The abdominal surgery is typically accompanied by significant tissue trauma and moderate to severe postoperative pain, with inflammatory activation. Uncontrolled pain can make it difficult to cough, breathe deeply, mobilize, sleep, pulmonary complications, gastrointestinal recovery and hospitalization can be prolonged. The traditional basis of perioperative analgesic is opioid; but increased exposure to opioids can induce nausea and vomiting, sedation, pruritus, urinary retention, and respiratory depression, as well as postoperative ileus. There has been growing interest in multimodal approaches to postoperative pain that involve using more than one agent that has a different mechanism of action because of the potential for adverse effects from opioids and continued opioid use after surgery [1-3].

The goal of multimodal analgesia is to achieve better pain control (and decrease the use of systemic opioids). The use of non-opioid drugs like acetaminophen, non-steroidal anti-inflammatory drugs, local anaesthetics, ketamine, and agents that activate the α2-adrenergic receptors is becoming more common in enhanced recovery pathways. Of these, low dose ketamine has been studied due to its antagonistic activity at N-methyl-D-aspartate receptors. Ketamine can inhibit central sensitization and nociceptive wind-up, which can help to reduce postoperative pain, opioid tolerance and opioid-induced hyperalgesia. It typically maintains the spontaneous respiration and cardiovascular stability at subanaesthetic doses, but can produce psychomimetic effects, hallucination, tachycardia and hypertension [4-6].

Dexmedetomidine is a highly selective agent of α2-adrenergic receptors that has sedative, anxiolytic, sympatholytic and analgesic properties. It decreases sympathetic outflow and inhibits nociceptive transmission in the CNS/SC. Most of its clinical benefits lie in its capacity to provide sedation and analgesic support with little respiratory depression. Previous studies have shown that dexmedetomidine given during the perioperative period decreases the amount of opioids used, early postoperative pain, and the quality of recovery. However, it can be restricted in use due to dose dependent bradycardia, hypotension and prolonged sedation, especially if administered at a high loading dose rate or in patients with underlying cardiovascular vulnerability [7, 8].

Although both ketamine and dexmedetomidine are recognized opioid-sparing adjuvants, evidence directly comparing their effectiveness in major abdominal surgery is still relatively limited. Differences in their pharmacological actions may lead to variation in analgesic efficacy, haemodynamic stability, sedation and adverse-event profiles. Identifying the more effective and better-tolerated agent may help clinicians optimize multimodal analgesia while limiting perioperative opioid exposure. Therefore, the present study was conducted to compare low-dose ketamine and dexmedetomidine in patients undergoing major abdominal surgery, with particular emphasis on postoperative opioid consumption, pain intensity, rescue analgesic requirement, haemodynamic effects, recovery characteristics and treatment-related complications.

This prospective, non-randomized, comparative study was conducted in the Department of Anaesthesiology at a tertiary care hospital of AJK from August 2025 and February 2026. A total of 93 adult patients scheduled for elective major abdominal surgery under general anaesthesia were included. Patients were enrolled through consecutive sampling and assigned to one of two treatment groups according to the anaesthetic management protocol and the decision of the attending anaesthesiologist. Group K comprised 47 patients who received low-dose ketamine, while Group D comprised 46 patients who received dexmedetomidine. No computer-generated random sequence, allocation concealment or trial registration was used.

A total of 93 eligible patients were recruited through consecutive sampling and into two study groups using a computer-generated random sequence. Group assignments were placed in sequentially numbered, that were opened immediately before preparation of the study medication. There were 47 patients in Group K (low dose ketamine) and 46 patients in Group D (dexmedetomidine). Both comparison and study drugs were formulated by an anaesthetist who was not involved in the intraoperative management, postoperative evaluation or data analysis. Group K was given intravenous ketamine at a loading dose of 0.3 mg/kg for 10 minutes and then infusion was continued at 0.1 mg/kg/hour until closure of the skin was achieved. In Group D, dexmedetomidine was given at a loading dose of 0.5 µg/kg over 10 minutes followed by infusion to the end of surgery at 0.3 µg/kg/hour.

