- Email: [email protected]
Haemodynamic effects of oxytocin in women with severe preeclampsia
International Journal of Obstetric Anesthesia (2011) 20, 26–29 0959-289X/$ - see front matter c 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2010.10.004
ORIGINAL ARTICLE
www.obstetanesthesia.com
Haemodynamic effects of oxytocin in women with severe preeclampsia E. Langesæter, L.A. Rosseland, A. Stubhaug Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway
ABSTRACT Background: Several previous publications demonstrate the significant haemodynamic effects of oxytocin in healthy pregnant women, but there is only one publication of the oxytocin effects in women with severe preeclampsia. We investigated the haemodynamic effects of oxytocin in women with severe preeclampsia using invasive haemodynamic monitoring. Methods: Eighteen women with severe preeclampsia were included in this observational study. All women had continuous invasive haemodynamic monitoring during spinal anaesthesia for caesarean section using the LiDCOplus monitor. Preeclamptic patients were given intravenous boluses of 5 IU oxytocin following delivery. Results: Following an intravenous bolus of 5 IU oxytocin all patients had an increase in heart rate, a decrease in systemic vascular resistance and a decrease in blood pressure. Five patients had a decrease in cardiac output due to an inability to increase stroke volume. Conclusions: The haemodynamic effects of oxytocin in women with severe preeclampsia may be less predictable compared to findings in healthy pregnant women, suggesting that oxytocin should be given with caution in women with severe preeclampsia. c 2010 Elsevier Ltd. All rights reserved.
Keywords: Severe preeclampsia; Neuraxial anaesthesia; Oxytocin; Cardiac output; Invasive monitoring; LiDCOplus
Introduction Preeclampsia is a multi-system disease affecting 5–10% of pregnant women.1 The disorder can result in severe complications including eclampsia, pulmonary oedema, HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome, or renal failure. Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. Although preeclamptic patients are often hypovolaemic with low cardiac output (CO) and increased systemic vascular resistance (SVR), this patient group is heterogeneous.2 Increased total vascular resistance, a high relative wall thickness of the left ventricle and a hypertrophied ventricle are independent predictors for developing maternal and fetal complications in preeclamptic pregnancy.3 Oxytocin is a vasodilator acting on vascular endothelial receptors producing a calcium-dependent response via stimulation of the nitric oxide pathway.4 There are several publications on the haemodynamic effects of oxytocin in healthy pregnant women,5–7 but only one Accepted October 2010 Correspondence to: Eldrid Langesæter, Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, N-0027 Oslo, Norway. E-mail address: [email protected]
previous study showing its effects in severe preeclampsia.8 The aim of our observational study was to examine the haemodynamic response to oxytocin in women with severe preeclampsia.
Methods Eighteen women with severe preeclampsia were included in this study conducted at Oslo University Hospital, Rikshospitalet from August 2005 to August 2008 (registered with clinicaltrials.gov: NCT00403572). The protocol was approved by The Regional Medical Research Ethics Committee for Southern Norway and women gave oral and written consent to participate. The only exclusion criterion was a contraindication to neuraxial anaesthesia. Severe preeclampsia was defined as a systolic arterial pressure (SAP) P 160 mmHg with proteinuria, and either headache, visual disturbance, dyspnoea or epigastric pain. Women with a SAP P 160 mmHg and symptoms were given magnesium sulphate (MgSO4) 4 g intravenously as a loading dose, followed by an infusion of 1 g/h for 24 h. After monitoring was established with electrocardiography and pulse oximetry, a 20-gauge cannula was
