Abstract
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. 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. 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. 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. 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. 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. 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.
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