|Year : 2022 | Volume
| Issue : 4 | Page : 337-343
Ultrasound-guided paravertebral block for inguinal herniorrhaphy: does neostigmine have a role?
Hani G Ali, Naglaa A.E Elnegeery
Departement of Anaesthesia, SICU, and Pain Management, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||04-Jul-2022|
|Date of Decision||30-Aug-2022|
|Date of Acceptance||06-Sep-2022|
|Date of Web Publication||29-Dec-2022|
MD Hani G Ali
Department of Anaesthesia, SICU, and Pain Management, Faculty of Medicine, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
Background There has been an increasing trend toward performing inguinal repair surgeries under regional anesthetic techniques like paravertebral block (PVB). Neostigmine has been used as an adjuvant to local anesthetics, but the existing research studies are few. This study was conducted to evaluate the efficacy of neostigmine as an adjuvant to local anesthesia used for PVB in inguinal hernia repair procedures.
Patients and methods This prospective randomized study included 72 patients prepared for elective inguinal hernia repair under PVB. They were allocated into two groups: the neostigmine group received a mixture of bupivacaine and neostigmine (5 μg/kg), whereas the control group received bupivacaine alone. During the postoperative period, pain score, hemodynamic parameters, first analgesic request, total analgesic consumption, and the incidence of adverse effects were noted and recorded.
Results Both groups showed comparable findings regarding age and weight. However, the number of patients requiring rescue analgesia showed a significant increase in the control group. Moreover, controls reported significantly earlier first analgesic requests. Both diclofenac and fentanyl consumptions were increased without neostigmine administration. Pain score was significantly better with neostigmine at 4 and 6 h after surgery. Hemodynamic parameters were almost comparable between the two groups.
Conclusion Neostigmine appears to be an efficient adjuvant to local anesthetics when administered during PVB as it significantly improves its analgesic profile. Its administration should be encouraged in clinical practice.
Keywords: inguinal hernia, neostigmine, paravertebral block
|How to cite this article:|
Ali HG, Elnegeery NA. Ultrasound-guided paravertebral block for inguinal herniorrhaphy: does neostigmine have a role?. Res Opin Anesth Intensive Care 2022;9:337-43
|How to cite this URL:|
Ali HG, Elnegeery NA. Ultrasound-guided paravertebral block for inguinal herniorrhaphy: does neostigmine have a role?. Res Opin Anesth Intensive Care [serial online] 2022 [cited 2023 Mar 26];9:337-43. Available from: http://www.roaic.eg.net/text.asp?2022/9/4/337/365793
| Introduction|| |
Inguinal hernias are the commonest type of hernias encountered in surgical practice, as it affects ∼5–10% of the population around the globe ,. Surgical repair is the ideal management for this condition ,. Inguinal hernia repair can be performed under general, spinal, or regional anesthesia .
In the recent era, paravertebral block (PVB) has been widely used for these surgical procedures. This regional anesthetic technique entails unilateral delivery of the local anesthetic drug to the nerve roots without affecting the central nervous system. The adverse effects of spinal anesthesia are also decreased ,. Its efficacy has been confirmed, and some physicians consider it comparable to epidural anesthesia, the gold standard pain management technique for thorax and abdomen ,.
Adjuvants are commonly used in combination with local anesthetics because of their synergistic actions. This leads to the prolongation of motor and sensory blocks. Moreover, the need for cumulative anesthetic dose is greatly decreased, thus decreasing the risk of toxicity .
Neostigmine, one of the nonopioid agents, could be used for the same purpose. Multiple studies have reported that neostigmine induced analgesia in both animals and humans without serious adverse effects compared with opioids. It only increases postoperative nausea and vomiting on intrathecal administration ,,. Others reported its safety when administered in the epidural space, with neither serious nor disturbing adverse effects ,,,.
The literature is poor with studies evaluating the role of neostigmine as an adjuvant for PVB. Therefore, this study was conducted to evaluate the efficacy of neostigmine as an adjuvant to local anesthesia used for PVB in inguinal hernia repair procedures.
| Patients and methods|| |
This prospective randomized, double-blinded study was conducted at Mansoura University Hospitals over 6 months, from February 2021 till July 2021. This was done after gaining approval from the local ethical committee and the Institutional Review Board of the Faculty of Medicine.
