Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Arai, 2007

Type of study:

randomized, controlled trial

Setting and country:

Aichi Medical University, School of Medicine, Aichi, Japan

Funding and conflicts of interest:

n.r.

Declaration of interest

n.r.

Inclusion criteria:

children aged 1–3 years, classified as ASA I, undergoing minor plastic surgery under general anaesthesia

Exclusion criteria:

(history of chronic illness, prematurity, or developmental delay

N total at baseline:60

Parental presence group (PP): 20

Parental presence + midazolam group (PPM): 20

Midazolam group (M):20

Important prognostic factors²:

Age median (range):

PP:2 (1-3)

PPM: 2 (1-3)

M:2 (1-3)

Sex:

IPP:60%M

PPM: 37%M

M:58%M)

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Mother went into the operating room with them and held them through induction of anaesthesia.

Describe control (treatment/procedure/test):

Midazolam premedication 0.5 mg/kg oral midazolam 40 min before induction of anaesthesia

Length of follow-up:

20 minutes

Loss-to-follow-up:

Two children were excluded as a result of refusal to take oral midazolam:

PPPM: n=1

M: n=1

Outcome measures and effect size (include 95%CI and p-value if available):

Emergence behaviour on a five-point scale

PP:4 (2-5)

PPM: 3 (2-4)

M:4 (2-5)

PPM significant different from other groups (p=0.05)

Byun, 2018

Type of study:

prospective, double-blind, randomised study

Setting and country:

Daegu Catholic University

South Korea

Funding and conflicts of interest:

Daegu Catholic University (grant numbers 20173026).

Declaration of interest

None declared.

Inclusion criteria:

Paediatric patients aged 2-8 yr with an ASA physical status (PS) of I or II, who were to undergo ophthalmology or otorhinolaryngology surgery requiring general anaesthesia, were enrolled.

Exclusion criteria:

(i) ASA PS III or IV;

(ii) presence of developmental delays or neurological diseases;

(iii) deafness or hearing impairments;

iii) deafness or hearing impairments;

(iv) history of allergies or contraindications to the use of ketamine

(increased intracranial pressure, open-globe injury, or a psychiatric or seizure disorder);

(v) maternal mutism;

(vi) absence of the mother.

N total at baseline:

Intervention: 33

Control: 33

Important prognostic factors²:

Age (range):

I:5.8 (3-8)

C: 5.7 (3-8)

Sex:

I: 58% M

C: 48% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

At the end of the operation, the recorded mother’s voice (Group M) was delivered through the noise-cancelling headphones.

Voice recording was done before the operation by an investigator who did not know the group allocation. In a calm environment, the mother was asked to speak the following sentences in her usual tone of voice:

‘OO (name of child), wake up. Let’s go home with mommy. OO, wake up. Open your eyes. Take a deep breath.’

Describe control (treatment/procedure/test):

At the end of the operation, the recorded stranger’s voice (Group S) was delivered through the noise-cancelling headphones.

Voice recording was done before the operation by an investigator who did not know the group allocation. In a calm environment, a woman who did not know the child was asked to speak the following sentences in her usual tone of voice:

‘OO (name of child), wake up. Let’s go home with mommy. OO, wake up. Open your eyes. Take a deep breath.’

Length of follow-up:

30 minutes

Loss-to-follow-up:

none

Outcome measures and effect size (include 95%CI and p-value if available):

The initial PAED score

Group M 9.8 (2.5)

Group S 12.5 (4.1)

P=0.002

PAED score 10 min after PACU admission

Group M 8.2 (3.0)

Group S10.1 (4.2)

P=0.04

The incidence of ED during

PACU stay

Group M: 24.2% (8/33)

Group S: 60.6% (20/33)

Odds ratio (95% confidence interval): 4.808 (1.667e13.862) p=0.006

Eijlers, 2019

Type of study:

Randomised controlled single-blind trial.

Setting and country:

single university children’s hospital in the Netherlands

Funding and conflicts of interest:

Zilveren Kruis foundation (project number: 2015233) and the Coolsingel

foundation (project number: 401).

Conflicts of interest: none.

Inclusion criteria:

consecutive children aged 4 to 12 years undergoing elective maxillofacial, dental or ENT day care surgery between March 2017 and October 2018.

Exclusion criteria:

mental retardation, inability of parents to read or write Dutch, epilepsy, visual

impairment, an American Society of Anaesthesiologists

(ASA) physical status at least III and need for pre-operative anxiolytic medication.

N total at baseline:

Intervention: 100

Control: 100

Important prognostic factors²:

Age (range):

I: 8.3 (6.7-10.2)

C: 7.5 (5.6-10.7)

Sex:

I: 45% M

C: 56% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

On the day of surgery, children receiving

VRE were exposed to a realistic child-friendly immersive virtual version of the operating theatre, so that they could get accustomed to the environment and general anaesthesia procedures.

