Patients with advanced cancer and pain were selected for intrathecal pain management after receiving different trials of systemic opioids. All consecutive patients with cancer pain receiving spinal analgesics were surveyed. They had unsuccessfully received different opioid trials (at least two routes—oral and IV—and two drugs, including fentanyl, morphine, or methadone) resulting in poor analgesia and adverse effects. They were selected for intrathecal treatment versus SL ketamine after receiving different trials with systemic opioids.

Patients received spinal treatment and presented with breakthrough pain, requiring alternative methods, including SL ketamine or intrathecal boluses of local anesthetics. Patients were able to choose between SL ketamine or intrathecal boluses of local anesthetic. Nine patients received intrathecal levobupivacaine boluses. Three patients received ketamine SL.

• N = 12
• KEY DISEASE CHARACTERISTICS: Consecutive patients with advanced cancer and pain

• LOCATION: Acute pain relief and palliative care unit in Italy

• Open clinical trial

• Pain intensity on a numerical scale from 0–10 and symptoms commonly associated with spinal local anesthetic injection (e.g., hypotension, sensory and motor block, bladder dysfunction) were recorded using a scale of 0--3 (absent, light, moderate, severe) at the time of injection, and then followed at one-minute intervals until pain level was less than 50% of the initial value.
• Assessed for adverse effects of ketamine (e.g., confusion, agitation, drowsiness) graded from 0–3 until pain decreased to 50% of the previous level.

Nineteen patients who experienced a mean of 2.4 breakthrough pain episodes per day responded to a mean of 27 mg of morphine IV per episode. Twelve subjects required an alternative treatment. No specific differences were found between these two groups in terms of previous systemic opioid doses or pain mechanisms. In the spinal anesthetic group, the median Karnofsky status at the time of admission was 40. The median breakthrough pain intensity was 9 (range 7--10). All patients received an adequate pain relief (less than 50% of initial pain) within five minutes. In the ketamine SL group, pain was controlled in almost all patients within five minutes. Adverse effects were of low intensity (0–1 of scale used).

• Data on the treatment of breakthrough pain in patients receiving a spinal treatment are lacking, and the use of spinal route for episodic (breakthrough) pain has never been reported.
• This was an open clinical trial with a very selective population.
• Small sample size
• Further studies need to be performed using a controlled trial with appropriate design.
• Patients were able to choose which treatment they wanted.
• Variability in availability of transmucosal drugs
• Tolerance to ketamine could be an issue long-term.

The administration of these drugs may pose some problems associated with sympathetic block and motor or urinary impairment. Local anesthetics typically have an individualized dose-effect relationship with a narrow therapeutic window. These intensive treatments should be reserved for a very select population and initiated in an appropriate setting with frequent monitoring facilities and skilled nursing. Spinal anesthesia should be reserved for a select number of patients with the best methods to prevent infection (increased manipulation of catheter).

To compare the safety and effectiveness of fentanyl buccal tablets and oral morphine for breakthrough cancer-related pain

After ensuring stable background pain control with severity less than or equal to four on a 10-point scale, patients were instructed to call for breakthrough medication when pain became severe or was distinguishable from chronic background pain. Patients randomly received either fentanyl buccal tablets or oral morphine in does proportional to doses used for ongoing analgesia. After receiving one medication per breakthrough, patients were crossed over to receive the alternative medication. Patients received each drug for two breakthrough episodes. Nurses recorded pain intensity just before drug administration, at 15 minutes, and at 20 minutes. The intensity of adverse effects was recorded.

• N = 68 (263 breakthrough episodes)
• MEAN AGE = 62.1 years (SD = 12.3 years)
• MALES: 60.5%, FEMALES: 39.5%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types with lung, gastrointestinal, and urogenital the most frequent
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had controlled background pain and one to three episodes of breakthrough pain per day.

• SITE: Multi-site  
• SETTING TYPE: Inpatient  
• LOCATION: Italy

• APPLICATIONS: Palliative care

Randomized, single-group, crossover study

• 10-point Numeric Rating Scale (NRS) for pain intensity
• Three-point scale for adverse effect severity

Both medications resulted in significant pain reductions (p = 0.0005). Pain intensity at 15 and 30 minutes was significantly lower with fentanyl buccal tablets (p < 0.0005) compared to oral morphine. There were no differences between groups in the severity of adverse effects. The most common adverse effect was nausea and vomiting, and these events were not severe. Of the patients who received both treatments, twice as many patients preferred the fentanyl tablets.

