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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.56 no.6 Campinas Nov./Dec. 2006
Clinical and therapeutic analysis of oncology patients treated at the Pain and Palliative Care Program of the Hospital Universitário Clementino Fraga Filho in 2003*
Análisis clínico y terapéutico de los pacientes oncológicos atendidos en el Programa de Dolor y Cuidados Paliativos del Hospital Universitario Clementino Fraga Filho en el año 2003
Giselane Lacerda Figueredo SalamondeI; Nubia VerçosaII; Louis BarrucandIII; Antônio Filpi Coimbra da CostaIV
em Anestesiologia do Curso de Pós-Graduação em Cirurgia
Geral, Setor Anestesiologia da FM/UFRJ; Responsável pelo Tratamento da
Dor e Cuidados Paliativos da Onco-Hematologia do Instituto de Puericultura e
Pediatria Martagão Gesteira (UFRJ); Anestesiologista do Instituto Nacional
de Traumato-Ortopedia (INTO)
IIProfessora Adjunta Mestre e Doutora do Departamento de Cirurgia da FM/UFRJ; Coordenadora da Graduação e Pós-Graduação em Anestesiologia da FM/UFRJ; Anestesiologista Responsável pelo Ambulatório de Avaliação Pré-Anestésica do Hospital Universitário Clementino Fraga Filho (HUCFF) da FM/UFRJ
IIIProfessor Titular de Patologia do Departamento de Anatomia Patológica da FM/UFRJ
IVMédico do Serviço de Psicologia Médica e Saúde Mental do HUCFF/UFRJ; Mestrando da Clínica Médica Reumatologia FM/UFRJ
METHODS: The 2003-oncology patients' charts were analyzed retrospectively. Several parameters were compared: age, race, gender, preexisting conditions organ the cancer originated from, type of pain and other symptoms, medications, hospital routine, and end of treatment.
RESULTS: The types of pain included nociceptive, neuropathic, and incidental, which were evaluated using the unidimensional faces pain rating scale. In the first week, patients were treated with home-based patient controlled analgesia (PCA) with oral methadone. After this period, the patient returned to the clinic to calculate the regular dose of methadone. Other opioids used included codeine, tramadol, morphine, and oxycodone. Besides pain, patients experienced: constipation, vomiting, delirium, sleep disturbances, and dyspnea. Neuroleptics, corticosteroids, and laxatives were also used as adjuvant therapy.
CONCLUSIONS: Patient controlled analgesia with methadone is safe and effective, since there were no significant side effects. The clinical and pharmacological knowledge of the anesthesiologist in the multidisciplinary team provided for better patient care, relief of symptoms, and humanization of the final stages of life.
MÉTODO: Se analizaron retrospectivamente las hojas clínicas de los pacientes oncológicos en el año de 2003. Se destacaron las variables: edad, raza, sexo, enfermedades preexistentes, órgano de origen del cáncer, tipo de dolor y otros síntomas, medicaciones utilizadas, rutinas hospitalarias y el término del tratamiento.
RESULTADOS: Los tipos de dolor encontrados fueron nociceptivo, neuropático e incidental evaluados utilizando la escala unidimensional de fases. Se verificó la analgesia controlada por el paciente (PCA) con metadona, vía oral, en ambiente domiciliar en la primera semana. Después de ese período, el paciente volvía al ambulatorio para el cálculo de la dosis regular de la metadona. Otros opioides utilizados fueron codeína, tramadol, morfina y oxicodona. Además del dolor, los pacientes presentaron: constipación, náuseas, vómitos, delirium, alteración del sueño y disnea. Los neurolépticos, corticoides y laxantes fueron usados como fármacos adyuvantes.
CONCLUSIONES: La analgesia controlada por el paciente utilizando la metadona se mostró segura y eficaz por la no incidencia de efectos colaterales significativos. El conocimiento clínico y farmacológico del anestesiólogo en el equipo multiprofesional proporcionó una mejor atención para el alivio de los síntomas de los pacientes y la humanización en el término de la vida.
