Cochrane · intervention · CD003877
Sedation of children undergoing dental treatment
Ashley, PF, Chaudhary, M, Lourenço‐Matharu, L · Cochrane Database of Systematic Reviews · 2018 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
19
current version
GRADE rated
17
No studies
1
Included studies
50
as reported
No studies 1 · 5.3%Ungraded 1 · 5.3%Very low 15 · 78.9%Low 1 · 5.3%Moderate 1 · 5.3%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Children and adolescents aged 0 to 16 years (including children with specific medical or behavioural problems) having simple restorative treatment with local anaesthesia (e.g. fillings, stainless steel crowns), simple extractions or management of dental trauma; children having complex surgical procedures excluded | Studies from 16 countries (greatest proportion USA, n=12, 24%); age 1 to 16 years (>=39 studies all subjects 6 or under); mean age approx 4.8 years; mean 74 participants per study; 3704 in total |
| Intervention | Any sedative agent via any route of administration that can be administered by a dentist, anaesthetist, sedationist or dental auxiliary in an outpatient/dental office setting; studies inducing deep sedation excluded | Chloral hydrate (n=3); Chloral hydrate + hydroxyzine (n=6); Chloral hydrate + hydroxyzine + midazolam (n=1); Chloral hydrate + promethazine (n=1); Dexmedetomidine (n=2); Diazepam (n=1); Hydroxyzine (n=3); Ketamine (n=7); Ketamine + promethazine (n=1); Ketamine + midazolam (n=3); Ketamine + midazolam + sevoflurane (n=1); Melatonin (n=1); Meperidine (n=1); Meperidine + promethazine (n=2); Midazolam (n=27); Midazolam + acetaminophen (n=1); Midazolam + fentanyl (n=1); Midazolam + hydroxyzine (n=1); Midazolam + nitrous oxide/oxygen (n=1); Midazolam + ketamine (n=5); Midazolam + sevoflurane + nitrous oxide/oxygen (n=2); Midazolam + tramadol (n=1); Nitrous oxide/oxygen (n=5); Promethazine (n=1); Propofol (n=1); Sevoflurane + nitrous oxide/oxygen (n=1); Sufentanil (n=1); Tramadol (n=1); Triazolam (n=1); Triclofos (n=2); Trimeprazine + methadone (n=1); Trimeprazine + physeptone (n=1); Zolpidem (n=2); Zolpidem + tramadol (n=1) |
| Comparison | Placebo (including no intervention); alternative sedation agent; different dosage of the same agent | Placebo (n=12); No intervention (n=1) |
| Outcomes | Behaviour (primary); Completion of treatment (yes/no); Postoperative anxiety; Adverse events | Behaviour (n=50); Completion of treatment (n=50); Postoperative anxiety (n=50); Adverse events (n=50) |
| Study designs | Randomised controlled trials (including cluster-randomised); quasi-randomised and cross-over trials excluded | Randomised controlled trials |
| Timing | Not reported | Not reported |
Search date: 22 February 2018. Databases: Cochrane Oral Health's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE Ovid; Embase Ovid
Questions and results
Current version onlyChloral hydrate vs Placebo (including no intervention)
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Good or better behaviour | RR 1.33 [0.80, 2.22] 176 [-106, 467] per 1000 | 1 study · 60 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour (Houpt/behavioural score) | SMD 0.69 [0.13, 1.26] | 1 study · 52 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour | Moreira 2013: 0.5 mg/kg midazolam + 3 mg/kg ketamine produced significantly better behaviour than placebo and oral midazolam (P=0.03); not included in meta-analysis / not GRADE-rated. Narrative. | 1 study | Ungraded |
Good or better behaviour | RR 5.33 [1.45, 19.64] 578 [60, 867] per 1000 | 1 study · 60 participants | Low Downgraded: risk of bias, imprecision |
Behaviour (Houpt/behavioural score) | SMD 0.62 [-0.28, 1.53] | 1 study · 20 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour (Houpt/behavioural score) | SMD 1.21 [0.24, 2.18] | 1 study · 20 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour (Houpt/behavioural score) | SMD 1.96 [1.59, 2.33] | 6 studies · 202 participants | Moderate Downgraded: risk of bias |
Midazolam (any mode of delivery) vs Different dosage of the same sedative
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Any behavioural score - Midazolam (any mode of delivery): 394 (10 studies); VERY LOW. Insufficient evidence to determine whether any specific dose of intranasal midazolam is effective; weak evidence oral midazolam… | 10 studies · 394 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Hydroxyzine: 30 (1 study); VERY LOW. Insufficient evidence to determine whether any specific dose of hydroxyzine is effective. | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Intravenous midazolam vs A different sedative agent
