Levobupivacaine versus Levobupivacaine Plus Dexmedetomidine in Transversus Abdominis Plane Block in Patients Undergoing Abdominal Aortic Surgery.

Background: Severe postoperative pain is a major dilemma for patients undergoing abdominal aortic surgery. Transversus abdominis plane (TAP) block has been described a successful pain management technique after major abdominal surgery. Dexmedetomidine was proved to enhance the analgesic action of local anesthetics. Aim: This study was aimed to assess the impact of adding dexmedetomidine to levobupivacaine during TAP block in patients undergoing abdominal aortic operations. Patients and
Methods: We included 114 patients in this prospective trial, and they were enrolled into two groups; the L group received levobupivacaine only, and the LD group received levobupivacaine plus dexmedetomidine. The block was performed before anesthetic induction. Postoperative pain score was our main outcome. Statistical Analysis: The collected data were tabulated and analyzed through the SPSS software program IBM's Statistical Package for the Social Sciences (SPSS) statistics for Windows (version 25, 2017) (IBM Corporation, Armonk, NY, USA). The categorical data were expressed as numbers and percentages and then compared using the Chi-square test. The continuous data were expressed as mean and standard deviation if normally distributed, or median and range if abnormally distributed. The former data were compared through the one-way ANOVA, while the latter were compared through the Kruskal-Wallis test. Any P < 0.05 was considered statistically significant.
Results: Group LD showed significantly earlier sensory blocks compared to the other group. Postoperative pain scores were comparable between the two groups for the initial 4 h following the surgery. Adjuvant dexmedetomidine was associated with better pain scores for the subsequent 12 h compared to Group L. The duration till the first analgesic request showed a significant increase in the LD group (13.3 vs. 11.09 h in Group L). In addition, the same group showed a significant decline in their opioid consumption after the operation (48.95 μg vs. 72.63 μg in the other group). Postoperative nausea and vomiting were significantly increased in Group L.
Conclusion: Adjuvant dexmedetomidine has a significant beneficial impact on postoperative analgesic profile. Its use as an adjuvant to peripheral and neuraxial nerve blocks should be recommended in pain management practice. Copyright:

INTRODUCTION

Abdominal aortic surgery is one of the major surgeries frequently encountered in the vascular surgical practice.[12] This operation, especially when performed through the open approach, is often associated with severe postoperative pain, which has negative consequences on patient recovery, hemodynamics, mobility, and overall satisfaction.[123]

Although epidural analgesia is still considered the best technique for pain management after such operations,[1] it could be associated with some complications such as hematoma and hemodynamic instability.[4]

Transversus abdominis plane (TAP) block has emerged as an effective pain management modality in patients undergoing major and minor abdominal surgery, either through the open or minimally invasive approaches.[5678] This technique provides an adequate sensory block for the abdominal wall through blocking the supplying nerves running in the neurovascular plane between the internal oblique and transversus abdominis muscles.[910] Most anesthesiologists and pain management physicians prefer to perform that block type as a part of the multimodal approach when managing pain in patients undergoing abdominal operations.[1112]

Clonidine and dexmedetomidine, alpha-2-adrenergic agonists, have been widely used for analgesia and sedation during different surgical procedures.[13] However, dexmedetomidine is highly specific for alpha-2 receptors.[14] If this medication was commenced as an adjuvant, it decreased the stress response related to anesthesia and surgery with no adverse events on hemodynamics or respiratory function.[15] Moreover, its administration beside local anesthetic agents enhances their efficacy, increases their duration of analgesia, and decreases postoperative rescue analgesic needs.[1617]

The addition of this adjuvant to the local anesthetic agent would prolong its action, decrease the need for cumulative doses, and thus, decrease the risk of systemic toxicity.[1819]

Although multiple reports have confirmed the efficacy of TAP block in achieving analgesia in patients following abdominal aortic surgery,[2021] there is a paucity of trials evaluating the role of dexmedetomidine as an adjuvant in such cases. Therefore, herein, we conducted the current investigation to elucidate the beneficial impact of adjuvant dexmedetomidine during TAP block in patients scheduled for abdominal aortic operations.

PATIENTS AND METHODS

After obtaining the approval from the Institutional Review Board and the Local Scientific Committee of Mansoura University with Reference Number R.22.03.1653 at March 27, 2022. We conducted this prospective randomized trial for patients aged between 20 and 50 years, scheduled for abdominal aortic surgery under general anesthesia. We included patients classified as Class I or II according to the American Society of Anesthesiologists (ASA) classification.[22] Patients with a higher class, uncontrolled systemic comorbidities, bleeding diathesis, psychiatric disorder, drug abuse, or chronic pain syndromes were excluded from our investigation.