The sample size was calculated using Power Analysis and Sample Size software program (PASS), version 15.0.5 for Windows (2017) based on data obtained from a pilot study conducted on 14 patients at the same hospital. The time for the first analgesic request was the primary outcome. Patients were allocated into two groups: neostigmine group and control group. Time till the first analgesic request had mean values of 8.29±1.023 h for the neostigmine group and 7.33±1.048 for the control group. A sample size of 32 patients in each group was needed to achieve 95% power (1-β or the probability of rejecting the null hypothesis when it is false) in the proposed study using a two-sided two-sample unequal-variance t test with a significance level (α or the probability of rejecting the null hypothesis when it is true) of 5%. A 10% dropout was expected, so 36 patients were enrolled in each group.
Based on the previous sample size, a total of 72 patients were included in the study, and all of them had signed informed consent after an explanation of the details, pros, and cons of each intervention. We included male patients aged between 17 and 65 years, classified as class II according to the American Society of Anesthesiologists, and prepared for elective inguinal hernia repair.
Conversely, we excluded patients with any of the following criteria: morbid obesity, spine deformity, coagulation abnormalities, active infection at the injection site, central neuropathy, psychiatric illness, alcohol abuse, American Society of Anesthesiologists class more than II, or known allergy to the study medications.
The included cases were randomly allocated into two groups based on computer-generated randomization. The first group included 36 patients who received bupivacaine with neostigmine (neostigmine group), and the second one included the remaining 36 patients who received bupivacaine only.
Before the operation, all patients were evaluated by our anesthetic team, and patients were taught how to express their pain by the visual analog scale (VAS), with 0 for no pain and 10 for the worst pain ever. Patients were ordered to keep NPO about 8 h before surgery. Moreover, oral diazepam 5 mg was commenced for all patients on the night before the operation.
An intrevenous line was established at the operation theater, and ringer lactate solution (10 ml/kg) was infused over 10 min before the block procedure. Additionally, basic hemodynamic monitoring was secured, including noninvasive blood pressure, heart rate (HR), ECG, and pulse oximetry.
The PVB was done while the patient was sitting. Under the complete aseptic condition, a linear assay probe (5–10 MHz) was used for guidance. It was placed vertically against the spine. The puncture site was initially anesthetized by intradermal lidocaine. After that, a 22-G echogenic needle was inserted under US guidance in a vertical-caudal direction toward the paravertebral space, which was defined as the space between transverse process, pleura, and costotransverse ligament.
Both groups received two-segment PVB at T10 and L1 levels. The control group received 25 ml of bupivacaine 0.5%; 15 ml was injected at the T10 level, and the remaining 10 ml were injected at the L1 level. In the neostigmine group, patients received 25 ml of the same drug mixed with neostigmine (5 μg/kg), and the same volumes were injected at the same levels as controls. Aspiration was performed before injection to exclude intravascular injection.
The block procedures were performed by the same experienced anesthesiologist, whereas patients and other staff involved in patient management and data collection were unaware of group assignment.
The success of the PVP procedure was confirmed by the decrease in pinprick sensation at the injected dermatomal level. Failure to achieve that within 15 min of application was considered as ‘block failure,’ and these cases were excluded from the study. Intraoperative bradycardia was defined as a HR less than 50 bpm, and it was managed by atropine increment (0.01 mg/kg). Hypotension was defined as a 20% decrease in systolic blood pressure, and it was managed by intravenous infusion of normal saline (5 ml/kg) together with ephedrine increments (0.1 mg/kg).
Clinical parameters like mean arterial pressure (MAP), HR, and VAS were recorded at Post-anesthesia care unit (PACU) at 2, 4, 6, 12, and 24 h after surgery. If the patient reported a VAS score of 4 or more, an intramuscular diclofenac ampoule was given (75 mg). The first call for analgesia and total analgesic consumption were calculated and recorded. Furthermore, adverse effects including nausea, vomiting, or other PVB-related complications (pneumothorax and vascular puncture) were recorded and managed.
Data collection, tabulation, and analysis were performed using the Statistical Package for the Social Sciences (SPSS; IBM, Inc., Chicago, Illinois, USA) version 26 for Windows. Quantitative data were tested for normality using Kolmogorov–Smirnov test and expressed as mean±SD or median and interquartile range. Categorical data were expressed as percentage and frequency. Independent sample t and Mann–Whitney tests were used for intergroup comparison of parametric and nonparametric continuous data, respectively. χ2 test or Fisher’s exact test was used for comparing two of categorical data. P value less than 0.05 was considered to be statistically significant.
| Results|| |
The mean age of the included participants was 48.31 and 43 years in the neostigmine and control groups, respectively (P=0.127). No significant difference was noted between the same groups regarding the patient’s weight.
