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Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 12  |  Issue : 2  |  Page : 333-337  

A comparative study of three vasopressors for maintenance of blood pressure during spinal anesthesia in lower abdominal surgeries


1 Department of Anaesthesiology, G. B. Pant Hospital, New Delhi, India
2 Department of Anaesthesiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication14-Jun-2018

Correspondence Address:
Dr. Amitesh Pathak
Department of Anaesthesiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_199_17

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   Abstract 

Introduction: Subarachnoid block, although being highly efficient with lesser drug doses, often has limitation such as hypotension, continues to be a matter of concern to the anesthetist. The present study was aimed to compare the use of phenylephrine, ephedrine, and mephentermine bolus for maintenance of blood pressure during spinal anesthesia in lower abdominal surgeries. Subjects and Methods: In a randomized, prospective study, 90 adult patients of either sex who developed hypotension during surgery under subarachnoid block were allocated into three groups to receive bolus phenylephrine, ephedrine, and mephentermine. The number of boluses and time taken to recover from hypotension was noted. Occurrence of adverse effects in the perioperative and postoperative period was also noted. Results: Results were analyzed by Student's paired t-test and Chi-square test. The ANOVA test was used to compare the group variances among the study groups. P < 0.05 was considered statistically significant. Thirty-four hypotensive events (average 1.03 events/patient) took place in mephentermine group. In phenylephrine group, a total of 53 hypotensive events took place. On an average, the group had a total of 1.61 hypotensive events per patient. No hypotensive event took place in ephedrine group after the first bolus of drug (average 1 event/patient). Mean heart rate in phenylephrine group was significantly lower as compared to the other two groups (P < 0.001). Conclusion: Mephentermine and ephedrine were similar in performance, offered a better hypotensive control, and had lower recurring events as compared to phenylephrine.

Keywords: Ephedrine, mephentermine, phenylephrine


How to cite this article:
Kaur D, Khan AL, Pathak A. A comparative study of three vasopressors for maintenance of blood pressure during spinal anesthesia in lower abdominal surgeries. Anesth Essays Res 2018;12:333-7

How to cite this URL:
Kaur D, Khan AL, Pathak A. A comparative study of three vasopressors for maintenance of blood pressure during spinal anesthesia in lower abdominal surgeries. Anesth Essays Res [serial online] 2018 [cited 2020 Apr 6];12:333-7. Available from: http://www.aeronline.org/text.asp?2018/12/2/333/234418


   Introduction Top


Regional blocks such as spinal, epidural, and a combination of spinal/epidural blocks have gained widespread popularity among the surgical fraternity. Although subarachnoid block is highly efficient with less drug doses, it has some limitations such as hypotension, lesser control over level of blockade, and limited duration of anesthesia.[1],[2] The incidence of hypotension can be as high as 70%–80% when pharmacological prophylaxis is not used.[3] Despite numerous attempts to restrict this incidence, it continues to be a cause of concern to the anesthetist.

Numerous pressor agents have been tried to counteract the hypotensive effect of subarachnoid block, usually by vasoconstriction and also by increasing the cardiac output.[4] In practice, the most commonly used drugs are the sympathomimetic agents which exert their effects through the adrenergic receptors, either acting directly or indirectly by inducing the release of noradrenaline which further acts on these receptors.

Phenylephrine is a direct-acting, potent alpha-1 agonist with no beta activity. It, therefore, causes a rapid increase in systemic vascular resistance and blood pressure.[5] Mephentermine acts by indirect stimulation of beta-adrenergic receptors causing release of norepinephrine from its storage sites. It has positive inotropic effect on the myocardium.[4] Ephedrine is a potent alpha and beta agonist, acting both directly and also indirectly. Its effects on vascular resistance are less pronounced than the other alpha agonists, but it also increases cardiac output thereby maintaining blood pressure.[4],[6]

The present study was aimed to compare the use of bolus phenylephrine, ephedrine, and mephentermine for maintenance of arterial pressure during spinal anesthesia in lower abdominal surgeries. It is surprising that comparative literature on use of these drugs in lower abdomen surgery cases is almost replete possibly owing to relatively lower incidence of hypotensive events in such surgeries, however, considering the fact that even a low incidence of hypotension has far-reaching effect on patient's well-being; it is essential that this issue should be explored further.