The anaesthetic was standardised in all patients. Continuous electrocardiography, pulse oximetry, non-invasive blood pressure, end-tidal carbon dioxide and neuromuscular monitoring were performed as routine monitoring. Intravenous drip propofol 2mg/kg and fentanyl 2µg/kg and atracurium 0.5mg/kg were administered to induce general anaesthesia and the patient was intubated. Sevoflurane was used for anaesthesia in oxygen-air mixture, and ventilation was adjusted to keep end-tidal carbon dioxide between 35 and 40 mmHg. When there was a greater than 20% rise in heart rate or mean arterial pressure (MAP) above the baseline, which excluded inadequate anaesthetic depth and/or surgical stimulation, additional doses of fentanyl (0.5 µg/kg) were administered. Preoperatively all patients were administered intravenous paracetamol 1 gram and ondansetron 4 mg before surgery was completed. Neuromuscular blockade was reversed with neostigmine and glycopyrrolate and patients were extubated when the criteria for clinical readiness were met. Intraoperative fluid administration, estimated blood loss, surgical duration, anaesthetic duration and total amount of fentanyl used were recorded.

The pain scale measured after surgery was an 11-point Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable). The pain scores were recorded at the time the patient arrived at the PACU and at 2, 4, 6, 12 and 24 hours following the operation. The primary outcome was overall opioid use in the first 24 hours following surgery, measured in intravenous morphine-equivalent milligrams (IV-MEM). Rescue analgesia was given intravenously as morphine 2 mg when the numerical rating scale score was equal to or above 4 and repeated as appropriate until the pain was adequately controlled. Secondary outcomes included the amount of fentanyl consumed during surgery, time to first rescue analgesia, number of doses of rescue analgesia, postoperative pain scores, sedation level, time to extubation, duration of stay in the recovery room, time to reach a (modified) Aldrete score ≥ 9, and patient satisfaction. Baseline data and data at regular points throughout the intra-operative period were obtained for heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and oxygen saturation. Bradycardia was considered heart rate < 50 beats per minute, hypotension was considered mean arterial pressure decrease > 20% from baseline, tachycardia was considered heart rate > 100 beats per minute and hypertension when mean arterial pressure increased > 20% from baseline. All adverse events such as nausea, vomiting, excessive sedation, respiratory depression, hallucination, emergence reactions, dizziness and bradycardia and hypotension were noted and treated as per institutional protocol.

The IBM SPSS Statistics version 26 software was used to input and analyze data. For continuous variables, a Shapiro-Wilk test and histogram were used to check for normality. Normally distributed variables were presented as mean ± standard deviation and compared between the groups using the independent-samples t-test. Data for variables that were not normally distributed was presented as the median (interquartile range) and compared by means of the Mann–Whitney U test. Categorical data were categorized and expressed as frequencies and percentages and analyzed by the chi-square test or Fisher's exact test when appropriate. Repeated postoperative pain and haemodynamic measurements were analysed by repeated-measures analysis of variance, looking at the interaction between group, time and group-by-time. A two-sided p-value of less than 0.05 was considered statistically significant. The analyses were conducted with the study groups as originally assigned and the confidentiality of patient information was preserved during the study.

A total of 93 patients who were undergoing major abdominal surgery were included in the study.Of these, 47 patients were given low-dose ketamine (Group K), and 46 patients were given dexmedetomidine (Group D).The average age of the participants was 46.9 ± 12.7 years and 51 patients (54.8%) were male.There were no statistically significant differences between the groups in baseline demographic, clinical and operative parameters including age, gender, BMI, ASA physical status, surgical procedure, surgery duration or preoperative haemodynamic parameters.

Table 1. Baseline demographic and operative characteristics of the study groups

Values are presented as mean ± standard deviation or frequency (percentage).

