Early Opioid Use

Early Opioid Use

PEP Topic 
Chronic Pain
Description 

Early opioid use refers to managing chronic pain by using opioids to treat levels of pain lower than the levels the World Health Organization’s (WHO's) three-step pain relief ladder specifies for treating with opiods. The WHO suggests beginning treatment at step 1, using nonopioids with or without adjuvant medication, and moving to step 2, using weak opioids, if pain persists. If pain persists with step 2 treatment, step 3 involves using strong opioids with or without adjuvant treatment. Researchers have evaluated early use of opioids for effectiveness in patients with chronic cancer-related pain.

Likely to Be Effective

Research Evidence Summaries

Bandieri, E., Romero, M., Ripamonti, C.I., Artioli, F., Sichetti, D., Fanizza, C., . . . Luppi, M. (2016). Randomized trial of low-dose morphine versus weak opioids in moderate cancer pain. Journal of Clinical Oncology, 34, 436–442. 

doi: 10.1200/JCO.2015.61.0733
Print

Study Purpose:

To evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients

Intervention Characteristics/Basic Study Process:

This multicenter, 28-day, open-label randomized controlled study for adults with moderate cancer pain assigned to receive either a weak opioid or low dose of morphine was designed to evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients. The weak opioid group received either tramadol or codeine with or without paracetamol. The morphine group received morphine after a three-day titration phase with normal release morphine up to 30 mg per day. The groups were assessed every seven days.

Sample Characteristics:

  • N = 240   
  • AGE = 59–74 years (WO group), 56–74 years (M group)
  • MEDIAN AGE = 68 years
  • MALES: 57% (WO group), 47.5% (M group); FEMALES: 43% (WO group), 52.5% (M group)
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Both solid tumors and hematologic tumors
  • OTHER KEY SAMPLE CHARACTERISTICS: Pain intensity, cancer symptoms, Karnofsky score, age, mental capacity

Setting:

  • SITE: Multi-site   
  • SETTING TYPE: Multiple settings    
  • LOCATION: 17 Italian oncology centers

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Multiple phases of care
  • APPLICATIONS: Elder care, palliative care 

Study Design:

  • Multicenter, 28-day, open-label, randomized controlled study

Measurement Instruments/Methods:

  • Numerical Response Scale (0–10) for pain
  • Karnofsky Performance Status Scale, 60% or higher for patient functioning 
  • Edmonton Symptom Assessment System (ESAS) used to assess nine symptoms commonly experienced by patients with cancer during the previous 24 hours (validated in the Italian language)

Results:

Primary endpoint of pain reduction of 20% or more from baseline was achieved in 88.2% of patients in the morphine group and 54.7% of patients in the weak opioid group (odds ratio = 6.18, 95% Cl [3.12, 12.24]; p < 0.001). Full adjustment for baseline covariates did not modify the results. The advantage of M over WO was evident at the first control at one week of observation (80.9% and 43.6%; p < 0.001) and remained constant at each follow-up. At the end of the observation period, a satisfactory pain control was reported in both groups, although with a statistically and clinically significant advantage of the M group. Also, a clinically (< 30%) and highly meaningful (< 50%) pain reduction was found more frequently in the M group. The general condition of patients based on the ESAS overall symptom score was better in the M group with a median score of 10 versus 19 (p < 0.001). Forty-one patients in WO switched to a strong opioid (35%) and 17 patients (15%) in the M group switched to another strong opioid (p = 0.001).

Conclusions:

In patients with cancer and moderate pain (4–6 out of 10), low-dose morphine reduced pain intensity significantly compared to weak opioids (tramadol or codeine) with a similarly good tolerability and adverse effects.

Limitations:

  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Key sample group differences that could influence results
  • Long accrual of patients
  • Open-label design

Nursing Implications:

This study is has very important patient and nursing implications. By not using step II, weak opioids, we could potentially have better control of our patient’s pain as well as decrease costs by not using some of the more expensive weak opioids. More research is needed to compare the most commonly used strong opioids as first-line medications for pain intensity and adverse effects. Future studies should prospectively determine the morphine equivalent daily doses. These studies may determine that step II opioids are less effective and more costly. Ending step II in the World Health Organization's (WHO) ladder could simplify pain management while giving better pain control in a more efficient manner.

Maltoni, M., Scarpi, E., Modonesi, C., Passardi, A., Calpona, S., Turriziani, A., . . . Amadori, D. (2005). A validation study of the WHO analgesic ladder: A two-step vs. three-step strategy. Supportive Care in Cancer, 13, 888–894.

doi: 10.1007/s00520-005-0807-6
Print

Study Purpose:

To determine if, on the WHO analgesic ladder, passing directly from step 1 to step 3 is more effective than the traditional three-step strategy for treating chronic cancer pain; to evaluate the tolerability and therapeutic index of both strategies

Intervention Characteristics/Basic Study Process:

Over 24 months, patients were monitored at home by telephone or a home health nurse. The study design included two arms: in one, patients moved from step 1 to step 3 (with treatment with strong opioids); in the other, patients moved from step 1, to step 2 (with treatment with weak opioids), to step 3.

