Traumatic cervical spinal cord injury: Comparison of two different blood pressure targets on neurological recovery.

BACKGROUND: Controversy exists whether blood pressure augmentation therapy benefits patients suffering from spinal cord injury (SCI). This retrospective comparative study was designed to assess the impact of two different mean arterial pressure (MAP) targets (85-90 mmHg vs. 65-85 mmHg) on neurological recovery after traumatic cervical SCI. METHODS: Fifty-one adult patients with traumatic cervical SCI were retrospectively divided into two groups according to their intensive care unit (ICU) MAP targets: 85-90 mmHg (higher MAP group, n = 32) and 65-85 mmHg (lower MAP group, n = 19). Invasive MAP measurements were stored as 2-min median values for 3-7 days. The severity of SCI (AIS grade and neurological level) was evaluated upon ICU stay and during rehabilitation. Neurological recovery was correlated with individual mean MAP values and with the proportion of MAP values ≥85 mmHg upon the first 3 days (3d-MAP%≥85 ). RESULTS: The initial AIS grades were A 29.4%, B 17.6%, C 31.4%, and D 21.6%. AIS grade improved in 24 patients (47.1%). During ICU care, 82.0% and 36.8% of the measured MAP values reached ≥85 mmHg in the higher and the lower MAP groups, respectively (p < .001). The medians of individual mean MAP values were different between the groups (90.2 mmHg vs. 81.4 mmHg, p < .001). Similarly, 3d-MAP%≥85 was higher in the higher MAP group (85.6% vs. 50.0%, p < .001). However, neurological recovery was not different between the groups, nor did it correlate with individual mean MAP values or 3d-MAP%≥85 . CONCLUSION: The currently recommended MAP target of 85-90 mmHg was not associated with improved outcomes compared to a lower target in patients with traumatic cervical SCI in this cohort.

Persistent pain in intensive care survivors: a systematic review.

BACKGROUND: According to earlier studies where the main aim has been quality of life, there is growing evidence of increased levels of persistent pain in survivors of critical illness. The cause of admission and several factors during intensive care may have associated risk factors for pain persistence. This systematic review aims to determine the incidence or prevalence of persistent pain after critical illness and to identify risk factors for it. METHODS: Six databases were searched, and eventually nine studies were included in the final systematic process. The validity of observational and cross-sectional studies was analysed using the National Institute of Health 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. RESULTS: The incidence of persistent pain after intensive care varied from 28% to 77%. Risk factors for persistent pain were acute pain at discharge from ICU, higher thoracic trauma score, surgery, pre-existing pain, organ failure, longer length of ventilator or hospital stay, and sepsis. No difference in incidence between medical and surgical patients was found. CONCLUSIONS: New systematic, observational studies are warranted to identify persistent pain-related factors in intensive care to improve pain management protocols and thereby diminish the risk of persistent pain after ICU stay.

National early warning score (NEWS) and the new alternative SpO2 scale during rapid response team reviews: a prospective observational study.

BACKGROUND: The national early warning score (NEWS) enables early detection of in-hospital patient deterioration and timely activation of hospital's rapid response team (RRT). NEWS was updated in 2017 to include a separate SpO2 scale for those patients with type II respiratory failure (T2RF). In this study we investigated whether NEWS with and without the new SpO2 scale for the T2RF patients is associated with immediate and in-hospital patient outcomes among the patients actually attended by the RRT. METHODS: We conducted a two-year prospective observational study including all adult RRT patients without limitations of medical treatment (LOMT) in a large Finnish university associated tertiary level hospital. According to the first vital signs measured by the RRT, we calculated NEWSs for the RRT patients and further utilized the new SpO2 scale for the patients with confirmed T2RF. We used multivariate logistic regression and area under the receiver operating characteristic analyses to test NEWS's accuracy to predict two distinct outcomes: RRT patient's I) immediate need for intensive care and/or new LOMT and 2) in-hospital death or discharge with cerebral performance category >2 and/or LOMT. RESULTS: The final cohort consisted of 886 RRT patients attended for the first time during their hospitalization. Most common reasons for RRT activation were respiratory (343, 39%) and circulatory (226, 26%) problems. Cohort's median (Q1, Q3) NEWS at RRT arrival was 8 (5, 10) and remained unchanged if the new SpO2 scale was applied for the 104 patients with confirmed T2RF. Higher NEWS was independently associated with both immediate (OR 1.28; 95% CI 1.22-1.35) and in-hospital (1.15; 1.10-1.21) adverse outcomes. Further, NEWS had fair discrimination for both the immediate (AUROC 0.73; 0.69-0.77) and in-hospital (0.68; 0.64-0.72) outcomes. Utilizing the new SpO2 scale for the patients with confirmed T2RF did not improve the discrimination capability (0.73; 0.69-0.76 and 0.68; 0.64-0.71) for these outcomes, respectively. CONCLUSIONS: We found that in patients attended by a RRT, the NEWS predicts patient's hospital outcome with moderate accuracy. We did not find any improvement using the new SpO2 scale in T2RF patients.

