Collection Angle Dependence of the Depolarization Ratio in Light Scattering Experiments

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Interpretation of blood pressure signal: physiological bases, clinical relevance, and objectives during shock states

Achievement of a mean blood pressure (MBP) target is one of the hemodynamic goals to ensure an adequate blood perfusion pressure in critically ill patients. Arterial catheter allows for a continuous and precise monitoring of arterial pressure signal. In addition to giving a precise MBP monitoring, analysis of the blood pressure wave provides information that may help the clinician to interpret hemodynamic status. The interpretation of BP wave requires the understanding of simple principles. In this review, we first discuss the physiological mechanism responsible for arterial pressure generation. We then emphasize the interpretation of the static indexes and the dynamic indexes generated by heart–lung interactions derived from arterial pressure wave. Finally, we focus on MBP value as a therapeutic target in critically ill patients. We discuss the recommended target MBP value by reviewing available data from experimental and clinical studies

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial

BACKGROUND: Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes. METHODS: ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality. RESULTS: FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders

Diastolic shock index and clinical outcomes in patients with septic shock

Background: Loss of vascular tone is a key pathophysiological feature of septic shock. Combination of gradual diastolic hypotension and tachycardia could reflect more serious vasodilatory conditions. We sought to evaluate the relationships between heart rate (HR) to diastolic arterial pressure (DAP) ratios and clinical outcomes during early phases of septic shock. Methods: Diastolic shock index (DSI) was defined as the ratio between HR and DAP. DSI calculated just before starting vasopressors (Pre-VPs/DSI) in a preliminary cohort of 337 patients with septic shock (January 2015 to February 2017) and at vasopressor start (VPs/DSI) in 424 patients with septic shock included in a recent randomized controlled trial (ANDROMEDA-SHOCK; March 2017 to April 2018) was partitioned into five quantiles to estimate the relative risks (RR) of death with respect to the mean risk of each population (assumed to be 1). Matched HR and DAP subsamples were created to evaluate the effect of the individual components of the DSI on RRs. In addition, time-course of DSI and interaction between DSI and vasopressor dose (DSI*NE.dose) were compared between survivors and non-survivors from both populations, while ROC curves were used to identify variables predicting mortality. Finally, as exploratory observation, effect of early start of vasopressors was evaluated at each Pre-VPs/DSI quintile from the preliminary cohort. Results: Risk of death progressively increased at gradual increments of Pre-VPs/DSI or VPs/DSI (One-way ANOVA, p < 0.001). Progressive DAP decrease or HR increase was associated with higher mortality risks only when DSI concomitantly increased. Areas under the ROC curve for Pre-VPs/DSI, SOFA and initial lactate were similar, while mean arterial pressure and systolic shock index showed poor performances to predict mortality. Time-course of DSI and DSI*NE.dose was significantly higher in non-survivors from both populations (repeated-measures ANOVA, p < 0.001). Very early start of vasopressors exhibited an apparent benefit at higher Pre-VPs/DSI quintile. Conclusions: DSI at pre-vasopressor and vasopressor start points might represent a very early identifier of patients at high risk of death. Isolated DAP or HR values do not clearly identify such risk. Usefulness of DSI to trigger or to direct therapeutic interventions in early resuscitation of septic shock need to be addressed in future studies

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

BACKGROUND: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes

Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study

__Introduction:__ The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups. __Methods:__ The study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 μg·kg-1·min-1(n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test. __Results:__ Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group; P = .02; MFIs 2.9. The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group. In addition, the heterogeneity index decreased only in the levosimendan group. There was no statistically significant correlation between systemic and microcirculatory flow variables within each group. __Conclusions:__ Compared to a standard dose of 5 μg·kg-1·min-1of dobutamine, levosimendan at 0.2 μg·kg-1·min-1improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels.Trial registration: NCT00800306

A hypoperfusion context may aid to interpret hyperlactatemia in sepsis-3 septic shock patients: a proof-of-concept study

__Background:__ Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation. __Results:__ We defined hypoperfusion context by the presence of a ScvO2 < 70%, or a P(cv-a)CO2 ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%). __Conclusions:__ Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO2, or high P(cv-a)CO2, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy

The mammalian gene function resource: The International Knockout Mouse Consortium

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

Pulmonary artery occlusion pressure

The bedside estimation of left ventricular (LV) performance of critically ill patients is an important aspect of the diagnosis and management of these patients. Ever since the introduction of the balloon flotation pulmonary catheterization, health care providers have used measurements of pulmonary artery occlusion pressure (Ppao) to estimate both pulmonary venous pressure and LV preload. However, the significance of any specific value for Ppao in the diagnosis and treatment of cardiovascular insufficiency in patients with diseases other than cardiogenic shock has never been validated. The reasons for this continued uncertainty reflect both intrinsic inaccuracies in the measurement of Ppao and misconceptions about their physiological significance. In this first Physiological Note we shall discuss problems in the accurate measurement of Ppao at the bedside, while in the second Physiological Note we shall discuss the physiological significance of Ppao measurements © 2006 Springer-Verlag Berlin Heidelberg