Hemodynamic effects and tolerance of dobutamine for myocardial dysfunction during septic shock: An observational multicenter prospective echocardiographic study.

Background: The role of dobutamine during septic shock resuscitation is still controversial. Methods: The aim of this prospective multicentre study was to comprehensively characterize the hemodynamic response of septic shock patients with systolic myocardial dysfunction to incremental doses of dobutamine (0, 5, 10, and 15 µg/kg/min). Results: Thirty two patients were included in three centers. Dobutamine significantly increased contractility indices of both ventricles [crude and afterload-adjusted left ventricular (LV) ejection fraction, global LV longitudinal peak systolic strain, tissue Doppler peak systolic wave at mitral and tricuspid lateral annulus, and tricuspid annular plane excursion) as well as global function indices (stroke volume and cardiac index) and diastolic function (increased e' and decreased E/e' ratio at lateral mitral annulus). Dobutamine also induced a significant decrease in arterial pressure and cardiac afterload indices (effective arterial elastance, systemic vascular resistance and diastolic shock index). Oxygen transport, oxygen consumption and carbon dioxide production all increased with dobutamine, without change in the respiratory quotient or lactate. Dobutamine was discontinued for poor tolerance in a majority of patients (n = 21, 66%) at any dose and half of patients (n = 15, 47%) at low-dose (5 µg/kg/min). Poor tolerance to low-dose dobutamine was more frequent in case of acidosis, was associated with lower vasopressor-free days and survival at day-14. Conclusion: In patients with septic myocardial dysfunction, dobutamine induced an overall improvement of echocardiographic parameters of diastolic and systolic function, but was poorly tolerated in nearly two thirds of patients, with worsening vasoplegia. Patients with severe acidosis seemed to have a worse response to dobutamine.

Critical illness-related corticosteroid insufficiency during difficult weaning from mechanical ventilation.

BACKGROUND: Critical illness-related corticosteroid insufficiency (CIRCI) is common during critical illness and is usually associated with poor outcomes, as prolonged duration of mechanical ventilation (MV) and higher mortality. CIRCI may alter cardiac and vascular functions. Weaning-induced pulmonary oedema (WiPO) is a major mechanism of weaning failure. The aim of this study was to evaluate the role of CIRCI in patients with difficult ventilator weaning and its possible relation with WiPO. METHODS: This is a prospective study conducted in the intensive care of a university hospital in France. Patients under MV for more than 24 h, meeting weaning criteria and having failed the first spontaneous breathing trial (SBT) underwent a corticotropin stimulation test, with assessment of total blood cortisol levels immediately before (T0) 0.25 mg iv of tetracosactrin and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0. CIRCI was defined as T0 < 10 µg/dL (276 nmol/L) and/or Δmax < 9 µg/dL (248 nmol/L) and inadequate adrenal reserve as Δmax < 9 µg/dL. Biomarkers (natriuretic peptide and protidemia) sampling and echocardiograms were performed during the second SBT and were used to diagnose WiPO, which was defined according to two definitions (one liberal and one conservative) derived from recent publications on the topic. Successful extubation was defined as patient alive without reintubation 7 days after extubation. A competing risk analysis was used to assess extubation failure and mortality. RESULTS: Seventy-six consecutive patients (63 ± 14 years; 49 men) with difficult weaning were enrolled. CIRCI and inadequate adrenal reserve occurred in 25 (33%) and 17 (22%) patients, respectively. The probability of successful extubation was significantly decreased in patients with CIRCI or inadequate adrenal reserve, as compared to their counterparts, and this association persisted after adjustment on severity (SOFA score at first SBT). WiPO occurred in 44 (58%) and 8 (11%) patients, according to the liberal and conservative definition, respectively. WiPO was not associated with CIRCI nor with inadequate adrenal reserve. CONCLUSION: CIRCI was common during difficult weaning and was associated with its prolongation. We did not find a significant association between CIRCI and WiPO.

Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and ß-Blockers.

BACKGROUND: Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. ß-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a ß-blocker (atenolol) during murine peritonitis. METHODS: Ivabradine (3 µg/g), atenolol (3 µg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile). RESULTS: As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224). CONCLUSIONS: Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

Acute Hippocampal Encephalopathy in Heavy Cannabis Users: About 2 Cases.

BACKGROUND: Cannabis use is increasing worldwide despite the various health effects of this substance. METHODS: We report 2 cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/d). RESULTS: In both male patients, acute encephalitis was suspected. Brain magnetic resonance imaging (MRI) diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis, and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological, and magnetic resonance imaging acute abnormalities improved within weeks. New exposure to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later. CONCLUSIONS: Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.

Myocardial ischemia during ventilator weaning: a prospective multicenter cohort study.

BACKGROUND: Weaning-induced cardiac pulmonary edema (WiPO) is one of the main mechanisms of weaning failure during mechanical ventilation. We hypothesized that weaning-induced cardiac ischemia (WiCI) may contribute to weaning failure from cardiac origin. METHODS: A prospective cohort study of patients mechanically ventilated for at least 24 h who failed a first spontaneous breathing trial (SBT) was conducted in four intensive care units. Patients were explored during a second SBT using multiple tools (echocardiography, continuous 12-lead ST monitoring, biomarkers) to scrutinize the mechanisms of weaning failure. WiPO definition was based on three criteria (echocardiographic signs of increased left atrial pressure, increase in B-type natriuretic peptides, or increase in protein concentration during SBT) according to a conservative definition (at least two criteria) and a liberal definition (at least one criterion). WiCI was diagnosed according to the third universal definition of myocardial infarction proposed by the European Society of Cardiology (ESC) and the American Heart Association (AHA) statement for exercise testing. RESULTS: Among patients who failed a first SBT, WiPO occurred in 124/208 (59.6%) and 44/208 (21.2%) patients, according to the liberal and conservative definition, respectively. Among patients with ST monitoring, WiCI was diagnosed in 36/177 (20.3%) and 12/177 (6.8%) of them, according to the ESC and AHA definitions, respectively. WiCI was not associated with WiPO and was not associated with weaning outcomes. Only two patients of the cohort were treated for an acute coronary syndrome after the second SBT, and seven other patients required coronary angiography during the weaning period. CONCLUSIONS: This observational study showed the common occurrence of pulmonary edema in mechanically ventilated patients who failed a first SBT, but the association with cardiac ischemia and weaning outcomes was weak.

A multiplex analysis of sepsis mediators during human septic shock: a preliminary study on myocardial depression and organ failures.

BACKGROUND: The mechanisms of organ failure during sepsis are not fully understood. The hypothesis of circulating factors has been suggested to explain septic myocardial dysfunction. We explored the biological coherence of a large panel of sepsis mediators and their clinical relevance in septic myocardial dysfunction and organ failures during human septic shock. METHODS: Plasma concentrations of 24 mediators were assessed on the first day of septic shock using a multi-analyte cytokine kit. Septic myocardial dysfunction and organ failures were assessed using left ventricle ejection fraction (LVEF) and the Sequential Organ Failure Assessment score, respectively. RESULTS: Seventy-four patients with septic shock (and without immunosuppression or chronic heart failure) were prospectively included. Twenty-four patients (32%) had septic myocardial dysfunction (as defined by LVEF < 45%) and 30 (41%) died in ICU. Hierarchical clustering identified three main clusters of sepsis mediators, which were clinically meaningful. One cluster involved inflammatory cytokines of innate immunity, most of which were associated with septic myocardial dysfunction, organ failures and death; inflammatory cytokines associated with septic myocardial dysfunction had an additive effect. Another cluster involving adaptive immunity and repair (with IL-17/IFN pathway and VEGF) correlated tightly with a surrogate of early sepsis resolution (lactate clearance) and ICU survival. CONCLUSIONS: In this preliminary study, we identified a cluster of cytokines involved in innate inflammatory response associated with septic myocardial dysfunction and organ failures, whereas the IL-17/IFN pathway was associated with a faster sepsis resolution and a better survival.

