Jacek Łuczak

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.

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.

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.

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.

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.