COMPARISON OF ANESTHETIC PROPERTIES OF KETOFOL ( KETAMINE WITH PROPOFOL ) AND PROPOFOL IN MINOR SURGICAL PROCEDURES

Karki SB, Rajbanshi LK, Ariyal B, Khanal K. Comparison of Anesthetic Properties of Ketofol (ketamine With Propofol) and Propofol in Minor Surgical Procedures. BJHS 2017;2(3)4 :287291 * Corresponding Author Dr. Shambhu Bahadur Karki Consultant Anaesthesiologist Department of Anaesthesia and Intensive Care Birat Medical College & Teaching Hospital Email: karkisb@yahoo.com ORA 45 Original Research Article


INTRODUCTION
Minor surgical procedures are outpa ent daycare procedures in which pa ents are admi ed, surgical interven ons are performed and discharged at the same day.Such outpa ent anesthesia demands a safe anesthesia method with the short ac ng intravenous anesthe c medica ons, which are able to provide rapid anesthesia depth and hemodynamic stability, rapid metabolism and minimum adverse effects in the recovery period.¹´²´³Propofol is a short ac ng anesthe c agent which is used widely for the induc on of anesthesia and for the seda on in minor surgical procedures.It is a non opioid, non barbiturate sedo-hypno c agent with rapid onset and short dura on of ac on.¹It produces good seda on and also has an eme c effect.²Its adverse effects are dose related respiratory and cardiovascular depression, bradycardia and pain during injec on.³´⁴Propofol is known to produce amnesia with seda ve and hypno c effects but it don't have analgesic property so combina on of analgesic molecule is required with propofol for the seda on in surgical procedures.³Ketamine is a phencyclidine deriva ve which blocks the NMDA receptors and provides dissocia ve anesthesia, profound analgesia and amnesia.⁵Ketamine increases heart rate, cardiac output and blood pressure and it has li le or no cardiovascular and respiratory depression.It's wide spread use as a sole anesthe c agent for procedural seda on in adults is limited because of its psychotomime c effects such as vomi ng and laryngospasm.The incidence of emergence hallucina on effects can be reduced by coadministra on of benzodiazepine, barbiturates or propofol.⁵Ketamine has similar effects as propofol at sedoanalgesic doses and even safer than propofol.³Ketamine and propofol has been used in separate syringes in the same pa ent successfully in variety of procedures including seda on of spinal anesthesia, minor opthalmological procedures, gynecological and surgical procedures in children and adults.³The main advantage of this combina on is the opposing effect in the hemodynamic and respiratory effects of each drug.⁴´⁶In a prospec ve study carried by Friedberg et al in 1264 pa ents undergoing anesthesia for the surgical procedures with Ketofol (ketamine with propofol), concluded that this combina on is safe and effec ve.³The combina on of ketamine with propofol has been shown to reduce the dose of either molecule required for the seda on and analgesia.The reduced doses of this combina on provides safe, cost effec ve and less toxic anesthes c agent than the either drug alone.³ The main objec ve of this study is to compare sedoanalgesia effects of both anesthe c drugs using Ramsay Seda on Score, intraopera ve complica ons with hemodynamic and respiratory changes, requirement of amount of anesthe c solu ons, recovery mes, cost of the either solu ons and postopera ve complica ons in minor surgical procedures.

METHODOLOGY
This is a prospec ve study conducted in the Birat Medical College teaching hospital, Biratnagar, Nepal a er obtaining approval from the ethical commi ee of the hospital and a er wri en informed consent from all par cipants from February 2017 to April 2017.Total 100 pa ents between 18-60 years old with the ASA physical status class I and II were included in the study.Inclusion criteria: 1. Age between 18-60 years 2. Pa ents with ASA physical status class I and II 3. Minor surgical procedures las ng for less than 30 min Exclusion Criteria: 1. Pa ents having allergy to the study solu ons 2. Pa ents with co morbid condi ons like cardiovascular diseases, acute respiratory tract infec ons, acute and chronic hepa c diseases, renal diseases, CNS diseases, psychiatric diseases and the pa ents with alcohol and drug addic on 3. Pregnant women 4. Pa ents with ASA physical status class III and IV 5. Surgical procedures las ng more than 30 min 6.Pa ents who refused to give consent for the study A rou ne preopera ve fas ng of 8 hours was mandatory for all pa ents.Pa ents were taken to opera ng room a er pre anesthesia evalua on and prepara on.Intravenous line was opened in opera ng room with 20G intravenous cannula and RL solu on was regularly infused.4 L/min of oxygen was delivered to all pa ents via face mask during surgery and recovery period.Parameters monitored in the opera ng room were ECG, NIBP, pulse oxymetry, respira on and seda on score were recorded as follows: -before induc on -a er incision -Every 5 min during surgery -at the end of the procedure All pa ents were induced with 1 mg of inj butorphanol and 2 mg of Inj midazolam intravenously.The study solu on of Group A was prepared with 50 mg (1 ml) of Ketamine, 50 mg (5 ml) of Propofol and 4 ml of Normal Saline (NS) in a 10 ml syringe.The ra o of 1:1 was designed for ketofol group.
Group A pa ents received 50 mg (5 ml) Ketofol (25 mg Hemodynamic parameters (pulse rate, NIBP) increased at the me of incision but were within the acceptable level.
Respira on rate was decreased and was shallow in many pa ents.SpO2 was decreased below 90% in 32 cases and apnea was seen in 12 cases, all treated with posi ve pressure ven la on with oxygen.Respiratory depression was seen more frequently in the Propofol group than in the Ketofol.In this study 19 pa ents had shallow and slow respira on and 5 pa ents had apnea in Propofol group where as 13 pa ents had shallow and slow respira on and 7 had apnea in Ketofol group.There was no significant change in vital parameters a er 5 min and at the end of the surgery.
There was no decrease in SBP and pulse rate seen in any cases.
Original Research Article ketamine and 25 mg propofol) and Group B received 50 mg (5 ml) of propofol.The top-ups of the anesthe c solu on were given up to the abolishment of eye lid reflex.The level of intraopera ve seda on was assessed by Ramsey Seda on Scale (RSS).Intraopera ve seda on was maintained up to the desired level (RSS 4, 5) by supplementa on of the study solu on.All the monitored parameters were recorded along with the requirement of the anesthe c solu on and intraopera ve complica ons.
For the analysis pa ents were randomly divided into the two groups according to the order of admission in the pre opera ve prepara on room.

