Intranasal Midazolam in Children: The Minimum Dosage for Smooth Separation from their Parents pre-operatively

2. THE MINIMUM DOSAGE & TIME
REQUIRED FOR SMOOTH
SEPARATION FROM PARENTS
PRE-OPERATIVELY
THE TITLE
INTRANASAL
MIDAZOLAM
PREMEDICATION IN
CHILDREN

3. Worker group
Guide: Professor Dr. Kazi M. Iqbal
MBBS, DA(London), FFARCS(I), FRCA(E), FCPS;
BSMMU, Dhaka.
Co-guide: Dr. Moinul Hossain
MBBS, FCPS; Assistant Professor, BSMMU, Dhaka.
Principal Investigator: Dr. (Maj) Md Rabiul Alam
MBBS, MCPS, FCPS; AFMC, Dhaka
Cantonment, Dhaka.

4. Introduction
• The anaesthesiologists face
the excited child as one of
the most common problems
in everyday experience
• This problem can be
handled with least success.
Ref: Smith RM. Anaesthesia for infants and children.
3rd Ed.: The CV Mosby Company, 1968: 5–31.

5. Introduction (Continued)
• Children admitted to hospital face a
new environment & separation from
their parents before induction further
upset them.
• Separation is an important cause of
neurotic anxiety.
• Separation anxiety is experienced
most intensely around the age of 4 yrs.
• Also cause often a noisy & unpleasant
situation in the OT.
Ref: Levy D. Psychic trauma of operations in children.
Am J Disabled Child 1945; 69: 7.

6. Introduction (Continued)
• Parental presence may not
always be beneficial.
• The unmotivated mothers may
further deteriorate the situation
Ref: Bevan JC, Johnston C, and Haig HJ: Pre-operative
parental anxiety predicts behavioural and emotional
responses to Induction of Anaesthesia in Children. Can J
Anaesth 37: 177–82.

7. Introduction (Continued)
• Anxiolysis & sedation by premedication is still
a common practice in paediatric anaesthesia.
• Key features of good premedication are:
• easy application
• rapid onset
• short duration
• lack of significant side effects
Ref: Meursing AEE. Psycological efffects of anaesthesia in
children. Curr Opin Anesthesiol 1989; 2: 335-8

8. Introduction (Continued)
• Midazolam meets these criteria with its :
• Multiple routes of administration (oral, nasal,
rectal)
• An onset time: 10-20 min
• Duration of action: approximately 30 min
• No interference with vital signs at doses < 0.5
mg.kg–1.
• Most widely used paediatric premedication in
Europe & the USA.
MIDAZOLAM
Ref: McMillan et al. Premedication of children with oral midazolam. Can J
Anaesth 1992; 39: 545-50.

9. Introduction (Continued)
• Advantages of intra-nasal route:
• Bypasses the first-pass effect
• Quick achievement of desired
serum level (even just slower
than the i. v. route)
• Good patients’ compliance (no
prick, no needle, nothing to
swallow, – specially in case of
children).
Ref: Henderson JM. Pre-induction of Anaesthesia in Paediatric patients
with nasally administered sufentanil. Anesthesiology, 1988. 68: 671-675.

10. Introduction (Continued)
• The therapeutic plasma concentration for
‘sedation’ with midazolam is 40 ng.ml–1.
• A mean peak of 72.2 ng.ml–1 can be achieved
within 10 minutes of intra-nasal midazolam at a
dose of 0.1 mg.kg–1.
• Parenteral formulation (15 mg in 3 ml) containing
0.33 mg/drop has been used for intra-nasal
administration.
Ref: Louon A, Reddy VG. Nasal midazolam and ketamine for paediatric
sedation during computerized tomography. Acta Anaesthesiol Scand
1994; 38(3): 259–61.

11. Objectives
To determine the minimum dosage &
time interval required for smooth
separation of children from their
parents at a plane of ‘conscious
sedation’ by intra-nasal instillation of
midazolam pre-operatively.

12. Methods
 Forty children were assigned
randomly to one of two groups of
twenties in BSMMU, Dhaka during
the tenure of Sep ’02 - Feb ’03.
 ASA- I & II
 Age: 1- 6 years

13. STUDY SUB-GROUPS
10 minutes
(Random)
Sub-group: Ia
20 minutes
(Random)
Sub-group: Ib
Random 20s
0.025 mg/kg
Group: I
10 minutes
(Random)
Sub-group: IIa
20 minutes
(Random)
Sub-group: IIb
Random 20s
0.05 mg/kg
Group: II
TOTAL: 40 CHILDREN

14. Methods(continued)
HR, SBP, sedation & anxiolysis scores
were assessed:
 before premedication (baseline)
 at separation from parents
 at application of a facemask for
induction.
Parental comments were also assessed
at the time of separation.

