Macaurthur & Riley 2007 - Vasopressors

8/19/2019 Macaurthur & Riley 2007 - Vasopressors

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Obstetric Anesthesia

Controversies: Vasopressor

Choice for Postspinal HypotensionDuring Cesarean Delivery

Alison Macarthur, MD*Mount Sinai HospitalToronto, Ontario, Canada

Edward T. Riley, MDw

Stanford University School of MedicineStanford, California

The use of spinal anesthesia for cesarean delivery has increased withthe introduction of small-gauge, noncutting spinal needles. Most womenin Canada, the United States, Australia, and Europe requiring electivecesarean delivery receive some variation of a spinal anesthetic techniqueowing to the perceived advantages of a clear end point in locating thesubarachnoid space, fast onset of local anesthetic effect, and reduced riskof local anesthetic toxicity. To successfully administer spinal anesthesiafor cesarean delivery, however, requires consistent attention to details tominimize side effects, the predominant one being maternal hypotension.

Maternal hypotension is an unwanted consequence of the physio-logic onset of spinal blockade, and causes both maternal and fetal effects.Maternal symptoms include nausea, vomiting, and a sense of ‘‘impend-ing doom’’ from inadequate cerebral perfusion. Inadequate treatmentof hypotension can ultimately end with the loss of consciousness andcardiovascular collapse. The fetus is indirectly affected by the develop-ment of hypotension, because of its dependency on maternal uterineartery pressure for adequate uterine blood flow. With a persistentreduction in uterine blood flow, fetal acidosis will occur; uterine bloodflow reductions of 65% led to acidosis in 10 minutes in the fetal lambmodel.1 Although anesthesiologists do not allow hypotension to persist,successful treatment can occasionally take longer than desired.

The incidence of maternal hypotension is reported to be 50% to80% depending upon the definition of hypotension used, the position of

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FROM THE *DEPARTMENT OF A NESTHESIOLOGY AND P AIN M ANAGEMENT, UNIVERSITY HEALTH NETWORK ; AND THEwDEPARTMENT OF A NESTHESIOLOGYR EPRINTS: DR A LISON M ACARTHUR , DEPARTMENT OF A NESTHESIA , R OOM 1514, MOUNT SINAI HOSPITAL, TORONTO,ONTARIO, C ANADA , M5G 1X5, E-MAIL: A LISON.M ACARTHUR @UHN.ON.CA


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the patient, the rate of spinal anesthetic agent injection, intravenousfluid loading, and whether the women is laboring or has associatedmorbidity such as pregnancy induced hypertension. Regardless of thedefinition and associated factors that change the incidence of hypoten-sion, this phenomenon is common enough that all anesthesiologistsmust be vigilant during cesarean delivery performed under spinalanesthesia.

’ Physiology of Postspinal Hypotension

The recommended dose of hyperbaric bupivacaine to achievepredictable anesthetic effect for cesarean delivery appears to be between

12.5 to 15 mg, depending upon whether lipophilic narcotics are added.2

With this dose, a block extends above the thoracic upper limit of theautonomic nervous system, and effectively removes sympathetic controlof the cardiovascular system. The induced sympathectomy causesvasodilation with a subsequent decrease in systemic vascular resistance(SVR). The decrease in SVR will compound the parturient’s predis-position to hypotension in the supine position.

The supine hypotensive syndrome was first reported in the 1930’s by a Swedish obstetrician, Gideon Ahltorp, who perceptively observed

the event and identified mechanical treatments including the proneposition, manual displacement of the uterus to the left, and immersionof the body in water to the neck.3 Approximately 2.5% to 20.6% (meanof 8%) of pregnant women, evaluated during the second and thirdtrimester, will develop the syndrome when positioned supine. FrankHolmes, a consultant anesthetist in Edinburgh, Scotland described theimplications of supine hypotension when combined with anesthesia,particularly regional anesthesia.4 He noted spinal anesthesia’s ability to‘‘reduce cardiac output to a dangerous degree’’ and that accompanying

hypotension likely contributed to maternal deaths occurring duringcesarean delivery. An electronic search of a medical database using terms spinal anesthesia+ maternal death led to more than 10 website pages of publications. In light of this predictable event, anesthesiologists must beprepared to prevent maternal hypotension, and to treat it quickly if itdoes occur.

