Paediatric drugs
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The issue of prescription of analgesics during lactation is clinically important but also complex. Most of the information available is based on single dose or short term studies, and for many drugs only a single or a few case reports have been published. As great methodological problems exist in the assessment of possible adverse drug reactions in neonates and infants, there is limited knowledge about the practical impact of the, often very low, concentrations found. ⋯ In general, if treatment of a lactating mother with an analgesic drug is considered necessary, the lowest effective maternal dose should be given. Moreover, infant exposure can be further reduced if breast-feeding is avoided at times of peak drug concentration in milk. As breast milk has considerable nutritional, immunological and other advantages over formula milk, the possible risks to the infant should always, and on an individual basis, be carefully weighed against the benefits of continuing breast-feeding.
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Supraventricular tachycardia is the most frequent form of symptomatic tachydysrhythmia in children. Neonates and infants with paroxysmal supraventricular tachycardias generally present with signs of acute congestive heart failure. In school-aged children and adolescents, palpitations are the leading symptom. ⋯ Although amiodarone has the highest antiarrhythmic potential, it should be used with caution because of its high rate of adverse effects. In school-aged children and adolescents, radiofrequency catheter ablation of the anatomical substrate is an attractive alternative to drug therapy, with a rate of permanent cessation of the tachycardia of up to 90%. Despite the clear advantages of this procedure, it should be performed only with unquestionable indication; the long term morphological and electrophysiological sequelae on the growing atrial and ventricular myocardium are still unknown.
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DTaP3-CB (Triacelluvax) is an acellular pertussis (aP) vaccine containing 3 antigens from purified Bordetella pertussis bacteria combined with diphtheria and tetanus toxoids (DT). In addition to purified filamentous haemagglutinin and pertactin, DTaP3-CB contains pertussis toxin which has been genetically rather than chemically detoxified. As shown in randomised, double-blind clinical trials in infants, DTaP3-CB elicits an immune response similar to or greater than that of whole cell (DTwP) vaccines. Results of a large multicentre study comparing DTaP3-CB with 12 acellular and 1 DTwP vaccine indicate that DTaP3-CB, like all acellular vaccines, induces variable immune responses to different pertussis antigens; however, antibody titres to pertussis toxin are normally higher after immunisation with the genetically detoxified vaccine than with other 3- or 4-component vaccines. When given as a fourth or fifth booster dose, DTaP3-CB produced a significant immune response in infants primed with 3 doses of either a DTaP or DTwP vaccine. Virtually all infants immunised with DTaP3-CB had a serological response to diphtheria and tetanus toxoids. Data from 2 very large efficacy studies indicate that DTaP3-CB has high and long lasting protective efficacy against culture-confirmed pertussis which is greater than that of a 2-component vaccine (DTaP2-SB) and the whole cell DTwP-CON vaccine after a 3-, 5- and 12-month immunisation schedule and after a 2-, 4- and 6-month schedule with the DTwP-CON vaccine. However, the DTwP-CON whole cell vaccine has been noted for its low immunogenicity in 1 study and low efficacy and immunogenicity in another study. On the other hand, DTaP3-CB vaccine has similar efficacy to DTaP3-SB (after immunisation at 2, 4 and 6 months), DTaP5-CON and DTwP-EVANS against culture-confirmed pertussis with > or =21 days cough in infants immunised according to a 3-, 5- and 12-month schedule. Infants immunised with DTaP3-CB experienced significantly fewer adverse events such as pain, redness, swelling and irritability than infants given DTwP. DTaP3-CB has a similar tolerability profile to other acellular vaccines and is associated with similar rates of local tenderness, irritability, fever (> or =40 degrees C) and persistent crying. Comparative trials have shown that infants immunised with DTaP3-CB had a lower incidence of pain at the site of injection and fever (> or =38 degrees C) compared with other acellular vaccines, although this may have little clinical significance. Concomitant administration of DTaP3-CB with hepatitis B, oral polio or Haemophilus influenzae type B vaccines did not affect the immunogenicity of these other paediatric vaccines. ⋯ Data from clinical trials with DTaP3-CB vaccine indicate that this vaccine induces high and long lasting efficacy. It is at least as efficacious as most whole cell vaccines and generally similar in efficacy to the most efficacious acellular pertussis vaccines containing 3 or more pertussis antigens. DTaP3-CB is better tolerated than whole cell vaccines and has a similar tolerability profile to other acellular vaccines; the possible lower risk of severe adverse events remains to be confirmed. The low reactogenicity of DTaP3-CB is likely to make it well tolerated and therefore well accepted for the immunisation of infants, thereby enabling wider implementation of vaccination programmes.
