Acta Anaesthesiol Scand 2014; 58: 851–857 Printed in Singapore. All rights reserved
© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/aas.12348
Umbilical cord blood acid–base status in pregnancy with congenital heart disease Q. Zhan, X. Wang, J. Yu and Y. Fan Department of Anesthesia, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: The risk of fetal and neonatal complications is higher in pregnant women with congenital heart disease (CHD). It remains unknown whether umbilical cord blood gas values are different between pregnant women with CHD and healthy women undergoing elective cesarean section during combined spinal-epidural anesthesia. The purpose of the present study was to compare umbilical cord blood acid–base status and gas values in pregnant women with CHD vs. healthy pregnant women undergoing elective cesarean section during combined spinal– epidural (CSE) anesthesia. Methods: Patients with singleton pregnancy undergoing elective cesarean delivery under CSE anesthesia were enrolled. Patients were divided into two groups: healthy pregnant women (group H) and pregnant with congenital heart disease (group CHD). Immediately after delivery, umbilical cord arterial blood sample and venous blood sample were collected and measured. The comparison between two groups was performed using grouped t-test.
Results: Forty-four women in group H and 33 women in group CHD were analyzed finally. Umbilical arterial blood pH, base excess (BE) and HCO3− (pH 7.29 ± 0.05, BE −1.4 ± 1.9 mmol/L, HCO3− 21.5 ± 1.4 mmol/L) were significantly lower in pregnant women with CHD than in healthy pregnant women (pH 7.33 ± 0.03, BE −0.1 ± 2.1 mmol/L, HCO3− 22.5 ± 1.4 mmol/L). Conclusions: The lower values of umbilical arterial blood pH, BE and HCO3− were observed in pregnant women with CHD than in healthy women undergoing elective cesarean section during CSE anesthesia.
W
and Gynaecology.7 Umbilical cord blood acid–base status and gas values can provide important information about the past, present and possibly the future condition of the infant. However, few studies have focused on the fetus and neonatal outcomes in women with pre-existing CHD. We hypothesized that umbilical cord blood acid–base status and gas values in pregnant women with CHD were different from healthy pregnant women undergoing elective cesarean section during CSE anesthesia.
ith recent advances in pediatric cardiology and cardiac surgery, the number of pregnant women with congenital heart disease (CHD) is increasing.1,2 The risk of fetal and neonatal complications is higher in pregnant women with CHD compared with healthy women.3,4 The adverse events include intrauterine growth restriction, premature birth, intracranial hemorrhage and fetal loss. Combined spinal–epidural (CSE) anesthesia has become a commonly used technique during cesarean section. Maintenance of adequate placental perfusion is an important aspect of anesthetic management.5,6 Changes of placental perfusion may impact on fetuses of pregnant women with CHD. To improve the care of these patients and their infants, it is very important to know the fetus intrauterine environment. Umbilical cord blood gas analysis is now recommended in all high-risk deliveries by both the British and American Colleges of Obstetrics
Accepted for publication 2 May 2014 © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
Methods This study was conducted at Shanghai Renji Hospital, Jiaotong University in Shanghai, China and was approved by the Hospital Ethics Committee (Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee, 1630 Dongfang Road, Shanghai, China). The protocol number is Renji
851 bs_bs_banner
Q. Zhan et al.
Hospital[2013]100K and it was approved on 1 January 2013. Our hospital is the obstetric center of pregnancy complicated with heart disease. Patients with singleton pregnancy undergoing elective cesarean section under CSE anesthesia were enrolled. Patients were divided into two groups: healthy pregnant women (group H) and pregnant with congenital heart disease (group CHD). In group H, women with uncomplicated singleton pregnancy at term undergoing elective cesarean section during CSE anesthesia were included in the study. In group CHD, criteria for inclusion were pregnant women with a prior diagnosis of CHD before pregnancy, first diagnosis in pregnancy by echocardiography and corrected CHD before pregnancy. Exclusion criteria in both groups were: patients with any complicated pregnancy, fetal compromise, need of emergency or in labor. All patients provided written informed consent. Noninvasive blood pressure (BP), electrocardiograph and SpO2 were monitored and recorded at 3-min intervals. A 20-gauge IV cannula was placed in the arm without the BP cuff. All patients received lactated Ringer solution. A CSE anesthesia technique was performed at the L2–3 interspace in the right lateral position. A 16-gauge Tuohy needle (Becton Dickinson, Franklin Lakes, NJ, USA) was placed in the epidural space using loss-of-resistance to saline. A 25-gauge Whitacre spinal needle was then placed through the Tuohy needle until the dura mater was punctured. Once free flow of clear cerebrospinal fluid was observed, 0.75% (wt/vol) isobaric ropivacaine (AstraZeneca, Södertälje, Sweden) solution 2 ml (15 mg) was injected into the subarachnoid space over 10 s using a 2 ml syringe. A 19-gauge closed-end epidural catheter with three side holes was then advanced 4 cm in the cephalic direction into the epidural space and secured. All pregnant women were then transferred to the supine position with left uterine displacement. Patients received incremental epidural boluses of 2% lidocaine to achieve a T4-6 anesthetic level for cesarean section. All women were monitored by electronic fetal heart rate (HR) monitor via a Doppler device before and after anesthesia. Hypotension (systolic BP < 90 mmHg or decrease > 20% below baseline) was treated with intravenous boluses of phenylephrine 100 µg. A decrease in HR to < 50 beats/min was treated with intravenous atropine 0.25–0.5 mg. Immediately after delivery, umbilical cords were clamped on both ends. Umbilical cord arterial blood sample and venous blood sample were collected
852
anaerobically in the pre-heparinized syringes. At the time of newborn delivery, maternal arterial blood sample was collected from maternal radial artery by another anesthesiologist. These samples were measured immediately after collection using a blood gas analyzer (i-STAT300F, Abbott Point of Care Inc., Abbott Park, IL, USA). Maternal age, body mass index (BMI), gestation week, time from induction of CSE to hysterotomy (TC-H) and hysterotomy to umbilical cord clamping (TH-U) were documented. Maternal systolic blood pressure (SBP) and HR were recorded at 3-min intervals, from baseline (before spinal injection) until 15 min after spinal injection. The total dose of phenylephrine from the time of spinal injection to delivery and intraoperative fluid were recorded as well. Birth weight and Apgar score at 1 min and 5 min were assessed by a trained physician after birth. A sample size of 30 in each group was required to find a difference in umbilical arterial pH of 0.03 units with 80% power and alpha = 0.05 (two sides). We recruited at least 35 patients in each group to account for dropouts. Values are expressed as number, mean and standard deviation (mean ± SD), or median (range). The comparison between two groups was performed using grouped t-test. Chisquare tests were used for categorical variables. Within- and between-group comparisons of hemodynamic variables from baseline to predefined time points (for 15 min after spinal injection) were performed using repeated-measures analysis of variance by Mixed Model. Analyses were performed using Excel 2000 (Microsoft, Redmond, WA, USA) and SPSS 11.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was defined at P < 0.05 (two sided).
