Dexmedetomidine as an Adjuvant to 0.25% Bupivacaine in Ultrasound Guided Femoral Nerve Block for Preoperative Positioning and Postoperative Analgesia in Patients Undergoing Elective Surgery for Fracture Shaft of Femur.

Background: Femur fracture causes excruciating pain and surgical repair is recommended. To obtain satisfactory patient co-operation in the perioperative period, various analgesics have been used. Femoral nerve block (FNB) provides an excellent alternative for analgesia in the perioperative period. Dexmedetomidine of up to 2 μg.kg-1 has been used in FNB as adjuvants in lower limb surgeries. Aims: The aim was to study the effect of addition of Dexmedetomidine to Bupivacaine in FNB on the comfort of positioning for subarachnoid block (SAB) and postoperative analgesia. Materials and
Methods: Prospective, randomized, double-blind design was followed. Seventy American Society of Anesthesiologist I and II patients aged 18-70 years of either gender were randomly allocated into Group B (20 mL 0.25% Bupivacaine + 2 mL Normal Saline) and Group BD (received 20 mL 0.25% Bupivacaine + Dexmedetomidine 2 μg.kg-1 diluted to 2 mL) for FNB. Numerical rating scale (NRS) was recorded before and after FNB and comfort of positioning graded. After 10 min, subarachnoid block (SAB) was administered. NRS was recorded postoperatively until 24 h.
Results: The comfort of positioning improved in both the groups after FNB but was statistically not significant when compared among the groups (P = 0.7). Duration of postoperative analgesia was significantly higher in the Group BD (741 min ± 97 min) compared to the Group B (440 min ± 45 min) (P = 0.001) and was statistically significant.
Conclusion: FNB improved the comfort of positioning for SAB, but the addition of Dexmedetomidine did not have any added advantages with respect to comfort of positioning. However, the addition of Dexmedetomidine significantly increased the duration of postoperative analgesia with minimal hemodynamic changes. Copyright:

INTRODUCTION

Femoral shaft fractures occur because of high-impact injury and need definitive surgery to correct the deformity.[123] Neuraxial blockade is the preferred mode of anesthetic technique compared to General Anesthesia (GA), but patients have excruciating pain for positioning for neuraxial block.[34] To obtain satisfactory patient comfort for positioning, various analgesic modalities such as midazolam, opioids, and ketamine are used.[2567] Femoral nerve block (FNB) provides an excellent alternative for analgesia in the perioperative period.[89] Conventionally, FNB was administered by landmark technique. After the advent of ultrasonography (USG), localization of the nerve has become easier and lesser doses of local anesthetic (LA) requirement.[10] Adjuvant drugs such as epinephrine, opioids, sodium bicarbonate, midazolam, and ketamine have been used to improve the duration of analgesia in perioperative period.[611] Dexmedetomidine is a newer α2 adrenergic agonist with anxiolytic, sedative, and analgesic properties with cardiovascular stability.[69] Its affinity for binding to the α2/α1 receptor is 1600:1 compared with 220:1 for clonidine.[11] Dexmedetomidine of up to 2 μg.kg−1 has been used in FNB for prolonging the duration of analgesia.[1112] However, there are minimal studies regarding the efficacy of Dexmedetomidine as an adjuvant to 0.25% Bupivacaine in FNB for comfort of positioning the patient for subarachnoid block (SAB) and postoperative analgesia in patients undergoing femur fracture surgery.

Objectives

Our primary objective is to assess patient comfort for positioning for spinal anesthesia

Secondary objective is:

To assess the duration of postoperative analgesia

To note the onset, duration, level of sensory block and motor block after SAB

Hemodynamic parameters any adverse effects.

MATERIALS AND METHODS

After institutional ethical committee approval (No. VIMS/STD. II/PG-EC/18/2018-19), Clinical Trial Registry of India (CTRI) registration (CTRI/2020/07/026467), and written informed consent from the patient, a double-blind, randomized, prospective clinical study was planned.

Expecting a 25% increase in the mean value for comfort of positioning from previous study, a confidence interval of 95%, and power of 80%, the sample size was calculated to be 31 in each group. Considering the dropout rate of 10%, the sample size is rounded to 35 patients in each group.

Seventy patients of American Society of Anesthesiologist (ASA) physical status Classes I and II, aged 18–70 years undergoing elective femur shaft fracture surgeries were enrolled for the study over a period of 2 years.

Patients with known allergy to LAs, peripheral neuropathy, coagulopathy, infection at the site of block, severe uncontrolled medical and psychiatric comorbidities were excluded from the study.

