There was no significant difference in total phenylephrine dose (0.38 mg; 95% CI: −0.13 to 0.88) (Table 3), or in the number of subjects requiring rescue bolus doses. In the HES group, all boluses were administered as a single intervention; in the HS group, 3 subjects received a single bolus and 5 received multiple boluses.
Fetal data are summarized in Table 4. There were no significant differences in umbilical cord gases or Apgar scores between groups. One neonate per group had a uterine artery pH <7.2. In the HES group, the neonate with the lowest uterine artery pH (pH = 7.18) had a uterine incision–delivery time of 5 minutes and 1- and 5-minute Apgar scores of 9 and 10. In the HS group, the lowest uterine artery pH was 7.07 with a uterine incision–delivery time of 2 minutes and 1- and 5-minute Apgar scores of 9 and 9.
The current study is one of few studies investigating CO changes with spinal anesthesia in the obstetric population and one of several investigating the relatively new but promising technique of fluid coloading. We showed no difference in CO variables, vasopressor requirement, or hemodynamic stability in women randomized to receive colloid versus crystalloid administered as a coload in combination with a phenylephrine infusion during spinal anesthesia for elective cesarean delivery.
The coloading technique developed after the efficacy of preloading was questioned. Crystalloid preloading is relatively ineffective for preventing hypotension18,19 despite infusing volumes of up to 30 mL/kg.20 Atrial natriuretic peptide release with subsequent vasodilator and diuretic effects compounded with time-related fluid redistribution are suggested causes of its ineffectiveness. Subsequent research compared crystalloid with colloid. Ueyama et al.3 measured blood volume and CO before and after preloading with crystalloid 1.5 L, and colloid 0.5 L and 1 L. After 30 minutes, 28% of the crystalloid remained in the circulation compared with 100% of the colloid. The investigators concluded that preloading volume, regardless of type of fluid, must be large enough to result in a significant increase in CO for effective prevention of hypotension. Tamilselvan et al.4 compared preload volumes of colloid 0.5 L and 1 L, and crystalloid 1.5 L; CO and FTc significantly increased in all groups before the initiation of anesthesia. After spinal anesthesia, this effect was maintained in only the colloid 1-L group; however, the incidence of hypotension was unchanged compared with the other groups. They concluded that the observed increase in CO could not compensate for reductions in SVR after spinal anesthesia. Even though the incidence of hypotension was not dramatically different among fluid groups in either of these studies, the fact that the increase in CO with colloid lasted longer is still important because CO correlates better with uteroplacental perfusion than changes in maternal BP.14
Dyer et al.9 investigated whether a crystalloid coload would be more effective than a preload and showed that 20 mL/kg crystalloid coload reduced hypotension compared with the equivalent preload volume. Teoh and Sia10 found that 15 mL/kg colloid preload but not coload, significantly increased maternal CO within the first 5 minutes after spinal injection, with no difference in the incidence of hypotension. However, the mean volume and duration of coload infusion was 1.1 L over 9 minutes, so it is difficult to know how much had infused within 5 minutes of spinal injection. Additionally, as acknowledged by the authors, baseline CO and SV were significantly lower in the coload group. These results differ from the current study in which we found CO to be transiently higher after spinal injection compared with baseline in both colloid and crystalloid groups, despite the coadministration of a phenylephrine infusion. Our increased rate of fluid administration (all subjects received 1 L of coload within 5 minutes) may account for this difference.
We compared crystalloid to colloid coloading because this combination had not been investigated and we also chose to administer a phenylephrine infusion in both groups to maintain bSBP following on work by Ngan Kee et al.21 Titrated phenylephrine infusions minimize maternal nausea, vomiting, and episodes of hypotension, and they result in higher neonatal pH and lower base deficits.1 Additionally, Ngan Kee et al.15 demonstrated a dramatic decrease in the incidence of hypotension by combining a crystalloid coload with a high-dose phenylephrine infusion compared with no coload. Our incidence of hypotension from spinal injection to delivery was 60% in the HS group versus 40% in the HES group, which is considerably higher than 1.9% observed by Ngan Kee et al.15 The definition of hypotension was the same in both studies. However, the coload volume in the Ngan Kee et al. study was almost double the volume we infused, and was administered over a longer period of time. Additionally, the mean spinal injection to delivery interval was longer in the current study than in the Ngan Kee et al. study (42 vs 27 minutes). The number of subjects in our study having >1 episode of hypotension was low (7% vs 27% in the HES and HS groups, respectively), suggesting hemodynamic control is better than the overall incidence of hypotension of 50% suggests. Our incidence of reactive hypertensive episodes was 30% in the HES group versus 40% in the HS group. Because of intermittent CO measurements, it is impossible to determine whether these were associated with a reduction in CO, although none was associated with bradycardia. Dyer et al.22 have shown CO change to correlate with HR changes after vasopressor administration, emphasizing the importance of HR as a surrogate indicator of CO.
