European Journal of Cardiovascular Medicine

Procedural Induction agents and analgesia (PSA) are pivotal in ensuring the humane and efficient performance of painful procedures during surgery or emergencies. Propofol and ketamine, widely used sedative agents, have distinct advantages and limitations that have prompted interest in their combined use as "ketofol." Propofol, a sedative-hypnotic agent with a rapid onset and short duration, is effective in producing an Induction agent but lacks analgesic properties. Its use is often associated with dose-dependent hypotension and respiratory depression, especially when combined with opioids. On the other hand, ketamine, a dissociative anaesthetic, provides both analgesia and amnesia, with minimal respiratory and cardiovascular depression but is limited by its association with emergence phenomena, emesis, and prolonged recovery time. These opposing physiologic effects suggest potential synergy when used together, thereby mitigating the shortcomings of each drug individually (1,2,3).

Ketofol, a combination of ketamine and propofol, has been increasingly utilized in various clinical settings. Administered as separate syringes or mixed in the same syringe, ketofol has demonstrated chemical stability and compatibility. Its combined use has shown benefits such as reduced propofol dosage requirements, decreased risk of adverse respiratory effects, improved hemodynamic stability, and shorter recovery times compared to ketamine alone. Ketofol has been employed successfully in procedures requiring deep Induction agent, including gynecologic, ophthalmologic, and cardiovascular interventions (1,3,4).

Despite the lack of a universally optimal ketamine-propofol ratio, studies have consistently highlighted the safety and efficacy of ketofol, particularly in terms of minimizing the individual toxicities of ketamine and propofol. The complementary properties of the two drugs provide an effective balance, enabling reliable Induction agent and analgesia with fewer complications during elective surgeries lasting over 30 minutes (2,4).

This study aims to evaluate and compare the hemodynamic effects of Ketofol and Propofol during induction in adult elective surgeries. Parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO₂), and postoperative outcomes were analyzed.

Study Design and Setting:

This retrospective observational study was conducted at Gandhi Surgical Hospital, Tagore Road, Gandhidam, Gujarat, India. The study reviewed patient records from August 1, 2024, to October 31, 2024. The study aimed to compare hemodynamic stability and recovery characteristics between patients receiving ketamine + propofol (ketofol) and propofol alone during elective surgeries lasting more than 30 minutes.

Study Population: The study included a total of 30 adult patients, with 15 patients in each group:

1. Group K (Ketofol Group): Patients who received a combination of ketamine and propofol.
2. Group P (Propofol Group): Patients who received propofol alone.

The inclusion criteria were:

• Adult patients aged 18–60 years.
• Undergoing elective surgeries lasting more than 30 minutes.
• American Society of Anesthesiologists (ASA) physical status I–II.

Exclusion criteria included:

• Known allergy to ketamine or propofol.
• Severe cardiovascular or respiratory conditions.
• Pregnancy or lactation.
• Patients requiring emergency surgeries.

Data Collection Procedure: Past medical records from the hospital’s electronic database were reviewed and extracted using a standardized data collection form. Data collection involved:

1. Patient Selection:
• The operation theatre logbook and anaesthesia records were reviewed to identify patients meeting the inclusion criteria.
• Patients were categorized into the ketofol or propofol group based on the anaesthesia regimen documented in their medical records.
2. Collected Variables:
• Demographics: Age, gender, and weight.
• Intraoperative Parameters: Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO2), and any adverse events.
• Recovery Characteristics: Time to extubation, recovery (the ability to follow commands), and postoperative complications (e.g., nausea, vomiting).
3. Standardization of Procedures:
• All patients underwent general anaesthesia according to standard hospital protocols.
• Ketofol was prepared using ketamine and propofol in a 1:1 ratio and administered as per the patient's weight and surgery duration. Propofol was administered in a titrated dose according to standard protocols.
• Hemodynamic variables were recorded at baseline (pre-induction), immediately after induction, and at 5-minute intervals intraoperatively.
4. Data Extraction and Review:
• Data were extracted and cross-verified by two independent researchers to ensure accuracy.
• Any missing or unclear data were clarified by consulting the anaesthesia and postoperative care records.

