Low Transmission of Airway Pressures to the Abdomen in Mechanically Ventilated Patients With or Without Acute Respiratory Failure and Intra-Abdominal Hypertension.

PURPOSE: Intra-abdominal pressure, measured at end expiration, may depend on ventilator settings and transmission of intrathoracic pressure. We determined the transmission of positive intrathoracic pressure during mechanical ventilation at inspiration and expiration into the abdominal compartment. METHODS AND RESULTS: We included 9 patients after uncomplicated cardiac surgery and 9 with acute respiratory failure. Intravesical pressures were measured thrice (reproducibility of 1.8%) and averaged, at the end of each inspiratory and expiratory hold maneuvers of 5 seconds. Transmission, the change in intra-abdominal over intrathoracic pressures from end inspiration to end expiration, was about 8%. End-expiratory intra-abdominal pressure was lower than "total" intra-abdominal pressure over the entire respiratory cycle by 0.34 cm H2O. It was 0.73 cm H2O higher than "true" intra-abdominal pressure over the entire respiratory cycle, taking transmission into account. The percentage error was 3% for total and 10% for true pressure. Results did not differ among patients with or without acute respiratory failure and decreased respiratory compliance or between those with (≥12 mm Hg, n = 5) or without intra-abdominal hypertension. CONCLUSIONS: Transmitted airway pressure only slightly affects intra-abdominal pressure in mechanically ventilated patients, irrespective of respiratory compliance and baseline intra-abdominal pressure values. End-expiratory measurements referenced against atmospheric pressure may suffice for clinical practice.

Targeting urine output and 30-day mortality in goal-directed therapy: a systematic review with meta-analysis and meta-regression.

BACKGROUND: Oliguria is associated with a decreased kidney- and organ perfusion, leading to organ damage and increased mortality. While the effects of correcting oliguria on renal outcome have been investigated frequently, whether urine output is a modifiable risk factor for mortality or simply an epiphenomenon remains unclear. We investigated whether targeting urine output, defined as achieving and maintaining urine output above a predefined threshold, in hemodynamic management protocols affects 30-day mortality in perioperative and critical care. METHODS: We performed a systematic review with a random-effects meta-analyses and meta-regression based on search strategy through MEDLINE, EMBASE and references in relevant articles. We included studies comparing conventional fluid management with goal-directed therapy and reporting whether urine output was used as target or not, and reporting 30-day mortality data in perioperative and critical care. RESULTS: We found 36 studies in which goal-directed therapy reduced 30-day mortality (OR 0.825; 95% CI 0.684-0.995; P = 0.045). Targeting urine output within goal-directed therapy increased 30-day mortality (OR 2.66; 95% CI 1.06-6.67; P = 0.037), but not in conventional fluid management (OR 1.77; 95% CI 0.59-5.34; P = 0.305). After adjusting for operative setting, hemodynamic monitoring device, underlying etiology, use of vasoactive medication and year of publication, we found insufficient evidence to associate targeting urine output with a change in 30-day mortality (goal-directed therapy: OR 1.17; 95% CI 0.54-2.56; P = 0.685; conventional fluid management: OR 0.74; 95% CI 0.39-1.38; P = 0.334). CONCLUSIONS: The principal finding of this meta-analysis is that after adjusting for confounders, there is insufficient evidence to associate targeting urine output with an effect on 30-day mortality. The paucity of direct data illustrates the need for further research on whether permissive oliguria should be a key component of fluid management protocols.

Predicting Fluid Responsiveness by Passive Leg Raising: A Systematic Review and Meta-Analysis of 23 Clinical Trials.

OBJECTIVE: Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables. DATA SOURCES: PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles. STUDY SELECTION: Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders. DATA EXTRACTION: Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve. DATA SYNTHESIS: Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79-92), pooled specificity of 92% (95% CI, 88-96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising-induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% [95% CI, 44-70] and specificity of 83% [95% CI, 68-92] vs sensitivity of 85% [95% CI, 78-90] and specificity of 92% [95% CI, 87-94], respectively; p < 0.001). CONCLUSIONS: Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.

Micafungin versus anidulafungin in critically ill patients with invasive candidiasis: a retrospective study.

