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Currently, there is no therapy targeting septic cardiomyopathy (SC), a key contributor to organ dysfunction in sepsis. In this study, we used a machine learning (ML) pipeline to explore transcriptomic, proteomic, and metabolomic data from patients with septic shock, and prospectively collected measurements of high-sensitive cardiac troponin and echocardiography. The purposes of the study were to suggest an exploratory methodology to identify and characterise the multiOMICs profile of (i) myocardial injury in patients with septic shock, and of (ii) cardiac dysfunction in patients with myocardial injury. The study included 27 adult patients admitted for septic shock. Peripheral blood samples for OMICS analysis and measurements of high-sensitive cardiac troponin T (hscTnT) were collected at two time points during the ICU stay. A ML-based study was designed and implemented to untangle the relations among the OMICS domains and the aforesaid biomarkers. The resulting ML pipeline consisted of two main experimental phases: recursive feature selection (FS) assessing the stability of biomarkers, and classification to characterise the multiOMICS profile of the target biomarkers. The application of a ML pipeline to circulate OMICS data in patients with septic shock has the potential to predict the risk of myocardial injury and the risk of cardiac dysfunction., SCOPUS: ar.j, info:eu-repo/semantics/published

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

BackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.ResultsIn both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend.ConclusionsThis pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock

BackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.ResultsIn both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend.ConclusionsThis pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory s

Background: Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock. Methods: We performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock. Results: In both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. Conclusions: This pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulator, SCOPUS: ar.j, info:eu-repo/semantics/published

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission., Peer Reviewed, Postprint (published version)

Objective: Several studies demonstrated that the lungs could produce lactate in patients with acute lung injury (ALI). Because after cardiopulmonary bypass (CPB) some patients develop ALI, the effect of CPB on pulmonary lactate release was investigated. Design: Prospective observational clinical study. Setting: Twenty-beds, surgical ICU at a university hospital. Patients: Sixteen deeply sedated, ventilated and post-cardiac surgery patients, all equipped with a pulmonary artery catheter. Measurements and results: Lactate concentration was measured using a lactate analyser in simultaneously drawn arterial (A) and mixed venous (V) blood samples. Three measurements per patients were taken at 30-min interval, after body temperature reached 37°C. Concomitantly, measurements of cardiac output were also obtained. Pulmonary lactate release was calculated as the product of transpulmonary A-V lactate and cardiac index. The mean cardiopulmonary bypass duration was 100±44min (SD), and the aortic cross-clamping time was 71±33min. After CPB, lactate release was 0.136±0.210mmol/min m−2. These values were not correlated with cardiopulmonary bypass duration. Conclusion: The present study shows that in patients receiving mechanical ventilation after CPB, the lung is a source of lactate production. This pulmonary release was not dependent on cardiopulmonary bypass duration

Various pacemakers can now track diverse hemodynamic parameters that are useful in the management of patients with heart failure. Among these indicators, pulmonary fluid status can be monitored. To the best of our knowledge, this is the first case describing an agreement between a simultaneous detection of an increase in lung water by transthoracic impedance monitoring (OptiVolTM (Medtronic, Inc., Minneapolis, MN), and the transpulmonary thermodilution method (PiCCOTM, Pulsion Medical Systems, Munich, Germany) in a patient with acute pulmonary oedema. The present case suggests that transthoracic impedance monitoring could be a useful tool to guide therapy in critically ill patients with implanted devices and lung fluid congestion

Cardiogenic shock is a common diagnosis in patients in the intensive care unit (ICU), and is characterized by a decreased cardiac output in the presence of adequate intravascular volume associated with an inadequate tissue perfusion including a physiological reduction in the splanchnic territory. It may occur in isolation as a reflection of cardiac pathology, or it may be part of a shock syndrome involving other pathogenic mechanisms. As the use of enteral nutrition (EN) is associated with an increase in mesenteric arterial output, EN could be deleterious by overwhelming the mechanisms of mesenteric adaptation. Accordingly, EN has been suspected to increase the risk of mesenteric ischaemia, bacterial translocation and sepsis in ICU patients with cardiogenic shock. International guidelines recommend a cautious use of EN within 72h following cardiogenic shock. Recent evidence indicates that mesenteric arterial output may decrease during parenteral nutrition administration, suggesting that parenteral nutrition could have a protective effect on splanchnic organs in ICU patients with cardiogenic shock. Contrary to former beliefs, several meta-analyses have shown that parenteral nutrition is not associated with increased mortality. Exclusive EN is associated with negative energy balance and the combination of EN with supplemental parenteral nutrition during the first days following ICU admission has been proposed to prevent negative energy balance. Such a nutritional strategy could also be beneficial for the mesenteric circulation in cardiogenic shock, and consequently may improve the clinical outcome of patients with cardiogenic shock. Clinical trials are warranted to verify these hypotheses

