|Year : 2019 | Volume
| Issue : 4 | Page : 393-398
Intrathecal atropine versus intravenous metoclopramide for prevention of nausea and vomiting during cesarean section under spinal anesthesia
Tamer El Metwally Farahat1, Mohamed S Abdelhafez2
1 Department of Anesthesiology and Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||19-Nov-2018|
|Date of Acceptance||17-Dec-2018|
|Date of Web Publication||06-Jan-2020|
MD Tamer El Metwally Farahat
Anesthesiology and Intensive Care, Faculty of Medicine, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
Background One of the most unpleasant sensation is the occurrence of intraoperative episodes of nausea and vomiting in mothers undergoing cesarean section (CS) under spinal anesthesia.
Objective The aim of the present study was to compare the use of prophylactic low-dose atropine in comparison with the effect of metoclopramide for prevention of perioperative nausea and vomiting in mothers undergoing CS under spinal anesthesia.
Patients and methods The present study was conducted in 60 full-term mothers of American Society of Anesthesiology Grade I and II, with age between 20 and 35 years with uncomplicated pregnancies. Patients were allocated into two equal groups. Atropine group (group A) included 30 patients who received intrathecal study solution which is a mixture of 2.5 ml of 0.5% hyperbaric bupivacaine, 25 μg fentanyl, and 100 μg of a 1 mg/ml of free atropine sulfate. Metoclopramide group (group M) included 30 patients who received intravenous solution of metoclopramide 10 mg in 2 ml in addition to intrathecal study solution (2.5 ml of 0.5 hyperbaric bupivacaine, 25 μg fentanyl and 100 μg of preservative-free saline 0.9% as a placebo) which was given after spinal anesthesia and before the start of surgical incision. The number of episodes of nausea and vomiting were recorded, and also any other adverse effects were recorded.
Results The incidence of intraoperative nausea and vomiting (IONV) and late nausea score were significantly decreased in group A compared with group M (P<0.05), and nearly equal incidence in early onset of nausea in both groups. No differences were noted in terms of postoperative pain or hypotensive episodes.
Conclusion Intrathecal atropine can be safely used to decrease intraoperative nausea and vomiting for mothers undergoing CS under spinal anesthesia.
Keywords: atropine, cesarean section, metoclopramide, nausea and vomiting
|How to cite this article:|
Farahat TM, Abdelhafez MS. Intrathecal atropine versus intravenous metoclopramide for prevention of nausea and vomiting during cesarean section under spinal anesthesia. Res Opin Anesth Intensive Care 2019;6:393-8
|How to cite this URL:|
Farahat TM, Abdelhafez MS. Intrathecal atropine versus intravenous metoclopramide for prevention of nausea and vomiting during cesarean section under spinal anesthesia. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2020 Apr 6];6:393-8. Available from: http://www.roaic.eg.net/text.asp?2019/6/4/393/275146
| Introduction|| |
Perioperative occurrence of nausea and vomiting is considered a common complication and unpleasant event to patients undergoing cesarean section (CS) under spinal anesthesia. The incidence of perioperative occurrence of nausea and vomiting differed in various studies ranging from 60 up to 80% .
Different risk factors related to anesthetic drugs and surgical factors may predispose to the incidence of nausea and vomiting during CS, such as hypotension, drug use as neuraxial and intravenous opioids, surgical manipulation, uterine exteriorization, vigorous movement of the patient, and finally using the uterotonic agents including oxytocin .
Many drugs given perioperatively affect the incidence of postoperative nausea and vomiting. One of these, metoclopramide is a derivative of para-aminobenzoic acid with gastrokinetic and antiemetic effects . However, recently, a meta-analysis reported that using a dose of 10 mg metoclopramide for antiemetic effects during and after CS was not better than placebo .
Atropine may be a safer anticholinergic agent as it does not cross the blood-brain or placental barriers at common dosage. Atropine delays gastric emptying and lowers esophageal tone, so premedication with atropine is considered as a method to decrease perioperative nausea and vomiting .