Pantoprazole in ICU patients at risk for gastrointestinal bleeding-1-year mortality in the SUP-ICU trial.

BACKGROUND: The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. METHODS: In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan. RESULTS: A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients. CONCLUSION: We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others; ClinicalTrials.gov number, NCT02467621).

Near-infrared spectroscopy after out-of-hospital cardiac arrest.

BACKGROUND: Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. METHODS: We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1-2) and poor (CPC 3-5) neurological outcome. RESULTS: The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4-25.0) µg/l in patients with good neurological outcome and 35.2 (22.6-95.8) µg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = - 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5-77.0%) in patients with good outcome and 71.8% (63.3-74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94-1.04, p = 0.635). CONCLUSIONS: We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Postoperative Delirium in Cardiac Surgery Patients.

OBJECTIVE: The authors studied the incidence of postoperative delirium among cardiac surgery patients using the Intensive Care Delirium Screening Checklist (ICDSC). DESIGN: Prospective screening. SETTING: Two university hospitals. PARTICIPANTS: A total of 1,036 consecutive patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively screened from day 1 to day 10 after surgery or until hospital discharge. Appropriate perioperative data were collected. The overall incidence of postoperative delirium was 11.5%. In the multivariate logistic regression analysis, age over 70 years, higher EuroSCORE points, longer aortic occlusion time, and profuse drainage increased the incidence of delirium. The duration of mechanical ventilation and intensive care unit length of stay were longer in the group of patients with delirium (10.6 hours [6.6-19.5] v 6.4 hours [4.9-8.6], p < 0.001, and 1.7 days [0.9-4.2] v 0.9 days [0.9-1], p < 0.001). CONCLUSIONS: Postoperative delirium is common after cardiac surgery, and it is associated with the duration of mechanical ventilation.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. METHODS: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. RESULTS: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. CONCLUSIONS: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

FOUR score in monitoring the level of consciousness of an intensive care patient: first experience of the use of the Finnish language version.

BACKGROUND: The goal was to increase the knowledge of Full Outline of UnResponsiveness (FOUR) score in Finland, release its Finnish version and to evaluate its usefulness in Finnish ICU patients. MATERIALS AND METHODS: The highest FOUR and Glasgow Coma Scale (GCS) scores of the adult ICU patients treated in Tampere University Hospital between 1st January and 31st October 2015 were analyzed retrospectively. In-hospital and 1-month mortality were the primary end-points. RESULTS: The Finnish version of FOUR performed comparably to previous studies. The ability of FOUR to predict mortality was equal to GCS. CONCLUSIONS: FOUR is at least equal to GCS in predicting mortality of ICU patients.

Targeting low- or high-normal Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation: study protocol for a randomized pilot trial.

BACKGROUND: Arterial carbon dioxide tension (PaCO2), oxygen tension (PaO2), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists. METHODS: The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 23 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO2, PaO2, and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest. DISCUSSION: The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study.

Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during intensive care unit stay.The 90-day mortality for all patients was 33.3%. Patients with admission lactate >2 mmol/L had higher 90-day mortality than those with admission lactate ≤2 mmol/L (43.4% vs. 22.6%, P < 0.001). Patients with persistent hyperlactatemia (>2 mmol/L) at ≥72 h had higher 90-day mortality compared with those with a lactate value of ≤2.0 mmol/L (52.0% vs. 24.3%, P < 0.001). Time-weighted mean lactate values were higher in non-survivors than in survivors, (median [IQR] 2.05 [1.38-4.22] mmol/L vs. 1.29 [0.98-1.77] mmol/L, P < 0.001). Time to normalization of lactate was comparable for 90-day non-survivors and survivors (median [IQR] 17.0 [3.5-43.5] vs. 15.0 [5.0-35.0] h, P = 0.67). In separate models, time-weighted mean lactate, lactate value at ≥72 h, and hyperlactatemia at ≥72 h were independently associated with 90-day mortality, but admission lactate and time to normalization of lactate were not. These findings may inform future clinical trials using combined surrogate endpoints for mortality in septic shock patients.

Three-year mortality in 30-day survivors of critical care with acute kidney injury: data from the prospective observational FINNAKI study.

BACKGROUND: The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. RESULTS: We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical-surgical ICUs in Finland during a 5-month period in 2011-2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6-26.4%) compared to 18.9% (17.0-20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86-1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1:1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5-23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5-24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. CONCLUSION: AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.

Long-term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial.

PURPOSE: We assessed the predefined long-term outcomes in patients randomised in the Transfusion Requirements in Septic Shock (TRISS) trial. METHODS: In 32 Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin of 9 g/dl or less to receive single units of leuko-reduced red cells when haemoglobin level was 7 g/dl or less (lower threshold) or 9 g/dl or less (higher threshold) during ICU stay. We assessed mortality rates 1 year after randomisation and again in all patients at time of longest follow-up in the intention-to-treat population (n = 998) and health-related quality of life (HRQoL) 1 year after randomisation in the Danish patients only (n = 777). RESULTS: Mortality rates in the lower- versus higher-threshold group at 1 year were 53.5 % (268/501 patients) versus 54.6 % (271/496) [relative risk 0.97; 95 % confidence interval (CI) 0.85-1.09; P = 0.62]; at longest follow-up (median 21 months), they were 56.7 % (284/501) versus 61.0 % (302/495) (hazard ratio 0.88; 95 % CI 0.75-1.03; P = 0.12). We obtained HRQoL data at 1 year in 629 of the 777 (81 %) Danish patients, and mean differences between the lower- and higher-threshold group in scores of physical HRQoL were 0.4 (95 % CI -2.4 to 3.1; P = 0.79) and in mental HRQoL 0.5 (95 % CI -3.1 to 4.0; P = 0.79). CONCLUSIONS: Long-term mortality rates and HRQoL did not differ in patients with septic shock and anaemia who were transfused at a haemoglobin threshold of 7 g/dl versus a threshold of 9 g/dl. We may reject a more than 3 % increased hazard of death in the lower- versus higher-threshold group at the time of longest follow-up.

Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial.

BACKGROUND: Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant. METHODS/DESIGN: The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of <2 mmol/L) and without any inotropic or vasopressor agent. Secondary outcomes include individual components of the primary outcome, days alive without renal replacement, days alive without mechanical ventilation in 30 days, and new acute kidney injury. The sample size enables detection of a 13.5-h difference in the primary outcome with a type 1 error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD 30) among the 30-day survivors. After 150 included patients the statistician masked for allocation group will recalculate the sample size potentially increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will review the safety data after 100 patients. DISCUSSION: The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02579525 . Registered on 19 October 2015.

Prognostic Value of Secretoneurin in Critically Ill Patients With Infections.

