3. Drug comparison study outcomes.
| Study ID | Sample | Intervention | Outcomes | Outcome results | Treatment completed |
| Chloral hydrate/hydroxyzine versus | |||||
| Avalos‐Arenas 1998 | n = 40 Mean age (SD) in months and gender: Group 1 (n = 20), 27.7 (2.9), 13 males and 7 females Group 2 (n = 20), 29.2 (3.6), 14 males and 6 females | Group 1: chloral hydrate (70 mg/kg) Group 2: chloral hydrate (70 mg/kg) + hydroxyzine (2 mg/kg) All oral | Houpt. Analysed using Kruskal‐Wallis and Mann‐Whitney U tests | No significant difference (P > 0.05) for overall behaviour evaluation (mean values reported at 7 different time intervals e.g. at injection mean behaviour Group 1 = 4.9 (SD 1.1), Group 2 = 5.0 (SD 0.68) Crying and movement evaluations significantly better (P < 0.05) at 45‐60 minutes after application of rubber dam for Group 1 Sleep mentioned Adverse effects: Group 1 15%‐30% children has oxygen saturation < 90% but in Group 2 range was 10%‐45% Monitoring: precordial stethoscope, pulse oximeter and sphygmomanometer |
All participants completed treatment |
| Meyer 1990 | n = 40 Mean age (age range) in months: Group 1 (n = 20), 44 (21 to 74) Group 2 (n = 20), 42 (23 to 64) | Group 1: chloral hydrate
(40 mg/kg) + hydroxyzine (25 mg)
Group 2: triazolam (0.02 mg/kg) All oral |
Houpt. Analysed using ANOVA and Chi2 test | No significant differences between groups (mean overall behaviour Group 1 and Group 2 the same with a value of 4.3 (SE 0.4354) Sleeping mentioned Adverse effects: vomiting (1 child in Group 1) Monitoring: pulse oximeter and precordial stethoscope |
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| Moody 1986 | n = 30 Mean age in months: Group 1 (n = 10), 39.6 Group 2 (n = 10), 42 Group 3 (n = 10), 38.4 | Group 1: chloral hydrate (50 mg/kg) (oral)
Group 2: chloral hydrate (50 mg/kg) (rectal)
Group 3: chloral hydrate (30 mg/kg) + hydroxyzine (25 mg) (oral) All received nitrous oxide inhalation 30%‐50% |
Modified Barker
Overall quality sedation Behavioural data not statistically analysed |
Good or excellent sedation achieved in 4/10, 7/10 and 7/10 of children in oral chloral hydrate, rectal chloral hydrate and oral chloral hydrate/hydroxyzine groups respectively Adverse effects: not mentioned Monitoring: precordial stethoscope and pulse oximeter |
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| Park 2006 | n = 31 Mean age in months (SD), gender, mean weight in kg (SD): CH Group 44.5 (14.1), 6 males and 9 females, 15.6 (2.7) CH‐M Group 34.3 (9.3), 11 males and 5 females, 15.1 (2.6) |
CH Group: chloral hydrate (60 mg/kg) + hydroxyzine (1 mg/kg) (both oral) CH‐M Group: chloral hydrate (60 mg/kg oral) + hydroxyzine (1 mg/kg oral) + midazolam (0.1 mg/kg submucosal) All received nitrous oxide inhalation 50% |
Houpt Requirement for restraint |
Subjects in the CH‐M Group showed better overall behaviour as measured by Houpt. Mean score 0.47 (SD 0.5) in CH Group versus 0.81 (0.39) in CH‐M Group, P = 0.004 Less restraint was required in the CH‐M Group (P < 0.05) Adverse effects: not reported Monitoring: pulse oximeter |
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| Reeves 1996 | n = 40 Mean age (age range) in months, gender: Group 1 (n = 20), 48 (32 to 73), 11 males and 9 females Group 2 (n = 20), 42 (27 to 70), 10 males and 10 females | Group 1: chloral hydrate (50 mg/kg) + hydroxyzine (25 mg) Group 2: midazolam (0.5 mg/kg) + acetaminophen (10 mg/kg) All oral | Modified Houpt Analysed using Wilcoxon matched pairs test and Chi2 test |
Subjects in chloral hydrate/hydroxyzine group were in a significantly deeper sleep (P < 0.05). Data presented graphically. Sleeping mentioned Adverse effects: not reported Monitoring: pulse oximeter, precordial stethoscope and capnograph |