’ Vasopressor Therapy

Despite maneuvers such as slow injection of spinal local anesthetics,administration of colloid intravenous fluid bolus, and the use of compressive leg devices, anesthesiologists will have to treat withvasopressor medications 40% to 60% of women undergoing cesareandelivery. The choice of vasopressors in North America includes

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ephedrine, phenylephrine, and epinephrine. Other sympathomimeticsare available, such as methoxamine, mephentermine, dopamine, andnorepinephrine; however, their use is uncommon with obstetric regionalanesthesia. One sympathomimetic not used in North America but usedwidely elsewhere is metaraminol. The ideal vasopressor is inexpensive,easily available, quick in onset, reliable, favorably affects maternal heartrate and minimizes detrimental effects upon the fetus and placentalperfusion. The choice between ephedrine and phenylephrine hasprovoked much debate. The advantages and disadvantages of each will

be discussed in the next sections.

’ Vasopressor Basic Science

Structure and Metabolism

The key element common to all vasopressors is their ability to mimicsome of the sympathetic nervous system activities. The differences

between them depend upon each drug’s ability to lead to a and b-receptor stimulation. The pharmacologic activity of each vasopressor isdependent upon its structural configuration.5 The basic structure of allsympathomimetics is the benzene-ring based b-phenylethylamine (Fig. 1).

a and b-receptor activity is maximized if hydroxyl groups areattached at the third and fourth carbons of the benzene ring.Compounds without hydroxyl groups on the third and fourth carbonare synthetic noncatecholamines. Included in this group are ephedrineand phenylephrine.

The metabolism of phenylephrine is by the same process as thenatural and synthetic catecholamines, which is rapid inactivation bycatchol-O-methyltranserease and monamine oxidase. Because of itsshort duration of action, it can be administered by intravenous bolusesof 50 to 200 mcg, or by intravenous infusion of 20 to 50 mcg/min.Ephedrine is not metabolized by catchol-O-methyltranserease enzymes

because it lacks hydroxyl groups, and monamine oxidase enzymedeamination does not occur because of its a-methyl group. Thus,ephedrine is excreted almost unchanged in urine. Its actions areprimarily ended by reuptake in terminal nerve endings. This differencein metabolism explains the relatively long duration of action of ephedrine compared to phenylephrine. The routes of administrationof ephedrine include oral, intramuscular and intravenous bolus.

Mechanism of Action

Ephedrine has both indirect and direct actions on the sympatheticnervous system. Its indirect effects are due to the stimulation of postganglionic sympathetic nerve endings to release norepinephrine.

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As norepinephrine is a weak b-2-receptor agonist, these effects areprimarily a and b-1-receptor mediated. Ephedrine’s direct effects areless potent than natural catecholamines, but do provide some b-2-receptor activation.

Phenylephrine, although structurally a synthetic noncatecholamine,functions similarly to norepinephrine with direct action at the a-1-receptor. However, it is less potent, and longer acting than norepi-nephrine. Unlike other synthetic noncatecholamines, phenylephrine’sindirect actions are minimal. Thus, phenylephrine will result invenoconstriction, which is greater than its arterial constriction, andpredictably increases blood pressure by increasing both SVR andpreload. Because of minimal b-2-receptor activity, phenylephrine doesnot cause tachycardia, but instead can cause reflex bradycardia withincreasing blood pressure.

Figure 1. Biochemical structure of basic vasopressors.



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Ephedrine

Ephedrine has become the standard vasopressor in obstetricanesthesia as a result of animal studies of the 1970s. Sol Shnider’s

group’s investigations, using the instrumented sheep model, demon-strated that ephedrine did not cause uterine artery vasoconstrictiondespite releasing norepinephrine at the preganglion.6 The result wasmaintenance of uterine artery blood flow and fetal pH, whereasmethoxamine, mephentermine, and metaraminol tended to decreaseuterine blood flow and pH.

