Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

PURPOSE: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. METHODS: Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). RESULTS: Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th-19.1375th to 13.9 ng/ml 9.625th-28.975th; p=0.026), indicating shedding and degradation of the EGX. CONCLUSION: A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches.

Response of patients with melanoma to immune checkpoint blockade - insights gleaned from analysis of a new mathematical mechanistic model.

Immune checkpoint inhibitors (ICI) are becoming widely used in the treatment of metastatic melanoma. However, the ability to predict the patient's benefit from these therapeutics remains an unmet clinical need. Mathematical models that predict melanoma patients' response to ICI can contribute to better informed clinical decisions. Here, we developed a simple mathematical population model for pembrolizumab-treated advanced melanoma patients, and analyzed the local and global dynamics of the system. Our results show that zero, one, or two steady states of the mathematical system exist in the phase plane, depending on the parameter values of individual patients. Without treatment, the simulated tumors grew uncontrollably. At increased efficacy of the immune system, e.g., due to immunotherapy, two steady states were found, one leading to uncontrollable tumor growth, and the other resulting in tumor size stabilization. Model analysis indicates that a sufficient increase in the activation of CD8+ T cells results in stable disease, whereas a significant reduction in T-cell exhaustion, another process contributing CD8+ T cell activity, temporarily reduces the tumor mass, but fails to control disease progression in the long run. Importantly, the initial tumor burden influences the response to treatment: small tumors respond better to treatment than larger tumors. In conclusion, our model suggests that disease progression and response to ICI depend on the ratio between activation and exhaustion rates of CD8+ T cells. The analysis of the model provides a foundation for the use of computational methods to personalize immunotherapy.

["Legal highs" (new psychoactive substances) : What does the anesthesiologist need to know?] / "Legal Highs" (neue psychoaktive Substanzen) : Was muss der Anästhesist wissen?

In recent years, the social media, the press and the internet have reported more about the topic of "legal highs" and new psychoactive substances (NPS). The use of these drugs is accompanied by a serious risk of undesired side effects, intoxication and even death. The often unknown chemical composition, unspecific clinical presentations and lack of quickly available routine diagnostic tests are aggravating factors in this situation. For anesthesiologists, knowledge of this dangerous substance class plays an important role in the field of preclinical treatment, perioperative management and intensive medical care.

[The spinal catheter in aortic surgery : Implications for anesthesia]. / Der Spinalkatheter in der Aortenchirurgie : Implikationen für die Anästhesie.

During surgical repair of aortic pathologies (e.g. dissection, aneurysms), cross-clamping of the aorta or overstenting of critical segmental arteries can lead to ischemia- and edema-related spinal cord damage with subsequent paraplegia. By regulating cerebrospinal fluid pressure, the spinal catheter is an effective method for prophylaxis and treatment of spinal cord ischemia. Due to the high complication rate of the spinal catheter a detailed risk-benefit assessment is obligatory: besides cerebrospinal fluid leakage, postpuncture headaches and local infections, feared complications, such as intracranial bleeding, meningitis and neuraxial hematomas can also occur, sometimes with a significant latent period after termination of the procedure. Adequate training of personnel in the perioperative handling of spinal catheters and meticulous adherence to drainage parameters are important components for increasing procedural safety. This is particularly true since the clinical aspects of catheter-associated complications only slightly differ from that of ischemic spinal cord injury.

State of the art in fluid and volume therapy : A user-friendly staged concept. English version.

