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CHARACTERISTICS OF INCLUDED STUDIES: Nitrous oxide

StudyParticipantsInterventions
Averley 2004 (Ref ID: 486)
RCT
Randomisation unit: Patient.
Trial held in UK.
Setting: primary care dental practice.
Funding :donation of drugs/equipment
Inclusion criteria: children between ages 6-14 years referred for dental treatment using anxiety management; adequate comprehension of treatment; accept EMLA and nasal hood.

Exclusion criteria: history of hypersensitivity to benzodiazqpines, sevoflurane, nitrous oxide or local anesthetics.

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - mixed - e.g. extractions, restorations, pulpotomies, brief. First procedure?: prior procedures.
ASA details: I-II. Learning disabilities: none mentioned.
Age: mixed; ages 6-14 years.
Gender: 45% (311) male; 55% (386) female.
Weight: all patients weighed more than 5 kg.

Planned sedation level: conscious sedation. Purpose: mixed.
Sedationist: anaesthetist.
Procedure carried out by: dental practitioner.
Sedation monitoring by: anaesthetist.
  1. 40% nitrous oxide/oxygen +iv midazolam 0.5 mg/min + topical anaesthesia + local anaesthesia [lidocaine injection]; volume: nitrous oxide continuous; midazolam titrated to level 3 on consciousness scale; (n=256).
  2. iv midazolam + inhaled medical air + topical anaesthesia + local anaesthesia [lidocaine injection]; volume: medical air continuous; midazolam titrated to level 3 on consciousness scale; (n=174).

Other interventions: inhaled combination of 0.3% sevoflurane and 40% nitrous oxide in oxygen + IV midazolam 0.5 mg/min until level 3 on consciousness scale reached.

Intervention concurrent medications: Local anesthetic only.
Control concurrent medications: same as intervention.

Intervention - achieved sedation: titrated. Control - achieved sedation: titrated.

Other analgesics therapy: not stated.

Monitoring for intervention: sedation monitored by anaesthetist during the procedure and by a nurse during recovery.
Monitoring for control: same as intervention.
Ekbom 2005 (Ref ID: 15942)
RCT
Randomisation unit: Patient.
Trial held in Sweden.
Setting: hospital - outpatients.
Funding :unclear/ not stated
Inclusion criteria: ASA I.

Exclusion criteria: .

Study comments: use of N2O for venous cannulation

Fasting: no solid food or liquid after midnight for glucose tolerance test.

Medical reason: intravenous line placement. Procedure type: Painful; intravenous catheter insertion. First procedure?: prior procedures.
ASA details: I. Learning disabilities: none mentioned.
Age: mixed; ages 6-18 years.
Gender: 27 male and 23 female.
Weight: all patients weighed more than 5 kg.

Planned sedation level: mild. Purpose: increase comfort.
Sedationist: nurse.
Procedure carried out by: nurse.
Sedation monitoring by: nurse.
  1. nitrous oxide [gradual stages starting with 2 l N2O /6 l O2 increasing to 4 l N2O] + topical anaesthesia [EMLA cream]; volume: gradual increase; (n=25).
  2. usual care + topical anaesthesia [EMLA cream] only; volume: n/a; (n=25).

Other interventions: none.

Intervention concurrent medications: not stated.
Control concurrent medications: same as intervention.

Intervention - achieved sedation: titrated. Control - achieved sedation: n/a.

Other analgesics therapy: not stated.

Monitoring for intervention: not stated.
Monitoring for control: same as intervention.
Fauroux 2004 (Ref ID: 546)
RCT
Randomisation unit: Patient.
Trial held in France.
Setting: tertiary referral teaching hospital.
Funding :unclear/ not stated
Inclusion criteria: eEligible if undergoing diagnostic or therapeutic FB.

Exclusion criteria: severe respiratory distress, hemodynamic instability, impaired consciousness, vit. B12 deficiency, intracranial hypertension, pneumothorax or fractures of facial bones.

Fasting: fasting variable depending on patient age.

Medical reason: elective thoracic. Procedure type: Painful; bronchoscopy. First procedure?: not known / unclear.
ASA details: Not stated. Learning disabilities: none mentioned.
Age: mixed; 1 month to 18 years.
Gender: 25.5% male (48.5) male.
Weight: not known / unclear; weight range of children not given.

