Werner Baulig

Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma.

BACKGROUND: We investigated whether hyperfibrinolysis and its severity was associated with outcome of traumatized and nontraumatized patients. METHODS: From April 2008 to April 2010, all emergency patients with hyperfibrinolysis were enrolled in this study. Hyperfibrinolysis patients were divided into traumatized (trauma hyperfibrinolysis group) and nontraumatized (nontrauma hyperfibrinolysis group). The trauma hyperfibrinolysis group was matched with 24 polytrauma patients without hyperfibrinolysis (matched trauma group). Data from rotational thromboelastometry measurements, blood gas analysis (metabolic state), laboratory analysis, injury severity score, and 30-day mortality were collected. RESULTS: Thirty-five patients with hyperfibrinolysis were identified (13 traumatized, 22 nontraumatized). Overall mortality for hyperfibrinolysis was 54%. Mortality in the trauma hyperfibrinolysis group (77% ± 12%) was significantly higher than in the nontrauma hyperfibrinolysis group (41% ± 10%; P = 0.001, 95% CI 5%–67%) and the matched trauma group (33% ± 10%; P = 0.009, 95% CI 13%–74%). Hyperfibrinolysis is significantly (P = 0.017) associated with mortality in trauma patients. In the blood gas analysis representing the metabolic state, only pH (P = 0.02) and potassium (P = 0.01) were significantly lower in the trauma hyperfibrinolysis group compared to the nontrauma hyperfibrinolysis group. CONCLUSIONS: Mortality from hyperfibrinolysis is significantly higher in trauma compared with nontrauma patients, and hyperfibrinolysis is an independent factor predicting mortality in trauma patients. Rotational thromboelastometry provides real-time recognition of hyperfibrinolysis allowing early treatment.

In vitro factor XIII supplementation increases clot firmness in Rotation Thromboelastometry (ROTEM

Factor XIII (F XIII) is an essential parameter for final clot stability. The purpose of this study was to determine the impact of the addition of factor (F)XIII on clot stability as assessed by Rotation Thromboelastometry (ROTEM). In 90 intensive care patients ROTEM measurements were performed after in vitro addition of F XIII 0.32 IU, 0.63 IU, 1.25 IU and compared to diluent controls (DC; aqua injectabile) resulting in approximate F XIII concentrations of 150, 300 and 600%. Baseline measurements without any additions were also performed. The following ROTEM parameters were measured in FIBTEM and EXTEM tests: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis (ML), maximum clot elasticity (MCE) and alpha-angle (alphaA). Additionally, laboratory values for FXIII, fibrinogen (FBG), platelets and haematocrit were contemporaneously determined. In the perioperative patient population mean FBG concentration was elevated at 5.2 g/l and mean FXIII concentration was low at 62%. The addition of FXIII led to a FBG concentration-dependent increase in MCF both in FIBTEM and EXTEM. Mean increases in MCF (FXIII vs. DC) of approximately 7 mm and 6 mm were observed in FIBTEM and EXTEM, respectively. F XIII addition also led to decreased CFT, increased alphaA, and reduced ML in FIBTEM and EXTEM. In vitro supplementation of FXIII to supraphysiologic levels increases maximum clot firmness, accelerates clot formation and increases clot stability in EXTEM and FIBTEM as assayed by ROTEM in perioperative patients with high fibrinogen and low FXIII levels.

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma

BACKGROUND Indications, efficacy, and safety of plasma products are highly debated. We compared the concentrations of haemostatic proteins and cytokines in solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). METHODS Concentrations of the following parameters were measured in 25 SDP and FFP samples: fibrinogen (FBG), factor (F) II, F V, F VII, F VIII, F IX, F X, F XIII, von Willebrand factor (vWF), D-Dimers, ADAMTS-13 protease, tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and IL-10. RESULTS Mean FBG concentrations in SDP and FFP were similar, but in FFP, the range was larger than in SDP (P<0.01). Mean F II, F VII, F VIII, F IX, and F XIII levels did not differ significantly. Higher concentrations of F V (P<0.01), F X (P<0.05), vWF (P<0.01), and ADAMTS-13 (P<0.01) were found in FFP. With the exception of F VIII and F IX, the range of concentrations for all of these factors was smaller (P<0.05) in SDP than in FFP. Concentrations of TNF-α, IL-8, and IL-10 (all P<0.01) were higher in FFP than in SDP, again with a higher variability and thus larger ranges (P<0.01). CONCLUSIONS Coagulation factor content is similar for SDP and FFP, with notable exceptions of less F V, vWF, and ADAMTS-13 in SDP. Cytokine concentrations (TNFα, IL-8, and IL-10) were significantly higher in FFP. The clinical relevance of these findings needs to be established in outcome studies.

