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Management of pain in patients on hemodialysis.

LEARNING OBJECTIVES

After reading this article, the reader will be able to:

* Describe the epidemiology and pathophysiology of pain in patients on hemodialysis.

* Identify methods for pain assessment in this population.

* Summarize an approach to pain management.

* Discuss appropriate pharmacologic and non-pharmacologic agents for pain management.

INTRODUCTION

The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" (Merskey & Bogduk, 1994, p. 210). Pain among patients on hemodialysis remains under-recognized and its severity underestimated, and is inadequately treated (Weisbord, Fried, et al., 2007; Davison, & Ferro, 2009; Abdel-Kader, Unruh, & Weisbord, 2009; Claxton, Blackball, Weisbord, & Holley, 2010; Koncicki, Unruh, & Schell, 2017). The aims of this article are to review the recent studies discussing pain assessment and management in patients on hemodialysis, and to investigate strategies that can be utilized in daily practice to address pain.

EPIDEMIOLOGY AND PATHOPHYSIOLOGY

Pain is one of the most commonly experienced symptoms in hemodialysis, with greater than 58% of patients affected and approximately half of these patients rating the intensity of pain as moderate to severe (Weisbord et al., 2003; Davison, 2003; Barakzoy & Moss, 2006; Davison, Koncicki, & Brennan, 2014). A systematic review reported rates of effective pain control in patients on hemodialysis varying from 17% to 38%, and up to 84% of patients reporting significant pain without receiving analgesia (Wyne, Rai, Cuerden, Clark, & Suri 2011). A recent study of patients on hemodialysis in the United States found that almost two-thirds of patients received at least one opioid prescription each year, and more than one-fifth received annual chronic opioid prescriptions (defined as greater than three months) (Kimmel et al., 2017; Han et al., 2017). Understanding the reasons for high prescription opioid use and misuse among hemodialysis patients can help identify strategies for supporting safe opioid prescribing and pain management.

Pain experienced by hemodialysis patients is often multifactorial, including nociceptive, somatic, visceral, neuropathic, and complex regional pain syndromes (Davison, 2003). The etiology of pain may be attributed to many reasons including: co-morbidities (e.g., diabetes, vascular disease), the primary renal disease (e.g., polycystic kidney disease), as a consequence of renal failure (e.g., calciphylaxis, renal osteodystrophy), or due to the dialysis treatment itself (e.g., recurrent needle insertion, arteriovenous access pain and cannulation) (Davison, 2003; Salisbury et al., 2009). Differentiating between the different types of pain and their potential causes is important for determining optimal management strategies.

BARRIERS TO PAIN MANAGEMENT

In order to develop optimal management pain strategies, it is important to consider the potential barriers in providing optimal interventions. In hemodialysis patients, there still remains paucity in literature that elucidates reasons for undertreatment, as there are currently few studies published explaining potential causes (Weisbord, 2016). One observational study has suggested that language has been a barrier to optimal pain management, with 42% of dialysis patients unable to speak English (Salisbury et al., 2009). A prospective cohort study with 45 hemodialysis patients attributed the widespread prevalence of untreated pain due to patients being unforthcoming about their pain, unless directly asked (Barakzoy & Moss, 2006). Other potential barriers include the healthcare provider's ability to recognize and treat pain (Koncicki, Unruh, & Schell, 2017). Almost 70% of nephrology providers report self-confidence in treating pain, yet only 37% assess for and treat pain regularly. This discrepancy may be due to insufficient training and experience with managing pain in this population (Salisbury et al., 2009, Green et al., 2012).

