Clinical factors affecting costs in patients receiving systemic antifungal therapy in intensive care units in Greece: Results from the ESTIMATOR study.

Invasive fungal infections are common in intensive care units (ICUs) but there is a great variability in factors affecting costs of different antifungal treatment strategies in clinical practice. To determine factors affecting treatment cost in adult ICU patients with or without documented invasive fungal infection receiving systemic antifungal therapy (SAT) we have performed a prospective, multicentre, observational study enrolling patients receiving SAT in participating ICUs in Greece. During the study period, 155 patients received SAT at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre-emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to have proven infection with Candida spp. (eight while on treatment). The most frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole (31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by SAT strategy was €20 458 (proven), €15 054 (prophylaxis), €23 594 (empiric) and €22 184 (pre-emptive). Factors associated with significantly increased cost were initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e. from admission until treatment start), fever and proven candidaemia (all P≤.05). CONCLUSION: Early administration of antifungal drugs was not a substantial component of total hospital costs. However, there was a significant adverse impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis of fungaemia was delayed before starting SAT, and with initial treatment failure. Awareness of potential candidaemia and initiation of pre-emptive or empirical strategy as early appropriate treatment may improve ICU patient outcomes while reducing direct medical costs.

COPD patients with ventilator-associated pneumonia: implications for management.

Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1%) had COPD; 79 (19.9%) patients with COPD and 332 (19.7%) patients without COPD developed VAP. ICU mortality increased by 17% (p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95% confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay (p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1% vs. 18.7%, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3% vs. 13.3%, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP.

Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

Demographic and clinical features of critically ill patients with COVID-19 in Greece: The burden of diabetes and obesity.

AIMS: The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. METHODS: In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. RESULTS: The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. CONCLUSIONS: Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece.

Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria.

Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

Serum of patients with septic shock stimulates the expression of Trem-1 on U937 monocytes.

OBJECTIVES: To describe the concentrations of sTREM-1 in patients with sepsis and to explore the effects of their serum on the expression of TREM-1 on U937 monocytes. METHODS: Blood was sampled at regular time intervals in 56 patients with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were measured. U937 monocytes were incubated in the presence of serum at sepsis onset. RESULTS: Median sTREM-1 concentration on day 1 for patients with septic shock was 915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL-1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of patients with septic shock evoked a significant increase of the expression of TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only after stimulating with sera of patients without shock, but not after stimulating with sera of patients with shock. CONCLUSIONS: Levels of sTREM-1 correlated with sepsis severity. sTREM-1 is considerably higher in patients with shock compared to patients without shock. The serum of shocked patients could stimulate the expression of TREM-1 on U937 monocytes.

Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

OBJECTIVES: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. METHODS: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. RESULTS: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). CONCLUSIONS: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

Transorbital sonographic monitoring of optic nerve diameter in patients with severe brain injury.

OBJECTIVE: We investigated whether alterations in the optic nerve diameter (OND) correlated with brain computed tomography (CT) imaging results among patients with brain injury and whether monitoring of OND could predict brain death. PATIENTS AND METHODS: We enrolled 54 patients with brain injury (Glasgow Coma Scale < 8) and 53 controls. OND measurements were performed 3 mm posterior to the papillae by means of transorbital sonography. The severity of the injury was classified according to a semiquantitative CT neuroimaging scale (1 to 4). All patients underwent 3 repeated evaluations of OND combined with synchronous CT scans. RESULTS: Twenty-two patients progressed to brain death, while 32 patients showed gradual clinical improvement. Upon admission, the patients showed significantly increased OND (4.84 +/- 1.2 mm) compared with the controls (3.49 +/- 1.1 mm; P < .001). The median intraobserver variation of OND was 0.2 mm (95% confidence intervals [CI]: 0.1-0.7). The median interobserver variation of OND was 0.3 mm (95% CI: 0.1-0.9). Alterations in the OND were significantly correlated with the neuroimaging scale on 3 repeated evaluations: r = .65, r = .70, and r = .73 (all P < .001). An OND greater than 5.9 mm (specificity = 65% and sensitivity = 74%; P < .01) and a 2.5 mm increased OND between repeated measurements (specificity = 70% and sensitivity = 81%; P < .01) were associated with a poor prognosis. CONCLUSIONS: Alterations in OND strongly correlated with neuroimaging results among patients with brain injury. However, monitoring of OND exhibited a low predictive value for brain death.

Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.

Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury.

BACKGROUND: Pulmonary capillary endothelium-bound (PCEB) angiotensin-converting ectoenzyme (ACE) activity alteration is an early, sensitive, and quantifiable lung injury index in animal models. We hypothesized that (1) PCEB-ACE alterations can be found in patients with acute lung injury (ALI) and (2) PCEB-ACE activity correlates with the severity of lung injury and may be used as a quantifiable marker of the underlying pulmonary capillary endothelial dysfunction. METHODS AND RESULTS: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis of the synthetic ACE substrate (3)H-benzoyl-Phe-Ala-Pro (BPAP) in 33 mechanically ventilated, critically ill patients with a lung injury score (LIS) ranging from 0 (no lung injury) to 3.7 (severe lung injury) and calculated the kinetic parameter A(max)/K(m). Both parameters decreased early during the ALI continuum and were inversely related to APACHE II score and LIS. Hydrolysis decreased with increasing cardiac output (CO), whereas 2 different patterns were observed between CO and A(max)/K(m). CONCLUSIONS: PCEB-ACE activity decreases early during ALI, correlates with the clinical severity of both the lung injury and the underlying disease, and may be used as a quantifiable marker of underlying pulmonary capillary endothelial dysfunction.

Elevated soluble endothelial protein C receptor levels at ICU admission are associated with sepsis development.

BACKGROUND: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in the septic process is under investigation. In this study, we assessed the role of sEPCR levels as an early indicator of sepsis development. METHODS: Plasma sEPCR levels were measured in 59 critically-ill non-septic patients at the time of admission to the intensive care unit (ICU). Multiple logistic regression analysis was performed to identify potential risk factors for sepsis development and Cox-Regression models were fitted for variables to examine their relationship with time to sepsis development. RESULTS: Thirty patients subsequently developed sepsis and 29 did not. At ICU admission, sequential organ failure assessment (SOFA) scores were significantly higher in the subsequent sepsis group as compared to the non sepsis group (mean ± SD: 6.4±2.7 and 5±2.3, respectively, P=0.037). sEPCR levels were also higher in the patients who subsequently developed sepsis compared to the patients who did not (median and interquartile range: 173.4 [104.5-223.5] ng/mL vs. 98.3 [69.8-147.7] ng/mL, respectively; P=0.004). Cox regression analysis identified sEPCR as the only parameter related to sepsis development with time (relative risk: 1.078, 95% confidence interval: 1.016-1.144, by 10 units; P=0.013). CONCLUSION: Upon ICU admission, sEPCR levels in initially non-septic critically-ill patients appear elevated in the subjects who will subsequently become septic.

Bloodstream infections in ICU with increased resistance: epidemiology and outcomes.

BACKGROUND: Aim of this study was to evaluate the epidemiology and outcomes of hospital-acquired bloodstream infections (HA-BSI) in Greek intensive care units (ICU). METHODS: Secondary analysis of data from 29 ICU collected during the EUROBACT study, a large prospective, observational, multination survey of HA-BSI. First episodes of HA-BSI acquired in the ICU or within 48 hours prior to admission were recorded. RESULTS: Gram-negative bacteria predominated namely Acinetobacter sp, Klebsiella sp, Pseudomonas sp (73.3% of monomicrobial infections) followed by Gram-positive cocci (18.3%); fungi (7.6%) and anaerobes (0.8%). Overall 73.3% of isolates were multidrug resistant (MDR), 47.1% extensively resistant (XDR) and 1.2% pan-drug resistant (PDR). Carbapenems were the most frequent empirically prescribed antibiotics, while colistin was the most frequently adequate; for both, calculated mean total daily doses were suboptimal. Overall 28-day all-cause mortality was 33.3%. In the multivariate analysis, factors adversely affecting outcome were higher SOFA score at HA-BSI onset (OR 1.19; 95% CI 1.08-1.31, P=0.0006), need for renal supportive therapy (OR 2.75; 95% CI 1.35-5.59, P=0.0053), and for vasopressors/inotropes (OR 2.68; CI 1.18-6.12, P=0.02); adequate empirical treatment had a protective effect (OR 0.48; CI 0.24-0.95, P=0.03). CONCLUSION: TIMELY administration of adequately dosed treatment regimens and early ICU admission of critically ill patients could help in improving outcomes.

