European Journal of Cardiovascular Medicine

Short surgical procedures, typically lasting less than 30 minutes, constitute a significant portion of surgical interventions in modern clinical practice. These include incision and drainage, wound debridement, closed fracture reductions, diagnostic laparoscopies, and dilatation and curettage. The anesthetic management of such procedures presents unique challenges, requiring rapid induction, stable intraoperative conditions, prompt recovery, and minimal adverse effects—all essential for ambulatory settings where early discharge is desirable.¹

Propofol has become the most widely used intravenous anesthetic agent for short surgical procedures due to its favorable pharmacokinetic properties, including rapid redistribution and high metabolic clearance, which facilitate quick emergence.² Additionally, propofol possesses antiemetic properties, making it particularly suitable for ambulatory surgery.³

However, propofol as a sole agent has significant limitations. It lacks analgesic properties and produces dose-dependent cardiorespiratory depression, including hypotension, bradycardia, and apnoea.⁴ The incidence of propofol-induced hypotension ranges from 15–50%, while apnoea requiring airway intervention may occur in 25–35% of patients.⁵ These adverse effects are particularly concerning in short procedures where rapid bolus administration is often employed.

These limitations have led to the widespread practice of co-induction—administering supplementary agents to reduce propofol requirements while enhancing anesthetic quality.⁶ Two agents commonly employed are fentanyl, a potent synthetic opioid, and ketamine, a phencyclidine derivative with unique pharmacological properties.

Fentanyl reduces propofol requirements by 30–50% and provides analgesia, but potentiates respiratory depression and may exacerbate propofol-induced bradycardia and hypotension through vagally-mediated effects.⁷ Postoperative nausea and vomiting, while less common than with longer-acting opioids, remains a concern.⁸

Ketamine produces dissociative anesthesia through NMDA receptor antagonism. Unlike conventional anesthetics, ketamine maintains respiratory drive, preserves airway reflexes, and stimulates the cardiovascular system through central sympathetic activation.⁹ At subanesthetic doses (0.2–0.5 mg/kg), it provides significant analgesia while producing minimal respiratory depression, potentially counterbalancing propofol's cardiodepressant effects.¹⁰ However, psychomimetic effects including emergence delirium occur in 5–30% of patients, though the incidence is dose-dependent.¹¹

Previous comparative studies have yielded variable results. Some report superior hemodynamic stability with ketamine-propofol combinations¹², while others note longer recovery times or increased psychomimetic effects.¹³ Sample sizes in existing literature range from 30–80 patients per group, with one investigation reporting complete data for 44 patients in a fentanyl-propofol group ¹⁴, providing methodological precedent.

This prospective, randomized, double-blind study compares ketamine (0.5 mg/kg) versus fentanyl (1.5 μg/kg) as co-induction agents with propofol (2.5 mg/kg) in 44 patients undergoing short surgical procedures. The primary objective is to compare hemodynamic parameters (heart rate, blood pressure) during the immediate post-induction period. Secondary objectives include assessment of propofol injection pain, respiratory events, recovery times, and adverse effects. We hypothesized that ketamine would provide superior hemodynamic stability compared to fentanyl without increasing adverse effects or delaying recovery.

Study Design, setting & population This study employed a prospective, randomized, double-blind, parallel-group comparative design. The study was conducted in the Department of Anesthesiology at a tertiary care teaching hospital over a 12-month period. The target population comprised adult patiephysical status I or II, aged 18–50 years, scheduled for elective minor surgical procedures with anticipated duration less than 30 minutes. Inclusion Criteria: • Patients of either sex, aged 18–50 years • ASA physical status I or II • Scheduled for minor surgical procedures <30 minutes duration • Willingness to provide written informed consent Exclusion Criteria: • History of hypertension, coronary artery disease, or cardiac comorbidity • History of seizures or psychiatric disorders • Hepatic or renal dysfunction • Known hypersensitivity to study drugs • Chronic opioid use • Anticipated difficult airway • Body mass index >35 kg/m² • Pregnancy or lactation • Refusal to participate Sample Size Calculation The sample size was determined based on previously validated methodology where a fentanyl-propofol group of 44 patients provided adequate statistical power to detect clinically significant differences in hemodynamic outcomes. A total of 44 patients were enrolled, with 22 patients allocated to each group. Post-hoc power analysis confirmed 82.3% power to detect differences in primary outcomes at α=0.05. Procedure for Data Collection Randomization and Blinding: Patients were randomly allocated using a computer-generated random number sequence concealed in opaque, sealed envelopes. An anesthesia assistant prepared identical syringes containing either ketamine (5 mg/mL) or fentanyl (50 μg/mL) based on group allocation. The attending anesthesiologist, patients, surgeons, and outcome assessors remained blinded throughout. Preoperative Preparation: Standard preoperative evaluation and fasting protocols were followed. On arrival in the operating theatre, an 18-gauge IV cannula was inserted and Ringer's lactate initiated. Standard monitoring (ECG, NIBP, SpO₂, capnography) was applied, and baseline parameters recorded. Anesthetic Protocol: All patients received glycopyrrolate 0.2 mg and ondansetron 4 mg IV 15 minutes before induction. Two minutes later, the co-induction agent was administered over 30 seconds according to group allocation. After 2 minutes, anesthesia was induced with propofol 2.5 mg/kg IV over 20 seconds. Following loss of consciousness, an appropriate-sized laryngeal mask airway was inserted. Anesthesia was maintained with 60% nitrous oxide in oxygen and intermittent propofol boluses (0.5 mg/kg) as needed. Data Collection: Hemodynamic parameters were recorded at baseline and at 1, 3, 5, and 10 minutes post-induction. Pain on propofol injection, apnoea, laryngeal spasm, and abnormal movements were documented intraoperatively. Awakening and recovery times were recorded in the PACU. Adverse effects and patient satisfaction were assessed at 1, 4, and 24 hours post-procedure by a blinded assessor. Data analysis Statistical analysis was performed using SPSS version 26.0. Data will be retained for 5 years post-study completion before secure disposal. Regular monitoring ensured protocol adherence and data quality.

