Effects of Colloid Preload on the Incidence of Hypotension in Spinal Anesthesia for Cesarean Section: A Systematic Review and Meta-Analysis
Cesarean section is one of the most commonly performed surgical procedures worldwide, with rates continuing to rise. In 2016, cesarean section rates were 24.5% in Western Europe, 32% in North America, and 41% in South America. In China, the overall annual rate of cesarean sections increased by 34.9% from 2008 to 2014. The anesthetic management of patients undergoing cesarean section is a significant challenge, particularly due to the high incidence of hypotension associated with spinal anesthesia (SA).
Spinal anesthesia is the preferred method for cesarean section, used in 80% to 90% of cases. However, SA frequently leads to hypotension, with an incidence ranging from 60% to 70%. This hypotension is primarily due to sympathetic nervous system blockade and the supine position of the parturient, which causes the gravid uterus to compress the inferior vena cava, reducing cardiac output and blood pressure. Prolonged hypotension can lead to organ ischemia, cardiovascular collapse, and adverse neonatal outcomes, including hypoxia, acidosis, and reduced Apgar scores. Therefore, maintaining blood pressure during cesarean section is crucial, especially during the perinatal period before fetal delivery.
Various strategies have been explored to prevent and treat hypotension during cesarean section, including fluid infusion, vasopressor administration, and maternal positioning. Among these, fluid infusion has been found to be relatively effective. However, the optimal fluid regimen remains controversial. Colloids and crystalloids are the two main types of fluids used, and they can be administered either before SA (preload) or with SA (coload). Colloids, such as hydroxyethyl starch (HES) and succinylated gelatin, are widely used in surgeries due to their ability to provide rapid volume expansion in the intravascular space. However, the appropriate infusion timing and volume of colloids remain unclear.
This systematic review and meta-analysis aimed to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section. The study also evaluated other hemodynamic variables, maternal outcomes, and neonatal outcomes to provide a comprehensive understanding of the efficacy and safety of colloid preload in this context.
The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered on PROSPERO. A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library from their inception dates to May 2020. The search strategy included keywords such as “colloid,” “preload,” “spinal anesthesia,” and “cesarean section,” along with their synonyms. Only randomized controlled trials (RCTs) published in English were included.
The inclusion criteria were as follows: healthy women with normal term pregnancy receiving elective cesarean section under SA; intervention group receiving colloid preload; control group receiving fluid coload or no preload; primary outcome of intra-operative hypotension and severe hypotension; secondary outcomes including the lowest intra-operative systolic blood pressure (SBP), maximal intra-operative heart rate (HR), intra-operative needs of ephedrine and phenylephrine, incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Studies that applied vasoactive drugs or other treatments continuously from the beginning of anesthesia to the end of the operation were excluded.
Two independent investigators reviewed the titles and abstracts of the identified studies to eliminate irrelevant trials and select potentially relevant publications. Full-text articles were then reviewed to determine eligibility. Data extraction was performed independently by two investigators, and any discrepancies were resolved by a third investigator. The Cochrane Collaboration tool was used to assess the risk of bias in individual studies, with studies classified as “low,” “unclear,” or “high risk” of bias.
Statistical analysis was performed using Review Manager 5.3 (RevMan 5.3). For continuous data, mean difference (MD) with 95% confidence intervals (CIs) was used, while odds ratio (OR) with 95% CIs was used for dichotomous outcomes. A random-effects model was employed, and heterogeneity was assessed using the Chi-squared test and the I² statistic. A P value of less than 0.05 was considered statistically significant.
The literature search identified 152 articles, of which 71 were selected after removing duplicates. After initial evaluation, 61 articles were excluded, leaving 10 articles for full-text review. Ultimately, nine RCTs with a total of 871 patients were included in the meta-analysis. These studies were published between 2001 and 2019 and included participants from China, Japan, the United States, Singapore, Lebanon, India, and Egypt.
The included studies used different types and volumes of colloid preload. Two studies used succinylated gelatin, while the others used HES. The volume of colloid preload varied, with three studies using 15 mL/kg, two studies using 10 mL/kg, and four studies using 500 mL. The control groups received either colloid coload or crystalloid coload, with volumes ranging from 10 mL/kg to 1000 mL.
The primary outcome of intra-operative hypotension was analyzed in eight studies, involving 831 patients. The results showed no significant differences between the colloid preload group and the control group (OR 0.83, 95% CI 0.53 to 1.28, P = 0.39). Similarly, three studies showed no significant differences in the incidence of severe hypotension between the two groups (OR 0.88, 95% CI 0.51 to 1.53, P = 0.66). Subgroup analysis based on the volume of colloid preload revealed that 15 mL/kg colloid preload significantly reduced the incidence of hypotension (OR 0.32, 95% CI 0.13 to 0.77, P = 0.01), while 500 mL and 10 mL/kg did not show significant effects.
Secondary outcomes, including the lowest intra-operative SBP and maximal HR, were analyzed in five and two studies, respectively. No significant differences were found between the colloid preload group and the control group for either outcome. The intra-operative needs of vasoactive agents (ephedrine and phenylephrine) were also analyzed, with no significant differences observed between the two groups.
The incidence of maternal nausea and/or vomiting was reported in six studies, with no significant differences between the colloid preload group and the control group (OR 0.84, 95% CI 0.50 to 1.40, P = 0.50). Neonatal outcomes, including umbilical artery pH and Apgar scores, were analyzed in seven and four studies, respectively. The umbilical artery pH was significantly lower in the colloid preload group (MD = -0.01, 95% CI -0.02 to -0.00, P = 0.04), but this difference was not clinically significant. Apgar scores at 1 min and 5 min after birth were not influenced by colloid preload.
The findings of this meta-analysis suggest that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section, except when a large volume of 15 mL/kg is used. However, the safety of such a large-volume infusion needs further investigation. The study also found no significant differences in other hemodynamic variables, maternal outcomes, or neonatal outcomes between the colloid preload group and the control group.
Several limitations should be considered when interpreting the results of this meta-analysis. First, the lack of blinding in some studies may have introduced selection bias. Second, the differences in the amount and speed of fluid infusion among studies may have influenced the results. Finally, the study did not evaluate long-term outcomes after cesarean delivery, which warrants further investigation.
In conclusion, colloid preload does not reduce the incidence of hypotension in women undergoing elective cesarean section, except when a large volume of 15 mL/kg is used. However, the safety and efficacy of such a large-volume infusion require further study. Given the limitations of the included studies, these conclusions need to be verified through more high-quality research.
doi.org/10.1097/CM9.0000000000001477
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