Emergency 2016; 6 (4): 192-195

OR I G I N A L RE S E A RC H

Comparing Two Different Doses of Intravenous Midazo-
lam in Pediatric Sedation and Analgesia
Hassan Barzegari1, Arash Forouzan1, Kambiz Masoumi1∗, Hassan Motamed1, Behzad Zohrevandi2, Shima
Zeynadini Meymand1

1. Department of Emergency Medicine, Imam Khomeini General Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2. Road trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran.

Received: May 2015; Accepted: September 2015

Abstract: Introduction: Midazolam has turned into a common drug for pediatric procedural sedation and analgesia.
However, there is not much data regarding its proper dose and potential side effects in the Iranian children
population. Therefore, the present study was done to compare 2 doses of IV midazolam in this regard. Methods:
The present clinical trial was performed to compare 0.1 and 0.3 m g /k g doses of IV midazolam in induction of
sedation for head trauma infant patients in need of brain computed tomography (CT) scan. Conscious infants
under 2 years old, with stable hemodynamics were included. Onset and duration of action as well as probable
side effects were compared between the two groups using SPSS version 22. Results: 110 infants with the mean
age of 14.0 ± 5.9 months (range: 4–24) and mean weight of 9.7 ± 2 k g (range: 5–15) were randomly allocated to
one of the 2 study groups (54.6% female). Success rate in 0.1 and 0.3 m g /k g groups were 38.2% (21 patients)
and 60% (33 patients), respectively (p = 0.018). Overall, 56 (50.9%) patients did not reach proper sedation and
were sedated receiving ketamine (22 patients) or another dose of midazolam (34 patients, mean additional dose
needed was 2.1±1.1 m g ). Conclusion: The results of the present study demonstrated the higher success rate and
longer duration of action for 0.3 m g /k g midazolam compared to 0.1 m g /k g . The groups were equal regarding
onset of action, effect on vital signs and probable side effects.

Keywords: Midazolam; conscious sedation; dose-response relationship, drug; infant; emergency service, hospital

© Copyright (2016) Shahid Beheshti University of Medical Sciences

Cite this article as: Barzegari H, Forouzan A, Masoumi K, Motamed H, Zohrevandi B, Zeynadini Meymand Sh. Comparing Two Different

Doses of Intravenous Midazolam in Pediatric Sedation and Analgesia. Emergency. 2016; 4(4):192-195.

1. Introduction

S
edation induction is one of the most important and

sometimes most difficult stages of carrying out a diag-

nostic or therapeutic procedure in children (1). Chil-

dren not cooperating for diagnostic evaluations such as com-

puted tomography (CT) scan and magnetic resonance imag-

ing are among the most common cases of using procedu-

ral sedation and analgesia (PSA) in emergency departments

(ED). An ideal sedative drug should be rapid and short-

acting, with minimum side effects on the patients respiratory

condition and hemodynamic.

Various drugs such as chloral hydrate, phenobarbital, propo-

∗Corresponding Author: Department of Emergency Medicine, Imam
Khomeini General Hospital, Ahvaz Jundishapur University of Medical Sci-
ences, Azadegan Avenue, Ahvaz, Khuzestan Province 6193673166, Iran;
Tel/Fax: +986112229166; Email: emdajums@yahoo.com.

fol, midazolam, and etomidate are among the available drugs

for this purpose Yet, selection of the safest and most efficient

drug and its proper dose for sedation are a matter of debate

(1–4). Many of pediatric patients do not receive enough drug

due to concerns about probable side effects of the drug (5).

Midazolam has turned into a common drug for induction of

sedation in EDs as a result of its short half-life, various meth-

ods of prescription and less pain at the time of injection. This

relatively short-acting benzodiazepine has anti-stress, seda-

tive, anti-seizure, and muscle relaxant effects.

Singh et al. showed that use of intravenous (IV ) midazo-

lam with a 0.2 m g /k g dose, can induce proper sedation with

minimum side effects for pediatric imaging (6). However,

there is not much data regarding its proper dose and poten-

tial side effects especially in the Iranian children population.

Therefore, the present study was done to compare 2 doses of

IV midazolam in sedation induction for doing brain imaging

in infants.

