Pain management for sickle cell disease.

BACKGROUND: Sickle cell disease is an inherited genetic disorder characterized by an abnormality of haemoglobin that predisposes to polymerization and consequent deformation ("sickling"). Sickle cell disease can cause episodes of acute severe pain. Chronic pain may also occur. Currently, pain is inadequately managed. OBJECTIVES: The primary aim of the review was to assess the effectiveness of pharmacological analgesic interventions for pain management in sickle cell disease, including the treatment of acute and chronic pain in children and adults. SEARCH STRATEGY: A pre-defined search strategy was used to electronically search the MEDLINE and EMBASE databases. Searches were also conducted on the Cochrane Controlled Trial Register (CCTR) and the Oxford pain randomised controlled trials citation database. The search period covered from January 1965 through to June 2002. Bibliographies of retrieved studies were searched for additional references. No language restriction was used. SELECTION CRITERIA: All randomised controlled trials involving pharmacological treatment of acute or chronic pain in children or adults with sickle cell disease were selected. Patients with haemoglobin SS, haemoglobin S ss thalassaemia and the haemoglobin SC group were included. DATA COLLECTION AND ANALYSIS: Trials were quality rated using the Oxford quality scale. Continuous measures of outcome were combined using weighted mean differences. Overall effect size was calculated with 95% confidence intervals. MAIN RESULTS: Nine randomised controlled trials were identified. All studies involved small numbers of patients with acute sickle cell pain only. Interventions included NSAIDs (versus placebo in four studies; versus strong opioids in one study), strong opioids (oral versus parenteral in one study; morphine versus alternate in one study) and corticosteroids (versus placebo in two studies). Lack of data, small patient numbers, variations in study design and outcome measures limited the review. Due to heterogeneity of methodologies and reporting, it was not possible to perform meaningful meta-analyses. AUTHORS' CONCLUSIONS: There were no studies addressing chronic pain in sickle cell disease. There is limited evidence for analgesic interventions in acute pain crises. Studies have been under-powered. There is not enough data for inter-trial comparisons. In one trial, there was no difference in the efficacy of sustained-release oral versus parenteral morphine, which suggests that oral morphine should be considered for acute pain. Parenteral corticosteroids appear to shorten the period over which analgesics are required and hospital length-of-stay, without producing short-term major adverse effects. More research is needed to improve pain management in sickle cell disease.

Cytokines and advanced cancer.

Cytokines have a major role in promoting the growth and spread of cancers. Elevated levels of several cytokines have been described in cancer patients. Evidence from animal and human studies suggests that cytokines may contribute to a wide range of symptoms in advanced cancer, including: asthenia, pain, drowsiness, cognitive failure, agitated delirium, autonomic dysfunction, anorexia, cachexia, fever and metabolic abnormalities. Considerable effort is being directed at finding anticytokine treatments, raising the possibility of new options for symptoms that are currently difficult to control.

Force output and energy metabolism during neuromuscular electrical stimulation: a 31P-NMR study.

The purpose of this study was to determine the acute physiologic effects of two electrical stimulation protocols commonly used for muscle rehabilitation. Surface electrodes were used to provide 12 stimulations of the calf musculature. In protocol A the duty cycle was fixed at 1:1 (10-second stimulation: 10-second rest); for protocol B it was 1:5 (10-second stimulation: 50-second rest). We continuously recorded isometric plantarflexor force in six healthy male subjects during stimulation using a load cell connected to a foot pedal ergometer. Metabolic changes in the stimulated gastrocnemius muscle were monitored in the supine position using 31P-NMR spectroscopy (Phillips 1.5 tesla NMR machine). Relative changes in phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH (pHi) were obtained during stimulation and recovery, using a 1.5 cm RF surface antenna. Over the 12 stimulations, protocol A produced a significantly (p < 0.001), greater force decline (protocol A: 30.4 +/- 1.3%, protocol B: 13 +/- 0.8%); a significantly (p < 0.005), greater increase in Pi/PCr (protocol A: 210%, protocol B: 50%); and a significantly (p <0.001), lower pHi (protocol A: 6.8 +/- 0.16, protocol B: 7.03 +/- 0.12). We conclude that the shorter duty cycle produces more fatigue throughout the stimulation period, possibly as a result of greater intracellular acidosis and reduced availability of the high energy phosphate PCr. The clinical application of this finding relates to the selection of a stimulation protocol that maximizes strength gains in atrophic vs healthy muscle.

On withholding nutrition and hydration in the terminally ill: has palliative medicine gone too far? A reply.

Patients who are dying of cancer usually give up eating and then stop drinking. This raises ethical dilemmas about providing nutritional support and fluid replacement. The decision-making process should be based on a knowledge of the risks and benefits of giving or withholding treatments. There is no clear evidence that increased nutritional support or fluid therapy alters comfort, mental status or survival of patients who are dying. Rarely, subcutaneous fluid administration in the dying patient may be justified if the family remain distressed despite due consideration of the lack of medical benefit versus the risks. Some cancer patients who are not imminently dying become dehydrated from reversible conditions such as hypercalcaemia. This may mimic the effects of advanced cancer. These conditions should be sought and fluid replacement therapy should be given along with the specific treatments for the condition.

Arrhythmias and Guillain-Barre syndrome.

We report two patients with severe Guillain-Barre syndrome who had serious cardiac arrhythmias. One patient died of asystolic cardiac arrest; the other patient survived with conservative management. The association between the syndrome and arrhythmias, and the difficulties in the management of the latter, are reviewed.

Transcranial conduction of acoustic-reflex-eliciting signals.

Conduction of a broad-band signal from a supra-aural earphone to an acoustic-immittance instrument coupled to the contralateral ear canal was studied using three commercial immittance instruments. Results indicated that portions of the broad-band signal reached the contralateral ear canal at presentation levels of 100-110 dB SPL. At levels as low as 100 dB SPL, the signal was detected by at least one of the acoustic-immittance instruments. At higher sound pressure levels the transmitted signal caused deflections of the acoustic-immittance meter similar to those associated with an acoustic-reflex response. However, these artifacts could be differentiated from acoustic-reflex responses in several respects and could be prevented by high-pass filtering of the broad-band test signal.