Objective: The interchangeability of continuous measurement of cardiac output (CO) with the traditional bolus method in patients after cardiopulmonary bypass (CPB) is uncertain. Design: Prospective observational clinical study. Setting: A20-bed surgical ICU at auniversity hospital. Patients: Fourteen deeply sedated, ventilated, post-cardiac surgery patients, all equipped with apulmonary artery catheter. Interventions: Six hours after the end of the CPB, 56 simultaneous bolus and continuous measurements were compared by alinear regression analysis and Bland-Altman analysis. Bolus CO was estimated by averaging triplicate injections of 10 ml room-temperature NaCl 0.9%, delivered randomly during the respiratory cycle. Astringent maximum difference of 0.55 l min—1 (about 10% of the mean bolus measured) was considered as aclinically acceptable agreement between the two types of measurements. To be interchangeable the limits of agreement (± 2 SD of the mean difference between the two methods) should not exceed the chosen acceptable difference. Measurements and results: Continuous was correlated with bolus CO, with acorrelation coefficient of r2 = 0.68. (p< 0.01). The Bland-Altman analysis demonstrated an objective mean bias of 0.33 ± 0.6 l min-1 (confidence interval of -0.87 - 1.58) with 34% of measured values falling outside of the clinically acceptable limits. Conclusion: Our results suggest that, in the first 6 h after CPB, continuous and bolus CO determinations are not interchangeable; one third of the values obtained by continuous CO fell outside the strict limits of clinically useful precision

Purpose: Monitoring using transpulmonary thermodilution (TPTD) via a single thermal indicator technique allows measurement of cardiac output, extravascular lung water (EVLW) and volumetric variables. Methods and results: This report describes two cases of systemic-venous circulation shunt generating early recirculation of thermal indicator with overestimation of EVLW. Conclusion: In the case of recirculation of thermal indicator, the observed overestimated EVLW in absence of gas exchanges abnormality could be an indicator suggesting the search for a circulatory shunt

Background: Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient's response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission. Methods: We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj < 0.01; Benjamini-Hochberg (BH)] and over time from T1 to T2 (48 h later) in R and NR independently (paired analysis, padj < 0.01; BH). Then the differences in gene expression trends over time were evaluated (Mann-Whitney, P <0.01). To identify enriched biological processes, we performed an over-representation analysis based on a right-sided hypergeometric test with Bonferroni step-down as multiple testing correction (padj < 0.05). Results: At ICU admission, we did not identify differentially expressed genes (DEGs) between the two groups. In the transition from T1 to T2, the activation of genes involved in T cell-mediated immunity, granulocyte and natural killer (NK) cell functions, and pathogen lipid clearance was noted in the R group. Genes involved in acute inflammation were downregulated in both groups. Conclusions: Within the limits of a small sample size, our results could suggest that early activation of genes of the adaptive immune response is associated with an improvement in organ f, SCOPUS: ar.j, info:eu-repo/semantics/published

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. Methods: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial ‘ShockOmics’ (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. Clinical trial registration: NCT02141607., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundThe ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock.Methods and designNinety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses.DiscussionShockOmics will provide new insights

BackgroundThe ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock.Methods and designNinety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses.DiscussionShockOmics will provide new insights

Background: The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Methods and Design: Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. Discussion:ShockOmics will provide new insights into, SCOPUS: ar.j, info:eu-repo/semantics/published

QC 20170510

In critical care, the monitoring is essential to the daily care of ICU patients, as the optimization of patient's hemodynamic, ventilation, temperature, nutrition, and metabolism is the key to improve patients' survival. Indeed, the decisive endpoint is the supply of oxygen to tissues according to their metabolic needs in order to fuel mitochondrial respiration and, therefore, life. In this sense, both oxygenation and perfusion must be monitored in the implementation of any resuscitation strategy. The emerging concept has been the enhancement of macrocirculation through sequential optimization of heart function and then judging the adequacy of perfusion/oxygenation on specific parameters in a strategy which was aptly coined "goal directed therapy." On the other hand, the maintenance of normal temperature is critical and should be regularly monitored. Regarding respiratory monitoring of ventilated ICU patients, it includes serial assessment of gas exchange, of respiratory system mechanics, and of patients' readiness for liberation from invasive positive pressure ventilation. Also, the monitoring of nutritional and metabolic care should allow controlling nutrients delivery, adequation between energy needs and delivery, and blood glucose. The present paper will describe the physiological basis, interpretation of, and clinical use of the major endpoints of perfusion/oxygenation adequacy and of temperature, respiratory, nutritional, and metabolic monitorings.

