To beta block or not to beta block; that is the question

The fast-acting β-1 blocker esmolol has been the center of attention since the landmark article by Morrelli and colleagues suggesting that, in patients with sepsis, reducing heart rate by administering esmolol can result in a survival benefit. However, the use of esmolol for the treatment of sepsis and the underlying mechanism responsible for this benefit remain controversial. This commentary discusses the study by Jacquet-Lagrèze and colleagues, who in a pig model of sepsis tested the hypothesis that administration of esmolol to reduce heart rate may correct sepsis-induced sublingual and gut microcirculatory alterations which are known to be associated with adverse outcome

Regional ischemia in hypertrophic Langendorff-perfused rat hearts

Myocardial hypertrophy decreases the muscle mass-to-vascularization ratio, thereby changing myocardial perfusion. The effect of these changes on myocardial oxygenation in hypertrophic Langendorff-perfused rat hearts was measured using epimyocardial NADH videofluorimetry, whereby ischemic myocardium displays a high fluorescence intensity. Hypertrophic hearts, in contrast to control hearts, developed ischemic areas during oxygen-saturated Langendorff perfusion. Reoxygenation of control hearts after a hypoxic episode resulted in a swift decrease of fluorescence in a heterogeneous pattern of small, evenly dispersed, highly fluorescent patches. Identical patterns could be evoked by occluding capillaries with microspheres 5.9 micrometer in diameter. Ten seconds after reoxygenation there were no more dysoxic areas, whereas reoxygenation in hypertrophic hearts showed larger ischemic areas that took significantly longer to return to normoxic fluorescence intensities. Hypothesizing that the larger areas originate at a vascular level proximal to the capillary network, we induced hypoxic patterns by embolizing control hearts with microspheres 9.8 and 15 micrometer in diameter. The frequency distribution histograms of these dysoxic surface areas matched those of hypertrophic hearts and differed significantly from those of hearts embolized with 5.9-micrometer microspheres. These results suggest the existence of areas in hypertrophic Langendorff-perfused hearts with suboptimal vascularization originating at the arteriolar and/or arterial level

Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: A hypothesis generating post hoc analysis

Background: Microcirculatory driving pressure is defined as the difference between post-arteriolar and venular pressure. In previous research, an absence of correlation between mean arterial blood pressure (MAP) and microcirculatory perfusion has been observed. However, the microcirculation may be considered as a low pressure compartment with capillary pressure closer to venous than to arterial pressure. From this perspective, it is conceivable that central venous pressure (CVP) plays a more important role in determination of capillary perfusion. We aimed to explore associations between CVP and microcirculatory perfusion.Methods: We performed a post-hoc analysis of a prospective study in septic patients who were resuscitated according a strict non-CVP guided treatment protocol. Simultaneous measurements of hemodynamics and sublingual Sidestream Dark Field imaging were obtained 0 and 30 minutes after fulfillment of resuscitation goals. Data were examined for differences in microcirculatory variables for CVP ≤ or > 12 mmHg and its evolution over time, as well as for predictors of a microvascular flow index (MFI) 12 mmHg) group as compared to patients in the 'low' CVP (≤12 mmHg) group (1.4 ± 0.9 vs. 1.9 ± 0.9, P = 0.006; and 88 ± 21% vs. 95 ± 8%, P = 0.006 respectively). Perfusion pressure (MAP-CVP) and cardiac output did not differ significantly between both CVP groups. From time point 0 to 30 minutes, a significant increase in MFI (from 1.6 ± 0.6 to 1.8 ± 0.9, P = 0.027) but not in PPV, was observed, while CVP and perfusion pressure significantly decreased in the same period. In a multivariate model CVP > 12 mmHg was the only significant predictor for a capillary MFI < 2.6 (Odds ratio 2.5 (95% confidence interval 1.1-5.8), P = 0.026).Conclusion: We observed a significant association between a higher CVP and impairment of microcirculatory blood flow. Further research is needed to elaborate on our hypothesis generating findings that an elevated CVP may act as an outflow obstruction of organ perfusion

A micro-perfusion chamber for single-cell fluorescence measurements

Abstract A versatile closed micro-perfusion chamber designed for single-cell fluorescence measurements under maximum microscopic magnification is described. Glass coverslips with adherent cells can be attached to the top or bottom of the chamber, depending on whether an inverted or an upright microscope is used. Eight conical holes drilled in the side of the chamber serve for the insertion of plugs with attachments for perfusion, rapid injection of small amounts of reagents, temperature measurements or for heating the interior of the chamber. Materials used in the construction of the chamber are non-toxic and resistant to standard sterilization procedures. Perfusion and temperature properties of the chamber are described. Single cell fluorescence measurements are presented in human monocyte-derived macrophages in which NAD(P)H and intracellular calcium are measured

