Physiologic Analysis and Clinical Performance of the Ventilatory Ratio in Acute Respiratory Distress Syndrome.

RATIONALE: Pulmonary dead space fraction (Vd/Vt) is an independent predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is seldom used in practice. The ventilatory ratio is a simple bedside index that can be calculated using routinely measured respiratory variables and is a measure of impaired ventilation. Ventilatory ratio is defined as [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5). OBJECTIVES: To determine the relation of ventilatory ratio with Vd/Vt in ARDS. METHODS: First, in a single-center, prospective observational study of ARDS, we tested the association of Vd/Vt with ventilatory ratio. With in-hospital mortality as the primary outcome and ventilator-free days as the secondary outcome, we tested the role of ventilatory ratio as an outcome predictor. The findings from this study were further verified in secondary analyses of two NHLBI ARDS Network randomized controlled trials. MEASUREMENTS AND MAIN RESULTS: Ventilatory ratio positively correlated with Vd/Vt. Ordinal groups of ventilatory ratio had significantly higher Vd/Vt. Ventilatory ratio was independently associated with increased risk of mortality after adjusting for PaO2/FiO2, and positive end-expiratory pressure (odds ratio, 1.51; P = 0.024) and after adjusting for Acute Physiologic Assessment and Chronic Health Evaluation II score (odds ratio, 1.59; P = 0.04). These findings were further replicated in secondary analyses of two separate NHLBI randomized controlled trials. CONCLUSIONS: Ventilatory ratio correlates well with Vd/Vt in ARDS, and higher values at baseline are associated with increased risk of adverse outcomes. These results are promising for the use of ventilatory ratio as a simple bedside index of impaired ventilation in ARDS.

Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units.

BACKGROUND: Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. METHODS: Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. RESULTS: Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. CONCLUSIONS: Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk models, and associated clinical decision rules, that provided acceptable discrimination for identifying patients at 'high risk' of Candida IFD. TRIAL REGISTRATION: The FIRE Study was reviewed and approved by the Bolton NHS Research Ethics Committee (reference: 08/H1009/85), the Scotland A Research Ethics Committee (reference: 09/MRE00/76) and the National Information Governance Board (approval number: PIAG 2-10(f)/2005).

The role of awake craniotomy in reducing intraoperative visual field deficits during tumor surgery.

OBJECTIVE: Homonymous hemianopia due to damage to the optic radiations or visual cortex is a possible consequence of tumor resection involving the temporal or occipital lobes. The purpose of this review is to present and analyze a series of studies regarding the use of awake craniotomy (AC) to decrease visual field deficits following neurosurgery. MATERIALS AND METHODS: A literature search was performed using the Medline and PubMed databases from 1970 and 2014 that compared various uses of AC other than intraoperative motor/somatosensory/language mapping with a focus on visual field mapping. RESULTS: For the 17 patients analyzed in this study, 14 surgeries resulted in quadrantanopia, 1 in hemianopia, and 2 without visual deficits. Overall, patient satisfaction with AC was high, and AC was a means to reduce surgery-related complications and cost related with the procedure. CONCLUSION: AC is a safe and tolerable procedure that can be used effectively to map optic radiations and the visual cortices in order to preserve visual function during resection of tumors infiltrating the temporal and occipital lobes. In the majority of cases, a homonymous hemianopia was prevented and patients were left with a quadrantanopia that did not interfere with daily function.

A biomarker panel (Bioscore) incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study.

INTRODUCTION: Ventilator-associated pneumonia (VAP) increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM)-1, would improve diagnostic accuracy. METHODS: A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP), and 31 non-ventilated controls (NVC), without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF) and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L) and soluble (IL-1ß, IL-6, IL-8, sTREM-1, Procalcitonin). Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel ('Bioscore'), was constructed, tested and validated, using Fisher's discriminant function analysis, to assess its value in distinguishing VAP from non VAP. RESULTS: The expression of TREM-1 on monocytes (mTREM-1) and neutrophils (nTREM-1) and concentrations of IL-1ß, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001). The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001). A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1ß, and serum CRP and IL-6) correctly identified 88.9% of VAP cases and 100% of non-VAP cases. CONCLUSION: A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.

Construct validity of the Chelsea critical care physical assessment tool: an observational study of recovery from critical illness.

