INTRODUCTION
Preeclampsia constitutes a significant cause of maternal and fetal morbidity and mortality, due to associated multiorgan dysfunction. Approximately 5%–8% of pregnancies get complicated due to preeclampsia.[ 1 ] It is characterized by hypertension and proteinuria after 20 weeks of gestation. The pathophysiologic basis of preeclampsia is deranged angiogenesis with incomplete trophoblastic invasion, leading to small, constricted myometrial spiral arteries with exaggerated vasomotor responsiveness, superficial placentation, and placental hypoperfusion.[ 2 ] Symptomatic preeclampsia reflects widespread endothelial dysfunction, in which placental-derived mediators cause multisystem organ dysfunction.[ 3 ] The choice of safe anesthetic, maintenance of intraoperative stability to ensure the delivery of a healthy neonate, and minimizing maternal morbidity and mortality is the focus of anesthetic management. In spinal anesthesia (SA), the concerns are centered on hypotension. In general anesthesia (GA), airway stimulation due to laryngoscopy and tracheal intubation may result in sudden hypertension, which can cause pulmonary edema, cerebral edema, or intracranial hemorrhages.[ 4 ] Historically, a pervasive belief of SA in patients with severe preeclampsia causing severe hypotension and decreased uteroplacental perfusion prevented the widespread use of SA in these patients.[ 1 ] One of the studies has shown that SA in severe preeclampsia was associated with clinically insignificant changes in cardiac output.[ 5 ] In severe preeclamptic patients, rapid sequence induction of GA and tracheal intubation can cause severe hypertension which is associated with a significant increase in maternal cerebral blood flow velocity.[ 6 ]
Hence, we proposed to study the effect of the type of anesthesia (GA or SA) on the maternal intraoperative hemodynamic changes and maternal and fetal outcomes (primary objective) in patients with preeclampsia who were posted for cesarean section delivery and to study the complications associated with the same (secondary objective).
MATERIALS AND METHODS
After institutional review board and ethics committee approval, 80 consenting preeclamptic female patients who underwent lower segment cesarean section in our tertiary care center from February 2014 to September 2015 were included in this prospective, observational clinical study designed to study the type of anesthesia and outcome in preeclamptic patients undergoing cesarean section. Preeclamptic patients with (1) antepartum hemorrhage such as placenta previa and abruptio placenta, (2) cardiac disease, and (3) chronic renal disease were excluded as these conditions may interfere with hemodynamics. These 80 study participants were grouped into two groups depending on the type of anesthesia they received: GA group – patients who received GA and SA group – Patients who received SA. The type of anesthesia administered was dependent on general condition of the patient as well as fetus and choice of the concerned anesthesiologist. A routine preoperative protocol was followed for all patients which included thorough evaluation and examination with measurement of baseline vital parameters. Baseline heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and oxygen saturation (SpO2 ) were recorded and maternal age in years, gestational age in weeks, maternal preoperative medication, indication for cesarean section, and maternal comorbidities such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, hypothyroidism, and gestational diabetes mellitus if any were noted. An intravenous (IV) cannula was secured and IV infusion of Ringer’s lactate 3–4 ml.kg.h was started. HR, SBP, DBP, MAP, and SpO2 were recorded. Patients who received SA, were given injection bupuivacaine 0.5% (H) 1.8-2.0 ml at L3-L4 interspace to achieve a block upto T4. It was administered in the sitting position under all aseptic precautions. Patients were placed in supine position with a wedge for left uterine displacement after the procedure, and supplemental oxygen 6 L/min was administered by Hudson’s mask. The patients requiring GA were those with fetal distress, HELLP syndrome, impending eclampsia, coagulopathy, patient refusal, etc. It was administered as per the standard institutional protocol (no opioid or benzodiazepine was given before baby delivery). Intraoperatively, HR, SBP, DBP, MAP, and SpO2 were recorded during the induction of anesthesia and then every 5 min for the first 30 min after the induction of anesthesia, every 15 min there after till the 2 h postoperatively. Use of colloids, blood and blood products, and details of vasopressor drugs administered to the patient were noted. Birth weight of the baby and Apgar score at 1 min and 5 min were also noted.
Complications
Hypotension was defined as reduction in MAP <20% of baseline MAP and was treated with injection ephedrine 5–10 mg IV bolus, if necessary repeated after 5–10 min (when HR <100/min), or with injection phenylephrine 10–20 mcg bolus, if necessary repeated after 5–10 min (when HR >100/min)
Hypertension was defined as increase in MAP >20% of baseline MAP and was treated with deepening the level of anesthesia, if necessary with injection labetalol 0.5 mg/kg IV slowly
Bradycardia was defined as reduction in HR <60/min and was treated with injection atropine 0.01 mg/kg in bolus.
