This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ngan Kee, W. D. Articles by Gin, T. Search for Related Content PubMed PubMed Citation Articles by Ngan Kee, W. D. Articles by Gin, T. Related Collections Obstetrics Regional Anesthesia Pharmacology

---

OBSTETRIC ANESTHESIA

A Prospective Comparison of Vasopressor Requirement and Hemodynamic Changes During Spinal Anesthesia for Cesarean Delivery in Patients with Multiple Gestation Versus Singleton Pregnancy

From the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.

Address correspondence to Warwick D. Ngan Kee, MBChB, MD, FANZCA, Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. Address e-mail to warwick{at}cuhk.edu.hk.

	Abstract

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
BACKGROUND: It is commonly taught that patients with multiple gestation pregnancy are prone to more severe hypotension during spinal and epidural anesthesia compared to those with singleton pregnancy. However, few quantitative data are available to support this claim. In this study, we prospectively compared vasopressor requirement and hemodynamic changes in patients with multiple gestation versus singleton pregnancy during spinal anesthesia for elective cesarean delivery.

METHODS: Forty parturients with multiple gestation and 60 singleton controls who had identical anesthetic management during spinal anesthesia for elective cesarean delivery were enrolled. After IV prehydration, patients received intrathecal bupivacaine-fentanyl and were tilted to the left. A metaraminol infusion was titrated with the target of maintaining systolic blood pressure at 90%–100% of baseline. Vasopressor dose, minimum and maximum values for systolic blood pressure and the incidences of hypotension, hypertension, and nausea/vomiting were compared.

RESULTS: All outcome variables were similar between groups. The total dose of metaraminol required until uterine incision was similar in multiple gestation pregnancy (median 2.9 [interquartile range 2.0–3.7] mg) when compared with singleton pregnancy (median 3.1 [interquartile range 2.3–3.9] mg, P = 0.25; median difference 0.30 mg, 95% confidence interval of difference –0.20 to 0.90 mg). Neonatal outcome was similar between groups.

CONCLUSION: Patients with multiple gestation pregnancy do not exhibit greater hemodynamic instability during spinal anesthesia for cesarean delivery compared to those with singleton pregnancy.

	Introduction

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
Patients with multiple gestation pregnancy frequently present for cesarean delivery. Although regional anesthesia is generally considered to be safe and appropriate for them (1), standard textbook teaching warns that they are prone to more frequent and severe hypotension compared to patients with singleton pregnancy (2,3). This is attributed to the likelihood of greater aortocaval compression and greater cephalad spread of block (1,4). However, despite widespread acceptance of this view, few quantitative data are available to support it.

The aim of our study was to prospectively compare vasopressor requirement and hemodynamic changes in patients with multiple gestation versus singleton pregnancy during spinal anesthesia for elective cesarean delivery. The primary outcome was defined as the total dose of vasopressor delivered when a strictly controlled infusion regimen was titrated with the objective of maintaining maternal systolic blood pressure (BP) within a predefined target range.

	METHODS

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
This prospective cohort study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong, and written informed consent was obtained from all patients. We prospectively enrolled 40 ASA physical status 1–2 patients with multiple gestation pregnancy who presented for elective cesarean delivery under spinal anesthesia. Patients with preexisting or pregnancy-induced hypertension or known cardiovascular or cerebrovascular disease were excluded. Patients were enrolled consecutively from the regular scheduled lists, provided the principal investigator was available. Control data were obtained from 60 patients with singleton pregnancy, who had spinal anesthesia for elective cesarean delivery during the study period. All of the control patients were participants in other randomized controlled trials that we performed during this period (5,6). In each of these trials, one study arm received a strict regimen for anesthesia and management of BP that was identical to that used in the multiple gestation pregnancy group; we used data from all eligible patients in these arms. Patients were ineligible as controls if they had preexisting or pregnancy-induced hypertension or known cardiovascular or cerebrovascular disease. Data collection for control patients was started at the same time as data collection for multiple gestation patients.