Planned sedation level: not stated / unknown. Purpose: mixed.
Sedationist: not stated / unknown.
Procedure carried out by: endoscopist.
Sedation monitoring by: physician and nurse.
  1. 50% nitrous oxide + local anesthesia (lidocaine spray); volume: Continuous inhalation; (n=53).
  2. 50% nitrogen/oxygen + local anesthesia (lidocaine spray); volume: continuous inhalation; (n=52).

Other interventions: none.

Intervention concurrent medications: none stated.
Control concurrent medications: same as intervention.

Intervention - achieved sedation: titrated. Control - achieved sedation: titrated.

Other analgesics therapy: not stated.

Monitoring for intervention: continuous monitoring via nurse and endoscopist, including puls oximetery, and videotape recorder.
Monitoring for control: same as intervention.
McCann 1996 (Ref ID: 1195)
RCT - crossover
Randomisation unit: Patient.
Trial held in USA.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: children requiring more than one sedation visit for completion of operative dentistry and who had exhibited uncooperative behaviours in previous procedures.

Exclusion criteria: not stated.

Study comments: there was not statistically significant difference in any physiologic or behavioral parameter as a function of inhalation agent.
Significant differneces fore found only as a function of procedural events.

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - mixed - e.g. extractions, restorations, pulpotomies, brief. First procedure?: prior procedures.
ASA details: I-II. Learning disabilities: none mentioned.
Age: 1 to 5 years of age; ages 36-60 months.
Gender: 26 males and 14 females.
Weight: all patients weighed more than 5 kg.

Planned sedation level: conscious sedation. Purpose: mixed.
Sedationist: operator - no more details.
Procedure carried out by: dental practitioner.
Sedation monitoring by: sedationist for both groups.
  1. 50% nitrous oxide/50% oxygen + topical anaesthesia + local anesthesia; volume: continuous flow; (n=20).
  2. 100% oxygen + topical anaesthesia + local anesthesia; volume: continuous flow; (n=20).

Other interventions: none.

Intervention concurrent medications: all children received chloral hydrate, 40 mg/kg and hydroxyzine, 2mg/kg po 45 minutes before treatment. Topical and local anesthetics were used during each procedure.
Control concurrent medications: same as intervention.

Washout period: time between treatments.

Intervention - achieved sedation: titrated. Control - achieved sedation: titrated.

Other analgesics therapy: not stated.

Monitoring for intervention: physiological parameters were recorded by automated monitor recorders and by an assistant.The automated counting system computer software program was used to quntify behavioral categories by a rater throughout the procedure.
Monitoring for control: same as intervention.
Primosch 1999 (Ref ID: 965)
RCT - crossover
Randomisation unit: Patient.
Trial held in USA.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: children 5-9 years old ASA I not taking any medications and without contraindications to nitrous oxidewho exhibited cooperative but anxious behaviour during previous dental treatment. At least two appointments of restorative dentristry with similar compl.

Exclusion criteria: not stated.

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - restorations. First procedure?: prior procedures.
ASA details: I-II. Learning disabilities: none mentioned.
Age: 5 to 12 years of age.
Gender: 10 males and 12 females.
Weight: not known / unclear.

Planned sedation level: mild. Purpose: mixed.
Sedationist: dental practitioner.
Procedure carried out by: dental practitioner.
Sedation monitoring by: another person - no details.
  1. 40% nitrous oxide/60% oxygen inhalation; volume: continuous administration; (n=22).
  2. 100% oxygen; volume: continuous administration; (n=22).

Other interventions: none.

Intervention concurrent medications: none stated.
Control concurrent medications: same as intervention.

Washout period: time to second appointment.

Intervention - achieved sedation: titrated. Control - achieved sedation: titrated.

Other analgesics therapy: not stated.

Monitoring for intervention: all patients were monitored continuously for RR, HR, and Oxygen saturation. The Ohio State University Behavior Rating Scale (OS)was performed each minute.
Monitoring for control: same as intervention.
Veerkamp 1993 (Ref ID: 1367)
RCT
Randomisation unit: Patient.
Trial held in The Netherlands.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: highly fearful children who had been referred to dental fear clinic. Ages 6-11 yers in normal primary school.

Exclusion criteria: none stated.

Study comments: behaviour was observed a using Veham anxiety scale for first and last session and average scores were was calculated. There was significantly lower anxiety in nitrous oxide group maintained throughout treatment

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - mixed - e.g. extractions, restorations, pulpotomies, brief. First procedure?: prior procedures.
ASA details: Not stated. Learning disabilities: none mentioned.
Age: mixed; ages 6-11 years.
Gender: matched on age and gender.
Weight: all patients weighed more than 5 kg.

