Regional anesthesia (RA) offers several advantages compared to general anesthesia, encompassing the reduction of the surgical stress response, avoidance of airway instrumentation, provision of effective post-operative analgesia, and facilitation of early ambulation with a decreased risk of deep vein thrombosis. However, the utilization of RA is not without considerations. One notable concern is the potential for accelerated hypotension due to sympathetic blockade, as Regional Anesthesia may affect the normal autonomic regulation of blood pressure. Additionally, ventilatory changes can occur due to the higher sensory blockade and patients may experience shoulder-tip pain resulting from diaphragmatic irritation. Another consideration is the possibility of increased surgical time, attributed to the constraints imposed by the intra-abdominal pressure during procedures performed under regional anaesthesia.[1,2] In routine practice, the conventional approach for securing the airway during laparoscopic surgery involves endotracheal intubation which is invariably associated with sympathetic stimulation which can lead to tachycardia, hypertension, and arrhythmias.[3] The hemodynamic changes induced by endotracheal intubation are typically transient, variable, and unpredictable. While these alterations may pose minimal risk to healthy individuals, they can be potentially hazardous in patients with history of pre-existing conditions such as hypertension, myocardial ischemia, cerebrovascular diseases, or elevated intraocular pressures.[4] Supraglottic airway devices have been advocated as an alternative approach in certain studies. However, concerns persist regarding their use in laparoscopic surgery. Another concern is the potential risk of gastroesophageal regurgitation, posing a risk of aspiration. Additionally, achieving effective ventilation is challenging due to the impact of artificial pneumoperitoneum and postural changes on airway pressure and pulmonary compliance.[5] The altered intra-abdominal pressure and patient positioning inherent in laparoscopic procedures affect the dynamics of air movement and increase the likelihood of complications. Therefore, although supraglottic airway devices may offer advantages, careful consideration of the potential issues is crucial in determining their appropriateness for specific cases, ensuring patient safety during laparoscopic interventions. However, the most common approach is general anesthesia with endotracheal intubation with controlled ventilation, offering airway protection and preventing aspiration pneumonia.[6,7]

The efficacy of admixture of various induction agents has been explored in recent years and synergism has been found between these induction agents. Propofol, a 2,6- diisopropylphenol developed in Europe during the 1970s, boasts rapid induction and recovery times, along with antiemetic and anticonvulsant effects. Despite these advantages, its major drawbacks include dose-dependent hypotension and respiratory depression. This evolving understanding of the interactions between induction agents opens avenues for refining anesthetic protocols to achieve optimal sedation while minimizing adverse effects.[8,9]. This antagonism results in the blockade of spinal nociceptive reflexes and therefore, is widely used as a preventive analgesic for managing acute postoperative pain. This multifaceted role highlights the versatility of ketamine in anesthesia, establishing it as a valuable tool for optimizing patient comfort and recovery in the perioperative setting.[10,11] Despite its distinctive benefits, when used as a sole induction agent, ketamine has limitations due to its psychomimetic and sympathomimetic effects.[12] Utilization of Ketamine as an anesthetic is limited by several side effects such as nausea, vomiting, emergence hallucinations, and an increase in blood pressure and heart rate, attributed to its sympathomimetic effects and its potential to elevate intracranial pressure.[13]

In recent years, efficacy of combining ketamine and propofol, commonly known as 'ketofol' has been thoroughly investigated. The synergistic effect of these agents has been linked to a hemodynamically favorable profile. Each drug in this combination is believed to counteract the undesirable effects of the other, establishing a balanced and well-tolerated mixture. Previous studies have provided evidence supporting the positive hemodynamic outcomes associated with 'ketofol,' and the safety and stability of this combination have been well-documented in various settings.[14,15] This combination has been particularly studied in the context of continuous infusions for procedural sedation in emergency departments. While existing research has predominantly focused on assessing the impact of continuous infusions of 'ketofol' for procedural sedation in emergency department settings, there remains a noticeable gap in data pertaining to fixed dosing regimens of 'ketofol' for the induction of general anesthesia. Additionally, the use of drug combinations, for example 'ketofol,' often results in a reduction of the total dose of each individual drug. This reduction can be advantageous in specific scenarios, such as managing patients in hemorrhagic shock, where minimizing the overall drug load may be a critical consideration for patient safety.[16]

