Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 366-370

The role of granisetron in the enhancement of recovery and home discharge in ambulatory surgery performed under spinal anesthesia


Department of Anesthesia and Intensive Care, Ain Shams University, Cairo, Egypt

Date of Submission12-Sep-2015
Date of Acceptance18-May-2016
Date of Web Publication31-Aug-2016

Correspondence Address:
Ayman Kasem
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, 11331
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.189563

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  Abstract 

Background
The popularity of day-care surgery has increased worldwide due to reduced costs and remarkable safety profile. Neuraxial anesthesia is a popular technique for day-case surgeries. Anesthetist should modify his/her techniques to optimize patient’s chance of early discharge. 5-Hydroxytryptamine type 3 receptor antagonists used to prevent and treat postoperative nausea and vomiting may affect the course of spinal anesthesia and prevent its associated hypotension.
Aim
The aim of this study was to evaluate the effects of granisetron in the reversal of hyperbaric bupivacaine spinal anesthesia and enhancement of home discharge in day surgeries.
Patients and methods
Sixty adult patients scheduled for elective day surgery under spinal anesthesia were randomly divided into two equal groups to receive either 1 mg of granisetron (the G group) intravenously diluted in 5 ml normal saline over 30 s, 5 min before spinal anesthesia, or an equal volume of intravenous normal saline (the S group) at the same time. Heart rate, mean arterial pressure, oxygen saturation, and sensory and motor block levels were monitored and recorded.
Results
Time to regression of sensory level by two dermatomes, time to regression of sensory level to S2, time to first void, and time to discharge readiness were significantly lower in group G. Moreover, the incidence of nausea and shivering was significantly lower in group G.
Conclusion
Administration of 1 mg of granisetron before spinal anesthesia in ambulatory surgeries resulted in a statistically faster sensory regression and earlier home discharge from the day-surgery unit.

Keywords: ambulatory surgery, granisetron, spinal anesthesia


How to cite this article:
Kasem A. The role of granisetron in the enhancement of recovery and home discharge in ambulatory surgery performed under spinal anesthesia. Ain-Shams J Anaesthesiol 2016;9:366-70

How to cite this URL:
Kasem A. The role of granisetron in the enhancement of recovery and home discharge in ambulatory surgery performed under spinal anesthesia. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Oct 17];9:366-70. Available from: http://www.asja.eg.net/text.asp?2016/9/3/366/189563


  Introduction Top


Day surgery encompasses a spectrum of surgical procedures that allow home discharge of the patient on the day of surgery, usually after a few hours. It represents high-quality patient care with reduced tissue trauma, effective analgesia, minimal adverse events, enhanced recovery, and postoperative support. Recently, the complexity of procedures has increased, with a wider range of patients now considered suitable for day surgery. Central neuraxial blockade can be used effectively for day surgery. Anesthetist should modify his/her techniques, helping the patient to be operated in a stressless and comfortable way and to optimize patient’s chance of early discharge [1],[2].

The 5-hydroxytryptamine type 3 receptor (5-HT3) antagonists are a class of drugs frequently used to prevent and treat nausea and vomiting. It has been reported that the prophylactic administration of ondansetron, one of the 5-HT3 antagonists, may provide a protective effect against hypotension associated with spinal anesthesia. This may be attributed to the inhibition of serotonin from the activation of the Bezold–Jarisch reflex in case of decreased venous return associated with spinal anesthesia through blocking of 5-HT3 receptors, or through blocking of 5-HT3 receptors located peripherally, such as cardiac chemoreceptors on the cardiac vagal afferent [3],[4].

It has been shown that a 5-HT3 receptor exists in the spinal nerves and located in the superficial laminae and substantia gelatinosa of the spinal cord [5]. Moreover, it has been reported that it affects pain control in animals as it plays a role in antinociception, which was reversed by a selective 5-HT3 receptor antagonist [6],[7]. In one study, ondansetron administered to prevent nausea and vomiting antagonizes the sensory block produced by intrathecal lidocaine [8].

The aim of this study was to evaluate the effects of granisetron, another (5-HT3) antagonist, in the reversal of 0.5% hyperbaric bupivacaine spinal anesthesia and enhancement of home discharge in day surgeries.


