Is bolus phenylephrine or ephedrine better for caesarean sections?

A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise. R.A. Dyer et al. International Journal of Obstetric Anesthesia (2018) 33, http://dx.doi.org/10.1016/j.ijoa.2017.08.001

 

BACKGROUND

Post-Spinal Hypotension due to sympathetic blockade can be deleterious to both the fetus and the mother. Studies have demonstrated that phenylephrine is associated with less fetal acidosis compared to ephedrine. Phenylephrine induced vasoconstriction reduces uteroplacental flow and increases efficiency of oxygen extraction which may prevent an adverse impact of phenylephrine on fetal acidosis or Apgar scores. There is an increase in oxygen demand as a result of ephedrine-induced stimulation of beta adrenoreceptor in the fetus resulting in increased metabolism. Fetuses with beta2 adrenoreceptor haplotype are at higher risk of clinically significant acidosis even with small doses of ephedrine. There is limited evidence regarding the efficacy and choice of vasopressor in non-elective cesarean deliveries in high-risk parturients.This was a prospective randomised control trial, to study the effects of bolus doses of ephedrine versus phenylephrine on management of post–spinal hypotension in women with severe preeclampsia with a non-reassuring fetal heart tracing undergoing non- elective caesarean delivery.

HYPOTHESIS

There is no difference in the mean Umbilical Artery base excess in severely preecclamptic patients who received ephedrine versus phenylephrine for control of spinal hypotension.

METHODS

Ethics committee approval was obtained for this prospective randomised control trial. After obtaining written informed consent following the decision for a caesarean delivery patient’s baseline MAP was recorded prior to spinal anaesthesia. 300 caesareanmls of 6% HES was used as preload and patients were randomised to receive either ephedrine 7.5 mg or phenylephrine 50mcg to treat a 20% decrease from baseline MAP.

Maternal Exclusion Criteria

C/I to spinal anaesthesia, BMI > 40 kg/m2, clinical signs of hypovolaemia, abruptio placentae, placenta praevia, coagulation abnormality, thrombocytopaenia (platelet count < 75 x 109/L), pulmonary oedema, local or generalised sepsis, spinal deformity, umbilical cord prolapse, prior non-obstetric abdominal surgery, more than two previous caesarean deliveries, HIV positive or AIDS.

Fetal exclusion criteria

Persistent fetal bradycardia or any other fetal condition contraindicating spinal anaesthesia, gestational age <28 weeks, estimated fetal weight <900 g, and twin pregnancy.

Primary outcomes were comparison of UA base excess and secondary outcomes were UA and UV pH, lactate level, venous BE and Apgar scores at 1 and 5 min in both groups.

RESULTS

Total of 133 women were recruited to this trial, with only 64 women requiring vasopressor treatment (ephedrine or phenylephrine) for spinal hypotension. They were randomised into two groups of 32 each with comparable patient characteristics.

  • Pre-delivery blood pressure changes were similar.
  • There was no significant difference (p=0.29) in mean umbilical artery base excess −4.9 [3.7] vs −6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively.
  • Mean umbilical arterial pH 7.25[0.08] vs 7.22 [0.10], venous pH 7.28 [0.07] vs 7.27 [0.10] and lactate concentrations 3.41 [2.18] vs 3.28 [2.44] mmol/L for ephedrine and phenylephrine respectively did not differ significantly.
  • The umbilical venous oxygen tension was significantly (p=0.02) higher in the ephedrine group.
  • There was no difference in 1 or 5-min Apgar scores and numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2.

AUTHORS’ CONCLUSION

In preecclamptic patients with fetal compromise the fetal acid base status is not affected by use of either ephedrine or phenylephrine and hence they are equally suitable options for managing spinal-induced hypotension. Hence the choice of vasopressor should be based upon maternal haemodynamic responses in the individual case.

DISCUSSION

Strengths

This was a randomised blinded prospective trial which addressed a clearly focussed issue. The primary and secondary outcomes were well defined. All patients were accounted for and the two groups were similar and treated equally aside from the experimental intervention.

Limitations

The study was carried out in a single centre. The sample size was small despite power analysis, calculated on basis of previous study in the same institution using ephedrine as a vasopressor for spinal induced hypotension in preeclampsia with non-reassuring fatal heart rate tracing. All the patients were pre-loaded with colloid and whether this affected the dosages of vasopressor required could be a possibility. Although a written informed consent was taken but it was done only after the patient was scheduled for a non elective caesarean delivery. The mean decision to delivery timing for the whole cohort was 67 minutes and there is no mention of the degree of urgency of the surgery which could have an effect on fetal outcomes.There is an increased sensitivity to vasopressors like ephedrine and phenylephrine in preeclamptic patients and thus correspondingly lower doses of vasopressors required which might have affected the outcomes in both groups.

CONCLUSIONS

It appears to be still unclear regarding which medication has a better safety profile in this setting. This is a valid trial but larger multicentre trials are warranted to determine the ideal dosing and safety of phenylephrine and ephedrine administration in high-risk parturients in presence of uteroplacental insufficiency.

According to the international consensus statement on management of hypotension with vasopressors during caesarean section with spinal anaesthesia, women with pre-eclampsia develop less hypotension after spinal anaesthesia than healthy women. Any sudden decreases in blood pressure can further compromise a decreased uteroplacental blood flow. A prophylactic vasopressor infusion may not be required but, if used, it should be started at a lower rate than for healthy women.

 

Summary by Dr Nidhi Gautam

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