Postoperative cognitive dysfunction after beach chair positioning compared to supine position in orthopaedic surgery in the elderly.

INTRODUCTION: Postoperative cognitive dysfunction (POCD) occurs in up to 26% of patients older than 60 years 1 week after non-cardiac surgery. Intraoperative beach chair positioning (BCP) is advantageous for some types of shoulder surgery. However, this kind of positioning leads to a downward bound redistribution of blood volume, with possible hypoperfusion of the brain. We hypothesized that patients > 60 years undergoing orthopaedic shoulder surgery in a BCP might experience more POCD than patients operated in the supine position (SP). MATERIAL AND METHODS: A single-centre, prospective observational trial of 114 orthopaedic patients was performed. Study groups were established according to the type of intraoperative positioning. Anaesthesiological management was carried out similarly in both groups, including types of anaesthetics and blood pressure levels. POCD was evaluated using the Trail Making Test, the Letter-Number Span and the Regensburger Word Fluency Test. The frequency of POCD 1 week after surgery was considered primary outcome. RESULTS: Baseline characteristics, including duration of surgery, were comparable in both groups. POCD after 1 week occurred in 10.5% of SP patients and in 21.1% of BCP patients (p = 0.123; hazard ratio 2.0 (CI 95% 0.794-5.038)). After 4 weeks, the incidence of POCD decreased (SP: 8.8% vs. BCP: 5.3%; p = 0.463). 12/18 patients with POCD showed changes in their Word Fluency Tests. Near-infrared spectroscopy (NIRS) values were not lower in patients with POCD compared to those without POCD (54% (50/61) vs. 57% (51/61); p = 0.671). CONCLUSION: POCD at 1 week after surgery tended to occur more often in patients operated in beach chair position compared to patients in supine position without being statistically significant.

[Inhalational anesthetics]. / Inhalationsanästhetika.

Inhalational anesthetics have been used for induction and maintenance of general anesthesia for more than 150 years. All of the currently used inhalational anesthetics are chlorinated and fluorinated derivatives of ether. Dosing is carried out using the minimal alveolar concentration (MAC) concept. The pharmacokinetic properties of the various inhalational anesthetics are governed by the specific distribution coefficients. Mechanisms of action include specific modulations of various receptors of the central nervous system as well as an unspecific interaction with the cell membrane. Organ toxicity of modern inhalational anesthetics is considered to be minimal. The role of inhalational anesthetics in the context of postoperative nausea and vomiting (PONV) has been reassessed in recent years. The superiority of inhalational anesthetics over intravenous hypnotics with respect to intraoperative awareness is undisputed. The organ protective mechanism of preconditioning is an exclusive property of inhalational anesthetics among all the currently available hypnotics.

No Differences in Renal Function between Balanced 6% Hydroxyethyl Starch (130/0.4) and 5% Albumin for Volume Replacement Therapy in Patients Undergoing Cystectomy: A Randomized Controlled Trial.

BACKGROUND: The use of artificial colloids has declined in critical care, whereas they are still used in perioperative medicine. Little is known about the nephrotoxic potential in noncritically ill patients during routine surgery. The objective of this trial was to evaluate the influences of albumin 5% and balanced hydroxyethyl starch 6% (130/0.4) on renal function and kidney injury. METHODS: One hundred urologic patients undergoing elective cystectomy were randomly assigned for this prospective, single-blinded, controlled study with two parallel groups to receive either albumin 5% or balanced hydroxyethyl starch 6% (130/0.4) as the only perioperative colloid. The primary endpoint was the ratio of serum cystatin C between the last visit at day 90 and the first preoperative visit. Secondary endpoints were estimated glomerular filtration rate and serum neutrophil gelatinase-associated lipocalin until the third postoperative day and risk, injury, failure, loss, and end-stage renal disease criteria at postoperative days 3 and 90. RESULTS: The median cystatin C ratio was 1.11 (interquartile range, 1.01 to 1.23) in the albumin and 1.08 (interquartile range, 1.00 to 1.20) in the hydroxyethyl starch group (median difference = 0.03; 95% CI, -0.09 to 0.08; P = 0.165). Also, there were no significant differences concerning serum cystatin C concentrations; estimated glomerular filtration rate; risk, injury, failure, loss, and end-stage renal disease criteria; and neutrophil gelatinase-associated lipocalin. Infusion requirements, transfusion rates, and perioperative hemodynamics were similar in both groups. CONCLUSIONS: With respect to renal function and kidney injury, this study indicates that albumin 5% and balanced hydroxyethyl starch 6% have comparable safety profiles in noncritically ill patients undergoing major surgery.

