Article Type : Research Article
Authors : Manjunath Kandiraju, Chethan Manohara Koteswara, Ratan Singh Deo, Avinash Basavapattana Maheshwarappa, Prajnyananda Das, Sanjiv S Bais, Mahmoud Hassanein and Manar Hassanein
Keywords : Premedication; Pediatrics; Psychosis; Midazolam; Ketamine; Honey; Anxiety; Psychosis
Background: Surgeries in pediatric age
group is more challenging, stressful as compared to adult population. Anxiety
and separation from parents is worrisome and there are no ideal premedications
to calm the pediatric patients. Hence this comparative study of effects of
Midazolam with honey & Ketamine with honey as oral premedication.
Methods: This study was undertaken in
different specialties of surgery department, 100 patients of either sex, aged
between 2-8 years were taken and randomly assigned into 2 groups of 50 patients
each; patients were selected by process of exclusion at every step for any
variation from normal. Patients of both
groups were premedicated orally with parenteral preparation of midazolam &
ketamine mixing with honey (0.2ml/kg body weight).
Group M Midazolam
0.75 mg/kg body weight.
Group K Ketamine 6mg/kg body weight.
Both the drugs were given 30 minutes prior
to proposed time of induction.
Patients were observed and compared in
between the two groups and results were tabulated.
Results: Onset of sedation in midazolam
group was 16.2± 3.6mins & in ketamine group 19.4 ?3.2 mins, 66% patients
were calm & sleepy compared to 56% with ketamine during separation from
their parents, 54% patients in midazolam group were unafraid and cooperative
during application of facemask compared to 44% in ketamine group, level of
sedation was satisfactory & similar in both groups.
In group M patients who received midazolam
orally; onset of sedation was quicker (P < 0.001), number of patients calm
and sleepy during separation from their parents and at the time of venepuncture
were more silent (P > 0.05) and degree of induction score was superior (P
<0.05). Undesired effects like increased secretion, vomiting, nystagmus,
random limb movement, and excitement before & after surgery were more in
ketamine group.
Conclusion: Both midazolam (0.75mg/kg) and
ketamine (6mg/kg) can be used as oral premedicants for children. However,
midazolam may be preferred because of its early onset of action, better effect
on allaying anxiety during separation from parents and lesser side effects.
Surgery is a terrifying and intimidating experience
for all ages. The fear psychosis of surgery in children is a traumatic
experience because of unfamiliar and intimidating environment of the operation
theatre and separation of the child from his/her parents. The objective of the
anesthesiologist in planning the preoperative care and premedication of
pediatric patients is to ensure as far as possible, to minimize the potential
adverse physiological and psychological effects of anesthesia and surgery. The goal
is achieved only, fully recognizes the problems, and then orders appropriate
preoperative care. Premedicating a pediatric patient has become unavoidable and
remains to be a challenge to the anesthesiologist. A wide variety of drugs and routes have been
tried and described. But the perfect
drug or combination and the route of premedication especially in children is
not yet available.
The ideal premedication for children should be
General objectives
The objective of the study was to compare the effects
of oral Midazolam and oral ketamine with honey preparation as pre-anesthetic
medication among 100 patients of either sex in the age group of 2-8 years for
elective surgery under general anesthesia in different specialties.
Specific objectives
To compare the effectiveness of oral ketamine and oral midazolam in achieving:
One
hundred patients of either sex (ASA-I&II) in the age group of 2 to 8 years
posted for elective surgery under general anaesthesia, in different specialties
during this study with due permission from the institutional authorities and
ethical committee.
Informed
consent was obtained from parents of the patients before being included in the
study.
Prior to taking up the cases for the study a detailed
clinical assessment of each patient was done to exclude any underlying systemic
disease. Detailed case history was
taken in all cases. Pulse rate and blood
pressure was checked and the weight of each patient was taken. Routine
laboratory investigations such as hemogram, routine and microscopic examination
of stool and urine was done.
Investigations like chest X-ray, Mantoux test, blood sugar, serum urea
and creatinine , liver function test, serum electrolytes were advised if
required. Any case showing gross deviation from normal was excluded from the
study.
