneous delivery of drugs using a syringe driver is common practice within specialist palliative care units. There is, however, little documented information regarding clinical practice. A survey performed in 1992 reported that at least 28 drugs were used in combination with others in a single syringe driver. The aim of the present study was to reassess practice in this field and to enquire more specifically about newer drugs. Postal questionnaires were sent to all adult specialist palliative care in-patient units in the UK and Eire (n = 208). One hundred and sixty-five units (79%) responded. The most common syringe driver in use was the Graseby 26 (61% of responding units). Most units delivered the contents of the syringe over 24 h, and water was usually used as the diluent in 90% of cases. The maximum number of drugs that respondents were prepared to mix in a single syringe was usually three (51%) or four (35%). In the UK, all units used diamorphine in doses from 2.5 mg/24 h upwards. All respondents also used haloperidol, in doses from 0.5 to 60 mg/24 h. A total of 28 different drugs were used in syringe drivers. The most common combinations were diamorphine and midazolam (37%), diamorphine and levomepromazine (35%), diamorphine and haloperidol (33%), and diamorphine and cyclizine (31%). In conclusion, there is much in common with regard to the way in which drugs are delivered in syringe drivers. However, a wide variety of drugs and drug combinations are still in use.

Sublingual fentanyl citrate for cancer-related breakthrough pain: a pilot study.

The effects of sublingual fentanyl citrate (SLFC) were assessed in 11 hospice inpatients with cancer-related breakthrough pain. Patients were asked to rate their pain, using a visual analogue scale, before SLFC, then after 3, 5, 10, 15, 30, 45 and 60 min. Six patients (55%) had reductions in pain scores at 10 min and nine patients (82%) at 15 min. Ratings for SLFC were very good (18%), good (36%), moderate (28%), and bad (18%). Compared to the usual breakthrough medication, SLFC was better (46%), the same (36%), or worse (18%). Advantages of SLFC included ease of use, quick onset of action and no associated drowsiness. No systemic adverse events were noted, but two patients reported dry mouth and two a bitter taste. Two patients found it difficult to retain the medication under the tongue. Seven patients (64%) said they would continue to use SLFC. Sublingual fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose ranging studies are required to confirm these findings.

An assessment of the safety, efficacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study.

The effects of intranasal fentanyl citrate (INFC) were assessed in 12 hospice inpatients with cancer-related breakthrough pain. Patients received 20 microg of fentanyl citrate and were asked to rate their pain using a visual analogue scale (VAS) before INFC, then after 3, 5, 10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in pain scores, four within 5 minutes and seven within 10 minutes of taking INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%), moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine, INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine patients (75%) said they would continue to use INFC. Of the three patients who did not experience a positive result, two were taking relatively higher baseline opioid doses and one was found to have a fracture. No systemic adverse events were noted; two patients reported nasal itching or discomfort on first use that disappeared with repeated use. Intranasal fentanyl citrate appears safe and well tolerated by these patients. Randomized placebo-controlled and dose-ranging studies are required to confirm these findings.

Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice.

A prospective survey was undertaken to determine the prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. Of 414 consecutive admissions, 33 patients were confused or too unwell to take part and 136 were pain-free. The remaining 245 reported 404 pains (range 1-5 per patient); of these patients, 218 (89%) had breakthrough pain and identified 361 pains (range 1-5 per patient). Breakthrough pain was classified as somatic (46%) visceral (30%), neuropathic (10%) or mixed etiology (16%). Thirty-eight percent of pains were severe or excruciating. The average number of daily breakthrough pain episodes was 4 [corrected] (range 1-14); 49% occurred suddenly. Most (59%) were unpredictable, and 72% lasted less than 30 minutes. Seventy-five percent of patients were dissatisfied with their pain control. Breakthrough pain is common among patients admitted to our hospice. It is frequent, short lasting, often unpredictable and not necessarily related to chronic pain making treatment difficult.

Nebulized scopolamine in the management of oral dribbling: three case reports.

Difficulty swallowing saliva or its excessive production may be problematic for some patients. The resulting oral dribbling is often embarrassing. Three patients were admitted for hospice care complaining of oral dribbling. Each patient was given nebulized scopolamine hydrobromide which helped lessen the dribbling.

How do terminally ill patients at home take their medication?

Compliance with prescribed medication was assessed in 111 terminally ill patients referred to a community palliative care team using semistructured interviews and pill counting. One-hundred-and-six patients were prescribed a total of 597 drugs; of these patients, 64 (60%) were noncompliant. Thirty-five patients (33%) took less medication than prescribed, usually due to experiencing, or anxieties about, adverse events; the commonest drugs involved were analgesics. Seventeen patients (16%) took additional medication, usually purchased over the counter in response to inadequate symptom control or to adverse events from other drugs; the most common preparations were vitamins and analgesics. Twelve patients (11%) both took less medication than prescribed and also purchased medication over the counter. Most patients (90%) had two or more prescribers; patients who saw their general practitioners as their main prescriber were more likely to adhere to their prescribed medication. Patients who omitted and/or reduced their medication were more likely to see the hospital as their main prescriber. Drugs prescribed four times daily were most likely to be omitted and/or reduced.

The palliation of dyspnea in terminal disease.

Dyspnea is a complex subjective experience that is common in terminal illness. Patients may present at any time during the course of their illness, although prevalence increases with disease progression. Dyspnea has physical, psychological, social and spiritual components; without recognizing how each of these contributes to the total suffering of dyspnea, management is unlikely to be successful. The management of dyspnea involves both pharmacological and non-pharmacological treatment. The main pharmacological palliative treatments are oxygen, opioids, and benzodiazepines, but the evidence to support these treatments is limited. More research is urgently needed to establish the efficacy of current treatments and to identify new ones.

Nebulized morphine in the palliation of dyspnoea.

Seventeen terminally ill cancer patients with primary or secondary intrathoracic malignancy complaining of breathlessness were treated with nebulized morphine in doses of 20 mg 4-hourly for 48 h. The effect on dyspnoea was evaluated using the Dyspnoea Assessment Questionnaire. Most patients felt less dyspnoeic after 24 h; the effect was maintained, but not improved upon, after 48 h.