Adequate intraoperative infusion therapy is essential for the perioperative outcome of a patient. Both hypo- and hypervolemia can lead to an increased rate of perioperative complications and to a worse outcome. Perioperative infusion therapy should therefore be needs-based. The primary objective is the maintenance of preoperative normovolemia using a rational infusion strategy. Perioperative fluid losses should be differentiated from volume losses due to surgical bleeding or protein losses into the interstitial space. Fluid loss via urine excretion or insensible perspiration (0.5-1.0 ml/kg/h) should be replaced with balanced, isooncotic, crystalloid infusion solutions in a ratio of 1:1. Volume therapy stage 1: intraoperative volume losses up to a blood loss corresponding to 20% of the patient's total blood volume are compensated for by balanced crystalloids in a ratio of 4-5:1. Stage 2: blood losses exceeding this level are to be treated with isooncotic colloids (preferably balanced) in a 1:1 ratio. In this regard taking into consideration the contraindications, e. g., sepsis, burns, critical illness (usually patients in the intensive care unit), impaired renal function or renal replacement therapy, intracranial hemorrhage, or severe coagulopathy, artificial colloids such as hydroxyethyl starch (HES) can be used perioperatively for volume replacement. Stage 3: if an allogeneic blood transfusion is indicated, blood and blood products are applied in a differentiated manner.

[Physiological changes during pregnancy]. / Physiologische Veränderungen in der Schwangerschaft.

The physiological state of a woman experiences multiple changes in the body during pregnancy. These alterations could be of particular importance in the medical care of pregnant women. This review article highlights the physiological developments of various organ systems throughout gestation with a focus on endocrinology, the cardiovascular system, hematology, the respiratory system and water balance.

[State of the art in fluid and volume therapy : A user-friendly staged concept]. / Stand der Wissenschaft in der Flüssigkeits- und Volumentherapie : Ein anwenderfreundliches Stufenkonzept.

Adequate fluid therapy is highly important for the perioperative outcome of our patients. Both, hypovolemia and hypervolemia can lead to an increase in perioperative complications and can impair the outcome. Therefore, perioperative infusion therapy should be target-oriented. The main target is to maintain the patient's preoperative normovolemia by using a sophisticated, rational infusion strategy.Perioperative fluid losses should be discriminated from volume losses (surgical blood loss or interstitial volume losses containing protein). Fluid losses as urine or perspiratio insensibilis (0.5-1.0 ml/kg/h) should be replaced by balanced crystalloids in a ratio of 1:1. Volume therapy step 1: Blood loss up to a maximum value of 20% of the patient's blood volume should be replaced by balanced crystalloids in a ratio of 4(-5):1. Volume therapy step 2: Higher blood losses should be treated by using iso-oncotic, preferential balanced colloids in a ratio of 1:1. For this purpose hydroxyethyl starch can also be used perioperatively if there is no respective contraindication, such as sepsis, burn injuries, critically ill patients, renal impairment or renal replacement therapy, and severe coagulopathy. Volume therapy step 3: If there is an indication for red cell concentrates or coagulation factors, a differentiated application of blood and blood products should be performed.

Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant.

BACKGROUND: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. METHODS: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. RESULTS: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. CONCLUSIONS: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment.

[Acute perioperative hemodilution without using hydroxyethyl starch : hemodynamic alterations under "controlled" hypovolemia]. / Akute perioperative Hämodilution ohne Verwendung von Hydroxyethylstärke : Hämodynamische Veränderungen unter "kontrollierter" Hypovolämie.

