|Year : 2017 | Volume
| Issue : 1 | Page : 247-252
Systemic granisetron can minimize hypotension and bradycardia during spinal anesthesia in patients undergoing elective lower-abdominal surgeries: a prospective, double-blind randomized controlled study
Waleed Abdalla, Mona A Ammar
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
20 Taksem Al-Awkaf, Presidential Palace Street, Al-Sawah, Cairo, Postal Code: 11646
Source of Support: None, Conflict of Interest: None
Introduction Although it is considered safe, spinal anesthesia has many side effects, including hypotension, and bradycardia. Increased activity of chemoreceptors (Bezold–Jarisch reflex) may play a role in this. The release of serotonin has been suggested as a possible trigger for Bezold–Jarisch reflex. Granisetron, a selective 5-HT3 receptor antagonist, may play a role in preventing hypotension and bradycardia.
Aim The aim of this study was to assess the effects of granisetron on hypotension, bradycardia, shivering, nausea, and vomiting after spinal anesthesia in patients undergoing elective lower-abdominal surgeries.
Patients and methods This study was designed as a randomized, double-blind, placebo-controlled trial. Fifty-four American Society of Anesthesiologists I–III patients, ages 25–55 years, scheduled for elective lower-abdominal surgeries under spinal anesthesia were included in this prospective study and were divided into two equal groups. Group G received 1 mg intravenous granisetron diluted in 0.9% normal saline to a total volume of 5 ml, and group C received 5 ml normal saline 5 min before undergoing spinal anesthesia. The mean arterial blood pressure, the heart rate, nausea, vomiting, and shivering were assessed.
Results The reduction in mean arterial blood pressure and heart rate was significantly lower in group G compared with group C. Regarding the incidence of complications, hypotension, bradycardia, nausea, and shivering were significantly lower in group G compared with group C. No significant difference was observed with regard to the incidence of vomiting.
Conclusion In lower-abdominal surgery, intravenously 1 mg granisetron before subarachnoid block decreased the incidence of hypotension and bradycardia significantly, besides being effective for the prevention of nausea, vomiting, and shivering.
Keywords: granisetron, hypotension, lower-abdominal surgery, spinal anesthesia
|How to cite this article:|
Abdalla W, Ammar MA. Systemic granisetron can minimize hypotension and bradycardia during spinal anesthesia in patients undergoing elective lower-abdominal surgeries: a prospective, double-blind randomized controlled study. Ain-Shams J Anaesthesiol 2017;10:247-52
|How to cite this URL:|
Abdalla W, Ammar MA. Systemic granisetron can minimize hypotension and bradycardia during spinal anesthesia in patients undergoing elective lower-abdominal surgeries: a prospective, double-blind randomized controlled study. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2020 Nov 29];10:247-52. Available from: http://www.asja.eg.net/text.asp?2017/10/1/247/238477
| Introduction|| |
Although it has been considered as a safe technique, spinal anesthesia has many side effects, including hypotension, bradycardia, nausea, and vomiting . The incidence of hypotension is 33% and that of bradycardia is 13% in nonobstetric populations . Factors influencing the level and the intensity of block include the injected drug, the level of injection, the needle type, the patient position, and patient characteristics, such as age, height, weight, pregnancy, and spinal anatomy .
Hypotension occurs from sympathetic block, which leads to a reduction in the systemic vascular resistance and the central venous pressure ,. Bradycardia can occur from autonomic imbalance with parasympathetic system predominance from the activation of left ventricular mechanoreceptors or from an increase in the baroreflex activity or the chemoreceptors Bezold–Jarisch reflex (BJR) . The release of serotonin during low-volume states has been suggested to be a possible trigger for BJR . It has been shown that a 5-HT3 receptor exists in the spinal nerves and affects pain control in animals. Binding sites for 5-HT3 are abundant at the spinal level .
Granisetron is a selective 5-HT3 receptor antagonist, and thus may play a role in preventing hypotension and bradycardia .
