Paediatrics & Child Health, 2017, 2–6

doi: 10.1093/pch/pxw011
Original Article
Advance Access publication 27 March 2017

Original Article

The use of ibuprofen and acetaminophen for acute headache in

the postconcussive youth: A pilot study
Tina Petrelli MN NP PhD1,2, Forough Farrokhyar MPhil PhD1,3, Patricia McGrath PhD4,
Chris Sulowski MD FRCPC2,5, Gita Sobhi BA BSc PHM2, Carol DeMatteo MSc Dip.P&OT6,
Lucia Giglia BSc MSc MD FRCPC(C)4, Sheila K. Singh MD PhD FRCSC1,2,7
Department of Surgery, McMaster University, Hamilton, Ontario; 2McMaster Children’s Hospital, Hamilton,
1

Ontario; 3Department of Clinical Epidemiology Biostatistics and Surgical Research Methodology, McMaster
University, Hamilton, Ontario; 4Pain Innovation Inc., London, Ontario; 5Department of Pediatrics, McMaster
University, Hamilton, Ontario; 6School of Rehabilitation Science and CanChild Centre for Childhood Disability
Research, McMaster University, Hamilton, Ontario; 7Stem Cell and Cancer Research Institute, Michael DeGroote
Centre for Learning and Discovery, McMaster University, Hamilton, Ontario
Correspondence: Dr Tina Petrelli, Division of Neurosurgery, McMaster Children’s Hospital, 1280 Main Street West, Hamilton,
Ontario L8N 3Z5. Telephone 905-521-2100 x 75237, e-mail petrelli@hhsc.ca

Abstract
Objective:  Acute postconcussive headaches are problematic for children after mild traumatic brain injury. There are no evi-
dence-based guidelines for their management. This pilot study aims to assess the feasibility and efficacy of routine analgesia
administration.
Methods:  A four-arm open-label randomized controlled trial pilot/feasibility study was conducted: (i) acetaminophen, (ii)
ibuprofen, (iii) alternating acetaminophen and ibuprofen and (iv) a control group. Children and youth 8 to 18 years of age
presenting to emergency department with headache within 48 hours of their first concussion were recruited consecutively
and sequentially randomized. Children with abnormal neuroimaging, history of previous concussions and bleeding disorder
were excluded. A headache survey was administered at recruitment. All participants were provided with standard concussion
management education and were also instructed on how to use the headache diary for the 1-week study follow-up period. The
diary captures (i) headache days, (ii) number of headaches, (iii) headache intensity and (iv) return-to-school information.
Feasibility was assessed based on study recruitment and compliance.
Results:  There were no feasibility concerns with the recruitment and no major compliance issues. Patients on acetamino-
phen, ibuprofen or both had significantly less headache days, episodes of headache and lower headache intensity than did the
standard care group. Patients on both ibuprofen and acetaminophen (79.0%) and on ibuprofen alone (61.0%) were more
likely to be back at school 1 week postinjury as compared with the acetaminophen group (33.3%) and the standard care
group (21.1%).
Conclusion:  Results showed routine analgesia administration was feasible and effective for postconcussive headache man-
agement. A larger full-scale randomized controlled trial is required to further assess the efficacy with longer follow-up, a wider
variety of patients and more concussion related outcomes.

L’utilisation d’ibuprofène et d’acétaminophène pour soulager les céphalées aiguës postcommotionnelles : une étude
pilote
Objectif :  Les céphalées postcommotionnelles posent problème chez les enfants après une légère commotion cérébrale. Il
n’y a pas de lignes directrices factuelles sur leur prise en charge. La présente étude pilote vise à évaluer la faisabilité et l’effica­
cité de l’administration systématique d’analgésiques.
Méthodologie :  Les chercheurs ont réalisé une étude pilote et de faisabilité ouverte, aléatoire et contrôlée en quatre volets :
i) acétaminophène, ii) ibuprofène, iii) alternance entre l’acétaminophène et l’ibuprofène et iv) groupe témoin. Des enfants
et des adolescents de huit à 18 ans qui ont consulté à l’urgence à cause de céphalées dans les 48 heures suivant une première
commotion ont été recrutés de manière consécutive, séquentielle et aléatoire. Les enfants dont la neuro-imagerie était anor-
male ou qui avaient des antécédents de commotion ou des troubles hémostatiques étaient exclus. Les enfants ont répondu

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Paediatrics & Child Health, 2017, Vol. 22, No. 1 3

