Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonar-guided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery

Abstract

Background:

Cooling of local anesthetic potentiates its action and increases its duration. Magnesium sulfate (MgSo₄) added to local anesthetic prolongs the duration of anesthesia and postoperative analgesia with minimal side effects.

Aim:

The aim of this prospective, randomized, double-blind study was to compare the effect of cold to 4°C bupivacaine 0.5% and Mg added to normal temperature (20–25°C) bupivacaine 0.5% during sonar-guided combined femoral and sciatic nerve blocks on the onset of sensory and motor block, intraoperative anesthesia, duration of sensory and motor block, and postoperative analgesia in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery.

Patients and Methods:

A total of 90 American Society of Anesthesiologists classes I and II patients who were scheduled to undergo elective ACL reconstruction were enrolled in the study. The patients were randomly allocated to 3 equal groups to receive sonar-guided femoral and sciatic nerve blocks. In Group I, 17 ml of room temperature (20–25°C) 0.5% bupivacaine and 3 ml of room temperature saline were injected for each nerve block whereas in Group II, 17 ml of cold (4°C) 0.5% bupivacaine and 3 ml of cold saline were injected for each nerve block. In Group III, 17 ml of room temperature 0.5% bupivacaine and 3 ml of MgSo₄ 5% were injected for each nerve block. The onset of sensory and motor block was evaluated every 3 min for 30 min. Surgery was started after complete sensory and motor block were achieved. Intraoperatively, the patients were evaluated for heart rate and mean arterial pressure, rescue analgesic and sedative requirements plus patient and surgeon satisfaction. Postoperatively, hemodynamics, duration of analgesia, resolution of motor block, time to first analgesic, total analgesic consumption, and the incidence of side effects were recorded.

Results:

There was no statistically significant difference in demographic data, mean arterial pressure, heart rate, and duration of surgery. Onset of both sensory and motor block was significantly shorter in both Groups II and III compared to Group I. Intraoperative anesthetic quality was comparable between groups with good patient and surgeon satisfaction. The time to first analgesia was significantly longer in Groups II and III compared to Group I with nonsignificant difference between each other. Moreover, the total opioid consumption was significantly lower in Groups II and III and duration of analgesia and motor block were significantly longer in Groups II and III compared to Group I. There was no difference in the incidence of side effects.

Conclusions:

The use of cold 0.5% bupivacaine or the addition of Mg to normal temperature 0.5% bupivacaine prolongs the sensory and motor block duration without increasing side effects and enhances the quality of intra- and post-operative analgesia with better patient satisfaction in sonar-guided femoral and sciatic nerve block for arthroscopic ACL reconstruction surgery.

INTRODUCTION

The most commonly used drug in nerve block is bupivacaine 0.5% as a local anesthetic. Enhancement of the local anesthetic effect is produced by a decrease in temperature to 4°C.[1] Temperature may thus be an interesting physical variable in the study of nerve blocking mechanisms.[2]

Several studies had reported that cooling a local anesthetic leads to an increase in the duration of the induced block.[1,2,3]

Local anesthetic alone for nerve block provides good operative conditions but has short duration of action and limited postoperative analgesia.

Different additives have been combined with local anesthetics to improve block quality, prolong the postoperative analgesia, and decrease the postoperative narcotic consumption, but none of them is without side effects.

The most common additives are fentanyl, midazolam, epinephrine, and magnesium sulfate (MgSo₄).[4]

Many studies have demonstrated the effect of intraoperative MgSo₄ on improving the postoperative analgesia. Mg has antinociceptive effect due to its antagonistic effect on the N-methyl-D-aspartate (NMDA) receptors. Its analgesic effect is based on its inhibitory properties on calcium channels.[4]

This study was carried out to compare cold bupivacaine (4°C) and MgSO₄ added to room temperature bupivacaine (20–25°C) in sonar-guided combined femoral and sciatic nerve blocks. We compared the onset of sensory and motor block, quality of anesthesia, duration of analgesia and motor block, success rate, postoperative analgesia, and incidence of side effects.

