|Year : 2015 | Volume
| Issue : 3 | Page : 443-449
Cerebral oxygen saturation monitoring: a comparative study between bolus doses of ephedrine and phenylephrine in elective cesarean section
Khaled M Maghwry, Ashraf E Elagamy MD , Wael I Tahir
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||05-Mar-2015|
|Date of Acceptance||21-Jun-2015|
|Date of Web Publication||29-Jul-2015|
Ashraf E Elagamy
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, PO Box 11331, Cairo
Source of Support: None, Conflict of Interest: None
Maternal hypotension is suspected to occur during cesarean section, especially under spinal anesthesia. Ephedrine and phenylephrine are the most common drugs used to treat this phenomenon. Phenylephrine has been claimed to decrease cerebral oxygen saturation (ScO 2 ) under general anesthesia but it is unclear whether it has the same effect in spinal anesthesia.
Patients and methods
A randomized double-blinded study was conducted that included 42 pregnant women for elective cesarean section under spinal anesthesia. A bolus dose of ephedrine (10 mg) or phenylephrine (0.1 mg) was given for treatment of hypotension. Frontal lobe oxygenation (ScO 2 ), mean arterial blood pressure (MAP), and heart rate (HR) were recorded, besides standard monitoring of other vitals.
There was a significant decrease in left ScO 2 in the phenylephrine group after bolus treatment in response to hypotension when compared with the ephedrine group (rate of change -6 ± 2 vs. +2 ± 1; P < 0.001), as well as in right ScO 2 (-8.65 ± 0.81 vs. +2.38 ± 0.9; P < 0.001). HR was significantly lower in the phenylephrine group than in the ephedrine group after the bolus dose (60 ± 7.3 vs. 71.1 ± 4.8; P < 0.001). There was no significant difference between the two groups as regards fetal outcome.
Bolus dose of phenylephrine for treatment of spinal anesthesia-induced hypotension in elective cesarean section causes more decrease in ScO 2 and maternal HR in comparison with a bolus dose of ephedrine, but both are effective in maintaining mean arterial blood pressure, with satisfactory fetal outcome.
Keywords: cerebral oxygen saturation, cesarean section, ephedrine, phenylephrine, spinal anesthesia
|How to cite this article:|
Maghwry KM, Elagamy AE, Tahir WI. Cerebral oxygen saturation monitoring: a comparative study between bolus doses of ephedrine and phenylephrine in elective cesarean section. Ain-Shams J Anaesthesiol 2015;8:443-9
|How to cite this URL:|
Maghwry KM, Elagamy AE, Tahir WI. Cerebral oxygen saturation monitoring: a comparative study between bolus doses of ephedrine and phenylephrine in elective cesarean section. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 May 9];8:443-9. Available from: http://www.asja.eg.net/text.asp?2015/8/3/443/161733
| Introduction|| |
Spinal anesthesia is considered the standard anesthetic technique for elective cesarean section in modern anesthetic practice  . There are many complications associated with spinal anesthesia, especially hypotension, which is a major limitation of this anesthetic technique, with incidence up to 80% if the patient did not receive any prophylactic measures , .
Hypotension in cesarean section causes undesirable side effects, such as dizziness, nausea, and vomiting, and also limits adequate perfusion of the fetus  . Different modalities are used to treat or prevent hypotension, such as tilting the pregnant woman to the left, administrating intravenous fluids, and use of vasopressors like ephedrine and/or phenylephrine  .
The pharmacological action of ephedrine and phenylephrine is different  . Ephedrine is a sympathomimetic agent that directly stimulates α- and β-adrenergic receptors and also leads to endogenous release of norepinephrine resulting in both positive inotropic and chronotropic effects  . However, phenylephrine is a selective α-adrenergic receptor agonist that increases the peripheral vascular resistance with subsequent increase in mean arterial blood pressure (MAP)  .
The effect of ephedrine and phenylephrine on maternal and fetal hemodynamics has been investigated in different studies ,, . Ephedrine was the only vasopressor recommended in obstetrics, but evidence suggests that ephedrine is not effective in all cases, and may also cause a reduction in fetal pH and base excess, although without affecting the Apgar score  . Phenylephrine infusion significantly lowers the incidence of spinal anesthesia-induced maternal hypotension, despite its limitations like bradycardia, hypertension, and reduced cardiac output at higher dose  .
Near-infrared spectroscopy (NIRS) use is increasing for noninvasive monitoring of cerebral oxygenation (ScO 2 ) in both general and spinal anesthesia, providing an estimation of brain tissue oxygenation  .
Both ephedrine and phenylephrine were used to antagonize hypotension after induction of general anesthesia with detection of their effect on ScO 2  .
In the present clinical study we investigated how ephedrine and phenylephrine boluses, given in response to hypotension, influence ScO 2 when used to antagonize hypotension during cesarean sections performed under spinal anesthesia.