Planned sedation level: not stated / unknown. Purpose: decrease fear.
Sedationist: not stated / unknown.
Procedure carried out by: dental practitioner.
Sedation monitoring by: not stated / unknown.
  1. nitrous oxide; volume: continuous flow; (n=27).
  2. behaviour management at dental fear clinic; volume: n/a; (n=25).

Other interventions: none.

Intervention concurrent medications: none stated.
Control concurrent medications: same as intervention.

Intervention - achieved sedation: titrated. Control - achieved sedation: n/a.

Other analgesics therapy: not stated but is usual dental practice.

Monitoring for intervention: all dental sessions were videotaped.
Monitoring for control: same as intervention.
Veerkamp 1995 (Ref ID: 1245)
RCT
Randomisation unit: Patient.
Trial held in The Netherlands.
Setting: primary care dental practice.
Funding :no funding
Inclusion criteria: native Dutch speakers in normal primary education who had jproved untreatable due to fear.

Exclusion criteria: no siblings.

Study comments: behavioural observations measured by Venham scale which has been validated in this age group. Anxiety scores were significantly less in nitrous oxide group than Behavior Modification Group and decreased anxiety appeared to continue over time.

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - mixed - e.g. extractions, restorations, pulpotomies, brief. First procedure?: prior procedures.
ASA details: Not stated. Learning disabilities: none mentioned.
Age: mixed; ages 6-11 years.
Gender: Groups were matched by sex and age.
Weight: all patients weighed more than 5 kg.

Planned sedation level: not stated / unknown. Purpose: decrease anxiety.
Sedationist: dental practitioner.
Procedure carried out by: dental practitioner.
Sedation monitoring by: not stated / unknown.
  1. nitrous oxide; volume: continuous; (n= 23).
  2. behavioural management; volume: n/a; (n=26).

Other interventions: none.

Intervention concurrent medications: None stated.
Control concurrent medications: same as intervention.

Intervention - achieved sedation: titrated. Control - achieved sedation: n/a.

Other analgesics therapy: not stated.

Monitoring for intervention: All sessions were recorded by video camera.
Monitoring for control: same as intervention.
Wilson 2002 (Ref ID: 711)
RCT - crossover
Randomisation unit: Patient.
Trial held in United Kingdom.
Setting: dental hospital.
Funding :unclear/ not stated
Inclusion criteria: patients referred to the sedation department at Newcastle Dental Hospital for orthodontic extraction of at least four teeth -premolars or canines- under local anaesthetic and sedation.

Exclusion criteria: not stated.

Study comments: behaviour was assessed using the Houpt Scale. Behaviour categories include excellent, very good, good and treatment aborted. There was no significant difference between groups

Fasting: not stated.

Medical reason: dental treatment. Procedure type: Painful; dental - extraction of teeth. First procedure?: not known / unclear.
ASA details: I. Learning disabilities: none mentioned.
Age: mixed; mean 12.5 years (range 10 to 16 years).
Gender: 16 male and 30 female.
Weight: not known / unclear.

Planned sedation level: mild. Purpose: mixed.
Sedationist: specialised sedationist.
Procedure carried out by: dental practitioner.
Sedation monitoring by: sedationist for both groups.
  1. nitrous oxide/70% oxygen [MDM quantified inhalation sedation unit] + distraction/reasurance + topical anaesthesia [gingivae for 2 mins] + local anaesthesia [2% lidocaine, 1:80,000 epinephrine]; volume: increments of 10% to a max of 30%; (n=26).
  2. oral midazolam + topical anaesthesia [gingivae for 2 mins] + local anaesthesia [2% lidocaine, 1:80,000 epinephrine]; volume: 0.5 mg/kg; (n=26).

Other interventions: none.

Intervention concurrent medications: on completion of treatment N2O flow was switched off and 100% oxygen administered for 2 mins before nasal mask removed.
Control concurrent medications: on completion of treatment pt transferred to recovery for at least 20 mins supervised by a parent and a sedation nurse; patient's fitness for discharge assessed and full writted and verbal postoperative sedation and surgical instructions provided.

Washout period: not stated.

Intervention - achieved sedation: titrated. Control - achieved sedation: bolus.

Other analgesics therapy: not stated.

