A Comparative Study of Phenylephrine, Ephedrine and Mephentermine For Maintainance of Arterial Pressure During Spinal Anaesthesia in Caesarean Section
A Comparative Study of Phenylephrine, Ephedrine and Mephentermine For Maintainance of Arterial Pressure During Spinal Anaesthesia in Caesarean Section
A Comparative Study of Phenylephrine, Ephedrine and Mephentermine For Maintainance of Arterial Pressure During Spinal Anaesthesia in Caesarean Section
e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 14, Issue 1 Ver.VII (Jan. 2015), PP 80-85
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2,3,4
Abstract: Hypotension following spinal anaesthesia for Caesarean section is the commonest serious problem
encountered by anaesthesiologists. Numerous methods have been tried to minimize hypotension which include
fluid preloading, left uterine displacement and use of vasopressor drugs. This study was aimed at comparing the
efficacy of three drugs Phenylephrine, Ephedrine and Mephentermine for maintenance of arterial blood
pressure during spinal anaesthesia in caesarean section. 60 patients between the age group of 18-35 years
undergoing elective as well as emergency caesarean section under spinal anaesthesia who developed
hypotension after subarachnoid block(SAB) were selected and randomly allocated into 3 groups of 20 each to
receive Group P -Phenylephrine 50mcg, Group E Ephedrine 6 mg, and Group M Mephentermine 6 mg as
bolus IV and repeated as required. Comparability of groups were analysed with Analysis of Variance (ANOVA)
test. All the 3 drugs effectively controlled SBP & DBP. On intergroup comparision rise of SBP and DBP in
phenylephrine group was more than in other two groups. Tachycardia was significantly less in Group P after
administration of the study drug. Phenylephrine causes reduction in heart rate, which may be advantageous in
cardiac patients and patients in whom tachycardia is undesirable.
Keywords: Caesarean section, Subarachnoid block, Hypotension, Vasopressor.
I.
Introduction
The delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting
and rewarding moments in medicine( Moir D D). With the increasing incidence of Caesarean section[1], the
anaesthesiologist has to take a decision about the type of anaesthetic technique to be employed which guarantees
the safety of both the mother and fetus.
In caesarean section under spinal anaesthesia hypotension has been reported in as many as 85% of the
patients.[2] Maternal hypotension is associated with symptoms like dizziness, nausea, vomiting and may also
interfere with surgical procedure and also can cause fetal bradycardia [3] and acidosis[4] Careful positioning and
volume preloading with crystalloid or colloids have been used to prevent it, but these are not complete measures
[5,6] and a vasopressor is frequently required to correct hypotension quickly[7]. Mephentermine and
ephedrine are routinely used.
The aim of this prospective study is to compare the efficacy of mephentermine, ephedrine and
phenylephrine for maintenance of blood pressure effectively in caesarean sections under spinal anaesthesia.
II.
Methodology
This comparative study was done on parturients coming for elective as well as emergency lower
segment Caesarean section conducted under spinal anesthesia in R.L .Jalappa Hospital and Research Centre,
Tamaka, Kolar. After approval from our institutional ethics committee, sixty parturients aged between 18-35
years, with ASA I and II scheduled for elective as well as emergency Caesarean section who developed
hypotension after subarachnoid block (SAB) were studied.
Patients with gross spinal abnormality, localized skin sepsis, hemorrhagic diathesis, neurological
involvement / diseases, known hypertensive patients, diabetic mellitus, cardiac, pulmonary, hepatic or renal disorders,
toxaemias of pregnancy, having inadequate subarachnoid blockade and who are later supplemented by general
anaesthesia and patients who do not develop hypotension during caesarean section under spinal anaesthesia, were
excluded from the study.
Hypotension is defined as fall in systolic pressure >20% from the baseline or a value less than
90mmHg. Patients were randomly allocated to one of the three groups to receive an I.V bolus of the following.
Group P -Inj Phenylephrine 50mcg i.v
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III.
Results
All the three groups were comparable in demographic profile and baseline parameters. Three groups
were comparable in skin incision to delivery time, uterine incision to delivery time and APGAR at 1 and 5 mins.
3.1 Systolic blood pressure (Table1, Graph 1)
Baseline systolic blood pressure for all the three groups were statistically similar. There was
statistically significant decrease in blood pressure at onset of hypotension. There was significant rise in blood
pressure after administration of the drug. On intergroup comparison, systolic blood pressure in phenylephrine
group was higher than in other groups.