Cannabis interferes with nest-building behavior in mice.

Nest-building, a behavioral model shown to be disrupted by hallucinogens, has never been used to answer questions concerning the psychotomimetic effects of delta9-THC. Several fractions of cannabis and tobacco pyrolysis products were tested consecutively in the same procedure. The following drugs were injected i.p. under a saline-drug-saline schedule: d-amphetamine (6 mg/kg), pentobarbital (25 mg/kg), delta9-THC (10 mg/kg, 5 mg/kg, 2.5 mg/kg), the cannabis fractions designated Is (water soluble products), IIs (nonsoluble, nonvolatile products, IIIs (it comprises what is inhaled by a common hashish smoker), and analogous fractions of tobacco pyrolysis products designated IIIB (what is inhaled by a common tobacco smoker), IIB and IB. The effects of delta9-THC (10 mg/kg), IIs, and IIIs were quite similar as far as the disruption of the normal behavioral pattern is concerned. d-Amphetamine, delta9-THC (5 mg/kg), and IIB disrupted the normal behavioral pattern as well. The similarity of the effects of IIs and IIIs was unexpected in view of the different contents of cannabinoids in these fractions. Also unexpected was the similarity of the effects of delta9-THC (10 mg/kg) and IIIs (40 mg/kg containing 7% delta9-THC) as well as the activity of fraction IIIB.

Accuracy assessment for three fiberoptic pulmonary artery catheters for SvO2 monitoring.

OBJECTIVE: To compare values of SvO2 obtained by reflectance spectrophotometry continuous monitoring with those obtained from blood samples measurements by transmission spectrophotometry (Co-Oximetry). DESIGN: Values of SvO2 recorded by three pulmonary artery catheters for continuous monitoring, SAT1, SAT2 and Oximetrix3 (OX3), were compared in a prospective manner to those measured on blood samples by a Co-Oximeter, using the statistical analysis of Bland and Altman. SETTING: Adult intensive care unit in an University Hospital. PATIENTS: 37 patients admitted for acute respiratory failure and/or shock who required hemodynamic monitoring. MAIN RESULTS: The bias (average under- or overestimation) was small for all comparative measurements: +1.3, -0.2 and +1.0 sat% for SAT1, SAT2 and OX3, respectively. However, limits of agreement were only acceptable for SAT2 (-8.3 to +7.9 sat%) and OX3 (-6.7 to +8.6 sat%), but not for SAT1 (-23.3 to +25.9 sat%). No significant drift during 24 h was found with the three catheters. However, in vitro calibration was only found acceptable for SAT2 and OX3. The results were not influenced by the numbers of wavelengths of the device (2 for SAT1 and SAT2, and 3 for OX3) nor did they correlate with any of the hemodynamic and biochemical variables tested. CONCLUSION: For usual monitoring in the ICU, SAT2 and OX3, gave SvO2 values which are in acceptable agreement with SvO2 measured on blood samples by Co-Oximetry.

Is intensive care justified for patients with haematological malignancies?