In dialysis patients, pain management is further complicated by taking the dialyzability of analgesics into consideration, which can alter the pharmacokinetic (the handling of drug by the body) and pharmacodynamic (the resulting effect of the drug on the body) properties of these medications. Factors to consider for the dialyzability of analgesics include: technical aspects of the dialysis procedure, lipophilicity, water solubility, volume of distribution, protein binding, and the extent of renal and non-renal clearance, for both parent drug and active metabolites (Li, McLin, & Castillo, 2015; de Castro, Murphy, & Battistella, 2013). For example, morphine-6-glucoronide, the active metabolite of morphine, is cleared renally and accumulates with decreased renal function. This increases the risk for adverse effects such as respiratory depression, which is why morphine should be avoided in patients on hemodialysis (Koncicki, Brennan, Vinen, & Davison, 2015; Koncicki, Unruh, & Schell, 2017). Effective prescribing must be balanced with the risks and benefits, taking careful safety consideration of patients at highest risk for adverse outcomes such as sedation, respiratory depression or falls, as these are commonly associated adverse effects of analgesics and can lead to death (Koncicki, Unruh, & Schell, 2017; Krashin, Murinova, Jumelle, & Ballantyne, 2015). Advanced age, multiple co-morbidities, and polypharmacy can increase the risk of analgesic toxicities (Nayak-Rao, 2011).

BURDEN OF PAIN

Moderate or severe pain negatively affects quality of life, being associated with increased rates of depression, insomnia, irritability, inability to cope with stress, increased perception of burden of disease, decreased perception of social support, and decreased life satisfaction (Davison & Jhangri, 2005; Cohen, Patel, Khetpal, Peterson, & Kimmel, 2007; Davison & Jhangri, 2010; Aitken et al., 2013; Koncicki, Unruh, & Schell, 2017). For patients undergoing hemodialysis, uncontrolled pain leads to shortened or missed treatments, increased hospitalizations, and increased emergency department visits (Weisbord et al., 2014). In maintenance dialysis patients, an association was found between opioid prescriptions and increased risk of death, dialysis discontinuation, and hospitalization (Kimmel et al., 2017; Han et al., 2017). Inadequate pain management leads to poorer outcome, in addition to higher cost to the healthcare system, which emphasizes the need for timely identification, assessment, and provision of appropriate analgesic management in these patients.

PAIN ASSESSMENT

Pain assessment involves an organized history to elucidate the cause of pain, its location, quality, severity, and the impact on physical, social, and emotional functioning (Barnard & Gwyther, 2006; Li, McLin, & Castillo, 2015). Symptom assessment tools currently validated for hemodialysis patients include: the modified Edmonton Symptom Assessment System (mESAS), Palliative Care Outcome Scale-Renal (POS-renal), Dialysis Symptom Index (DSI), and the Brief Pain Inventory (BPI) (Davison, 2003; Weisbord et al., 2004; Davison, Jhangri, & Johnson, 2006b; Murphy, Murtagh, Carey, & Sheerin, 2009; Davison, Koncicki, & Brennan, 2014; Upadhyay, Cameron, Murphy, & Battistella, 2014). A limitation with the mESAS tool is that it is not specific to pain and includes a visual 0-10 analog scale of 10 prevalent symptoms present in hemodialysis (Davison, Jhangri, & Johnson, 2006a; Davison, Koncicki, & Brennan, 2014). Other assessment tools include the McGill Pain Questionnaire; this, however, has not been validated in hemodialysis patients. Additional assessment tools have been validated in the renal population, including Kidney Dialysis Quality of Life-Short Form/36-item Short Form Health Survey (SF-36) and the CHOICE Health Experience Questionnaire, which are more extensive (Wu et al., 2001; Joshi, Mooppil, & Lim, 2010; Davison, Koncicki, & Brennan, 2014). The aim for regularly administered assessment tools would be improvement in pain identification and treatment for hemodialysis patients (Upadhyay et al., 2014).

PAIN MANAGEMENT

There have been recently published approaches to general pain management in hemodialysis patients (Table 1) (Davison & Jhangri, 2005; Davison, Koncicki, & Brennan, 2014; Dowell, Haegerich, & Chou, 2016; Koncicki, Unruh, & Schell, 2017; Raina, Krishnappa, & Gupta, 2017). The approach in Table 1 outlines key steps to effectively assess and manage pain in patients on hemodialysis in which the initial goal is to elicit a good history using the PQRST mnemonic for pain assessment. Providing patient education regarding pain management should follow. Assessing risks and benefits when deciding appropriate pharmacological and/or non-pharmacological agents for pain should be the next step. This is followed by the appropriate monitoring and follow-up in order to optimize pain management (Dowell, Haegerich, & Chou, 2016; Koncicki, Unruh, & Schell, 2017; Raina, Krishnappa, & Gupta, 2017).