Obesity-induced hyperleptinemia improves survival and immune response in a murine model of sepsis.

BACKGROUND: Obesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death. METHODS: The authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture. RESULTS: The authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10). CONCLUSIONS: Relative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy.

Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.

INTRODUCTION: Acute normovolemic hemodilution (ANH) and volume loading (VL) are standard blood-sparing procedures. However, VL is associated with hypervolemia, which may cause tissue edema, cardiopulmonary complications and a prolonged hospital stay. The body reacts to hypervolemia with release of atrial natriuretic peptide (ANP) from the heart. ANP has been shown to deteriorate the endothelial glycocalyx, a vital part of the vascular permeability barrier. The aim of the present study was to evaluate and compare ANP release and damage to the glycocalyx during ANH and VL. METHODS: ANH or VL with 6% hydroxyethyl starch 130/0.4 was administered prior to elective surgery in patients of good cardiopulmonary health (n =9 in each group). We measured concentrations of ANP in plasma and of three main constituent parts of the glycocalyx (hyaluronan, heparan sulfate and syndecan 1) in serum before and after ANH or VL. Heparan sulfate and syndecan 1 levels in urine were also determined. RESULTS: In contrast to ANH, VL (20 ml/kg) induced a significant release of ANP (approximately +100%, P <0.05) and increased the serum concentration of two glycocalyx constituents, hyaluronan and syndecan 1 (both by about 80%, P <0.05). Elevation of syndecan 1 was also detected in the urine of patients undergoing VL, but no increase was found in patients undergoing ANH. Heparan sulfate levels were not influenced by either procedure. CONCLUSION: These data suggest that hypervolemia increases the release of ANP and causes enhanced shedding of the endothelial glycocalyx. This perturbation must be expected to impair the vascular barrier, implying that VL may not be as safe as generally assumed and that it should be critically evaluated.

Protection of glycocalyx decreases platelet adhesion after ischaemia/reperfusion: an animal study.

BACKGROUND: Strategies targeting the protection of the vascular barrier, in particular the endothelial glycocalyx, are subjects of current research. Antithrombin III and hydrocortisone have been shown to reduce shedding of the glycocalyx following ischaemia/reperfusion. Platelet adhesion to endothelial cells is one consequence of ischaemia/reperfusion. OBJECTIVE: Our goal was to evaluate the effect of pharmacological protection of the glycocalyx on platelet adhesion. DESIGN: An experimental interventional animal study. SETTING: The study was carried out in a basic science laboratory at the University of Munich. ANIMALS: Eighty male guinea pigs (250 to 300 g) were used for the experiment. MAIN OUTCOME MEASURES: The effect of preischaemic treatment with hydrocortisone 10 µg ml(-1) or antithrombin 1 IU ml on adherence of platelets was evaluated in isolated, beating guinea pig hearts (Langendorff model). Hearts were subjected to warm ischaemia (20 min at 37 °C) and consecutive reperfusion. Platelets were injected at the beginning of reperfusion via the aortic cannula and platelet concentration was measured in the effluent (after passing through the coronary vascular system). RESULTS: Ischaemia and reperfusion led to significant shedding of the endothelial glycocalyx. Coronary venous release of syndecan-1 increased nine-fold, and heparan sulphate showed a 20.3-fold increase after ischaemia/reperfusion (both P < 0.01). Pretreatment with hydrocortisone or antithrombin III reduced endothelial glycocalyx shedding significantly (P < 0.05). Adherence of platelets to the coronary vascular bed increased more than 2.5-fold when they were injected during reperfusion. About 40% of this increase was blocked by pretreatment of hearts with hydrocortisone or antithrombin. CONCLUSION: Pretreatment with hydrocortisone or antithrombin III can reduce platelet adhesion during reperfusion after warm ischaemia by protection of the endothelial glycocalyx.

