Ralf Kuhlen

Influence of mild therapeutic hypothermia on the inflammatory response after successful resuscitation from cardiac arrest.

PURPOSE Although animal studies document conflicting data on the influence of hypothermia on cytokine release in various settings, no data exist if hypothermia affects the inflammatory response after successful cardiopulmonary resuscitation. MATERIALS AND METHODS Arrest- and treatment-related variables of 71 patients were documented, and serum samples were analyzed for levels of interleukin 6, tumor necrosis factor-alpha, C-reactive protein, and procalcitonin immediately after hospital admission and after 6, 24, and 120 hours. At day 14, patients were dichotomized in those with good and bad neurological outcome. RESULTS Regardless of outcomes, interleukin 6 levels were significantly elevated by the use of hypothermia (n = 39). The rate of bacterial colonization was significantly higher in hypothermic patients (64.1 vs 12.5 %; P < .001). On the contrary, procalcitonin levels were, independent of the use of hypothermia, only significantly elevated in patients with bad neurological outcome. Hypothermic patients showed a strong trend to reduced mortality. However, there was no influence on neurological recovery. CONCLUSIONS In this observational study, hypothermia influenced the inflammatory response after cardiopulmonary resuscitation and lead to a higher rate of bacterial colonization without altering ultimate neurologic recovery.

Evidence-based medicine in the therapy of the acute respiratory distress syndrome.

In 1972 Cochrane [1] coined the term “evidence-based medicine” (EBM) and suggested that scientific knowledge, especially prospective randomized controlled studies, is superior to personal experience. The principles of EBM were first used by Sackett [2] in 1986 for developing clinical recommendations on the use of antithrombotic agents. He classified five levels of scientific data resulting in three different grades of recommendation:

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.

Pressure support compared with controlled mechanical ventilation in experimental lung injury.

UNLABELLED It has been suggested that, in acute lung injury (ALI), spontaneous breathing activity may increase oxygenation because of an improvement of ventilation-perfusion distribution. Pressure support ventilation (PSV) is one of the assisted spontaneous breathing modes often used in critical care medicine. We sought to determine the prolonged effects of PSV on gas exchange in experimental ALI. We hypothesized that PSV may increase oxygenation because of an improvement in ventilation-perfusion distribution. Thus, ALI was induced in 20 pigs by using repetitive lung lavage. Thereafter, the animals were randomized to receive either PSV with a pressure level set to achieve a tidal volume >4 mL/kg and a respiratory rate <40 min(-1) (n = 10) or controlled mechanical ventilation (CMV) with a tidal volume of 10 mL/kg and a respiratory rate of 20 min(-1) (n = 10). Positive end-expiratory pressure was set at 10 cm H(2)O in both groups. Blood gas analyses and determination of ventilation-perfusion (.V(A)/.Q) distribution were performed at the onset of ALI and after 2, 4, 8, and 12 h. The main result was an improvement of oxygenation because of a decrease of pulmonary shunt and an increase of areas with normal .V(A)/.Q ratios during PSV (P < 0.005). However, during CMV, a more pronounced reduction of shunt was observed compared with PSV (P < 0.005). We conclude that, in this model of ALI, PSV improves gas exchange because of a reduction of .V(A)/.Q inequality. However, improvements in .V(A)/.Q distribution may be more effective with CMV than with PSV. IMPLICATIONS Assisted spontaneous breathing may have beneficial effects on gas exchange in acute lung injury. We tested this hypothesis for pressure support ventilation in an animal model of acute lung injury. Our results demonstrate that pressure support does not necessarily provide better gas exchange than controlled mechanical ventilation.

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.

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.

Quality indicators in intensive care medicine: why? Use or burden for the intensivist.

In order to improve quality (of therapy), one has to know, evaluate and make transparent, one’s own daily processes. This process of reflection can be supported by the presentation of key data or indicators, in which the real as-is state can be represented. Quality indicators are required in order to depict the as-is state. Quality indicators reflect adherence to specific quality measures. Continuing registration of an indicator is useless once it becomes irrelevant or adherence is 100%. In the field of intensive care medicine, studies of quality indicators have been performed in some countries. Quality indicators relevant for medical quality and outcome in critically ill patients have been identified by following standardized approaches. Different German societies of intensive care medicine have finally agreed on 10 core quality indicators that will be valid for two years and are currently recommended in German intensive care units (ICUs).

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.

Low tidal volume ventilation in a porcine model of acute lung injury improves cerebral tissue oxygenation.

BACKGROUND:In study, we investigated the effects of different tidal volumes on cerebral tissue oxygenation and cerebral metabolism in a porcine model of acute lung injury (ALI). We hypothesized that mechanical ventilation with low tidal (LT) volumes improves cerebral tissue oxygenation and metabolism after experimentally induced ALI. METHODS:After inducing experimental ALI by surfactant depletion, we studied two conditions in 10 female pigs: 1) LT volume ventilation with 6 mL/kg body weight, and 2) high tidal (HT) volume ventilation with 12 mL/kg body weight. Variables of gas exchange, hemodynamic, continuous cerebral tissue oxygen tension (ptiO2), cerebral microdialysis, and systemic cytokines were analyzed. After induction of ALI, data were collected at 2, 4, and 8 h. The primary end point was the change in ptiO2. For group comparisons, a t-test was used. A value of <0.05 was considered to indicate statistical significance. RESULTS:At baseline and after induction of ALI, no differences between groups were found in ptiO2; however, ptiO2 was significantly lower in the HT group after 4 and 8 h. Pao2 and Paco2 showed no significant differences between the groups at all timepoints. Regarding cerebral microdialysis, a significantly higher level of extracellular lactate could be demonstrated after 2, 4, and 8 h in the HT group. The release of cytokines resulted in higher values for interleukin-6 and interleukin-8 in the HT group. CONCLUSION:Protective ventilation with LT yielded a significant improvement in cerebral tissue oxygenation and metabolism compared to HT ventilation in a porcine model of ALI. There was dissociation between arterial and cerebral tissue oxygenation. Cerebral oxygenation and metabolism might have possibly been impaired by a more distinctive inflammatory response in the HT group.

Peer reviewing critical care: a pragmatic approach to quality management.

Critical care medicine frequently involves decisions and measures that may result in significant consequences for patients. In particular, mistakes may directly or indirectly derive from daily routine processes. In addition, consequences may result from the broader pharmaceutical and technological treatment options, which frequently involve multidimensional aspects. The increasing complexity of pharmaceutical and technological properties must be monitored and taken into account. Besides the presence of various disciplines involved, the provision of 24-hour care requires multiple handovers of significant information each day. Immediate expert action that is well coordinated is just as important as a professional handling of medicines limitations. Intensivists are increasingly facing professional quality management within the ICU (Intensive Care Unit). This article depicts a practical and effective approach to this complex topic and describes external evaluation of critical care according to peer reviewing processes, which have been successfully implemented in Germany and are likely to gain in significance.