Risk stratification and prognostic performance of the predisposition,infection, response,and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study

Introduction

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores.

Methods

Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems.

Results

Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD.

Conclusions

The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.     

Predicting six-month mortality of patients with traumatic brain injury: usefulness of common intensive care severity scores

Introduction

The aim of this study was to evaluate the usefulness of the APACHE II (Acute Physiology and Chronic Health Evaluation II), SAPS II (Simplified Acute Physiology Score II) and SOFA (Sequential Organ Failure Assessment) scores compared to simpler models based on age and Glasgow Coma Scale (GCS) in predicting long-term outcome of patients with moderate-to-severe traumatic brain injury (TBI) treated in the intensive care unit (ICU).

Methods

A national ICU database was screened for eligible TBI patients (age over 15 years, GCS 3–13) admitted in 2003–2012. Logistic regression was used for customization of APACHE II, SAPS II and SOFA score-based models for six-month mortality prediction. These models were compared to an adjusted SOFA-based model (including age) and a reference model (age and GCS). Internal validation was performed by a randomized split-sample technique. Prognostic performance was determined by assessing discrimination, calibration and precision.

Results

In total, 1,625 patients were included. The overall six-month mortality was 33%. The APACHE II and SAPS II-based models showed good discrimination (area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.75 to 0.82; and 0.80, 95% CI 0.77 to 0.83, respectively), calibration (P > 0.05) and precision (Brier score 0.166 to 0.167). The SOFA-based model showed poor discrimination (AUC 0.68, 95% CI 0.64 to 0.72) and precision (Brier score 0.201) but good calibration (P > 0.05). The AUC of the SOFA-based model was significantly improved after the insertion of age and GCS (∆AUC +0.11, P < 0.001). The performance of the reference model was comparable to the APACHE II and SAPS II in terms of discrimination (AUC 0.77; compared to APACHE II, ΔAUC −0.02, P = 0.425; compared to SAPS II, ΔAUC −0.03, P = 0.218), calibration (P > 0.05) and precision (Brier score 0.181).

Conclusions

A simple prognostic model, based only on age and GCS, displayed a fairly good prognostic performance in predicting six-month mortality of ICU-treated patients with TBI. The use of the more complex scoring systems APACHE II, SAPS II and SOFA added little to the prognostic performance.     

Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy

Background

Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM.

Methods

Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point.

Results

Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m²vs. 23.7 ± 5.8 ml/m², p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls.

Conclusions

Septal convexity is an additional previously undescribed feature of subclinical HCM.     

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

Background

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.

Methods

In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.

Results

Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m²; female > 78 g/m²). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).

Conclusion

In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.     

LOWER LIMB ASYMMETRIES IN RHYTHMIC GYMNASTICS ATHLETES

Background

Different limb training demands and limb preference may determine anthropometric and muscle force inter-limb asymmetries in Rhythmic Gymnastics (RG) athletes.

Purpose

The purpose of this study was to evaluate the influence of lateral preference of the lower extremity on anthropometric, range of motion, and isokinetic torque measurements of RG athletes.

Study Design

Cross sectional study

Methods

Lower limb anthropometric measurements (girth, estimated anatomical cross-sectional area), hip, knee and ankle range of motion, flexor and extensor isokinetic torques (angular velocities = 60, 180, e 240 °·s⁻¹) and bilateral asymmetry index were evaluated in 11 international level Rhythmic Gymnastics athletes (17.9 ± 4.0 years of age; 9.1 ± 5,1 years of experience; 26.8 ± 6.0 weekly training hours).

Results

The preferred limb showed larger thigh girth and anatomical cross-sectional area, higher ankle dorsiflexor range of motion, higher hip flexor torque at 60 °·s⁻¹ and higher plantarflexor torque at 180 °·s⁻¹ compared to the non-preferred limb.

Conclusions

The observed differences seem to be strictly related to lateral preference and rhythmic gymnastics training.

Levels of Evidence

3     

THE RELATIONSHIP BETWEEN PASSIVE GLENOHUMERAL TOTAL ROTATION AND THE STRENGTH OF THE INTERNAL AND EXTERNAL ROTATOR MUSCLES,A PRELIMINARY STUDY

Background

There is little research on how the amount of shoulder joint range of motion, specifically glenohumeral rotation, may be related to the muscle strength of the rotator cuff muscles. A long held belief is that a joint with excessive range of motion needs sufficient muscular strength for stability. However, no studies have examined this concept.

