Backlash in the Treatment of Cancer Pain: Use of Opioid Analgesics in a Finnish General Hospital in 1987, 1991, and 1994

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1 286 Journal of Pain and Symptom Management Vol. 14 No. 5 November 1997 Original Article Backlash in the Treatment of Cancer Pain: Use of Opioid Analgesics in a Finnish General Hospital in 1987, 1991, and 1994 Eero Vuorinen, MD, Anneli Vainio, MD, PhD, and Anssi Reponen, MB Kymenlaakso Central Hospital (E. V.), Kotka, and Helsinki University Hospital (A. V., A.R.), Helsinki, Finland Abstract Finland belongs to the group of countries in which the consumption of strong opioids is low. This seems to reflect the general quality of cancer pain treatment. During the last 10 years, many efforts have been made to improve the treatment of cancer pain in Finland. To assess one parameter of change, the present stud), compared the quantity of opioid and nonopioid analgesics used in the treatment of terminal cancer pain in a Finnish general hospital in 198Z 1991, and Specifically, the records of all patients who died of cancer in Kymenlaakso Central Hospital (KCH) in 1991 and in 1994 and during the last 6 months of 1987 were reviewed to acquire information about the use of analgesic medication. The total proportion of cancer patients receiving analgesic medication on a regular basis was 39% in 1987, 63% in 1991, and 52% in The mean daily dose of strong opioids changed JS'om 24 mg in 1987 to 58 mg in 1991, and to 43 mg in These data suggest a possible backlash in prescribing practices during recent years. In spite of various efforts to improve the treatment of cancer pain, the medical records demonstrate a decline in prescribing of the drugs needed for this treatment. J Pain Symptom Manage 1997;14: U.S. Cancer Pain Relief Committee, Key Words Analgesics, opioids, cancer pain treatment, medical practice, terminal care Introduction A newly published report, which describes pain-related outcomes in more than 2000 cancer patients treated over a 10-year period in a palliative care center demonstrated once again, that it is possible to control cancer pain in most cases using the World Health Organi- Address reprint requests to: Eero Vuorinen, MD, Karhula Hospital, Toivelinnankatu 2, Karhula, Finland. Accepted for publication:january 7, 199Z zation (WHO) three-step analgesic ladder. 1 Still, however, reports continue to indicate severe undertreatment. 2-7 There are many barriers to effective pain relief, s most importantly, the insufficient use of morphine and other oral analgesics. 9 The WHO has identified the relief of cancer pain as a priority in its global cancer control program. 1 In a similar manner, the Finnish authorities have paid special attention to the relief of pain in terminal cancer: instructions were given for terminal care in 1982,11 and a national policy of cancer U.S. Cancer Pain Relief Committee, /97/$17.00 Published by Elseviel, New York, New York PII S (97)

2 Vol. 14 No. 5 November 1997 Cancer Pain Treatment Backlash 287 Table 1 Patient Characteristics and Primary Tumor Sites in 1987, 1991, and Number of patients Mean age (range), years 64(29-84) 66(20-91) 65(31-92) Mean survival time, months Males, % Tumor sites (%) Gastrointestinal 37(42%) 49(33%) 18(20%) Genitourinary 16(18%) 19(13%) 17(19%) Lung 14(16%) 30(21%) 18(20%) Hematological 11 (12%) 17(12%) 21 (24%) Breast 6(7%) 11 (8%) 4(5%) Other 4(5%) 19(13%) 11 (12%) pain treatment was published in Individual hospitals, voluntary cancer organizations, and pain clinics have organized numerous training courses in the treatment of cancer pain for both physicians and nurses. Many suitable drugs in a wide range of formulations are available in Finland, and this provides a good basis for an effective management of cancer pain. The use of opioid drugs is one parameter by which to judge the adequacy of cancer pain management. The aim of this study was to compare the use of opioid analgesics for terminal cancer pain in the Kymenlaakso Central Hospital (KCH) in 1987, 1991, and Methods KCH is a tertiary care referral hospital that covers a population of 180,000 in Southern Finland. The hospital provides services in all basic specialities, and is the only oncological unit in the area. However, more than one-half of all cancer patients are treated