Bowel function during pain therapy with oxycodone/naloxone prolonged-release tablets in patients with advanced cancer.

BACKGROUND: The World Health Organization (WHO) step-III opioids are often required right from the start of pain therapy in order to achieve sufficient symptom control. Bowel dysfunction, particularly constipation, is one of the most frequent and persistent side effects of opioid therapy, and it is known to cause considerable distress in many patients. The aim of the study was to evaluate whether patients with advanced cancer and moderate to severe cancer pain will benefit from treatment with oxycodone/naloxone prolonged-release tablets (OXN), with particular regard to constipation. MATERIAL AND METHODS: In this exploratory, non-randomised, open-label, mono-centre study we evaluated the bowel function in palliative care patients treated with OXN. During the treatment phase patients were titrated up to an adequate pain control. The Bristol Stool Form Scale (BSFS) (type 1-7) and Bowel Function Index (BFI) (0-100) were used to assess consistency and frequency of bowel movements. Global patient satisfaction was assessed with Patient Global Impression of Change Scale (PGIC) (1-7). STATISTICS: mean ± SD, significance p<0.05. RESULTS: Twenty-six patients [10 male patients (38.5%)] were included; mean age 70.6 ± 14.0 years, length of stay 22.6 ± 21.2 days. At admission all patients had opioid-induced constipation. During the observation period of 14 days the daily mean dose of OX was 36.2 ± 17.2 mg and of N 15.4 ± 5.3 mg. In five cancer patients pain control was not sufficient under the approved maximum total daily dose of 40/20 mg OXN; therefore switching to hydromorphone. BFI improved significantly in 21 patients (72.4 ± 17.0 vs. 36.8 ± 13.4) (p<0.0001); stool consistency (BSFS) improved from type 2.0 ± 0.7 to 4.9 ± 1.0 (p<0.0001). PGIC at discharge was 1.9 ± 0.8. DISCUSSION: Patients with OXN treatment throughout the whole study phase showed a clinically relevant improvement in pain intensity and bowel function as well as increased satisfaction. Well-known disadvantages of laxative treatment might be spared or even circumvented under OXN treatment, if appropriate.

Impact of cafedrine/theodrenaline (Akrinor® ) on therapy of maternal hypotension during spinal anesthesia for Cesarean delivery: a retrospective study.

AIM: Maternal hypotension is the most frequent complication in spinal anesthesia for Cesarean delivery. Malperfusion of the foetus and nausea and vomiting of the mother are hallmarks of maternal hypotension. In this retrospective data analysis and anesthesia protocols we have investigated to explore the effects of therapeutic interventions for hypotension with cafedrine/theodrenaline (Akrinor® ) during spinal anesthesia for elective Cesarean section. METHODS: In a retrospective study anesthesia charts of 173 parturients undergoing spinal anesthesia for Cesarean delivery with 10mg hyperbaric bupivacaine + 5 µg sufentanil were reviewed for 30 min after onset of hypotension with respect to blood pressure, heart rate, respiration rate, as well as APGAR scores and umbilical arterial pH. Maternal data were compared to baseline values recorded and documented immediately before placing the spinal anesthesia in the operating room. The cohort was divided into two groups according to their hemodynamic response to spinal anesthesia: 117 parturients had a drop of systolic blood pressure to <120 mmHg or <80% of baseline blood pressure and were therefore treated with Akrinor® (cafedrine/theodrenaline; treatment group); 56 patients remained within the specified limits (non-treatment group). Maternal cardiovascular parameters and newborn outcome between the groups were compared. RESULTS: Both groups were comparable with regard to baseline characteristics. In the treatment group one minute after the first application of cafedrine (43 mg)/theodrenaline (2.2 mg) mean systolic blood pressure raised from 108.6 mmHg to 117.2 mmHg (P=0.0004), mean of maximal changes of systolic blood pressure after the first application of Akrinor® was 21.3 mmHg. Blood pressure levels of the non-treatment group were regained in the treatment group 8 min after hypotension onset and remained at that level until the end of 30 min observation. No clinically relevant changes of heart rate were detectable. While mean APGAR score one minute post partum was significantly higher in the treatment group (8.9±1.2 vs. 8.4±1.1 P=0.043), mean umbilical arterial cord pH was 7.3±0.1 and APGAR scores 5 and 10 minutes postpartum did not differ significantly. CONCLUSION: The results of this study confirm a rapid and sustained increase in blood pressure after application of Akrinor® for treatment of sympathicolysis induced hypotension. No negative impact of Akrinor® on umbilical arterial cord pH and APGAR scores was observed.