Describe control (treatment/procedure/test):

Care as usual

Length of follow-up:

2 weeks after surgery

Loss-to-follow-up:

Intervention: 6 (3%)

Control: 3 (1.5%)

Reasons

Nine children were excluded because of accidental

unblinding (n=5), noncompliance with the anaesthetic protocol (n=2), no data collection at T2 and T3, due to logistical reasons (n=1), or cancelled surgery (n=1).

Outcome measures and effect size (include 95%CI and p-value if available):

Emergence delier measured with PAED (observed at recovery room)

Intervention: 7.0 (range 5.0-9.0)

Control: 6.0 (range 5.0-9.0)

P=0.266

Hilly, 2015

Type of study:

prospective cohort study

Setting and country:

Department of Anesthesia and Intensive Care, Robert Debre Hospital, Paris, France

Funding and conflicts of interest:

Funded by institutional resources

Conflicts of interest: no conflicts of interest

Inclusion criteria:

patients aged more than 3 years and strictly younger than 19 years of age and ASA status 1 or 2.

Exclusion criteria:

patients aged <3 years, emergency surgery, decline of participation to the study, known neurological or cognitive impairment, and ASA status 3 and 4.

N total at baseline:56

Intervention: 28

Control: 28

Important prognostic factors²:

Age:median (range)

I: 7 (3-16)

C:5.5 (3-16)

Sex:

I: 43%M

C:43%M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

A) parental presence: received standard parental presence during induction of anesthesia;

B) ADVANCE: received family-centered behavioral preparation;

C) oral

midazolam

Describe control (treatment/procedure/test):

standard care: these participants did not receive premedication or have parental presence during induction of anesthesia.

Length of follow-up:

Immediately after surgery at recovery room

Loss-to-follow-up:

Intervention:

A: 7

B: 4

C: 3

Control: 7

Reasons:

Operating room schedule (e.g., cases delayed, cases moved between various operating rooms; n =21;

Outcome measures and effect size (include 95%CI and p-value if available):

Median PAED score 15 min after PACU admission (range)

I: 10 (0-20)

C:0 (0-20)

MD = 1.7 (95%CI: -2.5 – 4.2) p=0.67

The incidence of ED (PAED>9)

I: 41%

C:42%

OR = 0.94 (95%CI: 0.31-2.80) p=0.57

Kain, 2007

Type of study:

Randomized Controlled Trial

Setting and country:

Yale–New Haven Children’s Hospital, USA

Funding and conflicts of interest:

Dr. Kain is supported by grant Nos. R01HD37007 and R01HD048935 from the National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, Maryland. This research was also supported in part by General Clinical Research Center grant No. M01-RR00125 from the National Center for Research Resources, National Institutes of Health, awarded to Yale University School of Medicine.

The videotape was developed with funds provided by a grant from Donaghue Foundation for Medical Research (Hartford, Connecticut).

Conflicts of interest: not reported

Inclusion criteria:

parents and children (aged 2–10 yr old) who were in good health (American Society of Anesthesiology physical status I or II) and who were undergoing general anesthesia and elective, outpatient surgery between November 2000 and October 2004

Exclusion criteria:

children with a history of chronic illness, prematurity (fewer than 36 weeks’ gestation), or diagnosed developmental delay

N total at baseline:

Intervention:

A: 101

B: 100

C: 101

Control: 106

Important prognostic factors²:

Age ± SD:

A: 5.5±2

B: 5.6±2

C: 5.5±2

Control:5.4± 2

Sex:

A: 69%M

B: 62%M

C: 60%M

Control: 60%M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Family workshop 2 weeks before surgery: 1h group session describing and explaining the perioperative journey, from arrival at the surgical ward (or the ambulatory surgical unit) through the operative period (arrival in the operative room, induction of anesthesia, and recovery from anesthesia), then PACU stay, and the postoperative recovery either on the ward or at home.

This was performed using a scale model of Playmobil.

Describe control (treatment/procedure/test):

No workshop

Length of follow-up:

15 min after PACU admission

Loss-to-follow-up:

Intervention:

I: 1

C: 2

Reasons:

Incomplete data collection

Outcome measures and effect size (include 95%CI and p-value if available):

Emergence delier

1: no symptoms of emergence delirium

A: 57.1%

B: 50.0%

C: 42.5%

Control: 35.4%

3: moderate to severe symptoms of emergence delirium

A: 15.5%

B: 10.4%

C: 20.7%

Control: 24.2%

p=0.038

Rodriguez, 2019

Type of study:

prospective, randomized trial

Setting and country:

freestanding

academic pediatric hospital in Northern California, USA

Funding and conflicts of interest:

Philanthropic support from the Traverse Foundation

Conflicts of interest were not reported.

