Efficacy of the World Health Organization Analgesic Ladder to Treat Pain in End-Stage Renal Disease
Ahmad S. Barakzoy and
Alvin H. Moss
Section of Nephrology, Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia
Address correspondence to: Dr. Alvin H. Moss, Center for Health Ethics and Law, West Virginia University School of Medicine, PO Box 2022, Morgantown, WV 26506-9022. Phone: 304-293-7618; Fax: 304-293-7442; E-mail: amoss{at}hsc.wvu.edu
Received for publication May 15, 2006.
Accepted for publication August 7, 2006.
Pain is the one of the most common symptoms experienced by patientswith ESRD; it impairs their quality of life and is undertreated.Most pain clinicians believe that the pain management approachof the World Health Organization (WHO) three-step analgesicladder is applicable to the treatment of patients with ESRD,but this approach has not been validated for them. A cohortof 45 hemodialysis patients were assessed for type and severityof pain using the Short-Form McGill Pain Questionnaire and thentreated during a 4-wk period according to the WHO analgesicladder. Mean age was 65 ± 12.5 yr, and 22 (49%) patientshad diabetic nephropathy as the cause of ESRD. Initial painwas rated severe by 34 (76%) patients. There was no differencein initial pain rating by gender, age, race, or type of pain.Forty percent of patients reported nociceptive pain, 31% neuropathic,and 29% both. Adequate analgesia was achieved in 43 (96%) of45 patients. The mean pain score decreased from 7.8 ±1.2 to 1.6 ± 1.3 (P < 0.001). Patients who were 65yr and older had higher posttreatment scores than those whowere younger than 65 (2.1 ± 1.4 versus 0.94 ±0.93; P = 0.002) and more medication adverse effects. It isconcluded that the use of the WHO three-step analgesic ladderleads to effective pain relief in hemodialysis patients. Olderpatients will need more careful pain management to achieve thesame results as younger patients. Further studies are neededto confirm these results in a larger, more diverse dialysispopulation.
Pain has become an important concern for those who treat patientswith ESRD. There is an increasing recognition that pain is oneof the most common symptoms experienced by patients with ESRD,that it impairs their quality of life, and that it is undertreated(1–8). Most pain clinicians believe that the principlesof cancer pain management as described in the American PainSociety primer (9) and the World Health Organization (WHO) monograph(10) are applicable to the treatment of patients who have ESRDand are in pain. The approach of using the WHO analgesic ladderto treat patients who have ESRD and are in pain has been recommendedin two review articles in the nephrology literature (11,12),but it has not been validated prospectively. For this reason,we conducted this study to evaluate the efficacy of using theWHO three-step analgesic ladder to treat pain in patients withESRD.
Study Population
We conducted a prospective cohort study of hemodialysis patientswho were receiving standard care for pain and other symptomsbetween March and May 2005 in two dialysis units under the medicaldirectorship of the West Virginia University School of MedicineSection of Nephrology. To be eligible to participate in thestudy, patients had to be older than 18 yr, possess decision-makingcapacity, have no history of drug abuse and could not have beenreceiving continuous treatment for chronic pain so that theeffect of the treatment intervention could be assessed. Alldialysis patients in the two dialysis units who met these inclusioncriteria were approached for participation. From those who agreedto participate, we identified patients who were in pain andwere willing to undergo assessment and treatment by the studyinvestigators. Patients who completed the pre- and posttreatmentevaluation compose the subjects of this study. This study wasapproved by the West Virginia University Institutional ReviewBoard for the Protection of Human Subjects, and written informedconsent was obtained from all participants.
Baseline Characteristics and Instrument for Pain Assessment
Patients’ charts were reviewed for demographic data (age,gender, and race), dialysis adequacy, allergies, current medications,drug history, comorbidity, and liver function. We interviewedthose who agreed to participate in the study to identify patientswho were in pain and willing to undergo treatment, and one ofthe investigators (A.S.B.) administered the Short-Form McGillPain Questionnaire (SF-MPQ) to them. This questionnaire wasvalidated previously in patients with cancer, postsurgical,obstetric, and musculoskeletal pain (13,14). The original andlonger version of the SF-MPQ, the McGill Pain Questionnaire,has been used successfully in the assessment of patients withESRD (1). The SF-MPQ consists of 15 descriptors of pain (11sensory and four affective) that are rated on an intensity scaleas 0 = none, 1 = mild, 2 = moderate, or 3 = severe. Three painscores are derived from the sum of the intensity values of thewords chosen for sensory, affective, and total descriptors.In addition, the SF-MPQ includes a present pain intensity visualanalogue scale (VAS; 0 through 10) and an evaluative overallintensity of the total pain experience (0 = no pain, 1 = mildpain, 2 = discomforting pain, 3 = distressing pain, 4 = horriblepain, and 5 = excruciating pain). The three pain descriptorsare added to the VAS and the evaluative overall intensity toobtain a total score for the SF-MPQ. Patients who selected thesensory descriptors of "burning" and "stabbing" were classifiedas having neuropathic pain. Patients who selected the sensorydescriptors of "aching," "cramping," "gnawing," "sharp," "throbbing,"and "tender" were classified as having nociceptive pain (15).