Management of pain differs depending on the type of pain. Pain is categorized into nociceptive and neuropathic, with differing treatment approaches associated with each type. Nociceptive pain occurs through stimulation of receptors as a result of tissue damage. This is further categorized into two types: somatic (caused by inflammation of tissue and localized to a specific area) and visceral (initiated by pathology of internal organs and more difficult to localize). Neuropathic pain is caused by a lesion or disease of the somatosensory system (Jensen et al., 2011). Both nociceptive and neuropathic pain can equally affect the hemodialysis patient, and are not mutually exclusive (Koncicki, Unruh, & Schell, 2017).

NON-PHARMACOLOGIC AND PHARMACOLOGIC OPTIONS

Non-pharmacologic options include exercise, massage, acupuncture, and cognitive behavioural therapy, and these are preferred before initiating pharmacologic therapy (Koncicki, Unruh, & Schell, 2017; Pham et al., 2017).

There are many considerations with initiating pharmacologic therapy. Due to altered drug pharmacokinetics and physiological aspects in hemodialysis patients, individual dosing is advised (Koncicki, Unruh, & Schell, 2017; Pham et al., 2017). Important altered drug pharmacokinetics and physiological considerations include increased drug levels and associated adverse effects due to reduced drug renal clearance (Pham et al., 2017; Kamarzarian et al. 2016). Other considerations include accumulation of the parent compound and/or its metabolite, or increased free drug levels due to reduced protein binding associated with hypoproteinemia/hypoalbuminemia and/or acidemia (Pham et al., 2017; Kamarzarian et al., 2016). Because there are limited dosing recommendations published in literature for hemodialysis patients, close monitoring for efficacy and adverse effects is recommended (Koncicki, Unruh, & Schell, 2017; Pham et al., 2017). The removal of drug by dialysis must also be considered (Pham et al., 2017). Although there are no consensus guidelines for pain management, the World Health Organization (WHO) three-step analgesic ladder has been recommended in patients on hemodialysis (Davison, 2003; Davison & Jhangri, 2005; Koncicki, Unruh, & Schell, 2017). Validation studies have demonstrated that the implementation of the renal adaptation of the WHO analgesic ladder can reduce pain scores in hemodialysis patients (Barakzoy & Moss, 2006; Salisbury et al., 2009).

NOCICEPTIVE PAIN

A general overview for nociceptive pain management is provided by the WHO's three-step analgesic ladder (Table 2). Mild pain (step 1) should be treated by analgesics such as acetaminophen or NSAIDs (Barakzoy & Moss, 2006; Koncicki, Unruh, & Schell, 2017; Pham et al., 2017). Step 2 is for mild pain not responsive to acetaminophen or NSAIDs, or pain that is rated as moderate severity. Step 2 agents include tramadol and low-dose opiates such as oxycodone or hydromorphone. Agents in step 3 are for severe pain, including higher doses of opiates such as oxycodone or hydromorphone, or long-acting fentanyl for pain that is not adequately controlled by step 2 agents, or pain rated as severe (Barakzoy & Moss, 2006; Koncicki, Unruh, & Schell, 2017). Hydromorphone is the preferred short-acting opioid in patients on hemodialysis, as it is better tolerated than morphine with less neuro-excitatory effects (Davison, Koncicki, & Brennan, 2014; Koncicki, Unruh, & Schell, 2017). Oxycodone and tramadol can be used as short-acting agents. However, use of these agents requires caution because of their increased half-lives associated with decreased renal clearance (Davison, Koncicki, & Brennan, 2014; Kurella, Bennett, & Chertow, 2003; Lugo & Kern, 2004; Koncicki, Unruh, & Schell, 2017). For chronic pain, patients may benefit from long-acting medications such as long-acting transdermal fentanyl or oral methadone (Barakzoy & Moss, 2006; Koncicki, Unruh, & Schell, 2017). Methadone requires a referral to an experienced specialist. However, it remains to be a reasonable alternative that is well-tolerated (Koncicki et al., 2015). Oral buprenorphine requires further study to better understand its pharmacokinetic and pharmacodynamic properties in hemodialysis patients before safe and effective use can be recommended. The few studies conducted in hemodialysis patients have been in small sample sizes, and the transdermal formulation of buprenorphine was used (Filitz et al., 2006; Mordarski, 2009; Davison & Ferro, 2009; Koncicki, Unruh, & Schell, 2017). Medications to avoid due to altered pharmacokinetics and side effects secondary to decreased kidney function include: morphine, codeine, hydrocodone, and meperedine (Barakzoy & Moss, 2006; Murtagh et al., 2007; Salisbury et al., 2009; Li, McLin, & Castillo, 2015; Koncicki et al., 2015).