Purpose

The purpose of this study was to see if total arc of glenohumeral joint rotation (External rotation [ER]+Internal rotation [IR]) could predict peak isometric muscle strength of the IR or ER muscles of the shoulder.

Study Design

Cross‐sectional study design

Methods

Fifty‐three participants (41 females, 12 males) participated in the study. Passive glenohumeral joint internal rotation and external rotation motion was measured for each participant with a standard goniometer. Isometric muscle force of the ER and IR muscles were tested using a handheld dynamometer in three positions: end range ER, neutral 0°, and end range IR. Data were analyzed using a non‐parametric tree based regression method (CART) and then cross‐validated.

Results

The results showed that those with an increased total arc of motion of glenohumeral rotation (greater than 165.0°) had less muscle isometric muscle strength in all tests positions than those with less glenohumeral rotation.

Conclusion

Decreased force of the ER and IR muscles of the shoulder was noted in those with increased total arc glenohumeral rotation ( > 165.0°), specifically those with increased glenohumeral internal rotation ( > 80.0°) when compared to those with glenohumeral rotation ( < 165.0°) and glenohumeral internal rotation ( < 80.0°). Future studies should include more males and attempt to develop strategies to assist those with larger excursions of shoulder rotation who may be at risk of developing shoulder problems.

Level of Evidence

Level 2     

Effect of admission time on mortality in an intensive care unit in Mainland China: a propensity score matching analysis

Introduction

The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis.

Methods

A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types.

Results

Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001) patients. Moreover, NT admissions were related to higher ICU mortality [odds ratio (OR), 1.725 (95% CI 1.118–2.744), P = 0.01] and elevated mortality risk at 28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171–3.150), P = 0.01]. PSM showed that admission time remained related to ICU outcome (P = 0.045) and mortality risk at 28 days [OR, 2.187 (95% CI 1.119–4.271), P = 0.022]. However, no mortality difference was found between weekend and workday admissions (P = 0.849), even if weekend admissions were more related to higher APACHE II scores compared with workday admissions.

Conclusions

NT admission was associated with poor ICU outcomes. This finding may be related to shortage of onsite intensivists and qualified residents during NT. The current staffing model and training system should be improved in the future.     

Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients

Introduction

Early protein and energy feeding in critically ill patients is heavily debated and early protein feeding hardly studied.

Methods

A prospective database with mixed medical-surgical critically ill patients with prolonged mechanical ventilation (>72 hours) and measured energy expenditure was used in this study. Logistic regression analysis was used to analyse the relation between admission day-4 protein intake group (with cutoffs 0.8, 1.0, and 1.2 g/kg), energy overfeeding (ratio energy intake/measured energy expenditure > 1.1), and admission diagnosis of sepsis with hospital mortality after adjustment for APACHE II (Acute Physiology and Chronic Health Evaluation II) score.

Results

A total of 843 patients were included. Of these, 117 had sepsis. Of the 736 non-septic patients 307 were overfed. Mean day-4 protein intake was 1.0 g/kg pre-admission weight per day and hospital mortality was 36%. In the total cohort, day-4 protein intake group (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.73 to 0.99; P = 0.047), energy overfeeding (OR 1.62; 95%CI 1.07 to 2.44; P = 0.022), and sepsis (OR 1.77; 95%CI 1.18 to 2.65; P = 0.005) were independent risk factors for mortality besides APACHE II score. In patients with sepsis or energy overfeeding, day-4 protein intake was not associated with mortality. For non-septic, non-overfed patients (n = 419), mortality decreased with higher protein intake group: 37% for <0.8 g/kg, 35% for 0.8 to 1.0 g/kg, 27% for 1.0 to 1.2 g/kg, and 19% for ≥1.2 g/kg (P = 0.033). For these, a protein intake level of ≥1.2 g/kg was significantly associated with lower mortality (OR 0.42, 95%CI 0.21 to 0.83, P = 0.013).

Conclusions

In non-septic critically ill patients, early high protein intake was associated with lower mortality and early energy overfeeding with higher mortality. In septic patients early high protein intake had no beneficial effect on mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0701-z) contains supplementary material, which is available to authorized users.     

