Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Amin, 2011

Type of study: RCT

Setting and country: Department of Anesthesia, Tanta University Hospital, Tanta University, Tanta, Egypt

Funding and conflicts of interest:

“Source of Support: Nil, Conflict of Interest: None declared.”

Inclusion criteria:

children ASA I and II who underwent adenotonsillectomy, age group: between 4 and 6 years.

Exclusion criteria:

Exclusion criteria included diabetes, liver and/or kidney disease, hypersensitivity to drugs used, peritonsillar abscess, swallowing disorder, epilepsy or previous treatment with gabapentin or opioids analgesia.

N total at baseline:

Intervention: 35

Control: 35

Important prognostic factors:

Age (years) ± SD

I: 5.3±1.08

C: 4.8±1.24

Sex (M/F)

I: 19/16

C:20/15

Groups comparable at baseline.

Gabapentin 10 mg/kg was given orally 2 hours before induction of anesthesia (Gabapentin syrup 250 mg/5 ml)

Oral paracetamol 20 mg/kg was given orally 2 hours before induction of anesthesia.

Length of follow-up:

Not reported.

Loss-to-follow-up:

Not reported.

Incomplete outcome data:

Not reported.

Postoperative pain:

Visual analog scale graded from 0 to 10 (mean ± SD):

6 hours:

I: 4.050 ± 1.61

C: 5.20  +  0.89

Anxiety:

Not reported.

Opioid consumption:

Postoperative pethedine consumption in mg from the time of extubation (mean ± SD):

I: 8 ± 10.05

C: 16.25 ± 11.57

Time to postoperative mobilization: 

Not reported.

Complications:

Nausea:

“Incidence of nausea, vomiting, and sedation was comparable in both groups. Six patients in group I

received metoclopramide for controlling vomiting vs four patients in group II.”

Length of stay:

Not reported.

Author’s conclusion: Gabapentin 10 mg/kg administrated orally 2 hours before adenotonsillectomy in children significantly decreased postoperative pain score and pethedine requirements vs paracetamol premedication, with no reported side effects.

Anderson, 2020

Type of study: RCT

Setting and country:

Doernbecher Children’s Hospital, Oregon Health & Science University, USA

Funding:

No specific funding was obtained for this investigation.

Conflict of interest:

DEA (none), NTD (none), EBP (none), MFH (none).

Inclusion criteria were patients aged 10–19 years with idiopathic scoliosis, classified as American Society of Anesthesiology (ASA) Physical Status Classification I–III, and scheduled to undergo posterior spinal fusion for deformity correction.

Exclusion criteria included body mass index 35.0 or greater due to weight-based dosing restrictions and allergy to study medications.

N total at baseline:

Intervention: 27

Control: 28

Important prognostic factors:

Age (years) ± SD

I: 14.8 ± 2.0

C: 14.2 ± 2.1

Sex (M/F)

I: 5/19

C:7/19

Groups comparable at baseline.

Preoperative oral gabapentin (15 mg/kg)

Postoperative oral gabapentin (10 mg/kg every 8 h)

Preoperative oral placebo (15 mg/kg)

Postoperative oral placebo (10 mg/kg every 8 h)

Length of follow-up:

Not reported.

Loss-to-follow-up:

Intervention:

3 (11%)

Reasons: declined to participate after randomization (n=2), refused intervention due to taste (n=1)

Control:

2 (7%)

Reasons: declined to participate after randomization (n=1), refused intervention due to smell (n=1)

Incomplete outcome data:

Intervention:

4 (17%)

N=24 assessed for pain, hospitalization, and medication variables, n=20 assessed for parental satisfaction.

Control:

3 (12%)

N=26 assessed for pain, hospitalization, and medication variables, n=23 assessed for parental satisfaction.

Postoperative pain

VAS, 10-cm line (measured to nearest mm).

No absolute values only reported graphically. (The gabapentin group experienced a significant reduction (p = 0.02) in average VAS pain score on the operative day when compared with the placebo group. VAS pain scores were lower in the gabapentin group on Postoperative Days 1 (p = 0.09) and 2 (p = 0.07), and when averaged over the entire postoperative period (p = 0.07), but not to a level of statistical significance (Fig. 2). There was no statistically significant difference in average VAS score on Postoperative Days 3–5.)

Anxiety

Not reported.

Opioid consumption:

Morphine equivalent

Total medication mg/kg during postoperative days, mean ± SD

I: 3.38 ± 1.79

C: 5.05 ± 3.16

Time to postoperative mobilization 

Not reported.

Complications

Reports of nausea (mean ± SD)

I: 1.38 ± 1.86
C: 1.38 ± 1.86

Length of stay

Days hospitalized (mean ± SD)

I: 4.5 ± 0.7

C: 4.5 ± 0.9

Fenikowski, 2022

Type of study: RCT

Setting and country:  Department of Thoracic Surgery of the Institute of Tuberculosis and Lung Disease, Rabka Zdrój Branch, Poland

Funding: Publication costs were covered by grant no. 10.6/2022 (the statutory activity of the Institute

of Tuberculosis and Lung Diseases, Rabka-Zdrój Branch, Poland).

Conflicts of Interest: The authors declare no conflict of interest.