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Calfactant (Infasurt) is a natural bovine surfactant which has been evaluated for intratracheal use in the prevention and rescue treatment of respiratory distress syndrome (RDS) in preterm infants. In 2 randomised, double-blind, multicentre clinical trials of prophylactic use, calfactant 100 or 105 mg phospholipid per kg bodyweight (mg/kg) reduced RDS incidence, RDS severity and mortality rates to a greater extent than colfosceril palmitate (Exosurf Neonatal) 67.5 mg/kg and was generally similar to beractant (Survanta) 100 mg/kg. Although the rate of mortality before discharge from hospital was significantly higher in infants with birthweights <600 g who received calfactant than in those who received beractant, this may not be a typical result. As rescue treatment, calfactant 100 or 105 mg/kg reduced RDS severity, but not mortality rates, significantly more than colfosceril palmitate 67.5 mg/kg or beractant 100 mg/kg in 2 randomised, double-blind, multicentre clinical trials. In addition, the duration of effect of calfactant as prophylaxis or rescue treatment appeared to be longer than that of beractant. In other randomised trials, prophylaxis was more effective than rescue treatment with calfactant, particularly in infants of < or =29 weeks gestational age. The incidence of pulmonary air leak events was lower with calfactant than with colfosceril palmitate (12 vs 22%) but was identical with calfactant and beractant (15% with either agent). The incidence of other complications associated with RDS was usually similar with all 3 agents in clinical trials in preterm infants. The incidence of intraventricular haemorrhage was significantly higher in 1 clinical trial, and that of septicaemia was significantly lower in another, with calfactant versus colfosceril palmitate, but the combined incidences of these complications was similar with the 2 agents when results from different trials were pooled. The incidence of acute adverse events (i.e. those which occurred during administration of the drug) with calfactant was similar to that with beractant and higher than that with colfosceril palmitate; the difference may been related to reduced RDS severity in calfactant versus colfosceril palmitate recipients. Acute adverse events were usually transient and not severe. ⋯ Calfactant is a well tolerated natural bovine surfactant which is effective in the prevention and treatment of RDS in preterm infants. Further investigation is needed to more clearly determine the efficacy and tolerability of calfactant relative to that of other surfactant preparations. When more data are available, it is likely that calfactant will be useful as an alternative to beractant (at least in infants of birthweights >600 g), and calfactant may be preferred over colfosceril palmitate in both the prophylaxis and treatment of RDS.
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Sevoflurane is an ether inhalation anaesthetic agent with low pungency, a non-irritant odour and a low blood: gas partition coefficient. It can be rapidly and conveniently administered without discomfort, and its low solubility facilitates precise control over the depth of anaesthesia and a rapid and smooth induction of, and emergence from, general anaesthesia. As an induction and maintenance agent for ambulatory and nonambulatory surgery in children, sevoflurane provides more rapid induction of, and emergence from, anaesthesia than halothane, and has similar or better patient acceptability. Time to discharge from the recovery area is usually at least as fast with sevoflurane as with halothane. While rapid emergence from sevoflurane lessens the time spent under anaesthesia, postoperative pain may be more intense and occur earlier than during more gradual emergence. Sevoflurane has been used successfully as an induction agent for tracheal intubation and laryngeal mask airway (LMA) insertion: time to LMA insertion is faster with sevoflurane than halothane, but the 2 drugs provide similar conditions for tracheal intubation. The pattern and incidence of induction and emergence events such as cough, laryngospasm and agitation/excitement is similar with sevoflurane and halothane; however, sevoflurane may cause less postoperative nausea and vomiting. At present, differences have not been consistently shown between the 2 drugs in their propensity to cause postoperative excitement or agitation. Compared with halothane, sevoflurane has low potential for arrhythmogenicity. Clinical experience does not substantiate concerns over the potential nephrotoxicity of the sevoflurane byproducts pentafluoroisopropenyl fluoromethyl ether ('Compound A') and plasma F- ions; no renal impairment has been documented in children receiving sevoflurane in clinical trials. The potential for sevoflurane hepatotoxicity also appears negligible. There are few trials comparing sevoflurane with agents other than halothane in paediatric anaesthesia. As well, pharmacoeconomic analyses are scarce and incompletely published; further studies are needed to determine whether shortened times to emergence will translate into cost savings. ⋯ Sevoflurane is a preferred anaesthetic agent for induction and maintenance of paediatric anaesthesia because of its rapid induction and recovery characteristics, lack of pungency and agreeable odour, and acceptable cardiovascular profile. Although the issue of postoperative excitement requires clarification, sevoflurane anaesthesia can be considered a rational choice for ambulatory and nonambulatory surgery in children.