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Go Back       IAR Journal of Anaesthesiology and Critical Care | IAR J Anaes Crtic Cre. 2(3) | Volume:2 Issue:3 ( June 20, 2021 ) : 17-23
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DOI : 10.47310/iarjacc.2021.v02i03.004       Download PDF       HTML       XML

A Clinical Comparative Study of Propofol and Ketamine Combination (Ketofol) Versus Either Drug Alone In Short Surgeries and Procedures”


Article History

Received: 20.05.2021 Revision: 30.05.2021 Accepted: 10.06.2021 Published: 20.06.2021


Author Details

Dr Shruti Hiremath1, Dr Champa BV2


Authors Affiliations

1Assistant Professor, Department. Of Anaesthesia, Shivamogga Institute of Medical Sciences, Shivamogga, Karnataka, India.

2Associate Professor, Department. Of Anaesthesia, Shivamogga Institute of Medical Sciences, Shivamogga, Karnataka, India


Abstract: Introduction: TIVA has many advantages over inhalational anaesthesia To name a few like its role in Day care surgeries, faster recovery rate, Lesser hospital stay and so on. Various drugs have been tried in TIVA but no single drug have the ideal characteristics, hence various combinations of drugs are being used. One such drug combination is Ketofol (ketamine and propofol). Objective: To investigate ketofol as a suitable anaesthetic agent alternative to propofol, ketamine alone in short surgical procedures for onset, duration of anaesthesia, quality of analgesia, Haemodynamic and respiratory stability, adverse effects and recovery characteristics. Materials and Methods: In this prospective comparative study, 3 group i.e, ketamine (k) group, propofol (p) group, ketofol (kp) group consisting 50 patients in each group undergoing short surgical procedures were studied. Each assigned group were premedicated and induced with ketamine 2mg/kg bodyweight in k group, propofol 2mg/kg bodyweight in p group and ketofol (ketamine 1mg/kg body wt+ propofol 1mg/kg body wt). The parameters like onset of action, duration, quality of analgesia, cardiorespiratory stability, adverse effects and recovery characters were studied. Results: We found significant difference p value <0.05 among k, p and kp groups. Kp (ketofol) group had better induction qualities, haemodynamic stability and lesser adverse effects. Conclusion: We concluded that ketofol (ketamine+propofol) combination is a better intravenous anaesthetic agent than propofol or ketamine alone in TIVA procedures.


Keywords: Ketamine, Propofol, Total intravenous anaesthesia.


Introduction:

General anaesthesia has undergone a vast number of improvements and modifications and even its recently modified form Total intravenous anaesthesia(TIVA; induction and maintenance of anaesthesia with intravenous agents only) has undergone many improvements ever since its introduction into clinical practice1.TIVA has many advantages such as:, Used in day care surgeries, No sophisticated delivery system required, It can also be used in remote settings apart from its use in well equipped hospital (Bajwa, S. J. S. et al., 2010).Various drugs have been tried from time to time in TIVA. As none of them have ideal characteristics. In quest of that this study (ketofol) combination has been studied in short surgeries and procedures in comparison with ketamine and propofol alone for above mentioned anaesthetic characteristics.


KETOFOL (KETAMINE+PROPOFOL)

It is a novel intravenous anaesthetic agent. It consists of combination of i.v ketamine and i.v propofol. The dosage of propofol is reduced to 1mg/kg body weight and ketamine to 1 mg/kg body weight .The advantages of combining both is to counteract the side effects of each drug individually. Combination of ketamine with propofol provides excellent sedation and analgesia (Srivastava, U. et al., 2006; Atashkhoyi, S. et al., 2013; & Singh, R. et al., 2013) and appears to be safe and useful technique for short surgeries and procedures. The opposing haemodynamic and respiratory effects of each drug may enhance the utility of ketofol, increasing both safety and efficacy and allowing reduction in dose of propofol required to achieve the same.


MATERIALS AND METHODS

After approval of institutional ethical committee and informed consent, this prospective comparative study was conducted in the Department of Anaesthesiology of Shivamogga Institute of medical sciences, Shivamogga over a period of 1 year. Patients posted for procedures constituted the study group. They were allocated in to three groups by computerised random method.


GROUP K: Comprised of 50 patients received intravenous ketamine dose of 2mg/kg body wt. GROUP P: Comprised of 50 patients and received intravenous propofol dose of 2 mg/kg body wt. GROUP KP: Comprised of 50 patients and received a combination of ketamine 1mg/kg body wt followed by propofol of 1mg/kg body weight


Inclusion Criteria Age group between 18 to 60 years, both sexes, ASA I & II, Patient scheduled for short surgical procedures lasting for about 30 minutes. Patients who have not eaten solid food within 8 hours before or liquids in the two hours before.