Postoperatively, patients were shifted to the postanesthesia care unit (PACU) or intensive care unit (ICU) depending on general condition of the patient. HR, SBP, DBP, MAP, and SpO2 were recorded every 15 min till 2 h postoperatively. Maternal outcome including admission to ICU with or without ventilatory support or PACU was noted. Neonatal outcome including still birth/live birth/Apgar score, requirement of intubation, or ventilatory support was noted. Further, maternal and neonatal mortality was noted.
Statistical analysis
Demographic data were analyzed by Pearson’s Chi-square test. Changes in HR, SBP, DBP, and MAP were analyzed using Student’s t -test. P < 0.05 was considered to be statistically significant.
OBSERVATION AND RESULTS
In this prospective, observational clinical study, of the 80 patients, 67 patients received SA, 13 patients received GA.
The average age of the parturients in GA group was 26.92 years which was comparable to mean age of 26.01 years in the SA group. The average height being 155.85 cm in the GA group was comparable to 157.79 cm in the SA group.
Similarly, the mean gestational age of the cases was 37.38 weeks in GA group which was comparable to 37.42 weeks in SA group. Thus, demographic data were comparable in both the groups.
Mean SBP at baseline was comparable in the two groups (GA vs. SA). However, the difference in the mean lowest intraoperative SBP and also the mean highest intraoperative SBP was statistically significant in the two groups (P = 0.003) [Table 1 and Graph 1 ].
Table 1: Comparison of changes in mean systolic blood pressure, mean diastolic blood pressure, mean arterial pressure
Graph 1: Comparison of changes in mean systolic blood pressure. *significant by Student’s t -Test
When the mean DBP at baseline, the mean lowest intraoperative DBP, and the mean highest intraoperative DBP were compared in the two groups (GA vs. SA), the difference was statistically significant [Graph 2 ].
Graph 2: Comparison of changes in mean diastolic blood pressure
Further, 7.7% of the cases in the GA group and 29.9% in the SA group had SBP <100 mmHg, but difference was not statistically significant (P = 0.36).
More than 20% fall in MAP was seen in 30.8% of the cases in GA group as compared to 53.7% of cases in SA group, but the difference was not statistically significant (P = 0.13).
We found 84.6% of the cases in GA group with a HR <60 per min which was comparable to 92.5% in the SA group (P = 0.36).
Furthermore, not a single case in the GA group had received ephedrine drug as compared to 31.3% in the SA group received ephedrine compared to none in the GA group, and this difference was statistically significant (P = 0.02). In addition, 7.7% of the cases in GA group had received blood and not a single case in SA group, but difference was not statistically significant (P = 0.35).
In SA group, none required ICU care or ventilatory support whereas 61.5% of the cases in GA group required the above. This difference was statistically significant (P < 0.001). Of the 61.5%, 30.8% required ICU care and 7.7% required ventilatory support.
In SA group, 77.6% of the neonates had uneventful outcome as compared to 30.7% of the cases in GA group. Difference was statistically significant (P < 0.001).
In SA group, 19.4% of the neonates were shifted to neonatal ICU as compared to 46.2% of the cases in GA group. Difference was statistically significant.
In SA group, 3.0% of the neonates had required ventilatory support as compared to 15.4% (7.7% died and 7.7% recovered) of the cases in GA group [Table 2 and Graph 3 ].
Table 2: Comparison of neonatal outcome
Graph 3: Comparison of neonatal outcome
Mean Apgar score at 1 min after birth was significantly less in GA group as compared to in SA group (P < 0.001). Same was the case with Apgar scores at 5 min after birth (P < 0.001) [Table 3 and Graph 4 ].
Table 3: Comparison of mean Apgar score
Graph 4: Comparison of mean Apgar score
Thereafter, 15.4% of the cases in GA group showed <7 Apgar score at 1 min after birth as compared to 1.5% of the in SA group, but the difference was not statistically significant (P > 0.05). Same trend were observed at 5 min also [Table 4 and Graph 5 ].
