Anthony R. Reed

Hemodynamic Effects of Ephedrine, Phenylephrine, and the Coadministration of Phenylephrine with Oxytocin during Spinal Anesthesia for Elective Cesarean Delivery

Background:Hemodynamic responses to vasopressors used during spinal anesthesia for elective Cesarean delivery, have not been well described. This study compared the effects of bolus phenylephrine and ephedrine on maternal cardiac output (CO). The hypothesis was that phenylephrine, but not ephedrine, decreases CO when administered in response to hypotension during spinal anesthesia. Methods:Forty-three patients were randomized to receive 80 &mgr;g of phenylephrine or 10 mg of ephedrine. Both pulse wave form analysis and transthoracic bioimpedance changes were used to estimate stroke volume in each patient. Hemodynamic responses to spinal anesthesia and oxytocin were also recorded. A subgroup of 20 patients was randomized to receive oxytocin compared with oxytocin plus 80 &mgr;g of phenylephrine after delivery. Results:Mean CO and maximum absolute response in CO were significantly lower during the 150 s after phenylephrine administration than after ephedrine (6.2 vs. 8.1 l/min, P = 0.001, and 5.2 vs. 9.0 l/min, P < 0.0001, respectively for pulse wave form analysis, and 5.2 vs. 6.3 l/min, P = 0.01 and 4.5 vs. 6.7 l/min, P = 0.0001, respectively for bioimpedance changes). CO changes correlated with heart rate changes. Coadministration of phenylephrine obtunded oxytocin-induced decreases in systemic vascular resistance and increases in heart rate and CO. Trends in CO change were similar using either monitor. Conclusions:Bolus phenylephrine reduced maternal CO, and decreased CO when compared with ephedrine during elective spinal anesthesia for Cesarean delivery. CO changes correlated with heart rate changes after vasopressor administration, emphasizing the importance of heart rate as a surrogate indicator of CO. Coadministered phenylephrine obtunded hemodynamic responses to oxytocin.

Hemodynamic Changes Associated with Spinal Anesthesia for Cesarean Delivery in Severe Preeclampsia

Background:Hemodynamic responses to spinal anesthesia (SA) for cesarean delivery in patients with severe preeclampsia are poorly understood. This study used a beat-by-beat monitor of cardiac output (CO) to characterize the response to SA. The hypothesis was that CO would decrease from baseline values by less than 20%. Methods:Fifteen patients with severe preeclampsia consented to an observational study. The monitor employed used pulse wave form analysis to estimate nominal stroke volume. Calibration was by lithium dilution. CO and systemic vascular resistance were derived from the measured stroke volume, heart rate, and mean arterial pressure. In addition, the hemodynamic effects of phenylephrine, the response to delivery and oxytocin, and hemodynamics during recovery from SA were recorded. Hemodynamic values were averaged for defined time intervals before, during, and after SA. Results:Cardiac output remained stable from induction of SA until the time of request for analgesia. Mean arterial pressure and systemic vascular resistance decreased significantly from the time of adoption of the supine position until the end of surgery. After oxytocin administration, systemic vascular resistance decreased and heart rate and CO increased. Phenylephrine, 50 &mgr;g, increased mean arterial pressure to above target values and did not significantly change CO. At the time of recovery from SA, there were no clinically relevant changes from baseline hemodynamic values. Conclusions:Spinal anesthesia in severe preeclampsia was associated with clinically insignificant changes in CO. Phenylephrine restored mean arterial pressure but did not increase maternal CO. Oxytocin caused transient marked hypotension, tachycardia, and increases in CO.

The role of the anaesthetist in the management of the pre-eclamptic patient.

Purpose of review Recent literature on the anaesthetists role in the management of the patient with severe pre-eclampsia is reviewed, with particular emphasis on the role of regional anaesthesia. Recent findings Laboratory findings in pre-eclamptic women include increased levels of markers of oxidative stress and circulating tyrosine kinase 1, and inflammatory activation of leucocytes. Magnesium sulphate is the most effective agent for seizure prophylaxis. The optimal pharmacological agents for acute control of blood pressure remain controversial. The benefits of epidural analgesia in labour are well established. Single-shot spinal anaesthesia for caesarean section is safe in the absence of contraindications. Successful use of combined spinal-epidural anaesthesia has been described. Most studies on maternal haemodynamics have employed heart rate and blood pressure data as surrogate measures of cardiac output. Noninvasive cardiac output studies provide further insight into the haemodynamic response during neuraxial techniques for caesarean section. Summary The value of regional anaesthesia cannot be over-emphasized. Recent research into spinal anaesthesia for caesarean section suggests a lower susceptibility to hypotension and probably less impairment of cardiac output than in healthy parturients. Noninvasive cardiac output measurement may also have advantages in critical care management.

Spinal hypotension during elective cesarean delivery: closer to a solution.

