Intravenous versus inhalational anaesthesia for paediatric outpatient surgery

  • Review
  • Intervention

Authors

  • Ana C Ortiz,

    Corresponding author
    1. Universidade Federal de São Paulo, Department of Surgery/ Discipline of Anesthesiology, São Paulo, São Paulo, Brazil
    • Ana C Ortiz, Department of Surgery/ Discipline of Anesthesiology, Universidade Federal de São Paulo, Rua Napoleão de Barros 715 - 5th floor, São Paulo, São Paulo, 04024002, Brazil. ortizcarol@hotmail.com.

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  • Álvaro N Atallah,

    1. Centro de Estudos de Medicina Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, Brazil
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  • Delcio Matos,

    1. Escola Paulista de Medicina, Universidade Federal de São Paulo, Gastroenterological Surgery, São Paulo, São Paulo, Brazil
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  • Edina MK da Silva

    1. Universidade Federal de São Paulo, Emergency Medicine and Evidence Based Medicine, São Paulo, São Paulo, Brazil
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Abstract

Background

Ambulatory or outpatient anaesthesia is performed in patients who are discharged on the same day as their surgery. Perioperative complications such as postoperative nausea and vomiting (PONV), postoperative behavioural disturbances and cardiorespiratory complications should be minimized in ambulatory anaesthesia. The choice of anaesthetic agents and techniques can influence the occurrence of these complications and thus delay in discharge.

Objectives

The objective of this review was to evaluate the risk of complications (the risk of postoperative nausea and vomiting (PONV), admission or readmission to hospital, postoperative behavioural disturbances and perioperative respiratory and cardiovascular complications) and recovery times (time to discharge from recovery ward and time to discharge from hospital) comparing the use of intravenous to inhalational anaesthesia for paediatric outpatient surgery.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 8); MEDLINE (1948 to 1 October 2013); EMBASE (1974 to 1 October 2013); Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (1982 to 1 October 2013). We also handsearched relevant journals and searched the reference lists of the articles identified.

Selection criteria

We included randomized controlled trials comparing paediatric outpatient surgery using intravenous versus inhalational anaesthesia.

Data collection and analysis

Two review authors independently assessed trial quality and extracted the data. When necessary, we requested additional information and clarification of published data from the authors of individual trials.

Main results

We included 16 trials that involved 900 children in this review. Half of all the studies did not describe the generation of randomized sequence and most studies did not describe adequate allocation sequence concealment. The included studies showed variability in the types and combinations of drugs and the duration of anaesthesia, limiting the meta-analysis and interpretation of the results.

For the induction and maintenance of anaesthesia there was a significant difference favouring intravenous anaesthesia with propofol; the incidence of PONV was 32.6% for sevoflurane and 16.1% for propofol (odds ratio (OR) 2.96; 95% confidence interval (CI) 1.35 to 6.49, four studies, 176 children, low quality evidence). The risk of postoperative behavioural disturbances also favoured intravenous anaesthesiaas the incidence was 24.7% for sevoflurane and 11.5% for propofol (OR 2.67; 95% CI 1.14 to 6.23, four studies, 176 children, very low quality evidence). There were no differences between groups in the risk of intraoperative and postoperative respiratory and cardiovascular complications (OR 0.75; 95% CI 0.27 to 2.13, three studies,130 children, very low quality evidence) and there was no difference in the time to recovery from anaesthesia and discharge from hospital. These results should be interpreted with caution due to heterogeneity between studies in the type and duration of operations, types of reported complications and the high risk of bias in almost all studies. Two studies (105 participants) compared halothane to propofol and showed heterogeneity in duration of anaesthesia and in the type of ambulatory procedure. For the risk of PONV the results of the studies were conflicting, and for the risks of intraoperative and postoperative complications there were no significant differences between the groups.

For the maintenance of anaesthesia there was a significant difference favouring anaesthesia with propofol, with or without nitrous oxide (N2O), when compared to thiopentone and halothane + N2O (OR 3.23; 95% CI 1.49 to 7.02, four studies, 176 children, low quality evidence; and OR 7.44; 95% CI 2.60 to 21.26, two studies, 87 children, low quality evidence), respectively. For the time to discharge from the recovery room, there were no significant differences between groups. The studies were performed with different ambulatory surgeries and a high risk of bias.

Four studies (250 participants) compared the induction of anaesthesia by the inhalational or intravenous route, with inhalational anaesthesia for maintenance, and found no significant differences between groups in all outcomes (the risk of PONV, behavioural disturbances, respiratory and cardiovascular complications and time to discharge from recovery room). Meta-analysis was not done in this comparison because of significant clinical heterogeneity.

Readmission to hospital was not reported in any of the included studies. No other adverse effects were reported.

Authors' conclusions

There is insufficient evidence to determine whether intravenous anaesthesia with propofol for induction and maintenance of anaesthesia in paediatric outpatients undergoing surgery reduces the risk of postoperative nausea and vomiting and the risk of behavioural disturbances compared with inhaled anaesthesia. This evidence is of poor quality. More high-quality studies are needed to compare the different types of anaesthesia in different subsets of children undergoing ambulatory surgery.

Résumé scientifique

Anesthésie intraveineuse versus anesthésie par inhalation pour la chirurgie ambulatoire pédiatrique

Contexte

L'anesthésie en ambulatoire est réalisée chez les patients sortant le jour même de l'intervention. Les complications périopératoires, tels que les nausées et vomissements postopératoires (NVPO), les troubles comportementaux postopératoires et les complications cardiorespiratoires, devraient être minimisées dans l'anesthésie en ambulatoire. Le choix des agents et techniques anesthésiques peut avoir une influence sur la survenue de ces complications et ainsi sur le retard de sortie.

Objectifs

L'objectif de cette revue était d'évaluer le risque de complications (risque de nausées et de vomissements postopératoires (NVPO), admission ou réadmission à l'hôpital, troubles comportementaux postopératoires et complications respiratoires et cardiovasculaires périopératoires) et les délais de récupération (durée du séjour en salle de réveil et à l'hôpital) en comparant l'utilisation de l'anesthésie par voie intraveineuse et par inhalation dans la chirurgie ambulatoire pédiatrique.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL) dans la Bibliothèque Cochrane (2013, numéro 8) ; MEDLINE (de 1948 au 1er octobre 2013) ; EMBASE (de 1974 au 1er octobre 2013) ; et LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) (de 1982 au 1er octobre 2013). Nous avons également effectué des recherches manuelles dans les revues pertinentes et consulté les références bibliographiques des articles identifiés.

Critères de sélection

Nous avons inclus les essais contrôlés randomisés comparant l'utilisation de l'anesthésie par voie intraveineuse et par inhalation dans la chirurgie ambulatoire pédiatrique.

Recueil et analyse des données

Deux auteurs de la revue ont indépendamment évalué la qualité des essais et extrait les données. Lorsque cela était nécessaire, nous avons demandé des informations supplémentaires et des clarifications sur les données publiées auprès des auteurs d'essais individuels.

Résultats principaux

Nous avons inclus 16 essais portant sur 900 enfants dans cette revue. Dans la moitié de ces études, la génération de séquences randomisées n'était pas décrite, et la plupart des études ne comportaient pas une description de l'assignation secrète des séquences adéquate. Les études incluses présentaient une variabilité dans les types et combinaisons de médicaments et la durée de l'anesthésie, ce qui limitait la méta-analyse et l'interprétation des résultats.

Pour l'induction et l'entretien de l'anesthésie, il y avait une différence significative en faveur de l'anesthésie par voie intraveineuse au propofol ; l'incidence de NVPO était de 32,6 % pour le sévoflurane et de 16,1 % pour le propofol (rapport des cotes (RC) 2,96 ; intervalle de confiance (IC) à 95 % de 1,35 à 6,49, quatre études, 176 enfants, preuves de faible qualité). Le risque de troubles du comportement postopératoires était également favorable à l'anesthésie intraveineuse, l'incidence ayant été de 24,7 % pour le sévoflurane et de 11,5 % pour le propofol (RC 2,67 ; IC à 95 % 1,14 à 6,23, quatre études, 176 enfants, preuves de très faible qualité). Il n'y avait aucune différence entre les groupes dans le risque de complications respiratoires et cardiovasculaires peropératoires et postopératoires (RC 0,75 ; IC à 95 % 0,27 à 2,13, trois études, 130 enfants, preuves de très faible qualité), ni dans les délais de récupération de l'anesthésie et de sortie de l'hôpital. Ces résultats doivent être interprétés avec prudence en raison de l'hétérogénéité entre les études dans le type et la durée d'opération, les types de complications rapportées et le risque de biais élevé dans presque toutes les études. Deux études (105 participants) comparaient l'halothane au propofol et étaient hétérogènes en termes de durée de l'anesthésie et de type de procédure ambulatoire. Pour le risque de NVPO, les résultats des études étaient contradictoires, et pour les risques de complications peropératoires et postopératoires, il n'y avait aucune différence significative entre les groupes.

Pour le maintien de l'anesthésie, il y avait une différence significative en faveur de l'anesthésie au propofol, avec ou sans protoxyde d'azote (N2O), par rapport au thiopental et à l'halothane + N2O (RC 3,23 ; IC à 95 % 1,49 à 7,02, quatre études, 176 enfants, preuves de faible qualité ; et RC 7,44 ; IC à 95 % 2,60 à 21,26, deux études, 87 enfants, preuves de faible qualité), respectivement. Pour la durée du séjour en salle de réveil, il n'y avait aucune différence significative entre les groupes. Les études portaient sur différentes interventions de chirurgie ambulatoire et présentaient un risque élevé de biais.

Quatre études (250 participants) comparaient l'induction de l'anesthésie par inhalation ou par voie intraveineuse, avec l'anesthésie par inhalation pour le maintien, et n'ont trouvé aucune différence significative entre les groupes pour aucun critère de jugement (risque de NVPO, troubles du comportement, complications respiratoires et cardiovasculaires et durée du séjour en salle de réveil). Une méta-analyse n'a pas été effectuée pour cette comparaison en raison d'une hétérogénéité clinique significative.

Les réadmissions à l'hôpital n'étaient pas rapportées dans aucune des études incluses. Aucun autre effet indésirable n'a été rapporté.

Conclusions des auteurs

Il n'existe pas suffisamment de preuves pour déterminer si l'anesthésie intraveineuse au propofol pour l'induction et l'entretien de l'anesthésie en chirurgie ambulatoire pédiatrique réduit les risques de nausées et vomissements postopératoires et de troubles du comportement par rapport à l'anesthésie par inhalation. Ces preuves sont de mauvaise qualité. D'autres études de haute qualité sont nécessaires afin de comparer les différents types d'anesthésie dans les différents sous-ensembles d'enfants subissant une intervention chirurgicale en ambulatoire.

Plain language summary

Intravenous versus inhaled anaesthesia for children having day surgery procedures

Review question

We reviewed the evidence about the effects of general anaesthesia (GA) for children having day surgery. The GA was given to the children either by intravenous injection (injection of a drug such as propofol or thiopental) or by the child inhaling or breathing a gas such as sevoflurane or halothane through a mask. We found 16 studies that compared these two types of GA.

Background

We wanted to find out whether intravenous or inhaled anaesthesia reduced the risk of outcomes such as postoperative nausea and sickness (vomiting) (PONV) and behavioural problems in children having day surgery. PONV is one of the most common problems for children having day surgery. PONV is a common reason for delay in a child's hospital discharge and for their unplanned admission to hospital. Postoperative pain can cause behavioural problems in children. These behavioural problems may present as moaning, being restless and confused, and physical movements such as thrashing about in the bed. Mental disturbances such as hallucinations, delusions and confusion can also be evident as a child emerges from GA.

Search date

The evidence was current to 1 October 2013.

Study characteristics

We included 16 studies (900 participants) in this review. All participants were otherwise healthy children (aged under 15 years) who were scheduled for day surgery. The studies compared different types of intravenous and inhaled anaesthetic medications.

Key results

The authors found that when compared to inhaled anaesthesia with sevoflurane, intravenous anaesthesia with propofol may reduce the risk of PONV and the risk of behavioural problems with no difference in the time to recovery from anaesthesia and discharge from hospital in children having day surgery. The effect on complications was imprecise. The studies that compared other anaesthetic agents involved different types of surgical procedures, different procedure durations and drugs, making it difficult to sum the results.

Quality of evidence

Most of the trials included in this review were of poor quality and had high risk of bias. There was great variety in the included studies in the combinations of drugs, duration of anaesthesia and types of surgical procedures, which made the results uncertain. Further trials are needed to compare the types of anaesthesia used in children's ambulatory surgery.

