Download The Management of Pain in the Dialysed Patient

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.