Paradoxical brain embolism shadowing massive pulmonary embolism.

Patent foramen ovale is frequently observed in the general population. In case of massive pulmonary embolism, the sudden increase in the right heart cavity's pressure may cause a right-to-left shunting across this foramen, which could be associated with conflicting outcomes. Herein, we report a case of reversible cardiac arrest preceded by seizures, and followed by hemodynamic stability without any vasopressor. A brain CT-scan showed a limited ischemic stroke. Initial echocardiographic assessment revealed an acute cor pulmonale and a right-to-left intracardiac shunt across a large patent foramen ovale, suggesting the diagnosis of massive pulmonary embolism that was lately confirmed by a multidetector CT-angiography. Anticoagulation therapy was rapidly complicated by a hemorrhagic transformation of the ischemic stroke leading to a fatal outcome. This case illustrates the double-edged circulatory effect of shunting across a patent foramen ovale in case of massive pulmonary embolism: it may have limited circulatory failure but caused in the meanwhile a fatal paradoxical brain embolism.

Cardiac function during weaning failure: the role of diastolic dysfunction.

BACKGROUND: Cardiac dysfunction is a common cause of weaning failure. Weaning shares some similarities with a cardiac stress test and may challenge active phases of the cardiac cycle-like ventricular contractility and relaxation. This study aimed at assessing systolic and diastolic function during the weaning process and scrutinizing their dynamics during weaning trials. METHODS: Echocardiography was performed during baseline ventilator settings to assess cardiac function at the initiation of the weaning process and at the start and the end of consecutive weaning trials (performed at day-1, day-2, and before extubation if applicable) to explore the evolution of left ventricle contractility and relaxation in a subset of patients. RESULTS: Among 67 patients included, weaning was prolonged (≥ 7 days) in 18 (27%) patients and short (< 7 days) in 49 (73%). Prevalence of systolic dysfunction and isolated diastolic dysfunction before the initiation of weaning process were 37 and 17%, respectively. Isolated diastolic dysfunction was more frequent in patients with prolonged weaning as compared to their counterparts. Thirty-one patients were explored by echocardiography during consecutive weaning trials. An increase in filling pressures with an alteration of ventricular relaxation (as assessed by a decrease in tissue Doppler early mitral diastolic wave velocity) was found during failed weaning trials. CONCLUSIONS: Isolated diastolic dysfunction was associated with a prolongation of weaning. Increased filling pressures with left ventricle relaxation impairment may be a key mechanism of weaning trial failure.

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

BACKGROUND: Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. METHODS: Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. RESULTS: Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. CONCLUSION: Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

Left ventricular systolic dysfunction during septic shock: the role of loading conditions.

PURPOSE: The clinical significance of septic myocardial dysfunction is controversial, a fact that may be explained by the influence of loading conditions. Many indices may be useful to characterize cardiac function during septic shock, but their feasibility and physiological coherence in the clinical setting are unknown. METHODS: Hemodynamic and echocardiographic data with tissue Doppler and speckle tracking were prospectively recorded on the first 3 days of human septic shock. Hypokinesia, normokinesia, and hyperkinesia were defined as a left ventricular ejection fraction (LVEF) of <45, 45-60, and >60%, respectively. Twelve hemodynamic indices exploring contractility and loading conditions were assessed and analyzed. RESULTS: Two hundred and ninety-seven echocardiographies were performed in 132 patients. During the first 24 h (H1-24), 48 (36.4%) patients were hyperkinetic, 55 (41.7%) were normokinetic, and 29 (22.0%) patients were hypokinetic. Thirteen patients had a secondary hypokinesia absent at H1-24 but present at H25-48 or H49-72, for an overall incidence of 42 (31.8%) during the first 3 days. Despite a limited feasibility (<50%), global LV longitudinal peak systolic strain was impaired in a majority (>70%) of the patients assessed, including all those with depressed LVEF, and declined early in patients whose LVEF secondarily deteriorated. Most contractility indices were inversely correlated with afterload indices. Hyperkinetic patients exhibited the worst reduction in afterload indices. Hospital mortality was significantly higher in patients with LV hyperkinesia than in their counterparts: 30 (62.5%) vs. 35 (41.7%), p = 0.02. CONCLUSIONS: Speckle tracking-derived strain was reduced in the majority of patients with septic shock, revealing covert septic myocardial dysfunction, but had poor feasibility. We found an inverse correlation between most of the contractility and afterload indices. Precise evaluation of afterload is crucial for adequate interpretation of LV systolic function in this setting.

Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of intensive care patients with mild-to-moderate hypoxemia.

OBJECTIVES: Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noninvasive ventilation reduces desaturation during intubation of severely hypoxemic patients, it does not allow for per-procedure oxygenation and has not been evaluated in mild-to-moderate hypoxemic patients for whom high-flow nasal cannula oxygen may be an alternative. We sought to compare pre- and per-procedure oxygenation with either a nonrebreathing bag reservoir facemask or a high-flow nasal cannula oxygen during tracheal intubation of ICU patients. DESIGN: Prospective quasi-experimental before-after study (ClinicalTrials.gov: NCT01699880). SETTING: University hospital medico-surgical ICU. PATIENTS: All adult patients requiring tracheal intubation in the ICU were eligible. INTERVENTIONS: In the control (before) period, preoxygenation was performed with a nonrebreathing bag reservoir facemask and in the change of practice (after) period, with high-flow nasal cannula oxygen. MEASUREMENTS AND MAIN RESULTS: Primary outcome was median lowest SpO2 during intubation, and secondary outcomes were SpO2 after preoxygenation and number of patients with saturation less than 80%. One hundred one patients were included. Median lowest SpO2 during intubation were 94% (83-98.5) with the nonrebreathing bag reservoir facemask versus 100% (95-100) with high-flow nasal cannula oxygen (p < 0.0001). SpO2 values at the end of preoxygenation were higher with high-flow nasal cannula oxygen than with nonrebreathing bag reservoir facemask and were correlated with the lowest SpO2 reached during the intubation procedure (r = 0.38, p < 0.0001). Patients in the nonrebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2% vs 14%, p = 0.03). In the multivariate analysis, preoxygenation with high-flow nasal cannula oxygen was an independent protective factor of the occurrence of severe hypoxemia (odds ratio, 0.146; 95% CI, 0.01-0.90; p = 0.037). CONCLUSIONS: High-flow nasal cannula oxygen significantly improved preoxygenation and reduced prevalence of severe hypoxemia compared with nonrebreathing bag reservoir facemask. Its use could improve patient safety during intubation.

Acute kidney injury in critical care: experience of a conservative strategy.

PURPOSE: Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in intensive care unit (ICU), but the timing of its initiation remains open to debate. MATERIALS AND METHODS: We retrospectively analyzed ICU patients who had AKI associated with at least one usual RRT criteria: serum creatinine concentration greater than 300 µmol/L, serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate the risk of death associated with RRT adjusted for risk factors, we performed a marginal structural Cox model with inverse-probability-of-treatment-weighted estimator. RESULTS: Among 4173 patients admitted to the ICU, 203 patients fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and 112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of illness: Simplified Acute Physiology Score II (55±17 vs 60±19, respectively; P<.05) and Sequential Organ Failure Assessment score (8 [5-10] vs 9 [7-11], respectively; P=.01). Crude analysis indicated a lower ICU mortality for non-RRT compared with RRT patients (18% vs 45%; P<.001). In the marginal structural Cox model, RRT was associated with increased mortality (P<.01). CONCLUSION: A conservative approach of AKI was not associated with increased mortality.