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The Management of Pain in the Dialysed Patient Bernard J. Lapointe Associate Professor, department of Oncology and of Family Medicine Eric M. Flanders Chair in Palliative Medicine Potential conflict of interest • I have not received any support from the pharmaceutical industry in regard of the study or the clinical use of methadone. • I have received support from TEVA Canada for participating to advisory boards. • I have received support from Wex Technologies for participating to an advisory board. The disease burden in the dialysed patient: • Patients treated with chronic dialysis experience substantial decrements in health related and global quality of life • Multiple factors: loss of vocational capacity, effects of a chronic, physically demanding daily or thrice weekly therapy; decline in functional capacity, medication side effects; loss of social support and impact of multitude of physical and emotional symptoms. • Seminars in Dialysis, Weisbord (march-april 2016). The multiple burdens linked to the dialysis • HD patients: – Disfiguration from the fistula appearance – Commitment to the treatment ( twice a week) – Transport delays, difficulty negotiating schedules • PD patients – – – – Feeling bloated Fear of infection Negative body image from catheter Social isolation • For both groups: – Dietary and fluid restrictions – High medication burden Symptom prevalence in the dialysed patient: • • • • • • • • • • • fatigue/tiredness pruritus constipation anorexia pain sleep disturbance anxiety dyspnea nausea restless legs and depression 27% 71% 55% 53% 49% 47% 44% 38% 35% 33% 30% (12% to 97%), (10% to 77%), (8% to 57%), (25% to 61%), (8% to 82%), (20% to 83%), (12% to 52%), (11% to 55%), (15% to 48%), (8%to 52%), (5%to 58%). • Murthag FE, Adv Chronic Kidney Dis. 2007 Jan;14(1):82-99 Pain in dialysed patients: • Significant pain is experienced by more than 50% and is moderate to severe in at least half. • Commonest group is musculoskeletal pain • Specific to dialysis: – – – – – Cramps Headaches Fistula pain (HD) Abdominal pain (PD) pain of fistula needling Infections such as discitis (Linked with use of catheters for HD) – septic arthritis, peritonitis (PD) Prevalence of pain in dialysed patients: • • • • 18% had more than one identifiable cause 55% rated their pain as severe 74,8% noted inadequate treatment of pain 35,95 reported use of opioids to manage pain • (Davison, Am J Kidney Dis 2003) • The reported prevalence of long-term opioid use in the HD population ranged from 5%-36% in one systematic review • (Wyne, Rai, Clin J am Soc Nephrol 2011). In the Dialysed Patient Chronic Pain can also result from: • Calciphylaxis: – result from calcification of small vessels leading to tissue ischemia with the development of extreme pain. • Vascular seal secondary to an arteriovenous fistula or graft • And complications of polycystic kidney disease, diabetes and various musculoskeletal disorders. Impact of pain • Correlate significantly with depression • Moderate-severe 34% incidence of depression and 75% of insomnia compared to 18- and 35% with none or mild pain, reduced physical and mental quality of life and insomnia – (Davison Jhangri, j pain Symptom Manag 2010) Pain is also associated with : • Noncompliant behaviour • Consideration of dialysis discontinuation – (3 times more likely) • Health resource utilization • May be associated with increased mortality in patients on chronic dialysis. Is pain in the dialysed patient manageable ? • Not a lot of data from large-scale clinical trials on the efficacy of pharmacological and / or nonpharmacological analgesic therapy in patients receiving chronic dialysis. • 96% of patients on chronic hemodialysis who received treatment based on the WHO analgesic ladder reported a statistically significant decrease in the mean pain score ( form 7.8 +- 1,2 to 1,6+1.4) after a 4 week treatment. • Baakzoy and Moss J Am Soc Nephrol 2006) Obstacles to pain management in the dialysed patient • • • • Elderly patients with multiple co-morbidity Complex drug regimen Lack of recognition of the problem Complicated drug handling (as discussed before) • Fear of opioids The SMILE study: • randomized study looking at two strategies aiming at improving treatment of pain and depression in 220 HD patients. – Providers informed of the presence and severity of these symptoms – Providers informed of the presence and severity of these symptoms, trained nurses provided treatment recommendations based on evidence-based treatment algorithms and facilitated the implementation of therapy. • Trial failed to demonstrate a clinically significant difference between the two groups in the alleviation of depression or pain. • Trial did document however that fewer than 30% of patients with depression and less than 45% of patients with pain received treatment for these symptoms. The Management of Pain in the Dialysed Patient • According to the WHO ladder. • Multiple factors should be considered when prescribing pain medications for patients on dialysis, including the properties of the parent drug and its metabolites; the physical properties of the dialysis equipement )( eg. Filter pore size or flow rate) • (Harisingani, The Hospitalist, 2013) • Level One Pain Intensity: • Acetaminophen. Can be given at normal doses as clinically indicated. It is a dialyzable compound – Monitor dose used by the patient – Do not exceed 4gm /day A word about NSAIDS: • not recommended for patients who dialyse and have significant residual renal function because of the risk of further decline. • Where NSAIDS are clinically indicated for those who dialyse and individual