|Year : 2020 | Volume
| Issue : 2 | Page : 153-158
Nalbuphine versus neostigmine as an adjuvant to intrathecal hyperbaric bupivacaine-induced postoperative analgesia
Enas M Ashrey1, Bosat E Bosat2
1 Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt
2 Department of General Surgery, Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt
|Date of Submission||03-Feb-2020|
|Date of Decision||09-Feb-2020|
|Date of Acceptance||19-Feb-2020|
|Date of Web Publication||29-Jun-2020|
MD Enas M Ashrey
Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine for Girls, Al Azhar University, Alzahraa University Hospital Abbasia, Cairo, 11517
Source of Support: None, Conflict of Interest: None
Introduction Pain remains one of the most important patient complaints after hemorrhoid surgery; most anal surgical procedures are done as a day-case procedure, so medication to relieve or stop pain and provide analgesia should be administered preoperatively to provide postoperative analgesia.
Aim The aim of the study is to evaluate the effect of nalbuphine versus neostigmine as an adjuvant to intrathecal hyperbaric bupivacaine on duration of motor block and postoperative analgesia.
Patients and methods A total of 40 adult patients of both sexes, with American Society of Anesthetists status I–II, aged between 21 and 60 years, enlisted to undergo hemorrhoidectomy under spinal anesthesia were included. Patients were randomly divided into two groups. Group I was the nalbuphine group (n=20), which received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine+2 mg (0.1 ml) of nalbuphine HCl. Group II was the neostigmine group (n=20), which received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine+50 μg (0.1 ml) of neostigmine. The total volume administered in each group was 3.1 ml.
Results The onset of sensory block was significantly faster in nalbuphine group than neostigmine group, whereas onset of motor block was significant faster in neostigmine group than in nalbuphine group (P=0.0001). The time to two-segment sensory regression was significantly longer in nalbuphine group than in neostigmine group (P<0.0001). Duration of motor block was significantly prolonged in nalbuphine group compared with neostigmine group (P<0.0001). Postoperative visual analog scale was significantly less in nalbuphine group than in neostigmine group. Duration of postoperative analgesia was highly significantly longer in nalbuphine group than neostigmine group (P<0.0001). Postoperative total analgesic consumption in 24 h was less in nalbuphine group than in neostigmine group (P≤0.0001), with no significant adverse effect.
Conclusion Addition of either nalbuphine or neostigmine to intrathecal hyperbaric bupivacaine induces postoperative analgesia with no significant adverse effect. However, nalbuphine was superior to neostigmine in prolongation of duration of motor block and postoperative analgesia, with decreased postoperative analgesic requirement.
Keywords: hemorrhoid surgery, intrathecal hyperbaric bupivacaine, nalbuphine, neostigmine
|How to cite this article:|
Ashrey EM, Bosat BE. Nalbuphine versus neostigmine as an adjuvant to intrathecal hyperbaric bupivacaine-induced postoperative analgesia. Sci J Al-Azhar Med Fac Girls 2020;4:153-8
|How to cite this URL:|
Ashrey EM, Bosat BE. Nalbuphine versus neostigmine as an adjuvant to intrathecal hyperbaric bupivacaine-induced postoperative analgesia. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Jul 12];4:153-8. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/153/288264
| Introduction|| |
Pain remains one of the most important patient complaints after hemorrhoid surgery; it is believed that it may be related to individual pain threshold, operative techniques, anesthesia and analgesia given, or spasm of the internal sphincter . Most anal surgical procedures are done as day-case surgery, so medication to relieve or stop pain and provide analgesia should be administered preoperatively to provide postoperative analgesia. Intrathecal block is the technique of choice for anal surgery, as it provides anesthesia and analgesia intraoperatively with pain relief that may last for some time after surgery. Local anesthetics and different additives can be used as an adjuvant for intrathecal anesthesia to reduce pain over a wider region of the body .
Nalbuphine is a phenanthrene opioid derivative that is used for pain medication. It has an analgesic potency equivalent to morphine . It appears to be an agonist at kappa receptors and an antagonist or partial agonist at mu receptors, so it is considered as a competitive opioid antagonist and partial opioid agonist and provides analgesia with less nausea, pruritus, and respiratory depression when compared with morphine . Nalbuphine also does not increase cardiac index, pulmonary artery pressure, cardiac work, or systemic blood pressure . So when added as adjuvant to hyperbaric bupivacaine, it improved preoperative and postoperative analgesia .
