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ABSTRACT: PURPOSE OF REVIEW: Vascular permeability is traditionally explained by Starling's principle, describing two opposing forces across the endothelial cell line to maintain compartments in balance. Several contradictions to this principle have recently questioned its validity. RECENT FINDINGS: Hydraulic conductivity is kept low by a properly working endothelial surface layer, created by binding and intercalating plasma constituents with the structural elements of an endothelial glycocalyx. Limiting fluid filtration is not closely related to the interstitial protein concentration. Rather, the oncotic pressure difference pertinent to fluid homeostasis is built up between the intravascular space and a small protein-free zone beneath the protein-loaded endothelial glycocalyx. This crucial structure, and therefore the resistance of the barrier against outflow of large molecules, is endangered by ischaemia, inflammation and intravascular hypervolaemia. An intact endothelial surface layer retains iso-oncotic preparations of large molecules infused to compensate for acute bleeding. Crystalloids cannot be held back sufficiently, even if preload is warranted. SUMMARY: Starling's principle requires an adaptation to recognize that there is no inward-directed oncotic pressure gradient across the whole anatomical vessel wall. The carrier of vascular barrier competence is the intact endothelial surface layer which might be protected by avoiding intravascular hypervolaemia and limiting inflammation.
Current opinion in critical care 06/2013; · 2.67 Impact Factor
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ABSTRACT: Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.
Archiv für Kreislaufforschung 05/2013; 108(3):347. · 7.35 Impact Factor
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ABSTRACT: Maintaining cardiac preload throughout the perioperative period is a generally accepted target. As perioperative fasting is believed to cause intravascular hypovolaemia it traditionally triggers aggressive preemptive intravenous fluid infusion. Physiology suggests that extracellular losses via urinary output and evaporation decrease the extracellular compartment. Representing a relevant part of the latter, the intravascular space is also affected, even without blood loss. Measurements in humans, however, have revealed that even a prolonged fasting period does not decrease absolute blood volume. Beyond that, modern fasting guidelines recommend to refrain from clear liquids only two hours prior to surgery. Nevertheless, an intravenous colloid challenge can increase stroke volume after induction of anaesthesia in the majority of surgical patients. While perioperative stroke volume maximisation in high-risk surgery probably improves outcome, the implication of this observation for the routine patient remains unclear. It appears as though there are two important targets to preserve cardiac preload: normovolaemia and vasotension.
Best practice & research. Clinical anaesthesiology. 12/2012; 26(4):421-30.
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New England Journal of Medicine 09/2012; 367(13):1266; author reply 1267. · 53.30 Impact Factor
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ABSTRACT: The current pilot study compares the impact of an intravenous infusion of Ringer's lactate to an acetate-based solution with regard to acid-base balance. The study design included the variables of the Stewart approach and focused on the effective strong ion difference. Because adverse hemodynamic effects have been reported when using acetate buffered solutions in hemodialysis, hemodynamics were also evaluated.
Twenty-four women who had undergone abdominal gynecologic surgery and who had received either Ringer's lactate (Strong Ion Difference 28 mmol/L; n = 12) or an acetate-based solution (Strong Ion Difference 36.8 mmol/L; n = 12) according to an established clinical protocol and its precursor were included in the investigation. After induction of general anesthesia, a set of acid-base variables, hemodynamic values and serum electrolytes was measured three times during the next 120 minutes.
Patients received a mean dose of 4,054 ± 450 ml of either one or the other of the solutions. In terms of mean arterial blood pressure and norepinephrine requirements there were no differences to observe between the study groups. pH and serum HCO3- concentration decreased slightly but significantly only with Ringer's lactate. In addition, the acetate-based solution kept the plasma effective strong ion difference more stable than Ringer's lactate.
Both of the solutions provided hemodynamic stability. Concerning consistency of acid base parameters none of the solutions seemed to be inferior, either. Whether the slight advantages observed for the acetate-buffered solution in terms of stability of pH and plasma HCO3- are clinically relevant, needs to be investigated in a larger randomized controlled trial.
European journal of medical research. 07/2012; 17(1):21.