Results Demographic data We enrolled 46 patients in group H and 35 patients in group CHD during the period from 1 January 2013 to 1 September 2013. Two pregnant women in group CHD were excluded because of incomplete umbilical cord blood gas values. Two pregnant women in group H were excluded as well because of unsuccessful CSE anesthesia in one case and incomplete umbilical cord blood gas values in another case. Finally, data of 44 women in group H and 33 women in group CHD were analyzed statistically. The type of CHD in group CHD included 16 (48.5%) atrial septal defect (ASD), 14 (42.4%) ventricular septal defect (VSD) and 3 (9.1%) patent
Umbilical arterial blood pH in pregnant women with CHD Table 1
Table 2
The type of CHD in pregnant women.
Demographics, operation data, fluid before delivery, total phenylephrine dose from CSE to delivery and maternal arterial blood gas analysis at birth.
The type of CHD
n
Atrial septal defect With no pulmonary hypertension With mild pulmonary hypertension With moderate pulmonary hypertension Ventricular septal defect With no pulmonary hypertension With mild pulmonary hypertension With moderate pulmonary hypertension Patent ductus arteriosus With no pulmonary hypertension With mild pulmonary hypertension
16 7 6 3 14 8 5 1 3 2 1
Data are expressed as number.
ductus arteriosus (PDA) (Table 1). All pregnant women were diagnosed with CHD before pregnancy and none of them was corrected. There were 16 pregnant women with pulmonary artery hypertension in group CHD, of which 12 cases of mild (> 25 mmHg, < 40 mmHg) and 4 cases of moderate (51 mmHg, 55 mmHg, 58 mmHg and 60 mmHg respectively) (Table 1). The ejection fraction (EF) and cardiac output (CO) by echocardiography were normal in all pregnant women with CHD. No rightto-left shunt was found by echocardiography before operation. There were five maternal New York Heart Association (NYHA) functional classification III in group CHD. No pregnant woman took anticoagulant drugs or cardiac medications.
Maternal data The two groups had no significant differences with respect to maternal age and gestation week (Table 2). BMI was significantly smaller in group CHD than that in group H (P = 0.0005). NYHA functional classification was shown in Table 2. All pregnant women achieved a T4-6 anesthetic level for cesarean section under CSE without any epidural boluses of 2% lidocaine. The two groups had no significant differences with respect to time from induction of CSE to hysterotomy (TC-H), time from hysterotomy to umbilical cord clamping (TH-U) and fluid before delivery. Total phenylephrine dose from CSE to delivery was significantly higher in group CHD (97 ± 68 µg) than that in group H (61 ± 75 µg) (P = 0.04) (Table 2). Maternal HR increased significantly at 3 min, 6 min and 9 min after injection of CSE compared with baseline in both two groups (P < 0.05) (Table 3). HR was lower in group CHD than in group H, although there were no significant differences
Group H
Group CHD
(n = 44)
(n = 33)
Age (year) 29 ± 4 27 ± 4 Gestation week (week) 39 ± 1 38 ± 2 BMI (kg/m2) 28 ± 2 26 ± 3 NYHA classification I 28 10 II 16 18 III 0 5 TC-H (min) 11 ± 1 11 ± 1 52 ± 6 53 ± 6 TH-U (s) Fluid before delivery (ml) 728 ± 115 683 ± 82 Total phenylephrine 61 ± 75 97 ± 68 dose from CSE to delivery (µg) pH 7.42 ± 0.03 7.42 ± 0.05 PCO2 (mmHg) 31.0 ± 3.5 31.9 ± 5.1 PO2 (mmHg) 143.3 ± 60.7 131.4 ± 63.7 BE (mmol/L) −3.1 ± 1.7 −3.1 ± 1.8 HCO3− (mmol/L) 21.4 ± 1.2 21.7 ± 1.2 Lac (mmol/L) 1.6 ± 0.5 1.6 ± 0.7
P 0.14 0.06 0.0005 / / / 0.91 0.62 0.16 0.04 0.85 0.47 0.49 0.96 0.30 0.93
Data are expressed as mean ± SD and number. BMI, body mass index; NYHA classification, New York Heart Association functional classification; TC-H, time from induction of CSE to hysterotomy; TH-U, time from hysterotomy to umbilical cord clamping; BE, base excess; Lac, lactate concentrations.
between group H and group CHD in HR (Fig. 1). Maternal SBP decreased significantly overtime compared with baseline in both groups (P < 0.01) (Table 3). There are no significant differences between group H and group CHD in SBP (Fig. 1).
Neonatal data Neonatal data are presented in Table 4. Birth weight in group CHD (3.16 ± 0.23) was lighter than that in group H (3.26 ± 0.21 kg), but there was no statistically significant difference (P = 0.11). Apgar scores at 1 and 5 min were comparable between the two groups. Umbilical arterial blood pH [7.29; 95% confidence interval (CI): 7.28 to 7.32], base excess (BE) (−1.4; 95% CI: −2.1 to −0.7 mmol/L) and HCO3− (21.5; 95% CI: 21.0 to 22.0 mmol/L) were significantly lower in group CHD than in group H (pH 7.32; 95% CI: 7.31 to 7.34, BE −0.1; 95% CI: −0.9 to 0.6 mmol/L and HCO3− 22.5; 95% CI: 22.0 to 23.0 mmol/L) (P = 0.03, P = 0.03 and P = 0.007 respectively) (Table 4). No significant difference was seen in two groups with regard to umbilical venous blood gas analysis. The different values of pH (umbilical arterial blood vs. umbilical venous blood) were not significant (P > 0.05) (Table 4).
853
Q. Zhan et al. Table 3 HR and SBP data of pregnant women. Group HR (bpm) H (n = 44) CHD (n = 33) SBP (mmHg) H (n = 44) CHD (n = 33)
Baseline
3 min
6 min
9 min
12 min
15 min
97 ± 9 95 ± 7
108 ± 8* 104 ± 7*
109 ± 6* 104 ± 5*
107 ± 5* 100 ± 6*
100 ± 6 96 ± 6
93 ± 4 85 ± 6*
123 ± 8 124 ± 7
101 ± 10* 101 ± 10*
105 ± 9* 100 ± 3*
100 ± 6* 99 ± 3*
110 ± 6* 111 ± 9*
113 ± 8* 112 ± 8*
Data are expressed as mean ± SD. *P < 0.05 compared with baseline. HR, heart rate; SBP, systolic blood pressure.
Fetal heart monitoring was normal before and after anesthesia. No recurrence of CHD was found in the offspring.
