Juha Koskenkari

Leukocyte depleting filter attenuates myocardial injury during elective coronary artery bypass surgery

Background. Ischemia-reperfusion injury secondary to leukocyte activation has been widely recognized as one of the most relevant mechanism leading to postoperative organ dysfunction occurring after a period of ischemia. The aim of the present study was to evaluate in a prospective, randomized study, the value of leukocyte depleting filter in patients undergoing elective coronary artery bypass surgery. Methods. Twenty patients scheduled for elective on-pump coronary artery bypass surgery were randomized to undergo cardiopulmonary bypass either with a leukocyte depleting filter incorporated in the extracorporeal circulation arterial line or without a filter. Results. The main finding of this study was the significantly lower postoperative concentrations of cardiac troponin I in the leukocyte filter group (Tests of between-subjects effects: p = 0.024). There were also slightly better cardiac indices in the leukocyte filter group. A larger amount of blood units was infused intra- and postoperatively in patients undergoing cardiopulmonary bypass with leukocyte filtration (median, 600 [IQR, 0–1200] vs. 0 [IQR, 0–600], p = 0.08). Two patients in the leukocyte filter group underwent reoperation for bleeding but none in the control group (p = 0.48). Intra-and postoperative platelet count was lower in the leukocyte filter group (Tests of between-subjects effects: p = 0.08). Despite a significant increased concentration of C-reactive protein on the first postoperative day in the control group (p = 0.029), repeated-measures analysis failed to show any significant increase during the study period (p = 0.33). Conclusions. The results of this study suggest a myocardial protective effect of leukocyte filter in the setting of elective coronary artery bypass surgery.

Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study

Abstract Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72–1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22–0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.

Repolarization abnormalities in patients with subarachnoid and intracerebral hemorrhage: predisposing factors and association with outcome.

BACKGROUND:Electrocardiographic (ECG) abnormalities are frequent in patients with intracranial insult. In this study, we evaluated the factors predisposing to the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval, ischemic-like ECG changes and morphologic end-repolarization abnormalities, and examined the prognostic value of these abnormalities in patients with subarachnoid and intracerebral hemorrhages requiring intensive care. METHODS:This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, the level of consciousness, and findings in primary head computed tomography were recorded on admission. The study period was divided into three 2-day sections. In each section, a 12-lead ECG, transthoracic echocardiography, the results of standard blood electrolytes and cardiac troponin I, as well as the rate of vasoactive and sedative drug infusions were recorded. Repolarization abnormalities such as prolongation of the QTc interval (millisecond), ischemic-like ECG changes, and morphologic end-repolarization abnormalities (present/absent) were evaluated and analyzed. The 1-year functional outcome was determined using the Glasgow Outcome Score. RESULTS:During the 2-year study period, 108 patients were included in the study. Different repolarization abnormalities were frequent in both types of hemorrhage. Prolongation of the QTc interval was predisposed by female gender (&bgr;, 24.5; P = 0.010) and the use of propofol (&bgr;, 30.5; P = 0.001). The predisposing factor for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003) and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR, 13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients during the study period, and were associated with a poorer 1-year functional outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010). CONCLUSIONS:Each repolarization abnormality has characteristic predisposing factors. Ischemic-like ECG changes are common and are associated with a poorer 1-year functional outcome.

A New Endotoxin Adsorber in Septic Shock: Observational Case Series

Aims: Effects of a new endotoxin adsorber on the length of noradrenaline (NA) treatment, LPS (lipopolysaccharide) levels and SOFA (sequential organ failure assessment) scores in septic shock were evaluated. Methods: Two-hour hemoperfusion with LPS adsorber was initiated in patients with septic shock and endotoxemia. Controls were matched for age, focus and severity of illness. Results: Adsorption treatment (n = 9) exhibited a significant decrease in EAA (endotoxin activity assay) activity (0.55 [0.44–0.68] vs. 0.25 [0.13–0.41], p = 0.019) and NA infusion rate (0.217 µg/kg/min [0.119–0.0508] vs. 0 µg/kg/min [0–0.09], p = 0.026) from pretreatment to 24 h post-treatment. The median decrease in SOFA scores from pretreatment to 24 h was 3.0 points (1.5–4.5), p = 0.002. Duration of NA infusion was significantly shorter compared to controls (39 h [31–48] vs. 54 h [43–151], p = 0.03). Conclusions: LPS adsorber treatment was associated with a decrease in NA dose, decrease in SOFA scores and LPS concentrations.

Neurogenic pulmonary edema in patients with nontraumatic intracerebral hemorrhage: predictors and association with outcome.

BACKGROUND:Neurogenic pulmonary edema (NPE) is a well-recognized phenomenon after intracranial insult. In this study, we evaluated the predictors for NPE and its association with outcome in patients with intensive care unit–treated nontraumatic intracranial hemorrhage. METHODS:This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, level of consciousness, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were recorded on admission and the findings of primary head computed tomography were reviewed. A chest radiograph and arterial blood gas analysis were taken serially and NPE was determined as acute bilateral infiltrates in chest radiograph and hypoxemia. Echocardiography and cardiac and inflammatory markers were recorded. The 1-year outcome was assessed using the Glasgow Outcome Scale. RESULTS:NPE developed in 38 (35%) of the 108 patients included. Predictors for NPE were higher APACHE II score (≥20, odds ratio 6.17, P = 0.003) and higher interleukin-6 plasma concentration (>40 pg/mL, odds ratio 5.62, P = 0.003). Of patients with 0, 1, or 2 predictors mentioned above, 4%, 37%, and 65% had NPE, respectively. NPE was associated with a higher 1-year mortality (37% vs 14%, P = 0.007, respectively), but with an unchanged functional outcome after 1 year (Glasgow Outcome Scale score 1–3, 53% vs 51%, P > 0.9). CONCLUSIONS:Predictors for NPE are the severity of disease defined by APACHE II scores and higher levels of systemic inflammatory mediators. NPE is associated with a higher 1-year mortality, but not with a poorer 1-year functional outcome.