The mean dose of opioids during the surgery was significantly lower in the dexmedetomidine group than in the ketamine group. The mean dose of fentanyl used was 104.6 ± 28.9 µg for patients who received dexmedetomidine, and 121.7 ± 32.5 µg for patients who received ketamine (p=0.009). The amount of opioid use in the first 24 hours was also significantly less in Group D. The mean consumptions of intravenous morphine equivalents were 15.2 ± 5.1 mg in the dexmedetomidine group and 18.1 ± 5.8 mg in the ketamine group (p=0.012). Overall, this was a rough 16.0% decrease in postoperative opioid use with dexmedetomidine versus ketamine. Patients who received dexmedetomidine had a longer time to the initial request for rescue analgesics. The mean time was 7.3 ± 2.2 hours in Group D compared with 5.9 ± 2.0 hours in Group K (p=0.002). Likewise, less patients in Group D needed more than one dose of rescue analgesics on the first post-op day.

Table 2. Comparison of opioid consumption and rescue analgesic requirements

Pain scores were found to have gradually decreased in both groups after surgeries. There was no difference between the groups in terms of the mean pain scores at post-anaesthesia care unit admission. Patients treated with dexmedetomidine did, however, report significantly lower pain scores at 2, 4, 6 and 12 hours post surgery. At six hours, the mean numerical rating scale score was 4.2 ± 1.1 in Group K and 3.5 ± 1.0 in Group D (p=0.002). There was no difference in pain scores at 24 hours, indicating that the difference between the two agents might be greater during the early postoperative period.

Table 3. Postoperative numerical rating scale pain scores

In both study drugs an acceptable intraoperative haemodynamic control was observed. The mean heart rates of patients in the dexmedetomidine group were lower during surgery. The lowest average heart rate was 65.8 ± 7.9 beats per minute for Group D and 73.4 ± 8.6 beats per minute for Group K (p<0.001). The frequency of Bradycardia was higher in the dexmedetomidine group (15.2% in dexmedetomidine vs 2.1% in ketamine; p=0.028). Conversely, patients receiving ketamine had a higher number of intraoperative tachycards. The hypotension was numerically higher for Group D but without statistical significance.

Table 4. Intraoperative haemodynamic events

The mean time to extubation was slightly longer with dexmedetomidine use, but this was not significant. Sedation scores were higher in the early recovery period in patients in group D. But the time to a modified Aldrete score of 9 or higher was similar for both groups. Postoperative nausea and vomiting was experienced by 10 patients (21.3%) in Group K and 5 patients (10.9%) in Group D. However, this indicated a lower frequency for dexmedetomidine, but this was not statistically significant. Four patients receiving ketamine had hallucinations or emergence-related symptoms, but this was not seen in the dexmedetomidine group. There were no patients with severe respiratory depression or requiring unplanned mechanical ventilation postoperatively.

Table 5. Recovery outcomes and postoperative adverse effects

In patients undergoing major abdominal surgery, dexmedetomidine had higher opioid-sparing effect than low dose ketamine. It was correlated with lower intraoperative dose of fentanyl, lower 24-hour postoperative dose of morphine-equivalent dose, lower early postoperative pain scores, and longer time until first rescue dose of analgesia. Nonetheless, dexmedetomidine was found to be associated with an increased incidence of bradycardia and increased early postoperative sedation. Ketamine (low dose) resulted in an increased heart rate and blood pressure, in addition to causing more hallucinations and emergence-related symptoms. Overall, both agents were used effectively as multimodal analgesics, and dexmedetomidine was more effective at reducing opioid consumption and had earlier effects on the early analgesia.