More recent evaluations have elucidated the mechanisms contribut-ing to the preservation of uterine blood flow by ephedrine. Eisenachinitially identified a differential effect upon vascular beds of the

pregnant ewe model. Ephedrine causes substantial femoral arteryvasoconstriction but relatively little uterine artery vasoconstriction inthe pregnant ewe compared with the nonpregnant ewe.7 Later studiesidentified that nitric oxide synthase was increased in uterine arteryendothelium of pregnant ewes compared with nonpregnant ewes.8 Thislocalized increase would mediate increased local nitric oxide production,a potent vasodilator. Given these effects, ephedrine preferentially shunts

blood to the uterus during pregnancy.With the support of these findings, ephedrine quickly became the

vasopressor of choice in obstetrics. Two recent quantitative reviewssummarized ephedrine’s effectiveness in preventing hypotensioncompared with fluid boluses or expectant management.9,10 Bothreviews identified randomized clinical trials which administeredintramuscular or intravenous ephedrine before or immediately afterspinal anesthesia, compared with control groups receiving placebo, nointervention, or intravenous fluid boluses. The individual studies didnot show a benefit with the use of ephedrine; however, the meta-analysisof their findings was significant. Ephedrine was more effective than

controls in preventing maternal hypotension by almost 30% (relativerisk 0.73: 95% 0.63, 0.86). However, the incidence of hypotension in theephedrine group was still 32% to 55%.

Ephedrine Dosing

Perhaps the explanation of ephedrine’s failure in up to half of thestudy patients was a result of inadequate dose. The minimum effectivedose of ephedrine was reviewed in a paper by Lee et al,11 whichattempted to determine the dose-response from studies evaluatingvarious doses of ephedrine. Four randomized trials compared the effectof 0, 5, 10, 15, 20, 30 mg IV ephedrine boluses given simultaneouslywith or immediately after spinal anesthesia for elective cesareandelivery.12–15 The dose of spinal hyperbaric local anesthesia variedslightly with one study using 10 mg of tetracaine and the rest using



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bupivacaine 10 to 12.5 mg. A dose-response effect was identified withreduced risk of hypotension with increasing dose of ephedrine. This

benefit was balanced against the risk of maternal hypertension (usuallydefined as a maternal blood pressure >20% above baseline). The doseat which the authors felt the likelihood of benefit outweighed the riskof harm was 12 mg of ephedrine. This recommended dose contrastswith the commonly described dose in obstetric anesthesia texts, whichrecommend doses of 5 to 10 mg IV. Ephedrine’s ineffectiveness atpreventing hypotension in the other studies may have been the result of inadequate doses.

Another reason for ephedrine’s ineffectiveness may be that thetiming of administration does not coincide with the onset of anesthesia-induced hypotension. Studies administering ephedrine intramuscularlygave the medication at unspecified times prior to spinal anesthesia, 5 to25 minutes before the spinal, or after the administration of spinalanesthesia. None of the studies confirmed pharmacologic activity of thedrug before the administration of spinal anesthesia and its associatedsympathectomy and hypotension. Ephedrine was administered either asa bolus or as an infusion. Intravenous infusion rates ranged between 0.5and 5 mg/min, and bolus doses were between 5 and 30 mg precedingor after spinal anesthesia. Again, the activity of ephedrine likely lagged

behind the onset of those physiologic changes leading to hypotension. Itis possible that the timing of ephedrine administration has not beenoptimized. I have not identified any study, which attempted to increasematernal blood pressure with ephedrine before spinal anesthesia.Obviously concerns over this methodology would have to be considered,

but spinal-induced hypotension and its consequences are not incon-sequential.

Ephedrine and Umbilical Arterial Acidosis

Ephedrine has been associated with lower umbilical artery (UA) pHwhen compared with other vasopressors, such as phenylephrine, or tocontrols.13,16,17 The difference in mean umbilical arterial pH valueswas approximately – 0.03, with the range of mean pH in ephedrinegroups between 7.18 (SD 0.13) and 7.27 (SD 0.04). Although thedifference is statistically significant, the clinical relevance has yetto be determined. No study has shown a difference in long-termneonatal outcome. Only surrogate outcomes have been measured.However, 2 important predictors of poor outcomes for the neonate

are UA pH below 7.2 and UA negative base deficit lower than 12.Cooper et al18 found a greater number of neonates with an UA pH of less than 7.2 and NganKee et al19 found that ephedrine use wasassociated with a lower negative base excess compared with pheny-lephrine.



