European Journal of Cardiovascular Medicine

Patients with significant comorbidities frequently encounter challenges during general anesthesia, as it may compromise hemodynamic stability and elevate perioperative risk (1). Regional anesthesia has emerged as a safer and more efficient alternative, particularly for lower extremity procedures (2). Among regional anesthesia techniques, peripheral nerve blocks have gained considerable popularity for upper and lower limb surgeries, providing consistent intraoperative anesthesia, effective postoperative pain management, and substantial reduction in systemic opioid requirements (3).

The popliteal nerve block is considered one of the optimal techniques for below-knee surgical procedures (4). This approach is particularly beneficial for high-risk patients as it ensures significant sensory and motor blockade while preserving hemodynamic stability. Additional advantages include facilitation of early mobilization, prolonged postoperative analgesia, and reduced incidence of systemic complications (5). The integration of ultrasound guidance has revolutionized the safety and effectiveness of popliteal blocks by enabling real-time visualization of anatomical structures, minimizing vascular puncture risk, reducing needle passes, shortening onset time, and improving overall success rates (6).

Levobupivacaine, the S(-) enantiomer of bupivacaine, has become a preferred local anesthetic due to its favorable pharmacological profile (7). It provides prolonged sensory and motor blockade with lower cardiovascular and neurological toxicity compared to racemic bupivacaine, making it a safer alternative without compromising anesthetic quality (8). To enhance block onset, intensity, and duration, local anesthetics are frequently combined with adjuvants. Fentanyl, a synthetic opioid belonging to the phenylpiperidine group, is widely utilized due to its high lipid solubility, which promotes rapid nerve penetration and enhanced analgesic quality (9).

Recent studies have investigated various adjuvants including dexmedetomidine and dexamethasone to extend block duration and improve patient comfort (10). However, the specific effects of fentanyl as an adjuvant to levobupivacaine in popliteal blocks remain inadequately explored, particularly regarding onset characteristics and postoperative analgesia quality. Furthermore, comparative data evaluating the safety profile and hemodynamic effects of this combination in the context of ultrasound-guided popliteal blocks are limited.

This study was designed to evaluate the efficacy of adding fentanyl to levobupivacaine in ultrasound-guided popliteal blocks for below-knee surgeries. The primary objectives were to compare the onset and duration of sensory and motor blockade between the two groups. Secondary objectives included assessment of hemodynamic stability, postoperative pain scores, and incidence of adverse effects.

This prospective randomized clinical trial was conducted in the Department of Anaesthesiology. The study protocol received approval from the Institutional Ethics Committee, and written informed consent was obtained from all participants prior to enrolment.

Sample size was calculated based on anticipated differences in hemodynamic parameters between groups. Assuming a mean difference in diastolic blood pressure of 1.8 mmHg with standard deviations of 4.6 and 3.4 in the respective groups, a minimum of 57 patients per group (total 114) was required to achieve 80% power at a 5% significance level (two-sided). Patients aged 18-60 years of either gender, classified as American Society of Anesthesiologists (ASA) physical status I or II, scheduled for elective below-knee surgeries were eligible for inclusion. Exclusion criteria comprised ASA class III or IV status, local infection at the injection site, history of allergy to local anaesthetics or opioids, pregnant women, coagulopathy, and pre-existing peripheral neuropathy.

Enrolled patients were randomly allocated into two groups using computer-generated random numbers:

• Group A (Control): 20 ml of 0.5% levobupivacaine + 1 ml of 0.9% normal saline
• Group B (Study): 20 ml of 0.5% levobupivacaine + 50 mcg fentanyl (1 ml)

All patients underwent comprehensive preoperative evaluation including detailed history, physical examination, and airway assessment using Mallampati grading. Baseline investigations included complete blood count, random blood glucose, renal function tests, and coagulation profile. Patients were kept nil per oral for six hours before surgery.

Procedure: Patients were positioned prone, and under strict aseptic precautions, the popliteal fossa crease was identified. A high-frequency linear ultrasound transducer was placed proximal to the crease between the biceps femoris and semitendinosus/semimembranosus tendons. The tibial nerve was identified and scanning continued proximally to visualize the sciatic nerve before its bifurcation.