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Any behavioural score - Intravenous midazolam versus (other sedatives): 70 (2); VERY LOW | 2 studies · 70 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Ketamine versus (other sedatives): 494 (8); VERY LOW | 8 studies · 494 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Chloral hydrate/promethazine versus (other sedatives): 24 (1); VERY LOW | 1 study · 24 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour | Any behavioural score - Dexmedetomidine versus (other sedatives): 120 (2); VERY LOW | 2 studies · 120 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Chloral hydrate/hydroxyzine versus (other sedatives): 235 (6); VERY LOW | 6 studies · 235 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Rectal midazolam versus (other sedatives): 90 (1); VERY LOW | 1 study · 90 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour | Any behavioural score - Sevoflurane versus (other sedatives): 1140 (3); VERY LOW | 3 studies · 1140 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Behaviour | Any behavioural score - Ketamine/midazolam versus (other sedatives): 27 (1); VERY LOW | 1 study · 27 participants | Very low Downgraded: risk of bias, imprecision |
Behaviour | Any behavioural score - Oral midazolam versus (other sedatives): 654 (7); VERY LOW | 7 studies · 654 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Sedation
Population: Medically compromised children (ASA III+) or children with learning/behavioural difficulties needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | 'Some of the techniques described may be useful in the management of medically compromised patients, but at present there are no studies carried out in these groups.' (Discussion) Explicit evidence gap. | 0 studies | No studies |
Oral midazolam vs Placebo (including no intervention)
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | SMD 2.98 [1.58, 4.37] | 5 studies · 182 participants | Ungraded |
Behaviour | Moore 1984: no statistically significant difference between placebo and the three combined chloral hydrate groups for positive behaviour; airway issues at 60 mg/kg with N2O. Narrative. | 1 study | Ungraded |
Behaviour | Two trials (Nathan 1988; Veerkamp 1993) reported changes favouring nitrous oxide; no data available from Nathan; could not be pooled. Very weak evidence. Narrative. | 2 studies | Ungraded |
Behaviour | McKee 1990: meperidine significantly more effective than placebo for good/better behaviour (71% vs 13%, P<0.05); two aborted; more nausea/vomiting. Narrative. | 1 study | Ungraded |
Midazolam (intranasal or oral) vs Different dosage of midazolam
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Intranasal midazolam (Al-Rakaf 2001; Lam 2005; Lee-Kim 2004; Shashikiran 2006) and oral midazolam (Aydintug 2004; Isik 2008b) dose/route comparisons; conflicting results; insufficient evidence for any specific dose.… | 6 studies | Ungraded |
Behaviour | Faytrouny 2007: hydroxyzine 20 mg preoperatively + appointment dose vs appointment dose only; no differences between groups; all received 50% N2O. Narrative. | 1 study | Ungraded |
Chloral hydrate/promethazine vs A different sedative agent
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Sams 1993a (CH/promethazine vs meperidine/promethazine): drowsy/asleep more likely in CH/promethazine; no difference at LA injection; both completed treatment. Narrative. | 1 study | Ungraded |
Behaviour | Seven studies evaluated ketamine head-to-head (Abrams 1993; Alfonzo-Echeverri 1993; Bui 2002; Rai 2007; Roelofse 1996a; Roelofse 1996b; Roelofse 1998); results mixed; Rai 2007 higher behaviour scores for ketamine vs… | 7 studies | Ungraded |
Behaviour | Three trials (Averley 2004a; Averley 2004b; Lahoud 2002): sevoflurane/N2O significantly more effective / higher completion (Lahoud 2002 P<0.001; Averley 2004b completion 54/80/94%). Narrative. | 3 studies | Ungraded |
Behaviour | Jensen 1999 (rectal diazepam 0.7 mg/kg vs rectal midazolam 0.3 mg/kg): significant difference favouring diazepam at 1 hour. Narrative. | 1 study | Ungraded |
Behaviour | Five studies (Avalos-Arenas 1998; Meyer 1990; Moody 1986; Reeves 1996; Torres-Perez 2007): no consistent significant behaviour differences vs comparators. Narrative. | 5 studies | Ungraded |
Behaviour | Oral midazolam head-to-head (Baygin 2010; Koirala 2006; Singh 2002): premedication agents better than N2O alone; no significant difference midazolam+N2O vs hydroxyzine or midazolam/ketamine. Narrative. | 3 studies | Ungraded |
Sedation
