Effects of Preoperative Oral Carbohydrate on Perioperative Maternal Outcomes Undergoing Cesarean Section: A Systematic Review and Meta-Analysis

Purpose Preoperative oral carbohydrate (CHO) is a rapid postoperative rehabilitation protocol that improves perioperative outcomes and is widely used in adult surgical patients. However, pregnant women are excluded because of the possibility of aspiration due to delayed gastric emptying. This meta-analysis was conducted to evaluate the efficacy of preoperative oral CHO in elective cesarean section. Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 2023. Randomized controlled trials were included. The risk of bias was assessed using the Cochrane tool. Risk ratios and 95% confidence intervals were calculated. Meta-analysis was performed using random-effects models to estimate risk ratios and mean differences (MDs) with 95% confidence intervals (CIs). The outcomes included thirst and hunger scores, incidence of vomiting and nausea, time to flatus, and homeostatic model assessment of insulin resistance (HOMA-IR). Results A total of nine studies with 1211 patients were included in the analysis. The levels of thirst and hunger were evaluated using a 10-point visual analog scale, with 0 representing the best and 10 representing the worst. The severity of hunger (weighted mean difference (WMD: −2.34, 95% CI: −3.13 to −1.54), time to flatus (WMD: −3.51 hours, 95% CI: −6.85 to −0.17), and HOMA-IR (WMD: −1.04, 95% CI: −1.31 to −0.77) were significantly lower in the CHO group compared to the control group. However, there were no significant differences in the severity of thirst or the incidence of vomiting and nausea between the CHO and control groups. Conclusion Preoperative oral CHO during cesarean section alleviates thirst and hunger, shortens the time of postoperative flatus, and reduces HOMA-IR. However, the available evidence is insufficient to reach a clear consensus on the benefits or harms of preoperative oral CHO during cesarean section. Therefore, it is premature to make a definitive recommendation for or against its routine use.


Introduction
Pulmonary aspiration of gastric contents is a rare but potentially life-threatening complication, with 57% of aspiration events resulting in death and another 14% resulting in permanent serious injury [1].Pregnancy increases the risk of pulmonary aspiration during anesthesia and surgery due to decreased lower esophageal sphincter tone and delayed gastric emptying, so preoperative fasting has been recommended to minimize gastric contents [2,3].However, prolonged fasting before surgery may have adverse efects such as hunger, thirst, dry mouth, fatigue, anxiety, and postoperative insulin resistance [4].
Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway designed to achieve early recovery for patients undergoing major surgery and has been widely adopted in various settings [5][6][7].Shortening preoperative fasting time and preoperative oral carbohydrate consumption are the core recommendations of ERAS for patients undergoing elective surgery [8].Preoperative administration of oral carbohydrates is recognized for its ability to reduce metabolic stress and insulin resistance after surgery, leading to shorter hospital stays and improved wellbeing in patients undergoing abdominal, orthopedic, and cardiac surgery [9][10][11][12].However, compared to the practice of fasting at midnight, preoperative oral carbohydrate intake does not appear to improve patient satisfaction or well-being in individuals undergoing thyroidectomy [13].
Recently, several randomized controlled trials (RCTs) have shown that patients undergoing elective cesarean section who consumed carbohydrate solutions had fewer postoperative side efects and complications than those who fasted or received a placebo [14][15][16][17][18][19][20][21].Tis approach has also been shown to be safe and feasible in patients with gestational diabetes mellitus (GDM) [22].In addition, both a standard oral rehydration solution and a highcarbohydrate drink consumed prior to surgery have been shown to provide superior comfort compared to fasting [23].However, it is important to note that the sample size of each study was relatively small, limiting the reliability of the results, and no meta-analysis has been performed.In order to assess the impact and safety of preoperative oral carbohydrate intake in pregnant women who are scheduled for cesarean section, we decided to conduct an extensive systematic review and meta-analysis.

Material and Methods
In this study, we followed the guidelines set forth in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [24].Tis ensures that our research is conducted and reported in a transparent and comprehensive manner.Moreover, it was duly registered with the International Prospective Register of Systematic Reviews under the registration number CRD42020177211.

