No hyperfibrinolysis following subarachnoid or intracerebral haemorrhage: a prospective cohort study.

: Changes in fibrinolysis following subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) are sparsely investigated. To investigate fibrinolysis in the acute phase in SAH and ICH patients compared with healthy individuals, fibrinolysis after 24 h in ICH patients and the in-vivo effect of tranexamic acid (TXA) on fibrinolysis in SAH patients. Further, ex-vivo studies were performed by addition of several haemostatic agents to blood samples obtained at admission. Blood was sampled from 46 SAH and 41 ICH patients upon admission. In ICH patients, a second blood sample was obtained 24 h after symptom onset, and in SAH patients after TXA treatment. A sex-matched healthy control group was used for comparison. Fibrinolysis and clot stability were assessed by a dynamic fibrin clot lysis assay, and measurements of plasminogen activator inhibitor I, tissue plasminogen activator and coagulation factor XIII were performed. On admission, no difference in lysis time was found in SAH or ICH patients compared with healthy controls (all P values >0.15). For SAH and ICH patients, median plasminogen activator inhibitor I, tissue plasminogen activator and factor XIII levels were within the reference intervals. In ICH patients, lysis time remained within 24 h after symptom onset (P = 0.63). In SAH patients, the clot lysis curve showed a complete block of fibrinolysis after TXA administration. Ex-vivo addition of solulin and prothrombin complex concentrate reduced fibrinolysis (P < 0.001). SAH and ICH patients showed no hyperfibrinolysis on admission. Fibrinolysis remained normal in ICH patients, and TXA treatment obliterated fibrinolysis in SAH patients.

[Intensive therapy for patients with Guillian-Barré syndrome].

Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.

Intensive care delirium - effect on memories and health-related quality of life - a follow-up study.

AIMS AND OBJECTIVES: To investigate the effects of delirium in the intensive care unit on health-related quality of life, healthcare dependency and memory after discharge and to explore the association between health-related quality of life and memories, patient diaries and intensive care unit follow-up. BACKGROUND: Up to 83% of intensive care unit patients experience delirium. In addition to increased risk of mortality, morbidity and cognitive impairment, the experience itself is unpleasant. A number of studies have focused on memories associated with delirium, but the association between delirium, memories and health-related quality needs further investigation. DESIGN: We used an observational multicentre design with telephone interviews. METHODS: Adult intensive care unit patients (n = 360) were consecutively recruited and interviewed using the intensive care unit-Memory Tool one week after intensive care unit. Interviews were repeated after two and six months and supplemented with Short Form-36 and the Barthel Index. RESULTS: Delirium was detected in 60% of the patients in our study, and delirious patients had significantly fewer factual memories and more memories of delusion than nondelirious patients up to six months postintensive care unit discharge. Delirium, memories and intensive care unit diaries with follow-up did not affect health-related quality of life and healthcare dependency. Memories of delusions might have an impact on patients assessed as nondelirious. CONCLUSIONS: More than half of the patients in intensive care unit experience delirium, which is associated with fewer factual memories and more memories of delusions. Short Form-36 might not be sensitive to delirium-related outcomes. Future research should include the development of better assessment tools to determine the long-term consequences of intensive care unit delirium. RELEVANCE TO CLINICAL PRACTICE: We recommend regular assessment to prevent, detect and treat delirium. We also recommend an intensive care unit follow-up programme providing an opportunity for postintensive care unit patients, particularly previously delirious patients, to discuss their memories and experiences with intensive care unit professionals.

The effect of dietary fatty acids on post-operative inflammatory response in a porcine model.