The required sample size was estimated using the PASS Statistical Package for the Social Sciences (SPSS) statistics for Windows (version 25, 2017) (IBM corporation, Armonk, NY, USA). We considered that 6-h pain score was our primary outcome. The null hypothesis supposed the absence of superiority when dexmedetomidine was added to levobupivacaine during TAP block. Fifty-one patients were needed in each group to achieve an 80% power and a 5% effect size. As we expected six patients to drop out in each group, we finally decided to include 57 patients in each study group (total sample size = 114 cases).

All patients signed informed consent before the operation after explaining its benefits and risks. They also received the standard preoperative workup, including detailed history taking, clinical assessment, electrocardiography (ECG), and routine laboratory workup.

The included participants were randomly allocated into two groups; Group L included 57 patients who received the TAP block procedure using isobaric levobupivacaine 0.5% only (1 mg.kg−1 in a 20-mL volume), and Group LD included the remaining participants who received the same block using the same levobupivacaine dose and volume with adding dexmedetomidine as an adjuvant (10 μg). This randomization was done through the “sealed envelope method.” No one in the operative room was aware of the randomization code, making our study blind in nature.

On the operation day, the patients were transferred to the operative theater, where a peripheral cannula was inserted in a suitable forearm vein. All patients received intravenous (i.v.) midazolam 5 mg to decrease their anxiety. Routine hemodynamic monitoring was connected, including ECG, pulse oximetry, heart rate, and noninvasive blood pressure.

The TAP block procedure was done before the induction of general anesthesia. It was performed under ultrasound guidance using Toshiba Xario machine with its superficial transducer. Under aseptic conditions, the probe was placed longitudinally between the lower costal margin and the iliac crest. The three main muscle layers of the anterior abdominal wall were identified (external oblique, internal oblique, and transversus abdominis muscles from superficial to deep, respectively). A sonovisible needle was inserted till reaching the plane between the latter two muscles, and the prepared injectate was installed. Distension of the plane was noticed on ultrasound, indicating proper anesthetic installation. The procedure was also repeated on the opposite side through the same steps.

Abdominal wall sensation was tested through the pinprick test, and general anesthesia was induced after achieving the desired sensory block. Absent pinprick test discrimination for 15 min was considered “block failure,” and the patient was excluded from the study. The time to reach the sensory block was estimated and recorded in each group.

We induced general anesthesia by i.v. propofol 1–2 mg.kg−1, fentanyl 1 μg.kg−1, in addition to atracurium 0.5 mg.kg−1. Sevoflurane inhalation was used to maintain anesthesia at a minimal alveolar concentration of 2%. Continuous monitoring of hemodynamics was done throughout the procedure. Heart rate and mean arterial pressure (MAP) were recorded at baseline and then every 15 min till the operation ended. Hypotension, defined as systolic blood pressure decreased by 20% or more of its baseline value,[23] was managed by crystalloid infusion (5 mL.kg−1) and i.v. ephedrine (0.1 mg.kg−1). In addition, bradycardia, defined as heart rate below 50 bpm,[24] was managed by I.V. atropine (0.2–0.5 mg).

After the operation, patients were transferred to the postanesthesia care unit (PACU), then to the internal ward, where close monitoring and assessment were done. MAP and heart rates were also recorded every 15 min for 2 h after surgery. i.v. paracetamol (1 g. 8 h−1) and ketorolac (30 mg. 12 h−1) were commenced for all patients. They were instructed to express their pain through the Visual Analog Score (VAS), with 0 for no pain and 10 for the maximum pain sensation ever experienced.[25] These readings were recorded at PACU, then every 2 h for the initial 12 h after surgery, and finally at 16 and 24 h. If the patient reported a VAS of 4 or more, i.v. fentanyl 20–30 μg was commenced. The total postoperative opioid consumption was calculated and recorded. Any opioid-related adverse events, including respiratory depression, nausea, and vomiting, were noticed and recorded. The latter two complaints were managed by i.v. metoclopramide (10 mg).

Our primary outcome is postoperative pain scores but the secondary outcomes are hemodynamic changes, the time to sensory block, the time to the first analgesic request, postoperative opoid consumption and complication.

