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Research Article
Comparative study between propof, ketamine and theircombination (ketofol) as an induction agent
Hesham Aboeldahab
*
, Rania Samir, Hesham Hosny, Ahmed Omar
Anesthesia, Faculty of Medicine, Kasr El Aini Hospital, Cairo University, Cairo, Egypt
Received 18 March 2011; accepted 30 April 2011Available online 18 July 2011
KEYWORDS
Ketamine;Propofol;Ketofol;Bispectral index
Abstract
Introduction:
Ketofol is a new combination formed by mixing ketamine and propofol.This mixture was used for procedential sedation. However, little is known about its hypnotic char-acteristic as an induction agent.
Methods:
Sixty patients were allocated intothree equal groups (20 patients each) subjected to herniarepair surgeries under general anesthesia. These patients were anesthetized using propofol (groupP), ketamine (group K) and ketofol (group KP) as induction agents. The time needed for loss of verbal contact, eyelash reflex and their corresponding BIS values were recorded. Mean arterialblood pressure and heart rate were measured. Incidence of apnea, postoperative nausea and vom-iting, awareness and hallucination were noted.
Results:
The time needed for loss of verbal contact and eyelash reflex was earlier in group P fol-lowed by group KP and group K, respectively, the difference was statistically significant. Afterinduction, MAP decreased in group P, increased in group K while it remained comparable to base-line in group KP. The difference between groups was statistically significant. After intubation MAPincreased in the three groups, it was comparable between KP and P groups but remained signifi-cantly higher in K group. After induction, HR decreased in P group, increased in K group whileit remained comparable to baseline in KP group. The difference between groups was statisticallysignificant. After intubation HR increased in the three groups, it was significantly higher in groupK in comparison to groups P and KP, and as regards KP group HR was significantly higher than Pgroup. Afterwards, HR decreased in the three groups and remained stable and comparable for the
*Corresponding author. Tel.: +20 0237494909.E-mail address:h_dahab2005@yahoo.com(H. Aboeldahab).1110-1849
ª
2011 Egyptian Society of Anesthesiologists. Productionand hosting by Elsevier B.V. All rights reserved.PeerreviewunderresponsibilityofEgyptianSocietyofAnesthesiologists.doi:10.1016/j.egja.2011.04.007
Production and hosting by Elsevier
Egyptian Society of Anesthesiologists
Egyptian Journal of Anaesthesia
www.elsevier.com/locate/egjawww.sciencedirect.com
 
rest of the surgical time. The Bispectral index readings of ketofol group showed intermediate valuesbetween the other two groups.
Conclusion:
Ketofol is a safe, effective alternative induction agent that lacks many side effects of itstwo components.
ª
2011 Egyptian Society of Anesthesiologists. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction
Ketamine is an intravenous anesthetic developed in 1960s fromits precursor phencyclidine and its mode of action is throughcausing dissociative anesthesia[1]. Several advantages havebeen attributed to ketamine starting from its amnesic and anal-gesic effects, maintenance of muscle tone, protecting airway re-flexes and spontaneous respiration. However, ketamine hasmany side effects that limited its frequent use as an anesthetic.These side effects include nausea, vomiting, emergence halluci-nations, elevation of blood pressure and heart rate due to itssympathomimetic effects and also it was presumed to increaseintracranial pressure[2,3].Propofol is a 2,6-diisopropylphenol[4]which was devel-oped in Europe in the 1970s, it was utilized progressively inUSA in the subsequent two decades[4,5]. It produces generalanesthesia by facilitation of inhibitory neurotransmission med-iated by GABA. Its main advantages are its rapid inductionand recovery, antiemetic effects and anticonvulsant effects.Its main disadvantages lie in its dose dependent hypotensionand respiratory depression[6,7].It was postulated that combining both drugs will result in amixture which has additive effects so that we can decrease thedose used from each drug and benefit from advantages regard-ing amnesia, analgesia, hypnosis and hemodynamic stabilityand on the other hand lessen the disadvantages attributed toeither drugs[8]. This mixture was named ketofol and was as-sessed as a sedative agent in several studies mainly as in emer-gency departments with encouraging results[8]. In the presentstudy, we aimed to assess the value of ketofol, when used as aninduction agent, regarding its hypnotic criteria, both clinicallyand by BIS index readings, hemodynamic parameters, and theincidence of adverse effects of ketofol compared to its two con-stituents ketamine and propofol.
