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Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patients
IntroductionRecently, red cell distribution width (RDW), a measure of erythrocytes' size variability, has been shown to be a prognostic marker in critical illness. The aim of this study was to investigate whether adding RDW has the potential to improve the prognostic performance of the simplified acute physiology score (SAPS) to predict short and long term mortality in an independent, large and unselected population of intensive care unit (ICU) patients.
Methods:
This observational cohort study includes 17,922 ICU patients with available RDW measurements from different types of ICUs. We modeled the association between RDW and mortality using multivariable logistic regression, adjusting for demographic factors, comorbidities, hematocrit, and severity of illness using the SAPS.
Results:
ICU-, inhospital- and 1-year mortality rates in the 17,922 included patients were 7.6% (95%CI 7.2 to 8.0), 11.2% (95%CI 10.8 to 11.7) and 25.4% (95%CI 24.8 to 26.1). RDW was significantly associated with in-hospital mortality (OR per 1% increase in RDW [95%CI]) (1.14 (1.08, 1.19), P<0.0001), ICU mortality (1.10 (1.06, 1.15), P<0.0001), and 1-year mortality (1.20 (95%CI 1.14, 1.26), P<0.001). Adding RDW to SAPS significantly improved the AUC from 0.746 to 0.774 (P<0.001) for in-hospital mortality and 0.793 to 0.805 (P<0.001) for ICU mortality. Significant improvements in classification of SAPS were confirmed in reclassification analyses. Subgroups demonstrated robust results for gender, age categories, SAPS categories, anemia, hematocrit categories and renal failure.
Conclusions:
RDW is a promising independent short- and long-term prognostic marker in ICU patients and significantly improves risk stratification of SAPS. Further research is needed to better understand the pathophysiology underlying these effects.
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Combining intermediate levels of the endotoxin activity assay (EAA)
with other biomarkers in the assessment of patients with sepsis: results of an observational study
IntroductionThe Endotoxin Activity Assay (EAA) is a useful test to risk stratify patients with severe sepsis and assess for Gram negative infection. However, the significance of intermediate levels of EAA (0.4-0.59) at the bedside has not been well elucidated. The purpose of this study was to interpret intermediate EAA levels in clinical practice.
Methods:
This retrospective observational study included all adult patients with suspected sepsis admitted to our medico-surgical intensive care unit (ICU) in whom EAA was measured from July 2008 to September 2011. Data collected included EAA, white blood cell (WBC) count and differential, C-reactive protein (CRP), procalcitonin (PCT) and bacterial cultures. Data were analyzed by comparative statistics.
Results:
Two hundred and ten patients were studied. Ninety two (43 %) patients had culture documented gram negative infection. Patients with Gram-negative organisms in cultures had significantly higher EAA levels (0.47, IQR 0.27) than those without any Gram-negative organisms in cultures (0.34, IQR 0.22) (p < 0.0001). For patients with intermediate EAA levels (0.40 to 0.59), PCT levels and presence of left shift of WBC significantly differed between patients with Gram negative organisms in their blood oar other cultures and those who no organisms in any of the cultures (4.9 vs. 1.7 ng/mL, p < 0.05; 57.9 vs. 18.9 %, p < 0.0004, respectively).
Conclusions:
We confirm that high levels of EAA in our cohort of patients with suspected sepsis is strongly associated with gram negative infection. In those patients with intermediate elevation in EAA levels, use of PCT and WBC differential can provide additional diagnostic value to clinicians at the bedside.
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Apolipoprotein M - a new biomarker in sepsis
Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation.
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Multiple injuries after earthquakes: a retrospective analysis on 1871 injured patients from the 2008 Wenchuan earthquake
IntroductionMultiple injuries have been highlighted as an important clinical dimension of the injury profile following earthquakes, but studies are scarce. We investigated the pattern and combination of injuries among patients with two injuries following the 2008 Wenchuan earthquake. We also described the general injury profile, causes of injury, and socio-demographic characteristics of the injured patients.