PATIENTS AND METHODS

This prospective, randomized, double-blind study was performed in Tanta University Hospitals, Tanta, Egypt. Ninety adult patients aged between 25- and 40-year-old with the American Society of Anesthesiologists physical status I and II classification scheduled for arthroscopic anterior cruciate ligament (ACL) reconstruction surgery under sonar-guided combined femoral and sciatic nerve block were included in this study. Patients’ informed consent was taken and ethical committee approval was obtained. The present study was performed from August 2015 to February 2016.

Exclusion criteria included patients’ refusal, myasthenia gravis, peripheral vascular disease, bleeding disorders, chronic renal or liver diseases, drug allergy, and infection at the site of injection.

Patients were randomly classified using computer-generated random numbers in sealed envelopes into 3 equal groups, thirty patients each. Group I was control group and received 20 ml room temperature (20–25°C) solution composed of 17 ml of 0.5% bupivacaine plus 3 ml normal saline for each nerve block. Group II was cold bupivacaine group and received 20 ml solution composed of 17 ml of cold bupivacaine 0.5% to 4°C plus 3 ml of cold normal saline to 4°C for each nerve block. Group III, the Mg group, received 20 ml solution composed of 17 ml of room temperature (20–25°C) bupivacaine 0.5% plus 3 ml of MgSo₄ 5% for each nerve block. Cold solution to 4°C was obtained by putting it in the refrigerator until its use. The room temperature in our pharmacy is between 20°C and 25°C at the time of the study. An anesthesiologist who was not involved in the data collection or intervention prepared the drug syringes.

Preoperatively, the patients were assessed as regard to both medical and surgical histories and routine laboratory data were evaluated including complete blood picture, prothrombin time and activity, liver and renal function, and neurologic and physical examination. Sites of injections were examined to exclude any infection.

Routine intraoperative monitoring was used in all cases, including electrocardiography, oxygen saturation, and noninvasive blood pressure measurements. Intravenous access was obtained. The patients were given oxygen via a facemask at 2–3 L/min, with midazolam 2 mg and fentanyl 50 mcg given intravenously for sedation.

For femoral nerve block, the inguinal region was exposed and disinfected, the wide band transducer 5–10 MHz (Sonosite, Titan, Sonosite Inc., 21919, 30^th Drive SE Bothell WA 98021 USA) was placed on the inguinal region to allow visibility of the femoral artery and vein. After identifying the femoral nerve, a skin wheal of lidocaine 1% 2–3 ml was made on the lateral aspect of the thigh 1 cm away from the lateral edge of the transducer. A 22G isolated needle 5 cm long (Stimuplex A50^®, B. Braun, Germany) was inserted in-plane in a lateral-to-medial orientation and advanced toward the femoral nerve. It was introduced longitudinally to the ultrasound beam (in-plane technique) until the site of the nerve. When the needle tip had crossed fascia lata and fascia iliaca and into the femoral nerve compartment, aspiration was attempted with the syringe to check blood to ensure against accidental vascular puncture.

Once positioning was confirmed by imaging, injection was performed in boluses of 5 ml after aspiration to guard against intravascular injection and any resistance or pain on injection necessitated repositioning of the needle to avoid intraneural injection.

After the femoral block, the patient was placed in the lateral decubitus for the sciatic nerve block. The image was obtained by an ultrasound of the transgluteal region to identify the nerve structure. At this transgluteal level, the sciatic nerve is visualized in the short axis between the two hyperechoic bony prominences of the ischial tuberosity and the greater trochanter of the femur. Once positioning was confirmed by imaging, the needle was introduced after a skin wheal was performed with lidocaine 1% 2–3 ml and the site of injection was confirmed. Once positioning was confirmed by imaging, injection was performed in boluses of 5 ml after aspiration to guard against intravascular injection and any resistance or pain on injection necessitated repositioning of the needle to avoid intraneural injection.

For each block, onset of nerve blockade was evaluated every 5 min and continued for 30 min by independent anesthesiologists who were not involved in the study. If no block was present before induction of anesthesia, patients were excluded from the study.

Adequate femoral nerve block was defined as complete loss of pin-prick sensation in the anteromedial thigh with complete inability to elevate the foot of the operated limb from the operating table.

