Iranian Journal of Pediatric Hematology Oncology Vol3.

No1 187

Original Article

Effect of two Different Concentrations of Propofol and Ketamine
Combinations (Ketofol) in Pediatric Patients under Lumbar Puncture or Bone
Marrow Aspiration
Ghadami Yazdi A MD
1
, Ayatollahi V MD
1
, Hashemi A MD
2
, Behdad SH MD
1
, Ghadami Yazdi E MD
3
1. Department of Anesthesia, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
2.Department of Pediatrics, Hematology, Oncology and Genetics Research Center, Shahid Sadoughi University of Medical Sciences and
Health Services, Yazd, Iran.
3. Resident of Iranian Traditional Medicine, Tehran University of Medical Sciences Tehran, Iran.

Received: 14 December 2012
Accepted: 18 March 2013

Abstract
Background
Ketamine is an anesthetic drug that is importantly
analgesic without respiratory depression. Ketamine
increases blood pressure and heart rate. Propofol is an
anesthetic drug with good sedation, rapid recovery,
but it causes respiratory depression, low heart rate
and low blood pressure. Combination of Ketamine
and Propofol provides sedation, analgesia and rapid
recovery with hemodynamic stability and minimal
respiratory depression. The aim of this study was to
compare two different combinations of these two
drugs to reach necessary sedation scale for the Lp or
BMA in pediatric with ALL.
Materials and Methods
This randomized, double blinded study was designed
to compare the quality of sedation and side effects of
intravenous Ketofol on 60 patients of both gender.
Patients received titrated injection of a solution
containing combination of one part of Ketamine and
two parts of Propofol




(1:2) (group I) or one part of Ketamine and three
parts of Propofol (1:3) (group II) to reach almost near
5 sedation level (using Ramsay Sedation Scale).
Respiratory and hemodynamic profiles, amount of
drug injected and side effects were recorded.
Results
These drug combinations were used on 60 children
with a median age of 6.2 years. In this study,
recovery time and hallucination was significantly
high in group I, but in both groups hemodynamic
were stable, amnesia was enough, and there was no
respiratory depression.
Conclusion
Lower doses of Ketamine in these combinations have
lower psycho mimetic side effects, and shorter
recovery time.
Key words
Ketamine, Propofol, Spinal Puncture, Pediatrics


Corresponding Author:

Ayatollahi V, MD, Department of Anesthesiology, Shahid Sadoughi Hospital, Yazd, Iran. E-mail:
[email protected]
Introduction
The lumbar puncture (LP) or bone marrow aspiration
(BMA) in pediatric patients with hematological
diseases is often repeated at regular intervals (1, 2).
These procedures are painful and unpleasant for the
children, and a good sedation is essential in these
procedures (1, 2). An ideal sedation agent should not
only have rapid onset and a smooth recovery period,
but should also provide sufficient analgesia, sedation
with adequate cardiovascular and respiratory

function, amnesia, and motor control immobile
throughout the procedure (3). Ketamine is an
anesthetic drug that is importantly analgesic without
respiratory depression. Ketamine increases blood
pressure and heart rate (3, 4). Propofol is an
anesthetic drug with good sedation and rapid
recovery time, but also as a respiratory depression
that decreases heart rate and blood pressure (3, 4).
Combination of Ketamine and Propofol provides
sedation, analgesia and rapid recovery with
188 Iranian Journal of Pediatric Hematology Oncology Vol3.No1

