Levobupivacaine versus Levobupivacaine-Dexmedetomidine in Thoracic Paravertebral Block for Laparoscopic Sympathectomy.

BACKGROUND: Thoracic paravertebral block (TPVB) is a high-quality analgesic technique used for many types of surgery, trauma, and chronic pain. AIM: The aim of this study is to assess safety and efficacy of adding dexmedetomidine to levobupivacaine in TPVB for postoperative analgesia after unilateral laparoscopic thoracic sympathectomy. PATIENTS AND METHODS: Sixty adult patients of the American Society of Anesthesiologists physical status classes I and II, aged 20-45 years, of either sex, submitted for unilateral laparoscopic thoracic sympathectomy under general anesthesia at Mansoura University Hospital. Patients were classified into two groups such as levobupivacaine (GL): patients received isobaric 0.5% levobupivacaine 1 mg/kg in 20-ml volume for TPVB and levobupivacaine-dexmedetomidine (GLD): patients received isobaric 0.5% levobupivacaine 1 mg/kg and 10-μg dexmedetomidine in 20 ml volume for TPVB. STATISTICAL ANALYSIS: Data were first tested for normality by Kolmogorov-Smirnov test. Normally distributed continuous data were analyzed using unpaired Student's t-test. Nonnormally distributed continuous and ordinal data were analyzed using Mann-Whitney U-test. Categorical data were analyzed by Chi-square test or Fisher's exact test as appropriate.
RESULTS: A faster onset and longer duration of sensory blockade was significantly higher in group GLD with mean ± standard deviation (SD) (8.57 ± 7.22 min and 11.98 ± 1.42 h) than in group GL (15.21 ± 4.35 min and 9.75 ± 3.29 h). Sensory block regression time was significantly longer in group GLD with mean ± SD (10.8 ± 2.31 h) compared to group GL (8.82 ± 1.71 h). Furthermore, a significant reduction in visual analog scale occurred in group GLD compared with the GL group up to 24 h postoperatively (P < 0.05). No significant difference in Ramsay Sedation Scale (RSS) between both groups. The number of patients asked for postoperative analgesia was significantly fewer in group GLD compared with group GL (14 compared to 21)*. The time (hours) of first request for analgesia was significantly longer in group GLD compared with GL group (7.8 ± 3.22 compared to 9.7 ± 2.51*). The total postoperative fentanyl requirements in 24 h (in micrograms) was significantly less in GLD group compared to GL group (320 ± 110 compared to 190 ± 120*).
CONCLUSION: The addition of dexmedetomidine as adjuvant to levobupivacaine in TPVB for elective unilateral laparoscopic thoracic sympathectomy can markedly improve the postoperative analgesia with lower pain scores and a marked reduction of the postoperative analgesic requirements and low side effect profile.

INTRODUCTION

There is no doubt that pain management in the postoperative period is essential due to ethical and humanitarian reasons. Moreover, adequate pain management may shorten the duration of hospital stay with less economic burden,[1] especially during thoracic procedures.

In fact, pain originating from skin and muscle incision together with rib spreading is conducted through the intercostal nerves. On the other hand, painful stimuli arising from the mediastinum and diaphragmatic pleura are conducted through the phrenic and vagus nerves as well as the brachial plexus.[2]

Pain after sympathectomy is considerable, and restriction of the chest movement is frequently observed. Successful acute postoperative pain management remains challenging and if not adequately controlled may increase the likelihood of subsequent chronic pain in the operative area, movement restriction, and postoperative nausea and vomiting.[3]

General anesthesia (GA) alone is not sufficient for postoperative pain control due to the incision. Furthermore, GA (with exception of large doses of opioid) does not eliminate the surgical stress response and may cause unwanted side effects such as nausea and vomiting.[4] The administration of opioids in these cases further worsens the situation with prolonged recovery time and hospital stay with more costs.[5]

As a result of this problem, many regional anesthetic techniques for thoracic surgery have been implemented including local anesthetic (LA) infiltration, epidural anesthesia, intercostal nerve block, paravertebral block, and brachial plexus block.[6]

