Drug therapy in terminally ill patients.

The drug treatment of terminally ill patients is reviewed. The treatment of the major discomforting symptoms of degenerative diseases--pain, anxiety, nausea, vomiting and depression--is reviewed. The use of phenothiazines, anticholinergic drugs and corticosteroids is discussed. To help patients keep track of their drugs, use of a medication schedule card is recommended.     

Analgesia for terminally ill adult patients. Preserve quality of life

Adequate pain management is crucial in maintaining the best possible quality of life for terminally ill patients. This article examines pain management in the palliative care setting, based on a review of the literature using the standard Prescrire methodology. Accurate pain evaluation, preferably by the patient, is essential for guiding treatment decisions. Some causes of pain are amenable to specific treatments. The expected benefits and harms of the various treatment options and procedures must be weighed on a case by case basis. Quality of life should always be the first priority. The World Health Organization has developed a "three-step analgesic ladder", based on the use of increasingly potent analgesics: step I analgesics include paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs); codeine is the standard step II analgesic; and morphine is the standard step III analgesic. Fentanyl is an alternative to morphine. The daily morphine dose must be determined for each patient. Morphine titration starts with oral doses given every 4 hours, but additional doses can be taken every hour if necessary. Total consumption is then used to calculate the dose required the following day. A sustained-release product can be used to reduce the number of doses required when a consistently effective daily dose has been established. When patients are unable to take morphine orally, it can be given by subcutaneous injection, and by subcutaneous or intravenous infusion. Pumps allow the patient to self-administer morphine on demand. Fentanyl transdermal patches are another option for stable pain. Immediate-release oral forms and injections are useful for preventing or treating breakthrough pain. If morphine requirements increase during treatment, the most likely explanations are exacerbations of pain or an excessively long interval between doses. Pharmacological tolerance and psychological dependence are rare during palliative care. In case of renal failure, the morphine dose should be reduced, sustained-release morphine should be replaced by immediate-release morphine, or morphine should be replaced by fentanyl, as fentanyl metabolism is only slightly affected by renal function. The main adverse effects of morphine are constipation, nausea and vomiting. Drowsiness is frequent at initiation of treatment. Respiratory depression is rare when morphine is introduced gradually. Tricyclic antidepressants and carbamazepine have acceptable harm-benefit balances in patients with neuropathic pain. Cannabinoids are another option but have not been adequately assessed. Localised refractory pain may respond to local anaesthesia, chemical neurolysis or surgical ablation. In practice, it is best to allow patients to control their own analgesic consumption, within limits set by their physician to prevent dosing errors.     

Immune-modulating interventions in critically ill septic patients: pharmacological options

Critically ill patients with severe sepsis and septic shock are characterized by a systemic inflammatory response consisting of pro- and anti-inflammatory mediators. Owing to the high mortality of severe sepsis, great efforts have been undertaken within the last 30 years to develop an immune-modulating therapy to improve survival. Relatively few pharmacological immune-modulating interventions have demonstrated a beneficial impact on survival, while other studies have shown a detrimental effect of such interventions. Among the immune-modulating interventions tested, activated protein C and intensive insulin therapy have been shown to improve survival in septic patients. However, in later studies, it has been difficult to reproduce these beneficial effects. There appears to be a discrepancy between the promising effects of immune-modulating interventions in animal studies and the effects seen in the clinical setting. In the future, the onset of the proinflammatory versus the anti-inflammatory response must be better defined and the timing of treatment with immune-modulating agents should be better managed.     

药理营养素在重症患者中的应用

随着重病医学与临床营养的不断发展,越来越多的具有免疫药理作用的营养素应用于临床,如,谷氨酰胺,n-3多不饱和脂肪酸,n-9单不饱和脂肪酸,精氨酸等。本文主要对近年来研究较多的几种药理营养素的应用和进展进行综述。     

Patient-controlled analgesia in the terminally ill cancer patient

Patient-controlled analgesia (PCA) is a relatively new therapeutic modality which has allowed postsurgical patients to safely and effectively self-administer doses of intravenous narcotics via a syringe pump and sequencing device. A pilot study was designed to evaluate PCA's safety and effectiveness in the terminally ill cancer patient. Eight patients whose chronic pain was not adequately controlled by oral narcotics were permitted to use PCA for a minimum of 48 hours. Respiratory rates, sedation rankings, and pain rankings indicated these patients achieved satisfactory analgesia with a minimum of sedation and experienced no respiratory depression. Three patients were switched to oral regimens using PCA dosing as a guide. Pain and sedation rankings were similar to those registered while exclusively on PCA. This self-dosing technique was judged to be safe, effective, and able to accommodate wide fluctuations in analgesic need when treating pain in the terminally ill cancer patient. The results obtained in these patients support further trials using PCA to individualize oral analgesic regimens.     

Variability of morphine disposition during long-term subcutaneous infusion in terminally ill cancer patients

Objective: To study the plasma concentrations of morphine and its glucuronides to assess the intra- and interindividual variability of the disposition of morphine administered by subcutaneous infusion in cancer patients. Methods: Blood samples were taken repeatedly in eight patients with severe cancer pain who were being treated with morphine (60–3000 mg per day) via chronic (8–160 days) subcutaneous infusion. Venous blood samples were collected at least weekly and, when possible, on 3 consecutive days after dose adaptation or any other major change in the patients' treatment. Concentrations of morphine and its glucuronides in plasma were measured after solid-phase extraction using a validated high-performance liquid chromatography assay. The stability of the morphine solutions was determined by repeated measurement of the concentrations of morphine and its degradation products in the solutions. Results: The morphine concentration in the infusion solutions remained unchanged during storage and infusion. The plasma concentrations of morphine and its glucuronides were within the ranges reported in the literature. There was, as expected, a large interindividual variability: from patient to patient, the mean of the normalised plasma concentrations ranged from 0.3 ng · ml⁻¹ · mg⁻¹ to 0.8 ng · ml⁻¹ · mg⁻¹ for morphine, from 1.0 ng · ml⁻¹ · mg⁻¹ to 3.1 ng · ml⁻¹ · mg⁻¹ for morphine-6-glucuronide and from 6.8 ng · ml⁻¹ · mg⁻¹ to 24.3 ng · ml⁻¹ · mg⁻¹ for morphine-3-glucuronide. Intraindividual variability was also important. The residual standard deviation of the mean normalised plasma concentrations calculated for each patient ranged from 26% to 56% for morphine, from 20% to 51% for morphine-6-glucuronide and from 20% to 49% for morphine-3-glucuronide. The normalised plasma concentrations of morphine and its glucuronides did not increase with dose or time, and no explanation for the pronounced pharmacokinetic intraindividual variability was found. Conclusion: During subcutaneous infusion of morphine, there is a large intra- and interindividual variability of the morphine disposition which could be of clinical relevance. Received: 5 August 1997 / Accepted in revised form: 8 October 1997     

BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP

The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.