On the preoperative day, preanesthetic evaluation was performed, and the patient was counseled and familiarized regarding the Numerical Rating Scale (NRS) Figure 1. Patients were kept Nil Per Oral according to the Indian Society of Anesthesiologist guidelines.

Figure 1

Numerical rating scale

Patients were randomly divided into two groups (Group B and Group BD) based on the sequentially numbered, opaque, sealed envelope technique. A sealed envelope was randomly selected and opened by an assistant, with instructions to load the relevant drug. The syringe labeled with the patient name was handed over to the investigator, who performed the block. An independent observer (duty anesthesiologist, not included in the study) then observed the comfort of positioning; onset, level, duration of sensory and motor block after SAB; pain score; sedation score; hemodynamic parameter; and adverse events during the perioperative period until the end of the study. Blinding was opened at the end of the study.

On the day of surgery, after shifting the patients to the operative room, wide bore intravenous (i.v.) cannula was secured and i.v. fluid was started. Patients were connected to ASA standard monitors. Baseline values of noninvasive blood pressure, heart rate, ECG, SpO2 was recorded, and patients were assessed for NRS Scale.

Based on the groups allotted, patients in Group B received ultrasound-guided FNB with 20 mL of 0.25% Bupivacaine + 2 mL NS and Group BD received ultrasound-guided FNB with 20 mL of 0.25% Bupivacaine + 2 μg.kg−1 of Dexmedetomidine diluted to 2 mL before SAB in the operative room.

With the patient in a supine position, skin over the femoral crease was disinfected. The procedure was performed using MicroMaxx SonoSite™ ultrasound machine with a 38 mm linear probe of 6–13 MHz, the probe was placed transversely over the femoral crease. Femoral nerve was identified as a hyperechoic structure covered by fascia iliaca, located lateral to the femoral artery below the inguinal crease as shown in Figure 2. Once the femoral nerve is identified, a skin wheal of LA is made 1 cm away from the lateral edge of the transducer. The needle is inserted in-plane approach from lateral to medial direction using 20G 100 mm Locoplex needle and advanced toward the femoral nerve until the tip of the needle is visualized adjacent to the nerve.

Figure 2

Ultrasound image of the femoral region depicting femoral vein, femoral artery and femoral nerve from medial to lateral

After negative aspiration, and confirmation of needle placement with an initial 2 mL of LA injection, graded aliquots of LA is injected in the perineural space.

After performing USG-guided FNB, patients were assessed upto 10 min using NRS and comfort of positioning for the administration of SAB was graded.

After 10 min, patients in both groups were put into a sitting position and received SAB at L3-L4 space with 0.5% heavy Bupivacaine 15 mg using 25G Quincke needle. Patients who were not comfortable or required i.v. analgesic for positioning were excluded from the study.

Patients were monitored during the perioperative period for onset, level, and duration of sensory and motor block of SAB.

Postoperatively, patients were monitored every 2 h. Until 24 h for pain relief using NRS, rescue analgesia with injection diclofenac sodium 75 mg i.v. was administered when NRS >4 and time of administration of rescue analgesia were noted.

Sedation scores were assessed using Ramsay sedation score.

Hemodynamic parameters and any adverse effects (nausea, vomiting, bradycardia, and hypotension) were observed till the end of the study.

Comfort of positioning for subarachnoid block

Grade 0: Significant pain (NRS >7)*

Grade 1: Comfortable with tolerable pain (4–6). No i.v. analgesia needed

Grade 2: Fully comfortable (NRS <3).

Duration of analgesia is the time taken from the completion of injection of the drug for FNB till the patient requests for rescue analgesic in postoperative period.

The onset of sensory block is the time from the completion of injection of the drug for SAB till the patient does not feel pinprick at L1 dermatome.

Duration of sensory block is the time from the completion of injection of the drug for SAB till the patient feels sensation for pinprick at S1 dermatome.

The maximum level of sensory block is the time from the completion of injection of the drug for SAB till the maximum sensory block is attained.

The onset of motor block is the time from the completion of the drug for SAB till the patient develops modified Bromage score ≤4.

Duration of motor block is the time from the completion of the drug for SAB till the patient develops modified Bromage score ≥5.

Modified Bromage scale

Complete block (unable to move feet or knees)

Almost complete block (Able to move feet only)

Partial block (just able to move knees)

Detectable weakness of hip flexion (between scores 3 and 5)

No detectable weakness of hip flexion while supine (full flexion of knees)

Able to perform partial knee bend.

