Dietrich Henzler

Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury

IntroductionThe early application of fibrinogen could potentially reverse haemodilution-induced coagulopathy, although the impact of varying concentrations of fibrinogen to reverse dilutional coagulopathy has not been studied in vivo. We postulated that fibrinogen concentration is correlated with blood loss in a pig model of coagulopathy with blunt liver injury.MethodsCoagulopathy was induced in 18 anaesthetized pigs (32 ± 1.6 kg body weight) by replacing 80% of blood volume with hydroxyethylstarch 130/0.4 and Ringers lactated solution, and re-transfusion of erythrocytes. Animals were randomly assigned to receive either 70 mg kg-1 (F-70) or 200 mg kg-1 (F-200) fibrinogen or placebo before inducing blunt liver injury using a force of 225 ± 26 Newton. Haemodynamics, coagulation parameters and blood loss were monitored for 2 hours. After death, histological examination of internal organs was performed to assess the presence of emboli and the equality of liver injury.ResultsPlasma dilution caused severe coagulopathy. Measured by thromboelastography fibrinogen restored coagulation dose-dependently. Total blood loss was significantly lower and survival better in both fibrinogen groups as compared to controls (P < 0.05). Between the F-70 (1317 ± 113 ml) and the F-200 group (1155 ± 232 ml) no significant difference in total blood loss could be observed, despite improved coagulation parameters in the F-200 group (P < 0.05). Microscopy revealed even injury pattern and no (micro) thrombi for either group.ConclusionsRestoring fibrinogen with 70 or 200 mg kg-1 after severe dilutional coagulopathy safely improved coagulation and attenuated blood loss after experimental blunt liver trauma. The higher dosage of fibrinogen was not associated with a further reduction in blood loss.

Standardizing care and monitoring for anesthesia or procedural sedation delivered outside the operating room.

Purpose of review The purpose of this review is to summarize recommendations for the safe and efficient conductance of sedation and anesthesia at remote locations; and to define safety standards, monitoring techniques, quality of care and procedural eligibility. Recent findings Anesthesia outside of the operating room is rapidly increasing in numbers, which has seen a growth of older and sicker patients. These circumstances have created a need for guidelines, for both specialist anesthesia providers and nonanesthesia-trained practitioners, that define patient selection, minimum monitoring (hemodynamics and respiration), facility design and equipment, policy framework, recovery facilities and policies. The patients safety throughout all stages of sedation and/or anesthesia is the most pertinent goal. Recent data emphasize the importance of monitoring pulse oximetry and end-tidal carbon dioxide for any sedating or anesthetic procedure. Substandard monitoring combined with oversedation and subsequent respiratory depression are implicated as the main reasons for catastrophic sedation and anesthetic outcomes at remote locations. Summary Patient selection, procedure appropriateness and location appropriateness are the key elements defining the provision of safe anesthesia care outside the operating room. Titratable, short-acting intravenous drugs are preferred such as propofol and remifentanil.

Effects of partial ventilatory support modalities on respiratory function in severe hypoxemic lung injury.

Objective:The early phase of acute respiratory distress syndrome (ARDS) is characterized by impaired respiratory mechanics, ventilation-perfusion mismatch, and severe hypoxemia. Partial ventilatory support can effectively unload the respiratory workload and improve pulmonary gas exchange with less hemodynamic compromise. The partial ventilatory support mode most indicated in early phases of ARDS has not been determined. This study compares the effects of assisted ventilatory techniques on breathing pattern, gas exchange, hemodynamic function, and respiratory effort with those of controlled mechanical ventilation in similarly sedated subjects. Design:Prospectively randomized crossover animal study. Setting:Animal research laboratory. Subjects:Eleven anesthetized and mechanically ventilated pigs. Interventions:Acute lung injury was induced by lung lavage. Pressure-controlled ventilation (PCV), pressure-controlled assisted ventilation (P-ACV), bilevel positive airway pressure (BIPAP), and pressure support ventilation (PSV) with equal airway pressures and sedation were applied in random order. Measurements and Main Results:Gas exchange, respiratory effort, and hemodynamic function were measured, and ventilation-perfusion distributions were calculated by multiple inert-gas-elimination techniques. The results revealed that partial ventilatory support was superior to PCV in maintaining adequate oxygenation and hemodynamic function with reduced sedation. The effects of P-ACV, BIPAP, and PSV were comparable with respect to gas exchange and hemodynamic function, except for a more pronounced reduction in shunt during BIPAP. P-ACV and PSV were superior to BIPAP to reduce respiratory drive and work of breathing. PSV affected the pattern of breathing and deadspace to a greater degree than did P-ACV. Conclusions:In acute lung injury, P-ACV preserves oxygenation and hemodynamic function with less respiratory effort compared with BIPAP and reduces the need for sedation compared with PCV.