Discussion To our knowledge, this is the first study to analyze umbilical cord blood acid–base status and gas values at birth to understand the intrauterine environment in pregnant women with CHD undergoing cesarean delivery under CSE anesthesia. It was found that the values of umbilical arterial blood pH, BE and HCO3− were significantly lower in pregnant women with CHD than those in healthy pregnant women. Successful pregnancy has been feasible for most women with CHD. Most patients of ASD or VSD or PDA with normal right-sided pressures confer no added risk in pregnancy.8,9 Pulmonary hypertension (PH) (systolic pulmonary artery pressure > 50 mmHg) of any cause remains high risk for pregnancy. Elective cesarean delivery with neuraxial anesthesia is a common approach for pregnant women with CHD.8 Neuroaxial blockades can produce dramatic cardiovascular changes with sympathetic blockade, such as reduced systemic vascular resistance (SVR) caused by arteriolar dilatation. Reversal of the shunt due to a SVR decrease will lead to Eisenmenger’s syndrome.9 In women with PH, maternal and fetal mortality may reach 50%. The existing right-left shunt is likely to increase with the fall in SVR and can be exacerbated further by hypovolaemia.8 Avoiding significant decrease in SVR, therefore, is crucial during neuroaxial blockade.9 In present study, most of the pregnant women with CHD had no (17) or mild (11) PH. Moderate PH existed in four patients (51 mmHg, 55 mmHg, 58 mmHg and 60 mmHg respectively). No right-toleft shunt was found by echocardiography before
854
operation. After CSE, hypotension was immediately treated by phenylephrine in order to prevent a shunt reversal and maternal cyanosis did not take place. We conferred absence of right-to-left shunt after CSE from clinical manifestation. Some retrospective studies reported that the rate of neonatal complications in women with CHD reached 28%–36%.10,11 Independent risk factors for fetal complications (intrauterine growth retardation, premature birth, intracranial bleeding, spontaneous abortion, neonatal demise, stillbirth) have been defined: NYHA class > II; impaired function of systemic ventricle (ejection fraction < 40%); pressure gradient in the left ventricular outflow tract > 30 mmHg; maternal age < 20 or > 35 years; maternal smoking and maternal treatment with anticoagulants.3,4 In our study, we demonstrated no neonatal mortality and neonatal complications in group CHD. Neonatal birth weight and Apgar score were comparable. No recurrence of heart disease happened. It may be caused by lack of high-risk patients in the present study. There were four cases of moderate PH (PA systolic > 50 mmHg) in group CHD (n = 33). NYHA functional classification of most pregnant women with CHD was I–II, only five patients are NYHA III. And the EF and CO was normal in all pregnancy with CHD before operation. No anticoagulation and cardiac medications were administrated in this population. Most CHD patients in this study had mild disease and good NYHA functional status. They seemed be likely to be fit and well. There seemed no obvious maternal factors would affect neonatal complications. Additionally, we had done our best to control for some potential confounding factors. And there were no significant differences in gestational age, the time from induction of CSE to hysterotomy (TC-H) and time from hysterotomy to umbilical cord clamping (TH-U) between two groups. These relevant data
Umbilical arterial blood pH in pregnant women with CHD Table 4
A
Group H
130
Group CHD
* HR (bpm)
Birth-weight, Apgar scores at 1 and 5 min, umbilical cord blood (arterial-venous) gases immediately after birth and the different value of UA and UV.
*
*
110
90
70
*
*
* *
Baseline 3
6
9
12
15
Time (min)
B
Group H
SBP (mmHg)
140
120
Group CHD
*
*
*
*
*
*
* 100
80
* Baseline 3
* 6
* 9
12
15
Time (min) Fig. 1. (A) Heart rate (HR) vs. time. *P < 0.05 vs. baseline, group H and group congenital heart disease (CHD); No significant differences in HR between groups. (B) Systolic blood pressure (SBP) vs. time. *P < 0.01 vs. baseline, group H and group CHD. No significant differences between groups. Data are expressed as mean ± standard deviation (SD). Group H have unilateral error bars upward and group CHD downward.
showed that the two groups were under the similar condition of central neuraxial anesthesia. However, the values of umbilical arterial blood pH, BE and HCO3− were significantly lower in pregnant women with CHD than in healthy pregnant women. The CSE anesthesia is frequently associated with hypotension, which can decrease uteroplacental blood flow resulting in impaired fetal oxygenation and fetal acidosis. An initial decrease in SVR and increase in CO occurred immediately after spinal
Birth weight (kg) Apgar scores 1 min 5 min UA pH PCO2 (mmHg) PO2 (mmHg) BE (mmol/L) HCO3− (mmol/L) Lac (mmol/L) UV pH PCO2 (mmHg) PO2 (mmHg) BE (mmol/L) HCO3− (mmol/L) Lac (mmol/L) ΔUA-UV pH
Group H
Group CHD
(n = 44)
(n = 33)
P
3.26 ± 0.21
3.16 ± 0.23
0.11
9 (8–10) 10 (9–10)
9 (7–10) 10 (9–10)
0.84 0.98
7.32 ± 0.03 51.6 ± 6.7 22.0 ± 8.0 −0.1 ± 2.1 22.5 ± 1.4 2.1 ± 0.7
7.29 ± 0.05 51.6 ± 7.8 21.4 ± 9.3 −1.4 ± 1.9 21.5 ± 1.4 2.5 ± 1.2
0.03 0.99 0.88 0.03 0.007 0.16
7.35 ± 0.04 45.0 ± 5.6 30.5 ± 7.7 −0.9 ± 1.8 22.4 ± 1.5 2.1 ± 0.7
7.35 ± 0.05 43.8 ± 8.6 31.3 ± 9.6 −1.3 ± 1.7 21.9 ± 2.5 2.2 ± 1.2
0.98 0.55 0.75 0.44 0.40 0.67
0.04 ± 0.03
0.06 ± 0.05
0.07
Data are expressed as mean ± SD. UA, umbilical arterial blood gases; UV, umbilical venous blood gases; ΔUA-UV, the different value of umbilical arterial blood gases and umbilical venous blood gases; BE, base excess; Lac, lactate concentration.
injection.12,13 The intravenous fluid expansion and vasopressor administration would minimize reductions in SVR and maximize increases in CO. The intravenous fluid expansion is likely to overload the patients with heart disease. Direct acting alpha agonists (e.g. phenylephrine) are preferred.14 Studies have suggested that fetal acid–base status might be improved if phenylephrine is used during cesarean delivery instead of ephedrine.15,16 Our hospital routinely use phenylephrine to treat hypotension resulted from CSE. However, some studies claimed that the increase in CO occurred after spinal injection was transient, and HR and CO were also significantly lower in patients receiving the phenylephrine infusion.12,13 Dyer et al.17 measured CO continuously using pulse waveform analysis and thoracic bioimpedance. In patients who required a vasopressor to treat a 20% decrease in mean arterial blood pressure, there was a 35% decrease in SVR compared with baseline, accompanied by a 12% increase in HR and 23% increase in CO before vasopressor administration. CO and HR were significantly lower during the 150 s after administration of a phenylephrine bolus of 80 µg for the treatment of
