Kirsi-Maija Kaukonen

Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012

IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101,064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12,512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did not differ significantly between patients with severe sepsis and those with all other diagnoses (OR, 0.94 [95% CI, 0.94-0.95] vs 0.94 [95% CI, 0.94-0.94]; P = .37). The annual increase in rates of discharge to home was significantly greater in patients with severe sepsis compared with all other diagnoses (OR, 1.03 [95% CI, 1.02-1.03] vs 1.01 [95% CI, 1.01-1.01]; P < .001). Conversely, the annual increase in the rate of patients discharged to rehabilitation facilities was significantly less in severe sepsis compared with all other diagnoses (OR, 1.08 [95% CI, 1.07-1.09] vs 1.09 [95% CI, 1.09-1.10]; P < .001). In the absence of comorbidities and older age, mortality was less than 5%. CONCLUSIONS AND RELEVANCE In critically ill patients in Australia and New Zealand with severe sepsis with and without shock, there was a decrease in mortality from 2000 to 2012. These findings were accompanied by changes in the patterns of discharge to home, rehabilitation, and other hospitals.

Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis

BACKGROUND The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. METHODS We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. RESULTS Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. CONCLUSIONS The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.).

Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

IntroductionPositive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.MethodsWe conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.ResultsWe included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.ConclusionsPatients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults.

IntroductionThe aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients.MethodsA systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients.ResultsSafety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations.ConclusionConsensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events.

Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole

Methylprednisolone is a widely used glucocorticoid. In this study, a possible interaction of itraconazole, a potent inhibitor of CYP3A4, with orally administered methylprednisolone was examined.

Itraconazole increases plasma concentrations of quinidine

Quinidine is eliminated mainly by CYP3A4‐mediated metabolism. Itraconazole interacts with some but not all of the substrates of CYP3A4; it is therefore important to study the possible interaction of itraconazole with quinidine.

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

IntroductionKnowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis.MethodsWe identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis.ResultsOf 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI.ConclusionsThe findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.

Mild Hypothermia After Intravenous Thrombolysis in Patients With Acute Stroke: A Randomized Controlled Trial

Background and Purpose— Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury. We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis. Methods— Patients were randomized 1:1 to mild hypothermia (35°C) or to standard stroke unit care within 6 hours of symptom onset. Hypothermia was induced with a surface-cooling device and cold saline infusions. Active cooling was restrained gradually after 12 hours at <35.5°C. The primary outcome measure was the number of patients with <36°C body temperature for >80% of the 12-hour cooling period. Results— We included 36 patients with a median of National Institutes of Health Stroke Scale score of 9 one hour after thrombolysis. Fifteen of 18 (83%) patients achieved the primary end point. Sixteen (89%) patients reached <35.5°C in a median time of 10 hours (range, 7–16 hours) from symptom onset, spent 10.5 hours (1–17 hours) in hypothermia, and were back to normothermia in 23 hours (15–29 hours). Few serious adverse events were more common in the hypothermia group. At 3 months, 7 patients (39%) in both groups had good outcome (modified Ranking Scale, 0–2), whereas poor outcome (modified Ranking Scale, 4–6) was twice as common in the normothermia group (44% versus 22%). Conclusions— Mild hypothermia with a surface-cooling device in an acute stroke unit is safe and feasible in thrombolyzed, spontaneously breathing patients with stroke, despite the adverse events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987922.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis‐associated AKI demonstrate high‐hospital mortality. We evaluated the incidence of severe sepsis‐associated AKI and its association with outcome in intensive care units (ICUs) in Finland.

Population-based incidence, mortality and quality of life in critically ill patients treated with renal replacement therapy: a nationwide retrospective cohort study in finnish intensive care units

IntroductionAcute kidney injury (AKI) increases mortality and morbidity of critically ill patients. Mortality of patients treated with renal replacement therapy (RRT) is high. We aimed to evaluate the nationwide incidence of RRT-treated AKI in Finland, hospital and six-month mortality, and health-related quality of life (HRQoL) of these patients.MethodsWe performed a retrospective cohort study including all general intensive care unit (ICU) admissions in Finland in 2007 through 2008. We identified patients who had received RRT due to AKI (RRT patients) and compared these patients to ICU patients who were not treated with RRT (non-RRT patients). The HRQoL was assessed by the EQ-5D index and visual analogue scale (VAS).ResultsWe analysed the final cohort of 24,904 patients, of whom 1,686 received RRT due to AKI. The incidence of RRT-treated AKI was 6.8% (95% confidence interval (CI) 6.5 to 7.1%) among ≥ 15-year-old general ICU patients, which corresponds to a yearly population-based incidence of 19.2 per 100,000 (95% CI 17.9 to 20.5/100,000). According to RIFLE (Risk, Injury, Failure) classification 26.6% (95% CI 26.0 to 27.2%) of patients had AKI (RIFLE R-F). Hospital and six-month mortality of RRT patients were 35.0% and 49.4%. At six-months, RRT patients perceived their health as good as non-RRT patients by VAS.ConclusionsThe population-based incidence of AKI treated with RRT was 19.2 per 100,000 in Finland and 6.8% of all general ICU patients. The hospital and six-month mortality rates were lower than previously reported for ICU-treated RRT patients.