Dental treatment aborted in 1 participant from chloral hydrate/hydroxyzine group |
| Torres‐Perez 2007 | n = 54 Mean age (age range) in years; mean weight (range) in kg; gender: Group 1: 3.9 (4‐6), 11 males, 7 females, 18.1 (0.9‐22) Group 2: 2.83 (1‐8), 11 males, 7 females, 15 (10.4‐22.5) Group 3: 2.94 (1‐10), 10 males, 8 females, 16.33 (10.4‐20) |
Group 1: hydroxyzine (2 mg/kg 2 hours before, 1 mg/kg 20 minutes before) Group 2: midazolam (0.5 mg/kg) + hydroxyzine (1.5 mg/kg) Group 3: chloral hydrate (50 mg/kg) + hydroxyzine (1.5 mg/kg) All oral |
Ohio State Behavioral Rating Scale Analysed using Wilcoxon matched pairs test and Kruskal Wallis |
"Significantly quieter" (mean cardiac rate 152, 146 and 137 in Group 1, Group 2 and Group 3 respectively (no P value given). Data presented graphically suggesting less movement in Group 3 Adverse effects: in Group 3 1/18 experienced oxygen saturation < 90% Monitoring: oxygen saturation and cardiac rate |
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| Chloral hydrate/promethazine versus | |||||
| Sams 1993a | n = 24 Mean age (SD) in months: Group 1 (n = 13), 31.0 (8.6) Group 2 (n = 11), 35.8 (10.6) | Group 1: chloral hydrate (50 mg/kg) + promethazine (1 mg/kg) Group 2: meperidine (1 mg/kg) + promethazine (1 mg/kg) All oral | Modified Houpt Analysed using Hotelings T test and 2‐sample t‐test |
Chloral hydrate/promethazine group significantly "better" (P < 0.05) for overall evaluation at 4 of the 10 measured time intervals (e.g. mean overall behaviour 15 minutes post‐injection Group 1 = 5.2 (SD 1.1), Group 2 = 4.4 (SD 1.3), P < 0.05) Adverse effects: not reported Significantly more sleep in Group 1 than Group 2 |
All participants completed treatment and mean treatment duration was 50.8 (SD 13.3) and 50.9 (SD 17.6) in Groups 1 and 2 respectively |
| Dexmedetomidine versus | |||||
| Malhotra 2016 | n = 36 Age range = 3‐9 years Mean age (SD) in years: 4.60 + 1.99 Mean weight (SD): 15.62 + 4.21 |
Group 1: intranasal normal saline, oral midazolam (0.5 mg/kg) + oral ketamine (5 mg/kg) in 30 ml of mango juice Group 2: intranasal dexmedetomidine (1 µ/kg), 30 ml of mango juice Group 3: intranasal normal saline, 30 ml of mango juice |
Modified Observer Assessment of Alertness and Sedation (MOAAS) Houpt scale |
Significant difference (P = 0.007) in behaviour during treatment compared to baseline in Group 1 and Group 2 Significant difference in the level of sedation in Group 1 and Group 2 when a comparison is made at specific time stages (treatment‐baseline and, end of treatment‐baseline) e.g. for Group 1 treatment‐baseline comparison shows significant difference (P = 0.002) in the level of sedation No significant difference between Group 1 and Group 2 in sedative efficacy or anxiolysis potential Adverse effects: not reported Monitoring: blood pressure, heart rate, oxygen saturation |
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| Surendar 2014 | n = 84 Age range in years, mean age (SD) in years: Group 1 (n = 21) 7.34 (2.34) Group 2 (n = 21) 6.71 (2.31) Group 3 (n = 21) 7.76 (2.26) Group 4 (n = 21) 7.24 (2.36) |
Group 1: dexmedetomidine (1 µg/kg) Group 2: dexmedetomidine (1.5 µg/kg) Group 3: midazolam (0.2 mg/kg) Group 4: ketamine (5 mg/kg) All intranasal |
Modified AAPD Sedation Record Face, Legs, Activity, Cry and Consolability (FLACC) scale |