BACKGROUND: Up to now hydroxyethyl starch preparations have frequently been used to compensate for volume deficits accompanying blood withdrawal during acute normovolemic hemodilution. This approach was questioned with respect to the current limitations for use of hydroxyethyl starch solutions imposed by the European Medicines Agency. Because crystalloids distribute evenly across the whole extracellular compartment, 80 % of the infused solution will be "lost" to the interstitial space. Thus, a physiological adjustment of blood loss caused by hemodilution with crystalloids alone (1:5 ratio) seems hardly feasible and according to current data perhaps not even desirable. A 3:1 ratio (crystalloids versus blood loss) as applied in the current study can be regarded as a practical compromise between physiological needs and recommendations according to the literature (1.4:1) but will lead to moderate hypovolemia the hemodynamic consequences of which are not well described. AIM: The current study investigates the hemodynamic impact of a hemodilution with crystalloids under the precondition of a 3:1 substitution ratio compared to withdrawn blood. METHODS: In the context of acute perioperative hemodilution 10 otherwise healthy women graded I and II on the American Society of Anesthesiologists (ASA) classification scheduled for open gynecological cancer surgery underwent an average blood withdrawal of 1097 ± 285 ml which was substituted by an average of 3430 ± 806 ml of Ringer's lactate. The resulting deficit in blood volume was exactly quantified by a double tracer technique. Hemodynamic changes were evaluated by a combination of thermodilution and pulse contour analysis (PiCCO system®). Subsequently, the remaining volume deficit was compensated by 245 ± 64 ml of a 20 % albumin solution and hemodynamic parameters were again evaluated. RESULTS: When infusing Ringer's lactate in a 3:1 ratio compared to the actual blood loss, the blood volume decreased by 12 %. The volume effect of Ringer's lactate proved to be 17 %. While mean arterial pressure and heart rate remained constant, key hemodynamic parameters changed relevantly during the time course. A significant rise in cardiac output and myocardial contractility could be observed which was accompanied by a decrease in systemic vascular resistance. In contrast, cardiac preload and the parameters representing pulmonary vascular permeability remained unaltered. The infusion of 245 ± 64 ml of a 20 % albumin solution nearly completely restituted blood volume and led to an insignificant rise in systemic vascular resistance but did not normalize cardiac output or myocardial contractility. CONCLUSION: In the study population, the loss of intravascular fluid during perioperative haemodilution could be compensated by an increase in cardiac performance. However, whether patients with a reduced cardiac capacity (i.e. older patients) are capable to improve their cardiac output sufficiently in order to compensate hypovolemia accompanying perioperative haemodilution with crystalloids remains questionable.

[Limited applications for hydroxyethyl starch : background and alternative concepts]. / Anwendungsbeschränkung für Hydroxyäthylstärke : Hintergründe und alternative Konzepte.

BACKGROUND: Within the framework of a risk assessment procedure the Committee for Risk Assessment of Pharmacovigilance (PRAC) of the European Medicines Agency (EMA) came to the conclusion that the benefits of hydroxylethyl starch infusion solutions (HES) no longer outweighed the risks and on 14 June 2013 recommended that approval should be suspended. Until the procedure has finally been concluded, which could last several months, the Federal Institute for Drugs and Medical Products (BfArM) has recommended that HES should not be used. AIM: The aim of this article is to present the data situation in the most objective and compact way and to ultimately give the reader the foundations in order to be able to form a personal opinion. In addition an attempt will be made to describe a concept how infusion therapy can be carried out without using hydroxyethyl starch (HES). MATERIAL AND METHODS: The background to this decision is given based on a review of the literature and the relevance for intensive care, emergency and perioperative medicine is assessed. Furthermore, a concept of infusion therapy without hydroxyethyl starch is formulated also based on the results of current studies. RESULTS: For infusion regimens without HES it should be noted that gelatin represents a considerable risk for anaphylactic reactions, that transfer of the new variants of Creutzfeldt-Jacob disease (bovine spongiform encephalopathy BSE) cannot fundamentally be excluded and that some evidence has been found that gelatin can cause kidney injury, probably in a similar way to HES. With respect to the cost-benefit analysis of infusion solutions, blood loss in adults of approximately 1-1.5 l can be substituted by balanced crystalloids (basic therapy 4-5 times compared to the amount of blood lost). For larger blood losses small amounts of hyperoncotic albumin solution (20 %) or alternatively 5 % albumin solution can be used. The 20 % albumin solution seems to have some advantages because it has a higher volume effect (approximately 200 %) and can be more favourable for the fluid balance than 5 % albumin solution. Blood losses greater than 2-3 l normally also require administration of blood products (e.g. fresh frozen plasma FFP and erythrocyte concentrates EC). CONCLUSIONS: The third generation HES solutions cannot be completely replaced by other colloids and in future crystalloids will more strongly again broadly form the basis for infusion therapy. In this aspect balanced crystalloids have priority with respect to the acid-base equilibrium. The history of HES has impressively shown that infusion therapy must be adjusted on a scientifically founded basis, whether in intensive care medicine, perioperative or emergency medicine. Large prospective studies with clinically relevant endpoints are urgently needed.