Neostigmine is an acetylcholinesterase inhibitor. Intrathecal neostigmine produces analgesia by the inhibition of endogenous spinal neurotransmitter and acetylcholine destruction via muscarinic and cholinergic receptors located at dorsal horn of spinal cord, substantia gelatinosa, and in lesser amounts at lamina III and V . Activation of spinal muscarinic receptors is found to suppress spinal gamma-amino butyric acid receptor . The peripheral anticholinergic receptors have analgesic effect, which was effective to inhibit pain . Moreover, spinal administration of neostigmine reduces substance P . Acetylcholine released from preganglionic sympathetic fibers once intrathecal injection of neostigmine is given may counteract the sympatholytic actions of local anesthetics (reducing the degree of hypotension) .
The quality of postoperative analgesia is the primary outcome, whereas the effects on onset of sensory and motor blockade, analgesic requirement, assessment of hemodynamic changes, and adverse effects are the secondary outcomes.
| Patients and methods|| |
This is a prospective randomized controlled study conducted in Al-Zahraa University Hospital from January to June 2019 on 40 adult patients of both sexes, aged from 21 to 60 years, with American Society of Anesthetists status I–II, enlisted to undergo hemorrhoidectomy under spinal anesthesia.
Exclusion criteria were those with known allergy to nalbuphine or neostigmine, coagulation defects, and infection at puncture site. Moreover, patients with previous spinal surgical procedures, seizures, preexisting neurological deficits in lower extremities, and cardiovascular disease were excluded from the study.
After approval of the local ethical committee from the Research Ethics Committee (REC) of the Faculty of Medicine for Girls, Al Azhar University under registration number N0 REC 201907108, informed written consent was obtained from each patient.
Patients were randomly assign into two groups by using a computer-generated number and by using sealed opaque envelopes ([Figure 1]).
Patients were randomly allocated into two equal groups (20 patients in each). A CONSORT flow chart displaying the number of patients who were randomly allocated, lost, and analyzed is shown in [Figure 1].
- Group I was the nalbuphine group (n=20), which received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine (sunnpivacaine 0.5%, 5 mg/1 ml; Sunny Medical, Badr City, Cairo, Egypt) +2 mg (0.1 ml) of nalbuphine HCL (nalufin, 20 mg/1 ml; Amoun Pharmaceutical Co., Obour City, Cairo, Egypt), to a total volume of 3.1 ml.
- Group II was the neostigmine group (n=20), which received 15 mg (3 ml) of 0.5% hyperbaric bupivacaine+50 μg (0.1 ml) of neostigmine (neostigmine methylsulfate, 0.5 mg/ml; Amriya Pharmaceutical Co., Cairo, Egypt), to a total volume of 3.1 ml.
Upon arriving to the operating room, an intravenous cannula of 22–18 G was inserted. All patients were connected to standard monitors, including ECG, pulse oximeter, and noninvasive blood pressure, and preloaded by 500 ml of Ringer acetate solution over 15 min followed by an infusion of 6–10 ml/kg/h, without any premedication.
Spinal anesthesia was administered to the patients in supine position at the lumbar region of L4–L5 interspace by using 25-G Quincke spinal needle under complete aseptic techniques. A total volume of 3.1 ml of drugs was prepared, and according to the groups injected intrathecally. After intrathecal injection, the patient was placed immediately in the supine position with slight elevation of the head (15° Trendelenburg tilt) to achieve level of block of T10.
| Surgical technique|| |
There are many totally different surgical techniques for treating hemorrhoids that cause an individual discomfort. Surgeries aim to limit the blood supply and remove hemorrhoid. A surgeon performed the procedure after the patient received intrathecal block. The surgeon performed the surgical hemorrhoidectomy through the opening of the anus by gently cutting out the hemorrhoids by using a variety of surgical instruments, such as surgical scissors or a laser. After removing the hemorrhoids, the surgeon sealed the wounds or left the wound open or used a combination of both methods. All patients were heartened to ambulate early.
The following data were assessed:
- Hemodynamic monitoring:
- Baseline heart rate (HR), mean arterial blood pressure (MABP), and oxygen saturation were recorded before intrathecal injection of the drugs. After injection, HR, MABP, and oxygen saturation were recorded immediately, and then every 5 min till the end of the operation. In recovery room, MABP was recorded every 10 min for at least 30 min before discharge to the wards.
