European Journal of Cardiovascular Medicine

Spinal anesthesia for caesarean section has several advantages over general anaesthesia like decreased risk of failed intubation, decreased risk of pulmonary aspiration of gastric contents, avoidance of the depressant effects of general anesthetics on neonate etc. Developments in regional anaesthesia have increased the relative risk of fatality during general anaesthesia for caesarean delivery to more than 16 times.1  Single shot spinal is most commonly performed because it is simple, quicker, has faster onset with superior block and infrequent failure, lesser risk of systemic toxicity due to local anesthetic agent and lesser transfer to fetus as lower doses are used and its cost effectiveness. However, single shot spinal anesthesia has its own bag of adverse effects. The most common adverse effect is hypotension, primarily because of sympathectic block associated with spinal anaesthesia. The incidence of hypotension during spinal anaesthesia is as high as 75-85%.2 The clinical question of acceptable level of arterial blood pressure decrease after neuraxial block remains to be answered. However, placental perfusion may be reduced in supine parturient even when mean arterial blood pressure is measured normal.3 Hypotension during spinal anesthesia for cesarean delivery may thus further gets reduced and may result in fetal acidosis, hypoxia, neurological injury besides maternal nausea, vomiting, dizziness and sometimes severe hypotension  which  may result       in loss of consciousness and sudden cardiac arrest. 4 Several pharmacologic and non-pharmacologic methods have been used for management of hypotension, with no single method adequate or conclusively superior. Amongst the vasopressors used (ephedrine, phenylephrine, mephentermine) none is conclusively better over the other.5 Although ephedrine has been used as the agent of choice, but the position has been challenged because of potential to cause supraventricular tachycardia (SVT), tachyphylaxis and fetal acidosis.6,7,8  Recent studies favour phenylephrine, an α1 agonist which elevates arterial blood pressure by increasing systemic vascular resistance secondary to vasoconstriction. Since the primary mode of hypotension during spinal anesthesia is vasodilation, it seems physiologic to use the vasoconstrictor. However, it causes bradycardia and serial dilution for i.v. administration is source of error.9 Mephentermine, which has mechanism of action similar to ephedrine, has been used for treatment of hypotension during spinal anesthesia.10,11 Mephentermine is direct and indirect sympathomimetic action and probably the increase in arterial blood pressure is chiefly by increased cardiac output. This may be favourable for placental circulation.

AIM OF THE STUDY:

To compare bolus Phenylephrine and Mephentermine for control of hypotension during spinal      anaesthesia in women undergoing elective cesarean section.

After obtaining approval from the ethical committee, informed consent for participation in the study was taken from all the patients.Inclusion criteria: ASA grade I and II  parturients aged between 18 - 40 years with gestational  age from 34 to 40 weeks  scheduled for elective cesarean delivery under spinal anaesthesia.Exclusion Criteria : Base line heart rate less than 60 beats per minute, base line blood pressure less than 100/60 mm Hg, patients with a history of hypertension, pre-eclampsia/eclampsia, ischemic heart disease, heart block, left ventricular failure, severe renal or hepatic disease, glaucoma, occlusive  vascular disorders and any history of hypersensitivity to local anaesthesia drugs.

Randomisation was done using the website www.randomisation.com to divide the patients into two groups of 30 each, to receive either Phenylepherine (Group P) or Mephenteramine (Group M) randomly. The patients and the investigator enrolling the patients were blinded to the intervention. Allocation concealment was done using sequentially numbered opaque sealed envelopes (SNOSE technique). The study was carried out in operation theatre of Bhaskar General Hospital and the postoperative data were collected in the post operative ward. Once the patient was shifted to the operating room, standard monitors which included NIBP, pulse oximeter and ECG were connected to the patient. All the resuscitation equipments and the emergency drugs were kept ready. The anesthesia machine was also checked along with the oxygen delivery system. Intravenous access was secured with 18G IV cannula. All patients were preloaded with lactated Ringer's solution, 15 ml/kg body weight over 15-20 minute just before the anesthesia was administered. The preloading was done with patient in left lateral position and continuous monitoring of heart rate (HR) and blood pressure (BP). Baseline preoperative SBP, DBP, MAP and HR were calculated as mean of 3 consecutive measurements, 2 minutes apart. Patients were reassured and explained about the technique. Spinal anesthesia was administered, with patient in left lateral position with knees and chin flexed over the abdomen. Under strict aseptic precautions, after skin infiltration with 1ml of 2% lignocaine, lumbar puncture was performed by midline approach by using disposable Quincke Babcock spinal needle (25G) in L3-L4 intervertebral space. After free flow of CSF, 10 mg (2 ml) of hyperbaric bupivacaine, 0.5% was injected intrathecally and the patient returned to supine position with left uterine displacement.