All the data related to the variables of the study were collected, entered into an MS Excel sheet, and data were analyzed using IBM SPSS statistics for windows, v22.0. Armonk, NY, USA: IBM Corp. P < 0.05 was considered significant. Student's t-test and Chi-square test was used

RESULTS

The total number of patients included in the study was 70. The Consolidated Standards of Reporting Trials diagram is represented in Figure 3.

Figure 3

Consolidated Standard of Reporting Trials (CONSORT) flowchart representing enrollment, allocation, and analysis of the participants

The demographic data such as age, gender, height, weight, and ASA Status in both the groups were comparable and were not significant statistically [Table 1].

Table 1

Demographic data of Group BD and Group B

Demographic data	Group BD	Group B	P
Age (years)	38.2±13.5	38.7±14.3	0.885
Weight (kg)	62.4±6.2	62.5±6.1	0.969
Height (cm)	164.7±6.7	165.2±4.6	0.694
Gender (male/female)	27/8	28/7	0.771
ASA status (I/II)	27/8	28/7	0.771

ASA=American Society of Anesthesiologist

NRS in Group B before and after administration of FNB was 7.5 ± 1.2 and 1.5 ± 1.4 respectively (P = 0.013). NRS Scale in Group BD before and after administration of FNB was 7.3 ± 1.1 and 1.6 ± 1.2, respectively (P = 0.005), which is statistically significant [Table 2].

Table 2

Numerical rating scale before and after femoral nerve block

	Group BD	Group B	P
NRS before FNB	7.5±1.2	7.3±1.1	0.5
NRS after FNB	1.5±1.4	1.6±1.2	0.7
P	0.005	0.013

NRS=Numerical Rating Scale, FNB=Femoral Nerve Block

P value between Group B and Group BD before administration of FNB is 0.403 and P value between the groups after administration of FNB is 0.721 which is not statistically significant.

After administration of FNB, 30 out of 35 patients in Group B were comfortable and 31 out of 35 patients Group BD were comfortable for positioning for SAB [Table 3].

Table 3

Comfort of positioning for subarachnoid block

	Comfort before FNB	Comfort after FNB
Group BD
Grade 0	28	0
Grade 1	7	4
Grade 2	0	31
Group B
Grade 0	25	0
Grade 1	10	5
Grade 2	0	30
P	0.403	0.721

FNB=Femoral Nerve Block

The duration of postoperative analgesia was 741.1 ± 97 min in Group BD and 440.7 ± 45.5 min in Group B with a P < 0.001 which was statistically significant [Table 4 and Figure 4].

Table 4

Duration of postoperative analgesia

Duration	Group BD	Group B	P
Analgesia (min)	741.1±97	440.7±45.5	<0.001

Figure 4

Graph depicting duration of postoperative analgesia

Other secondary objectives such as onset, level, and duration of sensory and motor block in both groups were also comparable and statistically no significant difference was observed between the groups [Table 5]. Hemodynamic parameter and any adverse effects of both groups were comparable.

Table 5

Secondary objectives (sensory level, motor level, and postoperative complications)

Anesthetic data	Group BD	Group B	P
Sensory blockade
Onset
1 min	29	27	0.55
2 min	6	8
Maximum level
T4	23	23	0.336
T6	10	10
T8	2	0
Duration (min)	232.4±10.5	227.4±14.9	0.112
Motor block
Onset
1 min	26	24	0.597
2 min	9	11
Maximum level
Bromage 1	33	30	0.232
Bromage 2	2	5
Duration (min)	204±11.6	200.3±11.8	0.188
Postoperative complications
Hypotension	1	1	-
Nausea	1	1
Sedation	2	0

DISCUSSION

In the present era of trauma, patients with a shaft of femur fracture are routinely encountered in the emergency ward. Patients are observed to have severe pain, which causes spasms of thigh muscles, leading to the displacement of fracture segment.[713] Such patients require surgery to provide immobilization and prevent the displacement of fracture fragments.[12310]

Central neuraxial blockade is the preferred anesthetic technique of choice over GA in orthopedics for lower limb fractures.[123] While regional anesthesia is beneficial, patient positioning for neuraxial blockade may cause severe pain in patients with femur fractures. Various analgesic modalities are advocated to provide pain relief for positioning in these patients.[2456710] Among the systemic analgesics, opioids are widely used, but they are associated with side effects such as vomiting, urinary retention, and respiratory depression, especially in the elderly.[313] 3 in 1 block, FNB and fascia iliaca compartment block have all been recently used for providing pain relief and improving patient positioning for central neuraaxial blockade.[4610]