outside oncological units, which is a usual practice in Finland. The medical records of all patients who died of cancer in KCH during the last 6 months of 1987, in 1991, and in 1994 were reviewed. The consumption of analgesic medication (nonsteroidal anti-inflammatory drugs and opioids), both regularly predetermined daily doses and supplementary doses for breakthrough pain, was recorded for the last 7 days before death. The doses of so-called "strong" opioids (buprenorphine, morphine, and oxycodone) were converted into milligrams of intramuscular morphine using relevant literature for comparable analgesic potencies The con- vetted daily doses of strong opioids of patients who received these drugs were compared. Because the exact dose ratios of dextropropoxyphene and codeine to intramuscular morphine are not known in all dose ranges, these so-called "weak" opioids were not included in the comparison. Epidural opioids were excluded for the same reason. Resu/ts The number of patients who died of cancer in the KCH was 88 during the last 6 months in 1987, 145 in 1991, and 89 in The mean ages of these three patient samples were comparable (Table 1). The mean survival time from the diagnosis of cancer until death was 19 months in 1987, 12 months in 1991, and 27 months in From 1987 to 1994, the proportion of gastrointestinal cancers decreased from 42% to 18%, whereas the proportion of hematological cancers increased from 12% to 24% (Table 1). From 1987 to 1991, the proportion of patients receiving analgesic therapy regularly increased from 39% to 63%, but it decreased again to 52% in 1994 (Table 2). In 1987, 19% of the patients received regular daily doses of opioids; in 1991, 39% received these drugs; and in 1994, 36% received them. The frequency of parenterally administered morphine or oxycodone was 9% in 1987, 29% in 1991, and 17% in The main route of parenteral administration was continuous subcutaneous infusion. The proportion of patients receiving nonsteroidal antiinflammatory drugs (NSAIDs)in the treatment of terminal pain was 13% in 1987, 26% in 1991, and 19% in The proportion of

3 288 Vuorinen et al. Vol. 14 No. 5 November 1997 Table 2 Frequency of Regular Analgesic Treatment and Frequency of Supplementary Analgesics in 3 Days or More During the Last Week Before Death in 1987, 1991, and (N=88) 1991(~N~145) 1994(~89) % (95% CI) % (95% CI) % (95% CI) Regular analgesic 39 (28-50) 63 (54-71) 52 (41-62) Morphine, IM, IV 9 (4--17) 29 (22-37) 17 (10-26) Morphine, PO 5 ( 1-11 ) 7 (3-12) 11 (5-20) Buprenorphine, SL, IM 5 ( 1-11 ) 3 (1-8) 8 (3-16) Epidural 3 (1-10) 6 (3-I 2) 11 (5-20) NSAIDs 13 (6--21 ) 26 (19-34) 19 (12-29) Other analgesics 15 (8--24) 8 (4-13) 7 (3-14) Psychopharmacologic 10 (5-19) 5 (2-10) 6 (2-13) Supplementary, analgesics Opioid 49 (38-60) 30 (22-38) 78 (67-86) NSAIDs 11 (6-20) 11 (6-17) 45 (34-56) 95% CI, 95% confidence interval; NSAIDs, nonsteroidal anti-inflammatory drugs. patients receiving epidural opioids increased from 3% to 11% during the observation period. Combined drug preparations were prescribed to 15% of the patients in 1987, 8% in 1991 and 7% in Psychopharmacologic treatment, mainly phenothiazines and haloperidol, was prescribed to 10%, 5%, and 6% of the patients, respectively (Table 2). Among patients who received opioids, the mean daily dose of opioids converted to mgs of intramuscular morphine increased from 24 mg [standard error (SE) = 2 mg] in 1987 to 58 mg (SE = 8 mg) in 1991, but it diminished again to 43 mg (SE = 7 mg) in 1994 (Table 3). Discussion In cooperation with the International Narcotics Control Board (INCB), WHO monitors the consumption of morphine for medical purposes in different countries as an indicator of drug availability. Because strong opioids are the mainstay in the treatment of severe cancer pain, the consumption of these drugs reflects also the quality of pain treatment, as verified in nationwide questionnaire studies carried out in Finland, Norway, Denmark, and France. z'4'6'~<~7 In these studies, the mean daily doses of morphine suggested by the responding physicians to manage three simulated patient cases correlated with the level of morphine consumption in each country indicated in the statistics of the INCB. There are marked differences in morphine consumption between the industrialized countries. The