BACKGROUND: In critically ill patients the incidence of invasive fungal infections caused by Candida spp. has increased remarkably. Echinocandins are recommended as initial treatment for invasive fungal infections. The safety and efficacy of micafungin compared to caspofungin is similar, but no comparison is made between anidulafungin and micafungin concerning safety and efficacy. We therefore performed a retrospective study to assess these aspects in critically ill patients with invasive candidiasis. METHODS: All patients in the intensive care unit (ICU) with invasive candidiasis, who were only treated with anidulafungin or micafungin, between January 2012 and December 2014 were retrospectively included. Baseline demographic characteristics, infection characteristics and patient courses were assessed. RESULTS: A total of 63 patients received either anidulafungin (n = 30) or micafungin (n = 33) at the discretion of the attending intensivist. Baseline characteristics were comparable between the two groups, suggesting similar risk for developing invasive candidiasis. Patients with invasive candidiasis and liver failure were more often treated with anidulafungin than micafungin. Response rates were similar for both groups. No difference was observed in 28-day mortality, but 90-day mortality was higher in patients on anidulafungin. Multivariable cox regression analysis showed that age and serum bilirubin were the best parameters for the prediction of 90-day mortality, whereas APACHE II, Candida score and antifungal therapy did not contribute (P > 0.05). None of the patients developed impaired liver function related to antifungal use and no differences were seen in prothrombin time, serum transaminases and bilirubin levels between the groups, after exclusion of patients with liver injury or failure. CONCLUSION: Micafungin can be safely and effectively used in critically ill patients with invasive candidiasis. The observed increased 90-day mortality with anidulafungin can be explained by intensivists unnecessarily avoiding micafungin in patients with liver injury and failure.

The intensive care infection score - a novel marker for the prediction of infection and its severity.

BACKGROUND: The prediction of infection and its severity remains difficult in the critically ill. A novel, simple biomarker derived from five blood-cell derived parameters that characterize the innate immune response in routine blood samples, the intensive care infection score (ICIS), could be helpful in this respect. We therefore compared the predictive value of the ICIS with that of the white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) for infection and its severity in critically ill patients. METHODS: We performed a multicenter, cluster-randomized, crossover study in critically ill patients between January 2013 and September 2014. Patients with a suspected infection for which blood cultures were taken by the attending intensivist were included. Blood was taken at the same time for WBC, ICIS, CRP and PCT measurements in the control study periods. Results of imaging and cultures were collected. Patients were divided into groups of increasing likelihood of infection and invasiveness: group 1 without infection or with possible infection irrespective of cultures, group 2 with probable or microbiologically proven local infection without blood stream infection (BSI) and group 3 with BSI irrespective of local infection. Septic shock was assessed. RESULTS: In total, 301 patients were enrolled. CRP, PCT and ICIS were higher in groups 2 and 3 than group 1. The area under the receiver operating characteristic curve (AUROC) for the prediction of infection was 0.70 for CRP, 0.71 for PCT and 0.73 for ICIS (P < 0.001). For the prediction of septic shock the AUROC was 0.73 for CRP, 0.85 for PCT and 0.76 for ICIS. These AUROC did not differ from each other. CONCLUSION: The data suggest that the ICIS is potentially useful for the prediction of infection and its severity in critically ill patients, non-inferiorly to CRP and PCT. In contrast to CRP and PCT, the ICIS can be determined routinely without extra blood sampling and lower costs, yielding results within 15 minutes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ID NCT01847079 . Registered on 24 April 2013.

Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We investigated whether resuscitation protocols to achieve and maintain urine output above a predefined threshold-including oliguria reversal as a target--prevent acute renal failure (ARF). METHODS: We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included all studies that compared "conventional fluid management" (CFM) with "goal-directed therapy" (GDT) using cardiac output, urine output, or oxygen delivery parameters and reported the occurrence of ARF in critically ill or surgical patients. We divided studies into groups with and without oliguria reversal as a target for hemodynamic optimization. We calculated the combined odds ratio (OR) and 95% confidence intervals (CIs) using random-effects meta-analysis. RESULTS: We based our analyses on 28 studies. In the overall analysis, GDT resulted in less ARF than CFM (OR, 0.58; 95% CI, 0.44-0.76; P < 0.001; I = 34.3%; n = 28). GDT without oliguria reversal as a target resulted in less ARF (OR, 0.45; 95% CI, 0.34-0.61; P < 0.001; I = 7.1%; n = 7) when compared with CFM with oliguria reversal as a target. The studies comparing GDT with CFM in which the reversal of oliguria was targeted in both or in neither group did not provide enough evidence to conclude a superiority of GDT (targeting oliguria reversal in both protocols: OR, 0.63; 95% CI, 0.36-1.10; P = 0.09; I = 48.6%; n = 9, and in neither protocol: OR, 0.66; 95% CI, 0.37-1.16; P = 0.14; I = 20.2%; n = 12). CONCLUSIONS: Current literature favors targeting circulatory optimization by GDT without targeting oliguria reversal to prevent ARF. Future studies are needed to investigate the hypothesis that targeting oliguria reversal does not prevent ARF in critically ill and surgical patients.

Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.

Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta-analysis.

BACKGROUND: Interest in perioperative fluid restriction has increased, but it could lead to hypovolaemia. Urine output is viewed as a surrogate for renal perfusion and is frequently used to guide perioperative fluid therapy. However, the rationale behind targeting oliguria reversal - achieving and maintaining urine output above a previously defined threshold by additional fluid boluses - is often questioned. OBJECTIVE: We assessed whether restrictive fluid management had an effect on oliguria, acute renal failure (ARF) and fluid intake. We also investigated whether targeting oliguria reversal affected these parameters. DESIGN: Systematic review of randomised controlled trials with meta-analyses. We used the definitions of restrictive and conventional fluid management as provided by the individual studies. DATA SOURCES: We searched MEDLINE (1966 to present), EMBASE (1980 to present), and relevant reviews and articles. ELIGIBILITY CRITERIA: We included randomised controlled trials with adult patients undergoing surgery comparing restrictive fluid management with a conventional fluid management protocol and also reporting the occurrence of postoperative ARF. RESULTS: We included 15 studies with a total of 1594 patients. There was insufficient evidence to associate restrictive fluid management with an increase in oliguria [restrictive 83/186 vs. conventional 68/230; odds ratio (OR) 2.07; 95% confidence interval (CI), 0.97 to 4.44; P = 0.06; I = 23.7%; Nstudies = 5]. The frequency of ARF in restrictive and conventional fluid management was 20/795 and 20/799, respectively (OR 1.07; 95% CI, 0.60 to 1.92; P = 0.8; I = 17.5%; Nstudies = 15). There was no statistically significant difference in ARF occurrence between studies targeting oliguria reversal and not targeting oliguria reversal (OR 0.31; 95% CI, 0.08 to 1.22; P = 0.088). Intraoperative fluid intake was 1.89 l lower in restrictive than in conventional fluid management when not targeting oliguria reversal (95% CI, -2.59 to -1.20 l; P < 0.001; I = 96.6%; Nstudies = 7), and 1.63 l lower when targeting oliguria reversal (95% CI, -2.52 to -0.74 l; P < 0.001; I = 96.6%; Nstudies = 6). CONCLUSION: Our data suggest that, even though event numbers are small, perioperative restrictive fluid management does not increase oliguria or postoperative ARF while decreasing intraoperative fluid intake, irrespective of targeting reversal of oliguria or not.

Progressively heterogeneous mismatch of regional oxygen delivery to consumption during graded coronary stenosis in pig left ventricle.

In normal hearts, myocardial perfusion is fairly well matched to regional metabolic demand, although both are distributed heterogeneously. Nonuniform regional metabolic vulnerability during coronary stenosis would help to explain nonuniform necrosis during myocardial infarction. In the present study, we investigated whether metabolism-perfusion correlation diminishes during coronary stenosis, indicating increasing mismatch of regional oxygen supply to demand. Thirty anesthetized male pigs were studied: controls without coronary stenosis (n = 11); group I, left anterior descending (LAD) coronary stenosis leading to coronary perfusion pressure reduction to 70 mmHg (n = 6); group II, stenosis with perfusion pressure of about 35 mmHg (n = 6); and group III, stenosis with perfusion pressure of 45 mmHg combined with adenosine infusion (n = 7). [2-(13)C]- and [1,2-(13)C]acetate infusion was used to calculate regional O2 consumption from glutamate NMR spectra measured for multiple tissue samples of about 100 mg dry mass in the LAD region. Blood flow was measured with microspheres in the same regions. In control hearts without stenosis, regional oxygen extraction did not correlate with basal blood flow. Average myocardial O2 delivery and consumption decreased during coronary stenosis, but vasodilation with adenosine counteracted this. Regional oxygen extraction was on average decreased during stenosis, suggesting adaptation of metabolism to lower oxygen supply after half an hour of ischemia. Whereas regional O2 delivery correlated with O2 consumption in controls, this relation was progressively lost with graded coronary hypotension but partially reestablished by adenosine infusion. Therefore, coronary stenosis leads to heterogeneous metabolic stress indicated by decreasing regional O2 supply to demand matching in myocardium during partial coronary obstruction.