decision should be made; non renal side-effects are increased in ESRD; if used the lowest effective dose should be prescribed for as short a time as possible. • Ibuprofen is considered a safer option for patients on dialysis. – Ketoprofen dose reduction recommended for patients on dialysis – Ketorolac should be avoided (accumulate and not removed by dialysis) – Naproxen not recommended – Celecoxib unlikely to be removed by dialysis, therefore should be avoided Level 2 moderate pain • codeine to be avoided in patients on dialysis. • Tramadol 50mg four times a day can provide useful analgesia in patient dyalised. It is minimally cleared by dialysis (7%). • Cautious use in dialysis patients should include a reduction in dose and increase in dosing interval, for example starting at 50 mg bid and a maximum daily dose of 200mg. • extended release formulation of tramadol has not been studied and probably should be best avoided. Level 3, severe pain • Strong opioids: • Morphine not recommended • Hydromorphone: – H3g is removed by dialysis. Therefore hydromorphone is an option and can be used in patient dialysed with caution. – Dialysis removes 40-55% of pre-dialysis levels…. Risk of increased pain and maybe withdrawal symptoms during dialysis. • (Perlman, Pain, 2013) – If patient abandon dialysis, the use of hydromorphone needs to be re-evaluated (accumulation) Other strong opioids: • Oxycodone: – No evidence based recommendation at the present. – Unsure about efficacy of removal by dialysis of oxycodone and its metabolite. A case report suggest that it might not be removed. • Fentanyl and Alfentanyl: – Metabolized to inactive, non-toxic metabolites – Less than 10% excreted of fentanyl and 1% of alfentanyl excreted in urine – It is not expected that fentanyl is dialyzable . – Fentanyl transdermal and sc are good alternatives for dialysed patient • Buprenorphine: – Extensive metabolisation, metabolites eliminated in urine. – May play a larger role in the future but for now Very little known on its use in dialysed patients. • Methadone: – Inactive metabolites, both parent drug and metabolites are excreted in faeces and the urine – Less than 15% is removed by dialysis. ( no supplementation after dialysis needed) – Should only be used by those familiar with its use. The treatment of neuropathic pain in the dialysed patient. • Neuropathy diagnosed in 61,3% of dialysis patients. Majority ( 45% secondary to a systemic disease) Minority (16%) to uraemic neuropathy. – ( Mambelli, Clin Nephrol, 2012) • Carpal Tunnel Syndrome affects 28,5% of dialysis patients and is positively correlated with time on dialysis. • Ulnar neuropathy has been described in 41-60% of HD patients • IASP evidence based guidelines for the management of neuropathic pain. Treatment in the ESRD group follows these recommendations. The adjuvants for neuropathic pain: • Gabapentin and Pregabalin have been specifically evaluated in these patients and are the prefered medications for neuropathic pain. • Gabapentin has low protein binding favouring its ability to be dialysed with approximately 35% cleared with HD. • Gabapentin dosing recommended is 300mg daily with a supplemental dose of 200-300 mg after each dialysis. • (Davison, Clin J Am Soc Nephrol 2012). • However more conservative approach recommend to start with 100mg daily (qhs) with a supplemental dose of 100mg post dialysis. • (Davison, Semin Dial, 2014). • Pregabalin recommended daily dose is 25-75 with a supplemental dose equivalent to the daily dose after dialysis. Recommended starting dose is 25mg qhs • TCA’s anticholinergic effects may not be well tolerated by dialysis patients. – Desipramine or nortriptyline may be preferred if you are considering a TCA. Desipramine 10mg suggested as a starting dose. Intra-dialytic Pain Syndromes: • AV Access Pain. – Topical analgesic may be of benefit for cannulation pain (EMLA cream or ethyl chloride vapo-coolant spray. • Headaches. – Up to 48% of patients will experience this syndrome – Ethiology is unclear, headaches often develop during at least half of HD session and resolve within 72 hrs of HD – No treatment recommendation – However ergotamine should be avoided due to the risks of vasoconstrictive effects of the AVF • Muscle cramps. – Affect 33-85% and contribute to 18% of early discontinuation of treatment – Cramp reduction using Vitamin E (54%) – Vitamin C,(61%) – Combination (97%) and placebo (7%) Algorithm to treat severe chronic pain in dialysis patients. • start using hydromorphone 0,5mg – 1mg p.o. q4h, 0,5 mg q2h prn • titrate slowly upward q2-3 days, • if total daily dose exceeds 6mg /24hrs substitute with fentanyl transdermal 12mcg/hr in the patient with continuous pain. • titrate upward the same way using hydromorphone 1 mg prn q2h and adjusting transdermal fentanyl dose. • Consider using acetaminophen • and using other adjuvants when indicated • Ask, ask, ask… • Pain needs to be reassessed and side-effects monitored • Source of pain and medication should be documented • Identifying one provider of analgesics References: • Seminars in Dialysis. Koncicki, Brennan, Vinen, Davison. An Approach to Pain Management in End Stage Renal Disease: Considerations for General Management and Intra-dialytic Symptoms. July-August 2015. • Seminars in Dialysis, 2016. Weisbord (march-april). PatientCentered Dialysis Care: Depression, Pain and Quality of Life. • Palliative medicine in end-stage renal failure. Joanna Chambers. 4th edition of the Oxford textbook of palliative medicine. • Harinsingani, Saad, Cassagnol. How to manage Pain in Patients with Renal Insufficiency or End-stage Renal Disease on Dialysis. The Hospitalist, August 1, 2013.