|Year : 2013 | Volume
| Issue : 2 | Page : 84-90
A randomized double-blind comparison of low-dose and high-dose bupivacaine for caesarean section in severely preeclamptic women using invasive blood pressure monitoring
Kajal Jain1, Jeetinder Kaur Makkar1, Iswarya Anbarasan1, Sandhya Yadanappudi1, Shalini Gander2
1 Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||19-Dec-2013|
Department of Anaesthesia, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Background: The effect of a low dose of spinal local anesthetic on the incidence of hypotension has not been evaluated till date in severely preeclamptic women undergoing cesarean delivery. In this study, we compared the mean arterial pressure changes associated with low and conventional doses of spinal anesthetic in these women using invasive pressure monitoring.
Materials and Methods: Twenty four severely preeclamptic women scheduled for elective cesarean delivery were randomly allocated to receive 7.5 mg [Group 1] or 10 mg [Group 2] of bupivacaine with 20 μg of fentanyl for spinal anesthesia. Heart rate and mean arterial pressure (MAP) were measured continuously using invasive arterial pressure monitoring. Phenylephrine boluses were used to maintain the MAP of >80% of baseline. The incidence of hypotension was compared between the two groups. Neonatal outcome was assessed using Apgar scores, umbilical cord blood gases, and need for resuscitation.
Results: Incidence of hypotension was less in Group 1 as compared to Group 2 (41.6% vs. 91.6%, P = 0.009). Duration of hypotension was significantly longer in Group 2 compared to Group 1 (P = 0.005). Hypotensive episodes requiring vasopressors were more frequent in Group 2 (1.5 [1-3] vs. 0 [0-1]), P = 0.01) [Table 2]. There was no difference in Apgar scores, umbilical cord blood gases, and need for resuscitation between the two groups.
Conclusion: Low dose of spinal bupivacaine resulted in a lower incidence of hypotension, higher predelivery MAP and decreased use of vasopressors in severely pre-eclamptic women undergoing cesarean section.
Keywords: Bupivacaine, cesarean section, severe preeclampsia, spinal anesthesia
|How to cite this article:|
Jain K, Makkar JK, Anbarasan I, Yadanappudi S, Gander S. A randomized double-blind comparison of low-dose and high-dose bupivacaine for caesarean section in severely preeclamptic women using invasive blood pressure monitoring. J Obstet Anaesth Crit Care 2013;3:84-90
|How to cite this URL:|
Jain K, Makkar JK, Anbarasan I, Yadanappudi S, Gander S. A randomized double-blind comparison of low-dose and high-dose bupivacaine for caesarean section in severely preeclamptic women using invasive blood pressure monitoring. J Obstet Anaesth Crit Care [serial online] 2013 [cited 2019 Dec 11];3:84-90. Available from: http://www.joacc.com/text.asp?2013/3/2/84/123302
| Introduction|| |
Maternal hypotension is an unwanted consequence of spinal anesthesia (SA) for cesarean delivery (CD). It produces unpleasant symptoms such as nausea, vomiting, and light-headedness. It may also cause a decrease in uteroplacental blood flow and result in fetal acidosis. ,
The incidence of intrauterine growth retardation (IUGR), prematurity and fetal distress is very high in severe preeclampsia due to impaired perfusion. A decreased physiological reserve in these fetuses exposes them to a higher risk of antepartum asphyxia.  Any acute maternal deteriorations such as SA-induced hypotension may further decrease the uteroplacental perfusion.  Because of these reasons, SA was not used in severely preeclamptic women. However, a randomized trial in 1995 comparing SA with general anesthesia (GA) attested to the safety of SA.  In fact, current literature favors the use of SA in severly preeclamptic women, as they have been found to have less hypotension than normotensive women. ,,
Previous studies comparing different modes of anesthesia in severely preeclamptic women reported a higher incidence of hypotension after SA as compared to epidural or general anesthesia. ,, In these studies 8-12 mg of 0.5-0.75% bupivacaine was used for SA and non- invasive blood pressure was measured every minute or even less frequently. Invasive blood pressure monitoring enables early detection of the rapidly occurring blood pressure changes during evolving spinal block and facilitates early intervention.