Patients received oral premedication of rantidine 150 mg or famotidine 20 mg the night before and on the morning of surgery and 0.3M sodium citrate 30 mL on arrival to the operating room. Standard monitoring was attached, including noninvasive BP measurement, electrocardiography, and pulse oximetry. We allowed patients to rest undisturbed in the left-tilted supine position for several minutes, during which BP was measured every 1–2 min. BP measurements were continued until they became consistent (three successive measurements of systolic BP that had a difference of not more than 10%). Baseline systolic BP and heart rate were calculated as the mean of the three recordings.

We then inserted a 16-gauge IV cannula into a forearm vein under local anesthesia and gave IV prehydration of 20 mL/kg lactated Ringer’s solution over 15–20 min. The infusion was then adjusted to provide a minimal rate to maintain a slow continuous flush. We then turned the patient to the right lateral position and induced spinal anesthesia. After skin infiltration with lidocaine, a 25-gauge pencil point needle was inserted at what was estimated to be the L2–3 or L3–4 vertebral interspace and 2.0 mL hyperbaric 0.5% bupivacaine (10 mg) and fentanyl 15 µg were injected intrathecally. We then immediately turned the patient to the supine position. Lateral uterine displacement was achieved by tilting the operating table to the left. Oxygen 5 L/min was given by clear facemask until delivery.

BP was measured at 1-min intervals beginning 1 min after spinal injection. Hemodynamic data were downloaded to a computer from the anesthetic machine at 5-s intervals using software developed within our department. We used an infusion of metaraminol (0.5 mg/mL) to maintain BP using an identical regimen in all patients. The infusion was delivered into the IV fluid line via a three-way stopcock that was connected directly to the IV cannula. The vasopressor was started when systolic BP first decreased to <90% of the baseline value. An initial bolus of metaraminol 0.5 mg (1 mL) was given and the infusion was started at 0.25 mg/min (0.5 mL/min). After each measurement of arterial blood pressure, the infusion was continued at 0.25 mg/min if the systolic BP was between 80% and 100% of the baseline value, or increased to 0.25 mg/min if the systolic BP was <80% of the baseline value; if the systolic BP increased above the baseline value, the infusion was stopped, and restarted at 0.25 mg/min if systolic BP decreased below 90% of baseline again. The infusion protocol was continued until the time of uterine incision, after which the study was terminated and further management was at the discretion of the attending anesthesiologist.

The upper sensory level of anesthesia was measured 10 min after spinal injection by assessing loss of pinprick discrimination and preparation and surgery were allowed to start. The times of skin incision, uterine incision, and delivery were recorded by stopwatch. We recorded the total dose of metaraminol given up to the time of uterine incision as measured by the syringe pump. In addition, the average rate of metaraminol infusion for each patient was calculated by dividing the total dose given at the time of uterine incision by time between spinal injection and uterine incision.

We recorded the incidences of hypotension (defined as a decrease in systolic BP by more than 20% below baseline), reactive hypertension (defined as an increase in systolic BP by more than 20% above baseline), and minimum and maximum recorded values of systolic BP during the study period. We defined bradycardia as heart rate <50 bpm and treated it by stopping the metaraminol infusion, or if accompanied by hypotension, with IV atropine 0.6 mg. We recorded any incidences of nausea (when patients reported that they felt sick or felt like vomiting) or vomiting (when they were observed by an investigator to vomit).

After delivery, we gave oxytocin 5–10 IU by slow IV injection. Apgar scores were assessed at 1 and 5 min by the attending pediatrician and blood samples were taken from a double-clamped segment of umbilical cord for immediate blood gas analysis.