  Patients and methods Top


This study was conducted in the Day-Surgery Unit of Prince Sultan Hospital, Al-Madinah, Kingdom of Saudi Arabia, from February 2014 to March 2015. The procedure for this study was approved by the Ethics Committee of the Hospital. Sixty adults of American Society of Anesthesiologists physical status I or II of both sexes who were scheduled to undergo elective day surgery under spinal anesthesia were included in this study. The objective and methods of the study were explained to them before the operation, and all patients provided written informed consent. No preoperative sedations were given. Patients with difficulty in communication, those who had received drugs that could affect spinal anesthesia, such as a calcium channel blocking agent, or an α2 agonist, or drugs that act on serotonin receptors or affect the level of serotonin, and patients who had neurological diseases were excluded from the study.

Patients were randomly allocated into two equal groups (30 patients each) to receive either granisetron (the G group) or saline (the S group). The G group received 1 mg of granisetron intravenously (Kytril; Roche, Basel, Switzerland) diluted in 5 ml normal saline 0.9% over 30 s, 5 min before spinal anesthesia. The control group received an equal volume of intravenous 0.9% normal saline at the same time.

In the operating room, vital signs such as ECG, blood pressure, and oxygen saturation were monitored and recorded as baseline data. Before the induction of anesthesia, 10 ml/kg of lactated Ringer’s solution was intravenously injected over 20 min in all patients. Spinal anesthesia was induced by the same consultant of anesthesia for all patients in the sitting position at the level L4–L5 by means of intrathecal injection of 10 mg (2 ml) of 0.5% hyperbaric bupivacaine (Marcaine; AstraZeneca, Södertälje, Sweden) through a 27 G needle (Vygon, Ecouen, France) over 15 s, and then the patient adopted the supine position.

Patients were observed in the operating room and the recovery room by an anesthesiologist who had not participated in the study and blinded to the study drugs. This anesthesiologist recorded the heart rate, mean arterial pressure, and oxygen saturation from the start of spinal anesthesia at 3-min interval for 15 min and then at 5-min interval until the end of surgery. In addition, using an alcohol swab, the highest sensory block level was assessed by bilateral loss of cold sensation at the midclavicular line every 2 min until the fixation of the sensory level at two consecutive times. Thereafter, the sensory block level was assessed every 10 min and the time to the regression of sensory block by two dermatomes and that to recovery of sensory function at the S1 level were also recorded. Moreover, motor block was assessed every 2 min using the modified Bromage scale (0, able to move the hip, knee, ankle, and toes; 1, unable to move the hip, able to move knee, ankle, and toes; 2, unable to move the hip and knee, able to move ankle and toes; 3, unable to move hip, knee, and ankle, able to move toes; and 4, unable to move the hip, knee, ankle, or toes) until the complete motor block and then every 15 min until complete motor recovery. Moreover, the presences of nausea, vomiting, shivering, or inadequate analgesia were recorded.

A 20% decrease in systolic blood pressure below baseline was treated with 5 mg of ephedrine increments intravenously, and decrease in the heart rate below 45 bpm was treated with 0.6 mg of intravenous atropine. Shivering was treated with 20 mg of meperidine, and inadequate analgesia was treated with incremental fentanyl 0.5 μg/kg; if the doses exceeded 2 μg/kg it was considered as failed spinal anesthesia and excluded from the study. Moreover, time to the first void and that to home discharge from the day-surgery unit after fulfilling all discharge criteria were recorded. Any patient delayed in discharge due to surgical causes not related to anesthetic technique was excluded from the study.

The primary endpoint for this study was early home discharge from day-surgery unit and the secondary endpoints were less hemodynamic changes intraoperatively and postoperatively, early ambulation, voiding, less nausea, and vomiting.

Statistics

Sample size calculation was carried out using PASS 11 software program (NCSS LLC, Kaysville, Utah, USA). The power analysis was performed based on a pilot study in our department. Group sample sizes of 25 patients per group would achieve an 80% power to detect a difference of 20 min in the mean discharge time as the primary outcome and with estimated group SDs of 20 min and with a significance level (α) of 0.05 using a two-sided two-sample t-test.

The statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc., Chicago, Illinois, USA). Normally distributed data were analyzed using Student’s t-test and were expressed as mean values±SD; categorical variables were analyzed using the χ2-test and were expressed as numbers (%). P values less than 0.05 were considered statistically significant.


  Results Top


Spinal anesthesia was successful in all patients, with no intraoperative pain or fentanyl requirements and no hospital admission due to anesthetic or surgical cause was reported. There were no significant differences between the two groups as regards age, height, weight, sex, type of surgery, and duration of surgery [Table 1].
Table 1 Patient characteristic data

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As regards the course of spinal anesthesia, there were no significant differences between the two groups as regards the highest sensory block level, time to maximum sensory block, time to maximum motor block, time to motor recovery by one level, and the time to complete motor recovery. However, time to regression of sensory level by two dermatomes and time to regression of sensory level to S1 were significantly lower in group G (72.4±10.4 vs. 83.85±8.9 and 151.6±23.8 vs. 181.44±22.38, respectively). Moreover, time to first void and time to discharge readiness were significantly lower in group G (203.58±25.5 vs. 215.93±23 and 218.8±23.8 vs. 235.78±27.6, respectively) [Table 2].
Table 2 Spinal anesthesia course and discharge timing

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As regards the incidence of side effects, there were no significant differences between the two groups as regards the use of vasopressors or the occurrence of intraoperative bradycardia. However, the incidence of nausea and shivering was significantly lower in group G [Table 3].
Table 3 Incidence of side effects

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  Discussion Top


The popularity of day-care surgery continues to increase worldwide due to reduced health costs and remarkable safety profile. Anesthesia for day surgeries requires shifting the goals for the recovery of patients. Outpatients must be fully conscious, pain free, without nausea or vomiting, and be able to ambulate to leave the unit successfully and safely. Neuraxial anesthesia is an increasingly popular technique for day-case surgeries, as it is a cost-effective technique with little delay in turnover. Moreover, patients receiving spinal anesthesia are more alert, less nauseated, and more comfortable in the postanesthesia care unit than those receiving general anesthesia. However, it is still avoided by some practitioners in the day-care setting due to concerns as regards perioperative side effects, especially delayed recovery and discharge [9],[10].

Recent clinical studies have focused on the choice of local anesthetic drug or drug combination, which is considered the key element in the success of spinal anesthesia in ambulatory surgery that would result in ample duration for surgery while providing the fastest recovery time with the lowest side effect profile. Lidocaine, due to its short duration of action, is ideal for ambulatory setting but its safety has been questioned by reports of permanent and transient neurological symptoms. In contrast, bupivacaine has the lowest incidence of transient neurological symptoms (0–1.3%), making it a good alternative to lidocaine, but its long duration of action delaying home discharge is the only drawback [11],[12].

Studies comparing different doses of bupivacaine had been conducted and found that high doses of hyperbaric bupivacaine (10 or 15 mg) showed a significantly prolonged recovery, whereas lower dose (<7.5 mg) has a higher incidence of failure (25%). Moreover, studies comparing the effect of adding opioid adjuvants to bupivacaine in the day-case setting were carried out and showed a prolongation of discharge time and a higher incidence of pruritus but has the benefit of reducing the postoperative pain scores [13].

In this study, intravenous administration of 1mg of granisetron before intrathecal 0.5% hyperbaric bupivacaine resulted in faster recovery of the sensory block compared with the control group, but there was no effect on the motor block regression time. These results are in agreement with those of Mowafi et al. [14], who concluded the same when they studied the effects of intravenous granisetron on the sensory and motor blockade produced by intrathecal bupivacaine in patients operated for elective knee arthroscopy. Moreover, Rashad and Farmawy [15], who studied the effects of intravenous ondansetron and granisetron on hemodynamic changes and sensory and motor blockade induced by spinal anesthesia in parturients undergoing cesarean section, concluded that 1 mg of granisetron intravenously before spinal block induced faster sensory recovery compared with both the ondansetron and the saline groups; however, no difference as regards motor blockade was found among the three groups. Moreover, our results are in agreement with those of Fassoulaki et al. [8], who reported that intravenous ondansetron caused faster regression of the sensory block after intrathecal lidocaine. This discrepancy between sensory and motor effects may be explained by the existence of 5-HT3 receptor in the spinal nerves and their location in the superficial laminae and substantia gelatinosa of the spinal cord and was shown to play a role in pain control in animal studies [5],[6],[7].

