Unfortunately, to date there are no standardized criteria for the clinical diagnosis of increased microvascular permeability, because the assessment of fluid distribution and fluid balance in septic patients is very difficult. Clearly, early diagnosis of increased microvascular permeability would be valuable, because it would allow early and specified treatment as well as the evaluation of the efficacy of therapeutic efforts. It is important to distinguish between increased microvascular permeability and other hypo-oncotic conditions leading to fluid retention, that is, caused by renal or hepatic failure. Proposed criteria for clinical assessment of the microvascular leak syndrome so far either are nonspecific or have limited bedside applicability: Microvascular leak was defined as noncardiogenic generalized edema and hemodynamic instability or more than 3 percent increase of body weight within 24 hours, combined with generalized edema. In this context, it is worth noting that calculated fluid balances are not predictive for actual weight changes in critically ill patients. A dual-radionuclide method using 67Ga transferrin and 99mTc-labeled erythrocytes was used to measure pulmonary edema. This is certainly an interesting approach, but the required sophisticated technique is not widely available. The transcapillary escape rate of 125I-labeled albumin was suggested as a surrogate measurement of microvascular leak syndrome. This method is limited by the fact that the recirculation of radiolabeled albumin from the tissues via the lymphatic system cannot be quantified. Moreover, the clinical applicability of radioactive tracers is limited due to radioactive contamination and dye accumulation. The disadvantages, especially in repeated measurements, are obvious.

Increased extravascular lung water has been suggested as a morphological correlate of pulmonary edema and can be used for analysis of pulmonary microvascular leakage. Currently available systems measure extravascular lung water by a double-indicator (indocyanin green and heat) or a single-indicator thermodilution (heat) technique. The accuracy of both thermodilution techniques was demonstrated gravimet-rically. In animals, the sensitivity was 81 percent, the specificity was 97 percent. The coefficient of variation for repeated measurements of extravascular lung water was 8 to 9 percent in human beings and 6 to 7 percent in animals, respectively. The limitations of the thermal-dye method include overestimation of extravascular lung water at normal levels of water content and perfusion dependence. Severe alterations of lung perfusion may lead to an underestimation of the water content using the thermal dye dilution method. When significant proportions of pulmonary tissue are excluded from the pulmonary circulation, the indicators do not reach the nonperfused areas and, therefore, both intravas-cular and extravascular fluid pools can go undetected.

A modification of venous congestion plethysmography allows noninvasive assessment of the filtration capacity as a measure of microvascular permeability and isovolumetric venous pressure, a value that is related to the balance of filtration forces across the microvasculature. Using this method an increased microvascular permeability was demonstrated in septic shock patients. This technique requires a sedated or a cooperative patient, because movements cause artifacts. Furthermore, if the isovolumetric venous pressure is high and the diastolic blood pressure is low (as in some septic patients) the measurement of the filtration capacity is not accurate because fluid filtration is only observed at high cuff pressures that are close to the diastolic arterial pressure. In nonseptic blunt trauma patients renal albumin excretion can be used as a surrogate for microvascular leakage. However, this approach is not rec-ommendable in septic patients because of the frequent occurrence of renal dysfunction/failure. Our own group has recently suggested a set of noninvasive diagnostic determinants for the microvascular leak syndrome [7]. Initially reliability of a noninvasive measurement of extracellular fluid volume using bioelectrical impedance analysis compared with inulin was assessed. On that basis measurement of an increased extracellular fluid volume using bioelectrical impedance analysis combined with the response of colloid osmotic pressure to albumin infusion in septic shock patients was demonstrated as a noninvasive method for the diagnosis of sepsis-induced microvascular leak syndrome applicable at the bedside.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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