The analgesic effect for breakthrough pain was greater with the use of fentanyl buccal tablets compared to oral morphine, and the tablets were well-tolerated.

• Small sample (< 100)
• Risk of bias (no blinding)

Fentanyl buccal tablets were shown to have greater analgesic effects for breakthrough pain than oral morphine when both medications were given at doses proportional to background analgesia. Some studies suggested that transmucosal opioids need to be titrated, which can delay efficacy, but this study showed that proportional dosage administration was effective. Pain can be one of the most debilitating and problematic symptoms to manage, and it is important that patients have rapid and effective interventions for breakthrough pain. Nurses can advocate for the use of the most effective medications for pain management and the approaches that are preferred by patients. Significant differences in efficacy may justify the use of more expensive drugs.

To evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain

Fifty consecutive patients with advanced cancer and moderate-to-severe pain initially were given 50 mg doses of slow-release TP twice a day, along with oral morphine 5 mg (initial dose) as breakthrough medication. Doses were managed to provide adequate pain relief or dose-limiting toxicity. Non-opioid medications were continued, provided they were tolerated. Adjuvant symptom relief medications were continued. Patients were visited or contacted at least weekly in order to change therapy. Parameters were assessed before starting therapy and at weekly intervals for four weeks. Parameters included pain intensity (0–10), symptoms associated with pain therapy, quality of life using the Spitzer scale, TP escalation index percent at week 4 ([TP maximum dose - TP starting dose] / TP starting dose / days x 100), and the presence of neuropathic pain using the PainDETECT questionnaire.

• N = 50
• MEDIAN AGE = 66.3 years
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: Primary tumors were breast (n = 13), urogenital (n = 10), gastrointestinal (n = 9), lung (n = 7), pancreas (n = 5), and other (n = 6).
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with moderate-to-severe pain (greater than 4 on a 10-point scale); unresponsive to non-opioid drugs; with occasional use of opioids; who had a Karnofsky score of 50 or more; who did not have poor renal or hepatic function, history of substance abuse, cognitive failure, brain metastasis, or brain damage; who did not have a short anticipated survival

• SITE: Single site 
• SETTING TYPE: Not specified 
• LOCATION: University of Palermo, Italy (assumed to be a teaching facility but not clearly identified)

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care

• Prospective, single-arm intervention study

• Pain on a 0–10 scale
• Symptoms related to opioid therapy
• Quality of life measured with Spitzer scale
• TP escalation index percent ([TP maximum dose - TP starting dose] / TP starting dose / days x 100)
• PainDETECT to determine prevalence of neuropathic pain

Pain intensity significantly decreased from baseline to all week intervals. Some symptoms varied in intensity during the study. Drowsiness increased in week 1 and decreased at week 4. Dry mouth increased from weeks 1–3 and decreased from weeks 1–4. No significant changes were seen in intensity of confusion, nausea, or constipation. Quality of life increased each week. TP escalation index (TPEI) percent and TPEI in mg were 1.78 and 2.26, respectively. No relationship was found between TPEI indexes and primary tumor, pain mechanism, PainDETECT, age, or gender. TPEI was lower in this study than in prior studies with a similar design. This may reflect less tolerability of TP in this study. TP had low discontinuation levels and was well tolerated.

Pain levels significantly decreased during the study. TPEI in this study was lower than in prior studies with a similar design that may reflect less tolerability of TP. TP was well tolerated with low discontinuation levels.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Number of patients lost to follow-up

TP is not widely used in the United States and will require education of nurses on its use and side effects.

To evaluate the effectiveness of pregabalin as a coanalgesic on pain in patients with cancer-related pain

Patients were assigned randomly to receive either sustained-release morphine or sustained-release morphine and pregabalin in increasing doses up to 150 mg per day. Oral morphine in doses of about one-sixth of the baseline dose was used for breakthrough pain. Other drugs were allowed, and patients already receiving non-opioid analgesics of steroids, antidepressants, or anticonvulsants could continue use.