Hypotension during spinal anesthesia for cesarean delivery should be minimized, both for maternal safety and comfort, and fetal wellbeing. Traditional teaching is that aortocaval compression predisposes the parturient to decreased venous return and hence cardiac output and blood pressure during spinal anesthesia for cesarean delivery. However, a variety of measures to improve venous return, including lateral tilt and numerous fluid administration regimens, have failed to eliminate hypotension. Recent studies focusing on the arterial circulation as a source for hypotension suggest that in the fluid-replete parturient undergoing elective cesarean delivery, moderate spinal hypotension (20% decrease from baseline) primarily reflects decreased systemic vascular resistance. In most cases, venous return is initially maintained and consequently there is a partial compensatory increase in cardiac output, mediated by an increase in stroke volume and heart rate. In this situation, the rapidly acting -agonist phenylephrine seems to be the best option to restore baseline hemodynamics rapidly. Although ephedrine has traditionally been used to treat spinal anesthesia–induced hypotension, recent evidence suggests that ephedrine causes neonatal acidosis, and large doses may be harmful in a compromised fetus, by increasing oxygen demand and anaerobic metabolism. Ephedrine is also associated with a higher incidence of nausea and vomiting than phenylephrine. The dose and method of administration of phenylephrine have been the subject of extensive investigation. In this issue of Anesthesia & Analgesia, 2 articles address this subject. First, Allen et al. compared placebo with the use of 4 different infusion rates of phenylephrine, in combination with a crystalloid coload, and assessed “hemodynamic stability” by heart rate and blood pressure. The aim was to maintain blood pressure within 20% of baseline values. They demonstrated that infusing phenylephrine at a fixed rate of 75 or 100 g/min is associated with more episodes of hypertension than placebo, or the lower infusion rates of 25 or 50 g/min, respectively. Seven patients in the group receiving 100 g/min developed sinus bradycardia and were given glycopyrrolate. It may be more appropriate to treat baroreceptor-mediated bradycardia associated with a well-maintained blood pressure by discontinuing the infusion than by the administration of an anticholinergic. This would avert the reactive hypertension reported by the authors. This work suggests that to reduce hypotension and avoid hypertension and bradycardia, slower infusion rates of phenylephrine are a better starting point, with supplementary boluses as necessary, in keeping with the pharmacokinetic principle of the use of a bolus followed by an infusion to increase steady-state concentrations. Alternatively, the authors speculate, varying infusion rates could be used. The fact that some patients experienced bradycardia and hypertension even at the slower infusion rates suggests that bolus administration of phenylephrine, titrated as required in the individual case, may be a better option than prophylactic infusions. In the second important contribution, Stewart et al., using a suprasternal Doppler flow technique, described cardiac output changes associated with infusions of 25, 50, and 100 g/min phenylephrine, respectively, after the administration of a rapid crystalloid preload, during spinal anesthesia for elective cesarean delivery. The aim was to maintain baseline blood pressure. The infusion of phenylephrine at 100 g/min for 20 minutes was associated with a reduction in heart rate from 80 to 58 bpm and a reduction in cardiac output from 5.1 to 4.0 L/min. Neonatal outcomes were similar among groups. This is in agreement with a recent investigation of the hemodynamic effects of boluses of ephedrine and phenylephrine using pulse power analysis. Bolus administration of phenylephrine in response to hypotension (20% decrease from baseline blood pressure) was shown to reduce maternal cardiac output to close to baseline values (an effect strongly correlated with maternal heart rate) and restore blood pressure. In the non-obstetric population, phenylephrine (1:20,000) added to epidural lidocaine, and IV methoxamine administered during spinal anesthesia, have been shown to reduce cardiac output. The studies published in this issue examining the effects of phenylephrine infusions during spinal anesthesia for cesarean delivery suggest that the use of phenylephrine in doses that cause hypertension and sinus bradycardia is inappropriate. How does phenylephrine influence cardiac output? The effect of -agonists on venous return is controversial. It is From the Department of Anaesthesia, University of Cape Town and New Groote Schuur Hospital, Cape Town, South Africa.

Obstetric anaesthesia in low-resource settings

Close co-operation between obstetricians and obstetric anaesthesia providers is crucial for the safety and comfort of parturients, particularly in low-resource environments. Maternal and foetal mortality is unacceptably high, and the practice of obstetric anaesthesia has an important influence on outcome. Well-conducted national audits have identified the contributing factors to anaesthesia-related deaths. Spinal anaesthesia for caesarean section is the method of choice in the absence of contraindications, but is associated with significant morbidity and mortality. Minimum requirements for safe practice are adequate skills, anaesthesia monitors, disposables and drugs and relevant management protocols for each level of care. The importance of current outreach initiatives is emphasised, and educational resources and the available financial sources discussed. The difficulties of efficient procurement of equipment and drugs are outlined. Guiding principles for the practice of analgesia for labour, anaesthesia for caesarean section and the management of obstetric emergencies, where the anaesthetist also has a central role, are suggested.