The primary outcome of the study was defined as the total dose of vasopressor (metaraminol) given at the time of uterine incision. Sample size was based on recent historical data obtained from clinical cases in our department for which we had used a similar anesthetic and metaraminol regimen. Using the software package PASS 6.0 (NCSS, Kaysville, UT 84037), we calculated that a sample size of 40 patients in the multiple gestation group and 60 in the singleton group would have 90% power to detect a 20% difference between groups in total vasopressor dose at the 5% significance level. We considered a difference of 20%, or larger, to be clinically significant. Unequal sample sizes were chosen deliberately because, in the planning of this study, we anticipated that recruitment of patients with multiple gestation would be slow due to the limited number of suitable and consenting patients present in our unit, which performs approximately 6000 deliveries per year. Choosing more control patients permitted us to recruit a relatively smaller number of multiple gestation patients while maintaining adequate power.

We compared data using the Mann–Whitney U-test, the ² test, and Fisher’s exact test as appropriate. All analyses were performed using Statview for Windows 5.0.1 (SAS Institute, Cary, NC 27513), and Confidence Interval Analysis 2.0.0 (T. Bryant, University of Southampton, UK). P < 0.05 was considered significant.

	RESULTS

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
Data collection for patients with multiple gestation pregnancy was completed over a period of 5 yr and 11 mo from September 1999 to July 2005. There were 36 patients with twins and four patients with triplets. Data collection for control patients was completed over a period of 1 yr and 7 mo from January 1999 to July 2000. Surgery was completed under spinal anesthesia for all patients without the need for conversion to general anesthesia. Hemodynamic data were incomplete and were excluded from analysis in two control patients. Umbilical cord blood was unable to be obtained for analysis in five neonates in the multiple gestation group and three neonates in the control group. Four patients in the multiple gestation group were preterm (all 34 wk gestation), whereas all patients in the control group were at >36 wk gestation. Other patient characteristics were similar. The induction-to-delivery time and uterine incision-to-delivery time were shorter in the multiple gestation group compared with control group (Table 1).

The primary outcome, the total dose of metaraminol required until uterine incision, was similar in patients with multiple gestation pregnancy (median 2.9 [interquartile range 2.0–3.7] mg) when compared with patients with singleton pregnancy (median 3.1 [interquartile range 2.3–3.9] mg, P = 0.25; median difference 0.30 mg, 95% confidence interval of difference –0.20 to 0.90 mg). The rate of metaraminol consumption until uterine incision was similar in patients with multiple gestation pregnancy (median 0.098 [interquartile range 0.079–0.137] mg/min) compared to patients with singleton pregnancy (median 0.102 [interquartile range 0.082–0.126] mg/min, P = 0.77; median difference 0.002 mg/min, 95% confidence interval of difference –0.014 to 0.020 mg/min).

Baseline systolic BP, minimum and maximum recorded systolic BP, and the incidences of hypotension, hypertension, and nausea or vomiting were similar between patients with multiple gestation and singleton pregnancy (Table 2). No patient required atropine.

Neonatal outcome is summarized in Table 1. The birth weight of individual neonates was smaller in the multiple gestation group when compared with the singleton group, but the total birth weight (added birth weights of all newborns for each patient) was greater. There was no difference in umbilical arterial pH between groups. Three of 84 (3.6%) neonates in the multiple gestation group had Apgar scores of 6 at 1 min compared to one of 58 (2.5%) in the singleton gestation group (P = 0.65); all other scores were 7. All neonates in both groups had Apgar scores 7 at 5 min.

	DISCUSSION

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 
In this study we used the dose of vasopressor required during a strictly controlled infusion regimen as a quantitative measure of hemodynamic instability during spinal anesthesia for cesarean delivery. Our results showed that, with 95% confidence, there was no difference between patients with multiple gestation pregnancy when compared with patients with singleton pregnancy. In addition, there were no differences in the minimum and maximum recorded values of systolic BP and no differences in the incidences of hypotension, hypertension, and nausea or vomiting. Our results indicate that multiple gestation is not associated with greater potential to develop hypotension or more severe hypotension during spinal anesthesia for cesarean delivery when compared with singleton pregnancy—a finding that contradicts what is often assumed in standard textbooks on obstetric anesthesia (2,3).