Inclusion criteria:

children aged 4‐10 years; ASA Physical Status Classification (ASA) I or II; scheduled to undergo elective outpatient surgery; and naïve to general anesthesia

Exclusion criteria:

who received preoperative anxiolytic medication (such as midazolam); with significant cognitive impairment or developmental delays impacting language or vision; with a history of chronic illness; with a history of premature birth; and who were currently taking psychotropic medications

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

Age ± SD:

I: 6.8 ± 2.2

C: 6.7 ± 1.7

Sex:

I: 56% M

C: 52% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Bedside Entertainment and Relaxation Theater consists of the battery‐powered projector with a custom protective case and clamp mounted to the head the patient's gurney. There is an accompanying 2 foot by 3 foot corrugated plastic screen mounted to the foot of the bed by an additional clamp. BERT can be set up on a bed in under 1 minute and was loaded with five preselected age‐appropriate movies that children were able to choose from. Movies were started in the preoperative area and continued to play through mask induction of anesthesia.

Describe control (treatment/procedure/test):

Patients in the tablet arm of the study were given a Samsung Galaxy Tab E 9.6‐inch tablet in the preoperative area. Patients then chose from one of the five preselected age‐appropriate movies to watch in the preoperative area and through the induction process.

Length of follow-up:

Immediate after surgery till recovery room

Incomplete outcome data: Intervention: 5 (17%)

Reasons:

Did not have parent present induction (n = 3)

­Had prior general anesthesia (n = 1)

­Technology malfunction (n = 1)

Control: 3 (10%)

Reasons:

Did not have parent present induction (n = 1)

­Had prior general anesthesia (n = 2)

Outcome measures and effect size (include 95%CI and p-value if available):

Emergence delirium scores (PAED) were virtually equivalent between the

I: 7.63 ± 3.42,

C: 7.35 ± 2.66

(p = 0.748)

Behaviors consistent with emergence delirium (PAED score > 10)

C: 30.8%

I: 29.16%

Ryu, 2019

Type of study:

randomized controlled trial

Setting and country: Seoul National

University Bundang Hospital

Funding and conflicts of interest:

Grant (No

800‐20160254 to Pf Han) from the Seoul

National University College of Medicine,

Korea

The authors report no conflict of interest

Inclusion criteria:

children, aged 4‐10 years with the American Society of

Anesthesiologist (ASA) physical status of I or II, undergoing general

anesthesia and elective surgery

Exclusion criteria:

children requiring major surgery

or postoperative intensive care; those with a history of prematurity

or congenital disease; those with hearing impairment; those

with cognitive deficits or cognitive and intellectual developmental

disabilities; those who had an experience of anesthesia previously;

those taking psychoactive medications; and those with a history of

epilepsy or seizure

N total at baseline: 86

Intervention: 43

Control:43

Important prognostic factors²:

Age (range):

I: 6 (5-7)

C: 6 (5-8)

Sex:

I: 71% M

C: 54% M

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

The VR group received a VR‐guided tour of the operating theater via a smartphone application with a VR headset. After the intervention, an anesthesiologist asked each child and accompanying parent/guardian if they had any questions regarding

the perioperative procedures.

Describe control (treatment/procedure/test):

Children and parents/guardians in the control group received our

institution's standard preoperative educational procedure. The standard

preoperative education consisted of a detailed verbal explanation

about preoperative process by the anesthesia provider.

This education included an explanation and discussion on the process including that the child would be changed into a theater grown, an

intravenous catheter would be placed in the forearm by an intravenous access specialist with speed without local anesthesia, and that the child would be transported to the operating room with parents/

guardians on the stretcher car and monitoring device with facial mask (no flavor) would be applied during induction of anesthesia

with distraction technique (counting the number or singing the favorite song).

Length of follow-up:

Till patient was on the PACU.

Loss-to-follow-up:

Intervention: 0

Control: 3 (7%)

Reasons

Failure to check PAED (n=3)

Incomplete outcome data:

Intervention: 2 (5%)

Reasons

Cancellation of operation (n=2)

Control: 1 (2%)

Reasons

Cancellation of operation (n=1)

Outcome measures and effect size (include 95%CI and p-value if available):

Emergence delirium

I: 16 (39%)

C: 14 (36%)

RR (95% CI): 1.1 (0.5-2.8) p=0.773

PAED score

I: 8 (3.5-12.5)

C:8 (5-12)

MD -0.2 (-2.7-2.2)

P=0.791

Zhong, 2018

Type of study:

randomized, controlled trial

Setting and country:

Taizhou

Municipal Hospital, China

Funding and conflicts of interest:

