University Department of Anaesthesia, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE4 5PW, UK*Corresponding author
Accepted for publication: November 1, 2000
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Abstract |
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Br J Anaesth 2001; 86: 3726
Keywords: anaesthetic techniques, subarachnoid; anaesthesia, obstetric; sympathetic nervous system, pharmacology, ephedrine; sympathetic nervous system, pharmacology, phenylephrine
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Introduction |
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The usual approach to the use of vasopressors in this clinical setting is reactive rather than proactive; spinal anaesthesia-induced maternal hypotension is allowed to develop and is then treated accordingly. Given the frequency with which it occurs, a more logical approach to its prevention may be the administration of pre-emptive vasopressors. Intramuscular (i.m.) ephedrine 37.5 mg has been found to be safe for the fetus; however, it is associated with a persistently high incidence of maternal hypotension.6 The effect of ephedrine 45 mg i.m. has not been reported. No previous study has investigated the use of i.m. phenylephrine for the prevention of hypotension during spinal anaesthesia for Caesarean section, but it has been safely given via this route to healthy non-pregnant volunteers, including the elderly, in doses of 0.15 mg kg1 (up to 10 mg).7 8 In this randomized, double-blind, placebo-controlled study, we have evaluated phenylephrine 2 mg and 4 mg i.m., in comparison with ephedrine 45 mg i.m. and saline, given immediately after induction of spinal anaesthesia, in terms of haemodynamic stability, requirement for rescue i.v. vasopressor therapy and neonatal umbilical cord pH values.
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Patients and methods |
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Baseline non-invasive arterial pressure and heart rate readings were recorded at 1 min intervals by an automated non-invasive oscillometer (Criticon-Dinamapä) with data storage and printout facility, for 10 min before the start of the anaesthetic and continuing until surgery was completed. A 16-gauge i.v. cannula was sited in the non-dominant hand and 500 ml of Ringers lactate solution given as a preload. Combined spinalepidural anaesthesia (CSE) was instituted in the sitting position at L23 or L34, with a 26-gauge Sprotte spinal needle and 16-gauge Tuohy epidural needle, using a needle-through-needle technique. The i.m. injection of the study medication was given into the left vastus lateralis muscle immediately after the subarachnoid injection was completed. The time of i.m. injection was taken as time zero. The spinal injection contained 2.2 ml of 0.5% hyperbaric bupivacaine and fentanyl 20 mg, giving a total volume of 2.6 ml. The patient was then placed in the supine position, with a 15° left lateral tilt, after positioning of the epidural catheter to a depth of 34 cm in the epidural space. Block height was assessed with ethyl chloride spray at 5 and 15 min. Rescue i.v. bolus doses of ephedrine 6 mg were given if the patient became hypotensive or reported nausea, vomiting or dizziness. Hypotension was defined as a 25% decrease in mean arterial pressure (MAP) from baseline, which was taken as the lowest MAP recorded in the 10 min before receiving the study medication. (The lowest MAP value was chosen to minimize the influence of anxiety in patients with high initial MAP values.) The percentage change in MAP was calculated from the difference between baseline and the lowest recorded MAP, which occurred within the study period. The baseline heart rate was taken as the highest recorded heart rate before administration of the study drug. A printout of the haemodynamic data was obtained at the end of the operation. Neonatal Apgar scores at 1 and 5 min, and umbilical cord venous blood pH at delivery were also recorded. Top-ups for analgesia were not given via the epidural component of the CSE until the recording of data had been completed.
The number of patients required for enrolment in the study was calculated prospectively by assuming an incidence of hypotension of 80% in the untreated control group. We took a 35% reduction in the incidence of hypotension as being clinically significant. Therefore, taking =0.05 and ß=0.2, n=27 patients were required in each group to demonstrate these differences. Haemodynamic data, timing and dose of ephedrine required, together with physical characteristics were compared using analysis of variance with Dunnets post-hoc test for difference between the groups compared with control. Interval data (parity, dermatomal sensory levels, Apgar scores) were compared using the Kruskal-Wallis test. Categorical data (incidence of hypotension and incidence of use of rescue i.v. ephedrine therapy) were compared after constructing contingency tables and applying the chi-squared test or Fischers exact test as appropriate. Data were analysed using GraphPad PrismTM 2.0 on a personal computer running Microsoft Windows 98. A value of P<0.05 was considered statistically significant.