INTRODUCTION: Intensive care unit-acquired weakness (ICU-AW) is common in survivors of critical illness, resulting in global weakness and functional deficit. Although ICU-AW is well described subjectively in the literature, the value of objective measures has yet to be established. This project aimed to evaluate the construct validity of the Chelsea Critical Care Physical Assessment tool (CPAx) by analyzing the association between CPAx scores and hospital-discharge location, as a measure of functional outcome. METHODS: The CPAx was integrated into practice as a service-improvement initiative in an 11-bed intensive care unit (ICU). For patients admitted for more than 48 hours, between 10 May 2010 and 13 November 2013, the last CPAx score within 24 hours of step down from the ICU or death was recorded (n = 499). At hospital discharge, patients were separated into seven categories, based on continued rehabilitation and care needs. Descriptive statistics were used to explore the association between ICU discharge CPAx score and hospital-discharge location. RESULTS: Of the 499 patients, 171 (34.3%) returned home with no ongoing rehabilitation or care input; 131 (26.2%) required community support; 28 (5.6%) went to inpatient rehabilitation for <6 weeks; and 25 (5.0%) went to inpatient rehabilitation for >6 weeks; 27 (5.4%) required nursing home level of care; 80 (16.0%) died in the ICU, and 37 (7.4%) died in hospital. A significant difference was found in the median CPAx score between groups (P < 0.0001). Four patients (0.8%) scored full marks (50) on the CPAx, all of whom went home with no ongoing needs; 16 patients (3.2%) scored 0 on the CPAx, all of whom died within 24 hours. A 0.8% ceiling effect and a 3.2% floor effect of the CPAx is found in the ICU. Compliance with completion of the CPAx stabilized at 78% of all ICU admissions. CONCLUSION: The CPAx score at ICU discharge has displayed construct validity by crudely discriminating between groups with different functional needs at hospital discharge. The CPAx has a limited floor and ceiling effect in survivors of critical illness. A significant proportion of patients had a requirement for postdischarge care and rehabilitation.

Analysis of ventilatory ratio as a novel method to monitor ventilatory adequacy at the bedside.

INTRODUCTION: Due to complexities in its measurement, adequacy of ventilation is seldom used to categorize disease severity and guide ventilatory strategies. Ventilatory ratio (VR) is a novel index to monitor ventilatory adequacy at the bedside. VR=(VEmeasured × PaCO2measured)/(VEpredicted × PaCO2ideal). VEpredicted is 100 mL.Kg-1.min-1 and PaCO2ideal is 5 kPa. Physiological analysis shows that VR is influenced by dead space (VD/VT) and CO2 production (VCO2). Two studies were conducted to explore the physiological properties of VR and assess its use in clinical practice. METHODS: Both studies were conducted in adult mechanically ventilated ICU patients. In Study 1, volumetric capnography was used to estimate daily VD/VT and measure VCO2 in 48 patients. Simultaneously, ventilatory ratio was calculated using arterial blood gas measurements alongside respiratory and ventilatory variables. This data was used to explore the physiological properties of VR. In Study 2, 224 ventilated patients had daily VR and other respiratory variables, baseline characteristics, and outcome recorded. The database was used to examine the prognostic value of VR. RESULTS: Study 1 showed that there was significant positive correlation between VR and VD/VT (modified r = 0.71) and VCO2 (r = 0.14). The correlation between VR and VD/VT was stronger in mandatory ventilation compared to spontaneous ventilation. Linear regression analysis showed that VD/VT had a greater influence on VR than VCO2 (standardized regression coefficient 1/1-VD/VT: 0.78, VCO2: 0.44). Study 2 showed that VR was significantly higher in non-survivors compared to survivors (1.55 vs. 1.32; P < 0.01). Univariate logistic regression showed that higher VR was associated with mortality (OR 2.3, P < 0.01), this remained the case after adjusting for confounding variables (OR 2.34, P = 0.04). CONCLUSIONS: VR is an easy to calculate bedside index of ventilatory adequacy and appears to yield clinically useful information.

Comparison of volumetric capnography and mixed expired gas methods to calculate physiological dead space in mechanically ventilated ICU patients.

INTRODUCTION: Physiological dead space should be a routine measurement in ventilated patients but measuring dead space using the Douglas bag (DB) method is cumbersome and requires corrections for compressed ventilator gas. These factors make this method impractical in the critical care setting. Volumetric capnography (VCAP) offers a relatively simple solution to calculating dead space. Few studies have been conducted to directly compare dead space measured by VCAP and the DB method in critically unwell adults. METHOD: Prospective observational study of 48 mechanically ventilated adults ICU patients. Dead space was calculated simultaneously using VCAP (CO(2)SMO) and the Bohr-Enghoff equation. In total, 168 paired readings were taken. Single-breath CO(2) waveform areas under the curve were computed automatically by software to calculate physiological dead space. The calculated value of P(E(CO(2))) was also recorded from the CO(2)SMO device. Exhaust ventilator gas was collected in a 10-l mixing chamber. P(E(CO(2))) was measured in the chamber following correction for compressed gas. RESULTS: The study demonstrated good agreement between physiological V(D)/V(T) calculated by VCAP and corrected (mean bias 0.03), and uncorrected (mean bias 0.02) Bohr-Enghoff method. There was good correlation between the two methods of measurement (VCAP vs corrected r(2) = 0.90 P < 0.001, VCAP vs uncorrected r(2) = 0.90, P < 0.001). There was good correlation between [Formula: see text] calculated by the CO(2)SMO and in the exhaust collected gas (mean bias 0.08). CONCLUSIONS: VCAP shows good agreement with Douglas Bag method in measuring physiological V(D)/V(T) over a wide range of dead space fractions.