In this study, the aim was to find whether a reduction in dose of spinal bupivacaine decreases the incidence of hypotension and the requirement of vasopressors in severely preeclamptic women undergoing elective CD.
| Material and Methods|| |
After the approval of the Institute Ethics Committee (Post Graduate Institute of Medical Education and Research, Chandigarh, India) and written informed consent, 28 women aged 20-40 years, with severe preeclampsia scheduled for elective CD were recruited during the period 2008-10 in this randomized double-blind trial. Severe preeclampsia was defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >110 mmHg obtained on at least two separate occasions, or if the patient had symptoms of imminent eclampsia (namely severe headache, visual disturbance, epigastric pain, hyperreflexia, dizziness and fainting, or vomiting) and proteinuria on urine dipstick was 3+ or worse. Patient with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome were considered eligible for inclusion if the platelet count exceeded 75 × 10 9 /l.
We excluded women with any contraindication to SA, body mass index greater than 35 kg/m 2 , chronic hypertension/electrocardiogram (ECG) changes, antepartum hemorrhage, coagulation abnormality, twin pregnancy, active labor or non-reassuring fetal heart trace.
Relevant obstetric history and laboratory investigations including ECG, renal function tests, liver function tests, platelet counts and proteinuria were noted. All women underwent daily antenatal Doppler fetal assessment by a consultant obstetrician according to the institute protocol. Preoperative anti-hypertensive medications and the last dose of magnesium sulfate, if any, were recorded. All women received ranitidine 150 mg and metoclopramide 10 mg orally, 45 minutes prior to scheduled surgery. Mean of the three blood pressure recordings 1 minute apart, recorded prior to surgery was taken as the baseline value.
Women were randomized into two groups using computer generated random number table. Concealment of randomization was done using numbered, sealed opaque envelopes which were opened just before the start of anesthesia. The envelopes were opened and the spinal block performed by one of the two anesthesiologists not involved in clinical care and data collection. Women in Group 1 received 7.5 mg bupivacaine (1.5 ml of 0.5%) with 20 μg fentanyl (0.4 ml) and those in Group 2 received 10 mg bupivacaine (2 ml of 0.5%) with 20 μg of fentanyl (0.4 ml). The clinical management of the patient and data collection was done by an anesthesiologist blind to the spinal drug used.
On arrival to the operating room, venous access was secured with an 18G cannula. Intraoperative monitoring consisted of ECG, invasive MAP and oxygen saturation (SpO 2 ) (Datex Ohmeda, Avance Madison, USA). For invasive blood pressure monitoring, a 20G arterial cannula was introduced in the left-radial artery under local anesthesia.
All women received a co-load of 500 ml normal saline (NS). Lumbar puncture was performed using 26G Quincke needle at L3-L4 inter space by midline approach with patient in the flexed left lateral position. After free flow of cerebrospinal fluid (CSF), the drug was injected slowly over 20 seconds. Patient was then turned supine with left uterine displacement and supplemental oxygen was given using a venti mask (FiO 2 0.4). Level of sensory block was assessed bilaterally using pin prick technique till a level of T4-T5 was achieved. If the level was T6 and the patient complained of pain (VAS > 4) anytime during surgery, rescue analgesic was administered (1 μg/kg of fentanyl IV). A level <6 was considered as block failure and GA was administered. Intraoperative nausea and vomiting were recorded and treated with 4 mg of ondansteron IV
Hypotension was defined as a decrease in MAP by >20% of baseline value or <90 mmHg any time before delivery of the baby. Any episode of hypotension was treated with phenylephrine bolus (50 μg). If hypotension persisted after one minute, another bolus of phenylepherine was given. New episode of hypotension was said to occur if it was preceded by normotension. If patient did not respond after three boluses, ephedrine 5mg was given for subsequent treatment. Any episode of bradycardia (heart rate <50 beats/minute) with associated hypotension was treated using Inj Atropine 0.6 mg bolus. Number/duration of hypotension/hypertension and total dose of phenylephrine used were recorded.
