Low Cerebral Oxygenation Levels during Resuscitation in Out-of-hospital Cardiac Arrest Are Associated with Hyperfibrinolysis.

BACKGROUND: The authors investigated whether patients with out-of-hospital cardiac arrest with an initial low cerebral oxygen level during cardiopulmonary resuscitation are more prone to develop hyperfibrinolysis than patients with normal cerebral oxygenation levels and which part of the fibrinolytic system is involved in this response. METHODS: In 46 patients, hyperfibrinolysis was diagnosed immediately upon emergency department admission using rotational thromboelastometry and defined as a lysis more than 15%. Simultaneously, initial cerebral tissue oxygenation was measured using near-infrared spectroscopy, and oxygen desaturation was defined as a tissue oxygenation index (TOI) of 50% or less. Blood sample analysis included markers for hypoperfusion and fibrinolysis. RESULTS: There was no difference in prehospital cardiopulmonary resuscitation duration between patients with or without hyperfibrinolysis. An initial TOI of 50% or less was associated with more clot lysis (91% [17 to 100%; n = 16]) compared with patients with a normal TOI (6% [4 to 11%]; n = 30; P < 0.001), with lower levels of plasminogen (151.6 ± 61.0 vs. 225.3 ± 47.0 µg/ml; P < 0.001) and higher levels of tissue plasminogen activator (t-PA; 18.3 ± 7.4 vs. 7.9 ± 4.7 ng/ml; P < 0.001) and plasminogen activator inhibitor-1 (19.3 ± 8.9 vs. 12.1 ± 6.1 ng/ml; P = 0.013). There were no differences in (activated) protein C levels among groups. The initial TOI was negatively correlated with t-PA (r = -0.69; P < 0001). Mortality rates were highest in patients with hyperfibrinolysis. CONCLUSION: Activation of the fibrinolytic system is more common in out-of-hospital cardiac arrest patients with an initial cerebral tissue oxygenation value of 50% or less during resuscitation and is linked to increased levels of t-PA rather than involvement of protein C.

Lysis onset time as diagnostic rotational thromboelastometry parameter for fast detection of hyperfibrinolysis.

BACKGROUND: Rotational thromboelastometry is increasingly used to detect hyperfibrinolysis, which is a predictor of unfavorable outcome in patients with coagulation disturbances. In an in vitro study, the authors investigated which thromboelastometric hemostatic parameters could be valuable for fast diagnosis of the severity of hyperfibrinolysis and confirmed their findings in a patient population with hyperfibrinolysis. METHODS: Thromboelastometry was performed after adding increasing concentrations of tissue plasminogen activator (0 to 400 ng/ml) to citrated blood samples of 15 healthy volunteers. Lysis parameters included the clotting time, maximum clot firmness, maximum lysis, and lysis onset time (LOT). The relation of tissue plasminogen activator with the LOT was further investigated in a patient population with out-of-hospital cardiac arrest and hyperfibrinolysis. RESULTS: The LOT showed a dose-dependent association with increasing tissue plasminogen activator concentrations. Late, intermediate, or fulminant hyperfibrinolysis was associated with an average LOT (mean ± SD) of 42.7 ± 13.8, 23.2 ± 8.2, and 17.5 ± 4.6 min in the in vitro study and estimated 42.2 ± 8.3, 29.1 ± 1.2, and 14.6 ± 7.7 min in patients, respectively. The authors found a moderately negative correlation between patient plasma tissue plasminogen activator levels and the LOT (r = -0.67; P = 0.01). CONCLUSION: This study shows that the LOT may be used for fast detection of severe hyperfibrinolysis, with a better resolution than the maximum lysis, and should be further evaluated for optimization of therapeutic strategies in patients with severe clot breakdown.

The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD-study protocol for a randomized controlled non-inferiority trial.

BACKGROUND: The Netherlands Armed Forces have been successfully using deep-frozen (- 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. METHODS: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. DISCUSSION: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05502809. Registered on 16 August 2022.

Acute and delayed mild coagulopathy are related to outcome in patients with isolated traumatic brain injury.

INTRODUCTION: The relationship between isolated traumatic brain injury (TBI) associated coagulopathy and patient prognosis frequently lacks information regarding the time course of coagulation disorders throughout the post-traumatic period. This study was conducted to assess the prevalence and time course of post-traumatic coagulopathy in patients with isolated TBI and the relationship of these hemostatic disorders with outcome. METHODS: The local Human Subjects Committee approved the study. We retrospectively studied the medical records of computed tomography (CT)-confirmed isolated TBI patients with an extracranial abbreviated injury scale (AIS) <3 who were primarily referred to a Level 1 trauma centre in Amsterdam (n = 107). Hemostatic parameters including activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, hemoglobin, hematocrit, glucose, pH and lactate levels were recorded throughout a 72-hour period as part of a routine standardized follow-up of TBI. Coagulopathy was defined as a aPPT >40 seconds and/or a PTT in International Normalized Ratio (INR) >1.2 and/or a platelet count <120*109/l. RESULTS: Patients were mostly male, aged 48 ± 20 years with a median injury severity score of 25 (range 20 to 25). Early coagulopathy as diagnosed in the emergency department (ED) occurred in 24% of all patients. The occurrence of TBI-related coagulopathy increased to 54% in the first 24 hours post-trauma. In addition to an increased age and disturbed pupillary reflex, both coagulopathy upon ED arrival and during the first 24 hours post-trauma provided an independent prognostic factor for unfavorable outcome (odds ratio (OR) 3.75 (95% CI 1.07 to 12.51; P = 0.04) and OR 11.61 (2.79 to 48.34); P = 0.003). CONCLUSIONS: Our study confirms a high prevalence of early and delayed coagulopathy in patients with isolated TBI, which is strongly associated with an unfavorable outcome. These data support close monitoring of hemostasis after TBI and indicate that correction of coagulation disturbances might need to be considered.

Beat-to-beat hemodynamic monitoring during electroconvulsive therapy.

OBJECTIVES: Rapid parasympathetic and sympathetic hemodynamic effects during electroconvulsive therapy (ECT) may pose vulnerable patients to significant risk for cardiovascular complications. Here, we evaluated the clinical feasibility of noninvasive beat-to-beat arterial blood pressure (BP) measurements in patients undergoing ECT. METHODS: Beat-to-beat hemodynamic effects were measured with a noninvasive BP monitor in 24 individual patients undergoing ECT during general anesthesia. Heart rate, systolic (SBP), and diastolic BP (DBP) as well as cardiac output (CO) were measured continuously. A significant increase in pulse rate and/or BP was treated with intermittent administration of esmolol and ketanserin. Data are presented as mean ± SD. RESULTS: The ECT stimulus induced a transient drop in BP and pulse rate, followed by a sharp rise in both parameters. The parasympathetic phase lasted 17 ± 9 seconds and was characterized by a drop in heart rate from 89 ± 15 to 42 ± 24 beats per minute, in SBP from 143 ± 22 to 91 ± 31 mm Hg, in DBP from 82 ± 13 to 54 ± 22 mm Hg, and in CO from 5.7 ± 2.3 to 1.4 ± 1.0 L/min, respectively. During the subsequent sympathetic phase, the heart rate increased to 125 ± 26 beats per minute, the SBP to 192 ± 33 mm Hg, the DBP to 113 ± 21 mm Hg, and the CO to 7.4 ± 4.3 L/min. The time interval between the lowest and highest SBP was 60 ± 48 seconds. CONCLUSIONS: Noninvasive beat-to-beat BP measurements are feasible during ECT and may be used to guide rapid therapeutic interventions during ECT-induced hemodynamic effects.

Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta-analysis.

Prothrombin complex concentrate (PCC) is increasingly being used as a treatment for major bleeding in patients who are not taking anticoagulants. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of PCC administration for the treatment of bleeding in patients not taking anticoagulants. Studies investigating the effectivity of PCC to treat bleeding in adult patients and providing data on either mortality or blood loss were eligible. Data were pooled using Mantel-Haenszel random effects meta-analysis or inverse variance random effects meta-analysis. From 4668 identified studies, 17 observational studies were included. In all patient groups combined, PCC administration was not associated with mortality (odds ratio = 0.83; 95% confidence interval [CI], 0.66-1.06; P = .13; I2  = 0%). However, in trauma patients, PCC administration, in addition to fresh frozen plasma, was associated with reduced mortality (odds ratio = 0.64; CI, 0.46-0.88; P = .007; I2  = 0%). PCC administration was associated with a reduction in blood loss in cardiac surgery patients (mean difference: -384; CI, -640 to -128, P = .003, I2  = 81%) and a decreased need for red blood cell transfusions when compared with standard care across a wide range of bleeding patients not taking anticoagulants (mean difference: -1.80; CI, -3.22 to -0.38; P = .01; I2  = 92%). In conclusion, PCC administration was not associated with reduced mortality in the whole cohort but did reduce mortality in trauma patients. In bleeding patients, PCC reduced the need for red blood cell transfusions when compared with treatment strategies not involving PCC. In bleeding cardiac surgery patients, PCC administration reduced blood loss.