Shedding of the coronary endothelial glycocalyx: effects of hypoxia/reoxygenation vs ischaemia/reperfusion.

BACKGROUND: Vascular endothelium is covered by a glycocalyx. Damage to the glycocalyx after systemic inflammation or ischaemia/reperfusion contributes to increased vascular permeability and leucocyte adhesion. The underlying mechanisms leading to ischaemia/reperfusion-induced glycocalyx shedding are incompletely understood, in terms of lack of oxygen, absence of flow, or return of oxygen. METHODS: Isolated guinea pig hearts perfused with Krebs-Henseleit buffer at 37°C underwent 20 min of either stopped-flow ischaemia or hypoxic perfusion with subsequent reperfusion/reoxygenation (n = 6 each). Hearts perfused with normoxic buffer served as time controls. Epicardial transudate was collected to assess coronary net fluid filtration, colloid extravasation, and histamine release by mast cells. Syndecan-1 and heparan sulphate were measured in coronary effluent, together with lactate, purines, and the release of mast-cell tryptase ß. Additional hearts were perfusion-fixed to visualize the glycocalyx. RESULTS: Both ischaemia and hypoxia with reperfusion/reoxygenation resulted in significant increases in net fluid filtration (P < 0.05) and release of syndecan-1 and heparan sulphate in coronary effluent. These effects were already seen with the onset of hypoxic perfusion. Histamine was released during hypoxia and reoxygenation and also reperfusion, as was tryptase ß, and high concentrations of adenosine (>1 µmol litre⁻¹, hypoxia group) and inosine (> 7 µmol litre⁻¹, ischaemia group) were measured in effluent (P < 0.05). Damage to the coronary glycocalyx was evident upon electron microscopy. CONCLUSIONS: Both ischaemic and hypoxic hypoxia initiate glycocalyx degradation, promoting an increase in permeability. A contributing mechanism could be purine-mediated degranulation of resident mast cells, with liberated tryptase ß acting as potential 'sheddase'.

Sevoflurane preserves the endothelial glycocalyx against ischaemia-reperfusion injury.

BACKGROUND: Healthy vascular endothelium is coated by the glycocalyx, important in multiple endothelial functions, but destroyed by ischaemia-reperfusion. The impact of volatile anaesthetics on this fragile structure has not been investigated. We evaluated the effect of cardiac pre- and post-conditioning with sevoflurane on integrity of the endothelial glycocalyx in conjunction with coronary vascular function. METHODS: Isolated guinea pig hearts perfused with Krebs-Henseleit buffer underwent 20 min stopped-flow ischaemia (37 degrees C), either without or with 1 MAC sevoflurane. This was applied for 15 min before, for 20 min after, or both before and after ischaemia. Transudate was collected for assessing coronary net fluid extravasation and histamine release by mast cells. Coronary release of syndecan-1 and heparan sulphate was measured. In additional experiments with and without continuous sevoflurane, cathepsin B and tryptase beta-like protease activity were measured in effluent. Hearts were perfusion-fixed to visualize the endothelial glycocalyx. RESULTS: Ischaemia led to a significant (P<0.05) increase by 70% in transudate formation during reperfusion only in hearts without sevoflurane. This was accompanied by significant (P<0.05) increases in heparan sulphate (four-fold) and syndecan release (6.5-fold), with electron microscopy revealing massive degradation of glycocalyx. After ischaemia, histamine was released into transudate, and cathepsin B activity increased in effluent (P<0.05). Sevoflurane application attenuated all these changes, except for histamine release. CONCLUSIONS: Sevoflurane protects the endothelial glycocalyx from ischaemia-reperfusion-induced degradation, with both preconditioning and rapid post-conditioning being successful. The mechanism seems to involve attenuation of lysosomal cathepsin B release and to be independent from tissue mast cell degranulation.

