The systematic review was commissioned by the Australian National Health and Medical Research Council (NHMRC) to evaluate the scientific literature relating to the health effects of fluoride and fluoridation. The systematic review's research questions relate to the caries-reducing benefits and associated potential health risks of providing fluoride systemically (via addition to water, milk and salt) and the use of topical fluoride agents, such as toothpaste, gel, varnish and mouthrinse. Although the review summarises the recent evidence, it does not constitute health policy or clinical practice recommendations. A literature search was undertaken using the Medline and Embase databases (via www.embase.com
 ). In addition, the Cochrane Systematic Review and Clinical Trial databases were searched to help identify additional systematic reviews and original studies. Because of the availability of recent systematic reviews, searches were limited to publications from 1996 onwards . The search was conducted in December 2006 and limited to English-language publications. Based on types of intervention (individual or population) and the outcomes assessed (efficacy or safety), the hierarchy of study types considered most relevant for answering each of the clinical questions defined in this review was chosen (Table 1). The levels of evidence used by NHMRC for intervention and aetiological studies are summarised in Table 2.
 Screening of eligible studies was conducted by three reviewers. Data were extracted for all of the included systematic reviews and individual studies using standardised data-extraction forms. This included information about the study design, NHMRC level of evidence, population, intervention, comparator, outcome definitions and results. Information relating to potential biases and study quality were also extracted. Where appropriate, study results were pooled using standard meta-analysis techniques. In total, 5418 nonduplicate citations were identified. After applying the inclusion and exclusion criteria, 408 citations were considered potentially eligible for inclusion in the review. After the review of the full papers of potentially eligible articles, 77 citations were included in the review. The summary of findings was presented in the context of the research questions (Table 3).
 Fluoridation of drinking water remains the most effective and socially equitable means of achieving community-wide exposure to the caries prevention effects of fluoride. It is recommended (see also www.nhmrc.gov.au/news/media/rel07/_files/fluoride_flyer.pdf
 ) that water be fluoridated in the target range of 0.6–1.1 mg/l, depending on the climate, to balance reduction of dental caries and occurrence of dental fluorosis.n particular with reference to care in hospital for those following stroke.

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A systematic review of the efficacy and safety of fluoridation

Background
Sevoflurane is an inhaled volatile anaesthetic that is widely used in paediatric anaesthetic practice. Since its introduction, postoperative behavioural disturbance known as emergence agitation (EA) or emergence delirium (ED) has been recognized as a problem that may occur during recovery from sevoflurane anaesthesia. For the purpose of this systematic review, EA has been used to describe this clinical entity. A child with EA may be restless, may cause self-injury or may disrupt the dressing, surgical site or indwelling devices, leading to the potential for parents to be dissatisfied with their child's anaesthetic. To prevent such outcomes, the child may require pharmacological or physical restraint. Sevoflurane may be a major contributing factor in the development of EA. Therefore, an evidence-based understanding of the risk/benefit profile regarding sevoflurane compared with other general anaesthetic agents and adjuncts would facilitate its rational and optimal use.

Objectives
To compare sevoflurane with other general anaesthetic (GA) agents, with or without pharmacological or non-pharmacological adjuncts, with regard to risk of EA in children during emergence from anaesthesia. The primary outcome was risk of EA; secondary outcome was agitation score.

Search methods
We searched the following databases from the date of inception to 19 January 2013: CENTRAL, Ovid MEDLINE, Ovid EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost), Evidence-Based Medicine Reviews (EBMR) and the Web of Science, as well as the reference lists of other relevant articles and online trial registers.

Selection criteria
We included all randomized (or quasi-randomized) controlled trials investigating children < 18 years of age presenting for general anaesthesia with or without surgical intervention. We included any study in which a sevoflurane anaesthetic was compared with any other GA, and any study in which researchers investigated adjuncts (pharmacological or non-pharmacological) to sevoflurane anaesthesia compared with no adjunct or placebo.

Data collection and analysis
Two review authors independently searched the databases, decided on inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved differences between their results by discussion. Data were entered into RevMan 5.2 for analyses and presentation. Comparisons of the risk of EA were presented as risk ratios (RRs) with 95% confidence intervals (CIs). Sevoflurane is treated as the control anaesthesia in this review. Sensitivity analyses were performed as appropriate, to exclude studies with a high risk of bias and to investigate heterogeneity.

Main results
We included 158 studies involving 14,045 children. Interventions to prevent EA fell into two broad groups. First, alternative GA compared with sevoflurane anaesthesia (69 studies), and second, use of an adjunct with sevoflurane anaesthesia versus sevoflurane without an adjunct (100 studies). The overall risk of bias in included studies was low. The overall Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) assessment of the quality of the evidence was moderate to high. A wide range of EA scales were used, as were different levels of cutoff, to determine the presence or absence of EA. Some studies involved children receiving potentially inadequate or no analgesia intraoperatively during painful procedures.

Halothane (RR 0.51, 95% CI 0.41 to 0.63, 3534 participants, high quality of evidence) and propofol anaesthesia were associated with a lower risk of EA than sevoflurane anaesthesia. Propofol was effective when used throughout anaesthesia (RR 0.35, 95% CI 0.25 to 0.51, 1098 participants, high quality of evidence) and when used only during the maintenance phase of anaesthesia after sevoflurane induction (RR 0.59, 95% CI 0.46 to 0.76, 738 participants, high quality of evidence). No clear evidence was found of an effect on risk of EA of desflurane (RR 1.46, 95% CI 0.92 to 2.31, 408 participants, moderate quality of evidence) or isoflurane (RR 0.76, 95% CI 0.46 to 1.23, 379 participants, moderate quality of evidence) versus sevoflurane.