OBJECTIVES: Secretoneurin is produced in neuroendocrine cells, and the myocardium and circulating secretoneurin levels provide incremental prognostic information to established risk indices in cardiovascular disease. As myocardial dysfunction contributes to poor outcome in critically ill patients, we wanted to assess the prognostic value of secretoneurin in two cohorts of critically ill patients with infections. DESIGN: Two prospective, observational studies. SETTING: Twenty-four and twenty-five ICUs in Finland. PATIENTS: A total of 232 patients with severe sepsis (cohort #1) and 94 patients with infections and respiratory failure (cohort #2). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin levels by radioimmunoassay in samples obtained early after ICU admission and compared secretoneurin with other risk indices. In patients with severe sepsis, admission secretoneurin levels (logarithmically transformed) were associated with hospital mortality (odds ratio, 3.17 [95% CI, 1.12-9.00]; p = 0.030) and shock during the hospitalization (odds ratio, 2.17 [1.06-4.46]; p = 0.034) in analyses that adjusted for other risk factors available on ICU admission. Adding secretoneurin levels to age, which was also associated with hospital mortality in the multivariate model, improved the risk prediction as assessed by the category-free net reclassification index: 0.35 (95% CI, 0.06-0.64) (p = 0.02). In contrast, N-terminal pro-B-type natriuretic peptide levels were not associated with mortality in the multivariate model that included secretoneurin measurements, and N-terminal pro-B-type natriuretic peptide did not improve patient classification on top of age. Secretoneurin levels were also associated with hospital mortality after adjusting for other risk factors and improved patient classification in cohort #2. In both cohorts, the optimal cutoff for secretoneurin levels at ICU admission to predict hospital mortality was ≈ 175 pmol/L, and higher levels were associated with mortality also when adjusting for Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. CONCLUSIONS: Secretoneurin levels provide incremental information to established risk indices for the prediction of mortality and shock in critically ill patients with severe infections.

Severe Sepsis in Elderly Patients Undergoing Gastrointestinal Surgery-a Prospective Multicenter Follow-up Study of Finnish Intensive Care Units.

BACKGROUND: We aimed to evaluate the outcome of elderly patients with severe sepsis after alimentary tract surgery. METHODS: A prospective study was conducted in 24 intensive care units (ICU) in Finland. Four thousand five hundred consecutive patients were admitted to ICUs and 470 patients fulfilled the criteria for severe sepsis. All patients who had undergone gastrointestinal surgery were included. The outcomes of elderly (≥65 years) and younger patients were compared. The key factor under analysis was death from any cause during the hospitalization or within 1 year after the surgery. RESULTS: A total of 73 elderly patients (and 81 younger patients) were found to have severe alimentary tract surgery-related sepsis. The mean age of the elderly patients was 76.4 years, and 56.2 % were female. The most common indication for surgery was acute cholecystitis (21.9 %), followed by acute diverticulitis (13.7 %), and gastroduodenal ulcer (13.7 %). The anatomic site of the infection was intra-abdominal in 86.3 % of cases, the second most common being pulmonary (13.7 %). In-hospital mortality was 47.9 % and 1-year mortality 64.4 %. Of the discharged patients, 31.6 % died within 1 year. Patients who died were older and more frequently had concomitant conditions. The ICU scoring systems (APACHE, SAPS, and SOFA) and elevated lactate levels were predictive of increased mortality. CONCLUSION: Severe sepsis among the elderly is a rare but often-fatal infectious event. In addition to high in-hospital mortality, it is also associated with significant 1-year mortality.

Inhibition of monoamine oxidase A increases recovery after experimental cardiac arrest.

