Jyrki Tenhunen

Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review.

PurposeSystemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) positively correlate with the activation level of the immune system. We reviewed the usefulness of systemic levels of suPAR in the care of critically ill patients with sepsis, SIRS, and bacteremia, focusing on its diagnostic and prognostic value.MethodsA PubMed search on suPAR was conducted, including manual cross-referencing. The list of papers was narrowed to original studies of critically ill patients. Ten papers on original studies of critically ill patients were identified that report on suPAR in sepsis, SIRS, or bacteremia.ResultsSystematic levels of suPAR have little diagnostic value in critically ill patients with sepsis, SIRS, or bacteremia. Systemic levels of suPAR, however, have superior prognostic power over other commonly used biological markers in these patients. Mortality prediction by other biological markers or severity-of-disease classification system scores improves when combining them with suPAR. Systemic levels of suPAR correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of suPAR remain elevated for prolonged periods after admission and only tend to decline after several weeks. Notably, the type of assay used to measure suPAR as well as the age of the patients and underlying disease affect systemic levels of suPAR.ConclusionsThe diagnostic value of suPAR is low in patients with sepsis. Systemic levels of suPAR have prognostic value, and may add to prognostication of patients with sepsis or SIRS complementing severity-of-disease classification systems and other biological markers.

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial.

Background: Intravenous infusion of ice‐cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients.

Deeper chest compression – More complications for cardiac arrest patients?

AIM OF THE STUDY Sternal and rib fractures are frequent complications caused by chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate the potential association of CPR-related thoracic and abdominal injuries and compression depth measured with an accelerometer. METHODS We analysed the autopsy records, CT scans or chest radiographs of 170 adult patients, suffering in-hospital cardiac arrest at the Tampere University Hospital during the period 2009-2011 to investigate possible association of chest compressions and iatrogenic injuries. The quality of manual compressions during CPR was recorded on a Philips, HeartStart MRx Q-CPR™-defibrillator. RESULTS Patients were 110 males and 60 females. Injuries were found in 36% of male and 23% of female patients. Among male patients CPR-related injuries were associated with deeper mean - and peak compression depths (p<0.05). No such association was observed in women. The frequency of injuries in mean compression depth categories <5, 5-6 and >6 cm, was 28%, 27% and 49% (p=0.06). Of all patients 27% sustained rib fractures, 11% sternal fracture and eight patients had haematomas/ruptures in the myocardium. In addition, we observed one laceration of the stomach without bleeding, one ruptured spleen, one mediastinal haemorrhage and two pneumothoraxes. CONCLUSION The number of iatrogenic injuries in male patients was associated with chest compressions during cardiopulmonary resuscitation increased as the measured compression depth exceeded 6 cm. While there is an increased risk of complications with deeper compressions it is important to realize that the injuries were by and large not fatal.

Induction of therapeutic hypothermia during prehospital CPR using ice-cold intravenous fluid ☆

AIM OF THE STUDY Primarily, to investigate induction of therapeutic hypothermia during prehospital cardiopulmonary resuscitation (CPR) using ice-cold intravenous fluids. Effects on return of spontaneous circulation (ROSC), rate of rearrest, temperature and haemodynamics were assessed. Additionally, the outcome was followed until discharge from hospital. MATERIALS AND METHODS Seventeen adult prehospital patients without obvious external causes for cardiac arrest were included. During CPR and after ROSC, paramedics infused +4 degrees C Ringers acetate aiming at a target temperature of 33 degrees C. RESULTS ROSC was achieved in 13 patients, 11 of whom were admitted to hospital. Their mean initial nasopharyngeal temperature was 35.17+/-0.57 degrees C (95% CI), and their temperature on hospital admission was 33.83+/-0.77 degrees C (-1.34 degrees C, p<0.001). The mean infused volume of cold fluid was 1571+/-517 ml. The rate of rearrest after ROSC was not increased compared to previous reports. Hypotension was observed in five patients. Of the 17 patients, 1 survived to hospital discharge. CONCLUSION Induction of therapeutic hypothermia during prehospital CPR and after ROSC using ice-cold Ringers solution effectively decreased nasopharyngeal temperature. The treatment was easily carried out and well tolerated.

A severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant

Abstract A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.