855
Q. Zhan et al.
hypotension. In comparison with pre-vasopressor values, CO decreased by 14% with phenylephrine. The reduced CO with phenylephrine use remained above baseline, because CO values immediately before vasopressor administration were higher than baseline.17 Stroke volume remained stable throughout.18 The reduction in CO did not affect the neonatal outcomes in normal pregnancy.18 The fetal effects of a potential baroreceptor-mediated reduction in CO have yet to be fully evaluated, particularly in pregnancy with CHD. In our study, we administrated a bolus (100 µg) of phenylephrine to treat hypotension (systolic BP < 90 mmHg or decrease > 20% below baseline). Total phenylephrine dose from CSE to delivery in group CHD (97 ± 68 µg) was significantly more than that in group H (62 ± 75 µg) (P = 0.04). The mean phenylephrine dose in group CHD in our study was more than 80 µg; the referred dose in the study of Dyer et al.17 emphasized the importance of HR as a surrogate indicator of CO. Stewart et al.18 and Langesaeter et al.12 found a dosedependent reduction in HR with phenylephrine use that is associated with a decrease in maternal CO. Although we failed to measure CO directly, we may use HR to estimate CO. We recorded maternal HR and SBP data from baseline (before spinal injection) till 15 min after CSE anesthesia. The mean time from induction of CSE to umbilical cord clamping was about 12 min (Table 2). SBP was significantly decreased from spinal injection till 12 min after spinal injection and HR was significantly increased from spinal injection till 9 min after spinal injection in both two groups (Table 3), which were resulted from sympathectomy due to CSE anesthesia. When hypotension occurred, phenylephrine was administrated to preserve arterial blood pressure. Despite of no significant differences of HR and SBP between two groups, the HR was slower in group CHD than group H throughout and SBP in group CHD was nearby or slightly slower than group H (Fig. 1), which may be related to the larger mean phenylephrine dose in group CHD. We inferred a more reduced CO in group CHD from the slower HR. Above all, we speculated a reduced CO was occurred in group CHD, which may decrease uteroplacental blood flow leading to a low umbilical cord blood pH, BE and HCO3−. Of course, some factors would influence umbilical cord artery blood values. First, fetal pH value can be affected by maternal pH value.19 When the maternal metabolic acidosis or alkalosis occurred, the fetus acid–base status may also change accordingly. In our study, no maternal acidosis or alkalosis
856
occurred in both two groups (Table 2). We believe that the acid–base status in fetus of group CHD was not secondary to maternal. Second, it is significant to recognize that the umbilical cord can be obstructed before birth. Analysis of paired arterial and venous specimens can give insights into the etiology of the acidosis.20 Restriction of umbilical blood flow causes a progressive widening of veno-arterial difference (differences in pH of up to 0.3 units).20,21 In our study, the veno-arterial differences in pH were 0.04 ± 0.03 in healthy women and 0.06 ± 0.05 in pregnant women with CHD respectively. Therefore, we eliminated the effect of umbilical cord obstruction on umbilical artery blood values. There are some limitations to our study. First of all, most of the pregnant with CHD in this study belonged to the low-risk group22 of CHD. The patient sample was subject to selection bias in our study. Patients with severe cardiac complications might choose not to proceed with pregnancy, and our population may represent a subset of women with heart disease at lower cardiac risk. Further studies are required to determine the impact on fetuses at high risk of CHD under CSE. Second, the lower umbilical artery pH in group CHP was out of our expectations in sight of the low-risk group of CHD in our study. We did not monitor CO directly after CSE, nor assess the placental perfusion by Doppler technique. We have been preparing for use of these two measurements in the future research, in order to further understand the changes of maternal and neonatal situations after CSE. Third, we provided CSE for pregnant women with CHD in the light of the patients’ cardiovascular anatomy and physiology changes. Alternatively, general anesthesia may be dictated by cardiac, obstetric or anesthetic indications, such as hemodynamic instability, anticipation of excessive blood loss and contraindications to neuraxial techniques. General anesthesia is one of the risk factors for poorer immediate neonatal outcomes among growth-restricted neonates.23 Therefore, our results cannot represent those in patients with general anesthesia. In conclusion, despite low-risk patients with CHD in present study, the lower values of umbilical arterial blood pH, BE and HCO3− were observed in this population than in healthy women undergoing elective cesarean section during CSE anesthesia. Although the value of umbilical artery blood did not reach the standard of neonatal asphyxia and did not appear to be clinically important in this experiment, it pointed out us that close monitor and early intervention in clinical was very important in neonatal of
Umbilical arterial blood pH in pregnant women with CHD
pregnant women with CHD in spite of normal Apgar scores. Conflict of interest: None. Funding: None.
14. 15.
References 1. Wren C, O’Sullivan JJ. Survival with congenital heart disease and need for follow up in adult life. Heart 2001; 85: 438–43. 2. Nieminen HP, Jokinen EV, Sairanen HI. Late results of pediatric cardiac surgery in Finland: a population-based study with 96% follow-up. Circulation 2001; 104: 570–5. 3. Siu SC, Sermer M, Colman JM. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001; 104: 515–21. 4. Siu SC, Colman JM, Sorensen S. Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 2002; 105: 2179–84. 5. Reynolds F, Sharma SK, Seed PT. Analgesia in labor and fetal acid-base balance: a meta-analysis comparing epidural with systemic opioid analgesia. BJOG 2002; 109: 1344–53. 6. Chen LK, Lin CJ, Huang CH, Wang MH, Lin PL, Lee CN, Sun WZ. The effects of continuous epidural analgesia on Doppler velocimetry of uterine arteries during different periods of labour analgesia. Br J Anaesth 2006; 96: 226–30. 7. ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 348, November 2006: umbilical cord blood gas and acid-base analysis. Obstet Gynecol 2006; 108: 1319–22. 8. Head CE, Thorne SA. Congenital heart disease in pregnancy. Postgrad Med J 2005; 81: 292–8. 9. Gomar C, Errando CL. Neuroaxial anaesthesia in obstetrical patients with cardiac disease. Anaesthesiology 2005; 18: 507– 12. 10. Hidano G, Uezono S, Terui K. A retrospective survey of adverse maternal and neonatal outcomes for parturients with congenital heart disease. Int J Obstet Anesth 2011; 20: 229–35. 11. Khairy P, Ouyang DW, Fernandes SM, Lee-Parritz A, Economy KE, Landzberg MJ. Pregnancy outcomes in women with congenital heart disease. Circulation 2006; 113: 517–24. 12. 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. 13. McDonald S, Fernando R, Ashpole K, Columb M. Maternal cardiac output changes after crystalloid or colloid coload
16.
17.
18.
19. 20. 21. 22. 23.
following spinal anesthesia for elective cesarean delivery: a randomized controlled trial. Anesth Analg 2011; 113: 803–10. Ngan Kee WD, Khaw KS. Vasopressors in obstetrics: what should we be using? Curr Opin Anaesthesiol 2006; 19: 238– 43. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2002; 94: 920–6. Habib AS. A review of the Impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012; 114: 377–90. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, Greenwood J, James MF. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009; 111: 753–65. Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg 2010; 111: 1230–7. Roemer VM. Measured quantities in perinatal medicine-the PCO2. Z Geburtshilfe Neonatol 2005; 209: 90–9. Martin GC, Green RS, Holzman IR. Acidosis in newborns with nuchal cords and normal Apgar scores. J Perinatol 2005; 25: 162–5. Johnson JW, Richards DS. The etiology of fetal acidosis as determined by umbilical cord acid-base studies. Am J Obstet Gynecol 1997; 177: 274–80. Anselm U, Michael AG, Constantin K. Congenital heart disease in pregnancy. Dtsch Arztebl Int 2008; 105: 347–54. Levy BT, Dawson JD, Toth PP, Bowdler N. Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH among growth-stricted neonatal. Obstet Gynecol 1998; 91: 909–16.
