Midazolam: Safety of use in palliative care: A systematic critical review.

PURPOSE: The undesired effects of midazolam can be life-threatening. This paper delineates the findings related to the pharmacokinetics, adverse effects and drug-drug interactions as well as associated therapeutic implications for safe midazolam use. METHODS: A systematic review of literature was conducted. RESULTS: The pharmacokinetics of midazolam depends on hepatic and renal functions, fat tissue mass, route and duration of administration, as well as potential drug-drug interactions. Palliative care patients constitute a high-risk group prone to side effects of drugs, due to polytherapy and multi-organ failure. CONCLUSION: Midazolam is one of three most frequently administered drugs in palliative care. The indications for its use include anxiety, dyspnea, seizures, vomiting refractory to treatment, agitation, myoclonus, status epilepticus, restlessness, delirium, pruritus, hiccups, insomnia, analgosedation, palliative sedation and preventing or counteracting undesired effects of ketamine.

Managing metastatic bone pain: New perspectives, different solutions.

Bone metastases are the most frequent cause of cancer-induced bone pain (CIBP). Although palliative radiotherapy and pharmacotherapy conducted according to World Health Organization (WHO) analgesic ladder are the treatment of choice for CIBP reduction, these methods are not always successful, especially with regard to alleviation of incidental pain. Antiresorptive drugs (bisphosphonates) are able to inhibit bone destruction (loss), proliferation of cancer cells and angiogenesis, but their prolonged use may lead to a spectrum of adverse effects. In this paper, types of bone metastases, their complications, as well as diagnostic and therapeutic implications are presented. Moreover, the paper discusses presently used CIBP treatment methods and research directions for future methods, with special focus on bone metastases.

How much does care in palliative care wards cost in Poland?

INTRODUCTION: The main task of palliative care units is to provide a dignified life for people with advanced progressive chronic disease through appropriate symptom management, communication between medical specialists and the patient and his family, as well as the coordination of care. Many palliative care units struggle with low incomes from the National Health Fund (NHF), which causes serious economic problems. The aim of the study was to estimate of direct and administrative costs of care and the actual cost per patient per day in selected palliative care units and comparison of the results to the valuation of the NHF. MATERIAL AND METHODS: The study of the costs of hospitalization of 175 patients was conducted prospectively in five palliative care units (PCUs). The costs directly associated with care were recorded on the specially prepared forms in each unit and also personnel and administrative costs provided by the accounting departments. RESULTS: The total costs of analyzed units amounted to 209 002 EUR (898 712 PLN), while the payment for palliative care services from the NHF amounted to 126 010 EUR (541 844 PLN), which accounted for only 60% of the costs incurred by the units. The average cost per person per day of hospitalization, calculated according to the actual duration of hospitalization in the unit, was 83 EUR (357 PLN), and the average payment from the NHF was 52.8 EUR (227 PLN). Underpayment per person per day was approximately 29.2 EUR (125 PLN). CONCLUSIONS: The study showed a significant difference between the actual cost of palliative care units and the level of refund from the NHF. Based on the analysis of costs, the application has been submitted to the NHF to change the reimbursement amount of palliative care services in 2013.

Treatment of acute, severe epigastric/chest pain in a patient with stomach cancer following gastrectomy: A case report.

The treatment of acute chest pain can be a challenge in palliative care. Firstly, because acute chest pain is a symptom of a paucity of diseases, which makes diagnosis difficult and time consuming, while there is also a time constraint, due to the extreme suffering of the patient. Secondly, the condition of a patient with advanced cancer disease and co-morbidities does not always allow for required diagnostic procedures. The present report describes a case of acute, severe epigastric/chest pain in a patient with dynamic disease progression, who was receiving palliative care. This study also demonstrates that the pathophysiology of pain in a terminal patient may determine the treatment strategy. The patient in the present case was a 41-year-old male, who had previously undergone gastrectomy for stomach cancer, followed by postoperative chemotherapy. The patient was treated with palliative chemotherapy for metastases to the lungs, liver and lymph nodes, which led to the development of iatrogenic peripheral neuropathy. The patient was subsequently admitted to the Palliative Medicine In-patient Unit of the University Hospital of Lord's Transfiguration (Poznan, Poland) with the complaint of acute epigastric and chest pain. An electrocardiogram, echocardiogram, chest and abdomen computerized tomography scan, esophagoduodenoscopy and laboratory analyses were performed to determine the source of the pain. The patient was treated with morphine sulfate, metoclopramide, midazolam, diazepam, acetaminophen, ketamine, hyoscine butylbromide, propofol, dexamethasone and amoxycillin, and received parenteral nutrition. As the source of pain remained unclear, a second esophagoduodenoscopy was performed to determine a diagnosis, resulting in pain relief. Thus, in the present case, esophagoduodenoscopy was diagnostic and therapeutic. Furthermore, although the treatment of acute chest pain may be a challenge in palliative care, the present study indicates that pain treatment should be adjusted to anatomical, pathophysiological and pharmacological factors, and may pose risks due to the unavoidable parenteral co-administration of multiple agents with strong therapeutic effects.

Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care.

BACKGROUND: Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III "pain ladder" drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient's refusal of an invasive procedure necessitates that clinicians consider alternative options. OBJECTIVE: Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. CASES: We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25-0.5%, 1-2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05-0.1%, 100 mL every 4.5-11 hours). METHODS: Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. RESULTS: Effective pain control was achieved with intrathecal bupivacaine (0.077-0.154 mg·kg(-1)) and bupivacaine in enema (1.820 mg·kg(-1)). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL(-1) and 235.7 ng·mL(-1), respectively. Bupivacaine elimination was slower after rectal than after intrathecal administration (t½= 5.50 versus 2.02 hours, respectively). LIMITATIONS: This study reports two cases only, and there could be inter-patient variation. CONCLUSION: Bupivacaine in boluses administered intrathecally (0.25%, 2 mL) provided effective, safe analgesia in advanced cancer patients. Bupivacaine enema (100 mg·100 mL(-1)) was shown to be a valuable option for control of end-of-life tenesmoid cancer pain.

Lumbar paravertebral blockade as intractable pain management method in palliative care.

Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine's side effects were absent. Coadministered drugs could mask LA's toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine's elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours(-1)) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours(-1)) had an acceptable risk-benefits ratio, but was ineffective.

[Endovascular treatment, with "kissing stents" technique, of superior vena cava syndrome in patient with lung cancer]. / Zwezenie zyly glównej górnej w przebiegu raka pluca leczone wewnatrznaczyniowo technika "kissings stents".

Presented in the article an intravascular method of treatment with stents implantation was effective for symptoms relief and physical signs correction, in 63-year-old patient with advanced lung cancer and SVCS purely responsive to palliative radiotherapy, chemiotherapy (toxic haematological effects) and steroids. The treatment improved the patient's quality of life.

The role of tramadol in cancer pain treatment--a review.

In most cancer patients pain can be successfully treated with pharmacological measures using opioid analgesics alone or in combination with adjuvant analgesics (coanalgesics). Weak opioids are usually recommended in the treatment of moderate cancer pain. There is still a debate as to whether the second step of the WHO analgesic ladder comprising opioid analgesics such as tramadol, codeine, dihydrocodeine, and dextropropoxyphene is still needed for the treatment of cancer pain. On the basis of our experience and review of the literature we think that there is definitely a place for weak opioids in the treatment of moderate cancer pain. One of the most interesting and useful weak opioids is tramadol (Adolonta, Contramal, Nobligan, Top-Algic, Tramal, Tramal Long, Tramal Retard, Tramundin, Trodon, Ultram, Zydol). Its unique mechanism of action, analgesic efficacy and profile of adverse reactions have been the reason of performing many experimental and clinical studies with tramadol. In this article we summarize data on pharmacology, mechanisms of action, pharmacokinetics, side effects and clinical experience assessing analgesic efficacy, adverse reactions and safety of tramadol in cancer pain.

Quality assessment of morphine hydrochloride solutions.

The therapeutic substances in solution prepared in pharmaceutical laboratories (prescribed drugs) must preserve their activity. Therefore, they must be stable throughout the period of storage in home conditions. The maintenance of stability is particularly difficult for morphine hydrochloride solutions administered orally to cancer patients at the last stage of the disease being at home. This study, aiming at the assessment of stability of morphine hydrochloride solutions, was performed on samples of 0.5% water solutions of the drug alone, 0.25% and 0.5% solutions of the drug in water with chloroform as well as injection solutions (Morphinum hydrochloricum, 20 mg, Polfa Warsaw). All the samples were kept at 20 degrees C for six months. Throughout this time observations were made to detect changes in their appearence and pH values. Their qualitative composition was determined by TLC and the content of morphine was checked by UV spectrophotometry in an environment of 0.1 mol/l of hydrochloric acid at 285 nm. Results of the kinetic study permitted drawing conclusions as to the mechanism of the decomposition of morphine hydrochloride in the solutions studied - according to a simple first order reaction and determination of the rate constants (k, s(-1)) of the process. Results of the chromatographic and spectrophotometric study did not show differences in the stability of water and chloroform/water solutions of morphine hydrochloride studied after 4 weeks and 6 months. After that time the decrease of morphine content was 10 and 25%, respectively.