Pain Treatment Approach
Pain medications were prescribed according to the WHO three-stepanalgesic ladder (Figure 1) (10). In previous studies, the useof the WHO three-step analgesic ladder to treat pain has resultedin adequate analgesia in between 69 and 100% of patients (16)and now is recognized as global health policy and one of themajor advances in the treatment of patients with pain (17,18).Using the VAS in the SF-MPQ, patients rated their pain on ascale from 0 = no pain to 10 = the worst pain possible. Patientswho described their pain as nociceptive and rated their painbetween 1 and 4 were considered to have mild pain and were prescribedmedications in step 1 of the ladder. Patients who describedtheir pain as nociceptive and rated their pain 5 or 6 were consideredto have moderate pain and were prescribed medications in step2 of the ladder. Patients who described their pain as nociceptiveand rated their pain as 7 to 10 were considered to have severepain and were prescribed medications in step 3 of the ladder.Patients who described their pain as neuropathic were prescribedgabapentin or, when cost of medication was an issue, nortriptyline.Patients were seen weekly for 4 wk, and on subsequent visits,medication dosages were increased or medications were changedor added until the patients reported a pain score of <5 andsatisfaction with their degree of pain relief. Patients withmoderate to severe neuropathic pain despite the prescriptionand titration of gabapentin or nortriptyline had an opioid added.The approach for pain management in this study was similar tothat described in Davison’s review of recommended treatmentof chronic pain in patients with ESRD (12). Patients were consideredto have achieved adequate analgesia when they rated their posttreatmentpain as mild or none. At the completion of the treatment period,patients were readministered the SF-MPQ. In this study, painmedications for treatment of patients who had moderate (step2) and severe pain (step 3) were chosen on the basis of thepharmacokinetics of opioids and their metabolites to ensureuse of opioids with a reasonable safety profile in ESRD (11,19).
Figure 1. The World Health Organization three-step analgesic ladder modified to exclude drugs unsafe in renal failure. Patients were treated with medications in step 1 when they rated their pain as a 1 to 4 on a 10-point scale. Patients were treated with medications in step 2 when they rated their pain as a 5 or 6 on a 10-point scale. Patients were treated with medications in step 3 when they rated their pain as a 7 to 10 on a 10-point scale.
Statistical Analyses
Patients’ initial and posttreatment VAS pain scores werecompared for the entire population, gender, age (<65 versus65 yr), and race (white versus black) and for patients who reportedtheir pain as nociceptive or neuropathic. Patients’ initialand posttreatment total SF-MPQ scores were compared for theentire population. A t test was used for paired and independentsamples for continuous variables. Data are presented as means± SD. P < 0.05 is considered significant.
A total of 143 patients met inclusion criteria; of these, 78(54%) reported pain. Of the 78 patients, 17 refused to participatein the study because of concerns about medication costs or adverseeffects; of these 17, eight reported moderate pain and ninereported mild pain. Sixteen patients who were in pain and alreadyregularly taking pain medicines were excluded because it wouldnot be possible to assess the impact of the WHO analgesic ladderapproach in them. Forty-five agreed to participate in the study(Figure 2). Mean age for these patients was 65 ± 12.5yr. Fifty-three percent were men; 83% were white, and 17% wereblack. Twenty-two (49%) patients had diabetic nephropathy asthe cause of their ESRD. The mean dialysis Kt/V for the 45 patientswas 1.56 ± 0.28.
Figure 2. Study participants. A total of 143 of 172 potentially eligible hemodialysis patients met inclusion criteria: 78 (54%) patients reported pain; 45 (58% of the patients in pain) agreed to participate in the study.