The concept of combining ketamine with propofol, often referred as 'Ketofol,' has been suggested as a potential strategy to mitigate the hemodynamic adverse effects associated with each drug individually. This combination aims to achieve a stable hemodynamic profile during the induction of anesthesia, offering an additional advantage of reducing the incidence of postoperative nausea and vomiting (PONV) as well as postoperative shivering.[16,17]

Aim- title- to study hemodynamics variable post-induction with propofol versus ketofol.

This is a prospective observational study done in Department of anaesthesia at Shri Rawatpura Sarkar Institute of Medical Sciences and Research, Raipur Chhattisgarh:  1^st May 2024 to 1^st May 2025 in 72 patients.  This study will be approved by institutional ethical committee and written informed consent will be obtained from all participants before inclusion in the study. The study was conducted in following two groups of patients. Each group was consisting of 36 patients

• GROUP A - Patients received 1 mg/kg propofol plus 1 mg/kg ketamine (10 mg/ml dilution) diluted to 20 ml in a syringe as induction agent.
• GROUP B – Patients received 2 mg/kg propofol diluted to 20 ml with normal saline in a syringe as induction agent.

INCLUSION CRITERIA:

1. Patients willing to give written informed
2. ASA Grade I & II Patients
3. Age Groups-18-55 years of either sex
4. Undergoing Laparoscopic        Cholecystectomy        surgery      under     GA       requiring endotracheal intubation.

EXCLUSION CRITERIA:

1. Patients with history of drug allergy, egg
2. Patients with uncontrolled hypertension and diabetes
3. Patients with history of psychiatric
4. Pregnant patients
5. Patients with BMI >30kg/m2

Therefore, with this background we planned a randomised study to compare effect of Propofol vs Ketofol as induction agents on hemodynamic parameters. By comparing their parameters, the study aims to determine which drug Propofol or Ketofol provides better hemodynamic stability during critical phase of induction of anaesthesia. Our objective was to assess the variations in hemodynamic parameters (including Mean Heart Rate, Mean Systolic Blood Pressure, Mean Diastolic Blood Pressure, Mean Arterial Pressure, Mean SpO2, Mean Rate Pressure Product) at various time intervals (1, 3, 5, 10, 15 minutes) post-induction and to explore any associated side effects.

Hence, the purpose of our study is to find out which drug is better either propofol or Ketofol for induction of GA in terms of stability of haemodynamic variables (Mean Heart Rate, Mean Systolic Blood Pressure, Mean Diastolic Blood Pressure, Mean Arterial Pressure, Mean SpO2, Mean Rate Pressure Product).

PRE ANAESTHETIC CHECKUP

All selected patients underwent pre anaesthetic checkup, which included:

1. History
   • Any significant present/past medical/surgical history
   • History of any previous surgery with significant anaesthetic
   • History of present or past medication and history of any drug
2. General physical Examination including vitals & airway assessment for difficult
3. Systemic examination included assessment of Respiratory, Cardiovascular, Central nervous system & spine, Gastrointestinal tract and other systems.
4. Investigations

• Hematological - Hb%, TLC, DLC, Platelet Count, BT, CT, PT,
• Fasting / random blood
• Blood urea, Serum
• LFT, Serum
• Chest X-ray,
• Viral Markers

Informed and written consent was obtained after providing complete explanation regarding the study protocol and the procedure.

Data obtained in this study were processed in Microsoft Excel 2007. Qualitative datas were measured as percentages and proportions while quantitative data was measured as mean and standard deviation from mean (SD). Appropriate statistical tests of significance were applied for analysis of the data collected using IBM SPSS Statistics version 22. The Categorical data was presented as numbers (percent) and were compared among groups using Chi square test. The quantitative data was presented as mean and standard deviation and were compared by students t-test. Probability was considered to be significant if less than 0.05.

