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doi: 10.1097/ALN.0b013e3181a86306

Low-dose Spinal Anesthesia with Low-dose Phenylephrine Infusions for Cesarean Delivery: Better but Not Necessarily Best

Ngan Kee, Warwick D. M.B.Ch.B., M.D., F.A.N.Z.C.A., F.H.K.A.M.*; Khaw, Kim S. M.B.B.S., F.R.C.A., F.H.K.A.M.

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To the Editor:—

We read with interest the recently published report by Langesæter et al.1 together with the accompanying editorial,2 describing the use of minimally invasive continuous cardiac output monitoring during spinal anesthesia for cesarean delivery. Based on derived values for cardiac output, the authors advocated allowing a 10 to 20% decrease in blood pressure and questioned as unnecessary the use of higher doses of phenylephrine given to maintain blood pressure near baseline. The findings from this paper are important and are a substantial contribution to our knowledge of the hemodynamic changes during regional anesthesia in parturients. However, we believe that some caution is required when extrapolating these findings to recommendations for everyday clinical practice.
Although placement of peripheral arterial catheters was regarded as “minimally invasive,” we believe that most clinicians would find them difficult to justify in routine elective cases and will continue to rely on the use of noninvasive blood pressure monitoring, despite its intermittent nature of measurement. From our previous work, we consider that, when using noninvasive blood pressure monitoring, the clinically optimal approach is to titrate a phenylephrine infusion with the target of maintaining systolic blood pressure near to the baseline value. Using this approach, with both manual3–5 and automated6 control, the incidence of nausea and vomiting is significantly reduced, as compared with less strict blood pressure control4; this is a clearly defined and important endpoint, the clinical relevance of which is more immediately apparent as compared with derived values for cardiac output.
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When using phenylephrine to maintain maternal blood pressure, it is important to appreciate that although this potent vasopressor has a faster onset and can be more accurately titrated than ephedrine,7 control is not perfect and some variation (overshoot and undershoot) between target and actual blood pressure is to be anticipated. For example, in a previous study,4 when we targeted a systolic blood pressure of 80% of baseline (equivalent to allowing a 20% decrease as advocated by Langesæter et al.1), in actuality in the first 15 min after intrathecal injection, 96% of patients had one or more measurements < 80% of baseline with 25% of all measurements < 80% (fig. 1), and 52% of patients had one or more measurements < 70% of baseline with 7% of all measurements < 70%. As a consequence, 40% of patients experienced nausea or vomiting. In comparison, when we targeted a systolic blood pressure of 100% of baseline, 29% of patients had one or more measurements < 80% of baseline with 4.7% of all measurements < 80%; 8% of patients had one or more measurements < 70% of baseline with 2% of all measurements < 70%; and only 4% of patients experienced nausea or vomiting. Phrased in another way, our results suggest that to maintain maternal comfort, phenylephrine should be titrated whenever blood pressure begins to decrease. Delaying or withholding administration while permitting a decrease in blood pressure to some arbitrary percentage threshold below baseline as suggested by Langesæter et al.1 risks the likelihood that blood pressure will decrease further below the threshold and result in unpleasant symptoms.
Data from Langesæter et al.1 suggest that liberal administration of phenylephrine to achieve tight blood pressure control may result in lower cardiac output than a less aggressive approach. However, the clinical relevance of this in healthy elective patients is undetermined. Dyer and James2 stated that heart rate and blood pressure are used clinically as surrogate markers of maternal cardiac output, and that maximum changes in the latter correlate better with uteroplacental blood flow than with upper arm blood pressure. However, it has yet to be proven whether a global measure of cardiac output is the ideal parameter on which to base hemodynamic therapy in obstetric patients, since this does not necessarily represent regional flow in the uterus and placenta, which have widely dilated vasculature through which flow is largely pressure-dependent.8 Furthermore, studies in animals that have correlated fetal oxygen uptake with uterine blood flow have demonstrated that, under normal physiologic conditions, uterine blood flow is in excess of the minimum required to satisfy fetal oxygen demand.9 This confers a margin of safety that, to a degree, protects the fetus from fluctuations in uterine blood flow.10 If the same situation occurs in humans it could explain the lack of fetal acidosis observed when large doses of phenylephrine are used to maintain maternal blood pressure,3–5 despite evidence that this drug has the potential to decrease both cardiac output and uteroplacental blood flow. The implication of this is that in healthy parturients, within limits, even if hemodynamic control using phenylephrine does slightly reduce cardiac output and uteroplacental blood flow, it may still be clinically acceptable if this is balanced against other benefits such as maternal wellbeing.
Langesæter et al.1 concluded that that low-dose bupivacaine (with sufentanil), combined with a low-dose infusion of phenylephrine and moderate cohydration, gives the “best” hemodynamic stability. However, they can only validly make comparisons among the actual regimens included in their study. Because there were no direct comparisons with patients who received higher doses of phenylephrine or larger volumes of cohydration, it is speculative to assume that any of their regimens were superior to these other possible regimens. Moreover, a large proportion of their patients who received a low-dose phenylephrine infusion required supplementary boluses of vasopressors. Thus the mean phenylephrine requirement per patient was somewhat greater than the baseline 0.25 μg · kg−1 · min−1 and it cannot be excluded that a higher infusion rate may have provided more stable hemodynamic control. Also, when assessing the optimal regimen for hemodynamic control, we believe that ease of use is also a factor to be considered. In that respect, we consider a vasopressor infusion that is titrated to a defined endpoint to be superior to the use of a hybrid technique of a fixed rate low-dose infusion to which is added repeated “rescue” boluses for times when the infusion is inadequate. This is especially relevant during single-shot spinal anesthesia when small intrathecal doses as used by Langesæter et al.1 may not be appropriate.
We continue to advocate aggressive maintenance of blood pressure using phenylephrine in women having elective cesarean delivery under spinal anesthesia. Although it may be possible that cardiac output is slightly less with this method as compared with allowing blood pressure to drift 10 to 20% below baseline, unless evidence is produced that this is associated with a clinically important decrease in uteroplacental blood flow and with a detrimental effect on neonatal outcome, we believe that improved maternal comfort justifies our technique.
Warwick D. Ngan Kee, M.B.Ch.B., M.D., F.A.N.Z.C.A., F.H.K.A.M.*
Kim S. Khaw, M.B.B.S., F.R.C.A., F.H.K.A.M.
*The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
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1. Langesæter E, Rosseland LA, Stubhaug A: Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: A randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008; 109:856–63

