Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review

Sanfilippo, Filippo; Currò, Jessica Marika; Via, Luigi La; Dezio, Veronica; Brancati, Serena; Murabito, Paolo; Pappalardo, Federico; Astuto, Marinella

doi:10.1111/aor.14276

Cited by 25 publications

(14 citation statements)

References 46 publications

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“…A meta‐analysis 35 of adult and pediatric patients on ECMO reported a decrease in the risk of bleeding associated with Biv compared with UFH. The comparison of the risk of bleeding revealed no significant difference between Arg or NM and UFH, according to the results of two systematic reviews evaluating anticoagulation during ECMO 43,44 . The discrepancies in our findings might be explained by the limited number of included studies and other potential covariates.…”

Section: Discussioncontrasting

confidence: 48%

“…The comparison of the risk of bleeding revealed no significant difference between Arg or NM and UFH, according to the results of two systematic reviews evaluating anticoagulation during ECMO. 43,44 The discrepancies in our findings might be explained by the limited number of included studies and other potential covariates. In addition to excessive anticoagulation, surgical operation and underlying comorbidities also play an important role in the risk of bleeding in ECMO patients.…”

Section: Discussionmentioning

confidence: 59%

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Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta‐analysis and systematic review

Chen

Zhao

et al. 2023

Pharmacotherapy

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ObjectivesExtracorporeal membrane oxygenation (ECMO) plays an important role in providing temporary life support for patients with severe cardiac or pulmonary failure, but requires strict anticoagulation and monitoring. This network meta‐analysis systematically explored the most effective anticoagulation and monitoring strategies for patients receiving ECMO.MethodsMEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to January 31, 2023, for studies comparing unfractionated heparin (UFH), argatroban (Arg), bivalirudin (Biv), and/or nafamostat mesylate (NM) in patients receiving ECMO. The primary outcomes included device‐related thrombosis, patient‐related thrombosis, and major bleeding events. The secondary outcomes included ECMO survival, ECMO duration, and in‐hospital mortality.ResultsA total of 2522 patients from 23 trials were included in the study. Biv was associated with a decreased risk of device‐related thrombosis (odd ratio (OR) 0.51, 95% confidence interval (CI): 0.33‐0.84) compared with UFH, whereas NM (OR 2.2, 95% CI: 0.24‐65.0) and Arg (OR 0.92, 95% CI: 0.43‐2.0) did not reduce the risk of device‐related thrombosis compared with UFH. Biv was superior to Arg in decreasing the risk of device‐related thrombosis (OR 0.14, 95% CI: 0.03‐0.51). Biv reduced the risk of patient‐related thrombosis compared with UFH (OR 0.44, 95% CI: 0.18‐0.85); NM (OR 0.65, 95% CI: 0.14‐3.3) and Arg (OR 3.1, 95% CI: 0.94‐12.0) did not decrease risk of patient‐related thrombosis compared with UFH. No significant difference was observed in the risk of major bleeding between three alternatives and UFH: Biv (OR 0.54, 95% CI: 0.23‐1.3), Arg (OR 1.3, 95% CI: 0.34‐5.8), and NM (OR 0.60, 95% CI: 0.13‐2.6). NM showed a reduced risk of in‐hospital mortality compared with UFH (OR 0.27, 95% CI: 0.091‐0.77), whereas Arg (OR 0.43, 95% CI: 0.15‐1.2) and Biv (OR 0.75, 95% CI: 0.52‐1.1) did not decrease risk of in‐hospital mortality.ConclusionsCompared with UFH and Arg, Biv reduces the risk of thrombosis and appears to be a better choice for patients requiring ECMO. NM was associated with a reduced risk of in‐hospital mortality.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 59%

Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta‐analysis and systematic review