hemodynamic stability and minimal respiratory
depression (3-10). In a previous study, we compared
the effects of two types of Ketofol mixtures, equal
amounts of Propofol and Ketamine (1:1) or two parts
of Propofol plus one part of Ketamine (2:1) (4). We
observed that combination of 2:1 was better than 1:1,
because this combination minimizes the psycho
mimetic side effects and shortens the recovery time.
The aim of this study was to compare total doses,
recovery time, and adverse effects of combinations of
Ketamine and Propofol with different ratios (1:2 and
1:3) for necessary sedation scale in the LP or BMA in
pediatrics.
Materials and Methods
In this randomized and double blinded study, 60
children of 3 to 12 years old with ALL who were
referred to a pediatric hospital in Yazd for the BMA
or LP were studied. First, the patients and their
parents need to know about the type of sedation
method was given. Then Informed consent was
obtained. Inclusion criteria were all consecutive
children with hematological diseases undergoing
BMA or lumbar puncture admitted to the hospital.
Exclusion criteria included: prior sensitization or
allergic reaction to Propofol, Ketamine, soy or egg
products; hypotension head injury, increased
intracranial or intraocular pressure; use of drugs
known to interact with either study agent. Patients
with heart disease, cardiovascular, respiratory,
hepatic, and epilepsy were excluded. Patients were
randomly divided into two groups of 30. In the
waiting room, IV catheter was placed with using
Emla cream for the patient. Primary measures of RR,
HR, mean arterial pressure, and oxygen saturation
were recorded combination of Propofol - Ketamine
was provided by an anesthesia nurse who was not
involved in this case study. For Group I, 25 mg
Ketamine with 50 mg Propofol in the 5.5 cc and for
Group II, 50 mg Propofol plus 17 mg Ketamine with
distilled water to volume 5.5 cc was completed. Then
coded syringes were given to resident of anesthesia.
Drug was injected 0.07 cc/kg slowly, and then
repeated to reach of 5 Ramsay sedation scale.
Oxygen saturation, mean arterial pressure, heart rate
and respiratory rate were measured continuously, and
results were recorded in the three different times
(after injection, the time of the procedure, and the
time of the patient's arrival to the recovery room). If
patient had pain or movement during the procedure,
drug injection was repeated and repeated doses were
noted. Total drug usage was calculated at the end of
trial. Procedure duration was recorded. After the
procedure, patients were taken to the recovery room
until they reach Aldrete score of 9 to 10. Recovery
time from the end of the procedure to reach Aldrete
score of 9 to 10 was considered, and noted. Nausea,
vomiting and other side effects including
hallucinations, agitation and respiratory depression
were listed Vital signs of patients were evaluated
every 5 minutes. When the patients had stable vital
signs, they were alert and able to move without
assistance, and some symptoms such as nausea and
vomiting were not sensible, they discharged from
recovery room. Patients were monitored for at least 2
hours after the procedure. All data include sex, age
and weight recorded in a standard data collection
record.
Statistical Analysis
All data were analyzed by SPSS software version 15
with Student t-test, Fisher-exact, and Mann-Whitney.
Results
Analyzed data of 60 patients showed that
demographic characteristics (number, age, sex and
weight) were similar in two groups, and there were
no significant differences among two groups (Table
I). The mean of procedure durations were not
different in both groups (P-value= 0.57), but mean of
recovery time was longer in group I. This difference
was significant (P-value <0.001). Mean of recovery
time in group I and II was 11.30 min and 8.03 min,
respectively. Three patients in group I and one patient
in group II experienced nausea (P-value= 0.41).
Seven patients in group I and 1 in group II had
hallucination (P-value= 0.05). No respiratory
problem and vomiting were seen in both groups.
None of the children had bad memory, and all were
satisfied with the procedure. Table II shows that
Ramsay scores were similar in two groups after
injection of 0.07 ml/kg, and additional drug was
required to achieve Ramsay score of 5. The amount
of next injection was significantly different in two
groups, group II required more than group I. Total
volume of injected drugs and total Ketamine were
similar, but total Propofol in group II was more than
group I (P-value <0.001). Mean of Spo2, HR, MAP
and RR were similar for different times (Table II).



Iranian Journal of Pediatric Hematology Oncology Vol3.No1 189

Table I. Demographic, preoperative and side effects data
Group I
( K/P 1/2)
Group II
(K/P 1/3)
P- value Test
Sex (M/F) 23/7 21/9 0.77 Fisher-exact
Mean Age (yr) 6.1 6.3 0.78 T-test
Mean Weight (kg) 17.28 16.88 0.83 T-test
Procedure duration(min) 4.4 4.5 0.57 T-test
Recovery duration (min) 11.30 8.03 <0.001 T-test
Nausea 3 1 0.41 Fisher exact
Hallucination 7 1 0.05 Fisher exact

Table II. Data and Results of drugs in two groups






Mean of Group I
( K/P 1/2)
Group II
(K/P 1/3)
P- value Test
Ramsay score after first injection 0.07 cc/kg 4.43 4.17 0.113 Mann-Whitney
The next injection amount (cc) 0.58 1.18 <0.001 Mann-Whitney
Total volume of injected drugs (cc) 1.8 2.35 0.027 T-test
Total Propofol (mg/kg) 0.87 1.16 <0.001 T-test
Total Ketamine (mg/kg) 0.43 0.39 0.48 T-test
190 Iranian Journal of Pediatric Hematology Oncology Vol3.No1

Table III. Patients vital signs (T test)
Mean of Group I
( K/P 1/2)
Group II
(K/P 1/3)
P- value
SPO2 T1 96.6 96.7 0.41
T2 96.9 96.8 0.84
T3 96.7 97.0 0.35
HR T1 116.6 114.9 0.40
T2 115.7 115.5 0.93
T3 109.4 109.4 0.123
MAP T1 63.0 62.0 0.56
T2 64.6 63.5 0.57
T3 62.1 57.4 0.005
RR T1 20.1 18.6 0.02
T2 20.0 19.5 0.33
T3 18.8 17.2 0.005
T1: After drug injection -T2: Time of the procedure- T3: Time of the patient's arrival to the recovery room