Methods:
A retrospective hospital-based analysis of 1871 earthquake injured patients, totaling 3177 injuries, admitted between 12 and 31 May 2008 to the People's Hospital of Deyang city (PHDC). An electronic, webserver-based database with International Classification of Diseases (ICD)-10-based classification of earthquake-related injury diagnoses (IDs), anatomical sites, and additional background variables of the inpatients was used. We analyzed this dataset for injury profile and number of injuries per patient. We then included all patients (856) with two injuries for more in depth analysis. Possible spatial anatomical associations were determined a priori. Cross-tabulation and more complex frequency matrices for combination analyses were used to investigate the injury profile.
Results:
Out of the 1871 injured patients, 810 (43.3%) presented with a single injury. The rest had multiple injuries, 856 (45.8%) had two, 169 (9.0%) patients had three, 32 (1.7%) presented with four injuries while only 4 (0.2%) were diagnosed with five injuries. The injury diagnoses of patients presenting with two-injuries showed important anatomical intra-site or neighboring clustering, which explained 49.1% of the combinations. For fractures, the result was even more marked as spatial clustering, explaining 57.9% of the association pattern. The most frequent combination of IDs was a double-fracture, affecting 20.7% of the two-injury patients (n=177). Another 108 patients (12.6%) presented with fractures associated with crush injury and organ-soft tissue injury. Of the 3177 injuries, 1476 (46.5%) were fractures. Most injuries were located in the head (22.9%) and lower extremities (30.8%).
Conclusions:
Multiple injuries are put forward as an important component of the injury profile after this earthquake. A pattern of injury combinations and spatial aggregation of injuries was also found. Clinical diagnosis and treatment should be adapted to care of these patients. More studies are needed to generalize these findings.
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Review of "Neurology Emergencies" by Jonathon A. Edlow and Magdy H. Selim
None
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The intravascular volume effect of ringer's lactate is below 20%: a prospective study in humans
Introduction Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (e.g. human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise.Methods In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t-tests (according to Student) for the singular measurements were taken. P<0.05 was considered to be significant.Results 1,097+/-285 ml of whole blood were withdrawn (641+/-155 ml/m2 body surface area) and simultaneously replaced by 3,430+/-806 ml of ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459+/-185 ml; p<0.05) which did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+2,157+/-606 ml; p<0.05). The volume effect of ringer's lactate was 17+/-10%. The infusion of 245+/-64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184+/-63%.Conclusions Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the 3-fold amount of ringer's lactate impedes maintenance of intravascular normovolemia. Main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the 5-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous.
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A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase
IntroductionThe present study is a pilot prospective safety evaluation of a new closed loop computerized protocol on ventilation and oxygenation in stable, spontaneously breathing children weighting more than 7kg, during the weaning phase of mechanical ventilation.
Methods:
Mechanically ventilated children ready to start the weaning process were ventilated for 5 periods of 60 minutes in the following order: Pressure Support Ventilation (PSV), Adaptive Support Ventilation (ASV), ASV plus a ventilation controller (ASV-CO2), ASV-CO2 plus an oxygenation controller (ASV-CO2-O2) and PSV again. Based on breath by breath analysis, the percentage of time with normal ventilation as defined by a respiratory rate (RR) between 10 and 40 breath/min, a tidal volume (VT) > 5 ml/kg of predicted body weight and an end tidal CO2 between 25 and 55 mmHg. The number of manipulations and changes on the ventilator were also recorded.
Results:
Fifteen children, median aged 45 months, were investigated. No adverse event and no premature protocol termination were reported. ASV-CO2 and ASV-CO2-O2, kept the patients within normal ventilation for respectively 94% [91 - 96] and 94% [87 - 96]) of the time. VT, RR, Peak inspiratory airway pressure (Paw-peak) and minute ventilation were equivalent with all modalities, although there were more automatic setting changes in ASV-CO2 and ASV-CO2-O2. PEEP modifications by ASV-CO2-O2 needs further investigation.