Evaluation of a modified piezoresistive technique and a water-capsule technique for direct and continuous measurement of intra-abdominal pressure in a porcine model*

Objective:Intravesical pressure measurement is considered to be the gold standard for the assessment of intra-abdominal pressure. However, this method is indirect and depends on a physiologic bladder function. We evaluated a modified piezoresistive technique and a water-capsule technique for direct and continuous intra-abdominal pressure measurement. Design:Experimental study. Setting:Animal research laboratory. Subjects:Eleven male domestic pigs. Interventions:In anesthetized and mechanically ventilated animals, CO2 was insufflated to stepwise increase the intra-abdominal pressure to 30 mm Hg. Pressure was then held constant for 9 hrs followed by decompression. Piezoresistive measurement and water-capsule measurement probes were placed intra-abdominally. Measurements and Main Results:Readings of intravesical pressure measurement, piezoresistive measurement, and water-capsule measurement were taken hourly. Mean difference to insufflator readings, confidence intervals, and limits of agreement were calculated. Differences between applied pressure and intra-abdominal pressure readings were assessed using a two-factor analysis of variance. No significant differences between methods could be observed. During stepwise pressure increase, limits of agreements were −3.6 to 3.6 mm Hg. Confidence intervals were −3.4 to 3.5 (intravesical pressure measurement), −1.6 to 1.5 (piezoresistive measurement), and 0.5 to 2.9 mm Hg (water-capsule measurement). In the presence of constantly elevated intra-abdominal pressure, limits of agreement ranged from −8.2 to + 8.2 mm Hg. Confidence intervals were −0.4 to 6.2 (intravesical pressure measurement), −0.2 to 2.7 (piezoresistive measurement), and 1.1 to 5.1 mm Hg (water-capsule measurement). Conclusions:Both piezoresistive measurement and water-capsule measurement had smaller confidence intervals than intravesical pressure measurement, indicating higher precision, whereas water-capsule measurement had a significant offset. Piezoresistive measurement could be the most suitable device for continuous direct intra-abdominal pressure monitoring in specific patients.

Determination of cardiac output with multislice spiral computed tomography: a validation study.

Objective:To validate and to determine the reproducibility of cardiac output (CO) measurements based on a test-bolus examination in multislice spiral computed tomography (MSCT) in comparison with invasively measured CO using the thermal dilution technique. Material and Methods:In 8 swine, CO was determined by invasive thermal dilution technique and by analysis of enhancement data from dynamic MSCT test-bolus examinations. To assess reproducibility, all MSCT examinations were performed twice. Results were compared using Pearsons correlation coefficient and Bland-Altman plots. Results:Measure by thermal dilution technique CO was 3.71 ± 1.12 L/min, whereas CO was 3.67 ± 1.30 L/min using MSCT. Pearsons correlation coefficient was 0.89. The average deviation between MSCT and thermal dilution technique was 0.04 L/min with a standard deviation of 0.59 L/min. There was a good agreement between both MSCT measurements with a mean deviation of −0.03 L/min and a standard deviation of 0.51 L/min. Conclusion:CO can reliably be determined from MSCT by means of indicator dilution technique. Measurements are reproducible and provide valuable information on the overall cardiovascular performance without application of additional contrast material or radiation. As this technique does not require time-consuming postprocessing it can be added to routine reporting.

