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Prevention of Hypotension After Spinal Anesthesia for Cesarean Section: Six Percent Hetastarch Versus Lactated Ringer's Solution

Riley, Edward T. MD; Cohen, Sheila E. MB, ChB, FRCA; Rubenstein, Adam J. MD; Flanagan, Brendan MB, BS

Obstetric Anesthesia

This study was designed to determine whether preoperative administration of 6% hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean section.Forty nonlaboring ASA class I and II women having nonurgent cesarean sections were randomized to receive either 500 mL of 6% hetastarch plus 1 L lactated Ringer's solution (LR) (n = 20), or 2 L of LR (n = 20) prior to induction of spinal anesthesia. Hypotension occurred in 45% of patients who received hetastarch vs 85% of those who received only LR (P < 0.05), and minimum systolic blood pressure was lower in the LR group than in the hetastarch group (85 +/- 12 vs 93 +/- 12 mm Hg [mean +/- SD]; P < 0.05). In addition, the LR group had a higher maximum heart rate (115 +/- 17 vs 104 +/- 16 bpm), a shorter mean time to hypotension (7 +/- 4 vs 10 +/- 7 min), and required more 5-mg doses of ephedrine for treatment of hypotension (0 vs 2 [median]; P < 0.05) than the hetastarch group. Neonatal outcome, as determined by Apgar scores and cord blood gas analyses, was good and similar in both groups. We conclude that 6% hetastarch plus LR is more effective than LR alone and that its routine use before spinal anesthesia for cesarean section should be considered.

(Anesth Analg 1995;81:838-42)

Department of Anesthesia, Stanford University School of Medicine, Stanford, California.

Accepted for publication May 17, 1995.

Address correspondence to Edward T. Riley, MD, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305.

Hypotension after spinal anesthesia for cesarean section remains a common and potentially serious complication, despite the use of left uterine displacement, prophylactic ephedrine, and fluid loading with crystalloids [1]. Although Malthru et al. [2] found that administration of albumin (15 mL/kg) prior to spinal anesthesia for cesarean section completely prevented hypotension, albumin is not widely used for this purpose, perhaps because of its high cost. Other, less expensive, colloids are available, and gelatin has proved effective in decreasing the incidence of hypotension after spinal anesthesia for transurethral resection of the prostate [3]. Hetastarch [average molecular weight 70,000 [4]] has a similar colloid oncotic pressure (34 mm Hg) to that of serum (27 mm Hg) and should be as effective as albumin for the prevention of hypotension [5]. However, in studies comparing the effectiveness of hetastarch and crystalloid before epidural anesthesia for cesarean section, no difference was detected in the incidence of hypotension [6,7]. In this study we compared the efficacy of 6% hetastarch plus lactated Ringer's solution (LR) with a larger volume of LR given alone before spinal anesthesia for nonurgent cesarean section.

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After obtaining institutional review board approval and informed consent, 40 nonlaboring ASA class I and II women having nonurgent cesarean sections were enrolled in the study. Exclusion criteria included obesity (weight over 115 kg), height less than 152 cm, diabetes, pregnancy-induced hypertension, chronic hypertension, heart disease, multiple gestation, and age less than 18 or more than 40 yr. Patients did not receive intravenous (IV) fluids prior to entering the study. Subjects were randomly assigned to receive either 1 L of LR (Group LR; n = 20) or 500 mL of 6% hetastarch (Group H; n = 20). Nurses placed a brown paper bag over the IV solution to conceal its identity from the anesthesiologist collecting data for the study. Both groups then received an additional liter of lactated Ringer's solution. All patients received metoclopramide 10 mg IV and sodium citrate 30 mL orally immediately prior to anesthesia. Spinal anesthesia was performed at the L2-3 or L3-4 interspace with the patient in the sitting position with the side-port of the needle pointing cephalad. All subjects received 12 mg of 0.75% bupivacaine in 8.5% dextrose, morphine 0.2 mg, and fentanyl 10 micro gram delivered through a 24-gauge Sprotte needle. Immediately after injection, the patient was positioned supine with left uterine displacement and given ephedrine 10 mg IV. Blood pressure was measured with an automated blood pressure device (Dinamap Trademark; Critikon, Inc., Tampa, FL) every minute for 20 min and every 3 min thereafter. Hypotension was defined as a systolic blood pressure (SBP) less than 100 mm Hg and less than 80% of the baseline blood pressure. Baseline blood pressure was determined by calculating the mean of three blood pressure measurements made in the preoperative holding area before fluid loading commenced. Hypotension was treated with IV boluses of ephedrine 5 mg and additional rapid infusion of LR. Ephedrine treatment was repeated every 2 min if hypotension persisted or recurred.

