Anesthesia for cesarean delivery: general or regional anesthesia—a systematic review

General anesthesia and regional anesthesia are the anesthetic techniques of choice for cesarean delivery. These anesthetic techniques have their effects on both the fetus and mother. The choice of anesthetic techniques for cesarean delivery depends on several factors including physiological presentation of the patient, experience level of the practitioner, availability of drugs, and equipment, among others. However, whichever technique is used is chosen because of its safety profile and benefit to both mother and fetus. Therefore, this study aimed to compare the effects of general anesthesia against regional anesthesia on fetal and maternal outcomes for cesarean delivery. Search methods were conducted on PubMed, Scopus, Embase, and Cochrane library to identify eligible studies using the keywords, MeSH terms, and filters. Two review authors independently assessed the included studies for quality, bias, and accuracy. A total of fourteen (14) studies (1924 women) contributed data for this review. Findings showed that the 1st and 5th minute Apgar scores were higher in regional anesthesia than in general anesthesia while the 1st minute Apgar scores < 7 were more in general anesthesia. On the other hand, fetal umbilical arterial blood pH was lower in regional anesthesia. Also, intraoperative hypotension was more in regional anesthesia while heart rate and estimated blood loss significantly higher in general anesthesia. In conclusion, regional anesthesia emerges as a better option evidenced by its better fetal and maternal outcomes. However, both regional anesthesia and general anesthesia are still used for cesarean delivery.


Background
Cesarean delivery can be performed as either elective or as an emergency. Globally, there is an increasing proportion of women giving birth by cesarean delivery in both developed and developing countries which is either done by the woman's request or as a result of complications (Ghaffari et al. 2018). The rate of cesarean delivery in the USA is reported to be around 30% of all live births and 25-30% in Columbia (Páez and Navarro 2012). Also, it has been reported by Little et al. (Little et al. 2016) that the USA has a higher rate of cesarean delivery around 65%. An essential step in the choice of anesthetic technique for cesarean delivery is the safety and health benefits to the mother and fetus. With the advancement of anesthesia techniques, operations have become safer and secured over the years, but significant maternal and fetal mortality and morbidity (Sumikura et al. 2016) do exist. Anesthesia for cesarean delivery can be achieved either through general anesthesia (GA) or regional anesthesia (RA) such as spinal anesthesia (SA), epidural anesthesia (EA), or combined spinal-epidural anesthesia (CSE).
Regional anesthesia especially spinal anesthesia has been favored as the best choice for elective uncomplicated cesarean delivery due to its avoidance of the airway, less risk of aspiration of gastric content, and easy to perform (Shibli and Russell 2000;Kim et al. 2019). Regional anesthesia is safe and effective, but it does have complications such as hypotension, local anesthetic toxicity, post-dural puncture headache (PDPH), and nerve damage (Bakri et al. 2015;Bloom et al. 2005;Afolabi and Lesi 2012;Aregawi et al. 2018). However, general anesthesia is still used especially when regional anesthesia is contraindicated or failed. Advantages of general anesthesia include maintained patent airway, controlled ventilation, and less cardiovascular depression (Devroe et al. 2015). Complications such as failed intubation, failed ventilation, aspiration of gastric content, awareness, pain, and fetal depression (Yehuda Ginosar et al. 2013) are common in GA.
The essence of anesthesia for cesarean delivery is the safe delivery of the fetus and less or no complication to the mother. Therefore, it is important to compare both fetal and maternal outcomes associated with regional anesthesia and general anesthesia.
Several studies have made the attempt to compare fetal outcomes (1st and 5th minute Apgar scores, arterial blood pH) (Kolås et al. 2007;Sabol and Caughey 2016) and maternal outcomes (blood loss, blood pressure and heart rate, analgesia use and requirements) (Kimber Craig 2019). Two studies reported no difference in the 5th minute Apgar score between regional anesthesia and general anesthesia but concluded by stating that no sufficient evidence exists to prove that regional anesthesia stands superior to general anesthesia (Kim et al. 2019;Afolabi and Lesi 2012). However, other studies have reported that regional anesthesia is superior to general anesthesia in terms of fetal Apgar score and umbilical arterial blood pH (Kim et al. 2019;Nguyen-Lu et al. 2016).