Exclusion Criteria An acute lung infection, Coronary heart disease, CHD, and angina, Previous mild allergic reaction to ketamine, propofol, lidocaine, or egg albumin, Patient who refuses to provide informed consent.


Study Procedure: All patients received 0.5 mg of alprazolam orally on the night before surgery. On arrival to the operation theatre, a Teflon intravenous cannula (vasofix) was placed on the forearm, or dorsum of hand of the non-dominant arm for drug and fluid administration. Monitors like pulse oxymeter, non-invasive blood pressure(NIBP) & ECG were connected to the patients to monitor PR, NIBP, RR & SPO2.Patients were premedicated with glycopyrrolate 0.01mg/kg, pentazocine 0.5mg/kg & midazolam 0.05mg/kg body weight. Patients were then induced with the each assigned study drug i.e in P GROUP patient received a dose of 2mg/kg body wt was given as a 10mg/ml (1%) solution. In K GROUP patient received a dose of 2mg/kg body wt of ketamine from a 50mg/ml solution. In KP GROUP patient received a combination of ketamine 1 mg/kg body wt followed by propofol 1 mg /kg body wt. Loss of lid reflex were taken to indicate adequate induction, the incidence of pain on injection of the drug , excitatory phenomenon like tremors and involuntary movements were noted .Cessation of respiration for more than 20 seconds was considered as apnoea , it was treated by ventilation with 100% oxygen .Patients requiring additional doses of either of the study drugs were excluded from the study group. At the end of surgery patients were observed for PONV, delirum and emergence reactions. The duration of the surgery was noted. Recovery characteristics in terms of activity, respiration and circulation were studied.


STATISTICAL ANALYSIS: Mean and standard deviations were given for continuous data, number and percentages for categorical data. Group comparisons were made using Anova (Analysis of variance) test. p-value<0.05 were considered significant.


OBSERVATION AND RESULTS:


Table 1 Age and Sex wise distribution

Variable

Particulars

Anova

F

Significance

Sex

Male

Female

Between the groups & within the groups

0.2020

0.817

Non significant

Age in years

<18

18-40

40-60

>60

Between the groups & within the groups

0.449

0.63

Non significant


The three groups were compared with respect to age and sex by ANOVA test i.e, between the groups and with in the groups. The results showed non-significant.


Table 2 Onset of Action

Variable

Anova

F

Significance


Onset in seconds

Between the groups & within the groups

290.096

0.000

Significance


The three groups were compared in terms of onset of action between the groups and within the groups and found significant difference in the kp group compared to group p or group k.


Table 3. Duration of Action

Variable

Anova

F

Significance

Duration of action

Between the groups & within the groups

12.059

0.000

Significant


The three groups were compared in terms of duration of action and found significant difference as shown above with the value being <0.05, so there is a significance difference between the groups and within the groups. The kp group has extended/ longer duration of action.


HAEMODYNAMIC CHANGES


Table 4 Changes in Pulse Rate

PULSE 0

Between groups and within groups

8.141

0

Significant

PULSE 1

Between groups and within groups

2.546

0.082

Not Significant

PULSE 5

Between groups and within groups

17.092

0

Significant

PULSE 15

Between groups and within groups

36.148

0

Significant

PULSE 30

Between groups and within groups

54.033

0

Significant

PULSE 60

Between groups and within groups

106.787

0

Significant


There is significant difference in the pulse rate in KP group compared to the K group, p group. In kp group there was less variability (little change) in PR compared to k or p group.


GRAPH 1. Changes In Pulse Rate

Graph Image is available at PDF file


GRAPH 2 Changes in Pulse Rate

Graph Image is available at PDF file


Table 5 Changes in Systolic Bp and Diastolic Bp Anova




F value


0 SBP

Between groups and within groups

5.608

0.004

Significant

0DBP

Between groups and within groups

4.123

0.018

Significant

1 SBP

Between groups and within groups

19.46

0

Significant

1DBP

Between groups and within groups

15.369

0

Significant

5 SBP

Between groups and within groups

62.388

0

Significant

5DBP

Between groups and within groups

46.198

0

Significant

15 SBP

Between groups and within groups

74.714

0

Significant

15 DBP

Between groups and within groups

62.19

0

Significant

30 SBP

Between groups and within groups

106.912

0

Significant

30DBP

Between groups and within groups

98.211

0

Significant

60 SBP

Between groups and within groups

119.136

0

Significant

60 DBP

Between groups and within groups

134.034

0

Significant


There is significant difference in the SBP and DBP in the kp group compared to k group or p group i.e, in kp group there was less variability in terms of SBP and DBP compared to k or p groups