Monitoring for intervention: same as control plus the clinician made sure that once 30% NO2 level was reached, this was mantained throughout subsequent dental treatment.
Monitoring for control: dental sedationist monitored patient's clinical status throughout each session assisted by a trained nurse; patient also monitored in recovery area under supervision of a parent and sedation nurse; monitoring clinically and by pulse oximetry.
Wilson 2002 (Ref ID: 729)
RCT - crossover
Randomisation unit: Patient.
Trial held in UK.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: children ages 10-16 years requiring bilateral identical extractions on opposite sides of the mouth.

Exclusion criteria: non stated.

Study comments: may be subgroup of Wilson 2002 with 46 patients.
Behaviour was assessed using the Houpt Scale. Behaviour categories include excellent, very good, good and treatment aborted. There was not significant difference between groups, p>0.05

Fasting: ‘starve’ two hours prior to appointment.

Medical reason: dental treatment. Procedure type: Painful; dental - restorations. First procedure?: prior procedures.
ASA details: I-II. Learning disabilities: none mentioned.
Age: mixed; ages 10 - 16 years.
Gender: 12 male and 14 female.
Weight: not known / unclear.

Planned sedation level: conscious sedation. Purpose: mixed.
Sedationist: experienced sedationist.
Procedure carried out by: dental practitioner.
Sedation monitoring by: sedationist for both groups.
  1. nitrous oxide 30%/70% oxygen + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: titrated to treatment level of 30% nitrous oxide and then continuous; (n=22).
  2. oral midazolam [0.5 mg/kg] + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: dose weight dependant; (n=26).

Other interventions: none.

Intervention concurrent medications: none.
Control concurrent medications: same as intervention.

Washout period: time to second appointment.

Intervention - achieved sedation: titrated. Control - achieved sedation: bolus.

Other analgesics therapy: not stated.

Monitoring for intervention: the dental sedationist monitored the patient's clinical status throughout each session assisted by a trained dental sedation nurse.
Monitoring for control: same as intervention.
Wilson 2003 (Ref ID: 589)
RCT - crossover
Randomisation unit: Patient.
Trial held in UK.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: patients who required bilateral, identical extractions (upper or lower) on opposite sides of the mouth.

Exclusion criteria: not stated.

Study comments: the Houpt Behaviour Rating scale was used and patients were assessed as having excellen, very good, fair or poor behaviour. Only two patients in each group scored fair or poor

Fasting: 2 hours before treatment.

Medical reason: dental treatment. Procedure type: Painful; dental - extraction of teeth. First procedure?: prior procedures.
ASA details: I-II. Learning disabilities: none mentioned.
Age: older than 12 years; ages 12-16 years.
Gender: 10 male and 30 female.
Weight: all patients weighed more than 5 kg.

Planned sedation level: conscious sedation. Purpose: mixed.
Sedationist: experienced sedationist.
Procedure carried out by: dental practitioner.
Sedation monitoring by: sedationist for both groups.
  1. 30% nitrous oxide/70% oxygen + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: continuous flow; (n=40).
  2. iv midazolam [0.5 mg per minute to a maximum of 5 mg] + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: dose titrated up to 5 mg; (n=40).

Other interventions: none.

Intervention concurrent medications: none.
Control concurrent medications: same as intervention.

Washout period: time between appointments.

Intervention - achieved sedation: titrated. Control - achieved sedation: titrated.

Other analgesics therapy: not stated.

Monitoring for intervention: monitoring every two minutes by sedationist and dental nurse.
Monitoring for control: same as intervention.
Wilson 2006 (Ref ID: 204)
RCT - crossover
Randomisation unit: Patient.
Trial held in United Kingdom.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: ASA I-II pts referred to sedation department for extraction of 4 primary teeth, 1in each of 4 quadrants in mouth. After assessed for need and fitness of sedation, only recruited those who failed to have dental treatment carried out under local anaesthesia.

Exclusion criteria: not stated.

Study comments: behaviour during treatment was graded using Houpt Behaviour scale sections 1-3 No ‘disruptive’ behavour seen in nitrous oxide group but 8/35 children in the Midazolam group had some disruptive behaviour. Differences were not statistically significant

Fasting: fast from solids and liquids for 2 hours before treatment visit.