Inclusion criteria:

Patients were eligible for enrolment in the trial if they were between 9 and 17 years of age, with an American Society of Anesthesiologists (ASA) physical classification of 1 (normal healthy patients) or 2 (patients with mild systemic disease), scheduled for an elective Ravitch procedure.

Exclusion criteria:

Exclusion criteria were lack of postoperative chest drainage, inability to rate pain, a known allergy or sensitivity to gabapentin or morphine, chronic pain or daily analgesic use and those diagnosed with psychiatric disorders or epilepsy or treated oncologically, in whom postoperative thoracic epidural analgesia was used.

N total at baseline:

Intervention: 28

Control: 28

Important prognostic factors:

Age (years) Median [lower quartile, upper quartile]

I: 14 [13; 15]

C: 15 [13; 16]

Sex (M/F)

I: 27/1

C: 23/5

Groups comparable at baseline.

Gabapentin group (standard care + gabapentin;

experimental group)

In the experimental group, oral gabapentin was supplemented one hour before surgery (in a dose of 15 mg/kg), and 2 times per day on the first, second and third postoperative day (at 6.00 a.m. and 6.00 p.m. in a dose of 7.5 mg/kg).

Placebo group (standard care + placebo; control group)

Patients in the control group were given placebo capsules instead of gabapentin.

Length of follow-up:

Not reported.

Loss-to-follow-up:

I: 0

C: 0

Incomplete outcome data:

I: 0

C: 0

Postoperative pain

NRS 0-10

0 hours: Postoperative day 0 (median, lower and upper

quartile)

I: 0.3 [0.1; 0.8]

C: 0.8 [0.3; 1.1]

24 hours: Postoperative day 1 (median, lower and upper quartile)

I: 0.0 [0.0; 0.0]

C: 0.0 [0.0; 0.3]

Anxiety

The State-Trait Anxiety Inventory for adolescents (STAI) and children between 9 and 14 years of age (STAI-C) was used to measure state and trait anxiety. No difference between the gabapentin and placebo groups in terms of preoperative and postoperative anxiety state.

“Compared to preoperative anxiety, postoperative anxiety scores were significantly reduced both in the gabapentin group (median 6 [5; 6] vs. 5.5 [4; 6]; Z = 2.68; p = 0.007) and the placebo group (median 7 [5; 7] vs. 5.5 [3.5; 6]; Z = 3.65; p = 0.0002).”

Opioid consumption

Morphine consumption (mg), median [lower; upper quartile]

Postoperative Day 0

I: 34 [29; 37]

C: 36 [31; 48]

Postoperative Day 1

I: 21 [19; 24]

C: 25 [21; 32]

Postoperative Day 0-3 (total)

I: 18 [16; 21]

C: 21 [18; 28]

Complications

Nausea and vomiting, N(%):

I: 13 (46.4)

C: 15 (53.6)

Dizziness, N(%):

I: 0 (0.0)

C: 1 (3.6)

Filho, 2019

Type of study: RCT

Setting and country: Albert Sabin Children’s

Hospital, Fortaleza, Brazil

Funding/Support: There was no funding for this work.

Conflict of Interests: The authors declare that they have

no conflict of interests.

Inclusion criteria

Healthy children between 3 months and 16 years of age who were subject to unilateral lower limb surgery.

Exclusion criteria: presence of cardiac, pulmonary, renal, neurological diseases, allergy to any medication in protocols and refusal of children’s parents their gaurdians and patients themselves. All children’s gaurdians provided written informed consent.

N total at baseline:

Intervention: 42

Control: 45

Important prognostic factors:

Age (months) ± SD

I: 62.8 ± 59.2

C: 84.8 ± 67.4

Sex (M/F)

I: 22/18

C: 31/13

Groups comparable at baseline.

Gabapentin oral solution in a single dose of 10 mg/kg to 600 mg was administered 1 to 2 hours before surgery

A placebo syrup was administered 1 to 2 hours before surgery, both syrups had same flavor and features.

Length of follow-up:

Not reported.

Loss-to-follow-up:

Intervention:

2 (5%)

Reasons: patient did not swallow completely

Control:

1 (2%)

Reasons: patient did not swallow completely

Incomplete outcome data:

Intervention:

5 (13%)

Reasons: 5 patients had 18 hours of clinical evaluation before hospital discharge.

Control:

4 (9%)

Reasons: 4 patients had 18 hours of clinical evaluation before hospital discharge.

Postoperative pain

Classified according to 3 categories: without pain, mild pain, moderate pain. Category frequencies reported for both groups: At the 4th and 8th postoperative hour, there was lower pain intensity in the gabapentin group (only reported in bar graphs).

Anxiety

Not reported.

Opioid consumption

Use of Morphine in Percentage and Time in Hours of the 1st Administration. Daily consumption of morphine was similar, 0.09 mg/kg/day to gabapentin group and 0.08 mg/kg/day in control.

Time to postoperative mobilization 

Not reported.

Complications

Agitation in the first postoperative hour:

I: 12.5%

C: 36.3%

RR = 0.34 (95%CI 0.14, 0.85)

Length of stay

Not reported.