[Tuition in palliative medicine. Does it have an impact on future physicians' attitudes toward active euthanasia?]. / Palliativmedizinische Lehre : Gibt es einen Einfluss auf die Haltung zukünftiger Arzte zur aktiven Sterbehilfe?

BACKGROUND: The aim of this study was to examine the attitude of medical students with or without tuition in palliative medicine towards active euthanasia and whether this changes during the course of the study period. METHODS: A questionnaire was developed with 13 items (focus groups, preliminary tests) which takes knowledge and attitude into consideration. Students in the 2nd (2CS) and 6th (6CS) clinical semesters at 2 universities with (U1) and without (U2) palliative medicine as a compulsory subject were included. RESULTS: The initial approval rate for active euthanasia was high for students in 2CS at both universities (U1 and U2), remained stable for U2 and sank clearly for U1. At U1 the number of students who would consider active euthanasia for themselves was greatly reduced but only slightly for U2. Of all the students, 40.9% of U2 and 22.5% of U1 were of the opinion that they could practice active euthanasia on patients. The majority admitted to being frightened to have responsibility for incurable patients. Of the students in 6CS, only 12.2% from U1 and 7.1% from U2 considered themselves sufficiently prepared to be responsible for terminally ill patients. CONCLUSIONS: The results of this questionnaire demonstrated a clear influence of tuition in palliative medicine on the rejection attitude of students towards active euthanasia, however, the attitude proactive euthanasia was still high. The results indicate that tuition in palliative medicine must be modified and substantially intensified.

Morphine in the management of dyspnoea in ALS. A pilot study.

BACKGROUND AND PURPOSE: The study aimed to verify the efficacy and safety of morphine in the management of dyspnoea in patients with terminal amyotrophic lateral sclerosis (ALS). A further aim was to assess the effect of morphine on ventilation and the potential diminishing effect of nasal O(2)-insufflation preceding morphine administration on the intensity of dyspnoea. METHODS: Six dyspnoeic ALS patients were included in a prospective, non-randomized study. The intensity of dyspnoea was measured with a Numeric Rating Scale (NRS 0-10). Transcutaneous carbon dioxide partial pressure (tcpaCO(2)), oxygen saturation (SaO(2)) and pulse frequency were continuously monitored during the nasal insufflation of O(2) preceding the first morphine dose and also afterwards. RESULTS: A significant decrease was seen in both respiratory rate (from 42.0 +/- 6.0/min to 29.0 +/- 4.0) (P = 0.027) and the intensity of dyspnoea (from 7.5 +/- 1.9 to 1.8 +/- 0.8) (P = 0.027) 120 min after the morphine administration. Neither a significant tcpaCO(2) increase nor a SaO(2) decrease were seen. O(2)-insufflation did not significantly decrease the intensity of dyspnoea. The anxiety of choking correlated highly significantly with the intensity of dyspnoea (r = 0.861, P = 0.028) in all patients. There were no cases of respiratory depression. DISCUSSION: Therapeutic doses of morphine were effective and safe in the management of dyspnoea in ALS patients.

[Symptomatic treatment of dyspnoea in patients receiving palliative care: nasal delivery of oxygen compared with opioid administration]. / Symptomatische Therapie der Dyspnoe bei Patienten in der Palliativmedizin: Sauerstoff-Insufflation versus Opioidapplikation.

BACKGROUND AND OBJECTIVE: Dyspnoea frequently occurs in patients with advanced tumor disease receiving palliative care (prevalence > 50). Aim of the study was to assess, in dyspneic patients in palliative care, the efficacy of opioids in treating their dyspnoea and to determine whether or not nasal administration of oxygen previous to opioid administration would decrease the severity of dyspnoea. PATIENTS AND METHODS: In a prospective, non-randomised study 25 patients with cancer who had been admitted to our palliative care unit were investigated (aged 64.5 +/- 15.1 [40-90] years; 11 males [44 %]. 13 patients reported severe and 12 moderate dyspnoea. For symptomatic treatment of dyspnoea, 12 patients received morphine and 13 patients hydromorphine. The severity of of dyspnoea was rated according to a numeric scale (NRS 0-10). Recorded and compared was severity of dyspnoea at admission before any oxygen had been administered, after 30 minutes of nasal oxygen, and 30, 60, 90 and 120 minutes after the first administration of opioid without nasal oxygen. RESULTS: Whereas there was no change in the severity of dyspnoea during nasal oxygen administration, mean respiratory rate (f) 30 minutes after the first opioid application had significantly decreased. The intensity of dyspnoea had significantly diminished 90 minutes after the first opioid application. CONCLUSION: During nasal oxygen administration the severity of dyspnoea, as measured by use of NRS had not decreased, whereas it had significantly decreased after the first opioid administration.