Sample Characteristics:

  • The sample was composed of 54 patients.
  • Patients were age 18 and older.
  • The sample was composed of patients with multiple visceral or bone metastases or locally advanced disease.

Setting:

Italy

Study Design:

Randomized controlled trial

Measurement Instruments/Methods:

  • Numeric Rating Scale (NRS), 0–10, to measure pain
  • Five-step scale, 0–4, to measure other symptoms
  • Five-step scale, 0–4, to measure degree of patient satisfaction
  • Use of coanalgesics, adjuvants, and other treatments (as established by a yes/no answer)

Results:

  • Going from step 1 to step 3 resulted in a statistically significant advantage over the traditional progression. Authors did not report the P value.
  • Authors noted that all patients needed prophylactic treatment of constipation.

Conclusions:

Preliminary data suggest that a direct move to the third step is feasible and could reduce some pain scores. The two-step strategy this study supports requires careful management of side effects.

Limitations:

The study had a small sample size.

Nunes, B.C., Garcia, J.B., & Sakata, R.K. (2014). Morphine as first medication for treatment of cancer pain. Brazilian Journal of Anesthesiology, 64, 236–240. 

doi: 10.1016/j.bjane.2013.06.016
Print

Study Purpose:

To evaluate the use of morphine as a first-line medication for pain in patients with advanced or metastatic cancer instead of the World Health Organization (WHO) ladder

Intervention Characteristics/Basic Study Process:

This was a prospective, randomized study on the effectiveness of morphine as a first-line medication in two groups. The two groups were randomized using envelops. Patients in group 1 (G1) were treated according to the WHO analgesic ladder guidelines with paracetamol at 1 g every six hours (titrated up to a maximum of 4 g per day), codeine at 30 mg every four hours (360 mg per day), and morphine at 10 mg every four hours. Group 2 (G2) received morphine at 10 mg every four hours. G1 patients switched drugs according to pain intensity following the analgesic ladder, and G2 patients had their dose adjusted based on intensity, adjusting the dose of the analgesic drug. All additional adjuvant therapies were logged. Pain intensity was measured every two weeks using the Visual Analog Scale, quality of life and satisfaction with treatment were assessed, and physical capacity was determined by the Eastern Cooperative Oncology Group index.

Sample Characteristics:

  • N = 60  
  • AVERAGE AGE = G1 58.7 years (SD = 12.4 years); G2 57.5 years (SD = 12.7 years)    
  • MALES: G1 83.33%; G2 90%, FEMALES: G1 16.67%; G2 10%
  • KEY DISEASE CHARACTERISTICS: No specific disease was targeted although there was a high incidence of head and neck cancer. 

Setting:

  • SITE: Single site    
  • SETTING TYPE: Inpatient

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Multiple phases of care
  • APPLICATIONS: Elder care and palliative care 

Study Design:

Retrospective, randomized study

Measurement Instruments/Methods:

  • A confidence level of 95% and a study power of 80% were used. This determined that 30 patients per group were needed.
  • In total, 150 patients were screened, and 60 met inclusion criteria.

Results:

Twenty-four patients in G1 and 29 in G2 completed the study. There was no difference in patient satisfaction between the groups. There was a higher incidence of adverse effects (i.e., vomiting, nausea, constipation) in G2. This supported what is seen in the literature. These effects were manageable and did not negatively affect quality of life. The study was conducted over three months although the sample was obtained over two years and six months. There were no consistent differences in pain severity between the groups.

Conclusions:

This study demonstrated the efficacy of both methods for the reduction of pain intensity in both groups, and that both methods are comparable.

Limitations:

  • Small sample (< 100)
  • Other limitations/explanation: Double-blinding was not possible.

Nursing Implications:

Morphine as a first-line treatment for patients with advanced and moderate cancer appeared to be acceptable as a treatment for pain. The management of adverse symptoms was manageable and was comparable to traditional therapy. 

Takase, H., Sakata, T., Yamano, T., Sueta, T., Nomoto, S., & Nakagawa, T. (2011). Advantage of early induction of opioid to control pain induced by irradiation in head and neck cancer patients. Auris, Nasus, Larynx, 38(4), 495–500.

doi: 10.1016/j.anl.2010.12.012
Print

Study Purpose:

To determine whether early induction of low-dose opioid for the treatment of mild pain improves dietary and caloric intake and reduces weight loss among patients with head and neck cancer

Intervention Characteristics/Basic Study Process:

The low-dose opioid this study used was controlled-release oxycodone (CRO). The intial dose was 10 mg and the dose was titrated upward as needed. Because all patients agreed to use an opioid at some point, patients were classified into two groups, mild and moderate (referring to pain), according to when the opioid was introduced.