The intravascular volume effect of Ringer's lactate is below 20%: a prospective study in humans.

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/m(2) 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.

Perspectives in microvascular fluid handling: does the distribution of coagulation factors in human myocardium comply with plasma extravasation in venular coronary segments?

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Sevoflurane reduces leukocyte and platelet adhesion after ischemia-reperfusion by protecting the endothelial glycocalyx.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The glycocalyx of the human umbilical vein endothelial cell: an impressive structure ex vivo but not in culture.

Potter and Damiano recently assessed the hydrodynamic dimensions of the endothelial glycocalyx in vivo (mouse cremaster muscle venules) and in vitro (human umbilical vein and bovine aorta endothelium cultured in perfused microchannels) using fluorescent microparticle image velocimetry (Circ Res. 2008;102:770-776). Great discrepancy was observed, the glycocalyx presenting a zone of interaction extending approximately 0.52 microm into the vessel lumen in vivo, but only 0.02 to 0.03 microm from cultured cells. In an accompanying editorial, Barakat cautioned that the difference in hydrodynamic interaction did not allow one to conclude that the cultured cells totally lack a physical cell surface layer capable of mechanotransduction (Circ Res. 2008;102:747-748). To stabilize the glycocalyx for electron microscopic investigation, we perfusion-fixed 6 human umbilical veins and confluent and nonconfluent cultures (5 each) of human umbilical vein endothelial cells (HUVECs) with lanthanum/glutaraldehyde solution. Ex vivo, the thickness of glycocalyx of umbilical vein endothelium averaged 878 nm. HUVECs in vitro presented a glycocalyx with a dense-zone thickness of only 29.4 nm, plus sparse filaments reaching out on average to 118 nm, there being no difference between the nonconfluent and confluent cells. Immunohistology demonstrated the presence of heparan sulfates and syndecan-1, main constituents of the glycocalyx, both ex vivo and in vitro. These results support the observed discrepancy between glycocalyx thickness in vivo and in vitro, now for one and the same type of human cell. The presence of heparan sulfates and syndecan-1 also on cultured cells may explain why mechanotransduction phenomena can be observed even with a nonmature glycocalyx.

Pharmacology of peripheral opioid receptors.

PURPOSE OF REVIEW: Since the detection of morphine by the pharmacologist Friedrich Sertürner in 1806, opioids have been used as potent centrally acting analgesics. In addition to the central site of action, peripheral endogenous opioid analgesic systems have been extensively studied, especially in the past two decades. This review is not only mentioned to give a brief summary in this well investigated field of peripheral opioid receptors, but also to highlight the role of peripheral opioid receptors in other physiological and pathophysiological conditions. RECENT FINDINGS: A number of studies, which initially focused on nociception, also revealed an important role of the peripheral opioid receptor system in opioid-induced bowel dysfunction and pruritus, as well as in wound healing, cardioprotection, and the analgesic effects of celecoxib. SUMMARY: Efforts continue to develop opioid analgesics unable to cross the blood-brain barrier, which act only peripherally in low doses, thus providing adequate analgesia without central and systemic side-effects.The awareness of the influence of peripheral opioid receptors beyond nociception may also have therapeutic ramifications on the other fields mentioned above. For example, the treatment of opioid-induced bowel dysfunction by methylnaltrexone is one of the major findings in the previous years.

