Paediatric drugs
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Review Comparative Study
Ondansetron: a review of its use as an antiemetic in children.
Ondansetron, a selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT3 receptor antagonist, is an antiemetic agent available for use in adults and children. In children receiving ondansetron (multiple 5 mg/m2 or 0.15 mg/kg intravenous and/or oral doses) in addition to chemotherapy in 2 large (n > 100) non-comparative analyses, < or =2 emetic episodes were observed in 33 and 40% of cisplatin recipients, 48 and 68% of ifosfamide recipients, and 70 and 72% of patients receiving other chemotherapeutic regimens. In comparative trials, ondansetron was significantly more effective at reducing nausea and vomiting than metoclopramide or chlorpromazine (both combined with dexamethasone), although the incidence of delayed symptoms were similar between children receiving ondansetron and metoclopramide. In addition, dexamethasone significantly improved the antiemetic efficacy of ondansetron in 1 randomised trial. When used in children undergoing conditioning therapy (including total body irradiation) prior to bone marrow transplantation, ondansetron was significantly better at controlling nausea and vomiting than combined perphenazine and diphenhydramine therapy. In dose-ranging and large placebo-controlled trials, intravenous (0.075 to 0.15 mg/kg) or oral (0.1 mg/kg) ondansetron was significantly more effective than placebo in preventing emesis in children undergoing surgery associated with a high risk of postoperative nausea and vomiting (PONV) including tonsillectomy or strabismus repair. In comparative studies, intravenous administration of ondansetron 0.1 to 0.15 mg/kg was significantly superior to droperidol 0.02 to 0.075 mg/kg or metoclopramide 0.2 to 0.25 mg/kg in preventing emesis in children undergoing various surgical procedures. In comparison with other antiemetics, including prochlorperazine and dimenhydrinate, ondansetron generally showed greater prophylactic antiemetic efficacy. Ondansetron combined with dexamethasone was significantly more effective than ondansetron or dexamethasone alone, as was the combination of ondansetron with a propofol-based anaesthetic compared with either agent alone. Ondansetron is generally well tolerated in children, rarely necessitating treatment withdrawal. The most frequently reported adverse events were mild to moderate headache, constipation and diarrhoea in patients receiving chemotherapy. Wound problems, anxiety, headache, drowsiness and pyrexia were reported most frequently in patients postsurgery. ⋯ Ondansetron has shown good efficacy in the prevention of acute nausea and vomiting in children receiving moderately or highly emetogenic chemotherapy and/or irradiation, particularly when combined with dexamethasone. In the chemotherapy setting, ondansetron is significantly better than metoclopramide and chlorpromazine and has a more favourable tolerability profile. In children undergoing surgery, ondansetron demonstrated superior prophylactic antiemetic efficacy compared with placebo, droperidol and metoclopramide, and was relatively free of adverse events. Ondansetron is thus an effective first-line antiemetic in children undergoing chemotherapy, radiotherapy and surgery.
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Topiramate is an antiepileptic drug (AED) which appears to have a broad range of antiseizure activity in humans. A previous overview focused primarily on results of trials of topiramate in adults with epilepsy, and this review highlights the use of topiramate in children. Clinical trials have shown that topiramate is effective when used adjunctively in children with refractory partial-onset seizures and generalised tonic-clonic seizures. The drug significantly reduced seizure frequency compared with placebo in children with partial-onset epilepsy after 16 weeks of double-blind adjunctive treatment (33.1 vs 10.5%); the frequency of secondarily generalised seizures was also markedly reduced. During a nonblind extension of this trial, the mean dosage was titrated from 4.8 to 9 mg/kg/day and further reductions in the frequency of seizures were observed (71% compared with prestudy levels). In 2 mixed adult/paediatric populations with primary generalised tonic-clonic seizures, topiramate (target dosage 5.2 to 9.3 mg/kg/day) reduced the seizure rate compared with those receiving placebo. This difference was significant in one trial (56.7 vs 9%) but not in another (57.1 vs 33.2%). A subanalysis of the paediatric patients found that the favourable effect of topiramate on seizure rates was not age-related. Topiramate (median average dosage 5.1 mg/kg/day) was also found to be useful as adjunctive therapy in the management of Lennox-Gastaut syndrome and significantly reduced the mean frequency of drop attacks by 14.8% compared with an increase of 5.1% with placebo. Further gains in seizure control were made in a nonblind extension of this trial where the mean topiramate dosage was 10 mg/kg/day. Nine of 11 patients in 1 pilot trial of children with otherwise intractable West syndrome, and 5 of 10 in another, achieved a > or =50% reduction in seizure rate with topiramate (target dosage up to 24 mg/kg/day). In an 18-month extension of the former trial (mean dosage 29 mg/kg/day) a > or =50% reduction in seizures was maintained in 7 of 11 children. Adverse events associated with adjunctive topiramate therapy in children were predominantly neuropsychiatric and generally mild to moderate in severity. Behavioural and cognitive problems do occur and are a limiting factor in some children. Also, weight loss can be problematical in some individuals. Withdrawal rates were low in the controlled trials (4.8%), but appear to be more frequent in noncomparative and post-marketing studies. ⋯ Well controlled studies have demonstrated that topiramate is an effective agent for the adjunctive therapy of partial and generalised tonic-clonic seizures in children. Treatment-limiting adverse events do occur, but these may be managed by slow titration. Although comparative studies with the other newer AEDs used in adjuntive therapy are required, topiramate is an important extension to the range of drugs that may be used to treat refractory epilepsy in children.
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Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. ⋯ Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients.
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Intrathecal chemotherapy with antineoplastic agents is mainly utilised in children with leukaemia and lymphoma, and in selected brain tumours. In these diseases, intrathecal use is restricted to methotrexate (MTX), cytosine arabinoside (Ara-C) and corticosteroids. A number of other agents are, at the present time, under evaluation. ⋯ However, the development of this new approach is currently under evaluation in larger clinical studies. Neurological adverse effects may be expected with intrathecal chemotherapy and are increased by high dose systemic therapy, concomitant cranial radiotherapy or meningeal infiltration by neoplastic cells. Inadvertant intrathecal administration of antineoplastic agents that are indicated for systemic administration only, is dangerous and may result in a fatal outcome.
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Painful procedures are frequently required during treatment of children in the emergency department and are very stressful for the children, their parents and healthcare providers. Pharmacological methods to safely provide almost painless local anaesthesia, analgesia and anxiolysis have been increasingly studied in children. With knowledge of these methods, and patience, the emergency care provider can greatly reduce the distress often associated with emergency care of children. ⋯ Topical creams such as lidocaine/ prilocaine (EMLA) or tetracaine, iontophoresed lidocaine, or buffered lidocaine subcutaneously injected with fine needles can make intravenous catheter placement virtually 'painless'. When anxiety is significant, and mild to moderate analgesia/ anxiolysis/amnesia is needed, nitrous oxide can be administered if the proper delivery devices are available. Alternatively, when intensely painful fracture reduction, burn debridement, or abscess drainage is necessary, well tolerated and effective deep sedation can be achieved with careful use of midazolam and either ketamine or fentanyl.