The aim of this randomized double-blinded clinical trial was to evaluate the ScO 2 response to bolus administration of ephedrine versus phenylephrine given as a treatment for hypotension occurring after spinal anesthesia as a primary outcome. Secondary aims were to evaluate changes in maternal hemodynamics, umbilical cord pH, and fetal outcome.
| Patients and methods|| |
This prospective, randomized, double-blinded clinical study was carried out after obtaining approval from the Hospital Ethics Committee and written informed consent from healthy women undergoing elective cesarean section under spinal anesthesia at King Abdel Aziz Hospital in the Kingdom of Saudi Arabia from April 2014 to July 2014.
Patients included were older than 18 years, of ASA grade I or II, 160-175 cm in height, weighing 60-90 kg, and with a single uncomplicated pregnancy of gestational age more than 36 weeks.
Fetal malpresentation, pregnancy-induced hypertension, hypertension, cardiac disease, renal disease, fetal anomaly, diabetes mellitus, cerebrovascular disease, coagulopathy, patient refusal to participate, contraindication to spinal block, or reported allergy to ephedrine or phenylephrine were the criteria for exclusion from the study.
Upon arrival at the operating theater, the patient received 15 ml/kg of lactated Ringer's solution over 15 min, was tilted 15° to the left, and nasal supplementation of oxygen (2 l/min) was established. A cuff was applied to the arm to measure noninvasive systolic blood pressure, diastolic blood pressure, and MAP; other monitored vitals included ECG and SpO 2 (Aisys; Datex-Ohmeda Inc., operates as a subsidiary of General Electric Company, 3030 Ohmeda Drive, Madison, WI 53718 USA).
Spinal anesthesia was given at L 3 -L 4 or L 4 -L 5 interspaces with a 25-G Whitacre needle in the sitting position. A dose of 10 mg hyperbaric bupivacaine plus 25 μg of fentanyl was injected over 10-15 s. Thereafter, with the patient in the supine position, a pad was placed under the right flank to displace the uterus to the left, and the infusion of lactated Ringer's at a rate of 10 ml/kg/h was instituted. Surgery was started after confirming sensory block up to T4 dermatome by thermal response to application of cold sensation to the skin.
Regional cerebral oxygen saturation (ScO 2 ) was continuously monitored using NIRS with an INVOS 5100C cerebral oximeter (Somanetics, Troy, Michigan, USA). Before spinal anesthesia, after cleansing the skin area with alcohol, sensors for a cerebral oximeter were placed bilaterally on the right and left sides of the forehead according to the manufacturer's instructions with the caudal border about 1 cm above the eyebrow with the medial edge at the midline, as this position keeps the light source and sensors away from the frontal sinus and temporalis muscle. The NIRS-determined mean ScO 2 is based on optodes that emit and detect near-infrared light at two wavelengths (730 and 810 nm), and ScO 2 is calculated as the ratio between oxyhemoglobin and total hemoglobin.
The patients were allocated randomly into two groups (ephedrine or phenylephrine) on the basis of a computer-generated randomization list. Dose equivalence between phenylephrine (0.1 mg/ml) and ephedrine (10 mg/ml) was chosen according to previous trials and recommendations , . After establishment of spinal anesthesia, measurement of blood pressure was ensured every 3 min for the first 15 min and then every 5 min until the end of surgery. A bolus of either 10 mg ephedrine or 0.1 mg phenylephrine was to be administered according to group randomization if MAP decreased by more than 20%, or if the patient complained of symptoms of hypotension (dizziness, vomiting, faintness, nausea). If hypotension did not occur through the operation and thus there was no need for the vasopressor agent, the patient was excluded from the study.
Variables recorded from both groups included right ScO 2 and left ScO 2 , MAP, and heart rate (HR) before spinal anesthesia (baseline) and then every 5 min until the end of surgery. Cerebral desaturation is defined as decrease of ScO 2 by 20% from baseline that lasts more than 15 s; this condition was treated by increasing the arterial blood pressure with intravascular fluid administration and/or vasopressor drug administration according to the group assignment - that is, either 10 mg ephedrine or 0.1 mg phenylephrine.
Apgar score and umbilical arterial and venous pH variables from a double-clamped cord segment were recorded. Other data included duration of surgery, volume of crystalloid administered, and the vasopressor doses used.
The primary outcome included detection of changes in the ScO 2 in both groups from the baseline of the patient and after giving the vasopressor dose, whereas the secondary outcome included changes in maternal hemodynamics, Apgar score, and fetal umbilical pH.
On the basis of previous studies , it was calculated that a sample size of 15 patients per group will achieve 80% power to detect a difference of 10.6% between means of ScO 2 of 68.0-57.4 with estimated group standard deviations of 10.0 and 10.0 and with a significance level (α) of 0.05 using a two-sided two-sample t-test. Twenty-one patients were included per group to compensate for any dropouts or missing patients.