GRAPH 3. Changes in Systolic Blood Pressur

Graph Image is available at PDF file


GRAPH 4. Changes in Diastolic Blood Pressure

Graph Image is available at PDF file


Table 6 Changes in Respiratory Rate

Table Image is available at PDF file


There was no significant difference between the groups and within the groups at 0, 1, 5 mins, but at 15, 30 and 60 there was a significant difference i.e, more stable values of respiratory rate found in group kp compared to group k and group p.


Table 7 Changes in Spo2

Spo2(min)

Anova

F

Significance value

S/NS

0

Between the groups & within the groups

6.231

0.003

S

1

Between the groups & within the groups

13.27

0

S

5

Between the groups & within the groups

2.58

0.079

NS

15

Between the groups & within the groups

0.818

0.44

NS

30

Between the groups & within the groups

2.514

0.08

NS

60

Between the groups & within the groups

0.774

0.46

NS


There was a significance difference between the groups and within the groups at 0 and 1min but throughout the procedure there was not much changes in saturation in kp, p or k group.


Table 8 Adverse Reactions

ANOVA

 

 

 

 

 

F

Sig.

Gender

Between Groups

Within Groups

0.202

0.817

 

 

 

Quality of Analgesia

Between Groups

Within Groups

91.433

0

 

 

 

Rescue Analgesia

Between Groups

Within Groups

27.574

0

 

 

 




Adverse effects Pain

Between Groups

Within Groups

91.147

0

 

 

 

Adverse effect vomiting

Between Groups

Within Groups

40.695

0

 

 

 

Adverse effect Apnoea

Between Groups

Within Groups

16.805

0

 

 

 

Emergence reactions

Between Groups

Within Groups

17.241

0

 

 

 

In terms of adverse reactions, there was significant difference in terms of pain, vomiting, emergence reactions i.e, there were lesser incidence of above mentioned side effects in group kp than k or p group.


Table 9 Recovery Characteristics

Recovery

Anova

F

Significance value

S/NS

Activity

Respiration

Circulation

Between Groups

Within Groups

17.29

0

S

In terms of recovery there was significantly delayed recovery in group k and p compared to kp groups.


DISCUSSION

As day care surgeries are on rise for short surgical procedures. By combining propofol and ketamine (ketofol), there is an additive effect of GABA agonism by propofol and NMDA antagonism by ketamine leading to lesser doses of propofol required along with ketamin. Ketamine in subanaesthetic doses with propofol has gained attention in TIVA because of its powerful analgesic action (Srivastava, U. et al., 2006; Goh, P. K. et al., 2005; Atashkhoyi, S et al., 2013; & Aouad, M. T. et al., 2008) and effectiveness of two agents in combination has been recently demonstrated and may provide a novel inducing agent with favourable haemodynamic stability (Bajwa, S. J. S. et al., 2010; Yousef, G. T., & Elsayed, K. M. 2013; & Khutia, S. K. et al., 2012).

The two groups were comparable with respect to age, sex, weight, ASA grading and duration of surgery .and


HAEMODYNAMIC CHANGES: In propofol group there was significant fall in SBP and DBP in the range of 7 to 10 %. In ketamine group, there was significant rise in SBP and DBP in the range of 20 t 25 %. Where as in ketofol group , the fall in SBP and DBP is minimal i.e 3 to 4 % in other words throught out the procedure SBP & DBP remained stable .These findings coincide with the previous studies on ketofol conducted by Bajwa et al., (2010), Gamal T yousy et al., (2013), umasrivastaval et al., (2006), Goh PK et al.,(2005) all stated that ketofol produced stable haemodynamic s throught out procedure .


PULSE RATE: In ketofol group there was minimal change in pulse rate, when compared to significant variation in case of propofol or ketamine group. These findings coincide with the previous studies on ketofol conducted by Gamal T yousy et al., (2013), uma srivastaval et al., 2006.


RESPIRATORY RATE: In our study, there was insignificant difference in respiratory rate in all three groups (ketamine, propofol and ketofol) through out the procedure. SPO2 Oxygen saturation was maintained in all the groups through out the procedure and there were no Significant statistical differences between ketamine, propofol and ketofol groups.