Basic guidelines in prescribing opioids must be followed to avoid abuse and misuse. Important considerations include: preferential use of non-opioid over opioid therapy in chronic pain treatment; evaluating risks and benefits prior to initiation; determination and patient discussion of patient goals; use of lowest effective dose; avoidance of concurrent opioids and benzodiazepines whenever possible; and regular patient follow-up for the assessment of risks and benefits of continuing opioid use (Pham, et al., 2017). For patients with opioid use disorder, clinicians should offer or arrange evidence-based therapies, including medication-assisted treatment, and psychosocial support through behavioural change strategies (e.g. psychotherapeutic counselling and family therapy) (Pham, et al., 2017; Dowell, Haegerich, & Chou, 2016).

Whenever applicable and safe, topical administration of analgesics may be preferred over oral or non-topical parenteral routes to reduce systemic drug concentrations, and minimize drug interactions and systemic toxicities (Table 3) (Pham et al., 2017; Argoff, 2013). Topical analgesics including diclofenac have been shown in small studies to be effective in relieving both soft tissue injuries and various inflammatory musculoskeletal conditions. Although topical NSAIDs have been reported to have more favourable tolerability profiles, including gastrointestinal and cardiovascular events, compared with oral agents, data on renal toxicities are lacking (Pham et al., 2017; Argoff, 2013). There is literature that supports the use of topical lidocaine and capsaicin for neuropathic pain (Pham et al., 2017; Finnerup et al., 2015). However, despite lower blood levels with use of topical analgesics, caution is advised with prolonged or high-dose use due to the risk of adverse effects from skin absorption and systemic accumulation, and the lack of evidence comparing renal and fluid/electrolyte adverse effects between topical and systemic NSAIDs (Pham et al., 2017).

NEUROPATHIC PAIN

Neuropathic pain is common in hemodialysis, and can range from systemic causes such as diabetes, and causes related to dialysis such as secondary amyloid (Mambelli et al., 2012; Koncicki, Unruh, & Schell, 2017). Due to limited quality and quantity of evidence in the hemodialysis population, treatment should follow the guidelines published by the International Association for the Study of Pain (IASP) for management of neuropathic pain in the general population. Special considerations in addition to following these guidelines include altered clearance of medications and increased risk of adverse effects in the hemodialysis population (Innis, 2006; Dworkin et al., 2007; Naylor & Raymond, 2011). Common neuropathic symptoms include pain, numbness, or tingling in the elbow, distal arm, and medial hand of the fifth digit. Such symptoms can potentially lead to functional impairment if left untreated (Nardin, Chapman, & Raynor, 2005; Koncicki et al., 2015). First-line agents include calcium channel alpha-2-delta ligands (e.g., gabapentin and pregabalin), tricyclic antidepressants, and serotonin and norepinephrine reuptake inhibitors (Table 4) (Dworkin et al., 2007; Naylor & Raymond, 2011). Titration of these agents may be necessary to achieve relief and may also require opioids or tramadol as bridging therapy (Davison, Koncicki, & Brennan, 2014; Koncicki, Unruh, & Schell, 2017). Gabapentin and pregabalin have been specifically evaluated in patients on hemodialysis, and are the preferred agents of choice (Naylor & Raymond, 2011; Koncicki, Unruh, & Schell, 2017). They have been proven to show improvements in pain, depression, and subjective sleep and quality-of-life scores. However, these benefits must be balanced with the risks of many side effects such as drowsiness, dizziness, somnolence, and tremor (Biyik, et al., 2013; Atalay, et al., 2013; Koncicki, Unruh, & Schell, 2017).