Palliative Care is defined by the World Health Organization (WHO) as "Active and total care in diseases that do not respond to curative treatment. Control of pain and other symptoms, as well as psychological, social, and spiritual problems are the most important aspects. Its goal is to improve the quality of life of the patient and his/her family. Several aspects of Palliative Care can be used early on, along with the oncologic treatment" 1,2. The follow-up requires a multidisciplinary team composed of anesthesiologists, general doctors, surgeons, psychiatrists, physical therapists, nurses, social workers, psychologists, and, frequently, religious support.
In the United States, the first Palliative Care program was introduced in Connecticut in 1974. Nowadays there are about 1,500 programs. Nevertheless, 15% to 20% of the patients (400,000) die of cancer without being assisted by a Palliative Care team 3. In Brazil, the Palliative Care program was introduced in 1990 at the Instituto Nacional do Câncer (INCA) in Rio de Janeiro. Currently, it can be found in several states throughout the country. Three institutions disseminate this program: Sociedade Brasileira de Anestesiologia (SBA), Sociedade Brasileira para o Estudo da Dor (SBED), and Academia de Cuidados Paliativos.
Patients with terminal cancer face several problems simultaneously. The concept of total pain includes several components: fighting the disease and following several treatments, emotional problems (anger, depression, hopelessness, despair, guilt, death proximity), and changing life plans, giving up long-term plans while focusing on short-term goals 4.
The WHO declared that cancer pain is a worldwide medical emergency. Oncology patients experience severe pain. In advanced cases, it is present in 50% to 75% of the patients. Some of them present more than one type of pain. The Primeiro Consenso Nacional de Dor Oncológica determined that opioid analgesics should be the basis of the treatment of oncologic pain. The knowledge about and the use of the analgesic scale, as well as the knowledge about specific drugs, which can be administered by the oral route in 85% to 95% of the patients, are vital 4-6.
The aim of this work was to evaluate and analyze, clinically and pharmacologically, patients treated at the Chronic Pain Treatment and Palliative Care Program of the HUCFF/ UFRJ.
After approval by the Ethics Committee on Research of the Hospital Universitário Clementino Fraga Filho (HUCFF) of the Faculdade de Medicina da Universidade Federal do Rio de Janeiro (FM/UFRJ), 118 charts from the Institution's Medical Documentation Service were evaluated retrospectively. Patients treated in 2003 at the Chronic Pain Treatment and Palliative Care Program of the Community Service Division of the HUCFF/UFRJ were selected. Those patients were referred by the Oncology, Radiotherapy and Pulmonary Oncology Service to be evaluated.
Patients older than 18 years, with malignancies specific for the Palliative Care Program, and who had been seen more than three times at the clinic, were included in the study.
Exclusion criteria included patients with malignancies who were referred to the clinic only for pain control and returned to the oncology clinic; those who had been seen once or twice at the clinic; those followed up only as in-patients; and those whose charts did not have conclusive data.
All the data gathered from the charts were recorded on specific protocol forms.
Parameters studied included age, race, gender, organ the cancer originated from, preexisting conditions, incidence of pain and other symptoms, drugs used more often (especially opioids), hospital routine, and end of treatment.
The test of proportion, to evaluate the difference between two parameters; the Mann-Whitney test, to compare the non-parametric distributions; and the test t Student, to confront the means and the dispersion of normal values, were used for the statistical analysis. Differences were significant for a p < 0.05.
Of the 118 patients selected for the program in 2003, 85 were women. After analyzing the data in the charts, only 60 women were included in the study. Twenty-five patients were excluded for the following reasons: five were referred to the clinic, but did not show up for the appointment; four died in the beginning of 2003; nine were seen just once or twice in the clinic; and seven were referred for pain treatment and returned to the oncology service. The final study population included 33 men and 60 women.
The mean age of the entire group was 60.46 ± 12.52, with a mean age of 58.83 ± 12.93 for women and 63.29 ± 11.39 for men. As for race, the study population included whites (56), blacks (9), and mixed (28) (Table I).