No significant difference (P = 0.378) in overall behaviour was observed No significant difference (P = 0.242 and P = 0.120) in overall success rate of treatment and distribution of sedation levels between the groups Significant difference (P > 0.05) in intra and postoperative analgesic effects reported with Group 1, Group 2 and Group 4 significantly better than Group 3 e.g. intraoperative analgesia score Group 3 = 5.62 (SD 1.12) compared to Group 1 = 3.81 (0.81), Group 2 = 3.67 (0.91) and Group 4 = 3.52 (0.68) Significant difference (P > 0.05) in onset time, recovery time, pulse rate and systolic blood pressure of Group 1 and Group 2 compared to Group 3 and Group 4 was observed Adverse effects: not reported Monitoring: oxygen saturation, respiratory rate, blood pressure and respiratory rate |
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| Ketamine versus | |||||
| Abrams 1993 | n = 30 (10 per group with sufentanil divided into 2 subgroups of 5 each) Age range = 17 to 62 months | Group 1: ketamine (3 mg/kg)
Group 2: midazolam (0.4 mg/kg)
Group 3: sufentanil (1 µg) Group 4: sufentanil (1.5 µg) All intranasal |
Sedation scoring criteria No statistical tests used |
Groups 1 to 3 had mean sedation score of 4 (acceptable sedation), Group 4 had mean sedation score of 7 (heavy sedation) Mean recovery times (± SD) were 7 (± 7), 3 (± 2), 7 (± 13), and 58 (± 40) minutes for Groups 1‐4 respectively Sleeping mentioned Adverse effects: drowsiness (Group 1), mild obtundation and deep sedation (Group 3), desaturations in 4/5 children on high dose sufentanil Monitoring: pulse oximeter, automatic blood pressure and if necessary capnograph |
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| Rai 2007 | n = 30 (10 per group) Age range 3‐6 years |
Group 1: midazolam (0.1 mg/kg) (bolus) + 0.004 mg/kg/min (infusion) Group 2: propofol (1 mg/kg) (bolus) + 0.06 mg/kg/min (infusion) Group 3: ketamine (0.5 mg/kg) (bolus) + 0.01 mg/kg/min (infusion) All intravenous All children had premedication 1 hour before of 0.5 mg/kg midazolam and atropine (0.6 mg) |
Houpt Analysed Kruskal Wallis |
The maximum level of co‐operation was seen with ketamine then propofol and then midazolam (P < 0.001) At treatment end mean scores were 5.8 ± 0.42, 3.5 ± 1.08 and 3.2 ± 0.42 in ketamine, propofol and midazolam groups respectively Propofol showed the fastest postoperative recovery score followed by ketamine and the midazolam. Sleeping was reported Adverse effects: pain on injection with propofol and intermittent cough Monitoring: vital signs |
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| Roelofse 1996a | n = 100 Mean age (SD) in years, gender: Group 1 (n = 50), 4.3 (1), 24 males and 26 females Group 2 (n = 50), 4.3 (1.1), 22 males and 28 females | Group 1: ketamine (5 mg/kg) + midazolam (0.35 mg/kg) Group 2: midazolam (1 mg/kg) All rectal | Ramsay Sedation Score
Movement
Crying Overall sedation and behaviour Analysed using McNewman's test (sic), Chi2 and Fisher's Exact tests |
Significant differences in level of sedation with 71% subjects in Group 2 "orientated and calm" compared to 14% in Group 1 30 minutes after administration Significantly less movement and crying (P < 0.05) in Group 1 (58% no movement at all compared to 14% in Group 2) Sleep mentioned Adverse effects: hallucination (Groups 1 (14%) and 2 (42%)), nausea (Group 1) Monitoring: pulse oximeter |
Dental treatment aborted in 1 participant (ketamine/midazolam group) |
| Roelofse 1996b | n = 60 Mean age (SD) in years, gender: Group 1 (n = 30), 4.8 (1.3), 14 males and 16 females Group 2 (n = 30), 4.9 (1.3), 16 males and 14 females | Group 1: 0.5 ml/kg of trimeprazine 6 mg/ml + physeptone (methadone) (0.4 mg/ml) + droperidol (0.1 mg/kg) Group 2: ketamine (12.5 mg/kg) All oral | Anxiety Level of sedation Movement Crying Overall behaviour Analysed using McNemar test, Chi2 and Fisher's Exact tests | Sedation was significantly "better" (very good/excellent 80% and 93% of Group 1 and Group 2 respectively) Overall evaluation good/very good in 67% and 90% of Group 1 and Group 2 respectively Sleeping mentioned Adverse effects: hallucination (9 and 5), restless/irritation 4 and 1, in Group 1 and Group 2 Ketamine also 2 vomiting/nausea, 4 visual disturbances and 4 excess salivation Monitoring: pulse oximeter |
