Hydroxyethyl starch 130/0.4 for volume replacement therapy in surgical patients: a systematic review and meta-analysis of randomized controlled trials

Background The safety of perioperative intravenous hydroxyethyl starch (HES) products, specifically HES 130/0.4, continues to be the source of much debate. The aim of this meta-analysis was to update the existing evidence and gain further insight into the clinical effects of HES 130/0.4 on postoperative outcomes for volume replacement therapy in surgical patients. Methods MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2020 for relevant randomized controlled trials (RCTs) on perioperative use of HES 130/0.4 in adult surgical patients. The primary outcome was postoperative mortality and secondary outcomes were the incidence of acute kidney injury (AKI) and requirement for renal replacement therapy (RRT). The analysis was performed using the random-effects method and the risk ratio (RR) with a 95% confidence interval (CI). We performed the risk-of-bias assessment of eligible studies and assessed the overall quality of evidence for each outcome. Results Twenty-five RCTs with 4111 participants were finally included. There were no statistical differences between HES 130/0.4 and other fluids in mortality at 30 days (RR 1.28, 95% CI 0.88 to 1.86, p = 0.20), the incidence of AKI (RR 1.23, 95% CI 0.99 to 1.53, p = 0.07), or requirement for RRT (RR 0.75, 95% CI 0.37 to 1.53, p = 0.43). Overall, there was a moderate certainty of evidence for all the outcomes. There was no subgroup difference related to the type of surgery (p = 0.17) in the incidence of AKI. As for the type of comparator fluids, however, there was a trend that was not statistically significant (p = 0.06) towards the increased incidence of AKI in the HES 130/0.4 group (RR 1.22, 95% CI 0.97 to 1.54) compared with the crystalloid group (RR 1.21, 95% CI 0.27 to 3.91). Subgroup analyses according to the type of surgery demonstrated consistent findings. Conclusions This systematic review and meta-analysis suggests that the use of HES 130/0.4 for volume replacement therapy compared with other fluids resulted in no significant difference in postoperative mortality or kidney dysfunction among surgical patients. Given the absent evidence of confirmed benefit and the potential trend of increased kidney injury, we cannot recommend the routine clinical use of HES 130/0.4 for volume replacement therapy in surgical patients from the perspective of benefit/risk profile. However, the results need to be interpreted with caution due to the limited sample size, and further well-powered RCTs are warranted. Trial registration PROSPERO registry reference: CRD42020173058

Absence of Evidence and Evidence of Absence in the FLASH Trial: A Bayesian Reanalysis

The multicenter FLASH trial concluded that “Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES [hydroxyethyl starch] for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery.” Here we use Bayesian logistic regression to quantify the degree to which the data from the FLASH trial, considered in isolation, undercut the hypothesis that HES improves the primary outcome. The results show that the data from the FLASH trial mainly act to increase the plausibility that HES is ineffective, and decrease the plausibility that HES is helpful. These analysis, easily conducted in JASP (jasp-stats.org) or R (https://CRAN.R-project.org/package=abtest) arguably provide a more detailed perspective that supplements the statement that the results showed “no significant difference”.

Preoperative VolumE Replacement therapy in DIabetic patients undergoing coronary artery bypass grafting surgery: results from an open parallel group randomized Controlled Trial (VeRDiCT)

OBJECTIVES To investigate the effect of preoperative volume replacement therapy (VRT) on renal function, health outcome and time to fitness for discharge in diabetic patients undergoing coronary artery bypass grafting (CABG). METHODS In 2 parallel randomized controlled trials, diabetic patients were allocated to preoperative VRT (1 ml/kg/h of Hartmann’s solution for 12 h) or usual care. Primary outcome was time to fitness for discharge. Secondary outcomes included acute kidney injury, postoperative complications, patient-reported quality of life (QoL), hospital resource use and markers of renal, cardiac and inflammatory injury. RESULTS In total, 169 patients were randomized (84 VRT, 85 usual care; mean age 64 years; 88% male). Time to fitness for discharge was similar between groups [median 6 days; interquartile range 5.0–9.0 in both groups; hazard ratio 0.95, 95% confidence interval (CI) 0.65–1.38; P = 0.78]. Postoperative acute kidney injury was not statistically different (VRT: 27.7% vs usual care: 18.8%, odds ratio 1.72, 95% CI 0.82–3.59; P = 0.15). Estimated glomerular filtration rate (mean difference −0.92, 95% CI −4.18 to 2.25; P = 0.56), microalbumin/creatinine ratio [geometric mean ratio (GMR) 1.16, 95% CI 0.94–1.42; P = 0.16], N-acetyl-beta-d-glucosaminidase (GMR 1.08, 95% CI 0.83–1.40; P = 0.57), C-reactive protein (GMR 1.00, 95% CI 0.88–1.13; P = 0.94), troponin T (Trop-T; GMR 1.18, 95% CI 0.78–1.79; P = 0.39) and other secondary health outcomes were similar between groups. QoL improved in both groups at 3 months with no difference observed. CONCLUSIONS The use of preoperative VRT is not superior to usual care in diabetic patients undergoing CABG. Clinical trial registration number ISRCTN02159606.

Management of 2, 4- Dichlorophenoxyacetic Acid Intoxication by Hemodialysis: A Case Report

Background: The herbicide 2, 4-dichlorophenoxyacetic acid (2, 4-D) can cause moderate to lethal poisoning. Although urine alkalization has been recommended as the main treatment, hemodialysis (HD) may be more effective in severe cases. Case: On 24th June 2014, a 53- year-old man ingested a high amount of 40% 2, 4-D. He suffered from mouth and epigastric burning sensation, vomiting and nausea. He was treated, in Emam Reza’s Hospital of Mashhad University Of Medical Sciences, Mashhad , Iran, with maintenance daily fluid infusion plus 10 meq/L NaHCO3. Up to 9 hours after exposure, he became progressively stuporous. He developed diarrhea and hypotension, BP=100/60, unresponsive to volume replacement therapy. He received regular hemodialysis (HD) with bicarbonate for three hours. At the end of HD, his blood pressure rose to 110/70 and the level of consciousness began to improve. Four hours later, he was fully conscious with stable blood pressure (130/80 mmHg). Conclusion: HD may be an effective, safe and fast method for 2, 4-D high dose intoxication induced coma.