Non-invasive evaluation of macro- and microhemodynamic changes during induction of general anesthesia - A prospective observational single-blinded trial.

BACKGROUND: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support. OBJECTIVE: Determination of macro- and microhemodynamic changes during induction of general anesthesia. METHODS: We enrolled 150 female adults scheduled for gynaecological surgery into this prospective observational, single-blinded trial. Besides routinely measuring heart rate (HR) and mean arterial blood pressure (MAP), the non-invasive technique of thoracic electrical bioimpedance was applied to measure cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume variability (SVV) and index of myocardial contractility (ICON) before induction of anesthesia, 7 times during induction, and, finally, after surgery in the recovery room. Changes in microcirculation were assessed using sidestream dark field imaging to establish the perfused boundary region (PBR), a validated gauge of glycocalyx health. Comparisons were made with Friedman's or Wilcoxon test for paired data, and with Mann-Whitney-U test for unpaired data, with post-hoc corrections for multiple measurements by the Holm-Bonferroni method. RESULTS: 83 patients did not need vasopressor support, whereas 67 patients required therapy (norepinephrine, atropine or cafedrine/theodrenaline) to elevate MAP values to ≥70mmHg during induction, 54 of these receiving norepinephrine (NE) alone. Pre-interventional (basal) values of CO, CI, ICON, SV and SVV were all significantly lower in the group of patients later requiring NE (p < 0.04), whereas HR and MAP were identical for both groups. HR, MAP and CO decreased from baseline to 12 min after induction of general anesthesia in both the patients without and those with NE support. Heart rate decreased significantly by about 25% in both groups (-19 to -21 bpm). The median individual decrease of MAP amounted to -26.7% (19.7/33.3, p < 0.001) and -26.1% (11.6/33.2, p < 0.001), respectively, whereas for CO it was -40.7% (34.1/50.1, p < 0.001) and -43.5% (34.8/48.7). While these relative changes did not differ between the two groups, in absolute values there were significantly greater decreases in CO, CI, SV and ICON in the group requiring NE. Noteably, NE did not restore ICON or the other cardiac parameters to levels approaching those of the group without NE. PBR was measured in a total of 84 patients compiled from both groups, there being no intergroup differences. It increased 6.4% (p < 0.001) from pre-induction to the end of the operation, indicative of damage to microvascular glycocalyx. CONCLUSION: Non-invasive determination of CO provides additional hemodynamic information during anesthesia, showing that induction results in a significant decrease not only of MAP but also of CO and other cardiac factors at all timepoints compared to baseline values. The decrease of CO was greater than that of MAP and, in contrast to MAP, did not respond to NE. There was also no sign of a positive inotropic effect of NE in this situation. Support of MAP by NE must consequently result from an increase in peripheral arterial resistance, posing a risk for oxygen supply to tissue. In addition, general anesthesia and the operative stimulus lead to an impairment of the microcirculation.

TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin.

BACKGROUND: Healthy vascular endothelium is clothed by the endothelial glycocalyx. This structure plays a key role in the regulation of inflammation and vascular permeability and is known to be degraded by ischemic and inflammatory stress. Our aim was to show whether hydrocortisone and antithrombin stabilize the glycocalyx and, therefore, the vascular barrier, against damage induced by the inflammatory stimulus TNF-alpha, thus improving the cardio-vascular situation. METHODS: Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer for 20 min at constant flow (baseline perfusion pressure 70 cmH(2)O). Hydrocortisone in a stress dose (10 microg/ml) or antithrombin in a physiological dose (1 U/ml) were then applied for 15 min before infusion of TNF-alpha (4 ng/ml, 10 min). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Hearts were perfusion-fixed to visualize the glycocalyx. RESULTS: TNF-alpha induced severe degradation of the glycocalyx, increased coronary resistance, heightened vascular leak and permeability to hydroxyethyl starch and caused mast-cell degranulation. Hydrocortisone and antithrombin both reduced all of these effects. Electron microscopy revealed a mostly intact glycocalyx after treatment with either drug. CONCLUSIONS: Both hydrocortisone and antithrombin clearly preserve the endothelial glycocalyx in the face of inflammatory degradation initiated by TNF-alpha, however, with different mechanisms. This is an important new facet in the pathophysiology and therapy of sepsis, since preservation of the glycocalyx should help prevent vasoconstriction, tissue edema as well as leukocyte and platelet adhesion, thus mitigating inflammation and tissue hypoxia.