A 22-gauge needle was advanced through the biceps femoris muscle under real-time ultrasound guidance. After indenting the fascial sheath of the sciatic nerve, the needle tip was positioned between the tibial and common peroneal nerve components. Following negative aspiration for blood, the designated study solution was injected. Primary outcomes included onset time of sensory analgesia (time from injection to loss of pinprick sensation) and duration of sensory analgesia (time from onset to first rescue analgesic request). Duration of motor blockade was assessed using modified Bromage scale. Hemodynamic parameters including heart rate, mean arterial pressure (MAP), and oxygen saturation were recorded at baseline, 5, 15-, 30-, 45-, and 60-minutes post-block. Postoperative pain was assessed using the Visual Analog Scale (VAS; 0-10). Rescue analgesia was administered when VAS exceeded 4. Adverse effects including hematoma, nausea, vomiting, hypotension, bradycardia, nerve injury, and local anesthetic systemic toxicity (LAST) were documented.

Statistical Analysis: Data were compiled using Microsoft Excel and analyzed with SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. Independent t-test was used for normally distributed continuous variables, while Mann-Whitney U test was applied for non-parametric data. Chi-square test was used for categorical variables. A p-value less than 0.05 was considered statistically significant.

Figure 1: Consort flow diagram

A total of 114 patients were enrolled and randomized equally into two groups. Demographic data, heart rate, and mean arterial pressure (MAP) were not statistically significant. The mean age was 42.0 ± 10.4 years in Group A and 42.4 ± 9.7 years in Group B (p = 0.89). Both groups demonstrated male predominance (59.6%) with identical gender distribution. ASA grade distribution was similar, with ASA Grade I comprising 59.6% in Group A and 57.9% in Group B (p = 0.985).

Table 1: Demographic data

Data is represented as Mean±SD (standard deviation) or in numbers, ASA (American Society of Anaesthesiologists), BMI – Body Mass Index, Kg – Kilogram, p-value <0.05 is considered statistically significant.

Heart rate remained stable throughout the observation period in both groups with no statistically significant differences at any time point. At baseline, mean heart rate was 83.0 ± 10.2 bpm in Group A and 82.5 ± 7.9 bpm in Group B (p = 0.76). Similar stability was observed at subsequent intervals through 60 minutes.

Mean arterial pressure trends were comparable between groups across all time intervals. At baseline, MAP was 88.9 ± 7.7 mmHg in Group A and 90.4 ± 6.3 mmHg in Group B (p = 0.280). No clinically significant hypotension or hypertension episodes were recorded.

Table 2: Mean Heart Rate

Data is represented as Mean±SD (standard deviation) BPM – Beats per minute, p-value <0.05 is considered statistically significant.

Figure 2: Mean MAP

Data is represented as Mean±SD (standard deviation) MAP -  Mean Arterial Pressure, p-value <0.05 is considered statistically significant.

Group B demonstrated significantly faster onset of sensory blockade compared to Group A (7.3 ± 1.4 minutes versus 12.3 ± 1.5 minutes; p = 0.01). The duration of sensory analgesia was markedly prolonged in Group B (890.1 ± 99.1 minutes versus 573.7 ± 72.9 minutes; p = 0.01). Motor blockade duration was slightly longer in Group B (302.5 ± 31.9 minutes versus 293.0 ± 31.5 minutes; p = 0.21), though this difference did not reach statistical significance.

No adverse effects including hematoma, nausea, vomiting, hypotension, bradycardia, nerve injury, or LAST were observed in either group.

Table 3: Onset and duration of sensory and motor blockade between the groups

Data is represented as Mean±SD (standard deviation), *p-value <0.05 is considered statistically significant.

Table 4: Adverse Effects

Data is represented as percentage (%), p-value <0.05 is considered statistically significant.

Figure 3: Mean VAS score

Data is represented as Mean±SD (standard deviation), VAS – Visual Analogue Scale, *p-value <0.05 is considered statistically significant. The mean VAS score is significantly lower in group B (1.7 ± 0.6) compared to patients in group A (3.1 ± 0.5) (p<0.05), indicating superior analgesia quality.

The present study demonstrates that the addition of fentanyl to levobupivacaine significantly enhances the quality and duration of ultrasound-guided popliteal blocks for below-knee surgeries. The levobupivacaine-fentanyl combination achieved faster sensory blockade onset, prolonged analgesia duration, and superior postoperative pain control while maintaining excellent hemodynamic stability and safety profile.