Table 4: Comparison of Apgar score<7
Graph 5: Comparison of Apgar score less than 7
DISCUSSION
Preeclampsia is defined as a SBP of 140 mmHg or greater or a DBP of 90 mmHg or greater on two or more occasions at least 4 h apart with proteinuria (1+ or more on urine dip stick or greater than 300 mg protein in a 24-h urine specimen) or, alternatively, there is a protein/creatinine ratio of at least 0.3 occurring after 20 weeks of gestation.[ 7 ] Preeclampsia is a two-stage disorder. The asymptomatic first stage occurs early in pregnancy with impaired remodeling of the spiral arteries (the end branches of the uterine artery that supply the placenta). The symptomatic second stage of preeclampsia is marked by widespread endothelial activation/dysfunction. This may present as severe preeclampsia with one or more of the following features: (1) SBP ≥160 mmHg or DBP ≥10 mmHg on two or more occasions, at 6 h apart; (2) proteinuria of at least 5 g in 24 h or 3+ or greater on dipstick; (3) oliguria <500 ml in 24 h; (4) pulmonary edema; (5) liver function impairment, epigastric pain, (6) visual disturbances (photophobia, diplopia, blurred vision); (7) cerebral disturbances (drowsiness, altered sensorium); (8) decreased platelet count and HELLP syndrome, and (9) intrauterine growth retardation.[ 3 , 4 ]
In India, the incidence of preeclampsia is 7.6% during pregnancy of which 3.3% is severe preeclampsia and delivery of the infant and placenta is the only effective treatment. Women with preeclampsia have an increased rate of cesarean section delivery consequent upon the high incidence of intrauterine growth restriction, fetal distress, and prematurity.[ 7 , 8 ] Cesarean section, on the other hand, increases the risk of cardiopulmonary morbidity associated with preeclampsia.[ 9 ] The anesthesia modality does influence the fetal and maternal outcome. We conducted a prospective, randomized, observational clinical study in 80 preeclamptic patients who underwent cesarean section to study the type of anesthesia (GA vs. SA) and its effect on maternal as well as fetal outcome and well-being.
Demographic data including the gestational age were comparable in the two groups similar to Keerath and Cronje, Ramanathan et al. , Wallace et al. , and Chattopadhyay et al .[ 1 , 10–12 ]
Although baseline and mean SBP was comparable, the lowest as well as the highest intraoperative SBP was significantly higher in the GA group. Similar findings were noted by Keerath and Cronje and Jain et al .[ 1 , 13 ] Chattopadhyay et al . found SBP comparable in the two groups.[ 12 ]
The mean DBP at baseline, mean lowest intraoperative DBP, and mean highest intraoperative DBP were compared in the two groups (GA vs. SA), and the difference was statistically significant. Similarly, Keerath and Cronje found mean lowest intraoperative DBP higher in GA group, but the difference was not significant.[ 1 ] The same was observed by Chattopadhyay et al .[ 12 ]
We found fall in MAP to be comparable in the two groups. These findings were similar to Keerath and Cronje.[ 1 ] Ramanathan et al . noted significant difference in MAP at skin incision and postpartum period in the two groups.[ 10 ]
Hood and Curry, Visalyaputra et al. , and Berends et al . found comparable hemodynamics in patients who received SA versus those who received epidural anesthesia.[ 14–16 ] Ramkumar and Sharma compared visual analog scale scores and hemodynamics in three groups that is those receiving GA, SA, and epidural anesthesia. They concluded that pain relief was better in the epidural group, but hypotension was more common in the SA group. However, this hypotension was transient and easily treatable.[ 17 ]
Changes in the HR were comparable in our study. Jain et al . found significantly higher HR in the GA group from induction up to 7 min thereafter.[ 13 ]
Dyer et al . studied hemodynamic responses to SA for cesarean delivery in patients with severe preeclampsia. Cardiac output was measured using lithium dilution technique which remained stable from induction of SA until the time of request for analgesia although MAP and systemic vascular resistance decreased significantly from the time of adoption of the supine position until the end of surgery. They concluded that SA in severe preeclampsia was associated with clinically insignificant changes in cardiac output.[ 5 ]
Thus, we can explain the fall in the blood pressure (SBP and DBP) could be related to sympathetic blockade produced by SA and exaggerated in pregnant patients due to aortocaval compression in the third trimester. However, the fall in the blood pressure in the SA group was never severe and could be managed by IV fluids and vasopressors.
Similarly, Alemayehu et al . studied hemodynamics in preeclamptics versus nonpreeclamptics and concluded that hypotension was less severe in the preeclamptic group following SA.[ 18 ]
Significantly higher number of patients in the SA group (31.3%) required ephedrine compared to GA group (0%). This was similar to the findings by Keerath and Cronje, Chattopadhyay et al. , and Dyer et al .[ 1 , 12 , 19 ]
In our study, blood products were used only in one patient of the GA group who had HELLP syndrome. Colloid requirement was also higher in GA group (7.7%) as compared to SA group (3.0%). Difference was not statistically significant. This was similar to Dyer et al . and Keerath and Cronje.[ 1 , 19 ]
Significantly higher proportion of cases in the GA group required ICU care as against none in the SA group. These findings were consistent with Chattopadhyay et al . and Okafor and Okezie.[ 12 , 20 ] Keerath and Cronje and Ajuzieogu et al . found no significant differences in maternal morbidity and mortality between the SA and GA groups.[ 1 , 21 ]
Hood and Curry, Visalyaputra et al. , and Berends et al . found comparable fetal outcomes in patients who received SA versus those who received epidural anesthesia.[ 14–16 ]
In our study, 77.6% of the cases in SA group showed uneventful neonatal outcome which was statistically significant as compared to 30.7% of the cases in GA group. Furthermore, Apgar scores were significantly higher in the SA group.