2. Dyer RA, James MF: Maternal hemodynamic monitoring in obstetric anesthesia. Anesthesiology 2008; 109:765–7

3. Ngan Kee WD, Khaw KS, Ng FF, Lee BB: Prophylactic phenylephrine infusion for the prevention of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2004; 98:815–21

4. Ngan Kee WD, Khaw KS, Ng FF: Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for caesarean section. Br J Anaesth 2004; 92:469–74

5. Ngan Kee WD, Khaw KS, Ng FF: Prevention of hypotension during spinal anesthesia for cesarean delivery: An effective technique using combination phenylephrine infusion and crystalloid cohydration. Anesthesiology 2005; 103:744–50

6. Ngan Kee WD, Tam YH, Khaw KS, Ng FF, Critchley LA, Karmakar MK: Closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure during spinal anaesthesia for caesarean section: A preliminary descriptive study. Anaesthesia 2007; 62:1251–6

7. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T: A randomized double-blinded comparison of phenylephrine and ephedrine combinations given by infusion to maintain blood pressure during spinal anesthesia for cesarean delivery: Effects on fetal acid-base status and hemodynamic control. Anesth Analg 2008; 107:1295–302

8. Greiss FC Jr: Pressure-flow relationship in the gravid uterine vascular bed. Am J Obstet Gynecol 1966;96:41–7

9. Wilkening RB, Meschia G: Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow. Am J Physiol 1983; 244:H749–55

10. Meschia G: Safety margin of fetal oxygenation. J Reprod Med 1985; 30:308–11

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