This is a prospective observational study done in Department of anaesthesia at Shri Rawatpura Sarkar Institute of Medical Sciences and Research, Raipur, Chhattisgarh:  1^st March 2024 to 1^st march 2025 in 72 patients.  This study will be approved by institutional ethical committee and written informed consent will be obtained from all participants before inclusion in the study. The study was conducted in following two groups of patients. Each group was consisting of 36 patients. From this study following results found-

The mean age of patients in Group A was 37.38±9.56years and in Group B was 36.94±8.08 years. The difference of mean age between the study groups was statistically not significant (P >0.05). Hence these groups were comparable with respect to age. Female patients are 16 and 14 respectively in both groups. Difference in sex ratio between these groups were statistically not significant (P>0.05). Hence these groups were comparable with respect to sex.

Heart rate of patients in Group A was 85.1 ± 3.97 at baseline, 87.52 ± 2.93 just after induction of anaesthesia, 85.47 ± 2.71 immediately after intubation (T0), 85.14 ± 2.35 1 min(T1) after intubation, 81.23 ± 1.79 3 min after Intubation (T2), 82.1 ± 1.46 5 min after Intubation (T3), 81.99 ± 4.09 10 min after Intubation (T4), 81.45 ± 3.33 bpm 15 min after Intubation (T5) and 81.3 ± 4.83 just before pneumoperitoneum created and in group B was 85.48 ± 3.42 at baseline, 78.24 ± 2.72 just after induction of anaesthesia, 90.21 ± 4.14 immediately after intubation (T0), 82.14 ± 3.44 1 min(T1) after intubation, 86.12 ± 4.08 3 min after intubation (T2), 85.62 ± 3.15 5 min after intubation (T3), 85.33 ± 2.54 10 min after intubation (T4), 85.64 ± 3.17 bpm 15 min after intubation (T5) and 85.56 ± 2.02 just before pneumoperitoneum created. The difference of Mean Heart Rate between these groups was statistically significant (P <0.05) at these time intervals. Group A exhibited significantly lower and stable heart rate as compared to Group B.

Systolic Blood Pressure of patients in Group A was 127.69 ±3.70 at baseline, 117.24 ±2.53 at just after Induction of Anaesthesia, 125.38±2.12 Immediately after intubation (T0), 122.54±2.31 1 min after intubation (T1), 124.55±2.24 3 min after intubation (T2 ), 124.3±3.41 5 min after intubation (T3), 125.36±3.19 10 min after intubation (T4), 124.19±3.99 15 min after intubation (T5), 125.74±4.59 Just before pneumoperitoneum created and in Group B was 127.68±2.66 at baseline, 102.65±1.96 at just After Induction of Anaesthesia, 116.23±2.79 Immediately after Intubation (T0), 117.27±4.52 1 min after Intubation (T1 ), 118.64±4.48 3 min after Intubation (T2 ), 117.98±4.40 5 min after Intubation (T3), 119.24±0.85 10 min after Intubation (T4), 122.34±3.49 15 min after Intubation (T5), 125.74±4.29 Just before pneumoperitoneum created. The difference of Mean Systolic Blood Pressure between these groups was statistically significant (P <0.05) at these time intervals except just after pneumoperitoneum created. Group B exhibited significantly lower Mean SBP as compared to Group A.

Diastolic Blood Pressure of patients in Group A was 82.34 ±3.60 at baseline, 72.54 ±2.98 at just After Induction of Anaesthesia, 78.56±2.97 Immediately after Intubation (T0), 76.24±2.61 1 min after Intubation (T1), 78.22±3.71 3 min after Intubation (T2 ), 78.95±2.90 5 min after Intubation (T3), 79.96±3.55 10 min after Intubation (T4), 79.99±4.10 15 min after Intubation (T5), 80.1±3.68 Just before pneumoperitoneum created and in Group B was 82.25±4.53 at baseline, 60.45±2.96 at just After Induction of Anaesthesia, 69.24±4.07 Immediately after Intubation (T0), 70.32±4.01 1 min after Intubation (T1 ), 71.65±3.62 3 min after Intubation (T2 ), 72.45±3.20 5 min after Intubation (T3), 74.36±3.29 10 min after Intubation (T4), 77.22±3.10 15 min after Intubation (T5), 78.52±3.57 Just before pneumoperitoneum created. The difference of Mean Diastolic Blood Pressure between these groups was statistically significant (P <0.05) at these time intervals except just after pneumoperitoneum created. Group B exhibited significantly lower Mean DBP as compared to Group A.