Although it may appear surprising that our results differ from common textbook teaching, in fact, inspection of the reference lists of textbooks and a search of the literature reveal few data to support greater severity of hypotension in patients with multiple gestation during central neuraxial anesthesia. Indeed, the few studies that have addressed this issue support our findings. For example, Jawan et al. (4) investigated the spread of spinal anesthesia in patients with twin pregnancy compared to singleton pregnancy. Although they found a greater maximum cephalic spread of spinal anesthesia in patients with twin pregnancy, there was no difference in the incidence of hypotension and no difference between groups in the proportion of patients who required ephedrine. Behforouz et al. (7) compared patients with triplet and quadruplet pregnancy versus patients with singleton pregnancy and found that the incidence of hypotension during epidural anesthesia for cesarean delivery was similar, but that patients with singleton pregnancy received less ephedrine and IV fluid to support their BP. However, the authors pointed out that because their data were collected retrospectively, some uncertainty as to the scientific validity of their results was possible. In comparison, the data in our study were collected prospectively; therefore we believe that they provide good support for the contention that patients with multiple gestation are at no greater risk of hemodynamic instability during spinal anesthesia when compared with patients with singleton gestation.

However, there are some limitations to our study design that should be considered. First, we selected patients who were the participants in other concurrent studies as singleton controls. Because patient enrollment for these studies was faster than for patients with multiple gestation, this resulted in earlier completion of data collection for patients with singleton pregnancy than for patients with multiple gestation. Therefore, our data might potentially have been affected by any changes in practice or patient characteristics that occurred between the time when data collection was completed for the control group and when data collection was completed for the multiple gestation group. In retrospect, a better study design may have been to enroll matched control patients concurrently on a case-by-case basis. Second, although the selection criteria and patient characteristics (other than number of fetuses) for patients used as controls were similar to that used for patients with multiple gestation pregnancy, four patients (10%) in the multiple gestation group were at preterm (all 34 wk) gestation, whereas only patients with >36 wk gestation were enrolled in the control group. Although this may be viewed as a confounding factor, and because the patients in the multiple gestation group were selected from our routine elective booking lists, we believe that our results are relevant to what clinicians can expect in their normal clinical practice. Third, it was not practical to blind the investigators and clinicians in our study. The potential for bias would have been minimized by our use of a strict and objective management regimen that was identical for patients in both groups. However, it is noteworthy that the induction-to-delivery and uterine incision-to-delivery times were shorter in patients with multiple gestation pregnancy versus singleton pregnancy. This difference may have arisen because a more senior surgeon was more likely to have been in attendance for patients with multiple gestation compared to singleton patients. However, the difference in time intervals was small and we compensated for it in our analysis by comparing the rates of vasopressor infusion (total dose divided by induction-to-uterine incision time) which was similar between groups. Therefore, we consider it unlikely that this is a significant confounding factor.

Why are the results of our study contrary to expectation? Greater risk of hypotension in patients with multiple gestation pregnancy is usually ascribed to accentuated aortocaval compression (2,3). However, our results suggest that if greater aortocaval compression does occur, its effects may be mitigated by the greater increase in blood volume and cardiac output that occurs in multiple gestation (8) and/or that the measures we used to avoid aortocaval compression were adequate. Alternatively, it is possible that the effects of aortocaval compression may not in fact be greater in multiple gestation when compared with singleton pregnancies. Interestingly, to achieve uterine displacement, we simply rotated the operating table to the left without measuring or standardizing the degree of tilt. Although the optimal amount of tilt is unknown, and may vary among patients, it is commonly recommended that 15 degrees tilt be used (9). However, Jones et al. (10) reported that the degree of tilt applied is often over-estimated by anesthesiologists who position their patients by eye and that the actual degree of tilt applied is frequently <15°. In our study, as with our typical practice, we also estimated the degree of tilt by eye. However, when we have subsequently measured the actual amount of tilt we applied, we also noted that this is often <15°, consistent with the finding of Jones et al. (10) The degree of tilt should balance severity of aortocaval compression against patient comfort and surgical conditions. Further work is required to determine the optimal amount of tilt and whether this differs between patients with multiple gestation and singleton pregnancy.