All participants completed treatment |
| Roelofse 1998 | n = 100 Mean age (SD) in years, gender: Group 1 (n = 50), 4.1 (1.3), 27 males and 23 females Group 2 (n = 50), 4 (1.2), 29 males and 21 females | Group 1: ketamine (5 mg/kg) + midazolam (0.35 mg/kg) Group 2: trimeprazine (3 mg/kg) + methadone (0.2 mg/kg) All oral | Modified Houpt, Ramsay Sedation Score Analysed using McNemar's test, Chi2 and Fisher's Exact tests |
Significant differences (P < 0.05) in level of sedation immediately before treatment with 46% participants in Group 1 "oriented and calm" compared to 84% in Group 2 Overall surgeons rated 94% versus 78% of sedations as good/very good in Group 1 versus Group 2 Sedation rated as poor in significantly more children in Group 2 (24%) than Group 1 (6%) Sleeping mentioned Adverse effects: vomiting (n = 2) and hallucination (n = 10) in Group 1 Monitoring: pulse oximeter |
All participants completed treatment |
| Singh 2014 | n = 112 Age range = 1‐10 years Mean age (SD) in years, gender and weight (SD) in kg: Group 1 (n = 28), 6.54 (1.79), 14 males and 14 females, 18.89 (4.33) Group 2 (n = 28), 6.93 (2.05), 13 males and 15 females, 17.04 (5.33) Group 3 (n = 28), 7.21 (1.98), 11 males and 17 females, 16.93 (4.22) Group 4 (n = 28), 6.82 (2.22), 14 males and 14 females, 16.61 (4.92) |
Group 1: ketamine (8 mg/kg‐1) Group 2: dexmedetomidine (3 µg/kg‐1) Group 3: dexmedetomidine (4 µg/kg‐1) Group 4: dexmedetomidine (5 µg/kg‐1) All oral |
Onset time, recovery time Sedation rating scale modified from AAPD guidelines Face, Legs, Activity, Cry and Consolability Pain Scale (FLACC) Anterograde amnesia Behaviour score |
Group 4 had highest "adequate" depth of sedation and "satisfactory" completion of treatment (82.1%, 85.7% respectively), but was not significantly different to Group 1, Group 2 and Group 3 Significant difference (P < 0.001) in lowering of pulse rate and systolic blood pressure in Group 2, Group 3 and Group 4 compared to Group 1 Significant difference (P < 0.001) in onset time, recovery time (except Group 1 and Group 4), intra and postoperative pain scores when comparing the groups e.g. postoperative pain score in Group 1 = 1.54 (0.63) and Group 4 = 1.79 (0.74) were lower compared to Group 2 = 2.43 (0.88) and Group 3 = 2.11 (1.19) Adverse effects: in office vomiting (Group 1 n = 5, Group 4 n = 1), emergency reaction (Group 1 n = 2) Monitoring: oxygen saturation, respiratory rate, blood pressure and respiratory rate |
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| Alfonzo‐Echeverri 1993 | n = 40 Mean age (SD) in months: Group 1 (n = 20) 40.4 (10.2) Group 2 (n = 20) 37.5 (10.6) | Group 1: ketamine (6 mg/kg)
Group 2: meperidine (2.0 mg/kg) + promethazine (0.5 mg/kg)
All oral All received nitrous oxide 30%‐50% |
Modified Houpt Analysed using Chi2 test |
"Good sedation" in 65% of ketamine group and 45% of meperidine/promethazine Overall no statistically significant difference in distribution of sedation outcomes between groups (P = 0.07) Sedation onset time and recovery time both shorter for ketamine (P < 0.001 and P = 0.08 respectively) Adverse effects: vomiting (Groups 1 (n = 8) and 2 (n = 1)) Monitoring: precordial stethoscope and pulse oximeter |
Dental treatment aborted in 4 children receiving meperidine and none in ketamine group |
| Bui 2002 | n = 22 Mean age (SD) in months: Group 1 (n = 11) 34 (6.28) Group 2 (n = 11) 33 (6.65) | Group 1: ketamine (10 mg/kg) + promethazine (1.1 mg/kg)
Group 2: ketamine (10 mg/kg)
All oral All received nitrous oxide 50% |
Houpt Analysed using Mann‐Whitney U test |