Authors’ conclusion:

We conclude that gabapentin in a single dose associated with a peripheral blockade plus bupivacaine 0.125% in children subjected to unilateral lower limb surgery is superior to placebo results. Gabapentin attenuated hemodynamic response to orotracheal intubation. Gabapentin promotes pre-anesthetic and postoperative sedation, preventing agitation in the immediate postoperative period.

Gettis, 2022

Type of study: RCT

Setting and country: Children’s Healthcare of Atlanta, US

Funding:

This work was supported by the Dudley L. Moore Foundation, an internal funding source at Children’s Healthcare of Atlanta, Atlanta, GA.

Conflicts of interest: The author reports no conflict of interest.

Inclusion criteria:

Patients ages 3-18 years with an American Society of Anesthesiologists (ASA) physical classification of 1 or 2 scheduled for T/A in same day surgery location under the care of a single surgeon.

Exclusion criteria:

A body mass index (BMI) > 40, ASA score greater than II, history of renal insufficiency, chronic pain, or allergy to gabapentin.

N total at baseline:

Intervention: 26

Control: 23

Important prognostic factors:

Age (years) ± SD

I: 6.8 ± 4.61

C: 6.6 (SD not reported)

Sex (M/F)

I: 21/5

C: 15/8

Groups comparable at baseline.

Gabapentin oral suspension (10mg/mL) was compounded according to the extemporaneous preparation recipe in Lexicomp.

The gabapentin dose used was 15mg/kg (maximum 600mg) once orally.

The placebo oral suspension was prepared with the same formula but without active drug in it.

The placebo was a pharmaceutical solution of ORA Sweet or ORA Plus flavoured syrups in a 1 to 1 mixture.

Length of follow-up:

3 days after surgery.

Loss-to-follow-up:

N=2 ineligible after randomization (group not specified), N=1 lost to follow up (gabapentin group)

Postoperative pain

Pain scores collected based on Wong-Baker FACES Pain Rating scale or Visual Analog Scale at the time of drug administration each day. Median pain scores:

I: 4.05 (2.49)

C: 4.09 (2.33)

Anxiety

Not reported.

Opioid consumption

Oxycodone, hydrocodone, fentanyl, morphine, hydromorphine. Patients in the gabapentin group reported less use of opiates, but only the number of opioid doses were reported and not the actual consumption in mg.

Time to postoperative mobilization 

Not reported.

Complications

Nausea, N (%)

I: 3 (11.54)

C: 2 (8.7)

Dizziness, N ( %)

I: 2 (8)

C: 0 (0)

Length of stay

Not reported.

Authors’ conclusion:

Our findings demonstrate a reduction in opiate use during the immediate postoperative period in the PACU. There are few viable options for acute pain relief in the pediatric surgical population that do not include opiates. Identification of opiate alternatives that are effective, cost efficient and an excellent safety profile is needed for pediatric T/A patients. Additional multi-center studies are needed to identify ideal timing, dose, and efficacy of gabapentin as well other non-opiate medications such as dexamethasone, lidocaine and caffeine to mitigate postoperative pain.

Haddadi, 2020

Type of study: RCT

Setting and country: Amir-Al-Momenin Hospital of Guilan University of Medical Sciences, Guilan, Iran.

Funding and conflicts of interest:

Not reported.

Inclusion criteria:

Children within the age range of 7-15 years with the American Society of Anesthesiologists Physical Status I or II. The subjects were all candidates for elective adenotonsillectomy or adenoidectomy (as the inclusion criterion)

Exclusion criteria:

The exclusion criteria were a body weight of less than 15 kg at the baseline, allergy to acetaminophen, sensitivity to gabapentin, history of seizure, previous administration of gabapentin, inability to understand the pain score of visual analog scale (VAS) (in the opinion of the study staff), renal or hepatic disease, immunosuppression, history of gastric ulceration, indigestion, dehydration through diarrhea and/or vomiting, history of severe asthma (defined as previous steroid treatment or hospital admission), consumption of analgesics during the last 24 h, alcohol or drug abuse, known glucose-6-phosphate dehydrogenase deficiency, diarrhea, bleeding disorders, and surgical duration of above 90 min.

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors:

Age (years) ± SD

I: 10.40±2.84

C: 8.37±2.01

Sex (M/F)

Not reported.

Groups not comparable at baseline: “In the present study, although the differences in the weight and age of the children were statistically significant between the two groups and the subjects in the gabapentin group were approximately 3 kg heavier and 2 years older than those in the acetaminophen group, these differences did not affect the result of the study.”

Gabapentin group:

In the gabapentin group, the children received a 10 mg/kg dose of gabapentin suspension 2h before anesthesia, and the placebo (suppository) was used exactly similar in shape, size, and appearance to acetaminophen suppository after the intubation and maintenance of anesthesia. Each suppository was individually wrapped with identical foil.

Acetaminophen (control) group:

The standard anesthesia method was performed in the control group, similar to the gabapentin group. The children received the placebo gabapentin suspension simultaneous with that in the case group. The amount, appearance, smell, and taste of gabapentin and placebo suspension were identical. Following the intubation and maintenance of anesthesia, a 40 mg/kg dose of acetaminophen suppository was administered to the patients.