The aim of this study was to study the effects of granisetron on spinal induced hypotension, bradycardia, nausea, and vomiting after the injection of intrathecal hyperbaric bupivacaine in patients undergoing elective lower-abdominal surgeries.
| Patients and methods|| |
This randomized double-blinded controlled trial was performed in the Demerdash Hospital of Ain Shams University from October 2014 to August of 2015.
The study protocol was approved by the Ethics Committee of Ain Shams University Hospital, Cairo, Egypt. Fifty-four American Society of Anesthesiologists physical status I–III patients, ages 25–55 years, who were scheduled for elective lower-abdominal surgeries under spinal anesthesia were included in this prospective study, and written informed consents were obtained before surgery. Patients with contraindications for spinal anesthesia due to hemodynamic disturbances, coagulation defects, a history of hypersensitivity to any of the medications used, difficulty in communicating, patients with cardiovascular insufficiency, chronic pain, neurological diseases, and those receiving opioids, α2 agonists, and drugs that act on serotonin receptors or that affect the level of serotonin such as selective serotonin reuptake inhibitors or migraine medications were excluded from the study.
Patients were randomized into two equal groups: the granisetron (G) group (n=27) and the control (C) group (n=27). Randomization of patients was performed using the sealed-envelop design. All members of the surgical team, the nursing staff, patients, and the anesthetist were unaware of the allocation. Study drugs were prepared by an anesthesia staff who was not involved in the study, and envelops containing the information of the randomization were sealed and kept in the patient’s folder until the end of the study period. Prepared drugs with the same volume and shape were given to the anesthesiologist who was blinded to the allocation.
In the operating room, all patients were attached to standard monitors including ECG, noninvasive arterial blood pressure, and pulse oximeter. Baseline mean arterial blood pressure (MABP), heart rate (HR), and SpO2 were recorded. An 18- G intravenous (i.v.) cannula was placed on the dorsum of the nondominant hand of the patients, and 10 ml/kg lactated Ringer’s solution was infused before spinal anesthesia. Patients received 1 mg granisetron diluted in 0.9% normal saline to a total volume of 5 ml or the same volume of 0.9% normal saline solution i.v., according to the allocation 5 min before performing the spinal anesthesia. All patients received no premedication and received spinal anesthesia in the sitting position using a 25 G Quincke needle that was inserted by the midline approach into the L3–4 or the L4–5 interspaces; after ensuring the correct position of the needle, 15 mg hyperbaric 0.5% bupivacaine (Marcaine; AstraZeneca, Sodertalje, Sweden) was injected. Patients were immediately placed in the supine position after the block, and supplemental oxygen through a face mask was initiated.
The time of completion of subarachnoid injection was recorded as 0 min. After the subarachnoid block, HR and MABP were recorded every 2 min for the first 10 min and then every 5 min for the subsequent 20 min.
The sensory level was assessed by the bilateral loss of pinprick at the midclavicular line every 2 min till the fixation of the sensory level at two consecutive times, and this is the maximum sensory level. Motor block was assessed every 2 min by the modified Bromage scale until complete motor block.
The modified Bromage scale
- 0=able to move hip, knee, ankle, and toes.
- 1=unable to move hip; able to move knee, ankle, and toes.
- 2=unable to move hip and knee; able to move ankle and toes.
- 3=unable to move hip, knee, and ankle; able to move toes.
- 4=unable to move hip, knee, ankle, and toes.
Hypotension, defined as a decrease in MABP by more than 20% of the preoperative value, was treated with i.v. 6 mg ephedrine and an additional rapid bolus infusion (100 ml) of lactated Ringer’s solution. During episodes of hypotension, the blood pressure was measured every minute till normalization.
Bradycardia, defined as a decrease in the HR to less than 50 beats/min, was treated with 0.5 mg i.v. atropine.
Shivering was treated with i.v. 25 mg pethidine.
Nausea and vomiting were treated with i.v. 10 mg metoclopromide.
Before the study, a power analysis was performed to determine the minimal acceptable number of patients in each group. Group sample sizes of 24 in group G and 24 in group C achieved 82% power to detect a difference between the group proportions of 35% in the incidence of hypotension and bradycardia between the granisetron and the control groups. The statistical test used was the two-sided Z-test with pooled variance. The significance level of the test was targeted at 0.05. The significance level actually achieved by this design was 0.047.