The potential anti-inflammatory effects of dietary fish oil (FO) have been studied in numerous clinical trials. However, variation in lifestyle and morbidity among patients can be difficult to control. In the present study, the impact of a 3-week dietary pre-treatment with 10% (w/w) FO (n 28), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 < day ≤ 3), FO suppressed whole blood IL-8 and tumor necrosis factor-α responsiveness to LPS stimulation, decreased peripheral leukocyte IL-8 mRNA abundance, reinforced an increase in total leukocyte count, and counteracted a decrease in mononuclear leukocyte count compared with SO. In the late post-operative period (3 < day ≤ 14), FO increased total leukocyte count and showed higher maximum CRP and haptoglobin concentrations compared with SO. Compared with AF, FO decreased peripheral leukocyte IL-8 mRNA abundance in the early post-operative period, and increased total leukocyte count and maximum CRP concentration in the late post-operative period. In conclusion, the post-operative response in a number of inflammatory markers was affected by FO, and this was most apparent compared with SO.

Effects of dietary n-3 and n-6 fatty acids on clinical outcome in a porcine model on post-operative infection.

The present study was performed to evaluate the effects of dietary n-3 and n-6 long-chain PUFA (LC-PUFA) on clinical outcome in a porcine model on early aortic vascular prosthetic graft infection (AVPGI). A total of eighty-four pigs were randomised to a 35 d dietary treatment with 10 % (w/w) fish oil (rich in n-3 LC-PUFA), sunflower oil (rich in n-6 LC-PUFA) or animal fat. After 3 weeks of dietary treatment, the pigs had an aortic vascular prosthetic graft inserted, and it was inoculated with Staphylococcus aureus (106 colony-forming units). Changes in selected plasma and erythrocyte n-3 and n-6 LC-PUFA concentrations and in plasma PGE2 metabolite concentration were determined in the 3-week preoperative period. Clinical signs of infection, i.e. rectal temperature, hindquarter function, general appearance and feed intake, were monitored daily in the 14 d post-operative period, and, finally, daily body-weight gain was determined in both periods. The preoperative changes in plasma and erythrocyte n-3 and n-6 LC-PUFA concentrations reflected the fatty acid compositions of the dietary treatments given, and plasma PGE2 metabolite concentration decreased in the fish oil treatment (P < 0·001). In the post-operative period, feed intake (P = 0·004) and body-weight gain (P = 0·038) were higher in the fish oil treatment compared with the sunflower oil treatment. The dietary treatments did not affect the number of days pigs were showing fever, weakness in the hindquarters or impaired general appearance. In conclusion, preoperative treatment with dietary fish oil compared with sunflower oil improved clinical outcome in pigs with AVPGI by improving feed intake and body-weight gain post-operatively.

Lymphocyte apoptosis is resistant to erythropoietin in porcine endotoxemia.

Sepsis-induced lymphocyte apoptosis plays an important role in the development of immune suppression in septic patients. Erythropoietin (EPO) is a multifunctional cytokine with antiapoptotic properties. We hypothesized that EPO could mitigate mononuclear cell (MNC) apoptosis and modify the dynamic changes of MNCs during endotoxemia. Twenty-six pigs were randomized into three groups: (i) lipopolysaccharides (LPS), (ii) EPO (epoetin-α, 5000 IU/kg) administered 60 min prior to LPS, and (iii) sham. At 120 min of endotoxemia, the animals were fluid resuscitated and the LPS infusion was reduced. MNCs were isolated at 0, 60, 240, and 540 min of endotoxemia, and apoptosis was assessed by flow cytometry. Apoptosis in splenic biopsies was quantified by immunohistochemistry. Endotoxemia increased the number of apoptotic MNCs in the blood (p ≤ 0.01) and the spleen (p = 0.03), and EPO did not modify this increase. The number of T-helper and cytotoxic T cells declined during endotoxemia. The dynamic changes of the MNC subsets were not modified by treatment with EPO. In conclusion, EPO did not modify the LPS-induced changes of MNC subsets or mitigate the levels of apoptosis of MNCs in the blood or in the spleen. This study does not support that EPO confers protection against lymphocyte apoptosis.

Natural killer cells as biomarkers of hyperbaric stress during a dry heliox saturation dive.