Thoracic paravertebral block (TPVB) can provide high quality of analgesia which can be used in many types of surgery and also for patients with trauma and chronic pain in the thoracic region. There is a debate on the efficacy of unilateral TPVB assuming that it is not effective for midline surgeries. Bilateral TPVB has been used successfully in the thoracic, abdominal, and pelvic surgeries. Paravertebral analgesia is produced by installation of LA in the paravertebral space close to the exiting spinal intercostal nerves.[7] Recently, TPVB is performed under sonographic guidance either with transverse approach or using the paramedian longitudinal view.[8]

Many drugs had been used as an adjuvant to LAs in paravertebral block such as dexmedetomidine (Precedex). It has LA-like properties. Moreover, it acts by inhibitory neuronal actions on α2-adrenoceptor decreasing sympathetic tone with attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery decreasing the anesthetic and opioid requirements.[9]

We hypothesize that adding dexmedetomidine to levobupivacaine in TPVB can promote a more effective analgesia than levobupivacaine alone.

PATIENTS AND METHODS

After approval of the Institutional Review Board (IRB) of anesthesia and surgical intensive care department (IRB number R/16-5-101) on 6/6/2016, this prospective, randomized, double-blinded study was conducted on patients of the American Society of Anesthesiologists (ASA) I–II, aged 20–45 years, scheduled for unilateral thoracic sympathectomy under GA from May to December 2016. The duration of the study is approximately 8 months. Paravertebral block for postoperative analgesia was performed for all patients after written informed consent from them. This randomized controlled trial based on the revised CONSORT statement.[10]

Randomization was achieved through sealed opaque envelops to avoid bias. Sample size calculations were performed by sample size calculation program based on the power of dexmedetomidine analgesia when used as an adjuvant to the LA levobupivacaine implementing a pilot study involving five patients in each group, and it was 52 patients (26 in each group) to have a power of 95%. We considered a dropout of 15% in each group so that the total number would be 60 patients (30 patients in each group).

Inclusion criteria were adult patients of the ASA physical status I and II aged 20–45 years of either sex who were submitted for unilateral laparoscopic thoracic sympathectomy under GA.

Exclusion criteria were major uncompensated systemic disease, chronic chest disease, chronic pain disorders, drug abuse, allergy to any medication included in the study protocol, any psychiatric disorder, coagulation or bleeding disorders, and any contraindication to GA.

Methods

Patients were randomly divided into two groups using computer-generated randomization codes included in sealed closed opaque envelopes. All staff in the operating room were unaware of the patient randomization code. Patients were classified into two groups as follows:

Levobupivacaine group (Group L): Patients received isobaric 0.5% levobupivacaine (Shiono Finesse Co., Japan) 1 mg/kg in 20-ml volume for TPVB.

Levobupivacaine plus dexmedetomidine group (Group LD): Patients received isobaric 0.5% levobupivacaine 1 mg/kg and 10-μg dexmedetomidine (Emcure Pharmaceuticals, India) in 20-ml volume for TPVB.

The primary outcome is to evaluate the postoperative pain by visual analog pain score.

The secondary outcomes include the timing of first rescue analgesia, total opioid consumption of fentanyl in 24 h postoperatively, and the possible complications of the technique or the given medications.

Anesthetic management

Preoperative assessment

All patients were clinically assessed and examined before surgery by careful history taking and physical examination, electrocardiography (ECG) and chest X-ray, and routine laboratory studies (complete blood count, liver function, renal function, random blood sugar, and coagulation profiles). An intravenous cannula was inserted in suitable peripheral vein. Patients received 5 mg of midazolam as a premedication, and upon arrival of the patient into the operating room, ECG, pulse oximetry, and noninvasive blood pressure monitors were connected.

Anesthetic technique

Paravertebral block was initiated in the setting position with a 22-gauge needle at the T3 interspace. The solution syringes were prepared under aseptic conditions with a volume of 20 ml. The blockade was facilitated with sonographic guidance (Philips, ClearVue 350, USA) to detect the approximate depth to the paravertebral space, and a mark is put on the spinal needle using sterile pen to minimize the risk of pneumothorax using a curvilinear probe.

