Treating fever in children: paracetamol or ibuprofen?

Community health practitioners frequently prescribe or advise parents on antipyretic medications for children with fevers. This mini-review sets out to examine the evidence for the relative effectiveness of two of the most widely available and commonly used over-the-counter medicines - paracetamol and ibuprofen. A systematic literature search was undertaken to identify all studies comparing the effects of the two drugs. The Medline, Embase, Cinahl and RCN databases were searched. Eight randomized controlled trials that reported temperature differences at time-points between 1 and 6 hours after administration were identified. Statistical meta-analysis showed no clear benefit for one drug over another 1 hour after administration. However, by 6 hours after administration ibuprofen was clearly superior resulting in a mean temperature 0.58 degrees C lower than paracetamol. Both drugs appeared well tolerated and no evidence of difference in short-term adverse effects was observed. Both drugs are effective antipyretics but the longer action of ibuprofen may make it preferable in some circumstances.     

Therapeutic misadventure with paracetamol: fact or fiction?

As a consequence of its consistent safety profile and the low incidence of side effects, paracetamol is one of the most widely used analgesics, both in adults and children. However, paracetamol has the potential for hepatotoxicity, usually as a result of deliberate self-poisoning or, to a much lesser extent, accidental overdose. A variety of factors is thought to influence hepatotoxicity, including dose, concomitant use of microsome-inducing agents and other drugs, underlying disease, malnutrition, fasting, acute and chronic alcohol intake, ethnicity, and age. Unfortunately, none of these factors has been properly studied in humans. From a physiological standpoint, acute paracetamol hepatotoxicity at therapeutic doses is extremely unlikely despite reports of so-called therapeutic misadventure. It is clear that, in many of these cases, grossly excessive doses of paracetamol have been taken. Analyzing the various reports is difficult as the data are often incomplete. In summary, although hepatic toxicity is recognized in patients taking a major paracetamol overdose, the incidence of adverse events with its proper use is very low, particularly when considering with the enormous volume of drug use. Therapeutic misadventure is extremely uncommon and the facts are often misrepresented.     

NSAIDs: gastroprotection or selective COX-2 inhibitor?

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and cost-effective use of these drugs in the palliative care population.     

New marker for paracetamol poisoning-revolution or evolution?

There is a pressing need for new biomarkers that can improve the care of patients with paracetamol poisoning, a common clinical problem. In this issue of Clinical Toxicology a new marker is proposed that has a number of attractive properties. This commentary discusses the use of biomarkers in the context of the management of paracetamol-induced liver injury. New biomarkers should allow better triage and management of & "at risk" patients.     

The use of opioids in the treatment of osteoarthritis: When,why, and how?

As life expectancy increases every decade, the incidence and prevalence of osteoarthritis (OA) also will increase. Despite progress in our knowledge of the pathophysiology of OA, the management of OA-mediated pain continues to challenge physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2 inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in general has limited the use of these medications in the management of chronic non-cancer pain. Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care. When used as part of a multimodal approach to pain control, opioids are a safe and effective treatment for joint pain, including that of OA. Patients for whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol, and NSAID therapy is ineffective, may be started on low-dose opioids and titrated as needed and tolerated. Patient education and informed consent, exercise, complementary medicine, and the use of a controlled substance agreement increases the likelihood of patient compliance with treatment guidelines, improving functional capacity and quality of life.     

Analgesics and osteoarthritis: are treatment guidelines reflected in clinical practice?

Osteoarthritis (OA) treatment is complex and multifactorial, with pharmacological regimens requiring sufficient flexibility to be adapted to individual disease progression, flare ups, and response to treatment. Coexisting conditions are common and can lead to problems regarding polypharmacy. Several guidelines have been published for the management of OA pain. While differences exist, most recommend paracetamol as the initial oral drug for OA, based on its efficacy, tolerability, and cost; in patients who respond inadequately to paracetamol, supplementary or replacement analgesics should be recommended. This article considers the reality of analgesic use for OA in clinical practice and the extent to which guidelines are followed both in primary and secondary care. An international survey of rheumatologists (n = 610) found that paracetamol was recommended as first-choice analgesic for OA by 82% of those surveyed. Similarly, in a survey of French GPs, 90% of those surveyed recommended paracetamol first line; NSAIDs were recommended more frequently for stronger pain relief but were also recommended alongside paracetamol as a first-line treatment of mild to moderate pain by 43% of GPs. Finally, a UK patient survey, conducted at a London hospital (n = 200), found that 64% of patients were taking more than 1 drug for treatment of painful OA of the knee or hip; 76% were taking paracetamol and 40% were taking an NSAID. A further 39% had used an NSAID in the past but switched treatment, primarily due to side effects. These findings reinforce the case for the simple analgesic paracetamol to be seen as the cornerstone of pharmacological OA treatment, both as a first-line analgesic and as a foundation to which additional treatment modalities, including NSAIDs, can be added if and when necessary.     

Erythropoietin for stroke treatment: dead or alive?

Endothelial progenitor cell (EPC) mobilization from the bone marrow was considered to improve outcome after ischemic stroke. Erythropoietin (EPO) might be a potential candidate stroke drug that increases the number of circulating EPCs. In the previous issue of Critical Care, Yip and colleagues investigated the effect of EPO in stroke patients on both clinical outcome and EPC stimulation. Although beneficial effects of EPO were observed, several issues regarding EPO's suitability as a stroke drug remain.