The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial

Introduction

Acute renal failure (ARF) requiring renal replacement therapy (RRT) occurs frequently in ICU patients and significantly affects mortality rates. Previously, few large clinical trials investigated the impact of RRT modalities on patient outcomes. Here we investigated the effect of two major RRT strategies (intermittent hemodialysis (IHD) and continuous veno-venous hemofiltration (CVVH)) on mortality and renal-related outcome measures.

Methods

This single-center prospective randomized controlled trial (“CONVINT”) included 252 critically ill patients (159 male; mean age, 61.5 ± 13.9 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score, 28.6 ± 8.8) with dialysis-dependent ARF treated in the ICUs of a tertiary care academic center. Patients were randomized to receive either daily IHD or CVVH. The primary outcome measure was survival at 14 days after the end of RRT. Secondary outcome measures included 30-day-, intensive care unit-, and intrahospital mortality, as well as course of disease severity/biomarkers and need for organ-support therapy.

Results

At baseline, no differences in disease severity, distributions of age and gender, or suspected reasons for acute renal failure were observed. Survival rates at 14 days after RRT were 39.5% (IHD) versus 43.9% (CVVH) (odds ratio (OR), 0.84; 95% confidence interval (CI), 0.49 to 1.41; P = 0.50). 14-day-, 30-day, and all-cause intrahospital mortality rates were not different between the two groups (all P > 0.5). No differences were observed in days on RRT, vasopressor days, days on ventilator, or ICU-/intrahospital length of stay.

Conclusions

In a monocentric RCT, we observed no statistically significant differences between the investigated treatment modalities regarding mortality, renal-related outcome measures, or survival at 14 days after RRT. Our findings add to mounting data demonstrating that intermittent and continuous RRTs may be considered equivalent approaches for critically ill patients with dialysis-dependent acute renal failure.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT01228123","term_id":"NCT01228123"}}NCT01228123, clinicaltrials.gov     

A common cause of sudden and thunderclap headaches: reversible cerebral vasoconstriction syndrome

Background

Thunderclap headache (TCH) is a sudden headache (SH) with accepted criteria of severe intensity and onset to peak within one minute. It is a well-known presentation for subarachnoid hemorrhage (SAH) but most patients with TCH or SH run a benign course without identifiable causes. Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome characterized by recurrent TCH attacks, has been proposed to account for most of these patients.

Methods

We recruited consecutive patients presenting with SH at our headache clinic. Computed tomography and/or magnetic resonance imaging with angiography were performed to exclude structural causes and to identify vasoconstriction. Catheter angiography and lumbar puncture were performed with patients consent. Reversibility of vasoconstriction was confirmed by follow-up study.

Results

From July 2010 to June 2013, 31 patients with SH were recruited. Twenty-four (72.7%) of these SH patients exhibited headache fulfilling the TCH criteria. The diagnosis of RCVS was confirmed in 14 (45.2%) of patients with SH and 11 (45.8%) of patients with TCH. Other diagnoses were as follows: primary headaches (SH: 41.9%, TCH: 45.8%) and other secondary causes (SH: 12.9%, TCH: 8.3%). Compared with non-RCVS patients, patients with RCVS were older (50.8 ± 9.3 years vs. 40.8 ± 10.0 years, P = 0.006) and less likely to experience short headache duration of < 1 hour (23.1% vs. 78.6%, P = 0.007). Patients with RCVS were more likely to cite bathing (42.9% vs. 0%, P = 0.004) and less likely to cite exertion (0% vs. 29.4%, P = 0.048) as headache triggers.

Conclusions

Reversible cerebral vasoconstriction syndrome is a common cause of SH and TCH. Considering the potential mortality and morbidity of RCVS, systemic examination of cerebral vessels should be performed in these patients.     

Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database

Introduction

Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients.

Methods

We conducted a secondary analysis of pooled data collected prospectively from international nutrition studies. Eligible patients had a diagnosis of sepsis and/or pneumonia and were admitted to the ICU for ≥3 days, mechanically ventilated within 48 hours of ICU admission and only receiving EN. Patients receiving parenteral nutrition were excluded. Data were collected from ICU admission up to a maximum of 12 days. Regression models were used to examine the impact of calorie and protein intake on 60-day mortality and ventilator-free days.

