The Optimal Perioperative Clinical Infusion Management under HES Injection Marketing Being Suspended by the EMA

Shan-Dong Chen, MD¹, Chao Zhang, MD^2#

¹ Department of Anesthesia, Taihe Hospital, Hubei University of Medicine, No.32, Renmin South Road, Shiyan 442000, Hubei, China;

² Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China.

^#Corresponding Authors: Chao Zhang, MD, Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China. E-mail: zhangchao0803@126.com, Tel: +86 0719-8801071, Fax: +86 0719-8801071.

Currently, millions of people worldwide undergo cardiac surgery annually, which has significantly reduced cardiopath mortality. However, the extensive surgical stimulation experienced by patients during the perioperative period can lead to serious and complex complications. These complications include thrombosis of coronary artery graft, postoperative bleeding, renal failure, acute kidney injury (AKI), cerebrovascular accidents, atrial fibrillation, seizures, and in severe cases, even death[1, 2]. Therefore, reducing postoperative complications had become a crucial area of research. Existing evidence proposed that correct perioperative fluid therapy could positively impact postoperative outcomes, while improper fluid management might harm patients.

In 2013, the British Medical Journal published an article detailing the entire process of Boldt's falsification of data on the efficacy of hydroxyethyl starch (HES)[3]. Subsequently, nearly a hundred articles by Boldt were withdrawn one after another, and relevant clinical evidences recommending the use of HES injection was overturned, leading to the suspension of HES injection marketing authorization by the European Medicines Agency (EMA). As a result of this incident, HES was removed from the altar. In addition, perioperative fluid management in cardiac surgery had long been a subject of controversy. However, due to the lack of comprehensive systematic evaluations, it became imperative to compare the safety and effectiveness of crystalloid solutions and colloidal solutions. In order to provide clinical doctors with more authentic clinical evidence, it should be reconstructed without relying on the Boldt's research.

A significant body of clinical evidence suggested that selecting the appropriate type of liquid type could effectively decrease the occurrence of postoperative complications, shorten hospital stays, and facilitate patient recovery[4-7]. The current options for perioperative fluid management in clinical practice include crystalloid and colloidal solution. Crystalloid solution was a type of aqueous solution such as 0.9% sodium chloride, ringer's solution, and sodium bicarbonate ringer's solution, while colloidal solution was a type of macromolecular solution such as HES, gelatin, and albumin. They were included in different clinical guidelines and were widely used in perioperative and fluid resuscitation. Among the many issues regarding fluid therapy in current surgical clinical guidelines, part of issues had reached a consensus on the choice of crystalloid solutions and colloidal solutions, but there was still some controversy[8, 9].

The ongoing controversy over the optimal choice of fluid type mainly focused on its impact on patient prognosis. Regarding postoperative complications, previous prospective studies had indicated that the use of intraoperative colloidal solutions in patients underwent cardiac surgery did not offer superior outcomes when compared to crystalloid solutions. In fact, the use of colloidal solutions might even increase the risk of renal replacement therapy[10]. A review had further supported these findings by demonstrating that colloidal solutions were not effective in reducing postoperative complications in non-cardiac surgery, as compared to crystalloid solutions[10]. However, there was also the opposite view that the meta-analysis by Perel et al.[11] showed that crystalloid solutions did not reduce mortality in critically ill patients. Cardiac surgery, as a high-risk procedure for bleeding, requires the infusion of blood products during or after surgery for most patients. In the study by Skhirtladze et al.[12], it was miraculous that ringer's solution, as a crystalloid solution, although administered in larger amounts compared to the colloidal solution, reduced the patient's need for blood products and had a smaller impact on their renal function. There had also been studies showing that in patients underwent major non-cardiac surgeries, the colloidal and crystalloid solution in the targeted liquid therapy regimen had similar results[13]. For postoperative recovery, according to a double-blind randomized controlled trial conducted in 2013, it was found that both crystalloid and colloidal solutions did not decrease the total hospitalization time and ICU hospitalization time of ovarian cancer patients during postoperative recovery[14]. However, a meta-analysis of non-cardiac surgery patients in 2016 revealed that the HES group exhibited faster postoperative recovery and shorter hospitalization time[13]. The question of whether colloidal solution is truly superior to crystalloid solution in terms of the outcome of perioperative fluid resuscitation is a topic that requires further discussion. Additionally, considering the high surgical risk and multiple complications associated with cardiac surgery, it is also important to explore and investigate which type of fluid is most suitable.

The existing perioperative studies for crystalloid and colloidal solutions mainly concentrate on fluid resuscitation and treatment for critically ill patients, such as those with sepsis and shock. However, in patients undergoing cardiac surgery, it is necessary to establish new evidence to address the problem of unreliable evidence resulting from the Bolt scandal.

Author Contributions

Chao Zhang and Shan-Dong Chen: Leader and supporter of the whole project; critical reading of manuscript for important intellectual content and approval of final manuscript.

Conflict of Interest

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

None.

Ethical approval and consent to participate

Not applicable.

Availability of data and materials

Not applicable.

Acknowledgements

Not applicable.

References

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