To perform the block, the posterior aspect of thoracic spinous processes was identified. A mark was put before needle entry 2.5 cm lateral to each spinous process ipsilateral to the operative side. Under real ultrasound facilitation with the probe oriented in a transverse plane, an 18-gauge Tuohy needle was advanced midway under transverse process of T3 in an in-plane approach, from lateral to medial direction until the needle tip is seen close to the costotransverse ligament, as the needle was seen very close to the costotransverse ligament until the tip of the block needle is seen to lie in the posterior intercostal space or the apex of the TPVB. Loss of resistance to saline was performed to avoid pneumothorax. A test bolus of normal saline (2–3 ml) is then injected, and sonographic evidence is sought to ensure that the tip of the needle is in the apical part of the TPVS. After confirmation and negative aspiration, the desired volume of levobupivacaine 0.5% with or without dexmedetomidine is injected at the chosen level T3.

The patient was returned to supine position, and sensation was assessed using pinprick. Surgery was allowed to proceed after confirmation that T1–T5 sensory block has been established. Intravenous crystalloids and ephedrine were administrated to treat hypotension. Intravenous metoclopramide 10 mg was administrated for nausea or vomiting.

GA was initiated after assessment of the level of sensory block. The absence of pinprick discrimination within 15 min was taken as block failure and the patient was excluded from the study. Any episode of hypotension (as a decrease in systolic blood pressure (SBP) >20% of the baseline value or SBP <100 mmHg) was treated with intravenous boluses dose of ephedrine 0.1 mg/kg and 5 ml/kg crystalloid fluids. Any episode of bradycardia (as pulse rate of <50 beat/min) was treated with boluses of 0.2–0.5 mg of atropine. In both groups, GA was induced using intravenous 1–2 mg/kg of propofol, fentanyl 1 μg/kg, and atracurium 0.5 mg/kg. Anesthesia was maintained with sevoflurane at a minimum alveolar concentration (MAC) of 2%. Intraoperative patient monitoring of hemodynamics (heart rate [HR], mean arterial blood pressure [MAP], and SpO2) was recorded immediately before the paravertebral block and then every 5 min.

Before surgery, the time to reach a dermatomal sensory block, peak sensory level, and motor block was recorded. The regression time for sensory and motor sensations was recorded also. All durations were recorded considering the time of paravertebral block as time zero.

Postoperative data

In the postanesthetic care unit (PACU), hemodynamics (HR, MAP, and SpO2) were recorded every 15 min for 2 h. Patients were discharged from the PACU after sensory regression. Postoperative fentanyl requirements within 24 h were also recorded.

All patients were instructed to give scores for their pain both at rest and on shoulder abduction. Pain severity was assessed using visual analog scale (VAS) using a ruler measuring 10 cm which is unmarked on one side for the patient, and marks were put on the opposite side to give the actual pain score reported by the patient between 0 and 10 where 0 indicates no pain and 10 indicates the worst pain ever. Patients received 20–30 μg of fentanyl intravenously on request provided that the pain score is 4 or more. RSS was assessed (awake and anxious – 1; awake and cooperative – 2; awake and respond to light glabellar tap – 3; asleep with brisk response to glabellar tap – 4; asleep with sluggish response to light glabellar tap – 5; and asleep with no response – 6).

Sample size calculation is performed by sample size calculation program based on the power of dexmedetomidine analgesia when used as an adjuvant to the LA levobupivacaine implementing a pilot study involving five patients in each group, and it was 52 patients (26 in each group) to have a power of 95%. We considered a dropout of 15% in each group so that the total number would be 60 patients (30 patients in each group).

Statistical analysis

The statistical analysis of data was done using Excel program for figures and SPSS (FOR IBM). Program the Statistical Package for the Social Science version 22 (Armonk, NY, USA: IBM Corp).

The description of the data was done in the form of mean ± SD for quantitative data and frequency and proportion for qualitative data.

The normality of distribution was tested by Kolmogorov–Smirnov test and Shapiro–Wilk test. The analysis of the data was done to test statistical significant difference between groups. For nonparametric data, Mann–Whitney test was used to compare between two groups. For quantitative parametric data, independent t-test was used to compare between two groups, and Chi-square test was used for qualitative variable or odds ratio and 95% confidence interval were calculated P is significant if ≤0.05 at confidence interval 95%.