Search Strategy.
A methodical screening approach was implemented to identify pertinent literature in PubMed, Web of Science, Embase, and the Cochrane Library from the time of their establishment until July 2023.Te exploration strategy encompassed Medical Subject Headings (MeSH) terms: "carbohydrates," "dietary carbohydrates," "cesarean section," and "randomized controlled trial."Supplementary Appendix A provided additional terms for inclusion.Te National Library of Medicine's primary screening queries were monitored on a weekly basis until September 1, 2023, but no relevant fndings were discovered.Bibliographies of chosen articles were also assessed to identify eligible trials.

Study Selection
Criteria.Tis review included peerreviewed RCTs, with or without blinding.Inclusion criteria were as follows: (1) pregnant women undergoing elective cesarean section, (2) oral carbohydrate intervention before surgery, (3) one or more of the following outcomes: thirst, hunger, nausea, vomiting, HOMA-IR (homeostatic model assessment for insulin resistance), and time to fatus, and (4) RCT design.Exclusion criteria were (1) studies with missing data.No RCTs were excluded based on factors such as the defnition of intervention allocation or primary and secondary outcomes.

Data Extraction.
Before the review process began, an independent reviewer (BZ) prepared a standardized data extraction form.Following that, the required data from the included articles were independently extracted by two authors (HBS and CHZ).Tis extracted data included information such as the names of authors, publication year, country, type of anesthesia, number of patients, intervention and comparison groups, and outcomes.In case of any conficts during the data extraction process, a third author (BZ) resolved them.

Study Quality Assessment. Two authors (HBS and CHZ)
independently assessed the selected studies using the Cochrane risk-of-bias tool to determine their risk of bias and methodological quality [25].Te risk of bias was evaluated across seven domains, including selective reporting, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, random sequence generation, and other biases.Each study was categorized as having a low, high, or unclear risk of bias.In cases of disagreement, consensus was reached by involving another author (BZ).

Statistical Analysis.
Data processing was conducted using Review Manager Ver.5.3 (Copenhagen, Nordic Cochrane Centre, Cochrane Collaboration, 2014).Te Mantel-Haenszel test for random efects was used for data analysis.Risk ratios (RRs) with 95% confdence intervals (CIs) were reported for dichotomous outcomes.For continuous outcomes, weighted mean diferences (WMDs) were reported.Statistical signifcance was defned as a p value of ≤0.05.
We used the I 2 test to assess the heterogeneity of the articles.If I 2 was <50% and p was >0.1, heterogeneity between studies was considered low.Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), in which fasting blood insulin and glucose levels were measured according to the HOMA-IR formula.In cases where a randomized controlled trial (RCT) had an excess of two treatment arms, all pertinent information was incorporated.Subgroup meta-analyses were performed based on the control strategy used in the trials, which could be either placebo or fasting.Subgroup metaanalyses were conducted, taking into account the control strategy utilized in the trials, which might consist of either placebo or fasting.

Search Results
. A total of 4400 papers were identifed through a comprehensive search on various databases, including PubMed (n � 805), Web of Science (n � 1445), Embase (n � 1193), and the Cochrane Library (n � 957).After eliminating any duplicated papers, we proceeded to assess a total of 3269 articles for their suitability.Out of these, 3251 articles were excluded based on a thorough examination of their titles and abstracts.Te remaining 18 studies underwent a detailed review of their full texts, 2 Anesthesiology Research and Practice resulting in the exclusion of 5 studies due to inconsistency and 4 studies due to intervention mismatch with our research.Ultimately, we identifed 9 eligible randomized controlled trials (RCTs) for our analysis.Te fow diagram illustrating the PRISMA study process can be found in Figure 1.
Outcomes included thirst and hunger scores, incidence of vomiting and nausea, time to fatus, and insulin resistance.

Risk-of-Bias
Assessment.Te quality of the studies included in this analysis was evaluated using the Cochrane risk of bias tool.Out of the nine studies examined, eight [15][16][17][19][20][21][22][23] of them were found to be double-blind, indicating a low risk of performance and detection bias.However, fve studies [17,18,20,21,23] were considered with an unclear information on allocation concealment and random sequence generation.In addition, one study [23] excluded 40% of patients in the CHO group and 31.8% of patients in the fasting group due to loss to follow-up and discontinuation of the intervention, resulting in a high risk of attrition bias.Te quality of a study increased along with the higher number of low risks (green pluses) of bias assessments.Another study [16] that used a sponsored carbohydrate was also considered with an unclear information.Figure 2 presents the outcomes of the bias evaluation for each individual study.