Résumé simplifié

L'anesthésie intraveineuse contre l'anesthésie par inhalation pour les enfants subissant des actes de chirurgie de jour

Question de la revue

Nous avons examiné les preuves concernant les effets de l'anesthésie générale (AG) pour les enfants en chirurgie de jour. L'AG était administrée aux enfants soit par voie intraveineuse (injection d'un médicament tel que le propofol ou le thiopental) ou par inhalation en respirant un gaz tel que le sévoflurane ou l'halothane à travers un masque. Nous avons trouvé 16 études comparant ces deux types d'AG.

Contexte

Nous voulions découvrir si l'anesthésie par voie intraveineuse ou par inhalation réduisait le risque d'apparition de critères d'évaluation tels que les nausées et vomissements postopératoires (NVPO) et les troubles du comportement chez les enfants subissant une intervention en chirurgie de jour. Les NVPO sont l'un des problèmes les plus fréquents chez les enfants en chirurgie de jour et un motif fréquent pour retarder la sortie de l'hôpital des enfants et pour leur hospitalisation non planifiée. La douleur postopératoire peut entraîner chez les enfants des troubles du comportement, qui se manifestent par des gémissements, l'agitation et le désarroi, ou par des mouvements physiques tels qu'une agitation violente au lit. Des troubles mentaux, tels que des hallucinations, des idées délirantes ou une confusion, peuvent également être manifestes lorsque l'enfant émerge de l'AG.

Date de la recherche

Les preuves étaient à jour au 1er octobre 2013.

Caractéristiques des études

Nous avons inclus 16 études (900 participants) dans cette revue. Tous les participants étaient des enfants par ailleurs en bonne santé (âgés de moins de 15 ans) programmés pour une intervention en chirurgie de jour. Les études ont comparé différents types de médicaments anesthésiques administrés par voie intraveineuse ou par inhalation.

Résultats principaux

Les auteurs ont constaté que, en comparaison avec l'anesthésie par inhalation au sévoflurane, l'anesthésie intraveineuse au propofol peut réduire les risques de NVPO et de troubles comportementaux sans aucune différence dans les temps de récupération de l'anesthésie et de sortie de l'hôpital chez les enfants en chirurgie de jour. L'effet sur les complications était imprécis. Les études ayant comparé d'autres agents anesthésiques portaient sur différents types de procédures chirurgicales, avec des durées et des médicaments différents, rendant difficile un résumé de leurs résultats.

Qualité des preuves

La plupart des essais inclus dans cette revue étaient de mauvaise qualité et présentaient un risque élevé de biais. Il existait une grande variété parmi les études incluses dans les combinaisons de médicaments, la durée de l'anesthésie et le type de procédure chirurgicale, ce qui a rendu les résultats incertains. D'autres essais sont nécessaires afin de comparer les types d'anesthésie utilisés chez les enfants en chirurgie de jour.

Notes de traduction

Traduit par: French Cochrane Centre 15th June, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Summary of findings(Explanation)

Summary of findings for the main comparison. Induction and maintenance: sevoflurane + nitrous oxide (N2O) compared to propofol + N2O for paediatric outpatient surgery
  1. 1One study (Picard 2000) evaluated the risk of postoperative nausea and vomiting until discharge from recovery room and three (Baykara 1998; Guard 1998; Gurkan 1999) until 24 hours of postoperative.
    2 Three studies (Guard 1998; Gurkan 1999; Picard 2000) were classified as high risk of bias for allocation concealment and one study (Baykara 1998) was classified as unclear risk of bias for randomization and high for blinding of outcome assessment.
    3 The studies were conducted with different types of surgeries and duration of anaesthesia.
    4 Three studies reported the risk of postoperative behavioural disturbances until discharge recovery (Baykara 1998; Gurkan 1999; Picard 2000) and one (Guard 1998) reported during emergence of anaesthesia.
    5 Three studies (Baykara 1998; Guard 1998; Gurkan 1999) did not describe the postoperative behavioural disturbances criteria.
    6 One study (Baykara 1998) was classified as unclear risk of bias for randomization and high for blinding of outcome assessment and the other studies (Guard 1998; Gurkan 1999) were classified as high risk of bias for allocation concealment.
    7 Two studies (Baykara 1998; Guard 1998) reported respiratory complication (laryngospasm) in the recovery room and another study (Gurkan 1999) reported cardiac complication (bradycardia ) during the induction of anaesthesia. The meta-analysis of the studies showed significant heterogeneity (49%),probably because the complications were not equal and they were analysed in different periods with different surgical procedure.

    8The results are imprecise because the analysis of studies of respiratory complications were based on few patients(90 children) and few events(three).

Induction and maintenance: sevoflurane + nitrous oxide (N2O) compared to propofol + N2O for paediatric outpatient surgery
Patient or population: paediatric
Settings: outpatient surgery
Intervention: sevoflurane + N2O
Comparison: propofol + N2O
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Propofol + N2O Sevoflurane + N2O
Postoperative nausea and vomiting
Follow-up: until 24 hours1
Study population OR 2.96
(1.35 to 6.49)
176
(4 studies)
⊕⊕⊝⊝
low 2,3
 
161 per 1000 362 per 1000
(206 to 554)
Postoperative behavioural disturbances
Different scales
Follow-up: until discharge from recovery room4
Study population OR 2.67
(1.14 to 6.23)
176
(4 studies)
⊕⊝⊝⊝
very low 2,3,5
 
115 per 1000 257 per 1000
(129 to 447)
Intraoperative and postoperative respiratory and cardiovascular complications
Follow-up: until discharge from hospital (hours)
Study population OR 0.75
(0.27 to 2.13)
130
(3 studies)
⊕⊝⊝⊝
very low 6,7,8
 
246 per 1000 197 per 1000
(81 to 410)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Summary of findings 2 Maintenance anaesthesia: inhalational compared to intravenous for paediatric outpatient surgery

Summary of findings 2. Maintenance anaesthesia: inhalational compared to intravenous for paediatric outpatient surgery
  1. 1 Three studies (Crawford 1998; Hannallah 1994; Reimer 1993) reported these outcome in the recovery and 24hs after surgery and only one study (Borgeat 1990) reported these until discharge from recovery.
    2 In three studies (Borgeat 1990; Hannallah 1994; Reimer 1993) the method of randomization was unclear and they were classified as high risk of bias for the allocation concealment.Besides,the studies were in different ambulatory surgeries with duration varying from 36 to 75 minutes.
    3 Two studies (Crawford 1998; Reimer 1993) were classified as high risk of bias for the allocation concealment and in Reimer 1993 the method of randomization was unclear.

    4The results are imprecise because the analysis of studies of the risk of PONV were based on few patients (87 children).

Maintenance anaesthesia: inhalational compared to intravenous for paediatric outpatient surgery
Patient or population: paediatric
Settings: outpatient surgery
Intervention: inhalational
Comparison: intravenous
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Intravenous Maintenance: inhalational
Nausea and vomiting - subgroup analysis: thiopentone or halothane + N2O versus propofol or propofol + N2O
Follow-up: 24 hours after surgery1
Study population OR 3.23
(1.49 to 7.02)
176
(4 studies)
⊕⊕⊝⊝
low 2
 
310 per 1000 592 per 1000
(401 to 760)
Nausea and vomiting - subgroup analysis: thiopentone or halothane + N2O versus propofol or propofol + N2O
Follow-up: 24 hours after surgery
Study population OR 7.44
(2.6 to 21.26)
87
(2 studies)
⊕⊕⊝⊝
low 3,4
 
349 per 1000 799 per 1000
(582 to 919)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

The intention of ambulatory or outpatient anaesthesia is for the patient to be admitted and discharged on the same day as their surgical treatment, therapeutic procedure or diagnostic test. The patient is administered general, regional or combined anaesthesia and remains under medical supervision until they have full recovery of their mental and physical functions. They are usually well enough to go home on the same day as their procedure. Improvements in anaesthetic and surgical techniques have resulted in extremely good safety records, leading to a radical increase in the number of surgical procedures performed in ambulatory surgical units (Rabbitts 2010; Troy 2002).

Children make excellent candidates for day case surgery as they are usually healthy, free of systemic disease and typically require straightforward, minor or intermediate surgical procedures. The advantages of outpatient procedures include that the patients return home relatively quickly after their surgery; greater patient and parent comfort; reduced risk of nosocomial infections; the release of hospital beds; greater turnover in surgical centres and decreases in costs to the hospital (Ewah 2006; Troy 2002) and patients.

Description of the intervention

Inhalational and intravenous anaesthesia are two options available today for general anaesthesia in children. Since the first general anaesthetic was administered in 1846, inhalational anaesthetics have played a pivotal role in paediatric anaesthesia. The inhalational anaesthetics that are available for use today in children are sevoflurane, isoflurane, desflurane, enflurane, halothane and nitrous oxide. Intravenous anaesthesia is becoming more widely used due to the advent of improved drugs (rapid-acting total intravenous anaesthesia (TIVA) drugs), better understanding of pharmacokinetic or pharmacodynamic interactions, simpler and age-specific delivery systems, non-pollution of the theatre environment and independence from airway instrumentation (Mani 2010). However, there are some disadvantages such as the need for familiarity with the technique and limited availability of infusion pumps and monitoring devices (Lerman 2009) in some parts of the world.

Intravenous anaesthesia can be performed as a single technique or in combination with either inhalation anaesthetics or regional anaesthesia. The intravenous anaesthetics used in children are ketamine, propofol, thiopental, midazolam, dexmedetomidine and opioids (morphine, fentanyl, sufentanil, alfentanil and remifentanil). General anaesthesia with intravenous drugs only, or TIVA, is gaining increased acceptance because of the availability of short-acting hypnotics and opioids (Mani 2010; Pandit 1994).

How the intervention might work

Postoperative nausea and vomiting (PONV) is one of the most common complications (its incidence ranges from 8.9% to 42%) affecting patients undergoing ambulatory surgery and is a common reason for delaying hospital discharge and unanticipated hospital admissions (Blacoe 2008; Patel 1988). Prophylactic antiemetics have limited efficacy and they may cause mild side effects, such as sedation or headache, and serious life-threatening events for instance cardiac arrhythmias (Carlisle 2006; Watcha 2003). In paediatric day surgery, some studies suggest that  intravenous anaesthesia is associated with less vomiting in the first 24 hours postoperation than inhalational anaesthetics (Gürkan 1999; Hannallah 1994; Martin 1993; Ved 1996). Most of these studies found that the incidence of early vomiting was significantly different, but not after discharge from the hospital (Gürkan 1999; Hannallah 1994; Ved 1996). Other studies reported no difference in vomiting between anaesthetic techniques (Davis 1997; Picard 2000; Viitanen 1999). The use of nitrous oxide (N2O) during anaesthesia has been associated with increased postoperative vomiting (Tramer 1996; Watcha 2003). The studies have not found any differences in discharge times or admission rates between inhalational and intravenous anaesthesia (Davis 1997; Martin 1993; Pieters  2010; Ved 1996; Viitanen 1999).

The incidence of  postoperative pain and behavioural disturbances ranges from 25% to 80%, which can influence duration of stay and discharge from the postanaesthetic care unit (PACU) (Sikich 2004). Pain may increase the incidence of emergence delirium (Lynch 1998) and the behaviour of a child in pain can mimic emergence delirium (Voepel-Lewis 2003). Some studies suggest that intravenous anaesthetics are associated with less behavioural disturbance than inhalational anaesthesia, while others show conflicting results (König 2009; Pieters  2010; Uezono 2000).

Perioperative respiratory adverse events remain one of the major causes of morbidity and mortality during paediatric anaesthesia (Bhananker 2007; Murat 2004). Maintenance with sevoflurane was associated with an increased incidence of laryngospasm compared with propofol (Von Ungern-Sternberg 2010). However, propofol significantly increased the risk of bradycardia when compared with other anaesthetics, especially in the group of paediatric patients undergoing potentially arrhythmogenic procedures such as in surgeries for correction of strabismus. The types of anaesthesia induction and maintenance seem to greatly affect the risk of perioperative cardiorespiratory complications (Tramer 1997).

Why it is important to do this review

For day surgery to be an acceptable option, it is necessary for fast emergence and short recovery from anaesthesia with a low incidence of perioperative side effects (Picard 2000). Few children (around 1%) may require inpatient admission (Lonnqvist 2006). The factors found to be associated with duration of stay in the PACU and unplanned admission include postoperative pain, PONV and postoperative behavioural disturbances; these should be minimized (Shnaider 2006).

Both intravenous and inhalational anaesthetic agents are used for induction and maintenance of surgical anaesthesia. For this reason, the choice of an anaesthetic agent and technique has been seen as critical in the avoidance of perioperative complications and can therefore be an important factor in achieving rapid patient discharge (Moore 2002).

Objectives

The objective of this review was to evaluate the risk of complications (the risk of postoperative nausea and vomiting (PONV), admission or readmission to hospital, postoperative behavioural disturbances and perioperative respiratory and cardiovascular complications) and recovery times (time to discharge from recovery ward and time to discharge from hospital) comparing the use of intravenous to inhalational anaesthesia for paediatric outpatient surgery.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomized and quasi-randomized, published and unpublished controlled clinical studies.