Statistically significant difference in mean Houpt score favouring ketamine group (mean score 4.27, SD 0.5) (Group 1 (mean score 3.12, SD 0.29)) (P < 0.05) Adverse effects: 3 patients from Group 2 vomited. Most of the patients reported as being drowsy or asleep after 25 minutes |
Dental treatment aborted in 1 participant from Group 1 due to violent physical movement and crying |
| Ketamine/midazolam versus | |||||
| Gomes 2017 | Mean age (SD) in years, gender, mean weight (25% median to 75%) in kg: Group 1 (n = 13), 4.7 (0.6), 10 males, 3 females, 16.5 (15.7‐19.6) Group 2 (n = 14), 5.2 (0.8), 8 males, 6 females, 19.6 (16.7‐23.9) |
Group 1: midazolam (0.5 mg/kg) + ketamine (3 mg/kg) (oral) Group 2: midazolam (0.5 mg/kg) (oral) + ketamine (3 mg/kg) (oral) + sevoflurane (0.1%‐0.4% inhalation) |
Houpt Analysed using Mann‐Whitney U test Adverse events Analysed using Chi2 test |
No significant difference in overall Houpt score between the 2 groups (P > 0.05 data presented graphically) Adverse events: more children in Group 1 reported adverse events at 24 hours than Group 2 (Group 1 n = 10, Group 2 n = 4; P = 0.01) Adverse events seen in all children included: excessive drowsiness 22% (n = 6), vomiting 22% (n = 6) No apnoea /drop in oxygen saturation seen Monitoring: pulse oximeter |
Treatment not completed in 1 child from Group 1 due to poor co‐operation |
| Midazolam (oral) versus | |||||
| Baygin 2010 | n = 60 Mean age (unclear, possibly SD) in years, mean weight (unclear, possibly SD) in kg, gender: Group 1 (n = 15), 5.33 (0.62), 18.93 (2.31), 10 males and 5 females Group 2 (n = 15), 5.27 (0.80), 19.07 (3.62), 11 males and 4 females Group 3 (n = 15), 5.20 (0.41), 18.20 (2.34), 9 males and 6 females Group 4 (n = 15), 5.53 (0.99), 20.01 (3.99), 6 males and 9 females |
Group 1: hydroxyzine (1 mg/kg) (oral) Group 2: midazolam (0.7 mg/kg) Group 3: ketamine (3 mg/kg) + midazolam (0.25 mg/kg) Group 4: no oral premedication 40% nitrous oxide oxygen was administered to all participants |
Ramsay Sedation Score, Bispectral Index System | Ramsay Sedation Scores (RSS) were significantly greater in Group 2 compared to Groups 1, 3 and 4 (P < 0.05) RSS satisfactory/mid‐level satisfactory/unsatisfactory was as follows: Group 1: 13.3%/53.3%/33.3% Group 2: 54%/20%/26% Group 3: 33.3%/33.3%/33.3% Group 4: 6.7%/60%/33.3% P value or significance not reported Adverse effects: nausea/vomiting (n = 1/2/3/4), cough (4/4//), hiccough (/1//5), enuresis (/2//), bronchospasm (/1//), hypersalivation (//8/), otalgia (///2), hallucination (//2/), and epistaxis (///1) in patients in groups 1, 2, 3, and 4, respectively Monitoring: pulse oximeter |
Figure 5 used to extrapolate data with score 3 given to satisfactory, 2 middle level, 1 unsatisfactory All participants completed treatment |
| Bhatnagar 2012 | n = 60 Age range = 3‐9 years |
Group 1: midazolam (0.5 mg/kg) Group 2: tramadol (2 mg/kg) Group 3: triclofos (70 mg/kg) Group 4: zolpidem (0.4 mg/kg) All oral |
Sedation rating scale Ease of treatment completion |
Significant difference (P < 0.001) in the level of sedation (median scores) with Group 4 > Group 3 > Group 2 = Group 1 Mean score in the ease of treatment shown in the table of results reports Group 4 > Group 3 > Group 2 > Group 1 No statistical difference between (P > 0.05) between Group 1, Group 2, Group 3 in ease of treatment. Group 4 was found to have a statistical difference compared to the other groups (P < 0.001) Adverse effects: not mentioned |
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| Moreira 2013 | n = 44 Average age below 36 months Mean age (SD) in months, gender: Group 1 (n = 11), 27.1 (8.3), 6 males and 5 females Group 2 (n = 18, parents refused treatment for 2), 27.7 (5.5), 9 males and 7 females Group 3 (n = 15, parents refused treatment for 1), 27.3 (6.4), 9 males and 4 females |