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ABSTRACT: INTRODUCTION: Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (for example, human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise. METHODS: In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with Ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t tests (according to Student) for the singular measurements were taken. P < 0.05 was considered to be significant. RESULTS: A total of 1,097 ± 285 ml of whole blood were withdrawn (641 ± 155 ml/m2 body surface area) and simultaneously replaced by 3,430 ± 806 ml of Ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459 ± 185 ml; P < 0.05) that did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+2,157 ± 606 ml; P < 0.05). The volume effect of Ringer's lactate was 17 ± 10%. The infusion of 245 ± 64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184 ± 63%. CONCLUSIONS: Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the three-fold amount of Ringer's lactate impedes maintenance of intravascular normovolemia. The main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the five-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous.
Critical care (London, England) 05/2012; 16(3):R86. · 4.61 Impact Factor
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ABSTRACT: BACKGROUND: Although haematocrit and haemoglobin value are concentrations, they are commonly used to guide clinical decisions involving red cell and plasma volumes. A study challenging this convention systematically co-determined and compared these measures. MATERIALS AND METHODS: Using a non-radioactive double-tracer technique to assess blood volume components, measurements were taken once in 46 healthy male endurance athletes. The best predictors of blood composition were derived from the first 36 athletes by automated stepwise forward selection of non-invasive metric parameters (age, weight, height, body surface area and body mass index) and the resulting formulae validated in the remaining ten volunteers. Haematocrit, haemoglobin concentration, red cell volume and plasma volume were measured again 4 weeks later in eight randomly selected volunteers. RESULTS: Red cell volume (2,282±283 mL) did not correlate with either haematocrit (0.42±0.02) or haemoglobin concentration (14.2±0.8, P>0.05, resp.), but was predictable from body surface area (red cell volume [mL]=1,547 x body surface area [m(2)]-723; r=.88, P<0.01). A similar accuracy was unobtainable using any potential predictor for plasma or blood volume, haematocrit or haemoglobin concentration. Red cell volume showed high intra-individual stability when measured again after 4 weeks, whereas plasma volume oscillated in both directions by up to 22%. DISCUSSION: Only red cell volume shows sufficiently stable intra- and interindividual values to be an accurate, objective indicator of normality in blood composition. The measurement technique is feasible in the outpatient setting and this parameter provides effective, robust, and readily available diagnostic information that might be useful in numerous clinical situations. Its clinical significance does, however, remain to be demonstrated.
Blood transfusion = Trasfusione del sangue 05/2012; · 2.10 Impact Factor
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ABSTRACT: Adhesion of polymorphonuclear neutrophils and platelets to the vessel wall contributes to generating ischemia-reperfusion injury. Endothelial adhesion molecules are harbored within the glycocalyx, which covers every healthy vascular endothelium but is deteriorated by ischemia-reperfusion. Pretreating the heart with volatile anesthetics reduces myocardial infarct size and protects against ischemia-reperfusion injury. The authors analyzed a possible protective effect of sevoflurane on the glycocalyx and implications for postischemic cell adhesion.
Isolated guinea pig hearts were perfused with crystalloid buffer and subjected to 20 min of global warm ischemia and 10 min of reperfusion. An intracoronary bolus of 3 x 10(6) polymorphonuclear neutrophilic leukocytes or 1 x 10(9) platelets of human origin was applied after reperfusion, either with or without pretreating with 0.5 or 1 minimal alveolar concentration sevoflurane. The number of sequestered cells was calculated from the difference between coronary input and output. Coronary effluent was collected throughout reperfusion to measure shedding of the glycocalyx.
Ischemia-reperfusion induced a significant increase in median (interquartile range) adhesion versus control nonischemic hearts of both leukocytes (38.9 (36.3-42.9) vs. 14.5 (13.1-16.0)%) and platelets (25.0 (22.5-27.1) vs. 9.4 (8.4-10.7)%). Shedding was evidenced by eightfold increases in washout of syndecan-1 and heparan sulfate versus basal. Sevoflurane reduced cell adhesion to near basal at 1 minimal alveolar concentration (leukocytes: 21.2% (19.2-23.9%), platelets: 11.5% (10.4-12.0%). Shedding measurements and electron microscopy demonstrated that sevoflurane-treated hearts retained much of their 200 nm-thick glycocalyx.