[Pain treatment of patients with incurable malignant tumors]. / Schmerztherapie bei Patienten mit inkurablen Tumorerkrankungen.

BACKGROUND AND OBJECTIVE: Efficacious pain therapy is one of the main challenges in the management of patients with advanced cancer. It was the aim of this study to ascertain whether adequate pain treatment was achieved in a palliative care unit and what changes in medical treatment were undertaken during the patients stay in this unit. SUBJECTS AND METHODS: Medication against pain and pain intensity were documented during hospital care of 94 patients with cancer (mean age: 66.8 years; female/male 52.2/47.8%; discharged/deceased 58.5/41.5%) at admission and discharge. 32 patients were interviewed by phone after discharge about their current perception and intensity of pain, as well as their health. RESULTS: Highly significant reduction of pain intensity was achieved in all patients while receiving palliative care. Only those patients who were on oral morphine at admission to hospital required significantly raised morphine dosages while receiving palliative treatment. The other patients did not need significant changes of opioid medication. Pain reduction persisted even after discharge. CONCLUSION: In patients with advanced cancer the effects of psychological, social and spiritual factors on their perception of pain is probably of greater importance in achieving efficacious pain reduction than a change of medication. Further studies will be needed to confirm these findings.

[Opioids for cancer pain treatment. Efficacy and side effects]. / Opioide in der Tumorschmerztherapie. Wirksamkeit und Nebenwirkungen.

In Germany, about 400,000 people per year are diagnosed with cancer. In the terminal stage of their disease, up to 95% of cancer patients suffer from pain. In earlier stages, this is true for about 50% of patients. It is estimated that 220,000 people in Germany are in need of cancer pain therapy. If the pain therapy is going to be changed, this must be comprehensively discussed with the patient in advance, particularly when strong opioids are used which are mostly indicated in these patients. Opioids are effective and reliable drugs when pain therapy is performed according to the basic principles. It is widely agreed that the WHO analgesic ladder serves as orientation and that the choice of substances must be suited to the cause and pathophysiological type of pain. Even though a variety of other strong opioids is in clinical use, morphine remains the reference substance for efficacy and occurrence of side effects in opioids.

[Strong opioids and constipation]. / Stark wirksame Opioidanalgetika und Obstipation.

In cancer pain therapy treatment with strong opioids is essential. However, it may be accompanied by the occurrence of various adverse effects. The most frequent and persistent side effect in the course of opioid treatment is constipation. It is mainly caused by linkage of the opioid to the peripheral mu-receptors in the bowel and may increase as a result of certain concomitant circumstances, such as poor intake of fluids or electrolyte disorder. Present research indicates that there is a relation between type of opioid and degree of constipation, i.e. treatment with transdermal fentanyl or methadone tends to cause less constipation compared to morphine or hydromorphone. The route of administration of morphine--oral vs. subcutaneous--does not seem to affect the incidence of opioid-induced constipation. Furthermore, prophylaxis and efficient control of opioid-induced constipation still fail to be part of the routine in pain treatment.

[Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients]. / Cannabinoide in der Palliativtherapie des Anorexie-Kachexie-Syndroms.

Loss of appetite and cachexia are frequent symptoms in palliative care patients. However, therapeutic regimens often prove ineffective, and the quality of life of many patients is significantly impaired by these symptoms. Causes and pathophysiology of anorexia and cachexia are complex and must be identified and treated. Symptomatic pharmacological therapy aims at metabolic, neuroendocrinological and catabolic changes. Prokinetic drugs, corticosteroids and gestagenes are used for symptomatic therapy. Recently, the use of cannabinoids for treatment of loss of appetite and cachexia has become the focus of interest. In cancer patients, cannabinoids proved more effective than placebo but less than gestagenes. Compared to placebo, higher efficacy of cannabinoids could be demonstrated in patients with AIDS as well as in patients with Morbus Alzheimer. However, side effects, such as dizziness, tiredness and daze led to discontinuation of the cannabinoid therapy in some patients.