Objectives

  1. To compare the arterial pressure during spinal anesthesia in lower abdominal surgeries with the use of phenylephrine, ephedrine, or mephentermine
  2. To evaluate and compare the time taken for recovery from hypotension using different drugs being compared
  3. To monitor and record side effects, if any.



   Subjects and Methods Top


After obtaining approval by the Institutional Ethical Committee, a randomized, double-blinded, prospective, observational study was done. Written and informed consent was obtained from the eligible patients. Inclusion criteria were adult patients of either sex aged 20–50 years undergoing lower abdominal surgery under spinal anesthesia of <2 h duration with ASA physical status I and II, baseline systolic blood pressure between 100 and 140 mmHg and diastolic blood pressure between 70 and 89 mmHg and fulfilling the criteria of hypotension during the operation as defined. Exclusion criteria were patient refusal to enroll in the study, preexisting neurological deficit, coagulation disorder, comorbidities, and known allergy to test drugs.

Out of these, first 99 patients who developed hypotension during the surgery were enrolled. These patients were allocated into three groups of 33 each as follows:

Group P: phenylephrine 100 mg (0.1 mg) in 1 ml as intravenous (IV) bolus,

Group E: ephedrine 6 mg in 1 ml as IV bolus, and

Group M: mephentermine 6 mg in 1 ml as IV bolus was used as indicated.

Methods

All patients were kept nil per oral for at least 6 h, premedicated with oral ranitidine 150 mg, alprazolam 0.25 mg, and metoclopramide 10 mg the night before surgery. On arrival of the patients in operation theater, IV line was initiated with 18-G cannula; all patients received 20 ml/kg of Ringer's lactate solution intravascular loading before spinal anesthesia. After preloading, heart rate (HR), noninvasive blood pressure, respiratory rate, and peripheral oxygen saturation (SpO2) were monitored for the duration of study.

The patients were placed in the sitting position, and dural puncture was performed at L3–L4 or L2–L3 interspace (in case the lumbar puncture fails at L3–L4 interspace) using a standard midline approach with a 25-G Quincke spinal needle. Three milliliters of bupivacaine 0.5% (heavy) was injected intrathecally. The target block height achievable was equal to T8 or above. The patient received oxygen 4 L/min through venture's face mask throughout the procedure. Systolic, diastolic, and mean arterial pressure (MAP) were recorded as a baseline values immediately before subarachnoid block, then at every 2 min for first 10 min, thereafter, every 5 min till the end of surgery or 2 h whichever was earlier. Whenever hypotension occurred, the study drug was given IV and recordings were taken for every 2 min till the optimization of the blood pressure. Hypotension was defined as decrease in MAP below 20% of baseline or systolic pressure of <90 mmHg. The number of boluses and time taken to recover from hypotension was also noted. Bradycardia (HR <50 bpm) was treated by atropine 0.6 mg IV, if required.

Occurrence of adverse effects in the perioperative and postoperative periods was noted, particularly in relation to respiratory or cardiovascular problems (bradycardia, tachycardia), nausea or vomiting, and headache.

Sample size calculation

Sample size (n) = ([σ12+ σ22] [Zα+ Zβ]2)/d 2

σ1= standard deviation of Group I

σ2= standard deviation of Group II

d = mean standard deviation

α = type I error (5%)

β = type II error (10%)

power of study = (100 – β), i.e., 90%

Therefore, n = 30, adding 10% as wasting factor = 30 + 3 = 33 per group.

Thus, the minimum sample size required for each group was 33 samples. Considering this sample size to be too low for statistical considerations, the sample size will be kept in accordance with the central limit theorem that states a sample size ≥30 to be large enough for statistical considerations.

Statistical tools employed

The statistical analysis was done using IBM SPSS Statistics version 15.0 for Windows, Armonk, NY: IBM Corp. The values were represented in number (%), and mean ± standard deviation results were analyzed by Student's paired t-test and Chi-square test. The ANOVA test was used to compare the group variances among the study groups. P < 0.05 was considered statistically significant.


