Continuous �three-in-one� Femoral Block for Analgesia after Unilateral Total Knee Replacement; the Value of Adding Verapamil

Clinical Trial

Austin J Anesthesia and Analgesia. 2014;2(3): 1021.

Continuous “three–in–one” Femoral Block for Analgesia after Unilateral Total Knee Replacement; the Value of Adding Verapamil

Atef D. Demian*, Reem A El-Sharkawy, Amal R. Riad, Fady Y. Jacoup

Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Egypt

*Corresponding author: Atef D. Demian, Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Egypt.

Received: February 24, 2014; Accepted: April 04, 2014; Published: April 10, 2014


This study was designed to investigate the possible analgesic role of verapamil in the continuous 3–in–1femoral block after total knee replacement (TKR). Forty two patients scheduled for TKR were randomly assigned to one of two groups. Group “R” received 15 ml Ropivacaine 0.75 % and a bolus of 5 ml normal saline. Group “R–V” received 15 ml Ropivacaine 0.75 % and verapamil 2.5 mg diluted in 5 ml normal saline. General anesthesia was standardized for all study groups. After recovery: In group “R”, Ropivacaine 0.2 % was given in a rate of 5 ml ⁄ hr., whereas in group “R–V”, Ropivacaine 0.2 % mixed with verapamil was given at the same rate. Hemodynamic changes, intensity of resting and moving pain by VAS, consumption of systemic analgesia, amplitude of knee flexion, hospital stay and general or local adverse effects were assessed. Two cases were excluded due to complete failure. Both groups were comparable regarding the progress of sensory and motor block. The mean VAS scores were significantly lower (P<0.05) in group R–V than group R during rest and during physical therapy sessions. We concluded that the addition of verapamil potentiates the analgesic effect of Ropivacaine in 3–in–1 block without side effects. More studies are required to clarify dose–responses of verapamil.

Keywords: Knee Replacement; Analgesia; Femoral; Verapamil


Postoperative pain is a major concern after TKR. When inadequately treated, it intensifies reflex stress responses [1] and hinders early intensive physical therapy, the most influential factor for good postoperative knee rehabilitation [1,2]. Postoperative pain relief after TKR was achieved by a variety of techniques such as IV patient–controlled analgesia [3], epidural analgesia with narcotics and⁄or local anesthetics [4,5] and lumbar plexus blockade (3–in– 1–block) [6,7]. It has been shown that continuous femoral nerve block is a more effective pain reliever after TKA compared to IV patient controlled analgesia [8], epidural analgesia [6] or single injection block [9]. In an attempt to improve duration and potency of analgesia for continuous femoral nerve block, Ropivacaine in a concentration of 0.2% – 0.75% showed better analgesic quality than other anesthetic agents [10–12]. The mechanism of action of local anesthetics is primarily through sodium channel and axonal conduction block, but it also has extensive effects on presynaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, calcium channel blockers may potentiate the analgesic properties of both local anesthetics and opioids [13]. This fact was confirmed by demonstrating the potentiating anesthetic and analgesic effect of verapamil in epidural analgesia [14], spinal anesthesia [15], subcutaneous injection [16] and brachial plexus block [17]. According to that fact, we hypothesize that addition of verapamil to the local anesthetics for “3–in–1” continuous femoral nerve block may improve the analgesic quality after TKR. This study was designed to demonstrate if addition of verapamil to Ropivacaine for 3–in–1 femoral block would potentiate its analgesic effect or not.

Patients and Methods

This prospective randomized double–blind controlled study was carried out on 42 patients subjected to primary unilateral TKR at Mansoura University Hospital. After approval of the protocol by our institute, patients of ASA I or II, of either sex, aged 50 –70 years were included in the study. Patients were excluded if they have any contraindications to regional anesthesia, allergy to amide local anesthetics, pre–existing neurological diseases of lower extremities, preoperative use of opioids, have psychic diseases or failure of the technique. After routine preoperative assessment, the details of the technique and postoperative VAS pain scale assessment were discussed with the patient and a written consent was obtained. In the operating suit, patients were connected to non–invasive standard monitoring, basal hemodynamic parameters were recorded, I.V. line was secured and 500 ml normal saline was given.

Femoral nerve block

Midazolam (0.02 mg ⁄kg I.V.) was given before insertion of the femoral catheter. Continuous “three–in–one–block” was performed before induction of general anesthesia following Winnie et al landmarks [18]. An 18 G Tuohy needle ( Perifix; Braun, Melsungen, Germany) attached to the nerve stimulator (Neurosign 100, MAGSTIM,UK) was inserted just lateral to the femoral artery. With a starting output of 1.5 mA, the needle was advanced in a cephalad plane at an angle of 30o to the skin until contraction of the quadriceps femoris muscle (patella ascension) was elicited. Its position was then optimized and judged adequately when an output lower than 1 mA (usually 0.2–0.5 mA) still elicited contractions of the quadriceps. A 20–G multiperforated catheter was then threaded upwards 10–15 cm within the femoral nerve sheath.