Medical reason: dental treatment. Procedure type: Painful; dental - extraction of teeth. First procedure?: prior procedures.
ASA details: I-II; all but one were ASA physical status I. Learning disabilities: none mentioned.
Age: 5 to 12 years of age; mean: 7.4 years of age (range 5 to 10 years).
Gender: overall 54% (9/35) were male.
Weight: all patients weighed more than 5 kg; mean range 29.5 kg (range 17 to 55 kg).

Planned sedation level: mild. Purpose: not stated / unknown.
Sedationist: trained dental sedation nurse.
Procedure carried out by: dental practitioner.
Sedation monitoring by: not stated / unknown.
  1. nitrous oxide/oxygen [MDM quantified inhalation sedation unit] + distraction/reasurance [during procedure] + topical anaesthesia [bezocaine 20% for 2 min] + local anaesthesia [lidocaine2%, 1:80000 adrenaline]; volume: increments of 10% to a max of 30%; (n=42).
  2. oral midazolam [standard iv preparation] + topical anaesthesia [bezocaine 20% for 2 min] + local anaesthesia [lidocaine2%, 1:80000 adrenaline]; volume: minimum of 0.3 mg/kg [mean dose:8.6 mg (range 3.3-16.5mg)]; 1child did not manage to swallow full prescribed dose accounting for the minimum of 3.3 mg; mean range dose administered 8.6 (range 3.3 to 16.5) mg; (n=42).

Other interventions: none.

Intervention concurrent medications: on completion of sedation, 100% oxygen administered for 3 mins before nasal mask removed; pt transferred to recovery with a parent & supervised by sedation nurse & remained in recovery for at least 20 min after treatment.
Control concurrent medications: on completion of treatment pt transferred to recovery with a parent & supervised by sedation nurse & remained in recovery for at least 60 min after treatment.

Washout period: 2hr before treatment visit.

Intervention - achieved sedation: titrated. Control - achieved sedation: bolus.

Other analgesics therapy: not stated.

Monitoring for intervention: clinician made sure the 30% NO2 level of sedation was mantained throughout dental procedure; monitoring same as control.
Monitoring for control: sedation-trained nurse monitored pts throughout int effect (20-30min); BP, pulse, O2 saturation, respiration, colour/responsiveness monitored & recorded every 2min for first 20 min & every 5 min thereafter using Brietkopf & Buttner emotional status.
Wilson 2007 (Ref ID: 111)
RCT - crossover
Randomisation unit: Patient.
Trial held in UK.
Setting: primary care dental practice.
Funding :unclear/ not stated
Inclusion criteria: children aged 10-16 years, ASA I & II who had been referred for orthodontic extractions of four premolar teeth under sedation and local analgesia.

Exclusion criteria: children considered to be mouth breathers, those on central nervous system depressants and those sensitive to benzodiazepines were excluded.

Study comments: study is underpowered as only 36 of the required 40 patients completed the study. 45 patients were recruited but nine withdrew.
Spielberger Scal was used to assess anxiety for all subjects but a comparison between the two drug interventions was not made

Fasting: 2 hours prior to treatment.

Medical reason: dental treatment. Procedure type: Painful; dental - extraction of teeth. First procedure?: first procedure.
ASA details: I-II. Learning disabilities: none mentioned.
Age: mixed; ages 10-16.
Gender: 10 male and 26 female.
Weight: all patients weighed more than 5 kg.

Planned sedation level: mild. Purpose: mixed.
Sedationist: experienced sedationist.
Procedure carried out by: dental practitioner.
Sedation monitoring by: sedationist for both groups.
  1. 30% Nitrous oxide/70% oxygen + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: continuous administration; (n=36).
  2. transmucosal midazolam syrup [10 mg/ml supplied with a 1 ml syringe] + local anaesthesia [20% benzocaine, lidocaine 2% with 1:80,000 epinephrine]; volume: 0.2 mg/kg; (n=36).

Other interventions: none.

Intervention concurrent medications: none.
Control concurrent medications: same as intervention.

Washout period: time between appointments.

Intervention - achieved sedation: titrated. Control - achieved sedation: bolus.

Other analgesics therapy: not stated.

Monitoring for intervention: continuous monitoring during procedure of blood pressure, pulse, oxygen saturation and respiration.
Monitoring for control: same as intervention.

From: Appendix D, Evidence Tables

Cover of Sedation in Children and Young People
Sedation in Children and Young People: Sedation for Diagnostic and Therapeutic Procedures in Children and Young People [Internet].
NICE Clinical Guidelines, No. 112.
National Clinical Guideline Centre (UK).
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