The demographic characteristics of our study population align with previously published literature on peripheral nerve blocks for lower extremity surgeries (11). The comparable baseline characteristics between groups strengthen the validity of our comparative findings and minimize potential confounding variables.

The significantly faster onset of sensory blockade in the fentanyl group (7.3 versus 12.3 minutes) can be attributed to the high lipid solubility of fentanyl, which facilitates rapid penetration through neural membranes and enhances local anesthetic action (12). This finding is consistent with studies by Tripathi et al., who reported mean sensory block onset times of 4.25 ± 1.30 minutes with combined local anesthetic-opioid preparations (13). The accelerated onset has significant clinical implications, potentially reducing preoperative waiting times and improving operating room efficiency.

The prolonged duration of sensory analgesia observed in Group B (890.1 versus 573.7 minutes) represents a clinically meaningful difference exceeding five hours. This extended analgesia can be explained by the synergistic action between levobupivacaine and fentanyl at peripheral opioid receptors, which are upregulated in the presence of tissue inflammation (14). Fournier et al. demonstrated that 0.5% levobupivacaine provides longer analgesia compared to equivalent doses of ropivacaine in sciatic nerve blocks, with median duration reaching 1605 minutes (16). The addition of opioid adjuvants further augments this duration.

Hemodynamic stability was maintained throughout the observation period in both groups, with no significant differences in heart rate or mean arterial pressure. This finding underscores the safety advantage of peripheral nerve blocks over central neuraxial techniques or general anesthesia, particularly in patients with cardiovascular comorbidities (16). The stable hemodynamics observed are consistent with the mechanism of popliteal blocks, which provide selective lower extremity anesthesia without affecting sympathetic tone to vital organs. The significantly lower postoperative VAS scores in the fentanyl group (1.7 versus 3.1) indicate superior pain control quality, which has implications for patient satisfaction, early mobilization, and reduced opioid consumption. Pujol et al. reported similar findings, noting that patients receiving enhanced popliteal block formulations demonstrated VAS scores below 2 at 24 hours postoperatively (17). Li et al. also confirmed that sciatic nerve blocks with adjuvants significantly reduce postoperative VAS scores and rescue analgesic requirements (18).

The absence of adverse effects in both groups is reassuring and supports the safety of adding low-dose fentanyl (50 mcg) to levobupivacaine for peripheral nerve blocks. This finding aligns with the established safety profile of both agents when used at appropriate doses with ultrasound guidance (19). The use of ultrasound has been shown to minimize complications by enabling precise needle placement and avoiding intravascular injection (20).

It is concluded that the addition of Inj. Fentanyl 50mcg to 0.5% levobupivacaine significantly improves the efficacy of ultrasound guided popliteal block for below knee surgeries. Use of levobupivacaine-fentanyl combination in popliteal block improves perioperative analgesia, enhances patient’s comfort and potentially reduces systemic opioid requirements in lower limb surgical procedures.

Limitations of the study:

Several limitations warrant consideration. The single-center design may limit generalizability, and longer-term follow-up would provide additional information regarding sustained benefits and delayed complications. Future multicentre studies with larger sample sizes and evaluation of different fentanyl doses would strengthen these findings

