Argon reduces neurohistopathological damage and preserves functional recovery after cardiac arrest in rats.

BACKGROUND: Xenon has profound neuroprotective effects after neurological injury and is currently undergoing phase 2 clinical trials in cardiac arrest patients. However, xenon is very costly, which might preclude its widespread use. We hypothesized argon, which is more available, might also protect central nervous tissues and allow better functional recovery in a rodent model of global cerebral ischaemia. METHODS: Fourteen male Sprague-Dawley rats were subjected to 7 min of cardiac arrest and 3 min of cardiopulmonary resuscitation (CPR). One hour after successful CPR, animals were randomized to either ventilation with 70% argon in oxygen (n = 7) for 1 h or 70% nitrogen (controls, n=7). A neurological deficit score (NDS) was calculated daily for the following 7 days, then the animals were killed and the brains harvested for histopathological analyses. RESULTS: All animals survived. Control rats had severe neurological dysfunction, while argon-treated animals showed significant improvements in the NDS at all time points. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region. CONCLUSIONS: Our study demonstrates that a single 1 h application of 70% argon significantly reduced histopathological damage of the neocortex and hippocampus, associated with a marked improvement in functional neurological recovery.

Recombinant factor VIIa reduces bleeding after blunt liver injury in coagulopathic, hypofibrinogenaemic pigs.

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been successfully used in various clinical conditions to treat severe coagulopathy, but its efficacy may be affected by the underlying conditions. We therefore investigated the efficacy of rFVIIa treatment under conditions of hypofibrinogenaemia in a pig model of blunt liver injury. METHODS: Severe haemodilution was instigated in four groups of seven anaesthetized pigs. Before inflicting liver injury, animals were assigned to receive either 70 mg kg(-1) fibrinogen (fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 µg kg(-1)) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups) was administered. Haemodynamic variables, coagulation parameters, and blood loss were monitored for 2 h. Histology was examined to evaluate the presence of thrombi and the consistency of liver injury. RESULTS: At the end of the observation period, total blood loss [median (range)] decreased in all intervention groups [fibrinogen: 1275 (1221-1439) ml, P=0.036; rFVIIa: 966 (923-1136) ml, P=0.008; fibrinogen+rFVIIa: 678 (475-756) ml, P=0.008] when compared with control animals [blood loss: 1752 (1735-2221) ml]. The mortality rate in the control group was 100%, whereas only 42% of fibrinogen-substituted animals died (P=0.023). All animals treated with rFVIIa or fibrinogen+rFVIIa (P<0.001) survived and no signs of thromboembolism were observed. CONCLUSIONS: rFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact on coagulation parameters and a reduction in blood loss. These effects were significantly improved after prior substitution with fibrinogen.

[Hyperbaric oxygenation: characteristics of intensive care and emergency therapy]. / Hyperbare Sauerstofftherapie: Notfall- und intensivmedizinische Besonderheiten.

Hyperbaric oxygenation (HBO) is a decisive component of a comprehensive interdisciplinary intensive care therapy for numerous disorders, such as gas embolism, severe decompression illness or carbon monoxide (CO) intoxication. However, barochambers with 24 h accessibility are often not readily available, thus, requiring an interhospital transport of critically ill patients. In order to minimise additional risks, a skilled transportation team should be involved. Furthermore, the specific physical and physiological features of HBO require that the transportation personnel must be trained adequately. Specific characteristics of the interhospital transfer of HBO patients are described as well as adverse effects and their specific therapy.

[Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. / Diagnose und Therapie der Sepsis. S2-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

Life-threatening postoperative blood loss in a Jehovah's Witness, treated with high-dose erythropoietin.