United Kingdom, United States, Canada, Australia, and the Scandinavian countries except Finland represent a wellestablished level of morphine consumption, whereas in Finland, France, Spain, German}; Belgium, Greece, and Japan, the consumption is very low (Table 4). ls-2 As seen in Table 4, morphine consumption in Finland increased by about 25% during the first three 4-year periods, but this increase stopped in The reason for this is unknown. According to the statistics of the Finnish National Agency for Medicines, the consumption of morphine in Finland has been 380 defined daily doses (DDD) per million inhabitants in 1987, 460 DDD in 1991, and 540 DDD in There is no major difference in the consumption among the hospital districts in the country. In 1995, the consumption of morphine was 590 DDD in the whole country and 570 DDD in the district of KCH. zl The consumption of morphine in Finland is still onetenth of the consumption in Denmark and about one-fifth of that in the other Scandinavian countries. The patients in this study represent a general Finnish terminal cancer patient population. In 1987, only approximately one-half of 7hble 3 Daily Doses of Opioids Among Patients Who Received Opioids for the Last 7 Days Before Death in 1987, 1991, and 1994 Mean Median Range (mg) (mg) (mg) 1987 (N= 17) (N = 57) (N = 32)

4 Vol. 14 No. 5 :Vovember 1997 Cancer Pain Treatment Backlash 289 Table 4 Average Daily Consumption of Defined Daily Doses of Morphine Per Million Inhabitants in Different Countries During , , , and Country, Denmark New Zealand United Kingdom Iceland Canada Norway Ireland Australia Sweden United States Switzerland South Africa Portugal Netherlands Austria Finland Israel Belgium Germany France Spain Hungary, Japan Bulgaria Greece the patients dying in the KCH was included in this study. However, there has propably been no major differences in the current practice of pain treatment between the first and the second half of the year, and the total number of patients in the 1987 sample is comparable to the samples of 1991 and The assessment of a 50% sample, therefore, probably has no effect on the results. Compared to 1987, a clear improvement in the treatment of terminal cancer pain was observed in 1991 in the KCH, as indicated by both the proportion of patients receiving analgesic treatment regularly and by the daily dose of opioids used. In 1994, these figures were lower again. Among the patients who died in KCH in 1994 there were more hematological cancers and less gastrointestinal cancers than in 1987 or The former are known to have less pain, whereas the latter often have pain at terminal stages. 22 This may have explained the use of lower doses of opioids. In the 1990s there has been a tendency in KCH to transfer terminal cancer patients to primary care hospitals for their last weeks of life. Therefore, fewer cancer patients were dying in KCH in The oncological ward was formed in the KCH in Comparing the use of opioids between different specialities in 1991 and 1994, the patients on the oncological ward had the highest daily doses of opioids, and the patients most often received regular analgesic treatment in both years. They also received supplementary opioids less often than other patients, suggesting that their doses of regular analgesic medication were more sufficient than in the wards of other specialities. The differences between the specialities are in accordance with earlier results obtained by Vainio et al. in Finland z and Cleeland et al. in the United States. 23 The practice of treating cancer patients on the wards of different disciplines according to the primary site of their cancer is typical of the Finnish hospital practice. The patient selection is not based on the stage of the disease, nor on the amount of pain of the patients. Small patient groups and patient selection may have influenced the results in the comparison between the specialties. This study does not explain the undertreatment of cancer pain, but confirms the low dose range of opioids usually prescribed by the Finnish physicians already demonstrated by Vainio et al. 9'4 It also indicates that progress