Sevoflurane reduces glycocalyx shedding in the postischemic coronary bed, maintaining the natural cover for endothelial adhesion molecules and, thus, reducing cell adhesion. This may explain beneficial outcomes linked to clinical use of volatile anesthetics after ischemia-reperfusion.
Anesthesiology 09/2011; 115(3):483-91. · 5.36 Impact Factor
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ABSTRACT: Background: Adhesion of polymorphonuclear neutrophils and platelets to the vessel wall contributes to generating ischemia–reperfusion injury. Endothelial adhesion molecules are harbored within the glycocalyx, which covers every healthy vascular endothelium but is deteriorated by ischemia–reperfusion. Pretreating the heart with volatile anesthetics reduces myocardial infarct size and protects against ischemia–reperfusion injury. The authors analyzed a possible protective effect of sevoflurane on the glycocalyx and implications for postischemic cell adhesion.
Anesthesiology 08/2011; 115(3):483–491. · 5.36 Impact Factor
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ABSTRACT: The present study investigates why shedding of the endothelial glycocalyx occurs both in patients undergoing on- and off-pump coronary artery bypass surgery. Release of atrial natriuretic peptide (ANP) was of special interest, because ANP initiates shedding ex vivo. Three major constituents of the glycocalyx (syndecan-1, heparan sulfate and hyaluronan) were measured in arterial blood of patients undergoing coronary artery bypass surgery with (n = 15) and without (n = 15) cardiopulmonary bypass at various phases of the procedure. Additionally, the levels of the inflammatory cytokines interleukin (IL)-6, -8, and -10 and of ANP were evaluated. Elevations of all three components of the glycocalyx were detected in blood of patients undergoing on- (maximum increases: syndecan-1 15-fold, heparan sulfate ninefold, hyaluronan fivefold basal) and off-pump (maximum increases: syndecan-1 fourfold, heparan sulfate twofold, hyaluronan threefold basal) coronary artery surgery. Maximum ANP concentrations increased three- and fourfold basal in on- and off-pump coronary artery surgery, respectively (P < 0.05). There were significant increases in the three cytokine concentrations in both on- (maximum increases: IL-6 146-fold, IL-8 23-fold, IL-10 238-fold basal) and off-pump (maximum increases: IL-6 77-fold, IL-8 eightfold, IL-10 58-fold basal) coronary artery surgery. However, the elevations of ANP preceded those of the cytokines and coincided with or even preceded shedding of the human endothelial glycocalyx in both surgical procedures. These data suggest that release of ANP may lead to perturbation of the endothelial glycocalyx in both on- and off-pump coronary artery bypass surgery.
Archiv für Kreislaufforschung 07/2011; 106(6):1111-21. · 7.35 Impact Factor
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MMW Fortschritte der Medizin 06/2011; 153(22):50-2.
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ABSTRACT: Overview on the perioperative metabolism of diabetic patients. The text provides important information for the clinician and summarises the evidence in the international literature. Important studies, background of the diabetic perioperative metabolism, patient screening, existing oral diabetes therapies and insulin regimes, differences between regional and general anesthesia, and important laboratory parameters are discussed. Oral antidiabetics used in Germany, different classes of insulins and possible regimes for the intraoperative management of insulin therapies and important aspects of the postoperative management are presented.
