Effect of intravenous vasopressor on spread of spinal anaesthesia and fetal acid-base equilibrium

James Cook University, Townsville, Queensland, Australia
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 05/2007; 98(5):649-56. DOI: 10.1093/bja/aem056
Source: PubMed


We previously found rostral spread of spinal plain levobupivacaine to be less with prophylactic i.v. phenylephrine than with ephedrine during Caesarean delivery. This study investigated whether rostral spread of spinal hyperbaric bupivacaine is also less with phenylephrine than with ephedrine.
The study was randomized and double blind. It compared phenylephrine 100 microg ml-1 (phenylephrine group, n=27), and ephedrine 4.5 mg ml-1 (ephedrine group, n=27), given by infusion during spinal anaesthesia for Caesarean delivery. Block height was assessed to cold and light touch sensation at 15, 30, 60, and 90-min after the spinal injection of 2.8 ml of hyperbaric 0.5% w/v bupivacaine, combined with 0.4 ml diamorphine (1 mg ml-1). Umbilical blood gas values were monitored during the study.
Block height was similar for both groups at all of the assessment times. Umbilical artery pH was higher with phenylephrine [median 7.32 (IQR 7.28-7.34)] than with ephedrine [7.20 (7.10-7.28)] (P<0.0001). There was a strong negative correlation between umbilical artery pH and spinal-delivery interval, but only with ephedrine: phenylephrine group, r2=0.09 (P=0.17), and ephedrine group, r2=0.53 (P<0.0001). Five-minute Apgar scores were higher with phenylephrine [10 (9-10)] than ephedrine [9 (9-9)] (P=0.009).
In contrast to its effect on spinal plain levobupivacaine, we did not find rostral spread of spinal hyperbaric bupivacaine to be less with prophylactic phenylephrine than with ephedrine. We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase the risk of fetal acidosis developing with ephedrine, but not phenylephrine.

