|Year : 2014 | Volume
| Issue : 4 | Page : 518-523
Assessment of intubating conditions with propofol versus different concentrations of ketofol without muscle relaxation
Omyma Sh M Khalifa, Abeer A M Hassanin
Department of Anesthesia, Faculty of Medicine, El-Minia University, El-Minia, Egypt
|Date of Submission||09-May-2014|
|Date of Acceptance||01-Jul-2014|
|Date of Web Publication||28-Nov-2014|
Omyma Sh M Khalifa
Department of Anesthesia and Intensive Care, Faculty of Medicine, El-Minia University, 190 El-Horria Street, El-Minia City 61511
Source of Support: None, Conflict of Interest: None
Ketofol is a new combination formed by mixing ketamine and propofol. Little is known about its intubating characteristics, and therefore this study was conducted to evaluate and compare intubating conditions with propofol versus different concentrations of ketofol without muscle relaxation.
Settings and design
It was a randomized double-blind study.
Patients and methods
A total of 60 patients, with ASA I or II status, aged 18-45 years were randomized into three equal groups of 20 patients each. Propofol 'P group' received 2.5 mg/kg propofol, ketofol 2 'keto2 group' received ketofol in concentration 1 : 2, and ketofol 4 'keto4 group' received ketofol in concentration 1 : 4. Hemodynamic and intubating conditions in the form of jaw relaxation, vocal cord position, and intubating response were assessed.
There was a significant difference in the intubation score (including jaw relaxation, vocal cord position, and intubation response) between the keto2 and keto4 groups when compared with the P group, with the most acceptable intubating condition observed in the keto4 group. Although a good intubation score was detected in the three groups, the grading of this score was different. Comparison of blood pressure and heart rate between groups showed no significant difference.
Good intubating conditions without using muscle relaxant are possible with 2.5 mg/kg propofol, ketofol in concentration 1: 2 and 1: 4, with the best intubating score in ketofol concentration 1: 4 group. In addition, more hemodynamic stability was achieved in both the ketofol groups
Keywords: intubating condition, ketofol, propofol
|How to cite this article:|
Khalifa OM, Hassanin AA. Assessment of intubating conditions with propofol versus different concentrations of ketofol without muscle relaxation. Ain-Shams J Anaesthesiol 2014;7:518-23
|How to cite this URL:|
Khalifa OM, Hassanin AA. Assessment of intubating conditions with propofol versus different concentrations of ketofol without muscle relaxation. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 Sep 17];7:518-23. Available from: http://www.asja.eg.net/text.asp?2014/7/4/518/145688
| Introduction|| |
Ketamine, which has been used as an induction agent during general anesthesia since the 1960s, has been shown to cause dissociative anesthesia and a potent analgesic effect. Its use was limited because of its sympathomimetic effect, hallucination during emergence, nausea, and vomiting .
Propofol is another induction agent that has been discovered since the 1970s. It has a rapid onset of action with antiemetic and anticonvulsive effects; however, it may cause severe myocardial depression and hypotension .
Combining both drugs will result in a mixture with less side effects than either drug alone, because their complementary effects enable the use of lower doses of each drug, and on the contrary, we benefit from advantages regarding amnesia, analgesia, hypnosis, and hemodynamic stability .
Endotracheal intubation during anesthesia induction is frequently facilitated by muscle relaxants. When using muscle relaxants is undesirable or contraindicated, it is important to administer other proper induction agents to provide good intubating conditions. Studies have investigated the use of propofol alone and propofol combined with other drugs (usually fentanyl, alfentanil, or remifentanil) for intubation without using a neuromuscular blockade; the findings have shown that intubation with all of these methods was successful [4,5].
This study was conducted to evaluate the possibility of endotracheal intubation by using ketofol without using muscle relaxants, and compare intubating conditions of propofol versus two different concentrations of ketofol without muscle relaxants.
| Patients and methods|| |
This study was conducted in El-Minia University Hospital during the period from January 2013 to September 2013.
A total of 60 patients, with ASA class I and II, scheduled for elective operations under general anesthesia, aged 18-45 years, were enrolled in this study. After obtaining approval from the local ethical committee, informed consent was obtained from each patient. Patients with clinically significant cardiovascular problems, reactive airway diseases, epileptic patients, a history of gastroesophageal reflux, drug or alcohol abuse, anticipated difficult intubation, and sensitivity to the drugs used were excluded from the study.