Patients rated their nausea on a scale of 0 to 3 (0 = no nausea and 3 = severe nausea or vomiting) before volume loading, after volume loading, and 10 min after induction of spinal anesthesia. A nausea score was also recorded any time the patient complained of nausea or vomited. Other variables recorded included the maximum height of the block as assessed by pinprick, other drugs used and their doses, and the amount of additional IV fluid given prior to delivery. Neonatal outcome was assessed using Apgar scores and umbilical arterial and venous blood gases obtained from a doubly clamped segment of umbilical cord.

Nonparametric and parametric continuous data were compared using Mann-Whitney U-test and Student's t-test, respectively, and proportionate data were compared with chi squared analysis. Repeated-measures analysis of variance was used to compare measurements of blood pressure and pulse over time. A P value of <or=to0.5 was considered significant. Values are reported as mean +/- SD except where noted otherwise.

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The groups were similar with respect to maternal height and weight, gestational age, and upper level of spinal blockade Table 1 and Table 2. Despite random assignment to treatments, the maternal age of Group H was slightly greater than that of Group LR Table 1.

Table 1

Table 1

Table 2

Table 2

Both groups had similar preinduction SBP and heart rates (HR). However, after spinal anesthesia minimum SBP was significantly lower and maximum HR higher in the LR group Table 2. Also, the incidence of hypotension was significantly higher in Group LR than in Group H and hypotension occurred earlier in Group LR Table 2; Figure 1. When only the first 15 min after spinal anesthesia are considered, the difference in the incidence of hypotension was even greater (Group LR 85% vs Group H 35%; P < 0.003). Group LR required more doses of ephedrine Table 2 indicating more recurrent episodes of hypotension. There was also a trend for group LR to receive a larger volume of additional IV fluid before delivery, but this difference was not significant Table 2.

Figure 1

Figure 1

Although mean SBP values were higher and mean HR values lower in Group H throughout the study Figure 1, repeated-measures analysis of variance did not demonstrate a significant difference between the groups. This is probably because patients were excluded from analysis when they received additional ephedrine. Thus, the patients with the greatest hemodynamic instability were not represented in ongoing comparisons of blood pressure and pulse over time.

Nausea after induction of spinal anesthesia was a minor problem and occurred with similar frequency in both groups. Only three patients in each group reported any nausea at 10 min, and only one in each group had a nausea score of 3 at any time. Nausea, when it occurred, was only transient. Neonatal outcome was excellent and similar in both groups Table 3. Only one neonate in each group had a 1-min Apgar score less than 7, and none had a 5-min score less than 7. Arterial and venous umbilical cord blood gases did not reveal significant acidosis in any neonate, and there were no differences between the groups in mean values Table 3. When neonates were grouped as to whether their mothers were hypotensive, there were also no differences in the umbilical cord blood gases.

Table 3

Table 3

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In this study, patients receiving hetastarch had a lower incidence of hypotension and a lower HR after spinal anesthesia than those receiving only crystalloid. This is consistent with the findings of others who have compared colloid and crystalloid fluid administration prior to spinal anesthesia. Malthru et al. [2] found no hypotension (defined as systolic blood pressure less than 100 mm Hg) when patients received 15 mL/kg of 5% albumin prior to spinal anesthesia for cesarean section. The control group, which received 15 mL/kg of 5% dextrose in LR, had a 29% incidence of hypotension. In males having spinal anesthesia for transurethral resection of the prostate, Baraka et al. [3] reported an 11% incidence of hypotension after administration of 7 mL/kg of 3% gelatin compared with 52% after the same volume of crystalloid. In a preliminary report, Sharma et al. [8] recently observed that patients given 500 mL of hetastarch had a 21% incidence of hypotension after spinal anesthesia with lidocaine for postpartum tubal ligation compared to a 55% incidence in patients given 1000 mL of LR.

The more stable hemodynamic status observed after colloid administration probably relates to their remaining in the intravascular compartment longer than crystalloids. Extravascular redistribution of crystalloids may be so rapid that it may be impossible to infuse them fast enough to maintain intravascular volume and avoid hypotension during spinal anesthesia [9]. Colloid solutions contain large molecules that do not immediately redistribute throughout the extracellular fluid compartment. Therefore, they should not decrease plasma colloid oncotic pressure (COP) as much as crystalloid solutions and intravascular volume should be better maintained [10,11]. Wennberg et al. [10] reported that COP decreased by only 1.7 mm Hg after preloading with 3% dextran 70 before epidural anesthesia for cesarean section, compared with a 5.6 mm Hg decrease after preloading with LR. In the same study population, Ramanathan et al. [11] found that a preload of 5% albumin given with LR decreased COP by 2 mm Hg compared with a 4-mm Hg decrease after LR alone; preloading with 25% albumin and LR actually increased COP by 2 mm Hg.