Fluid resuscitation after severe trauma injury : U-shaped associations between tetrastarch dose and survival time or frequency of acute kidney failure.

BACKGROUND: Using tetrastarch for fluid resuscitation after a severe trauma injury may increase risks of death and acute kidney injury. The importance of tetrastarch dose, however, is unknown. METHODS: A retrospective observational study was performed in two trauma centres using data on type and amount of fluids (balanced crystalloids or tetrastarch) used for pre- and acute in-hospital shock management. We evaluate independent associations between the relative and absolute volumes of tetrastarch and 90-day survival time or the frequency of severe acute kidney failure (AKF). RESULTS: We studied 271 patients who had sustained a severe blunt trauma injury (average predicted mortality according to the Revised Injury Severity Classification Score (RISC) 15.1 ± 1.4% [mean, standard deviation]), and who had required more than 2 days of intensive care therapy. In all, 75.3% of patients had received tetrastarch with a crystalloid/colloid ratio of 2.93 ± 2.60. The 90-day mortality was 11.1%, and 7.8% of the patients developed severe AKF. After adjusting for confounders, we found a U-shaped, nonlinear association between absolute or relative volumes of tetrastarch and survival time (p = 0.003 and 0.025, respectively). Optimal relative volumes of tetrastarch approximately ranged from 20 to 30% of total fluids. Giving less than about 1000 ml, or more than about 2000 ml tetrastarch was significantly associated with an increased risk of developing severe AKF (p = 0.023). CONCLUSIONS: There was a complex U­shaped association between the tetrastarch dose and morbidity/mortality of patients after a severe trauma injury. The optimal crystalloid/tetrastarch ratio for acute shock management appears to range from about 2.5 to 4.0.

Early loss of mammalian target of rapamycin complex 1 (mTORC1) signalling and reduction in cell size during dominant-negative suppression of hepatic nuclear factor 1-alpha (HNF1A) function in INS-1 insulinoma cells.

AIMS/HYPOTHESIS: Mutations in the HNF1A (previously known as TCF1) gene encoding hepatocyte nuclear factor-1alpha (HNF1A) lead to the development of maturity-onset diabetes of the young, type 3 (HNF1A-MODY), characterised by impaired insulin secretion and a reduction in beta cell mass. HNF1A plays an important role in pancreatic beta cell differentiation and survival. The mammalian target of rapamycin (mTOR) is a central growth factor- and nutrient-activated protein kinase controlling cell metabolism, growth and survival. We investigated the role of mTOR inactivation in the decline in beta cell mass in a cellular model of HNF1A-MODY. METHODS: Previously we showed that suppression of HNF1A function via expression of a dominant-negative mutant (DN-HNF1A) decreases insulin gene transcription in insulinoma (INS-1) cells. We investigated the signalling of two distinct mTOR protein complexes, mTORC1 and mTORC2, in response to DN-HNF1A induction. RESULTS: We observed delayed inactivation of mTORC2 48 h after DN-HNF1A induction, evidenced by a reduction in serine 473 phosphorylation of thymoma viral proto-oncogene 1 (AKT1). We also observed an early inactivation of mTORC1 24 h after DN-HNF1A induction, which was detected by decreases in threonine 389 phosphorylation of p70 ribosomal protein S6 kinase (S6K1) and serine 65 phosphorylation of translational inhibitor eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). Flow cytometry and gene expression analysis demonstrated a pre-apoptotic decrease in INS-1 cell size in response to DN-HNF1A induction, and an increase in the level of the mTORC1-regulated cell-cycle inhibitor, cyclin-dependent kinase inhibitor 1B p27. CONCLUSIONS/INTERPRETATION: Our data suggest that mTOR kinase and signalling through mTORC1 are highly sensitive to suppression of HNF1A function, and may contribute to disturbance of cell-size regulation and cell-cycle progression in HNF1A-MODY.

