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Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of i
- Tiina Erkinaro, Seppo Alahuhta, Juha Räsänen (3 March 2006)
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Phenylephrine is still the drug of choice for pregnant humans.
- Edward T. Riley (2 March 2006)
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Tiina Erkinaro, Anaesthesiologist Oulu University Hospital, Seppo Alahuhta, Juha Räsänen
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Dear Editor, We would like to thank Professor Riley for his interest towards our article (1). We totally agree with Professor Riley in that the results obtained from animal experiments should never be applied to humans as such but interpreted with great caution. Consequently, we were careful not to draw any conclusions regarding the use of vasopressors during human fetal compromise. Like Professor Riley, we rather consider our findings as an indicator of the urgent need to address this question in humans and are eagerly waiting for the answer. However, we feel that we are not simply replicating the findings of others as our fetal sheep model (1-4) has some improvements compared with previous studies on pregnant ewes (5,6). Unlike Ralston et al. (5), who administered vasopressors to normotensive ewes, we treated short-term hypotension induced by epidural anaesthesia. In contrast with the study of McGrath et al. (6), we assessed our ewes in the typical supine position, allowing free venous return from the extremities. Most importantly, as opposed to all previous work in this field, we have included extensive invasive and noninvasive monitoring of fetal (3, 4) and umbilicoplacental (1-4) haemodynamics in our protocol. Although the Doppler ultrasonographic assessment of our fetuses necessitates the use of simultaneous general anaesthesia, we hope that our model is useful in adding to the understanding of fetal cardiovascular physiology and will help future investigators in choosing the main parameters of interest for vasopressor research. Sincerely, Tiina Erkinaro, Seppo Alahuhta & Juha Räsänen 1. Erkinaro T, Kavasmaa T, Päkkilä M, Acharya G, Mäkikallio K, Alahuhta S, Räsänen J. Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of increased placental vascular resistance. Br J Anaesth 2006; 96: 231-7 2. Erkinaro T, Mäkikallio K, Kavasmaa T, Alahuhta S & Räsänen J. Effects of ephedrine and phenylephrine on uterine and placental circulations and fetal outcome following fetal hypoxaemia and epidural- induced hypotension in a sheep model. Br J Anaesth 2004; 93: 825-32 3. Mäkikallio K , Erkinaro T , Niemi N, Kavasmaa T, Acharya G, Päkkilä M & Räsänen J. Fetal oxygenation and Doppler ultrasonography of cardiovascular hemodynamics in a chronic near term sheep model. Am J Obstet Gynecol 2006; 194: 542-50 4. Acharya G, Erkinaro T, Mäkikallio K, Lappalainen T & Räsänen J. Relationships among Doppler-derived umbilical artery absolute velocities, cardiac function, and placental volume blood flow and resistance in fetal sheep. Am J Physiol Heart Circ Physiol 2004; 286: H1266-72 5. 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: 354-70 6. McGrath JM, Chestnut DH, Vincent RD, DeBruyn CS, Atkins BL, Poduska DJ & Chatterjee P. Ephedrine remains the vasopressor of choice for treatment of hypotension during ritodrine infusion and epidural anesthesia. Anesthesiology 1994; 80: Conflict of Interest:None declared |
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Edward T. Riley, Anesthesiologist Stanford University School of Medicine
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I read with interest the paper by Erkinaro et al.1 and want to congratulate the authors on addressing the issue of whether the effects of ephedrine or phenylephrine are different in an animal model with compromised placental blood flow. This is the next important question that must be answered with regard to spinal anesthesia, hypotension, and Cesarean delivery. Current data shows that phenylephrine is the better vasopressor in the healthy, human maternal-fetal unit. However, we have no idea whether this finding holds true for the compromised maternal-fetal unit. Previously these authors had shown that maternal epidural-induced hypotension with ephedrine or phenylephrine after short-term fetal hypoxaemia in a chronic sheep model with undisturbed placental circulation results in comparable fetal blood gas values and lactate concentrations.2 In the current paper, in which they induced an increase in uterine vascular resistance, they found that phenylephrine administration was associated with impaired uterine and placental haemodynamics and increased fetal lactate concentrations. The question at hand is whether these results apply to humans? Unfortunately, when we look at how previous sheep model work with vasopressors has translated to humans, we have to say that these results cannot be applied to humans at this time. Previous work has found in sheep models that ephedrine is superior to other pressors in terms of preserving uterine artery blood flow and maintaining a better pH balance in the fetus.3,4 Therefore, the current paper by Erkinaro et al.1 essentially replicates the findings of others who have worked in the healthy pregnant ewe model. Data from those studies lead us to conclude that ephedrine was the correct drug to use in pregnant humans. However, human studies would suggest other vasopressors are better for the human fetus. When ephedrine is given to pregnant humans, there is an increase in fetal acidosis5 or signs of stress when assessing the fetal heart rate.6 Although I applaud Erkinaro et al. for tackling an important question, we must take great care in extrapolating these data to humans. I also must add that I am not criticizing the fact that they did not address this issue directly in humans. I have been trying to design a study of the effects of various pressors on patients with compromised placental blood flow for several years without success. Hopefully someone will give us the data that will tell us how to take care of the compromised fetus in the near future. Literature Cited 1. Erkinaro T, Kavasmaa T, Pakkila M, Acharya G, Makikallio K, Alahuhta S, Rasanen J: Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of increased placental vascular resistance. Br J Anaesth 2006; 96: 231-7 2. Erkinaro T, Makikallio K, Kavasmaa T, Alahuhta S, Rasanen J: Effects of ephedrine and phenylephrine on uterine and placental circulations and fetal outcome following fetal hypoxaemia and epidural-induced hypotension in a sheep model. Br J Anaesth 2004; 93: 825-32 3. McGrath JM, Chestnut DH, Vincent RD, DeBruyn CS, Atkins BL, Poduska DJ, Chatterjee P: Ephedrine remains the vasopressor of choice for treatment of hypotension during ritodrine infusion and epidural anesthesia. Anesthesiology 1994; 80: 1073-81; discussion 28A 4. 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: 354-70 5. 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: 920-6, table of contents 6. Wright RG, Shnider SM, Levinson G, Rolbin SH, Parer JT: The effect of maternal administration of ephedrine on fetal heart rate and variability. Obstet Gynecol 1981; 57: 734-8 Conflict of Interest:None declared |
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