Length of follow-up:

24h after surgery.

Loss-to-follow-up:

Not reported.

Incomplete outcome data:

Not reported.

Postoperative pain

Pain severity was recorded based on the VAS (with Wong-Baker Faces Pain Rating Scale), Mean ± SD:

0 hours:

I: 3.20±1.94

C: 2.73 ±1.57

6th hour:

I: 1.33±0.84

C: 1.53±1.07

24th hour:

I: 0.93±1.26

C: 0.60±0.62

Anxiety

Not reported.

Opioid consumption

Not reported.

Time to postoperative mobilization 

Not reported.

Complications

Nausea

Nausea and vomiting reported at 0, 2, 4, 6, 12 and 24^th hour. Differences were described as not significant, but no incidence (% of patients experiencing nausea and vomiting) per group was reported.

C: 0.17±.38 

Length of stay

Not reported.

Authors’ conclusion:

The obtained results of this study showed that the preoperative administration of low-dose gabapentin can reduce the severity of pain in the patients undergoing adenotonsillectomy without any adverse effects. The effects of acetaminophen suppository and gabapentin suspension on pain severity and nausea with the control of the confounding variables of age, weight, duration of surgery, and use of analgesic and antinausea drugs were not significant.

Helenius, 2020

Type of study: RCT

Setting and country:  Turku University Hospital, Turku University, Turku, Finland.

Funding and conflicts of interest: This study was supported by grants from Finska Läkaresällskapet, the Foundation for Paediatric Research, The Swedish Cultural Foundation in Finland, Medtronic International, and K2M via Innosurge. The funding bodies did not play a role in the investigation or writing of the manuscript. The funds were only used for salary for a research nurse and funding research leaves. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article.

Inclusion criteria:

Adolescent (defined as 10 to 21 years of age for the purposes of the present study) who was scheduled to undergo posterior spinal surgery with all-pedicle-screw instrumentation for the treatment of AIS, high-grade spondylolisthesis, or Scheuermann kyphosis. The patients had an American Society of Anesthesiologists (ASA) physical status of grade II or less.

Exclusion criteria:

Neurological disease, other spinal abnormality, an associated medical condition (neuromuscular scoliosis), need for anterior surgery or vertebral column resection, and preoperative opioid use.

N total at baseline:

Intervention: 33

Control: 31

Important prognostic factors:

Age (years) ± SD

I: 15.8 ± 2.3

C: 15.5 ± 2.0

Sex (M/F)

I: 11/21

C:10/21

Groups comparable at baseline.

Pregabalin group:

Patients in the pregabalin group received an oral 2-mg/kg dose of pregabalin, rounded up to the next 25 mg, on the preoperative evening, 12 hours before the induction of anesthesia. The patients received the second dose preoperatively, approximately 2 hours before the induction of anesthesia. The maximum dose of pregabalin for any patient was 150 mg twice a day. The study drug was continued twice a day for 5 days.

If the patient reported signs of neural injury or neuropathic pain after surgery, pregabalin treatment was initiated. In these patients, the study drugs (pregabalin or placebo) were withdrawn without unblinding.

Placebo group:

Patients in the placebo group received the same amount of similar-looking capsules with similar timing.

If the patient reported signs of neural injury or neuropathic pain after surgery, pregabalin treatment was initiated. In these patients, the study drugs (pregabalin or placebo) were withdrawn without unblinding.

Length of follow-up:

Outcomes measured until 48h after surgery.

Loss-to-follow-up:

I: N=1

After completion of the study protocol, 1 patient was excluded from the final analysis because of the presence of an osteoid osteoma.

C: N=0

Postoperative pain

Postoperative pain (on a verbal numerical rating scale from 0 to 10) at rest  in subgroup analysis of patients with AIS, mean ± SD

8 hr after surgery:

3.1 ± 2.3

3.3 ± 2.2

24 hr:

I: (N=25) 3.3 ± 2.6

C (N=26): 3.5 ± 2.2

Anxiety

Not reported.

Opioid consumption

Cumulative oxycodone consumption in mg/kg, median (95% CI)

After 24 hr:

I: 0.70 (0.63, 0.81)

C: 0.72 (0.66, 0.87)

At discharge (total consumption):

I: 2.90 (2.75, 3.51)

C: 3.07 (2.96, 3.88)

Subgroup analysis of patients with AIS, mean (95% CI)

After 24 hr :

I (N=25): 0.69 (0.58, 0.79)

C (N=26): 0.78 (0.65, 0.90)

At discharge (total consumption):

I (N=25): 3.08 (2.61, 3.55)

C (N=26): 3.56 (3.06, 4.07)

Complications

Nausea

17-24hr

I: 3

C: 6

Length of stay

Length of hospital stay in days, mean [range]

I: 6.5  [4- 10]

C: 6.8 [5-9]

Authors’ conclusion:

In conclusion, perioperative pregabalin did not reduce the immediate postoperative opioid consumption or pain scores in adolescents undergoing posterior spinal fusion in comparison with the findings in the placebo group. Perioperative pregabalin does not provide short-term benefit in adolescents undergoing posterior spinal fusion, but its long-term effects remain to be evaluated.

