Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.56 no.3 Campinas May/June 2006
Ephedrine and etilefrine as vasopressor to correct maternal arterial hypotension during elective cesarean section under spinal anesthesia. Comparative study*
Estudio comparativo entre efedrina y etilefrina como vasopresor para correción de la hipotensión materna en cesáreas electivas con raquianestesia
Sérgio D. Belzarena, TSA
Anestesiologista da Santa Casa de Misericórdia de Santana do Livramento, RS
OBJECTIVES: Ephedrine is the most popular vasopressor for obstetrics and
etilefrine is widely used in regional anesthesia. This study aimed at comparing
ephedrine and etilefrine to correct maternal arterial hypotension during elective
Cesarean section under spinal anesthesia.
METHODS: Participated in this study 120 pregnant patients who were randomly distributed in two equal groups. All patients received spinal anesthesia with bupivacaine, fentanyl and morphine. Noninvasive blood pressure and heart rate were monitored. Neonates were evaluated by the Apgar score. The incidence of hypotension, the amount of vasopressor needed to correct it and adverse effects were recorded.
RESULTS: Maternal hypotension was similar in both groups (68% etilefrine group and 63% ephedrine group). The first vasopressor dose was enough to correct hypotension in most patients, with no difference between groups (66% etilefrine, 58% ephedrine). Few patients needed two or more doses to correct hypotension or presented reactive hypertension (24% and 10% in etilefrine and 34% and 8% in ephedrine groups, respectively), without statistically significant differences. There were no differences in adverse effects and neonate tests.
CONCLUSIONS: With the administration method and selected vasopressor doses, there have been no differences between ephedrine and etilefrine used to correct maternal hypotension during Cesarean section under spinal anesthesia.
Key Words: ANESTHESIA, Regional: spinal block; DRUGS: ephedrine, etilefrine; SURGERY, Obstetric: Cesarean section
Y OBJETIVOS: La efedrina es el vasopresor más utilizado en obstetricia
y la etilefrina es muy usada en anestesia regional. El objetivo de este estudio
fue el de comparar la efedrina con la etilefrina para la corrección de
la hipotensión arterial materna durante raquianestesia para cesárea
MÉTODO: Se estudiaron 120 embarazadas divididas aleatoriamente en dos grupos iguales. Todas recibieron raquianestesia con bupivacaína, fentanil y morfina. Se les midió la presión arterial no invasiva y la frecuencia cardiaca. Los recién nacidos fueron evaluados con el índice de Apgar. La incidencia de hipotensión arterial, la cantidad de vasopresor necesaria para corrección y los efectos adversos fueron registrados.
RESULTADOS: Ocurrió hipotensión arterial materna con frecuencia en los dos grupos, siendo un 68% del grupo etilefrina y un 63% del grupo efedrina. En la mayoría de las embrazadas, se corrigió con la primera dosis del vasopresor, sin diferencia entre los grupos (66% etilefrina, 58% efedrina). La hipotensión arterial necesitó dos o más dosis de vasopresor para ser corregida o se registró hipertensión reactiva en pocas pacientes (un 24% y un 10% del grupo etilefrina y 34% y 8% del grupo efedrina, respectivamente), sin diferencia estadística significativa. No hubo diferencia en los efectos adversos y en las pruebas de los recién nacidos.
CONCLUSIONES: Con el método de administración empleado y con las dosis de vasopresor seleccionadas no hubo diferencia entre la efedrina y la etilefrina cuando se utilizaron para corregir la hipotensión arterial materna en cesáreas con raquianestesia.
Arterial hypotension may be present even with volume expansion and uterine displacement during regional anesthesia for Cesarean section, and is preferably treated with vasopressors.
A traditional study with ewes has shown that ephedrine was the drug of choice to treat hypotension during pregnancy as compared to other vasopressors 1. Currently, the conclusions of this study are being reviewed and drugs with different pharmacological profiles are also being used, showing that they are at least as effective as ephedrine or even suggesting that the may present additional advantages 2,3.
Etilefrine is widely used to correct hypotension during regional anesthesia 4-7, but has not been specifically evaluated in obstetrics.
This study aimed at comparing etilefrine and ephedrine to treat hypotension during Cesarean section.
After the Ethical Committee, Santa Casa de Misericórdia, Livramento approval and their informed consent, participated in this study 120 patients eligible for elective Cesarean section and not in labor, who were randomly distributed in two groups (according to computer-generated table) to receive ephedrine or etilefrine in case of hypotension. Exclusion criteria were patients with pre-existing hypertension or with pregnancy-induced hypertension. Vasopressor drugs were prepared by diluting in a 10 mL syringe, that is 9 mL distilled water and 1 mL of the vial with 50 mg ephedrine or 10 mg etilefrine. Medication was prepared by a nurse who has not participated in the surgical procedure and before the patient was referred to the operating room.