15. Sedationlevels
Sedationlevel Score
Alert/active 1
Awake/calm 2
Drowsy,butrespondsreadilytoverbalcommands,lighttouch 3
Asleep 4
Sedation levels
Sedation level Score
Alert/active 1
Awake/calm 2
Drowsy, but responds readily to verbal commands, light touch 3
Asleep 4
Sedation levels
Sedation level Score
Alert/active 1
Awake/calm 2
Drowsy, but responds readily to verbal commands, light touch 3
Asleep 4
Sedation levels Score
Alert / active 1
Awake / calm 2
Drowsy, but responds readily to
verbal commands or light touch 3
Asleep 4
Sedation scores
CONSCIOUS
SEDATION

16. Anxiolysis levels Score
Tearful / combative 1
Anxious, but can be easily reassured 2
Calm 3
Asleep 4
Anxiolysis score levels
Score 2 & 3 were considered as ‘conscious sedation’Scores 2 & 3 were considered as ‘conscious sedation’

17. 1. Did you feel that your child was
adequately relaxed while waiting for
surgery?
2. Did you feel that your child was
adequately relaxed at the time
of separation from you to enter the
operation theatre?
PARENTAL
QUESTIONNAIRE

18. RESULTS
 HR & SBP were slightly increased during
application of facemask in all four sub-
groups.
 Sedation & Anxiolysis scores at separation &
induction were significantly higher in the
particular dosage-group of 0.05 mg.kg–1.
 No significant differences between the interval-
subgroups of 10 & 20 minutes of the 0.05
mg.kg–1 dosage group.
 Parental comments of those sub-groups were
satisfactory.

19. Report
4.000 14.100 1.30
10 10 10
1.700 4.280 .48
3.950 16.500 1.40
10 10 10
1.301 3.923 .52
4.400 14.500 1.10
10 10 10
1.468 4.410 .32
3.700 15.150 1.60
10 10 10
1.183 4.177 .52
4.012 15.063 1.35
40 40 40
1.394 4.140 .48
Mean
N
Std. Deviation
Mean
N
Std. Deviation
Mean
N
Std. Deviation
Mean
N
Std. Deviation
Mean
N
Std. Deviation
Sub-group
Ia
Ib
IIa
IIb
Total
Age (years)
Body
weight (kg) Sex
DEMOGRAPHIC DATA
Mean Age:
4.012 years
Mean Body
weight:
15.062 kg
Required mean
dose:
3 drops /case

20. Sex differences in sub-groups

21. Paired Samples Correlations
40 .310 .052
40 -.012 .940
40 -.168 .301
40 -.168 .301
Sub-group & Baseline
SBP (mmHg)
Pair
1
Sub-group & Baseline
HR (beats/min)
Pair
2
Sub-group & Baseline
sedation score
Pair
3
Sub-group & Baseline
anxiolysis score
Pair
4
N Correlation Sig.
p values of baseline SBP, HR,
Sedation & Anxiolysis scores
of different sub-groups
p values
None was below 0.05

22. Systolic BP changes
Sub-group
IIbIIaIbIa
Mean
120
110
100
90
80
Baseline SBP (mmHg)
SBP at separation (m
Hg)
SBP at induction (mm
Hg)
SBP
changes
almost
similar
in IIa &
IIb

23. Heart rate changes
Sub-group
IIbIIaIbIa
Mean
114
112
110
108
106
104
102
100
Baseline HR (beats/m
in)
HR at separation (be
ats/min)
HR at induction (bea
ts/min)
p-values of IIa
& IIb were >
0.05

24. Sedation scores
Sub-group
IIbIIaIbIa
Mean
3.0
2.5
2.0
1.5
1.0
Baseline sedation sc
ore
Sedation score at se
paration
Sedation score at in
duction
 Scores in
IIa & IIb

25. Anxiolysis score
Sub-group
IIbIIaIbIa
Mean
3.0
2.5
2.0
1.5
1.0
Baseline anxiolysis
score
Anxiolysis score at
separation
Anxiolysis score at
induction
 Scores in
IIa & IIb

26. Parental comments
Sub-groups Good Satisfactory Unsatisfactory Not responded
Ia 2 5 2 1
Ib 2 7 1 0
IIa 4 5 0 1
IIb 6 3 0 1

41. INTRA-NASAL
MIDAZOLAM
Minimum dose:
0.05 mg.kg-1
Time required:
10 minutes

42. CONCLUSION
So, we conclude that:
Children may be separated from their
parents smoothly & safely without exactly
inducing them asleep rather keeping them
at a plane of ‘conscious sedation’
within 10 minutes after administering
intra-nasal midazolam at a dose of
0.05 mg.kg–1.