Perioperative Dextrose Infusion and Postoperative Nausea and Vomiting: A Meta-analysis of Randomized Trials : Anesthesia & Analgesia

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Perioperative Medicine

Perioperative Dextrose Infusion and Postoperative Nausea and Vomiting: A Meta-analysis of Randomized Trials

Zorrilla-Vaca, Andres BS*; Marmolejo-Posso, Diana BS*; Stone, Alexander MD; Li, Jinlei MD; Grant, Michael C. MD§

Author Information
Anesthesia & Analgesia 129(4):p 943-950, October 2019. | DOI: 10.1213/ANE.0000000000004019

Abstract

KEY POINTS

  • Question: Does perioperative dextrose infusion reduce the incidence of postoperative nausea and vomiting?
  • Findings: The use of a perioperative dextrose infusion was not associated with a
  • significant reduction in postoperative nausea and vomiting in the postanesthesia care unit or within 24 h of surgery.
  • Meaning: Perioperative dextrose infusions are not recommended for routine
  • prevention of postoperative nausea and vomiting. Further studies are necessary to verify the impact of perioperative dextrose infusions on severity of postoperative nausea and vomiting and antiemetic administration.

Although advances have been made in postoperative nausea and vomiting prophylaxis, a significant proportion of patients, particularly those with established patient and surgical risk factors, suffer from postoperative nausea and vomiting.1–3 Interval published guidelines provide an algorithm for identification of relevant postoperative nausea and vomiting risk factors as well as selection of appropriate prophylactic and treatment antiemetics.3 Among the described therapies is the concerted use of perioperative crystalloid to ensure adequate resuscitation, which has been shown to be associated with a reduction in both the incidence and severity of postoperative nausea and vomiting.4 More recently, researchers have introduced an additional fluid-related measure in the form of perioperative dextrose infusions. While some studies have reported a significant reduction in postoperative nausea and vomiting incidence and antiemetic requirements through the use of a perioperative dextrose infusion,5–7 results are more conflicted among other trials.8,9 Given the controversy and the potential implications for perioperative postoperative nausea and vomiting management, our group conducted a meta-analysis of published randomized controlled trials to determine the impact of a perioperative dextrose infusion on the incidence of postoperative nausea and vomiting.

METHODS

Search Strategy

The Preferred Reporting Items for Systematic Review and Meta-analyses was used to perform this study and it complied with the recommendations of the Cochrane Collaboration.10,11 The protocol for this review has been registered at the PROSPERO International Prospective Register of Systematic Reviews (CRD42018084477). A systematic search was performed of medical literature repositories, including MEDLINE/PubMed (from 1950 to February 2018), Google Scholar (from 1960 to February 2018), Embase (from 1980 to February 2018), and Cochrane Library (from 1990 to February 2018). Search terms included “dextrose,” “carbohydrate solution,” “postoperative nausea and vomiting,” “nausea,” and “vomiting.” Inclusion criteria included: (1) population: studies involving adult (age >18 years) human subjects undergoing elective surgery under general anesthesia; (2) intervention: perioperative dextrose infusion administered either in the intraoperative or initial postoperative periods; (3) predefined primary outcomes: incidence of postoperative nausea and vomiting (defined as a categorical “yes/no” for the presence of nausea and/or vomiting based on the individual author’s designation) in the postanesthesia care unit (PACU) and within 24 h of surgery; and (4) design: randomized controlled trials published in full-text versions. Results were not restricted by language, geographical origin, or sample size. In addition, individual citations of articles were reviewed to ensure inclusion of relevant studies not captured in the initial literature search.

Data Extraction

Titles and abstracts that resulted from the initial literature search were screened independently by 2 authors (A.Z.-V., D.M.-P.). These same authors performed independent reviews of full-text articles. Any discrepancies were resolved by group consensus. Demographic data, including year of publication, sample size, mean age, percentage of female patients, and type of surgery were extracted and transferred to a predefined electronic database. Secondary clinical outcomes, including antiemetic medication administration (based on individual trial criteria), dose and timing of dextrose infusion, postoperative plasma glucose levels, and length of PACU stay were also collected and analyzed.

Assessment of Methodological Quality

Each included study was assessed for overall quality based on the Cochrane Risk of Bias review criteria for randomized studies.11 A score was calculated and recorded based on 7 domains of risk (random sequence generation, allocation concealment, blinding of personnel who administered the infusion of dextrose, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias).