- Spinal blockade assessment:
- Sensory block assessment: it was done using pinprick test by 25 G needle, for the time taken for the sensory block after intrathecal injection every 5 min till reach to T10 dermatome.
- Motor block assessment: the intensity of motor block were assessed by Bromage scale every 5 min intervals for the first 20 min after intrathecal injection of the drug, 1 ‑ free movements of legs and feet (no motor block ‑ 0%); 2 ‑ able to move knee with free movement of feet (partial motor block ‑ 33%); 3 ‑ unable to flex knee with free movement of feet (near complete motor block ‑ 66%); and 4 ‑ unable to move any part of lower limb (complete motor block ‑ 100%) . Duration of motor block, the time from onset of motor block after drug administration to the time the patient was able to raise his/her limb, was recorded.
- Visual analog scale (VAS): pain assessment was done by using VAS, which is a horizontal line from 0 to 10 cm, where 0 score represents no pain and 10 score corresponds to the worst imaginable pain. VAS was recorded immediately after transport to postanesthesia care unit at rest and then after 2, 4, 6, 12, 18, and 24 h postoperatively.
- Duration of analgesia: the time taken from intrathecal drug injection till the patients’ asks for rescue analgesics or VAS more than or equal to 4 was recorded.
- Time to first request for rescue analgesics (min): the time interval from the end of surgery till the first request analgesia required/min was recorded. Intramuscular ketorolac tromethamine (Adolor; Pharco B International for Pharco pharmaceutical Co., Alameria, Alexenderia, Egypt) 30 mg/2 ml was administered as an analgesic supplement.
- Total analgesic consumption/24 h was recorded.
- Adverse effects: hypotension, when MABP fall greater than 20% from baseline, was treated with incremental doses of intravenous ephedrine (5 mg) and by fluid administration. Bradycardia, when HR is less than 60 beats/min, was treated with atropine (0.01 mg/kg). Moreover, postoperative nausea and vomiting (PONV) was treated with metoclopramide (10–20 mg) intravenously.
- Sample size justification: MedCalc Software version (126.96.36.199 program) (Ostend, Belgium), which is a statistical calculator based on 95% confidence interval and power of the study 80% with α error of 5%, was used for calculations of sample size. Based on the previous studies, the sample size was calculated according to these values. A minimal sample size of 38 cases was enough to find such a difference. Assuming a dropout rate of 5%, the sample size was 20 patients in each group to provide reliable results.
Data were collected, revised, coded, and entered to the Statistical Package for Social Science (IBM SPSS), version 20 (IBM Company, Chicago, Illions, USA). The quantitative data were presented as mean, SD, and range for parametric data, whereas nonparametric data were presented as median with interquartile range. Moreover, qualitative variables were presented as number and percentages. The comparison between groups with qualitative data was done by using χ2 test and Fisher exact test, whereas the comparisons between two independent groups with quantitative data and parametric distribution were done by using independent t test. Significant level was taken at P value less than 0.05.
| Results|| |
Regarding patient characteristics and hemodynamic data, there were no significant differences between both groups (P>0.05) ([Table 1]).
Onset of sensory block was significantly faster (6.6±1.4 min) in nalbuphine group than (9.6±2.8 min) in neostigmine group (P=0.0001), whereas onset of motor block was significant lower (10±1.6 min) in group II than (12±1.2 min) in group I (P=0.0001). The time for two-segment regression of sensory block was significantly longer in group I (280±7.61 min) than in group II (259±6.33 min) (P<0.0001). Duration of motor block was significantly prolonged in nalbuphine group (440±25.3 min) compared with neostigmine group (320±10.2 min) (P<0.0001) ([Table 2]).
|Table 2 Onset of sensory, motor block, and time for two-segment regression (min)|
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Visual analog scale
VAS score was less in nalbuphine group than neostigmine group, which was significantly different between the groups ([Table 3]).
Duration of analgesia, total analgesic consumption, and adverse effects
Regarding duration of analgesia (min), it was highly significantly longer in group I (460±55.3 min) than in group II (320±37.2 min) (P<0.0001). First request for rescue analgesics (min) was highly significantly longer in group I (400±20.2 min) than in group II (320±12.4 min) (P<0.0001). Total analgesic consumption was highly significant less in group I (60±12.1 mg) than in group II (90±18.3 mg) (P<0.0001). Adverse effect showed no significant difference between both groups ([Table 4]).
|Table 4 Duration of analgesia, first request for analgesics, total analgesic consumption, and adverse effects|
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| Discussion|| |
Awareness of the problem of postoperative pain made acute pain service management a priority for perioperative care . Regional anesthesia is one of the fundamental components of acute pain management that provides important value to perioperative care for pain relief, reduction of anesthesia and opioid adverse effects, and also reduced hospital stay .
