Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest.

AIM: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies. METHODS: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. RESULTS: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) µg/L vs. 8.5 (5.8-13.2) µg/L at 24 h and 20.4 (8.1-56.6) µg/L vs. 8.2 (5.9-12.1) µg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. CONCLUSION: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.

Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome.

BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines. METHODS: The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. RESULTS: A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low- to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders. CONCLUSION: This guideline emphasizes the paucity of evidence of benefit - and potential for harm - of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.

Scandinavian clinical practice guideline on mechanical ventilation in adults with the acute respiratory distress syndrome

BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials. METHODS: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process. RESULTS: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end-expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high-quality evidence, we strongly recommend not to use high-frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non-invasive ventilation. CONCLUSION: We strongly recommend pressure- and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.(AU)

Scandinavian clinical practice guideline on mechanical ventilation in adults with the acute respiratory distress syndrome.

BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials. METHODS: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process. RESULTS: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end-expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high-quality evidence, we strongly recommend not to use high-frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non-invasive ventilation. CONCLUSION: We strongly recommend pressure- and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.

Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in critically ill patients with ventilatory support.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been introduced as an early and sensitive biomarker of acute kidney injury (AKI), with an increased risk for renal replacement therapy (RRT) and adverse outcome in selected critically ill patient groups. Acute respiratory failure is the most common organ dysfunction in critically ill patients with an increased risk for AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse outcome in a heterogeneous group of critically ill adult patients with acute respiratory failure. DESIGN AND SETTING: Prospective, multi-centre study in 25 Finnish intensive care units. PATIENTS AND METHODS: pNGAL was measured from critically ill patients with acute respiratory failure. We evaluated the predictive value of pNGAL for RRT, and hospital and 90-day mortality first separately, second in addition to the Simplified Acute Physiology Score (SAPS II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) AKI classification. Additionally, we assessed the factors associated with pNGAL by linear regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 369 patients. Median (interquartile range) baseline pNGAL was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656-0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520-0.645) for 90-day mortality. Present infection, baseline creatinine, operative status, and pancreatitis were independently associated with baseline pNGAL. CONCLUSIONS: Baseline pNGAL gives no additional value into prediction of hospital and 90-day mortality compared with RIFLE or SAPS II, and has only moderate predictive power regarding RRT in critically ill adult patients with acute respiratory failure.

Association of automated data collection and data completeness with outcomes of intensive care. A new customised model for outcome prediction.

BACKGROUND: The Finnish Intensive Care Consortium coordinates a national intensive care benchmarking programme. Clinical information systems (CISs) that collect data automatically are widely used. The aim of this study was to explore whether the severity of illness-adjusted hospital mortality of Finnish intensive care unit (ICU) patients has changed in recent years and whether the changes reflect genuine improvements in the quality of care or are explained by changes in measuring severity of illness. METHODS: We retrospectively analysed data collected prospectively to the database of the Consortium. During the years 2001-2008, there were 116,065 admissions to the participating ICUs. We excluded readmissions, cardiac surgery patients, patients under 18 years of age and those discharged from an ICU to another hospital's ICU. The study population comprised 85,547 patients. The Simplified Acute Physiology Score II (SAPS II) was used to measure severity of illness and to calculate standardised mortality ratios (SMRs, the number of observed deaths divided by the number of expected deaths). RESULTS: The overall hospital mortality rate was 18.4%. The SAPS II-based SMRs were 0.74 in 2001-2004 and 0.64 in 2005-2008. The severity of illness-adjusted odds of death were 24% lower in 2005-2008 than in 2001-2004. One fifth of this computational difference could be explained by differences in data completeness and the automation of data collection with a CIS. CONCLUSION: The use of a CIS and improving data completeness do decrease severity-adjusted mortality rates. However, this explains only one fifth of the improvement in measured outcomes of intensive care in Finland.

Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland.

