Calculated Blood Volume Research Articles

Incremental residual polarization caused by aging in human skin.

The study of the effect of aging on the optical properties of biological tissues, in particular polarization, is important in the development of new diagnostic approaches. This work aims to provide a comprehensive analysis of the factors and mechanisms that contribute to the alteration of skin polarization properties caused by aging, using polarization-sensitive hyperspectral imaging measurements and Monte Carlo simulation. Our investigation involved both experimental studies of in vivo human skin of volunteers of different ages and computational modeling that accounted for changes in the absorption and scattering properties of the skin model. Specifically, we analyzed alterations in the degree of linear polarization (DOLP) to better understand the impact of aging on skin polarization properties. A statistically significant increase in the DOLP was found for the elderly group. At the same time, there was no correlation between changes in polarization and the calculated blood volume fraction parameter for different ages. According to the simulation results, it was also found that a change in the scattering properties of biological tissues has a more significant effect on the change in polarizing light compared to the change in absorption. The results of the work prove that the sensitivity of polarization imaging to age- or pathological-related skin changes may be primarily due to changes in scattering, which in turn is associated with changes in the collagen fibers of the dermis. The proposed technique shows promise for in vivo non-invasive real-time assessment of age-associated skin changes and can also be extended to monitor changes associated with the development of age-related pathologies.

Incidence and Perioperative Risk Factors of Delayed Extubation following Pediatric Craniotomy for Intracranial Tumor: A 10-Year Retrospective Analysis in a Thailand Hospital

Abstract Background The determination of extubation (early or delayed) after pediatric craniotomy for intracranial tumor should be carefully considered because each has its pros and cons. The aim of this study was to investigate the incidence of the delayed extubation in these patients. The secondary goal was to identify the perioperative factors influencing the determination of delayed extubation. Methods This retrospective study was performed in pediatric patients with intracranial tumor who underwent craniotomy at a university hospital between April 2010 and March 2020. Preoperative and intraoperative variables were examined. The variables were compared between the delayed extubation and early extubation group. Results Forty-two of 286 pediatric patients were in the delayed extubation group with an incidence of 14.69%. According to multivariate analyses, the risk factors that prompted delayed extubation were the intracranial tumor size ≥ 55 mm (adjusted odds ratio [AOR], 2.338; 95% confidence interval [CI], 1.032–5.295; p = 0.042), estimated blood loss (EBL) ≥ 40% of calculated blood volume (AOR, 11.959; 95% CI, 3.457–41.377; p < 0.001), blood transfusion (AOR, 3.093; 95% CI, 1.069–8.951; p = 0.037), duration of surgery ≥ 300 minutes (AOR, 2.593; 95% CI, 1.099–6.120; p = 0.030), and completion of the operation after working hours (AOR, 13.832; 95% CI, 2.997–63.835; p = 0.001). Conclusions The incidence of delayed extubation after pediatric craniotomy was 14.69%. The predictive factors were the size of tumor ≥ 55 mm, EBL ≥ 40% of calculated blood volume, blood transfusion, duration of surgery ≥ 300 minutes, and completion of surgery after routine working hours.

Vasovagal syncope triggered by recent moderate weight loss?

In adults, the onset of vasovagal syncope is often unexplained. We wished to explore if moderate weight loss triggers the onset of vasovagal syncope (VVS). A retrospective case-control study comparing demographic characteristic, syncope symptoms, and tilt-table results of patients who had recently lost weight (n=57), with randomly selected weight-stable patients (n=73), and controls, patients without syncope (n=24). VVS was diagnosed in 480 out of 1,209 clinic patients of whom 57 (11.9%) reported moderate weight loss. The mean (SD) reported weight loss was 11.5 (7) kg over 18.7 (13) months. Age and gender did not differ between groups: in the weight loss, weight stable, and control groups the mean age was 44.8, 45.2, and 44 years respectively; and proportion female 60%, 64%, and 54%. Body weight, mass index and calculated blood volume at presentation were also similar in the different groups. Weight loss preceded or coincided the onset of syncope in 80% of patients; the length of time over which weight loss occurred was associated with the length of time of syncope symptoms, product moment correlation coefficient 0.45, p=0.001. Syncope in childhood and teenage years was less frequent in the weight loss group compared to the weight stable group: 37% vs 53%. After 10 minutes of head-up tilt, stroke volume was preserved in both syncope groups compared to controls; percentage of baseline mean (SD) in the weight loss, weight stable, and control groups: 71(18), 69(10), and 61 (11) respectively; despite lower blood pressure in the weight loss groups with mean (SD) 90 (14) mmHg, 93 (13) and 103 (14) respectively. Some patients have onset of VVS within a few months of weight loss resulting in earlier presentation to clinic. The physiological mechanism for this is uncertain.