ains · Anästhesiologie · Intensivmedizin 04/2011; 46(4):258-66; quiz 267. · 0.41 Impact Factor
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Anesthesiology 03/2011; 114(3):483-4. · 5.36 Impact Factor
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ABSTRACT: Current concepts of vascular permeability are largely still based on the Starling principle of 1896. Starling's contribution to understanding vascular fluid homeostasis comes from realising that the transport of fluid to and from the interstitial space of peripheral tissues follows the balance between opposing oncotic and hydrostatic pressures. It is presumed that in peripheral tissues fluid is readily filtered from blood to tissues at the arterial/arteriolar side of the circulation and largely reabsorbed at the venular/venous aspect, excess fluid being removed from the tissue by the lymphatic system. This balance is determined particularly by the properties of the vascular barrier. Recent studies have shown that the endothelial glycocalyx, located with a thickness of at least 200 nm on the luminal side of healthy vasculature, plays a vital role in vascular permeability by constituting the vascular barrier together with the endothelial cells themselves. While water and electrolytes can freely pass through the glycocalyx, plasma proteins, especially albumin, interact strongly. Binding and intercalating plasma constituents with the structural elements of the glycocalyx creates the so-called endothelial surface layer. This is the actual interface between flowing blood and the endothelial cell membrane in vivo. The oncotic pressure difference pertinent to fluid homeostasis is not built up between the intravascular and the interstitial tissue spaces, but within a small protein-free zone beneath the glycocalyx surface layer. This explains why perturbation of the glycocalyx leads to a breakdown of both fluid and protein handling in the coronary vascular bed. Preventing damage to the glycocalyx seems to be a promising goal in cardioprotection in many clinical scenarios, including acute ischaemia, hypoxia and inflammation, and chronic vascular disease as in atherosclerosis, diabetes and hypertension.
Archiv für Kreislaufforschung 11/2010; 105(6):687-701. · 7.35 Impact Factor
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ABSTRACT: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels.
Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle.
Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart.
Journal of Vascular Research 11/2010; 48(3):219-26. · 2.65 Impact Factor
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ABSTRACT: Adhesion of polymorphonuclear neutrophils (PMN) to coronary endothelium is a key event for cardiac ischemia/reperfusion injury. Adhesion molecules are normally harbored within the glycocalyx, clothing every healthy vascular endothelium, but shed by ischemia/reperfusion. Our aim was to show whether protection of the glycocalyx with either hydrocortisone or antithrombin can reduce postischemic leukocyte adhesion. Isolated guinea pig hearts, perfused with Krebs-Henseleit buffer, were subjected to 20 min of warm (37 degrees C) no-flow ischemia and consecutive 10 min of reperfusion, either in the absence or presence of hydrocortisone (10 microg/mL) or antithrombin (1 U/mL). An intracoronary bolus of 3 x 10 PMN was applied at the end of reperfusion but without prior contact to the drugs. The sequestration of PMN was calculated from the difference between coronary input and output of cells. Expression of the integrin CD11b on PMN was measured before and after coronary passage. Ischemia/reperfusion induced severe degradation of the glycocalyx (coronary venous syndecan-1 release, 171 +/- 15 ng/g heart vs. basal, 19 +/- 2 ng/g; heparan sulfate, 5.27 +/- 0.28 microg/g vs. basal, 0.26 +/- 0.06 microg/g) and increased PMN adhesion (38.1% +/- 3.5% vs. basal, 11.7% +/- 3.1%). Hydrocortisone and antithrombin both not only reduced glycocalyx shedding (syndecan-1 release, 34 +/- 6 ng/g and 26 +/- 5 ng/g; heparan sulfate, 1.96 +/- 0.24 microg/g and 1.28 +/- 0.2 microg/g, respectively), but also PMN adhesion (17.3% +/- 2.2% and 25.4% +/- 3.3%, respectively) after ischemia/reperfusion. Electron microscopy revealed a mostly intact coronary glycocalyx after pretreatment with either drug. Activation of PMN upon coronary passage was not influenced. Preservation of the glycocalyx mitigates postischemic PMN adhesion. Preconditioning with either hydrocortisone or antithrombin should, thus, alleviate vascular leakage, tissue edema, and inflammation.