OBJECTIVE: To evaluate the incidence, treatment, and outcome of influenza A(H1N1) in Finnish intensive care units (ICUs) with special reference to corticosteroid treatment. METHODS: During the H1N1 outbreak in Finland between 11 October and 31 December 2009, we prospectively evaluated all consecutive ICU patients with high suspicion of or confirmed pandemic influenza A(H1N1) infection. We assessed severity of acute disease and daily organ dysfunction. Ventilatory support and other concomitant treatments were evaluated and recorded daily throughout the ICU stay. The primary outcome was hospital mortality. RESULTS: During the 3-month period altogether 132 ICU patients were tested polymerase chain reaction-positive for influenza A(H1N1). Of these patients, 78% needed non-invasive or invasive ventilatory support. The median (interquartile) length of ICU stay was 4 [2-12] days. Hospital mortality was 10 of 132 [8%, 95% confidence interval (CI) 3-12%]. Corticosteroids were administered to 72 (55%) patients, but rescue therapies except prone positioning were infrequently used. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores in patients with and without corticosteroid treatment were 31 [24-36] and 6 [2-8] vs. 22 [5-30] and 3 [2-6], respectively. The crude hospital mortality was not different in patients with corticosteroid treatment compared to those without: 8 of 72 (11%, 95% CI 4-19%) vs. 2 of 60 (3%, 95% CI 0-8%) (P = 0.11). CONCLUSIONS: The majority of H1N1 patients in ICUs received ventilatory support. Corticosteroids were administered to more than half of the patients. Despite being more severely ill, patients given corticosteroids had comparable hospital outcome with patients not given corticosteroids.

Serum zinc in critically ill adult patients with acute respiratory failure.

BACKGROUND AND AIMS: Zinc deficiency leads to susceptibility to infections and may affect pulmonary epithelial cell integrity. Low zinc levels have also been associated with a degree of organ failure and decreased survival in critically ill children. Accordingly, the purpose of the study was to assess serum zinc in adult patients with acute respiratory failure, its association with ventilatory support time, intensive care unit (ICU) length of stay (LOS), organ dysfunction and 30-day mortality. METHODS: We included consecutive patients with acute respiratory failure during an eight-week prospective, observational multicentre study (the FINNALI-study). Acute respiratory failure was defined as a need for either non-invasive or invasive positive pressure ventilation for >6 h regardless of the underlying cause or risk factors. After informed consent, a sample for zinc measurement was drawn at 6 h after the start of treatment and analysed from 551 of these patients. RESULTS: Low serum zinc was frequent (95.8%) at the onset acute respiratory failure. The median interquartile range [IQR] was 4.7 [3.0-6.9] µmol/l. The median [IQR] serum zinc levels in non-infectious, sepsis and septic shock patients were 5.0 [3.1-7.1], 5.1 [3.5-7.3] and 3.8 [2.6-5.9] µmol/l, respectively, P<0.01. Baseline zinc levels were not associated with ventilatory support time (P=0.98) or ICU LOS (P=0.053). The area under curve in receiver operating characteristics analysis for serum zinc regarding 30-day mortality was 0.55 (95% CI 0.49-0.60). CONCLUSIONS: Serum zinc on initiation of ventilation had no predictive value for 30-day mortality, ventilatory support time or intensive care unit LOS.

N-terminal-pro-BNP in critically ill patients with acute respiratory failure: a prospective cohort study.

BACKGROUND: The aim of this study was to evaluate the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in unselected critically ill patients with acute respiratory failure (ARF). METHODS: Prospective, observational cohort study in 25 intensive care units in Finland. This study included a total of 602 patients with laboratory samples from 958 consecutive patients with ARF treated either with invasive or with non-invasive ventilatory support (the FINNALI study). Plasma NT-pro-BNP samples were drawn after the onset of ventilatory support (day 0) and on the morning of the second day. RESULTS: The median [interquartile ranges (IQR)] NT-pro-BNP-values were significantly higher at baseline in 90-day non-survivors than the survivors, 4378 pg/ml (1400-13,943 pg/ml) vs. 1052 pg/ml (232-4076 pg/ml), respectively. The median (IQR) NT-pro-BNP values were significantly higher in patients with chronic cardiac disease or cardiac surgery than in non-cardiac patients, 1947 pg/ml (801-4687 pg/ml) vs. 417 pg/ml (153-1735 pg/ml), respectively, if renal function was normal. With deteriorating renal function, the NT-pro-BNP values showed a significant increase. The area under curve for baseline NT-pro-BNP predicting 90-day mortality was moderate: 0.718 (95% confidence interval 0.674-0.761). Baseline NT-pro-BNP over 1765 pg/ml was independently associated with 90-day mortality by logistic regression analysis (P<0.001). CONCLUSIONS: NT-pro-BNP on admission is commonly elevated and independently associated with 90-day mortality in critically ill ARF patients. However, the routine use of NT-pro-BNP for prognostic purpose does not seem to add value to clinical data in ARF patients.