Of the 62 patients who were in pain and not already regularlytaking pain medicine, 53 (86%) reported pain that was moderateor severe. Of the 45 patients in the study, initial pain wasrated severe by 34 (76%) patients. There was no difference ininitial pain rating by gender, age, race, or type of pain (nociceptiveor neuropathic; Figures 3 and 4). Forty percent of patientsreported nociceptive pain, 31% neuropathic, and 29% both. Burningwas the most frequent descriptor used by patients to reporttheir pain; 25 patients selected it. Twelve patients reportedaching pain; 10 sharp pain; five stabbing; four throbbing; andtwo each cramping, gnawing, and tender. The following descriptorsin the SF-MPQ were not selected by any patients: Shooting, heavy,splitting, tiring, sickening, fearful, and punishing.
Figure 3. Mean pretreatment pain score by gender, age, and race. Mean pretreatment scores for all groups were in the severe range (7.4 to 8.0). There was no difference in mean pretreatment pain score on the basis of gender, age, or race. The bars depict mean score ± 1 SD.
Figure 4. Mean pre- and posttreatment pain scores by type of pain. Mean pretreatment scores for patients who reported neuropathic and nociceptive pain both were in the severe range (8.1 ± 1.2 versus 7.4 ± 1.2; P = 0.11). There was comparable reduction in pain scores for both groups to the mild range (1.5 ± 1.1 versus 1.8 ± 1.5, P = 0.524). The bars depict mean score ± 1 SD.
Adequate analgesia was achieved in 43 (96%) of 45 patients.The mean pain score decreased from 7.8 ± 1.2 to 1.6 ±1.3 (P < 0.001). The two patients in whom adequate analgesiawas not obtained were 68 and 74 yr of age. On the overall intensityof the pain experience rating completed at the end of the study,11 (24%) patients indicated no pain, 32 (71%) patients indicatedmild pain, and two (4%) patients indicated discomforting pain(moderate level). No patients reported pain that was distressing,horrible, or excruciating. Comparable pain relief was achievedfor patients with nociceptive and neuropathic pain (Figure 4).Patients who were 65 yr and older had higher posttreatment painscores than those who were younger than 65 yr (Figure 5). Thetotal SF-MPQ score was reduced from 17.3 ± 3.8 to 4.3± 3.0 (P < 0.001). The percentages of patients whowere treated with particular pain medications were as follows(the numbers do not add up to 100% because 24% of patients wereprescribed more than one pain medication): Gabapentin, 38%;hydrocodone, 27%; tramadol, 24%; oxycodone, 20%; nortriptyline,16%, and propoxyphene, 2%. The use of propoxyphene in kidneydisease is not recommended (11); this patient had previouslyused propoxyphene safely and requested it again. Opioid neurotoxicitywas not noted during the study. Adverse effects were observedin three patients, all of whom were older than 65 yr. In twopatients, the dosage of gabapentin was reduced from 300 mg atbedtime to 100 mg because of "grogginess" and somnolence. Oneelderly patient was switched from an oxycodone-acetaminophencombination to tramadol because of dizziness.
Figure 5. Response to pain treatment by age. Both age groups had reduction of their mean pain scores from the severe to the mild range. Patients who were younger than 65 yr had a significantly lower posttreatment pain score than those who were 65 yr and older (0.94 ± 0.93 versus 2.1 ± 1.4, P = 0.003). The bars depict mean score ± 1 SD.
A formal assessment of the impact of pain treatment on patients’quality of life was not conducted, but 22 patients made unsolicitedcomments. The comments were analyzed and coded into three generaldomains: More restful sleep, improved function, and better abilityto tolerate dialysis. Representative comments were as follows:"I have more energy because I am resting better at night"; "Iam able to walk to my mail box, something I could not do beforebecause of hip and leg pain"; and, "I am able to tolerate 4hr of dialysis without the severe back pain."
This study has four major findings. First, use of the WHO three-stepanalgesic ladder approach to treating pain led to effectivepain treatment in >90% of our hemodialysis patients. Second,we note that treatment of pain is more difficult in elderlydialysis patients. Third, we confirm the high prevalence ofpain in the hemodialysis population and undertreatment of painin the majority of dialysis patients. Fourth, the SF-MPQ wasa useful and efficient tool to assess pain in hemodialysis patients.
With the WHO analgesic ladder approach, 96% of our patientswere treated adequately on the basis of their posttreatmentreport of pain. At the conclusion of our study, 43 (96%) of45 patients reported mild pain at worst, and two reported moderatepain. No patients reported severe pain. These findings indicatethat use of the WHO three-step analgesic ladder results in effectivepain relief in the vast majority of dialysis patients; theseoutcomes in dialysis patient pain management are comparableto those for cancer patients and patients with other chronicillnesses (16).