• N = 44
• MEAN AGE = 65.5 years (SD = 10.3 years)
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: Not reported

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Italy

• PHASE OF CARE: Late effects and survivorship

• RCT

• Brief Pain Inventory
• Pain intensity numeric rating scale
• Symptoms assessed on a 1–3 scale

No significant differences were seen between groups in pain intensity or symptoms. Pain declined overall in both study groups. In both groups, opioid dosage used over time significantly increased.

Findings did support improvement in chronic, uncontrolled pain with the use of pregabalin as a coanalgesic. Sample size was insufficient to analyze differences in neuropathic pain specifically.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Subject withdrawals 10% or more

Findings did not show a benefit of adding pregabalin to strong opioids for improved management of uncontrolled cancer-related pain; however, the study had a small sample size because of loss of patients to follow-up–a typical challenge for studies in patients with advanced disease. Further research is needed into the appropriate role, dosage, and effective use of drugs such as pregabalin as coanalgesics.

STUDY PURPOSE: To evaluate the role of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) for cancer pain

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, PubMed, CANCERLIT, EMBASE

KEYWORDS: Anti-inflammatory drugs or paracetamol or acetaminophen and/or cancer pain

INCLUSION CRITERIA: Randomized, controlled trial in patients with cancer

EXCLUSION CRITERIA: Not specified, but did exclude several studies in which patients were treated with a combination of hydrocodone or oxycodone and in which patients received transdermal fentanyl or morphine

TOTAL REFERENCES RETRIEVED = 3,703

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No specific quality rating was applied–study limitations are described in the summary of findings of each study

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 175
• SAMPLE RANGE ACROSS STUDIES: 22–172
• KEY SAMPLE CHARACTERISTICS: Studies involved a mix of patients who did and did not also receive morphine for chronic pain management

APPLICATIONS: Palliative care

Five studies evaluated paracetamol. None of these demonstrated a meaningful benefit on pain intensity. Only one study reported a significant difference in pain intensity, but this difference was only 0.4 on a 10-point scale. Four studies evaluated NSAIDs. In all of these, patients were also on opioids. One of these compared two different NSAIDs. In the following three studies, use of NSAIDs appeared to have an opioid-sparing effect. Multiple study limitations were identified.

No proof exists that paracetamol or NSAIDs should be used as the first step of the analgesic ladder. No evidence exists of benefit of paracetamol in combination with opioids. NSAIDs may have benefit in patients receiving opioids; however, further research is needed to confirm this.

• Relatively few studies
• Although one inclusion criterion was randomized, controlled trial, one study included was a non-randomized trial.

Findings show that no evidence exists to show efficacy of the addition of acetaminophen to opioids for cancer pain management. Findings suggest that NSAIDs may provide additional benefit to patients on opioids for cancer pain; however, the evidence is limited, and studies done have not involved prolonged use. Nurses need to be aware of potential complications of long-term use of NSAIDs and educate patients regarding these. Selection of adjuvant pain management approaches needs to be made on an individual basis, and continued use needs to be determined on the basis of patient response.

To assess the tolerability and effectiveness of intranasal fentanyl (INFS) for breakthrough pain in opioid-tolerant patients over six months

Patients receiving INFS for breakthrough pain were recruited and data were obtained from patients via survey and clinical records. Patients were followed at three months and six months in person, and data were obtained monthly for six months.

• N = 34 (three months), 12 (six months)
• MEAN AGE = 64.8 years (SD = 12.7 years)
• MALES:  86.7%, FEMALES: 13.3%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types 
• OTHER KEY SAMPLE CHARACTERISTICS: Mean opioid doses for background analgesia ranged from 111–180 mg per day, and mean INFS doses ranged from 87–119 mcg.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

Observational cohort

• Four-point scale for general impression of efficacy from 1 (poor) to 5 (excellent)
• Adverse reactions graded from 0 (none) to 3 (severe)
• Quality of sleep graded from 0 (disturbed) to 3 (very good)

No patients discontinued treatment because of adverse effects. The high drop-out rate over time was caused by death and loss to follow-up. Only minor adverse effects were reported, and they were considered to be related to the opioid therapy used for background pain. Overall, 22% of participants had moderate adverse effects at one month, and 11% had effects at four months. At other time periods, less than 6% had any adverse effects. The most frequent adverse effect was drowsiness. Most patients were receiving buprenorphine, transdermal fentanyl, or oxycodone for background pain. Sleep scores improved significantly over the first four months (p < 0.05). Efficacy scores improved over the first three months overall (p = 0.0005). After three months, the majority of patients reported efficacy levels at 4 or 5.