Population: Medically compromised children (ASA III+) or children with learning/behavioural difficulties needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | 'Some of the techniques described may be useful in the management of medically compromised patients, but at present there are no studies carried out in these groups.' (Discussion) Explicit evidence gap. | 0 studies | No studies |
Flunitrazepam vs Placebo (including no intervention)
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Gallardo 1984: significant difference in all behavioural variables favouring flunitrazepam vs placebo. Narrative; not pooled. | 1 study | Ungraded |
Behaviour | Three studies (Evans 1966; Houpt 1989; Moore 1984): Houpt 1989 and Moore 1984 significant behaviour differences favouring oral chloral hydrate; Evans 1966 not effective. Narrative; not pooled. | 3 studies | Ungraded |
Behaviour | Four studies (Lindsay 1980; Nathan 1988; Primosch 1999; Veerkamp 1993) reported changes favouring nitrous oxide. Narrative; not pooled. | 4 studies | Ungraded |
Behaviour | Five diazepam placebo studies (oral x4; rectal x1): Gallardo 1984 and Yanase 1996 significant; Flaitz 1985a (rectal) significant; Lindsay 1985a/1985b no difference. Narrative; not pooled. | 5 studies | Ungraded |
Behaviour | Two studies (Gallardo 1994; Lima 2003) reported oral midazolam significantly improved all parameters vs placebo; a further study (Kapur 2004) of oral transmucosal midazolam also found significant differences favouring… | 2 studies | Ungraded |
Behaviour | McKee 1990 (IM meperidine): significantly more effective than placebo in behavioural rating. Narrative; not pooled. | 1 study | Ungraded |
Oral temazepam vs Different dosage of temazepam
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | El Magboul 1995: increasing oral temazepam 0.3 to 0.5 mg/kg made no difference. Narrative. | 1 study | Ungraded |
Behaviour | Sullivan 2001: no significant behaviour differences across ketamine 4-10 mg/kg + diazepam 0.1 mg/kg. Narrative. | 1 study | Ungraded |
Behaviour | Fuks 1994 (intranasal) no difference; Al-Rakaf 2001 (intranasal) behaviour improved with dose; Marshall 1999 (oral) improved with dose. Narrative. | 3 studies | Ungraded |
Behaviour | Three studies (Houpt 1985a; Houpt 1985b; Wilson 1993): mixed; higher doses tended to less crying/movement. Narrative. | 3 studies | Ungraded |
Intravenous midazolam vs A different sedative agent
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Wilson 2003: IV midazolam as effective as nitrous oxide for orthodontic extractions in teenagers; baseline anxiety not recorded. Narrative. | 1 study | Ungraded |
Behaviour | Songvasin 1990 and Sams 1993: CH/promethazine comparisons; mixed. Narrative. | NR | Ungraded |
Behaviour | Jensen 1999 (rectal midazolam vs rectal diazepam): more children agitated with diazepam at 1 hour; Lokken 1994 (rectal). Narrative. | NR | Ungraded |
Behaviour | Ketamine head-to-head (Abrams 1993; Alfonzo-Ech. 1993; Bui 2002; Roelofse 1996b; Roelofse 1998): mixed; ketamine favoured on some overall-evaluation outcomes. Narrative. | NR | Ungraded |
Behaviour | Lahoud 2002 (sevoflurane/N2O vs N2O) significant; Averley 2004a/2004b (sevoflurane/N2O + IV midazolam vs IV midazolam +/- N2O) more completed treatments (significant in full study Averley 2004b). Narrative. | 3 studies | Ungraded |
Behaviour | Lokken 1994 and Roelofse 1996a: ketamine/midazolam combinations; no significant anxiety/pain differences. Narrative. | NR | Ungraded |
Behaviour | Chloral hydrate/hydroxyzine head-to-head (Moody 1986; Meyer 1990; Poorman 1990; Tsinidou 1992; Reeves 1996; Avalos-Arena 1998): mostly no significant behaviour differences. Narrative. | NR | Ungraded |
Behaviour | Oral midazolam head-to-head (Haas 1996; Singh 2002; Musial 2003; Shapira 2004; Myers 2004 submucosal midazolam/CH; Reeves 1996; Dallman 2001): mostly no significant differences; Singh 2002 favoured midazolam. Narrative. | NR | Ungraded |
Sedation
Population: Medically compromised children (ASA III+) or children with learning/behavioural difficulties needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | 'Some of the techniques described may be useful in the management of medically compromised patients, at present there are no studies carried out in these groups.' (Discussion) Explicit evidence gap. | 0 studies | No studies |
Oral midazolam vs Placebo (including no intervention)
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Gallardo 1994 (oral midazolam 7.5 mg): significantly improved all parameters evaluated vs placebo. Narrative; not pooled. | 1 study | Ungraded |
Behaviour | Gallardo 1984: significant difference in all behavioural variables favouring flunitrazepam vs placebo (15 vs 42 unsatisfactory sedations). Narrative; not pooled. | 1 study | Ungraded |
