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- 1. Prolonged treatment with opioids of selected patients with
severe chronic non-cancer pain is still medically accepted “good practice”.
- 2. Long term opioid treatment can be undertaken by the patient’s GP who knows the
patient and his social situation well.
- 3. Patients and doctors must be informed and must fully realize,
before starting a trial of opioid therapy, that long-term opioid treatment requires considerable effort by both patient and doctor.
- 4. Qualified resources must be available to handle “problematic
prescription opioid use” and the more serious, chronic neuro biological disease “addiction”, should these complications arise.
A Double le-blin blind Mult ltip iple le Intrav avenous Test t for Evalu luat atio ion of Opio ioid id Sensit itiv ivity ty in in the Cli linic ic
Jan Persson1,2 , Monica Pedersen1,2
1Pain Clinic, Department of Anesthesia, Karolinska University Hospital, Huddinge, 2CLINTEC, Karolinska Institutet, Stockholm, Sweden
Aim of investigation
Exploring a method for quasi-objective evaluation of
- pioid pain relief as an aid in clinical decision-making as
well as patient motivation.
Methods
Different opioids are given i.v. in two doses. The size of the dose is based on the clinical dose used to treat the
- patient. Doses have ranged from 2.5 mg to 40 mg of
Morphine equivalents. Midazolam is used as an active
- placebo. Each solution is given as a double-blinded 100
ml i.v. infusion during 20 minutes when the patient requires pain relief. The patients rate their pain using a visual analogue scale (VAS 0-10) before and twenty minutes after the infusion. After the test has been completed it is decoded. In the evaluation several factors are considered. The pain intensity difference (PID) for each dose of a certain opioid is calculated giving an opportunity for comparison of the effect of different opioids and doses. Since each opioid is administered in two doses a dose response analysis can be performed. An opioid responsive pattern (fig 1) would be characterized by a large PID and a consistent dose-response pattern (fig 3), compared to a non- responsive one (fig 2). The result of the test and the recommendations based upon it, are discussed with the patient. Results We have been using the test in our clinical work over many years and a wealth of clinical experience has been collected. The results indicate that the method is an aid in the choice of appropriate opioid therapy. It has often helped us to wean the patients from
- pioids while being reasonably sure that we are not
depriving them of pain relief.
Fig 1: Test results from a patient classified as having an
Fig 2: Test results from a patient classified as having a non opioid-responsive pain
Discussion
Opioid treatment may offer pain relief with increased activity and functioning, higher quality of life and negligible side effects, in selected patients. Clinical utility is mainly contingent on opioid sensitivity and responsiveness. Variations in opioid sensitivity is a contentious issue. Although most patients with a poor response to opioids would be expected to discontinue their opioid use, some do not. The reasons are non-analgesic opioid effects such as anxiolysis, sedation and addiction. Several caveats have to be addressed concerning the validity of the test. The tenet that all
- pioids basically are the same can be questioned (Kindler 2011). A
general “opioid responsiveness” perhaps cannot be defined. Even if such an entity can be useful the validity of the test in identifying it has not been rigorously proven. Carry-over effects from previous doses can furthermore confound interpretation. Notwithstanding these objections, we have found that analyzing the test results in terms of a general “opioid-response” pattern, usually results in a relatively clear-cut result. In particular, the negative predictive value appears to be of great clinical importance (fig 4).
Conclusion We have found the double blind multiple-opioid intravenous test to be a valuable clinical tool, mainly in that it provides a base for the dialogue between clinician and patient . It is easy to perform and can be administered by nurses. The test has not yet been validated as a scientific instrument. References: Kindler LL et al J Pain. 2011 Mar;12(3):340-51
Fig 3: General dose-response curve for opioid response Fig 4: Predictive values for test outcomes
Drug, dose (mg) VASbefore VASafter
Buprenorphine 0.3 8 8 Buprenorphine 0.6 8 8 Cetobemidone 5 8 7 Cetobemidone 10 8 8 Fentanyl 0.05 7 5 Fentanyl 0.1 9 8 Methadone 5 7 7 Methadone 10 8 8 Midazolam 2 8 8 Midazolam 2 5 4
Drug, dose (mg) VASbefore VASafter
Buprenorphine 0.3 5 Buprenorphine 0.6 4 Cetobemidone 5 4 1 Cetobemidone 10 4 1 Fentanyl 0.05 5 Fentanyl 0.1 5 Methadone 5 6 5 Methadone 10 5 Midazolam 2 5 4 Midazolam 2 4 4
Can we test for opioid sensitivity?