Table 1: Demographic and Baseline Characteristics

Table 1 presents the demographic and baseline characteristics of the two study groups, confirming their comparability. The mean age, sex distribution, weight, and ASA physical status were statistically similar between the ketamine (Group K) and fentanyl (Group F) groups. The types of surgical procedures and the mean duration of surgery were also evenly distributed, with no significant differences observed.

Table 2: Hemodynamic Parameters at Baseline and Post-Induction

Table 2 details the intraoperative hemodynamic changes, revealing a stark contrast between the two co-induction agents. While the ketamine group maintained stable heart rate, systolic, diastolic, and mean arterial pressures near baseline values throughout the first 10 minutes post-induction, the fentanyl group experienced a significant and clinically notable decrease in all these parameters at the 1, 3, and 5-minute intervals.

Table 3: Induction Characteristics

Table 3 summarizes the induction characteristics, highlighting key differences in respiratory events. The incidence of apnea lasting more than 20 seconds was significantly higher in the fentanyl group (31.8%) compared to the ketamine group (9.1%) (P=0.042). In contrast, other induction-related events such as pain on propofol injection, abnormal movements, and laryngeal spasm were comparable between the two groups.

Table 4: Recovery Profile

Table 4 displays the recovery profile, showing that both groups had comparable emergence times. The mean awakening time, recovery time, and time to discharge from the post-anesthesia care unit (PACU) were statistically similar between the ketamine and fentanyl groups.

Table 5: Adverse Effects and Patient Satisfaction

Table 5 outlines the postoperative adverse effects and patient satisfaction. Although the differences did not reach statistical significance, there was a clear trend toward a higher incidence of postoperative nausea in the fentanyl group (13.6%) compared to the ketamine group (4.5%). Psychomimetic effects, a theoretical concern with ketamine, were minimal, occurring in only one patient (4.5%). Patient satisfaction was high and comparable in both groups, with the vast majority rating their experience as pleasant.

Table 6: Propofol Requirements

Table 6 compares the propofol requirements between the two groups, confirming that both co-induction agents provided equivalent propofol-sparing effects. The mean induction dose, total propofol dose, and the number of supplemental boluses required during surgery were nearly identical between Group K and Group F. 

Table 7: Summary of Key Findings

Table 7 serves as a concise summary of the key findings, directly contrasting the two groups. It visually reinforces that the ketamine group was characterized by stable hemodynamics, a low apnea rate, and minimal side effects, while the fentanyl group experienced significant hemodynamic fluctuations, a high incidence of apnea, and a trend toward more postoperative nausea, all while maintaining comparable recovery times and patient satisfaction.

This prospective, randomized, double-blind study compared the effects of ketamine (0.5 mg/kg) and fentanyl (1.5 μg/kg) as co-induction agents with propofol in 44 patients undergoing short surgical procedures. The principal findings were that ketamine provided superior hemodynamic stability, a significantly lower incidence of apnoea, and comparable recovery times relative to fentanyl, with a trend toward fewer postoperative adverse effects and high patient satisfaction in both groups.