Marouf, 2018

Type of study: RCT

Setting and country: Tanta university hospital, Egypt

Conflicts of interest:

There are no conflicts of interest.

Financial support and sponsorship: Nil.

Inclusion criteria included children aged 4–10 years, had American Society of Anesthesiologists physical status Class I and II, and prepared for adenotonsillectomy using sevoflurane anesthesia.

Exclusion criteria included mental or developmental retardation, allergy to the study medications, hyperactivity disorders, or use of psychiatric medications.

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors:

Age (years) ± SD

I: 6.9 ± 1.68

C: 6.7 ± 1.84

Sex (M/F)

I: 16/14

C: 17/13

Groups comparable at baseline?

pregabalin group (Group P):

Thirty minutes before the commencement of anesthesia patients in in Group P received pregabalin syrup (trade name is Averopreg, Its concentration is 100 mg/ml, manufactured by Averroes pharma, Sadat City, Egypt) 1.5 mg/kg.

control group (Group C):

Thirty minutes before the commencement of anesthesia patients in Group C received placebo syrup (composed of sugar and saline and its taste is sweet) looked like pregabalin syrup. Both syrups were formulated by the pharmacy in equal volumes of 5 ml.

Length of follow-up:

Not reported.

Loss-to-follow-up:

No child was excluded from the study.

Postoperative pain

Faces Pain Scale-Revised (0 = no pain and 10 = very much pain) at 30 min, 2, 4, 6, and 8 h postoperatively. No absolute data reported.

Complications

Agitation: Emergence agitation (1 = sleeping; 2 = awake, calm; 3 = irritable, crying; 4 = inconsolable crying; 5 = intense restlessness, disorientation)

10 min postoperative (mean ± SD):

I: 2.66 ± 1.18

C: 3.4 ± 1

20 min postoperative:

I: 2.2 ± 1.12

C: 3.16 ± 0.87

30 min postoperative:

I:2 ± 1.01

C: 3.06 ± 0.78

Vomiting n(%):

I: 5 (16)

C: 14 (46)

Dizziness n(%):

I: 0 (0)

C: 0 (0)

Authors’ conclusion:

Preoperative pregabalin was associated with less postoperative EAS, analgesic requirement, and vomiting in pediatrics undergoing adenotonsillectomy using sevoflurane anesthesia without effect on time to open the eye or extubation and PACU duration of stay.

Mayell, 2014

Type of study: RCT

Setting and country: Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada

Funding: The Pain

Management Fund of the Sick Kids Foundation funded

the study.

Conflict of interest:

No conflicts of interest declared.

Inclusion criteria:

Patients aged 10–17 years, scheduled for elective surgical correction of idiopathic scoliosis, and who were able to operate a patient-controlled analgesia (PCA) pump were eligible for the study.

Exclusion criteria:

Patients were excluded if they were unable to cooperate, unable to operate the PCA pump, unable to rate pain, had a known allergy or sensitivity to gabapentin or morphine, or had a history of chronic pain or daily analgesic use. Patients were also excluded if they had taken acetaminophen, NSAID, or an antacid within a 24 h period prior to surgery.

N total at baseline:

Intervention: 18

Control: 18

Important prognostic factors:

Age (years) ± SD

I: 14.7 ± 1.8

C: 15.0 ± 1.4

Sex (M/F)

I: 2/16

C: 4/13

Groups comparable at baseline.

Gabapentin group:

The patient received capsules, prepared by pharmacy, containing

gabapentin 600 mg 1 h before surgery.

Control group:

The patient received identical capsules, prepared by pharmacy, containing placebo, 1 h before surgery.

Length of follow-up:

6 weeks

Loss-to-follow-up:

N=1 participant withdrawn in control group (had nonidiopathic scoliosis)

One participant in intervention group only took one of the two study capsules, not withdrawn.

Postoperative pain

Pain scores (NRS) at rest

1, 4, 8, 12, 24, 48, 72 h, and 1 week postoperatively, and at the 6-week outpatient follow-up visit. No absolute data reported, only graphically in a plot.

Anxiety

Not reported.

Opioid consumption

Provided as morphine equivalents, cumulative morphine consumption: mg·kg^-1

24h

I: 1.29 ± 0.44

C: 1.46 ± 0.68

Time to postoperative mobilization 

Not reported.

Complications

Dizziness and nausea incidence over 72h were reported but only the total number of incidences, not the number of patients who experienced dizziness or nausea.

Length of stay

Not reported.

Authors’ conclusion:

A single preoperative dose of gabapentin did not have an impact on pain outcomes arising from scoliosis surgery in this study. Furthermore, pain was often in the moderate to severe range in our study confirming that pediatric pain continues to be undertreated. Further research is required to evaluate the safety and efficacy of other analgesic modalities for moderate and major surgery, to prevent and minimize pain in children and adolescents undergoing major surgery.

Rusy, 2010

Type of study: RCT

Setting and country: Children’s Hospital of Wisconsin, US

Funding:

Supported by Jane B. Pettit Pain Fund, Children’s Hospital of Wisconsin

Foundation.

Conflicts of interest: Not reported.