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study.

INTRODUCTION: Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase. METHODS: We prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 µg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests. RESULTS: Patients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar. CONCLUSIONS: Even though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

Postural change in volunteers: sympathetic tone determines microvascular response to cardiac preload and output increases.

PURPOSE: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. METHODS: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30° passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). RESULTS: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. CONCLUSION: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best parameter to use when evaluating fluid responsiveness independent of changes in sympathetic tone.

Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients.

AIM: Peripheral perfusion may predict harmful hypovolemic hypotension during fluid withdrawal by continuous veno-venous hemofiltration (CVVH) in critically ill patients with acute kidney injury. METHODS: Twenty-three critically ill AKI patients were subjected to progressive fluid withdrawal. Systemic hemodynamics and peripheral perfusion index (PPI) by pulse oximetry, forearm-to-fingertip skin temperature gradient (Tskin-diff) and tissue oxygen saturation (StO2, near infra-red spectroscopy) were measured. RESULTS: Most hemodynamic values decreased with fluid withdrawal, particularly in the hypotensive group, except for stroke volume (SV) and cardiac output, which decreased to a great extent in the non-hypotensive patients. Increases in systemic vascular resistance (SVR) were less in hypotension. Baseline pulse pressure and PPI were lower in hypotensive (n = 10) than non-hypotensive patients and subsequent PPI values paralleled SV decreases. A baseline PPI ≤0.82 AU predicted hypotension with a sensitivity of 70%, and a specificity of 92% (AUC 0.80 ± 0.11, p = 0.004). CONCLUSION: Progressive fluid withdrawal during CVVH is poorly tolerated in patients with less increases in SVR. The occurrence of hypotension can be predicted by low baseline PPI.

Coagulation, Fibrinolysis and Inhibitors in Failing Filters during Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: Effect of Anticoagulation Modalities.

INTRODUCTION: The mechanisms of early filter failure and clotting with different anticoagulation modalities during continuous venovenous hemofiltration (CVVH) are largely unknown. METHODS: Citrate, heparin and no anticoagulation were compared. Blood was drawn pre- and post filter up to 720 min. Concentrations of the thrombin-antithrombin (TAT), activated protein C-protein C inhibitor (APC-PCI), and type I plasminogen activator inhibitor (PAI-1) were determined. RESULTS: In case of early filter failure (<24 h), inlet concentrations of TAT and APC-PCI were higher over time, irrespective of anticoagulation. There was more production of APC-PCI and platelet-derived PAI-1 in the filter after 10 min in the heparin group than in other groups. In clotting filters, production of APC-PCI and PAI was also higher with heparin than citrate. CONCLUSION: Coagulation activation in plasma and inhibition of anticoagulation in plasma and filter may partly determine early CVVH filter failure due to clotting, particularly when heparin is used. Regional anticoagulation by citrate circumvents the inhibition of anticoagulation and fibrinolysis by platelet activation following heparin.

Putative novel mediators of acute kidney injury in critically ill patients: handling by continuous venovenous hemofiltration and effect of anticoagulation modalities.

BACKGROUND: Novel putative mediators of acute kidney injury (AKI) include immune-cell derived tumour necrosis factor-like weak inducer of apoptosis (TWEAK), angiopoietin-2 (Ang-2) and protein pentraxin-3 (PTX3). The effect of continuous venovenous hemofiltration (CVVH) and different anticoagulation regimens on plasma levels were studied. METHODS: At 0, 10, 60, 180 and 720 min of CVVH, samples were collected from pre- and postfilter blood and ultrafiltrate. No anticoagulation (n = 13), unfractionated heparin (n = 8) or trisodium citrate (n = 21) were compared. RESULTS: Concentrations of TWEAK, Ang-2 and PTX3 were hardly affected by CVVH since the mediators were not (TWEAK, PTX3) or hardly (Ang-2) detectable in ultrafiltrate, indicating negligible clearance by the filter in spite of molecular sizes (TWEAK, PTX3) at or below the cutoff of the membrane. Heparin use, however, was associated with an increase in in- and outlet plasma TWEAK. CONCLUSION: Novel AKI mediators are not cleared nor produced by CVVH. However, heparin anticoagulation increased TWEAK levels in patient's plasma whereas citrate did not, favouring the latter as anticoagulant in CVVH for AKI.