Monitoring consisted of SpO2, automatic noninvasive blood pressure (ANIP) and ECG. After venoclysis, lactated Ringer's infusion was started at the rate of 60 g.min-1. There has been no previous volume expansion and anesthesia was performed in sequence.
Spinal anesthesia was performed in all cases with patients in the sitting position with 27G needle and the administration of 10 mg of 0.5% hyperbaric bupivacaine, 20 µg fentanyl and 100 µg morphine. After spinal anesthesia, patients were placed in the supine position and the uterus was manually displaced.
Blood pressure was measured with the automatic Criticare 507 monitor with frequency established in one minute. Initial pressure was defined as the mean of the first three measurements. Hypotension was defined as 20 mmHg decrease in systolic or mean blood pressure. The moment in which blood pressure decreased was recorded. Hypotension was treated with 2 mL intravenous solution adding 500 mL lactated Ringer's infusion with additional 4 mL of the solution. If not corrected in 2 minutes, additional 2 mL of the solution were administered in bolus. Reactive hypertension was defined as blood pressure increase above 20 mmHg of the initial pressure and increased heart rate above 110 bpm was considered reactive tachycardia.
Nausea and vomiting were treated with 10 mg metoclopramide and bradycardia (heart rate equal to or below 60 bpm) was treated with 0.5 mg atropine.
Time between beginning of anesthesia and beginning of surgery and time for fetal extraction were recorded. The room pediatrician evaluated neonates, and those with Apgar scores equal to or above 8 at the 1st and 5th minutes were considered non-depressed.
Student's t test was used for statistical analysis of continuous measures and Chi-square test was used for categorical data, considering significant p < 0.05.
There were no differences between groups in demographics data (Table I).
Hypotension was frequent among studied patients, that is, 41 etilefrine group patients (68%) and 38 ephedrine group patients (63%), without statistical difference between groups. Blood pressure has decreased after blockade in most patients, but some patients have only presented hypotension after fetal extraction, when oxytocin infusion was started.
The frequency of hypotension correction with the first vasopressor dose was similar, being 27 (66%) etilefrine group patients and 22 (58%) ephedrine group patients, the same being true for the incidence of reactive hypertension, in 4 (10%) and 3 (8%) patients, respectively. Most patients in whom more vasopressor doses were needed to correct hypotension have returned to baseline values with the second dose. There has been bradycardia in 12 (29%) etilefrine group patients and 14 (37%) ephedrine group patients. In virtually all cases, heart rate decrease was simultaneous to blood pressure decrease and has improved with vasopressor administration. Only three patients received atropine. Tachycardia was present in few patients, in general after vasopressor administration and of short duration. There were no differences in the incidence of nausea and vomiting (Table II).
Apgar scores were similar for both groups. Two etilefrine group neonates presented Apgar score below 8 at the first minute and in one case the mother had no hypotension (Table III).
Time between spinal solution injection and beginning of the surgical procedure was 5 ± 1 minute and time until fetal extraction was 9 ± 3 minutes after surgical incision.
The primary result of our study was the lack of differences between ephedrine and etilefrine to treat hypotension, which is frequent after spinal anesthesia for Cesarean section.
The treatment of hypotension in obstetrics has always been linked to the triad volume expansion, uterine displacement and vasopressors. The practice of previously expanding volume with large volumes before inducing anesthesia has been recently questioned, because it has been shown that this practice is ineffective and may cause noxious effects to mother and fetus 8-11. Uterine displacement is important to release cava and aorta flow. Vasopressors are useful in the presence of hypotension, because it is known that prompt correction brings maternal and fetal benefits 12,13.
Ephedrine recommendation, firstly made by a study with ewes 1, had new favorable arguments when other important revelations appeared in the literature. The first publication by Tong and Eisenach have shown that uterine artery muscles had lower contractile response to ephedrine as compared to other vasopressors and this is useful to preserve placental flow 13. In a second article 14 the same authors have shown that, differently from other vasopressors, ephedrine in addition to its decreased regional vasoconstrictor effect also releases nitric oxide in the uterine artery and this may also help placental flow.
However, hypotension is very frequent in pregnant patients not in labor and the incidence varies in different studies more due to differences in method (hypotension values and definition) than to recorded pressure changes. In studies with stricter criteria, such as this, the incidence of hypotension is very high. Records were above 60% in both groups, showing that volume and displacement are not enough, and that vasopressors are mandatory for most pregnant patients.
Interestingly, in some pregnant patients decreased blood pressure was only present after fetal extraction, showing that vigilance should be continuous and that regional anesthesia-induced sympathetic block has a role probably as important as the aorta-cava compression to generate hypotension.