5 290 Vuorinen et al. Vol. 14 ~ b. 5 November 1997 in improving pain management is slow despite educational efforts and publicity. However, the proportion of patients receiving opioids on a regular basis had constantly increased during 8 years in KCH, and the daily doses in 1994 were almost doubled compared to A key element in improving pain treatment is to "make pain visible" by measuring it. Without monitoring the result of the treatment of pain in individual patients, the judgment of the adequacy of the treatment is difficult. In the present stud~; the notes of pain in the patient records were incidental, and visual analogue scale or other scoring systems were used only in one case. Another obstacle to good pain treatment may be our medical tradition, which neglects patients' "subjective" clues. 24 "Opiophobia" is also strong in our medical tradition. 25'26 The widely known fact that the therapeutic use of opioids rarely results in addiction z7 has not weakened this fear. The international experience also demonstrates that the use of opioid analgesics can increase significantly,~ithout a concurrent increase in opioid diversion and abuse. 98 In addition to the physicians, many patients and family members have the same phobia. 29 One reason for the opiophobia and reluctance to using higher doses of opioids in Finland has probably been the "methadone scandal" that happened in Finland in A group of physicians was sued severely after having prescibed methadone tablets to drug addicts. The National Board of Health undertook several regulation systems, for example, personal prescription sheets and special prescription rules, to control prescription of opioids both in hospitals and for outpatients. These procedures received much publicity, and, as a result, prescription of opioids became practically criminalized in the public opinion. Many doctors ceased to treat pain with opioids. Consequently, the effort to educate physicians in the 1980s started from a situation in which opioid prescription for cancer pain was nearly zero, as indicated in the results of this study, in the study by Vainio et al., 2"4 and in the statistics of the INCB. ~s-2 In spite of various efforts to improve the treatment of cancer pain in Finland, the medical records reviewed for the present study suggest only modest and slow development in current practices. References 1. Zech DFJ, Grond S, L}~ch J, Hertel D, Lehmann KA. Validation of World Health Organization guidlines for cancer pain relief: a 10-year prospective stud): Pain 1995;63: Vainio A. Treatment of terminal cancer pain in Finland. A questionnaire survey. Acta Anaesthesiol Scand 1988;63: Dorrepaal KL, Aaronson NK, van Dam FSAM. Pain experience and pain management among hospitalized cancer patients: a clinical study. Cancer 1989;63: Vainio A. Treatment of terminal cancer pain in Finland: a second look. Acta Anaesthesiol Scand 1992;36: Larue F, Colleau SM, Brasseur L, Cleeland CS. Multicentre study of cancer pain and its treatment in France. BMJ 1995;310: Vainio A. Treatment of terminal cancer pain in France: a questionnaire stud}: Pain 1995;62: Zenz M, Zenz T, Tryba M, Stumpf M. Severe undertreaunent of cancer pain: a 3-year survey of German situation. J Pain Symptom Manage 1995;10:18% Cleeland CS. Strategies for improving cancer pain management. J Pain Symptom Manage 1993;8: Expert Working Group of the European Association for palliative care. Morphine in cancer pain: modes of administration. BMJ 1996;312: WHO Expert Committee. Cancer pain relief and palliative care. Geneva: World Health Organization, National Board of Health (Finland). Instructions for terminal care. Letter no. 3024/02/80. Helsinki: National Board of Health (Finland), Beaver WT, Wallenstein SL, Rogers A, Houde RW. Analgesic studies of codeine and oxycodone in patients with cancer. Comparisons of oral and intramuscular codeine and of oral with intramuscular o~ codone. J Pharmacol Exp Ther 1978;207: Paalzov L, Nilsson L, Stenberg P. Pharmacokinetic basis of optimal methadone treatment of pain in cancer patients. Acta Anaesthesiol Scand Suppl 1982;74: Pane A, SfiweJ, Dahlstr6m B, Paalzow L, Kager L. Pharmacological treatment of cancer pain with special reference to the oral use of morphine. Acta Anaesthesiol Scand Suppl 1982;74: Tigerstedt I, Tammisto T. Double-blind, multipledose comparison of buprenorphine and morphine in postoperative pain. Acta Anaesthesiol Scand 1980;24:

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