Regarding analgesic profile, 28 (77.8%) patients called for rescue analgesia in the control group compared with only 12 (33.3%) patients in the neostigmine group, with a significant increase in controls (P<0.001). Moreover, the first analgesic request showed a significant prolongation with neostigmine administration (10.5 vs. 8.07 h in controls − P=0.039).
Both diclofenac and fentanyl consumptions showed a significant decrease in the neostigmine group. The former had mean values of 0.5 and 1.39 ampoule, whereas the latter had mean values of 6.11 and 22.36 μg in the neostigmine and control groups, respectively.
The incidence of nausea and vomiting was comparable between the two groups (0.722). No PVB-related complications were encountered in the current study. The previous data are summarized in [Table 1].
|Table 1 Age, weight, postoperative analgesic profile, and complications in the studied groups|
Click here to view
HR changes showed no significant difference between the two groups during the early 24 h, apart from the 6 h reading, which was significantly increased in the control group. Despite its statistical significance (P=0.046), the difference was clinically acceptable (87.58 vs. 95.97 bpm in the neostigmine and control groups, respectively). [Table 2] shows these data.
As shown in [Table 3], no significant difference was noted between the two groups regarding MAP changes during the early 24 h after the operation.
Although no significant difference was noted between the two groups regarding VAS scores, neither at PACU nor after 2 h, the subsequent two readings (2 and 6 h) showed a significant decrease in the neostigmine group (P<0.05). These data are shown in [Table 4].
| Discussion|| |
PVB has proved its efficacy in inguinal hernia repair procedures. It provides unilateral sensory block and decreases postoperative pain and its consequences, leading to improvement of patient satisfaction ,.
Neostigmine is a parasympathomimetic agent that proved its efficacy as an adjuvant to local anesthetics during spinal anesthesia ,,. Nevertheless, its application in regional anesthesia has not been extensively discussed.
This study was conducted to evaluate the efficacy of neostigmine as an adjuvant to local anesthesia used for PVB in inguinal hernia repair procedures. The included 72 patients were divided into two groups: neostigmine and control groups (36 patients in each group).
One can notice no significant difference between the two study groups regarding the preoperative characteristics, and this indicates proper randomization technique. This should also negate any bias that might have skewed results in favor of one group rather than the other one.
In the current study, no significant differences were detected between the two groups regarding postoperative hemodynamic parameters (MAP and HR), apart from the 6-h reading, which was significantly increased in the control group. Despite its clinical irrelevance, this rise could be a result of increased pain scores in the control group.
Another previous study also reported that the application of neostigmine as an adjuvant in axillary nerve block was not associated with significant changes in hemodynamic parameters (MAP and HR) when compared with controls (P>0.05) . Alkan and Kaya  reported that the epidural neostigmine group had comparable HR readings compared with controls during the postoperative period.
Other authors reported that neostigmine could increase both HR and MAP when administered at large doses through the intrathecal route (>100 μg) in sheep due to preganglionic sympathetic neurons . In contrast, it induces bradycardia when systemically administered ,.
In our study, fentanyl consumption showed a significant decrease with neostigmine administration, as it had mean values of 6.11 and 22.36 μg in the neostigmine and control groups, respectively (P=0.004).
The exact mechanism by which neostigmine induces analgesia is still unclear. Researchers suggest that it induces its peripheral action via inhibition of presynaptic glutamatergic afferents, leading to an increase in endogenous acetylcholine . When administered through the intrathecal route, it inhibits the cholinesterase enzyme leading to a decrease in acetylcholine degradation and its accumulation at the cholinergic neurons located at the dorsal horn .
Abdelhamid and colleagues evaluated the efficacy of neostigmine as an adjuvant to local anesthesia in serratus anterior block performed for mastectomy operation. Neostigmine administration led to a significant reduction of intraoperative fentanyl consumption, which had a mean value of 111.67 μg compared with 131.67 μg in controls (P<0.05) . This is in accordance with our findings.
In the current study, the first analgesic request showed a significant prolongation with neostigmine administration (10.5 vs. 8.07 h in controls − P=0.039).