The course of 260 adults with haematological malignancies admitted to a medical intensive care unit was studied to evaluate the value of life support techniques and to research predictive factors. The overall in the medical intensive care unit (MICU) and hospital mortality rates were respectively 43% (113 patients) and 57% (148 patients). Among survivors, 64% (49 patients) were still alive after 6 months and 44% (35 patients) after 1 year. Among 34 haemodialysed patients, the MICU mortality was 67% (23 patients) and among 111 mechanically ventilated patients 85% (94 patients). Prolonged mechanical ventilation, more than seven days, was performed in 11 of the 17 survivors and did not influence long term survival. No individual predictor of mortality was found comparing survivors and non-survivors. However, SAPS, intractable sepsis and failure of more than one organ system were significantly different in non-survivors (p less than 0.001). Among the 20 patients requiring both mechanical ventilation and haemodialysis, only two left the MICU and both died soon thereafter. We conclude that life support therapy should be initiated in patients with haematological disorders and that prolonged mechanical ventilation is compatible with long term survival. However, the combination of mechanical ventilation and haemodialysis is always associated with a poor prognosis and therefore the use of both techniques simultaneously for one patient is questionable.

Causes of error of respiratory pressure-volume curves in paralyzed subjects.

Respiratory pressure-volume (PV) curves are commonly obtained in paralyzed patients by relating airway pressure to volume changes of a syringe (Vsyr). This is based on the implicit assumption that changes in thoracic volume (Vtho) and Vsyr are equal. We undertook to verify this assumption through simultaneous measurements of Vtho by respiratory inductive plethysmography and Vsyr in six comatose, paralyzed, intubated patients. At any constant Vsyr, Vtho fell and was smaller on deflation than on inflation during inflation-deflation (ID) cycle. The rate of fall was 110 +/- 64 (SD) ml/min. During ID cycles lasting 76 +/- 7 s, thoracic PV curves showed less hysteresis and a larger compliance on deflation than PVsyr curves (12 +/- 2 vs. 18 +/- 6% and 73 +/- 13 vs. 67 +/- 12 ml/cmH2O, P less than 0.05). With PVsyr curves, hysteresis increased and compliance on deflation decreased with increasing rate of fall of Vtho. We submit that the difference between changes in Vsyr and Vtho is best explained by gas exchange and should be taken into account when performing PV curves with a syringe in paralyzed patients.

Mechanical effects of PEEP in patients with adult respiratory distress syndrome.

In 10 patients with adult respiratory distress syndrome, we studied the effects on respiratory system mechanics of two levels of positive end-expiratory pressure (PEEP), best PEEP (BP) and half of this value (HBP), using a respiratory inductive plethysmograph (RIP) combined with a super syringe. We found the following. 1) Inflation compliance of pressure-volume (PV) curves did not change significantly. 2) End-expiratory volume increased with HBP and further with BP (278 +/- 186 and 464 +/- 313 ml, respectively, P less than 0.01). This increase was positively correlated with inflation compliance for HBP and BP (r = 0.794, P less than 0.01 and r = 0.876, P less than 0.01, respectively). 3) No dynamic hyper-inflation was detected on mechanical ventilation at zero end-expiratory pressure (ZEEP), and the time constant of the respiratory system was in the normal range (0.79 +/- 0.21 s). 4) Hysteresis of PVrip curves, which were corrected for gas exchange, decreased significantly with PEEP (P less than 0.05). We conclude that PEEP does not change inflation PV curve but induces an increase in intrathoracic volume whose magnitude is related to compliance and PEEP level. The reduction of hysteresis with PEEP suggests less gas trapping and thus a functional improvement.

Changes in thoracopulmonary compliance and hemodynamic effects of positive end-expiratory pressure in patients with or without heart failure.