Shock (Augusta, Ga.) 08/2010; 34(2):133-9. · 2.87 Impact Factor
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ABSTRACT: Damage of the endothelial glycocalyx, which ranges from 200 to 2000 nm in thickness, decreases vascular barrier function and leads to protein extravasation and tissue oedema, loss of nutritional blood flow, and an increase in platelet and leucocyte adhesion. Thus, its protection or the restoration of an already damaged glycocalyx seems to be a promising therapeutic target both in an acute critical care setting and in the treatment of chronic vascular disease. Drugs that can specifically increase the synthesis of glycocalyx components, refurbish it, or selectively prevent its enzymatic degradation do not seem to be available. Pharmacological blockers of radical production may be useful to diminish the oxygen radical stress on the glycocalyx. Tenable options are the application of hydrocortisone (inhibiting mast-cell degranulation), use of antithrombin III (lowering susceptibility to enzymatic attack), direct inhibition of the cytokine tumour necrosis factor-alpha, and avoidance of the liberation of natriuretic peptides (as in volume loading and heart surgery). Infusion of human plasma albumin (to maintain mechanical and chemical stability of the endothelial surface layer) seems the easiest treatment to implement.
Cardiovascular research 06/2010; 87(2):300-10. · 5.80 Impact Factor
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ABSTRACT: Perioperative patient handling should urgently be updated according to current evidence and, if none is available, at least according to physiological knowledge. To prevent pulmonary aspiration, preoperative fasting for 2 h (clear fluids) and 6 h (solid food) and abdication of 20 min for smoking is sufficient. Beta-blockage requires an indication. Bowel preparation should be abandoned and minimal invasive surgery as well as local and regional anaesthesia should be used where possible. Fluid therapy should be rational and requirement-adapted, and hypothermia, postoperative nausea and vomiting, unnecessary drains, tubes and catheters avoided. A multi-modal opioid-sparing pain therapy, sufficient oxygenation as well as early nutrition and mobilisation all play an important role for patient outcome. Recent studies have postulated that combining single-modality evidence-based care principles into a multi-modal effort to enhance postoperative recovery has improved patient outcome. Henrik Kehlet termed such a principle the 'fast-track concept', comprehending the entire perioperative phase starting with preoperative preparation, over atraumatic surgical and anaesthesiological techniques reducing the neuroendocrine stress response and also comprising the postoperative treatment. This strategy has been shown to positively influence organ function, homeostasis, morbidity, need for hospitalisation and convalescence and, therefore, to reduce costs. Despite these promising results, general implementation of evidence-based measures leaves a lot to be desired. Further development of surgical minimally invasive techniques and ongoing evaluation of procedure-specific strategies is urgently warranted.
Baillière' s Best Practice and Research in Clinical Anaesthesiology 06/2010; 24(2):267-81.
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ABSTRACT: Regional anaesthesia has gained increasing importance during the last decades. Successful regional anaesthesia for shoulder surgery requires a detailed knowledge of the relevant anatomy. Interscalene nerve blocks are most frequently used to anaesthetize the shoulder and among them the techniques according to Winnie, Meier, Pippa and Borgeat are the most popular. The techniques described by Meier and Borgeat are characterized by low complication rates. They are efficient for the majority of surgical procedures and therefore offer an interesting supplementation or an alternative to general anaesthesia. When carried out as a catheter-technique they provide a high quality postoperative pain therapy.
ains · Anästhesiologie · Intensivmedizin 08/2009; 44(7-8):522-9. · 0.41 Impact Factor
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ABSTRACT: For decades, the 'third space' was looked upon as an actively consuming compartment. Therefore, perioperative fluid regimens were traditionally based on a generous replacement of this assumed primary loss, in addition to deficits due to insensible perspiration and fasting. The practical consequence was an extremely positive fluid balance in order to maintain blood volume during major surgery. Whereas the insensible perspiration and the preoperative deficits are in fact often negligible, and the third space appears to be only a fictional construct, the excess fluid most likely accumulates interstitially. Such shifting is related to a destruction of the endothelial glycocalyx, a key structure of the vascular barrier, by traumatic inflammation and iatrogenic hypervolaemia. This explains why patients undergoing major surgical interventions benefit significantly from an infusion regimen which does not substitute but avoids 'third-space shifting'. In summary, eradicating this notion from our minds could be a further key to achieving perioperative fluid optimisation.
Baillière' s Best Practice and Research in Clinical Anaesthesiology 07/2009; 23(2):145-57.