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193 Emergency 2016; 6 (4): 193-195

2. Methods

2.1. Study design

The present clinical trial was performed to compare 0.1 and

0.3 m g /k g doses of IV midazolam in induction of seda-

tion for infants in need of brain CT scan following head

trauma. The infants presented to the ED of Golestan and

Imam Khomeini Hospitals, Ahvaz, Iran, during April 2014

to March 2015 were studied. After completely explaining

the study protocol to the parents, informed consent form

was filled for each participant to enter the study. All the

researchers adhered to Helsinki declaration. If the parents

were not content with the study process or did not want

their infant to continue participating at any stage, the infant

was excluded. The present study has been registered on the

Iranian Registry of Clinical Trials (IRCT) under the number

IRCT201592121289N2 and approved by the Ethics Commit-

tee of Ahvaz Jundishapour University of Medical Sciences.

2.2. Participants

Infants presented to the ED following head trauma in need

of sedation induction for undergoing brain CT scan were

enrolled. Conscious infants under 2 years old, with stable

hemodynamics were included. Exclusion criteria consisted

of high probability of difficult airway, history of uremia and

allergy to benzodiazepine, presence of hemodynamic insta-

bility, congestive heart failure, liver diseases, decreased level

of consciousness, uncontrolled vomiting, history of reflux,

and simultaneous use of opioids.

2.3. Procedure

All patients were prepared with a proper peripheral IV line

and continuous heart, blood pressure, pulse rate, and pulse

oximetry monitoring. Participants underwent low-flow oxy-

gen therapy via nasal cannula during the procedure. They

were divided into equal groups of A and B, using 4-block

randomization. Group A, received IV midazolam with 0.1

m g /k g dose, while the dose was 0.3 mg/kg for group B. The

goal was reaching sedation level of 3 or 4 based on Ramsay

scale (7). Not reaching the desired level of sedation was con-

sidered as sedation failure. In these cases IV ketamine with

1 m g /k g dose or another dose of midazolam was used. All

injections were done via the peripheral vessel using a blue or

yellow angiocatheter, and slowly during 10 seconds. Brain CT

scan indication was decided by an emergency medicine spe-

cialist based on the standard protocols of advanced trauma

life support (ATLS). Injections were done by trained nurses

under supervision of a senior emergency medicine resident.

Over the course of the procedure, all the required equip-

ment for probable need for airway management were present

at the patients bedside. Midazolam ampule containing 5

m g /c c was used. We should note that the physician prescrib-

Table 1: Baseline characteristics of studied patients

Variable Groups P value
0.1 m g /k g 0.3 m g /k g

Sex
Boy 26 (47.3) 24 (43.6) < 0.424
Girl 29 (52.7) 31 (56.4)

Age (Month) 15.7 ± 5.4 12.4 ± 6.0 0.003
Weight (K g ) 9.8 ± 1.9 9.5 ± 2.0 0.465
The number of patients in each group = 55; measures pre-
sented as number (%) or mean ± standard deviation.

ing the drugs and the patientsâĂŹ parents were blinded to the

drug dose.

2.4. Data gathering

A checklist consisting of demographic data and pharmaco-

dynamics (onset and duration of action and side effects) was

filled for all the patients in both groups. Drop of oxygen sat-

uration to < 95, decreased blood pressure, inconsolable cry-
ing, restlessness and anxiety, hiccup, opisthotonus, seizure,

nausea and vomiting, and respiratory depression and apnea

were among the studied side effects.

2.5. Statistical analysis

Data were analyzed using SPSS statistical software version 22.

Quantitative data were reported as frequency and percent-

age, and qualitative ones as mean ± standard deviation. Chi-
square and Independent sample t-test were used for compar-

ing data between two groups. P < 0.05 was considered as sig-
nificance level.

3. Results

110 infants with the mean age of 14.0 ± 5.9 months (range:
4–24) and mean weight of 9.7 ± 2 k g (range: 5–15) were
randomly allocated to one of the 2 study groups (54.6% fe-

male). Table 1 shows the baseline characteristics of the pa-

tients. Success rate in 0.1 and 0.3 m g /k g groups were 38.2%

(21 patients) and 60% (33 patients), respectively (p = 0.018).
Overall, 56 (50.9%) patients did not reach proper sedation

and were sedated receiving ketamine (22 patients) or an-

other dose of midazolam (34 patients, mean additional dose

needed was 2.1 ± 1.1 m g ). Table 2 compares the therapeutic
characteristics and side effects of the 2 doses of midazolam.