Bupivacaine is used as LA for peripheral nerve blocks for lower limb surgeries in the concentration of 0.25%–0.5%.[11114] Various adjuvants to LAs have been tried such as epinephrine, midazolam, ketamine, clonidine, and opioids to prolong the duration of action, but with limited success due to adverse effects.[61516]

Dexmedetomidine being a newer α2 agonist has been shown to prolong the duration of peripheral nerve blocks. Perineural Dexmedetomidine acts by blockade of the hyperpolarization-activated cation current (Ih), which alters the resting membrane potential.[17] This effect seems to be more pronounced in the unmyelinated C fibers (pain), thereby producing analgesia.[18] There is limited study on the dose of Dexmedetomidine used for FNB s in lower limb surgeries and doses of up to 2 μg.kg−1 have been tried.[612]

Here, we hypothesized that the addition of Dexmedetomidine 2 μg.kg−1 to 0.25% Bupivacaine in FNB would provide a superior level of comfort for positioning for SAB and increase the duration of postoperative analgesia.

In our study, there was no significant difference between the Group B and Group BD, regarding the age, gender, height and weight, ASA status of the patients, and mean duration of surgery.

In our study, the mean NRS Scale in Group B before administration of FNB is 7.3 ± 1.1 and after administration of FNB is 1.6 ± 1.2 (P = 0.013) which is statistically significant. The mean NRS Scale of Group BD before administration of FNB is 7.5 ± 1.2 and after administration of FNB is 1.5 ± 1.4 (P = 0.0005) which is statistically significant.

P value between Group B and Group BD before administration of FNB is 0.5 and P value between the groups after administration of FNB is 0.7 which is not statistically significant.

After administration of FNB, 30 out of 35 patients in Group B were comfortable and 31 out of 35 patients Group BD were comfortable when compared with before administration of block, where none of the patients in both groups were comfortable for positioning for SAB.

A similar study conducted by Natarajan P et al.,[1] who compared 0.2% Bupivacaine to 0.2% Ropivacaine for FNB, concluded that the mean visual analog scale for positioning for SAB were significantly lower in Bupivacaine group compared to Ropivacaine group and that Bupivacaine group had better comfort of positioning.

Our study also compares with Jadon et al.[4] and Sia et al.[7] who compared FNB to IV Fentanyl and concluded that FNB provided superior comfort of positioning for SAB compared to the fentanyl group.

In our study, the mean duration of analgesia in Group B was 440.7 ± 45.5 min and Group BD was 741.1 ± 97 min, which is significantly higher in Group BD compared to Group B (P < 0.001).

Our study compares with a study conducted by Packiasabapathy et al.[11] who compared 1 μg.kg−1 and 2 μg.kg−1 of Dexmedetomidine to plain 0.25% Bupivacaine. They found a significantly prolonged duration of analgesia in the group with 2 μg.kg−1 (duration 6.66 ± 1.27 h) compared to the group with 1 μg.kg−1 (duration 5.70 ± 1.30 h) and plain Bupivacaine group (duration 4.55 ± 1.47 h).

Our study compares with another study conducted by Abdulatif et al.[14] who compared 25, 50, and 75 μg Dexmedetomidine with Bupivacaine to Control group (plain Bupivacaine). They observed statistically significant prolonged duration of analgesia with 75 μg group (duration 28.6 ± 10 h) compared to 50 μg group (duration 21.8 ± 3 h), 25 μg group (duration 11.0 ± 7.1 h), and plain Bupivacaine group (duration 10.8 ± 1.6 h).

Other secondary objective parameters such as onset, duration, level of sensory, and motor block in our study are comparable between the groups, and no statistical significance was found.

In our study, hemodynamic parameters such as heart rate, systolic BP, diastolic BP, mean arterial pressure, and SpO2 were comparable between the groups and was not statistically significant, which was comparable to other similar studies.[11]

Out of 35 patients, 2 patients in Group BD developed sedation according to Ramsay sedation score and none of the patients in Group B developed sedation, which was comparable and statistically insignificant.

CONCLUSION

FNB is an effective method to alleviate pain prior to positioning for SAB, but the addition of Dexmedetomidine at a dose of 2 μg.kg−1 as an adjunct to 0.25% Bupivacaine did not have added advantage in providing the comfort of positioning.

The addition of Dexmedetomidine as an adjuvant in FNB enhanced the duration of postoperative analgesia with minimum hemodynamic changes. We also observed that Dexmedetomidine as an adjuvant to 0.25% Bupivacaine in FNB did not alter the onset, level, and duration of motor or sensory block.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.