An Italian Expert Consensus on the Use of Opioids for the Management of Chronic Non-Oncological Pain in Clinical Practice: Focus on Buprenorphine.

Figures & data

Table 1 List of Statements with the Respective Level of Consensus Reached During the First and Second Round

Statement*	First Round (N=84)		Second Round (N=89)
A.General concepts	N (%) with agreement ≥4	Median (IQR)	N (%) with agreement ≥4	Median (IQR)
1. The concept of nociception, ie the activation of peripheral nociceptors and the transmission of pain impulses to brain, must be distinguished from the concept of pain, i.e, the central elaboration of such stimulus, in a totally personal way.	70 (84.3%)^§	5 (1)	67 (75.3%)	4 (1)
4. The choice of the most adequate drug for pain management must be based on the identification of the pain generator as well, ie the underlying pathogenic mechanisms, in order to distinguish nociception from the neuropathic-dysfunctional component.	82 (97.6%)	5 (1)	83 (93.3%)	5 (1)
3. The 3-step approach of the WHO analgesic ladder for oncological pain is also appropriate for non-oncological chronic pain.	38 (45.2%)	3 (1.25)	31 (34.8%)	3 (2)
34. General Practitioners requesting specialist pain management support, should refer to temporal criteria, type of pain and drug resistance.	56 (66.7%)	4 (2)	65 (73%)	4 (2)
36. Communication (which is one of the important aspects of any therapeutic regimen), can strongly affect (express the degree of agreement with each option): 36. a therapy adherence; 36. b the evaluation of the obtained antalgic effects.	83 (98.8%)	5 (0)	84 (95.5%)^# 80 (90.9%)^#	5 (1) 5 (1)
B. Non opioid therapy
5. In patients with chronic osteoarticular pain without identified pain generator, pain treatment should include the association of analgesic drugs with agents for neuropathic pain.	23 (27.7%)^§	3 (2)	40 (44.9%)	3 (2)
7. The fear of an opioid epidemic leads to excess use of NSAIDS in the managements of chronic pain, although their long-term use is not recommended.	66 (78.6%)	5 (1)	74 (83.1%)	4 (1)
8. The chronic use of COXIB is not safe and is not devoid of side effects for the patient.	70 (83.3%)	5 (1)	69 (77.5%)	4 (1)
9. Paracetamol is not an anti-inflammatory drug; it is a central analgesic, crossing the brain blood barrier and exerting its pharmacologic action at different levels in the CNS.	78 (92.9%)	5 (1)	78 (87.6%)	5 (1)
10. Palmitoylethanolamide (PEA), a modulator of inflammation both in peripheral tissues and in CNS, is useful in various pain conditions.	65 (77.4%)	4.(1)	63 (71.6%)	4 (2)
C. Opioid therapy
2. In the efficacy evaluation of opioid therapy, the global improvement of QoL, including potential side effects, are to be assessed beyond analgesia.	76 (90.5%)	5 (1)	86 (96.6%)	5 (1)
6. Patients with therapy-controlled non-oncological chronic pain may develop flares, ie exacerbation periods lasting days, in which pain gradually increases and then slowly decreases. In these cases, it is recommended: a. To increase ongoing therapy only in case of pain increase lasting >1 week b. Plan rescue drugs or dosages in advance, which the patient can manage autonomously	57 (67.9%)**	4 (1.25)	23 (27.5%) 65 (73%)	3 (2) 4 (2)
11. The use of high potency analgesic opioids at low doses rather than low potency opioids at higher doses may be favorable in patients with moderate chronic non-oncological pain, if low starting dosages and a slow up-titration are applied.	63 (75%)	4 (1.25)	59 (66.3%)	4 (2)
12. The different degrees of affinity for MOR of individual opioids can have an impact on the development of side effects associated with acute opioid administration, such as respiratory depression and gastrointestinal disorders.	58 (69.0%)	4 (1)	61 (68.5%)	4 (1)
13. Androgen deficiency during chronic opioid therapy (opioid-induced androgen deficiency, OPIAD) is more marked with agents with higher intrinsic activity on MOP receptors (such as morphine, fentanyl and oxycodone) than with agents with lower intrinsic activity (such as buprenorphine and tapentadol).	46 (56.1%)^§§	4 (1)	59 (66.3%)	4 (2)
14. Certain opioid side effects occurring in all patients (with different frequency) tend to diminish in the long term, whereas constipation remains.	62 (73.8%)	4 (2)	67 (75.3%)	4 (1)
15. A proper opioid titration (starting with low doses and gradually increasing dosages) is a pre-condition to avoid the development of opioid-induced cognitive disorders, especially in the elderly.	72 (85.7%)	5 (1)	79 (88.8%)	5 (1)