Arterial pressure of patients in Group A was 97.45 ±2.54 at baseline, 87.44 ±4.77 at just After Induction of Anaesthesia, 94.1667±3.64 Immediately after Intubation (T0), 91.6733±3.25 1 min after Intubation (T1), 93.6633±3.69 3 min after Intubation (T2 ), 94.0667±3.51 5 min after Intubation (T3), 95.0933±4.83 10 min after Intubation (T4), 95.5567±4.68 15 min after Intubation (T5), 96.5467±4.19 Just before pneumoperitoneum created and in Group B was 97.39±2.29 at baseline, 74.5167±3.36 at just After Induction of Anaesthesia, 84.90333±3.50 Immediately after Intubation (T0), 85.97±2.87 1 min after Intubation (T1 ), 87.3133±2.88 3 min after Intubation (T2 ), 87.6267±3.02 5 min after Intubation (T3), 89.32±3.69 10 min after Intubation (T4), 92.59±3.10 15 min after Intubation (T5), 95.3233±2.84 Just before pneumoperitoneum created. The difference of Mean Arterial Blood Pressure between these groups was statistically significant (P <0.05) at these time intervals except just after pneumoperitoneum created it was not significant. Thus, in our study Group B showed significantly lower MAP as compared to Group A.

Oxygen Saturation of patients in Group A was 98.41±1.42 at baseline, 98.58±1.38 at just After Induction of Anaesthesia, 98.88±1.23 Immediately after Intubation (T0), 99±1.04 1 min after Intubation (T1), 99±1.24 3 min after Intubation (T2 ), 99.19±0.78 5 min after Intubation (T3), 99.13±0.86 10 min after Intubation (T4), 99±0.86 15 min after Intubation (T5), 99.02±0.84 Just before pneumoperitoneum created and in Group B was 98.98±1.45 at baseline, 98.75±1.22 at just After Induction of Anaesthesia, 99.05±1.04 Immediately after Intubation (T0), 99.02±1.05 1 min after Intubation (T1 ), 99.11±1.03 3 min after Intubation (T2 ), 99.05±1.04 5 min after Intubation (T3), 99.11±0.85 10 min after Intubation (T4), 99.08±0.84 15 min after Intubation (T5), 99.11±0.82 Just before pneumoperitoneum created. The difference of Mean Oxygen Saturation between these groups was statistically not significant (P >0.05) at these time intervals. Hence these groups were comparable with respect to Mean Oxygen Saturation at these time intervals.

The Mean Rate Pressure Product of patients in Group A was 10866.42±527.008 at baseline, 10260.84±347.99 at just After Induction of Anaesthesia, 10716.23±403.923 Immediately after Intubation (T0), 10433.06±315.578 1 min after Intubation (T1), 10117.2±258.698 3 min after Intubation (T2 ), 10191.36±321.11 5 min after Intubation (T3), 10210.57±589.76 10 min after Intubation (T4), 10096.65±509.813 15 min after Intubation (T5), 10222.66±658.376 Just before pneumoperitoneum created and in Group B was 10914.09±454.81 at baseline, 8031.336±380.34 at just After Induction of Anaesthesia, 10485.11±574.91 Immediately after Intubation (T0), 9398.018±557.49 1 min after Intubation (T1 ), 10217.28±659.81 3 min after Intubation (T2), 10067.23±553.60 5 min after Intubation (T3), 10211.71±483.94 10 min after Intubation (T4), 10478.53±509.74 15 min after Intubation (T5), 10742.06±424.51 Just before pneumoperitoneum created. The difference of Mean Rate Pressure Product between these groups was statistically significant (P <0.05) just after induction of anaesthesia, 1 min after Intubation (T1 ), 15 min after Intubation (T5) and just before pneumoperitoneum created. The difference of Mean Rate Pressure Product between these groups was statistically not significant (P >0.05) at all other time intervals. Hence these groups were comparable with respect to Mean RPP at these time intervals.