3.2 Diastolic blood pressure (Table2 , Graph 2)
No statistically significant differences were found in all the 3 groups with regards to baseline diastolic
blood pressure.There was also significant rise of diastolic blood pressure post administration of the drug but
rise was more in phenylephrine group than in ephedrine and mephentermine group. There was no significant
difference in the change in blood pressure between ephedrine and mephentermine group.
3.3 Heart Rate (Table 3 , Graph 3)
Baseline heart rate in all the three groups were not statistically similar. Heart rate was raised in all the
three groups during hypotension, which was significant, but post drug administration there was significant drop
in heart rate in phenylephrine group as compared to Ephedrine and Mephentermine group (there was a rise in
heart rate post administration of the drug). No significant differences were observed between heart rate changes
in Ephedrine and Mephentermine group.
3.4 Number Of Bolus (Table 4, Graph 4)
The mean and standard deviation of no of bolus in group P was 4.001.16 , in group E was 2.450.99
and in group M was 2.551.46. There was significant statistical difference in the total dose of Phenylephrine,
Ephedrine and Mephentermine used (p<0.05). Number of boluses are significantly more in Group P with P =
<0.001**.
IV.
Discussion
Although, Caesarean section is one of the oldest operations in recorded history, anaesthesia for
Caesarean section is just a century old and is not bereft of controversies. On one hand, anaesthetic techniques
like local anaesthesia have been scoffed at, by both anaesthesiologists and obstetricians. While, on the other
hand, the obstetric airway with its ensuing complications have instilled fear into the anaesthesiologists. Thus
general anaesthesia for parturients was approached with great degree of caution and decision making.
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Amount of local anaesthetic injected was found to produce a higher level of anaesthesia in pregnant term
females than in pregnant females.
2. Factors causing hypotension after spinal anaesthesia which are common to both pregnant and non pregnant
females like sympathetic blockade leading to vasodilatation and consequent decrease in preload and cardiac
output.
3. Additional factors that may accentuate the cardiovascular response to sympathetic denervation include
i. Large amounts of blood present in uterus.
ii. Weight of uterus impairs venous return from extremities during spinal anaesthesia, especially in supine
position, thus decreasing cardiac output.
iii. Bearing down of patient causes abdominal muscle contraction which further decreases venous return to
heart.
Thus, there has been a constant ongoing search by anesthesiologists to recognize this dangerous
haemodynamic instability and correct it promptly.
Careful positioning and volume preloading with intravenous crystalloid solution or colloid solution
have been standard practice for prevention of hypotension, but these are not complete measures. As
vasodilatation is the primary cause of arterial pressure reduction, it seems logical to use vasopressor to correct it.
It has been shown that the percentage decrease in placental perfusion is related to the percentage reduction in
maternal arterial pressure and not to the absolute reduction in pressure.
The place of IV vasopressors for treatment of hypotension during caesarean section is well established.
Ephedrine and mephentermine have got a mixed action directly as well as indirectly on alpha and beta receptors,
whereas phenylephrine has pure alpha receptor activity. Although phenylephrine reduces uterine blood flow,
studies proved that it does not affect fetal outcome and can be used safely during spinal anaesthesia for
caesarean section.
In this study all the three vasopressor effectively maintained arterial pressure within 20% limit of
baseline value though phenylephrine maintained better as compared to ephedrine and mephentermine. This may
be due to that, phenylephrine has peak effect within one minute, whereas ephedrine has 2-5 minutes and
mephentermine has 5 minutes.
Moran and Colleagues gave ephedrine 10 mg or phenylephrine 80 mcg IV bolus to maintain systolic
arterial pressure above 100 mmHg. They concluded that phenylephrine is as effective as ephedrine and when
used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, non
laboring parturient. [16]
In our study cardiovascular stability was better with phenylephrine. It caused significant reduction in
heart rate after the bolus dose, which is a consistent effect in phenylephrine treated women in their studies also.
In ephedrine and mephentermine group the heart rate increased compared to preoperative values which we
found as statistically significant consistent with the study by Dinesh Sahu.[14] It may be due to beta adrenergic
effect of ephedrine and mephentermine which the phenylephrine lacks.
There was no significant effect of vasopressor on fetus in terms of Apgar score at 1 and 5 minutes
which correlated well with the study by Dinesh Sahu. In our study we found only nausea and vomiting as side
effects.