The number of subjects requiring rescue phenylephrine boluses was small suggesting good BP control with the phenylephrine infusion. All boluses administered in the HES group were as a single intervention, whereas most of the boluses in the HS group were repeated. This finding suggests that HES may have an advantage over HS, although a larger study is necessary to confirm this finding. We propose that phenylephrine requirements were similar because CO did not fall below baseline in both groups. PV and FTc were significantly higher than baseline in the colloid group throughout, but not the crystalloid group; this may indicate preservation of adequate intravascular expansion. SV was significantly higher than baseline at all time points in both groups but CO was only transiently significantly higher and this can be attributed to the observed reduction in HR. Stewart et al.23 and Langesaeter et al.24 found a dose-dependent reduction in HR with phenylephrine use that is associated with a decrease in maternal CO. This emphasizes the fine balance between the maintenance of BP with α agonists and a potential baroreceptor-mediated reduction in CO, the fetal effects of which have yet to be fully evaluated, particularly in the emergency cesarean setting. Maintaining intravascular volume by filling of the venous system provides energy in the form of elastic recoil to create the pressure gradient allowing blood from the capacitance vessels to empty into the right atrium.
Langesaeter et al.24 compared CO and hemodynamic changes, using the LidCO® CO monitor, with different spinal anesthetic doses. All subjects received 0.75 L crystalloid coload over 20 minutes and half received a phenylephrine infusion. An initial decrease in SVR and increase in CO occurred in all patients immediately after spinal injection and a significantly slower HR and decrease in CO occurred in the phenylephrine groups. Dyer et al.,22 using a LidCO monitor, also demonstrated reductions in CO with phenylephrine use but found that CO remained above baseline because CO values immediately before vasopressor administration were higher than baseline. In these 2 studies, similar to ours, all subjects received a coload. It would be interesting to compare CO immediately before and after vasopressor administration in subjects receiving different volumes of coload to determine whether the coloading technique itself prevents CO from decreasing to below baseline after vasopressor administration.
More frequent CO measurements in the immediate postspinal period would have allowed us to compare our data with those of Langesaeter et al.24 Unfortunately, we could not perform CO measurements more frequently than every 5 minutes without compromising maternal comfort. Our highest BP readings occurred within 2 minutes of spinal injection, suggesting that our vasopressor infusion could be reduced at this time. This view differs from that of Langesaeter et al.24 who suggested an additional bolus of vasopressor at induction of spinal anesthesia. Of note, they used a much slower and smaller volume of coload as well as a lower phenylephrine infusion dose. Further work to investigate immediate CO changes after spinal injection with different combinations of fluids and vasopressors would be valuable because this is probably the time when the mother and fetus are at most risk.
Our finding that colloid offers no advantage over crystalloid in maintaining CO and reducing vasopressor requirement is important because colloid use is linked with pruritus, hypocoagulability, and allergic reactions, thus crystalloid is preferable to colloid if colloid offers no advantages. The risk of pulmonary edema and dilutional anemia with large volumes of crystalloid, however, should also be considered. It would be interesting to repeat our study using smaller coloading volumes.
HES was our colloid of choice because the incidence of anaphylactoid reactions with starches is lower compared with gelatins,25 the 2 most widely used colloids in our institution. We observed no adverse reactions to HES in this small study. The lower weight limit for inclusion criteria to our study was 50 kg; therefore, our coload volume of 1 L did not exceed the recommended daily dose of 20 mL/kg. We could have improved our study design by administering fluid on a volume/weight basis; however, from a practical point of view, we chose a fixed volume. We also chose not to include a control group, that is, a group receiving a phenylephrine infusion with no coload, because previous work by Ngan Kee et al.15 has shown that omitting a coload in this situation significantly increases the incidence of maternal hypotension.
In summary, we showed no difference in CO variables, vasopressor requirement, or hemodynamic stability between colloid and crystalloid and conclude no benefit in using colloid over crystalloid as a coload when used in combination with a phenylephrine infusion for spinal anesthesia for elective cesarean delivery.
Loan of the SupraQ, suprasternal Doppler machine was received from Deltex Medical, Chichester, UK; Drs. McDonald and Ashpole were supported by an unrestricted research grant from Smiths Medical, USA. Dr. Fernando was supported by the University College London Hospitals/University College London Comprehensive Biomedical Research Centre, which receives a proportion of funding from the United Kingdom Department of Health's National Institute of Health Research Biomedical Research Centers funding scheme.
Dr. McDonald is currently affiliated with the Department of Anesthesia, Guy's and St. Thomas' NHS Foundation Trust, London; Dr. Fernando is currently affiliated with the Department of Anesthesia, University College London Hospitals NHS Foundation Trust, London; Dr. Ashpole is currently affiliated with the Department of Anesthesia, Chelsea and Westminster NHS Foundation Trust, London; and Dr. Columb is currently affiliated with the Department of Anesthesia, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe, Manchester, United Kingdom.
Name: Sarah McDonald, FRCA.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Sarah McDonald has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Roshan Fernando, FRCA.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Roshan Fernando has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Keri Ashpole, FRCA.
Contribution: This author helped design the study.
Attestation: Keri Ashpole has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Malachy Columb, FRCA.
Contribution: This author helped design the study, analyze the data, and write the manuscript.
Attestation: Malachy Columb has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
This manuscript was handled by: Cynthia A. Wong, MD.
a Ashpole K, Fernando R, Tamilselvan P, Columb M. Maternal cardiac output changes with phenylephrine and ephedrine infusions after spinal anaesthesia for caesarean section. Int J Obstet Anesth 2005;14:S5.
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© 2011 International Anesthesia Research Society
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