Aim of the study
The aim of this systematic review was to compare the effects of general anesthesia with regional anesthesia on fetal and maternal outcomes for cesarean delivery. The fetal outcome variables were 1st and 5th minute Apgar scores and umbilical arterial blood pH while the maternal outcome variables were blood loss, blood pressure and heart rate, and analgesia requirement.

Material and method
A systematic review study was conducted. A search strategy was used to search on PubMed, Embase, Scopus, and Cochrane using keywords, MeSH terms, and filters as shown in Table 1. Randomized clinical trials and observational studies that compared the effects of general anesthesia and regional anesthesia on maternal and fetal outcomes during cesarean delivery were included. The included studies were reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). All the included studies were subjectively and independently assessed for risk of biases ( All included studies were assigned a judgment of "high," "low," or "unclear" risk of bias across the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Disagreements were resolved by a discussion between the two assessors and a third outside assessor (SWJ), who provided arbitration. Data extraction was independently done by the authors, and discrepancies were resolved through a consensus discussion.

Study selection
The search results and reasons for exclusion from the study are shown in Fig. 2. Initially, we screened a total of 2538 articles from PubMed, Embase, Scopus, and Cochrane. We had 476 duplicated studies removed, and  2003 articles not meeting the inclusion criteria were also excluded. The remaining 59 studies' full text was reviewed, and 45 studies were excluded due to the method and study design used. Finally, 14 randomized controlled trials and observational studies comparing general anesthesia and regional anesthesia were included.

Results
The 1st minute fetal Apgar scores between combined spinal-epidural and general anesthesia showed no significant difference (8.98 ± 0.89, 9.01 ± 0.98, P value 0.863) (Chen et al. 2019;Abdallah et al. 2014). However, the 1st minute Apgar scores of fetuses born to mothers exposed to spinal anesthesia were higher than those exposed to general anesthesia (7.5 ± 1.7, 6.3 ± 1.12, P < 0.005) (Saygi et al. 2015;Solangi et al. 2012;Açıkel et al. 2017;Madkour et al. 2019;Edipoglu et al. 2018;Abdallah et al. 2014;Havas et al. 2013). This showed that babies who were recorded to have lower fetal Apgar scores were likely to be resuscitated or kept under close monitoring. Again, the number of babies with 1st minute Apgar scores < 7 was higher in general anesthesia, followed by spinal anesthesia which was converted to general anesthesia and spinal anesthesia as the least. Also, the median 5th minute Apgar scores > 7 were higher in spinal anesthesia followed by spinal anesthesia converted to general anesthesia and least in general anesthesia (Madkour et al. 2019).
No difference was found in the 5th minute Apgar scores comparing between regional anesthesia and general anesthesia, but the former had a better score (Chen et al. 2019;Abdallah et al. 2014;Havas et al. 2013). Also, there was no difference between low-dose spinal and general anesthesia with regard to the 1st and 5th minute Apgar scores (Jain et al. 2013).
Regarding fetal umbilical arterial blood pH, only one of our included studies found a significant difference between regional anesthesia and general anesthesia. Umbilical arterial blood pH was lower (acidic) in regional anesthesia than in general anesthesia (pH 7.23 ± 0.06 and 7.27 ± 0.04, respectively) (Jain et al. 2013).
As part of the standard anesthesia protocols, blood pressure and heart rate are always monitored during surgeries. There were no significant changes in the blood pressure and heart rate during the preoperative period (Jain et al. 2013;Chen et al. 2019;Edipoglu et al. 2018;Abdallah et al. 2014). However, intraoperative hypotension was more in regional anesthesia (Jain et al. 2013;Chen et al. 2019;Saygi et al. 2015;Arslantas and Umuroglu 2019;Abdallah et al. 2014;Havas et al. 2013). Also, higher heart rates were recorded in general anesthesia than in regional anesthesia (Jain et al. 2013;Chen et al. 2019;Madkour et al. 2019;Edipoglu et al. 2018). With hypotension recorded in regional anesthesia, more intravenous fluids were used than in general anesthesia (Havas et al. 2013) to prevent or reduce the hypotension. Again, the use of vasopressors like ephedrine (Staikou et al. 2013;Havas et al. 2013) and phenylephrine (Jain et al. 2013) to treat hypotension was higher (range 0-50 mg against 0-10 mg) in regional anesthesia than in general anesthesia.
Furthermore, there was a higher intraoperative analgesia requirement (2 μg/kg versus 20 μg of fentanyl) in general anesthesia (Kessous et al. 2012) while the first postoperative analgesia requirement time was recorded to be longer in regional anesthesia (Saygi et al. 2015;Madkour et al. 2019;Saracoglu et al. 2012;Arslantas and Umuroglu 2019). For instance, the first postoperative analgesia requirement time in regional anesthesia was recorded to be 320 min, against 175 min in general anesthesia. This supports the high quantity of total fentanyl use in general anesthesia than in regional anesthesia (638 mcg fentanyl against 320 mcg fentanyl, respectively) (Saracoglu et al. 2012). Also, blood loss recorded was more (about 400 ml) in general anesthesia (Chen et al. 2019) but did not have any significant effect on the rate of blood transfusion. Return of bowel sounds  and gas discharge took a longer time (9.7 ± 1.3, 6.8 ± 1.6 h, P = 0.001) in general anesthesia (Saygi et al. 2015;Madkour et al. 2019) while the first postoperative urine output was more in regional anesthesia (Madkour et al. 2019). Also, patients were more satisfied with regional anesthesia (Açıkel et al. 2017;Saracoglu et al. 2012) during cesarean delivery and would choose it again if the need arises. Contrary to this, one of our included studies showed that postoperative patient satisfaction was higher in general anesthesia (Chen et al. 2019).