In this study, we hypothesized that intrathecal low-dose atropine will decrease the incidence of nausea and vomiting in mothers undergoing CS under spinal anesthesia in comparison with intravenous metoclopramide.
| Patients and methods|| |
This prospective randomized controlled study was done from December 2017 to October 2018 in Mansoura Main University Hospital (MMUH). Written informed consents were obtained after approval from the Institutional Review Board (IRB), Mansoura Faculty of Medicine, from 60 patients with American Society of Anesthesiologist Physical Status Classes I–II, having indication for CS other than fetal or maternal pathology, such as previous CS, noncephalic presentation, maternal request, and indication for and parturient’s agreement to spinal anesthesia.
Patients with history of preeclampsia; eclampsia; psychological disturbances; a gastrointestinal disturbance; allergy to the drug used; infection at the site of spinal anesthesia; patient using antiemetic agent in the last 24 h; renal, hepatic, and cardiac disorders; prescription of sedative; and analgesic medications during operation or high spinal block were excluded.
All mothers included in the study were randomly allocated into two equal groups using computer-generated randomization table:
- Atropine group (group A): 30 patients received intrathecal study solution which is a mixture of 2.5 ml of 0.5% hyperbaric bupivacaine, 25 μg fentanyl, and 100 μg of a 1 mg/ml of free atropine sulfate.
- Metoclopramide group (group M): 30 patients received intravenous solution of metoclopramide 10 mg in 2 ml in addition to intrathecal study solution (2.5 ml of 0.5 hyperbaric bupivacaine, 25 μg fentanyl, and 100 μg of preservative-free saline 0.9% as a placebo).
All mothers were instructed to start fasting. Ringer’s lactate solution was infused at a rate of 1.5 ml/kg/1 h. Patients were monitored for basal value of ECG, automated noninvasive systolic and diastolic blood pressure, and O2 saturation.
On arrival to the OR, spinal anesthesia was performed using an aseptic technique while the mothers sat in the sitting position, and then skin infiltration was done using 0.5 ml of 1% lidocaine at the level of either between L3 and 4 or level between L4 and 5 using spinal needle with 25-G pencil (point type), till free flow of clear cerebrospinal fluid was obtained. Thereafter, the study solution was injected intrathecally according to the group allocation. After that, mothers’ position was changed to supine position with left lateral tilt to decrease the aortocaval compression caused by the uterus so as to decrease hypotension occurrence after spinal anesthesia. Oxygen supplementation was done at 4 l/min through facemask. Assessment of dermatomal level of sensory block was done through pinprick technique, achieving T5 block which was the accepted level for starting surgical incision.
Heart rate and systolic and diastolic blood pressures were recorded every 1-min interval during the first 10 min, and then every 5-min interval throughout the whole time of surgery. Intraoperative occurrence of hypotensive episodes, in which hypotension less than 20% of the basal reading was noted, was treated by increasing the Ringer’s lactate infusion and intravenous injection of increments of 3 mg ephedrine hydrochloride, whereas intravenous injection of atropine sulfate (0.5 mg) was given when heart rate less than 50 beats/min occurred. Just after delivery of the baby and umbilical cord clamping, the patients were given 10 units of oxytocin incrementally, and the total amount of oxytocin units used was recorded. The time of uterine exteriorization was also recorded. Postoperative pain was assessed by visual analog scale (VAS) during postoperative 24 h.
The incidence of intraoperative nausea and vomiting (IONV) was defined as at least one episode of nausea as well as any clinical manifestations (retching or vomiting) and any requests for antiemetic medication.
Our primary outcome was the incidence of occurrence of nausea and vomiting during the intraoperative period and in the early (0–2 h) and late (2–6 h) postoperative period. Intraoperative nausea was recorded as no nausea equal 0, nausea only equal 1, and nausea and vomiting equal 2.
At the end of surgical procedure of the CS, mothers were transferred to the postanesthesia care unit in which routine monitoring of blood pressure, ECG, and SpO2 was done. Then, all mothers in the study protocol were transferred to the ward. Data collection was done by a trained investigator blinded to the study protocol.