E. Langesæter et al.
27
inserted in a radial artery after local skin infiltration with lidocaine. In addition to continuous invasive blood pressure monitoring, we used the LiDCOplus monitor (LiDCO Ltd., Cambridge, UK) which provided continuous haemodynamic measurements of stroke volume (SV), CO and SVR.9 None of the patients had a central venous catheter, and a central venous pressure (CVP) of 5 mmHg was assumed for the calculation of SVR. Preeclamptic patients received spinal anaesthesia for caesarean section. The intrathecal dose of isobaric bupivacaine was not standardised, but individualized according to height, weight and gestational age. An intravenous crystalloid infusion was started concurrently with spinal anaesthesia and a 5 IU bolus of oxytocin was administered after delivery of the baby. Haemodynamic data were stored in the LiDCOplusmonitor and downloaded as csv-files (text-files) for each patient. Construction of the data set was done using MatLab version R2007a (The MathWorks, Natick, MA). The baseline was defined as the mean of 30 s before oxytocin was given. Extreme values identified as artefact/noise were removed from the dataset. All data were analyzed in SPSS statistical program version 16.0 (Statistical Package for Social Sciences Inc., Chicago, IL) using the independent samples t test.
Results Eighteen women with severe preeclampsia were included in this observational study. Maternal characteristics are presented in Table 1. Three patients had previous pregnancies with preeclampsia. Three patients had diabetes mellitus and were on insulin therapy. All but one patient had symptoms such as headache, visual disturbances, dyspnoea, or epigastric pain; two patients had HELLP syndrome. Sixteen patients received labetolol before delivery and 12 were treated with MgSO4. The mean bupivacaine dose for spinal anaesthesia was 10.6 mg with the addition of sufentanil (4–5 lg) or fentanyl (10–25 lg). Nine patients had an intravenous phenylephrine infusion started simultaneously with spinal
Table 1
Maternal characteristics and drug therapy
Age (years) Gestation (weeks) Weight (kg) Height (cm) Body mass index (kg/m2) Nulliparous In vitro fertilisation pregnancy Essential hypertension HELLP syndrome U-protein/creatinine Blood loss (mL) Data are mean [range] or number.
32 [19–40] 33 [26–38] 93 [67–130] 168 [156–178] 33 [21–59] 13 5 3 2 421 [260–740] 458 [150–900]
Table 2 Haemodynamic variables before spinal anaesthesia and after oxytocin
Cardiac output (L/min) Systolic arterial pressure (mmHg) Mean arterial pressure (mmHg) Systemic vascular resistance (dyns.s.cm 5) Stroke volume (mL) Heart rate (beats/min)
Pre-spinal
Change post oxytocin (%)
7.1 (1.2) 181 (20)
+32 (46) 36 (10)
128 (15)
38 (7)
1421 (315)
52 (13)
82 (14) 87 (12)
+6 (27) +22 (19)
Data are mean (SD); Compared with values 30 s before oxytocin administration.
anaesthesia. Baseline haemodynamic values before spinal anaesthesia are presented in Table 2. All 18 patients were given 5 IU of oxytocin. All patients had a decrease in SAP and SVR after oxytocin, and all had a compensatory increase in heart rate (Table 2 and Fig. 1). Five of the patients had a decrease in CO due to a decrease in SV.
Discussion This observational study describes the haemodynamic findings in 18 women with severe preeclampsia in clinical practice, demonstrating the heterogenous response to oxytocin within this group of patients. Whilst a decrease in SAP and SVR was observed in all patients, five had a decrease in CO after oxytocin. All patients had an increase in heart rate (HR), and the decrease in CO in the five patients was due to a decrease in SV. Baseline haemodynamic values in our preeclamptic patients were similar to the findings of Dyer et al.8 Baseline CO and SVR demonstrate the heterogeneity amongst those with severe preeclampsia. The haemodynamic effects following a 2.5-IU bolus of oxytocin used in Dyer’s study also differed in their patients, showing a minor increase in SV. None had a decrease in CO although one patient demonstrated no increase in CO. This indicates that lowering the oxytocin dose results in less haemodynamic instability, and we recommend giving a lower dose of 0.5–1 IU oxytocin to preeclamptic women.10,11 Comparing the 18 preeclamptic patients given 5 IU oxytocin to healthy patients given the same dose, the preeclamptic patients had a much smaller increase in CO, SV, and HR. All 80 healthy pregnant women, included in another study during the same time period, had an increase in cardiac output.7 In contrast, five of the preeclamptic patients had a decrease in CO. The relative decrease in SAP after oxytocin was not different between preeclamptic and healthy women. Thus, blood pressure monitoring alone might not detect the haemodynamic differences between these groups.