Patients were randomized into three equal groups of 20 patients each, by using a computer-generated table numbers. The study was prospectively assigned in a double-blind manner (neither the anesthetist who performed the intubation nor the patient knew the nature of the drugs given). After a small pilot study, we found that intubation conditions with ketofol concentration 1: 1 (equal parts of ketamine and propofol) were inadequate, and therefore we changed our study plan to avoid any hazard to the patients and this concentration was cancelled.
After weighing the patients, the required doses and the different concentrations of the studied drugs were prepared by the authors in similar syringes and supplied to the anesthetist who was blinded to the randomized groups (always an experienced anesthetist who performed the intubation and graded the intubating score).
The protocol of the three groups was as follows: the P group received 2.5 mg/kg of propofol, the keto2 group received ketofol in concentration of 1: 2 (for simplicity, the total dose was calculated as 2.5 mg/kg and then divided into three parts, one part of ketamine and two parts of propofol, which was equal to 1.7 mg/kg propofol and 0.8 mg/kg ketamine) and the keto4 group received ketofol in concentration 1: 4 (also 2.5 mg/kg divided into five parts, one part of ketamine and four parts of propofol, which was equal to 2 mg/kg propofol and 0.5 mg/kg ketamine).
On the operating table, each patient was attached to ECG monitor, pulse oximeter, and NIBP (non invasive blood pressure) and these preoperative data were recorded. The patients were cannulated and 10 ml/kg of Ringer's lactate solution was given before induction, together with 0.01 mg/kg atropine.
All patients were preoxygenated for 3 min with 100% oxygen, and then premedicated with midazolam (0.03 mg/kg) (in our study, we considered after premedication readings as basal to avoid any effect of stress on the patients).
Then fentanyl (1 μg/kg) was injected intravenously over 20-25 s, 45 s after the injection of fentanyl and lidocaine (1.5 mg/kg) intravenously was injected. As fentanyl takes 5-7 min for its plasma concentration to equilibrate with that of brain concentration, we waited for 5 min after giving fentanyl, and then propofol or ketofol was injected according to the precalculated amount. After 90 s of the completion of propofol or ketofol injection, using a Macintosh 3 blade (Flexicare Medical Ltd, Cyanon Valley Business Park, Mountain Ash, CF45 4ER, UK), direct laryngoscopy and intubation were performed. We waited for 90 s because good to excellent intubating conditions are reported 90 s after hypnotic doses of propofol. Oxygen with 2 MAC (minimum alveolar concentration) sevoflurane was delivered through a facemask until laryngoscopy and intubation were performed. All patients were intubated with a cuffed endotracheal tube of proper size.
For success only one attempt at laryngoscopy and intubation was considered, and assessment of all the variables was made from this attempt. These variables include: jaw relaxation, vocal cord position, and intubation response. If patients could not be intubated, they were given muscle relaxant to optimize conditions and excluded from the research. The criteria used for ranking these variables are shown in [Table 1].
Hemodynamic data were recorded at: preoperatively, after premedication (considered as baseline), after induction, after intubation, and 5, 10, and 15 min after intubation, and then anesthesia was maintained at the discretion of attending anesthesiologists.
Data entry and analysis were carried out with IBM compatible computer using software (SPSS for Windows version 20). Quantitative data were presented by mean and SD and compared by analysis of variance test followed by post-hoc test if there was significance and paired t-test was used to compare the mean values in the same group. Qualitative data were presented by number and percentage and compared by χ2 -test. A P-value of 0.05 was considered statistically significant. The sample size was calculated by comparing means of difference between groups by 95% confidence interval and study power 80%.
| Results|| |
There were no statistically significant differences between the three groups with regard to age, weight, sex, ASA class, or occurrence of excessive salivation during intubation ([Table 2]).
There was no significant difference between the groups with regard to mean arterial pressure (MAP) at different times of measurements ([Table 3]). Within P and keto2 groups, there was a significant decrease in MAP after induction and at 5, 10, and 15 min in comparison with after premedication (baseline) ([Table 4]).
|Table 3 Comparison of mean arterial blood pressure (mmHg) in the studied groups (mean ± SD)|
Click here to view
In keto4, significant decrease in mean blood pressure only occurred after induction and at 10 min in comparison with baseline ([Table 4]).
|Table 4 Comparison of mean arterial blood pressure at various intervals (mmHg) within each group|
Click here to view
A significant increase in MAP occurred after intubation in comparison with after induction in the P and keto4 groups only. In comparing MAP after intubation with that of baseline, it did not exceed the baseline level; on the contrary, it was significantly lower in the P group ([Table 4]).