Laryngeal damage due to an unexpectedly large and inappropriately designed cuffed pediatric tracheal tube in a 13-month-old child.

PurposeTo present a case of laryngeal damage in an infant caused by a too large and inappropriately designed cuffed tracheal tube.Clinical featuresA 13-month-old child undergoing cardiac surgery was intubated with an uncuffed endotracheal tube with an internal diameter (ID) of 4.0 mm. Because of an important air leak around the tracheal tube during mechanical ventilation, a cuffed endotracheal tube lD 4.0 mm was inserted. The air leak with the tube cuff not inflated was acceptable at 25 cm H2O airway pressure. After extubation on the third postoperative day the patient showed increasing stridor and respiratory deterioration. Fibreoptic laryngoscopy of the spontaneously breathing patient showed a large intra-laryngeal web. After surgical removal of the web, the child rapidly recovered and was discharged from the hospital on the 12th postoperative day.Inspection of the 4.0 mm (ID) cuffed tracheal tube revealed a cuff positioned inappropriately high and an increase of 0.7 mm in outer tube diameter compared to the 4.0 mm (lD) uncuffed tracheal tube from the same manufacturer. The tube cuff is likely to be situated within the larynx when placed in accordance to insertion depth formulas or radiological criteria, as used for uncuffed tracheal tubes in children.ConclusionThe larger than expected tracheal tube with its intralaryngeal cuff position in a 13-month-old child likely caused mucosal damage and an inflammatory reaction within the larynx resulting in granulation tissue formation and fibrous healing around the tracheal tube.RésuméObjectifPrésenter un cas de lésion laryngée causée, chez un enfant, par un tube trachéal à ballonnet, trop grand et mal conçu. Élémentscliniques : Un enfant de 13 mois devant subir une intervention cardiaque a été intubé avec un tube endotrachéal sans ballonnet d’un diamètre interne (Dl) de 4,0 mm. Étant donné l’importante fuite d’air autour du tube trachéal pendant la ventilation mécanique, un tube endotrachéal à ballonnet de 4,0 mm de Dl a été inséré. La fuite d’air notée autour du ballonnet non gonflé était acceptable pour une pression des voies aériennes de 25 cm H2O. Après l’extubation, au troisième jour postopératoire, le patient a présenté un stridor croissant et une détérioration respiratoire. La fibroscopie du larynx pendant la respiration spontanée a montré une grande membrane intralaryngée. Après le retrait chirurgical de la membrane, l’enfant s’est rapidement rétabli et a quitté l’hôpital le 12e jour.Lexamen du tube à ballonnet de 4,0 mm a révélé un ballonnet placé trop haut et une augmentation de 0,7 mm du diamètre extérieur du tube, comparé au tube sans ballonnet de 4,0 mm réalisé par le même fabricant. Le ballonnet se situe à l’intérieur du larynx quand on place le tube selon les formules d’insertion ou les critères radiologiques, comme on le fait avec les tubes trachéaux sans ballonnets chez les enfants.ConclusionLe tube trachéal, plus gros que prévu, placé dans le larynx dans la position indiquée pour un tube à ballonnet chez un enfant de 13 mois, a causé une lésion de la muqueuse et une réaction inflammatoire dans le larynx, ce qui a entraîné la formation de tissu de granulation et une cicatrisation fibreuse autour du tube trachéal.

The Influence of Laboratory Coagulation Tests and Clotting Factor Levels on Rotation Thromboelastometry (rotem®) During Major Surgery with Hemorrhage