Therapeutic hypothermia after cardiac arrest: implementation and outcome in Finnish intensive care units.

BACKGROUND: Therapeutic hypothermia (TH) has been shown to increase survival after out-of-hospital resuscitation. The aim of our study was to find out nationwide implementation and the actual utilization of TH after cardiac arrest in Finnish intensive care units (ICUs). We also determined the outcomes and describe demographic variables of the patients treated with TH. METHODS: We analyzed a nationwide prospective database and included all adult patients (1,555) treated in ICUs after cardiac arrest during 2004 and 2005. RESULTS: During 2004 and 2005, 407 patients were treated with TH and TH was used in 19 out of the 20 ICUs. The proportion of cardiac arrest patients treated with TH had increased from 4% in 2002 to 28% in 2005. The incidence of cardiac arrest patients admitted to ICUs was 15/100,000 inhabitants/year. The use of TH varied in different areas of the country from 3.4 to 5.0/100,000 inhabitants/year. In-hospital mortality of TH patients was 32.7% and increased from 13.2% in age group <45 years to 46.0% in age group >75 years (P = 0.0002). Six-month survival was 55.3%. Median (interquartile range) length of stay in the ICU was 3.7 (2.7-5.3) days. CONCLUSION: In Finland, TH is implemented in almost all ICUs but it is applied only to a selected group of patients. Six months after cardiac arrest, more than half of the patients treated with TH were alive. Among patients treated with TH, younger patients had lower in-hospital mortality.

Assessment of CPR-D skills of nurses in Göteborg, Sweden and Espoo, Finland: teaching leadership makes a difference.

INTRODUCTION: Construction of an effective in-hospital resuscitation programme is challenging. To document and analyse resuscitation skills assessment must provide reliable data. Benchmarking with a hospital having documented excellent results of in-hospital resuscitation is beneficial. The purpose of this study was to assess the resuscitation skills to facilitate construction of an educational programme. MATERIALS AND METHODS: Nurses working in a university hospital Jorvi, Espoo (n=110), Finland and Sahlgrenska University Hospital, Göteborg (n=40), Sweden were compared. The nurses were trained in the same way in both hospitals except for the defining and teaching of leadership applied in Sahlgrenska. Jorvi nurses are not trained to be, nor do they act as, leaders in a resuscitation situation. Their cardiopulmonary resuscitation (CPR) skills using an automated external defibrillator (AED) were assessed using Objective Structured Clinical Examination (OSCE) which was build up as a case of cardiac arrest with ventricular fibrillation (VF) as the initial rhythm. The subjects were tested in pairs, each pair alone. Group-working skills were registered. RESULTS: All Sahlgrenska nurses, but only 49% of Jorvi nurses, were able to defibrillate. Seventy percent of the nurses working in the Sahlgrenska hospital (mean score 35/49) and 27% of the nurses in Jorvi (mean score 26/49) would have passed the OSCE test. Statistically significant differences were found in activating the alarm (P<0.001), activating the AED without delay (P<0.01), setting the lower defibrillation electrode correctly (P<0.001) and using the correct resuscitation technique (P<0.05). The group-working skills of Sahlgrenska nurses were also significantly better than those of Jorvi nurses. CONCLUSIONS: Assessment of CPR-D skills gave valuable information for further education in both hospitals. Defining and teaching leadership seems to improve resuscitation performance.

Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome.

BACKGROUND: Airway pressure release ventilation (APRV) is a ventilatory mode, which allows unsupported spontaneous breathing at any phase of the ventilatory cycle. Airway pressure release ventilation as compared with pressure support (PS), another partial ventilatory mode, has been shown to improve gas exchange and cardiac output. We hypothesized whether the use of APRV with maintained unsupported spontaneous breathing as an initial mode of ventilatory support promotes faster recovery from respiratory failure in patients with acute respiratory distress syndrome (ARDS) than PS combined with synchronized intermittent ventilation (SIMV-group). METHODS: In a randomized trial 58 patients were randomized to receive either APRV or SIMV after a predefined stabilization period. Both groups shared common physiological targets, and uniform principles of general care were followed. RESULTS: Inspiratory pressure was significantly lower in the APRV-group (25.9 +/- 0.6 vs. 28.6 +/- 0.7 cmH2O) within the first week of the study (P = 0.007). PEEP-levels and physiological variables (PaO2/FiO2-ratio, PaCO2, pH, minute ventilation, mean arterial pressure, cardiac output) were comparable between the groups. At day 28, the number of ventilator-free days was similar (13.4 +/- 1.7 in the APRV-group and 12.2 +/- 1.5 in the SIMV-group), as was the mortality (17% and 18%, respectively). CONCLUSION: We conclude that when used as a primary ventilatory mode in patients with ARDS, APRV did not differ from SIMV with PS in clinically relevant outcome.