Results

Of the 13,630 patients included in the dataset, 2,270 met the study inclusion criteria. Patients received a mean amount of 1,057 kcal/d (14.5 kcal/kg/day) and 49 g protein/day (0.7 g/kg/d) by EN alone. Patients were mechanically ventilated for a median of 8.4 days and 60-day mortality was 30.5%. An increase of 1,000 kcal was associated with reduced 60-day mortality (odds ratio (OR) 0.61; 95% confidence interval (CI) 0.48 to 0.77, P <0.001) and more ventilator-free days (2.81 days, 95% CI 0.53 to 5.08, P = 0.02) as was an increase of 30 g protein per day (OR 0.76; 95% CI 0.65 to 0.87, P <0.001 and 1.92 days, 95% CI 0.58 to 3.27, P = 0.005, respectively).

Conclusions

In critically ill septic patients, a calorie and protein delivery closer to recommended amounts by EN in the early phase of ICU stay was associated with a more favorable outcome.     

Cognitive processing of cluster headache patients: evidence from event-related potentials

Background

The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Event-related potentials confer advantages in the functional evaluation of the cortex, but few studies thus far have employed this method in cluster headache.

Methods

Seventeen cluster patients (15 males; mean age = 35.4 years) and 15 age-matched healthy participants (13 males; mean age = 34.6 years) were recruited. A visual oddball paradigm was employed to analyze target processing using event-related potentials. We investigated the P3/P3d components in the experiment.

Results

P3/P3d amplitudes were decreased in CH patients (P3, 3.82 μV; P3d, 5.8 μV) compared with controls (P3, 7.28 μV; P3d, 8.95 μV), F(1,30) = 4.919, p < 0.05, η2 = 0.141 for P3 and F(1,30) = 8.514, p < 0.05, η2 = 0.221 for P3d, respectively). Moreover, the amplitudes of P3/P3d were no significantl difference in the side of pain as compared to contralateral one (p > 0.05).

Conclusions

These results provide evidence of dysfunction in the cognitive processing of CH patients, which may also contribute to the pathophysiology of CH.     

One-year mortality in patients requiring prolonged mechanical ventilation: multicenter evaluation of the ProVent score

Introduction

Current severity-of-illness indexes are unable to assess the long-term prognosis of patients requiring prolonged mechanical ventilation. A prognostic scoring system (Prognosis for Prolonged Ventilation score - ProVent - score) seems able to evaluate one-year mortality of such patients. However, testing of the model outside the developers'' centers has not been reported. So, it is unclear how the ProVent score performs in non-US and non-tertiary ICUs. The goal of our study was to evaluate its performances in a French multicenter, community hospital-based setting.

Methods

In three primary ICUs, 201 patients requiring mechanical ventilation for at least 21 days were enrolled in a retrospective cohort study. ICU mortality was abstracted from medical records and, for patients discharged alive from the ICU, one-year mortality was determined by telephone calls to patients’ general practitioners.

Results

One-year mortality was 60% (n = 120). On day 21 of ventilation, ProVent score value was 0 in 19 patients (9%), 1 in 63 patients (31%), 2 in 64 patients (32%), 3 in 37 patients (18%), and ≥4 in 18 patients (9%), respectively. For ProVent score values ranging from 0 to ≥4, one-year mortality rates were 21%, 43%, 67%, 78%, and 94%, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve for the ProVent score was 0.74 (95% confidence interval 0.671 to 0.809). Stepwise logistic regression analysis showed that only three variables (age ≥65 years, vasopressors, and hemodialysis) were independently associated with one-year mortality in our population. In assigning one point to each variable, we created a French ProVent score. The Hosmer-Lemeshow goodness-of-fit statistic was 1.36 (DF = 6, P = 0.857) and the AUC of the ROC curve was 0.742 (95% confidence interval 0.673 to 0.810). One-year mortality rates for French ProVent score ranging from 0 to 3 were 34.6%, 70.9%, 83.3% and 100%, respectively (P <0.0001).

Conclusions

The ProVent score is able, even in non-US ICUs and in community hospitals, to accurately identify among patients requiring prolonged mechanical ventilation those who are at high risk of one-year mortality. Its simplification appears possible. However, further validation of this French ProVent score in a larger external sample is indicated.     