4. Discussion

The results of the present study demonstrated the higher suc-

cess rate and longer duration of action for 0.3 m g /k g mida-

zolam compared to 0.1 m g /k g . The groups were equal re-

garding onset of action, effect on vital signs and probable side

effects.

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Barzegari et al. 194

Table 2: Baseline characteristics of studied patients

Variable Groups P value
0.1 m g /k g 0.3 m g /k g

Sex
Boy 26 (47.3) 24 (43.6) < 0.424
Girl 29 (52.7) 31 (56.4)

Age (Month) 15.7 ± 5.4 12.4 ± 6.0 0.003
Weight (K g ) 9.8 ± 1.9 9.5 ± 2.0 0.465
The number of patients in each group = 55; measures pre-
sented as number (%) or mean ± standard deviation.

Facing children in ED has always been special. Presentation

of a pediatric trauma patient, accompanied by restless par-

ents, to an overcrowded ED has been a nightmare for emer-

gency medicine physicians, especially if a diagnostic and

therapeutic procedure is required. The need for keeping the

child motionless during procedures, has made using PSA in-

evitable for this age group. Being familiar with various kinds

of available drugs and their dosage is a necessary skill for all

emergency physicians. Therefore, the present study was de-

signed and carried out to compare the effectiveness and side

effects of two different IV midazolam doses.

In the study by Singh et al., midazolam’s onset of action was

shorter than this study (6). This difference may be due to

the differences in age distribution of the participants in the 2

studies and the chief complaints on admission. In both stud-

ies, a relatively significant number of the patients needed ad-

ditional doses to reach proper sedation and a single dose of

the drug had a significant failure rate. In addition, in a study

by Sutherland et al., use of 0.2 m g /k g alone was not enough

to induce proper sedation for undergoing CT scan in most

children; it was efficient for only 19% of them (2). Regard-

ing onset of action, the results of the present study were in

line with those of Jevdjic et al. in their 2011 study, especially

in the 0.1 m g /k g dose (8). Additionally, regarding proba-

ble side effects and effects on vital signs a thorough corre-

lation was seen between the results of this study and Rah-

man study (9). Treatment success rate in this study was less

than 50% for both doses. This means that about half the pa-

tients need higher doses of midazolam or other drugs such

as ketamine to reach the proper level of sedation. The re-

sults of a review study in 2007 showed that despite the similar

effects of midazolam and ketamine, ketamine was the drug

of choice for both parents and physicians to sedate children

(10). Therefore, it seems that although midazolam is safe and

emergency physicians are familiar with its probable side ef-

fects, its success rate, at least with the doses mentioned in the

present study, is not high. Therefore, we should either revise

the dose of this drug, or use other drugs with higher success

probability. The importance of this matter is that most of the

time, when children are not sedated with the initial injection,

it makes the parents more anxious and therefore makes the

atmosphere more chaotic. It is suggested to carry out other

trials with various doses and bigger sample size, to find the

proper dose of drug. Parents not being content about their

children participating in the study was among the limitations

of the present study, which made case collection somehow

difficult.

5. Conclusion

The results of the present study demonstrated the higher suc-

cess rate and longer duration of action for 0.3 m g /k g mida-

zolam compared to 0.1 m g /k g . The groups were equal re-

garding onset of action, effect on vital signs and probable side

effects.

6. Appendix

6.1. Acknowledgements

This article was extracted from the emergency medicine res-

idency thesis of Dr. Shima Zeynadini Meymand.

6.2. Author contribution

All authors passed four criteria for authorship contribution

based on recommendations of the International Committee

of Medical Journal Editors.

6.3. Funding

This article is extracted from a project funded by

Jundishapour University of Medical Sciences, which was

registered under the number GP93044.

6.4. Conflict of interest

None.

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	Introduction
	Methods
	Results
	Discussion
	Conclusion
	Appendix
	References