Types of participants

We included outpatients under 18 years old receiving general anaesthesia.

We excluded neonates (defined as postnatal age maximum of 28 days after reaching 40 weeks corrected gestational age).

Types of interventions

  • Inhalational versus intravenous induction

  • Maintenance of anaesthesia with a volatile anaesthetic versus intravenous anaesthetic agent

We excluded participants who received premedication with benzodiazepines and antiemetics.

Types of outcome measures

Primary outcomes
  1. The risk of postoperative nausea and vomiting (PONV)

  2. The risk of admission or readmission to hospital

  3. The risk of postoperative behavioural disturbances (defined as disturbances during the recovery from general anaesthesia that consist of hallucinations, delusions and confusion manifested by moaning, restlessness, involuntary physical activity and thrashing about in the bed)

Secondary outcomes

4. The risk of intraoperative and postoperative respiratory and cardiovascular complications (defined as laryngospasm, bronchospasm, oxygen desaturation to less than 90%, bradycardia, arrhythmia, hypotension or hypertension episodes requiring intervention)

5. Time to discharge from recovery room (time in minutes from discontinuation of anaesthetic to achieving the criteria for discharge from recovery room)

6. Time to discharge from hospital (time in minutes from discontinuation of anaesthetic to discharge)

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 8); MEDLINE (1948 to 1 October 2013); EMBASE (1974 to 1 October 2013); Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (1982 to 1 October 2013). We searched the literature with both subject headings and free text words. We have provided our MEDLINE search in Appendix 1; LILACS in Appendix 2; EMBASE in Appendix 3 and CENTRAL in Appendix 4.

We searched for ongoing trials in the Current Controlled Trials website (http://www.controlled-trials.com/).

We did not impose a language restriction. We identified the trials from the sources listed above.

Searching other resources

We scrutinized the reference lists of any identified relevant studies for additional citations.

We contacted specialists in the field, authors of the included trials and pharmaceutical manufacturers for any possible unpublished data.

Data collection and analysis

Selection of studies

Two authors (ACO and EMKS) independently screened the trials identified by the literature search. We documented the reasons for exclusion. See Appendix 5 for the study selection form. We consulted a third author (ANA) if any disagreements arose (at this or at any other stage listed below). We did not include data from the trials in question until a consensus was reached.

Data extraction and management

Two authors (ACO and EMKS) extracted data independently and collected the data on a paper form (see Appendix 6). We cross-checked the data and resolved any discrepancies by discussion. We used double data entry to prevent data entry errors. We used a standard form to extract the following information:

  • characteristics of the study (design, methods of randomization);

  • participants;

  • interventions and outcomes (types of outcome measures, timing of outcomes, adverse events).

Assessment of risk of bias in included studies

In order to assess the risk of bias we independently assessed the studies included in the review according to the criteria described by Higgins (Higgins 2011a) (see Appendix 7).

We assessed the following domains as 'Yes' (that is low risk of bias), 'Unclear' (uncertain risk of bias) or 'No' (that is high risk of bias).

  1. Selection bias: was the sequence generation adequate?

  2. Selection bias: was allocation adequately concealed?

  3. Detection bias: was there a blinded assessment of outcomes?

  4. Attrition bias: were incomplete outcome data adequately addressed?

  5. Selective reporting bias: are reports of the study free of the suggestion of selective outcome reporting?

  6. Other potential bias: was the study apparently free of other problems that could put it at a high risk of bias?

Measures of treatment effect

For dichotomous variables, we calculated the odds ratio (OR) and 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI.

Unit of analysis issues

The unit of analysis was based on the individual participant (unit to be randomized for interventions to be compared); that is, the number of observations in the analysis should match the number of individuals randomized.

Dealing with missing data

Irrespective of the type of data, we reported dropout rates in the Characteristics of included studies table and used intention-to-treat (ITT) analysis (Higgins 2011b).

Assessment of heterogeneity

We quantified inconsistencies among the pooled estimates using the I2 = ((Q - df)/Q) x 100% statistic, where Q is the Chi2 statistic and df its degrees of freedom. This illustrates the percentage of the variability in effect estimates resulting from heterogeneity rather than sampling error (Higgins 2003; Higgins 2011a).

The thresholds for the interpretation of I2 were as follows:

  1. 0% to 25% low heterogeneity;

  2. 25% to 75% moderate; and

  3. more than 75% significant heterogeneity (Higgins 2003).

We found significant heterogeneity in some secondary outcomes but there were insufficient data to conduct meta-analyses by subgroups. In subsequent updates of this review, we will further investigate the possible causes of heterogeneity by exploring the impact of methodological quality and the condition of the individuals (that is patient characteristics, type and duration of surgery, type of disease, nature of the intervention, duration of the intervention, adjuvant drugs). When we found sources of heterogeneity, and if there were sufficient data, we conducted meta-analyses by subgroups.

When no significant heterogeneity was identified, we computed pooled estimates of the treatment effect for each outcome under a fixed-effect model. When we detected significant heterogeneity despite subgroups analysis, we calculated the pooled estimate of treatment effects using random-effects models.

Assessment of reporting biases

We did not evaluate reporting biases or small study effects by drawing a funnel plot (trial effect versus trial size) because there was an insufficient number of studies. In subsequent updates we will assess if a sufficient number of studies (more than 10) are included in the review.

Data synthesis

Qualitative information

We synthesized qualitative information relative to methods, risk of bias, description of participants and outcomes measures and inserted this information in the Characteristics of included studies table.

Quantitative information

For dichotomous variables, we calculated the odds ratio (OR). For continuous variables, we calculated the mean difference (MD). In subsequent updates of this review if continuous data are available for the same aspect but are measured with different instruments (different and not interchangeable units of measure), we will pool these data using the standardized mean difference (SMD). For all statistical methods, we will report the 95% CI when pooling data.

When we identified no significant heterogeneity, we computed pooled estimates of the treatment effect for each outcome using a fixed-effect model. However, if significant heterogeneity was identified we performed a random-effects model analysis.

Subgroup analysis and investigation of heterogeneity

We found significant heterogeneity in some secondary outcomes but there were insufficient data to conduct meta-analyses by subgroups.

In subsequent updates of this review, we will investigate the possible causes of this heterogeneity by further exploring the impact of methodological quality and the condition of the individuals. Thus we will conduct meta-analyses by subgroups:

  1. age and gender of the children;

  2. different inhalation and intravenous anaesthetics;

  3. use of nitrous oxide;

  4. use of loco-regional anaesthesia;

  5. use of antiemetics;

  6. type and duration of surgery (tonsillectomy and adenoidectomy, strabismus and others)

Sensitivity analysis

In subsequent updates of this review, once the number of available studies are adequate, we will perform a sensitivity analysis to explore the causes of heterogeneity and the robustness of the results. We will include the following factors in the sensitivity analysis, separating studies according to: allocation concealment quality (adequate or unclear or inadequate); blinding outcome assessment (adequate or unclear or inadequate or not performed); rate of withdrawals for each outcome; length of follow-up; patient characteristics; type of intervention; type of outcome.

Summary of findings

We used the principles of the GRADE system (Guyatt 2008) to assess the quality of the body of evidence associated with specific outcomes (the risk of PONV, the risk of admission or readmission to hospital, the risk of postoperative behavioural disturbances, the risk of intraoperative and postoperative respiratory and cardiovascular complications) in our review and we constructed a summary of findings (SoF) table using the GRADE software. The GRADE approach appraises the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The assessment of the quality of a body of evidence considers within study risk of bias (methodological quality), the directness of the evidence, heterogeneity of the data, precision of effect estimates and risk of publication bias.

Results

Description of studies

See Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

Results of the search

See Figure 1.

Figure 1.

Study flow diagram.

We identified 917 citations from the database searches. After screening by title and abstract we obtained full paper copies for 35 citations that were potentially eligible for inclusion in the review. Of these 35 citations, 19 did not fulfil our inclusion criteria and were excluded for the reasons described in the Characteristics of excluded studies. Therefore, we included 16 studies in this review (see Characteristics of included studies).

Two studies (Gouda 2002; Moussa 1995) were found to be incomplete for the assessment of risks of bias and data extraction. We are waiting for the authors to release the full papers (see Characteristics of studies awaiting classification). We did not find any ongoing and unpublished studies.

Included studies

We included 16 studies (Annila 1999; Baykara 1998; Borgeat 1990; Cohen 2003; Cohen 2004; Crawford 1998; Glaisyer 2005; Guard 1998; Gurkan 1999; Hannallah 1994; Madan 2001; Picard 2000; Reimer 1993; Viitanen 1998; Viitanen 1999; Weir 1993) in this review. Of those 16 studies, one study was in Turkish (Baykara 1998). The 16 studies enrolled a total of 900 participants. Two articles analysed the same sample, reporting different outcomes in each publication (Cohen 2003; Cohen 2004).

One study used a cross-over design (Glaisyer 2005) whereby two interventions were studied in the same group of patients. The order of the intervention was randomized. All other studies claimed to be randomized controlled trials (RCTs).

Types of participants

All participants were healthy children (aged under 15 years), American Society of Anesthesiology (ASA) grades one and two (ASA I and II), who were scheduled for elective outpatient surgery.

Six studies involved elective ear, nose and throat (ENT) procedures (Annila 1999; Baykara 1998; Borgeat 1990; Picard 2000; Viitanen 1998; Viitanen 1999); four ophthalmic procedures, three of these were strabismus surgery (Gurkan 1999; Reimer 1993; Weir 1993) and one a non-invasive diagnostic ophthalmic procedure (Madan 2001). In addition, six other studies (Cohen 2003; Cohen 2004; Crawford 1998; Glaisyer 2005; Guard 1998; Hannallah 1994) involved other ambulatory surgical procedures (urological, general surgery, dental, orthopaedic, plastic surgery).

Types of interventions

Eight studies compared sevoflurane anaesthesia to propofol (Baykara 1998; Cohen 2003; Cohen 2004; Glaisyer 2005; Guard 1998; Gurkan 1999; Picard 2000; Viitanen 1999) while three studies compared halothane anaesthesia to propofol (Annila 1999; Hannallah 1994; Madan 2001). Four studies compared the induction of anaesthesia with thiopental and maintenance with halothane to propofol anaesthesia (Borgeat 1990; Crawford 1998; Hannallah 1994; Reimer 1993). One study compared the induction of anaesthesia with thiopental to halothane (Viitanen 1998) and another study compared the maintenance of anaesthesia with halothane to propofol (Weir 1993).

Types of outcome measures

Ten studies reported the risk of PONV (Borgeat 1990; Cohen 2004; Glaisyer 2005; Gurkan 1999; Hannallah 1994; Madan 2001; Picard 2000; Reimer 1993; Viitanen 1999; Weir 1993) and four studies reported the incidence of vomiting alone (Baykara 1998; Cohen 2003; Guard 1998; Viitanen 1998). Nine studies reported the incidence of postoperative nausea or vomiting, or both, until 24 hours after surgery (Baykara 1998; Cohen 2004; Crawford 1998; Guard 1998; Gurkan 1999; Hannallah 1994; Reimer 1993; Viitanen 1999; Weir 1993) and one reported it until discharge from recovery (Borgeat 1990).

Eight studies reported the risk of behavioural disturbances in the recovery room (Baykara 1998; Borgeat 1990; Cohen 2003; Glaisyer 2005; Gurkan 1999; Picard 2000; Viitanen 1998; Viitanen 1999). The risk of admission or readmission to hospital was not reported in any study.

The time to discharge from the recovery room was reported in 12 studies (Baykara 1998; Borgeat 1990; Cohen 2004; Crawford 1998; Glaisyer 2005; Guard 1998; Hannallah 1994; Madan 2001; Picard 2000; Reimer 1993; Viitanen 1998; Viitanen 1999) and time to discharge from hospital was reported in two studies (Baykara 1998; Guard 1998).

The intraoperative and postoperative respiratory and cardiovascular complications that were reported are listed in the table Characteristics of included studies.

Excluded studies

We excluded 19 studies for the reasons described in the table Characteristics of excluded studies. We excluded seven studies because the patients were premedicated with benzodiazepines. The use of premedication can change the following outcomes: time to emergence, the incidence of nausea or vomiting, or both, and the incidence of behavioural disturbances.

Three trials (Elliott 2002; Elliott 2003; Moore 2003) were potentially based on the same subset of patients.

Risk of bias in included studies

See Figure 2; Figure 3.

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

In eight studies, the procedure for randomization was performed using a computer-based random listing or a table of random numbers and in eight studies the methods used for randomization were unclear. See Characteristics of included studies.

Most studies (12) probably did not perform an adequate method of allocation sequence concealment (see Figure 2).