The statistical analysis was performed using a standard SPSS software package, version 17 (SPSS Inc., Chicago, Illinois, USA). Normally distributed numerical data are presented as mean±SD, and differences between groups were compared using the independent Student’s t-test; data not normally distributed were compared using the Mann–Whitney test and are presented as median (interquartile range), and categorical variables were analyzed using the χ2-test or the Fisher exact test, and are presented as number (%). All P values were two-sided. P value less than 0.05 was considered statistically significant and P value less than 0.001 was considered highly significant.
| Results|| |
Out of 67 patients scheduled for elective lower-abdominal surgery, 12 were excluded: seven did not meet the inclusion criteria and five refused to participate. One was lost to follow-up and excluded due to spinal block failure. Finally, 54 patients were allocated for statistical analysis ([Figure 1]).
There were no significant differences between the two groups with regard to the demographic data (age, sex, BMI, or American Society of Anesthesiologists physical status of the patients) and the operative time ([Table 1]).
There was no significant difference between both groups with regard to the basal MABP or the HR, but after the induction of spinal anesthesia, a significant decrease in the MABP and the HR was observed compared with baseline values; the reduction that occurred was lesser in the granisetron (G) group compared with the control (C) group. Patients in the C group had significantly lower MABP and HR between 2 and 30 min in comparison with those in G group ([Table 2] and [Table 3]; [Figure 2] and [Figure 3]).
|Table 2 Comparison of the mean arterial blood pressure (mmHg) between groups|
Click here to view
|Figure 2 Mean arterial blood pressure (mmHg) changes in both groups. Data are expressed as mean±SD. Lines represent the mean MABP, and error bars are SD. MABP, mean arterial blood pressure.|
Click here to view
|Figure 3 Heart rate (beat/min) changes in both groups. Data are expressed as mean±SD. Lines represent the mean MABP, and error bars are SD. MABP, mean arterial blood pressure.|
Click here to view
Regarding the incidence of complications, there were seven patients (25.9%) in group C who suffered from bradycardia and were treated with atropine 0.5 mg. Moreover, the number of patients who developed hypotension in groups C was larger than that in group G [nine (33.3%) and one (3.7%), respectively]. Each episode of hypotension was treated with ephedrine 6 mg and 100 ml of lactated Ringer’s ([Table 4]).
There were statistically significant differences in the incidence of shivering between both groups, with a higher incidence in group C compared with group G (48.1 and 7.4%, respectively). Shivering was treated successfully with i.v. pethidine ([Table 4]).
There was a significantly larger number of cases that experienced nausea in group C than in group G (59.3 vs. 11.1%, respectively). No patient in group G suffered from vomiting, whereas three patients (11.1%) in group C developed vomiting, which was treated with i.v. metoclopromide, with no statistically significant difference ([Table 4]).
| Discussion|| |
Despite significant advances in understanding the pathophysiology of spinal anesthesia, complications still occur. The search for new therapies that can improve the outcome remains of considerable importance. In the current study, we found a new use for a familiar and inexpensive drug.
This study revealed that granisetron significantly reduced the decrease in MABP, bradycardia, and the use of ephedrine, when used as a premedication before spinal anesthesia in abdominal surgery.
A study by White et al.  revealed that granisetron was significantly effective at preventing paradoxical bradycardia and preventing a decrease in the systolic blood pressure due to bleeding.
Eldaba and Amr  studied the effectiveness of i.v. granisetron in the prevention of hypotension and bradycardia during spinal anesthesia in cesarean delivery; they concluded that premedication with 1 mg i.v. granisetron reduced hypotension, bradycardia, and the use of vasopressors significantly.
These findings agree with those of Tsikouris et al. , who observed that the infusion of granisetron diminished heart-rate fluctuations and decreased systolic blood pressure changes during head-up tilt-table tests, which are likely related to the BJR.
In contrast to the present study, Mowafi et al.  and Rashad and Farmawy  found that i.v. granisetron administration had no effect on hemodynamic variables.