   Results Top


Difference in none of the above anthropometric variables of the patients of the above three groups was found to be statistically significant [Table 1].
Table 1: Patient characteristics

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At baseline (T1), difference in hemodynamic variables of above three groups was not found to be statistically significant [Table 2].
Table 2: Intergroup comparison of baseline hemodynamic variables of study population

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Proportion of patients with only single hypotensive event was found to be higher in Group E (100.0%) and Group M (97.67%) as compared to Group P (66.67%). Proportional differences in number of hypotensive events among the groups were found to be statistically significant (P = 0.001) [Table 3].
Table 3: Intergroup comparison of hypotension events in study population

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At the times of first interventional bolus (B1T0), HR of Group P was found to be higher than Group M and Group P but the difference was not statistically significant (P = 0.266). However, there was a decrease in HR in Group P as compared to Group M, and Group E was found to be statistically significant between B1T2 and B1T10 (P< 0.001), thus reflecting reflex bradycardia of phenylephrine. After 2nd intervention (B2), there was more decrease seen in HR of Group P as compared to Group M, and this difference was statistically significant from 2nd min to 10th min after second intervention (P< 0.001). Group M achieved its baseline HR in first 10 min after 1st interventional bolus (B1) while Group P showed a decreasing trend in HR, thus reflecting reflex bradycardia. Continued reflex bradycardia action of phenylephrine was observed in Group P even after 3rd and 4th interventional bolus (B3, B4) [Table 4].
Table 4: Intergroup comparison of heart rate at different time intervals of intervention

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At the time of first intervention (B1T0), MAP of Group P was found to be higher than Group M and Group E, and this difference was found to be statistically significant between B1T0 and B1T8 (<0.001). At the time of second intervention (B2), MAP of Group P was found to be higher than Group M and was found to be statistically significant between 2nd min (B2T2) and 10th min (B2T19). However, second intervention was not required in Group E. There was no need of third (B3) and fourth (B4) intervention in Group M and Group E. After second intervention, baseline MAP was achieved by Group P at 6th min (B2T6) while Group M did not achieve the baseline MAP in first 10 min (B2T10). After third intervention, Group E achieved MAP at 6th min (B3T6) and at 6th min (B4T6) in the fourth intervention [Table 5].
Table 5: Intergroup comparison of mean arterial pressure at different time intervals of intervention

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   Discussion Top


Hypotensive effects of spinal anesthesia are widely studied in cesarean procedures owing to the compounding effect of aortocaval compression. Despite numerous attempts to restrict this incidence, it continues to be a cause of concern to the anesthetist. The present study was aimed to compare the use of bolus phenylephrine, ephedrine, and mephentermine for maintenance of arterial pressure during spinal anesthesia in lower abdominal surgeries.

Mean HR in phenylephrine group was significantly lower as compared to the other two groups (P< 0.001). With respect to HR, the findings of present study were in consonance with the observation made by Bhattarai et al.[7] who reported a significant reduction in HR in phenylephrine group as compared to mephentermine and ephedrine groups when administered a bolus dose in cases undergoing cesarean section. Mohta et al. also reported that the maternal HR is significantly higher after ephedrine administration, while the incidence of maternal bradycardia is significantly greater after phenylephrine administration, though these differences do not appear to significantly impact clinical outcomes in high-risk obstetric patients.[8] In the present study, this effect lasted till 10 min and culminated in 31 subsequent hypotensive events in phenylephrine group probably owing to a higher dose used (100 μg in the present study as compared to 25 μg in the cited study).

Similar to study done by Mahajan et al.,[9] in our study, both ephedrine and mephentermine groups were found to be comparable as far as hemodynamic control and HR are concerned. Contrary to the results of the present study, Adigun et al.[10] found bolus IV phenylephrine 100 μg to be as effective as ephedrine 5 mg with no significant difference in HR between two groups and an equivalent hypotensive control. This may be attributed to the lower dose of ephedrine used in their study.

Mean blood pressure was found to be higher in phenylephrine group as compared to the other two groups up to 6–8 min time interval (P< 0.001). With respect to blood pressure, the observations in the present study were in agreement with the findings of Sahu et al.[11] who found the elevation of systolic arterial pressure in phenylephrine group to be significantly high for first 6 min of bolus dose as compared to ephedrine and mephentermine groups. Ephedrine and mephentermine have got a mixed action directly as well as indirectly on a and b receptors, whereas phenylephrine has pure a receptors' activity.[12],[13],[14] Similar observations were also made by Ganeshnavar et al.[15] who also found identical results as obtained in the present study.