Imminent ischemia in normal and hypertrophic Langendorff rat hearts; effects of fatty acids and superoxyde dismutase monitored by NADH surface fluorescence

Hypertrophic hearts contain areas of hypoperfusion which can be visualized by increased NADH surface fluorescence during in vitro perfusion without oxygen-carrying particles under constant pressure and pacing. By contrast, fluorescence remained low when non-hypertrophic hearts were used instead. When during perfusion of normal hearts the pH of the medium was lowered from 7.5 to 7.0, areas of high fluorescence appeared in a few minutes. The high fluorescent areas under conditions of cardiac hypertrophy or pH 7.0 perfusion could be reduced by addtion of superoxide dismutase. It indicates that oxygen free radicals interfere with proper flow regulation in areas of low pH. Fluorescence in hypertrophic hearts also diminished during addition of albumin-bound oleate to the standard, glucose-containing, medium. This is in agreement with our earlier findin of fatty acid protection from acidosis-initiated loss of capillary flow (Biochim. Biophys. Acta, 1033 (1990) 214–218). In contrast to low concentrations of free fatty acids, high concentrations interfere with tissue oxygenation. This has been illustrated by the use of 1 mM octanoate, which after a few min caused the appearance of high fluorescent areas. We conclude that decompensation of flow in hypoperfused areas of heart, as occurs in hypertrophy, may be stimulated by acidosis and oxygen free radicals

The vulnerable microcirculation in the critically ill pediatric patient

In neonates, cardiovascular system development does not stop after the transition from intra-uterine to extra-uterine life and is not limited to the macrocirculation. The microcirculation (MC), which is essential for oxygen, nutrient, and drug delivery to tissues and cells, also develops. Developmental changes in the microcirculatory structure continue to occur during the initial weeks of life in healthy neonates. The physiologic hallmarks of neonates and developing children make them particularly vulnerable during critical illness; however, the cardiovascular monitoring possibilities are limited compared with critically ill adult patients. Therefore, the development of non-invasive methods for monitoring the MC is necessary in pediatric critical care for early identification of impending deterioration and to enable the initiation and titration of therapy to ensure cell survival. To date, the MC may be non-invasively monitored at the bedside using hand-held videomicroscopy, which provides useful information regarding the microcirculation. There is an increasing number of studies on the MC in neonates and pediatric patients; however, additional steps are necessary to transition MC monitoring from bench to bedside. The recently introduced concept of hemodynamic coherence describes the relationship between changes in the MC and macrocirculation. The loss of hemodynamic coherence may result in a depressed MC despite an improvement in the macrocirculation, which represents a condition associated with adverse outcomes. In the pediatric intensive care unit, the concept of hemodynamic coherence may function as a framework to develop microcirculatory measurements towards implementation in daily clinical practice

Clinical review: Circulatory shock - an update: a tribute to Professor Max Harry Weil

Circulatory shock is common and associated with high morbidity and mortality. Appropriate shock treatment relies on a good understanding of the pathophysiological mechanisms underlying shock. In this article, we provide an update on the description, classification, and management of shock states built on foundations laid by Dr Max Harry Weil, a key early contributor to this field

Tonometry to assess the adequacy of splanchnic oxygenation in the critically ill patient

Tonometry, a relatively non-invasive technique for indirectly measuring the intramucosal pH (pHi) of the gastrointestinal tract, has recently been developed for use in critically ill patients. Reports in the literature suggest that the technique is of greatest benefit to patients at risk of developing reductions in splanchnic oxygenation (decreased O2 delivery) in whom early detection of the ischemic episode could possibly guide treatment. Tonometry, although still at a relatively early stage in its clinical development, could be of value for selected patient groups although further evaluation of the technique is necessary

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

Background: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Methods: Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Results: Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Conclusions: Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in r

A simple device to inject indicator gas for wash-out tests during mechanical ventilation

Objective: To evaluate a simple device which injects a constant fraction of indicator gas to the inspiratory mixture for performing multi-breath wash-out tests during controlled ventilation. Design: the technique in which the indicator gas is injected at the mouth of the patient (post-mix) is compared with the technique where the indicator gas is administered in the bellows of the ventilator (pre-mix). Setting: Surgical Intensive Care Unit of a University Hospital. Patients: 10 post-operative mechanically ventilated patients. Interventions: None. Measurements and results: 3 wash-out tests with the post-mix and 3 wash-out tests with the pre-mix method were performed within an hour on every patient. The calculated mean end expiratory lung volume (EEV) was 1.91±0.871 with the post-mix technique and 1.89±0.881 with the premix technique. There was a good agreement with a mean difference of -1.9±6.5% in the calculated EEV values by the two different techniques. Conclusion: The described injector is an affordable device, is easy to assemble and can be incorporated in most electronically regulated ventilators to perform multi-breath indicator gas wash-out tests for pulmonary monitoring at the bed side of ICU patients