Group 1: midazolam (0.5 mg/kg) + ketamine (3 mg/kg) Group 2: midazolam (1 mg/kg) Group 3: no sedation Group 1 and 2 oral |
Ohio State University Behavior Rating Scale (OSUBRS) | Significant difference in behaviour (P = 0.003) between Group 1 and Group 2 and Group 1 and Group 3 (P = 0.03) when sedatives used Behaviour during various stages of treatment sessions was observed e.g. for local anaesthetic administration OSUBRS score for Group 1 was lower than Group 2 (P = 0.06) and Group 3 (P = 0.02) During rubber dam placement OSUBRS score for Group 1 was lower than Group 2 (P = 0.01) and Group 3 (P = 0.07). All Groups showed same behavioural pattern at the end of the treatment session (P = 0.25) Sleep mentioned Adverse effects: within 24 hour postoperatively Group 1 presented with agitation and vomiting in 3 children |
All participants completed treatment |
| Koirala 2006 | n = 120 (20 per group) Age range: 2‐9 years |
Group 1: midazolam (9.5 mg/kg) Group 2: ketamine (5 mg/kg) Group 3: zolpidem (0.4 mg/kg) Group 4: midazolam (0.4 mg/kg) + ketamine (3 mg/kg) Group 5: midazolam (0.5 mg/kg) + tramadol (2 mg/kg) Group 6: zolpidem (0.4 mg/kg) + tramadol (2 mg/kg) All oral |
Onset of action Level of sedation Ease of treatment completion |
Group 4 and 5 the "best" and Groups 3 and 6 the "worst" when compared on level of sedation (P < 0.001) Group 4 had the shortest time of onset of sedation (Data presented graphically) No adverse effects were reported |
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| Singh 2002 | n = 90 (30 per group) Age range: 3‐9 years | Group 1: midazolam (0.5 mg/kg) Group 2: triclofos (70 mg/kg) Group 3: promethazine (1.2 mg/kg) All oral | Degree of sedation Time of onset, time of recovery Statistical techniques not described |
Transformed sedative scores Group 1: 3.3 ± 0.7 (best) Group 2: 3.07 ± 0.6 Group 3: 2.73 ± 0.5 Both Groups 1 and 2 were statistically significantly better than Group 3 (P < 0.05) Time of onset and time of recovery were both shortest in Group 1 Adverse effects: not mentioned Monitoring: blood pressure, heart and respiratory rate |
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| Özen 2012 | n = 240 (n = 60 per group) Mean age (SD) in months 57.02 (9.31) |
Group 1: midazolam (0.20 mg/kg (40 mg/ml)) (intranasally) + inhalation sedation 50%–50% nitrous oxide/oxygen Group 2: midazolam (0.75 mg/kg (15 mg/3 ml)) (orally) + inhalation sedation 50%–50% nitrous oxide/oxygen Group 3: midazolam (0.50 mg/kg (15 mg/3 ml)) (orally) + inhalation sedation 50%–50% nitrous oxide/oxygen Group 4: inhalation sedation 50%–50% nitrous oxide/oxygen |
Bispectral Index System (BIS) Modified scale to classify behaviour Vancouver Recovery Scale |
Modified scale used to classify behaviour/ respond to treatment/sedation was highest in Group 1 (87%) followed by Group 2 (79%), Group 3 (72%) and Group 4 (55%) respectively No significant difference (P = 0.230 and P = 0.399) in overall success rate between Group 1 and Group 2, Group 2 and Group 3 respectively. Significant difference (P < 0.05) between Group 1 and Group 3. Significant difference Group 4 compared to all other groups BIS values recorded every 5 minutes, Group 2 was most sedated except for at 30 minutes. From 15 minutes to end of treatment all groups had BIS value above 90 Recovery time in minutes was shorter for intranasal midazolam (22.3) compared to 0.50 mg/kg oral midazolam (27.5) and 0.75 mg/kg oral midazolam (29.2) Sleep mentioned Adverse effects: ‐ drug administration: vomiting in oral midazolam group (4), nose bleeding intranasal midazolam group (1), transient burning and discomfort nasal midazolam group (not reported) ‐ recovery period: vomiting in oral midazolam group (7), coughing in intranasal midazolam group (1), transient burning and discomfort nasal midazolam group (not reported) ‐ after discharge: irritability (42%), crying (34%), sleepiness (31%), nausea (5%) |