OBJECTIVES: Perioperative myocardial infarction (MI) with ischaemia-reperfusion injury (IRI) is a devastating entity occurring in 1-2% of patients after cardiac surgery. The molecular pathway leading to myocardial cellular destruction after MI may include monoamine oxidases. We experimentally investigated whether moclobemide, a monoamine oxidase inhibitor, enhances myocardial recovery after cardiac arrest and MI. METHODS: Fifty-six syngeneic Fischer rats underwent heterotopic cardiac transplantation to induce reversible IRI after cardiac arrest. Twenty-eight rats also underwent permanent ligation of the left anterior descending coronary artery to induce MI after cardiac arrest. Twenty-eight rats with or without MI were treated with subcutaneous moclobemide 10 mg/kg/day. Methods used to study myocardial recovery were microdialysis for intramyocardial metabolism, histology and quantitative reverse-transcription polymerase chain reaction for high-mobility group box-1 (HMGB1), haeme oxygenase-1 (HO-1), interleukin-6, hypoxia-inducible factor 1α and macrophages (CD68). RESULTS: Pyruvate increased in MI treated with moclobemide versus IRI with moclobemide (29.19 ± 7.64 vs 13.86 ± 8.49 µM, P = 0.028), reflecting metabolic activity after cardiac arrest and reperfusion. Myocardial inflammation increased in MI compared with IRI after 1 h (0.80 ± 0.56 vs 0, point score units [PSUs], P = 0.003), but decreased after 5 days in MI treated with moclobemide versus MI alone (0.80 ± 0.83 vs 2.00 ± 0.70, PSU, P = 0.033). Expressions of HMGB1, CD68 and HO-1 decreased in MI treated with moclobemide versus MI alone (1.33 ± 0.20 vs 1.75 ± 0.24, fold changes [FCs], P = 0.028; 5.15 ± 1.10 vs 9.59 ± 2.75, FC, P = 0.050; 10.41 ± 4.17 vs 21.28 ± 10.01, FC, P = 0.047), indicating myocardial recovery and increased cellularity of remote intramyocardial arteries. CONCLUSIONS: Moclobemide enhances myocardial recovery after cardiac arrest and MI; inhibition of remote myocardial changes may be achieved by targeting treatment against monoamine oxidase.

Predicting one-year mortality of critically ill patients with early acute kidney injury: data from the prospective multicenter FINNAKI study.

INTRODUCTION: No predictive models for long-term mortality in critically ill patients with acute kidney injury (AKI) exist. We aimed to develop and validate two predictive models for one-year mortality in patients with AKI based on data (1) on intensive care unit (ICU) admission and (2) on the third day (D3) in the ICU. METHODS: This substudy of the FINNAKI study comprised 774 patients with early AKI (diagnosed within 24 hours of ICU admission). We selected predictors a priori based on previous studies, clinical judgment, and differences between one-year survivors and non-survivors in patients with AKI. We validated the models internally with bootstrapping. RESULTS: Of 774 patients, 308 (39.8%, 95% confidence interval (CI) 36.3 to 43.3) died during one year. Predictors of one-year mortality on admission were: advanced age, diminished premorbid functional performance, co-morbidities, emergency admission, and resuscitation or hypotension preceding ICU admission. The area under the receiver operating characteristic curve (AUC) (95% CI) for the admission model was 0.76 (0.72 to 0.79) and the mean bootstrap-adjusted AUC 0.75 (0.74 to 0.75). Advanced age, need for mechanical ventilation on D3, number of co-morbidities, higher modified SAPS II score, the highest bilirubin value by D3, and the lowest base excess value on D3 remained predictors of one-year mortality on D3. The AUC (95% CI) for the D3 model was 0.80 (0.75 to 0.85) and by bootstrapping 0.79 (0.77 to 0.80). CONCLUSIONS: The prognostic performance of the admission data-based model was acceptable, but not good. The D3 model for one-year mortality performed fairly well in patients with early AKI.

Comparing the prognostic performance of ASSIST to interleukin-6 and procalcitonin in patients with severe sepsis or septic shock.

CONTEXT: We recently derived and validated a multi-biomarker-based model (ASSIST) to stratify patients with sepsis based on initial mortality risk. OBJECTIVE: The objective of this study was to compare the performance of ASSIST to interleukin-6 (IL6) and procalcitonin (PCT). METHODS: The area-under-the-receiver operating characteristic curve for predicting 28-d mortality using ASSIST was compared with that of IL6 (n = 452) and PCT (n = 235). RESULTS: The area under the curve for ASSIST was greater than that of IL6 and PCT. CONCLUSIONS: ASSIST estimated the probability of mortality more reliably than IL6 and PCT in this cohort of patients with sepsis.

Lower versus higher hemoglobin threshold for transfusion in septic shock.

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS: We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).