Summary
Objective
Acute respiratory distress syndrome (ARDS) frequently complicates critical illness. We hypothesized that an infusion of recombinant human activated protein C (rh‐APC), a natural ...anticoagulant, would attenuate pulmonary coagulopathy and injury.
Methods
In this sub study of a multicenter open‐label randomized controlled trial of patients with ARDS, we compared an intravenous (i.v.) infusion of rh‐APC (24 mcg kg−1 h−1 for 96 h) with placebo. Patients with sepsis or septic shock were excluded.
Results
In 27 patients serial non‐directed bronchoalveolar lavage fluid (NBLF) samples were obtained: 16 patients were treated with rh‐APC and 11 patients with placebo. The rh‐APC infusion was associated with higher APC levels in plasma during the infusion period of 4 days (P = 0.001), as well as higher APC levels in NBLF up to day 5 after the start of the infusion (P = 0.028). An infusion of rh‐APC was associated with lower levels of thrombin–antithrombin complexes (P = 0.009) and soluble tissue factor (P = 0.011) in NBLF, compared with treatment with placebo. An infusion of rh‐APC affected fibrinolysis, as plasminogen activator activity levels in NBLF were higher in the patients treated with rh‐APC (P = 0.01), presumably as a result of lower NBLF levels of plasminogen activator inhibitor 1, (P = 0.01). The rh‐APC infusion decreased the lung injury score (P = 0.005) and simplified the acute physiology score (P = 0.013) on day 5, when compared with baseline. The rh‐APC infusion was not associated with bleeding complications.
Conclusion
An infusion of rh‐APC in patients with ARDS attenuates pulmonary coagulopathy and injury.
Abstract Objectives Mild therapeutic hypothermia (MTH) is being used to improve neurological outcome and survival in patients successfully resuscitated after cardiac arrest. The impact on coagulation ...may be difficult to assess since most coagulation parameters are measured at 37 °C and not at actual body core temperature. Therefore we investigated the effects of MTH both at body core (target) temperature of 32 °C and at 37 °C. Methods Patients admitted at the ICU after cardiac arrest treated with MTH. Baseline blood samples, measured at 37 °C were taken directly at arrival. The second and third samples were drawn within 1 h and 24 h after reaching target temperature and were measured at 32 °C and 37 °C. A final sample was drawn when the patient returned to normotemperature (measured at 37 °C). Clotting time (CT) and maximum clotting formation (MCF) were measured with thromboelastometry. Results Upon reaching target temperature (32 °C) Extem and Intem CT were increased compared to baseline with 57 s (49–75) to 65 s (59–72) and 165 s (144–183) to 193 s (167–212) respectively (median with IQR; P < 0.05), with a further significant increase after 24 h of hypothermia with 68 s (57–80) and 221 s (196–266). Samples analyzed at 32 °C showed a significant longer CT of 12 s in Extem and 33 s in Intem compared to 37 °C. MCF was not affected by MTH or adjustment of temperature. Conclusion The mild effect of MTH on coagulation parameters remains unidentified when measured at 37 °C. Although measurements at 32 °C differ from those at 37 °C, this does not appear to be of clinical relevance as all values were still within the reference range.
Herpes simplex virus type 1 (HSV-1) has been associated with pulmonary disease, mostly in severely immunocompromised patients. After reactivation and shedding in the oropharynx, the virus may reach ...the lower respiratory tract by aspiration or by contiguous spread. HSV-1 can be detected in clinical specimens by virus culture or quantitatively by nucleic acid amplification techniques. With these techniques, HSV-1 is often detected in the respiratory secretions of critically-ill patients. However, a clear diagnosis of HSV-1 pneumonia is difficult to establish because clinical criteria, radiological features and laboratory findings all lack specificity. Lower respiratory tract HSV-1 infections have not been associated with specific risk-factors. There is also an absence of consistent data concerning the effect of antiviral treatment on the outcome of critically-ill patients. Further studies are needed to better define the pathogenic role of HSV-1 in the lower respiratory tract of these patients, to improve the diagnosis, and, especially, to assess the need for antiviral treatment in the individual patient.
Aim of this study was to investigate the long-term endocrine effects of treatment of childhood non-Hodgkin lymphoma (NHL).
A single-center cohort of 84 survivors (22 females) was included in this ...retrospective study. Median age was 21 years (9–40 years) and time after cessation of therapy 12 years (4–30 years). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMDTB) and bone mineral density of lumbar spine (BMDLS) were measured. Thyroid-stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), inhibin B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls.
Height was lower in survivors mean standard deviation score (SDS) -0.36, P = 0.002, but further analysis showed that shorter stature was already present at diagnosis (mean SDS -0.28, P = 0.023). Body mass index, percentage fat, BMC, BMDTB and BMDLS were not different from controls. LBM was lower in survivors (mean SDS -0.47, P = 0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three of 20 adult females had low AMH levels and 23 of 42 adult males had low inhibin B levels.
Twelve years after cessation of treatment, NHL survivors did not develop adiposity, osteoporosis or thyroid disease. Male survivors may be at risk for infertility.
Acquired haemophilia is a rare but life-threatening phenomenon in patients who have undergone surgical treatment. We describe a patient with a history of pancreatic cancer and a conventional ...pancreaticoduodenectomy, who underwent elective resection of an enterocutaneous fistula, complicated by fulminant haemorrhagic shock, caused by acquired haemophilia A. Eventually, the bleeding was controlled by a combination of aggressive haemostatic and immunosuppressive therapy. Prompt diagnosis of acquired haemophilia is crucial to allow early and appropriate haemostatic treatment and reduce the period of increased bleeding risk by eradicating the inhibitor with immunosuppressive therapy.
The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials ...investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.
For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.
Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p < 0.001).
Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
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