In addition to pharmacologic therapy, innovative methods to improve pain management in hemodialysis patients include implementing initiatives from various members of the multidisciplinary healthcare team (Weisbord et al., 2013; Koncicki, Unruh, & Schell, 2017). For example, the Symptom Management Involving End-Stage Renal Disease (SMILE) Study evaluated the impact of a trained nurse intervention on symptom management in hemodialysis patients (Weisbord et al., 2013). Although no statistically significant outcomes were found for nursing interventions in improving pain compared to the control arm, the study highlighted that a multidisciplinary nephrology team can help identify and treat symptoms, and this is a potential area for further research (Weisbord et al., 2013; Koncicki, Unruh, & Schell, 2017).

CONCLUSION

Chronic pain is a common and disabling symptom for patients on hemodialysis. With effective pain management, patients can have increased comfort, safety, and satisfaction of care that can improve their overall quality of life (Williams & Manias, 2008). Routine pain assessments, use of practice guidelines that are evidence-based, and engaging other inter-professional healthcare team members are all strategies that can be implemented to improve patient care quality. Opportunities for further research include implementing multidisciplinary strategies for pain assessment and management, conducting updated pharmacokinetic studies, and composing and validating practice guidelines to help guide clinicians with optimal pain management for hemodialysis patients.

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By Rachel Liu and Marisa Battistella

ABOUT THE AUTHORS

Rachel Liu, PharmD, Pharmacy Resident, University Health Network, Toronto, ON

Marisa Battistella, PharmD, ACPR, Clinician Scientist, Assistant Professor, Leslie Dan Faculty of Pharmacy, University of Toronto, Pharmacy Clinician Scientist, Clinical Pharmacist--Nephrology, University Health Network, Toronto, ON

Address for correspondence: Marisa Battistella, University Health Network, 200 Elizabeth Street, EB 214, Toronto, ON M5G 2C4

Email: marisa.battistella@uhn.ca

Copyright [c] 2018 Canadian Association of Nephrology Nurses and Technologists
Table 1. General Pain Management Approach Tool for Hemodialysis Patients

Steps             Considerations

Pain assessment   * "P": Precipitating or palliating factors:
                    What makes the pain better? What
                    makes the pain feel worse?
                  * "Q": Quality: Can you describe what
                    the pain feels like? Is it stabbing,
                    throbbing, or burning?
                  * "R": Region or radiation: Can you point
                    with 1 finger where the pain is? Does it
                    stay in 1 spot or does it move?
                  * "S": Severity: How would you rate the
                    pain from 1 to 10, with 10 being the
                    worst?
                  * "T": Timing: When did the pain first
                    start? Is it constant or does it come
                    and go throughout the day?
Use the           * Caution with decreased clearance as
World Health        there is an increased risk of adverse
Organization        effects
(WHO) three-      * Start low, titrate slow
step analgesic    * Give medications orally if possible and
ladder for          on a scheduled basis
nociceptive pain  * Extra or "breakthrough" doses should
                    be available for pain uncontrolled
                    by scheduled medications and/or for
                    incidental pain
Set realistic     * Pain free should not be the end goal,
goals of therapy    but a reduction in pain in order to
                    improve functional status and quality
                    of life
Follow-up         * Schedule close evaluation of adequate
                    pain relief and assessment of total
                    daily dosage of medication used
                    based on patient use
Monitor for       * If adverse effects are intolerable,
adverse effects     consider switching to a medication on
                    the same "step"

(Davison & Jhangri, 2005; Davison, Koncicki, & Brennan, 2014; Konicicki
Unruh, & Schell, 2017)

Table 2. WHO Analgesic Ladder Adapted for Hemodialysis Nociceptive Pain

WHO          Analgesic
Ladder

Step 1:      Acetaminophen
Mild Pain


             NSAIDs



Step 2:      Oxycodone
Moderate     (short-acting)
Pain
             Tramadol
             (short-acting)







Step 3:      Hydromorphone
Severe Pain  (short-acting)





             Fentanyl
             (long-acting)