2. Patients and methods
After approval of the ethical research committee in Kasr ElAini hospital Cairo University and obtaining informed writtenconsent, 60 adult participants aging 20–50 years old, ASAphysical status I and II, without history of cardiovascular orneurologic disease undergoing hernia repair operations wereenrolled in a randomized prospective comparative study. Nopremedication was given to the patients and no medicationswere allowed within 12 h prior to surgery. Upon arrival atthe operating room, preoxygenation was started for 5 min dur-ing which the standard monitors; electrocardiogram, non-inva-sive blood pressure and pulse oximetry were attached to thepatient. BIS monitor electrodes (Aspect Medical System, Vis-ta
TM
, MA, USA) were placed on the skin of the forehead aftercleansing with alcohol. Thereafter baseline vital parameterswere recorded and five successive readings of BIS at 30 s inter-vals were taken to obtain baseline value while the patients werefully awake, then patients were randomized into three groups,20 patients each, group K (ketamine), group P (propofol),group KP (ketofol). Methods of randomisation was by aclosed envelope chosen by the surgeon.Prior to induction, all patients in the three groups received2 ml of lidocaine intravenously to lessen pain on injection espe-cially in the P and KP groups.Induction of general anesthesia started as follows:
Group K received intravenous ketamine in a dose of 2 mg/kg over 20 s, syringe contained 200 mg ketamine HCL(50 mg/ml) mixed with16 ml normal saline to reach a totalvolume of 20 ml given that each ml contained 10 mg of ket-amine and hence 1 ml ketamine syringe for every 5 kg.
Group P received intravenous propofol 1% in a dose of 2 mg/kg over 20 s, given that each ml contained 10 mg pro-pofol and hence 1 ml propofol syringe for every 5 kg.
Group KP received intravenous ketofol, prepared in a ratioof 1:1 as follows, 100 mg ketamine (50 mg/ml) diluted withglucose 5% to reach a volume of 10 ml + 100 mg propofol1%, total volume is 20 ml each ml containing 5 mg propo-fol + 5 mg ketamine, the dose given was 1 ml for every 5 kgsupposed to be equipotent to the dose used of each drugsolely in the other two groups.After 2 min of the start of induction, all patients received2 ucg/kg fentanyl and 0.5 mg/kg atracurium and were mechan-ically ventilated with isoflurane 1.5% end tidal in 100% O
2
using the following parameters: tidal volume 6–8 ml/kg, respi-ratory rate 10–12 min to achieve end tidal CO
2
of 30– 35 MmHg, 3 min later the patients were intubated, and main-tained on 1.5% end tidal isoflurane. Intermittent boluses of atracurium were given throughout the operation and at theend of the surgery any residual neuromuscular block was re-versed using neostigmine 0.05 mg/kg and atropine 0.02 mg/kg.The patients were then transferred to the post anesthesia careunit (PACU) and discharged when Alderete score was 10[9].
3. Data collected
Time needed for loss of verbal contact.
Time needed for loss of eyelash reflex.
BIS values were recorded at the following interval: at base-line, 5 s after loss of verbal contact, 5 s after loss of eyelashreflex, 2 min after induction, just before intubation, 1 minafter intubation then every 15 min till end of surgery.
Hemodynamic parameters (mean blood pressure and heartrate) were recorded before induction (taken as a baselinevalue), 2 min after induction, after intubation, 5 min afterintubation and every 15 min till the end of surgery.
All the patients were asked about recall of events or aware-ness and assessed for hallucinations and euphoria in thePACU.
Incidence of apnea and postoperative nausea and vomitingwas recorded.146 H. Aboeldahab et al.
 
4. Statistical analysis
Data are statistically described in terms of mean ± SD, fre-quencies (number of cases) and percentages as appropriate.Continuous data were analyzed done using two-way ANOVAfor repeated measurements with post hoc Tukey’s honest sig-nificant difference test. Qualitative data were compared usingChi-squared (
v
2
) test with Yates correction.
P
-values less than0.05 were considered statistically significant. All data were ana-lyzed using SPSS 15.0 for windows (SPSS Inc., Chicago, IL,USA).