Coefficient of glucose variation is independently associated with mortality in critically ill patients receiving intravenous insulin

Introduction

Both patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill.

Methods

We used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL.

Results

We studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001).

Conclusions

Blood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.     

Elevated plasma thrombomodulin and angiopoietin-2 predict the development of acute kidney injury in patients with acute myocardial infarction

Introduction

Acute kidney injury (AKI) following acute myocardial infarction (AMI) is associated with unfavorable prognosis. Endothelial activation and injury were found to play a critical role in the development of both AKI and AMI. This pilot study aimed to determine whether the plasma markers of endothelial injury and activation could serve as independent predictors for AKI in patients with AMI.

Methods

This prospective study was conducted from March 2010 to July 2012 and enrolled consecutive 132 patients with AMI receiving percutaneous coronary intervention (PCI). Plasma levels of thrombomodulin (TM), von Willebrand factor (vWF), angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) were measured on day 1 of AMI. AKI was defined as elevation of serum creatinine of more than 0.3 mg/dL within 48 hours.

Results

In total, 13 out of 132 (9.8%) patients with AMI developed AKI within 48 hours. Compared with patients without AKI, patients with AKI had increased plasma levels of Ang-2 (6338.28 ± 5862.77 versus 2412.03 ± 1256.58 pg/mL, P = 0.033) and sTM (7.6 ± 2.26 versus 5.34 ± 2.0 ng/mL, P < 0.001), and lower estimated glomerular filtration rate (eGFR) (46.5 ± 20.2 versus 92.5 ± 25.5 mL/min/1.73 m², P < 0.001). Furthermore, the areas under the receiver operating curves demonstrated that plasma thrombomodulin (TM) and Ang-2 levels on day 1 of AMI had modest discriminative powers for predicting AKI development following AMI (0.796, P <0.001; 0.833, P <0.001; respectively).

Conclusions

Endothelial activation, quantified by plasma levels of TM and Ang-2 may play an important role in development of AKI in patients with AMI.     

The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials

Introduction

The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.

Methods

We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.

Results

In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I² = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I² = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I² = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).

Conclusions

The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0570-5) contains supplementary material, which is available to authorized users.     

Cardiac output and cardiac index measured with cardiovascular magnetic resonance in healthy subjects,elite athletes and patients with congestive heart failure

Background

Cardiovascular Magnetic Resonance (CMR) enables non-invasive quantification of cardiac output (CO) and thereby cardiac index (CI, CO indexed to body surface area). The aim of this study was to establish if CI decreases with age and compare the values to CI for athletes and for patients with congestive heart failure (CHF).

Methods

CI was measured in 144 healthy volunteers (39 ± 16 years, range 21–81 years, 68 females), in 60 athletes (29 ± 6 years, 30 females) and in 157 CHF patients with ejection fraction (EF) below 40% (60 ± 13 years, 33 females). CI was calculated using aortic flow by velocity-encoded CMR and is presented as mean ± SD. Flow was validated in vitro using a flow phantom and in 25 subjects with aorta and pulmonary flow measurements.

Results

There was a slight decrease of CI with age in healthy subjects (8 ml/min/m² per year, r² = 0.07, p = 0.001). CI in males (3.2 ± 0.5 l/min/m²) and females (3.1 ± 0.4 l/min/m²) did not differ (p = 0.64). The mean ± SD of CI in healthy subjects in the age range of 20–29 was 3.3 ± 0.4 l/min/m², in 30–39 years 3.3 ± 0.5 l/min/m², in 40–49 years 3.1 ± 0.5 l/min/m², 50–59 years 3.0 ± 0.4 l/min/m² and >60 years 3.0 ± 0.4 l/min/m². There was no difference in CI between athletes and age-controlled healthy subjects but HR was lower and indexed SV higher in athletes. CI in CHF patients (2.3 ± 0.6 l/min/m²) was lower compared to the healthy population (p < 0.001). There was a weak correlation between CI and EF in CHF patients (r² = 0.07, p < 0.001) but CI did not differ between patients with NYHA-classes I-II compared to III-IV (n = 97, p = 0.16) or patients with or without hospitalization in the previous year (n = 100, p = 0.72). In vitro phantom validation showed low bias (−0.8 ± 19.8 ml/s) and in vivo validation in 25 subjects also showed low bias (0.26 ± 0.61 l/min, QP/QS 1.04 ± 0.09) between pulmonary and aortic flow.