             Methadone




Medications  * Morphine--accumulation of active metabolite
             (morphine-6-glucuronide); case reports of patients with
to avoid in  decreased kidney function experiencing respiratory and CNS
             depression, myoclonus, and death
decreased    * Codeine--reduced clearance and prolonged half-life;
             adverse effects reported include: nausea, vomiting,
kidney       hypotension, CNS depression, respiratory arrest
function:    * Hydrocodone--limited information in these patients;
             reduced clearance of parent compound and metabolites
             * Meperidine--active metabolite (normeperidine) has
             prolonged half-life; adverse effects reported include:
             myoclonus, altered mental status, seizures
             * Buprenorphine--newer agent that requires further study
             in these patients

WHO          Recommendation/Considerations
Ladder

Step 1:      Recommended by the National Kidney Foundation as the
Mild Pain    preferred analgesic for hemodialysis.


             Can be used in hemodialysis patients for short-term
             periods under close supervision for adverse effects.
             NSAIDs and COX-2 inhibitors likely adversely affect renal
             hemodynamics equally.
Step 2:      Use cautiously due to increased half-life with decreased
Moderate     renal clearance.
Pain
             Use cautiously due to increased half-life as active
             metabolites are predominantly cleared renally, and
             clearance with dialysis is minimal. Reduction in dose and
             dosing frequency is recommended.





Step 3:      Preferred short-acting opioid in patients with advanced
Severe Pain  kidney disease. Approximately 50% of medication is
             removed with dialysis; however, no data regarding active
             metabolite accumulation exist. Reduction in dose and
             increasing dosing interval is recommended.


             For chronic pain, long-acting medications can be used if
             patients are not opioid-naive and have been previously
             treated with opioids. Should not be used first-line in
             opioid-naive patients because of higher probability of
             non-fatal overdose compared with immediate-release or
             short-acting medications in the first 2 weeks of treatment.
             Transition to long-acting should occur when the patient is
             well-controlled on a stable regimen; however, caution is
             advised as titration can be difficult.
             If patient is transitioning to long-acting medication,
             acute
             exacerbations of pain may occur ("breakthrough pain").
             Having a short-acting medication available is suggested.
             Appears to be well tolerated. There is increased
             elimination through the gastrointestinal tract in
             individuals
             with decreased kidney function so reduced dose is
             recommended.

Medications  * Morphine--accumulation of active metabolite
             (morphine-6-glucuronide); case reports of patients with
to avoid in  decreased kidney function experiencing respiratory and CNS
             depression, myoclonus, and death
decreased    * Codeine--reduced clearance and prolonged half-life;
             adverse effects reported include: nausea, vomiting,
kidney       hypotension, CNS depression, respiratory arrest
function:    * Hydrocodone--limited information in these patients;
             reduced clearance of parent compound and metabolites
             * Meperidine--active metabolite (normeperidine) has
             prolonged half-life; adverse effects reported include:
             myoclonus, altered mental status, seizures
             * Buprenorphine--newer agent that requires further study
             in these patients

WHO          Monitoring
Ladder

Step 1:      Hepatotoxicity with underlying
Mild Pain    liver disease or long-term
             alcohol use exceeding
             4,000 mg/day
             Worsening hypertension,
             volume retention, hyperkalemia,
             gastrointestinal bleed, or loss of
             residual kidney function
Step 2:      Nausea, CNS depression,
Moderate     constipation
Pain
             Nausea, CNS depression,
             constipation

             May cause seizures in conditions
             associated with lower seizure
             threshold
             Risk for serotonin syndrome
             with concomitant serotonergic
             medications
Step 3:      Nausea, CNS depression,
Severe Pain  constipation

             Metabolite accumulation may
             cause neuro-excitation with
             agitation, confusion, and
             hallucinations.
             Nausea, CNS depression,
             constipation