As for the organ the cancer originated from, it was more common in the lungs (33 patients) and uterus (22), accounting for 59% of the total. Other locations, in decreasing order, included large bowel, breast, prostate, bone marrow, kidney, liver, stomach, pancreas, and small bowel (Table II)
There were several preexisting conditions in this study population, but some patients presented more than one. They presented a total of 113 diseases (74 for women and 39 for men). The most common were smoking, hypertension, diabetes, and alcoholism, accounting for 81.4% of the total (Table III). Hypertension and diabetes were more frequent in women (22 and 10) than in men (7 and 3). Pulmonary disease was significantly more common in women (3) than in men (1) (p = 0.0473, by the proportion test). As for symptoms, every patient presented more than four. The most prevalent were pain, gastrointestinal, psychiatric, and respiratory symptoms. The study group presented 370 symptoms, 235 for the women and 135 for the men. Eight-two patients presented pain. However, 11 of them did not complain of pain. Comparing gender, there was a significant difference for this age Group. Constipation, vomiting, anorexia, and nausea were the main gastrointestinal complaints. The most prevalent psychiatric symptoms (64%) were delirium and sleep disorders. Forty-seven per cent of the patients complained of dyspnea; it affected more men than women, but this difference was not significant (p = 0.0130). There were also skin, genitourinary, neurological, vascular, and metabolic changes (Tables IV and V).
There was a significant gender difference regarding neuropathic, nociceptive, and incidental pain (Table VI). The Home Follow-up Form, standardized for the program (Chart I), was used to analyze patients' opioid use. This form was given to every patient or his/her caretaker in the first appointment to record the dose of analgesics taken.
For the subjective pain evaluation, the unidimensional face pain rating scale (FS) was used, according to the WHO criteria, in which each face representation is given a score in increasing order (Figure 1).
A standardized treatment, using patient controlled analgesia, after characterizing the pain and assessing its severity through the faces pain rating scale, was designed for pain relief. Titration of methadone was done according to the following criteria: 1) it started with 2.5 mg; 2) 30-minute waiting period; 3) pain severity was evaluated again; 4) if FS score was > 2, another 2.5 mg of methadone was administered; 5) new evaluation after 30 minutes; 6) if score was > 2, another 2.5 mg of methadone was administered, followed by another 30-minute waiting period and another evaluation; 7) if score > 2, the patient received another dose of 2.5 mg of methadone, and the process was repeated until a FS of zero or 1 was achieved, when the titration ended. The final dose was the sum of all the doses.
The patient was then sent home with the following instructions: the titrated dose of methadone could be repeated every four hours in case of pain and if the FS score were > 2. The program established that PCA should be done at home by the oral route. If the patient experienced disagreeable symptoms, he/she could call the physician for orientation, which would also clarify whatever doubts the patient might have.
The Home Follow-up Form was evaluated at the clinic after seven days, observing the dose used in the previous three days. Finally, a fixed dose of methadone at a regular interval was prescribed. The patient and his/her caretaker returned once a week or once every two weeks to have the pain and doses of methadone evaluated, both the regular and rescue ones. The answers to a small questionnaire were evaluated, as well as complaints of gastrointestinal, respiratory, psychiatric, or other symptoms.
Morphine was prescribed at a regular four-hour interval after titration at the clinic.
Analgesic drugs prescribed for the patients in this study included strong and weak opioids and analgesics (Table VII). Daily opioid doses, minimal, maximal, and median were 2.5 mg, 180 mg, and 25 mg for methadone; 15 mg, 420 mg, and 60 mg for morphine; and 60 mg, 360 mg, and 180 mg for codeine.
To treat other symptoms, adjuvant drugs, such as neuroleptics (haloperidol, 18 patients); benzodiazepines (14); antidepressants (imipramine 18, amitriptyline 14, fluoxetine 11); anticonvulsants (carbamazepine 24); corticosteroids (prednisona 27); laxatives (magnesium salt 28, senne tea 27, milk of magnesia 12). Note that laxatives were the drugs used more often, followed by antidepressants, corticosteroids, and neuroleptics (Table VIII).