[Dronabinol (delta9-tetrahydrocannabinol) in long-term treatment. Symptom control in patients with multiple sclerosis and spasticity, neuropathic pain, loss of appetite and cachexia]. / Dronabinol (deltag-tetrahydrocannabinol) in der Langzeittherapie. Symptomkontrolle bei multipler Sklerose mit Spastik, neuropathischen Schmerzen, Appetitlosigkeit und Kachexie.

Cannabinoid drugs have been used increasingly in the treatment of neuropathic pain and spasticity. Even though the evidence still is scarce, patients with multiple sclerosis seem to benefit substiantially from cannabinoid therapy. In a case report dose finding and long-term therapie with delta9-tetrahydrocannabinol are described. Dronabinol proved effective and was well tolerated in long-term treatment. Pain was reduced significantly and opioid requirements decreased. At the same time spasticity was reduced and appetite and weight increased. It still needs to bei discussed whether or not part of the positive effect on symptoms was probably mediated by psychomimetic effects. This case report shows, that dronabinol offers an additional therapeutic option in a palliative treatment concept for patiens with high symptom load.

Attitudes on euthanasia, physician-assisted suicide and terminal sedation--a survey of the members of the German Association for Palliative Medicine.

BACKGROUND: Due to recent legislations on euthanasia and its current practice in the Netherlands and Belgium, issues of end-of-life medicine have become very vital in many European countries. In 2002, the Ethics Working Group of the German Association for Palliative Medicine (DGP) has conducted a survey among its physician members in order to evaluate their attitudes towards different end-of-life medical practices, such as euthanasia (EUT), physician-assisted suicide (PAS), and terminal sedation (TS). METHODS: An anonymous questionnaire was sent to the 411 DGP physicians, consisting of 14 multiple choice questions on positions that might be adopted in different hypothetical scenarios on situations of "intolerable suffering" in end-of-life care. For the sake of clarification, several definitions and legal judgements of different terms used in the German debate on premature termination of life were included. For statistical analysis t-tests and Pearson-correlations were used. RESULTS: The response rate was 61% (n = 251). The proportions of the respondents who were opposed to legalizing different forms of premature termination of life were: 90% opposed to EUT, 75% to PAS, 94% to PAS for psychiatric patients. Terminal sedation was accepted by 94% of the members. The main decisional bases drawn on for the answers were personal ethical values, professional experience with palliative care, knowledge of alternative approaches, knowledge of ethical guidelines and of the national legal frame. CONCLUSIONS: In sharp contrast to similar surveys conducted in other countries, only a minority of 9.6% of the DGP physicians supported the legalization of EUT. The misuse of medical knowledge for inhumane killing in the Nazi period did not play a relevant role for the respondents' negative attitude towards EUT. Palliative care needs to be stronger established and promoted within the German health care system in order to improve the quality of end-of-life situations which subsequently is expected to lead to decreasing requests for EUT by terminally ill patients.

Constipation--modern laxative therapy.

It is estimated that one third of the population in Western industrial countries suffers from constipation at least from time to time. Constipation may have somatopathic or functional causes. Furthermore, a great number of substances are known to cause medication-induced constipation, i.e. opioid-induced constipation is caused by linkage of the opioid to opioid receptors in the bowel and the central nerve system. Whenever possible, causal therapy should be undertaken. Patients in palliative care mostly suffer from chronic functional constipation. The treatment consists of basic measures and the application of laxatives. According to their mode of action, they are divided into bulk-forming laxatives, osmotic laxatives, stimulant laxatives, lubricating agents and others. Bulk-forming laxatives are not recommended for use in palliative care patients, for such patients are normally not able to take in the required amount of fluids. Osmotic laxatives are divided into (magnesium) salts, saccharine, alcohols and macrogols. Lactulose is the most popular saccharine laxative. Because of its side effects (flatulence, bloating and abdominal cramping), lactulose is not a laxative of our choice; instead, we prefer to give macrogol. Orally administered, macrogol is not metabolised and pH value and bowel flora remain unchanged. Macrogol hydrates hardened stools, increases stool volume, decreases the duration of colon passage and dilates the bowel wall that then triggers the defecation reflex. Even when given for some time, the effectiveness of macrogol will not decrease. Because of its high effectiveness and commonly good tolerance, macrogol has become the laxative of first choice in palliative care patients with all kinds of chronic constipation, if these patients are able to take in the necessary amount of fluids. From the general medical point of view, lubricating agents have become obsolete. In palliative care patients, however, they are still important laxatives for prophylactic treatment or therapy of constipation. Due to clinical experience, in palliative care a laxative ladder has proven successful.