S-100 protein and neurohistopathologic changes in a porcine model of acute lung injury

Background: Survivors of acute respiratory distress syndrome exhibit neuropsychological sequelae that might be attributable to hippocampal damage. The authors sought to determine the effects of hypoxemia in a pig model of acute lung injury on the hippocampal region and the release of S-100 protein in comparison to a control group in which hypoxemia was induced by reducing the inspired oxygen fraction. Methods: Hypoxemia was induced in 14 female pigs by repeated lung lavages (lung injury group; n = 7) or by reducing the inspired oxygen fraction (hypoxia-only group; n = 7). Hemodynamic variables, gas exchange, and serum concentrations of S-100 protein were measured at baseline, after induction of acute lung injury, and subsequently for 12 h. Animals were euthanized, and the brains were removed for histopathologic examination. Results: Comparable blood gases were seen in both groups. Serum S-100 protein concentrations were comparable for both groups at baseline. At all other time points, S-100 concentrations were significantly higher in the lung injury group. Neuropathologic examination showed basophilic and shrunken neurons of the pyramidal cell layer in the hippocampal CA1 subregion of all pigs in the lung injury group. Few abnormalities were seen in the hypoxia-only group. Conclusions: The same degree of hypoxemia induced in a lavage model of acute lung injury results in greater brain damage assessed by S-100 protein and histopathologic findings when compared to a group in which hypoxemia at the same degree was induced by reducing the inspired oxygen fraction. This suggests that acute lung injury leads to neuropathologic changes independent of hypoxemia.

Early modifiable factors associated with fatal outcome in patients with severe traumatic brain injury: a case control study.

Objective:Survival of patients with severe traumatic brain injury may be improved by minimizing secondary brain injury. We aimed to identify potentially modifiable contributors to secondary brain injury that may persist and adversely affect patient outcome. Design:Retrospective case control study. Nonsurviving patients with traumatic brain injury were selected and matched 1:1 for age, Glasgow Coma Scale score, Abbreviated Injury Scale: Head (AISHEAD), Revised Trauma Score, and Injury Severity Score with survivors. Potentially modifiable contributors to secondary brain injury were examined and compared in both groups. Setting:A level I trauma center in Melbourne, Australia. Patients:Patients with traumatic brain injury caused by blunt trauma with an AISHEAD ≥4 were identified from a prospective intensive care database. Interventions:None. Measurements and Main Results:Between January 1, 1999, and July 30, 2000, 74 patients, including 37 nonsurvivors, were identified. By design, the groups were well matched for injury severity and baseline conditions. In nonsurvivors, mean arterial pressure was similar to that of survivors at hospital arrival but was lower at 4 hrs after arrival (71 ± 16 vs. 80 ± 15 mm Hg, p = .016). A mean arterial pressure ≤65 mm Hg during this 4-hr period was associated with a four-fold increase in the odds of nonsurvival (95% confidence interval, 1.25–12.8). Intracranial pressure monitoring and intensive care unit admission tended to be initiated later in nonsurvivors, potentially delaying recognition and management of inadequate cerebral perfusion pressure. In nonsurvivors, hypothermia did not normalize during the first 24 hrs after injury. Conclusions:In patients with severe traumatic brain injury, lower blood pressure in the first 4 hrs after admission was associated with mortality and may have increased the rate of secondary brain injury. Outcomes of patients with severe traumatic brain injury may potentially be improved by early targeting of the higher mean arterial pressure observed in survivors (mean arterial pressure 80 mm Hg), which may facilitate improved cerebral perfusion. Slower initiation of intracranial pressure monitoring and of intensive care unit admission may also have adversely affected outcomes, whereas persistent hypothermia was associated with nonsurvival.