16. Despite having high affinity for all opioid receptors (MOR, KOR and DOR), buprenorphine exerts a partial agonist activity on MOR opioid receptors.	65 (78.3%)^§	4 (1)	68 (77.3%)	4 (1)
17. Buprenorphine exerts a biphasic action on hyperalgesia and can be useful in opioid-induced hyperalgesia.	64 (76.2%)	4 (1)	63 (70.8%)	4 (2)
18. Buprenorphine is lacking intrinsic immune-suppressive activity.	48 (57.1%)	4 (2)	60 (67.4%)	4 (1)
19. Buprenorphine is not likely to cause tolerance or physical and psychological addiction.	59 (70.2%)	4 (2)	54 (60.7%)	4 (1)
20. Buprenorphine treatment, by blocking the central sensitization mechanism involved in hyperalgesia and allodynia: a. is useful for refractory neuropathic and nociceptive pain. b. Is indicated also in patients not controlled by a previous analgesic treatment with opioids	53 (63.1%)**	4 (1)	57 (64.8%)^# 60 (68.2%)^#	4 (1) 4 (1)
21. Buprenorphine is an optimal therapeutic option in patients with renal dysfunction (even severe).	73 (86.9%)	5 (1)	76 (85.4%)	5 (1)
22. Buprenorphine can be administered in elderly patients treated with oral anticoagulants and antiplatelet agents.	76 (90.5%)	5 (1)	80 (89.9%)	5 (1)
23. Transdermal administration warrants constant plasma concentrations, without peaks, which often cause adverse events.	72 (85.7%)	5 (1)	72 (80.9%)	5 (1)
24. Transdermal administration is particularly useful in elderly patients, thanks to its ease of use, which favors treatment adherence.	77 (91.7%)	5 (1)	80 (90.9%)^#	5 (1)
25. In order to interrupt opioid therapy without causing abstinence symptoms, doses must be gradually decreased, by 10–25% every week.	65 (78.3%)^§	4 (1)	75 (84.3%)	4 (1)
26. Opioid rotation can be considered a good dose tapering technique in patients treated with high potency opioids who do not achieve a good balance between analgesic efficacy and side effects.	73 (86.9%)	4 ((1)	76 (85.4%)	4 (1)
35. Following AIFA disposition in June 2020, opioid drug packaging should report “It contains opioids. It may induce addiction”: it is therefore advisable, when an opioid-based therapy is started, to inform patient about the type of drug he is going to take, asking his written informed consent.	53 (63.1)	4 (2)	63 (70.8%)	4 (1)
D. Interventional therapy
27. In patients with Failed Back Surgery Syndrome (FBSS), the use of invasive analgesic techniques should be preferred to a new surgical intervention.	66 (78.6%)	4 (1)	75 (84.3%)	5 (1)
28. Chronic post-surgical pain treatment should consist of a multimodal approach including opioids, adjuvant agents and non-pharmacologic interventions.	77 (91.7%)	5 (1)	77 (86.5%)	5 (1)
29. In complex regional pain syndrome (CRPS), or sympathetic reflex dystrophy, the reported pain does not correspond in terms of intensity or duration to what is expected according to the causative trauma.	75 (89.3%)	4 (1)	73 (82%)	4 (1)
30. Epidural block with steroids is effective in the midterm, especially in patients with radicular pain.	71 (84.5%)	4 (0)	68 (77.3%)	4 (1)
31. O2O3 application, together with steroid and local anesthetics, amplifies the therapeutic benefits induced by a higher anti-inflammatory and anti-oxidant action at the transforaminal level.	42 (50.6%)^§	4 (1)	49 (55.7%)^#	4 (1)
32. In the facet joint syndrome, a simple pain test in the involved region, through injection of a small volume of local anesthetic, will cause a partial and temporary symptom remission, confirming diagnosis.	73 (86.9%)	4 (1)	76 (85.4%)	4 (1)
33. Spinal cord stimulation (SCS) (express the degree of agreement with each option): a. Represents the gold standard approach to FBSS and type I and type II CRPS; b. Must be performed in specialized centers.	60 (71.4%)	4 (2)	62 (69.7%) 83 (94.3%)^#	4 (2) 5 (1)

Notes: *The statements presented refers to the questionnaire as presented to the participants in the second round. **Statements 6 and 20 were modified in the second round also with the addition of statements 6b and 20b (not present in the first-round questionnaire). ^§Out of N=83 respondents (1 of the 84 answering panelists did not express his agreement on this specific statement). ^§§Out of N=82 respondents (2 of the 84 answering panelists did not express their agreement on this specific statement). ^#Out of N=88 respondents (1 of the 89 answering panelists did not express his agreement on this specific statement).