Cardiac Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine.

Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular comorbidity.After 3 h of hemorrhage (removal of 30% of the calculated blood volume and subsequent titration of mean arterial pressure to 40 mm Hg) 19 anesthetized, mechanically ventilated, and instrumented pigs received FIO2 = 0.3(control) or hyperoxia(FIO2 = 1.0) during the first 24 h. Before, at the end of and every 12 h after shock, hemodynamics, blood gases, metabolism, cytokines, and cardiac function (pulmonary artery thermodilution, left ventricular pressure-conductance catheterization) were recorded. At 48 h, cardiac tissue was harvested for western blotting, immunohistochemistry, and mitochondrial respiration.Except for higher left ventricular end-diastolic pressures at 24 h (hyperoxia 21 (17;24), control 17 (15;18) mm Hg; P = 0.046), hyperoxia affected neither left ventricular function cardiac injury (max. Troponin I at 12 h: hyperoxia:9 (6;23), control:17 (11;24) ng mL; P = 0.395), nor plasma cytokines (except for interleukin-1β: hyperoxia 10 (10;10) and 10 (10;10)/control 14 (10;22), 12 (10;15) pg mL, P = 0.023 and 0.021 at 12 and 24 h, respectively), oxidation and nitrosative stress, and mitochondrial respiration. However, hyperoxia decreased cardiac tissue three-nitrotyrosine formation (P < 0.001) and inducible nitric oxide synthase expression (P = 0.016). Ultimately, survival did not differ significantly either.In conclusion, in contrast to our previous study in swine with coronary artery disease, hyperoxia did not beneficially affect cardiac function or tissue injury in healthy swine, but was devoid of deleterious side effects.

Alda-1 Prevents Pulmonary Epithelial Barrier Dysfunction following Severe Hemorrhagic Shock through Clearance of Reactive Aldehydes

Severe hemorrhagic shock and resuscitation (HS/R) can lead to lung injury, resulting in respiratory insufficiency. We investigated whether treatment with Alda-1, an ALDH2 activator, decreased lung injury induced by severe HS/R in a rat model. Male Sprague-Dawley rats were randomized into three groups, hemorrhagic shock + placebo, hemorrhagic shock + Alda-1, and sham. All animals were heparinized, and then 50% of the total calculated blood volume was collected over 60 minutes. After 40 minutes of hemorrhagic shock, animals were reinfused with the shed blood over 40 minutes and then observed for an additional 2 hours. Concentrations of 4-HNE, TNF-α, IL-6, and ALDH2 activity were detected; lung injury and lung wet-to-dry weight ratios were assessed. Expression of occludin and ZO-1 proteins in lung tissues was also determined. At 2 hours after resuscitation, lung injury was significantly reduced and the wet-to-dry weight ratio was notably decreased in the Alda-1 group compared with placebo (P<0.05). Alda-1 treatment also significantly increased the activity of ALDH2 and decreased the levels of toxic 4-HNE (P<0.05). In the Alda-1 group, IL-6 and TNF-α were dramatically decreased compared with placebo-treated animals (P<0.05). Expression of occludin and ZO-1 proteins was significantly decreased in the placebo group compared with the Alda-1 group (P<0.05). Thus, in a rat model of severe HS/R, treatment with Alda-1 increased the activity of ALDH2, significantly accelerated the clearance of reactive aldehydes, and concomitantly alleviated lung injury through improvement of pulmonary epithelial barrier integrity resulting in decreased alveolar epithelial tissue permeability, lung edema, and diffuse infiltration of inflammatory cells.