1. Okolo D, Ugorji WS, Gopep NS, Oragui CC, Ubajaka CC, Okobi OE. Perioperative Management of Anesthesia in Patients With Cardiovascular Disease: A Review of Current Guidelines in the United States. Cureus. 2025;17(2):e79355. DOI: 10.7759/cureus.79355
2. Tripathi R, Parikh SN, Vaidya V, Baranda M, Patel P. Ultrasound guided popliteal nerve block in foot and ankle surgeries. Eur J Cardiovasc Med. 2024;14(3):156-162.
3. Shah P, Jain A, Saini P, Singh AV. Levobupivacaine vs levobupivacaine with dexamethasone on the duration of postoperative analgesia in popliteal block for below knee surgeries. J Cardiovasc Dis Res. 2023;11(5):19-24.
4. White L, Bright M, Velli G, Boon M, Thang C. Efficacy and safety of proximal popliteal sciatic nerve block compared with distal sciatic bifurcation or selective tibial and peroneal nerve block: a systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2022;129(6):e158-e162. DOI: 10.1016/j.bja.2022.08.036
5. Kang C, Hwang DS, Song JH, Lee GS, Lee JK, Hwang SJ, et al. Clinical analyses of ultrasound-guided nerve block in lower-extremity surgery: a retrospective study. J Orthop Surg. 2021;29(1):2309499021989102. DOI: 10.1177/2309499021989102
6. Zhu LJ, Gong CJ, Zhang ZF, Zhang QW, Peng PP, Ni Y. Efficacy and safety of ultrasound-guided above-knee lateral approach for popliteal sciatic nerve block in surgeries below the knee: a randomized controlled trial. Ann Palliat Med. 2021;10(5):5185-5197. DOI: 10.21037/apm-20-1077
7. Li Y, Zhang Q, Wang Y, Yin C, Guo J, Qin S, et al. Ultrasound-guided single popliteal sciatic nerve block is an effective postoperative analgesia strategy for calcaneal fracture: a randomized clinical trial. BMC Musculoskelet Disord. 2021;22:764. DOI: 10.1186/s12891-021-04645-z
8. Chitnis SS, Tang R, Mariano ER. The role of regional analgesia in personalized postoperative pain management. Korean J Anesthesiol. 2020;73(5):363-371. DOI: 10.4097/kja.20166
9. Arjun BK, Prijith RS, Sreeraghu GM, Narendrababu MC. Ultrasound-guided popliteal sciatic and adductor canal block for below-knee surgeries in high-risk patients. Indian J Anaesth. 2019;63(8):635-639. DOI: 10.4103/ija.IJA_183_19
10. Joshi G, Gandhi K, Shah N, Gadsden J, Corman SL. Peripheral nerve blocks in the management of postoperative pain: challenges and opportunities. J Clin Anesth. 2016;35:524-529. DOI: 10.1016/j.jclinane.2016.09.004
11. Lewis SR, Price A, Walker KJ, McGrattan K, Smith AF. Ultrasound guidance for upper and lower limb blocks. Cochrane Database Syst Rev. 2015;2015(9):CD006459. DOI: 10.1002/14651858.CD006459.pub3
12. Vardanyan RS, Hruby VJ. Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications. Future Med Chem. 2014;6(4):385-412. DOI: 10.4155/fmc.13.215
13. Bajwa SJS, Kaur J. Clinical profile of levobupivacaine in regional anesthesia: A systematic review. J Anaesthesiol Clin Pharmacol. 2013;29(4):530-539. DOI: 10.4103/0970-9185.119172
14. Perlas A, Wong P, Abdallah F, Hazrati LN, Tse C, Chan V. Ultrasound-guided popliteal block through a common paraneural sheath versus conventional injection: a prospective, randomized, double-blind study. Reg Anesth Pain Med. 2013;38(3):218-225. DOI: 10.1097/AAP.0b013e31828db12f
15. Wadhwa A, Kandadai SK, Tongpresert S, Obal D, Gebhard RE. Ultrasound guidance for deep peripheral nerve blocks: a brief review. Anesthesiol Res Pract. 2011;2011:262070. DOI: 10.1155/2011/262070
16. Brummett CM, Hong EK, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current. Anesthesiology. 2011;115(4):836-843. DOI: 10.1097/ALN.0b013e318221fcc9
17. Fournier R, Faust A, Chassot O, Gamulin Z. Levobupivacaine 0.5% provides longer analgesia after sciatic nerve block using the Labat approach than the same dose of ropivacaine in foot and ankle surgery. Anesth Analg. 2010;110(5):1486-1489. DOI: 10.1213/ANE.0b013e3181d3e80f
18. Pujol E, Faulí A, Anglada MT, López A, Pons M, Fàbregas N. Ultrasound-guided single dose injection of 0.5% levobupivacaine or 0.5% ropivacaine for a popliteal fossa nerve block in unilateral hallux valgus surgery. Rev Esp Anestesiol Reanim. 2010;57(5):288-292. DOI: 10.1016/S0034-9356(10)70227-1
19. Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59(3):551-579. DOI: 10.2165/00003495-200059030-00013
20. Feierman DE, Lasker JM. Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4. Drug Metab Dispos. 1996;24(9):932-939. PMID: 8886601