BACKGROUND: The aim of this study was to determine the association between standard laboratory tests, coagulation factor concentrations, and Rotation Thromboelastometry (ROTEM® delta, TEM® International GmbH, Munich, Germany) in patients undergoing major surgery with hemorrhage. METHODS: In 45 patient’s fibrinogen, factor VIII, factor XIII, International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, hemoglobin, leukocytes, and platelet count were simultaneously measured intraoperatively with ROTEM (EXTEM, INTEM, FIBTEM, APTEM) measurements. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and &agr;-angle. Demographic and laboratory data were expressed as mean ± SD and median [range]; nonparametric Spearman rank correlations and multiple linear regressions were performed; P-values ⩽0.003 were considered significant. RESULTS: Significant correlations (P ⩽ 0.003) were found for CFT, &agr;-angle, and MCF, in EXTEM, INTEM, and APTEM with platelets, INR, and fibrinogen. Factor VIII (18 measurements) showed a strong correlation (r ≥ 0.7 or r ⩽ −0.7; all P ⩽ 0.003) with MCF, CFT, and &agr;-angle of EXTEM, INTEM, MCF of FIBTEM excluding CT of EXTEM, INTEM, FIBTEM and strong significant correlation for &agr;-angle of APTEM and moderate for CFT and MCF of APTEM. A significant moderate to strong correlation of factor XIII with MCF of EXTEM, INTEM, FIBTEM, and APTEM was found. Hemoglobin was moderately correlated (r = 0.3–0.7 or r = −0.3 to −0.7) with MCF in APTEM (P = 0.003). A moderate to strong correlation of the standard coagulation tests with all ROTEM parameters was found, in particular the CT. The aPTT correlated significantly moderate to strong with CT, CFT, &agr;-angle, and MCF of INTEM. However, multiple linear regressions were not able to show an influence of INR on ROTEM parameters except for APTEM-MCF. A significant impact of the aPTT on INTEM-CT was found. EXTEM, INTEM, and APTEM are significantly influenced by fibrinogen and platelets. CONCLUSIONS: The results confirm the clinical assumption that EXTEM, INTEM, and APTEM are associated with fibrinogen and platelets levels; INTEM-CT significantly to aPTT; and FIBTEM significantly to fibrinogen. Factor VIII showed a significant correlation with all ROTEM parameters except CT of EXTEM, INTEM, FIBTEM, and CFT and MCF of APTEM.

Late pharmacologic conditioning with volatile anesthetics after cardiac surgery

IntroductionThe aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.MethodsAnesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.ResultsFifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).ConclusionsThe data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.Trial registrationClinicalTrials.gov: NCT00924222.

Changes in Coagulation in Standard Laboratory Tests and Rotem in Trauma Patients Between On-scene and Arrival in the Emergency Department

BACKGROUND:When trauma patients arrive in the emergency department (ED), coagulopathy frequently is present. The time course, however, in which this coagulopathy develops is poorly understood. No study has fully evaluated the coagulation status, including thromboelastometry on-scene and at hospital arrival. We hypothesized that measured coagulation variables might change when measured at the scene of injury and upon arrival to the ED. METHODS:We performed a prospective, single-center, observational study investigating coagulation status in 50 trauma patients on-scene and at arrival in the ED. Measurements included arterial blood gases, ROTEM®, protein S100, protein C activity, protein S, Quick value, international normalized ratio, activated partial thromboplastin time, D-dimer, coagulation factor V (FV), coagulation factor XIII (FXIII), fibrinogen, hemoglobin, hematocrit, platelets, and volume and blood products being administered during the first 24 hours. RESULTS:Significant changes between on-scene and the ED were observed for the following values: partial venous oxygen pressure increased and sodium, glucose, and lactate decreased. For EXTEM, INTEM, and APTEM, clotting time and clot formation time increased significantly, whereas maximal clot firmness and angle &agr; decreased significantly (all P ⩽ 0.004). For FIBTEM, clotting time increased significantly and maximal clot firmness decreased significantly. In the laboratory, significant reductions in hemoglobin, hematocrit, platelets, activated partial thromboplastin time, fibrinogen, FV, FXIII, protein C activity, protein S, and protein S100 were observed (all P ⩽ 0.001). CONCLUSIONS:Although most all laboratory and rotational thromboelastometry coagulation tests worsened over time when measured on-scene and in the ED, monitoring coagulation at the scene of trauma does not provide clinically important information in a majority of trauma patients. One hour after injury, significant activation and consumption of fibrinogen, FV, FXIII, protein C activity, and protein S were observed.