Discussion
BMA and LP are two processes that should be
repeated in children with ALL. Both process are
painful and unpleasant, and can cause fear and
anxiety in children, especially in later process (1, 2
and 4). The ideal medication provides analgesia,
sedation, amnesia, and has not adverse effects on
hemodynamic and respiratory system. Also it should
have minimal additional side effects (3). There is not
a drug with all of these specifications, and we have to
use the multiple drugs (3). Ketamine is an anesthetic
drug that produces analgesia and amnesia without
respiratory depression. Ketamine increases
hemodynamic parameters non-dose-dependently, but
it sometimes causes nausea, vomiting or hallucination
(3-13). Propofol is an anesthetic drug with good
sedation, low amnesia and rapid recovery, but
respiratory depression. Propofol decreases heart rate
and blood pressure dose dependently (3-13). The

combination of these two drugs can cause sedation,
analgesia, amnesia and rapid recovery with
hemodynamic stability and minimal respiratory
depression (4-13).
Our previous study (2011) was performed using a
mixture of the 1:1 compared1:2Ketamine Propofol.
Nausea, hallucination and recovery time were also
more in1:1 ratio (4). Due to the better results of 1:2
ratio in comparison with 1:1 ratio it was more
preferred to compare 1:2 with 1:3 ratio. In this study,
we observed that 1:3 ratio was better than 1:2,
because it had a shorter recovery time, and total drug
usage was reduced in this group. Incidence of
hallucination and nausea were lower, although were
not statically significant. Bardineath et al reported
that ratio of 1:5 Ketofol with local anesthesia
provides good analgesia and sedation for breast
biopsy procedure (5). Andolfatto G et al reported 1:1
ratio of Ketofol is highly effective in pediatric
emergency procedures (6). The results are different.
Mean recovery time in their study was 14 min but it

Iranian Journal of Pediatric Hematology Oncology Vol3.No1 191

was 11.3 min for ratio 1:2 and 8.0 min for 1:3 in our
study. Then low level of Ketamine decreases
recovery time with good sedation and analgesia.
Silva PS et al used Ketofol of 1:1 to reach Ramsay
score of 3-4in children with hematological diseases
(7). The mean total dose of Ketofol administered was
1.25 mg/kg per each of Propofol and Ketamine while
it was lower in our study to reach higher Ramsay
score of 5. So, using of high dose Ketamine cannot
help to increase sedation and analgesia. Whetheral A
et al observed that Ketofol infusion successfully
produced deep sedation for prolonged (153 min)
pediatric orthopedic procedures in conjunction with
regional analgesia (8). Similar to our study, they
reported that Ketofol is safe and good combination
for children. Erdogan kayhan G et al compared
Ketofol1:1 with Propofol in electroconvulsive
therapy. Ketofol had better results in their study (9).
Erdogan Ma et al compaired Propofol with Ketofol
in laryngeal mask insertion in elderly patient (10).
They showed that the number of patients who
required ephedrine and the total ephedrine dose were
lower, and apnea duration was increased in the
Ketofol group. Ephedrine treat hypotension and
bradycardia due to Propofol and Ketamine can also
do so. But increased apnea duration in their study
could be related to high age. So, Ketamine similar to
ephedrine improves the hemodynamic effects of
Propofol. Phillips w et al studied the effect of
Propofol versus Propofol/Ketamine for brief painful
procedures (11). Similar to our study, none of the
patient in either group had respiratory depression or
required any intervention. The combination of
Propofol and Ketamine provided an appropriate
combination for painful procedural sedation in the
emergency department. Compared to Propofol alone,
Ketofol provided less hypotension, better sedation,
and increased patient comfort and safety. In another
study by Andolfatto G et al, sedation and analgesia
effects of Propofol alone versus Ketofol were
compared (12). Ketofol did not show any result
regarding to reduce incidence of adverse respiratory
events compared with Propofol alone. Induction time,
efficacy and sedation time were similar but, sedation
depth presented to be more consistent with Ketofol.
In this study we showed, the combination of the two
drugs reduced the dose of each drug alone.
Smischney NG et al studied hemodynamic effects of
Ketofol in induction of general anesthesia (13). They
observed that Ketofol improved hemodynamic during
the first 10 minutes after induction, and it was a good
induction agent. This finding is consistent with
hemodynamic stability in our study.


Conclusion
According to this finding, Ketofol is a good
combination for sedation and analgesia in painful
short procedures in children. This mixture has
hemodynamic and respiratory safety. Use of low
Ketamine in this combination decreases recovery
time with minimal side effects such as nausea and
hallucination. Combination of 1:3 Ketamine-Propofol
is an appropriate ratio, and we mentioned the use of
it.
Acknowledgment
The authors would like to thank hematologic
pediatric ward nurses of Shahid Sadoughi Hospital.
This study was a thesis presented by Dr Ghadami
Yandi A, resident of anesthesiology.
Conflict of Interest
The authors have no conflict of interest.
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