Albumin rather than C-reactive protein may be valuable in predicting and monitoring the severity and course of acute respiratory distress syndrome in critically ill patients with or at risk for the syndrome after new onset fever.

BACKGROUND: We studied the value of routine biochemical variables albumin, C-reactive protein (CRP) and lactate dehydrogenase (LDH) to improve prediction and monitoring of acute respiratory distress syndrome (ARDS) severity in the intensive care unit. METHODS: In 101 critically ill patients, with or at risk for ARDS after new onset fever, data were collected on days (D) 0, 1, 2, and 7 after inclusion. ARDS was defined by the Berlin definition and lung injury score (LIS). RESULTS: At baseline, 48 patients had mild to severe ARDS according to Berlin and 87 according to LIS (Rs = 0.54, P < 0.001). Low baseline albumin levels were moderately associated with maximum Berlin and LIS categories within 7 days; an elevated CRP level was moderately associated with maximum Berlin categories only. The day-by-day Berlin and LIS categories were inversely associated with albumin levels (P = 0.01, P < 0.001) and directly with CRP levels (P = 0.02, P = 0.04, respectively). Low albumin levels had monitoring value for ARDS severity on all study days (area under the receiver operating characteristic curve, AUROC, 0.62-0.82, P < 0.001-0.03), whereas supranormal CRP levels performed less . When the Berlin or LIS category increased, albumin levels decreased ≥1 g/L (AUROC 0.72-0.77, P = 0.001) and CRP increased ≥104 mg/L (only significant for Berlin, AUROC 0.69, P = 0.04). When the LIS decreased, albumin levels increased ≥1 g/L (AUROC 0.68, P = 0.02). LDH was higher in 28-day non-survivors than survivors (P = 0.007). CONCLUSIONS: Overall, albumin may be of greater value than CRP in predicting and monitoring the severity and course of ARDS in critically patients with or at risk for the syndrome after new onset fever. Albumin levels below 20 g/L as well as a decline over a week are associated with ARDS of increasing severity, irrespective of its definition. LDH levels predicted 28-day mortality.

Low tidal volume ventilation ameliorates left ventricular dysfunction in mechanically ventilated rats following LPS-induced lung injury.

BACKGROUND: High tidal volume ventilation has shown to cause ventilator-induced lung injury (VILI), possibly contributing to concomitant extrapulmonary organ dysfunction. The present study examined whether left ventricular (LV) function is dependent on tidal volume size and whether this effect is augmented during lipopolysaccharide(LPS)-induced lung injury. METHODS: Twenty male Wistar rats were sedated, paralyzed and then randomized in four groups receiving mechanical ventilation with tidal volumes of 6 ml/kg or 19 ml/kg with or without intrapulmonary administration of LPS. A conductance catheter was placed in the left ventricle to generate pressure-volume loops, which were also obtained within a few seconds of vena cava occlusion to obtain relatively load-independent LV systolic and diastolic function parameters. The end-systolic elastance / effective arterial elastance (Ees/Ea) ratio was used as the primary parameter of LV systolic function with the end-diastolic elastance (Eed) as primary LV diastolic function. RESULTS: Ees/Ea decreased over time in rats receiving LPS (p = 0.045) and high tidal volume ventilation (p = 0.007), with a lower Ees/Ea in the rats with high tidal volume ventilation plus LPS compared to the other groups (p < 0.001). Eed increased over time in all groups except for the rats receiving low tidal volume ventilation without LPS (p = 0.223). A significant interaction (p < 0.001) was found between tidal ventilation and LPS for Ees/Ea and Eed, and all rats receiving high tidal volume ventilation plus LPS died before the end of the experiment. CONCLUSIONS: Low tidal volume ventilation ameliorated LV systolic and diastolic dysfunction while preventing death following LPS-induced lung injury in mechanically ventilated rats. Our data advocates the use of low tidal volumes, not only to avoid VILI, but to avert ventilator-induced myocardial dysfunction as well.

Increased Thyroxin During Therapeutic Hypothermia Predicts Death in Comatose Patients After Cardiac Arrest.