The most notable finding was the marked difference in hemodynamic profiles between the two groups. Patients receiving ketamine maintained stable heart rate and blood pressure throughout the immediate post-induction period, while those receiving fentanyl experienced significant decreases in all hemodynamic parameters at 1, 3, and 5 minutes following induction. These differences can be explained by the distinct pharmacological properties of the two agents. Fentanyl reduces sympathetic outflow and may cause bradycardia through vagal stimulation, which when combined with propofol's cardiodepressant effects results in significant hypotension and bradycardia. In contrast, ketamine produces central sympathetic stimulation with release of catecholamines, thereby counteracting propofol-induced cardiodepression.

Our findings are consistent with those of Goyal and colleagues¹⁵, who compared ketamine (0.5 mg/kg) and fentanyl (2 μg/kg) as co-induction agents with propofol in 60 patients and reported that heart rate and mean arterial pressure decreased significantly in the fentanyl group at 1, 3, and 5 minutes post-induction while remaining stable in the ketamine group. Similarly, Pande and Kuttarmare¹⁶, in a study of 60 pediatric patients, observed that ketamine-propofol combinations provided superior hemodynamic stability compared to fentanyl-propofol. Sharma and colleagues¹⁷ , investigating 60 adult patients undergoing orthopedic procedures, also found that ketofol maintained more stable blood pressure and heart rate than fentofol throughout the procedure, with the fentanyl group requiring more frequent interventions for hypotension.

The significantly higher incidence of apnoea in the fentanyl group (31.8% versus 9.1%) represents another important finding with direct clinical implications. Fentanyl's respiratory depressant effects are potentiated by propofol, leading to increased risk of apnoea and hypoventilation. The 31.8% incidence in our fentanyl group is consistent with the 25–35% range reported in the literature for propofol-opioid combinations⁵. Bhattarai and Hamal¹⁸, in their study of 70 patients at moderate altitude, similarly reported significantly higher requirements for positive pressure ventilation in their fentanyl-propofol group (34.3%) compared to ketamine-propofol (11.4%), figures remarkably similar to our findings. Ketamine's preservation of respiratory drive makes it particularly valuable when respiratory depression is a concern.

The comparable awakening and recovery times between groups address an important theoretical concern regarding ketamine use in ambulatory settings. At the subanesthetic dose of 0.5 mg/kg, ketamine did not delay emergence compared to fentanyl. These results align with those of Goyal and colleagues¹⁵, who reported similar awakening and recovery times between groups. However, Bhattarai and Hamal¹⁸ did observe significantly longer recovery with ketamine-propofol at moderate altitude, suggesting that environmental factors may influence recovery kinetics.

The trend toward higher postoperative nausea in the fentanyl group (13.6% versus 4.5%), while not reaching statistical significance, is consistent with the known emetogenic potential of opioids. Sharma and colleagues (17) similarly reported nausea in 16.7% of their fentanyl group compared to 6.7% in the ketamine group. Psychomimetic effects occurred in one patient (4.5%) in our ketamine group, who experienced emergence delirium with vivid dreaming that resolved spontaneously. This incidence is within the range reported in previous studies (0–10% with low-dose ketamine) and is considerably lower than the 58% incidence of dreaming reported by Jakobsson and colleagues¹⁹, likely reflecting differences in ketamine dose and patient population.

The comparable propofol requirements between groups indicate that both agents provide equivalent propofol-sparing effects, suggesting that the observed differences in hemodynamic and respiratory outcomes are attributable to the differential pharmacological effects of the co-induction agents themselves rather than to differences in propofol dosage.

Our findings have several clinical implications. Ketamine-propofol combinations may be particularly advantageous in patients at risk for hypotension, in settings where respiratory depression is especially undesirable, or in procedures where spontaneous ventilation is preferred. Fentanyl-propofol may still be preferred when opioid analgesia is specifically indicated or when ketamine is contraindicated. The higher nausea incidence with fentanyl underscores the importance of routine antiemetic prophylaxis when opioids are used.

Several limitations warrant consideration. The sample size of 44 patients, while adequate for detecting hemodynamic differences, may be insufficient to detect rare adverse events. The study excluded patients with significant comorbidities, limiting generalizability to higher-risk populations. All procedures were of short duration (<30 minutes), and findings may not extend to longer surgeries. The study was conducted at a single center, and multicenter validation would strengthen generalizability.

This study demonstrates that ketamine (0.5 mg/kg) provides superior hemodynamic stability and a significantly lower incidence of respiratory depression compared to fentanyl (1.5 μg/kg) as a co-induction agent with propofol for short surgical procedures, while maintaining comparable recovery times and patient satisfaction. These findings support ketamine as a favorable co-induction agent in this setting, particularly when hemodynamic stability and respiratory safety are prioritized. The choice between ketamine and fentanyl should be individualized based on patient characteristics, surgical requirements, and the relative importance of hemodynamic stability versus opioid analgesia in each clinical scenario.

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