The findings of this study suggested that INFS for breakthrough pain was well-tolerated and effective for several months.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: High loss to follow-up with resulting low sample sizes at follow-up periods; measurement methods not validated or shown to be reliable; methods of data collection not clear; not clear if patients were directly surveyed or data were obtained from medical records or provider evaluations

There is little information on the long-term efficacy and side effects of INFS for breakthrough pain. This study provided some information in this area, suggesting that INFS was well-tolerated and continued to be effective for the majority of patients in a four- to six-month timeframe.

To compare the analgesic activity and tolerability of orally administered and rectally administered tramadol

In this crossover trial, 30 patients started with orally administered tramadol and switched to rectally administered tramadol and 30 patients started with rectally administered tramadol and switched to orally administered tramadol.

• The sample was composed of 60 patients, with moderate to severe cancer pain (a score of 4 or greater on a 0–10 scale) of nonneurpoathic origin, who were no longer responsive to nonopioid drugs.
• Of all participants, 36 were female and 24 were male. Forty-four patients completed both periods.
• Mean patient age was 66.1 years.
• The sample contained multiple types of primary tumors.

The study was conducted in Italy.

Multicenter, randomized double-blind, double-dummy crossover trial

• Numeric scale, 0–10, Likert verbal (0 = none, 1 = slight, 2 = moderate, 3 = severe), to measure pain intensity 
• Numeric scale, 0–10, to measure pain relief
• Likert verbal scale (none, slight, moderate, severe), to measure pain relief
• Likert scale, 0–3 (none, slight, moderate, severe), to measure symptoms
• Scale, 0–4 (0 = disturbed, 1 = frequent waking, 2 = not restorative, 3 = good, 4 = very good), to measure sleep
• Whether rectal passage occured within one hour of rectal administration
• Physican's and patient's judgment of efficacy of treatment (0 = absent, 1 = poor, 2 = slight, 3 = good, 4 = excellent), assessed at the end of each crossover phase
• Patients' rating of global satisfaction (0 = absent, 1 = poor, 2 = slight, 3 = good, 4 = excellent) with treatment

• Fifteen patients dropped out because of adverse effects; one patient refused treatment.
• Most physicians and patients favored oral administration.Three patients eliminated suppository within one hour of rectal administration.
• Authors found no differences in the adverse effect profiles of orally and rectally administered tramadol.

Rectal administration of tramadol appears to be a reliable, noninvasive alternative method of pain control for patients who are no longer responsive to nonopioid analgesics and who are unable to take oral tramadol. Rectal administration of tramadol appears to be as safe and effective as oral administration.

The study had a high dropout rate, with 25% of patients dropping out.

Rectal irritation has occurred with rectal administration of tramadol. If the patient is neutropenic or thrombocytopenic, rectal administration may be contraindicated. Patients with diarrhea will have difficulty maintaining and absorbing tramadol. Patients with lack of rectal tone will not be able to keep the suppository in the rectal vault.

IV morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to basal opioid regimen. 53 couples of breakthrough events each treated with IV-MO and OTFC. Treatments were recorded. Patients were given both IV-MO and OTFC for each couple of breakthrough events. Order of administration was computer generated. Time between both pain flares was at least 6 hours. Doses of IV-MO 4 mg per 60 mg oral morphine basal and OTFC 200 µcg per 60 mg oral morphine basal.

25 patients with cancer receiving stable dose opioid. Patients were receiving doses of more than 60 mg morphine or equivalent, had acceptable pain relief, and had no more than twopain flares / day. Patients had pain flares between 700 and 1,900.

Comparative study

At episode (T0), 15 (T1) minutes and 30 minutes (T2) after treatment, pain intensity, and opioid-related symptoms were recorded. Decrease in pain intensity of at least more than 33% at T1, not requiring further treatment for next 2 hours was considered effective.