The present study compared low-dose ketamine with dexmedetomidine as opioid-sparing components of multimodal analgesia in patients undergoing major abdominal surgery. Dexmedetomidine was associated with lower intraoperative fentanyl requirements, reduced 24-hour postoperative morphine-equivalent consumption, fewer rescue analgesic doses and a longer interval before the first request for rescue analgesia. Early postoperative pain scores at 2, 4, 6 and 12 hours were also lower in the dexmedetomidine group, although pain intensity became comparable between the groups at 24 hours. These findings suggest that both drugs provided clinically useful analgesia, but dexmedetomidine produced a stronger opioid-sparing effect during the early postoperative period. This observation is consistent with evidence that perioperative α2-adrenergic agonists reduce sympathetic activity, inhibit nociceptive transmission and decrease perioperative opioid requirements [9, 10]. Meta-analytical evidence has similarly demonstrated that intravenous dexmedetomidine can reduce 24-hour opioid consumption, decrease the need for rescue analgesia and prolong the time to the first analgesic request [11]

Lower postoperative opioid utilisation with dexmedetomidine is substantiated by previous studies on abdominal surgery. In abdominal colectomy patients, dexmedetomidine was administered intraoperatively to improve the postoperative recovery process and decrease the need for patient-controlled analgesia (PCA), while enhancing postoperative analgesia with morphine [12]. These advantages have also been observed after abdominal hysterectomy, in which case dexmedetomidine decreased the amount of morphine needed after surgery and improved quality of recovery scores [12]. Dexmedetomidine has also been studied in a randomized trial of Roux-en-Y gastric bypass surgery and had beneficial postoperative outcomes in terms of pain and opioids use [13]. Moreover, long-term use of dexmedetomidine infusion has been proven to be effective for analgesia and to decrease the amount of morphine used during abdominal surgery without causing respiratory depression [14]. The current results thus build upon previous evidence by directly comparing dexmedetomidine with low-dose ketamine, and not with placebo or a traditional opioid/paracetamol use.

In the current study, low dose ketamine had also provided significant postoperative pain control, but its opioid-sparing effect was not as great as dexmedetomidine. Ketamine's primary mechanism of action is non-competitive antagonism of the N-methyl-D-aspartate receptors which decreases central sensitization, wind-up and opioid-related hyperalgesia. A Cochrane review found that perioperatively administered ketamine likely decreases the intensity of pain and analgesic use in all surgical populations [15]. Low-dose ketamine has been shown in previous major abdominal surgeries to decrease morphine use, especially after surgery [16]. Other studies have demonstrated small dose ketamine can also reduce postoperative opioid use [17]. However, the results of ketamine have not been uniform; some studies have found no significant difference in postoperative pain or in the amount of pain medication needed [18]. These differences may be due to different doses or durations of infusion, severity of surgery, background analgesia and when the outcomes were assessed.

The haemodynamic and adverse-effect findings are relevant to an important balance between analgesic efficacy and tolerability. Higher rates of bradycardia, lower heart rate and mean arterial pressure were noted with dexmedetomidine. This effect is of a pharmacologic nature as α2-receptor activation in the CNS decreases sympathetic outflow and circulating catecholamine activity. Bradycardia and hypotension are well known dose-dependent side effects of dexmedetomidine, especially in patients who have a pre-existing vulnerability to those effects [19]. The large POFA randomized trial was halted prematurely due to severe bradycardia in the dexmedetomidine-based opioid-free arm and despite a decrease in postoperative morphine consumption and nausea and vomiting [20]. Ketamine, on the other hand, was related to more tachycardia and hypertension that highlight its sympathomimetic activity. Hallucinations and emergence-related symptoms were also more common when taking ketamine, but severe respiratory depression did not occur much in either group. The results indicate that there is a need to carefully monitor the haemodynamics and adjust the dosage of these medications individually instead of indiscriminately using them.

There are several limitations to this study that should be taken into account when interpreting the results. It was carried out at one centre and had a relatively small number of patients (93) which can make the results difficult to generalise and could mean that rare side effects were not picked up. Various types of large abdominal surgery were included in this study and the size of the incision, length of surgery, and surgical approach may have affected the postoperative pain and opioid use. Follow-up was only possible for the first 24 postoperative hours, making it impossible to assess possible effects on persistent postsurgical pain, bowel recovery, functional rehabilitation, and longer-term opioid use. Furthermore, use of a standardized protocol may result in clinical variability due to the administration of rescue analgesics and to converting doses of administered morphine equivalents. Larger numbers, procedure specific sub-group analyses, longer follow-up periods, quality of recovery and assessment of cost-effectiveness should be incorporated into future multicentre trials. Additionally, dose-ranging studies are needed to determine if lower infusion rates of dexmedetomidine can maintain the opioid-sparing properties without incurring excessive sedations or bradycardia.