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Riley20 hypothesized the pathophysiology of ephedrine’s associationwith lower UA pH in 2004. He was concerned by accumulatingevidence that ‘‘doses of ephedrine large enough to maintain homeostasisafter the induction of spinal anesthesia may be detrimental to the fetus.’’He suggested that ephedrine, which crosses the placenta, led toincreased fetal metabolic activity and subsequent reductions in fetalarterial pH. Presuming that much of the argument againstephedrine is based upon its effect on UA pH or umbilical basedeficit, we must define a deleterious pH and base deficit. What arethe implications of an UA pH of 7.20, 7.10, or 7.00, and whenshould we be concerned that acidotic intrapartum conditions areresponsible for long-term, deleterious neonatal outcomes? In 1999, aconsensus paper of the American, Canadian, and Australian obstetricsocieties defined the evidence required to identify a significantintrapartum asphyxial event severe enough to be cause neonatalneurologic injury.21 The committee concluded that an intrapartumasphyxial event was associated with a significant metabolic acidosis,defined as an UA pH 12 mmol/L. In thestudies to date, which have been carried out on healthy, uncomplicatedelective cesareans, ephedrine use has caused a reduction in umbilicalarterial pH primarily because of elevated fetal CO2 levels, indicating arespiratory acidosis. Numerous pediatric and obstetric papers haveidentified that respiratory acidosis alone is not associated with newborncomplications.22,23 It seems that ephedrine is not deleterious to theuncompromised fetus. Ephedrine’s effect on the compromised fetus isunknown.

If maternal ephedrine increases fetal catecholamines andmetabolic activity, similar to the effect of labor, might this be beneficial?The incidence of transient tachypnea of the newborn (TTN) issignificantly reduced amongst babies born following a laborcompared with babies born at elective cesarean delivery. Thisconcept was tested in a blinded, randomized clinical trial evaluatingthe effectiveness of terbutaline administered to mothers 2 hours

before an elective cesarean delivery.24 The authors hypothesizedthat the b-adrenergic stimulation of terbutaline would simulate laborand improve respiratory function and glucose homeostasis in thenewborn. Twenty-five babies were studied, after 13 mothersreceived terbutaline and 12 received saline placebo. Initial respira-tory rates of the babies in the terbutaline group were significantly lowerthan the placebo group, and serum glucose levels were maintained overthe first 2 hours at a higher level in the terbutaline group. Babies of mothers who received terbutaline also had significantly lower airwayresistance and higher lung compliance than controls, as measured bypneumotachometer. Two babies in the control group were diagnosedwith TTN. However, the UA base deficit was significantly higher for the



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treatment group, with a BE of – 5.2 compared with – 2.7 for the controlgroup.

The last issue to address is what is the relative importance of ephedrine’s contribution to UA pH changes compared with othervariables. A retrospective study of all elective cesarean deliveriesperformed under hyperbaric bupivacaine spinal anesthesia identified12 explanatory variables and assessed their contribution towardsthe prediction of final UA pH.25 The explanatory variables includedpatient demographics (age, weight, height, neonatal birth weight),anesthesia-related information (block height, use of prehydration,vasopressor used, maximum decrease in systolic pressure, andlength of hypotension) and relevant obstetric information (inductionto delivery time, skin incision to delivery time, uterine incision todelivery time). Each variable was evaluated in a multivariate linearregression model, a statistical technique that allows for evaluation of each variable’s effect adjusting for the other variables effect on theoutcome, UA pH. The final predictive model concluded that theimportant variables to predict the UA pH were whether ephedrine wasused, the length of uterine incision to delivery time, the maximumdecrease in systolic pressure in mm Hg, and the duration of hypotensionin minutes. An interaction term was identified in the model, betweenephedrine use and duration of hypotension, indicating that the womenreceiving ephedrine had a further deleterious effect depending uponthe duration of hypotension.

The final mathematical model to predict UA pH in this populationof healthy women under spinal anesthesia was:

UA pH = 7.413 to 0.042 (if ephedrine used) – 0.014durationof hypotension in minutes (if ephedrine used) – 0.001maximumdecrease in systolic arterial pressure in mm Hg – 0.0002uterineincision to delivery time+ 0.0002duration of hypotension inminutes.

Although this formula seems overwhelming, its applicability can beseen using a case of extreme pathophysiology: a woman for electivecesarean delivery under spinal anesthesia has a significant reduction of systolic arterial pressure of 40 mm Hg, who then receives ephedrine andhas a hypotensive episode of 5 minutes and then experiences a longerthan usual uterine incision to delivery time of 32 seconds. In this case,the above formula predicts the resulting UA pH to be 7.25. Thisdemonstrates that there is a large reserve for protecting the fetus fromacidosis.26–28

Ephedrine, with its longer duration of action, still has a role inobstetric anesthesia to prevent or treat spinal-induced hypotensionwhen given in an appropriate dose. The optimal method to administerephedrine, whether combined with other vasopressor therapy ornonmedication therapy, awaits future study.