28
Haemodynamics in preeclampsia Haemodynamic effects of oxytocin 5 units CO (L/min)
10 8
SBP (mmHg)
SVR (dyns.s.cm−5)
6
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
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0
10
20
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100
0
10
20
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50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
1400 1200 1000 800 600 160 140 120
SV (ml)
100 90 80 70 110
HR
100 90 80 70
Time (in seconds) Fig. 1
The haemodynamic effects of 5 IU oxytocin in 18 patients with severe preeclampsia Oxytocin is given at time 0.
The effects of antihypertensive treatment in preeclamptic patients could explain some of the differences in haemodynamic response to oxytocin in preeclamptic as compared to healthy pregnant women, with a much lesser cardiac compensation to oxytocin in preeclamptic patients. But it is difficult to explain why five patients with severe preeclampsia were unable to increase SV and had a decrease in CO. Our findings could suggest a diastolic dysfunction in some women with severe preeclampsia; they might not be able to increase CO, SV, and HR in the same way as healthy pregnant women in response to the vasodilatory effect of oxytocin. The much reduced increase in SV in preeclampsia is an interesting finding. There are few publications on diastolic dysfunction in preeclamptic patients. Andrietti et al.12 found that women who had previously suffered with preeclampsia and had a low plasma volume (present in 30%) had persistent diastolic dysfunction. Aardenburg et al.13 demonstrated that women who had previously suffered preeclampsia with subnormal plasma volume were unable to increase SV with moderate exercise. Furthermore, Bamfo et al.14 found that preeclamptic women
had impairment in diastolic function due to both intrinsic contractility and reduced diastolic filling. Our sample size was small but our findings suggest that patients with preeclampsia may have a more unpredictable response to oxytocin. A lower plasma volume could explain why some women with preeclampsia cannot increase their SV as a response to the vasodilatory effects of oxytocin. Whatever the cause of the variable haemodynamic effects of oxytocin in preeclamptic patients, clinicians should be aware of the paradoxical effects of oxytocin in a large proportion of these patients. In our view, patients with severe preeclampsia must be treated on an individual basis. In our department, an arterial line is routine during caesarean section in women with severe preeclampsia, and we continue invasive monitoring postoperatively. The CO monitor used in this study has been validated in other patient groups,15,16 and there have been recent reports of its use in pregnant women.8,17,18 As we did not use a central venous catheter, CVP was given a value of 5 mmHg. This would not have any important impact on the calculation of SVR, as CVP is much lower compared to mean arterial pressure.
E. Langesæter et al. Oxytocin doses were reduced in our hospital during the study period of four years as we observed the prominent haemodynamic effects of oxytocin both in the preeclamptic patients and in healthy pregnant women included in different studies conducted in the same time period. Previously, our standard dose of oxytocin was 5 IU, but this dose has been reduced both in preeclamptic and in healthy patients. Our results are suggestive of the heterogeneity in a clinical setting of women with severe preeclampsia with a less predictable haemodynamic response to oxytocin compared to healthy pregnant women. The haemodynamic response to oxytocin in women with severe preeclampsia should be further investigated in a prospective controlled study to verify these findings, and to see if haemodynamic decompensation can be predicted.
Acknowledgements The authors thank Tor H. Hauge (MSc, PhD, Oslo, Norway) for data handling in MatLab, and Mike S. Dodgson (BSc MB ChB FRCA, Consultant Anaesthetist, Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway) for linguistic advice.
29
6.
7.
8.
9.
10.
11.
12.
13.
14.
References 1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99. 2. Mei S, Gu H, Wang Q, Zhang S, Zeng Y. Pre-eclampsia outcomes in different hemodynamic models. J Obstet Gynaecol Res 2008;34:179–88. 3. Vasapollo B, Novelli GP, Valensise H. Total vascular resistance and left ventricular morphology as screening tools for complications in pregnancy. Hypertension 2008;51:1020–6. 4. Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik SC, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology 1999;140:1301–9. 5. Pinder AJ, Dresner M, Calow C, Shorten GD, O’Riordan J, Johnson R. Haemodynamic changes caused by oxytocin during
15. 16.