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Conclusion
Based on the present clinical comparative study, the following conclusions can be made: All three
vasopressors effectively maintained arterial blood pressure during spinal anaesthesia for caesarean
section.Phenylephrine has quicker peak effect , but more bolus doses were required to control the hypotension in
our study. Phenylephrine caused significant reduction in heart rate than ephedrine and mephentermine. All drugs
did not have any adverse effects on the fetus or the mother. Thus it can be concluded that IV Phenylephrine,
Ephedrine and Mephentermine can be safely used during spinal anaesthesia for caesarean section for treatment
of hypotension.
References
[1]. 1.Pernoll ML, Mandell JE. Caesarean section. Chapter 30, Principles and Practice of Obstetric Analgesia and Anaesthesia, 2nd Ed n.,
Bonica JJ and McDonald JS,Williams and Wilkins, 1995:968-1009.
[2]. 2. Riley ET, Cohen SE, Rubenstein AJ, Flanagan B. Prevention of hypotension after spinal anaesthesia for caesarean section : 6%
hetastarch versus lactated Ringers solution. Anaesthesia and Analgesia 1995;81:838-42.
[3]. 3. Eloner H, Barcohana J, Bartosheck AK. Influence of postsponal hypotension on fetal electrogram. Ameri can Journal of Obstetrics
and Gynaecology 1960;80:560-572.
[4]. 4.Corke BC, Datta S, Ostheinar GW et al. Spinal anaesthesia for caesarean section. The influence of hypotension on neonatal outcome.
Anaesthesia1982;37:658-662.
[5]. 5. Jackson R, Reid JA, Thorburn J. Volume preloading is not essential to prevent spinal induced hypotension at caesarean section.
British Journal of Anaesthesia 1995;75:262-5.
[6]. 6. Karinen J, Rasonen J, Alahuhta S, Jouppila R and Jouppila P. Effect of crystalloid and colloid preloading on uter oplacental and
maternal Hemodynamic state during spinal anaesthesia for caesarean section. British Journal of Anaesthesia 1998.75:531-35.
[7]. 7. McCrae AF, Wild Smith JAW. Prevention and treatment of hypotension during central neural block. British Journal of Anaesthesia
1993;70:672-680.
[8]. 8. Reynolds F, Seed PT. Anaesthesia for caesarean section and neonatal acid base status : A meta analysis. Anaesthesia 2005;6 0:636653.
[9]. 9. Chan WS, Irwin MG, Tong WN, Lam YH. Prevention of hypotension during spinal anesthesia for caesarean section : ephedrine
infusion versus fluid preload. Anaesthesia 1997;52:908-913.
[10]. 10. Ngan Kee WD, Khaw KS, Lee BB, Lau TK, Gin T. a dose response study of prophylactic intravenous ephedrine for the prevention
of hypotension during spinal anaesthesia for Caesarean delivery. Anaesthesia and Analgesia 2000;90:1390-5.
[11]. 11. Rout Cc, Akoojee SS, Rocke DA, Gouws E. rapid administration of crystalloid preload does not decrease the incidence of
hypotension after spinal anaesthesia for elective Caesarean section. British Journal of Anaesthesia 1992;68:394-397.
[12]. 12. Rout CC, Rocke DA, Levin J, Gouws E, Reddy D. A reevaluation of the role of crystalloid preload in the prevention of
hypotension associated with spinal anaesthesia for elective Caesarean section. Anaesthesiology 1993;79:262-269.
[13]. 13. Datta S, Milton HA, Ostheimer GW, Weiss JB. Method of ephedrine administration and nausea and hypotension during spinal
anaesthesia for Caesarean section. Anaesthesiology 1982;56: 68-70.
[14]. 14. Sahu D, Kothari D, Mehrotra A. Comparison of Bolus Phenylephrine, Ephedrine, and Mephentermine for maintenance of arterial
pressure during spinal anesthesia in caesarean section a clinical study. Indian J Anaesth 2003;47:125-128.
[15]. 15. Greene NM, Brull SJ. Obstetric physiology. Chapter-8, Physiology of spinal anaesthesia, 4th Edn., Baltimore, Williams and
Wilkins, 1993:309-343.
[16]. 16. Moran DH, Dutta S, Perillo M, Laporta RF, Bader A. Phenylephrine is the prevention of hypotension following spinal anaest hesia
for caesarean delivery. Journal of Clinical Anaesthesia 1991;3:301-305.