In addition to helping prevent hypotension, maintaining a higher plasma COP should result in less tissue edema provided capillary permeability remains normal. Although Wennberg et al. [10] found less lung water after dextran as compared with LR, Ramanathan et al. [11] found no differences in the aveolar-arterial oxygen difference or pulmonary morbidity (incidence of cough, rales, and fever) between parturients receiving colloids versus those receiving crystalloid. However, as patients in the latter study were young, healthy women, it is questionable whether significant pulmonary pathology would have been expected after a 2-L fluid load.

The incidence of hypotension in both groups in the current study was higher than in other studies of spinal anesthesia for cesarean section. For example Malthru et al. [2] reported no hypotension after colloid infusion, whereas we had an incidence of 45%. This may be a result of the larger colloid volume (1 L of albumin) used by Malthru et al. compared with the 500 mL hetastarch we administered. Rout et al. [12] reported a 43% incidence of hypotension in patients preloaded with only 20 mL/kg of crystalloid, whereas our LR group received a 30-mL/kg preload, yet had an 85% incidence of hypotension. In Rout et al.'s study [12] patients who received no fluid had a 71% incidence of hypotension, a lower incidence than in our patients who received a large crystalloid administration. There may be several reasons for the higher incidence of hypotension in the current study. First, opioids were not added to the local anesthetic in either of the other two studies. We added both morphine and fentanyl, which may increase the incidence of hypotension [13]. Second, we used a larger dose of local anesthetic (hyperbaric bupivacaine 12 mg) than did Rout et al. [12] (isobaric bupivacaine 7.5 mg) or Malthru et al. [2] (hyperbaric tetracaine 6-8 mg). The larger local anesthetic dose might be expected to cause a higher block and a more extensive sympathectomy than smaller doses. In support of this hypothesis, our patients had a higher average sensory block level than did those in Malthru et al's study [2] (T3-4 vs T6-8, respectively). However, Rout et al. [12] reported similar sensory block levels to ours. A third hypothesis to explain our higher incidence of hypotension is that the relatively large preload given our LR group may, paradoxically, have caused more hypotension. Although most studies [12,14,15] have demonstrated less hypotension after crystalloid before spinal anesthesia, Carvalho et al. [16] found a greater incidence of hypotension after volume loading with a 20 mL/kg vs a 10 mL/kg preload of LR. They postulated that the larger fluid load diluted plasma proteins, lowering COP to a greater extent than the smaller volume, resulting in greater extravasation of fluid into the extracellular fluid compartment. Finally, definitions of hypotension varied among the different studies, so that it may be inappropriate to directly compare their incidences of hypotension.

Despite a significant difference in the incidence and severity of hypotension in the LR group, neonatal outcome was uniformly good in both groups. This reflects the experience that transient decreases in blood pressure, rapidly treated with ephedrine, do not usually affect fetal acid-base status [17,18]. Although in parturients nausea often accompanies hypotension, the incidence in this study was very low. Few hypotensive patients became nauseated, and this was unaffected by the type of fluid preload. The metoclopramide given preoperatively and the prophylactic ephedrine probably played a major role in preventing nausea and vomiting [19].

No adverse reactions to hetastarch occurred in this study and no serious reactions have occurred during several years of routine use in our obstetric service. Although the incidence of allergic reactions with artificial colloids can be high, severe anaphylactic or anaphylactoid reactions have been rare with hetastarch [one case in 16,405 infusions [20]]. Thus, we believe that it is safe to use hetastarch on a routine basis.

Although hetastarch is cheaper than albumin ($50 versus $67 for 500 mL), it is still much more expensive than LR ($1 per L). Considering that neonatal outcome was similar in both the crystalloid and colloid groups, is it appropriate to use hetastarch routinely instead of crystalloid alone as a preload before spinal anesthesia for cesarean section? It is not likely that clinical trials with small sample sizes will demonstrate outcome differences between patients preloaded with colloid versus crystalloid, nor is it likely that a large, multicenter clinical trial will be conducted to answer this question. However, it is well known that prolonged or severe maternal hypotension can cause serious adverse fetal and neonatal effects [21]. Furthermore, spinal anesthesia can cause profound hypotension and bradycardia which on occasion has resulted in death [22]. The incidence or severity of such life-threatening events might conceivably be reduced by the routine use of colloid preloads. As hypotension carries potentially serious consequences for both the mother and fetus, we believe that, despite its cost, hetastarch is warranted in this circumstance.

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