17.
18.
caesarean section under spinal anaesthesia. Int J Obstet Anesth 2002;11:156–9. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing caesarean section. Br J Anaesth 2007;98:116–9. Langesaeter E, Rosseland LA, Stubhaug A. Hemodynamic effects of oxytocin during cesarean delivery. Int J Gynecol Obstet 2006;95:46–7. Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology 2008;108:802–11. Pearse RM, Ikram K, Barry J. Equipment review: an appraisal of the LiDCO plus method of measuring cardiac output. Crit Care 2004;8:190–5. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for labor arrest. Obstet Gynecol 2006;107:45–50. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a dose-finding study. Obstet Gynecol 2004;104:1005–10. Andrietti S, Kruse AJ, Bekkers SC, Sep S, Spaanderman M, Peeters LL. Cardiac adaptation to pregnancy in women with a history of preeclampsia and a subnormal plasma volume. Reprod Sci 2008;15:1059–65. Aardenburg R, Spaanderman ME, van Eijndhoven HW, de Leeuw PW, Peeters LL. Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise. J Soc Gynecol Investig 2005;12:599–603. Bamfo JE, Kametas NA, Chambers JB, Nicolaides KH. Maternal cardiac function in normotensive and pre-eclamptic intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;32:682–6. Morgan P, Al-Subaie N, Rhodes A. Minimally invasive cardiac output monitoring. Curr Opin Crit Care 2008;14:322–6. Pittman J, Bar-Yosef S, SumPing J, Sherwood M, Mark J. Continuous cardiac output monitoring with pulse contour analysis: a comparison with lithium indicator dilution cardiac output measurement. Crit Care Med 2005;33:2015–21. Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856–63. Dyer RA, James MF. Maternal hemodynamic monitoring in obstetric anesthesia. Anesthesiology 2008;109:765–7.
ORIGINAL ARTICLE
www.obstetanesthesia.com
Haemodynamic effects of oxytocin in women with severe preeclampsia E. Langesæter, L.A. Rosseland, A. Stubhaug Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway
ABSTRACT Background: Several previous publications demonstrate the significant haemodynamic effects of oxytocin in healthy pregnant women, but there is only one publication of the oxytocin effects in women with severe preeclampsia. We investigated the haemodynamic effects of oxytocin in women with severe preeclampsia using invasive haemodynamic monitoring. Methods: Eighteen women with severe preeclampsia were included in this observational study. All women had continuous invasive haemodynamic monitoring during spinal anaesthesia for caesarean section using the LiDCOplus monitor. Preeclamptic patients were given intravenous boluses of 5 IU oxytocin following delivery. Results: Following an intravenous bolus of 5 IU oxytocin all patients had an increase in heart rate, a decrease in systemic vascular resistance and a decrease in blood pressure. Five patients had a decrease in cardiac output due to an inability to increase stroke volume. Conclusions: The haemodynamic effects of oxytocin in women with severe preeclampsia may be less predictable compared to findings in healthy pregnant women, suggesting that oxytocin should be given with caution in women with severe preeclampsia. c 2010 Elsevier Ltd. All rights reserved.
Keywords: Severe preeclampsia; Neuraxial anaesthesia; Oxytocin; Cardiac output; Invasive monitoring; LiDCOplus
Introduction Preeclampsia is a multi-system disease affecting 5–10% of pregnant women.1 The disorder can result in severe complications including eclampsia, pulmonary oedema, HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome, or renal failure. Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. Although preeclamptic patients are often hypovolaemic with low cardiac output (CO) and increased systemic vascular resistance (SVR), this patient group is heterogeneous.2 Increased total vascular resistance, a high relative wall thickness of the left ventricle and a hypertrophied ventricle are independent predictors for developing maternal and fetal complications in preeclamptic pregnancy.3 Oxytocin is a vasodilator acting on vascular endothelial receptors producing a calcium-dependent response via stimulation of the nitric oxide pathway.4 There are several publications on the haemodynamic effects of oxytocin in healthy pregnant women,5–7 but only one Accepted October 2010 Correspondence to: Eldrid Langesæter, Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, N-0027 Oslo, Norway. E-mail address: [email protected]
previous study showing its effects in severe preeclampsia.8 The aim of our observational study was to examine the haemodynamic response to oxytocin in women with severe preeclampsia.