Sonographic real-time imaging of tissue perfusion in a porcine haemorrhagic shock model

Injection of fluorescence-labelled microspheres (FMs) in pigs allows only the postmortem determination of organ perfusion. Colour duplex ultrasound (CDU) and contrast-enhanced ultrasound were established as techniques for real-time imaging of tissue perfusion in a porcine haemorrhagic shock model. Haemorrhagic shock was provoked in nine domestic pigs by taking at least 15% of the calculated blood volume. Ultrasound examinations were performed with a Hitachi HI VISION Ascendus. SonoVue was injected for contrast-enhanced ultrasound. Monitoring of the resistive index and time-to-peak ratio enabled quantification of tissue perfusion in vivo during the entire study, allowing real-time differentiation of animals with systemic shock versus failing shock effect. Postmortem analyses of injected FMs confirmed the sonographic in vivo results. Determination of the resistive index and time-to-peak ratio by CDU and contrast-enhanced ultrasound allowed real-time monitoring of tissue perfusion. Effects of haemorrhagic shock and therapeutic approaches related to organ perfusion can be observed live and in vivo.

Fast Fourier Transformation of Peripheral Venous Pressure Changes More Than Vital Signs with Hemorrhage.

Vital signs are included in the determination of shock secondary to hemorrhage; however, more granular predictors are needed. We hypothesized that fast Fourier transformation (FFT) would have a greater percent change after hemorrhage than heart rate (HR) or systolic blood pressure (SBP). Using a porcine model, nine 17 kg pigs were hemorrhaged 10% of their calculated blood volume. Peripheral venous pressure waveforms, HR and SBP were collected at baseline and after 10% blood loss. FFT was performed on the peripheral venous pressure waveforms and the peak between 1 and 3 hertz (f1) corresponded to HR. To normalize values for comparison, percent change was calculated for f1, SBP, and HR. The mean percent change for f1 was an 18.8% decrease; SBP was a 3.31% decrease; and HR was a 0.95% increase. Using analysis of variance, FFT at f1 demonstrates a statistically significant greater change than HR or SBP after loss of 10% of circulating blood volume (p = 0.0023). Further work is needed to determine if this could be used in field triage to guide resuscitation.

Outcome After Operation for Aortic Dissection Type A in Morbidly Obese Patients

The number of obese patients is increasing, and more obese patients are likely to present for surgical repair of aortic dissection type A (ADA). We evaluated the effect of this procedure on the postoperative outcome of patients based on their body mass index (BMI; calculated as kg/m2). A total of 667 patients who underwent surgical repair of ADA between 2003 and 2017 were retrospectively analyzed. Patients were divided into four groups according to BMI: normal weight (BMI: 18 to <25, n= 186), overweight (BMI: 25 to <30, n= 238), obese (BMI: 30 to <35, n= 144), and morbidly obese (BMI ≥35, n= 99). We compared clinical features and outcomes. No statistical difference was found regarding clinical presentation or proximal or distal aortic repair. Postoperative complications were similar among all groups. Although the rate for reintubation, tracheotomy, and the length of stay in the intensive care unit tended to be similar, the time to extubation (p= 0.010) and the total length of hospital stay (p= 0.017) were significantly longer in morbidly obese patients. Significantly more blood was transfused and replaced in the normal weight patients compared with the obese patients: in median 69% of the calculated blood volume was replaced in the normal weight patients compared with 32% in the morbidly obese patients (p < 0.001). In-hospital mortality and late survival were similar among all weight groups. Despite the comorbidities that are associated with obesity, obese patients undergoing surgical repair of ADA are not at greater risk of death or other adverse outcomes. An immediate surgical approach should be considered in all patients independent of weight.