Tirst.
Five studies [16,19,20,22,23] involving 480 patients compared the preoperative thirst levels between the groups receiving CHO and the control groups.Tirst levels were measured using the Visual Analog Scale (VAS), which ranges from 0 to 10, with 0 indicating no thirst and 10 indicating the highest level of thirst.Among the fve control groups, four [16,19,20,22] used water and one [23] used a low concentration of CHO.In addition to comparing CHO with water or low CHO concentration, three [19,20,23] of the studies also compared CHO with fasting.Subgroup analysis was performed according to whether the control group was placebo or fasting.In summary, the pooled results revealed no signifcant diference between CHO and placebo.However, it was observed that the CHO group showed a signifcant decrease in thirst levels, as compared to the fasting group (WMD: −3.55, 95% CI: −5.29 to −1.81) (Figure 3).Furthermore, one study [19] reported that preoperative oral CHO or water before surgery can quench thirst with a VAS score of 0.

Vomiting and Nausea.
Tree [15,19,21] studies involving a total of 319 patients were conducted to compare the incidence of vomiting between the CHO and control groups.Te pooled result of these studies revealed that CHO did not have a signifcant impact on the incidence of vomiting compared to water (RR � 0.70; 95% CI: 0.28 to 1.77) or fasting (RR � 0.46; 95% CI: 0.20 to 1.09).Te overall outcome indicated that preoperative oral CHO did not result in a signifcant diference in the incidence of vomiting compared to the control group (RR � 0.56; 95% CI: 0.30 to 1.05).Similarly, in three [19,21,22] studies involving 291 patients, the incidence of nausea was compared between the CHO and control groups.Te pooled result for nausea revealed that CHO did not afect the incidence of nausea compared to water (RR � 0.59; 95% CI: 0. Anesthesiology Research and Practice indicated that preoperative oral CHO did not result in a signifcant diference in the incidence of nausea compared to the control group (RR � 0.51; 95% CI: 0.22 to 1.16) (Figure 5).

Time to Flatus.
Tree studies [15,19,22] involving 286 patients compared the time to return of fatus after cesarean section between the CHO and control groups.Te pooled result indicated that CHO did not signifcantly alter the time to fatus compared to water (WMD: −2.84 hours, 95% CI: −9.26 to 3.58).However, the pooled result demonstrated a signifcantly shorter time to fatus in the CHO group compared to the fasting group (WMD: −3.89, 95% CI: −7.48 to −0.30).Overall, the fndings demonstrated that preoperative oral CHO led to a shorter time to fatus compared to the control group (WMD: −3.51, 95% CI: −6.85 to −0.17) (Figure 6).

Zohreh Ghorashi 2014
Figure 2: Risk-of-bias summary of the included studies.A green "+" indicates that the quality element was met, a red "−" indicates that the element was not met, and a yellow "?" indicates that it was uncertain whether the element was met.
6 Anesthesiology Research and Practice groups and controls.In one study [18], the CHO group received 150 mL of 10% CHO orally 1 hour before induction of general anesthesia, while the control group was fasted.In another study [23], the CHO group received 355 mL of 14% CHO orally 2 to 4 hours before induction of spinal anesthesia, while the control group received 355 mL of 5.9% CHO or fasted.Also, no patient in any group experienced gastric aspiration.
3.9.3.Apgar Score.Two studies [19,23] involving 135 patients, respectively, reported Apgar scores at 1 and 5 minutes after birth.One study [23] showed that there was no Apgar score less than 7 at 5 minutes after birth.Also, another study [19] showed that the 1-minute Apgar scores were all 10 in both the CHO and control groups.