Exclusion criteria
History of intolerance to oral administration of
drugs, Hypersensitivity to either drug, Cyanotic heart disease, Convulsive
disorders, Liver diseases, Respiratory diseases, Renal diseases, Neurological
disorders, Emergency surgeries were excluded
Grouping
For the purpose of this study patients were randomly
allocated to two groups of 50 each to receive either Midazolam or Ketamine
mixed with honey as oral premedication.
Group M :
Midazolam 0.75 mg/kg body weight
Group K :
Ketamine 6 mg/kg body weight.
Preparation
All the patients were
visited in the evening before operation.
During this time a detailed clinical reevaluation was done. Parents were explained about the
pre-operative preparations. Patients were not allowed to take milk or solid
diet orally for 8 hours prior to administration of premedication. But, oral intake of clear fluids, such as
glucose water, and green coconut water were permitted up to 4 hours prior to
premedication.
On the day of surgery, the patients were brought to
the preanaesthesia room near the operation theatre about 45 minutes before
operation. In the pre-anaesthesia room
necessary arrangements were made for
administration of the studied drugs, monitoring of the child, emergency drugs
and equipment’s to tackle any untoward effects of the drugs. Patient’s pulse, BP and body weight were
recorded.
Premedication
In the pre-anaesthesia
room, premedicants were given in presence of parents 30 minutes prior to
proposed time of induction time of 6mg/kg body weight. Here, parenteral
(Intravenous or intramuscular) preparations of midazolam
containing 5mg of midazolam hydrochloride per ml and ketamine containing 50 mg
of ketamine hydrochloride per ml were used.
Though the suggested oral dose of midazolam varies from 0.45 to 0.75
mg/kg body weight and ketamine varies from 3 to 10mg/kg body weight; midazolam
0.75mg/kg and ketamine 6mg/kg body weight were selected as they appeared to
fulfil the criteria of a safe and satisfactory premedicants without increasing
untoward side effects. Calculated dose of the drugs and honey were measured
with the help of a plastic 2ml syringe, mixed by the anesthetist and
administered by the mother with the help of a teaspoon having approximate
measurement of 5ml. Thirty minutes following premedication patients were
separated from their parents and brought to the operation theatre. Intravenous
cannulation was done with appropriate size I.V.canula, pedolyte infusion was
started and drip rate was adjusted according to calculation on body weight basis. Pulse oximeter, NIBP, and ECG.
After pre-oxygenation with 100% O2 for 5 minutes,
patients were induced with propofol 3-5 mg/kg body weight followed by
succinylcholine 1.5 mg/kg i.v. and ventilation was supported till sufficient
relaxation occurred as observed by jaw relaxation. After visualizing the
laryngeal inlet under direct laryngoscopy patients were intubated with
appropriate sized uncuffed/ cuffed (according to age) endotracheal tubes. All
the patients were ventilated with 100% oxygen via endotracheal tube till return
of spontaneous respiration. Jackson-Ree’s modification of Ayre’s T-piece was
used in patients weighing less than 20 kg. Maintenance of anaesthesia was done
with nitrous oxide (50%), Oxygen (50%), non-depolarizing muscle relaxants &
sevoflurane was used as maintenance of anesthesia.
Recovery
At the end of surgical procedure patients were
reversed with neostigmine 0.05mg/kg and atropine 0.02 mg/kg. Thorough suctioning of the oral cavity and
pharynx was done and patients were extubated after presence of all protective
reflexes were guaranteed. Then 100%
oxygen was administered for 5-10 minutes.
All the patients left the operating room awake.
Monitoring
Heart rate, ECG, and oxygen saturation was monitored
by using pulse oximeter, NIBP, Capnography and continuous visual vigilance and
intermittent auscultation of the chest.
Recording
Heart rate blood pressure and respiratory rate before
administration of premedication were recorded as base line (pre-drug) values
and findings.15 minutes and 30 minutes after premedication i.e. just before
induction findings were again recorded.
Continuous monitoring for HR, ECG and Oxygen saturation was done
perioperatively.
Preinduction
observations
These observations were done in the pre-anaesthesia
room during the interval between administration of drug and induction of
anaesthesia. These were as follows:
Level of sedation
This
was assessed at 0, 5, 10, 15,20,25,30 minute after premedication by using a
5-points sedation scale.
Scale used to assess
sedation
Score1- Barely
arousable (Sleep, needs shaking or shouting to arouse).