Sensory evaluation of the sciatic nerve was assessed by evaluating the presence or loss of pin-prick sensation in the lateral aspect of the calf and plantar aspect of the foot.

Motor blockade was evaluated simultaneously for the two main branches of the sciatic nerve, the common peroneal and tibial nerves (dorsiflexion and plantar flexion of the foot against manual resistance, respectively).

The onset time of the sensory block and the motor block was defined as the interval between end of injection of local anesthetic and a complete block. Block resolution was defined as complete recovery when both sensory and motor blocks in all distributions returned to baseline. The nurse or resident in charge of the patient tested the resolution of sensory (pin-prick test) and motor block (movement) every hour after surgery until complete regression. Duration of analgesia and motor block is the time between the onset and complete resolution of sensory and motor block.

Intraoperatively, an independent investigator assessed the patient satisfaction which was scored as 3 - “perfect,” 2 - “minor problems not requiring sedation or analgesia,” 1 - “need for sedation and analgesia,” and 0 - “insufferable pain, general anesthesia required.” Surgical satisfaction was scored as 2 - “satisfactory,” 1 - “acceptable,” and 0 - “not acceptable.” The presence of side effects, additional drug requirements, and the presence or absence of nausea and vomiting were also recorded.

If needed, midazolam was used first for tactile discomfort during surgery at incremental doses with 1 mg. To attenuate pain, 50 µg fentanyl was available to be administered alternatively as needed.

Hemodynamics (heart rate and mean arterial blood pressure) were recorded before block and every 15 min intraoperatively and every 30 min for 2 h postoperatively.

Postoperatively, patients were given morphine 3 mg intravenously and then when needed.

Postoperatively, the duration of both sensory and motor block, the time to first analgesia, the analgesic consumption and the occurrence of any complications associated with nerve blockade (venous puncture, paresthesia), and the use of local anesthetics (signs of toxicity) were also recorded by an independent anesthesiologists who were not involved in the study.

Statistical methods

The statistical software, namely, SAS 9.2 (SAS Institute Inc., Cary, NC, USA) and SPSS 20.0 (SPSS Inc., Chicago, USA) were used for the analysis of the data.

Data were presented as mean ± standard deviation and numbers (percentage).

For comparison of groups regarding quantitative variables, multiple analysis of variance test was used for independent samples and Chi-square and Fisher's exact tests for qualitative variables. A P < 0.05 (or 5%) was considered statistically significant.

The sample size was calculated using OpenEpi software (opensource.org, version 3.03a, Emory University, Atlanta, USA), and 30 patients in each group would be required to identify a significant difference in analgesic consumption between the groups, with a probability of type-I error equal to 0.05 and 84% power.

RESULTS

This study included thirty patients in each examined group. All the patients completed the study. The patient demographic data (age and weight) showed a nonsignificant difference in the three groups and so did the duration of the surgery [Table 1].

Table 1.

Patient demographic data and duration of surgery

The onset of sensory block was 16.3 ± 0.6 min in Group I whereas 12.9 ± 0.3 min in Group II and 12.3 ± 0.6 min in Group III. The onset was significantly shorter in Groups II and III compared to Group I (P = 0.012) with nonsignificant difference between each other (P > 0.05) [Table 2]. Also, the onset of motor block was 19.1 ± 0.01 min in Group I whereas 15 ± 0.1 min in Group II and 15.1 ± 0.04 min in Group III. The onset of motor block was significantly shorter in Groups II and III compared to Group I (P = 0.008) with nonsignificant difference between each other (P > 0.05) [Table 2].

Table 2.

Onset of sensory and motor block (min)

The block was successful in 29 cases in Group I whereas thirty cases in Groups II and III [Table 3].

Table 3.

Success rate in different groups

The duration of sensory block was significantly shorter in Group I (360.5 ± 14.1 min) compared to either Group II (412 ± 12.3 min) or Group III (444.5 ± 16.1 min) (P = 0.001) while it was nonsignificantly longer in Group III compared to Group II (444.5 ± 16.1 vs. 412 ± 12.3 min) (P > 0.05) [Table 4].

Table 4.