Normally distributed numerical data are presented as mean ± SD, and differences between groups were compared using the independent Student's t-test, and one-way ANOVA for intragroup comparison. Data not normally distributed were compared using the Mann-Whitney test and were presented as median (interquartile range), and categorical variables were analyzed using the χ2 -test and were presented as n (%). All P values are two-sided. P values less than 0.05 were considered statistically significant.
| Results|| |
Written informed consent was taken from 68 pregnant women to participate in this study, 42 of whom were subsequently randomized [Figure 1]. Personal data of patients in the two groups showed no statistically significant differences [Table 1].
Changes in MAP during surgery were comparable between the two groups at the onset of hypotension and after giving the vasopressor dose. However, significant decrease occurred in MAP in each group at the onset of hypotension when compared with baseline. Rate of change in MAP was not statistically significant between ephedrine and phenylephrine groups (13.9 ± 3.1 vs. 16 ± 4, respectively; P = 0.27) [Table 2].
At the onset of hypotension, HR decreased in both groups to a significantly lower level compared with the baseline value, without significant difference between the two groups. However, at the peak increase of MAP after administration of phenylephrine, there was significant decrease in HR compared with baseline (60 ± 7.3 vs. 81.3 ± 6.4) [Table 3]. In addition, there was significant decrease in comparison with the ephedrine group (60 ± 7.3 vs. 71.1 ± 4.8, respectively; P < 0.001) [Table 3].
The rate of change in HR at the highest and lowest MAP reading showed significantly lower value in the phenylephrine group compared with the ephedrine group (-7.95 ± 0.97 vs. +9.1 ± 1.4 respectively; P < 0.001) [Table 3].
There was significant decrease in left ScO 2 in the phenylephrine group at the peak increase of MAP in comparison with the baseline value (58.2 ± 3.8 vs. 64.76 ± 3.7) and also in comparison with the onset of hypotension. The decrease lasted 15-45 s and disappeared spontaneously without intervention. In contrast, it was maintained after ephedrine dose (68 ± 5 vs. 69.76 ± 4.6) [Table 4]. This means that ephedrine did not decrease ScO 2 , whereas phenylephrine did. It was apparent in the rate of change of ScO 2 at the highest and lowest MAP reading that phenylephrine significantly decreased ScO 2 compared with ephedrine (-6 ± 2 vs. +2 ± 1, respectively; P < 0.001) [Table 4] and [Figure 2].
Similar changes were found between right and left ScO 2 in the ephedrine and phenylephrine groups [Table 5] and [Figure 3].
There were no significant differences between the two groups as regards duration of surgery or amount of crystalloid given intraoperatively [Table 6]. However, a significantly higher number of doses of phenylephrine was given compared with ephedrine [5 (4-5) vs. 3 (2-3), respectively; P < 0.001].
Fetal outcomes in both groups were similar regarding the arterial and venous pH [Table 7]. Apgar scores at 1 and 5 min were comparable in both groups [Table 7] and [Figure 4].
| Discussion|| |
The present study showed that ephedrine and phenylephrine bolus doses are safe and effective in maintaining MAP in patients undergoing cesarean section under spinal anesthesia with decrease of HR in response to phenylephrine. The new finding is that, in spinal anesthesia, ephedrine is capable of activating both α- and β-adrenergic receptors, causing preservation of the near-infrared-determined frontal lobe oxygenation (ScO 2 ), whereas ScO 2 was reduced in patients allocated to the phenylephrine group, a selective α-adrenergic receptor agonist.
Cerebral oxygenation is determined by two main factors: oxygen delivery to the brain and oxygen consumption by the brain (CMRO 2 ). Oxygen delivery to the brain depends on cerebral blood flow (CBF) and arterial blood oxygen content. Studies have shown that changes in ScO 2 correlate with changes in CBF  if CMRO 2 and arterial blood oxygen content are kept constant.
In the present study, we considered CMRO 2 to be constant because our patients were under spinal anesthesia and received bolus doses of ephedrine or phenylephrine in response to hypotension to maintain MAP and hence the CBF. We considered also that arterial oxygen content is constant as there was no extensive surgical hemorrhage or signs of arterial desaturation; therefore, the changes in ScO 2 were mainly attributed to changes in CBF.
Spinal anesthesia influences MAP because of sympathetic blockade, and during cesarean section inferior caval compression may reduce venous return to the heart and thus CO  . Different degrees of hypotension can be expected during cesarean section, specifically under spinal anesthesia. Hypotension is considered when maternal MAP decreases by 20-30% from baseline reading , . In the present study, MAP did not fall to what is considered to be the lower limit of cerebral autoregulation, which is a wide range, and the patients were not expected to be exposed to cerebral hypoperfusion and a reduction in ScO 2  . MAP values between 122 (range 110-140) and 48 (range 34-75) mmHg were seen in cerebral autoregulation  .