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| Tyagi 2012 | n = 40 Age range = 2‐10 years |
Group 1: midazolam (0.5 mg/kg) (oral) Group 2: diazepam (0.5 mg/kg) (oral) Group 3: midazolam (0.06 mg/kg) (intravenous) Group 4: placebo |
Houpt scale Child behaviour questionnaire |
Behaviour was assessed in terms of sleep, crying and movement at 30 minutes postdrug administration in Group 1, Group 2 and Group 4 or 5 minutes in Group 3. At placement of blood pressure cuff, during administration of local anaesthesia or use of hand piece and every 15 minutes thereafter e.g. at administration of local anaesthetic agent or use of hand piece significantly lower (P < 0.001) sleep in Group 4 compared to other groups. Significantly less crying in Group 3 compared to Group 1, Group 2 and Group 4 (P < 0.001, P < 0.01 and P < 0.05 respectively) Overall behaviour rating was significantly better (P < 0.001) in Group 3 compared to other groups Positive behaviour postsedation: no significant difference between Group 1 and Group 2. Significant improvement (P < 0.05) in Group 3 compared to Group 2 Sleeping mentioned Adverse effects: not reported Monitoring: oxygen saturation, respiratory rate, blood pressure and respiratory rate |
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| Midazolam (intravenous) versus | |||||
| Kaviani 2015 | n = 38 Age range = 4‐9 years Gender, mean age in years: Group 1 (n = 18), 8 males and 10 females, 6.27 Group 2 (n = 20), 12 males and 8 females, 6.75 |
Group 1: midazolam (0.05 mg/kg) + ketamine (0.5 mg/kg)
Group 2: midazolam (0.05 mg/kg) + fentanyl (0.5 µg/kg) All intravenous, administered by an anaesthesiologist |
Dental Sedation Teacher Groups System Frankl behaviour rating scale |
No significant difference (P > 0.05) in intraoperative sedation score and score of operative conditions at 10th, 20th, 30th and 40th minute Significant difference (P < 0.05) in the sedation score and score of operating condition in Group 1 and Group 2 at 10‐20 minutes, 10‐30 minutes Adverse effects: not reported |
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| Eshghi 2016 | n = 32 Age range = 3‐7 years Mean age (SD) in years: 4.36 (1.6) Group 1 (n = 16), 7 males and 9 females Group 2 (n = 16), 8 males and 8 females |
Group 1: remifentanil (0.1 µg/kg/min) + midazolam (0.01 mg/kg) + propofol (0.5 mg/kg) Group 2: ketamine (0.5 mg/kg) + midazolam (0.1 mg/kg) + propofol (0.5 mg/kg) All intravenous |
Bispectral Index System (BIS) DSTG scale |
Significant difference (P = 0.003) with higher BIS values in Group 1 compared to Group 2 DSTG score noted at 9 different time intervals was 5 (eyes closed, no response to mild physical stimulus) in Group 1 and Group 2 Heart rate and respiratory rate showed no significant difference between Group 1 and Group 2 (P = 0.884, P = 0.775 respectively) Significant difference (P < 0.001) with Group 1 having quicker recovery compared to Group 2 ( 9.23 + 2.77, 30.83 + 5.96 minutes) Adverse effects: severe nausea and vomiting was reported in Group 1, number not reported Monitoring: heart rate, respiratory rate, oxygen saturation |
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| Midazolam (rectal) versus | |||||
| Jensen 1999 | n = 90 Median age (age range) in months and gender: Group 1 (n = 45), 32 (18 to 44), 23 males and 22 females Group 2 (n = 45), 29 (15 to 44), 23 males and 22 females | Group 1: diazepam (0.7 mg/kg) Group 2: midazolam (0.3 mg/kg) All rectal | Wilton's sedation scale