Methods Eighteen women with severe preeclampsia were included in this study conducted at Oslo University Hospital, Rikshospitalet from August 2005 to August 2008 (registered with clinicaltrials.gov: NCT00403572). The protocol was approved by The Regional Medical Research Ethics Committee for Southern Norway and women gave oral and written consent to participate. The only exclusion criterion was a contraindication to neuraxial anaesthesia. Severe preeclampsia was defined as a systolic arterial pressure (SAP) P 160 mmHg with proteinuria, and either headache, visual disturbance, dyspnoea or epigastric pain. Women with a SAP P 160 mmHg and symptoms were given magnesium sulphate (MgSO4) 4 g intravenously as a loading dose, followed by an infusion of 1 g/h for 24 h. After monitoring was established with electrocardiography and pulse oximetry, a 20-gauge cannula was
E. Langesæter et al.
27
inserted in a radial artery after local skin infiltration with lidocaine. In addition to continuous invasive blood pressure monitoring, we used the LiDCOplus monitor (LiDCO Ltd., Cambridge, UK) which provided continuous haemodynamic measurements of stroke volume (SV), CO and SVR.9 None of the patients had a central venous catheter, and a central venous pressure (CVP) of 5 mmHg was assumed for the calculation of SVR. Preeclamptic patients received spinal anaesthesia for caesarean section. The intrathecal dose of isobaric bupivacaine was not standardised, but individualized according to height, weight and gestational age. An intravenous crystalloid infusion was started concurrently with spinal anaesthesia and a 5 IU bolus of oxytocin was administered after delivery of the baby. Haemodynamic data were stored in the LiDCOplusmonitor and downloaded as csv-files (text-files) for each patient. Construction of the data set was done using MatLab version R2007a (The MathWorks, Natick, MA). The baseline was defined as the mean of 30 s before oxytocin was given. Extreme values identified as artefact/noise were removed from the dataset. All data were analyzed in SPSS statistical program version 16.0 (Statistical Package for Social Sciences Inc., Chicago, IL) using the independent samples t test.
Results Eighteen women with severe preeclampsia were included in this observational study. Maternal characteristics are presented in Table 1. Three patients had previous pregnancies with preeclampsia. Three patients had diabetes mellitus and were on insulin therapy. All but one patient had symptoms such as headache, visual disturbances, dyspnoea, or epigastric pain; two patients had HELLP syndrome. Sixteen patients received labetolol before delivery and 12 were treated with MgSO4. The mean bupivacaine dose for spinal anaesthesia was 10.6 mg with the addition of sufentanil (4–5 lg) or fentanyl (10–25 lg). Nine patients had an intravenous phenylephrine infusion started simultaneously with spinal
Table 1
Maternal characteristics and drug therapy
Age (years) Gestation (weeks) Weight (kg) Height (cm) Body mass index (kg/m2) Nulliparous In vitro fertilisation pregnancy Essential hypertension HELLP syndrome U-protein/creatinine Blood loss (mL) Data are mean [range] or number.