Combined effects of prone positioning and airway pressure release ventilation on gas exchange in patients with acute lung injury.

BACKGROUND: Prone positioning has been shown to improve oxygenation in 60-70% of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Another way to improve matching of ventilation to perfusion is the use of partial ventilatory support. Preserving spontaneous breathing during mechanical ventilation has been shown to improve oxygenation in comparison with controlled mechanical ventilation. However, no randomized studies are available exploring the effects of preserved spontaneous breathing on gas exchange in combination with prone positioning. Our aim was to determine whether the response of oxygenation to the prone position differs between pressure-controlled synchronized intermittent mandatory ventilation with pressure support (SIMV-PC/PS) and airway pressure release ventilation with unsupported spontaneous breathing (APRV). METHODS: We undertook a prospective randomized intervention study in a medical-surgical adult intensive care unit of a university hospital. Of 45, 33 ALI patients (acute lung injury) within 72 h after initiation of mechanical ventilation, and in whom the prone position was applied according to a predefined strategy, were included in the study. After initial stabilization the patients were randomized to receive either SIMV-PC/PS or APRV with predefined general ventilatory goals (PEEP, tidal volume, inspiratory pressure and PaCO2-level). The protocol for prone positioning was the same for both treatment arms. Prone positioning was triggered by finding a PaO2/FiO2-ratio below 200 mmHg evaluated twice per day. The duration of each prone episode was 6 h. RESULTS: The first two episodes of prone positioning were analyzed. Gas exchange was measured before and at the end of prone positioning. Of the 45 patients enrolled, 33 were turned prone once and 28 twice. No significant differences were detected in baseline characteristics. Changes in oxygenation were analyzed in response to the first and second prone episodes 5 h and 24 h after randomization and initiation of SIMV-PC/PS or APRV respectively. Before the first prone episode the PaO2/FiO2-ratio was significantly better (P = 0.02) in the APRV-group (median; interquartile range) (162; 108-192 mmHg) than in the SIMV-PC/PS-group (123; 78-154 mmHg). The response in oxygenation to the first prone episode was similar in both groups: PaO2/FiO2-ratio increased 39.5; 17.75-77.5 mmHg in the SIMV-PC/PS-group and 75.0; 9.0-125.0 mmHg in the APRV-group (P = 0.49). Before the second prone episode, the PaO2/FiO2-ratio was comparable (SIMV-PC/PS 130.5; 61.0-161.0 mmHg vs. APRV 134; 98.3-175.0 mmHg). Improvement in oxygenation was significantly (P = 0.02) greater in the APRV group (82; 37.0-141.0 mmHg) than in the SIMV-PC/PS group (50; 24.0-68.8 mmHg) during the second prone episode. General ventilatory and hemodynamic variables and use of sedatives were similar in both groups during the study. CONCLUSIONS: APRV during prone positioning is feasible in the treatment of ALI patients. APRV after 24 h appears to enhance improvement in oxygenation in response to prone positioning.

On what are our end-of-life decisions based?

BACKGROUND: The incidence of withholding and withdrawing life support from the critically ill has increased in recent years. The aim of this study was to assess the degree of consistency between the weight assigned by intensivists to different determinants and their relation to end-of-life decisions, and to evaluate the current concepts in withholding or withdrawing intensive care in Nordic countries. METHODS: Forty-one intensivists from Nordic countries completed a questionnaire sent by e-mail: consistency between contributing factors and the decisions regarding 10 actual cases was evaluated by logistic regression analysis and by the classification (leave-one-out) method. Concepts in management after the withdrawal decision were also analyzed. RESULTS: The median (range) number of withdrawals per physician was four (range 0-10) out of 10 cases. No single factor was an independent covariant of all decisions made. The classification method revealed that approximately 70% only of decisions could be predicted correctly. Different actions taken after a decision to withdraw intensive care varied from 9.8% (discontinuing ventilator therapy) to 97.6% (informing relatives). CONCLUSIONS: No generally accepted grounds for end-of-life decisions could be detected among Nordic intensivists. In addition, the current concept of management after decision to withdraw therapy varies markedly. This study has implications in further assessment of the individual decision-making process and the uniformity of actions after withdrawal decisions.