Blinding

In three trials, outcome assessment was probably not blinded (Baykara 1998; Borgeat 1990; Viitanen 1998). In most trials the outcomes were assessed by an investigator who was blind to the type of anaesthesia used (Annila 1999; Cohen 2003; Cohen 2004; Crawford 1998; Glaisyer 2005; Guard 1998; Gurkan 1999; Hannallah 1994; Madan 2001; Picard 2000; Reimer 1993; Viitanen 1999; Weir 1993).

Incomplete outcome data

In nine studies follow-up was 100% and the analysis included all participants with outcome data. Outcome data were incomplete in the other studies.

Selective reporting

In three studies (Baykara 1998; Gurkan 1999; Weir 1993) some specific outcomes were not well described.

In two other studies (Cohen 2003; Viitanen 1998) the pre-specified outcomes were not reported in the results (see the details in Characteristics of included studies).

Other potential sources of bias

The outcomes of the included studies were analysed in different periods: one study evaluated the risk of PONV until discharge from the recovery room (Borgeat 1990) and nine until 24 hours postoperation. Three studies reported the risk of postoperative behavioural disturbances until discharge from the recovery room (Baykara 1998; Gurkan 1999; Picard 2000) and one during emergence from anaesthesia (Guard 1998). The studies used different scales to define this outcome.

The number of included studies was also insufficient to evaluate reporting biases and small study effects by constructing a funnel plot.

Effects of interventions

See: Summary of findings for the main comparison Induction and maintenance: sevoflurane + nitrous oxide (N2O) compared to propofol + N2O for paediatric outpatient surgery; Summary of findings 2 Maintenance anaesthesia: inhalational compared to intravenous for paediatric outpatient surgery

Induction and maintenance: inhalational versus intravenous

In this comparison we have grouped the studies that used induction and maintenance of anaesthesia with the same intravenous or inhaled drugs in both periods.

1. Sevoflurane versus propofol

Four studies (176 participants) were included in the comparison of sevoflurane versus propofol with all patients receiving nitrous oxide (Baykara 1998; Guard 1998; Gurkan 1999; Picard 2000). Among the studies, different surgeries were performed with the duration of anaesthesia ranging from 50 to 88 minutes. Three studies (Guard 1998; Gurkan 1999; Picard 2000) were classified as at high risk of bias for allocation concealment and one study (Baykara 1998) was classified as unclear for method of randomization and high risk for blinding of outcome assessment. A significant difference was observed favouring the intravenous anaesthesia in the risk of presenting with nausea and vomiting postoperatively, OR of 2.96 (95% CI 1.35 to 6.49) (Analysis 1.1). However, Baykara 1998 and Picard 2000 studied children undergoing tonsillectomy and in Gurkan 1999 the children underwent strabismus surgery. These types of operations are associated with an increased risk of vomiting in children independent of the type of anaesthetic used.

For postoperative behavioural disturbances, the meta-analysis of these four studies showed a significant difference with less risk in the group receiving intravenous anaesthesia (OR 2.67; 95% CI 1.14 to 6.23) (Analysis 1.2). However, three of these studies (Baykara 1998; Guard 1998; Gurkan 1999) did not describe their definition of behavioural disturbances.

For intraoperative and postoperative respiratory and cardiovascular complications, three studies (130 participants) reported this outcome (Baykara 1998; Guard 1998; Gurkan 1999) and there were no differences between the groups (Analysis 1.3). Two studies (Baykara 1998; Guard 1998) reported respiratory complications (laryngospasm) in the recovery room and another study (Gurkan 1999) reported bradycardia during the induction of anaesthesia. The meta-analysis of the studies showed significant heterogeneity (49%).

In three studies (136 participants) the time to discharge from the recovery room was reported (Baykara 1998; Guard 1998; Picard 2000) and there was no significant difference between the groups (MD 3.61; 95% CI 0.32 to 6.90) (Analysis 1.4). For time to discharge from hospital, only two studies (83 participants) reported this outcome (Baykara 1998; Guard 1998) and there was no significant difference between the groups, however, this analysis showed moderate heterogeneity (I2 = 74%) (Analysis 1.5). The risk of admission or readmission to hospital was not reported in the studies.

2. Halothane versus propofol

Two studies (105 participants) that compared halothane to propofol during induction and maintenance of anaesthesia showed heterogeneity in the duration of anaesthesia (maximum time of eight minutes in Madan 2001 and 88 minutes in Hannallah 1994), and the type of procedure was different between the studies. Besides that, in Madan 2001 only the halothane group received nitrous oxide while in Hannallah 1994 both groups did. For the risk of PONV, one study did not report any cases of nausea and vomiting in either group (Madan 2001) while Hannallah 1994 reported a significant decrease of this outcome in the group receiving intravenous anaesthesia with propofol (OR 22.15; 95% CI 2.58 to 189.95). For intraoperative and postoperative respiratory and cardiovascular complications, the two studies analysed this outcome and there were no significant differences between the groups. Conflicting results were observed between the two studies in the time to discharge from the recovery room. In Madan 2001 the group receiving inhalational anaesthesia had a better outcome in contrast to Hannallah 1994 in which a better outcome was observed in the intravenous group. The time to discharge from hospital and the risk of postoperative behavioural disturbances were not reported in these studies.

Maintenance of anaesthesia: inhalational versus intravenous

Seven studies were included in this analysis (Borgeat 1990; Cohen 2004; Crawford 1998; Glaisyer 2005; Hannallah 1994; Reimer 1993; Weir 1993). The included studies analysed different drug combinations making it difficult to sum the results.

Four studies (176 participants) compared thiopentone and halothane + N2O versus propofol and propofol + N2O (Borgeat 1990; Crawford 1998; Hannallah 1994; Reimer 1993) for different ambulatory surgeries with the duration varying from 36 to 75 minutes. Regarding the risk of PONV, a significant difference was observed favouring the group receiving intravenous anaesthesia with propofol (OR 3.23; 95% CI 1.49 to 7.02) (Analysis 2.1). Nevertheless, Borgeat 1990 and Reimer 1993 studied children undergoing otorhinolaryngology and strabismus surgery, respectively, and in two other studies different ambulatory surgeries were performed. Moreover, in three studies (Borgeat 1990; Hannallah 1994; Reimer 1993) the method of randomization was unclear and all four studies were classified as high risk of bias for the allocation concealment. Three of these studies (125 participants) reported the time to discharge from the recovery room (Borgeat 1990; Crawford 1998; Reimer 1993) and there were no significant differences between groups, with significant heterogeneity in the analysis (Analysis 2.2). The criteria used for recovery room discharge were different. No other outcomes were reported in these studies.

Two studies (87 participants) compared thiopentone and halothane + N2O versus propofol and propofol (Crawford 1998; Reimer 1993) for ambulatory surgeries lasting less than 60 minutes. The risk of PONV favoured the group receiving intravenous anaesthesia with propofol (OR 7.44; 95% CI 2.60 to 21.26) (Analysis 2.1). There were no significant differences between groups (Analysis 2.2) for the time to discharge from the recovery room. However, the studies were classified as at high risk of bias for the concealment of allocation and randomization.

Weir 1993 (78 participants) compared halothane + N2O and halothane + N2O versus halothane + N2O and propofol + N2O and there was significantly less PONV in the intravenous group (OR 2.91; 95% CI 1.15 to 7.37), the only outcome reported in the study.

Glaisyer 2005 (21 participants) compared propofol and sevoflurane + N2O versus propofol and propofol in painful procedures lasting less than five minutes in a cross-over trial, and a significant difference was observed favouring intravenous anaesthesia in the time to discharge from recovery (MD 18.60; 95% CI 8.35 to 28.85) in an analysis of the two periods (42 observations). There was no episode of PONV or difference in the risk of postoperative behavioural disturbances between the groups.

Cohen 2004 (56 participants) compared sevoflurane + N2O and sevoflurane + N2O versus sevoflurane + N2O and propofol + N2O for ambulatory surgical procedures, and no significant difference between groups was observed in the risk of PONV and in the time to discharge from the recovery room. In Cohen 2003, which probably analysed the same sample as in Cohen 2004, there was no difference in the risk of postoperative behavioural disturbances between the groups.

Induction of anaesthesia: inhalational versus intravenous

Only four studies (250 participants) compared the induction of anaesthesia by inhalational (halothane or sevoflurane) or intravenous (thiopentone or propofol) administration, with the maintenance phase being equal in both groups; all the participants received inhalation anaesthesia with halothane or sevoflurane for maintenance (Annila 1999; Hannallah 1994; Viitanen 1998; Viitanen 1999). The included studies analysed different drug combinations and the duration of the surgeries ranged from 22 minutes to 68 minutes, therefore a meta-analysis was not performed. There were no significant differences between groups in all outcomes (PONV, behavioural disturbances, respiratory and cardiovascular complications and time to discharge from recovery room).

Discussion

Summary of main results

There were 16 studies comparing the outcomes following paediatric outpatient surgery between intravenous and inhalational anaesthesia. There was significant clinical heterogeneity between the included studies, such as types and combinations of drugs, the nature of the surgical procedure and the duration of the anaesthesia, limiting the usefulness of the results.

Fourteen studies (697 children) compared intravenous anaesthesia to inhalational anaesthesia. Six of the studies were for ENT procedures, four were for ophthalmic surgery and four were for other procedures. The risk of postoperative nausea and vomiting (PONV) was considered within a period of 24 hours because the included studies looked at this outcome at different periods of time. The use of intravenous anaesthesia (propofol) for both induction and maintenance of anaesthesia decreased the risk of PONV compared to the use of inhalational anaesthesia (sevoflurane) (OR 2.96; 95% CI 1.35 to 6.49, four studies, 176 children) (Summary of findings for the main comparison). The risk of PONV also decreased for the induction and maintenance of anaesthesia with propofol (+ N2O) versus induction with thiopental and maintenance with halothane and N2O (OR 3.23; 95% CI 3.28 to 23.44, four studies, 176 children); and induction and maintenance with propofol versus induction with thiopentone and maintenance with halothane plus N2O (OR 7.44; 95% CI 2.60 to 21.26, two studies, 87 children) (Summary of findings 2). However, there was heterogeneity between studies in the type and duration of the operations and there were significant problems with the quality of these randomized trials (Summary of findings for the main comparison; Summary of findings 2). The risk of admission or readmission to hospital was not reported in these studies.

The selected studies used different scales and most of them did not describe the postoperative behavioural disturbances criteria. The use of propofol reduced the risk of postoperative agitation compared to inhalational anaesthesia with sevoflurane (OR 2.67; 95% CI 1.14 to 6.23, four studies, 176 children) (Summary of findings for the main comparison). There were no differences between the sevoflurane and propofol groups in the risk of intraoperative and postoperative respiratory and cardiovascular complications (Summary of findings for the main comparison). The types of reported complications were not the same among the studies and they were analysed at different times in the perioperative period. There was no difference between groups for time to discharge from the recovery room and hospital. The different studies used different discharge scoring criteria to complete patient assessments and ensure patient readiness for discharge that were predetermined by institutional standing orders and the duration and nature of the surgery.

So far the evidence does not allow us to recommend the use of propofol alone in the induction or maintenance of anaesthesia in relation to these outcomes.

Overall completeness and applicability of evidence

The results of this review show that the use of propofol may be associated with a reduction in the risk of PONV within the first 24 hour period when compared to sevoflurane or mixed anaesthesia (thiopental with halothane), and a reduction of postoperative behavioural disturbances when compared to sevoflurane; these results were based on studies with high risk of bias and significant clinical heterogeneity, such as different durations and types of procedures and the use of different scales for behavioural assessment.

Quality of the evidence

The drugs used, how they were combined and the duration of the anaesthesia varied greatly in the included studies, which made it difficult to provide a meaningful analysis. Besides, there was no study classified as providing high or moderate quality evidence for the specific outcomes (the risk of PONV and postoperative behavioural disturbances). Most studies probably did not conceal allocation, half of them did not describe the generation of a randomized sequence, and three studies probably did not have blinded outcome assessment. Thus, the results of this review are limited and should be considered with caution.

Potential biases in the review process

We attempted to minimize bias in a number of ways; two review authors assessed eligibility for inclusion, carried out data extraction and assessed risk of bias. Each worked independently. The non-surrogate endpoint in outpatient settings is the risk of admission or readmission to hospital caused by postoperative complications (dehydration, vomiting, agitation, pain), but no studies in this review reported this outcome. The risk of PONV, the risk of postoperative behavioural disturbances, and the risk of intraoperative and postoperative respiratory and cardiovascular complications were probably used as surrogate endpoints. There are a number of reasons why children vomit besides the type of anaesthetic agent, such as type and duration of surgery and the use of opioids. Only six studies in this review used opioids in the perioperative period. In an attempt to reduce bias, this review excluded studies in which participants received antiemetics and premedication with a benzodiazepine because they reduce postoperative vomiting and behavioural changes.