Address: Xiangrui Wang Department of Anesthesia Shanghai Renji Hospital Jiaotong University 1630 Dongfang Road Shanghai 200127 China e-mail: [email protected]
857
© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/aas.12348
Umbilical cord blood acid–base status in pregnancy with congenital heart disease Q. Zhan, X. Wang, J. Yu and Y. Fan Department of Anesthesia, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: The risk of fetal and neonatal complications is higher in pregnant women with congenital heart disease (CHD). It remains unknown whether umbilical cord blood gas values are different between pregnant women with CHD and healthy women undergoing elective cesarean section during combined spinal-epidural anesthesia. The purpose of the present study was to compare umbilical cord blood acid–base status and gas values in pregnant women with CHD vs. healthy pregnant women undergoing elective cesarean section during combined spinal– epidural (CSE) anesthesia. Methods: Patients with singleton pregnancy undergoing elective cesarean delivery under CSE anesthesia were enrolled. Patients were divided into two groups: healthy pregnant women (group H) and pregnant with congenital heart disease (group CHD). Immediately after delivery, umbilical cord arterial blood sample and venous blood sample were collected and measured. The comparison between two groups was performed using grouped t-test.
Results: Forty-four women in group H and 33 women in group CHD were analyzed finally. Umbilical arterial blood pH, base excess (BE) and HCO3− (pH 7.29 ± 0.05, BE −1.4 ± 1.9 mmol/L, HCO3− 21.5 ± 1.4 mmol/L) were significantly lower in pregnant women with CHD than in healthy pregnant women (pH 7.33 ± 0.03, BE −0.1 ± 2.1 mmol/L, HCO3− 22.5 ± 1.4 mmol/L). Conclusions: The lower values of umbilical arterial blood pH, BE and HCO3− were observed in pregnant women with CHD than in healthy women undergoing elective cesarean section during CSE anesthesia.
W
and Gynaecology.7 Umbilical cord blood acid–base status and gas values can provide important information about the past, present and possibly the future condition of the infant. However, few studies have focused on the fetus and neonatal outcomes in women with pre-existing CHD. We hypothesized that umbilical cord blood acid–base status and gas values in pregnant women with CHD were different from healthy pregnant women undergoing elective cesarean section during CSE anesthesia.
ith recent advances in pediatric cardiology and cardiac surgery, the number of pregnant women with congenital heart disease (CHD) is increasing.1,2 The risk of fetal and neonatal complications is higher in pregnant women with CHD compared with healthy women.3,4 The adverse events include intrauterine growth restriction, premature birth, intracranial hemorrhage and fetal loss. Combined spinal–epidural (CSE) anesthesia has become a commonly used technique during cesarean section. Maintenance of adequate placental perfusion is an important aspect of anesthetic management.5,6 Changes of placental perfusion may impact on fetuses of pregnant women with CHD. To improve the care of these patients and their infants, it is very important to know the fetus intrauterine environment. Umbilical cord blood gas analysis is now recommended in all high-risk deliveries by both the British and American Colleges of Obstetrics
Accepted for publication 2 May 2014 © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
Methods This study was conducted at Shanghai Renji Hospital, Jiaotong University in Shanghai, China and was approved by the Hospital Ethics Committee (Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee, 1630 Dongfang Road, Shanghai, China). The protocol number is Renji
851 bs_bs_banner
Q. Zhan et al.
Hospital[2013]100K and it was approved on 1 January 2013. Our hospital is the obstetric center of pregnancy complicated with heart disease. Patients with singleton pregnancy undergoing elective cesarean section under CSE anesthesia were enrolled. Patients were divided into two groups: healthy pregnant women (group H) and pregnant with congenital heart disease (group CHD). In group H, women with uncomplicated singleton pregnancy at term undergoing elective cesarean section during CSE anesthesia were included in the study. In group CHD, criteria for inclusion were pregnant women with a prior diagnosis of CHD before pregnancy, first diagnosis in pregnancy by echocardiography and corrected CHD before pregnancy. Exclusion criteria in both groups were: patients with any complicated pregnancy, fetal compromise, need of emergency or in labor. All patients provided written informed consent. Noninvasive blood pressure (BP), electrocardiograph and SpO2 were monitored and recorded at 3-min intervals. A 20-gauge IV cannula was placed in the arm without the BP cuff. All patients received lactated Ringer solution. A CSE anesthesia technique was performed at the L2–3 interspace in the right lateral position. A 16-gauge Tuohy needle (Becton Dickinson, Franklin Lakes, NJ, USA) was placed in the epidural space using loss-of-resistance to saline. A 25-gauge Whitacre spinal needle was then placed through the Tuohy needle until the dura mater was punctured. Once free flow of clear cerebrospinal fluid was observed, 0.75% (wt/vol) isobaric ropivacaine (AstraZeneca, Södertälje, Sweden) solution 2 ml (15 mg) was injected into the subarachnoid space over 10 s using a 2 ml syringe. A 19-gauge closed-end epidural catheter with three side holes was then advanced 4 cm in the cephalic direction into the epidural space and secured. All pregnant women were then transferred to the supine position with left uterine displacement. Patients received incremental epidural boluses of 2% lidocaine to achieve a T4-6 anesthetic level for cesarean section. All women were monitored by electronic fetal heart rate (HR) monitor via a Doppler device before and after anesthesia. Hypotension (systolic BP < 90 mmHg or decrease > 20% below baseline) was treated with intravenous boluses of phenylephrine 100 µg. A decrease in HR to < 50 beats/min was treated with intravenous atropine 0.25–0.5 mg. Immediately after delivery, umbilical cords were clamped on both ends. Umbilical cord arterial blood sample and venous blood sample were collected
852
anaerobically in the pre-heparinized syringes. At the time of newborn delivery, maternal arterial blood sample was collected from maternal radial artery by another anesthesiologist. These samples were measured immediately after collection using a blood gas analyzer (i-STAT300F, Abbott Point of Care Inc., Abbott Park, IL, USA). Maternal age, body mass index (BMI), gestation week, time from induction of CSE to hysterotomy (TC-H) and hysterotomy to umbilical cord clamping (TH-U) were documented. Maternal systolic blood pressure (SBP) and HR were recorded at 3-min intervals, from baseline (before spinal injection) until 15 min after spinal injection. The total dose of phenylephrine from the time of spinal injection to delivery and intraoperative fluid were recorded as well. Birth weight and Apgar score at 1 min and 5 min were assessed by a trained physician after birth. A sample size of 30 in each group was required to find a difference in umbilical arterial pH of 0.03 units with 80% power and alpha = 0.05 (two sides). We recruited at least 35 patients in each group to account for dropouts. Values are expressed as number, mean and standard deviation (mean ± SD), or median (range). The comparison between two groups was performed using grouped t-test. Chisquare tests were used for categorical variables. Within- and between-group comparisons of hemodynamic variables from baseline to predefined time points (for 15 min after spinal injection) were performed using repeated-measures analysis of variance by Mixed Model. Analyses were performed using Excel 2000 (Microsoft, Redmond, WA, USA) and SPSS 11.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was defined at P < 0.05 (two sided).