All of our patients were Asian, and their average body size was relatively small compared to some other ethnic groups. Furthermore, our sample did not include any patients who had symptomatic supine hypotension before delivery. Therefore, care should be exercised in extrapolating our findings to patients who have a large body mass or who exhibit preoperative symptoms suggestive of aortocaval compression, because our study did not exclude the possibility of increased hemodynamic instability in these groups.

Finally, our study focused on hypotension associated with spinal anesthesia until the time of delivery. Although we found no difference between patients with multiple gestation and singleton pregnancy, it is important to note that multiple gestation may be associated with an increase in other risks such as uterine atony, hemorrhage, and preeclampsia. Although our results indicate that hypotension from spinal anesthesia need not be treated differently in multiple gestation pregnancy than in singleton pregnancy, nonetheless the anesthetic technique chosen may still need to consider these other risks.

In summary, our study showed that in the presence of left lateral tilt, patients with multiple gestation pregnancy exhibit no greater hemodynamic instability when compared with patients with singleton pregnancy during spinal anesthesia for cesarean delivery.

	ACKNOWLEDGMENTS

 
The authors thank the midwives of the Labor Ward, Prince of Wales Hospital, Shatin, Hong Kong, China for their kind assistance and cooperation with this study. This work is attributed to Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, China.

	Footnotes

 
Accepted for publication October 13, 2006.

Supported solely by departmental and institutional funding.

Reprints will not be available from the authors.

	REFERENCES

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 

1. Marino T, Goudas LC, Steinbok V, et al. The anesthetic management of triplet cesarean delivery: a retrospective case series of maternal outcomes. Anesth Analg 2001;93:991–5.[Abstract/Free Full Text]
2. Gorman Maloney SR, Levinson G. Anesthesia for abnormal positions and presentations, shoulder dystocia, and multiple births. In: Hughes SC, Levinson G, Rosen MA, eds. Anesthesia for obstetrics. Philadelphia: Lippincott Williams and Wilkins, 2002:287–95.
3. Koffel B. Abnormal presentation and multiple gestation. In: Chestnut DH, ed. Obstetric anesthesia. St. Louis: Mosby, 1999:694–710.
4. Jawan B, Lee JH, Chong ZK, Chang CS. Spread of spinal anaesthesia for caesarean section in singleton and twin pregnancies. Br J Anaesth 1993;70:639–41.[Abstract/Free Full Text]
5. Ngan Kee WD, Lau TK, Khaw KS, Lee BB. Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section. Anesthesiology 2001;95:307–13.[Web of Science][Medline]
6. Ngan Kee WD, Khaw KS, Lee BB, et al. Metaraminol infusion for maintenance of arterial pressure during spinal anesthesia for cesarean delivery: the effect of a crystalloid bolus. Anesth Analg 2001;93:703–8.[Abstract/Free Full Text]
7. Behforouz N, Dounas M, Benhamou D. Epidural anaesthesia for caesarean delivery in triple and quadruple pregnancies. Acta Anaesthesiol Scand 1998;42:1088–91.[Web of Science][Medline]
8. Kametas NA, McAuliffe F, Krampl E, et al. Maternal cardiac function in twin pregnancy. Obstet Gynecol 2003;102:806–15.[Web of Science][Medline]
9. Crawford JS, Burton M, Davies P. Time and lateral tilt at caesarean section. Br J Anaesth 1972;44:477–84.[Abstract/Free Full Text]
10. Jones SJ, Kinsella SM, Donald FA. Comparison of measured and estimated angles of table tilt at caesarean section. Br J Anaesth 2003;90:86–7.[Abstract/Free Full Text]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ngan Kee, W. D. Articles by Gin, T. Search for Related Content PubMed PubMed Citation Articles by Ngan Kee, W. D. Articles by Gin, T. Related Collections Obstetrics Regional Anesthesia Pharmacology