Pain intensity Score
No pain 0 Slight pain 1

Moderate pain 2
Severe pain 3

Unbearable pain 4
The intermi ent top ups was administered to the either group according to the autonomic (pulling extremi es, eye opening, crying) and hemodynamic (tachycardia, hypertension) responses.The seda on level was evaluated with the help of Ramsey Seda on Scale (RSS) and was maintained between 4-5 score.All vital parameters were recorded before induc on of anesthesia, just a er incision and every 5 min during the procedure.The induc on me, surgical and recovery mes were recorded and analyzed using mean with SD and listed in Table 5. Pa ents were transferred to postopera ve room when they were able to open their eye, protrude the tongue and obey the verbal command according to the AVPU recovery scale.All parameters were closely monitored in postopera ve room along with any adverse events and requirement of addi onal drugs.Inj diclofenac sodium 75 mg IM prescribed for the management of postopera ve pain and Inj metoclopramide 10 mg IV for the postopera ve nausea vomi ng (PONV).
All recorded intraopera ve and post opera ve data were collected and analyzed using SPSS.Results are expressed as mean ± SD percentage and frequency.

RESULTS
The study was conducted during 3 months period in which 50 pa ents had procedural seda on with ketofol (propofol and ketamine) and 50 pa ents with propofol.Pa ent demographics are listed in table 3. The demographic data of the both groups were similar and comparable.No sta s cal differences seen between the groups for pa ent's age, sex, weight and ASA classifica on.The level of seda on was assessed using Ramsey Seda on Scale The mean induc on me required for the Ketofol group was 32.18±4.17sec and for propofol group it was 39.34±5.12sec.
Similarly the mean surgical and recovery me also comparable in both groups.The minimum requirement of anesthe c solu on in Ketofol group was 5 ml and in Propofol group it was 8 ml.The average requirement of seda on was 9.16±4.32ml in Ketofol group was and 13.42±3.24ml in Propofol group.The requirement of the anesthe c solu on in ketofol group was much less than the propofol group and is sta s cally significant (P˂0.05).The average surgical me was 16.19±7.5min in Ketofol group and was 17.26±5.4min in Propofol group and was sta s cally comparable (P˃0.05).
No intra opera ve nausea and vomi ng seen in any case of both groups.The AVPU scale was used to assess the recovery status of all pa ents and all transferred to the post opera ve room only a er the verbal response.The average recovery me was 4.26±2.19min in Ketofol group and 5.16±3.48min in Propofol group.
(RSS) and in the both groups RSS, opera ng me and recovery me were comparable (P˃0.05).All postopera ve pa ents were kept at least for 4 hours in post opera ve room and then discharged if there were no any adverse events.Post opera ve pain was assessed with Verbal Ra ng Scale (VRS) using 0 for no pain, 1 for slight pain, 2 for moderate and 3 for the severe pain and 4 for the severe unbearable pain (Table 2).Intramuscular analgesic solu on diclofenac sodium was prescribed when VRS was 3 or more.Out of 100 analyzed pa ents 23 pa ents demanded analgesia, 9 from the ketofol group and 14 from propofol group due to severe pain (VRS 3, 4) and were treated with IM injec on of 75 mg of diclofenac sodium.Rest of the pa ents had minimal pain or bearable pain.acts primarily as an antagonist of the NMDA receptors.´ According to WHO 2 mg per kg of ketamine given intravenously over 60 seconds produces surgical anesthesia within 30 seconds which con nues for 5-10 min and 10 11 resolves completely in 1-2 hours.´ Analgesic effect of ketamine can be obtained by intravenous administra on of 12 0.2-0.75mg/kg (WHO).Ketamine is a mild respiratory depressant and also has a bronchodilatory effect with 5 13 maintained pharyngeal and laryngeal reflexes.´ Ketamine is only available intravenous anesthe c agent having analgesic, sedo-hypno c and amnes c proper es and least 9 economical than any other similar agents.So ketamine can be successfully used as an ideal anesthe c agent producing 5 9 analgesia, unconsciousness, amnesia and akinesia.´ Being all the benefits, ketamine is four mes cheaper than the propofol so its cost effec veness is also responsive for its increased use in opera ng room, emergency and intensive  respiratory complica ons.⁶´In this study minor respiratory complica ons seen in the both groups and were transient apnea and decrease in SpO2 below 90% and all treated with posi ve pressure ven la on with O2.
The minimum dose of study solu on required in Ketofol group was 5 ml and in Propofol group it was 8 ml and the average requirement of Ketofol was 9.16±4.32ml and in Original Research Article Propofol group 13.42±3.24ml.This study was also carried out to find the cost effec veness of the mixture of ketamine and propofol too.The average requirement of study solu on in Group A was 9.16 ml means 45.8 mg of propofol and 45.8 mg of ketamine.The price of 10 mg of propofol is 16 rupees and 10 mg of ketamine is 4 rupees, so the price of 9.16 ml of study solu on of group A is 91.6 rupees, however in the propofol group the cost of the 13.42 ml (134.2mg) of the solu on is 214.72 rupees.In this study ketofol group provided similar anesthesia for minor surgical procedures with more than two mes cheaper than the propofol group and is sta s cally significant (P˂0.05).
All pa ents were comfortable in the postopera ve room and discharged a er four hours of surgery and no any pa ent was admi ed due to the postopera ve complica ons.The only seen postopera ve complica ons were pain, hallucina ons, nausea and vomi ng and all treated successfully and discharged at the same day.