Hydroxyethylstarch 200/0.5--the horse has bolted.

Hydroxyethylstarch (HES) 200/0.5 is associated with renal failure. Several studies have suggested that renal function is affected but the subsequent arguments leave the clinician in no man's land. A recent study in Critical Care by Simon and colleagues using a two hit animal model of shock demonstrates that the use of a higher molecular weight starch, HES 200/0.5, is associated with impaired renal function when compared with ringers acetate, gelatin or a lower molecular weight starch, HES 130/0.42. The authors conclude that both the lower molecular weight starch and the ringers acetate 'preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline'. Added to the previous evidence, the renal effects of HES200/0.5 are probably real. Many clinicians have already moved to the lower molecular weight starches on the basis of doubt rather than certainty, but this study tips the balance. The cause remains elusive and the lack of a mechanism should be seen as a problem.

Deadspace ventilation: a waste of breath!

Problems with ventilatory efficiency results in abnormal CO(2) clearance. Measuring deadspace ventilation should be the most reliable method of monitoring ventilatory efficiency in mechanically ventilated patients. Since its first description by Bohr in the late 19th century to the current use of single-breath test for volumetric CO(2), our understanding of the physiological deadspace has vastly improved. Yet indices of oxygenation seem to be the mainstay when instigating or fine-tuning ventilatory strategies. Deadspace and with it ventilatory efficiency has been largely forgotten. Recently though there has been a resurgence of interest in ventilatory efficiency. Several indices have been described that either predict deadspace or track ventilatory efficiency at the bedside. Thus making it more accessible and easy to monitor and study in large groups of patients, factors which have perhaps resulted in its under-utilisation in critical care. This review revisits the physiological concepts and methods of measuring deadspace. Described are the various clinical applications of deadspace measurements in the critically unwell. The potential reasons that have led to the variable being under-used are also examined. Finally we describe the indices currently available to track ventilatory efficiency at the bedside.

A balanced view of balanced solutions.

The present review of fluid therapy studies using balanced solutions versus isotonic saline fluids (both crystalloids and colloids) aims to address recent controversy in this topic. The change to the acid-base equilibrium based on fluid selection is described. Key terms such as dilutional-hyperchloraemic acidosis (correctly used instead of dilutional acidosis or hyperchloraemic metabolic acidosis to account for both the Henderson-Hasselbalch and Stewart equations), isotonic saline and balanced solutions are defined. The review concludes that dilutional-hyperchloraemic acidosis is a side effect, mainly observed after the administration of large volumes of isotonic saline as a crystalloid. Its effect is moderate and relatively transient, and is minimised by limiting crystalloid administration through the use of colloids (in any carrier). Convincing evidence for clinically relevant adverse effects of dilutional-hyperchloraemic acidosis on renal function, coagulation, blood loss, the need for transfusion, gastrointestinal function or mortality cannot be found. In view of the long-term use of isotonic saline either as a crystalloid or as a colloid carrier, the paucity of data documenting detrimental effects of dilutional-hyperchloraemic acidosis and the limited published information on the effects of balanced solutions on outcome, we cannot currently recommend changing fluid therapy to the use of a balanced colloid preparation.

Ten years of hemovigilance reports of transfusion-related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma.

BACKGROUND AND METHODS: From 1996 through 2006, 195 cases were reported as transfusion-related acute lung injury (TRALI) to the Serious Hazards of Transfusion scheme and from 1999 onward classified by probability, using clinical features and HLA and/or HNA typing. From late 2003, the National Blood Service provided 80 to 90 percent of fresh-frozen plasma (FFP) and plasma for platelet (PLT) pools from male donors. RESULTS: Forty-nine percent of reports were highly likely/probable TRALI, and 51 percent possible/unlikely. Of 96 investigations, donor antibodies recognizing recipient antigens were found in 73 cases (65%), with HLA Class I in 25 of those (40%), HLA Class II antibodies in 38 (62%), and granulocyte antibodies in 12 (17%). A review in 2003 revealed that the TRALI risk/component was 6.9 times higher for FFP and 8.2 times higher for PLTs than for red blood cells, and that in donors of implicated FFP/PLTs, white blood cell antibodies were found 3.6 times more often than by chance (p

Plasma volume measurement in septic patients using an albumin dilution technique: comparison with the standard radio-labelled albumin method.