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’ Phenylephrine

Concerns With Using a -1-agonist Agents

Standard obstetric anesthesia textbooks up until the 1990s con-demned the use of a-1-agonists in the treatment or prevention of maternal hypotension. These recommendations were based on sheepstudies, which detailed drastic reductions in uterine blood flow after theadministration of methoxamine, metaraminol, or phenylephrine.29

However, in the 1990s clinical researchers reported on the effectivenessof phenylephrine in treating spinal anesthesia-induced hypotension.30

The incentive to evaluate this vasopressor arose from the failure of ephedrine when used in the recommended 5 to 10 mg IV bolus doses,

and a desire to reduce the tachycardia elicited by ephedrine that wasundesirable in some parturients.Between 1991 and 2001, 7 studies compared ephedrine with

phenylephrine among women undergoing elective cesarean deliveryunder spinal anesthesia.31–37 These studies were summarized by Leeet al38 in a quantitative review. The summary concluded that ephedrineand phenylephrine were not different in preventing or treatinghypotension (refer to Table 1). The only difference identified in thestudies was that women given phenylephrine had neonates with higher

umbilical arterial pH values, by 0.03 pH units. Umbilical arterial baseexcess was greatest amongst neonates born to mothers receivingphenylephrine (weighted mean difference = 1.41; 95% confidenceinterval, 0.81–2.02).

This unexpected finding of improved neonatal parameters withphenylephrine may be explained by the lack of fetal metabolic effect ascompared with ephedrine. Although UA resistance may be increasedwith phenylephrine, the oxygen consumption by the fetus is not, andtherefore the net oxygen balance is more favorable than ephedrine.

Phenylephrine has been incorporated into the clinical practice of North American obstetric anesthesiologists as the evidence grows that it is notmore harmful than ephedrine.

Table 1. Maternal and Fetal Outcomes—Comparing Ephedrine to Phenylephrine

Outcome (Ephedrine Control Group) Relative Risk

Trials preventing maternal hypotension 1.09 (95% CI, 0.71-1.69)

Trials treating maternal hypotension 1.00 (95% CI, 0.95-1.05)

Overall effect in management of maternal hypotension 1.00 (95% CI, 0.96-1.06)Umbilical arterial pH values WMD

0.03 (95% CI, 0.02-0.04)

Fetal acidosis 0.78 (95% CI, 0.16-3.92)

CI indicates confidence interval; WMD, weighted mean difference.



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Phenylephrine has proven to be a useful, immediate remedy tomaternal hypotension, and may in fact reduce the incidence of maternalintraoperative nausea and vomiting better than ephedrine. Two studiesof a-agonists (metaraminol and phenylephrine) compared with ephe-drine in double-blind randomized trials documented the incidenceof maternal nausea and vomiting.18,19 The studies compared bothvasopressors given as infusions with maintain systemic blood pressure at

baseline values immediately after the administration of 10 to 12.5 mgspinal hyperbaric bupivacaine. Patients were repeatedly asked duringthe intraoperative period about nausea and the number of vomitingepisodes was documented. Combining these results using a meta-analytic technique, the risk of nausea or vomiting was reduced by almost80% in the women receiving a-agonists (refer to Fig. 2).

Optimal Method of Phenylephrine Administration

The evolution of vasopressor therapy in obstetrics has moved fromthe avoidance of vasoactive agents except when maternal blood pressuredropped significantly, to a philosophy that any reduction in maternal

blood pressure is undesirable. Ngan Kee et al39 compared the use of prophylactic phenylephrine with phenylephrine used only when systolicarterial blood pressure dropped Z20% from baseline. A prophylacticinfusion of 100 mcg/min of phenylephrine was started immediately afterthe administration of 10 mg hyperbaric bupivacaine in half the studypopulation and adjusted according to 1-minute blood pressure evalua-tions. The control group only received 100 mcg boluses of phenyle-phrine when the blood pressure dropped to r80% of baseline. Theprimary outcome was the UA pH, to indirectly assess fetal acid-basestatus. Despite almost tripling the dose of phenylephrine in theprophylactic group (median 1260 mcg; first/third quartiles 1010,1640 mcg) compared with the treatment-only group (median 450 mcg;first/third quartiles 300, 750 mcg) fetal arterial blood gas results were nodifferent, and only 1 neonate in each group had UA pH


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F i g u

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2 .