Results Demographic data We enrolled 46 patients in group H and 35 patients in group CHD during the period from 1 January 2013 to 1 September 2013. Two pregnant women in group CHD were excluded because of incomplete umbilical cord blood gas values. Two pregnant women in group H were excluded as well because of unsuccessful CSE anesthesia in one case and incomplete umbilical cord blood gas values in another case. Finally, data of 44 women in group H and 33 women in group CHD were analyzed statistically. The type of CHD in group CHD included 16 (48.5%) atrial septal defect (ASD), 14 (42.4%) ventricular septal defect (VSD) and 3 (9.1%) patent
Umbilical arterial blood pH in pregnant women with CHD Table 1
Table 2
The type of CHD in pregnant women.
Demographics, operation data, fluid before delivery, total phenylephrine dose from CSE to delivery and maternal arterial blood gas analysis at birth.
The type of CHD
n
Atrial septal defect With no pulmonary hypertension With mild pulmonary hypertension With moderate pulmonary hypertension Ventricular septal defect With no pulmonary hypertension With mild pulmonary hypertension With moderate pulmonary hypertension Patent ductus arteriosus With no pulmonary hypertension With mild pulmonary hypertension
16 7 6 3 14 8 5 1 3 2 1
Data are expressed as number.
ductus arteriosus (PDA) (Table 1). All pregnant women were diagnosed with CHD before pregnancy and none of them was corrected. There were 16 pregnant women with pulmonary artery hypertension in group CHD, of which 12 cases of mild (> 25 mmHg, < 40 mmHg) and 4 cases of moderate (51 mmHg, 55 mmHg, 58 mmHg and 60 mmHg respectively) (Table 1). The ejection fraction (EF) and cardiac output (CO) by echocardiography were normal in all pregnant women with CHD. No rightto-left shunt was found by echocardiography before operation. There were five maternal New York Heart Association (NYHA) functional classification III in group CHD. No pregnant woman took anticoagulant drugs or cardiac medications.
Maternal data The two groups had no significant differences with respect to maternal age and gestation week (Table 2). BMI was significantly smaller in group CHD than that in group H (P = 0.0005). NYHA functional classification was shown in Table 2. All pregnant women achieved a T4-6 anesthetic level for cesarean section under CSE without any epidural boluses of 2% lidocaine. The two groups had no significant differences with respect to time from induction of CSE to hysterotomy (TC-H), time from hysterotomy to umbilical cord clamping (TH-U) and fluid before delivery. Total phenylephrine dose from CSE to delivery was significantly higher in group CHD (97 ± 68 µg) than that in group H (61 ± 75 µg) (P = 0.04) (Table 2). Maternal HR increased significantly at 3 min, 6 min and 9 min after injection of CSE compared with baseline in both two groups (P < 0.05) (Table 3). HR was lower in group CHD than in group H, although there were no significant differences
Group H
Group CHD
(n = 44)
(n = 33)
Age (year) 29 ± 4 27 ± 4 Gestation week (week) 39 ± 1 38 ± 2 BMI (kg/m2) 28 ± 2 26 ± 3 NYHA classification I 28 10 II 16 18 III 0 5 TC-H (min) 11 ± 1 11 ± 1 52 ± 6 53 ± 6 TH-U (s) Fluid before delivery (ml) 728 ± 115 683 ± 82 Total phenylephrine 61 ± 75 97 ± 68 dose from CSE to delivery (µg) pH 7.42 ± 0.03 7.42 ± 0.05 PCO2 (mmHg) 31.0 ± 3.5 31.9 ± 5.1 PO2 (mmHg) 143.3 ± 60.7 131.4 ± 63.7 BE (mmol/L) −3.1 ± 1.7 −3.1 ± 1.8 HCO3− (mmol/L) 21.4 ± 1.2 21.7 ± 1.2 Lac (mmol/L) 1.6 ± 0.5 1.6 ± 0.7
P 0.14 0.06 0.0005 / / / 0.91 0.62 0.16 0.04 0.85 0.47 0.49 0.96 0.30 0.93
Data are expressed as mean ± SD and number. BMI, body mass index; NYHA classification, New York Heart Association functional classification; TC-H, time from induction of CSE to hysterotomy; TH-U, time from hysterotomy to umbilical cord clamping; BE, base excess; Lac, lactate concentrations.
between group H and group CHD in HR (Fig. 1). Maternal SBP decreased significantly overtime compared with baseline in both groups (P < 0.01) (Table 3). There are no significant differences between group H and group CHD in SBP (Fig. 1).
Neonatal data Neonatal data are presented in Table 4. Birth weight in group CHD (3.16 ± 0.23) was lighter than that in group H (3.26 ± 0.21 kg), but there was no statistically significant difference (P = 0.11). Apgar scores at 1 and 5 min were comparable between the two groups. Umbilical arterial blood pH [7.29; 95% confidence interval (CI): 7.28 to 7.32], base excess (BE) (−1.4; 95% CI: −2.1 to −0.7 mmol/L) and HCO3− (21.5; 95% CI: 21.0 to 22.0 mmol/L) were significantly lower in group CHD than in group H (pH 7.32; 95% CI: 7.31 to 7.34, BE −0.1; 95% CI: −0.9 to 0.6 mmol/L and HCO3− 22.5; 95% CI: 22.0 to 23.0 mmol/L) (P = 0.03, P = 0.03 and P = 0.007 respectively) (Table 4). No significant difference was seen in two groups with regard to umbilical venous blood gas analysis. The different values of pH (umbilical arterial blood vs. umbilical venous blood) were not significant (P > 0.05) (Table 4).
853
Q. Zhan et al. Table 3 HR and SBP data of pregnant women. Group HR (bpm) H (n = 44) CHD (n = 33) SBP (mmHg) H (n = 44) CHD (n = 33)
Baseline
3 min
6 min
9 min
12 min
15 min
97 ± 9 95 ± 7
108 ± 8* 104 ± 7*
109 ± 6* 104 ± 5*
107 ± 5* 100 ± 6*
100 ± 6 96 ± 6
93 ± 4 85 ± 6*
123 ± 8 124 ± 7
101 ± 10* 101 ± 10*
105 ± 9* 100 ± 3*
100 ± 6* 99 ± 3*
110 ± 6* 111 ± 9*
113 ± 8* 112 ± 8*
Data are expressed as mean ± SD. *P < 0.05 compared with baseline. HR, heart rate; SBP, systolic blood pressure.
Fetal heart monitoring was normal before and after anesthesia. No recurrence of CHD was found in the offspring.