Patterns of Microvascular Response to Refractory Shock and Their Modulation by Vasoactive Resuscitations

Objective: Progressive hemorrhagic shock (HS) causes splanchnic vasoconstriction and hypo-perfusion together with profound depletions of cellular cytosolic energy phosphates (ATP). Cellular energy failure and the splanchnic hypo-perfusion are critical to the pathogenesis of shock decompensation and the subsequent death from cardiocirculatory arrest. We recently demonstrated post-resuscitation survival benefit for cellular cytosolic ATP replenishment but not for vasopressors use in a rat model of refractory HS. The aim of this study was to determine the effects of progressive HS on the splanchnic microvasculature, and to compare the effects of adjuvant resuscitations with either norepinephrine, vasopressin or lipid vesicles encapsulating ATP (ATPv) on this microvasculature. Methods: 40-male Sprague-Dawley rats were randomized into 4 groups of 10 each: HS/conventionalresuscitation (CR), HS/CR+Norepinephrine, HS/CR+Vasopressin, and HS/CR+ATPv. HS=initial removal of 30% of the calculated blood volume plus subsequent transection of the spleen for uncontrolled haemorrhage until a predefined intervention set-point was achieved; CR=shed blood returned+double the shed blood volume as lactated Ringer’s solution. Four-level intestinal microvascular A1 through A4 arterioles (100–8 μm diameter) in the terminalileum were continuously monitored with intravital-microscopy, and their diameters were measured at baseline, during shock, after completion of resuscitation, and during a 2 h post-resuscitation observation period. In addition, we recorded measurements of the mean arterial pressure, shock index, blood-gas profiles, and complete metabolic panels. Results: Progressive HS caused bimodal arteriole responses with progressive vasoconstriction from baseline of first-order A1 and second-order A2 (-22.1 ± 1.9%), a progressive vasodilation of the third-order A3 and fourth-order A4 arterioles (+22.2 ± 2.8%). Resuscitation initially restored A1 and A2 diameters to near baseline. This was followed by post-resuscitation A1 and A2 vasoconstriction in all groups, except the ATPv group (-8.1 ± 3.4%). The hemorrhage-induced vasodilation of the A3 and A4 arterioles was maintained during the post-resuscitation observation period in the CR (+55.3 ± 6.4%) and the ATPv groups (+39.5 ± 5.2%), but remarkably attenuated in the norepinephrine (+9.6 ± 5.8%) and vasopressin (+9.4 ± 8.8) groups. Conclusions: Severe hemorrhagic shock causes specific splanchnic microvascular bimodal response that is dependent on arteriolar level. First-order A1 and second-order A2 arterioles exhibit progressive vasoconstriction, whereas, third-order A3 and fourth-order A4 arterioles show progressive vasodilation. Temporary administration of either norepinephrine or vasopressin along with conventional resuscitation exerted deleterious effects at all splanchnic microvascular levels by virtue of their peripheral vascular actions. The cellular cytosolic ATP replenishment maintained a better microvascular profile when compared with the two vasopressors.

Surgical Correction of Craniosynostosis. A Single Institution’s Outcome Analysis of 70 Patients

Purpose. The goal of the current study is to provide outcome data for open cranial vault reconstruction at a single institution by a single craniofacial-neurosurgical team. Patients and Methods. A total of 70 patient records were reviewed. The inclusion criteria were patients less than 3 years of age undergoing primary surgery with open cranial vault reshaping and a minimum follow up time of 2 years. Findings. Of the 70 patients meeting the selection criteria (32 female, 38 male), 5 were syndromic and 65 nonsyndromic. Average age and weight were 8.8 months and 9 kg respectively. The oldest child was 21 months and the youngest 3.5 months at the time of surgery. The estimated blood volume lost was 35.8% of total calculated blood volume. Average surgical time was 223.2 minutes. Conclusion. Our review of 70 open repairs of patients with craniosynostosis demonstrates good long-term results with an overall low complication rate and represents open cranial vault reconstruction as a valuable method for repair of such defects.

Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine With Preexisting Coronary Artery Disease.