Airway pressure release ventilation and prone positioning in severe acute respiratory distress syndrome.

BACKGROUND: Implementation of lung protective strategy in the treatment of severe Acute Respiratory Distress Syndrome (ARDS) has been reported to be associated with improved outcome. To fulfil this approach, sedation, neuromuscular blocking agents and full mechanical ventilatory support are often used in critical failure of gas exchange. CASE REPORT: We present a patient who developed multiple organ failure, including severe ARDS, after severe skin injuries and septic shock. Ventilatory strategy consisted of lung protective approach, permissive hypercapnia and prone positioning. Airway pressure release ventilation (APRV) with the patient's superimposed spontaneous breathing was implemented and maintained, also during prone episodes. Improvement of gas exhange occurred after application of combined use of APRV and prone positioning. CONCLUSION: APRV and maintenance of patients' spontaneous ventilation is feasible during prone positioning, and this approach may have beneficial synergistic effects on gas exhange in patients with severe acute lung injury.

Safety of granulocyte colony-stimulating factor (filgrastim) in intubated patients in the intensive care unit: interim analysis of a prospective, placebo-controlled, double-blind study.

OBJECTIVE: To investigate the safety of the granulocyte colony-stimulating factor filgrastim in the prevention of nosocomial infections in intubated patients in the intensive care unit (ICU), with special emphasis on the possible deleterious effect on acute respiratory distress syndrome (ARDS) and the development of multiple organ dysfunction (MOD). DESIGN: Predetermined, interim analysis of a prospective, randomized, placebo-controlled, double-blind trial. SETTING: University hospital medical-surgical ICU. PATIENTS: A total of 59 consecutive ICU patients, aged >18 yrs, admitted to the ICU no more than 12 hrs before the study, intubated because of ventilatory insufficiency no more than 48 hrs before the study, expected to stay in the ICU for >48 hrs, and had informed consent from the next relative. INTERVENTIONS: Patients were randomized to receive either placebo or 300 microg of filgrastim subcutaneously once daily for 7 days. MEASUREMENTS AND MAIN RESULTS: No significant differences were found in the number of patients developing ARDS (2 of 20 in the placebo group vs. 0 of 22 in the filgrastim group), disseminated intravascular coagulation (3 of 27 vs. 3 of 29), acute renal failure (1 of 27 vs. 1 of 23), or change in MOD. Data analysis showed nosocomial infections in 11 of 29 patients in the placebo group and in 7 of 30 patients in the filgrastim group (p = .266). The median (range) length of ICU stay was 8 (1-34) days in the placebo group and 6 days (1-28) in the filgrastim group. The day 28 mortality rate was 17% (5 of 29) in the placebo group and 13% (4 of 30) in the filgrastim group. No drug-related adverse events occurred. CONCLUSION: Filgrastim is safe in intubated ICU patients, with no excess risk for development of ARDS or MOD.

Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis.

OBJECTIVE: To evaluate with electromyography the incidence and the time of appearance of neuromuscular abnormality in patients with systemic inflammatory response syndrome (SIRS) and/or sepsis. DESIGN: Follow-up study. SETTING: Intensive care unit of Helsinki University Hospital, Finland. PATIENTS: Nine mechanically ventilated patients with SIRS and/or sepsis. INTERVENTIONS: Electromyography and conduction velocity measurements on the 2nd-5th day after admission to the intensive care unit. MEASUREMENTS AND RESULTS: In all nine patients electromyography revealed signs of neuromuscular abnormality. The means of compound muscle action potential amplitudes of the median and ulnar nerves were decreased. Fibrillation was observed in four patients out of nine. CONCLUSION: Because neuromuscular abnormalities seem to develop earlier than previously reported, electroneuromyography should be used more frequently as a diagnostic test.

Late steroid therapy in primary acute lung injury.

OBJECTIVE: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia. DESIGN: Retrospective study. SETTING: Multidisciplinary intensive care unit (ICU) in a university hospital. PATIENTS: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls. MEASUREMENTS AND RESULTS: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU. The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10. The PaO2/FiO2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently. No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident. CONCLUSIONS: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction.