Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy

Kalbhenn, Johannes; Wittau, N; Schmutz, Axel; Zieger, Barbara; Schmidt, René

doi:10.1177/0267659115579714

Cited by 82 publications

(76 citation statements)

References 30 publications

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“…20 These changes are believed to occur as a result of both adsorption of proteins and blood cellular components onto the artificial surface, proinflammatory effects of the circuit, and physical trauma to the blood caused by passage through the pump and membrane lung. [21][22][23] In the current series, there was a progressive thrombocytopenia (defined as a >50% reduction from baseline levels in keeping with diagnostic criteria for other conditions 24 ) in keeping with previous ECMO studies and with previous animal studies using the same device. 25 There was no bleeding associated with this degree of thrombocytopenia despite the simultaneous presence of moderate anticoagulation with heparin.…”

Section: Discussionsupporting

confidence: 69%

A Retrospective Observational Case Series of Low-Flow Venovenous Extracorporeal Carbon Dioxide Removal Use in Patients with Respiratory Failure

et al. 2016

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We aimed to describe the use of venovenous extracorporeal carbon dioxide removal (ECCO2R) in patients with hypercapnic respiratory failure. We performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit and commenced on ECCO2R from August 2013 to February 2015. Fourteen patients received ECCO2R. Demographic data, physiologic data (including pH and partial pressure of carbon dioxide in arterial blood [PaCO2]) when starting ECCO2R (t = 0), at 4 hourly intervals for the first 24 hours, then at 24 hour intervals until cessation of ECCO2R, and overall outcome were recorded. Patients are reported separately depending on whether the indication for ECCO2R was an exacerbation of chronic obstructive pulmonary disease (COPD; n = 5), or acute respiratory distress syndrome (ARDS) and persisting hypercapnoea (n = 9). Patients were managed with ECCO2R (Hemolung, ALung Inc, Pittsburgh, PA). Median duration of ECCO2R was 5 days. Four complications related to ECCO2R were reported, none resulting in serious adverse outcomes. Ten patients were discharged from intensive care unit (ICU) alive. A statistically significant improvement in pH (p = 0.012) was demonstrated. Our observational series of ECCO2R shows that this technique can be safely used to achieve therapeutic goals in patients requiring lung protection, and in COPD, in line with current publications in this area.

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Section: Discussionsupporting

confidence: 69%

A Retrospective Observational Case Series of Low-Flow Venovenous Extracorporeal Carbon Dioxide Removal Use in Patients with Respiratory Failure

et al. 2016

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“…Nonetheless, although V-V patients showed 50% less chance to suffer from a CNS event, they also showed to be at higher risk for brain hemorrhage than V-A patients (7,8). Cerebral bleeding is certainly not a single-factor event, and several aspects and factors may play a variable role in the genesis of such a complication, ranging from coagulation disorder (12) to perfusion impairment, from local or systemic inflammatory and tissue alterations, from vascular spasm due to altered autoregulatory capacity of the brain to endothelial injury. Furthermore, the mechanisms underlying the high rate of cerebral hemorrhage experienced in V-V subjects might be different from the same event observed in V-A patients, who, instead, have higher rates of brain death and ischemic injury.…”

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confidence: 99%

“…The main issue in this field, and it is indeed an admission of "clinical weakness", is represented by the lack of knowledge about the effects and changes of brain perfusion during ECLS, how the patient metabolic and blood gas states influence brain integrity, and finally about the appropriate management of anticoagulation or control and management of coagulation disorders often observed during ECLS (12). Besides the understanding of underlying mechanisms of CNS events during ECLS, monitoring and timely recognition of the adequacy of brain perfusion or the onset of maladaptive changes and cerebral injury, either perfusion or structurerelated, is paramount, but mostly lacking in ECLS patients.…”

mentioning

confidence: 99%

“…Besides the understanding of underlying mechanisms of CNS events during ECLS, monitoring and timely recognition of the adequacy of brain perfusion or the onset of maladaptive changes and cerebral injury, either perfusion or structurerelated, is paramount, but mostly lacking in ECLS patients. On-line information about appropriateness of anticoagulation state and presence and extent of coagulation disorder, brain perfusion and onset of cerebral tissue injury, as well as information about vascular structural and functional integrity, are all part of the complex puzzle which constitutes the ECLS/ patient interplay which is, at the moment, poorly defined and understood (12)(13)(14)(15)(16)(17)(18). As mentioned, it is likely that CNS event-related etiology is multifactorial, but we are still far from understanding why some patients develop such brain damages and some not.…”

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confidence: 99%

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Extracorporeal life support and neurologic complications: still a long way to go

Lorusso

2017

J. Thorac. Dis.

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The actual impact of neurological complications on patient outcome during extracorporeal life support (ECLS) has emerged only since a few years (1,2) despite the use of such a temporary heart/lung support for more than four decades.The recent appraisal of the rather high incidence and ominous prognosis of these adverse events in ECLS patients have now alerted attending physicians and personnel upon continuous surveillance and early recognition. Nonetheless, it is increasingly evident that the mechanisms underlying the occurrence are not simply linked to embolization, bleeding, or low-flow related brain hypoxia (3-5) which were thought to represent the sole source of injury of the brain in ECLS patients.Following a study addressing the neurologic complications in the neonatal population (6), other two studies realized by analysing the Registry of the Extracorporeal Life Support Organization (ELSO), have recently investigated and clearly shown the entity of neurologic adverse events in veno-arterial (V-A) and veno-venous (V-V) ECLS configurations in adult patient populations (7,8). Incidence rates of brain injury were 15% in V-A and 7% in V-V patients, respectively, with an in-hospital survival of 10% in the first group, and 25% in the second, underlining the ominous prognosis once a neurological event occurs in the ECLS patients (7,8). These studies analyzed also the type of brain damage, according to the ELSO reporting system (embolism, hemorrhage, seizures, brain death) but also, more importantly, the trends of the overall CNS complications and of the single typerelated rates of such adverse events during a 20-year period whose assessment provided interesting findings (7,8).The difference of neurologic complication rates between V-A and V-V is not surprising. However, the two studies, as also highlighted by the comments provided by Pappalardo, Hirose, and Perico herewith enclosed (9-11), have provided several relevant clues for further interpretation and discussion. Interestingly, the incidence of CNS events in V-A ECLS patients steadily declined in the recent years, whereas no substantial change was observed in the V-V ECLS population (7,8). It is well-known that patients undergoing V-A ECLS, by definition and as also confirmed by the ELSO Registry data, are usually more prone to experience bleeding and hemodynamic instability after ECLS implant than V-V cases, therefore at higher risk also for brain injury. This is due to either the underlying disease, settings, and clinical conditions of the ECLS candidates or to the ECLS access (arterial cannulation certainly at higher risk of bleeding than venous access). V-A ECLS, indeed, is often applied nowadays in patients suffering from cardiac arrest, condition which is directly linked to brain hypoperfusion

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“…Thus, it could be assessed where minimal concentration of coagulation factors would be necessary, so a surface can activate the hemostasis [11]. Conversely, the information could be important for extracorporeal systems, how much volume can be added, without affecting the coagulation and becoming detrimental for the patient [12,13].…”

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confidence: 99%

Influence of coagulation parameters by stabilization of fibrinogen

Wegmann

Kalmbach

Schmidt

et al. 2017

JCB

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Abstract. INTRODUCTION:Besides a sodium chloride solution, a hydroxyethyl starch solution, and an immunoglobulin G solution, a human albumin solution is more frequently used in infusion solutions. To prevent negative influence of volume replacement solutions on hemostasis, additional administration of fibrinogen has been used in this assignment with the intention of keeping the plasmatic hemostasis stable. Therefore, in this study possible effects on hemostasis by plasma dilution with HES along with the effects of other clinically applied volume replacement solutions will be analyzed. MATERIAL AND METHODS:Whilst maintaining the concentration of fibrinogen the experiment used four different volume replacement solutions in increments of 1 : 3, 1 : 6 and 1 : 11. To evaluate the changed hemostasis the coagulation parameters PT, PTT and thrombin time have been measured and assessed. RESULTS: A consistent increase of PT is observable in all four dilution solutions. The undiluted samples have a mean value of 11.44 sec. For example, the highest increase of PT of all dilution factors could be detected in samples treated with human albumin solution, where 19.54 sec was the mean value of the 1 : 3 dilution, whereas values of the 1 : 11 dilution nearly tripled (85.00 sec). Lower values could be achieved in measurements where solutions were diluted with NaCl and HES. However, PT values for the NaCl and HES dilutions (1 : 6) were 39.26 seconds and 36.55 seconds and have exceeded the corresponding human albumin dilution value. However, the steepest curves are achieved using immunoglobulin G solution as dilution agent. CONCLUSION: All results explicitly show that a dilution of the plasma results in worsening the hemostasis. However, the thrombin time can be considered as an exception, as even with a stronger dilution the solutions do not show an increase. Additionally, it could be established that the intrinsic factors are stronger influenced in their function than the extrinsic factors.

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Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy

Cited by 82 publications

References 30 publications

A Retrospective Observational Case Series of Low-Flow Venovenous Extracorporeal Carbon Dioxide Removal Use in Patients with Respiratory Failure

A Retrospective Observational Case Series of Low-Flow Venovenous Extracorporeal Carbon Dioxide Removal Use in Patients with Respiratory Failure

Extracorporeal life support and neurologic complications: still a long way to go

Influence of coagulation parameters by stabilization of fibrinogen

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