Agreements and disagreements with other studies or reviews

One meta-analysis (Sneyd 1998) reported on paediatric patients and adults undergoing the following types of surgery under general anaesthesia: arthroscopy or minor orthopaedic; breast; eye; facial; oral or dental; ear, nose and throat; gynaecological laparoscopy, other gynaecological; squint; and other or unspecified surgery. The objective of this review was to investigate the incidence of PONV following maintenance of anaesthesia with propofol compared with inhalational agents. This meta-analysis has not been updated since. Thirteen paediatric studies were included. The conclusion of this review (Sneyd 1998) was that patients who received maintenance of anaesthesia with propofol had a significantly lower incidence of PONV when compared with inhalational agents. This lower incidence was regardless of induction agent, the choice of inhalational agent, the presence or absence of nitrous oxide (N2O), the patient's age, or use of opiates.

Authors' conclusions

Implications for practice

From the data available to date, there is insufficient evidence to show that intravenous anaesthesia with propofol during induction and maintenance of anaesthesia reduces the risk of postoperative nausea and vomiting and the risk of behavioural disturbances when compared with inhaled anaesthesia. Overall, the studies have not found any differences in discharge times in relation to the type of anaesthetic used and there was significant heterogeneity in the results. The results of this review should be viewed with caution because of the small number of studies and participants, poor methodological quality of the included studies, differences in the type and duration of surgery and the variability in the combinations of drugs.

Implications for research

Well designed randomized trials and use of other intravenous and inhalation drugs such as ketamine, midazolam, dexmedetomidine, desflurane and isoflurane are needed to allow us to reach a conclusion on the use of intravenous anaesthesia in comparison to inhalation anaesthesia in relation to the primary outcomes (the risk of postoperative nausea and vomiting, behavioural disturbances and the risk of admission or readmission to hospital). Further studies need to compare specific subsets of ambulatory surgery in children, with standardized and validated measurement of outcomes.

Acknowledgements

We thank Jane Cracknell (Managing Editor of the Cochrane Anaesthesia Review Group (CARG)), Humberto Saconato (statistician) and Maria Eduarda dos Santos Puga (librarian) for their help during the preparation of this review. We would also like to thank Mathew Zacharias (content editor), Nathan Pace and Cathal Walsh (statistical editors), Karen Hovhannisyan (CARG Trials Search Co-ordinator), Egidio Barbi, Jerrold Lerman, Vaughan L Thomas and Dominic A Cave (peer reviewers) and Janet Wale (consumer editor) for their help and editorial advice during the preparation of this systematic review.

Data and analyses

Download statistical data

Comparison 1. Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Nausea and vomiting4176Odds Ratio (M-H, Fixed, 95% CI)2.96 [1.35, 6.49]
2 Postoperative behavioural disturbances4176Odds Ratio (M-H, Fixed, 95% CI)2.67 [1.14, 6.23]
3 intraoperative and postoperative respiratory and cardiovascular complications3130Odds Ratio (M-H, Fixed, 95% CI)0.75 [0.27, 2.13]
4 Time to discharge recovery (min)3136Mean Difference (IV, Fixed, 95% CI)3.61 [0.32, 6.90]
5 Time to discharge from hospital (min)283Mean Difference (IV, Random, 95% CI)19.54 [-10.51, 49.59]
Analysis 1.1.

Comparison 1 Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O, Outcome 1 Nausea and vomiting.

Analysis 1.2.

Comparison 1 Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O, Outcome 2 Postoperative behavioural disturbances.

Analysis 1.3.

Comparison 1 Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O, Outcome 3 intraoperative and postoperative respiratory and cardiovascular complications.

Analysis 1.4.

Comparison 1 Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O, Outcome 4 Time to discharge recovery (min).

Analysis 1.5.

Comparison 1 Induction and maintenance: sevoflurane + nitrous oxide (N2O) versus propofol + N2O, Outcome 5 Time to discharge from hospital (min).

Comparison 2. Maintenance: inhalational versus intravenous
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Nausea and vomiting4 Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 Thiopentone\Halothane+N2O vs Propofol\Propofol+N2O4176Odds Ratio (M-H, Fixed, 95% CI)3.23 [1.49, 7.02]
1.2 Thiopentone\Halothane+N2O vs Propofol\Propofol287Odds Ratio (M-H, Fixed, 95% CI)7.44 [2.60, 21.26]
2 Time to discharge from recovery (min)3 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 Thiopentone\Halothane + N2O vsPropofol\Propofol + N2O3125Mean Difference (IV, Random, 95% CI)11.07 [-3.83, 25.97]
2.2 Thiopentone\Halothane +N2O vs Propofol\Propofol287Mean Difference (IV, Random, 95% CI)-1.61 [-10.37, 7.16]
Analysis 2.1.

Comparison 2 Maintenance: inhalational versus intravenous, Outcome 1 Nausea and vomiting.

Analysis 2.2.

Comparison 2 Maintenance: inhalational versus intravenous, Outcome 2 Time to discharge from recovery (min).

Appendices

Appendix 1. Search strategy - MEDLINE (OvidSP)

1     exp Ambulatory Surgical Procedures/ or (surg* adj3 (ambulat* or outpatient* or day or office)).mp.

 2     Anesthesia, Intravenous/ or Anesthesia, Inhalation/ or (an?esthe* adj2 (intravenous or inhalation)).mp. 

3     1 and 2

4     (child* or p?ediat*).af.

5     adult*.af.

 6     3 not (5 not (4 and 5)) 

7     ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (animals not (humans and animals)).sh. 

8     6 and 7

Appendix 2. Search strategy - LILACS via BIREME

("Procedimentos Cirúrgicos Ambulatórios" or "Procedimentos Cirúrgicos Ambulatoriais" OR "Cirurgia no Consultório"  or "Cirurgia do Paciente Externo" or "Cirurgia de Dia" or "Cirurgia Ambulatorial") and ("Anesthesia,Intravenous" or "Anestesia Intravenosa" or "Anestesia Endovenosa" OR "Anesthesia Intravenous" or "Anestesia por Inalação" or "Anestesia por Insuflação" or "Anestesia por Inhalación" or "Anesthesia Inhalation")

Appendix 3. Search strategy - EMBASE (OvidSP)

1     exp ambulatory surgery/ or outpatient/ or (surg* adj3 (ambulat* or outpatient* or day or office)).mp.

2     intravenous anesthesia/ or inhalation anesthesia/ or (an?esthe* adj2 (intravenous or inhalation)).mp.

3     1 and 2

 4     (child* or p?ediat*).af.

5     adult*.af. 

6     3 not (5 not (4 and 5))

7     (randomized-controlled-trial/ or randomization/ or controlled-study/ or multicenter-study/ or phase-3-clinical-trial/ or phase-4-clinical-trial/ or double-blind-procedure/ or single-blind-procedure/ or (random* or cross?over* or multicenter* or factorial* or placebo* or volunteer*).mp. or ((singl* or doubl* or trebl* or tripl*) adj3 (blind* or mask*)).ti,ab. or (latin adj square).mp.) not (animals not (humans and animals)).sh. 

8     6 and 7

Appendix 4. CENTRAL, The Cochrane Library

#1 MeSH descriptor Ambulatory Surgical Procedures explode all trees

#2 (surg* near (ambulat* or outpatient* or day or office))

#3 (#1 OR #2)

#4 MeSH descriptor Anesthesia, Intravenous explode all trees

#5 MeSH descriptor Anesthesia, Inhalation explode all trees

#6 (anaesthe* near (intravenous or inhalation))

#7 (#4 OR #5 OR #6)

#8 (#3 AND #7)

Appendix 5. Study Selection Form

Study eligibility - Intravenous versus inhalational anaesthesia for paediatric outpatient surgery

First authorJournal/Conference Proceedings etcYear
   
RCT/Quasi RCT

Relevant participants

Outpatients under 18 years old receiving general anaesthesia.

Relevant interventions

Inhalational versus intravenous induction.

Maintenance of anaesthesia with a volatile anaesthetic versus intravenous anaesthesia.

Relevant outcomes

Postoperative nausea and vomiting, time to discharge recovery, length of hospital stay, the risk of admission or readmission to hospital, time to induction, time to extubation,postoperative behavioural disturbances, intraoperative and postoperative respiratory and cardiovascular complications

Yes / No / UnclearYes / No / UnclearYes / No / UnclearYes / No* / Unclear 

                

Do not proceed if any of the above answers are ‘No’. If study to be included in ‘Excluded studies’ section of the review, record below the information to be inserted into ‘Table of excluded studies’.
 

                                                    

References to trial

 

Check other references identified in searches. If there are further references to this trial link the papers now & list below. All references to a trial should be linked under one Study ID in RevMan. 

Code each paperAuthor (s)Journal/Conference Proceedings etcYear
A The paper listed above  
B Further papers  

Appendix 6. Data Extraction Form

Intravenous versus inhalational anaesthesia for paediatric outpatient surgery

Code of the paper:
 Outcome Reported in paper (circle)
Risk of postoperative nausea and vomitingYes / No
Time to discharge recoveryYes / No
Length of hospital stayYes / No
Time to inductionYes / No
Time to extubationYes / No
The risk of admission or readmission to hospital ,Yes / No
Postoperative behavioural disturbancesYes / No
Intraoperative and postoperative respiratory and cardiovascular complicationsYes / No
For Continuous data

 

Code of paper

 

 

Outcomes (rename)

 

 

Unit of measurement

Intervention groupControl groupDetails if outcome only described in text
nMean (SD)nMean (SD)  
 Time to discharge recovery          
 Length of hospital stay          
 Time to induction      
 Time to extubation      
For Dichotomous data
Code of paperOutcomes (rename)Intervention group (n)Control group (n)
ARisk of postoperative nausea and vomiting  
 The risk of admission or readmission to hospital  
 Postoperative behavioural disturbances  
 Intraoperative and postoperative respiratory and cardiovascular complications  

Appendix 7. Methodological Quality Form

 

Code of paper:
Random sequence Generation
was the sequence generation adequate? 

 

 

Yes - random number table, computer random number generator, coin tossing, shuffling cards or envelopes, throwing dice, drawing of lots
No - sequence generated by odd or even date of birth, rule based on date, record number, judgement of the clinician, preference of participant, results of tests or availability of the intervention
Unclear - insufficient information

 

Concealment of allocation

Process used to prevent foreknowledge of group assignment in a RCT, which should be seen as distinct from blinding.

was allocation adequately concealed? 
 Yes - central allocation, sequential numbered drug containers of identical appearance or opaque and sealed envelopes
No - open random allocation schedule, envelopes without appropriate safeguards, alternation or rotation, any other unconcealed procedure
Unclear - insufficient information

Blinding of outcome assessment

was there a blinded assessment of outcomes?

 Yes - assessors unaware of the assigned treatment
No - assessors aware of the assigned treatment
Unclear - insufficient information
Incomplete outcome data
were incomplete outcome data adequately addressed? 
 Yes - no missing outcome data or less than 20% and equal for both groups
No - greater than 20% or unequal for comparison groups
Unclear - insufficient information

Selective outcome reporting

State how the possibility of selective outcome reporting was examined by the review authors, and what was found.

Are reports of the study free of suggestion of selective outcome reporting? 
 Yes - the published reports include all expected outcomes
No - not all of the study's pre-specified primary outcomes have been reported or were reported incompletely
Unclear - insufficient information

Other sources of bias

State any important concerns about bias not addressed in the other domains in the tool.

was the study apparently free of other problems that could put it at a high risk of bias? 
 Yes - the study appears to be free of other sources of bias
No - there is at least one important risk of bias
Unclear - insufficient information

Contributions of authors

Conceiving the review: Ana Carolina Ortiz (ACO), Edina Mariko Koga da Silva (EMKS)

Designing the review: ACO, EMKS

Co-ordinating the review: Alvaro Nagib Atallah (ANA)

Undertaking manual searches: ACO

Screening search results: ACO, EMKS

Organizing retrieval of papers: ACO

Screening retrieved papers against inclusion criteria: ACO, EMKS

Appraising quality of papers: ACO, EMKS

Abstracting data from papers: ACO, EMKS

Writing to authors of papers for additional information: ACO

Providing additional data about papers: ACO, EMKS

Obtaining and screening data on unpublished studies: ACO

Data management for the review: ACO

Entering data into Review Manager (RevMan 5.1): ACO, EMKS

RevMan statistical data: ANA

Other statistical analysis not using RevMan: ANA

Double entry of data: (data entered by person one: ACO; data entered by person two: EMKS)

Interpretation of data: ACO, EMKS, ANA

Statistical inferences: ANA

Writing the review: ACO

Providing guidance on the review: Delcio Matos (DM), ANA

Securing funding for the review: ANA

Performing previous work that was the foundation of the present study: None

Guarantor for the review (one author): ACO

Person responsible for reading and checking review before submission: DM

Declarations of interest

Ana C Ortiz: none known

Álvaro N Atallah: none known

Delcio Matos: none known

Edina MK da Silva: none known

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • no sources of support, Not specified.