Behaviour | Four studies (Lindsay 1980; Nathan 1988; Primosch 1999; Veerkamp 1993) all reported changes in behaviour or anxiety favouring nitrous oxide (50:50 to 20:80 N2O:O2). Narrative; not pooled. | 4 studies | Ungraded |
Behaviour | Three studies (Evans 1966; Houpt 1989; Moore 1984): Houpt 1989 and Moore 1984 reported significant behaviour differences favouring oral chloral hydrate (Moore only at 60 mg/kg); Evans 1966 found chloral… | 3 studies | Ungraded |
Behaviour | Five diazepam placebo studies (oral x4; rectal x1): Gallardo 1984 (0.5 mg/kg) and Yanase 1996 (0.3 mg/kg) significant behaviour improvement; Flaitz 1985a (rectal 0.6 mg/kg) significantly reduced interfering movements;… | 5 studies | Ungraded |
Behaviour | McKee 1990 (IM meperidine 0.55-2.2 mg/kg): significantly more effective than placebo in behavioural rating; two aborted treatment; nausea/vomiting increased at higher doses. Narrative; not pooled. | 1 study | Ungraded |
Midazolam (intranasal or oral) vs Different dosage of midazolam
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Fuks 1994 (intranasal 0.2 vs 0.3 mg/kg) no difference; Al-Rakaf 2001 (intranasal 0.3-0.5 mg/kg) behaviour improved with dose; Marshall 1999 (oral 0.5-0.75 mg/kg) improved anxiety/treatment success with dose. Narrative. | 3 studies | Ungraded |
Behaviour | El Magboul 1995: increasing oral temazepam 0.3 to 0.5 mg/kg made no difference in behaviour. Narrative. | 1 study | Ungraded |
Behaviour | Sullivan 2001: ketamine 4-10 mg/kg + diazepam 0.1 mg/kg; no significant behaviour differences; nine aborted treatments per group. Narrative. | 1 study | Ungraded |
Behaviour | Three studies (Houpt 1985a; Houpt 1985b; Wilson 1993): Houpt 1985a no difference 75 vs 50 mg/kg; Houpt 1985b less crying/movement at higher dose; Wilson 1993 significant differences favouring higher dose. Narrative. | 3 studies | Ungraded |
Rectal midazolam vs A different sedative agent
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Behaviour | Jensen 1999 (rectal midazolam vs rectal diazepam): more children agitated with diazepam at 1 hour. Narrative. | NR | Ungraded |
Behaviour | Lahoud 2002 (sevoflurane/N2O vs N2O alone): sevoflurane significantly more effective; greater number completing treatment. Narrative. | 1 study | Ungraded |
Behaviour | Head-to-head chloral hydrate/hydroxyzine studies (Moody 1986; Meyer 1990 vs triazolam; Poorman 1990 +/-meperidine; Tsinidou 1992 vs temazepam; Reeves 1996 vs midazolam/acetaminophen; Avalos-Arena 1998 vs chloral… | NR | Ungraded |
Behaviour | Songvasin 1990 (diazepam/hydroxyzine vs CH/promethazine, both with N2O) favoured diazepam/hydroxyzine; Sams 1993 (CH/promethazine vs meperidine/promethazine) favoured CH/promethazine on sleep/movement/crying. Narrative. | NR | Ungraded |
Behaviour | Ketamine head-to-head: Abrams 1993 (vs midazolam/sufentanil); Alfonzo-Ech. 1993 (vs meperidine/promethazine, no behaviour difference); Bui 2002 (ketamine vs ketamine/promethazine, favoured ketamine); Roelofse… | NR | Ungraded |
Behaviour | Lokken 1994 (midazolam vs midazolam/ketamine) no significant anxiety/pain difference; Roelofse 1996a (rectal ketamine/midazolam vs rectal midazolam) fewer adverse effects, reliably good sedation. Narrative. | NR | Ungraded |
Behaviour | Oral midazolam head-to-head: Haas 1996 (vs chloral hydrate); Singh 2002 (vs triclofos/promethazine, midazolam best); Reeves 1996 (midazolam/acetaminophen vs CH/H); Dallman 2001 and Hartgraves 1994 (nasal midazolam vs… | NR | Ungraded |
Sedation
Population: Medically compromised children (ASA III+) or children with learning/behavioural difficulties needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | 'Some of the techniques described may be useful in the management of medically compromised patients, at present there are no studies carried out in these groups.' (Discussion) Explicit evidence gap. | 0 studies | No studies |
Sedative (any agent) vs Placebo (including no intervention)
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Protocol: planned comparison of sedative agents with placebo; no studies included yet. | NR | No studies |
Sedative (any agent) vs Different dosage of the same sedative
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Protocol: planned comparison of different dosages of the same agent; no studies included yet. | NR | No studies |
Sedative (any agent) vs A different (alternative) sedative agent
Population: Children and adolescents (0 to 16 years) needing dental treatment
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Protocol: planned comparison of sedative agents with each other; no studies included yet. | NR | No studies |