The collected data were tabulated and analyzed through the SPSS software program IBM's Statistical Package for the Social Sciences (SPSS) statistics for Windows (version 25, 2017) (IBM Corporation, Armonk, NY, USA). The categorical data were expressed as numbers and percentages and then compared using the Chi-square test. The continuous data were expressed as mean and standard deviation if normally distributed, or median and range if abnormally distributed. The former data were compared through the one-way ANOVA, while the latter were compared through the Kruskal–Wallis test. Any P < 0.05 was considered statistically significant.

RESULTS

General patient criteria were statistically comparable between our two study groups. Staring with age, it had mean values of 37.7 and 36.12 years in the L and LD groups, respectively. Regarding their gender, men constituted 64.9% and 75.4% of patients in the same two groups, respectively. The remaining percentage was occupied by women. Patients with ASA Class I formed 61.4% and 63.2% of cases in the same study groups, respectively. The rest of the cases had ASA Class II.

The time to sensory block was significantly earlier in Group LD (8.95 min vs. 11.05 min in Group L – P = 0.003). However, operative time showed no significant difference between the same groups (215.2 vs. 218.9 in Groups L and LD, respectively).

The incidence of opioid-related complications showed a significant increase in Group L. Nausea was reported in 29.8% and 10.5% of cases, whereas vomiting occurred in 12.3% and 1.8% of cases in the L and LD groups, respectively. Table 1 summarizes the previous data.

Table 1

Demographic criteria, time to sensory block, operative time, and opioid-related postoperative complications

	Group L (n=57), n (%)	Group LD (n=57), n (%)	95% CI/OR	P
Age (years)	37.70±7.312	36.12±7.018	−1.1-4.2	0.242
Sex
Male	37 (64.9)	43 (75.4)	-	0.219
Female	20 (35.1)	14 (24.6)
ASA
I	35 (61.4)	36 (63.2)	-	0.847
II	22 (38.6)	21 (36.8)
Time to sensory block (min)	11.05±3.627	8.95±3.748	0.74-3.47	0.003
Duration of surgery (min)	215.2±49.5	218.9±47.3	−21.6-14.3	0.722
Postoperative complications
Respiratory depression	0	0	1	1
Nausea	17 (29.8)	6 (10.5)	0.28	0.010
Vomiting	7 (12.3)	1 (1.8)	0.13	0.028

CI: Confidence interval, OR: Odds ratio, ASA: American Society of Anesthesiologists

Adjuvant dexmedetomidine administration was associated with lower heart rate readings during the surgical procedure in the LD group compared to the other one. This effect was also evident for 120 min after the surgical procedure [Figure 1].

Figure 1

Heart rate changes in the two study groups. PACU: Postanesthesia care unit

The LD group expressed lower MAP values throughout the surgical procedure when compared to Group L, and that persisted for 2 h following the operation [Figure 2].

Figure 2

MAP changes in the two study groups. PACU: Postanesthesia care unit, MAP: Mean arterial pressure

For the initial 4 h following the surgery, pain scores did not express significant differences between our two groups. However, adjuvant dexmedetomidine was associated with better pain scores for the subsequent 12 h compared to the L group (P < 0.05). That significance faded away at the last reading (24-h value). The previous data are summarized in Table 2.

Table 2

Visual Analog Score changes in the two study groups

VAS	Group L (n=57)	Group LD (n=57)	95% CI	P
PACU	0.84±0.702	0.91±0.576	−0.3-0.2	0.491
2 h	1.18±0.848	1.18±0.685	−0.3-0.3	0.886
4 h	1.74±0.917	1.40±0.863	0.0-0.7	0.067
6 h	2.46±1.036	1.91±0.912	0.2-0.9	0.008
8 h	3.32±1.003	2.63±1.046	0.3-1.1	0.002
10 h	4.02±1.009	3.18±1.104	0.4-1.2	<0.001
12 h	4.39±1.013	3.84±1.131	0.1-0.9	0.012
16 h	4.70±1.085	4.30±1.017	0.0-0.8	0.029
24 h	4.86±0.953	4.56±1.035	−0.1-0.7	0.190

VAS: Visual Analog Score, PACU: Postanesthesia care unit, CI: Confidence interval

The duration till the first analgesic request showed a significant increase in the LD group (13.3 vs. 11.09 h in the L group – P = 0.005) as mentioned in Table 3. In addition, the same group showed a significant decline in their opioid consumption after the operation (48.95 μg vs. 72.63 μg – P < 0.001).