Number of patients developed Shivering between the two study groups. In group A 28 patients experienced grade 0, 5 patients experienced grade 1, 2 patients experienced grade 2, 1 patient experienced grade 3 Shivering out of 36 patients and in group B 15 patients experienced grade 0 ,11 patients experienced grade 1, 5 patients experienced grade 2, 4 patient experienced grade 3 Shivering out of 36 patients. The difference of incidence of Shivering between the study groups was statistically significant (P <0.05). Significantly more number of patients suffered from shivering in group B as compared to group A.

The comparison of number of patients developed hypotension between the two study groups. In group A 2 patients had hypotension out of 36 patients and in group B 10 patients had hypotension out of 36 patients. The difference of incidence of hypotension between the study groups was statistically significant (P <0.05), showing more incidence of hypotension in group B as compared to group A.

The comparison of number of patients developed hypertension between the two study groups. In group A 5 patients had hypertension out of 36 patients and in group B 1 patient had hypertension out of 36 patients. The difference of incidence of hypertension between the study groups was statistically not significant.

The comparison of number of patients developed bradycardia between the two study groups. In group A 1 patient had bradycardia out of 36 patients and in group B 5 patients had bradycardia out of 36 patients. The difference of incidence of bradycardia between the study groups was statistically not significant.

The comparison of number of patients developed tachycardia between the two study groups. In group A 4 patients had tachycardia out of 36 patients and in group B 2 patient had tachycardia out of 36 patients. The difference of incidence of tachycardia between the study groups was statistically not significant.

The comparison of number of patients developed postoperative respiratory depression between the two study groups. In group A 2 patients had respiratory depression out of 36 patients and in group B 6 patients had respiratory depression out of 36 patients. The difference of incidence of respiratory depression between the study groups was statistically not significant.

Hemodynamic stability during surgery is one of the main goals of any anaesthesiologist. The anaesthesia associated transient hemodynamic instability may be seen during induction owing to specific characteristics of induction agent and also due to laryngoscopy and intubation associated symapathetic stimulation, surgical incision and during extubation. Surgery specific reasons of hemodynamic stability has to be kept in mind also. Hemodynamic changes during anaesthesia induction and intubation are well tolerated by normal healthy patients without any comorbities but can be deleterious for patients with significant cardiac morbities. Therefore, maintaining a stable hemodynamic profile at the time of induction, intubation and surgical incision is very important and should be taken care of during anaesthesia and surgery.

Propofol mixed with ketamine (ketofol) is popular for short procedural sedation and analgesia because it has the advantage of reduced adverse effects of each drug counteracting the undesirable effect of one drug with beneficial effect of another. There are a number of recent studies demonstrating the advantages of combination of ketamine and propofol, providing cardiovascular stability which could be comparable to etomidate, on the other hand, this combination does not lead to adverse effects of etomidate- associated adrenal insufficiency in critically ill or septic patients. However, there is scarcity of data which show comparable efficacy of combination of ketamine-propofol (ketofol) versus propofol as single drug as induction agents on haemodynamic stability during induction and intubation. This prompted us to undertake present study to evaluate effect of propofol and ketofol on haemodynamic response following induction and intubation during general anaesthesia. So, in our study, we aim to compare ketofol (ketamine + propofol) and propofol as an induction agents to achieve a stable hemodynamic profile during intubation and until creation of pneumoperitoneum in laparoscopic cholecystectomy.