In contrast, Samra et al. [16], in agreement with the findings of Rashad and Farmawy [15], proved in their study that intravenous ondansetron did not affect sensory or motor block of intrathecal bupivacaine. Moreover, Kim et al. [17] concluded that intravenous injection of 0.075 mg palonosetron, another 5-HT3 antagonist, had no effect on the sensory block level and recovery from sensory and motor block in spinal anesthesia performed using bupivacaine.

Although, ondansetron, granisetron, and palonosetron belong to the same group, 5-HT3 receptor antagonists, and have the same mechanism of action and proved to be effective antiemetic drugs with minimal side effects, their effects on the course of spinal anesthesia were different. This may be due to the fact that granisetron is highly selective, potent, and produces irreversible block of 5-HT3 receptors [18].

In this study, we also found that the granisetron group (the G group) had a significantly faster return of the ability to void and shorter timing for home discharge compared with the control group (the S group). The return of the ability to void is a complicated process, and there remains room for further study into the area. Although it is subjected to many variables, regression of sensory block to S2 has been argued to be a marker for the ability to void [19]. That is why the granisetron group, which had faster sensory regression, also had faster return of the ability to void. Although difference in home discharge time is statistically significant between the two groups, the difference is only 17 min, which can be considered as clinically nonsignificant.

Limitations in this study included not comparing different doses of granisetron as we used 1 mg granisetron, which is recommended by Food and Drug Administration as a prophylaxis against postoperative nausea and vomiting (PONV). However, in recent studies, Basu et al. [20] used 3 mg of granisetron and Gupta et al. [18] used 2 mg of granisetron as a prophylaxis against PONV in comparison with ondansetron and palonosetron. Moreover, the absence of monitoring of pain scores and timing of rescue analgesics given due to early regression of sensory block was included in the study limitations.


  Conclusion Top


Administration of 1 mg of granisetron before spinal anesthesia in ambulatory surgeries resulted in statistically faster sensory regression and earlier home discharge from the day-surgery unit. However, further studies are recommended to evaluate different doses of granisetron as a reversal of spinal anesthesia and to adjust the dose of bupivacaine injected intrathecally according to the expected duration of surgery in patient on granisetron or received it as a prophylactic drug against PONV.

Financial support and sponsorship

Nil.

Conflicts of interest

There is no conflict of interest.

 
  References Top

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Nair GS, Abrishami A, Lermitte J, Chung F. Systematic review of spinal anaesthesia using bupivacaine for ambulatory knee arthroscopy. Br J Anaesth 2009;102:307–315.  Back to cited text no. 13
    
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Mowafi HA, Arab SA, Ismail SA, Al-Ghamdi A. The effects of intravenous granisetron on the sensory and motor blockade produced by intrathecal bupivacaine. Anesth Analg 2008;106:1322–1325.  Back to cited text no. 14
    
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Rashad MM, Farmawy MS. Effects of intravenous ondansetron and granisetron on hemodynamic changes and motor and sensory blockade induced by spinal anesthesia in parturients undergoing cesarean section. Egypt J Anaesth 2013;29:369–374.  Back to cited text no. 15
    
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Myoung-Hun Kim, Seunghee Ki, Kwangrae Cho, Wonjin Lee, Sang-Min Sin. The intravenously administered palonosetron does not affect the spinal anesthesia. Korean J Anesthesiol 2013;65:51–52.  Back to cited text no. 17
    
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Gupta K, Singh I, Gupta PK, Chauhan H, Jain M, Rastogi B Palonosetron, ondansetron, and granisetron for antiemetic prophylaxis of postoperative nausea and vomiting − A comparative evaluation. Anesth Essays Res 2014;8:197–201.  Back to cited text no. 18
    
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Basu A, Saha D, Hembrom BP, Roy A, Naaz A Comparison of palanosetron, granisetron and ondansetron as anti-emetics for prevention of postoperative nausea and vomiting in patients undergoing middle ear surgery. J Indian Med Assoc 2011;109:327–329.  Back to cited text no. 20
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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