Hemocompatibility of a Miniaturized Extracorporeal Membrane Oxygenation and a Pumpless Interventional Lung Assist in Experimental Lung Injury

Extracorporeal membrane oxygenation (ECMO) is used for most severe acute respiratory distress syndrome cases in specialized centers. Hemocompatibility of devices depends on the size and modification of blood contacting surfaces as well as blood flow rates. An interventional lung assist using arteriovenous perfusion of a low-resistance oxygenator without a blood pump (Novalung, Hechingen, Germany) or a miniaturized ECMO with reduced filling volume and a diagonal blood pump (Deltastream, Medos AG, Stolberg, Germany) could optimize hemocompatibility. The aim of the study was to compare hemocompatibility with conventional ECMO. Female pigs were connected to extracorporeal circulation for 24 h after lavage induced lung injury (eight per group). Activation of coagulation and immune system as well as blood cell damage was measured. A P value <0.05 was considered significant. Plasmatic coagulation was slightly activated in all groups demonstrated by increased thrombin-anti-thrombin III-complex. No clinical signs of bleeding or thromboembolism occurred. Thrombelastography revealed decreased clotting capacities after miniaturized ECMO, probably due to significantly reduced platelet count. These resulted in reduced dosage of intravenous heparin. Scanning electron microscopy of oxygenator fibers showed significantly increased binding and shape change of platelets after interventional lung assist. In all groups, hemolysis remained negligible, indicated by low plasma hemoglobin concentration. Interleukin 8 and tumor necrosis factor-alpha concentration as well as leukocyte count remained unchanged. Both devices demonstrated adequate hemocompatibility for safe clinical application, although a missing blood pump did not increase hemocompatibility. Further studies seem necessary to analyze the influence of different blood pumps on platelet drop systematically.

Partial Ventilatory Support Modalities in Acute Lung Injury and Acute Respiratory Distress Syndrome—A Systematic Review

Purpose The efficacy of partial ventilatory support modes that allow spontaneous breathing in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is unclear. The objective of this scoping review was to assess the effects of partial ventilatory support on mortality, duration of mechanical ventilation, and both hospital and intensive care unit (ICU) lengths of stay (LOS) for patients with ALI and ARDS; the secondary objective was to describe physiologic effects on hemodynamics, respiratory system and other organ function. Methods MEDLINE (1966–2009), Cochrane, and EmBase (1980–2009) databases were searched using common ventilator modes as keywords and reference lists from retrieved manuscripts hand searched for additional studies. Two researchers independently reviewed and graded the studies using a modified Oxford Centre for Evidence-Based Medicine grading system. Studies in adult ALI/ARDS patients were included for primary objectives and pre-clinical studies for supporting evidence. Results Two randomized controlled trials (RCTs) were identified, in addition to six prospective cohort studies, one retrospective cohort study, one case control study, 41 clinical physiologic studies and 28 pre-clinical studies. No study was powered to assess mortality, one RCT showed shorter ICU length of stay, and the other demonstrated more ventilator free days. Beneficial effects of preserved spontaneous breathing were mainly physiological effects demonstrated as improvement of gas exchange, hemodynamics and non-pulmonary organ perfusion and function. Conclusions The use of partial ventilatory support modalities is often feasible in patients with ALI/ARDS, and may be associated with short-term physiological benefits without appreciable impact on clinically important outcomes.

A miniaturized extracorporeal membrane oxygenator with integrated rotary blood pump: preclinical in vivo testing.

Extracorporeal membrane oxygenation can achieve sufficient gas exchange in severe acute respiratory distress syndrome. A highly integrated extracorporeal membrane oxygenator (HEXMO) was developed to reduce filling volume and simplify management. Six female pigs were connected to venovenous HEXMO with a total priming volume of 125 ml for 4 hours during hypoxemia induced by a hypoxic inspired gas mixture. Animals were anticoagulated with intravenous heparin. Gas exchange, hemodynamics, hemolysis, and coagulation activation were examined. One device failed at the magnetic motor coupling of the integrated diagonal pump. In the remaining five experiments, the oxygenation increased significantly (arterial oxygen saturation [SaO2] from 79 ± 5% before HEXMO to 92% ± 11% after 4 hours) facilitated by a mean oxygen transfer of 66 ± 29 ml/dl through the oxygenator. The CO2 elimination by the HEXMO reduced arterial PaCO2 only marginal. Extracorporeal blood flow was maintained at 32% ± 6% of cardiac output. Hemodynamic instability or hemolysis was not observed. The plasmatic coagulation was only mildly activated without significant platelet consumption. The HEXMO prototype provided sufficient gas exchange to prevent hypoxemia. This proof of concept study supports further development and design modifications to increase performance and to reduce coagulation activation for potential long-term application.