[Laxative use and efficacy in palliative care of patients with cancer pain and morphine therapy. A retrospective study with special regard to polyethylene glycol]. / Einsatz und Effektivität von Laxanzien in der palliativen Therapie tumorkranker Patienten mit einer Morphintherapie. Eine retrospektive Studie unter besonderer Berücksichtigung des Wirkstoffs Macrogol.

GOAL: Goal of this study was the assessment of the frequency of constipation in patients of palliative care medicine and the efficacy of the use of laxatives. METHODS: In a retrospective study the computerized data of 206 patients were analysed by descriptive statistics. RESULTS: Constipation occurred in 42.7% of patients. Constipation appeared in 34% of 159 patients, who were treated with morphine. There was no correlation to gastrointestinal tumors. Laxatives were given to 74.3% of patients. Laxative use was uncomplicated in 78.4%. For therapy of constipation combined administration of polyethylene glycol, sodium picosulphate and paraffin was most effective. CONCLUSION: In palliative care patients the use of polyethylene glycol is recommended for treating morphine-related-constipation.

[Pain treatment today--current standing of pain treatment in Germany]. / Schmerztherapie heute--Stand der Schmerztherapie in Deutschland.

Beyond doubt the provision of pain therapy for patients with acute and chronic pain in Germany has improved over the last 30 years. This positive development comprises i. e. the growing impact of acute pain services on the treatment of patients with postoperative pain and the implementation of new developments in research into the clinical setting of obstetric pain therapy. Nevertheless, the provision of pain therapy for patients with chronic pain syndromes, for children, and in the fields of cancer pain and palliative medicine is neither qualitatively nor quantitatively sufficient.

[Palliative medicine--physician's responsibility]. / Palliativmedizin--Eine ärztliche Verpflichtung.

When caring for patients with an incurable progressive disease, the physician experiences a feeling of powerlessness because there is no curative treatment that he can offer. The reaction to this must not be resignation, but active palliative medicine to achieve the best possible quality of life for the remaining time. Palliative medicine is a holistic concept of treatment in an outpatient or inpatient setting, integrating physical, psychological, social and spiritual aspects. Palliative medicine started in Germany in the 1980s with a manifest delay compared to Great Britain and the Scandinavian countries and developed in the 90s with a growing dynamic. Even so, we are still a long way from a satisfactory situation in the field of palliative medicine in Germany. This is true for the practical implementation of palliative medicine in the outpatient or inpatient setting, for the training of physicians and nurses and for teaching and research at universities. The decision-makers in our health care system are called upon to support palliative medicine and ensure access to palliative care all over the country. Palliative medicine was started to ease suffering, preserve or restore autonomy and maintain dignity. As an active life aid it is, in our opinion, an alternative to any demand for euthanasia.

[The role of pychosocial care and bereavement counselling]. / Möglichkeiten und Ziele psychosozialer Betreuung und Trauerbegleitung.

Within their psychosocial problems, badly ill patients and their families often feel left alone by caregivers, as there are physicians and nurses. It is the caregiver's task to allow patients to communicate all their feelings, not seeking to mollify, or banish them by attempting to cheer up or distract the patient. Sharing means to communicate the patient's and his family's anger, sorrows, social pains, spiritual questions, anxiety, as well as their hope and special aims to reach. The first step for the caregiver is, to set up a profound psychosocial diagnosis and to establish some kind of a hierarchy among all the needs. Both of them, caregiver and patient have to find out their primary goals and challenges in the process of dying and come to an agreement. Communicating with a dying patient and being with him in the last period of his life presupposes a deepened communication with oneself and the own hopes and fears.

[Development and state of palliative treatment in Germany]. / Entwicklung und Stand der Palliativmedizin in Deutschland.

Since the early nineties of the 20th century palliative medicine developed in a dynamic way. 65 palliative care units (p.c.u.), 81 hospices and some 600 outpatient services were in existence in spring 2000. Germany provides 7 beds in p.c.u. and 8 beds in hospices per 1 Mill. inhabitants. Stillitt is a long way to diminish the existing deficits in pain therapy, the control of other physical symptoms as well as the psychological, social and spiritual support.