RESULTS

Table 1 showed that the demographic data of patients showed no significant difference among the studied groups, regarding age, sex, body mass index, duration of surgery, and ASA physical status.

Table 1

Demographic data in the studied groups (n=30)

Table 2 showed a more rapid onset and longer duration of sensory blockade significantly in group levobupivacaine–dexmedetomidine (GLD) with mean ± SD (8.57 ± 7.22 min and 11.98 ± 1.42 h) compared to levobupivacaine group (GL) alone with mean ± SD (15.21 ± 4.35 min and 9.75 ± 3.29 h. Furthermore, the sensory block regression time was significantly more prolonged in group GLD with mean ± SD (10.8 ± 2.31 h) compared with group GL (8.82 ± 1.71 h).

Table 2

Characteristics of sensory block in the studied groups (n=30)

Table 3 showed a significant reduction in VAS values in group GLD compared with the GL alone 30 min after recovery until 24 h postoperatively with P < 0.001, while there was no significant difference in RSS when compared with the basal value inside each group.

Table 3

Postoperative Ramsay Sedation Scale and visual analog pain score in the studied groups (n=30)

Table 4 showed that the number of patients who asked for postoperative analgesia was significantly lower in group GLD compared with GL, P = 0.041. Moreover, the time of first request for analgesia was significantly longer in group GLD compared with GL group, P = 0.038. Furthermore, the total postoperative fentanyl requirement in 24 h was significantly less in GLD group compared with GL group, P < 0.001.

Table 4

Number of patients asked for analgesia number (%), time of first rescue analgesia (hours), and total 24 h postoperative fentanyl requirement (μg/kg) in the studied groups (n=30)

In Table 5, there was an insignificant difference in the incidence of postoperative complications regarding (nausea, vomiting, hypotension, bradycardia, and pneumothorax) between the studied groups.

Table 5

Postoperative complications of the paravertebral block and the used drugs in the studied groups (n=30)

Figure 1 showed that MAP was significantly lower in GLD group compared to GL group 30 min up to 8 h postoperatively with P = 0.047.

Figure 1

Perioperative mean arterial blood pressure (mmHg) in the studied groups. Data are expressed as mean ± standard deviation. *P value is significant if ≤0.05. GL=Levobupivacaine group, GLD=Levobupivacaine plus dexmedetomidine, MAP=Mean arterial blood pressure

Furthermore, group GLD showed a significant decrease in MAP 30 min after intubation up to 1 h postoperatively compared to the basal value, while GLD showed a significant decrease in mean blood pressure (MBP) 5 min after intubation up to 8 h postoperatively compared to the basal value.

Figure 2 showed that HR was significantly lower in GLD group compared to GL group immediately after TPVB, P = 0.03. Furthermore, group GL showed a significant increase in HR 30 min after intubation then a significant decrease 1 h and 8 h after recovery P = 0.04, while group GLD showed a significant decrease in HR immediately after TPVB then 1 h and 4 h postoperatively compared with the basal value with P = 0.04.

Figure 2

Perioperative heart rate (beat/min) in the studied groups. Data are expressed as mean ± standard deviation. *P value is significant if <0.05. GL=Levobupivacaine group, GLD=Levobupivacaine plus dexmedetomidine, HR=Heart rate, IO=Intraoperative, PO=Postoperative

DISCUSSION

In our literature, patients who received levobupivacaine–dexmedetomidine in TPVB under GA showed superior postoperative analgesia that determined by the lower values of VAS, prolonged time to first rescue analgesic requirement, and reduced total 24 h postoperative IV fentanyl consumption in patients who received levobupivacaine plus dexmedetomidine (GLD) as compared with patients who received levobupivacaine alone (GL).