Comparison of the heart rate (HR) between the groups showed no significant difference ([Table 5]).
|Table 5 Comparison of heart rate (beats/min) in the studied groups (mean ± SD)|
Click here to view
Baseline HR was comparable between the three groups. However, after induction, HR values significantly decreased in the three groups in comparison with the baseline level, and significantly increased after intubation in comparison with both the baseline and after induction values. This significant increase extended to 5 min after intubation in relation to baseline level in the keto2 group only ([Table 6]).
|Table 6 Comparison of heart rate (beats/min) at various intervals within the groups|
Click here to view
With regard to the intubation score, there was a significant difference between the keto2 and keto4 groups when compared with the propofol group, with the most acceptable intubating condition observed in the keto4 group. Although a good intubation score was detected in the three groups, the grading of this score was different as shown in [Table 7] and [Figure 1].
|Figure 1: Number and percentage of patients in different grades of intubation score|
Click here to view
Looking at the statistical details of the intubation score in jaw relaxation significant difference was detected in the keto2 group when compared with the propofol group. However, in intubation reflex and vocal cord position, there was a significant difference between all three groups ([Table 8]).
|Table 8 Comparison of jaw relaxation, vocal cord position, and intubation refl ex in the three groups|
Click here to view
| Discussion|| |
Previous studies have concluded that tracheal intubation is possible without the use of muscle relaxant. Keaveny and Knell  were among the earliest who achieved 95% success rate of intubation without neuromuscular blocking agents, only with propofol (2.5 mg/kg).
As anesthesiologists have tried to formulate combination of drugs that help to intubate patients without coughing or bucking in the absence of muscle relaxants, this present research tried to study the effect of different concentrations of ketofol on intubation without muscle relaxant and compared these concentrations with propofol in addition to midazolam (0.03 mg/kg), fentanyl (1 μg/kg), and lidocaine (1.5/mg kg) in all groups.
In our study, good intubating conditions achieved in 100% of patients in the P and keto2 groups, whereas in the keto4 group 20% excellent intubation condition and 80% good intubation condition were obtained.
In a study by Gore and Harnagale , it was found that propofol (2.5 mg/kg) with fentanyl (2 mg/kg) had achieved clinically acceptable intubating conditions in 96.70% of patients, and only 3.30% of patients could not be intubated and were given muscle relaxants.
In addition, Davidson and Gillespie  found clinically acceptable intubating conditions in 93% of the patients with propofol (2.5 mg/kg) and alfentanil (20 μg/kg) with 1 mg/kg lidocaine, and in 73% of the patients without lidocaine.
Alcock et al.  found 86% clinically acceptable intubating conditions with 2.5 mg/kg propofol and alfentanil (10 μg/kg), and Saarnivaara and Klemola  could achieve 89% success in intubation with 2.5 mg/kg propofol and 30 μg/kg alfentanil without muscle relaxation.
On the contrary, Mulholland and Carlisle  compared tracheal intubation with 2.5 mg/kg propofol with or without 1.5 mg/kg lidocaine without any opioids or muscle relaxants. They found that dose of 2.5 mg/kg propofol is sufficient to intubate the trachea without muscle relaxants, and addition of lidocaine (1.5 mg/kg) attenuates the stress response to intubation well. Clinically acceptable intubating condition was found in only 66% of patients, as the authors did not use any opioids; this may be the cause for lower success rate.
Lieutaud et al.  found clinically acceptable intubating conditions in only 35% of the patients with propofol (2.5 mg/kg) and (fentanyl μg/kg). They performed laryngoscopy and intubation 3 min after fentanyl injection, whereas we performed laryngoscopy and intubation at 7 min after fentanyl injection.
In our study, significant decrease in blood pressure after induction compared with baseline was detected in the three groups, which increased after intubation in comparison with after induction, but it was not returned to baseline values; however, this increase was statistically insignificant in the keto2 group. Whereas in the propofol group, the decline in MAP was noticed all over the recorded times in comparison with the baseline level, more stability was recorded in the ketofol groups with the best dose of keto4. In line with our results, Akin et al. , who investigated the effects of propofol and propofol-ketamine on hemodynamics, sedation level, and recovery period in pediatric patients undergoing cardiac catheterization, found that propofol combined with low-dose ketamine preserves MAP better without affecting the recovery. This is consistent with the result of Aboeldahab et al. , who studied 60 patients subjected to hernia repair surgeries under general anesthesia using propofol, ketamine, and ketofol as induction agents. The ketofol group showed more stable hemodynamics in comparison with either propofol or ketamine groups. Smischney et al.  who assessed the hemodynamics in patients undergoing standardized induction with propofol alone or with 'ketofol', concluded that 'ketofol' is associated with better hemodynamic stability during the first 10 min after induction. In addition, Yousef and Elsayed  have investigated ketofol as a suitable induction alternative to propofol for insertion of laryngeal mask airway (LMA) in children, considering insertion conditions and hemodynamic stability. They found that ketofol provided better LMA insertion conditions, more hemodynamic stability with less prolonged apnea when compared with propofol.
