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Intraoperative extracorporeal blood purification therapy during major septic vascular surgery

The development of complex surgical procedures requires simultaneous development of enhanced intraoperative resuscitation therapies. Procedures such as extracorporeal organ support, usually performed in intensive care units (ICU), could be transferred to operating rooms.

Continuous renal replacement therapy (CRRT) may improve metabolic homeostasis during surgeries with ischemia–reperfusion [1]. Other extracorporeal blood purification therapies (EBP) such as hemoperfusion may decrease surgery-associated inflammation by removing inflammatory mediators from the blood. Cytokine adsorbers have been used safely during cardiopulmonary bypass [2]. Seraph® 100 (Exthera Medical, Martinez, CA, USA) is a new hemoadsorption device designed to adsorb pathogens [3, 4]. Since it decreases the blood pathogen load, it may attenuate sepsis when initiated early after bacterial release in the blood.

Surgery for aortic vascular or endovascular graft infection (VEGI) requires aortic clamping and may cause disseminated pathogenemia, resulting in major inflammation and metastatic infection. This surgery is associated with prolonged postoperative ICU stay (14 ± 12 days), high incidence of complications, and in-hospital mortality may reach up to 50% [5]. We hypothesized that an intraoperative enhanced resuscitation protocol combining CRRT and Seraph® 100 is safe and feasible and could improve outcomes. This letter provides the protocol description and the outcomes of the first patients consecutively treated and discusses the benefits and limitations of this procedure.

After VEGI confirmation, patients were scheduled for surgery with intraoperative CRRT and Seraph® 100. Empirical broad-spectrum antimicrobial therapy was initiated preoperatively, immediately after bacteriological sampling.

In the operating room, general anesthesia was performed according to standard practices. After induction, a dialysis catheter was inserted and continuous venovenous hemodialysis (CVVHD) was initiated with regional citrate anticoagulation (RCA). An EMiC®2 hemofilter was used and the Seraph® 100 cartridge incorporated between the blood pump and the hemofilter. Blood flow was set between 100 and 120 mL min−1 and dialysate flow between 25 and 30 mL kg−1 h−1. An ICU nurse, trained in CVVHD and Seraph® 100 use, was in charge of the session monitoring. Dialysate composition, citrate, and calcium replacement were adjusted during surgery as needed. At the end of surgery, blood was returned to the patient before transfer to the ICU where CRRT could be resumed (or not) depending on hemodynamic and metabolic status.

Between December 2021 and May 2022, 6 patients underwent excision of vascular graft and infected tissues associated with in situ reconstruction using cryopreserved arterial allografts. They all received intraoperative CRRT and Seraph® 100. The median [interquartile range, IQR] end-of-surgery lactate and potassium levels were 3.7 [3.2–5] and 4.2 [4.1–4.9] mmol l−1. The median [IQR] postoperative ICU length of stay was 6.5 [4.5–10] days. All patients were alive 3 months after the procedure. One patient required a secondary surgical procedure at postoperative day 6 for mesenteric ischemia. Three patients exhibited intraoperative ionized hypocalcemia. No other EBP therapy-related adverse event was observed (Table 1).

Table 1 Patient characteristics

The procedure was easily implemented thanks to a productive collaboration between anesthesiologists and intensivists and met broad support from the surgical team as it did not interfere with the surgical procedure and was perceived as improving intraoperative hemodynamic stability. However, it required the presence of a dedicated and trained ICU nurse.

Because vascular clamping is prolonged during VEGI surgeries, patients often present major metabolic disturbances and up to 50% of them require RRT at ICU admission [5]. We initiated intraoperative RRT to target metabolic homeostasis, and none of these patients experienced severe acidosis or hyperkalemia. Importantly, RCA enabled EBP without heparin anticoagulation, which is safer in this surgical context. RRT was discontinued within 48 h after ICU admission for all patients.

The use of Seraph® 100 might have improved the intraoperative hemodynamic stability, as this pathogens’ adsorption device may offer a better control of inflammation. All of intraoperative blood cultures remained negative, and we hypothesized that preoperative administration of antimicrobials decreased their sensitivity. Drug removal through the extracorporeal circuit should be questioned, although no interference with anesthesia was observed.

We report the first cases of intraoperative EBP combining RRT and pathogen hemoadsorption for VEGI surgeries. This treatment is feasible and associated with excellent outcomes compared to what is usually observed. Despite severe preoperative conditions, all patients were alive after 3 months. Intraoperative extracorporeal kidney and immunologic support may be combined in other specific situations including endocarditis, composite tissue allografts, and complex liver surgery. These findings need to be further evaluated in interventional trials.

Availability of data and materials

The dataset is available from the corresponding author on reasonable request.

Abbreviations

CRRT:

Continuous renal replacement therapy

CVVHD:

Continuous venovenous hemodialysis

EBP:

Extracorporeal blood purification

ICU:

Intensive care unit

IQR:

Interquartile range

RCA:

Regional citrate anticoagulation

RRT:

Renal replacement therapy

VEGI:

Vascular or endovascular graft infection

References

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Acknowledgements

The authors thank the ICU and anesthetic nurses, particularly Caroline Frno (Service d’Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France), for their active and determinant contribution in this protocol. They also thank Pr Xavier Armory, PharmD, PhD (Pharmacy department, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France), and Dr Andre Boibieux, MD (Unité mobile de maladies infectieuses, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France), for their support, as well as Valérie Cerro (Service d’Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France) and Hélène Boyer, PhD, (Hospices Civils de Lyon) for their help in manuscript preparation.

Funding

This study was not funded. Exthera Medical provided the Seraph 100® cartridges for the study at no charge. However, the company did not participate in the protocol development, data collection, analysis, and interpretation, nor in the manuscript writing.

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CM and TR developed the protocol, collected and interpreted data, and drafted the manuscript. PT and XJT developed the protocol, participated in patients’ enrollment, and critically reviewed the manuscript. AL and FB participated in patients’ enrollment and critically reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Céline Monard.

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Signed informed consent for publication of case report was obtained from all patients, and all of them had the opportunity to read the manuscript.

Competing interests

CM has received speakers fees from Fresenius Medical Care. PT has no competing interest to declare. AL has no competing interest to declare. FB has no competing interest to declare. XJT has no competing interest to declare. TR has received speakers fees from Fresenius Medical Care and Exthera Medical.

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Monard, C., Tresson, P., Lamblin, A. et al. Intraoperative extracorporeal blood purification therapy during major septic vascular surgery. Crit Care 26, 404 (2022). https://doi.org/10.1186/s13054-022-04284-7

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