32 [19–40] 33 [26–38] 93 [67–130] 168 [156–178] 33 [21–59] 13 5 3 2 421 [260–740] 458 [150–900]
Table 2 Haemodynamic variables before spinal anaesthesia and after oxytocin
Cardiac output (L/min) Systolic arterial pressure (mmHg) Mean arterial pressure (mmHg) Systemic vascular resistance (dyns.s.cm 5) Stroke volume (mL) Heart rate (beats/min)
Pre-spinal
Change post oxytocin (%)
7.1 (1.2) 181 (20)
+32 (46) 36 (10)
128 (15)
38 (7)
1421 (315)
52 (13)
82 (14) 87 (12)
+6 (27) +22 (19)
Data are mean (SD); Compared with values 30 s before oxytocin administration.
anaesthesia. Baseline haemodynamic values before spinal anaesthesia are presented in Table 2. All 18 patients were given 5 IU of oxytocin. All patients had a decrease in SAP and SVR after oxytocin, and all had a compensatory increase in heart rate (Table 2 and Fig. 1). Five of the patients had a decrease in CO due to a decrease in SV.
Discussion This observational study describes the haemodynamic findings in 18 women with severe preeclampsia in clinical practice, demonstrating the heterogenous response to oxytocin within this group of patients. Whilst a decrease in SAP and SVR was observed in all patients, five had a decrease in CO after oxytocin. All patients had an increase in heart rate (HR), and the decrease in CO in the five patients was due to a decrease in SV. Baseline haemodynamic values in our preeclamptic patients were similar to the findings of Dyer et al.8 Baseline CO and SVR demonstrate the heterogeneity amongst those with severe preeclampsia. The haemodynamic effects following a 2.5-IU bolus of oxytocin used in Dyer’s study also differed in their patients, showing a minor increase in SV. None had a decrease in CO although one patient demonstrated no increase in CO. This indicates that lowering the oxytocin dose results in less haemodynamic instability, and we recommend giving a lower dose of 0.5–1 IU oxytocin to preeclamptic women.10,11 Comparing the 18 preeclamptic patients given 5 IU oxytocin to healthy patients given the same dose, the preeclamptic patients had a much smaller increase in CO, SV, and HR. All 80 healthy pregnant women, included in another study during the same time period, had an increase in cardiac output.7 In contrast, five of the preeclamptic patients had a decrease in CO. The relative decrease in SAP after oxytocin was not different between preeclamptic and healthy women. Thus, blood pressure monitoring alone might not detect the haemodynamic differences between these groups.
28
Haemodynamics in preeclampsia Haemodynamic effects of oxytocin 5 units CO (L/min)
10 8
SBP (mmHg)
SVR (dyns.s.cm−5)
6
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
1400 1200 1000 800 600 160 140 120
SV (ml)
100 90 80 70 110
HR
100 90 80 70
Time (in seconds) Fig. 1
The haemodynamic effects of 5 IU oxytocin in 18 patients with severe preeclampsia Oxytocin is given at time 0.
The effects of antihypertensive treatment in preeclamptic patients could explain some of the differences in haemodynamic response to oxytocin in preeclamptic as compared to healthy pregnant women, with a much lesser cardiac compensation to oxytocin in preeclamptic patients. But it is difficult to explain why five patients with severe preeclampsia were unable to increase SV and had a decrease in CO. Our findings could suggest a diastolic dysfunction in some women with severe preeclampsia; they might not be able to increase CO, SV, and HR in the same way as healthy pregnant women in response to the vasodilatory effect of oxytocin. The much reduced increase in SV in preeclampsia is an interesting finding. There are few publications on diastolic dysfunction in preeclamptic patients. Andrietti et al.12 found that women who had previously suffered with preeclampsia and had a low plasma volume (present in 30%) had persistent diastolic dysfunction. Aardenburg et al.13 demonstrated that women who had previously suffered preeclampsia with subnormal plasma volume were unable to increase SV with moderate exercise. Furthermore, Bamfo et al.14 found that preeclamptic women
had impairment in diastolic function due to both intrinsic contractility and reduced diastolic filling. Our sample size was small but our findings suggest that patients with preeclampsia may have a more unpredictable response to oxytocin. A lower plasma volume could explain why some women with preeclampsia cannot increase their SV as a response to the vasodilatory effects of oxytocin. Whatever the cause of the variable haemodynamic effects of oxytocin in preeclamptic patients, clinicians should be aware of the paradoxical effects of oxytocin in a large proportion of these patients. In our view, patients with severe preeclampsia must be treated on an individual basis. In our department, an arterial line is routine during caesarean section in women with severe preeclampsia, and we continue invasive monitoring postoperatively. The CO monitor used in this study has been validated in other patient groups,15,16 and there have been recent reports of its use in pregnant women.8,17,18 As we did not use a central venous catheter, CVP was given a value of 5 mmHg. This would not have any important impact on the calculation of SVR, as CVP is much lower compared to mean arterial pressure.