[Hypernatremic alkalosis. Possible counterpart of hyperchloremic acidosis in intensive care patients?]. / Hypernatriämische Alkalose. Pendant zur hyperchlorämischen Acidose in der Intensivmedizin?

BACKGROUND: With broad acceptance of Stewart's acid-base model "hyperchloremic acidosis" is regarded as an independent form of metabolic disorder. It is unknown whether hypernatremia plays a corresponding role with respect to the development of alkalosis. METHODS: A total of 201 artificially ventilated, critically ill patients were monitored for hypernatremic episodes. Inclusion criterion was a serum sodium concentration above 145 mmol/l. RESULTS: In 20 patients a total of 78 periods of elevated plasma sodium levels lasting at least 24 h were observed. In 86% of these cases sodium and chloride concentrations were simultaneously increased. The development of alkalosis correlated with the strong ion difference (r=0.80, p<0.01) but not with the serum sodium concentration (r=-0.031, p=0.78). In cases without accompanying hyperchloremia (13%) metabolic alkalosis regularly occurred and a correlation between serum sodium concentration and base excess could be verified (r=0.66, p=0.03). Alkalosis occurred in 84.8% of cases where the strong on difference exceeded 39 mmol/l. CONCLUSION: From the available data hypernatremic alkalosis could not be defined as an independent metabolic disorder. In would seem more appropriate to use the term "strong ion alkalosis" in this context.

[Peridural anaesthesia with ropivacaine for a patient with Friedrich's ataxia. Caesarean section after dorsal stabilisation of the spinal column (Th5-L1)]. / Periduralanästhesie mit Ropivacain bei Friedreich-Ataxie. Sectio bei einer Patientin nach dorsaler Stabilisierung der Wirbelsäule (Th5-L1).

Friedreich's ataxia (FA) is a hereditary disease, which leads to degenerative changes in the spinal cord and cerebellum (incidence 1:50,000). These changes are caused by a defect in the gene that encodes a mitochondrial gene called frataxin and causes muscle weakness, scoliosis, cardiomyopathy and impaired glucose tolerance. Therefore, these patients require special care during anaesthesia. We report the case of a 25-year-old primigravida with a history of FA and dorsal stabilisation of the vertebral column, who was admitted to our hospital for elective caesarean section. Due to increased sensitivity to muscle relaxants, peridural anaesthesia with 8 ml 0.75% ropivacaine and 10 microg sufentanil was used in this case. The perioperative neurological consultation revealed no undue exacerbation of symptoms.

Blood volume is normal after pre-operative overnight fasting.

BACKGROUND: Pre-operative fasting is assumed to cause a deficit in intravascular blood volume (BV), as a result of ongoing urine production and insensible perspiration. Standard regimes consist of volume loading prior or simultaneous to any anaesthetic procedure to minimise the risk of hypotension. However, fluid overload in the context of major abdominal surgery has been shown to deteriorate patient outcome. Our study aimed to quantify total intravascular BV after fasting by direct measurements and to compare it with calculated normal values in comparable non-fasted patients. METHODS: After 10 h of fasting, total plasma volume (PV) and red cell volume (RCV) were measured via the double-label technique (indocyanine green dilution and erythrocytes labelled with fluorescein, respectively) following induction of general anaesthesia in 53 gynaecological patients suffering from malignoma of the cervix. The corresponding normal values were calculated individually from age, body height and body weight. RESULTS: Measured BV, RCV and PV after fasting were 4123+/-589, 1244+/-196 and 2879+/-496 ml, respectively. The differences to the corresponding calculated normal values were not significant (3882+/-366, 1474+/-134 and 2413+/-232 ml, respectively). The measured haematocrit reflected a slight anaemic state (0.35+/-0.03). CONCLUSION: Our data suggest that even after prolonged pre-operative fasting, cardio-pulmonary healthy patients remain intravascularly normovolaemic. Therefore, hypotension associated with induction of general or neuraxial anaesthesia should perhaps be treated with moderate doses of vasopressors rather than with undifferentiated volume loading.