In a study by Shrestha et al. , they concluded that granisetron given i.v. does not decrease the incidence of hypotension and bradycardia after subarachnoid block in patients undergoing lower-abdominal surgery. However, it attenuates the decrease in diastolic and mean arterial pressures during spinal anesthesia.
The current study also showed a decreased incidence of associated complications such as nausea, vomiting, and shivering, as granisetron and ondansetron are used primarily for the prophylaxis or the treatment of postoperative nausea and vomiting; many studies support our results in this aspect: Del Giglio et al  concluded that both granisetron and ondansetron have similar antiemetic efficacy for the prophylaxis of chemotherapy-induced nausea and vomiting, and Gupta et al.  found that both granisetron and ondansetron are superior to metoclopramide in the prophylactic therapy for postoperative nausea and vomiting.
A study by Dasgupta et al.  revealed that the prophylactic use of granisetron is effective in preventing emetic episodes 24 h after the administration of spinal anesthesia for cesarean delivery.
| Conclusion|| |
We concluded that in lower-abdominal surgery, i.v. 1 mg granisetron before subarachnoid block decreased the incidence of hypotension and bradycardia significantly, besides being effective in the prevention of nausea, vomiting, and shivering.
- Different doses of granisetron were not compared.
- The protocol allowed the use of ephedrine because of availability issues for phenylephrine in our hospitals.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R. Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992; 76:906–916.
Arndt JO, Bömer W, Krauth J, Marquardt B. Incidence and time course of cardiovascular side effects during spinal anesthesia after prophylactic administration of intravenous fluids or vasoconstrictors. Anesth Analg 1998; 87:347–354.
Hocking G, Wildsmith JA. Intrathecal drug spread. Br J Anaesth 2004; 93:568–578
Norris MC. Spinal anesthesia for cesarean delivery. In: Norris MC, editor, Handbook of obstetric anesthesia
. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2000. 309–312.
Butterworth J. Physiology of spinal anesthesia: what are the implications for management? Reg Anesth Pain Med 1998; 23:370–373 discussion 384–387.
Adams VR, Valley AW. Granisetron: the second serotonin-receptor antagonist. Ann Pharmacother 1995; 29:1240–1251.
Boess FG, Martin IL. Molecular biology of 5-HT receptors. Neuropharmacology 1994; 33:275–317.
Van Wijngaarden I, Tulp MT, Soudijn W. The concept of selectivity in 5-HT receptor research. Eur J Pharmacol 1990; 188:301–312.
White CM, Chow MS, Fan C, Kluger J, Bazunga M. Efficacy of intravenous granisetron in suppressing the bradycardia and hypotension associated with a rabbit model of the Bezold-Jarisch reflex. J Clin Pharmacol 1998; 38:172–177.
Eldaba AA, Amr YM. Intravenous granisetron attenuates hypotension during spinal anesthesia in cesarean delivery: a double-blind, prospective randomized controlled study. J Anaesthesiol Clin Pharmacol 2015; 31:329–332.
] [Full text]
Tsikouris JP, Kluger J, Chow MS, White CM. Usefulness of intravenous granisetron for prevention of neurally mediated hypotension upon head upright tilt testing. Am J Cardiol 2000; 85:1262–1264.
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.
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.
Shrestha BK, Acharya SP, Marhatta MN. Use of Granisetron for prevention of hypotension and bradycardia due to spinal anesthesia: a double blind randomised control trial. J Soc Anesth Nepal 2014; 1:36–39.
Del Giglio A, Soares HP, Caparroz C, Castro PC. Granisetron is equivalent to ondansetron for prophylaxis of chemotherapy-induced nausea and vomiting: results of a meta-analysis of randomized controlled trials. Cancer 2000; 89:2301–2308.
Gupta V, Wakhloo R, Lahori VU, Mahajan MK, Gupta DS. Prophylactic antiemetic therapy with ondansetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy under general anaesthesia. Internet J Anesthesiol 2007; 14:1–5.
Dasgupta M, Biswas BN, Chatterjee S, Mazumder P, Bhanja Chowdhury M. Randomized, placebo-controlled trial of granisetron for control of nausea and vomiting during cesarean delivery under spinal anesthesia. J Obstet Gynaecol India 2012; 62:419–423.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]