Sensory level of anesthesia was tested with pin prick. With the onset of sensory blockade to T4-T6 level and grade 3 motor blockade using Bromage scale, the surgery was started. SBP, DBP, MAP and HR recorded 1,2,3,5 and10 mins after sub arachnoid block and every 5 min thereafter till the completion of surgery. Spinal hypotension was defined as fall of greater than 20% mean arterial pressure (MAP) from baseline and intravenous Mephentermine 6 mg or phenylephrine 100 mcg was given to treat hypotension, the dose was repeated at 5 minutes interval if necessary. Total number of doses required and intra operative fluid requirement also was noted.

STATISTICAL ANALYSIS: Appropriate statistical tests were done to compare between qualitative data and quantitative data. The qualitative data were presented in the form of number and percentage and the quantitative data were presented in the form of mean and standard deviation. Statistical analyses were performed using the SPSS version 17.0 program for Windows. Student’s t-test was used for continuous, normal variables. For categorical data, Chisquare test was used to compare the differences in variables between the two groups. P value of <0.05 was considered statistically significant.

Data from 60 patients was analyzed in this study.

     TABLE 1 : DISTRIBUTION  BASED  ON  VARIOUS  PARAMETERS

There was no significant difference in the demographic profile of the two groups with respect to age, height, weight and the average duration of surgeries.

TABLE 2: Distribution of average SBP within 5 mins of SAB and 1st minute after giving vasopressor

Table shows that within 5 minutes of Sub arachnoid block, there is no significant difference between Group-P and Group-M on drop of average SPB at different minutes. But after administering the drug, the Group P shows very high average SBP compared to Group-M which is statistically highly significant (p<0.0001)

TABLE  3: Distribution of average DBP within 5 mins of SAB and 1st minute after giving vasopressor

Table shows that Within 5 minutes of Sub arachnoid block, there is no significant difference between Group-P and Group -M on drop of average DBP at different minutes. But after administering the drug, the ‘P’ group shows very high average DBP compared to Group-M which is statistically highly significant (p<0.0001).

TABLE 4: Distribution of average MAP within 5 mts of SAB and 1st minute after giving vasopressor

Table shows that Within 5 minutes of Sub arachnoid block, there is no significant difference between Group-P and Group-M on drop of average MAP at different minutes. But after administering the drug, the ‘P’ group shows very high average SBP compared to Group-M which is statistically highly significant (p<0.0001)

       Table 5: Distribution of average HR during Winthin 5mins of SAB and 1st minute after giving               vasopressor

Table shows that within 5 minutes of SAB, there is no significant difference between Group-P and Group-M on average HR at different minutes.But after administering the drug, the ‘P’ group shows a fall in the heart rate compared to Group-M which is statistically highly significant (p<0.0001).

Table 6: Distribution of SBP after giving Vasopressor intraoperatively

Table reveals that there is significant difference of average SBP between two groups upto 5 minutes, after giving vasopressor but subsequently there is no significant difference. Average SBP at the first minute in Group-P and Group- M are 145 mm Hg and 109 mm Hg respectively.

Table 7: Distribution of DBP after giving Vasopressor intraoperatively

Table reveals that there is significant difference of average DBP between two groups upto 5 minutes, after giving vasopressor but subsequently there is no significant difference. Average DBP at the first minute in Group-P and Group-M are 89 mm Hg and 67 mm Hg respectively.

Table 8: Distribution of MAP after giving Vasopressor Intraoperatively

Table reveals that there is significant difference of average MAP between two groups upto 5 minutes, after giving vasopressor but subsequently there is no significant difference. Average MAP at the first minute in Group-P and Group-M are 107 mm Hg and 78 mm Hg respectively.

Table 9: Distribution of HR after giving Vasopressor Intraoperatively

Table reveals that there is significant difference of average HR between two groups throughout the intraoperative period. The heart rate of Group-M is always higher than the Group-P which is statistically significant.