In the present study, as far as number of subsequent hypotensive events was concerned, mephentermine group had only 1 (3.33%) subsequent hypotensive event. Thus, in total, a total of 34 hypotensive events (Average 1.03 events/patient) took place in mephentermine group. In phenylephrine group, a total of 53 hypotensive events took place. There were 11 patients in whom more than one hypotensive events took place. In phenylephrine group, a total of 5 (15.15%) patients had 2 hypotensive events, 3 (9.09%) patients had 3 hypotensive events, and 3 (9.09%) had 4 hypotensive. On an average, the group had a total of 1.61 hypotensive events per patient. In ephedrine group, no hypotensive event took place after the first bolus of drug. Thus, in this group, the average number of hypotensive events following administration of first bolus dose was only 1.


   Conclusion Top


On the basis of the above results, it can be concluded that phenylephrine has a fast-acting but short-lived normotensive effect coupled with a bradycardia tendency. However, ephedrine and mephentermine had a relatively steady progression and stable normotensive effect with no bradycardia effect. Hence, mephentermine and ephedrine were similar in performance, offered a better hypotensive control, and had lower recurring events as compared to phenylephrine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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Caplan RA, Ward RJ, Posner K, Cheney FW. Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing factors. Anesthesiology 1988;68:5-11.  Back to cited text no. 1
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Mitra JK, Roy J, Bhattacharyya P, Yunus M, Lyngdoh NM. Changing trends in the management of hypotension following spinal anesthesia in cesarean section. J Postgrad Med 2013;59:121-6.  Back to cited text no. 2
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Johnston I. Vasopressors for sub-arachnoid anaesthesia in obstetrics. Update Anaesth 2005;20:2-6.  Back to cited text no. 4
    
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das Neves JF, Monteiro GA, de Almeida JR, Sant'Anna RS, Bonin HB, Macedo CF, et al. Phenylephrine for blood pressure control in elective cesarean section: Therapeutic versus prophylactic doses. Rev Bras Anestesiol 2010;60:391-8.  Back to cited text no. 5
    
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7.
Bhattarai B, Bhat SY, Upadya M. Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anesthesia in cesarean section. JNMA J Nepal Med Assoc 2010;49:23-8.  Back to cited text no. 7
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Mohta M, Aggarwal M, Sethi AK, Harisinghani P, Guleria K. Randomized double-blind comparison of ephedrine and phenylephrine for management of post-spinal hypotension in potential fetal compromise. Int J Obstet Anesth 2016;27:32-40.  Back to cited text no. 8
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Mahajan L, Anand LK, Gomber KK. A randomized double-blinded comparison of ephedrine, phenylephrine and mephentermine infusions to maintain blood pressure during spinal anaesthesia for cesarean delivery: The effects on fetal acid-base status and haemodynamic control. J Anaesth Clin Pharmacol 2009;25:427-32.  Back to cited text no. 9
    
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Adigun TA, Amanor-Boadu SD, Soyannwo OA. Comparison of intravenous ephedrine with phenylephrine for the maintenance of arterial blood pressure during elective caesarean section under spinal anaesthesia. Afr J Med Med Sci 2010;39:13-20.  Back to cited text no. 10
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Sahu D, Kothari D, Mehrotra A. Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anaesthesia in caesarean section – A clinical study. Indian J Anaesth 2003;47:125-8.  Back to cited text no. 11
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12.
Mohta M, Janani SS, Sethi AK, Agarwal D, Tyagi A. Comparison of phenylephrine hydrochloride and mephentermine sulphate for prevention of post spinal hypotension. Anaesthesia 2010;65:1200-5.  Back to cited text no. 12
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Ramesh R, Dayananda VP, Bhaskara P. Evaluation of pre-emptive inrtramuscular phenylnephrine at different dose for reduction of hypotension under spinal anaesthesia. Int J Recent Trends Sci Tech 2014;12:137-40.  Back to cited text no. 13
    
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Ganeshnavar A, Uday SA, Adarsh ES, Prakashappa DS, Ramesh K, Ravi R. Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anaesthesia in caesarean section. J Clin Diagn Res 2011;5:94.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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