E. Langesæter et al. Oxytocin doses were reduced in our hospital during the study period of four years as we observed the prominent haemodynamic effects of oxytocin both in the preeclamptic patients and in healthy pregnant women included in different studies conducted in the same time period. Previously, our standard dose of oxytocin was 5 IU, but this dose has been reduced both in preeclamptic and in healthy patients. Our results are suggestive of the heterogeneity in a clinical setting of women with severe preeclampsia with a less predictable haemodynamic response to oxytocin compared to healthy pregnant women. The haemodynamic response to oxytocin in women with severe preeclampsia should be further investigated in a prospective controlled study to verify these findings, and to see if haemodynamic decompensation can be predicted.
Acknowledgements The authors thank Tor H. Hauge (MSc, PhD, Oslo, Norway) for data handling in MatLab, and Mike S. Dodgson (BSc MB ChB FRCA, Consultant Anaesthetist, Division of Anaesthesia and Intensive Care Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway) for linguistic advice.
29
6.
7.
8.
9.
10.
11.
12.
13.
14.
References 1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99. 2. Mei S, Gu H, Wang Q, Zhang S, Zeng Y. Pre-eclampsia outcomes in different hemodynamic models. J Obstet Gynaecol Res 2008;34:179–88. 3. Vasapollo B, Novelli GP, Valensise H. Total vascular resistance and left ventricular morphology as screening tools for complications in pregnancy. Hypertension 2008;51:1020–6. 4. Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik SC, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology 1999;140:1301–9. 5. Pinder AJ, Dresner M, Calow C, Shorten GD, O’Riordan J, Johnson R. Haemodynamic changes caused by oxytocin during
15. 16.
17.
18.
caesarean section under spinal anaesthesia. Int J Obstet Anesth 2002;11:156–9. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing caesarean section. Br J Anaesth 2007;98:116–9. Langesaeter E, Rosseland LA, Stubhaug A. Hemodynamic effects of oxytocin during cesarean delivery. Int J Gynecol Obstet 2006;95:46–7. Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology 2008;108:802–11. Pearse RM, Ikram K, Barry J. Equipment review: an appraisal of the LiDCO plus method of measuring cardiac output. Crit Care 2004;8:190–5. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for labor arrest. Obstet Gynecol 2006;107:45–50. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a dose-finding study. Obstet Gynecol 2004;104:1005–10. Andrietti S, Kruse AJ, Bekkers SC, Sep S, Spaanderman M, Peeters LL. Cardiac adaptation to pregnancy in women with a history of preeclampsia and a subnormal plasma volume. Reprod Sci 2008;15:1059–65. Aardenburg R, Spaanderman ME, van Eijndhoven HW, de Leeuw PW, Peeters LL. Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise. J Soc Gynecol Investig 2005;12:599–603. Bamfo JE, Kametas NA, Chambers JB, Nicolaides KH. Maternal cardiac function in normotensive and pre-eclamptic intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;32:682–6. Morgan P, Al-Subaie N, Rhodes A. Minimally invasive cardiac output monitoring. Curr Opin Crit Care 2008;14:322–6. Pittman J, Bar-Yosef S, SumPing J, Sherwood M, Mark J. Continuous cardiac output monitoring with pulse contour analysis: a comparison with lithium indicator dilution cardiac output measurement. Crit Care Med 2005;33:2015–21. Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856–63. Dyer RA, James MF. Maternal hemodynamic monitoring in obstetric anesthesia. Anesthesiology 2008;109:765–7.