R a n d o m e f f e c t s m e t a - a n a l y s i s o f n a u s e a a n d v o m i t i n g r i s k .



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blood pressure was kept within the assigned group’s range. The primaryoutcome was the difference in UA pH between the 3 groups, andsecondary outcomes of the incidence of hypotension, reactive hyperten-sion, nausea, and vomiting. Despite an almost 2-fold increase in themean phenylephrine dose administered, women in the 100% baselinegroup had fewer episodes of nausea or vomiting (4% vs. 16%, 40%) andtheir neonatal mean umbilical arterial pH was higher (7.32 ± 0.04 vs.7.30 ± 0.03 for both other groups). The unpleasant symptoms of hypotension are better controlled with tight control of blood pressureusing aggressive vasopressor administration. Maximizing uterine arteryperfusion after the sympathectomy of spinal anesthesia may be moreimportant in maintaining uterine blood flow and fetal well being thanpreviously understood.

Our concern with a-1-agonists’ vasoconstrictive effects on theuterine artery has distracted us from their effects across differentvascular beds. In an elegant study of pregnant and nonpregnant sheep,Magness et al41 demonstrated that the pregnant uterine artery was lessresponsive to a-1-agonist stimulation than the nonpregnant uterineartery. Figure 3 illustrates the relative changes in pregnant andnonpregnant uterine vascular resistance, SVR, mean arterial pressure,

Figure 3. Relationship between the percent change in uterine vascular resistance (* ) and blood flow (D ) with mean arterial pressure (& ) and SVR ( ̂) during systemic infusions of phenylephrine in nonpregnant sheep.



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and an 80% incidence in the ephedrine only group. The authorsconcluded that the initial bolus doses were inadequate in both groups,and that perhaps an infusion method may have been more efficient inpreventing hypotension.

Cooper et al18 compared 3 different infusion regimes of vasopres-sors; phenylephrine 100 mcg/mL, ephedrine 3 mg/mL, and combinationof 50 mcg/mL phenylephrine with 1.5 mg/mL ephedrine started at20 mL/h after the administration of spinal anesthesia. The bupi-vacaine dose was 12.5 mg with added fentanyl. This study’s primaryoutcome was different, in that the authors were interested in theincidence of fetal acidosis (defined as UA pH


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’ Conclusions

With adequate dosages of bupivacaine for spinal anesthesia,pregnant women will develop significant, unpleasant hypotension if anesthesia vigilance and appropriate response are lacking. Nonphar-macologic methods can reduce the incidence of hypotension; however,the incidence of hypotension is still substantial, requiring vasopressorrescue.

Ephedrine has been recommended in the past as the mostappropriate vasopressor agent for pregnant patients. However, humanresearch has identified its association with lower UA pH values, likelydue to increased fetal metabolic activity. The benefits of ephedrineinclude its longer length of action compared to phenylephrine, and itschronotropic effect. However, the reliability of effect requires using adose of ephedrine between 10 to 15 mg by intravenous bolus, orinfusion of >2 mg/min. Among academic obstetric anesthetists, ephe-drine’s use has declined and has often been relegated to a second lineagent. Phenylephrine, on the other hand, has entered a renaissanceperiod with the recognition that the vasoconstriction it causes does nothave a detrimental effect on placental perfusion, and instead is a reliableand fast agent to prevent or treat maternal hypotension. Its onlydrawbacks are its short duration of action, necessitating infusiontherapy, and its predictable carotid sinus reflex effect resultingoccasionally in profound maternal bradycardia. The combination of phenylephrine with ephedrine to take advantage of both agents’ effectsat reduced dosages appears to work best when administered as aninfusion. What is left to determine is whether phenylephrine’s potentvasoconstricting effects are significant when given to a woman with acompromised fetal-placental unit.

Perhaps the most interesting study to date identified the originalconcept of intravenous fluid preloading has a place when administeredrapidly at the same time as the spinal anesthetic and with a prophylacticvasopressor infusion. Future development of sophisticated computer-driven devices will reduce the difficulties of attempting to administerthese therapies with spinal anesthesia.

’ References

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Macaurthur & Riley 2007 - Vasopressors