Table 3

Postoperative analgesic profile in the two study groups

VAS	Group L (n=57)	Group LD (n=57)	95% CI	P
Timing of first rescue analgesia (h)	11.09±5.292	13.30±5.271	−4.2-−0.3	0.005
Total consumption of fentanyl in 24 h postoperatively (µg)	72.63±26.560	48.95±23.121	14.4−32.9	<0.001

CI: Confidence interval, VAS: Visual Analog Score

DISCUSSION

The current investigation was conducted to elucidate if using dexmedetomidine as an adjuvant to levobupivacaine would enhance the analgesic action of TAP block in patients undergoing abdominal aortic surgery.

Our study was randomized in nature, and this is evident when looking at our preoperative variables, which were statistically comparable between the two groups. This should negate any bias skewing our findings in favor of one group rather than the other.

First of all, we preferred to install the Levo form of bupivacaine instead of its racemic one because of its equal potency and superior safety profile. Even if systemic absorption has occurred, it is associated with a decreased risk of both cardio- and neurotoxicities.[26]

We noticed a significantly earlier onset of sensory block in the LD group. In the same context, other studies have reported that same impact but with epidural anesthesia. There was a significant shortening in the onset of sensory block in association with its administration.[2728]

Our findings showed better pain control in association with adjuvant dexmedetomidine. Although postoperative pain scores were comparable between the two groups for the initial 4 h following the surgery, adjuvant dexmedetomidine was associated with better pain scores for the subsequent 12 h compared to the L group.

The better analgesic profile obtained by adjuvant dexmedetomidine could be explained by its local vasoconstrictor action leading to decreased systemic absorption of the injected local anesthetic agent[29] or through direct inhibition of the peripheral nerves located in that plane.[30] This was supported by previous research, which noted a dose-dependent improvement of the analgesic profile when added to the local anesthetics in animals[31] and humans.[32]

Almarakbi and Kaki also reported that adjuvant dexmedetomidine was associated with a marked decrease in pain scores for the initial 8 h after surgery when compared to the group receiving the local anesthetic agent alone.[33] Other studies also confirmed the previous finding in different abdominal operations.[343536]

It is worth mentioning that dexmedetomidine also has additional mechanisms of analgesia when injected through the i.v. route. These effects are mediated through the spinal, supraspinal, ganglionic, and peripheral actions.[1437] Its analgesic actions are mediated through the hyperpolarization of interneurons and inhibition of nociceptive neurotransmitter release.[1338]

This point was emphasized by Gurajala et al., who noted a significant increase in patient sedation with the use of this adjuvant in brachial plexus block, suggesting its systemic absorption.[39] In a more recent study, El Sherif et al. reported that systemic absorption of dexmedetomidine was common in patients undergoing TAP blocks with this adjuvant in the injectate. Systemic amounts of this drug were detected in the sera of 11 out of the investigated 12 cases.[38]

Along with its local action, dexmedetomidine can be partially absorbed into the systemic circulation to enhance its analgesic actions through the previously mentioned systemic mechanisms. We think that more studies should be conducted to elucidate the pharmacokinetics of this medication when used as an adjuvant in different plane blocks.

The previously mentioned mechanism of systemic absorption could explain the decreased heart rate and MAP values in the LD group compared to the other one. This is mediated through the decreased sympathetic outflow secondary to presynaptic stimulation of adrenergic alpha-2 receptors.[40] One should also mention that these hemodynamic changes were subtle and within the normal reference ranges and were not associated with increased perioperative morbidity.

Owing to the better analgesic profile in Group LD, these patients showed a significant delay in the time to the first analgesic request compared to the other group. Furthermore, rescue analgesic consumption significantly declined in the same group. As a natural consequence, opioid-related side effects were decreased in the same group.

Another study confirmed the previous findings in hysterectomy patients. Patients who received dexmedetomidine as an adjuvant in the TAP block showed a longer time till the first analgesic request (470 min vs. 280 min in controls – P < 0.001).[33]

The current investigation has some limitations, including the relatively small sample size, which was gathered from a single institution. Furthermore, the impact of adjuvant administration on the incidence of chronic postsurgical pain should have been evaluated. These cons should be handled in the upcoming studies.

CONCLUSION

Adjuvant dexmedetomidine has a significant beneficial impact on postoperative analgesic profile. It enhances the analgesic action of TAP block leading to less pain, analgesic consumption, and opioid side effects. Its use as an adjuvant to peripheral and neuraxial nerve blocks should be recommended in pain management practice.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.