High Temporal Summation of Pain Predicts Immediate Analgesic Effect of Acupuncture in Chronic Pain Patients-A Prospective Cohort Study.

Objectives: This prospective cohort study explored whether two distinguished sensory parameters predicted acupuncture effects in chronic pain patients; namely high temporal summation of pain (TS) indicating spinal synaptic facilitation as well as a low vibration detection threshold (VDT) indicating a loss of Aß-fiber function. Methods: Pinprick induced TS and VDT were assessed by standardized, validated methods at the most painful body site and a pain free control site in 100 chronic pain patients receiving six acupuncture sessions as part of an interdisciplinary multimodal pain treatment (IMPT). Immediate change in pain intensity after the first acupuncture session (first treatment on the first day of IMPT) was assessed by the verbal rating scale (VRS, 0-100). After 4 weeks of treatment, patients indicated in a questionnaire whether acupuncture had relieved pain immediately and whether it had contributed to overall pain reduction and well-being after IMPT. Results: Logistic regression analysis revealed an association between high TS at the control site and a reduction in pain intensity of at least 30% (VRS) after the first acupuncture (OR [95%-CI] 4.3 [1.6-11.8]). Questionnaire ratings of immediate pain relief after acupuncture were associated with high TS at the control site (OR [95%-CI] 3.8 [1.4-10.2] any pain relief, OR [95%-CI] 5.5 [1.7-17.1] over 50% pain reduction) and at the pain site (OR [95%-CI] 3.2 [1.2-8.9] any pain relief). Appraisals of the contribution of acupuncture to overall pain reduction and well-being after IMPT were not associated with TS. The VDT was not associated with any outcome. Conclusion: This explorative study provides first-time evidence that high TS, especially at a pain free control site, but not VDT, might predict immediate analgesic response to acupuncture in chronic pain patients. Thus, highly centrally sensitized chronic pain patients might respond particularly well to acupuncture.

Effects of balanced hydroxyethyl starch 6% (130/0.4) and albumin 5% on clot formation and glycocalyx shedding: Subgroup analysis of a prospective randomized trial.

BACKGROUND: Intravenous fluids can impair coagulation and affect the endothelial glycocalyx, whereas glycocalyx shedding itself can cause an impairment of clot formation and firmness. We hypothesized that hydroxyethyl starch 6% (130/0.4) has a more distinct effect on coagulation and glycocalyx shedding than albumin 5%. METHODS: Presented data derive from an exploratory subgroup analysis of a prospective randomized, single-blinded trial comparing albumin 5% versus balanced hydroxyethyl starch 6% (130/0.4). Patients between 46 and 85 years undergoing cystectomy were included. Prothrombin time, plasma fibrinogen concentration, partial thromboplastin time, thrombelastometry and platelet function were analyzed before and after surgery. Glycocalyx components were assessed before and after surgery, 2 to 4 h after surgery and at 1st and 3rd postoperative day. Primary outcome parameter was the change of thrombelastometric variables at the end of surgery. Further variables included calculated blood loss, infusion amount and transfusion rate. RESULTS: 55 patients (albumin group n = 28; hydroxyethyl starch group n = 27) were included. Thrombelastometric variables were significantly more compromised in the hydroxyethyl starch than in the albumin group whereas platelet function, glycocalyx shedding, partial thromboplastin time, prothrombin time and fibrinogen were not different between groups. Mean intraoperative calculated blood loss was higher in the hydroxyethyl starch group (1557 ±â€¯825 ml versus 1245 ±â€¯709 ml; p = 0.042). Transfusion requirements did not differ. CONCLUSION: Rotational thrombelastometric variables were significantly more reduced when hydroxyethyl starch was used compared to albumin 5%. This effect was independent from a shedding of the endothelial glycocalyx. However, results presented here are from a subgroup analysis and must be considered with caution. Trial registration EudraCT number 2010-018343-34.

Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia.

BACKGROUND: The astonishing thickness of the endothelial glycocalyx, which rivals that of endothelial cells in the microvasculature, was disclosed in the last 15 years. As already demonstrated, this structure plays a key role in the regulation of inflammation and vascular permeability. METHODS AND RESULTS: Two components of the glycocalyx, syndecan-1 and heparan sulfate, were measured in arterial blood of 18 patients undergoing surgery of the ascending aorta with cardiopulmonary bypass (n=12 with and n=6 without deep hypothermic circulatory arrest) and of 14 patients undergoing surgery for infrarenal aortic aneurysm. Basal values of syndecan-1 (1.2 microg/dL) and heparan sulfate (590 microg/dL) of patients were similar to those of control subjects. Anesthesia and initiation of surgery caused no changes. Global ischemia with circulatory arrest (n=12) was followed by transient 42- and 10-fold increases in syndecan-1 and heparan sulfate, respectively, during early reperfusion (0 to 15 minutes). After regional ischemia of heart and lungs (cardiopulmonary bypass; n=6), syndecan-1 increased 65-fold, and heparan sulfate increased 19-fold. Infrarenal ischemia was followed by 15- and 3-fold increases, respectively (n=14). The early postischemic rises were positively correlated (r=0.76, P<0.001). Plasma concentrations of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 did not change. Circulating polymorphonuclear granulocytes and the level of postischemic heparan sulfate corresponded negatively. Immunohistochemical imaging and immunoassay of isolated hearts (guinea pig) substantiated syndecan-1 and heparan sulfate as components of the endothelial glycocalyx released into the coronary venous effluent. Electron microscopy revealed shedding of the glycocalyx after ischemia/reperfusion. CONCLUSIONS: This study provides the first evidence in humans for shedding of the endothelial glycocalyx during ischemia/reperfusion procedures.

Methylnaltrexone, a new peripheral mu-receptor antagonist for the prevention and treatment of opioid-induced extracerebral side effects.

Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.

A rational approach to perioperative fluid management.

Replacement of assumed preoperative deficits, in addition to generous substitution of an unsubstantiated increased insensible perspiration and third space loss, plays an important role in current perioperative fluid regimens. The consequence is a positive fluid balance and weight gain of up to 10 kg, which may be related to severe complications. Because the intravascular blood volume remains unchanged and insensible perspiration is negligible, the fluid must accumulate inside the body. This concept brings into question common liberal infusion regimens. Blood volume after fasting is normal, and a fluid-consuming third space has never been reliably shown. Crystalloids physiologically load the interstitial space, whereas colloidal volume loading deteriorates a vital part of the vascular barrier. The endothelial glycocalyx plays a key role and is destroyed not only by ischemia and surgery, but also by acute hypervolemia. Therefore, undifferentiated fluid handling may increase the shift toward the interstitial space. Using the right kind of fluid in appropriate amounts at the right time might improve patient outcome.

Opioid-induced constipation in intensive care patients: relief in sight?

Constipation is the most common gastrointestinal complication associated with opioid therapy in chronic pain patients, and also frequently occurs in sedated intensive care unit patients. Conventional therapy may not provide sufficient relief from constipation, which can be severe enough to limit opioid use or the dose. In a recent study on terminally ill patients suffering from laxative-resistant opioid-induced constipation, Thomas and colleagues demonstrated subcutaneous methylnaltrexone to rapidly induce defecation. This appealing result might also have favourable prospects for intensive care patients, as their outcome is often codetermined by recovery of bowel functioning.