Hospital routines specified how long patients waited for an appointment, which averaged 3.9 days (3.7 days for women and 4.3 for men). Each patient had a mean of 12 appointments. The mean clinical follow-up was 150 days. Eight patients were resuscitated after being admitted to the hospital. More patients died at home (55) than in the hospital (33). There were no differences between genders for all of those parameters. At the end of the study, five patients were still alive (Table IX).
The Pain Clinic was organized and directed by Dr. Peter Spiegel between 1983 and the beginning of 1997. In 2001, besides all the other options available, it instituted the use of patient controlled analgesia (PCA) with methadone for the treatment of pain in Palliative Care. Patients were oriented regarding the dose in the clinic. Pain controlled analgesia was chosen because it can balance the drug in the plasma and relieve the pain of the patients in Palliative Care. It proved to be a safe and low cost method, and can be administered orally and at home. It did not present important complications with the doses employed. Usually, PCA is done in hospitalized patients using the IV route, what requires an infusion pump and special IV tubing, increasing the cost of the treatment.
The role of an anesthesiologist in setting up a pain and palliative treatment clinic is relevant when one wants to provide patients proper pain relief, since pain is an obstacle, imposing limitations and hindering the proper adaptation to their daily needs.
Palliative care demands follow-up by a multidisciplinary team (anesthesiologists, psychiatrists, general doctors, psychologists, physical therapists, nurses, social workers, and pharmacists) to provide a better quality of life to the patient, decreasing his/her pain. The increasing physical dependence that comes with the progression of the disease (loss of mobility, urinary changes) makes it more difficult to deal with pain, influencing negatively the quality of life (QL). Quality of life is defined as the "the patient's perception on his physical, emotional, and social condition!" 4.
As for the organ the cancer originated from, lung and uterine cervix were more prevalent. Note that the Oncopulmonary Service at the HUCFF has a good rapport with the palliative care team, always referring patients to this program.
In the literature, breast cancer is the number one cause of death in Brazilian women 7. Surprisingly, the number of patients referred to the program with this cancer was very low.
Prostate cancer is the second cause of death in Brazilian men 7. In this study, only four patients with this diagnosis were followed-up by the Palliative Care Program, a surprisingly reduced number. These data show how important it is the bond created among the Palliative Care physicians and oncologists. It has been observed that specialists do not refer patients to this type of care very often. In 1950, Bonica 8, in the USA, had already reported on that. This difficulty would decrease if in the beginning of the treatment the Palliative Care team saw the patient along with the oncologists.
Among the preexisting conditions, cigarette smoking was more frequent, followed by hypertension, diabetes mellitus, and alcoholism. Diabetes mellitus and hypertension were also prevalent in another study 9.
Cancer patients may also present heart failure, chronic obstructive pulmonary disease, and Alzheimer's, making it difficult to control the symptoms. Patients with these conditions tend to present progressive dyspnea, which is difficult to control. It is more difficult to provide Alzheimer's patients the necessary comfort due to their difficulty to communicate 10. In this study there were no patients with this disease.
The results confirm that pain was the most prevalent symptom (88% of patients). Most patients with advanced cancer presented two types of pain simultaneously: nociceptive and neuropathic. Some patients also complained of incidental pain. This data confirmed those reported on the literature 4,5.
Some problems make it more difficult to control pain, such as incidental pain, neuropathic pain, tolerance, and a history of psychological disturbances and substance abuse 4. Addiction is not an issue in those patients because pain relief is important, since pain is usually very severe, associated with the prognosis of the disease, with is always "somber".
The evaluation of pain in cancer patients is fundamental and extremely important. Pain should be characterized focusing on the following attributes: location, irradiation, severity, temporal variation, and factors that improve or worsen it. One should also determine whether the patient has any pain syndrome associated with the cancer or the treatment, or due to the cancer itself, which is the most common cause of oncologic pain 5,6.