Score2- Asleep
(Eyes closed, arousable with soft voice or light touch).
Score3- Sleepy
(Eyes opened but less active and responsive).
Score4- Awake.
Score5- Agitated.
Scores up to 3 was considered as acceptable level of
sedation
Time of onset of
sedation
It is the time from oral premedication till the child
is sleepy (Score 3)
Anxiolysis (Emotional
state)
Emotional state of the children were observed during
separation from their parents and at the time of venepuncture by using a
4-point scale
Emotional scale
Score1 - Calm
and sleepy
Score2 -
Apprehensive (not smiling) behaviour and withdrawn.
Score3 -
Crying
Score4 -
Thrashing
Undesired effects
Patients were also observed for presence of
Increased secretion
Vomiting
Nystagmus
Random limb movement
Hallucinations
Airway obstruction.
Increased secretion was determined by presence of
dribbling of saliva from the angle of mouth of a sedated child or noisy
respiration, which became normal after suction of oral cavity.
Intravenous
Cannulations:
In the operation theater, reaction to placement of intravenous catheter
was observed, if it was possible without much resistance from the child it was
considered as evidence of analgesia.
Quality
of Induction: It was assessed by noting child’s
response to application of facemask and i.v. administration of drugs during
induction by using a 4-point scale.
Induction scale: Score
Poor
- Afraid, combative, crying 1
Fair -
Moderate fear at mask, not easily calmed 2
Good -
Slight fear at mask, easily calmed 3
Excellent
- Unafraid, co-operative, accepts mask
readily 4
Increased
secretions: Patients were observed for presence
of any increased secretions during direct laryngoscopy.
Anaesthesia
time:
Total time in minutes from beginning of indication to eye opening and
return of protective reflexes after cessation of anesthetic agents was noted.
Post
Anaesthesia Observations
Observations made during recovery when patient were
placed in recovery room (post anaesthesia care unit), before transfer to
respective wards.
Crying:
After awakening whether crying without any external stimulation was marked or
not.
Other
observations: Patients were also observed for
Airway support, Nystagmus, Incidence of postoperative nausea & vomiting,
Excitement or restlessness, Presence of laryngospasm, Emergence phenomena.
24 Hours after surgical procedure, parents were asked following questions like:
Based on these parental responses, it was 1) pleasant,
2) Acceptable and 3) unpleasant.
Similarly, every child was also enquired about his/her
pre &Postoperative experiences like:
Would you choose these drugs in future?
Answers of child’s responses were also marked as 1)
Pleasant 2) acceptable and 3) unpleasant.
The children were also asked “if he or she remembered going to sleep”
before the operation or remembered the application of “facemask”.
The study was carried out in 100 patients in two
different groups of 50 patients each, meant for elective surgery of 40-60
minutes duration. The two groups were premedicated with midazolmam 0.75-mg/kg
body weight (group M) or ketamine 6mg/kg body weight (group K). Both the drugs
are given orally 30 min prior to proposed time of induction. In this study
honey was used to mask the bitter taste of ketamine and to make it acceptable
to children. It is chemically inert, can prevent interfere hypoglycaemia and
does not interfere with gastric pH, and volume. Moreover it is easily
available, cheap and of better taste and flavour.
Patients were observed in relation to
The above table shows the demographic patterns of
patients in the two groups according to their age, sex and body weight. The
mean ages in the two groups are almost identical. The male: female ratio in each group and
average body weight was also similar in both the groups. Thus both groups were
comparable with respect to age, sex and weight.
The above table shows no of patients according to the
type of surgery. It is evident that no of particular operations in both groups
were comparable.
The above table shows sedation score at different time
intervals in both groups. Score 3 was
considered as an acceptable level of
sedation, After 25 minutes of premedication i.e. before the time of separation
of the children from their parents all of them in both groups were sleepy
(Achieved score 3 or less).
The above table shows in midazolam group 33 (66%)
children were calm and sleepy during separation from their parents where as it
was 28(56%) with ketamine. Midazolam found to have better anxiolytic action
than ketamine (p<0.05)
The above table shows effect of midazolam and ketamine
premedication on vital parameters before induction of anaesthesia. There were
no significant changes in the cardiorespiratory status of the patients in both
the groups. As seen in the table, there were side effects like increased
secretions, vomiting, nystagmus and random limb movement in ketamine groups
compared to midazolam group in the preoperative period.