5. Results
There were no significant differences in demographic data be-tween the three groups as regards patients’ age, sex, height,body weight and ASA physical status (Table 1).Regarding the time needed for loss of verbal contact andloss of eyelash reflex, patients in group K showed higher read-ings which were statistically significant relative to the othertwo groups. Patients in group KP lost the reflexes later thanpatients in group P, and there were a statistically significantdifference between the two groups (Table 2).
5.1. Regarding hermodynamic effects between groups
At baseline mean arterial blood pressure was comparablebetween groups.
After induction, MAP decreased in group P, increased ingroup K while it remained comparable to baseline in groupKP. The difference between groups was analyzed and foundto be statistically significant.
After intubation MAP increased in the three groups, it wascomparable between KP and P groups but remained signif-icantly higher in K group. Afterwards, MAP was compara-ble among the three groups (Table 3).
5.2. Regarding heart rate between groups
Base line heart rate (HR) was comparable between the threegroups.
After induction, HR decreased in P group, increased in Kgroup while it remained comparable to baseline in KPgroup. The difference between groups was analyzed andfound to be statistically significant.
After intubation HR increased in the three groups, it wassignificantly higher in group K in comparison to groups Pand KP, and as regards KP group HR was significantlyhigher than P group.
Afterwards, HR decreased in the three groups especially ingroup K, and remained stable and comparable for the restof the surgical time.
5.3. Regarding BIS value between groups
Regarding BIS value, all groups showed BIS values around 95before induction.With the start of IV induction, patients in the three groupsshowed progressive loss of consciousness proved by loss of ver-bal and eyelash reflexes. BIS values were significantly differentamong the three groups as follows:
In group P, BIS started to decrease with the initiation of IVinjection to reach readings around 65 five seconds after lossof verbal contact and around 50 five seconds after loss of eyelash reflex, values continued to decrease to reach
Table 1
Demographic data (data are expressed as mean ±standard deviation or ratio).
Group P Group K Group KPAge (years) 30.3 ± 6.3 31.6 ± 6.9 33.45 ± 7.7Sex; M/F 17/3 16/4 18/2Height (cm) 166.9 ± 7.16 164.7 ± 7.1 163.3 ± 7.7Body weight (kg) 81.8 ± 9.26 83.6 ± 8.6 79.2 ± 9.8ASA grade I/II 10/10 11/9 12/8
Table 2
Time needed for loss of verbal contact and loss of eyelash reflex (data are expressed as mean ± SD).
Group P Group K Group KPTime for loss of verbal contact (s) 31.80 ± 1.64 46.05 ± 1.93
a
37.40 ± 2.50
b
Time for loss of eyelash reex (s) 36.90 ± 2.07 54.20 ± 2.82
a
45.60 ± 2.41
ba
Statistically significant relative to the other two groups.
b
Statistically significant relative to group P.
Table 3
Mean blood pressure (MAP) in MmHg (data areexpressed as mean ± SD) during the follow-up period.
Group P (
n
= 20) K (
n
= 20) KP (
n
= 20)Baseline 81.50 ± 4.51382.95 ± 4.98 80.10 ± 4.40After induction 76.65 ± 4.42
c
88.30 ± 4.04
a,c
80.65 ± 4.00
b
After intubation 83.25 ± 4.14 91.50 ± 3.54
a,c
83.10 ± 4.095
00
80.00 ± 3.86 80.25 ± 2.97 82.15 ± 4.2020
00
82.70 ± 3.65 81.25 ± 2.35 81.20 ± 3.7535
00
81.30 ± 2.77 81.60 ± 2.23 82.60 ± 3.1150
00
81.88 ± 2.47 82.40 ± 2.23 81.00 ± 3.1765
00
82.11 ± 2.14 84.20 ± 2.44 83.10 ± 5.0380
00
79.40 ± 1.63 80.85 ± 2.92 80.47 ± 3.65Extubation 85.66 ± 3.43 85.75 ± 2.67 83.90 ± 3.30P; K; KP.
a
Statistically significant relative to the other two groups.
b
Statistically significant relative to group P.
c
Statistically significant relative to baseline.
Comparative study between propof, ketamine and their combination (ketofol) as an induction agent 147

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