The power analysis of this study was prospectively measured using the G Power analysis program. Using the incidence of nausea and vomiting during the operation and assuming type I error protection of 0.05 with the effect size convention of 0.8, a total sample size of 52 was calculated. Then, we added 3 cases in each group to protect against dropout cases, so the total number of cases was 60 case (30 patient for each group).
The data were analyzed using SPSS (version 20). Chi-square test was used for the association variables for categorical data. Fisher exact test was used when one expected cell or more less than or equal 5. Comparison of quantitative variables was done using Unpaired t-test, whereas Paired t-test was used for comparison between quantitative variables in the same group. P value <0.05 was considered significant.
| Results|| |
The results of this study showed that as regarding age, height, and weight, there were no statistically significant differences in the studied groups. The studied groups were comparable regarding systolic blood pressure, diastolic blood pressure, and heart rate, and showed that there was no statistically significant difference between groups. Moreover, there were no significant differences between studied groups regarding the duration of operation, exteriorization of uterus, and total dose of oxytocin ([Table 1]).
Intraoperatively there was a significant difference between studied groups regarding the occurrence of IONV, where seven (23.3%) patients in group A complained of at least one attack of intraoperative nausea compared with 16 (53.3%) patients in group M (P<0.05). The overall incidence of IONV was 38.3% ([Table 2]).
|Table 2 Perioperative nausea and vomiting and hypotensive episodes in the studied groups|
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Regarding early nausea score (0–2 h), 36.7, 46.7, and 16.6% of patients in group A have score of 0, 1, and 2, respectively, compared with 33.3, 46.7, and 20.0% of patients in group M have score of 0, 1, and 2, respectively, with no significant difference between them (P>0.05) ([Table 2]).
Regarding late nausea score (2–6 h), 43.3, 50.0, and 6.7% of patients in group A have score of 0, 1, and 2, respectively, compared with 10.0, 63.3, and 26.7% of patients in group M have score of 0, 1, and 2, respectively. Group M has a significant higher score of late onset of nausea than group A (P<0.05) ([Table 2]).
Regarding VAS score for postoperative pain and hypotensive episodes, there was no statistical significant difference between both studied groups (P>0.05) ([Table 2]).
In addition, in [Table 3], there was a correlation between occurrence of hypotension and incidence of IONV, whereas there was no correlation between IONV and heart rate, duration of surgery, oxytocin dosage, or exteriorization of the uterus ([Table 3]).
|Table 3 Multivariable risk factor analysis for IONV (logistic regression)|
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| Discussion|| |
One of the most distressing complication for patients, obstetricians, and anesthetists is the intraoperative nausea and vomiting which may increase the risk of injury and visceral penetration during surgery owing to involuntary abdominal movements during vomiting. Intraoperative nausea and vomiting remains unknown, and it may occur owing to several factors . One of the commonest cause for perioperative nausea and vomiting in mothers undergoing CS is the occurrence of hypotension caused by spinal anesthesia which leads to cerebral hypoperfusion , and also the emetic symptoms aggravated by uterotonic drugs . So treatment of hypotension in mothers undergoing CS using spinal anesthesia is considered an important factor for the avoidance of perioperative nausea and vomiting.
Metoclopramide is known for antagonizing dopamine-mediated relaxation effect on gastrointestinal smooth muscle in which it leads to enhancement of the response to cholinergic stimulation causing an increase of gastric emptying into the intestines. It also strengthens the lower esophagus sphincter, so it prevents acid reflux . However, owing to its lack of efficacy in low dose, it is rarely used for the management of nausea and vomiting caused by neuraxial anesthesia .
To the best of the authors knowledge, there are no comparative and clinical studies evaluating the efficacy of intrathecal low-dose atropine and intravenous metoclopramide as antiemetic agent to decrease the incidence of perioperative nausea and vomiting during CS under spinal anesthesia. Our results highlight a clear and clinically significant antiemetic effect of the drug, at least when administered with IT bupivacaine and fentanyl for scheduled CS. The effect is not shared by small-dose, preoperative atropine injected intravenously. Intrathecal atropine did not manifestly interfere with cardiac rhythm or pain relief in the studied period.