Statistical Analysis

An initial exploratory qualitative analysis was conducted to describe the characteristics of the studies included in this meta-analysis. Thereafter, the incidence of postoperative nausea and vomiting was extracted as a dichotomous variable (present or absent) and expressed as a risk ratio with respective 95% CI based on a random-effect model (DerSimonian and Laird method).12 Meta-analysis of quantitative variables (ie, glucose level, length of hospital stays) was presented using standardized mean difference. We used forest plots to illustrate the estimates of overall effect sizes (pooled risk ratio represented as a solid diamond at the bottom of the forest plot). Subgroup analysis, specified a priori, for the primary outcome was based on the timing of dextrose administration (intraoperative versus postoperative). Heterogeneity of each meta-analyzed value was assessed by (I2) and statistical significance was assessed using the χ2 test. I2 < 50% and I2 > 50% were considered irrelevant and relevant heterogeneity, respectively. We performed leave-one-out sensitivity analysis to determine the robustness of the pooled estimate by sequentially removing each study and reanalyzing the remaining data sets. Publication bias was calculated using the Egger test. Funnel plots were constructed to represent any tendency for publishing in favor of the positive effect. Significant publication bias was considered when there was asymmetry in the funnel plot (meaning that smaller studies tend to show larger risk ratios) and a statistically significant bias coefficient according to the Egger test. P values <.05 were considered as statistically significant in all statistical analyses. The meta-analysis was performed using Stata version 13.0 (Stata, College Station, TX).

RESULTS

Study Characteristics

T1
Table.:
Characteristics of Included Trials
F1
Figure 1.:
Preferred Reporting Items for Systematic Review and Meta-analyses flow chart for the selection of studies.

Of the 581 articles that resulted from the initial literature search, a total of 19 full-text versions met the relevant inclusion criteria and were fully reviewed. Following exclusion of trials that did not assess the desired intervention or outcome of interest, a total of 10 randomized controlled trials were included in this meta-analysis.5–9,13–17Figure 1 outlines the selection of studies and the Table summarizes study characteristics. Of the included trials, 6 randomized controlled trials were performed in gynecologic surgery (eg, diagnostic laparoscopy, hysterectomy), 3 in laparoscopic cholecystectomy, and 1 in otorhinolaryngology surgery (ie, tympanoplasty), respectively. A total of 987 patients were included, divided between those receiving a perioperative dextrose infusion (n = 465) and control (n = 461 for crystalloid placebo; n = 61 for null intervention). The timing of dextrose infusion administration varied, but included those infused during surgery (n = 4 randomized controlled trials), before surgery (n = 1), and after surgery (n = 5). Whereas all studies administered a 5% dextrose concentration, the dose (ie, rate of infusion) varied as shown in the Table.

Primary Outcome

F2
Figure 2.:
Pooled effect of perioperative dextrose infusion on postoperative nausea and vomiting in the postanesthesia care unit. RR indicates risk ratio.
F3
Figure 3.:
Pooled effect of perioperative dextrose infusion on postoperative nausea and vomiting within 24 h of surgery. RR indicates risk ratio.

Seven randomized controlled trials examined the incidence of postoperative nausea and vomiting.5,6,8,9,13,14,17 Overall, the use of a dextrose infusion was not associated with a significant reduction in postoperative nausea and vomiting in the PACU (Figure 2; risk ratio = 0.91, 95% CI, 0.73–1.15, P = .44; I2 = 6.7%, P for heterogeneity = .38) or within the first 24 h of surgery (Figure 3; risk ratio = 0.76, 95% CI, 0.55–1.04, P = .088; I2 = 68%; P for heterogeneity = .004) compared to control. Subgroup analysis of dextrose infusion administered intraoperatively (risk ratio = 0.87, 95% CI, 0.54–1.39, P = .56, I2 = 11%; P for heterogeneity = .32) or postoperatively (risk ratio = 0.91, 95% CI, 0.71–1.56, P = .43, I2 = 52%; P for heterogeneity = .12) was not associated with a reduction in postoperative nausea and vomiting in the PACU compared to controls. Whereas subgroup analysis that included only trials that administered a dextrose infusion during surgery did not yield an association within 24 h (risk ratio = 0.96, 95% CI, 0.49–1.87, P = .90; I2 = 61%; P for heterogeneity = .07), analysis isolated to administration of dextrose infusion after surgery was associated with a statistically significant reduction in postoperative nausea and vomiting within 24 h (risk ratio = 0.69, 95% CI, 0.47–1.00, P = .05; I2 = 76%; P for heterogeneity = .005) compared to controls. Sensitivity analysis revealed no significant differences in these outcomes. There was no evidence of publication bias in our analyses (Egger test bias = −0.05; P = .96).

Secondary Outcomes

Antiemetic Requirement.

F4
Figure 4.:
Pooled effect of perioperative dextrose infusion on postoperative antiemetic administration within the first 24 h. RR indicates risk ratio.