Group P
Group E
Group M
0 minute
2 minutes
4 minutes
6 minutes
8 minutes
10 minutes
12 minutes
14 minutes
16 minutes
18 minutes
20 minutes
25 minutes
30 minutes
114.857.29
102.659.94
113.053.73
113.354.86
113.3511.09
99.911.61
10211.57
100.1510.59
101.16.88
103.56.04
105.4511.09
104.559.51
105.46.60
112.910.00
102.412.78
102.4513.95
105.4514.58
107.5513.92
111.7511.69
111.7512.95
110.8512.18
110.5510.43
10911.20
107.810.17
109.959.15
111.057.59
117.110.70
96.3512.36
102.0513.98
105.314.37
107.7516.69
113.3519.11
113.415.39
106.9513.86
106.6513.65
106.8515.14
106.713.57
107.710.25
107.89.25
Overall
P value
0.378
0.168
0.005**
0.065+
0.282
0.009**
0.019*
0.026*
0.025*
0.315
0.818
0.215
0.084+
Significance
P-E
P-M
0.791
0.733
0.998
0.216
0.015*
0.011*
0.108
0.100
0.339
0.364
0.034*
0.014*
0.064+
0.025*
0.021*
0.195
0.019*
0.236
0.288
0.625
0.801
0.939
0.189
0.560
0.069+
0.604
E-M
0.344
0.243
0.993
0.999
0.999
0.936
0.920
0.577
0.485
0.823
0.952
0.742
0.399
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Group P
Group E
Group M
71.56.25
60.255.26
71.109.63
73.709.65
70.4510.53
59.58.95
61.610.44
59.656.99
58.057.33
58.77.74
62.49.72
61.78.14
64.15.27
75.55.86
62.5510.36
63.3510.00
65.2511.13
65.910.51
66.610.21
66.68.83
64.857.90
62.957.87
62.459.68
59.8510.15
60.69.13
64.44.41
73.66.84
56.9511.43
61.311.12
62.110.45
64.1513.47
66.7513.06
64.857.39
61.28.36
60.1510.16
60.89.41
61.558.99
64.37.17
64.58.09
Overall
P value
0.145
0.176
<0.001**
0.003**
0.216
0.063+
0.211
0.104
0.200
0.422
0.697
0.347
0.977
Significance
P-E
0.122
0.721
<0.001**
0.034*
0.434
0.106
0.192
0.096+
0.174
0.390
0.682
0.905
0.987
P-M
0.549
0.513
<0.001**
0.002**
0.207
0.097+
0.491
0.804
0.718
0.741
0.958
0.577
0.977
E-M
0.612
0.153
0.804
0.608
0.882
0.999
0.812
0.306
0.557
0.831
0.843
0.333
0.999
Table 3: Comparison of heart rate (beats per minute) in three groups of patients studied
Heart rate
Group P
Group E
Group M
0 minute
2 minutes
4 minutes
6 minutes
8 minutes
10 minutes
12 minutes
14 minutes
16 minutes
18 minutes
20 minutes
25 minutes
30 minutes
92.759.87
92.3016.89
93.7015.84
83.6016.44
72.2017.07
76.7019.81
82.8016.06
82.6017.01
76.5518.63
74.6018.34
70.8017.95
71.2519.43
65.6517.41
90.2019.19
91.9021.04
91.7520.47
97.7019.70
98.3022.76
99.4521.30
96.5516.30
95.7515.60
99.5013.87
100.1011.52
102.8514.22
101.1515.27
96.5017.81
100.2016.14
104.2517.8
94.8019.95
94.5021.02
94.7016.00
96.7019.16
93.4514.66
92.7013.53
96.3512.76
99.1010.70
99.0011.95
97.1515.61
95.2514.94
Overall
P value
0.117
0.067+
0.875
0.059*
<0.001**
0.001**
0.019*
0.024*
<0.001**
<0.001**
<0.001**
<0.001**
<0.001**
Significance
P-E
0.863
0.997
0.943
0.060+
<0.001**
0.002**
0.020*
0.025*
<0.001**
<0.001**
<0.001**
<0.001**
<0.001**
P-M
0.292
0.115
0.981
0.179
0.001**
0.007**
0.090+
0.106
<0.001**
<0.001**
<0.001**
<0.001**
<0.001**
E-M
0.114
0.100
0.866
0.858
0.818
0.902
0.807
0.807
0.793
0.972
0.695
0.735
0.970
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Group P
No
1
0
5
8
6
20
4.001.16
%
5.0
0.0
25.0
40.0
30.0
100.0
Group E
No
4
6
7
3
0
20
2.450.99
%
20.0
30.0
35.0
15.0
0.0
100.0
Group M
No
5
7
4
1
3
20
2.551.46
%
25.0
35.0
20.0
5.0
15.0
100.0
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