Table 10: Comparison of number of doses of vasopressors used to correct hypotention

Number of repeated doses required is more in Group-M compared to Group-P

Table 11: Comparison of incidence of other effects between groups

After subarachnoid block for caesarean section, hypotension can be minimized by the use of intravenous fluid preload, avoidance of aortocaval compression and judicious use of vasopressor agent. 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.12 For the purpose of this study, hypotension was defined as a decrease in arterial pressure greater than 20% from baseline systolic pressure. The current study was conducted to compare the two commonly used vasopressors for their efficacy at maintaining the arterial blood pressure. After the selection of the participants, they were allocated to receive i.v bolus of either phenylephrine 100 mcg. or mephentermine 6 mg on developing hypotension. The method of randomization was allocation by sealed envelope technique. Data was collected and the results were summarized and analyzed statistically by appropriate method.

The demographic data, baseline parameters were comparable in both groups. The hemodynamic parameters at the development of hypotension were also comparable between the groups. The mean time to development of hypotension after administration of spinal anaesthesia was 7.3778 ± 2.20834 (mean ± SD) minutes in group P and 6.9778 ± 2.47247 (mean ± SD) minutes in group M. The values were comparable with p=0.420. The systolic, diastolic and mean arterial pressure were decreased statistically

significant at the onset of hypotension and increased after the bolus dose of drugs. The pressures generally remained high in both. Systolic blood pressure was generally highest in Phenylephrine group immediately after the administration. The diastolic blood pressure was also greater in Phenylephrine group when compared Mephentermine group., especially after 2nd and 4th minute, after administration of the drug. This finding is consistent with the onset of action and efficacy of the drug that Phenylephrine has quicker onset of action and better maintenance of arterial pressures when compared with the Mephentermine group. The primary mechanism of elevation of arterial blood pressure by phenylephrine is by vasoconstriction due to predominantly α1 agonist activity whereas mephentermine increases MAP by augmenting cardiac output by increasing heart rate and myocardial contractility due to its α and β agonist activity. The significant differences in diastolic blood pressure in the current study presumably reflect the predominantly α1 mediated vasoconstriction increased SVR due to phenylephrine.

Dinesh Sahu et al13 studied the effects of bolus Ephedrine, Mephentermine, Phenylephrine for the maintenance of arterial pressure during spinal anesthesia for LSCS. In their study all the three vasopressors effectively maintained arterial pressure within 20% of baseline value though Phenylephrine maintained better in first 6minutes of bolus dose as compared with Ephedrine and Mephentermine and Phenylephrine has a quicker peak effect.

Garima Sinha et al14   studied the effectiveness of intravenous boluses of phenylephrine, ephedrine and mephentermine as vasopressors for management of perioperative hypotension in elective lower segment caesarean section under spinal anaesthesia. All three vasopressors effectively maintained arterial blood pressure during the subarachnoid block for caesarean section. Phenylephrine caused a significant reduction in heart rate compared to ephedrine or mephentermine. These   findings are comparable to the present study.

We found that the maternal heart rate was decreased with Phenylephrine group compared with Mephentermine group. This is consistent with the mechanism of action of these drugs that the decrease in heart rate found in Phenylephrine group was due to pure α receptor activity compared with Mephentermine group, it has mixed action acts directly as well as indirectly on α and ß receptors. Similar results were seen in many studies which was consistent with the present study.

Dinesh Sahu et al13 Phenylephrine was found to cause significant reduction in heart rate after the bolus dose,which is similar with the  present study. In the systematic review by Ngan Kee et al15 he concluded that Phenylephrine may decrease maternal heart rate and cardiac output.

The time to first repeat dose of vasopressor was comparable in both the groups. However mean number of doses was significantly more in group M. The incidence of nausea and vomiting and other effects was comparable between the two groups.

Ethical Clearance: Ethical Clearance was obtained from the institutional ethics committee of Bhaskar Medical College prior to the commencement of study.

Source of funding: Self

Conflict of interest: Nil

In conclusion from the study that both, phenylephrine and mephentermine maintain systolic blood pressure above hypotensive range, though phenylephrine might be better because number of doses needed is less and since phenylephrine increases diastolic blood pressure more than mephentermine and hence mean arterial pressure is increased. Thus, it can probably enhance organ blood flow more than mephentermine. Mephentermine increases heart rate and thus may be avoided in population where the effect may be detrimental.

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