Impact of Restrictive Intravenous Fluid Replacement and Combined Epidural Analgesia on Perioperative Volume Balance and Renal Function Within a Fast Track Program

BACKGROUND AND OBJECTIVE Key factors of Fast Track (FT) programs are fluid restriction and epidural analgesia (EDA). We aimed to challenge the preconception that the combination of fluid restriction and EDA might induce hypotension and renal dysfunction. METHODS A recent randomized trial (NCT00556790) showed reduced complications after colectomy in FT patients compared with standard care (SC). Patients with an effective EDA were compared with regard to hemodynamics and renal function. RESULTS 61/76 FT patients and 59/75 patients in the SC group had an effective EDA. Both groups were comparable regarding demographics and surgery-related characteristics. FT patients received significantly less i.v. fluids intraoperatively (1900 mL [range 1100-4100] versus 2900 mL [1600-5900], P < 0.0001) and postoperatively (700 mL [400-1500] versus 2300 mL [1800-3800], P < 0.0001). Intraoperatively, 30 FT compared with 19 SC patients needed colloids or vasopressors, but this was statistically not significant (P = 0.066). Postoperative requirements were low in both groups (3 versus 5 patients; P = 0.487). Pre- and postoperative values for creatinine, hematocrit, sodium, and potassium were similar, and no patient developed renal dysfunction in either group. Only one of 82 patients having an EDA without a bladder catheter had urinary retention. Overall, FT patients had fewer postoperative complications (6 versus 20 patients; P = 0.002) and a shorter median hospital stay (5 [2-30] versus 9 d [6-30]; P< 0.0001) compared with the SC group. CONCLUSIONS Fluid restriction and EDA in FT programs are not associated with clinically relevant hemodynamic instability or renal dysfunction.

Iron core/shell nanoparticles as magnetic drug carriers: possible interactions with the vascular compartment

AIMS Nanomagnets with metal cores have recently been shown to be promising candidates for magnetic drug delivery due to higher magnetic moments compared with commonly used metal oxides. Successful application strongly relies on a safe implementation that goes along with detailed knowledge of interactions and effects that nanomagnets might impart once entering the body. MATERIALS & METHODS In this work, we put a particular focus on the interactions of ultra-strong metal nanomagnets (≥ three-times higher in magnetization compared with oxide nanoparticles) within the vascular compartment. Individual aspects of possible effects are addressed, including interactions with the coagulation cascade, the complement system, phagocytes and toxic or inflammatory reactions both by blood and endothelial cells in response to nanomagnet exposure. RESULTS We show that carbon-coated metal nanomagnets are well-tolerated by cells of the vascular compartment and have only minor effects on blood coagulation. CONCLUSION These findings provide the fundament to initiate successful first in vivo evaluations opening metal nanomagnets with improved magnetic properties to fascinating applications in nanomedicine.

The revised digital transcutaneous PCO2/SpO2 ear sensor is a reliable noninvasive monitoring tool in patients after cardiac surgery.

OBJECTIVE The aim of this study was to validate the revised SenTec V-Sign 2 sensor (SenTec AG, Therwil, Switzerland) for combined noninvasive continuous assessment of pulse rate, pulse oximetry (SpO(2)), and transcutaneous carbon dioxide tension (PtcCO(2)) in adults after cardiac surgery. DESIGN A prospective clinical study. SETTING A single-center university hospital. PARTICIPANTS Twenty adult patients aged 36 to 84 years after cardiac surgery. INTERVENTIONS SpO(2) and PtcCO(2) values of three V-Sign 2 sensors (SenTec AG) attached at the earlobe, forehead, and cheek and SpO(2) values of the Nellcor Durasensor (Model DS-100A; Nellcor Puritan Bennett Inc, Pleasanton, CA) were compared with simultaneous measurements of blood gases and end-expiratory carbon dioxide. MEASUREMENTS AND MAIN RESULTS Measurements were performed during periods of hyper-, normo-, and hypocapnia and then at 30-minute intervals up to 5 hours. Bland-Altman analysis and simple regression analysis were used. RESULTS The detection failures for PtcCO(2) were 0.3% to 1.3%, for SpO(2) 10% to 25%, and for pulse rate 5% to 10%. The V-Sign 2 earlobe sensor provided the best results. The mean bias and limits of agreement for PtcCO(2ear) and PaCO(2) were 1.1 and -3.4/+5.5 mmHg. The drift of PtcCO(2) was negligible at all locations. The mean bias and limits of agreement of V-Sign SpO(2ear) and SaO(2), as well as V-Sign pulse rate and the electrocardiogram, were -1.7% and -6.8/+3.9% and 1.2 beats/min and -3.3/+5.8 beats/min. End-expiratory carbon dioxide showed a weak correlation with PaCO(2) (r(2) = 0.47). CONCLUSIONS Transcutaneous capnometry using the revised V-Sign 2 sensor at the earlobe is a reliable monitoring tool during the recovery period of patients after cardiac surgery. This approach has the potential to reduce the number of arterial blood gas samples.