Inclusion criteria:

preschool children aged from 3 to 6 years with American Society of Anesthesiologists (ASA) physical status I or II scheduled for tonsillectomy under sevoflurane anesthesia

Exclusion criteria:

a history of surgery,

psychological or neurological disorders, developmental delay, parental

refusal, upper tract infection and recent administration of sedatives or

analgesics

N total at baseline:

Intervention:

RV: 23

PV: 23

Important prognostic factors²:

For example

age ± SD:

PV: 4.60 ± 1.03

RV: 4.52 ± 0.99

RP: 4.65 ± 0.88

Sex:

PV: 52%

RV: 61%

RP: 61%

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

the anesthetist guided preschool children and

their parents visit waiting areas, operation room, recovery room, made

them understand the operation process, displayed the instrument, explained the feeling during induction and recovery of anesthesia and answered all other questions about surgery

Describe control (treatment/procedure/test):

routine preoperative

visit group (RV):

the anaesthetist visited preschool children and their

parents in wards.

routine preoperative visit plus propofol (RP):

the anesthetist visited preschool children and their

parents in wards plus administrated of propofol at the end of anesthesia

Length of follow-up:

Till patient was on the PACU.

Loss-to-follow-up:

none

Outcome measures and effect size (include 95%CI and p-value if available):

PAED

PV: 6.04 ± 2.63

RV: 11.26 ± 3.60

RP: 6.30 ± 2.36

P<0.01

Incidence of emergence delier

PV: 21.7%

RV: 73.9%

RP: 21.7%

P<0.05

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Arai, 2007

Eligible children and

their mothers were allocated to one of three groups

using computer-generated random numbers

Unlikely

Unlikely

Unclear

Unlikely

Blinded observer

Unclear

Unlikely

Unclear

Byun, 2018

Subjects were randomly assigned to listen to the mother’s voice or a stranger’s voice with a 1:1 ratio. A random sequence was generated using a computerised online tool (www.Randomization.com) and kept within sealed opaque envelopes by an assistant not involved in this study.

Unlikely

Unlikely

Unlikely

Unlikely

Unclear

Unlikely

Unlikely

An intention-to-treat analysis was performed, and missing data were replaced with the last observation carried forward method.

Eijlers, 2019

Block randomisation was performed, stratified by type of surgery: adenoidectomy and/or tonsillectomy, insertion of tympanostomy tubes, maxillofacial and dental procedures or other ENT procedures.

Unclear

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Nine children were excluded because of accidental unblinding (n=5), noncompliance with the anaesthetic protocol (n=2), no data collection at T2 and T3, due to logistical reasons (n=1), or cancelled surgery (n=1).

Unlikely

Intention-to-treat (ITT) analyses were performed for all

randomised participants.

Kain, 2007

Based on a computer-generated random number table, participants were randomized into four experimental conditions. This randomization sequence was concealed before interventions were assigned, and all participants were randomized in strict order as assigned by the random number table.

Unlikely

Unclear

participants could not be blinded to group assignment

Unlikely

Unlikely

Raters were as blind to group assignment as possible; assignment could not be absolutely blinded as far as whether parents were present

Unclear

Unlikely

A number

of patients, however, could not receive the designated interventions because of issues related to the operating room schedule (e.g., cases delayed, cases moved between various operating rooms; n =21 (3 to 7 in each group)

Unlikely

Using intention-to-treat analysis, we nonetheless included data that were available from these patients that were lost to follow up.

Rodriguez, 2019

The intervention was randomly preassigned by blind‐picking from an envelope containing an equal number of intervention and control indicators.

Unlikely

Unclear

Unclear

Unclear

Unlikely

Unclear

Lost to follow up

Intervention group: 5 (of 30)

Control group: 3 (of 30)

Unclear

Ryu, 2019

Randomization was conducted by an independent anesthesiologist who was in charge of patient allocation at 2 hours prior to arrival at the preoperative reception area of the operating theater. A computer‐ generated randomized code with nontransparent envelopes that contained sequential numbers was used.

Unlikely

Unclear

Unlikely

Unlikely

Unlikely

Unclear

Lost to follow up

Intervention group: 0 (of 43)

Control group: 3 (of 43)

Unclear

Zhong, 2018

patients were randomly allocated to one

of the three groups by using a computer-generated randomization program

Unlikely

Unclear

Likely

Unclear

Unclear

Unlikely

Unclear

Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?¹

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?²

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?³

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?⁴

(unlikely/likely/unclear)

Hilly, 2-15

Unclear

During the study period, 1050 patients were proposed to participate in the workshop and 28 agreed to participate in the workshop and the study. All patients proposed to participate in the comparison group agreed.

Unlikely

Unclear

Cut-off point PAED-score >9, which differs from other studies.

Unclear