HEMODYNAMIC PARAMETERS

We compared the hemodynamic variables between the two groups (HR, SBP, DBP, MAP) at various time intervals (baseline, just before induction of anaesthesia, immediately after intubation (T0) and then at 1 min, 3 min, 5 min, 10 min, 15 min after intubation and just before Pneumoperitoneum created. The Mean baseline heart rate in Group A was 85.12 ± 3.97 bpm while in Group B was 85.48 ± 3.42 (p value 0.664). The Mean baseline systolic blood pressure in Group A was

127.69 ± 3.70 mmHg while in Group B was 127.68 ± 2.66 mmHg (p value 0.989). The Mean baseline diastolic blood pressure in Group A was 82.34 ± 3.60 mmHg while in Group B was 82.25 ± 4.53 mmHg (p value 0.925). The Mean arterial blood pressure in

Group A was 97.45 ± 2.54 mmHg while in Group B was 97.39 ± 2.29 mm Hg (p value 0.916). The Mean oxygen saturation in Group A was 98.41 ± 1.42 while in Group B was 98.98 ± 1.45 (p value 0.929). The Mean rate pressure product in Group A was 10866.42 ± 527.008 while in Group B was 10914.09 ± 454.81 (p value 0.682). Thus, both the groups were comparable with respect to mean baseline hemodynamic parameters.

HEART RATE

In our study we observed that in Group B, heart rate was significantly decreased in comparison to Group A just after induction, but after intubation heart rate increased and the difference between Group A (ketofol) & Group B (propofol) was significant. While in Group A heart rate showed a comparatively stable pattern from intubation to just before the creation of pneumoperitoneum. This shows stabilizing effect of ketofol on heart rate irrespective of stimulus like intubation and surgical incision.

These findings were similar to study done by Raman et. al[26] where the heart rate followed the stable trend after induction, during intubation, post-intubation after creation of pneumoperitoneum with ketofol. Similarly,

Hamid Kayalha et. al[23] also found that heart rate was significantly lower in propofol group after induction, 5 min and 10 min after intubation when compared to ketofol group. In ketofol group, they found that heart rate followed a stable pattern after induction, 5 min and 10 min after intubation. The results of their study were consistent with our study. Aboeldahab H et. al[19] in a similar study also found ketofol more hemodynamically stable and their results were similar to our study. Seyoum Hailu et. al[25] also found the similar results where heart rate was significantly lower in the propofol group compared to ketofol group. Machhar et. al[27] also observed stable heart rate post induction with ketofol.

Such stable trend in ketofol group is probably due to decrease in sympathetic stimulation by somatic pain stimulatory input. Ketamine increases SVR and heart rate due to sympathetic stimulation from inhibition of norepinephrin reuptake whereas Propofol decreases SVR and increases heart rate due to arteriolar vasodilation. It theoretically seems that combined use of ketamine and propofol as ketofol counterbalances each drug’s opposite haemodynamic effects. The initial rise in the mean heart rate in the propofol group is probably due to the inhibition of cardiovagal fibres in the brainstem and later heart rate decreases due to inhibition of cardiac sympathetic nerves and arteriolar vasodilation.

SYSTOLIC BLOOD PRESSURE

In our study we observed that after induction, systolic blood pressure was less in group B as compared to Group A. This difference was statistically significant, although the fall in the blood pressure in Group B could not be categorized under hypotension i.e it didn’t require any vasopressor support or fluid therapy. In Group A systolic blood pressure remained stable from induction to 10 min post intubation.

Our study was comparable with study conducted by Machhar et. al. [27] in which they also observed that ketofol group was better in respect of haemodynamic variations compared to propofol and etomidate alone. The findings were similar in another study done by Seyoum Hailu et. al[25] that the administration of ketofol for induction of general anesthesia provided stable systolic blood pressure than propofol during the first 30 min after induction. Similarly, Aboeldahab H et. al[19] also observed significantly lower systolic blood pressure in propofol group compared to ketofol post induction, post intubation at 5 min & 10 min. Similar results were observed by Ebru TK et. al[24] where ketofol group had comparatively more stable hemodynamics.

Our findings have attributed that the presence of ketamine in the ketofol due to its sympathomimetic effects which counterbalances the hypotensive effect of propofol.