In the pregnant women enrolled in this study, however, there was significant decrease in MAP at the onset of hypotension in both ephedrine and phenylephrine groups before giving the bolus dose (57.4 ± 3.68 vs. 54.3 ± 6.2, respectively; P0.06). These low MAP values did not reach the lower limit of cerebral autoregulation and thus left [Table 4] and [Figure 2] and right [Table 5] and [Figure 3] ScO 2 was maintained in both groups when compared with baseline values. Hypotension was corrected after giving the bolus dose in both groups, reflecting the efficacy of both drugs in the management of hypotension induced by spinal anesthesia in pregnant women. However, the use of phenylephrine leads to a significant reduction in left and right ScO 2 when compared with ephedrine, which maintains ScO 2 , as detected in the rate of change (−6 ± 2 in the left and −8.65 ± 0.81 in the right; P < 0.001 for both sides). This means that phenylephrine decreases ScO 2 by ~9-11% after its administration. In contrast, in the ephedrine group there was maintenance of left and right ScO 2 after the bolus dose as detected in the rate of change (+2 ± 1 in the left and +2.38 ± 0.9 in the right). Previous studies showed that a 50% reduction in middle cerebral artery mean flow velocity and a 10-15% reduction in ScO 2 are associated with presyncopal symptoms , and gravity-induced loss of consciousness is reported at ~15% decrease in ScO 2  . Therefore, the 9-11% reduction found in our results in ScO 2 following the bolus dose of phenylephrine was not trivial. In the present study female patients were conscious and able to report cerebral hypoperfusion symptoms like dizziness, nausea, and vomiting but no complaints were noticed by patients associated with decreased values. There were also no behavioral changes in these patients in the early postoperative period in the form of disorientation of place, time, or people. This may be attributed to the short time of attacks of cerebral desaturation that resolved spontaneously without intervention.
The mechanism of how phenylephrine administration leads to decreased cerebral oxygenation is not yet clear. It has been found that sympathetic outflow originating from the superior cervical ganglion increases apparently after pharmacologically (including phenylephrine) induced rapid increase in arterial pressure  . It is well known that the cerebral vasculature is largely innervated by the superior cervical ganglion. This might be the cause that phenylephrine bolus treatment may constrict cerebral resistance vessels indirectly through its α-agonistic effect. The results of our study are supported by the findings that cerebral arteries are abundantly innervated by sympathetic nerve fibers and that both α- and b-adrenoceptors are demonstrated in the vascular walls in the brain  . It is also known that stellate ganglion block leads to a decreased cerebral vascular tone  .
In the present study, there was a significant decrease in HR in ephedrine and phenylephrine groups at the onset of hypotension (63 ± 5.31 vs. 82 ± 4.9; and 65 ± 3.4 vs. 81.3 ± 6.4, respectively). However in the phenylephrine group there was significant decrease after administration of the bolus dose of the drug when compared with the ephedrine group (60 ± 7.3 vs. 71.1 ± 4.8, respectively; P < 0.001). Our finding was in agreement with that of Nissen et al.  , who found that administration of phenylephrine bolus causes bradycardia but in patients under general anesthesia. It is well known that phenylephrine causes bradycardia secondary to vagal reflex  . In another study conducted by Das et al.  , the authors found that the baseline maternal HR can be better maintained by using infusion of phenylephrine at variable rates with supplementary boluses of phenylephrine, especially in the presence of a maintained blood pressure. In contrast, in our ephedrine group, HR increased after administration of the bolus dose (63 ± 5.31 to 71.1 ± 4.8) [Table 3], mostly because of its indirect sympathomimetic effect  .
When the ephedrine and phenylephrine groups were compared with regard to the number of boluses needed in each group for treatment of hypotension, a significantly lower number of doses per patient was found in the ephedrine group [3 (2-3) vs. 5 (4-5), respectively; P < 0.001] [Table 6]. It is well known that both vasoconstrictors have a short half-life, and therefore other studies used them in the infusion regimen , . Our study enforced that phenylephrine has a shorter half-life than ephedrine, as seen by the more frequent doses given to patients.
As regards fetal outcome in both groups there were no statistically significant differences in umbilical artery and vein pH, or in Apgar scores at 1 and 5 min [Table 7] and [Figure 4]. This shows that both drugs are safe on fetal outcome. Our results are in agreement with other studies that predicted the effects of ephedrine and phenylephrine on fetal outcome ,, .
| Conclusion|| |
This study emphasizes that both ephedrine and phenylephrine bolus doses are effective in maintaining the MAP during elective cesarean section under spinal anesthesia; however, phenylephrine causes decreased ScO 2 and maternal HR.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]