Blood pressure has returned to baseline values in 2/3 of patients of both groups, but 1/3 of them needed additional vasopressor or presented hypertension. These data showed, on one hand a similar effect of both drugs, and on the other hand that dose adjustments or administration method should be investigated to obtain more consistent results.
Hypotension was followed by decreased heart rate in several patients, which has also shown the influence of sympathetic block on hemodynamic changes. Correction (and in some cases the presence of tachycardia) showed the vasopressor effect and suggested that there are peculiar effects by direct activation of the adrenergic receptor in addition to those exclusively depending on norepinephrine release, although this release is of major importance. These data were also suggested by a recent experimental animal study 15.
Neonates were evaluated by the Apgar score, which is routine in our hospital. A recent study comparing Apgar scores to other fetal indicators (umbilical blood values) has shown in almost 300 thousand neonates that the Apgar score has the same predictive value of umbilical blood gases analysis and that this is applicable both to term neonates and those born before the 36th week of gestation 16. Since there is a different study showing that the incidence of neonatal acidosis may be higher with ephedrine 17 it would be interesting to perform this evaluation associating umbilical blood gases analysis and reminding that few patients participated in the later study. Another element which might have influenced results was the short surgical time until fetal extraction.
In conclusion, with this model of study there were no differences between etilefrine and ephedrine used to treat hypotension during Cesarean section under spinal anesthesia. Given the similarities between drugs and the difference in cost, etilefrine should be considered an alternative vasopressor for obstetric procedures.
01. Ralston DH, Shnider SM, DeLorimier AA - Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology, 1974;40:354-370. [ Links ]
02. Ngan Kee WD, Lau TK, Khaw KS et al - Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section. Anesthesiology, 2001;95:307-313. [ Links ]
03. Lee A, Ngan Kee WD, Gin T - A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg, 2002;94:920-926. [ Links ]
04. Glaser C, Marhofer P, Zimpfer G et al - Levobupivacaine versus racemic bupivacaine for spinal anesthesia. Anesth Analg, 2002;94:194-198. [ Links ]
05. Fanelli G, Borghi B, Casati A et al - Unilateral bupivacaine spinal anesthesia for outpatient knee arthroscopy. Can J Anaesth, 2000;47:746-751. [ Links ]
06. Leoni A, Magrin S, Mascotto G et al - Cervical plexus anesthesia for carotid endarterectomy: comparison of ropivacaine and mepivacaine. Can J Anaesth, 2000;47:185-187. [ Links ]
07. Casati A, Magistris L, Fanelli G et al - Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve block with 0.75% ropivacaine for foot surgery. Anesth Analg, 2000;91:388-392. [ Links ]
08. Rout CC, Akoojee SS, Rocke DA et al - Rapid administration of crystalloid preload does not decrease the incidence of hypotension after spinal anaesthesia for elective caesarean section. Br J Anaesth 1992;68:394-397. [ Links ]
09. Morgan PJ, Halpern SH, Tarshis J - The effects of an increase of central blood volume before spinal anesthesia for cesarean delivery: a qualitative systematic review. Anesth Analg, 2001;92:997-1005. [ Links ]
10. Rout CC, Rocke DA, Levin J et al - A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology, 1993;79:262-269. [ Links ]
11. Corke BC, Datta S, Ostheimer GW et al - Spinal anaesthesia for Caesarean section. The influence of hypotension on neonatal outcome. Anaesthesia, 1982;37:658-662. [ Links ]
12. Datta S, Alper MH, Ostheimer GW et al - Method of ephedrine administration and nausea and hypotension during spinal anesthesia for cesarean section. Anesthesiology, 1982;56:68-70 [ Links ]
13. Tong C, Eisenach JC - The vascular mechanism of ephedrine's beneficial effect on uterine perfusion during pregnancy. Anesthesiology 1992;76:792-798. [ Links ]
14. Li P, Tong C, Eisenach JC - Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine arteries. Anesth Analg, 1996;82:288-293. [ Links ]
15. Kobayashi S, Endou M, Sakuraya F et al - The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release? Anesth Analg, 2003; 97:1239-1245. [ Links ]
16. Casey BM, McIntire DD, Leveno KJ - The continuing value of the Apgar score for the assessment of newborn infants. N Engl J Med, 2001;344:467-471. [ Links ]
17. Cooper DW, Carpenter M, Mowbray P et al - Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology, 2002;97:1582-1590. [ Links ]
Dr. Sérgio D. Belzarena
Rua Jose Américo Domingues, 96
97574-710 Livramento, RS
Submitted for publication
20 de julho de 2005
Accepted for publication 30 de janeiro de 2006
* Received from Serviço de Anestesiologia da Santa Casa de Misericórdia de Santana do Livramento, Livramento, RS