Ethical Considerations: Institutional ethical approval was obtained before the study. The data were anonymized to maintain patient confidentiality, and no identifying information was included in the analysis.

The comparison of demographic and procedural variables between the Ketofol and Propofol groups reveals notable age differences but no significant differences in weight or surgical time. The mean age of patients in the Ketofol group was significantly higher (55.73 ± 9.48 years) compared to the Propofol group (46.27 ± 17.99 years), with a p-value of 0.005, suggesting an older population in the Ketofol group. However, weight was similar between the groups (Ketofol: 65.73 ± 8.25 kg; Propofol: 62.67 ± 9.42 kg, p = 0.424), and surgical time also showed no significant difference (Ketofol: 21.60 ± 9.25 minutes; Propofol: 18.00 ± 5.92 minutes, p = 0.142). These findings indicate that age may need consideration in interpreting the outcomes, but both groups were comparable in weight and procedural duration. (Table 1)

Table 1: Comparison of demographic and procedural variables between the Ketofol and Propofol groups

Gender Distribution: The gender distribution between the Ketofol and Propofol groups shows no significant difference. In the Ketofol group, 40% were female and 60% were male, while in the Propofol group, 60% were female and 40% were male. The Chi-Square value of 1.200 (p = 0.273) indicates that gender does not significantly impact the choice between the two anesthetic agents. (Table 2)

ASA Classification: The distribution of ASA classification (I and II) between the two groups also showed no significant difference. In the Ketofol group, 46.7% were ASA I and 53.3% were ASA II, while in the Propofol group, 60% were ASA I and 40% were ASA II. The Chi-Square value of 0.536 (p = 0.464) suggests that the ASA classification is similarly distributed between the groups.  (Table 2)

The study demonstrated that Ketofol and Propofol exhibit similar hemodynamic stability during induction, with no significant differences in heart rate or blood pressure parameters. However, recovery, as measured by time to ambulation, was significantly faster in the Propofol group, which may make it a preferable choice when quicker postoperative recovery is a priority. (Table 3)

Heart Rate (HR): The mean heart rate (HR) in the Ketofol group was slightly lower (75.13 ± 7.61 bpm) than in the Propofol group (77.13 ± 6.46 bpm). However, the difference was not statistically significant (p = 0.444), suggesting that both agents maintain comparable hemodynamic stability regarding heart rate during induction. (Table 3)

Systolic Blood Pressure (SBP): The mean systolic blood pressure in the Ketofol group (130.47 ± 6.95 mmHg) was slightly lower than in the Propofol group (134.47 ± 14.68 mmHg). Although there was a trend towards better SBP stability with Ketofol, the difference did not reach statistical significance (p = 0.348), indicating that both agents perform similarly in maintaining systolic blood pressure. (Table 3)

Diastolic Blood Pressure (DBP): The Ketofol group showed a slightly higher mean diastolic blood pressure (79.93 ± 4.76 mmHg) compared to the Propofol group (75.60 ± 7.72 mmHg). While the observed difference suggests a tendency for Ketofol to provide better DBP stability, the result was not statistically significant (p = 0.075). (Table 3)

Time to Ambulation: A significant difference was observed in the time to ambulation between the two groups. The Ketofol group had a considerably longer ambulation time (78.67 ± 30.85 minutes) compared to the Propofol group (40.33 ± 9.90 minutes), with a p-value < 0.001. This finding highlights a notable difference in recovery profiles, with Propofol allowing for quicker ambulation post-surgery. (Table 3)

Table 3: Ketofol and Propofol in hemodynamic stability

Postoperative Nausea (PON): Postoperative nausea was more common in the Ketofol group, with 6.7% of patients experiencing PON. In the Propofol group, none of the patients reported PON. However, the Chi-Square value of 1.034 (p = 0.309) indicates no significant difference in the occurrence of PON between the two groups, despite the higher incidence in the Ketofol group. (Fig 1) Postoperative Complications: Both groups had very low rates of postoperative complications, with only one patient in the Ketofol group experiencing a complication (6.7%). The Propofol group had no complications. The Chi-Square value of 1.034 (p = 0.309) shows no significant difference in postoperative complications between the two groups. (Fig 2)