Episodic and temporary pain (type breakthrough pain) is characterized by pain of short duration (40 minutes), and may occur when the patient is moving around 4,11. Currently in the United States and United Kingdom, transmucosal fentanyl citrate is used as a rescue medication. It is a fast acting drug with a short duration, about 2 and 40 minutes, respectively 4,11-13. In this study, 23 patients presented incidental pain and were treated with rescue doses of morphine, since transmucosal fentanyl is not available in Brazil. This medication is very expensive, which is an obstacle to its use. The prevalence of incidental pain was higher in women than in men. Eleven of them had breast cancer and 14 lung cancer; these locations were also the ones that presented the greatest incidence of bone metastasis. In men, the organs where the cancer originated from most often were prostate (4) and lung (19). Incidental pain can also affect patients with cervical cancer during urination, evacuation, and intercourse. In this study, 22 patients were included in this context. These results are similar to other works in the literature 11,12.
The use of weak opioids is very important in the treatment of oncologic pain. The WHO elected codeine as the standard drug in the second analgesic step. Its advantages include decreased incidence of vomiting, treatment of cough, and is also available as an oral solution. Its disadvantages include increased incidence of constipation, that can be difficult to treat, and the short intervals between doses (four hours) 4,14. In this study, 34 patients used codeine. Four patients used tramadol, which had already been prescribed. Doses and intervals were optimized before implementing strong opioids.
Concerning the third analgesic step, methadone was the opioid of first choice because it is absorbed very well by the oral route, its low cost, it treats both nociceptive and neuropathic pain, and acts on NMDA receptors 4,14-16. It does not have active metabolites and impregnates other tissues (a mean of five days). It can be prescribed with a longer interval between doses 17-20. The dose of methadone was individualized in the first week, with a great variability among patients, and its interaction with other drugs (riphampin, fenitoin, spironolactone, alcohol, verapamil, estrogens) decreased its plasma concentration, which are the major obstacles to its use 21-23.
Sixty to 90% of a dose of methadone binds to plasma proteins, and acid alpha-1-glycoprotein determines the free fraction of this opioid and of other strong opioids, except for morphine that binds to albumin. This is important because this protein is elevated in cancer patients and in patients treated with amitriptyline, decreasing the free fraction of this medication, leading to an increase in its dose, and decreasing the interval, until a balance between tissues and plasma is achieved. Urine pH is very important in reducing the clearance of methadone, i.e., the lower the urine pH the lower the blood concentration of methadone 19-22. In this study, after PCA with methadone in the first week patients did not present side effects, such as sedation, nausea and vomiting, myoclonus, respiratory depression, and hallucination. There is a study 23 that used PCA whose results agree with ours. Other studies 24-26 used fixed doses of methadone in the first week. In this study, after the first week, patients used fixed doses at regular intervals, which provided relief of pain and improved patient's conditions and quality of life. Methadone can be administered through the oral, epidural, venous, rectal, and subcutaneous routes 27-29. Patients in this study used only the oral form.
There is a report in the literature of patients who used methadone along with other drugs and developed ventricular disrhythmias 30. In this study, the daily dose of some patients was higher than 100 mg, but they did not develop cardiac arrhythmias. This evaluation was done through the physical exam (cardiac auscultation and palpation of the radial pulse).
In specific situations it is necessary to change the strong opioids because uncontrollable side effects might develop when the analgesic dose is achieved. Some studies 12,31 suggested rotating opioids, indicating that methadone should be one of the drugs included in the rotation. In this study, opioids were changed in some patients, but the reason for this was not recorded in the charts.
Regarding other symptoms, those reported more often in the literature 32-35 are fatigue, anorexia, cachexia, nausea and vomiting, constipation, delirium, and dyspnea. In this study, fatigue and cachexia were not so frequent.