Duration of sensory and motor block (min)

The duration of motor block was significantly shorter in Group I (295.6 ± 25.5 min) compared to either Group II (350.3 ± 28.1 min) or Group III (370 ± 22.3 min) (P = 0.001) [Table 4]. The duration of motor block was nonsignificantly longer in Group III compared to Group II (P > 0.05) [Table 4].

As regard to intra- or post-operative hemodynamic changes, there were no significant changes at all the studied times and no patients developed any hypotension, hypertension, or bradycardia [Tables 5 and 6].

Table 5.

Intraoperative hemodynamic changes

Table 6.

Postoperative hemodynamic changes

As regard to intraoperative quality of anesthesia, it was comparable in the three studied groups with none of the patients required any sedation or analgesia with good patient and surgeon satisfaction.

The time to first analgesia was significantly shorter in Group I (6.9 ± 2.7 h) compared to either Group II (8.5 ± 6.4 h) or Group III (9.9 ± 4.4 h) (P < 0.001) while it was nonsignificantly longer in Group III compared to Group II (9.9 ± 4.4 vs. 8.5 ± 6.4 h) (P > 0.05) [Table 7].

Table 7.

Time to first analgesic and analgesic consumption

The analgesic consumption was significantly higher in Group I compared to either Group II or III (9.8 ± 2.2 mg morphine in Group I vs. 6.1 ± 0.5 mg morphine in Group II and 5.71 ± 0.8 mg morphine in Group III) (P = 0.001) and there was no significant difference between Group II and III (P > 0.05) [Table 7].

There was no significant difference between the three studied groups as regard to complications with self-limited nausea in one patient in Group I and two patients in Group II. No pain or swelling at the injection sites and no neurologic motor or sensory complications (motor paralysis, paresis, or paresthesia) were observed in any group.

DISCUSSION

In this study, it was found that the use of cold bupivacaine 0.5% and 150 mg MgSo₄ added to normal temperature bupivacaine 0.5% for sonar-guided combined femoral and sciatic nerve block in arthroscopic knee surgery resulted in good intra- and post-operative analgesia. The quality of both anesthesia and analgesia, which was studied in this, work included the onset of both sensory and motor block, intraoperative anesthesia, intra- and post-operative hemodynamic changes, duration of sensory and motor block, patient numeric rating scale for pain assessment, time of first analgesic request, consumption of analgesics, and incidence of possible side effects of both technique and drugs used.

In this study, we have rapid onset of both sensory and motor block in both groups as compared to control group with nonsignificant difference between each other.

As regards to the quality of anesthesia in all groups, there was good anesthetic condition as none of the patients required either midazolam or fentanyl supplements with stable hemodynamic changes and good patient and surgeon satisfaction.

In this work, we have used a multimodal approach to have high success rate and increase the quality of the nerve block with highest intra- and post-operative analgesia. This approach included the use of sonar-guided nerve block, use of combined femoral and sciatic nerve block with resultant analgesia of both anterior and posterior knee sides, and use of either cold bupivacaine or additive of MgSo₄ to normal temperature bupivacaine. The use of ultrasound facilitates accurate needle placement and drug delivery is the key to achieve success in nerve blocks with resultant more rapid block onset, lesser complications due to intravascular or intraneural injection of the local anesthetic,[5,6] prolonged block duration,[7] with the added advantages of a decrease in drug dosage and a reduction in the incidence of local anesthetic toxicity.[8,9] Reduction in procedural pain and better patient satisfaction has also been demonstrated with ultrasound-guided nerve block.[10]

The onset time in the three studied groups was more rapid than the study of Beaulieu et al., in which the onset time ranged between 18 and 22 min for sensory and between 25 and 28 min for motor block.[11]

The use of cold bupivacaine in Group II resulted in a rapid onset of both sensory and motor block, adequate quality of anesthesia, and longer duration of the combined femoral and sciatic nerve block with good postoperative analgesia manifested by long time to first analgesic and lower analgesic consumption.