A Spotlight on Obstetric Anesthesia in the Developing World: Finally Getting the Attention It Deserves

June 2015 • Volume 120 • Number 6 www.anesthesia-analgesia.org 1179 Copyright

A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise

BACKGROUND Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia. METHODS Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores. RESULTS Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2. CONCLUSIONS In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension.

Maternal cardiac output response to colloid preload and vasopressor therapy during spinal anaesthesia for caesarean section in patients with severe pre‐eclampsia: a randomised, controlled trial

We examined the haemodynamic effects of colloid preload, and phenylephrine and ephedrine administered for spinal hypotension, during caesarean section in 42 women with severe early onset pre‐eclampsia. Twenty patients with pre‐delivery spinal hypotension were randomly allocated to receive an initial dose of either 50 μg phenylephrine or 7.5 mg ephedrine; the primary outcome was percentage change in cardiac index. After a 300‐ml colloid preload, mean (SD) cardiac index increased from 4.9 (1.1) to 5.6 (1.2) l.min−1.m−2 (p < 0.01), resulting from an increase in both heart rate, from 81.3 (17.2) to 86.3 (16.5) beats.min−1 (p = 0.2), and stroke volume, from 111.8 (19.0) to 119.8 (17.9) ml (p = 0.049). Fourteen (33%) and 23 (54.8%) patients exhibited a stroke volume response > 10% and > 5%, respectively; a significant negative correlation was found between heart rate and stroke volume changes. Spinal hypotension in 20 patients was associated with an increase from baseline in cardiac index of 0.6 l.min−1.m−2 (mean difference 11.5%; p < 0.0001). After a median [range] dose of 50 [50–150] μg phenylephrine or 15 [7.5–37.5] mg ephedrine, the percentage change in cardiac index during the measurement period of 150 s was greater, and negative, in patients receiving phenylephrine vs. ephedrine, at −12.0 (7.3)% vs. 2.6 (6.0)%, respectively (p = 0.0001). The percentage change in heart rate after vasopressor was higher in patients receiving phenylephrine, at −9.1 (3.4)% vs. 5.3 (12.6)% (p = 0.0027), as was the change in systemic vascular resistance, at 22.3 (7.5) vs. −1.9 (10.5)% (p < 0.0001). Phenylephrine effectively reverses spinal anaesthesia‐induced haemodynamic changes in severe pre‐eclampsia, if left ventricular systolic function is preserved.

National priorities for perioperative research in South Africa

BACKGROUND Perioperative research is currently unco-ordinated in South Africa (SA), with no clear research agenda. OBJECTIVE To determine the top ten national research priorities for perioperative research in SA. METHODS A Delphi technique was used to establish consensus on the top ten research priorities. RESULTS The top ten research priorities were as follows: (i) establishment of a national database of (a) critical care outcomes, and (b) critical care resources; (ii) a randomised controlled trial of preoperative B-type natriuretic peptide-guided medical therapy to decrease major adverse cardiac events following non-cardiac surgery; (iii) a national prospective observational study of the outcomes associated with paediatric surgical cases; (iv) a national observational study of maternal and fetal outcomes following operative delivery in SA; (v) a stepped-wedge trial of an enhanced recovery after surgery programme for (a) surgery, (b) obstetrics, (c) emergency surgery, and (d) trauma surgery; (vi) a stepped-wedge trial of a surgical safety checklist on patient outcomes in SA; (vii) a prospective observational study of perioperative outcomes after surgery in district general hospitals in SA; (viii) short-course interventions to improve anaesthetic skills in rural doctors; (ix) studies of the efficacy of simulation training to improve (a) patient outcomes, (b) team dynamics, and (c) leadership; and (x) development and validation of a risk stratification tool for SA surgery based on the South African Surgical Outcomes Study (SASOS) data. CONCLUSIONS These research priorities provide the structure for an intermediate-term research agenda.

Drug administration errors: time for national action

these include educating and raising awareness about medication safety, reading and re-reading labels on drug ampoules, checking the ampoule label with a second person or device (e.g. bar code reader), labelling all syringes in theatre, adhering to the international standard of colour-coded syringe labels, improving the organisation of drug drawers and work space, informing anaesthetists of new formulations or packaging of drugs, and establishing a mechanism for reporting and reviewing errors. In this issue of the SAMJ, Labuschagne et al. report on errors in drug administration by anaesthetists in public hospitals in the Free State province. 11 They confirm the problem of drug administration errors in anaesthesia, with nearly 40% of respondents admitting to making a drug administration error at some stage in their career. Their investigation, which polled full-time and occasional anaesthetic providers, supports the 90% incidence of responders reporting errors in previous South African surveys. 12,13 An expected finding in surveys of this nature is that a longer, full-time career in the specialty is more likely to be associated with a higher incidence of errors. This type of survey is useful to measure the occurrence of uncommon but potentially severe consequences, as it measures errors in very large numbers of cases, but lacks a denominator. 14