The above table shows 26(52%) children in midazolam
group were calm & sleepy during venepuncture compared to 23(46%) children
in ketamine group (P < 0.05)
The above table shows distribution of induction score
in both groups. Midazolam had a superior
degree of induction, excellent in 27(54%) children compared to 22(44%) with
ketamine. So midazolam is significantly better (P<0.05)
Above table
shows there was increased secretions during direct laryngoscopy more in
ketamine group seen in 19 (38% ) children compared to midazolam group where it is seen in 5(10%)
children (P < 0.005)
The above table shows the incidence of side effects
during post - anaesthesia period.
Findings appear to be in favour of midazolam as incidence of side
effects were more with ketamine (Tables 1-12).
# Child’s ability to recall going to sleep.
* Child’s ability to recall application of face mask.
Response score refer to
1 = Pleasant
2 = Acceptable
3 = Unpleasant
Group M had better response compared to Group K.
The results show that oral ketamine produced sedation
levels comparable to midazolam, with a faster onset of action, indicating its
potential as a valuable sedative option for pediatric patients undergoing
surgical procedures. Although the side
effects of the ketamine were recorded and noted such as increased secretions,
nystagmus, increased muscle tone and post-operative nausea and vomiting 10.
Onset of sedation in midazolam group was 16.2± 3.6mins & in ketamine group
19.4 ±3.2
mins, 66% patients were calm & sleepy compared to 56% with ketamine during
separation from their parents, 54% patients in midazolam group were unafraid
and cooperative during application of facemask compared to 44% in ketamine
group, level of sedation was satisfactory & similar in both groups. In
group M patients who received midazolam orally; onset of sedation was quicker
(P < 0.001), number of patients calm and sleepy during separation from their
parents and at the time of venepuncture were more silent (P > 0.05) and
degree of induction score was superior (P <0.05). Midazolam undergoes
extensive first-pass hepatic extraction [1,2]. Therefore, the bioavailability
of midazolam has appeared to be less than 50 % after enteral administration
[1,3] and about 30 % after administration by mouth [3]. On this basis, the dose
range used here was comparable to a rectal dose of 0.3 mg /kg2. The
anxiolytic effect of midazolam in the present study seemed also to be
comparable to the results obtained by Saint-Maurice and colleagues [4-6]. Dilip
Kothari, compared the dose of oral midazolam between 0.5mg/kg & 0.75mg/kg
[7-11]. They found oral midazolam in a dose of 0.75mg/kg offer effective
sedation and, better emotional control without fear of needle prick and side
effects. This study was comparable with the present study. W. Funk, observed
and recommended the dose of 6mg/kg as satisfactory & ketamine alone is safe
for premedication for pediatric population without side effects [12].
Emergence phenomena have been reported, albeit
sporadically, after parenteral ketamine in children. To date, none have been
reported after oral administration of ketamine [2,4,5]. The absence of
emergence phenomena after oral ketamine may be explained by (a) an increased
ratio of Nor ketamine to ketamine after oral ketamine [6,7] (b)blockade of the
side effects of N-methyl-D-aspartate receptor antagonists (such as ketamine)
with barbiturates or anticholinergics [7,8] and (c) too limited an experience
oral ketamine to comment on a rare phenomenon. These explanations individually
or in combination may explain the absence of emergence phenomena after oral
ketamine in this study. Honey was used as the vehicle of administration for
both ketamine and midazolam to counteract the bitter taste and to make it
acceptable to children. It is chemically inert, can prevent interfere
hypoglycaemia and does not interfere with gastric pH, and volume. Different
authors has used orange juice, apple juice, flavouring extracts (cherry &
banana), coke and flavoured gelatin with or without sugars [9]. Hence honey was
used in this study, since it is easily available, cheap and of better taste and
flavour.
Both midazolam (0.75mg/kg) and ketamine (6mg/kg) can
be used as oral premedicants for children. However, midazolam may be preferred
because of its early onset of action, better effect on allaying anxiety during
separation from parents and lesser side effects. Honey is the preferrable
choice as a vehicle of administration as its cheap, easily available, cost
effective, easily palatable and acceptable in pediatric population.