INTRODUCTION: Diving, hyperbaric oxygen, and decompression have been described as inducers of alterations in various components of the human immune system, such as the distribution of circulating lymphocytes. Hypothetically, the monitoring of specific lymphocyte subsets during hyperbaric exposure, including T- and NK-cell subsets, can serve as biomarkers of hyperbaric stress. METHODS: Eight experienced saturation divers and eight reference subjects, naive to deep saturation diving, were examined. Peripheral blood mononuclear cells were isolated before and at different points during a 19.3-d dry heliox saturation dive to 2.64 MPa (254 msw). The NK cell cytotoxicity was estimated in a 4-h 51Cr-release assay using the NK cell sensitive tumor cell-line K562 as target cells. The major lymphocyte subpopulations, with special emphasis on the NK cell subsets, were phenotypically delineated by the use of 4-color flow cytometry. RESULTS: Although NK cell cytotoxicity increased significantly in the divers during the compression phase and the reference subjects who remained in normoxic conditions outside the chamber, the NK cell cytotoxicity was significantly higher in the divers. DISCUSSION: This finding, together with augmentation in the absolute number of circulating NK cells in the divers due to a possible activation of specific parts of the innate cellular immune system during hyperbaric exposure, suggests the monitoring of specific immune functions can be useful as biomarkers of hyperbaric-induced inflammatory stress.

Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: a randomized clinical trial.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) can be difficult to manage and may delay recovery. Recent studies have suggested that periarticular infiltration with local anesthetics may improve outcome. METHODS: 80 patients undergoing TKA under spinal anesthesia were randomized to receive continuous femoral nerve block (group F) or peri- and intraarticular infiltration and injection (group I). Group I received a solution of 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine by infiltration of the knee at the end of surgery, and 2 postoperative injections of these substances through an intraarticular catheter. RESULTS: More patients in group I than in group F could walk < 3 m on the first postoperative day (29/39 vs. 7/37, p < 0.001). Group I also had significantly lower pain scores during activity and lower consumption of opioids on the first postoperative day. No differences between groups were seen regarding side effects or length of stay. INTERPRETATION: Peri- and intraarticular application of analgesics by infiltration and bolus injections can improve early analgesia and mobilization for patients undergoing TKA. Further studies of optimal drugs, dosage, and duration of this treatment are warranted.

[Critical care research]. / Forskning i kritisk sygdom.

Critical care research has facilitated the development of clinical guidelines to improve the outcome of critically-ill patients. The high mortality needs to be reduced further, by means of increased research to the benefit of patients, relatives and society. Clinicians, researchers, public officials and politicians at all levels must work together towards this aim.

[Sepsis in the critically-ill patient]. / Sepsis hos den kritisk syge patient.

SIRS, sepsis, severe sepsis, and septic shock are complex syndromes ranging from early signs of infection to multiple organ dysfunction and shock. The reported incidence of sepsis is as high as 35% with mortality rates from 27% to 54% in sepsis and septic shock, respectively. Though aetiology and pathogenesis can vary significantly between septic patients, emphasis has been made to preserve sepsis as a clinical diagnosis ensuring high sensitivity. Since 2001 several new treatment strategies have been implemented, but early diagnosis, optimization of haemodynamics, rapid identification of pathogen and adequate antibiotic treatment are still of the highest importance.

[The systematic inflammatory response after major trauma]. / Det systemisk inflammatoriske respons ved akutte traumer.

Few investigations have elucidated the acute inflammatory response after accidental trauma before the patients were anesthetized and treated with analgetics and intravenous fluid. The cellular immunological response seems to be characterized by an initial activation followed by suppression. In major tissue trauma, the granulocytes are the major effector cells. Activated granulocytes are redistributed from the peripheral blood into the tissues, where release of proteolytic enzymes and oxygen-free radicals participate in the development of systemic inflammation and organ dysfunction. The antigen presentation capacity of monocytes and the cytotoxicity of NK-cells are reduced following major trauma. High concentrations of proinflammatory and antiinflammatory cytokines can be measured locally in the injured tissue. In uncomplicated cases, elevated cytokine concentrations are measured in the blood for a few days, whereas a sustained high cytokine production seems to correlate with organ dysfunction and mortality.