In critical care, the monitoring is essential to the daily care of ICU patients, as the optimization of patient's hemodynamic, ventilation, temperature, nutrition, and metabolism is the key to improve patients' survival. Indeed, the decisive endpoint is the supply of oxygen to tissues according to their metabolic needs in order to fuel mitochondrial respiration and, therefore, life. In this sense, both oxygenation and perfusion must be monitored in the implementation of any resuscitation strategy. The emerging concept has been the enhancement of macrocirculation through sequential optimization of heart function and then judging the adequacy of perfusion/oxygenation on specific parameters in a strategy which was aptly coined "goal directed therapy." On the other hand, the maintenance of normal temperature is critical and should be regularly monitored. Regarding respiratory monitoring of ventilated ICU patients, it includes serial assessment of gas exchange, of respiratory system mechanics, and of patients' readiness for liberation from invasive positive pressure ventilation. Also, the monitoring of nutritional and metabolic care should allow controlling nutrients delivery, adequation between energy needs and delivery, and blood glucose. The present paper will describe the physiological basis, interpretation of, and clinical use of the major endpoints of perfusion/oxygenation adequacy and of temperature, respiratory, nutritional, and metabolic monitorings.

Electrocardiogram (ECG) is a standard type of monitoring in intensive care medicine. Several studies suggest that changes in ECG morphology may reflect changes in volume status. The "Brody effect”, a theoretical analysis of left ventricular (LV) chamber size influence on QRS-wave amplitude, is the key element of this phenomenon. It is characterised by an increase in QRS-wave amplitude that is induced by an increase in ventricular preload. This study investigated the influence of changes in intravascular volume status on respiratory variations of QRS-wave amplitudes (ΔECG) compared with respiratory pulse pressure variations (ΔPP), considered as a reference standard. In 17 pigs, ECG and arterial pressure were recorded. QRS-wave amplitude was measured from the Biopac recording to ensure that in all animals ECG electrodes were always at the same location. Maximal QRS amplitude (ECGmax) and minimal QRS amplitude (ECGmin) were determined over one respiratory cycle. ΔECG was calculated as 100×[(ECGmax−ECGmin)/(ECGmax+ECGmin)/2]. ΔECG and ΔPP were simultaneously recorded. Measurements were performed at different time points: during normovolemic conditions, after haemorrhage (25mL/kg), and following re-transfusion (25mL/kg) with constant tidal volume (10mL/kg) and respiration rate (15 breath/min). At baseline, ΔPP and ΔECG were both <12%. ΔPP were significantly correlated with ΔECG (r2=0.89, p<0.001). Volume loss induced by haemorrhage increased significantly ΔPP and ΔECG. Moreover, during this state, ΔPP were significantly correlated with ΔECG (r2=0.86, p<0.001). Re-transfusion significantly decreased ΔPP and ΔECG, and ΔPP were significantly correlated with ΔECG (r2=0.90, p<0.001). The observed correlations between ΔPP and ΔECG at each time point of the study suggest that ΔECG is a reliable parameter to estimate the changes in intravascular volume status and provide experimental confirmation of the "Brody effect.”

Objectives: In septic patients, reliable non-invasive predictors of fluid responsiveness are needed. We hypothesised that the respiratory changes in the amplitude of the plethysmographic pulse wave (ΔPPLET) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. Design: Prospective clinical investigation. Setting: An 11-bed hospital medical intensive care unit. Patients: Twenty-three deeply sedated septic patients mechanically ventilated with tidal volume ≥ 8 ml/kg and equipped with an arterial catheter and apulse oximetry plethysmographic sensor. Interventions: Respiratory changes in pulse pressure (ΔPP), ΔPPLET and cardiac index (transthoracic Doppler echocardiography) were determined before and after volume infusion of colloids (8 ml/kg). Measurements and main results: Twenty-eight volume challenges were performed in 23 patients. Before volume expansion, ΔPP correlated with ΔPPLET (r 2 = 0.71, p < 0.001). Changes in cardiac index after volume expansion significantly (p < 0.001) correlated with baseline ΔPP (r 2 = 0.76) and ΔPPLET (r 2 = 0.50). The patients were defined as responders to fluid challenge when cardiac index increased by at least 15% after the fluid challenge. Such an event occurred 18 times. Before volume challenge, aΔPP value of 12% and aΔPPLET value of 14% allowed discrimination between responders and non-responders with sensitivity of 100% and 94% respectively and specificity of 70% and 80% respectively. Comparison of areas under the receiver operator characteristic curves showed that ΔPP and ΔPPLET predicted similarly fluid responsiveness. Conclusion: The present study found ΔPPLET to be as accurate as ΔPP for predicting fluid responsiveness in mechanically ventilated septic patients