Although elderly patients reported reduction in their pain aftertreatment to the mild range, their mean pain level at the endof the study was statistically higher than for younger patients;the clinical significance of this finding bears further research.The only two patients who reported more than mild pain at theconclusion of the study both were older than 65 yr. Also, adverseeffects from pain medication occurred only in elderly patients.These findings underscore that pain treatment is more difficultin elderly hemodialysis patients as it is in other elderly patientpopulations (20).
In our study, we identified pain in 54% of dialysis patients.Similarly, in the most comprehensive study of pain in dialysispatients to date, Davison (1) found that 103 (50%) of 205 patientsin four Canadian hemodialysis units reported pain. In the Davisonstudy, musculoskeletal pain was the most common type of painreported (63% of patients), followed by pain related to thedialysis procedure (14%) and peripheral neuropathy (13%). Asin our study, in Davison’s study, nociceptive pain wasequally severe to neuropathic and responded equally well totreatment.
Our patients were receiving standard care at the time of thisstudy, but only 21% of the patients whom we identified to bein pain were receiving pain medication at the start of our study.Davison’s study found undertreatment of pain in 75% ofpatients (1). Of the 62 patients who were in pain and not receivingpain medication at the initiation of our study, >80% ratedtheir pain as moderate or severe. Clearly, these patients werebeing undertreated for pain. How can we account for the widespreadprevalence of untreated pain in our population, especially becausebefore our study, the patients were being seen weekly by a nephrologistor a nephrology nurse practitioner? The answer relates to howpain is assessed. Unless our patients were asked explicitlyabout their pain, they did not report it. This finding is truefor other patient populations as well (21,22). The implicationof this finding is that for dialysis patients to receive adequatetreatment for their pain, an explicit pain assessment must bepart of the treatment that they receive.
Our finding of the undertreatment of pain in the hemodialysispopulation has significance for the quality of life of patientswith ESRD. Pain may induce depression, anxiety, insomnia, anddecreased functional capacity and interfere with the abilityto interact socially (2,6,23). An inverse relationship betweenthe existence of pain and other symptoms and dialysis patients’self-reported quality of life has been reported (2,4).
The SF-MPQ was used in this study. It took only 5 to 10 minto administer, and its use for pain assessment resulted in adequatepain management in 96% of hemodialysis patients. Our patientsselected none of the four affective descriptors of pain in theSF-MPQ and only eight of the 11 sensory descriptors. The VASresults were validated by the overall intensity of total painexperience ratings. If our findings are confirmed in other studiesof dialysis patients, then it may be possible to construct aneven shorter pain assessment form that could be used convenientlyonce a month in dialysis units.
This study has six limitations. First, the racial distributionof the patients in this study underrepresents minorities becauseof the homogeneity of the population in West Virginia. Althoughthere was no difference in initial pain rating or response topain management by race, further studies will be needed to establishthe generalizability of our findings. Second, this was a short-termstudy of only 4 wk; however, the average duration of pain treatmentin some of the original WHO validation studies was only 66 to77 d (24,25). The long-term efficacy of the WHO analgesic ladderapproach in ESRD as well as the development of tolerance andadverse effects over time remain to be studied. Third, thisstudy contains a small sample size, but, again, many of theoriginal WHO validation studies had fewer than 100 patients(13). Fourth, this study did not measure formally the impactof the pain reduction on patients’ quality of life. Fifth,our population included only hemodialysis patients; a studyon the efficacy of using the WHO three-step analgesic ladderin peritoneal dialysis patients remains to be performed. Sixth,our study used the SF-MPQ, the use of which has not been validatedin an ESRD population; the use of the longer version, the McGillPain Questionnaire, has been.
Use of the SF-MPQ for pain assessment and the WHO three-stepanalgesic ladder approach for pain management in hemodialysispatients led to effective pain relief in 96% of patients. Becauseolder patients had higher posttreatment pain scores and adverseeffects from treatment, they will need more careful managementto achieve the same results as younger patients. Longer termstudies will be needed to confirm these results in a larger,more diverse dialysis population.
Acknowledgments
This research was supported in part by a grant from the Mei-YingHuang Research and Education Fund of the West Virginia UniversityCenter for Health Ethics and Law.
Footnotes
Published online ahead of print. Publication date availableat www.jasn.org.
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Top
Abstract
Introduction
65 yr), and race (white versus black) and for patients who reported their pain as nociceptive or neuropathic. Patients’ initial and posttreatment total SF-MPQ scores were compared for the entire population. A t test was used for paired and independent samples for continuous variables. Data are presented as means ± SD. P < 0.05 is considered significant. 