             Nausea, CNS depression,

             constipation

             High potential for drug
             interactions
Medications  * Morphine--accumulation of active metabolite
             (morphine-6-glucuronide); case reports of patients with
to avoid in  decreased kidney function experiencing respiratory and CNS
             depression, myoclonus, and death
decreased    * Codeine--reduced clearance and prolonged half-life;
             adverse effects reported include: nausea, vomiting,
kidney       hypotension, CNS depression, respiratory arrest
function:    * Hydrocodone--limited information in these patients;
             reduced clearance of parent compound and metabolites
             * Meperidine--active metabolite (normeperidine) has
             prolonged half-life; adverse effects reported include:
             myoclonus, altered mental status, seizures
             * Buprenorphine--newer agent that requires further study
             in these patients

(Barakzoy & Moss, 2006; Filitz, Griessinger, Sittl, Likar, Schuttler, &
Koppert, 2006; Murtagh, et al., 2007; Mordarski, 2009; Salisbury, et
al., 2009; Li, McLin, & Castillo, 2015; Koncicki, Brennan, Vinen, &
Davison, 2015; Miller, Barber, & Leatherman, 2015; Dowell, Haegerich, &
Chou, 2016; Koncicki, Unruh, & Schell, 2017; Pham et al., 2017; Raina,
Krishnappa, & Gupta, 2017)

Table 3. Topical analgesics in the management of acute and chronic pain
in hemodialysis

Analgesic             Considerations

Diclofenac 1.16% gel  Topical NSAIDs are more widely studied than other
                      agents. Evidence
                      suggests topical NSAIDs can be recommended for
                      short-term pain relief in
                      patients with acute soft tissue injuries or
                      chronic joint-related conditions
                      such as osteoarthritis
Lidocaine 5% cream    Evidence suggests better pain control of
                      post-herpetic neuralgia compared
(e.g., MaxileneTM)    with oral pregabalin
Capsaicin 0.025-      Limited evidence
0.025% cream

Analgesic             Monitoring

Diclofenac 1.16% gel
                      Pruritus, burning,

                      erythema, local allergy,

                      and blistering

Lidocaine 5% cream
                      Pruritus, erythema, and
(e.g., MaxileneTM)    edema
Capsaicin 0.025-      Local pain, stinging,
0.025% cream          burning, erythema

(Argoff, 2013; Davison, Koncicki, & Brennan, 2014; Pham et al., 2017;
Finnerup et al., 2015)

Table 4. Analgesics for neuropathic pain in hemodialysis

Analgesic                  Considerations

Gabapentin                 * May be partially cleared with dialysis,
                           thus recommended
Pregabalin                 to dose after dialysis
                           * May require titration to effect
                           * Caution use in elderly to avoid
                           potential adverse effects

Tricyclic antidepressants  * More effective than serotonin and
                           norepinephrine
(e.g. amitriptyline,       reuptake inhibitors for neuropathic pain
desipramine,               * Less anticholinergic side effects with
                           desipramine,
nortriptyline)             nortriptyline
Selective serotonin        * Limited evidence in hemodialysis patients
and norepinephrine         * Doses should start low with slow titration
                           and close
reuptake inhibitors        monitoring for adverse effects.
(e.g., venlafaxine,
duloxetine)

Analgesic                  Monitoring

Gabapentin
                           Gabapentin: somnolence, drowsiness,
Pregabalin                 dizziness, ataxia, fatigue, nystagmus,
                           and tremor

                           Pregabalin: dizziness, somnolence,
                           peripheral edema, and dry mouth
Tricyclic antidepressants
                           Orthostatic hypotension, sedation,
(e.g. amitriptyline,       anticholinergic effects (e.g., blurred
desipramine,
                           vision, delirium, constipation, dry
nortriptyline)             mouth, urinary retention, sedation)
Selective serotonin        Drowsiness, insomnia, dizziness,
and norepinephrine
                           nausea, weakness
reuptake inhibitors
(e.g., venlafaxine,
duloxetine)

(Koncicki, Brennan, Vinen, & Davison, 2015; Koncicki, Unruh, & Schell,
2017; Davison, Brennan, & Koncicki, 2014; Innis, 2006; Naylor &
Raymond, 2011; Kurella, Bennett, & Chertow, 2003)
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Title Annotation:CONTINUING EDUCATION SERIES
Author:Liu, Rachel; Battistella, Marisa
Publication:CANNT Journal
Article Type:Report
Date:Apr 1, 2018
Words:5728
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