Chen

Zhao

et al. 2023

Pharmacotherapy

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“…Previous studies have compared the effects of no-anticoagulant and NM on filter life during CKRT [ 22 , 23 ]. Studies have also compared the effects of citrate anticoagulation and NM on filter life and bleeding during CKRT in children [ 24 ] and the effects of NM and UFH on coagulation and bleeding events during veno-arterial extracorporeal membrane oxygenation [ 12 , 25 , 26 ]. However, few studies have directly compared the effects of NM and UFH on filter life in CKRT.…”

Section: Discussionmentioning

confidence: 99%

“…It has a short half-life of approximately 8 min; thus, it is supposed to act regionally in the circuit [9,10]. Since COVID-19 became a pandemic, in which thromboembolic complications are common and some patients need extracorporeal membrane oxygenation, the property of NM as an anticoagulant has attracted clinicians in various countries [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Unfractionated heparin versus nafamostat mesylate for anticoagulation during continuous kidney replacement therapy: an observational study

et al. 2023

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Background Unfractionated heparin sodium and nafamostat mesylate have long been used as anticoagulants in continuous kidney replacement therapy (CKRT) where citrate is unavailable. This study aimed to determine whether heparin or nafamostat mesylate used during CKRT was associated with a longer filter life. Methods In this single-centre observational study, we included adult patients who required CKRT and used heparin or nafamostat mesylate for their first CKRT in the intensive care unit from September 1, 2013, to December 31, 2020. The primary outcome was filter life (from the start to the end of using the first filter). We used propensity score matching to adjust for the imbalance in patients’ characteristics and laboratory data at the start of CKRT and compared the outcomes between the two groups. We also performed restricted mean survival time analysis to compare the filter survival times. Results We included 286 patients, 157 patients on heparin and 129 patients on nafamostat mesylate. After propensity score matching, the mean filter life with heparin was 1.58 days (N = 91, Standard deviation [SD], 1.52) and with nafamostat mesylate was 1.06 days (N = 91, SD, 0.94, p = 0.006). Multivariable regression analysis adjusted for confounding factors supported that heparin was associated with a longer filter life compared with nafamostat mesylate (regression coefficient, days, 0.52 [95% CI, 0.15, 0.89]). The between group difference of the restricted mean filter survival time in the matched cohort was 0.29 (95% CI, 0.07–0.50, p = 0.008). Conclusion Compared to nafamostat mesylate, heparin was associated with one-third to one-half a day longer filter life. Trial registration Not applicable.

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“…Higher doses of bivalirudin are needed in children on renal replacement therapy [ 72 ]. Blood stagnation must be avoided in the ECMO circuit while on bivalirudin due to its short half-life and proteolysis, which can lead to circuit thrombosis [ 73 ]. Although aPTT is not a validated laboratory assay to monitor DTI therapy, the dosing is adjusted by maintaining aPTT ratios of 1.5–2.5.…”

Section: Non-heparin Anticoagulantsmentioning

confidence: 99%

Management of Anticoagulation during Extracorporeal Membrane Oxygenation in Children

2022

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Extracorporeal Membrane Oxygenation (ECMO) is often used in critically ill children with severe cardiopulmonary failure. Worldwide, about 3600 children are supported by ECMO each year, with an increase of 10% in cases per year. Although anticoagulation is necessary to prevent circuit thrombosis during ECMO support, bleeding and thrombosis are associated with significantly increased mortality risk. In addition, maintaining balanced hemostasis is a challenging task during ECMO support. While heparin is a standard anticoagulation therapy in ECMO, recently, newer anticoagulant agents are also in use. Currently, there is a wide variation in anticoagulation management and diagnostic monitoring in children receiving ECMO. This review intends to describe the pathophysiology of coagulation during ECMO support, review of literature on current and newer anticoagulant agents, and outline various diagnostic tests used for anticoagulation monitoring. We will also discuss knowledge gaps and future areas of research.

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Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review

Cited by 25 publications

References 46 publications

Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta‐analysis and systematic review

Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta‐analysis and systematic review

Unfractionated heparin versus nafamostat mesylate for anticoagulation during continuous kidney replacement therapy: an observational study

Management of Anticoagulation during Extracorporeal Membrane Oxygenation in Children

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