In our study, despite decrease in the mean values of HR after induction and increase after intubation, statistical analysis of the data showed insignificant differences between the groups. However, within the individual group, significant decrease followed by significant increase was observed upon comparing after-induction and after-intubation values to the baseline level, respectively. In addition, HR significantly increased when after-intubation HR was compared with after-induction HR. This significant increase extended only in the keto2 group to 5 min after intubation when compared with baseline values. These limited changes may be explained by the combined use of midazolam, fentanyl, and lidocaine.
There was no problem in mask ventilation in all groups. In addition, there was a slight increased salivation in the keto2 group, but it did not interfere with laryngoscopy and intubation.
Thus, in conclusion, good intubating conditions for intubation without using muscle relaxants are possible with 2.5 mg/kg propofol and ketofol in concentration 1: 2 and 1: 4 with 1 μg/kg fentanyl and 1.5 mg/kg lidocaine. Stress response to laryngoscopy and intubation gets attenuated well, in addition to better hemodynamic conditions with ketofol use.
This technique may be appropriate for tracheal intubation when neuromuscular blockade is undesirable or not required for the planned surgical procedure.
| Acknowledgements|| |
| References|| |
Warncke T, Stubhaug A, Jorum E. Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn induced secondary hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo. Pain 1997; 72:99-106.
Bassett KE, Anderson JL, Pribble CG, Guenther E. Propofol for procedural sedation in the emergency department. Ann Emerg Med 2003; 42:773-782.
Morse Z, Sano K, Kanri T. Effects of propofol-ketamine admixture inhuman volunteers. Pac Health Dialog 2003; 10:51-54.
Imani F, Alebouyeh MR, Taghipour-Anvari Z, Faiz SHR. Use of remifentanil and alfentanil in endotracheal intubation: a comparative study. Anesthesiol Pain Med 2011; 1:61-65.
Hanci V, Erdogan G, Okyay RD, Yurtlu BS, Ayoglu H, Baydilek Y, et al.
Effects of fentanyl - lidocaine - propofol and dexmedetomidine - lidocaine - propofol on tracheal intubation without use of muscle relaxants. Kaohsiung J Med Sci 2010;26:244-250.
Gore MS, Harnagale KD. Evaluation of intubating conditions with varying doses of propofol without muscle relaxants. J Anaesthesiol Clin Pharmacol 2011; 27:27-30.
Keaveny JP, Knell PJ. Intubation under induction doses of propofol. Anaesthesia1988; 43:80-81.
Davidson JA, Gillespie JA. Tracheal intubation after induction of anesthesia with propofol, alfentanil and i.v. lignocaine. Br J Anaesth 1993; 70:163-166.
Alcock R, Peachey T, Lynch M, Mcewan T. Comparison of alfentanil with suxamethonium in facilitating nasotracheal intubation in day-case anesthesia. Br J Anaesth 1993; 70:34-37.
Saarnivaara L, Klemola VM. Injection pain, intubation conditions and cardiovascular changes following induction of anesthesia with propofol alone or in combination with alfentanil. Acta Anesthesiol Scand 1991; 35:19-23.
Mulholland D, Carlisle RJ. Intubation with propofol augmented with intravenous lignocaine. Anaesthesia 1991; 46:312-313.
Lietaud T, Billard V, Khalaf H, Debaene B. Muscle relaxation and increasing doses of propofol improve intubating conditions. Can J Anaesth 2003; 50:121-126.
Akin A, Esmaoglu A, Guler G, Demircioglu R, Narin N, Boyaci A. Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol 2005; 26:553-557.
Aboeldahab H, Samir R, Hosny H, Omar A. Comparative study between propofol, ketamine and their combination (ketofol) as an induction agent. Egypt J Anaesthesia 2011; 27:145-150.
Smischney NJ, Beach ML, Loftus RW, Dodds TM, Koff MD. Ketamine/propofol admixture (ketofol) is associated with improved hemodynamics as an induction agent: a randomized, controlled trial. J Trauma Acute Care Surg 2012; 73:94-101.
Yousef GT, Elsayed KM. A clinical comparison of ketofol (ketamine and propofol admixture) versus propofol as an induction agent on quality of laryngeal mask airway insertion and hemodynamic stability in children. Anesth Essays Res 2013; 7:194-199.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]