Compared with no adjunct, effective adjuncts for reducing the risk of EA during sevoflurane anaesthesia included dexmedetomidine (RR 0.37, 95% CI 0.29 to 0.47, 851 participants, high quality of evidence), clonidine (RR 0.45, 95% CI 0.31 to 0.66, 739 participants, high quality of evidence), opioids, in particular fentanyl (RR 0.37, 95% CI 0.27 to 0.50, 1247 participants, high quality of evidence) and a bolus of propofol (RR 0.58, 95% CI 0.38 to 0.89, 394 participants, moderate quality of evidence), ketamine (RR 0.30, 95% CI 0.13 to 0.69, 231 participants, moderate quality of evidence) or midazolam (RR 0.57, 95% CI 0.41 to 0.81, 116 participants, moderate quality of evidence) at the end of anaesthesia. Midazolam oral premedication (RR 0.81, 95% CI 0.59 to 1.12, 370 participants, moderate quality of evidence) and parental presence at emergence (RR 0.91, 95% CI 0.51 to 1.60, 180 participants, moderate quality of evidence) did not reduce the risk of EA.

One or more factors designated as high risk of bias were noted in less than 10% of the included studies. Sensitivity analyses of these studies showed no clinically relevant changes in the risk of EA. Heterogeneity was significant with respect to these comparisons: halothane; clonidine; fentanyl; midazolam premedication; propofol 1 mg/kg bolus at end; and ketamine 0.25 mg/kg bolus at end of anaesthesia. With investigation of heterogeneity, the only clinically relevant changes to findings were seen in the context of potential pain, namely, the setting of adenoidectomy/adenotonsillectomy (propofol bolus; midazolam premedication) and the absence of a regional block (clonidine).

Authors' conclusions
Propofol, halothane, alpha-2 agonists (dexmedetomidine, clonidine), opioids (e.g. fentanyl) and ketamine reduce the risk of EA compared with sevoflurane anaesthesia, whereas no clear evidence shows an effect for desflurane, isoflurane, midazolam premedication and parental presence at emergence. Therefore anaesthetists can consider several effective strategies to reduce the risk of EA in their clinical practice. Future studies should ensure adequate analgesia in the control group, for which pain may be a contributing or confounding factor in the diagnosis of EA. Regardless of the EA scale used, it would be helpful for study authors to report the risk of EA, so that this might be included in future meta-analyses. Researchers should also consider combining effective interventions as a multi-modal approach to further reduce the risk of EA.

Effects of sevoflurane versus other general anaesthesia on emergence agitation in children

Sevoflurane anesthesia in young children has been associated with an increased incidence of emergence agitation compared with halothane. Postoperative pain may be an etiologic factor. We designed a study to compare the incidence of emergence agitation after halothane and sevoflurane anesthesia in ch

The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia.

BACKGROUND:Respiratory complications were associated with half of pediatric malpractice claims from the 1970s to 1980s in the ASA Closed Claims Database. Advances in pediatric anesthesia practice have occurred in the 1980s and 1990s and may be reflected in liability trends.METHODS:We reviewed 532 pe

An update on pediatric anesthesia liability: a closed claims analysis.

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.

Conclusion: 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.

Sevoflurane in paediatric anaesthesia: a review.

SUMMARY

Induction, emergence and recovery characteristics were compared during sevoflurane or halothane anaesthetic in a large (428) multicentre, international study of children undergoing elective inpatient surgical procedures. Two hundred and fourteen children in each group underwent inhalation induction with nitrous oxide/oxygen and sevoflurane or halothane. Incremental doses of either study drug were added until loss of eyelash reflex was achieved. Steady state concentrations of anaesthesia were maintained until the end of surgery when anaesthetic agents were terminated simultaneously. Time variables were recorded for induction, emergence and the first need for analgesia in the recovery room. In addition, in 86 of the children in both groups, venous blood samples were drawn for plasma fluoride levels during and after surgery. There was a trend toward smoother induction (induction of anaesthesia without coughing, breath holding, excitement laryngospasm, bronchospasm, increased secretion, and vomiting) in the sevoflurane group with faster induction (2.1 min vs 2.9 min, P= 0.037) and rapid emergence times (10.3 min vs 13.9 min, P= 0.003). Among the children given sevoflurane, 2% developed bradycardia compared with 11% in the halothane group. Postoperatively, 46% of the children in the halothane group developed nausea and or vomiting versus 31% in the sevoflurane group (P= 0.002). Two children in the halothane group developed cardiac dysrhythmia and were dropped from the study. In addition, a child in the halothane group developed malignant hyperthermia, received dantrolene, and had an uneventful recovery. Mean maximum inorganic fluoride concentration was 18.3 μM˙l−1. The fluoride concentrations peaked within one h of termination of sevoflurane anaesthetic and returned rapidly to baseline within 48 h. This study suggests that sevoflurane may be the drug of choice for the anaesthetic management of children.

Klaus Van Ackern

Papers

A comparison of sevoflurane to halothane in paediatric surgical patients: Results of a multicentre international study