Time intervals from spinal injection to maximum blockade, start of surgery, uterine incision and delivery of baby were recorded. Neonatal weight, Apgar score at 1 and 5 minutes, maternal arterial and umbilical cord blood gases (Cobas b 121 system, Roche Diagnostics, Germany) were recorded. Need for assisted ventilation in the form of facemask ventilation, intubation and ventilation or cardiopulmonary resuscitation were also recorded. Assessment of neonate at follow-up for the next 24-48 hours included need for admission to neonatal intensive care unit, any evidence of respiratory distress or need for respiratory support i.e. nasal continuous positive airway pressure (CPAP) and intermittent positive pressure ventilation (IPPV).
The primary outcome of the study was to compare the incidence of hypotension (with invasive blood pressure monitoring) in severely preeclamptic women receiving two doses of spinal bupivacaine for elective CD.
The secondary outcomes measured were total dose of vasopressors used and neonatal outcome as assessed by cord blood gases (fetal acidosis: pH ≤ 7.2, base deficit ≥8 mmol/L), Apgar scores (depressed: scores <7 at 1, 5 minutes) and need for neonatal resuscitation.
There is no data available in English literature regarding use of different doses of spinal bupivacaine for CD in severely preeclamptic women. Although, these women are at an increased risk for CD due to IUGR, prematurity and fetal distress, very small percentage of them undergo elective CD.  Therefore, we conducted a pilot study of 28 severely preeclamptic women for planned CD.
Demographic data, intraoperative data and duration of hypotension were expressed as median [interquartile range (IQR)] and analyzed using Mann-Whitney U test. Incidence of hypotension was compared using Chi square test (χ2 ). Repeated Measures Analysis of variance was used to compare the hemodynamic changes after spinal anesthesia from baseline within each group. Results were considered significant at P < 0.05.
| Results|| |
A total of 28 pregnant women with severe preeclampsia, were enrolled in the study over a period of 24 months at the maternity unit of our hospital. Of these, four patients were excluded due to non-reassuring fetal heart rate pattern (n = 2), or lack of consent for invasive blood pressure monitoring (n = 2) [Figure 1]. A total of 24 women were randomized to two groups of 12 each. The various indications for elective CD in these women and antihypertensive drugs received by these patients preoperatively are given in [Table 1] and [Table 2]. All patients were on anti-hypertensive medications. In addition, two women received loading dose of MgSO 4 for uncontrolled blood pressure. The severity of preeclampsia as judged by the preoperative laboratory function tests like liver function tests, renal function tests, and proteinuria were comparable between the two groups [Table 3].
Demographic data are given in [Table 4]. No patient was excluded because of inadequate block height. The maximum sensory block height achieved was T 4-5 in both the groups. The median [IQR] time required for maximum spinal block was 4.0 [2.3-4.8] minutes in Group 1 as compared to 2.5 [2.0-3.8] minutes in Group 2 ( P = 0.05).
Incidence of hypotension was less in Group 1 as compared to Group 2 (41.6% vs. 91.6%, P = 0.009) (Chi Square test). [Table 5]. Duration of hypotension was significantly longer in Group 2 compared to Group 1 (P = 0.005) (Mann-Whitney U test). Hypotensive episodes requiring vasopressors were more frequent in Group 2 (1.5 [1-3] vs. 0 [0-1]), P = 0.01) [Table 5].