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Results |
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Discussion |
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The prevention and treatment of maternal hypotension associated with spinal anaesthesia for Caesarean section remains a difficult problem, with no consensus as to the optimal mode of management. Hypotension is defined arbitrarily in most studies, with values ranging from a 2030% reduction from baseline systolic arterial pressures (SAP) to absolute values less than 90100 mm Hg.1 3 6 The incidence of hypotension clearly depends on its definition and on the trigger for rescue ephedrine use. The trigger for rescue i.v. ephedrine use in our study was not only a 25% reduction in MAP, but also the presence of nausea, vomiting or dizziness which is the standard practice in our institution. Hence, we observed a high incidence of requirement for some rescue i.v. ephedrine therapy in all groups. However, our data demonstrated a reduction both in the severity of hypotension (in terms of percentage decrease in MAP) and the total dose of rescue i.v. ephedrine given. We chose the lowest MAP value in the 10-min stabilization period to allow anxious patients to settle and avoid spuriously high MAP values, which might have influenced the baseline measurement.
Measurement of SAP and MAP using non-invasive automated oscillometry has been found to be a valid method for non-invasive measurement of arterial pressure.9 We chose MAP rather than SAP, as this is the component of arterial pressure that is most accurately determined by this method. Continuous invasive arterial pressure measurement is a more sensitive method of detecting hypotension, but is not usually indicated in a healthy population and would not be used in routine obstetric anaesthesia practice. In this study, we investigated the effect of i.m. vasopressors, given before the onset of hypotension, and found a therapeutically useful effect. We did not measure the effect of these agents on CO and derived systemic vascular resistance index (SVRI). However, this has been done in other studies.4 10 11 Phenylephrine effectively restores SAP, MAP and diastolic arterial pressure, but decreases heart rate and CO when given by infusion to patients undergoing elective surgery under spinal anaesthesia.10 Another study found a 58% incidence of bradycardia (heart rate <60 beats min1) when phenylephrine was given as an i.v. bolus after the induction of spinal anaesthesia.5 None of the patients in the present study developed bradycardia. This may have been because of the overriding chronotropic effect of ephedrine when it was given as a rescue vasopressor. Alternatively, the absence of bradycardia may have been because of a baroreceptor-mediated reflex tachycardia in response to the reduction in systemic vascular resistance after the induction of spinal anaesthesia. Metaraminol, another -agonist, has also been shown to be effective in restoring SAP and SVRI within 1015 min, when given by continuous infusion in an elderly population.11 Ephedrine is not a potent arterial vasoconstrictor; it maintains SAP mainly by increases in CO and heart rate.4 All groups showed an increase in heart rate. As expected, the greatest increase was in the group receiving ephedrine 45 mg (Fig. 2), which can be explained by its ß1-adrenoreceptor activity.
The place of i.v. vasopressors for treatment of hypotension during Caesarean section is well established.5 12 13 However, giving i.m. vasopressors before a spinal anaesthetic is more controversial because of concerns about reactive hypertension and adequacy of placental perfusion if the subarachnoid block fails.14 We justified delaying the administration of i.m. vasopressors until the induction of spinal anaesthesia because of these concerns. A study comparing ephedrine 37.5 mg i.m., with placebo showed improved cardiovascular stability in the ephedrine group, but with a persistent 50% incidence of hypotension.6 Sternlo and colleagues found ephedrine 0.6 mg kg1 i.m., was effective in reducing the incidence of hypotension in patients undergoing hip arthroplasty under spinal anesthesia.15 In spite of the differing patient populations, this dose is consistent with the findings in our i.m. ephedrine 45 mg group. Although, we have shown a reduction in the severity of spinal anaesthesia-induced hypotension with i.m. vasopressor therapy, there is still a persistently high incidence of hypotension. Perhaps earlier vasopressor administration or a larger dose may have reduced this further.
The timing of i.m. drug administration to achieve optimum efficacy can be unpredictable. Pharmacokinetic studies have suggested that the peak effect of i.m. phenylephrine or ephedrine is 1015 min after administration.16 The onset of subarachnoid block in this study occurred simultaneously with administration of the i.m. vasopressors, yet despite this, significant reductions in MAP were observed within a few minutes of establishment of the block. Nonetheless, we have demonstrated a reduction in the severity of hypotension, but no difference in the time to first requirement for rescue i.v. ephedrine. This suggests that giving i.m. vasopressors immediately after the intrathecal injection is not too late to achieve a beneficial effect. In addition, no hypertension was observed 30 min after i.m. vasopressor administration, when a peak vasopressor effect might have been expected, because of the continuing influence of spinal anaesthesia.
There was no impact on the fetus of any of our vasopressor therapy regimes in terms of umbilical cord venous blood pH and Apgar scores, but we did not undertake neurobehavioural studies.
In conclusion, we have shown that phenylephrine 4 mg i.m., and ephedrine 45 mg i.m., reduce the severity of hypotension and the total dose of rescue i.v. ephedrine therapy during spinal anaesthesia for Caesarean section. Further studies are warranted to determine the optimum dosage and timing of i.m. phenylephrine and ephedrine in terms of efficacy and safety before they can be recommended for routine clinical use in obstetric anaesthesia.
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References |
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