Five trials reported data on rescue antiemetic administration.5–7,15,16 Provision of a perioperative dextrose infusion was associated with a significant reduction in antiemetic administration within 24 h (Figure 4; risk ratio = 0.55, 95% CI, 0.45–0.69, P < .001, I2 = 7%; P for heterogeneity = .36) of surgery compared to control. Subgroup analysis suggested there was a significant reduction in the need for rescue antiemetic administration when dextrose was given intraoperatively (2 trials; risk ratio = 0.49, 95% CI, 0.37–0.67, P < .001, I2 = 0%; P for heterogeneity = .70) and postoperatively (3 trials; risk ratio = 0.59, 95% CI, 0.42–0.84, P = .004, I2 = 39%; P for heterogeneity = .19).

Postoperative Nausea and Vomiting Severity.

Postoperative nausea and vomiting severity was measured in 8 of the 10 studies included in this meta-analysis.5–7,9,14–17 For this purpose, 4 assessment tools were used, including the Verbal Descriptive Scale (4-point scale),9,15 the Verbal Rating Scale (11-point scale),14,16 the Visual Analog Scale (11-point scale),6,7 and the Bellville scale (4-point scale).17 Only 3 trials found an association between a perioperative dextrose infusion and a reduction in postoperative nausea and vomiting severity.5,7,16 We were unable to conduct a quantitative meta-analysis for this outcome due to the inconsistent use of assessment scales between included trials.

Vomiting Episodes.

Individual and aggregate vomiting episodes were captured by 6 studies.7–9,13,14,16 Three trials reported that the use of a perioperative dextrose infusion was associated with a decrease in the average number of vomiting episodes per patient. These data were not amenable to meta-analysis given the variability in reporting metrics.

Glucose Level.

F5
Figure 5.:
Pooled effect of perioperative dextrose infusion on postoperative serum glucose. SMD indicates standardized mean difference.

Meta-analysis of 4 trials7–9,16 that reported on postoperative plasma glucose levels showed that a perioperative dextrose infusion was associated with a significantly increased plasma glucose (Figure 5; standardized mean difference = 3.43, 95% CI, 1.41–5.47, P < .001, I2 = 97.9%; P for heterogeneity < .001) in the PACU compared to control. However, 3 trials reported on glucose levels at 2, 3, and 6 h, respectively, and did not find a significant difference between dextrose and controls.5,13,17

PACU Length of Stay.

Three studies reported on PACU length of stay.9,14,15 Two of these report a significantly shorter PACU length of stay in the dextrose group compared to controls.14,15 We were unable to perform a meta-analysis for this outcome due to variation in reporting metrics (ie, medians, ranges, means).

Methodological Quality Assessment

The assessment of study quality and the risk for bias is shown in Supplemental Digital Content, Figure 1, https://links.lww.com/AA/C704. Overall, 8 studies were classified at a low risk and 2 at a moderate risk of bias. Given these results, further sensitivity analysis was not performed based on risk of bias assessment. Leave-one-out sensitivity analysis did not significantly impact study results for the primary outcome.

DISCUSSION

The results of this systematic review and meta-analysis revealed that the overall use of a perioperative dextrose infusion did not lead to a significant reduction in the incidence of postoperative nausea and vomiting either in the PACU or within the first 24 h of surgery. Subgroup analysis of studies based on timing of dextrose administration generally yielded similar results. Although 1 subgroup analysis suggested an association between an early postoperative dextrose infusion and postoperative nausea and vomiting within 24 h, a similar association was not found for postoperative nausea and vomiting in the PACU with that same dosing strategy. Perioperative dextrose yielded inconsistent results among secondary end points as well. Although its use was associated with a reduction in antiemetic administration within the first 24 h in overall analysis, it also led to a significant elevation in postoperative plasma glucose.

Prevention and management of postoperative nausea and vomiting remain an important research topic as it continues to be among the most common postoperative adverse events with incidences ranging from 20 to as high as 80% among high-risk patients.18 Prior guidelines have established the role of a formal risk stratification among patients undergoing surgery with evaluation of patient- and surgery-related risk factors that include sex, history of postoperative nausea and vomiting, use of perioperative opioids, smoking status, and surgical procedure. Administration of adequate perioperative hydration represents 1 strategy to reduce risk of postoperative nausea and vomiting (evidence A2),3 despite an unclear mechanism for its clinical effect. And while there is reasonable evidence regarding the effectiveness of crystalloids, it is less clear how perioperative dextrose infusions may assist in the prevention of postoperative nausea and vomiting. Of note, although the majority of the trials utilized dextrose-containing resuscitative crystalloid formulations (ie, lactated Ringer’s solution or normal saline), perioperative dextrose infusions were nonetheless shown to provide little to no efficacy for the prevention of postoperative nausea and vomiting either in the PACU or within 24 h of surgery.