Investigation of the effects of hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease. Prospective, controlled, randomized trial. University animal research laboratory. Nineteen hypercholesterolemic pigs with preexisting coronary artery disease. Anesthetized, mechanically ventilated, and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal of 30% of the calculated blood volume and subsequent titration of mean arterial blood pressure ≈40 mm Hg). Postshock resuscitation (48 hr) comprised retransfusion of shed blood, crystalloids (balanced electrolyte solution), and norepinephrine support. Pigs were randomly assigned to "control" (FIO2 0.3, adjusted for arterial oxygen saturation ≥ 90%) and "hyperoxia" (FIO2 1.0 for 24 hr) groups. Before, at the end of shock and every 12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood gases, cytokines, and cardiac and renal function were recorded. Postmortem, organs were sampled for immunohistochemistry, western blotting, and mitochondrial high-resolution respirometry. Survival rates were 50% and 89% in the control and hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant τ at 24 hours, hyperoxia did not affect cardiac function. However, troponin values were lower (2.2 [0.9-6.2] vs 6.9 [4.8-9.8] ng/mL; p < 0.05) at the end of the experiment. Furthermore, hyperoxia decreased cardiac 3-nitrotyrosine formation and increased inducible nitric oxide synthase expression. Plasma creatinine values were lower in the hyperoxia group during resuscitation coinciding with significantly improved renal mitochondrial respiratory capacity and lower 3-nitrotyrosine formation. Hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease reduced renal dysfunction and cardiac injury, potentially resulting in improved survival, most likely due to increased mitochondrial respiratory capacity and decreased oxidative and nitrosative stress. Compared with our previous study, the present results suggest a higher benefit of hyperoxia in comorbid swine due to an increased susceptibility to hemorrhagic shock.

Improved Post-Resuscitation Survival Time with Adjuvant Cytosolic Energy Replenishment in a Murine Model of Hemorrhagic Refractory Shock

Objective: A refractory haemorrhagic hypovolemic shock (HS) resuscitation is challenging. HS is associated with profound depletions of cellular energy nucleotides that can cause death from a cardio-circulatory arrest. To prevent an imminent cardio-circulatory arrest, vasopressors, commonly norepinephrine is usually temporarily administered to manage a persistent hypotension that is not corrected by aggressive resuscitation efforts. The objective of this study is to determine the post-resuscitation survival time after adjuvant resuscitations of a refractory HS with norepinephrine, vasopressin or direct cytosolic energy (adenosine-5`-triphosphate, ATP) replenishment using lipid vesicles encapsulating ATP (ATPv). Methods: 50 male Sprague-Dawley rats were randomized to 5 groups of 10 each: HS/conventional resuscitation (CR), HS/CR+Norepinephrine, HS/CR+Vasopressin, HS/CR+Vesicles, and HS/CR+ATPv. (HS=initial removal of 30% of the calculated blood volume, a 60 min hypotensive phase, and a subsequent transection of the spleen for uncontrolled haemorrhage until persistent shock index (SI)>5 and mean arterial pressure (MAP)<35 mmHg were achieved; CR=shed blood returned+double the shed blood volume as lactated Ringer’s solution). Direct cytosolic ATP replenishment was accomplished with ATPv, which are highly fusogenic lipid vesicles encapsulating ATP. Fusion of the ATPv with the cell membrane on contact, allows for direct cytosolic ATP delivery. We determined the post-resuscitation survival time as the end-point of the study. Results: All animals displayed the same class of shock as demonstrated by the SI and MAP. Median postresuscitation survival times (computed by the Kaplan-Meier survival curves and the long-rank Mantel-Cox test) were as follows: HS/CR=35.5 min; HS/CR+Norepinephrine=38.5 min; HS/CR+Vasopressin=20 min; HS/CR+Lipid Vesicles control=88.5 min; and HS/CR+ATPv=158.5 min (p<0.001). Conclusion: The replenishment of the depleted cellular cytosolic energy stores in a refractory haemorrhagic hypotensive shock prolongs post-resuscitation survival time and delays cardio-circulatory arrest. This buys time for the initiation of definitive resuscitation protocols. Cellular energy failure appears to contribute to the pathogenesis of shock refractoriness to resuscitation efforts. The temporary administration of vasopressors for pressure-support resuscitation of a refractory haemorrhagic hypovolemic shock exerts no survival benefits.

Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock.

Polyethylene glycol-20k (PEG-20k) is highly effective for low-volume resuscitation (LVR) by increasing tolerance to the low-volume state. In our rodent shock model, PEG-20k increased survival and expanded the "golden hour" 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low-flow ischemia resulting in efficient microvascular exchange. The objective of this study was to evaluate PEG-20k as an LVR solution for hemorrhagic shock in a preclinical model. Anesthetized male Yorkshire pigs (30-40 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 to 40 mm Hg. Once lactate reached 7 mmol/L, either saline (n = 5) or 10% PEG-20k (n = 5) was rapidly infused at 10% calculated blood volume. The primary outcome was LVR time, defined by the time from LVR administration to the time when lactate again reached 7 mmol/L. Other outcomes measured included MAP, heart rate, cardiac output, mixed venous oxygen saturation, splanchnic blood flow, and hemoglobin. Relative to saline, PEG-20k given after controlled hemorrhage increased LVR time by 16-fold, a conservative estimate given that the lactate never rose after LVR in the PEG-20k group. Survival was 80% for PEG-20k LVR compared to 0% for the saline controls (p < 0.05). Polyethylene glycol-20k also significantly decreased heart rate after hemorrhage and increased cardiac output, MAP, splanchnic flow, and mixed venous oxygen saturation. Falling hemoglobin concentrations suggested sizable hemodilution from fluid shifts into the intravascular compartment. In a preclinical model of controlled hemorrhagic shock, PEG-20k-based LVR solution increased tolerance to the shock state 16-fold compared to saline. Polyethylene glycol-20k is a superior crystalloid for LVR that may increase safe transport times in the prehospital setting and find use in hospital emergency departments and operating rooms for patients awaiting volume replacement or normalization of cell, tissue, and compartment fluid volumes.

Analysis of thromboelastography, PT, APTT and fibrinogen in intraosseous and venous samples-an experimental study.

BackgroundLaboratory analysis of coagulation is often important in emergencies. If vascular access is challenging, intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters in intraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.MethodsTen anesthetized pigs received central venous and intraosseous catheters and samples were taken for analysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume and resuscitation with crystalloid. Intraosseous and venous values were compared.ResultsBleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time was shorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution. Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differences were demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, making analysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude and α-angle, and fibrinogen concentration, were decreased and PT increased.DiscussionThe intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortened reaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in the sampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogen concentration and a lower TEG maximal amplitude were observed.ConclusionsAlthough the sample is small, these data indicate that intraosseous samples are hypercoagulable, which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.Electronic supplementary materialThe online version of this article (doi:10.1186/s13049-016-0318-0) contains supplementary material, which is available to authorized users.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage.

To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Normalizing Oral Fluid Hydrocodone Data Using Calculated Blood Volume.

Oral fluid testing to assist in the assessment of treatment adherence for chronic pain patients is attractive for a number of reasons. However, efforts focused on interpreting patient results have been modest when compared to urine drug testing. This work details a retrospective approach developed to transform and normalize oral fluid testing results to provide a historical picture of patient values in this important test fluid. Using this approach, a model was developed using data from 6,800 independent patients who were both prescribed hydrocodone and tested positive (with limitations: reporting cutoff < X < upper limit of quantitation) by liquid chromatography-mass spectrometry. Patient demographic data were used to calculate the relevant parameters (e.g., calculated blood volume (CBV)) used in the transformation and normalization of the oral fluid data. The crucial normalizing factor in oral fluids was found to be the CBV which parallels the use of creatinine to normalize drug concentration levels in urine and is consistent with the view that oral fluid samples reflect plasma concentrations of the respective drugs. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from oral fluid testing.

The role of retroperitoneal hemorrhage in the development of enteroparesis (clinical and experimental study)

В статье авторы отразили результаты эксперимента на 20 беспородных кроликах, которым в забрюшинное простран-ство вводили собственную кровь по разработанной самими авторами методике, осуществляя забор крови из ушной веныи тем самым, моделируя забрюшинное кровоизлияние. Эксперимент проводился под эфирным наркозом с соблюдением всехправил асептики и антисептики. В ходе эксперимента 10 кроликам в забрюшинное пространство вводили по 5% объемасобственной циркулирующей крови, 10 кроликам вводили по 10% рассчитанного объема циркулирующей крови. За объемциркулирующей крови принимали 7% массы тела животного. На 3 сутки подопытные животные выводились из экспери-мента летальными дозами наркотического препарата. Аутопсия показала, что в группе подопытных животных, кото-рым вводили 5% объема циркулирующей крови парез кишечника развился у 1 (10%) животного, а в группе, которым вводилипо 10% объема циркулирующей крови парез развился у 6 (60%) животных. Тем самым авторы доказали непосредственнуюпричастность забрюшинного кровоизлияния в развитии пареза кишечника, причем частота развития пареза напрямуюзависела от объема крови введенного в забрюшинное пространство. Анализ клинического материала 156 пострадавших стравматическими забрюшинными кровоизлияниями показал, что забрюшинное кровоизлияние осложняет закрытую трав-му живота более чем в половине случаев и в 68,6% случаев сопровождается интраабдоминальной гипертензией разныхстепеней тяжести вплоть до развития синдрома интраабдоминальной гипертензии.Ключевые слова. Забрюшинное кровоизлияние, парез кишечника

An Assessment of the Differences in Erythropoiesis Between Transfused Males and Females with β Thalassaemia Major

▪Background: β thalassemia major results in ineffective erythropoiesis. Blood transfusion aims, in part, to suppress this and to limit morbidity from anaemia, bone marrow expansion and extra-medullary hemopoiesis (EMH), thereby increasing survival. According to current international guidelines, males and females are transfused equally.Aims: We sought to assess the adequacy of suppression of erythropoiesis in all 126 transfused adult (>18 years) males and females with β thalassemia major at our centre by: (1) assessing readily available pre-transfusion indices of erythropoiesis, including erythropoietin (EPO) levels; (2) determining the volume of blood transfused per kilogram (kg) and per calculated blood volume; and (3) assessing the incidence of para-spinal EMH masses based on magnetic resonance imaging (MRI).Methods: We analysed pre-transfusion (i.e., the day of transfusion) hemoglobin (Hb), reticulocyte count, red blood cell count (RCC), nucleated red blood cell (NRBC) count, EPO and ferritin levels in patients receiving stable, regular blood transfusion. Automated and manual NRBC and reticulocyte enumerations were performed. Blood volume was calculated using Nadler’s formula. MRI performed to assess cardiac function and hepatic and cardiac iron loading was reviewed for the presence of para-spinal EMH.Results: One hundred and sixteen adult patients (51 males and 65 females) provided pre-transfusion blood samples (Table 1). The 10 patients not included were either not available or declined testing. The mean pre-transfusion Hb was 98-99g/l with no difference between males or females (Table 2). Therefore, our data reflect long-standing adherence to current international transfusion recommendations. EPO levels and NRBC count (manual and automated) were significantly higher in males compared to females. RCC, reticulocyte count (manual and automated) and ferritin levels were not different between males and females. Males received less blood per kg of body weight and per calculated blood volume. The incidence of para-spinal EMH was 13% (14/110) and was significantly higher in males (11/50) compared to females (3/60)(22% versus 5%, respectively, (p = 0.01)). The incidence of splenectomy was higher in males.Conclusions: These findings confirm that erythropoiesis is not equally suppressed in males and females and that males are more prone to complications from being under-transfused with current transfusion practices. This work has major clinical implications for transfusion practices in the management of β thalassemia major.Abstract 4045. Table 1Summary of patients included in the studyVariableOverallMalesFemalesp valueNumber1165165-Age (years)39.3 ± 9.340.0 ± 9.638.8 ± 9.10.511Weight (kg)60.0 ± 11.664.9 ± 9.855.7 ± 12.4< 0.0001Height (cm)159 ± 10.5166 ± 8.3153 ± 8.1< 0.0001Transfusion interval (weeks)3.2 ± 0.63.2 ± 0.73.1 ± 0.50.168No. RBC units per transfusion3.03 ± 0.633.22 ± 0.762.89 ± 0.480.006Estimated annual transfused volume (l)13.5 (10.1-13.5)14.0 (14.0-14.0)14.0 (10.0-14.0)< 0.0001Estimated annual transfused volume per kg (ml/kg)215 (185-255)202 (185-225)225 (188-263)0.028Estimated patient blood volume (l)3.79 ± 0.734.39 ± 0.503.32 ± 0.52< 0.0001Ratio of estimated annual transfused volume (l) per estimated patient blood volume (l)3.33 (2.84-4.01)2.98 (2.68-3.28)3.79 (3.3-4.35)< 0.0001Splenectomy49.5%61%40%0.031Data are mean ± standard deviation, median (interquartile range) or percentage. Transfused volumes are calculated on the assumption that each unit contains 260ml red cells (Australia Red Cross Blood Service red cell unit mean volume = 259 ± 23ml). Nadler’s formula for total blood volume (TBV): men TBV (ml) = 604 + (367 x height3(m3)) + (32.2 x weight (kg)); women TBV = 183 + (356 x height3(m3)) + 33.1 x weight (kg)).Table 2Laboratory indices of pre-transfusion erythropoiesis for all patientsVariableOverallMaleFemalep valueHemoglobin (g/l)98 ± 8.998 ± 9.999 ± 8.10.36Red cell count (x 1012/l)3.4 ± 0.353.45 ± 0.403.50 ± 0.320.46Ferritin (mcg/l)821 (604-1300)754 (582-1139)943 (639-1356)0.11Erythropoietin (mIU/ml)58 (37-99)72 (41-149)52 (35-89)0.006Manual NRBC (number NRBC/100 WBC counted)6 (1-54)21 (2-98)3 (1-28)0.003Automated NRBC (number NRBC/100 WBC counted)5 (0-34)17 (0-54)1 (0-20)0.014Data are mean ± standard deviation or median (interquartile range). DisclosuresNo relevant conflicts of interest to declare.

Surgical correction of craniosynostosis. A review of 100 cases

PurposeProvide outcome data for open cranial vault reshaping at a single institution by a single craniofacial surgeon treating 100 patients. Methods and subjectsA total of 100 patient records were reviewed. Criteria for selection included patients less than three years of age undergoing primary surgery with open cranial vault reshaping and a minimum follow up time of 2 years. ResultsOf the 100 patients (27 female, 73 male) treated 6 were syndromic and 94 nonsyndromic. Average age and weight were 8.9 months and 9.51 kg, respectively. The oldest child was 30 months and the youngest 5 months at the time of surgery. The estimated blood volume lost was 42.7% of total calculated blood volume ranging from 16.6% to 336%. Average surgical time was 216.7 min. Complications included 2 hematomas, 2 wound infections, 1 subgaleal abscess, 6 dural tears, 3 patients requiring reoperation for residual deformity, 4 cases requiring coronal scar revision, 1 sagittal sinus bleed, and 1 intraoperative death. ConclusionsOur review of 100 open repairs of patients with craniosynostosis demonstrates good long-term results with an overall low complication rate. The outcome data will assist in developing future prospective studies aimed at improving the multidisciplinary care of these patients.

Inhaled thrombolytics reduce lung microclot and leukocyte infiltration after acute blood loss.

We showed previously that a 30% blood loss in rats, without resuscitation, caused significant accumulation of microthrombi and leukocytes within the pulmonary circulation by 24 h. We hypothesized that the microthrombi formed spontaneously as a consequence of hemorrhage-induced stasis within the low-pressure pulmonary circuit and that the leukocytes were attracted to them. This suggested that elimination of the microthrombi, using an inhaled thrombolytic agent, could prevent the neutrophil sequestration after blood loss. To test this hypothesis, we removed 30% of the calculated blood volume from isoflurane-anesthetized, male Sprague-Dawley rats (350-500 g) over 5 min and allowed them to recover. Six hours later, we re-anesthetized the rats and nebulized tissue plasminogen activator (80 or 320 µg/kg), lactated Ringer's solution (LRS), or ipratropium bromide (i-bromide) into their lungs. We used i-bromide as a control after we discovered that nebulized LRS had thrombolytic properties. At 24 h, we removed and fixed the lungs and prepared sections for immunohistochemistry using antibodies against fibrinogen (microthrombi) and CD16 (leukocytes). Digital images of each section were obtained using a confocal microscope. Pixel counts of the images showed significantly less accumulation of microthrombi and leukocytes in lungs nebulized with tissue plasminogen activator or LRS than in non-nebulized lungs or in lungs nebulized with i-bromide (P ≤ 0.05). Lactated Ringer's solution becomes positively charged when nebulized (unlike i-bromide), suggesting that it eliminated microthrombi by fibrin depolymerization. We confirmed this using an in vitro assay. Our results demonstrate that lyses of microthrombi that accumulate in the lung after acute blood loss prevent subsequent leukocyte sequestration.