In the same context, Alkan and Kaya  reported that epidural administration of neostigmine during cesarean section was associated with a significant prolongation of the duration to first analgesic request, compared with controls. It had mean values of 6.5 and 2.7 h in neostigmine and control groups, respectively.
This response is expected to be dose dependent, as reported by Nakayama and colleagues. They reported that neuraxial administration of neostigmine (10 µg/kg) was associated with more prolongation of the duration to the first analgesia, compared with administering 5 µg/kg of the same drug .
On the contrary, another study stated that adding neostigmine to the local anesthetic agent was not associated with a significant prolongation of the time to the first analgesic request. It had mean values of 6.67 and 5.89 h in the neostigmine and control groups, respectively (P>0.05) . The authors attributed these comparable findings to the hydrophilic nature of neostigmine which led to rapid systemic absorption. This, in turn, would lead to the loss of its peripheral mechanism of action.
Our findings showed that postoperative analgesic consumption decreased significantly with neostigmine administration. Diclofenac consumption had mean values of 0.5 and 1.39 ampoules in the neostigmine and control groups, respectively.
Bouderka and colleagues reported that adding neostigmine to the local anesthetic agent during axillary plexus block led to a significant decrease in postoperative ketoprofen consumption (P<0.05), as it had mean values of 127 and 200 mg in the neostigmine and control groups, respectively. Of note, subcutaneous injection of the same agent besides axillary block led to a decrease in analgesic consumption compared with controls (150 mg) . This was confirmed by our findings.
Another study confirmed the previous findings with epidural anesthesia. The authors reported that epidural neostigmine was associated with a significant decrease in additional analgesic consumption compared with controls. The neostigmine group even showed comparable results with the morphine group .
Conversely, in the recent study conducted by Abdelhamid and colleagues on mastectomy cases, adding neostigmine to the serratus anterior block was not associated with a significant decrease in postoperative morphine consumption (P>0.05). However, the neostigmine group showed less need for the previous drug, as total consumption had median values of 1.5 and 3 mg in the neostigmine and control groups, respectively .
Our findings showed that two- and 6-h pain scores were significantly lower in the neostigmine group.
In line with our findings, a previous study evaluated the role of neostigmine as an adjuvant in axillary plexus block. The included patients were allocated into controls, patients who had neostigmine mixed with local anesthesia, and patients who received subcutaneous neostigmine. VAS had mean values of 45, 21, and 31 mm in the three groups, respectively (P<0.05), with a significant improvement of pain scores with neostigmine administration, whatever route used. However, its addition to the local anesthetic agent was more effective .
On the contrary, McCartney et al.  denied any significant analgesic or anesthetic effect of neostigmine (1 mg) when added to lidocaine during intravenous regional anesthesia.
When it comes to the complications, the incidence of nausea and vomiting was comparable between the two groups (0.722).
Likewise, other authors noted no significant difference in the incidence of nausea and vomiting with neostigmine administration. Nausea was reported by 23.3 and 23.3% of patients in the neostigmine and control groups, respectively, whereas vomiting was reported by 13.3% of patients in both groups . Other authors confirmed the previous findings .
One should mention that intrathecal neostigmine administration has been severely restricted in anesthetic practice due to the high incidence of nausea and vomiting. However, numerous studies have confirmed its safety with regional administration ,.
No PVB-related complications were encountered in the current study. Although PVB is technically easy to perform, it has a 13% failure rate . Naja and Lönnqvist reported a failure rate of 6.1%. Complications encountered included vascular puncture (6.8%), hypotension (4%), epidural or intrathecal spread (1%), pleural puncture (0.8%), and pneumothorax (0.5%) . Of course, ultrasound guidance will help to decrease these complications ,, as performed in our study.
Despite the previous advantages of neostigmine as an adjuvant, one must consider neurotoxicity associated with its perineural administration. Animal studies showed conflicting results. However, human studies revealed that it is dose-related. It is recommended to administer neostigmine with a dose of less than 50 µg to decrease the risk of its adverse effects ,,,.
The current study has some limitations; it is a single-center study that included a relatively small sample size. Moreover, we should have compared different doses of neostigmine to identify the optimum dose sufficient to achieve longer analgesia without serious adverse effects. These drawbacks should be discussed in the upcoming studies.
| Conclusion|| |
- Based on the previous data, neostigmine appears to be an efficient adjuvant to local anesthetics when administered during PVB, as it significantly improves its analgesic profile. Its administration should be encouraged in clinical practice.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]