Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock.

BACKGROUND: Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited. METHODS: Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK). RESULTS: Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large. CONCLUSIONS: Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia.

BACKGROUND: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). METHODS: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90-2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. RESULTS: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. CONCLUSIONS: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.

White blood cell concentrations during lower body negative pressure and blood loss in humans.

NEW FINDINGS: What is the central question of this study? Is lower body negative pressure a useful surrogate to study white blood cell responses to haemorrhage in humans? What is the main finding and its importance? We found that lower body negative pressure appears to be a useful surrogate to study the early white blood cell mobilization response during blood loss. Hypovolaemia has been associated with an immune response that might be secondary to sympathoexcitation. We tested the hypothesis that simulated hypovolaemia using lower body negative pressure (LBNP) and real hypovolaemia induced via experimental blood loss (BL) cause similar increases in the white blood cell concentration ([WBC]). We measured [WBC] and catecholamine concentrations in 12 men who underwent an LBNP and a BL protocol in a randomized order. We compared 45 mmHg of LBNP with 1000 ml of BL; therefore, [WBC] and catecholamine concentrations were plotted against central venous pressure to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Mean regression line slopes were similar for total [WBC] (LBNP 183 ± 4 µl-1  mmHg-1 versus BL 155 ± 109 µl-1  mmHg-1 , P = 0.15), neutrophils (LBNP 110 ± 2 µl-1  mmHg-1 versus BL 96 ± 72 µl-1  mmHg-1 , P = 0.15) and lymphocytes (LBNP 65 ± 21 µl-1  mmHg-1  versus BL 59 ± 38 µl-1  mmHg-1 , P = 0.90). Mean regression line slopes for adrenaline were similar (LBNP 15 ± 5 pg ml-1  mmHg-1 versus BL 16 ± 4 pg ml-1  mmHg-1 , P = 0.84) and were steeper during LBNP for noradrenaline (LBNP 28 ± 6 pg ml-1  mmHg-1 versus BL 9 ± 6 pg ml-1  mmHg-1 , P = 0.01). These data indicate that central hypovolaemia elicits a relative leucocytosis with a predominantly neutrophil-based response. Additionally, our results indicate that LBNP models the stimulus-response relationship between central venous pressure and [WBC] observed during BL.

Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.

Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia.

Effect of hemorrhage rate on early hemodynamic responses in conscious sheep.

Physiological compensatory mechanisms can mask the extent of hemorrhage in conscious mammals, which can be further complicated by individual tolerance and variations in hemorrhage onset and duration. We assessed the effect of hemorrhage rate on tolerance and early physiologic responses to hemorrhage in conscious sheep. Eight Merino ewes (37.4 ± 1.1 kg) were subjected to fast (1.25 mL/kg/min) and slow (0.25 mL/kg/min) hemorrhages separated by at least 3 days. Blood was withdrawn until a drop in mean arterial pressure (MAP) of >30 mmHg and returned at the end of the experiment. Continuous monitoring includedMAP, central venous pressure, pulmonary artery pressure, pulse oximetry, and tissue oximetry. Cardiac output by thermodilution and arterial blood samples were also measured. The effects of fast versus slow hemorrhage rates were compared for total volume of blood removed and stoppage time (whenMAP < 30 mmHg of baseline) and physiological responses during and after the hemorrhage. Estimated blood volume removed whenMAPdropped 30 mmHg was 27.0 ± 4.2% (mean ± standard error) in the slow and 27.3 ± 3.2% in the fast hemorrhage (P = 0.47, pairedttest between rates). Pressure and tissue oximetry responses were similar between hemorrhage rates. Heart rate increased at earlier levels of blood loss during the fast hemorrhage, but hemorrhage rate was not a significant factor for individual hemorrhage tolerance or hemodynamic responses. In 5/16 hemorrhages MAP stopping criteria was reached with <25% of blood volume removed. This study presents the physiological responses leading up to a significant drop in blood pressure in a large conscious animal model and how they are altered by the rate of hemorrhage.

Comparison of midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients: a randomized pilot study.

GOALS: In this pilot study, we compared midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction (PICD). BACKGROUND: PICD with pronounced arterial vasodilatation in cirrhotics with tense ascites can be prevented by the infusion of albumin, which is an expensive treatment modality. Various vasoconstrictors have also been used to prevent PICD, but there are few studies about the usage of midodrine. STUDY: Fifty patients with cirrhosis and tense refractory ascites were randomly assigned to be treated with either midodrine (n=25) (12.5 mg 3 times/d; over 3 d) or albumin (n=25) (8 g/L of removed ascites) after a large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring serum creatinine, serum sodium, plasma renin activity, and aldosterone concentration before and 6 days after paracentesis. RESULTS: Midodrine therapy was cheaper compared with albumin therapy, but serum creatinine, serum sodium, plasma renin activity, and plasma aldosterone concentration values after treatment [0.99±0.19 to 3.02±2.58 mg/dL (P=0.001), 132.36±3.2 to 130.2±4.1 mEq/L (P<0.001), 3.03±0.33 to 4.2±0.76 ng/mL/h (P<0.001), and 166.72±64.26 to 298.64±130 pg/mL (P<0.001), respectively] significantly differed in the midodrine group from that in the albumin group [1.10±0.22 to 1.11±0.161 mg/dL (P=0.885), 132.2±3.524 to 131.88±3.09 mEq/L (P=0.246), 4±0.91 to 4.11±0.74 ng/mL/h (P=0.440), and 204.88±115.9 to 177.08±100.5 pg/mL (P<0.001), respectively]. Seven patients, among whom 6 were hepatocellular carcinoma (HCC) positive, in the midodrine group of our study died as a consequence of liver failure complicated by acute renal failure, followed by hepatic encephalopathy. Whereas in the albumin group, even among the 7 patients with HCC, no patient died or developed hepatorenal syndrome or developed hepatic encephalopathy. CONCLUSIONS: This pilot study suggests that midodrine is not as effective as intravenous albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and tense ascites, especially with HCC-positive patients.

Mixed venous O2 saturation and fluid responsiveness after cardiac or major vascular surgery.

BACKGROUND: It is unclear if and how SvO2 can serve as an indicator of fluid responsiveness in patients after cardiac or major vascular surgery. METHODS: This was a substudy of a randomized single-blinded clinical trial reported earlier on critically ill patients with clinical hypovolemia after cardiac or major vascular surgery. Colloid fluid loading was done for 90 min, guided by changes in pulmonary artery occlusion pressure (PAOP) or central venous pressure (CVP). Fluid responsiveness was defined as ≥15% increase in cardiac index (CI). Hemodynamics, including transpulmonary dilution-derived global end-diastolic volume index (GEDVI) and global ejection fraction (GEF), were measured and blood samples taken. RESULTS: Whereas baseline SvO2 (>70% in 68% of patients) did not differ, the SvO2 increased in patients responding to fluid loading (≥15% in CI in n = 26) versus those not responding (n = 11; P = 0.03). The increase in GEDVI was also greater in responders (P = 0.005). The area under the receiver operating characteristic curve for fluid responsiveness of changes in SvO2 was 0.73 (P = 0.007), with an optimal cutoff of 2%, and of those in GEDVI 0.82 (P < 0.001), while the areas did not differ. However, the value of SvO2 increases to reflect CI increases with fluid loading was greatest when GEF was ≤20% (in 53% of patients). CONCLUSIONS: An increase in SvO2 ≥2%, irrespective of a relatively high baseline value, can thus be used as a monitor of fluid responsiveness in clinically hypovolemic patients after cardiac or major vascular surgery, particularly in those with systolic cardiac dysfunction. Fluid responsiveness concurs with increased tissue O2 delivery.

Red blood cell transfusion compared with gelatin solution and no infusion after cardiac surgery: effect on microvascular perfusion, vascular density, hemoglobin, and oxygen saturation.

BACKGROUND: After cardiac surgery, red blood cell (RBC) transfusion may improve systemic hemodynamics and thereby microvascular blood flow and O2 delivery (DO2). STUDY DESIGN AND METHODS: In a nonrandomized prospective observational study on post-cardiac surgery patients, systemic hemodynamics and microvascular blood flow, vascular density (sidestream dark-field imaging), hemoglobin (Hb) content, and saturation (reflectance spectrophotometry) were measured before and 1 hour after start of transfusion of 1 to 2 units of leukoreduced RBCs (270±203 mL), 500 mL of gelatin solution, or control (no infusion), when patients were considered clinically hypovolemic with (RBC group, n=12) or without (gelatin group, n=14) anemia (Hb<10 g/dL) or not (n=13), respectively. RESULTS: Systemic Hb was lower and increased in the RBC transfusion but not in gelatin and control groups. There were no differences in changes in systemic DO2, O2 uptake, and extraction between groups. RBC transfusion, compared with gelatin or control, increased medium-sized vascular density, Hb content, and saturation in the microcirculation, while blood flow remained unchanged. Changes of microvascular Hb and saturation paralleled changes in systemic Hb. CONCLUSION: The data argue in favor of efficacy of RBC transfusion after cardiac surgery. RBC transfusion increases systemic Hb and this in turn increases medium-sized vascular density and DO2 in the sublingual microcirculation, independently of systemic hemodynamics and volume status.

The involvement of adenosine triphosphate-sensitive potassium channels in the different effects of sevoflurane and propofol on glucose metabolism in fed rats.

BACKGROUND: Recently, we reported marked differences in the effects of sevoflurane and propofol on glucose metabolism; glucose use is impaired by sevoflurane, but not by propofol. Opening of adenosine triphosphate-sensitive potassium channels (K(ATP) channels) in ß islet cells attenuates insulin secretion, while inhibition of K(ATP) channels in ß islet cells increases insulin secretion. It is reported that volatile anesthetics open K(ATP) channels, whereas propofol inhibits K(ATP) channels. In this study, we examined the effects of sevoflurane and propofol on glucose metabolism under normovolemic and hypovolemic conditions, focusing on insulin secretion. METHODS: Anesthesia was induced with sevoflurane (3% in 1 L/min oxygen) in all rats. After surgical preparation, rats were assigned to 2 groups. Anesthesia was maintained with sevoflurane (2% in 1 L/min oxygen) in the 1st group, and with propofol (a bolus dose of 30 mg/kg followed by continuous infusion at a rate of 30 mg · kg(-1) · h(-1)) in the 2nd group. Each group was divided into 3 subgroups: rats without pretreatment, rats pretreated with glibenclamide, and rats pretreated with nicorandil. After a 30-minute stabilization period, we withdrew 15 mL/kg of blood to induce hypovolemia. We evaluated glucose metabolism under both normovolemic and hypovolemic conditions by measuring blood glucose levels and plasma insulin levels. RESULTS: Under both normovolemia and hypovolemia, glucose levels in rats anesthetized with sevoflurane were significantly higher than those in rats anesthetized with propofol, and insulin levels in rats anesthetized with sevoflurane were significantly lower than those in rats anesthetized with propofol. Glibenclamide, a K(ATP) channel inhibitor, significantly decreased glucose levels and significantly increased insulin levels under sevoflurane anesthesia, suggesting that sevoflurane decreases insulin secretion by opening K(ATP) channels in ß islet cells. Glibenclamide significantly decreased glucose levels and significantly increased insulin levels under propofol anesthesia as well; however, insulin levels in rats pretreated with glibenclamide under propofol anesthesia were much higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. Furthermore, insulin levels in rats without pretreatment under propofol anesthesia seemed to be equal to or higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. These results suggest that there are marked differences in the effects of sevoflurane and propofol on insulin secretion regulated by K(ATP) channels in ß islet cells. Nicorandil, a K(ATP) channel opener, produced no significant effects on glucose metabolism under both sevoflurane and propofol anesthesia. CONCLUSIONS: Insulin secretion regulated by K(ATP) channels in ß islet cells is involved, at least in part, in the different effects of sevoflurane and propofol on glucose metabolism.

Preliminary study on changes in coagulation function and component transfusion time in patients with massive hemorrhage.

INTRODUCTION: To investigate the changes in coagulation function and component transfusion time in patients with massive hemorrhage. METHODS: Sixty-two patients with massive hemorrhage were enrolled in the study. Blood samples were collected from each patient when the blood loss reached 1000, 1500, 1700 and 2000 ml. The parameters FIB, PT, APTT, HGB, HCT, PLT and MAP were recorded for all patients. RESULTS: Sixty-two, 30, 20 and 8 patients showed blood loss exceeding 1000, 1500, 1700 and 2000 ml, respectively. Blood samples were successfully collected from all patients when the volume of blood lost reached 1000, 1500, 1700 and 2000 ml. However, at this time point, FIB, MAP, HGB, HCT and PLT were significantly lower than the baseline/preoperative values. These indices decreased progressively with increasing blood loss. PT and APTT were significantly higher than at baseline and increased progressively with increased blood loss. FIB, HCT and HGB were below the normal reference range when blood loss was 1500 ml. During surgery, FIB, MAP, HCT, HGB and PLT decreased substantially, whereas APTT and PT increased when blood loss exceeded 1500 ml. PT and MAP were beyond the normal range when blood loss reached 2000 ml. There was a correlation between FIB, HCT and HGB with intraoperative blood loss; the correlation coefficient was greatest between and FIB and blood loss. CONCLUSION: There were marked correlations between FIB, HCT and HGB with intraoperative blood loss, and the correlation was greatest with FIB.

Preload responsiveness is associated with increased interleukin-6 and lower organ yield from brain-dead donors.

OBJECTIVE: Brain death induces dramatic changes in hemodynamics. Ischemic injury and inflammation resulting from inadequate resuscitation might influence organ yield for transplantation. Using functional hemodynamic monitoring in brain-dead organ donors, we test the hypothesis that donor preload (fluid) responsiveness is associated with increased inflammatory response and lower organ yield for transplantation. DESIGN: Prospective, observational, pilot study. SETTING: A large intensive care unit of a university hospital in the United States. PATIENTS: Twenty-one brain-dead organ donors between July 2006 and April 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Following declaration of brain death, we collected data on donor demographics, mechanism of brain death, and number of organs procured and transplanted. Functional hemodynamics were monitored using pulse contour analysis technique. Plasma tumor necrosis factor, interleukin-6, and interleukin-10 concentrations were measured at study enrollment, after 4 hrs, and immediately before organ procurement for transplantation. Preload responsiveness (pulse pressure variation >13%) was observed in 48% of donors (mean +/- sd pulse pressure variation, 19.2% +/- 4.8%). Plasma interleukin-6 and tumor necrosis factor concentrations at study enrollment were greater in preload responsive donors: mean concentrations of interleukin-6 in preload responsive vs. unresponsive donors were 5420 +/- 9102 vs. 378 +/- 631 pg/mL (p = .009), and mean concentrations of tumor necrosis factor were 60.5 +/- 103.6 vs. 15.7 +/- 10.1 pg/mL (p = .048). Preload responsive compared with unresponsive donors had significantly increased interleukin-6 (p = .013) and tumor necrosis factor (p = .044) concentrations over time. Fewer organs were transplanted from preload responsive donors: mean organs transplanted from preload responsive vs. unresponsive donors were 1.8 +/- 0.9 vs. 3.7 +/- 2.5 (p = .034). In multivariable regression, older donor age (p = .028) and increased plasma interleukin-6 concentration (p = .035) were significantly associated with lower number of organs transplanted. CONCLUSIONS: Preload responsiveness is common in brain-dead organ donors and is associated with higher inflammatory response and lower organ yield. A controlled trial of preload optimization is warranted in brain-dead donors.

[Hypovolemia and oxidative stress in patients with burn injuries]. / A hypovolaemia és oxidatív stressz vizsgálata égési sérülést szenvedett betegek körében.

UNLABELLED: Adequate treatment of the developing hypovolemia caused by marked oedema formation plays a key role in the care of burned patients. Oxidative stress may be an underlying cause of the excessive oedema formation. The aim of the study was to asses how can different resuscitation schemata be adapted better to the requirement of each individual patient. Effect of the use of different schemata on organ-function and developing oxidative stress and correlation between the extent of burn and oxidative stress has also been studied. METHODS: Patients admitted to our level one intensive ward were involved in the study. Inclusion criterion was the start of our fluid resuscitation schema at least 3 hours after injury. Hemodynamic measurements were performed by transpulmonary thermodilution technique. Blood samples were taken on admission and on the 5 consecutive days thereafter. White blood cell count of the patients, the percentage of granulocytes, lymphocytes and monocytes, the levels of malondialdehyde, protein sulfhydryl groups in plasma, reduced glutathione, catalase, and superoxide dismutase enzyme activities, and phorbol myristate acetate induced free radical generating capacity were assessed. RESULTS: Significantly more fluid was administered than predicted by the Parkland formula (p < 0.05). Patients in whom fluid resuscitation was guided by invasive hemodynamic parameters ScvO 2 was significantly higher (p < 0.05), multi organ dysfunction scores were lower (p < 0.05) than in the hourly urine output group. Patients whom fluid resuscitation was guided by invasive hemodynamic parameters relative number of the granulocytes and maximal rate of reactive oxygen species production (p < 0.05) were significantly higher (p < 0.05), the lag phases were significantly shorter (p < 0.05). CONCLUSIONS: With the use of correction factors the Parkland formula can be more precise, still, fluid resuscitation guided by invasive hemodynamic measurements can provide the best results. The type of fluid resuscitation schema influences mainly the pro-oxidant system.

Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?

OBJECTIVES: Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this. METHODS: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1+2, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and D-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. RESULTS: A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high D-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days. CONCLUSIONS: Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

Plasma vasopressin concentrations and Fos protein expression in the supraoptic nucleus following osmotic stimulation or hypovolaemia in the ovariectomized rat: effect of oestradiol replacement.

The set points for vasopressin release in response to increasing plasma osmolality and hypovolaemia alter with reproductive status. Here, we studied stimulated vasopressin release following ovariectomy and oestrogen replacement, neuronal activity being measured in terms of immediate early gene expression. Observations were carried out on three groups of female Sprague-Dawley rats. The first group were ovariectomized. The second group were given a subcutaneous oestrogen implant (20 microg/ml oestradiol-17 beta) at the time of ovariectomy. The final group were left intact and observations performed at oestrus. Two weeks after ovariectomy, vascular cannulae were implanted under anaesthesia and at least 48 h allowed for recovery before hormone release was stimulated by infusion of 1.5 M NaCl for 90 min, or hypovolaemia induced by the removal of 10 mg/kg body weight taken in 1-ml aliquots. Blood pressure was monitored, and blood samples were taken for determination of packed cell volume and plasma vasopressin and osmolality. After a minimum of 48 h, the challenge was repeated, the rats anaesthetized, and perfused with 4% paraformaldehyde. Brain sections were processed for immunocytochemical detection of Fos protein. Vasopressin release in response to both stimuli was reduced in ovariectomized compared to intact rats and the response could be substantially restored by oestradiol replacement. The number of Fos positive cells in the supraoptic nucleus of oestrogen-replaced rats was significantly higher than in the ovariectomized group and not statistically different from the intact group.

Changes in circulating blood volume after cardiac surgery measured by a novel method using hydroxyethyl starch.

OBJECTIVE: To determine the incidence and extent of postoperative blood volume (BV) changes in patients after elective cardiac surgery using a new method based on dilution of hydroxyethyl-starch. DESIGN: Prospective, clinical, and laboratory investigation. SETTING: University hospital intensive care unit. PATIENTS: A total of thirty-five patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). INTERVENTIONS: Perioperative measurements of circulating BV, systemic hemodynamics, lactate, and collection of clinical data. MEASUREMENTS AND MAIN RESULTS: Measurements were made before and 1 to 72 hrs after CPB. The majority of patients undergoing cardiac surgery showed postoperative BV deficits compared with preoperative BV despite marked positive fluid balances after CPB. At 1 hr and 5 hrs after CPB, 18% and 33% of the patients, respectively, had BV deficits in the range of 0.5 L and 1.5 L, and in 3% to 10% of the cases, postoperative BV deficits exceeded 1.5 L. Concomitantly, at 5 hrs after CPB, mean arterial pressure was maximally reduced, and heart rate and lactate levels were maximally elevated. Thereafter, BV began to normalize, and at 24 hrs after CPB, pre- and postoperative mean BV were no longer significantly different. At 48 hrs and 72 hrs, even a BV surplus of more than 1 L could be observed in 6% and 14% of the patients, respectively. CONCLUSIONS: During the first hours after CPB, a high percentage of patients had significantly reduced BV and, concomitantly, showed cardiovascular dysfunction and hyperlactemia. Because hypovolemia is associated with increases of perioperative morbidity and mortality, rapid determination of BV is warranted to guide fluid therapy and optimize treatment in patients undergoing cardiac surgery.