The time to first rescue analgesia was longer in GLD (9.7 ± 2.51 h) when compared with GL (7.81 ± 3.22 h). There was a reduction in number of patients who requested analgesia in GLD where the number was 14 patients (47%) in comparison with GL where the number was 21 patients (70%). Furthermore, there was a reduction in total 24 h postoperative fentanyl requirements in GLD (190 ± 120 mcg) compared to GL (320 ± 110 mcg). This prolonged analgesic effect is due to an α2-agonist action of dexmedetomidine which produces spinal cord cognition modulation and processing of sensation leading to inhibition of norepinephrine release.[11]

Patients undergoing laparoscopic sympathectomy can gain benefit from TPVB as it provides a good analgesia equal to epidural analgesia. LA adjuvants such as dexmedetomidine can be used to increase LA properties, reducing opioid requirements for intra- and postoperative periods.[12] Moreover, dexmedetomidine can provide more patient comfort with less need for sedation and more patient satisfaction.[13]

In our study, there was a significant difference between both groups regarding the sensory block. The sensory block was characterized by a faster onset, prolonged duration, and prolonged regression time in GLD compared to GL where the onset was 8.57 ± 7.22 compared to 15.21 ± 4.35 min, duration of sensory blockade was 11.98 ± 1.42 compared to 9.75 ± 3.29 h, and regression time was 10.8 ± 2.31 compared to 8.82 ± 1.71 h. This is in agreement with Mohamed et al.[14] who proved that using dexmedetomidine (1 ug/kg) as an adjunctive analgesic with 0.25% bupivacaine in TPVB in patients undergoing modified radical mastectomy improved the quality and the duration of analgesia where the time of first rescue analgesia was significantly prolonged and the total amount of intravenous tramadol consumption in the PACU and during the postoperative period was significantly less in GLD compared with GL. This is in agreement with a meta-analysis studying the facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block. It was confirmed that dexmedetomidine added to LA delayed the time to first analgesia request compared to LA alone. Furthermore, it was found that there was a delay in the time to first analgesic request compared with LA alone during brachial plexus blockade.[15]

This study also showed that when dexmedetomidine was used for peripheral nerve block and neuraxial blocks in upper limb surgeries, it hastened sensory block onset and prolonged sensory block duration. The results of these previous studies coincide with ours.[15] A few clinical studies have assessed an epidural dose of 1–21 ug/kg dexmedetomidine in thoracic and upper abdominal surgery, and it proved that epidural dexmedetomidine potentiates the effect of LAs, decreases the intraoperative anesthetic requirements, and improves postoperative analgesia with subsequent reduction in the incidence of pulmonary complications associated with thoracotomy.[1617]

Moreover, this study demonstrated that the MAP and HR were lower in levobupivacaine–dexmedetomidine group (GLD) than levobupivacaine group (GL) after TPVB both intraoperatively and postoperatively, this means in other words that dexmedetomidine markedly attenuated the stress response in GLD than GLD. These hemodynamic effects on MBP and HR can be attributed to the central sympatholytic effect of dexmedetomidine on vasomotor center with substantial reduction of plasma levels of norepinephrine leading to a marked reduction in the hemodynamic values (SBP, diastolic blood pressure [DBP], and HR). Mohamed et al.[14] concluded in their study when using dexmedetomidine as adjuvant to bupivacaine in TPVB that there was a significant reduction in pulse rate and DBP which coincide with our results.

The limitations of our study are that our sample size is relatively of medium size, so larger sample size may be required. Furthermore, the dose of dexmedetomidine may not be the optimal dose to have the best effect, so different doses in TPVB in further study may be required to achieve the best effect. Furthermore, ultrasound may not ensure 100% prevention of pneumothorax despite it allows accurate determination of the paravertebral space as one case developed pneumothorax, so better techniques may be discovered to completely eliminate the possibility of pneumothorax. Furthermore, no opioids were added to the anesthetic mixture which can prolong the duration of postoperative analgesia. Future studies may implement a larger sample size. Furthermore, we may compare different adjuvants to the LA to find out which is the ideal adjuvant for LAs during regional anesthesia.

CONCLUSION

The present study demonstrates that the addition of dexmedetomidine as adjuvant to levobupivacaine in TPVB under ultrasound guidance for elective unilateral laparoscopic thoracic sympathectomy can markedly improve the postoperative analgesia with lower pain scores and a marked reduction of the postoperative analgesic requirements during the first 24 h with better hemodynamic stability and low side effect profile.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.