Episodes treated with IV-MO or OTFC showed a decrease in pain intensity. Statistical significance between interventions occurred at T1. AE were comparable

IV-MO and OTFC in doses proportionate to daily scheduled dose are safe and effective. IV-MO may have a shorter onset than OTFC.

Lack of blindness. No placebo control was considered. Double dummy was not feasible. Low number of participants is of concern and most likely due to drop out rates. However, strict inclusion criteria limit this bias.

OTFC given in doses proportionate to basal morphine was effective and safe. It is recommended to research this further.

To evaluate the effectiveness of intrathecal thoracic analgesia compared to continuous epidural analgesia for postoperative pain management

One group of patients received continuous epidural analgesia started prior to surgery, and the other group received an intrathecal catheter that was placed prior to surgery. Data for pain levels, vomiting, and drowsiness were obtained at discharge from the recovery room and at one, two, four, eight, 12, 24, and 48 hours. In both groups, the continuous infusion was of levobupivacaine, which was preceded by a morphine bolus preoperatively.

• N = 48  
• MEAN AGE = 63.7 years
• MALES: 56.4%, FEMALES: 43.6%
• KEY DISEASE CHARACTERISTICS: Disease types were not reported, but most patients had colorectal surgery. All patients were undergoing elective abdominal surgery.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

Randomized, parallel-group trial

• Numeric Rating Scale (NRS) for pain
• Side effects were scored on a three-point Likert scale.
• Vital signs
• Motor blockade (modified four-point Bromage scale)
• Four-point sedation level scale

There were no significant differences between groups in pain intensity or total morphine consumption. There also were no significant differences between groups in Bromage scores, sedation scores, or vital signs.

Continuous intrathecal analgesia provided similar analgesic effects as continuous epidural infusion in the first two postoperative days.

• Small sample (< 100)
• Risk of bias (no blinding)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: A percentage of patients was not included in the final analysis because of protocol violations or missing data. No intention to treat analysis was done.

Intrathecal analgesic infusion provided results similar to those of continuous epidural analgesia in terms of postoperative pain relief and side effects of pain management. This approach provides an alternative mechanism for acute pain management.

To explore research literature related to the use of guided imagery as an intervention for fatigue.

Databases searched were MEDLINE, CINAHL, PsycARTICLES, PsycINFO, and Psychology and Behavioral Sciences Collection from 1980 through 2008, as well as the Cochrane Database of Systematic Reviews and a review of reference lists.

Search keywords were fatigue, tiredness, imagery, guided, and guided imagery.

Inclusion critieria were not specified.

Studies were excluded if they

• Were dissertations
• Used music alone or in combination with guided imagery
• Used hypnosis
• Had relaxation as a keyword.
   

A total of 5,968 references were retrieved. No quality rating was used. A narrative approach was used.

• A total of eight studies were included in the final analysis, with 364 patients (223 in three studies involved patients with cancer).
• The sample range across studies was 8 to 139 patients.
• Of the studies included, two included women with breast cancer, one included patients with colon cancer prior to surgery, one included patients with HIV, one included patients with asthma, one included patients with multiple sclerosis, and one included patients with chronic obstructive pulmonary disease (COPD).
   

Five studies showed no effect, one showed mixed effect, and two demonstrated a statistically significant positive effect in patients with asthma or HIV. Effect sizes from the studies were not reported. Studies varied in measures of fatigue used and intensity of the intervention. The types of images used also varied substantially, which can be expected to influence the results. Study lengths ranged from a single session to multiple daily use for six weeks. The authors noted that the studies that demonstrated significant improvement included the greatest total duration of exposure to guided imagery.

The findings were inconsistent across the studies, and those including patients with cancer did not show a significant effect. Duration of exposure may influence effectiveness. This review did not support the effectiveness of guided imagery alone for fatigue in patients with cancer. 

• The study included a small number of studies with varied sample characteristics, different study measures, and intensity of interventions studied.
• Studies were eliminated that included relaxation because guided imagery and progressive muscle relaxation often are used together.

Insufficient evidence exists from this review to recommend use of guided imagery alone. Additional well-designed research and evidence synthesis encompassing the combination of relaxation and guided imagery are needed.