PURPOSE: The purpose of this study was to confirm that positive end-expiratory pressure (PEEP) has a different effect on cardiac index (CI) in patients with or without heart failure, even after controlling for differences in thoracopulmonary compliance (Ctp) and minimizing the secondary effects of PEEP related changes in oxygenation and breathing effort. MATERIALS AND METHODS: The hemodynamic effects of PEEP were evaluated in two groups of sedated and paralyzed patients with a low Ctp at 0 PEEP: 12 patients with normal pulmonary artery occlusion pressure (Ppao) and a CI > 2.5 L/min and 12 patients with a CI < 2.5 L/min and increased oxygen extraction ratio, despite a Ppao > 15 mm Hg. RESULTS: In patients with low CI and high Ppao, PEEP had no hemodynamic effect and Ctp remained low at all PEEP levels. However, PEEP-induced CI reduction in patients with normal cardiovascular function was associated with an increase in Ctp with incremental PEEP. Concerning PEEP-related hemodynamic effects, the significance between group differences persisted when data were analyzed after controlling for Ctp changes. However, Ctp changes with PEEP were the most significant correlators and discriminators of the magnitude and direction of PEEP-induced CI change. CONCLUSIONS: We conclude that (1) the observed different effect of PEEP on CI in patients with and without heart failure persists after the elimination of secondary effects due to underlying differences in Ctp, oxygenation, and breathing effort; and (2) PEEP-related changes in Ctp should be taken into consideration when dealing with the cardiovascular effects of PEEP. Our data support the hypothesis that, in addition to the transmission of PEEP to the pleural space, changes in lung volume are a significant determinant of PEEP-induced CI changes.

[Relation of oxygen transport and consumption. Role of impaired tissue uptake]. / Relation transport-consommation d'oxygène. Rôle d'une altération de l'extraction tissulaire.

In healthy subjects, when oxygen transport is gradually decreased, oxygen consumption is maintained as tissue oxygen extraction is increased. When delivery is decreased further, there is a critical level below which tissue extraction cannot increase in proportion to the reduced delivery, and oxygen consumption falls. Blood lactate levels then rise, a sign of tissue hypoxia, despite further increases in oxygen extraction as delivery drops below this critical level. There are two major mechanisms which tend to prevent tissue hypoxia in case of reduced oxygen delivery: regional redistribution of blood flow and an increase in the number of perfused capillaries. This possibility of regulating blood flow distribution may be lost during disseminated intravascular coagulation, alpha-adrenergic receptor blockade, hypothermia, arteriovenous shunting. All these alterations have been reported as occurring in sepsis. An abnormal dependency on oxygen supply is observed during bacteriaemia or endotoxinaemia. This is secondary to a reduced ability, at the whole body level, to extract oxygen from a limited supply. The inability to increase oxygen extraction is related to a maldistribution of the cardiac output, with "stealing" of blood, i.e. overperfusion of some organs (skeletal muscle) rather than those where perfusion is rapidly compromised (small intestine). Endotoxin also reduces the efficacy of oxygen extraction within the isolated intestinal segment, whereas that within other organs is preserved. These observations are similar to findings in patients with sepsis who seem to have both an increased demand in oxygen, and a reduced ability to extract it at the tissue level.

[Weaning from artificial respiration: value of continuous monitoring of mixed venous oxygen saturation]. / Sevrage de la ventilation artificielle: intérêt du monitorage continu de la SvO2.

Weaning from mechanical ventilation is particularly difficult in patients with combined cardiac and respiratory failure. Continuous monitoring of mixed venous blood oxygen saturation (SvO2) redefines weaning in terms of tissue oxygenation. A stable SvO2 greater than 60% during weaning is a reliable index of weanability. However, further studies are required to establish a tolerance threshold for SvO2 during weaning. In the limited experience reported here, an immediate and abrupt fall in SvO2, when the patient started to breathe spontaneously was invariably associated with difficulties in weaning. In some patients, other signs of left ventricular dysfunction rapidly ensued, with a fall in cardiac index. Weaning remained possible if the treatment was capable of increasing cardiac output and normalizing SvO2. If, during spontaneous breathing, SvO2 remained stable in the 50-55% range, with no significant decrease in cardiac output, abrupt and unpredictable drops of SvO2 under 40% range occurred. Such falls always preceded signs of tissue hypoxia, leading to a resumption of controlled mechanical ventilation. However, further studies are required to fully delineate the role of SvO2 in the fine tuning of inotropic support and ventilatory assistance in the difficult weaning of patients recovering from cardio-respiratory failure.