Fatigue has multiple components, such as tiredness, lack of energy, decreased mental capacity, and weakness associated with difficulty to perform daily tasks. Its treatment associates non-pharmacological measures, such as resting between tasks. Dexametasone (2 to 20 mg a day in a single dose in the morning) 36 is the drug used more often. In this study, prednisona was the corticosteroid used more often.
The consumptive syndrome is characterized by decreased appetite (anorexia), fatigue, and cachexia (weight loss). Cachexia associated with cancer is secondary to the production of inflammatory substances, such as tumor necrosis factor, interferon, and cytokines, that cause metabolic changes, i.e., there is increased protein catabolism and decreased protein synthesis. There is no correlation between the size of the tumor and the degree of cachexia. The change in weight cannot be corrected by changing ones diet 36,37.
Some patients do not have good oral absorption due to vomiting and gastric stasis, so the subcutaneous route is preferred 14,15. In 70% of the study patients, symptoms such as nausea and vomiting were prevalent, hindering quality of life. The most common causes of these symptoms were opioids and chemotherapy. The Palliative Care Program used haloperidol (0.5 to 2 mg) up to every 6 hours by mouth, to a maximum of 10 to 15 mg a day. It acts in the vomiting trigger center in the central nervous system. In selected situations, prokinetic drugs (bromopride) or antihistamines (prometazine) were associated 3-40.
Constipation was the most frequent gastrointestinal symptom (78 patients). It is normally caused by opioids and other associated drugs. Laxatives, such as senne tea and magnesium sulphate, were used prophylactically. These results are similar to those reported by other authors 40-43.
Psychiatric symptoms are relevant regarding the quality of life of patients and caretakers (people who take care of the patient, family members or not). The most frequent are delirium (change in the level of consciousness, attention, and perception, frequently along with visual hallucinations, especially at night, with organic changes, which differs from insanity, a change in thought process) and changes in sleep pattern (sleep-awake cycle). Delirium can be triggered by constipation, opioids, and benzodiazepines. In this study, 27 patients presented delirium and 18 of those were treated with haloperidol. The sleep changes reported by patients were induced by psychological and physical factors, such as pain, dyspnea, and frequency of awakening at night to urinate or take medication 44-47.
Dyspnea was the most frequent respiratory symptom. Several authors 48-50 reported that it affect 70% of the patients. The severity of dyspnea depends on the extension of lung involvement by the cancer and anxiety. Pharmacological treatment includes strong opioids and sedatives. Non-pharmacological treatment includes maneuvers to activate the V cranial nerve, such as a ventilator directed to the patient's face (decreasing his/her dyspnea), relaxation, recreation, and massage. These results were confirmed by other studies 48-50.
Concerning hospital routines, it was noticed that patients preferred to die at home. Eight patients that were hospitalized were resuscitated.
The fundamental basis of patient treatment in the Palliative Care Program is not to hasten nor prolong the process of death, but to provide relief of pain and other symptoms. The involvement of a multidisciplinary team, including an anesthesiologist whose main goal is pain relief, in order to humanize and dignify the moment of death is essential.
We conclude that the anesthesiologist's pharmacologic and clinical knowledge provided for better pain relief of patients in the Palliative Care Program, with special attention to the method of pain control used, home-based patient controlled analgesia with methadone, as a safe and effective option without significant side effects. The relationship among the different subspecialty clinics is very important. It allows every oncology patient to have an early follow-up by the Palliative Care Program. In this study, the Oncopulmonary and Radiotherapy Service referred most of the patients to the program due to the good relationship between the teams.
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Dra. Giselane Lacerda Figueredo Salamonde
Rua Homem de Melo, 55/403 Bloco 1 Tijuca
20510-180 Rio de Janeiro, RJ
Submitted for publication
05 de janeiro de 2006
Accepted for publication 29 de agosto de 2006
* Received from Programa de Pós-Graduação em Cirurgia Geral, Setor de Anestesiologia do Departamento de Cirurgia da Faculdade de Medicina da Universidade Federal do Rio de Janeiro (FM/UFRJ), Rio de Janeiro, RJ