Discussion
Tis meta-analysis consisted of nine RCTs that systematically evaluated the efects of oral carbohydrate intake on perioperative maternal outcomes following cesarean section.Preoperative oral CHO undergoing cesarean section signifcantly alleviated thirst and hunger, shortened time to fatus and colostrum, and reduced postoperative insulin resistance compared with the fasting group, while there was no diference in the incidence of nausea, vomiting, and aspiration.In addition, oral CHO could signifcantly alleviate hunger and reduce postoperative insulin resistance compared with the water group.Terefore, oral administration of CHO before cesarean section appears to be a feasible procedure to minimize patient discomfort without additional risk.
Preoperative fasting has become a standard procedure due to the risk of anesthesia-related aspiration [26][27][28].However, fasting can lead to patient discomfort and increase insulin resistance.[29].One meta-analysis found that preoperative CHO loading may reduce patient discomfort in several elective procedures, including cesarean delivery, without safety concerns [30].Conversely, another metaanalysis concluded that there is insufcient evidence to support the claim that preoperative CHO administration    reduces patient discomfort.Nevertheless, preoperative CHO loading has been associated with postoperative insulin resistance and the incidence of postoperative infection [31].
Our review included nine RCTs with 1211 participants.Two [18,23] of these RCTs with 458 patients reported the incidence of aspiration in both the CHO groups and the control groups undergoing cesarean section.With oral 150 mL of 10% CHO 1 hour before induction of general anesthesia or oral 355 mL of 14% CHO 2 to 4 hours before induction of spinal anesthesia, no patient in either group experienced gastric aspiration.Two [19,20] studies involving 163 patients showed that preoperative oral CHO reduced insulin resistance compared with controls.Preoperative administration of CHO may minimize patient discomfort and did not increase the risk of aspiration.Te efects of this intervention may be infuenced by the inclusion of nine studies with varying amounts and concentrations of CHO consumed.Te concentrations of CHO used in the nine studies varied from 5.9% to 14.2%, and patients were given 300 to 400 mL of these CHO 2 hours before surgery.Tis was found to have no adverse efect on patient safety compared with fasting after midnight.In addition, a study [18] of 411 patients found that ingestion of 150 mL of a 10% CHO solution 1 hour before surgery did not result in aspiration in patients under general anesthesia.Terefore, a regimen of 300 to 400 mL of 5.9% to 14.2% CHO 2 hours before anesthesia is safely recommended instead of fasting after midnight the night before surgery.In addition, a study [23] comparing 14% and 5.9% CHO showed that the higher concentration of CHO improved hunger.However, either a low concentration rehydration drink or a high concentration of CHO consumed preoperatively resulted in superior comfort compared to fasting.Two studies [15,17] compared the time to colostrum after surgery and found that   Total (95% CI) Heterogeneity: tau 2 = 0.05; chi 2 = 8.60, df = 3 (P = 0.04); I 2 = 65% Test for overall effect: Z = 7.56 (P < 0.00001) Test for subgroup differences: chi 2 = 0.08.df = 1 (P = 0.78).I 2 = 0% Favours (control)  Anesthesiology Research and Practice the OCH group had a signifcantly shorter time compared to the water or fasting groups.It is worth noting that there is a signifcant diference in the mean time between the two groups, which may be due to racial diferences, and more research is needed to confrm this.Te study has some limitations that should be considered.First, it is important to note that the methods of anesthesia used in the included studies varied.While eight studies utilized intraspinal anesthesia, only one study used general anesthesia.Tis diference in anesthesia methods may potentially afect the incidence of aspiration.Second, there is a paucity of studies examining various observational indicators, such as colostrum secretion time and Apgar score.Terefore, more research in these areas is still necessary.Finally, it is worth mentioning that the concentration and dose of carbohydrates in the studies were inconsistent, leading to signifcant heterogeneity.As a result, the determination of the optimal concentration and dose remains uncertain.

Conclusion
In conclusion, preoperative CHO intake alleviated patient discomfort as assessed by thirst, hunger, incidence of vomiting and nausea, insulin resistance, and time to fatus.Due to the low cost and convenience of CHO, preoperative CHO is feasible as a strategy to improve postoperative recovery.However, for the few studies, whether it is used as a routine operation of cesarean section still needs further research.

Figure 4 :
Figure 4: Forest plot showing the mean diference in hunger scores between CHO and control groups in randomized controlled trials of cesarean section.

Figure 5 :
Figure 5: Forest plot showing the incidence of vomiting and nausea between the CHO and control groups.

Figure 6 :
Figure 6: Forest plot showing the mean diference in time to fatus after cesarean section between CHO and control groups.

Figure 7 :
Figure 7: Forest plot showing insulin resistance between CHO and control with HOMA-IR.

Table 1 :
Details of included studies.
18to 1.97) or fasting (RR � 0.44; 95% CI: 0.14 to 1.38).Te overall outcome Figure 1: Flowchart of the literature search and selection of the included randomized controlled trials.
Figure 3: Forest plot showing the mean diference in thirst scores between CHO and control groups in randomized controlled trials of cesarean section.