No significant difference in number of AEs; acetaminophen and ibuprofen are effective and well-tolerated for acute migraine, with acetaminophen having faster onset but slightly less effect and ibuprofen giving best relief
Pothmann and Lobisch, 2000, Germany, NR
RCT, cross-over
Ambulatory clinic + home 6–12
Tension-type headache (IHS criteria)
(i) Flupirtine (6–8 years = 50 mg, 9–12 y = 100 mg) (ii) Acetaminophen (6–8 y = 250 mg, 9–12 y = 500 mg),
NR
Relevant side effects could not be observed
Soriani et al., 2001, Italy, NR
NRCT
ED mean 12.8 (SD 3.1)
Migraine (≥6-month duration and ≥1 attacks/month)
(i) Acetaminophen (15 mg/kg), (ii) Nimesulide (2.5 mg/kg),
Mild abdominal discomfort, nausea
No significant difference in side effects; nimesulide associated with low occurrence of ADRs especially in GI tract; effects in liver are within or below the general incidence with other NSAIDs
Lewis et al., 2002, USA, NR
RCT
Home 6–12
Migraine (IHS-R criteria)
(i) Ibuprofen (7.5 mg/kg), (ii) Placebo,
Nausea, vomiting, photophobia, phonophobia
Children’s ibuprofen suspension (7.5 mg/kg) is effective and well-tolerated for pain relief in acute treatment of migraine, particularly in boys.
Tanabe et al., 2002, USA, grants from multiple nonindustry sources
NRCT
ED 5–17
Minor extremity trauma including and distal to elbow and knee
(i) Standard care (ice, elevation, and immobilization), (ii) Standard care + distraction (e.g., guided imagery, music therapy, reading, or being read to), (iii) Standard care + ibuprofen (10 mg/kg),
NR
One child experienced nausea after taking ibuprofen
Wille et al., 2005, France, NR
Prospective cohort (single arm)
ED 0.5–6
Injuries to extremities with deformation; burns requiring hospitalization
Morphine (0.5 mg/kg),
Nausea, vomiting, decrease in oxygen saturation, drowsiness
No serious AEs and few minor side effects; oral morphine monotherapy can be given within an analgesic protocol with few minor side effects
Drendel et al., 2006, USA, NR
Cross-sectional survey
Hospital-based pediatric orthopedic clinic 1–18
Isolated extremity fracture receiving follow-up care at orthopedic clinic within 10 days of injury
Patients () received ibuprofen, acetaminophen + codeine, acetaminophen, other narcotics (hydrocodone, oxycodone, and rofecoxib), or a combination of ibuprofen, acetaminophen, and acetaminophen + codeine; 6 patients received no pain medication; 3 were unsure
“Other” effects from the medication
AEs not reported by drug; those receiving acetaminophen + codeine appeared to experience more other effects. Physicians and caregivers may have concerns about these side effects when dosing the medication
Evers et al., 2006, Germany, NR
RCT
Outpatient clinic 6–18
Migraine with and without aura
(i) Zolmitriptan (2.5 mg), (ii) Ibuprofen (200 mg for children <12 or 400 mg for adolescents), (iii) Placebo,
Dizziness, somnolence, gastrointestinal
No serious AEs occurred; all AEs were mild and resolved completely; zolmitriptan but not ibuprofen produced significantly more AEs than placebo
Clark et al., 2007, Canada, Hospital Research Institute
RCT
ED 6–17
Musculoskeletal injury (to extremities, neck, or back) occurring within 48 h
(i) Codeine (1 mg/kg, max 60 mg), (ii) Acetaminophen (15 mg/kg, max 650 mg), (iii) Ibuprofen (10 mg/kg, max 600 mg),
Minor AEs such as nausea, sleepiness, constipation
AEs were minimal; no significant difference between groups for minor AEs (nausea, sleepiness, constipation)
Cukiernik et al., 2007, Canada, Health Research Institutes
RCT
ED 8–14
Isolated soft tissue injury of ankle (no history of gastric ulcers or allergy to acetaminophen or naproxen)
(i) Naproxen (20 mg/kg), (ii) Acetaminophen (15 mg/kg),
NR
No significant difference in efficacy or AEs. Given acetaminophen’s wider safety margin and a large experience in children, acetaminophen may be the preferred agent for therapy of soft tissue injury in children and adolescents
Ismail et al., 2007, UK, NR
Case report
GP clinic 8
2-day history of neck and back pain
(i) Acetaminophen (500 mg) and ibuprofen (200 mg),