This study demonstrated that when nalbuphine (2 mg) or neostigmine (50 μg) was added to intrathecal hyperbaric bupivacaine, it induced postoperative analgesia with no significant adverse effect. However, nalbuphine provided prolonged duration of motor block and postoperative analgesia than neostigmine, evidenced by lower VAS scores for pain and decreased number of rescue analgesia.
In the present study, hemodynamic data, when compared between both groups, showed nonsignificant difference. Similar to our study, Manjula et al.  showed that addition of 1-mg nalbuphine to intrathecal hyperbaric bupivacaine 0.5% does not cause any hemodynamic changes. Contradicting our finding, Pandey et al.  found that when intrathecal neostigmine of 50 μg was added to bupivacaine, it produced better hemodynamic stability.
Our study found faster onset of sensory block with prolonged motor block and duration of analgesia in nalbuphine group (460±55.3 min and about 7.67 h) than neostigmine group (320±37.2 min and 5.33 h). This coincides with Bansal et al.  who demonstrated faster onset of sensory and motor block with nalbuphine when compared with clonidine and nalbuphine as intrathecal adjuvants to 0.5% hyperbaric bupivacaine.
In the present study, nalbuphine significantly prolonged the time for two-segment regression intrathecally when compared with neostigmine. The time for two-segment regression was higher in intrathecal nalbuphine group (280±7.6 min) than in neostigmine group (259±6.33 min). This was supported by Tiwari et al. .
The current study demonstrated that nalbuphine produced a longer duration of postoperative analgesia when compared with neostigmine. These results coincide with Verma et al.  who concluded that intrathecal nalbuphine (2 mg) is effective in improving postoperative analgesia compared with bupivacaine alone or with tramadol. However, Abo-Elhussein et al.  reported that intrathecal nalbuphine and transverse abdominis plane block provided significant prolonged postoperative analgesia and reduced postoperative analgesic consumption with significant advantages of intrathecal nalbuphine over transverse abdominis plane block. Moreover, Tan et al.  noted that duration of analgesia was longer in intrathecal morphine group (615.3±64.7 min) than in neostigmine group (443.2±25 min).
Our study was also comparable to the results of Tan et al.  who found addition of 50 µg neostigmine to intrathecal bupivacaine enhanced motor onset of anesthesia and also prolonged motor block through acetylcholine-mediated reduction in motor neuron outflow, with duration of motor block (5.7±0.46 h). On the contrary, Dubey et al.  found that addition of 50 µg neostigmine to bupivacaine intrathecally prolonged the duration of effective analgesia, and sensory and motor block without any significant adverse effects. In contrast to the current study, Saini et al.  found that intrathecal neostigmine of 50 μg was inadequate for analgesia with increased occurring of vomiting, whereas intrathecal neostigmine of 150 μg prolonged postoperative analgesia up to 10 h, with increased incidence of PONV, sweating, and salivation. Moreover, in disagreement with our study, Gupta  recorded that intrathecal neostigmine of 75 μg with bupivacaine provided better postoperative analgesia when compared with 50 μg and was associated with increased frequency of bradycardia, hypotension, and PONV.Our results regarding time to first request for analgesia was shorter in neostigmine group than nalbuphine group, whereas total analgesic consumption was higher in neostigmine group. Similar to our results, Ahmed  demonstrated that nalbuphine decreased postoperative analgesic requirement and increased the duration of postoperative analgesia than fentanyl. Supporting our study, Tan et al.  noted that duration of analgesia and the time to first request for analgesia were shorter in intrathecal neostigmine group when compared with the morphine group.
The current study recorded no significant differences between the intrathecal nalbuphine and neostigmine groups regarding incidence of PONV, or hypotension. Previous studies done by further research ,,,, are similar to our results.
| Conclusion|| |
Addition of either nalbuphine or neostigmine to intrathecal hyperbaric bupivacaine induces postoperative analgesia with no significant adverse effect. However, nalbuphine was superior to neostigmine in prolongation of duration of motor block and postoperative analgesia with decreased postoperative analgesic requirement.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]