Baseline MAP was compared with MAP in first 10 minutes after spinal. In Group 1, MAP was different from baseline at 5 minutes to 8 minutes and at 6 to 10 minutes in Group 2 [Table 6]. The maximum decrease in MAP from baseline values were 13.5% in Group 1 (P = 0.18) and 19% in Group 2 (P = 0.09) [Figure 2].
|Figure 2: Changes in mean arterial pressure between group 1 and 2 till delivery of baby|
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|Table 6: Analysis of intra group difference in mean arterial pressure from baseline at different time intervals|
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On intergroup comparison, baseline MAP was not different between two groups. Only difference was found at 5 minutes when MAP was 98.25 mmHg in group 1 and 99.08 mmHg in Group 2 (P = 0.036, student's t-test). There was no significant difference in median heart rate and systolic blood pressure between the two.
[Figure 3] represents the box plot which shows phenylephrine usage in both groups.
|Figure 3: Comparison of requirement of dosage of phenylephrine in group 1 and 2. Significant difference between the groups P < 0.05|
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No complaints of nausea or vomiting were noted during the surgery in either of the two groups. Maternal blood gases obtained before delivery of the baby were comparable in both the groups [Table 7].
|Table 7: Blood gas data in mother and Umbilical arterial blood of neonates|
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Neonatal birth weight was lower in both the groups [Table 8]. Cord blood gases (arterial and venous) were comparable in both the groups [Table 8]. There was no correlation between umbilical arterial pH and the lowest MAP predelivery or percentage change in MAP from baseline value in either groups. On considering categorical data, two neonates, one in each group showed Apgar score <7 at 1 and 5 minutes. There was also associated fetal acidosis (UA pH < 7.2). Both these neonates required intubation and assisted ventilation with 100% O 2 . On follow-up, there was no evidence of neurological deterioration in the form of seizures, lethargy, or encephalopathy. Apart from this, another neonate in Group 1 was acidotic, yet vigorous (Apgar > 7). Overall requirements for resuscitation in operating room were similar in both the groups.
| Discussion|| |
This study demonstrates that 10 mg spinal bupivacaine was associated with lower predelivery mean arterial pressures as compared to a dose of 7.5 mg in severely preeclamptic women. More phenylephrine boluses were required in this group to restore the target MAP (>80% of baseline). Neonatal outcome was comparable in both the groups. The quality of surgical anesthesia was similar in both the groups.
Spinal anesthesia provides a rapid, reliable and safe form of surgical anesthesia for cesarean sections. Currently, spinal anesthesia has become popular for CD of severely preeclamptic parturients as it has been seen that these women suffer less hypotension, probably due to preeclampsia related factors. ,, Aya et al. reported a decreased incidence of hypotension (a decrease of 30% from baseline) in severely preeclamptic women as compared to normal term parturients (16.6% vs. 53.3%) while using standard spinal doses.  The incidence of hypotension varies between 1.9%-71% depending upon the definition of hypotension used in the study.  Best maternal and fetal outcome is seen on maintaining baseline hemodynamics, but it may not be feasible in severely preeclamptics due to a risk of worsening their hypertensio. This is because this technique of maintaining baseline blood pressure in healthy patients undergoing CD was associated with 47% incidence of hypertension. ,
Apart from this we used invasive monitoring and limited the use of crystalloids. As the beat to beat data set obtained from the first minute contains a lot of disturbances since the patients are changing from lateral to supine position after spinal anesthesia, we took mean of three non-invasive readings before surgery as baseline.  The first study with continuous invasive monitoring in healthy pregnant women was done by Langestear et al.  Authors found that 10 mg of bupivacaine increased the risk of hypotension (20% reduction of baseline systolic blood pressure (SBP)) with a reduced risk (RR) of 1.6 as compared to 7 mg of the drug. We also found that with 10 mg spinal bupivacaine more mothers suffered predelivery hypotension and required vasopressors. Using invasive monitoring Dyer et al. also found that cardiac output remained stable when radial artery pressure was maintained using vasopressors.  To prevent hemodynamic instability in severely preeclamptics most of the previous studies recorded blood pressure non-invasively at 1-2 minutes interval or even less frequently. ,, The distinct advantage of invasive monitoring is that it detects rapid hemodynamic changes after spinal drug administration which may be avoided if blood pressure is measured non-invasively.  Another reason for the higher incidence of hypotension in our study was that we infused lesser volume of crystalloids. Aya et al. preloaded the patients with 1.5 litres of ringer lactate.  An aggressive IV fluid preloading increases the risk of pulmonary edema in these patients due to low plasma oncotic pressure,  and increased permeability of pulmonary alveolar capillaries.  We administered IV crystalloids at a rate of 2 ml/kg during the surgery as maintenance fluids.