Age of red blood cells and outcome in acute kidney injury

IntroductionTransfusion of red blood cells (RBCs) and, in particular, older RBCs has been associated with increased short-term mortality in critically ill patients. We evaluated the association between age of transfused RBCs and acute kidney injury (AKI), hospital, and 90-day mortality in critically ill patients.MethodsWe conducted a prospective, observational, predefined sub-study within the FINNish Acute Kidney Injury (FINNAKI) study. This study included all elective ICU admissions with expected ICU stay of more than 24 hours and all emergency admissions from September to November 2011. To study the age of RBCs, we classified transfused patients into quartiles according to the age of oldest transfused RBC unit in the ICU. AKI was defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria.ResultsOut of 1798 patients, 652 received at least one RBC unit. The median [interquartile range] age of the oldest RBC unit transfused was 12 [11-13] days in the freshest quartile and 21 [17-27] days in the quartiles 2 to 4. On logistic regression, RBC age was not associated with the development of KDIGO stage 3 AKI. Patients in the quartile of freshest RBCs had lower crude hospital and 90-day mortality rates compared to those in the quartiles of older blood. After adjustments, older RBC age was associated with significantly increased risk for hospital mortality. Age, Simplified Acute Physiology Score II (SAPS II)-score without age points, maximum Sequental Organ Failure Assessment (SOFA) score and the total number of transfused RBC units were independently associated with 90-day mortality.ConclusionsThe age of transfused RBC units was independently associated with hospital mortality but not with 90-day mortality or KDIGO stage 3 AKI. The number of transfused RBC units was an independent risk factor for 90-day mortality.

Improved outcome after trauma care in university‐level intensive care units

Background: Centralized trauma care has been shown to be associated with improved patient outcome. We compared the outcomes of trauma patients in relation to the size of the intensive care unit (ICU) using a large Finnish database.

Risk factors for 1-year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care.

Mortality in patients with intracranial hemorrhage remains high. The aim of this study was to determine the 1‐year survival and potential risk factors for 1‐year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care.

Leukocyte filter enhances neutrophil activation during combined aortic valve and coronary artery bypass surgery.

OBJECTIVE Cardiopulmonary bypass-induced systemic inflammatory reaction involving the expression of neutrophil surface adhesion molecules is the main mechanism leading to myocardial ischemia-reperfusion injury as well as multiorgan dysfunction. Patients undergoing prolonged cardiopulmonary bypass are especially at risk in this regard. The aim of this prospective, randomized study was to evaluate the impact of continuous leukocyte filtration on the perioperative expression of neutrophil adhesion molecules along with the markers of systemic inflammation during combined coronary artery revascularization and aortic valve surgery due to aortic stenosis. PATIENT AND METHODS Twenty patients scheduled for combined coronary artery revascularization and aortic valve surgery due to aortic stenosis were randomized to undergo cardiopulmonary bypass with or without a leukocyte filter (LeukoGuard LG6). The expression of neutrophil adhesion molecules and proinflammatory cytokine response were measured. RESULTS The use of the leukocyte filter significantly increased neutrophil CD11b expression (Pg = .003) compared to the control group, which was followed by a faster rise in interleukin-6 levels 5 minutes (median, 125 versus 34 pg/mL) and 2 hours after cardiopulmonary bypass (median, 158 versus 92 pg/mL, Pt x g < .001), respectively. No marked differences in terms of levels of CD11a, CD62L, cardiac troponin-I, or oxyhemodynamics were observed. CONCLUSIONS The observed increased neutrophil activation and enhanced inflammatory response do not support the use of continuous leukofiltration in patients undergoing prolonged cardiopulmonary bypass.

Apotransferrin, C1‐esterase inhibitor, and alpha 1‐acid glycoprotein for cerebral protection during experimental hypothermic circulatory arrest

Background—Because of current limitations in improving metabolic support to the brain during hypothermic circulatory arrest (HCA), attenuation of ischemia‐reperfusion injury remains an area of therapeutic intervention of relevance. Apotransferrin (Apo‐Tf), alpha 1‐acid glycoprotein (AGP), and C1‐esterase inhibitor (C1‐INH) have been herein evaluated as potential beneficial agents in reducing the ischemia‐reperfusion injury in a surviving model of HCA. Methods—Apo‐Tf 100 mg/kg (n = 6), C1‐INH 50 IU/kg (n = 6), AGP 100 mg/kg (n = 6), or NaCl 0.9% 2 ml/kg (n = 6) were randomly administered to 24 juvenile pigs after a 75‐min period HCA at a brain temperature of 18°C. Results—Animals in the Apo‐Tf group had a slightly better 7‐day survival (66.7%) compared with the other study groups (50%), but such a difference was not statistically significant. Some favorable changes in the brain glucose metabolism parameters were observed in the AGP, C1‐INH, and Apo‐Tf groups, but these did not reach statistical significance. Semiquantitative analysis of the histopathological findings did not show any significant difference between the study groups. However, only two out of four surviving animals in the Apo‐Tf group developed brain infarction, whereas all three survivors of the remaining study groups developed brain infarction. Conclusions—Although the small size of the study groups may affect the present findings, none of the metabolic and hemodynamic parameters as well as outcome endpoints indicate a substantial therapeutic efficacy of Apo‐Tf, AGP, and C1‐INH as neuroprotective agents after experimental HCA.