CONCLUSION
The combina on of ketamine and propofol has several advantages over the propofol alone for the anesthesia in minor surgical procedures.The combina on is cost effec ve, be er seda on and analgesia, hemodynamic stability and quick recovery seen in the opera ng room.The combina on has less adverse effects than the either drug alone due to their complementary effects of lowering the dose of both drugs.

Three awake levels and three asleep levels 1 .
AWAKE Pa ent anxious, agitated or restless or both 2. Pa ent coopera ve, oriented and tranquil 3. Pa ent respond to commands 4. ASLEEP A brisk response to a light glabellar tap or loud auditory s mulus 5.A sluggish response to light glabellar tap or loud auditory s mulus 6. Asleep, no response to light glabellar tap or loud auditory s mulus

Figure 1 : 3 -
Figure 1: Comparison of cost of study solu onPostopera ve nausea vomi ng seen in 8 pa ents where 5 pa ents developed nausea in ketofol group and 2 in propofol, however vomi ng seen only in 1 pa ent of ketofol group and all treated with 10 mg of intravenous injec on of metoclopramide.Ketamine induced psychotomime c effect seen in 3 pa ents and were managed by closed observa on and no any pharmacological interven on was required

5 care
department and field surgery.The combina on of propofol and ketamine produces more stable hemodynamic condi on than ketamine or propofol used individually.Ketamine with propofol for the seda on is gaining popularity due to the increased analgesic effect of ketamine and reduc on of the side effects of propofol.⁶Ketamine and propofol in combina on in separate syringes has been used successfully for the analgesia for minor procedures in adults and children by several authors.³This combina on has the property of the opposite respiratory and cardiovascular effects of each drugs.³Friedbourg inves gated 1264 pa ents for surgical procedures with ketamine and propofol and concluded that the combina on is safe and effec ve.³This combina on also reduces the dose of expensive drug propofol to achieve the desired effect.The combina on has the less adverse effects than the either drug alone due to their complementary effects of 4 lowering the dose of both drugs.Ketamine is a strong analgesic which effec vely reduces the injec on pain of 14 propofol by a enua ng the afferent pain pathways.Ketofol is mixture of ketamine and propofol in a same syringe in various concentra on used effec vely as an inducing agent in opera ng room and in ambulatory 15 se ng.It is also believed that these two agents have synergis c effect for the seda on and at the same me 4 counteract the side effect of each other.In a study by Khajabi et al the ketofol has shown to have an effec ve seda ve property and is be er than other combina on of 16 propofol with fentany and pethidine.In addi on, the ketofol combina on has low incidence of psychomime c 10,11 reac on of ketamine seen in the postopera ve room.

Table 6 . Postopera ve Complica ons.
These two molecules can be successfully mixed in a single syringe in 1:1 propor on without any chemical changes which was inves gated by several authors and found that such propor ons is safe and efficient for analgesia and 4 seda on.It is also reported that ketamine and propofol are physically compa ble and chemically stable and can be 4 mixed in a single syringe and the mixture can be stored too.Triss LA inves gated about the compa bility of propofol with other various agents and reported that ketamine and