Conclusions

CI decreases in healthy subjects with age but does not differ between males and females. We found no difference in CI between athletes and healthy subjects at rest but CI was lower in patients with congestive heart failure. The presented values can be used as reference values for flow velocity mapping CMR.     

Prediction of response to cardiac resynchronization therapy using left ventricular pacing lead position and cardiovascular magnetic resonance derived wall motion patterns: a prospective cohort study

Background

Despite marked benefits in many heart failure patients, a considerable proportion of patients treated with cardiac resynchronization therapy (CRT) fail to respond appropriately. Recently, a “U-shaped” (type II) wall motion pattern identified by cardiovascular magnetic resonance (CMR) has been associated with improved CRT response compared to a homogenous (type I) wall motion pattern. There is also evidence that a left ventricular (LV) lead localized to the latest contracting LV site predicts superior response, compared to an LV lead localized remotely from the latest contracting LV site.

Methods

We prospectively evaluated patients undergoing CRT with pre-procedural CMR to determine the presence of type I and type II wall motion patterns and pre-procedural echocardiography to determine end systolic volume (ESV). We assessed the final LV lead position on post-procedural fluoroscopic images to determine whether the lead was positioned concordant to or remote from the latest contracting LV site. CRT response was defined as a ≥ 15 % reduction in ESV on a 6 month follow-up echocardiogram.

Results

The study included 33 patients meeting conventional indications for CRT with a mean New York Heart Association class of 2.8 ± 0.4 and mean LV ejection fraction of 28 ± 9 %. Overall, 55 % of patients were echocardiographic responders by ESV criteria. Patients with both a type II pattern and an LV lead concordant to the latest contracting site (T2CL) had a response rate of 92 %, compared to a response rate of 33 % for those without T2CL (p = 0.003). T2CL was the only independent predictor of response on multivariate analysis (odds ratio 18, 95 % confidence interval 1.6-206; p = 0.018). T2CL resulted in significant incremental improvement in prediction of echocardiographic response (increase in the area under the receiver operator curve from 0.69 to 0.84; p = 0.038).

Conclusions

The presence of a type II wall motion pattern on CMR and a concordant LV lead predicts superior CRT response. Improving patient selection by evaluating wall motion pattern and targeting LV lead placement may ultimately improve the response rate to CRT.     

Serum butyrylcholinesterase predicts survival after extracorporeal membrane oxygenation after cardiovascular surgery

Introduction

Risk stratification in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery remains challenging, because data on specific outcome predictors are limited. Serum butyrylcholinesterase demonstrated a strong inverse association with all-cause and cardiovascular mortality in non-critically ill patients. We therefore evaluated the predictive value of preoperative serum butyrylcholinesterase levels in patients undergoing venoarterial ECMO support after cardiovascular surgery.

Methods

We prospectively included 191 patients undergoing venoarterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care center in our registry.

Results

All-cause and cardiovascular mortality were defined as primary study end points. During a median follow-up time of 51 months (IQR, 34 to 71) corresponding to 4,197 overall months of follow-up, 65% of patients died. Cox proportional hazard regression analysis revealed a significant and independent inverse association between higher butyrylcholinesterase levels and all-cause mortality with an adjusted hazard ratio (HR) of 0.44 (95% CI, 0.25 to 0.78; P = 0.005), as well as cardiovascular mortality, with an adjusted HR of 0.38 (95% CI, 0.21 to 0.70; P = 0.002), comparing the third with the first tertile. Survival rates were higher in patients within the third tertile of butyrylcholinesterase compared with patients within the first tertile at 30 days (68% versus 44%) as well as at 6 years (47% versus 21%).

Conclusions

The current study revealed serum butyrylcholinesterase as a strong and independent inverse predictor of all-cause and cardiovascular mortality in patients undergoing venoarterial ECMO therapy after cardiovascular surgery. These findings advance the limited knowledge on risk stratification in patients undergoing ECMO support and represent a valuable addition for a comprehensive decision making before ECMO implantation.