Differences between protocol and review

We added an additional author to the review team (Delcio Matos). Dr Matos is now the person responsible for reading and checking the review.

The following definitions of outcomes were changed from the protocol (Ortiz 2011).

  1. Time to discharge from recovery room: defined as time in minutes from recovery room to return to the postoperative ward, changed to time in minutes from discontinuation of anaesthetic to achieve the criteria for discharge from recovery room.

  2. The length of hospital stay: defined as time in minutes from admission to discharge, changed to time to discharge from hospital defined as time in minutes from discontinuation of anaesthetic to discharge. This occurred because we did not find the length of hospital stay outcome and found two articles (Baykara 1998; Guard 1998) with time to discharge from hospital that seemed more suitable.

  3. We deleted the outcomes: time to induction and time to extubation.

  4. We added the following sentence in the methods section: "We excluded participants who received premedication with benzodiazepines and antiemetics".

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Annila 1999

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 90 children
Generation of allocation: Each child was randomly allocated by computer-based random listing to one of three groups. Blinded assessment of treatment allocation: the Holter-ECG recordings were analysed separately by a physician who was unaware of the induction method. Withdrawals:reported four patients.The Holter-ECG recordings were not readable due to technical disturbances in two patients in groups PA and H. Follow up: The study period extended from the application of the Holter-ECG leads until 3min after tracheal intubation, after which anaesthesia was continued in accordance with the preferences of the consultant anaesthetist.
Participants90 patients. Sex: Group TS -15 male and 15 female; Group PA - 17 male and 13 female; Group H - 19 male and 11 female. Age (mean): Group TS - 1.9 years; Group PA - 2.1 years; Group H - 2.0 years. Inclusion criteria: children (ASA I-II) aged 1–3 years undergoing adenoidectomy in the ENT unit participated in the study. Exclusion criteria: not reported
Interventions

In group TS, the anaesthesia was induced with thiopentone and suxamethonium; In group PA, was with alfentanil and propofol and group H was induced using 5 vol% inspired halothane with 70% nitrous oxide in oxygen with facemask

In all groups after tracheal intubation, anaesthesia was maintained with 1–3 vol% halothane with 70% nitrous oxide in oxygen delivered via a Bain coaxial breathing system

OutcomesThe incidence of dysrhythmias (supraventricular extrasystole, bradycardia) and desaturation (less than 92%) during induction of anaesthesia
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk Quote: "Each child was randomly allocated by computer based random listing to one of three groups"
Allocation concealment (selection bias)Unclear riskComment: no information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Tracheal intubation was always preformed by the same senior anaesthetist , who was unaware of the induction method"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "the Holter-ECG recordings were analysed separately by a physician who was unaware of the induction method."
Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "The Holter-ECG recordings were not readable due to technical disturbances in two patients in groups PA and H"
Selective reporting (reporting bias)Low riskQuote:"Outcomes: The incidence of dysrhythmias( supraventricular extrasystole,bradycardia) and desaturation (less than 92%)during induction of anaesthesia."
Other biasLow riskComment: the study appears to be free of other sources of bias

Baykara 1998

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 40 children
Generation of allocation: not reported. Allocation concealment: not reported. Blinded assessment of treatment allocation: not reported. Withdrawals: none. Follow up: The time of discharge and time of extubation were recorded. The incidence of side effects (laryngospasm, agitation, vomiting) were recorded in the recovery room and the incidence of vomiting was recorded 24hrs after surgery
Participants40 patients. Sex: Group propofol - 15 male and 5 female; Group sevoflurane - 14 male and 6 female. Age (mean): Group Propofol - 6.54 years; Group sevoflurane - 6.6 years. Inclusion criteria: children, ASA I, aged 3–12 years undergoing tonsillectomy and\or adenoidectomy outpatient surgery. Exclusion criteria: not reported
Interventions

Group Propofol: induction was achieved with propofol and maintained by propofol + 60% N2O

Group Sevoflurane: induction was achieved with 4-7% sevoflurane + 60% N2O and anaesthesia was maintained by 2-3% sevoflurane + 60% N2O

Outcomes

Time to extubation

Time to discharge from hospital

Time to discharge from recovery room

The incidence of side effects during recovery:

  • Laryngospasm

  • Agitation

The incidence of vomiting:

  • In the recovery room

  • 24hrs after surgery

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: no information provided
Allocation concealment (selection bias)Unclear riskComment: no information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: probably not done
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)High riskComment: the study did not describe the definition of postoperative agitation
Other biasLow riskComment: the study appears to be free of other sources of bias

Borgeat 1990

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 40 children. Generation of allocation: Children were randomly allocated in an open study to either group A (propofol) or group B (thiopental/halothane). Allocation concealment: not reported. Blinded assessment of treatment allocation: not reported. Follow up: interval between end of drug administration and extubation and discharge from the recovery room
Participants40 patients. Sex: Group propofol - 9 male and 11 female; Group Thiopental/halothane - 8 male and 12 female. Age (mean): Group Propofol - 6.09 years and Group Thiopental\Halothane - 5.11 years. Inclusion criteria: children (ASA I) aged 3-8 years undergoing short elective ENT procedures participated in the study. Exclusion criteria: included known allergy to the anaesthetic drugs or their constituents, a history of previous adverse experience to general anaesthesia, the presence of psychomotor retardation, and general anaesthesia with halothane within the last 3 months
InterventionsIn group A (propofol), the anaesthesia was induced with propofol and immediately followed by a continuous infusion of propofol and N2O 66% and in Group B (Thiopental\Halothane) patients were given thiopental with maintenance of anaesthesia provided by halothane (0.5%-1.5%) + N2O 66%
Outcomes

Time to extubation (minutes): the interval between the end of the administration of propofol or halothane and extubation

Time to discharge from recovery room (minutes): the time between the end of the administration of propofol or halothane and the completion of the criteria for discharge from the recovery room

The incidence of postoperative nausea and vomiting

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "Children were randomly allocated in an open study to either group A (propofol) or group B (thiopental/halothane)."

Comment: I do not know  if it was done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: probably not done
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)Low riskOutcomes: "Time to extubation (minutes): the interval between the end of the administration of propofol or halothane and extubation; time to discharge from recovery room (minutes): the time between the end of the administration of propofol or halothane and the completion of the criteria for discharge from the recovery room and the incidence of postoperative nausea and vomiting."
Other biasLow riskComment: the study appears to be free of other sources of bias

Cohen 2003

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 53 children. Generation of allocation: not reported. Blinded assessment of treatment allocation: an observer blinded to the anaesthetic technique recorded degree of agitation. Withdrawals: none. Follow up: The degree of agitation was recorded in the Postanaesthesia Care Unit (PACU). The time to extubation was recorded. Parents were contacted 24 hours after surgery to follow up on the incidence of agitation and pain at home
Participants53 patients. Age (mean): Group Propofol - 15.3 months; Group Sevoflurane - 12.9 months. Gender: Group Propofol - 18\8; Group Sevoflurane 18\9. Inclusion criteria: healthy children, aged 2-36 months, ASA Physical Status I or II scheduled for ambulatory surgical procedures. Exclusion criteria: less than 40 weeks postconceptional age, signs of developmental delay
Interventions

The anaesthesia was induced with 60% N2O and 8% sevoflurane in all cases

Group Propofol (27 participants): anaesthesia was maintained with propofol and 60% N2O

Group Sevoflurane (26 participants): anaesthesia was maintained with sevoflurane (1.5 to 2.5%) and 60% N2O

Outcomes

Time to extubation

Degree of agitation: scored on a 3-point scale

1 = calm

2 = agitated but consolable

3 = severely agitated, inconsolable

The incidence of vomiting in the recovery room

Time to discharge from the PACU

NotesAnalgesia was supplied by either a caudal block with bupivacaine 0.25% or fentanyl ,according to surgical procedure. There was no significant difference between the sevoflurane and propofol groups in the type of analgesia technique that was used during surgery
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote:"...were randomized to receive sevoflurane or propofol for maintenance anaesthesia."

Comment: I do not know if it was done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "...an observer blinded to the anaesthetic technique recorded degree of agitation..."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)High riskThe pre-specified "Time to discharge from the PACU" outcome was not reported in the results
Other biasLow risk Comment: the study appears to be free of other sources of bias

Cohen 2004

MethodsDesign: randomized, open-label, comparative, parallel-group study. Single-centre. Period: not reported. Sample size: 56 children. Generation of allocation:not reported. Blinded assessment of treatment allocation:assessment was performed by investigator blinded to the anaesthetic technique. Withdrawals:none. Follow up:the time to extubation and time to complete recovery were recorded.In addition,measurement of ionised calcium and ionised magnesium concentrations were collected at baseline; at 5, 10, 15 and 30 min during anaesthesia; at the end of study drug administration and 30 min after the end of anaesthesia and telephone contact was made with the parents after 24 hours to determine if any adverse events occurred after discharge
Participants56 patients. Age (mean): Group Propofol - 14.7 months; Group Sevoflurane - 13.2 months. Inclusion criteria: children younger than 3 years of age classified under ASA Physical Status I or II scheduled for ambulatory surgical procedures Exclusion criteria: not reported
Interventions

In all patients, anaesthesia was induced with nitrous oxide (60%), oxygen and sevoflurane (8%)

Group Propofol: the anaesthesia was maintained with propofol and nitrous oxide 60%
Group Sevoflurane: the anaesthesia was maintained with sevoflurane (1.5-2.5%) + nitrous oxide 60%

Outcomes

Time to extubation

Measurement of ionised calcium and ionised magnesium concentrations: were collected at baseline; at 5,10,15 and 30 min during anaesthesia; at the end of study drug administration and 30 minutes after the end of anaesthesia

The incidence of postoperative vomiting

NotesPatients undergoing lower body procedures received a caudal block with 0.25% bupivacaine and patients undergoing eye and airway surgeries received fentanyl. The use of regional blocks and fentanyl was comparable between the propofol and sevoflurane groups
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "...were randomly assigned to receive either propofol or sevoflurane."

Comment: I do not know if it was done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Assessment (time to extubation and time to complete recovery) was performed by investigator blinded to the anaesthetic technique"
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Crawford 1998

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 60 children
Generation of allocation: "They were assigned using a table of random numbers to one of three anaesthetic regimens". Blinded assessment of treatment allocation:"postoperative data were gathered by an investigator who was unaware of the anaesthetic regimen administered".Withdrawals:data from six children who received regional anaesthesia after induction of anaesthesia were excluded from the analysis.Follow up:recovery scores were assessed on arrival in the PACU and at 5,10,20,30,40,50 and 60 minutes after the end of anaesthesia.The incidence of emesis were determined both in the PACU and for the first 24h after discharge
Participants54 patients. Age (mean): Group Propofol- 6.7 years; Group Propofol+N2O -6.2 years; Group Thio\Halothane -6.1 years. Inclusion criteria: children aged 3-12 years presenting for elective outpatient surgery lasting approximately one hour. Exclusion criteria: if they had a history of cardiorespiratory, gastrointestinal or central nervous system disease, or if they requested either premedication or an inhalational induction
Interventions

Group Propofol: anaesthesia with propofol

Group Propofol + N20 : propofol and N2O 70%

Group Thiopental\Halothane: thiopental followed by halothane and N2O 70% in oxygen for maintenance

Outcomes

The incidence of postoperative emesis:

  • In the PACU

  • 24h after discharge

Time to extubation: time from discontinuation of anaesthetic until extubation of the trachea

Time to discharge from PACU: time from discontinuation of anaesthetic until full recovery (modified Aldrete score ≥ 8)

NotesWhen appropriate, ilioinguinal\iliohypogastric nerve blocks (bupivacaine 0,25%) were administered at the end of surgery. There were no statistically significant differences in the number of children who received iliohypogastric\ilioinguinal nerve blocks
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "They were assigned using a table of random numbers to one of three anaesthetic regimens"

Comment: done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "Postoperative data were gathered by an investigator who was unaware of the anaesthetic regimen administered"

Comment: done

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Quote: "Data from six children who received regional anaesthesia after induction of anaesthesia were excluded from the analysis"

Comment: missing outcome data have similar reasons

Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Glaisyer 2005

MethodsDesign: the study design was single-blind. Single-centre. Period: not reported. Sample size: 21 children
Generation of allocation: "For the first procedure, children were randomized to receive one of two anaesthetic techniques; the other technique was used subsequently and both techniques were therefore studied by within-patient comparisons". Blinded assessment of treatment allocation:"children, parents, and recovery staff were unaware which technique had been used, but, during the procedure itself, the two anaesthetic techniques could not be disguised". Withdrawals: Only eight participants were evaluated at the time which were children ready for discharge from the hospital. Follow up: The primary outcome variable was the time taken to achieve recovery discharge criteria after the end of procedure. In the recovery room, distress behaviour, bradycardia, oxygen saturations < 94% were assessed
Participants21 patients. The mean age of the patients was 6 years and 6 months. Inclusion criteria: children, aged 2 to 10 years, were recruited if they were scheduled to undergo 2 similar painful procedures separated by no more than 2 week. Exclusion criteria:Patients were excluded if they were ASA physical status grade III, were unable to respond appropriately to verbal commands, or if they had been in pain, been nauseated, or received sedative or analgesic medication within the previous 12 hours
Interventions

In all groups, anaesthesia was induced with propofol

Anaesthesia was maintained either by:

Group PR: remifentanil with propofol

Group PSN: inhaled sevoflurane with nitrous oxide 66%

Outcomes

Distress behaviour was assessed using a simple scoring system, modified from that of Hannallah 1987, in which crying, moving and agitation were scored separately (0, 1, or 2, maximum distress score 6) in the recovery room

The incidence of nausea or\and vomiting in the recovery room

The time at which children were ready for discharge from the recovery ward (after the end of procedure) was recorded

Bradycardia (< 60 beats/min) occurred during recovery

Desaturation:oxygen saturations < 94% during or after anaesthesia

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "For the first procedure, children were randomized to receive one of two anaesthetic techniques; the other technique was used subsequently and both techniques were therefore studied by within-patient comparison"

Comment: Insufficient information about the sequence generation

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Quote: "Children, parents, and recovery staff were unaware which technique had been used, but, during the procedure itself, the two anaesthetic techniques could not be disguised"

Comment: Probably not done

Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "Children, parents, and recovery staff were unaware which technique had been used, but, during the procedure itself, the two anaesthetic techniques could not be disguised"

Comment: Problably done

Incomplete outcome data (attrition bias)
All outcomes
High riskOnly eight participants were evaluated at the time which they were ready for discharge from the hospital
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasHigh risk

Quote: "...the behavior of children varies from day to day and, as an example, one child who was disturbed after propofol was calm on subsequent occasions with the same technique."