NA
Ibuprofen is generally safe and effective as antipyretic and analgesic; risk of acute papillary necrosis, particularly in dehydrated children
Koller et al., 2007, USA, Academic
RCT
ED
Suspected orthopedic injury; patients with baseline score of ≥4 on faces pain scale
Minor AEs in both groups; itching less in oxycodone group
Drendel et al., 2009, USA, hospital foundation
RCT
ED 4–18
Fracture of radius, ulna, or humerus (no open fracture)
(i) Acetaminophen + codeine (120 mg/5 mg per 5 mL), (ii) Ibuprofen (100 mg/5 mL),
Nausea, vomiting, drowsy, dizzy, constipation, other
Children receiving ibuprofen had significantly fewer AEs; both children and parents were more satisfied with ibuprofen; significantly higher rates of nausea and vomiting for children receiving acetaminophen + codeine
Friday et al., 2009, USA, NR
RCT
ED
Isolated extremity injury with tenderness to palpation from clavicle or femoral neck to distal phalanges; pain score ≥ 5 (of 10) at triage
(i) Acetaminophen + codeine (1 mg/kg, max 60 mg), (ii) Ibuprofen (10 mg/kg, max 400 mg),
Vomiting, pruritus, nausea
AEs were minimal
Shepherd and Aickin, 2009, New Zealand, no funding
RCT
ED 5–14
Fracture management within 24 h of injury; acute, nonpathological fracture of distal humerus, any part of radius, ulna, tibia, or fibula; patient able to be managed as outpatient
(i) Acetaminophen (15 mg/kg), (ii) Ibuprofen (10 mg/kg),
Vomiting, tiredness, dizziness
Parent-reported sleep quality did not differ between groups; no significant differences in side effects between groups
Richer et al., 2010, Canada, hospital foundation, national health funding agency
Chart review
ED 5–17
Migraine (headache at time of physician assessment and diagnosis of migraine by emergency physician)
(i) Ibuprofen (various doses) (ii) Acetaminophen (various doses) 1694 patients in study
NA
No serious AEs; dystonia, agitation, hypotension, and paresthesias were observed in association with a dopamine receptor antagonist
Ruperto et al., 2011, Italy, industry, research agency
RCT
ED 6–12
Pharyngotonsillitis
(i) Acetaminophen (12 mg/kg corresponding to 1 mL/2 kg), (ii) Ketoprofen lysine salt (40 mg), (iii) Placebo,
Bronchitis, rash, diarrhoea, cough
No serious AE; no events were related to the drugs or placebo
Le May et al., 2013, Canada, hospital research centre, national agency, industry
RCT
ED 7–18
Musculoskeletal injury to limb within 72 h; pain score > 3 on 0–10 VAS; bony tenderness, swelling, limited ROM, or angulation < 30°
(i) Codeine (1 mg/kg, max 60 mg) + Ibuprofen (10 mg/kg, max 600 mg), (ii) Ibuprofen + placebo (10 mg/kg, max 600 mg),
Drowsiness, nausea, vomiting, dizziness
1 patient in experimental group with nausea; no other side effects or AEs reported in either group; side effects were minimal
Neri et al., 2013, Italy, NR
RCT
ED 4–17
Suspected fracture or dislocation
(i) Ketorolac (0.5 mg/kg, to a max of 20 mg (= 0.025 mL/kg of the solution, maximum 1 mL), (ii) Tramadol (2 mg/kg, to a max of 100 mg, 0.020 mL/kg mL of the solution, and maximum of 1 mL), (iii) Placebo, = unclear
Vomiting, vomiting, dry mouth
No significant differences in AEs; fewer side effects reported in ketorolac group
Poonai et al., 2014, Canada, university research grant
(i) Morphine (0.5 mg/kg, to a max of 10 mg), (ii) Ibuprofen (10 mg/kg, to a max of 600 mg),
NR
No severe adverse drug reactions (e.g., immune-mediated hypersensitivity) were reported by any of the participants, and there were no deaths. Significantly more participants in the morphine group had adverse effects, the most common of which was drowsiness
Only five studies described how AEs were measured: Bertin et al. 1991 (on basis of clinical criteria); Evers et al. 2006 (patients or parents recorded adverse events at baseline and at 0.5, 1, 2, 4, and 24 hours after drug intake); Wille et al. 2005 (evaluated by nurse); Drendel et al. 2006 (26-question survey from patient’s caregiver); Drendel et al. 2009 (caregivers and their children used diary to record tolerability of assigned medication daily).