Sample Characteristics:

  • The sample was composed of 43 patients, 23 in the mild-pain group and 20 in the moderate-pain group.
  • In the mild group, mean patient age was 63.6 years. In the moderate group, mean patient age was 63.7 years.
  • In the mild group, 2 patients were female and 21 patients were male. In the moderate group, 2 patients were female and 18 were male.
  • All patients had head and ceck cancers and were receiving radiation therapy from 40 Gy to a high of 60 Gy. (Not all patients received the highest dose.)

Setting:

  • Single site
  • Inpatient
  • Department of Otorhinolaryngology, Fukuoka University Hospital, Fukuoka, Japan

Study Design:

Prospective descriptive study

Measurement Instruments/Methods:

  • Visual analog scale (VAS) (0 = no pain, 100 = unbearable pain), to measure pain
  • Caloric intake – caloric intake rate (Caloric intake rate was calculated by dividing the caloric intake by the basal energy expenditure [BEE]. Caloric intake was estimated from inpatient dietary forms and from what patients actually ate.)
  • Weight loss
  • Duration of time on a regular diet before the switch to a softer or liquid diet

Results:

  • VAS pain scores were significantly lower in the mild group than in the moderate group, at 25–50 Gy.
  • The amount of oxycodone used for pain was significantly lower in the mild group than in the moderate group.
  • Patients in the mild group maintained a regular diet for a significantly longer period than did patients in the moderate group.
  • Caloric intake was significantly higher in the mild group, at more than 20 Gy.
  • Weight loss was significantly lower in the mild group, at more than 20 Gy.
  • The incidence of side effects was equal in both groups. Constipation and nausea were the most frequent side effects, followed by sleepiness, diarrhea, vomiting, itching, and dysuria.

Conclusions:

Results indicated that the introduction of opioids for mild pain during radiotherapy controls the level of pain and increases the food intake of head and neck cancer patients. For such patients, use of opioids, beginning when pain is mild, may help to ensure a better dietary intake during radiotherapy.

Limitations:

  • The study had a small sample, with fewer than 100 patients.
  • Researchers took almost four years to gather data.
  • The validity of the caloric-intake measures, based on what patients may have eaten, is questionable.

Nursing Implications:

For the population of patients with head and neck cancer, maintaining food intake is a challenge, so this study is relevant. The intervention uses a standard pain control agent; the point at issue is the advisability of early intervention (early in terms of the World Health Organization ladder). The patient population pertinent to the study is very specific; the study is not generalizable.

Tessaro, L., Bandieri, E., Costa, G., Fornasier, G., Iorno, V., Pizza, C., . . . Micheletto, G. (2010). Use of oxycodone controlled-release immediately after NSAIDs: A new approach to obtain good pain control. European Review for Medical and Pharmacological Sciences, 14(2), 113–121.

Print

Study Purpose:

To evaluate the efficacy and tolerability of controlled-release (CR) oxycodone as first-line therapy in patients with chronic pain not relieved by nonsteroidal anti-inflammatory drugs (NSAIDs).

Intervention Characteristics/Basic Study Process:

Patients with NSAID-refractory chronic pain were treated with oral oxycodone CR twice daily for at least 28 days. Dosage was individualized for each patient and up-titrated over the first week of treatment. Primary end point was reduction in numeric rating scale (NRS) for pain. Secondary end points were tolerability, quality of life, and patient assessment of treatment efficiency.

Sample Characteristics:

  • The sample was composed of 309 patients.
  • Mean patient age was 67.1 years. Age range was 31–94 years.
  • Of all patients, 50% were female and 50% were male.
  • All patients had moderate to severe cancer or noncancer pain (that is, pain rated 4–10 on the 0–10 NRS). Of all patients, 24.3% had somatic pain, 14.1% had neuropathic pain, 8.2% had visceral pain, and 53.4% had mixed pain. Patients had had no previous or ongoing treatment with opioids.

Setting:

Multisite

Study Design:

Prospective

Measurement Instruments/Methods:

  • Numeric Rating Scale (NRS)
  • Brief Pain Inventory (BPI)

Results:

Data revealed a significant decrease (57%) in pain intensity during the first week of therapy: a  decrease in NRS pain score from 7.85 + 1.4 to 3.35 + 1.8 (p < 0.00001). Overall, by the end of the study, NRS pain score had decreased 72.3% from baseline. Quality of life improved significantly (p < 0.005) during oxycodone therapy, and 91% of patients rated the treatment as effective or very effective.

Conclusions:

Historically, according to guidelines of the World Health Organization, oxycodone CR has been reserved for step 3 of treatment. This study examines earlier use of oxycodone CR in the management of chronic cancer and noncancer pain, as a first-line treatment after NSAIDs. The results of this study warrant consideration because earlier, more effective pain control enhances quality of life.

Limitations:

The study has a risk of bias due to no appropriate control group.

Nursing Implications:

Pain management must be individualized. Controlled-release opioids may be useful as an intervention after NSAIDs. However, randomized control-group research comparing the results of studies that use CR opioids in step 2 would be of value.

Menu