Bile high-mobility group box 1 contributes to gut barrier dysfunction in experimental endotoxemia

Lipopolysaccharide (LPS) is an important factor in sepsis. LPS given by intraperitoneal injection induces intestinal hyperpermeability and bacterial translocation in animals and stimulates hepatic Kupffer cells to release TNF-alpha into the bile. This study aims to test the hypothesis that in response to LPS stimulation, hepatic Kupffer cells and extrahepatic macrophages release a large amount of the inflammatory cytokine high-mobility group box 1 (HMGB1) into the bile and that bile containing HMGB1 contributes to gut barrier dysfunction in experimental endotoxemia. To test this, rat common bile ducts were catheterized and bile flow rate was monitored before and during the LPS administration. Eight hours after LPS challenge, anti-HMGB1 neutralizing antibody or nonimmune (sham) IgG was injected into the duodenal lumen of endotoxemic rats; normal mice were also gavaged with normal or endotoxemic rat bile (bile collected from LPS-treated rats). We found that after LPS challenge, the bile flow rate in rats was significantly decreased at the 4- to 12-h time points, TNF-alpha concentration in the bile was markedly elevated at the 3- to 4-h time points, and bile HMGB1 levels were significantly increased at the 8- to 12-h time points. Duodenal injection with anti-HMGB1 antibody reversed LPS-induced gut barrier dysfunction in rats. In addition, feeding endotoxemic rat bile to normal mice significantly increased both mucosal permeability and bacterial translocation. The increase in permeability and bacterial translocation was reversible following removal of HMGB1 from the endotoxemic rat bile. These findings document that bile HMGB1 mediates gut barrier dysfunction in experimental endotoxemia.

Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest

AIM The quality of cardiopulmonary resuscitation (CPR) is associated with the rate of return of spontaneous circulation (ROSC) during human cardiac arrest. Current advances in defibrillator technology enable measurement of CPR quality during resuscitation, but it is not known whether this is directly reflected in cerebral oxygenation. In this descriptive study we aimed to evaluate whether the quality of feedback-monitored CPR during in-hospital cardiac arrest is reflected in near infrared frontal cerebral spectroscopy (NIRS). METHODS Nine patients suffering an in-hospital cardiac arrest in a university hospital were included. All patients underwent quality-controlled CPR performed by a dedicated medical emergency team using a Philips HeartStart MRx defibrillator (Philips, Eindhoven, Netherlands) with a CPR quality (Q-CPR, Laerdal Medical, Stavanger, Norway) analysis feature. Simultaneously, bilateral frontal cerebral oximetry was measured using INVOS 5100c (Somanetics, Troy, MI, USA) NIRS. RESULTS During quality controlled resuscitation, regional cerebral oxygenation (rSO(2)) as measured with NIRS was low but it improved during CPR (p=0.043) and 8 min after ROSC (p=0.022). After the onset of NIRS recording, there were four episodes exceeding 30s, during which the quality of CPR was substandard. When CPR technique was corrected and maintained for 2 min, a minor non-significant increase in rSO(2) was observed in two cases. CONCLUSIONS High quality CPR was not significantly reflected in cerebral oxygenation as quantified using NIRS. Even after ROSC and subsequent significant increase in cerebral oxygenation, rSO(2) readings were below previously suggested threshold of cerebral ischaemia. Improving CPR technique after an episode of low quality CPR did not significantly increase rSO(2).

Vascular adhesion protein‐1 and syndecan‐1 in septic shock

Constituents of vascular endothelial surface layer (glycocalyx), e.g. an anchor protein syndecan‐1 (SDC‐1), can be detected in plasma in many inflammatory conditions. In inflammation, vascular adhesion protein‐1 (VAP‐1) is rapidly translocated to the apical side of the endothelial cells and may be released to plasma in a soluble form. We hypothesized that glycocalyx injury coincides with VAP‐1 activation on endothelial cells. To test the hypothesis, we measured SDC‐1 and VAP‐1 levels in 20 patients with septic shock.

The proportion of intensive care unit admissions related to alcohol use: a prospective cohort study

Background:  Alcohol abuse is a risk factor for serious illnesses, and a history of chronic alcohol abuse adversely affects the outcome of critically ill patients. It is not known what proportion of intensive care unit (ICU) admissions is related to alcohol use. Therefore, we investigated the proportion of emergency admissions related to alcohol.

High mobility group B1 impairs hepatocyte regeneration in acetaminophen hepatotoxicity

BackgroundAcetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose.MethodsMale C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses.Results24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration.ConclusionHMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.