Inclusion criteria were children (aged 9–18 years) with idiopathic spinal scoliosis undergoing posterior spinal fusion surgery of at least 9 levels. ASA physical status was III or less. Operations were performed by 1 of 5 surgeons.

Exclusion criteria

were obstructive sleep apnea; severe, concomitant disease (neuromuscular scoliosis or neurodegenerative disease); current opioid use or admission of illicit drug use; pregnancy; anterior spinal fusion; spinal reoperation; morbid obesity (body mass index >40); and allergies to morphine, hydromorphone, or gabapentin.

N total at baseline:

Intervention: 32 (29 analysed)

Control: 31 (30 analysed)

Important prognostic factors:

Age (years) ± SD

I: 14.8 ± 2.1

C: 14.2 ± 1.8

Sex (M/F)

I: 7/22

C: 7/23

Groups comparable at baseline.

Study drug (gabapentin 15 mg/kg) was given with premedication in the usual marketed capsule form or liquid, 25 to 30 minutes before being transported to the operating room. Study drug and placebo were identical in appearance. Dosing was based on adult data from several studies12,18–20 in which 17 to 20 mg/kg gabapentin in a single dose decreased opioid consumption.

Additional gabapentin was administered 3 times per day, starting on postoperative day 1 for 5 days at a dose of 5 mg/kg/dose.

A placebo was given with premedication in the usual marketed capsule form or liquid, 25 to 30 minutes before being transported to the operating room. Study drug and placebo were identical in appearance.

Additional gabapentin was administered 3 times per day, starting on postoperative day 1 for 5 days at a dose of 5 mg/kg/dose. Patients in the placebo group received an identical capsule or liquid 3 times daily for 5 days.

Length of follow-up:

Not reported.

Loss-to-follow-up:

Intervention:

2 (6%)

Reasons: feeling of sedation (n=1), development of rash (n=1)

Control:

1 (3%)

Reason: changed to anterior spinal fusion by surgeon.

Incomplete outcome data:

Intervention:

1 (3%)

Reason: excluded from analysis for violation of study criteria

Control:

0 (0)

Postoperative pain

Verbal numeric rating scale (0 –10), measured multiple times per shift, with movement and at rest.

At 0 hours (PARU), mean ± SD:

I: 2.5 ± 2.8

C: 6.0 ± 2.4

Anxiety

Not reported.

Opioid consumption

Total morphine consumption is presented in a graph until 4 days after surgery.

Time to postoperative mobilization 

Not reported.

Complications

Not reported.

Length of stay

Not reported.

Authors’ conclusion:

In conclusion, an initial preoperative loading dose and continued use of oral gabapentin decreased early total morphine consumption and pain scores in pediatric patients undergoing spinal fusion up to 2 days after surgery. Continued maintenance dosing of gabapentin beyond 2 days did not show benefit in pain management in this group of patients.

Salman, 2013

Type of study: RCT

Setting and country: Department of Anesthesiology and Reanimation, Başkent University Faculty of Medicine, Ankara, Turkey

Conflict-of-interest issues regarding the authorship

or article: None declared.

Funding: not reported.

Inclusion criteria:

Healthy children 3-12 years old, ASA class I or II, undergoing elective tonsillectomy and adenoidectomy were included in this prospective randomized double blind study.

Exclusion criteria:

The children with obstructive sleep apnea were excluded from the study.

N total at baseline:

Intervention: 23

Control: 23

Important prognostic factors:

Age (years): mean, [median], (range)

I: 5.6 [5] (3-9)

C: 5.3 [4] (3-11)

Sex (M/F)

I: 8/15

C: 11/12

Groups comparable at baseline.

gabapentin group

(Group G):

The patients in Group G received gabapentin (Neurontin® Pfizer Goedecke GmbH, Freiburg Germany), 15 mg.kg-1 dissolved in 10 ml of saline orally, 30 min. before the induction of anesthesia

control group (Group C):

The patients in Group C received 10 ml of saline 30 min. before the induction of anesthesia

Length of follow-up:

24 hours after surgery.

Loss-to-follow-up:

Not reported.

Postoperative pain

OPS (Objective pain scale) used to measure postoperative pain, obtained scores not reported.

Complications

Emergence agitation score (scale 1-5: 1: sleeping; 2: awake, calm; 3: irritable, crying; 4: inconsolable crying; 5: severe restlessness, disorientation.), median scores  (range):

Postoperative 10 min

I: 4 (1-5)

C: 5 (3-5)

Postoperative 20 min

I: 3 (1-5)

C: 4 (2-5)

Postoperative 30 min

I: 2 (2-5)

C: 4 (2-5)

Dizziness:

Dizziness was not stated at all after discharge from the hospital by parents.

Authors’ conclusion:

As a conclusion; gabapentin premedication decreases postoperative 24 hour analgesic consumption and attenuates emergence agitation after sevoflurane anesthesia. Further investigations are required to determine a dose–response relationship and the effect of timing.

Tomaszek, 2020

Type of study: RCT

Setting and country: Department of Thoracic Surgery, Institute of Tuberculosis and Lung Diseases, Rabka-Zdrój Branch, Rabka-Zdrój, Poland

Funding sources: This work was supported by the National Tuberculosis and Lung Diseases Research Institute, Poland (grant number 10.11).