Acceptance of treatment (Holst) Analysed using Wilcoxon matched pair test and Fisher's exact test |
No difference in acceptance of dental procedures (P = 0.07) At 1 hour significantly more children agitated in the diazepam group 13/45 (29%) versus 1/45 (2%) (P = 0.006) Data presented graphically Adverse effects: lasting effect: aggressiveness, tiredness and unco‐ordinated movements in diazepam group, children unusually quiet or lively on next day in Group 2 |
Some children did not complete treatment however, it is not possible to extract exact numbers as these data were only presented as bar chart |
| Sevoflurane versus | |||||
| Lahoud 2002 | n = 411 Mean age (SD) in years: Group 1 (n = 170), 6.2 (1.9) Group 2 (n = 241), 6 (1.7) | Group 1: 40:60 nitrous oxide/oxygen Group 2: 40:60 nitrous oxide/oxygen + 0.1%‐0.3% sevoflurane All inhalation |
Venham scale level of sedation and failure rate Analysed using Mann‐Whitney U test and Chi2 test |
Effective sedation: Group 1 215/241 (89%); Group 2 89/170 (52%); (P < 0.0001) Venham scale ‐ relaxed: Group 1 = 32%; Group 2 = 67% Significantly less failure in sevoflurane/nitrous oxide Group 1 48% failed (P < 0.0001); Group 2 11% failed Adverse effects: none mentioned Monitoring: pulse oximeter, capnograph, pretracheal stethoscope, visual assessment, auscultation and visualization of chest movements |
89% sevoflurane group completed treatment compared to 52% of nitrous oxide group |
| Averley 2004a | n = 65 Gender, mean weight (SD) in kg, mean age (SD) in years: Group 1: 13 males and 7 females, 33.6 (11.2), 9.3 (2.2) Group 2: 15 males and 5 females, 37.6 (14.6), 9.6 (2.3) Group 3: 4 males and 16 females, 36.1 (11.8), 9.9 (2.2) | Group 1: midazolam (0.5 mg/min) (intravenous) + air (nasal inhalation) Group 2: midazolam (0.5 mg/min) (intravenous) + nitrous oxide (40%) (nasal inhalation) Group 3: midazolam (0.5 mg/min) (intravenous) + nitrous oxide (40%) (nasal inhalation) + sevoflurane (0.3%) (nasal inhalation) | Primary: completion of treatment
Secondary: level of co‐operation during treatment, recovery time, perception of anxiety and pain and parent's satisfaction Analysed using Chi2 test |
Treatment completion: Group 1: 10/20 (50%) Group 2: 16/22 (73%) Group 3: 19/23 (83%) (Chi2 = 5.53, df = 2, P = 0.07) Of the 16 treatment failures in Groups 1 and 2, 9 were subsequently successfully treated with the addition of sevoflurane + nitrous oxide No adverse effects reported Monitoring: pulse oximeter, blood pressure, ECG |
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| Averley 2004b | n = 664 Gender, mean weight (SD) in kg, mean age (SD) in years: Group 1 (n = 222), 81 males, 36.3 (13.4), 9.1 (2.7) Group 2 (n = 306), 127 males, 37.8 (14.1), 9.5 (2.7) Group 3 (n = 320), 103 males, 37.7 (14), 9.6 (2.5) | Group 1: midazolam (0.5 mg/min) (intravenous) + air (nasal inhalation) Group 2: midazolam (0.5 mg/min) (intravenous) + nitrous oxide (40%) (nasal inhalation) Group 3: midazolam (0.5 mg/min) (intravenous) + nitrous oxide (40%) (nasal inhalation) + sevoflurane (0.3%) (nasal inhalation) | Primary: completion of treatment
Secondary: level of co‐operation during treatment, recovery time, perception of anxiety and pain and parent's satisfaction Analysed using Chi2 test |
Treatment completion: Group 1: 94/174 (54%) Group 2: 204/256 (80%) Group 3: 249/267 (93%) Chi2 = 9.64, df = 2, P < 0.001 Adverse effects: 1 faint in Group 1, 6 vomited in Group 3 Monitoring: pulse oximeter, blood pressure, ECG |
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AAPD = American Academy of Pediatric Dentistry; DSTG scale = Dental Sedation Teachers Group scale; df = degrees of freedom; ECG = electrocardiogram; n = number; SD = standard deviation; SE = standard error.