Similar finding were noted by Keerath and Cronje, who found significantly more proportion of babies with lower Apgar scores and higher proportion of neonatal morbidity in the GA group.[ 1 ] Chattopadhyay et al . and Okafor and Okezie found poor neonatal outcome (resuscitation or mortality) was associated with GA.[ 12 , 20 ]
Wallace et al . found neonatal outcomes to be similar in both groups as assessed by Apgar scores and umbilical arterial blood gas determinations.[ 11 ]
Aya et al . found that 5 min Apgar scores were similar in both groups, but 1 min Apgar scores were lower in severe preeclamptic group, which may be due to low body weight and low gestational age of newborns in this group.[ 22 ]
Ajuzieogu et al . found no significant difference between the two groups in perinatal mortality, but there was significantly higher proportion of birth asphyxia in babies of women who received GA.[ 21 ]
Dyer et al . compared SA versus GA in patients with preeclampsia presenting for emergency cesarean section with a nonreassuring fetal HR. Lower neonatal umbilical artery pH and greater base deficit were found in the spinal group. GA group was found to have lower apgar scores at 1 min.Whereas no difference was found in the no of babies with umbilical artery PH of less than 7.2 or Apgar of less than 7 at 1 and 5 min. There was no difference in the two groups with regards to need for resuscitation.[ 19 ]
Levy et al . found that neonates exposed to GA were more likely to be intubated and had lower mean 1-min (4.0 vs. 7.0) and 5-min (6.5 vs. 8.4) Apgar scores than those in all other anesthetic groups. They also had significantly lower umbilical artery pH values than neonates who received epidural or no anesthesia.[ 23 ]
Dasgupta et al . also confirmed that babies of mothers who received GA required resuscitation at birth more commonly than those who received SA. However, the 5-min APGAR scores were comparable in both the groups.[ 24 ]
Hood and Curry, Visalyaputra et al. , and Berends et al . found comparable neonatal outcomes in patients who received SA versus those who received epidural anesthesia.[ 14–16 ]
In our study, lower Apgar scores in babies to mothers who received GA (n = 13) cannot solely be attributed to placental transfer of GA agents. The other contributing factors could be because either more proportion of the mothers was sicker or the fetus was compromised in the GA group. Two patients had HELLP syndrome in the GA group as compared to none in the SA group. Proportion of patients who had fetal distress was significantly more in the GA group (30.7%) as compared to SA group (5.9%). Another factor contributing to fetal outcome may be the pathophysiology of preeclampsia causing fetomaternal compromise.
In our study, there was no maternal mortality in both SA and GA groups.
Ramanathan et al . found that MAP and middle cerebral artery flow velocity (Vm) significantly increased after rapid sequence induction of GA and tracheal intubation in women with severe preeclampsia. They found a direct relationship between MAP and Vm.[ 6 ]
Moodley et al . found that around 14% maternal death was due to hypertensive disorders of pregnancy.[ 25 ]
Berhan and Endeshaw found that the case fatality rate of hypertensive disorder of pregnancy was among the highest in the world and a delay in initiation of treatment because of delay in healthcare-seeking contributed to the majority of maternal deaths.[ 26 ] Hawkins et al . found the out of all maternal death, 18% was related to pregnancy-induced hypertension and 3% was anesthesia-related deaths.[ 27 ]
Further, Izci et al. , Spencer, and Munnur and Suresh concluded airway changes related to pregnancy increased chances of unanticipated difficult intubation.[ 28–30 ] Further. Sharwood-Smith et al. , Ramkumar and Sharma, and Leslie and Collis reiterated the fact that regional anesthesia is the preferred choice for cesarean section.[ 3 , 17 , 31 ]
CONCLUSION
In our study, the SA group had favorable maternal outcome as compared to GA group. Hypotension occurred more frequently during SA but could be successfully managed with titrated doses of IV vasopressor drugs such as ephedrine or phenylephrine. The neonatal outcome and Apgar score were poorer in GA group but cannot exclusively be attributed to the choice of anesthesia.
It can thus be concluded from our study that, SA is the preferred anesthetic choice as compared to GA in patients with preeclampsia undergoing cesarean section delivery, unless it is contraindicated.
Limitations
Our study was however limited by the number of cases. The unequal distribution of sample size in the two groups decreases the power of the study, which decreases the chances of detecting significant difference between the two groups. In addition, no long-term follow-up could be kept.
Financial support and sponsorship
Department of Anaesthesia, LTMMC and LTMGH, Sion, supported the study.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
We would like to acknowledge Department of Anaesthesia, LTMMC and LTMGH, Sion.
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