Conflicts of interest: We have no conflicts of interest.

Inclusion criteria were patients aged nine to 17 years undergoing elective correction of the anterior thoracic wall by the Ravitch modified method, with postoperative chest drainage, in whom postoperative thoracic epidural analgesia was used.

Exclusion criteria were known allergy to any of the study medications, history of chronic pain or daily analgesic use, diagnosed with psychiatric disorders or epilepsy, treated oncologically, with impaired verbal communication, and American Society of Anesthesiologists physical status >3.

N total at baseline:

Intervention: 21

Control: 21

Important prognostic factors:

Age (years): median (lower and upper quartile)

I: 13 (10–15)

C: 15 (13–16)

Sex (M/F)

I: 16/4

C: 18/2

Groups comparable at baseline.

Gabapentin group:

The patients received preoperative (one hour before surgery) gabapentin in a dose of 15 mg/kg and after surgery gabapentin in a dose of 7.5 mg/kg two times per day (at 6.00 AM and 6.00 PM) for three days.

Placebo group:

The patients received preoperative (one hour before surgery) a placebo, and after surgery a placebo two times per day (at 6.00 AM and 6.00 PM) for three days.

Length of follow-up:

Not reported.

Loss-to-follow-up:

Intervention:

1 (5%)

Reason: lack of postoperative chest drainage

Control:

1 (5%)

Reason: symptoms of systemic toxicity

Postoperative pain

NRS (0-10),  median average pain scores at rest (upper and lower quartile)

PD0

I: 0.5 (0.3–0.8)

C: 0.5 (0.3–1.0)

PD1

I: 0.4 (0.0–0.7)

C: 0.1 (0.0–0.8)

PD2

I: 0.0 (0.0–0.7)

C: 0.5 (0.0–1.0)

PD3

I: 0.0 (0.0–0.6)

C: 0.5 (0.0–1.1)

Anxiety

Postoperative state anxiety levels (range 1–10 sten) reported in a figure.

I: the level of state anxiety on PD3 was significantly lower than before surgery (6 vs 7, Z=2.67, P < 0.01)

C: the level of postoperative anxiety remained at a similar level as preoperatively (6 vs 6, Z=1.78, P = 0.07)

Opioid consumption

Fentanyl total in µg mean ± SD

I: 1,279 ± 384

C: 1,266 ± 396

Time to postoperative mobilization 

Not reported.

Complications

Nausea incidence PD0–PD3, number (%)

I: 0 (0)

C: 2 (10)

Dizziness incidence PD0–PD3, number (%)

I: 0 (0)

C: 1 (5)

Authors’ conclusion:

Perioperative administration of gabapentin resulted in a decrease of postoperative anxiety in pediatric patients undergoing the Ravitch procedure.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Amin, 2011

Probably yes

Reason:

Patients were randomly allocated equally (35 patients) in each group

Definitely yes

Reason:

The randomization was performed using sealed numbered envelopes indicating the group of each patient.

Probably yes

Reason:

A blind nurse who did not participate in patients’ follow up read the number and made group assignments.

A blinded chief nurse who did not participate in data collection confirmed that each patient ingested the

medications as was scheduled.

The pain intensity was assisted by a person who was blind to study.

No information on outcome assessors and data-analysts.

Probably yes

Reason:

No loss to follow-up reported

Probably yes

Reason:

No research protocol available. Outcomes mentioned in methods section are reported.

No information.

LOW (all outcomes)

Anderson, 2020

Probably yes

Reason:

Subjects were randomized into either the experimental or control group by the OHSU research pharmacy via block randomization upon patient enrollment to result in equal-sized groups at study completion.

No information

Probably yes

Reason:

Patients, caretakers, and providers remained blinded to group assignments.

In protocol: Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

(blinding of data analysts not reported)

Definitely yes

Reason:

Loss to follow-up was infrequent and similar in both groups

Definitely yes

Reason:

All relevant outcomes from protocol/ methods section are reported.

No information.

LOW (all outcomes)

Fenikowski, 2022

Probably yes

Reason:

Randomized, (allocation ratio 1:1)

No information

Probably yes

Reason:

From protocol: Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

The children and their parents, nursing staff, surgeons, anaesthesiologists, investigators and data analysts were blinded to group assignments. It should be noted that the principal investigator performed both the duties of the study director and was responsible for data analysis.

Definitely yes

Reason:

Lost to follow-up n=0 reported for both groups

Probably/definitely yes

Reason:

All relevant outcomes from protocol/ methods section are reported.

No information.

LOW (all outcomes)

Filho, 2019

Probably yes

Reason:

Our team randomized patients with a drawing software.

No information

Probably yes

Reason:

The pharmacologist was blinded to solutions. For operative and postoperative period, the professionals didn’t know the group they had evaluated.

(blinding of data analysts not reported)

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from protocol/ methods section are reported.

No information.

LOW (all outcomes)

Gettis, 2022

Definitely yes

Reason:

Patients were randomized at a 1:1 ratio. Randomization was performed using random permuted blocks of size 2 and 4. Only the IDS pharmacist had access to the table.