 Patient Satisfaction Scores: The Ketofol group had higher patient satisfaction, with 73.3% of patients giving a score of 8. In contrast, in the Propofol group, 53.3% rated it 8, and 46.7% gave it a score of 9. However, the Chi-Square value of 3.074 (p = 0.215) indicates that the difference in patient satisfaction between the two groups is not statistically significant. (Figure 3)

The choice of sedative agents in procedural and operative settings is pivotal for ensuring patient safety, optimal outcomes, and satisfaction. Ketofol, a combination of ketamine and propofol, has gained attention as a balanced sedative due to its complementary pharmacological properties. Ketamine provides analgesia and maintains hemodynamic stability, while propofol ensures Induction agent and rapid recovery. This study aimed to compare Ketofol and propofol in terms of hemodynamic stability, recovery profile, complications, and patient satisfaction, contributing to the growing body of evidence regarding their clinical utility.

Our findings align with and extend the results of previous studies comparing Ketofol and propofol. Hemodynamic stability, as evidenced by heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP), was comparable between the two groups, with no statistically significant differences. These results are consistent with studies by Coulter et al. (6) and Nalini et al. (7), which reported stable hemodynamic parameters during Ketofol administration. However, Nalini et al. (7) noted a lower reduction in blood pressure and oxygen saturation in the Ketofol group compared to a propofol-fentanyl regimen, emphasizing Ketofol's potential advantage in maintaining cardiovascular stability.

Recovery profiles differed significantly between the two groups, with Ketofol showing a notably longer time to ambulation than propofol. This finding aligns with observations by Coulter et al. (6), who reported that higher ketamine concentrations or prolonged Ketofol infusions could extend recovery times. In our study, the extended recovery time with Ketofol may reflect ketamine's pharmacokinetic profile, including its slower metabolism and residual sedative effects. This prolonged recovery time must be weighed against the clinical need for a rapid return to baseline function, particularly in outpatient or emergency settings.

Postoperative complications and nausea rates were low in both groups, with no significant differences observed. These findings are comparable to the prospective case series by Nalini et al. (7) and other studies, which reported minimal adverse events with Ketofol. Notably, Coulter et al. (6) highlighted the need for careful titration to minimize recovery agitation and apnea, suggesting that individualized dosing strategies can enhance safety.

Patient satisfaction scores, while not significantly different, favored the Ketofol group, with higher proportions reporting satisfactory Induction agent experiences. This is consistent with the randomized trial by Coulter et al. (6), where the propofol-ketamine combination achieved higher satisfaction rates compared to propofol alone. The analgesic effect of ketamine likely contributed to improved patient comfort, making Ketofol a preferred option in procedures requiring deeper analgesia.

Overall, our study corroborates the evidence that Ketofol provides comparable hemodynamic stability and improved patient satisfaction but is associated with prolonged recovery times compared to propofol. These findings support the use of Ketofol in settings where extended recovery time is not a limitation and when a balance of Induction agent and analgesia is critical. Future studies should explore optimized dosing regimens to further enhance Ketofol's safety and efficacy profile.

This study demonstrates that both Ketofol and propofol are effective sedative agents, providing comparable hemodynamic stability and low rates of adverse effects. While Ketofol offers the advantage of enhanced analgesia and slightly higher patient satisfaction, it is associated with a longer recovery time. These findings suggest that Ketofol may be a preferred option for procedures where analgesia is critical, and recovery time is less of a concern. On the other hand, propofol may be better suited for scenarios requiring rapid recovery. Future research focusing on optimized dosing strategies could further refine the clinical utility of Ketofol, particularly in diverse procedural and patient settings.

Conflict of interest: Nil

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