Discussion
Similar to our findings, Dyer et al. (Dyer et al. 2003) in their study showed higher 1st minute Apgar scores in spinal anesthesia than in general anesthesia with the 1st minute Apgar scores < 7 recorded more in general anesthesia. Also, no significant difference in the 1st and 5th minute Apgar scores was found, but higher 1st and 5th minute Apgar scores were recorded in regional anesthesia (Harazim et al. 2019;Shek et al. 2012). It is clearly understood as to why fetal asphyxia, fetal distress, depression, and resuscitation were recorded less in regional anesthesia as the babies were born very active. Caglar et al. (Caglar et al. 2013) in their study did not find much difference in umbilical arterial blood pH, but our findings showed a lower umbilical artery blood pH (acidic) in regional anesthesia than in general anesthesia. This did not have any significant effect on the baby because no cyanosis, body color change, or respiratory distress, although no further investigations were carried out to find the course of low umbilical arterial blood pH.
As part of the maternal outcome, our findings did not show any significant difference in blood loss between regional anesthesia and general anesthesia. Therefore, patients who have regional anesthesia for cesarean delivery are less likely to receive a blood transfusion, unless there is an underlying condition or complications which may either occur before or after the procedure. Aksoy et al. in their study demonstrated that regional anesthesia was associated with less risk of operative blood loss and transfusion. However, in low-risk patients, four patients (2%) under general anesthesia received nine units of blood transfusion (Aksoy et al. 2015). Khan et al. (Khan et al. 2019) stated that hypotension was common in spinal and epidural anesthesia. Similar to our findings, severe intraoperative hypotension was higher in regional anesthesia. Aregawi et al. (Aregawi et al. 2018) stated that the vasodilation and venous pooling effects of the local anesthetic drugs used for regional anesthesia resulted in severe hypotension. Hypotension was treated with intravenous fluids, phenylephrine (Nguyen-Lu et al. 2016), and ephedrine (Bakri et al. 2015;Dyer et al. 2003). However, Kim et al. (Kim et al. 2019) stated that fetal umbilical arterial blood pH was adversely affected by the use of ephedrine. This explains why babies whose mothers had received greater ephedrine were found to have low umbilical arterial blood pH (acidic).
Furthermore, the first postoperative analgesia requirement time was longer in regional anesthesia while the postoperative total analgesia consumption was higher in general anesthesia which is in congruent with the other studies (Páez and Navarro 2012;Bakri et al. 2015;Afolabi and Lesi 2012). Patients were more satisfied with regional anesthesia as they could see the surgery being done and hear the cry of the baby (Páez and Navarro 2012;Bakri et al. 2015) while general anesthesia was associated with discomfort, pain, nausea, and vomiting, among others (Tsen and Kodali 2010).

Limitation of the study
Only randomized clinical trials and observational study methods met the inclusion criteria for this study. Again, the search duration was also limited to studies between 2010 and 2019. Therefore, all these were limitations of the study.

Conclusion
In conclusion, both anesthetic techniques are reliable and well-tolerated for cesarean delivery. However, regional anesthesia emerged as a better option for elective cesarean delivery. Regional anesthesia benefits for maternal and fetal outcome are superior to general anesthesia.