There are several proposed mechanisms through which perioperative dextrose may impact postoperative nausea and vomiting. One theory suggests that caloric supplementation may reduce the magnitude of the hormonal stress response, thereby preventing delays in gastric emptying as well as reducing postoperative catabolism and insulin resistance.19 Work done with oral glucose supplementation suggested a mechanism whereby its administration led to a reduction in muscle contraction within the gastrointestinal tract due to increases in osmotic pressure.20 Interestingly, it has been further proposed that hyperglycemia, facilitated by IV dextrose, may decrease gastric acid secretion, inhibit vagal cholinergic pathways on the parietal cells, and reduce gastric contraction and subsequent nausea.21 Regardless, the results of our analysis suggest that despite there being a potential mechanism, dextrose infusions may not lead to clinically meaningful prevention of postoperative nausea and vomiting.

In the era of enhanced recovery after surgery, many perioperative protocols have promoted preoperative nutritional supplementation, liberation of fasting and diets containing oral carbohydrates to improve metabolic response, cardiac function, psychosomatic function, and attenuation of postoperative insulin resistance.22–24 Researchers have therefore devised trials that examine the use of dextrose infusions as natural extentions of this strategy as a compliment to risk-stratified postoperative nausea and vomiting prevention. Interestingly, our analysis shows that perioperative dextrose infusions were associated with a reduction in antiemetic administration. One potential explanation for these results might be that postoperative dextrose infusions lessen the severity of nausea and vomiting symptoms, thereby reducing the need for antiemetic administration. Several of the included studies specifically evaluated for the severity of nausea and vomiting and concluded that dextrose provided a benefit in this regard. Unfortunately, these data were not provided in a manner that facilitated formal pooling and subsequent analysis. Further, trials did not provide rescue antiemetics in a uniform and consistent manner, which limits interpretation of the results.

One objective of this meta-analysis was to attempt to establish a relation between timing of dextrose administration and its effectiveness in prevention of postoperative nausea and vomiting. While subgroup analysis of postoperative administration suggested there may be some efficacy, these results should be interpreted with extreme caution. Given the likely temporary nature of the intervention, evidenced by transient elevations in plasma glucose in the initial postoperative period, it seems unlikely that the intervention might yield an impact on postoperative nausea and vomiting at 24 h. In addition, the results of this subgroup were associated with a high degree of heterogeneity, which limits the ability to fully interpret the finding. Given that this represents a finding from an a priori subgroup analysis, it should be considered an opportunity for hypothesis generation rather than evidence of potential efficacy. While interesting, additional trials that specifically examine the timing of administration and the associated impact on postoperative nausea and vomiting are necessary.

There are several other important limitations to our study. Certain results were associated with a high degree of heterogeneity. Although this is addressed in part through the use of random-effects modeling and subgroup analyses based on timing of dextrose administration, our results should nonetheless be interpreted with caution. Heterogeneity is likely secondary to varied infusion rates as well as patient- and surgery-related factors. Second, as previously stated, we were unable to perform formal meta-analysis of certain secondary variables due to the variation in reporting metrics between studies. These results are reported in qualitative form. We are unable to comment definitively on the safety of dextrose administration, particularly for patients with a history of diabetes mellitus. It is, however, advisable that patients have their plasma glucose levels monitored to identify and treat hyperglycemia should it occur. The decision to administer dextrose infusions should be weighed against the potential risks associated with patient covariables, the surgical subtype, and the impact of hyperglycemia on patient outcomes. This meta-analysis is not designed to comment specifically on those outcomes. Finally, the sample size was small, with few included trials, for certain secondary outcomes (ie, surgical site infection rates). Larger trials specifically designed to evaluate for these outcomes would lend considerable clarity to the literature in this area.

Analysis of pooled data involving perioperative dextrose infusions does not support their routine administration for the prevention of postoperative nausea and vomiting either in the PACU or within 24 h of surgery. Although subgroup analysis suggested some impact on rescue antiemetic use or on the basis of the timing of administration, further large, prospective randomized controlled trials are necessary to determine if a postoperative dextrose infusion has a role in prevention of postoperative nausea and vomiting.

DISCLOSURES

Name: Andres Zorrilla-Vaca, BS.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Name: Diana Marmolejo-Posso, BS.

Contribution: This author helped conduct the literature search and write the manuscript.

Name: Alexander Stone, MD.

Contribution: This author helped conduct the study, perform the quality assessment of the studies, and write the manuscript.

Name: Jinlei Li, MD.

Contribution: This author helped conduct the study, perform the quality assessment of the studies, and write the manuscript.

Name: Michael C. Grant, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

This manuscript was handled by: Tong J. Gan, MD.

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