No information

Probably yes

Reason:

All ambulatory surgery staff, patients, and families as well as the research team were blinded to group assignments. […] the IDS pharmacist assigned a patient identification number sequentially and dispensed either gabapentin or placebo according to the randomization table.

(blinding of data analysts not reported)

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from protocol/ methods section are reported.

No information.

LOW (all outcomes)

Hadaddi , 2020

Definitely yes

Reason:

The children were divided into two groups (..) based on quadruple random blocks. At the initiation of the study, the  equences of the blocks were selected by simple random sampling, (..) The subjects were assigned into two groups based on the gradual referral of the patients who met the inclusion criteria.

Definitely yes

Reason:

Random sampling, sealed in the envelopes, and stored at Anesthesiology Research Center.

Probably yes

Reason:

The children, anesthesiologist, and ear, nose, throat surgeon were blinded to the study groups. The anesthesiologist performing the study was unaware of the constituents of the drugs and allocation of the groups. An anesthetist who was responsible for the questionnaires with different parameters was also unaware of group assignment; accordingly, blinding was satisfactorily maintained throughout the study course.

(blinding of data analysts not reported)

Probably yes

Reason:

No loss to follow-up reported.

Probably yes:

Reason:

All relevant outcomes from methods section/ trial registration are reported.

Funding and conflicts of interest not reported.

Groups not comparable at baseline: the differences in the weight and age of the children were statistically significant between the two groups and the subjects in the gabapentin group were approximately 3 kg heavier and 2 years older than those in the acetaminophen group.

Some concerns (all outcomes)

Helenius , 2020

Probably yes

Reason:

Randomization to the study groups (1:1) was performed by the Department of Pharmacy on the basis of a predetermined list with blocks of 20 patients.

No information

Probably yes

Reason:

The investigators, patients, parents, nursing staff, and

surgeons were blinded to group assignment.

(blinding of data collectors and analysts not reported)

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from methods section/ trial registration are reported.

No information.

LOW (all outcomes)

Marouf, 2018

Probably yes

Reason:

Randomization was performed using computer program to create a list of numbers.

Definitely yes

Reason:

Each number (which referred to one group) was sealed in an opaque envelope. Each parent was asked to choose one envelope and give it to a person who compared the number with the computer-created list and then allocated the child to one group.

Probably yes

Reason:

The individual who assigned the patient to the group was different from the one who formulated the drugs. The anesthesiologist who gave anesthesia and collected data and the child and his parents were unaware of the child's group.

(blinding of outcome assessors and data analysts not reported)

Definitely yes

Reason:

No child was excluded from the study.

Probably yes

Reason:

All relevant outcomes from methods section are reported.

No information.

LOW (all outcomes)

Mayell, 2014

Probably yes

Reason:

Patients were randomized using a standardized randomization by our Department of Pharmacy.

No information

Probably yes

Reason:

randomized

double-blinded placebo-controlled study,

All outcome measurements were taken by blinded observers.

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from methods section are reported.

No information.

LOW (all outcomes)

Rusy, 2010

Probably yes

Reason:

A hospital pharmacy clinical coordinator randomized participants to each study group (gabapentin or placebo), with stratification by surgeon before premedication for surgery.

No information

Definitely yes

Reason:

The patients, parents, nursing staff, surgeons, acute pain staff managing the patients, and study principal investigator collecting postoperative data were blinded to group assignment.

(blinding of data analysts not reported)

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from methods section/ trial registration are reported.

No information on conflicts of interest.

LOW (all outcomes)

Salman, 2013

Probably yes

Reason:

The patients were randomly assigned (…) using a

randomization list.

No information

Probably yes

Reason:

Drugs were prepared by an investigator who was not involved in the group assignment. The anesthesiologists and data collectors and parents and observers in the recovery room were blinded to treatment group.

Anesthesia duration, and time to eye opening and extubation times were recorded by an observer blinded to the group assignment.

(blinding of data analysts not reported)

Probably yes

Reason:

No loss to follow-up reported.

Probably yes

Reason:

All relevant outcomes from methods section are reported.

Funding not reported.

LOW (all outcomes)

Tomaszek, 2020

Definitely yes

Reason:

Patients were randomly assigned to one of two parallel groups (gabapentin vs placebo) in a 1:1 ratio.

The hospital pharmacy was responsible for assigning patients to individual groups (gabapentin and placebo) based on a computer-generated list that was prepared before recruitment by the study director.

Definitely yes

Reason:

Next, the capsules, packed in an envelope marked with the personal identity number code of the patient, were delivered to the ward. The nurses administered the medicine given in the individual order card as “gabapentin.” In a second sealed envelope, which was stored in a designated place in the operating suite, the pharmacist placed the information about whether the patient received gabapentin or placebo; the envelope could be opened only in the case of life-threatening complications. After the treatment was finished, the sealed envelope was returned to the pharmacist.

Definitely yes

Reason:

With the exception of the hospital pharmacy, participants, care providers (physicians, nurses, psychologist), investigators, and data analysts were blinded. One of the principal investigators had several roles to fulfill in the study as study director and data analyst.

Probably yes

Reason:

Loss to follow-up was infrequent in intervention and control group.

Probably yes

Reason:

All relevant outcomes from methods section/ trial registration are reported.

No information.

LOW (all outcomes)