Six hours after an uncomplicated extended resection of ovarian cancer, postoperative arterial bleeding led to life-threatening blood loss in a 44-yr-old Jehovah's Witness who refused blood transfusion. Haemoglobin (Hb) decreased from 2.5 g dl(-1) directly after the emergency laparotomy, followed by a 10 h immeasurable period (below detectable minimum value of the analyser), to a measurable minimum of 1.5 g dl(-1) after 20 h. Haematopoiesis was induced by high-dose i.v. erythropoietin therapy (600 IU kg(-1)) and continued on days 3, 6, 8, 10 and 13. Iron, folic acid and vitamins were given as supplements. The patient needed ventilatory assistance for 18 days and some inotropic support. Complications included increases in pancreatic enzymes and liver enzymes, jaundice and skin necrosis at the fingertips and toes. Myopathy led to transient tetraparesis. Haemoglobin rose from 1.5 to 3.4 g dl(-1) (day 10) and the patient was discharged from the intensive care unit with haemoglobin 6.5 g dl(-1) on day 24. She made a full recovery and is still free of cancer in remission.

Magnesium as part of balanced general anaesthesia with propofol, remifentanil and mivacurium: a double-blind, randomized prospective study in 50 patients.

BACKGROUND AND OBJECTIVE: To test the hypothesis that magnesium sulphate reduces the amount of remifentanil needed for general anaesthesia in combination with propofol and mivacurium, we studied 50 patients undergoing elective pars plana vitrectomy in a double-blind, randomized prospective fashion. METHODS: Magnesium sulphate (50 mg kg(-1) body weight) or placebo (equal volume of NaCl) was given slowly intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1). Anaesthesia was maintained with propofol (using electroencephalographic control), mivacurium (according to train-of-four monitoring of neuromuscular blockade) and remifentanil (according to heart rate and arterial pressure). RESULTS: We observed a significant reduction in remifentanil consumption from 0.14 to 0.09 microg kg(-1) min(-1) (P < 0.01). Mivacurium consumption was also markedly reduced from 0.01 to 0.008 mg kg(-1) min(-1) (P < 0.01), whereas propofol consumption remained unchanged. There was a trend towards lower postoperative pain scores, less pain medication requirements in 24 h after surgery and less postoperative nausea and vomiting in the magnesium group but not statistically significant. No side-effects were observed. CONCLUSION: We can recommend the use of magnesium sulphate as a safe and cost-effective supplement to a general anaesthetic regimen with propofol, remifentanil and mivacurium, although we cannot clearly distinguish between a mechanism as a (co)analgesic agent at the NMDA-receptor site or its properties as a sympatholytic. The effect of a single bolus dose of 50 mg kg(-1) on induction lasts for about 2 h. For longer cases, either a continuous infusion or repeated bolus doses might be necessary.

Effects of combined high-dose partial liquid ventilation and almitrine on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury.

OBJECTIVES: To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN AND SETTING: Prospective, controlled animal study in an animal research facility of a university hospital. INTERVENTIONS: ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6). MEASUREMENT AND RESULTS: Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone. CONCLUSIONS: In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.

[Hyperbaric oxygen therapy (HBO): current standing]. / Hyperbare Oxygenationstherapie (HBO): eine Standortbestimmung.

For more than thirty years hyperbaric oxygen therapy (HBO) has been an important and ultimate therapeutic tool in special indications. Hyperbaric oxygen improves tissue oxygenation, stimulates important mechanisms in wound healing and exerts beneficial effects on other biochemical and cellular processes. The properties of hyperbaric oxygen have built the rationale for its use as therapy of choice in patients with severe carbon monoxide poisoning, decompression sickness and arterial gas embolism, and as adjunctive therapy for the treatment of osteoradionecrosis, necrotizing fasciitis and compromised skin grafts and flaps. The efficacy of adjunctive hyperbaric oxygen in the treatment of lower extremity problem wounds in diabetic patients seems to be proven. There is little scientific support for other uses of hyperbaric oxygen and its therapeutical benefit should be further investigated. When used according to standard protocols hyperbaric oxygen treatment is a safe therapy with little adverse effects.

Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension.

OBJECTIVE: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs. DESIGN: Prospective, controlled animal study. SETTING: Animal research facilities of an university hospital. INTERVENTIONS: After reducing the fraction of inspired oxygen (FIO(2)) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng x kg(-1) x min(-1)). RESULTS: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO(2) 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng x kg(-1) x min(-1) prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study. CONCLUSIONS: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.