This is in agreement with previous results which revealed that cooling of local anesthetic to 4°C resulted in increasing its potency with rapid onset and longer duration of anesthesia. Dabarakis et al.[12] found that the decrease of temperature of plain mepivacaine to 4°C shortened the onset and prolonged the duration of analgesia during pulpal anesthesia. Also, in another study, the effect of lidocaine in blocking nerve impulse was potentiated both in vitro and in vivo by cooling.[13,14,15,16] Another study by Butterworth et al. found that cooling potentiated lidocaine inhibition of median nerve sensory fibers.[2] Goto and Itano[17] and other researchers[18,19] have proved that the increased pKa of lidocaine at low temperature resulted in increased amount of ionized form of lidocaine which has more powerful inhibitors of the Na⁺ channel with more potent anesthesia.

On the contrary, studies with local anesthetics suggest that warming at 37°C makes the onset significantly faster.[20,21]

The postoperative analgesic properties in both cold bupivacaine and Mg groups were better than control group. This included the prolonged time to first analgesic, the longer analgesic and motor duration and the smaller amount of analgesic consumed.

The analgesic benefit observed in Mg group is consistent with that reported by Gunduz et al.[22] and Lee et al.[23] who investigated the effect of perineural or systemic Mg on the duration of axillary plexus and interscalene block. Also, Ekmekci et al.[24] found a good beneficial effect of Mg added to levobupivacaine for femoral nerve block on postoperative analgesia in patients undergoing ACL reconstruction.

On the other hand, Lee et al.[23] found that the addition of Mg to bupivacaine and epinephrine in interscalene brachial plexus block increased the analgesic duration but without decreasing the postoperative analgesic consumption. Systemic,[25] neuraxial[26] administration of Mg, or its use for peripheral nerve block (PNB)[22] is associated with a reduced analgesic requirement and less discomfort in the postoperative period. This analgesia is produced by a mechanism of action which is not clear. The antagonism of the NMDA receptors leading to loss of central sensitization from peripheral painful stimulation and decrease in tissue injury painful sensation can explain the analgesic effect of systemic and neuraxial Mg administration. For action of Mg, during PNB, another mechanism is involved. This mechanism is the theory of surface charge in which external Mg concentration bathing a nerve bundle resulted in enhancement of the nerve blockade due to local anesthetics.[27] Also, a high concentration of divalent ions (Mg²⁺ and Ca²⁺) attracted by the negative charges of the outer membrane surface affected Na⁺ channel gating and could cause hyperpolarization during which it is more difficult to achieve the threshold level, and it results in nerve conduction block.[28,29]

In this study, none of the patients had any complications related to the drugs or the technique either intraoperative or postoperative. This is in agreement with the work of Zaric et al.[30] who found very low side effects in PNB group compared to epidural group; Fowler et al.[31] who observed that continuous 3-in-1block induces nearly 4 times fewer side effects than epidural analgesia; Kumar et al.[32] reported that PNB may provide effective unilateral analgesia with lower incidence of opioid-related and autonomic side effects and fewer serious neurological complication compared with epidural analgesia; and Kumar et al.[32] also found no complication intraoperative or postoperative.

The safety of perineural adjuvants has recently been the subject of debate that centers on the potential for neurotoxicity of the adjuvant drug itself or any co-administered preservatives.[33]

To the best of our knowledge, no studies had compared cold bupivacaine to 4°C 0.5% with MgSo₄ added to room temperature bupivacaine (20–25°C) for sonar guided combined femoral and sciatic nerve block. In this study, we tried to use only cold bupivacaine to 4°C alone without additives and test its efficacy for both anesthesia and postoperative analgesia. Our results should be considered in light of several limitations including the need of larger number of patients, different types of surgeries, another types and techniques of nerve block, and the lack of data on patient feedback; all these are needed to mitigate the shortcomings of this study.

CONCLUSIONS

From this study, it can be concluded that either cold bupivacaine to 4°C or Mg sulfate 150 mg added to room temperature bupivacaine injected for sonar-guided combined femoral and sciatic nerve block during arthroscopic ACL reconstruction surgery succeeded comparably in having a good quality of intraoperative anesthesia with regard to sensory and motor block with good patient and surgeon satisfaction.

Good postoperative analgesia manifested by longer time of first analgesia request, lower total analgesic consumption, and minimal self-limited side effects was obtained in both groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.