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Available from: David W Cooper, Apr 24, 2014
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    • "< 100 kg Exclusion: cardiac, pulmonary or renal diseases, or systemic diseases that could influence haemodynamic responses, including pre- eclampsia, hypertension, and diabetes; taking or had a history of taking any medications that could influence haemodynamic responses, including magnesium sulphate, terbutaline, or ß-blockers Spinal: 12 mg hyperbaric bupivacaine 0.75%, 10 lg fentanyl, 200 lg morphine; sitting position 10 ml.kg À1 lactated Ringer's solution within 15 min Ephedrine 10 mg (n = 20) with or without phenylephrine 40 lg (n = 20) Automated non-invasive, 1-min intervals until delivery SBP ≤ 80% of baseline or < 100 mmHg ND ND Saravanan et al. 2006 [24] Inclusion: ASA 1 or 2, elective section, > 18 years, 50– 120 kg, 150– 180 cm, normal singleton pregnancy, > 36 weeks' gestation CSE: 13 mg hyperbaric bupivacaine 0.5%, 400 lg spinal diamorphine Saline 0.9% 500 ml infusion commenced after iv access was established Up-down titration; ephedrine increased by 5 mg when preceding dose ineffective, decreased by 5 mg when preceding dose effective Non-invasive SBP < 75% of baseline or < 100 mmHg ND Before delivery, or 30 min after spinal, whichever was earlier © 2013 The Association of Anaesthetists of Great Britain and Ireland 155 Heesen et al. | Prophylactic phenylephrine for spinal anaesthesia Anaesthesia 2014, 69, 143–165 Table 3. (Continued) Study Inclusion/exclusion criteria Spinal anaesthesia Intravenous preload Intervention Blood pressure monitoring Definitions Observation period Hypotension Hypertension Exclusion: pregnancy- induced hypertension, history of diabetes, cardiovascular and cerebrovascular problems, fetal abnormalities and contra- indications to spinal anaesthesia (n = 40), or phenylephrine increased by 50 lg when preceding dose ineffective, decreased by 50 lg when preceding dose effective (n = 40) Cooper et al. 2007 [25] "
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    ABSTRACT: We conducted a systematic review to determine the harm and benefit associated with prophylactic phenylephrine for caesarean section under spinal anaesthesia. We included 21 randomised controlled trials with 1504 women. The relative risk (95% CI) of hypotension with phenylephrine infusion – as defined by authors – before delivery was 0.36 (0.18–0.73) vs placebo, p = 0.004; 0.58 (0.39–0.88) vs an ephedrine infusion, p = 0.009; and 0.73 (0.55–0.96) when added to an ephedrine infusion, p = 0.02. After delivery, the relative risks of hypotension and nausea and vomiting with phenylephrine compared with placebo were 0.37 (0.19–0.71), p = 0.003, and 0.39 (0.17–0.91), p = 0.03, respectively. There was no evidence that hypertension, bradycardia or neonatal endpoints were affected. Phenylephrine reduced the risk for hypotension and nausea and vomiting after spinal doses of bupivacaine generally exceeding 8 mg, but there was no evidence that it reduced other maternal or neonatal morbidities.
    Anaesthesia 02/2014; 69(2):143-65. DOI:10.1111/anae.12445 · 3.38 Impact Factor
    • "Combining two vasopressors with different mechanisms of action appeared promising as the consumption of individual drug is presumed to be less, thereby minimizing untoward effects of each drug . Different studies assumed different potency ratios of phenylephrine and ephedrine like (80:1),[2] (60:1),[11] (45:1)[12] and (33:1).[13] We followed the 33:1 potency ratio (100 mg of phenylephrine was considered equivalent to 3 mg of ephedrine) for our study to use proportionately more phenylephrine than ephedrine because the literature[9–12] indicates that this would result in better haemodynamic control. "
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    ABSTRACT: This randomized double blind study was started with an objective of management of spinal anaesthesia-induced hypotension in elective caesarean section by combining two commonly used vasopressors - ephedrine and phenylephrine in half of their usual doses with an expectation of reducing their foetomaternal side effects. One hundred and thirty two patients were randomized into three groups to receive either 100 μg/ml phenylephrine (group-P, n=31) or 3 μg/ml ephedrine (group-E, n=33) or 50 mg phenylephrine plus 1.5 mg ephedrine/ml (group-PE, n=29). Immediately after spinal injection the study solution was started prophylactically in every patient at the rate of 40 ml/h. A predefined algorithm was used to adjust the infusion rate according to the systolic blood pressure (SBP). Mean fall of SBP was significantly more in group-E than group-P (P=0.009) and group-PE (P=0.013). This was not significantly different when compared between group-P and group-PE (P=0.9). Episodes of hypotension and tachycardia were more in group-E than the other two groups. Statistically significant tachycardia was seen in Group-E than that in other two groups. Incidence of bradycardia and hypertension did not differ significantly among the groups. Maternal nausea and Apgar score were also comparable in three groups. Current study claims that prophylactic phenylephrine 100 mg/ml is a better choice than ephedrine (3 mg/ml) or 50 mcg phenylephrine plus 1.5 mg ephedrine/ml in prevention of spinal anaesthesia-induced hypotension in elective caesarean section. Combination of two drugs in half the usual dose has no added advantage over phenylephrine, but this is better than ephedrine alone.
    Indian journal of anaesthesia 11/2011; 55(6):578-83. DOI:10.4103/0019-5049.90612
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    • "The incidence of tachycardia was significantly higher in the ephedrine group, possibly due to difficulty in accurate titration of ephedrine because of its initial slow response and longer duration of action. Our results are in agreement with a number of other studies where significant tachycardia was observed with ephedrine usage [15, 28]. However, Loughery's et al. [29] found no cases of rebound hypertension with ephedrine, while Magalhaes et al. [30] reported comparable numbers of both bradycardia and reactive hypertension with ephedrine and phenylephrine. "
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    ABSTRACT: Hypotensive episodes are a common complication of spinal anesthesia during Cesarean section. The purpose of this study was to compare the effectiveness and the side effects of vasopressors, ephedrine and phenylephrine, administered for hypotension during elective Cesarean section under spinal anesthesia. The study consisted of 100 selected ASA I/II females scheduled for elective Cesarean section under spinal anesthesia. Each patient was randomly assigned to one of the two double-blind study groups. Group E received 1 ml ephedrine (5 mg/ml) with normal saline if hypotension was present (n=50). Group P received 1 ml phenylephrine (100 µg/ml) with normal saline if hypotension developed (n=50). Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) were compared within and between groups to basal levels at time increments of 0, 2, 4, 6, 8, 10, 15, 20, 25, 30, 45, and 60 min from start of surgery. Incidence of side effects and neonatal outcomes were studied between groups. All patients required vasopressor therapy for hypotension. Administration of phenylephrine was associated with significant drop in HR. Changes in SBP, DBP, and MAP were similar in both groups for most observed times. The incidences of nausea/vomiting and tachycardia were significantly higher in the ephedrine group. Phenylephrine and ephedrine are acceptable choices to combat maternal hypotension related to spinal anesthesia in elective Cesarean section. Complications of intra-operative nausea and vomiting, tachycardia and bradycardia should be considered when choosing a vasopressor, suggesting phenylephrine may be more appropriate when considering maternal well-being.
    04/2010; 6(2):257-63. DOI:10.5114/aoms.2010.13905
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