DIASTOLIC BLOOD PRESSURE

In our study we observed that Mean Diastolic Blood Pressure was significantly lower in group B than group A at post induction, T0, T1, T2, T3, T4. Although no significant hypotension occurred and blood pressure were within normal range. It shows that group A was better at maintaining diastolic blood pressure as compared to group B. Similar findings were also observed in study conducted by Aboeldahab et. al. [19] Another study done by Manickam et. al[22] found the similar results. Raman et. al[26] also observed that ketofol group was better at maintaining hemodynamic stability in terms of heart rate, systolic blood pressure, Diastolic blood pressure and mean arterial pressure. Smischney et. al[20] in a similar study observed that patients in the ketofol group demonstrated fewer reductions of 92% in systolic blood pressure, diastolic blood pressure and mean arterial pressure without significant increases in these parameters. They demonstrated that Ketofol used in the correct dose combination is associated with improved hemodynamics and little risk of adverse side effects when compared with propofol.

Our findings indicate that although both propofol and ketofol seem to decrease cardiac output from baseline but propofol causes more peripheral vasodilation than ketofol. This explains why the patients in the propofol group demonstrated greater decreases in diastolic blood pressure.

MEAN ARTERIAL PRESSURE

In our study we observed that the mean arterial pressure was significantly lower in group B than group A at various time intervals. Thus it shows that group A was better at maintaining hemodynamic stability as compared to group B.

Our study is comparable with the study carried by Raman et al[26] which demonstrated that ketofol(1:1 mixture) produced better haemodynamic stability when compared to propofol group. Another study by Smischney NJ et al [20] also observed that combination of ketamine-propofol provide better hemodynamic stability during first 10 minutes after induction as compared to propofol used alone. Similarly, Aboeldahab H et al [19] where mean arterial pressure decreased in Group propofol after induction when compared to Group ketofol which is similar to our study. Similar results were found in a study conducted by Atashkhoyi S et. al[21] where mean arterial pressure decreased during induction in placebo group when compared to ketofol group. In a similar study Ramakrishna et. al[28] found there is decrease in mean arterial pressure in propofol group when compared with ketofol group which is similar to our study.

The reason for increase in heart rate and blood pressure could be because the Ketamine has sympathomimetic properties which increases blood pressure and heart rate. Propofol group showed signicantly lower HR SBP, DBP and MAP values which may be due to unique property of propofol causing hypotension as reduction of sympathetic activity causes vasodilatation, direct effect on intracellular calcium mobilization, inhibition of prostaglandin synthesis in endothelial cells. When combined in ketofol both drugs exhibit a synergistic reaction to each other and offset each other’s effect on hemodynamic variables. Positive chronotropic and inotropic effect of Ketamine nullify the hypotensive effect of Propofol.

Moreover even after skin incision, Ketofol group presented with stable pattern of blood pressure and heart rate which is probably due to decrease in sympathetic stimulation by somatic pain stimulatory input. This implies the fact that a major barrier to hemodynamic stability is the overactivation of sympathetic nervous system.

OXYGEN SATURATION

The difference of Mean Oxygen Saturation between both the groups was statistically not significant (P >0.05) at various time intervals. Hence these groups were comparable with respect to Mean Oxygen Saturation at these time intervals.

MEAN RATE PRESSURE PRODUCT

Rate pressure product was stable throughout the study in group A while in group B there was a significant drop in rate pressure product after induction and intubation. After induction rate pressure product went up to 8031.336±380.34 in group B, the reason being hypotension and bradycardia associated with propofol. The findings are consistent with observations made by M Paulin et al[30] and Mangesh S Gore et al.[31] Rate pressure product is considered as surrogate marker of myocardial stress and oxygen consumption. The optimum range of RPP is said to be between 10,000 to 14,000 which gives minimal myocardial stress and myocardial oxygen demand. Both the drugs exhibit good safety profile in terms of levels of Rate pressure product. Levels of RPP>20,000 are more commonly associated with Myocardial ischemia and angina. So in both the groups in response to intubation, incision and creation of pneumoperitoneum, RPP didn’t critically rise, Hence it shows cardio stability of both the drugs.

Our study concluded that induction of general anaesthesia in patients undergoing laparoscopic cholecystectomy with Ketofol is associated with a more stable haemodynamic stability without apparent side effects as compared to Propofol. Hence, the combination of ketamine and propofol proved to be significantly better than propofol alone.

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