Because atropine does not cross the blood-brain or placental barriers at common dosage, atropine may be a safer alternative to metoclopramide. However, as seen in the study by Salmenpera et al. , atropine’s half-life of 2–3 h after intravenous administration may be too brief to cover the whole duration of action of IT morphine; this may be particularly apparent when smaller doses are used to avoid undesired tachycardia, xerostomia, or other typical systemic effects. As first observed by Ramaioli and De Amici , IT atropine might, in theory, exert its central nervous system effects with minimal (or no) involvement of extraneural muscarinic receptors.
In the current study, the overall incidence of IONV was 38.3%. Intraoperatively a significant difference was found between studied groups regarding the occurrence of IONV, where seven (23.3%) patients in group A complained of at least one attack of intraoperative nausea compared with 16 (53.3%) patients in group M (P<0.05). Magni et al.  in their study reported an overall incidence of IONV was 32% during SA for CS and not significantly different between the groups. The finding of the present study was in parallel with an RCT and a meta-analysis by Moghadam and Khosravi  and Mishriky and Habib , respectively, with a comparable observation period.
In the study by Endalew et al. , there was a significantly decreased occurrence of intraoperative nausea in treatment group in comparison with the other group (21.2 vs. 39.4%, P=0.008). It also showed decreased occurrence of vomiting in the treatment group in comparison with the other group (10.6 vs. 27.3%, P=0.026). These results could be owing to adequate rehydration of all patients, prophylactic administration of intravenous ephedrine, and addition of fentanyl with bupivacaine.
Regarding early nausea score (0–2 h), 36.7, 46.7, and 16.6% of patients in group A have score of 0, 1, and 2, respectively, compared with 33.3, 46.7, and 20.0% of patients in group M have score of 0, 1, and 2, respectively, without significant difference between them (P>0.05). However, in late nausea score (2–6 h), 43.3, 50.0, and 6.7% of patients in group A have score of 0, 1, and 2, respectively, compared with 10.0, 63.3, and 26.7% of patients in group M have score of 0, 1, and 2, respectively. Group M has a significant higher score of late onset of nausea than group A (P<0.05).
In the study by Endalew et al. , nausea occurrence during CS, at 2 h, and 4 h postoperatively was decreased significantly in the metoclopramide group in comparison with the other group.
In a study by Moghadam and Khosravi , there was decreased nausea score up to the sixth hour after surgery in elective CS under spinal anesthesia in comparison with the placebo.
In contrast to the present study, a previous study by Biswas et al.  reported no significant decreased in the total incidence of nausea and vomiting during surgery which may be owing to the small sample size used in the study and shorter follow-up period compared with our study.
Regarding VAS score for postoperative pain and hypotensive episodes, no statistical significant difference was found between both the groups (P>0.05). Several studies found a correlation between hypotension and increased incidence of IONV . Another study by Ngan Kee et al.  reported that the incidence of IONV increased in correlation with hypotensive episodes in combination with aortocaval compression during spinal anesthesia for CS, with inadequate lateral tilt .The current study reported absence of sedation, headache, pruritus, respiratory depression, or extrapyramidal adverse effects in atropine or metoclopramide groups. In agreement with our results, extrapyramidal adverse effects were evaluated by Lussos and colleagues ,,,,, without occurrence in any of the patients. Moreover, in the studies by Numazaki and colleagues ,,, sedation was assessed, and there were no differences among the groups. Headache was investigated in two studies by Pan and colleagues , without any significant difference regarding the comparison with the placebo group. Duman et al. , in their study reported that regarding pruritus, there was no differences between the studied groups.
Regarding the occurrence of respiratory depression, there were several studies, such as by Pan and colleagues ,,, which reported that there was no respiratory depression in any of the patients.
| Conclusion|| |
Intrathecal administration of prophylactic atropine can effectively decrease the incidence and severity of perioperative nausea and vomiting in comparison with metoclopramide group.
So the authors recommend intrathecal administration of atropine for mothers undergoing emergency CS under spinal anesthesia.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]