Comment: Probably done

Guard 1998

MethodsDesign: RCT. Single centre. Period: not reported. Sample size: 50 children
Generation of allocation: "Randomization was achieved using random number tables prepared in advance of commencing the study". Blinded assessment of treatment allocation:the data were recorded by a research nurse who was blinded to the anaesthetic assignment. Withdrawals:none. Follow up: During postoperative recovery, time to extubation and time to recovery were recorded. All adverse events during emergence (haemoglobin oxygen desaturation and vomiting) and recovery (pain and vomiting) until discharge from hospital were recorded. On the day after surgery, the children's parents were interviewed by phone to determine the presence of adverse events (nausea and vomiting)
Participants50 patients. Sex: Group Sevoflurane - 23 male and 2 female; Group Propofol - 22 male and 3 female. Age (mean): Group Sevoflurane - 4.6 years and Group Propofol - 4.2 years. Inclusion criteria:children, ASA I-II, two to eight years of age, fasted, scheduled for urological surgery as outpatients Exclusion criteria: not reported
Interventions

Group Sevoflurane: anaesthesia was induced using stepwise increases in the inspired concentration of sevoflurane
(2% increments every two breaths to a maximum inspired concentration of 8%) and N2O 70% and was maintained with an end-tidal sevoflurane concentration of 2.5% + N2O 70%;

Group Propofol: anaesthesia was with propofol and N2O 70%

Outcomes

Haemoglobin oxygen desaturation < 90%:

  • during emergence

  • during recovery

Laryngospasm, bronchospasm, excitation:

  • during emergence

Vomiting:

  • during emergence

  • during recovery until discharge from hospital

  • day after surgery (24h)

Time to extubation: the interval from discontinuation of the anaesthetic until extubation

Time to recovery: time from discontinuation of the anaesthetic to eligibility for discharge from the recovery room (defined as a modified Aldrete score of 8)

Time to discharge from hospital: time from discontinuation of anaesthetic to eligibility for discharge from the hospital

Notes"Before surgical incision, a lumbar or caudal epidural block was established in all children using bupivacaine 0.175% without epinephrine."
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "Randomization was achieved using random number tables prepared in advance of commencing the study."

Comment: probably done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "...were recorded by a research nurse who was blinded to the anaesthetic assignment."

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasHigh risk

Quote: "The relatively small incidence of postoperative vomiting in this study may be attributed to the avoidance of gastric inflation before tracheal intubation, the opioid-sparing action of the epidural blocks and the postanaesthetic policy of elective oral fluid administration."

Comment: probably done

Gurkan 1999

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 40 children. Generation of allocation: "patients were randomly allocated (using a random number table) to two groups of 20 patients". Blinded assessment of treatment allocation:"the timing of each vomiting episode, was recorded by a blinded nurse observer". Withdrawals: none. Follow up: "...during anaesthesia and postoperative until the day after surgery (at home). The parents were contacted the day after surgery by a blinded nurse and reported vomiting or any other surgical or anaesthesia-related problems."
Participants40 patients. Sex: Group 1 - 11 male and 9 female; Group 2 - 13 male and 7 female. Age (mean): Group 1 - 8 years and Group 2 - 8 years. Inclusion criteria: children aged 3-15 years, ASA I presenting for strabismus surgery. Exclusion criteria: patients were excluded if they had an allergy to any of the drugs to be used or they had a symptomatic medical illness
InterventionsIn group 1, the anaesthesia was induced with propofol, and maintained with a propofol and N2O 66%. In group 2, anaesthesia was induced and maintained with N2O 66% and sevoflurane
Outcomes

The incidence of nausea and\or vomiting before the patient left Postanaesthesia Care Unit (PACU), before discharge from the hospital and the day after surgery.

The incidence of oculo cardiac reflex: defined as an acute decrease in heart rate of 20% or greater associated with traction on an eye muscle

The incidence of agitation in the PACU

Bradycardia during induction

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned using a table of random numbers to 2 groups of 20 patients."
Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "The timing of each vomiting episode,was recorded by a blinded nurse observer."

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)High riskComment: to evaluate the presence of agitation, did not include any score
Other biasLow riskComment: the study appears to be free of other sources of bias

Hannallah 1994

MethodsDesign: open, comparative, parallel, randomized study. Single-centre. Period: not reported. Sample size: 100 children. Generation of allocation: "... were randomized to receive one of four possible induction/maintenance combinations". Allocation concealment: not reported. Blinded assessment of treatment allocation: "Recovery from anaesthesia was objectively evaluated in the Post Anaesthesia Care Unit (PACU) by a research nurse, who was not aware of the anaesthetic sequence". Withdrawals: 18 patients were not evaluated regarding for the incidence of vomiting at home. Follow up: The time to induction, time to extubation, time to recovery from PACU were recorded. The incidence of vomiting in the hospital and at home (24hrs after surgery)
Participants100 patients. Age (mean): Group 1 - 7.6 years and Group 2- 7.1 years; Group 3 - 6.3 years; Group 4 - 5.2 years. Inclusion criteria: children, ASA I or II, 3-12 years old undergoing ambulatory surgical procedures. Exclusion criteria: not recorded
Interventions

Group 1 (PROP/PROP) received propofol
Group 2 (PROP/HAL) received propofol and halothane 0.5-2% inspired concentration

Group 3 (THIO/HAL) received thiopentone and halothane 0.5-2%

Group 4 (HAL/HAL) received halothane for both anaesthesia induction and maintenance

Nitrous oxide (60-70%) was combined with oxygen as the carrier gases in all cases

Outcomes

The incidence of hypotension (defined as two consecutive systolic blood pressure readings that were at least 20% below baseline) during the anaesthesia induction and maintenance

Time to induction of anaesthesia

Time to extubation: was calculated from the moment propofol or halothane was turned off until tracheal extubation

Time to recovery: time from discontinuation of anaesthetic agents to reach a score of six on the Steward recovery scale. The Steward recovery scale is based on assessment of three criteria (consciousness, airway, and movement), where a score of 0 to 2 is assigned to each criterion with a maximum total score of 6 when the child is fully awake

The incidence of nausea or vomiting:

  • in the hospital

  • at home ( 24hrs after surgery)

Notes"At the conclusion of surgery, bupivacaine 0.25% was infiltrated around the incision site when appropriate..."
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "... were randomized to receive one of four possible induction/maintenance combinations."

Comment: I do not know if it was done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Recovery from anaesthesia was objectively evaluated in the Post Anaesthesia Care Unit (PACU) by a research nurse, who was not aware of the anaesthetic sequence..."
Incomplete outcome data (attrition bias)
All outcomes
High risk

Quote: "The incidence of vomiting at home for the 82 patients who were successfully contacted by phone 24 hr after surgery..."

Comment: it does not describe if the loss to follow up of postoperative vomiting was similar in the groups

Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Madan 2001

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 55 children. Generation of allocation: they were randomly allocated (using a random number table) to receive either TIVA with propofol (group P) or inhalational anaesthesia using halothane in 70% nitrous oxide and oxygen (group H). Blinded assessment of treatment allocation: recovery was assessed by the recovery room nurse (independent, blinded). Withdrawals: none. Follow up: until discharge from the recovery area
Participants55 patients. Sex: Group P(propofol) - 16 male and 13 female; Group H (halothane) - 14 male and 12 female. Age (mean): Group P - 2.36 years and Group H - 2.42 years. Inclusion criteria: children aged less than 5 years, ASA I or II, presenting for non-invasive diagnostic ophthalmic procedures. Exclusion criteria were: respiratory tract infection, difficult airway, congenital abnormalities, increased intracranial or intraocular pressure and known or suspected allergy to egg and/or propofol
InterventionsIn group P (29 participants), anaesthesia was induced and maintained with propofol. In group H (26 participants), anaesthesia was induced and maintained with halothane 2-4% + N2O 70%
Outcomes

All side effects and adverse reactions in the perioperative period were recorded (laryngeal spasm, haemodynamic changes/dysrhythmias)

The time taken for induction (from injection of bolus to tolerance of eye speculum)

The time to recovery (from stoppage of infusion to OAA/S score 5). All children were discharged to the care of the parents at an Observer Assessment of Alertness/Sedation Scale (OAA/S) score of 5 at each level and only if no evidence of obstruction or respiratory difficulty was present

The episodes of restlessness, incessant crying or nausea/vomiting

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "They were randomly allocated (using a random number table) to receive either TIVA with propofol (group P) or inhalational anaesthesia..."
Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Recovery was assessed by the recovery room nurse (independent, blinded)."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasHigh risk"... usage of a different recovery endpoint scale (OAA/S score, 5 at each level) could have accounted for slight variability in recovery times compared with that reported in the literature."

Picard 2000

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 50 children. Generation of allocation: "A random numbers table was used to assign children to receive either propofol (group P) or sevoflurane anaesthesia (group S)". Blinded assessment of treatment allocation: "All observations and measurements were recorded by an independent anaesthesiologist who was blinded to the anaesthetic given". Withdrawals: "..two children were excluded because of postoperative bleeding and two others because of missing data. Thus, data from 24 children receiving sevoflurane and 22 children receiving propofol were analysed". Follow up: until discharge from the recovery area
Participants46 patients. Sex: Group P (propofol) - 13 male and 9 female; Group S (sevoflurane) - 12 male and 12 female. Age (mean): Group P - 5.2 years and Group S - 6 years. Inclusion criteria: healthy children (ASA I or II) undergoing elective tonsillectomy. Exclusion criteria: children who were screaming before arrival in the operating room were excluded from the study
InterventionsIn group P, anaesthesia was induced with a bolus of propofol, and maintained with a propofol and N2O 60%. In group S, anaesthesia was induced and maintained with sevoflurane 7 vol% and 2–3 vol%, respectively + N20 60%
Outcomes

The time to extubation (from the end of anaesthesia to extubation)

Time spent in the recovery room

The incidence of adverse events such as nausea, vomiting, laryngospasm and bronchospasm were noted and scored as follow: 1=mild, 2=moderate, 3=severe

The assessment of postoperative agitation was made using a four-point scale: 1=calm; 2=not calm but could be easily calmed; 3=moderately agitated or restless; 4=combative, excited or disoriented. Grades 1 and 2 were considered non-problematic behaviour, and grades 3 and 4 were considered to indicate agitation

NotesAt the completion of surgery, the operative site was infiltrated with bupivacaine 0.25% for postoperative analgesia
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "A random numbers table was used to assign children to receive either propofol (group P) or sevoflurane anaesthesia (group S)"
Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All observations and measurements were recorded by an independent anaesthesiologist who was blinded to the anaesthetic given"
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Quote: "Of the 50 patients enrolled in the study, two children were excluded because of postoperative bleeding and two others because of missing data. Thus, data from 24 children receiving sevoflurane and 22 children receiving propofol were analysed"

Comment: missing outcome data balanced in numbers across intervention groups,with similar reasons for missing data across groups

Selective reporting (reporting bias)Low riskComment: the study appears to be free of reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Reimer 1993

MethodsDesign: RCT. Single-centre. Period: not reported. Sample size: 75 children
Generation of allocation: "Patients were assigned to receive one of three anaesthetic regimens...". Allocation concealment: not reported. Blinded assessment of treatment allocation: "In the recovery room, recovery and emesis were observed by trained, recovery room nursing staff who were blinded to the group assignment". Withdrawals:discharge was delayed for surgical reasons in one patient in the P/N20 group. Recovery data relating to times of discharge and emesis data after discharge in this patient were excluded from analysis. Follow up: the incidence of emesis were observed in the recovery room and after discharge from hospital was recorded by telephone interview for the following intervals; during transport home, during the first 12 hr after discharge, and during the second 12 hours after discharge
Participants75 patients. Sex: Group Thio\Halothane - 7 male and 18 female; Group Propofol\O2 - 11 male and 14 female; Group Propofol\N2O - 9 male and 16 female. Age (mean): Group Thio\Halothane - 6.2years and Group Propofol\O2 - 6.3 years; Group Propofol\N2O - 5.1years. Inclusion criteria: healthy children, ASA physical status I or II, aged 2-12 years, scheduled for elective outpatient, strabismus surgery. Exclusion criteria: patients were excluded if they had an allergy to any of the drugs to be used or they had a symptomatic medical illness
InterventionsGroup(T\H): thiopentone followed by halothane 0.5-1.5% and nitrous oxide 70%/oxygen for maintenance
Group (P\O2): propofol
Group (P\N2O): propofol and nitrous oxide
Outcomes

The incidence of emesis (Involuntary retching was scored as emesis but nausea was not evaluated):

after discharge from hospital was recorded by telephone interview for the following intervals:during transport to home, during the first 12 hours after discharge, and during the second 12 hours after discharge. Overall emesis was defined as the total incidence of emesis at any of the study intervals

The length of stay in the PACU and the day care unit (DCU) were recorded

The time from arrival in the postanaesthetic recovery room (PACU) until a score of six was recorded as the recovery time (the Steward 6 recovery score)

The time to extubation was measured from the time of discontinuation of anaesthetic agents to the time of tracheal extubation

NotesAll patients were observed for two hours after discontinuation of the anaesthetic by recovery room nursing staff
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: " Patients were assigned to receive one of three anaesthetic regimens..."

Comment: insufficient information about the sequence generation

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Parents and the patient were not informed of the anaesthetic technique until the conclusion of the telephone interview."
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "In the recovery room, recovery and emesis were observed by trained, recovery room nursing staff who were blinded to the group assignment."
Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Discharge was delayed for surgical reasons in one patient in the P/N20 group. Recovery data relating to times of discharge and emesis data after discharge in this patient were excluded from analysis."
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Viitanen 1999

MethodsDesign: RCT. Two centres: the Helsinki University Central Hospital and the Central Hospital of Seiniijoki. Period: not reported. Sample size: 52 children. Generation of allocation: "Each child was randomly assigned, by computer-based random numbers listing, to receive intravenous induction with propofol (propofol group) or inhalational induction with sevoflurane 8% (inspired concentration) via a face mask (sevoflurane group)". Blinded assessment of treatment allocation: Intubation was performed and assessed by an anaesthesiologist blinded to the method of induction. Recovery was assessed by a trained nurse who was unaware of the induction method. Withdrawals: "All the questionnaires except for two from the propofol group were returned". Follow up: in the recovery room were recorded The Pain\Disconfort Scale to evaluate the quality of emergence from anaesthesia. In addition, the time to achieve discharge criteria were recorded. A postoperative questionnaire was given to the parents who were asked to record the well-being (pain, nausea, tiredness, drinking ability, sleep) of the child at home until 24hr after surgery
Participants52 patients. Age (mean): Group Propofol - 27 months and Group Sevoflurane - 24 months. Inclusion criteria: children, ASA physical status I or II, aged 1-3 years, presenting for ambulatory adenoidectomy with or without myringotomy. Exclusion criteria: patients were excluded if they had an allergy to any of the drugs to be used or they had a symptomatic medical illness
Interventions

Group Propofol: intravenous induction with propofol

Group Sevoflurane: inhalational induction with sevoflurane 8% (inspired concentration) via a face mask

In both groups anaesthesia was continued with sevoflurane in nitrous oxide 70% in oxygen

Outcomes

The incidence of nausea and\or vomiting:

  • Recovery room

  • Home (until 24hr after surgery)

The haemodynamic responses to induction and intubation:

Bradycardia

Hypontension

Time to extubation was defined as the time from discontinuation of sevoflurane and nitrous oxide to recovery of spontaneous breathing and removal of the tracheal tube

The Pain/Discomfort scale according to Hannallah 1987 is was used to evaluate the quality of emergence from anaesthesia. If the total score on the Pain/Discomfort scale at any evaluation point exceeded the sum of three, emergence was regarded as delirious

Time to recovery: time from discontinuation of sevoflurane to achieve discharge criteria

The incidence of laryngospasm in the recovery room

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Each child was randomly assigned, by computer-based random numbers listing, to receive ..."
Allocation concealment (selection bias)Unclear riskComment: no information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Recovery was assessed by a speciaUy trained nurse who was unaware of the induction method."
Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "All the questionnaires except for two from the propofol group were returned."
Selective reporting (reporting bias)Low riskComment: the study appears to be free of the reporting bias
Other biasLow riskComment: the study appears to be free of other sources of bias

Viitanen 1998

MethodsDesign: RCT. Single centre. Period: not reported. Sample size: 93 children
Generation of allocation: Each child was allocated randomly to one of three groups using a computer-generated random number table. Blinded assessment of treatment allocation: "In the recovery room, the recovery and behaviour of the children were assessed by the same nurse, who was unaware of the induction method used". Withdrawals: none. Follow up: in the recovery room were recorded sedation, crying, restlessness (motor activity) and agitation using an open scale scoring from 1-9. Scores were recorded at 10 minute intervals for the first hour and then every 30 minutes until discharge. In addition, the time to achieve discharge criteria from the recovery room were recorded. A postoperative questionnaire was given to the parents who were asked to record the well-being (pain, nausea, tiredness, drinking ability, sleep) and the behaviour of the child at home until 24hr after discharge
Participants93 patients. The three groups were comparable in age, weight, duration of anaesthesia and surgery. Inclusion criteria: children, ASA physical status I or II, aged 1-3 years, presenting for ambulatory adenoidectomy. Exclusion criteria: not reported
InterventionsGroup TH (31 participants) received thiopental 5mg\kg, group PAH (31 participants) received propofol and alfentanil and Group HH (31 participants) 5% inspired halothane for induction of anaesthesia.In all groups, anaesthesia was maintained with 1-3% halothane and 70% nitrous oxide delivered in oxygen
Outcomes

Sedation, crying, restlessness (motor activity) and agitation were evaluated using an open scale scoring from 1-9 (best to worst). If the child at any point of evaluation scored six or more for crying, restlessness or agitation, recovery from anaesthesia was considered delirious

Time (from discontinuation of halothane ) taken to achieve the criteria for discharge from the recovery room was recorded

The incidence of vomiting in the recovery room

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Each child was allocated randomly to one of three groups using a computer-generated random number table ..."
Allocation concealment (selection bias)Unclear riskComment: no information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "In the recovery room, the recovery and behaviour of the children were assessed by the same nurse, who was unaware of the induction method used."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)High risk

Quote: "A postoperative questionnaire was given to the parents who were asked to record the well-being (pain,nausea, tiredness, drinking ability, sleep) and the behaviour of the child at home until 24hr after discharge."

"At home, the well-being and recovery of the children were similar in all groups."

Comment: However, the data of these endpoints were not shown in the study

Other biasLow riskComment: the study appears to be free of other sources of bias

Weir 1993

  1. a

    ASA = American Society of Anesthesiologists; ECG = electrocardiography; ENT = ears, nose and throat; PACU = postanaesthesia care unit; RCT = randomized controlled trial

MethodsDesign: RCT. Single centre. Period: not reported. Sample size: 78children
Generation of allocation: "Patients were assigned randomly to one of two groups". Allocation concealment: not reported. Blinded assessment of treatment allocation: "The incidence of nausea, retching,or vomiting was recorded by a blinded observer". Withdrawals: none. Follow up: in the recovery room were recorded the incidence of nausea, retching, or vomiting. The family was contacted after 24 hours by telephone to determine the incidence of nausea and\or vomiting at home
Participants78 patients. Sex: Group A (Halothane) - 14 male and 25 female; Group B (Propofol) - 19 male and 20 female. Age (mean): Group A - 5.4 years and Group B - 5.4 years. Inclusion criteria: children, ASA class I or II, aged between 3 and 12 years and undergoing strabismus surgery as outpatients. Exclusion criteria: not reported
InterventionsThe anaesthesia was induced in all patients by inhalation of nitrous oxide, oxygen, and halothane via a mask. In group A (halothane), anaesthesia was maintained using halothane. The group B (propofol) received propofol; both groups received 66% nitrous oxide in oxygen throughout surgery
Outcomes

The incidences of both nausea and vomiting and vomiting alone occurring in the first 24 hours postoperatively

Time to discharge

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "Patients were assigned randomly to one of two groups"

Comment: I do not know if it was done

Allocation concealment (selection bias)High riskComment: probably not done
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: probably not done
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "...the incidence of nausea, retching,or vomiting was recorded by a blinded observer"
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no missing outcome data
Selective reporting (reporting bias)High risk

Quote: "Patient readiness for discharge was assessed by standard criteria; namely the patient being alert and oriented, at least 1.5 hours after tracheal extubation, and more than 1 hour after the administration of opioid analgesia"

Comment: the time to discharge was poorly defined

Other biasLow riskComment: the study appears to be free of other sources of bias

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Cheng 1998The study was classified as high risk of bias for randomization and blinding
Davis 1991Compared the maintenance of anaesthesia with and without opioid (halothane and N2O versus halothane and N2O and alfentanil)
Davis 1997All children in the study were premedicated with midazolam. The use of premedication can change the following outcome: time to emergence, the incidence of nausea or vomiting or both and the incidence of agitation
Elliott 2002The study compared inhalation anaesthesia (induction and maintenance with sevoflurane) versus balanced anaesthesia (induction with propofol and maintenance with halothane). However, the inhalational agents were different and this complicates the analysis of data
Elliott 2003The study compared inhalation anaesthesia (induction and maintenance with sevoflurane) versus balanced anaesthesia (induction with propofol and maintenance with halothane). However, the inhalational agents were different and this complicates the analysis of data
Konig 2009Patients received antiemetic: dexamethasone
Kotiniemi 1996All children in the study were premedicated with diazepam and meperidine. The use of premedication can change the following outcome: time to emergence, the incidence of nausea and vomiting and the incidence of agitation
Kubo 2001Some children in the study were premedicated with midazolam. The use of premedication can change the following outcome: time to emergence, the incidence of nausea and vomiting and the incidence of agitation
Laiq 2008The study compared inhalation anaesthesia (induction and maintenance with sevoflurane + N2O) versus balanced anaesthesia (induction with propofol and maintenance with halothane + N2O). However, the inhalational agents were different and this complicates the analysis of data
Martin 1993All children in the study were premedicated with diazepam and meperidine. The use of premedication can change the following outcome: time to emergence, the incidence of nausea and vomiting and the incidence of agitation
Moore 1994The outcomes were not relevant: time from end of surgery to eye opening; time from end of surgery to responding to commands; quality of anaesthesia (good, fair or poor)
Moore 2003The study compared inhalation anaesthesia (induction and maintenance with sevoflurane) versus balanced anaesthesia (induction with propofol and maintenance with halothane). However, the inhalational agents were different and this complicates the analysis of data
Oh 2010The study compared the maintenance of sevoflurane anaesthesia with or without opioid
Ozer 2001The children in the study were premedicated with midazolam. The use of premedication can change the following outcome: time to emergence, the incidence of nausea and vomiting and the incidence of agitation
Tsai 2008The children in the study were premedicated with midazolam. The use of premedication can change the following outcome: time to emergence, the incidence of nausea and vomiting and the incidence of agitation
Ved 1996Some patients received antiemetic (dexamethasone)
Watcha 1991Some patients received antiemetic (droperidol)
Woodward 1997The procedures were not ambulatory
Yelken 2004The children in the study were premedicated with midazolam

Characteristics of studies awaiting assessment [ordered by study ID]

Gouda 2002

MethodsThere is no data in the abstract (not yet assessed)
ParticipantsPreschool children undergoing day case surgery
InterventionsSevoflurane anaesthesia versus total intravenous anaesthesia with propofol
OutcomesNot known
Notes 

Moussa 1995

MethodsNot known
ParticipantsNot known
InterventionsAnaesthesia with propofol versus thiopentone with isoflurane and nitrous oxide
OutcomesTime to recovery and quality of recovery
Notes 

Ancillary