Discussion To our knowledge, this is the first study to analyze umbilical cord blood acid–base status and gas values at birth to understand the intrauterine environment in pregnant women with CHD undergoing cesarean delivery under CSE anesthesia. It was found that the values of umbilical arterial blood pH, BE and HCO3− were significantly lower in pregnant women with CHD than those in healthy pregnant women. Successful pregnancy has been feasible for most women with CHD. Most patients of ASD or VSD or PDA with normal right-sided pressures confer no added risk in pregnancy.8,9 Pulmonary hypertension (PH) (systolic pulmonary artery pressure > 50 mmHg) of any cause remains high risk for pregnancy. Elective cesarean delivery with neuraxial anesthesia is a common approach for pregnant women with CHD.8 Neuroaxial blockades can produce dramatic cardiovascular changes with sympathetic blockade, such as reduced systemic vascular resistance (SVR) caused by arteriolar dilatation. Reversal of the shunt due to a SVR decrease will lead to Eisenmenger’s syndrome.9 In women with PH, maternal and fetal mortality may reach 50%. The existing right-left shunt is likely to increase with the fall in SVR and can be exacerbated further by hypovolaemia.8 Avoiding significant decrease in SVR, therefore, is crucial during neuroaxial blockade.9 In present study, most of the pregnant women with CHD had no (17) or mild (11) PH. Moderate PH existed in four patients (51 mmHg, 55 mmHg, 58 mmHg and 60 mmHg respectively). No right-toleft shunt was found by echocardiography before
854
operation. After CSE, hypotension was immediately treated by phenylephrine in order to prevent a shunt reversal and maternal cyanosis did not take place. We conferred absence of right-to-left shunt after CSE from clinical manifestation. Some retrospective studies reported that the rate of neonatal complications in women with CHD reached 28%–36%.10,11 Independent risk factors for fetal complications (intrauterine growth retardation, premature birth, intracranial bleeding, spontaneous abortion, neonatal demise, stillbirth) have been defined: NYHA class > II; impaired function of systemic ventricle (ejection fraction < 40%); pressure gradient in the left ventricular outflow tract > 30 mmHg; maternal age < 20 or > 35 years; maternal smoking and maternal treatment with anticoagulants.3,4 In our study, we demonstrated no neonatal mortality and neonatal complications in group CHD. Neonatal birth weight and Apgar score were comparable. No recurrence of heart disease happened. It may be caused by lack of high-risk patients in the present study. There were four cases of moderate PH (PA systolic > 50 mmHg) in group CHD (n = 33). NYHA functional classification of most pregnant women with CHD was I–II, only five patients are NYHA III. And the EF and CO was normal in all pregnancy with CHD before operation. No anticoagulation and cardiac medications were administrated in this population. Most CHD patients in this study had mild disease and good NYHA functional status. They seemed be likely to be fit and well. There seemed no obvious maternal factors would affect neonatal complications. Additionally, we had done our best to control for some potential confounding factors. And there were no significant differences in gestational age, the time from induction of CSE to hysterotomy (TC-H) and time from hysterotomy to umbilical cord clamping (TH-U) between two groups. These relevant data
Umbilical arterial blood pH in pregnant women with CHD Table 4
A
Group H
130
Group CHD
* HR (bpm)
Birth-weight, Apgar scores at 1 and 5 min, umbilical cord blood (arterial-venous) gases immediately after birth and the different value of UA and UV.
*
*
110
90
70
*
*
* *
Baseline 3
6
9
12
15
Time (min)
B
Group H
SBP (mmHg)
140
120
Group CHD
*
*
*
*
*
*
* 100
80
* Baseline 3
* 6
* 9
12
15
Time (min) Fig. 1. (A) Heart rate (HR) vs. time. *P < 0.05 vs. baseline, group H and group congenital heart disease (CHD); No significant differences in HR between groups. (B) Systolic blood pressure (SBP) vs. time. *P < 0.01 vs. baseline, group H and group CHD. No significant differences between groups. Data are expressed as mean ± standard deviation (SD). Group H have unilateral error bars upward and group CHD downward.
showed that the two groups were under the similar condition of central neuraxial anesthesia. However, the values of umbilical arterial blood pH, BE and HCO3− were significantly lower in pregnant women with CHD than in healthy pregnant women. The CSE anesthesia is frequently associated with hypotension, which can decrease uteroplacental blood flow resulting in impaired fetal oxygenation and fetal acidosis. An initial decrease in SVR and increase in CO occurred immediately after spinal
Birth weight (kg) Apgar scores 1 min 5 min UA pH PCO2 (mmHg) PO2 (mmHg) BE (mmol/L) HCO3− (mmol/L) Lac (mmol/L) UV pH PCO2 (mmHg) PO2 (mmHg) BE (mmol/L) HCO3− (mmol/L) Lac (mmol/L) ΔUA-UV pH
Group H
Group CHD
(n = 44)
(n = 33)
P
3.26 ± 0.21
3.16 ± 0.23
0.11
9 (8–10) 10 (9–10)
9 (7–10) 10 (9–10)
0.84 0.98
7.32 ± 0.03 51.6 ± 6.7 22.0 ± 8.0 −0.1 ± 2.1 22.5 ± 1.4 2.1 ± 0.7
7.29 ± 0.05 51.6 ± 7.8 21.4 ± 9.3 −1.4 ± 1.9 21.5 ± 1.4 2.5 ± 1.2
0.03 0.99 0.88 0.03 0.007 0.16
7.35 ± 0.04 45.0 ± 5.6 30.5 ± 7.7 −0.9 ± 1.8 22.4 ± 1.5 2.1 ± 0.7
7.35 ± 0.05 43.8 ± 8.6 31.3 ± 9.6 −1.3 ± 1.7 21.9 ± 2.5 2.2 ± 1.2
0.98 0.55 0.75 0.44 0.40 0.67
0.04 ± 0.03
0.06 ± 0.05
0.07
Data are expressed as mean ± SD. UA, umbilical arterial blood gases; UV, umbilical venous blood gases; ΔUA-UV, the different value of umbilical arterial blood gases and umbilical venous blood gases; BE, base excess; Lac, lactate concentration.
injection.12,13 The intravenous fluid expansion and vasopressor administration would minimize reductions in SVR and maximize increases in CO. The intravenous fluid expansion is likely to overload the patients with heart disease. Direct acting alpha agonists (e.g. phenylephrine) are preferred.14 Studies have suggested that fetal acid–base status might be improved if phenylephrine is used during cesarean delivery instead of ephedrine.15,16 Our hospital routinely use phenylephrine to treat hypotension resulted from CSE. However, some studies claimed that the increase in CO occurred after spinal injection was transient, and HR and CO were also significantly lower in patients receiving the phenylephrine infusion.12,13 Dyer et al.17 measured CO continuously using pulse waveform analysis and thoracic bioimpedance. In patients who required a vasopressor to treat a 20% decrease in mean arterial blood pressure, there was a 35% decrease in SVR compared with baseline, accompanied by a 12% increase in HR and 23% increase in CO before vasopressor administration. CO and HR were significantly lower during the 150 s after administration of a phenylephrine bolus of 80 µg for the treatment of