Lowering the dose of spinal anesthetic is associated with reduced incidence of maternal hypotension, requirement of vasopressors and episodes of nausea or vomiting. ,,,[19 ] But lower doses may reduce the quality of block and cause breakthrough pain.  We chose this dose because we had institutional experience with this dose for cesarean section and also published data in women with pregnancy induced hypotension.  Addition of fentanyl allows successful use of a lower dose of bupivacaine. Along with this, other factors such as increased sensitivity to local anesthetics during pregnancy and enhanced spread of subarachnoid local anaesthetic (LA) may have also contributed to the adequacy of the blocks.  Although, our study reports no instance of breakthrough pain, this can be attributed to small sample size. In making inference from result with zero nominator, the corrected upper limit is approximately equal to 3/N (3/24 = 12.5%). So the exact confidence interval of zero incidence of block failure in our patients extends from 0 to 12.5% (95% CI). 
Mean duration of surgery was less than one hour in the present study (40.536.5-44.5 min in Group 1 and 42.537.5-45.0 in Group 2). Roofthooft and Van de Velde reported that using 6.5 mg with sufenatnil as a part of combined spinal epidural (CSE) technique, the need to top the epidural catheter was rare if surgery finished within one hour.  Nevertheless, a backup catheter offers the flexibility of extending the block if anesthesia is inadequate or surgery gets prolonged without conversion to general anesthesia. It also allows successful use of a low dose with efficient anesthesia and minimal incidence of hypotension. ,, Owing to the risk of failed intubation and hemodynamic responses to intubation, GA is hazardous in this population and should be reserved for women for whom neuraxial anesthesia is contraindicated.  Although, a backup catheter is strongly recommended with the use of low dose spinal, according to a recent editorial, its usefulness if the epidural catheter is untested or not correctly sited as compared to single shot spinal anesthesia is speculative. 
Lower MAP changes as well as decreased use of vasopressor may particularly be beneficial in high risk pregnancies, for example, early onset preeclampsia, coexisting cardiac disease. In a recent publication, 20% of preeclamptic women at term had evidence of myocardial damage and 40% had global diastolic dysfunction. There is increasing evidence for raised levels of pro-brain natriuretic peptide (BNP), a biomarker for cardiac failure, in patients with early-onset preeclampsia compared with healthy pregnant women.  These findings have implications for management of fluids and vasopressors during SA for cesarean section and postpartum in these women.
Apgar scores as well as fetal pH surrogate markers of adequacy of uteroplacental blood flow blood flow were comparable in both the groups in our study. Dyer et al. reported lower fetal UA pH with the use SA in severely preeclamptic women requiring emergency CD with non-reassuring fetal heart rate.  Women in our study were under strict antenatal surveillance for planned CD. Neonates who showed low Apgar scores with or without fetal acidosis in our study had no associated maternal hemodynamic compromise. However, there was evidence of reversed end diastolic flow or raised S/D ratio (>7.5) on Doppler study, which indicates severe impairment of uteroplacental perfusion. Salafia et al. studied antenatal doppler in cases of absent and reversed end diastolic flow in umbilical arteries and reported a mean pH of 7.15 and 6.94, respectively, suggesting that these indices are associated with serious fetal impairment. 
In the present study we report higher predelivery MAP values with reduced use of vasopressor therapy in severely preeclamptic women undergoing elective CD with the use of 7.5 mg of spinal bupivacaine with fentanyl. But we suggest that a combined spinal-epidural anesthesia technique should be preferable to a single shot anesthesia as the indwelling catheter can be activated without conversion to GA which is particularly hazardous in these women.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]