According to addition of verapamil or not to the injected solution, eligible patients were randomly allocated into 2 equal groups by using a computer -generated list of random permutations. Group “R” received 15 ml Ropivacaine 0.75 % (Narophin® Astra, Dietikon, Switzerland) and a bolus of 5 ml normal saline in separate syringes. Group “R–V” received 15 ml Ropivacaine 0.75 % and verapamil 2.5 mg (Isopten®; Knoll AG, Ludwigshafen, Germany) diluted in 5 ml normal saline in separate syringes. The study solutions were prepared and injected by an attending anesthetist who was not involved in the patient care or data collection while the managing anesthetist was masked about the used solution. The sensory block of the 3 nerves was assessed every 10 minutes during the first 30 minutes post injection using a 25–G needle. Testing was performed on the anterior aspect of the knee (femoral nerve), medial aspect of the knee (Obturator nerve) and lateral aspect of the thigh (lateral femoral cutaneous nerve). The block was considered complete when no sensation was observed to pinprick test, partial when sensation to pinprick test was decreasedand absent when normal sensation to pinprick test was observed. Motor block was assessed during the same period by testing knee extension (complete, partial or failure). A block failure was definedas a complete absence of both sensory and motor block in each nerve territory after 30 minutes. In case of failure, the patient was excluded from the study and systemic analgesia was given according to our institutional policy.

General anesthesia

After ensuring the success of the femoral block, general anesthesia was standardized for all study groups. Induction was done by Fentanyl (1 µg⁄kg), thiopentone (3–5 mg⁄kg) and maintenance by N2O–O2, atracurium, Isoflurane and incremental doses of Fentanyl (0.25 µg ⁄kg). One of 3 surgeons belonging to the same team (using the same technique) performed all the operations.

Recovery and analgesic protocol

After full recovery, patients were transferred to the post anesthesia care unit (PACU) and stayed there for 6 hours under full monitoring. The postoperative analgesic protocol was initiated in PACU and continued in the surgical ward for 48 hours. Infusion pumps containing the randomized analgesic solution were activated immediately after recovery. In group “R”, Ropivacaine (0.2 %) in 50 ml was given in a rate of 5 ml ⁄ hr., whereas in group “R–V”, Ropivacaine (0.2 %) mixed with verapamil (2.5 mg) in 50 ml was given at the same rate. The intensity of resting pain was determined by VAS and recorded 1, 2, 4, 6, 12, 24, and 48 hours after recovery. Early rehabilitation was initiated on the 1st day after surgery by asking patients to put patella up (contraction of quadriceps muscles) and by using continuous passive movement splint. In accordance with the surgical team, knee flexion of 40° was progressively attempted for 30 minutes on 1st postoperative day and of 50° on the 2nd postoperative day. Pain during mobilization was evaluated during target flexion at the 1st and 2nd postoperative days. Excessive pain (VAS > 5) was avoided by decreasing the amplitude of flexion.

Acquisition of the clinical variables

The primary outcome was the quality of postoperative analgesia as assessed by VAS. If VAS was > 5, non steroidal anti–inflammatory drugs e.g. Diclofenac 75 mg I .M. were given. Other secondary outcomes included: Time and dose of systemic analgesia, amplitude of knee flexion, hospital stay and general or local adverse effects. Hemodynamic changes (Heart rate and Mean arterial blood pressure) were recorded in the following times: basal, 30 minutes after FNB, during GA (30 min, 1 h, 2 h), in PACU (1 h, 2 h and 6 h).On the morning of the 3rd postoperative day, the pump was deactivated and the catheter was removed.

Statistical analysis

The power of this clinical trial was retrospectively calculated using the GPower analysis program. Using post–hoc power analysis with accuracy mode calculations and assuming type–I error protection of 0.05 and medium effect size convention of 0.3, a total sample size of 42 patients produced a power of 0.98.

Data were collected and analyzed by SPSS program Version 14. Normal distribution of the collected data was first verified with the Kolmogrov–Smirnov test. Normally distributed data was compared with Student t–test. Paired sample t–test was used for intragroup comparison. Chi–square test was used for comparison of proportions. P value < 0.05 was considered as a level of significance.


Two patients (one from each group) were excluded from the study due to complete sensory and motor block failure. The patients' characteristics showed no significant differences between the 2 studied groups. Hypertension and Diabetes were the most common preoperative co–morbid diseases (table 1).