Conclusions:
Over the short study period and in this specific population, ASV-CO2 and ASV-CO2-O2 were safe and kept the patient with normal ventilation most of the time. Further research is needed, especially for PEEP modifications by ASV-CO2-O2.Trial registration: NCT01095406
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Antipsychotic use and diagnosis of delirium in the intensive care unit
IntroductionDelirium is an independent risk factor for prolonged hospital length of stay (LOS) and increased mortality. Several antipsychotics have been studied for the treatment of intensive care unit (ICU) delirium that has lead to a high variability in prescribing patterns for these medications. We hypothesize that in clinical practice the documentation of delirium is lower than the incidence of delirium reported in prospective clinical trials. The objective of this study was to document the incidence of delirium diagnosed in ICU patients and to describe the utilization of antipsychotics in the ICU.
Methods:
Retrospective observational cohort study conducted at seventy-one United States academic medical centers that reported data to the University HealthSystem Consortium Clinical Database/Resource Manager. Included all patients 18 years of age and older admitted to the hospital between January 1, 2010 and June 30, 2010 with at least one day in the ICU.
Results:
Delirium was diagnosed in 6% (10,034 of 164,996) of hospitalizations with an ICU admission. Antipsychotics were administered to 11% (17,764 of 164,996) of patients. Of the antipsychotics studied, the most frequently used were haloperidol (62%; n=10,958) and quetiapine (31%; n=5,448). Delirium was associated with increased ICU LOS (5 vs. 3 days, P<0.001) and hospital LOS (11 vs. 6 days, P<0.001), but not in-hospital mortality (8% vs. 9%, P=0.419). Antipsychotic exposure was associated with increased ICU LOS (8 vs. 3 days, P<0.001), hospital LOS (14 vs. 5 days, P<0.001) and mortality (12% vs. 8%, P<0.001). Of patients with antipsychotic exposure in the ICU, absence of a documented mental disorder (32%, n=5,760) was associated with increased ICU LOS (9 vs. 7 days, P<0.001), hospital LOS (16 vs. 13 days, P<0.001) and in-hospital mortality (19% vs. 9%, P<0.001) compared to patients with a documented mental disorder (68%, n=12,004).
Conclusions:
The incidence of documented delirium in ICU patients is lower than that documented in previous prospective studies with active screening. Antipsychotics are administered to one in every ten ICU patients. When administration occurs in the absence of a documented mental disorder, antipsychotic use is associated with an even higher ICU and hospital LOS, as well as in-hospital mortality.
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Early course of microcirculatory perfusion in eye and digestive tract during hypodynamic sepsis
IntroductionThe aim of the study is to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, mucosa of jejunum and rectum.
Methods:
Pigs were randomly assigned to sepsis (n=9) and sham (n=4) groups. The sepsis group received a fixed dose of alive Escherichia coli infusion over 1 hour (1.8 * 109 /kg colony-forming units). Animals were observed 5 hours after the start of Escherichia coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal and rectal evaluation of microcirculation using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, 3 and 5 hours after the start of live Escherichia coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done using a semi-quantitative method.
Results:
Infusion of Escherichia coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decrease in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal and rectal lodges 3 and 5 hours after start of Escherichia coli infusion in comparison to baseline variables. Correlation between sublingual and conjunctival (r=0.80, p=0.036), sublingual and jejunal (r=0.80, p=0.044), sublingual and rectal (r=0.79, p=0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of Escherichia coli infusion. Overall, the sublingual mucosa exhibited the most pronounced alterations of microcirculatory flow in comparison to conjunctival, jejunal and rectal microvasculature (p<0.05).
Conclusions:
In this pig model there is a time dependent correlation between sublingual and microvascular beds during the course of hypodynamic state of sepsis.
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Insulin Therapy Improves Protein Metabolism in the Critically Ill
Critical illness, trauma and burns are associated with profound metabolic abnormalities, of which protein catabolism, hyperglycemia and insulin resistance are hallmarks of these conditions. Increased protein breakdown and loss results in muscle wasting, weakness and diminished functioning. Interestingly, hyperglycemia and insulin resistance augment catabolic responses. Insulin, which is routinely administered to critically ill patients to prevent excessive hyperglycemia, also stimulates protein synthesis and prevents whole-body protein loss. The present commentary highlights the results of a recent study published in Critical Care and discusses whether moderate insulin therapy is equally as beneficial as conventional insulin therapy in preventing protein catabolism and loss.
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