à un sondage sur les céphalées au moment de leur recrutement. Tous les participants ont reçu une formation normale sur la
prise en charge des céphalées et ont également appris à utiliser un journal des céphalées pendant la période de suivi d’une
semaine. Le journal a permis de saisir : i) les journées comportant des céphalées, ii) le nombre de céphalées, iii) l’intensité des
céphalées et iv) l’information sur le retour à l’école. Les auteurs ont évalué la faisabilité d’après le recrutement dans l’étude et
la compliance aux directives.
Résultats :  Le recrutement ne soulevait aucune inquiétude quant à la faisabilité et aucun problème de compliance impor­
tant. Les patients qui prenaient de l’acétaminophène, de l’ibuprofène ou ces deux médicaments présentaient beaucoup moins
de journées comportant des céphalées, moins d’épisodes de céphalées et une intensité de céphalée plus faible que le groupe
témoin. Les patients qui prenaient à la fois de l’ibuprofène et de l’acétaminophène (79,0 %) ou de l’ibuprofène seul (61,0 %)
étaient plus susceptibles d’avoir repris l’école une semaine après leur commotion que ceux qui prenaient de l’acétaminophène
(33,3 %) et le groupe témoin (21,1 %).
Conclusion :  Les résultats ont démontré qu’il était possible d’administrer systématiquement des analgésiques pour prendre
en charge les céphalées postcommotionnelles et que ce traitement était efficace. Une étude aléatoire et contrôlée à plus grande
échelle s’impose pour mieux évaluer l’efficacité de ces traitements dans le cadre d’un suivi plus long, auprès d’un plus vaste
éventail de patients et de patients présentant plus de résultats cliniques liés aux commotions.

Keywords:  Acetaminophen; Acute headache; Adolescents; Analgesia; Children; Concussion; Headache; Mild traumatic brain
injury; Nonsteroidal anti-inflammatory drugs.

Postinjury concussions and headaches are increasingly recognized as signifi-
cant problems for children and youth who sustain mild traumatic brain inju-
ries (mTBIs) (1–7). Headache is the most commonly reported symptom of
concussion (2–4) and a symptom of postconcussive syndrome (PCS) (5).
Researchers have reported that post-traumatic headache is more common after
mTBI than after a severe traumatic brain injury. While postconcussion head-
ache generally resolves within 7 to 10 days (72% to 93% (5–7)), a significant
proportion of children and youth experience prolonged headache as a symptom
of PCS. A study of children and youth with mTBI aged 1 month to 18 years
revealed that 58% had headache 1 month postinjury and 9 of 670 (1.3%) had
persistent headache 12 months after injury (5). Despite the fact that most chil-
dren and youth recover clinically and return to normal activities within 1 month
postinjury, prolonged time away from school and restrictions on social and rec-
reational activities results in adverse consequences such as life stress, depression
and falling behind in school (8).
Although headache has been identified as a key predictive factor in the
development of PCS in children and adolescents after mTBI (9,10), there
are no evidence-based treatment guidelines available to guide the manage-
ment of acute postconcussive headache specific to the paediatric and adult
population. A  recent systematic review concluded that there was no strong
evidence available to direct the treatment of post-traumatic headache. The
Ontario Neurotrauma Foundation (ONTF) recently published Guidelines for
Diagnosing and Managing Pediatric Concussion (http://onf.org/documents/
guidelines-diagnosing-and-managing-pediatric-concussion); however, this
does not address acute postconcussive headache management. To date, there
are no guidelines in the literature worldwide to guide acute postconcussive
headache management (15). Physical and cognitive rest are the mainstay of ini-
tial concussion management (11–14).
Acetaminophen and ibuprofen have both been shown to be efficacious in the
treatment of headache in the paediatric population. Therefore, this pilot study
aims to assess the feasibility of and the efficacy of these analgesics administra-
tion during the acute postconcussive period.
PATIENTS AND METHODS
A prospective, four-arm open-label randomized controlled pilot/feasibility
study was conducted from October 2013 through April 2014 at McMaster
Children’s Hospital. Prior to study commencement, research ethics board
approval was obtained and the study protocol registered at ClinicalTrials.gov as
NCT02268058. Children and youth 8 to 18 years of age presenting to the emer-
gency department (ED) with headache within 48 hours following a concus-
sive event were approached for study participation. Further inclusion criteria
required that the children and youth must be able to understand and complete
a headache diary in English. Children and youth were excluded if they had (i) a
previous history of concussion, (ii) intracranial pathology on computed tomog-
raphy or MRI scan, (iii) a Glascow Coma Scale (GCS) score of less than 15, (iv)
a bleeding disorder or (v) a history of gastrointestinal ulcers.
Following consent, demographic information was collected and a headache
survey using modified International Headache Society Headache Criteria
(IHS) (16) for migraine and tension type headaches, excluding the temporal
criteria, was administered by the research assistant. The IHS headache criteria
are considered the gold standard in headache classification. As part of standard
practice, all participating families received education and written material from
a member of the ED staff on the CanChild Concussion management guidelines
on return to activity and return to school. Participants were sequentially ran-
domized to one of the four treatment arms: (i) acetaminophen for 72 hours
(10 mg/kg to 15 mg/kg, every 4 hours, maximum 75 mg/kg/day or 4 g/day);
(ii) ibuprofen for 72 hours (10  mg/kg, every 8 hours, maximum 3200  mg/
day); (iii) both acetaminophen and ibuprofen (dosed as per arms (i) and (ii));
and (iv) standard treatment for headache (no recommendation of routine
analgesia). Participants in all the study groups were instructed to document
medications taken during the 7-day study period in their headache diary. The
randomization sequence was computer generated in random block sizes of 4
and 8, and sent to the pharmacist where the treatment protocol was made and
sealed by the pharmacy. Prepackaged kits for all study arms were stored in the
ED and were given to the patients once enrolled in the study. The prepackaged
treatment kits contained the headache survey, educational material, headache
diary and medication form with standardized dosing calculations for ibuprofen
and/or acetaminophen based on the child’s weight. Study medications were
then allocated to the first three treatment arms specific to their analgesics and
dosing requirements. The standard group were told they could take acetamin-
ophen and ibuprofen as needed for their headaches and were provided with
dosing information. The headache diary required that the patient or parent
over 1 week capture (i) number of days with headache, (ii) number of head-
aches episodes per day, (iii) headache intensity rated 1 to 10 and (iv) return-to-
school status. For patients receiving medication, the dosing schedule for their
4 Paediatrics & Child Health, 2017, Vol. 22, No. 1

medication regimen was highlighted on the diary for the first 72-hour period.
Study participants were called once during the study week and a follow-up visit
was booked on day 7. During this visit, the diaries were obtained and return-to-
school status was documented. Study medication was collected at the end of
the week in the first three arms and measured by the research assistant to ensure
medications were taken routinely. This was an open-label trial with no blinding.
The feasibility outcome measures were: (i) monthly recruitment rate and (ii)
compliance with study protocol as evidenced by diary completion and return of
diary and medications.
The sample size was not formally calculated as this was a pilot study but the
goal was to enroll 80 patients.
No formal statistical analyses were planned for this pilot study. Baseline char-
acteristics were reported using descriptive statistics. Categorical variables were
reported in frequencies and relative frequencies. Continuous variables were
reported as mean with SD and median with minimum (min) and maximum (max).
Mean and median episodes of headaches and intensity of headaches are reported.
SPSS version 22.0 (SPSS Inc., Chicago, IL) was used for statistical analysis.
RESULTS
Of 289 patients screened, 80 (27.6%) patients were enrolled in the 7 months
of the study (Figure 1). Of the 198 patients excluded from the study, 161 did
not meet the inclusion criteria, 12 refused to participate and 25 presented when
there was no research assistant available. One participant from the ibuprofen
treatment arm was excluded from the analysis because of an incomplete diary.
All other diaries were completed and for the first three study arms, all medica-
tions were returned and measured indicating 100% compliance with taking the
recommended analgesics.
Baseline characteristics
The demographic data and headache classification are presented in Table 1. The
mean age of the study population was 12.9 years (50% female). Among the four
randomized groups, the primary aetiology of concussion was sports-related
(ranging from 57.0% to 68.4%) followed by falls.
At time of recruitment, 44 (55.7%) of all headaches were unclassifiable
based on the modified tensions type and migraine type criteria used in the
IHS headache survey. Thirty-one (39.2%) were migraine-like and 4 (5%) were
tension-like.
Headache days, headache episodes per day and
headache intensity
The number of reported headache days over the 7-day follow-up period was
7 days for both the acetaminophen and standard care treatment groups, 5 days
for the ibuprofen treatment group and 4  days for the combined analgesia
(Table 2).
Mean (SD) and median (min and max) of headache episodes per day
and headache intensity over the 7  day period are presented in Table  2 with
the number and intensity of headaches appearing to favour the combined
analgesia group.
None of the standard care group took analgesics on a regular basis and did
not have a preference for type of analgesic. Of the 20 patients, 8 took at least
one dose of an analgesic and only 6 (30%) ever took more than two doses per
day and only 5 (25%) took analgesics beyond 48 hours. Sixty-five percent of
analgesics in this group were taken in the late afternoon and evening and those
who took analgesics documented headache intensity between 5 and 9.
At 1 week postinjury, the frequency of return to school was 79% in the com-
bined analgesia group, 61% in the ibuprofen group, 33% in the acetaminophen
group and 21% in the control group.
DISCUSSION
There were no feasibility concerns with the recruitment and enrollment of
children in the trial and compliance with medications and diary completion
was excellent. However, the research assistant reported that it was very time

Assessed for
eligibility (n=289)

Excluded (n= 198)

Not meeng inclusion
criteria (n=161)
Refused to parcipate (n =
12)
Other reasons (n=25)
Presented to the ER outside
of study hours

Randomized (n=80)

Allocated to standard care Allocated to Allocated to ibuprofen Allocated to acetaminophen

arm acetaminophen are (n=20) arm (n=20) and ibuprofen arm
(n= 20) Received allocated Received allocated (n=20)
Received allocated Received allocated intervenon
intervenon (n= 20) intervenon (n= 20)
intervenon (n= 20) (n= 20)

Lost to follow up (n= 1)

Lost to follow up (n= 0) Lost to follow up (n= 0) Reason: did not complete study diary
Lost to follow up (n= 0)

Analysed (n= 20 ) Analysed (n= 20) Analysed (n=19 ) Analysed (n=20 )

Figure 1.  CONSORT diagram of study recruitment and follow through

Paediatrics & Child Health, 2017, Vol. 22, No. 1 5

Table 1.  Baseline characteristics of 79 patients with mild traumatic brain injury

Routine analgesia that they were Acetaminophen, n=20 Ibuprofen, n=20 Both analgesics, n=19 Standard care, n=20
randomized to for the first 72 h

Mean age in years (SD) 14.1 (2.2) 13.0 (2.6) 12.3 (3.0) 12.3 (2.4)
Gender
 Male 12 (57.0) 5 (26.3) 11 (58.0) 11 (55.0)
 Female 9 (43.0) 14 (73.7) 8 (42.0) 9 (45.0)
Aetiology of concussion
 Fall 3 (14.3) 5 (26.3) 4 (21.0) 5 (25.0)
 Sports 12 (57.0) 12 (63.2) 13 (68.4) 12 (60.0)
  Motor vehicle accident 2 (9.5) 0 0 1 (5.0)
 Assault 1 (4.8) 2 (10.5) 0 0
 Other 3 (14.3) 0 2 (10.5) 2 (10.0)
Headache classification
 Migraine 8 (38.0) 11 (58.0) 7 (36.8) 5 (25.0)
 Tension 0 1 (5.2) 0 3 (15.0)
 Unclassified 13 (62.0) 7 (36.8) 12 (63.2) 12 (60.0)
Q1: headache location
  1 front 11 (52.4%) 10 (52.6) 8 (45.0) 9 (45.0)
  2 back 4 (19.0) 5 (26.3) 5 (26.3) 7 (35.0)
  3 right side 7 (33.3) 12 (63.2) 3 (15.8) 7 (35.0)
  4 left side 9 (43.0) 9 (47.4) 8 (42.0) 9 (45.0)
  5 all over 6 (28.6) 3 (15.8) 5 (26.3) 8 (40.0)
Q2: headache description
 Pounding 7 (33.3) 8 (42.0) 8 (47.4) 10 (50.0)
 Pressing 10 (47.6) 9 (47.5) 9 (47.4) 10 (50.0)
 Unclassified 4 (19.0) 2 (10.5) 1 (5.3) 0
Q3: What number do you give your head-
ache intensity? (range 1–10)
  Median (min, max) 6 (1, 10) 6 (2, 8) 6 (2, 9) 5.5 (3, 9)
Q4: Does your headache get worse with 12 (57.0) 11 (58.0) 11 (58.0) 6 (30.0)
physical activity?
Q5: Do you feel sick or like you might 10 (47.6) 12 (63.2) 5 (26.3) 3 (15.0)
vomit?
Q6: Does light bother you? 15 (71.4) 8 (42.0) 12 (63.2) 10 (50.0)
Q7: Do noises bother you? 9 (43.0) 7 (36.8) 9 (47.4) 8 (40.0)
Q8a: Do you see flickering lights, spots or 3 (14.3) 4 (21.0) 2 (10.5) 5 (25.0)
lines or have you lost vision?
Q8b: Do you feel pins needles, or numbness 2 (9.5) 0 1 (5.3) 1 (5.0)
in you arms/legs?
Q8c: Have you lost your ability to walk? 1 (4.5) 0 1 (5.3) 1 (5.0)

consuming to obtain the diaries and medications back from participating
families.
This study is the first clinical trial to investigate the use of routine analge-
sics for headache during the acute postconcussive period in adults or children.
The study findings indicate that the routine administration of analgesia for 72
hours appeared to decrease the headache frequency as well as headache inten-
sity over a 7-day period and to result in earlier return to school; results were
always most favourable in the group that received both acetaminophen and
ibuprofen. Participants in this study were patients presenting to ED with first
time concussions and headache in the very acute stage. Therefore, generalizabil-
ity of the findings for all acute concussive patients is not possible as data were
not collected on past headache history or family history of migraines which are
important predictors of PCS.
Southey et al. (17) conducted a systematic review and meta-analysis of the
clinical safety and tolerability of ibuprofen compared with acetaminophen in
paediatric pain and fever and reported them to be generally safe with similar
tolerability and safety profiles. Safety data were not formally collected in this
pilot study.
One limitation is that we did not collect data on outcomes beyond 1 week
or on adverse events. One reason for choosing the open-label design was to
simplify proper dosing of the study medications using both liquid and pills
for the range of dosing required for the paediatric population. Another barrier
to a blinded trial was the cost of making liquid placebos. Interpretation of the
return-to-school data must be approached with caution as many factors influ-
ence a child’s return to school.
In our attempt to classify the acute postconcussive headache on presenta-
tion to ED, we realized that the modified IHS criteria (omitting the temporal
criteria) did not allow us to classify these headache as either tension-like or
migraine-like. Hence, the majority of headaches were unclassifiable. A reliable
classification of these acute concussive headaches would require a prospective
study design incorporating the use of reliable and valid methodologies to cap-
ture the time component and symptoms specific to concussion.
6 Paediatrics & Child Health, 2017, Vol. 22, No. 1

Table 2.  Number of headache days, headache episodes per day and headache intensity from the children and youth with concussion incident diaries over 7 days follow-up

Day Both, n=19 Ibuprofen, n=18 Acetaminophen, n=21 Standard care, n=19

1 # headaches/patient/day
  Median (min, max) 3 (2, 4) 3 (3, 4) 4 (2, 5) 4 (4, 6)
Intensity
  Median (min, max) 7 (4, 8) 8 (6, 9) 8 (6, 9) 8 (6, 9)
2 # headaches/patient/day
  Median (min, max) 2 (2, 4) 3 (3, 4) 4 (3, 4) 4 (3, 5)
Intensity
  Median (min, max) 5 (2, 6) 6 (4, 6) 6 (5, 7) 8 (6, 9)
3 # headache/patient/day
  Median (min, max) 2 (1, 3) 3 (2, 3) 3 (2, 4) 4 (3, 5)
Intensity
  Median (min, max) 3 (2, 4) 4 (3, 5) 5 (4, 6) 6 (4, 8)
4 # headache/patient/day
  Median (min, max) 1 (1, 1) 2 (1, 3) 3 (2, 4) 4 (3, 5)
Intensity
  Median (min, max) 2.5 (2, 3) 3 (2, 4) 5 (3, 6) 6 (4, 7)
5 # headache/patient/day
  Median (min, max) 1 (1, 1) 3 (1, 4) 4 (3, 4)
Intensity
  Median (min, max) 3 (2, 3) 4 (3, 6) 5 (5, 7)
6 # headache/patient/day
  Median (min, max) 2 (1, 3) 3 (1, 5)
Intensity
  Median (min, max) 4 (3, 5) 5 (4, 7)
7 # headache/patient/day
  Median (min, max) 1 (1, 1) 3 (1, 4)
Intensity
  Median (min, max) 3.5 (3, 6) 5 (3, 6)

CONCLUSION 6. Blinman T, Houseknecht E, Snyder C. Post concussive symptoms in hospitalized pedi-

The routine administration of both ibuprofen and acetaminophen or ibuprofen
alone for treatment of headache during the acute concussive period appeared
to be effective in decreasing (i) the number of headache days, (ii) the number
of headache episodes per day, (iii) headache intensity and in (iii) facilitating
return to school 1 week postinjury. A  large randomized controlled trial with
longer follow-up should be designed, incorporating children and youth with
concussion history with attention to premorbid factors impacting headache.
Acknowledgements
All phases of this study were supported by a New Investigator Fund, Hamilton Health
Sciences. All authors have no financial relationships relevant for this study and no conflicts
of interest to disclose.
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