855
Q. Zhan et al.
hypotension. In comparison with pre-vasopressor values, CO decreased by 14% with phenylephrine. The reduced CO with phenylephrine use remained above baseline, because CO values immediately before vasopressor administration were higher than baseline.17 Stroke volume remained stable throughout.18 The reduction in CO did not affect the neonatal outcomes in normal pregnancy.18 The fetal effects of a potential baroreceptor-mediated reduction in CO have yet to be fully evaluated, particularly in pregnancy with CHD. In our study, we administrated a bolus (100 µg) of phenylephrine to treat hypotension (systolic BP < 90 mmHg or decrease > 20% below baseline). Total phenylephrine dose from CSE to delivery in group CHD (97 ± 68 µg) was significantly more than that in group H (62 ± 75 µg) (P = 0.04). The mean phenylephrine dose in group CHD in our study was more than 80 µg; the referred dose in the study of Dyer et al.17 emphasized the importance of HR as a surrogate indicator of CO. Stewart et al.18 and Langesaeter et al.12 found a dosedependent reduction in HR with phenylephrine use that is associated with a decrease in maternal CO. Although we failed to measure CO directly, we may use HR to estimate CO. We recorded maternal HR and SBP data from baseline (before spinal injection) till 15 min after CSE anesthesia. The mean time from induction of CSE to umbilical cord clamping was about 12 min (Table 2). SBP was significantly decreased from spinal injection till 12 min after spinal injection and HR was significantly increased from spinal injection till 9 min after spinal injection in both two groups (Table 3), which were resulted from sympathectomy due to CSE anesthesia. When hypotension occurred, phenylephrine was administrated to preserve arterial blood pressure. Despite of no significant differences of HR and SBP between two groups, the HR was slower in group CHD than group H throughout and SBP in group CHD was nearby or slightly slower than group H (Fig. 1), which may be related to the larger mean phenylephrine dose in group CHD. We inferred a more reduced CO in group CHD from the slower HR. Above all, we speculated a reduced CO was occurred in group CHD, which may decrease uteroplacental blood flow leading to a low umbilical cord blood pH, BE and HCO3−. Of course, some factors would influence umbilical cord artery blood values. First, fetal pH value can be affected by maternal pH value.19 When the maternal metabolic acidosis or alkalosis occurred, the fetus acid–base status may also change accordingly. In our study, no maternal acidosis or alkalosis
856
occurred in both two groups (Table 2). We believe that the acid–base status in fetus of group CHD was not secondary to maternal. Second, it is significant to recognize that the umbilical cord can be obstructed before birth. Analysis of paired arterial and venous specimens can give insights into the etiology of the acidosis.20 Restriction of umbilical blood flow causes a progressive widening of veno-arterial difference (differences in pH of up to 0.3 units).20,21 In our study, the veno-arterial differences in pH were 0.04 ± 0.03 in healthy women and 0.06 ± 0.05 in pregnant women with CHD respectively. Therefore, we eliminated the effect of umbilical cord obstruction on umbilical artery blood values. There are some limitations to our study. First of all, most of the pregnant with CHD in this study belonged to the low-risk group22 of CHD. The patient sample was subject to selection bias in our study. Patients with severe cardiac complications might choose not to proceed with pregnancy, and our population may represent a subset of women with heart disease at lower cardiac risk. Further studies are required to determine the impact on fetuses at high risk of CHD under CSE. Second, the lower umbilical artery pH in group CHP was out of our expectations in sight of the low-risk group of CHD in our study. We did not monitor CO directly after CSE, nor assess the placental perfusion by Doppler technique. We have been preparing for use of these two measurements in the future research, in order to further understand the changes of maternal and neonatal situations after CSE. Third, we provided CSE for pregnant women with CHD in the light of the patients’ cardiovascular anatomy and physiology changes. Alternatively, general anesthesia may be dictated by cardiac, obstetric or anesthetic indications, such as hemodynamic instability, anticipation of excessive blood loss and contraindications to neuraxial techniques. General anesthesia is one of the risk factors for poorer immediate neonatal outcomes among growth-restricted neonates.23 Therefore, our results cannot represent those in patients with general anesthesia. In conclusion, despite low-risk patients with CHD in present study, the lower values of umbilical arterial blood pH, BE and HCO3− were observed in this population than in healthy women undergoing elective cesarean section during CSE anesthesia. Although the value of umbilical artery blood did not reach the standard of neonatal asphyxia and did not appear to be clinically important in this experiment, it pointed out us that close monitor and early intervention in clinical was very important in neonatal of
Umbilical arterial blood pH in pregnant women with CHD
pregnant women with CHD in spite of normal Apgar scores. Conflict of interest: None. Funding: None.
14. 15.
References 1. Wren C, O’Sullivan JJ. Survival with congenital heart disease and need for follow up in adult life. Heart 2001; 85: 438–43. 2. Nieminen HP, Jokinen EV, Sairanen HI. Late results of pediatric cardiac surgery in Finland: a population-based study with 96% follow-up. Circulation 2001; 104: 570–5. 3. Siu SC, Sermer M, Colman JM. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001; 104: 515–21. 4. Siu SC, Colman JM, Sorensen S. Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 2002; 105: 2179–84. 5. Reynolds F, Sharma SK, Seed PT. Analgesia in labor and fetal acid-base balance: a meta-analysis comparing epidural with systemic opioid analgesia. BJOG 2002; 109: 1344–53. 6. Chen LK, Lin CJ, Huang CH, Wang MH, Lin PL, Lee CN, Sun WZ. The effects of continuous epidural analgesia on Doppler velocimetry of uterine arteries during different periods of labour analgesia. Br J Anaesth 2006; 96: 226–30. 7. ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 348, November 2006: umbilical cord blood gas and acid-base analysis. Obstet Gynecol 2006; 108: 1319–22. 8. Head CE, Thorne SA. Congenital heart disease in pregnancy. Postgrad Med J 2005; 81: 292–8. 9. Gomar C, Errando CL. Neuroaxial anaesthesia in obstetrical patients with cardiac disease. Anaesthesiology 2005; 18: 507– 12. 10. Hidano G, Uezono S, Terui K. A retrospective survey of adverse maternal and neonatal outcomes for parturients with congenital heart disease. Int J Obstet Anesth 2011; 20: 229–35. 11. Khairy P, Ouyang DW, Fernandes SM, Lee-Parritz A, Economy KE, Landzberg MJ. Pregnancy outcomes in women with congenital heart disease. Circulation 2006; 113: 517–24. 12. 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. 13. McDonald S, Fernando R, Ashpole K, Columb M. Maternal cardiac output changes after crystalloid or colloid coload
16.
17.
18.
19. 20. 21. 22. 23.
following spinal anesthesia for elective cesarean delivery: a randomized controlled trial. Anesth Analg 2011; 113: 803–10. Ngan Kee WD, Khaw KS. Vasopressors in obstetrics: what should we be using? Curr Opin Anaesthesiol 2006; 19: 238– 43. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2002; 94: 920–6. Habib AS. A review of the Impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012; 114: 377–90. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, Greenwood J, James MF. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009; 111: 753–65. Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg 2010; 111: 1230–7. Roemer VM. Measured quantities in perinatal medicine-the PCO2. Z Geburtshilfe Neonatol 2005; 209: 90–9. Martin GC, Green RS, Holzman IR. Acidosis in newborns with nuchal cords and normal Apgar scores. J Perinatol 2005; 25: 162–5. Johnson JW, Richards DS. The etiology of fetal acidosis as determined by umbilical cord acid-base studies. Am J Obstet Gynecol 1997; 177: 274–80. Anselm U, Michael AG, Constantin K. Congenital heart disease in pregnancy. Dtsch Arztebl Int 2008; 105: 347–54. Levy BT, Dawson JD, Toth PP, Bowdler N. Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH among growth-stricted neonatal. Obstet Gynecol 1998; 91: 909–16.
Address: Xiangrui Wang Department of Anesthesia Shanghai Renji Hospital Jiaotong University 1630 Dongfang Road Shanghai 200127 China e-mail: [email protected]
857