Both low-dose ketamine and dexmedetomidine were effective components of multimodal analgesia in patients undergoing major abdominal surgery. However, dexmedetomidine provided a greater opioid-sparing effect, demonstrated by lower intraoperative fentanyl use, reduced 24-hour postoperative morphine consumption, lower early pain scores and delayed requirement for rescue analgesia. This benefit was accompanied by a higher occurrence of bradycardia and early postoperative sedation. Low-dose ketamine provided acceptable analgesia and greater haemodynamic preservation but was associated with more tachycardia, hypertension and emergence-related symptoms. Dexmedetomidine may therefore be preferred when maximum opioid reduction is required, provided that patients are carefully selected and closely monitored for haemodynamic adverse effects.

1. McEvoy, M.D., B.L. Raymond, and A.J.A.c. Krige, Opioid-sparing perioperative analgesia within enhanced recovery programs. 2022. 40(1): p. 35-58.
2. Siu, E.Y. and T.S.J.I.a.c. Moon, Opioid-free and opioid-sparing anesthesia. 2020. 58(2): p. 34-41.
3. O’Rourke, K. and C.J.D.M.R. Jones, Reducing opioid use perioperatively: a narrative review. 2021. 4.
4. Ustun, Y.B., et al., Comparison of ketamine, dexmedetomidine and lidocaine in multimodal analgesia management following sleeve gastrectomy surgery: a randomized double-blind trial. 2022. 37(6): p. 820-826.
5. Kovac, A.L.J.P.D., Postoperative nausea and vomiting in pediatric patients. 2021. 23(1): p. 11-37.
6. Kanishka, R., et al., Enhanced recovery after surgery: opioid sparing strategies after discharge: a review. 2022. 26(2): p. 93-102.
7. Zhan, W., et al., Analgesic effect and safety of postoperative low-dose ketamine/midazolam combination vis-à-vis dexmedetomidine in non-cardiac surgery. 2020. 19(11).
8. Kaye, A.D., et al., Dexmedetomidine in enhanced recovery after surgery (ERAS) protocols for postoperative pain. 2020. 24(5): p. 21.
9. Blaudszun, G., et al., Effect of perioperative systemic alpha-2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. 2012.
10. Schnabel, A., et al., Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. 2013. 154(7): p. 1140-1149.
11. Wang, K., et al., Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. 2019. 123(6): p. 777-794.
12. Ge, D.-J., et al., Intraoperative dexmedetomidine promotes postoperative analgesia and recovery in patients after abdominal hysterectomy: a double-blind, randomized clinical trial. 2016. 6(1): p. 21514.
13. Tufanogullari, B., et al., Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. 2008. 106(6): p. 1741-1748.
14. Gurbet, A., et al., Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. 2006. 53(7): p. 646-652.
15. Brinck, E., Ketamine for postoperative pain in adults. 2021.
16. Zakine, J., et al., Postoperative ketamine administration decreases morphine consumption in major abdominal surgery: a prospective, randomized, double-blind, controlled study. 2008. 106(6): p. 1856-1861.
17. Zhu, Y., et al., Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol. 2023. 15: p. 1298661.
18. Aubrun, F., et al., Effect of a low-dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double-blind, placebo-controlled trial. 2008. 25(2): p. 97-105.
19. Naaz, S., E.J.J.o.c. Ozair, and d.r. JCDR, Dexmedetomidine in current anaesthesia practice-a review. 2014. 8(10): p. GE01.
20. Beloeil, H., et al., Balanced opioid-free anesthesia with dexmedetomidine versus balanced anesthesia with remifentanil for major or intermediate noncardiac surgery: the postoperative and opioid-free anesthesia (POFA) randomized clinical trial. 2021. 134(4): p. 541-551.