OBJECTIVE: To investigate a technique using 20% albumin for measurement of plasma volume in critically ill patients. DESIGN AND SETTING: Laboratory and clinical investigation in the adult intensive care unit and anaesthetic laboratories of a university hospital. PATIENTS: 12 patients fulfilling ACCP/SCCM criteria for septic shock. INTERVENTIONS AND MEASUREMENTS: Each patient received (125)I-labelled albumin, and the volume of distribution was measured at 1 and 10 min. The accepted standard plasma volume measurement (98% of the 10-min volume of distribution) was calculated. Immediately thereafter 200 ml 20% human albumin was given. Albumin concentrations were measured before and 1 min after this 40-g bolus, and the volume of distribution calculated using a formula that corrected for the 200 ml fluid in which the albumin was dissolved. RESULTS: Plasma volumes measured using the albumin dilution technique at 1 min were smaller than the standard technique by 110+/-280 ml; limits of agreement were from -660 to +440 ml (-16% to +11%). Plasma volumes measured by (125)I-albumin at 1 min were smaller than the standard by 120+/-110 ml; limits of agreement were from -330 to +100 ml (-8 to +2%). CONCLUSIONS: Non-labelled albumin can be used easily and quickly to measure a plasma volume in ICU patients and gives a moderately accurate estimate when compared with the (125)I-labelled albumin methods. The normal isotope method over-estimates plasma volumes in septic patients because excessive transcapillary escape of albumin is inadequately compensated for by the standard correction factor.

Relaparotomy for suspected intraperitoneal sepsis after abdominal surgery.

Relaparotomy may be beneficial in patients developing intraperitoneal sepsis after abdominal procedures. We determined whether joint clinical assessment by intensivist and surgeon (clinician assessment) identified patients with surgically correctable intraperitoneal sepsis. We also assessed the effect of patient age and sex, disease presentation and severity, interval to relaparotomy, and the number of relaparotomies on survival after relaparotomy. Data on clinical, laboratory, and radiologic abnormalities prior to relaparotomy, relaparotomy findings, and in-hospital survival were prospectively collected on a general hospital intensive care unit (ICU) database between January 1997 and January 2002. Altogether, 65 of 1482 (4.4%) patients admitted to the ICU after abdominal surgery underwent relaparotomy at a median of 5 days after the initial procedure. There was an 83% probability of identifying surgically treatable sepsis and 43% in-hospital mortality. Abdominal imaging contributed accurate information in 50% of cases where clinician assessment was uncertain. Patient age and multiorgan failure prior to relaparotomy-but not urgency of initial laparotomy or the acute physiology and chronic health evaluation (APACHE II) score prior to relaparotomy, interval to relaparotomy, or number of relaparotomies-affected the outcome. Clinician assessment after abdominal surgery had a high probability of predicting intraperitoneal sepsis at relaparotomy. The 43% mortality after relaparotomy was unlikely to be greater than with nonoperative treatment of intraabdominal sepsis, but the 78% mortality after relaparotomy in patients older than 75 years of age raised doubts about this approach in the elderly. The identification of intraperitoneal sepsis and performance of relaparotomy earlier after the initial abdominal surgery might reduce the high rate (60%) of multiorgan failure prior to relaparotomy and improve survival after it.

Effects of albumin supplementation on microvascular permeability in septic patients.

Albumin has a stabilizing effect on endothelium and helps maintain capillary permeability to macromolecules. Critically ill patients with sepsis may have profound hypoalbuminemia, but the effect of this hypoalbuminemia on microvascular permeability is unknown. To determine the degree and potential importance of this effect, we measured the transcapillary escape rate (TER) of (125)I-labeled albumin in 12 adult patients fulfilling American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock. We measured TER over a 90-min baseline period and then repeated these measurements immediately after the rapid infusion of 200 ml of 20% albumin. At baseline, patients had a mean serum albumin concentration of 10.3 +/- 3.8 g/l, which, at 30 min after the albumin infusion, was 18.5 +/- 3.7 g/l. The baseline TER was 6.7 +/- 1.5%/h, with a postinfusion TER of 6.4 +/- 2.1%/h (P = 0.550). Albumin supplementation sufficient to nearly double serum concentrations in profoundly hypoalbuminemic septic patients had no clinically significant effect in reducing microvascular permeability.