ONSET: All the patients in ketofol group there was showed quicker onset of action when compared to ketamine or propofol group and there was significant statistical difference between all the three groups. These findings coincide with the previous studies conducted by, sukhminderjitsinghbajwa et al., (2013) umasrivastaval et al., (2006), Khutia SK et al., (2012).


DURATION OF ACTION: There was extended duration of action in ketofol group compared to either ketamine or propofol group.


ADVERSE REACTIONS

In our study the incidence of adverse effects during the procedure like pain on injection, apnoea, delirum, need of rescue analgesia, were more in ketamine and propofol groups .There was significant differences among all the three groups i.e there was lesser incidence of all the adverse effects in ketofol.


CONCLUSION

It is fair to conclude from this study that ketofol (combination of ketamine+propofol) is a better inducing agent in TIVA for short surface surgeries and procedures than ketamine or propofol alone with the following advantages like quicker onset of action extended duration of action, stable haemodynamic conditions, lesser incidence of adverse effects, smoother and faster recovery.


REFERENCES

  1. Bajwa, S. J. S., Bajwa, S. K., & Kaur, J. (2010). Comparison of two drug combinations in total intravenous anesthesia: Propofol–ketamine and propofol–fentanyl. Saudi journal of anaesthesia4(2), 72.

  2. Vora, K. S., Prabodhachandran, M. S., Bhosale, G. P., Singhal, N., Parikh, G. P., & Shah, V. R. (2005). Comparison of admixtures of propofol-thiopentone, propofol-ketamine and propofol in ambulatory surgery. Journal of Anaesthesiology Clinical Pharmacology21(4), 413-418.

  3. Yousef, G. T., & Elsayed, K. M. (2013). 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. Anesthesia, essays and researches7(2), 194.

  4. Srivastava, U., Sharma, N., Kumar, A., & Saxena, S. (2006). Small dose propofol or ketamine as an alternative to midazolam co-induction to propofol. Indian J Anaesth50(2), 112-114.

  5. Thomas, M. C., Jennett-Reznek, A. M., & Patanwala, A. E. (2011). Combination of ketamine and propofol versus either agent alone for procedural sedation in the emergency department. American Journal of Health-System Pharmacy68(23), 2248-2256.

  6. Khutia, S. K., Mandal, M. C., Das, S., & Basu, S. R. (2012). Intravenous infusion of ketamine-propofol can be an alternative to intravenous infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients undergoing emergency short surgical procedures. Indian journal of anaesthesia56(2), 145.

  7. Goh, P. K., Chiu, C. L., Wang, C. Y., Chan, Y. K., & Loo, P. L. (2005). Randomized double-blind comparison of ketamine-propofol, fentanyl-propofol and propofol-saline on haemodynamics and laryngeal mask airway insertion conditions. Anaesthesia and intensive care33(2), 223-228.

  8. Atashkhoyi, S., Negargar, S., & Hatami-Marandi, P. (2013). Effects of the addition of low-dose ketamine to propofol-fentanyl anaesthesia during diagnostic gynaecological laparoscopy. European Journal of Obstetrics & Gynecology and Reproductive Biology170(1), 247-250.

  9. Singh, R., Ghazanwy, M., & Vajifdar, H. (2013). A randomized controlled trial to compare fentanyl-propofol and ketamine-propofol combination for procedural sedation and analgesia in laparoscopic tubal ligation. Saudi journal of anaesthesia7(1), 24.

  10. Aouad, M. T., Moussa, A. R., Dagher, C. M., Muwakkit, S. A., Jabbour‐Khoury, S. I., Zbeidy, R. A., ... & Kanazi, G. E. (2008). Addition of ketamine to propofol for initiation of procedural anesthesia in children reduces propofol consumption and preserves hemodynamic stability. Acta Anaesthesiologica Scandinavica52(4), 561-565.

  11. Khutia, S. K., Mandal, M. C., Das, S., & Basu, S. R. (2012). Intravenous infusion of ketamine-propofol can be an alternative to intravenous infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients undergoing emergency short surgical procedures. Indian journal of anaesthesia56(2), 145–50. 

  12. Akin, A., Guler, G., Esmaoglu, A., Bedirli, N., & Boyaci, A. (2005). A comparison of fentanyl-propofol with a ketamine-propofol combination for sedation during endometrial biopsy. Journal of clinical anesthesia17(3), 187-190.

  13. Nalini, K. B., Cherian, A., Balachander, H., & Kumar, Y. (2014). Comparison of propofol and ketamine versus propofol and fentanyl for puerperal sterilization, a randomized clinical trial. Journal of clinical and diagnostic research: JCDR8(5), GC01.

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