BACKGROUND: The course and prognostic value of pituitary-thyroid axis hormones is not well studied after cardiac arrest. We aimed to study the prognostic role of the pituitary-thyroid axis response to resuscitation from cardiac arrest before, during and after therapeutic hypothermia. METHODS: We conducted a retrospective cohort study in consecutive comatose patients after out-of-hospital cardiac arrest who were sampled before, during and up to 48 h after a 24-h period of therapeutic hypothermia in the intensive care unit (ICU). Thyroid-stimulating hormone, total and free thyroxine (T4) and triiodothyronine (T3) were determined and compared between ICU outcome groups. RESULTS: We included twenty-nine patients. TSH levels were comparable in non-survivors (n = 17) and survivors (n = 12). The free T4 levels were higher in non-survivors than in survivors (P = 0.001), whereas the free T3 levels were comparable. All samples' results similarly declined in both outcome groups up to 72 h after start of 24 h hypothermia. ROC curves analyses showed a maximum AUC of 0.83 (P = 0.003) for free T4 at the end of hypothermia with an optimal cut off ≥17.8 pmol/L to obtain 100 % specificity and positive predictive value for non-survival. CONCLUSION: Non-survival after cardiac arrest, coma, and therapeutic hypothermia following successful resuscitation is associated with a transient increase in free T4, most probably due to inhibition of free T4 to T3 conversion. However, before routine clinical application, external validation of our finding to assess generalizability is warranted.

Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock: an observational study.

BACKGROUND: Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES: To compare calibrated arterial pressure waveform analysis-derived CO (COap, VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with transpulmonary thermodilution derived CO (COtptd). DESIGN: A prospective, observational, single-centre study. SETTING: ICU of a general teaching hospital. PATIENTS: Twenty consecutive patients with severe sepsis or septic shock requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical ventilation. INTERVENTION: Connection of FloTrac/Vigileo to radial artery catheter already in situ. MAIN OUTCOME MEASURES: Radial (COfv) and femoral (COap) arterial waveform-derived CO measurements were compared with COtptd with respect to bias, precision, limits of agreement and percentage error, and the percentage error in the course of time since the last calibration of COap by COtptd. RESULTS: In comparing COap with COtptd (n = 267 paired measurements), the bias was 0.02 and limits of agreement were -2.49 to 2.52 l min, with a percentage error of 31%. The percentage error between COap and COtptd remained less than 30% until 8 h after calibration. In comparing COfv with COtptd (n = 301), the bias was -0.86 l min and limits of agreement were -4.48 to 2.77 l min, with a percentage error of 48%. The biases of COap and COfv correlated with systemic vascular resistance [r = 0.13 (P = 0.029) and r = 0.42 (P < 0.001), respectively]. Clinically significant changes in COap and COfv correlated positively with COtptd at r = 0.51 (P < 0.001) and r = 0.64 (P < 0.001), respectively. CONCLUSION: There was moderate agreement when measuring CO with either arterial waveform analysis technique. Compared with the uncalibrated COfv, the recently introduced calibrated arterial pressure waveform analysis-derived COap was more accurate and less dependent on vascular tone for up to 8 hours after callibation when monitoring CO in patients with severe sepsis and septic shock. The COap and COfv methods have poor to moderate CO-tracking abilities.

Tissue perfusion and oxygenation to monitor fluid responsiveness in critically ill, septic patients after initial resuscitation: a prospective observational study.

Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a ≥5 or 10% increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF.

The case for 0.9% NaCl: is the undefendable, defensible?

Although 0.9% NaCl solution is by far the most-used fluid for fluid therapy in resuscitation, it is difficult to find a paper advocating its use over other types of crystalloid solutions. Literature on the deleterious effects of 0.9% NaCl has accumulated over the last decade, but critical appraisal of alternative crystalloid solutions is lacking. As such, the literature seems to suggest that 0.9% NaCl should be avoided at all costs, whereas alternative crystalloid solutions can be used without scrutiny. The basis of this negative evaluation of 0.9% NaCl is almost exclusively its effect on acid-base homeostasis, whereas the potentially deleterious effects present in other types of crystalloids are neglected. We have the challenging task of defending the use of 0.9% NaCl and reviewing its positive attributes, while an accompanying paper will argue against the use of 0.9% NaCl. It is challenging because of the large amount of literature, including our own, showing adverse effects of 0.9% NaCl. We will discuss why 0.9% NaCl solution is the most frequently used resuscitation fluid. Although it has some deleterious effects, all fluids share common features of concern. As such the emphasis on fluid resuscitation should be on volume rather than on composition and should be accompanied by a physiological assessment of the impact of fluids. In this paper, we hope to discuss the context within which fluids, specifically 0.9% NaCl, can be given in a safe and effective manner.