Estimated Blood Volume Research Articles

Probing the glioma microvasculature: a case series of the comparison between perfusion MRI and intraoperative high-frame-rate ultrafast Doppler ultrasound

BackgroundWe aimed to describe the microvascular features of three types of adult-type diffuse glioma by comparing dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) with intraoperative high-frame-rate ultrafast Doppler ultrasound.MethodsCase series of seven patients with primary brain tumours underwent both DSC perfusion MRI and intra-operative high-frame-rate ultrafast Doppler ultrasound. From the ultrasound images, three-dimensional vessel segmentation was obtained of the tumour vascular bed. Relative cerebral blood volume (rCBV) maps were generated with leakage correction and normalised to the contralateral normal-appearing white matter. From tumour histograms, median, mean, and maximum rCBV ratios were extracted.ResultsLow-grade gliomas (LGGs) showed lower perfusion than high-grade gliomas (HGGs), as expected. Within the LGG subgroup, oligodendroglioma showed higher perfusion than astrocytoma. In HGG, the median rCBV ratio for glioblastoma was 3.1 while astrocytoma grade 4 showed low perfusion with a median rCBV of 1.2. On the high-frame-rate ultrafast Doppler ultrasound images, all tumours showed a range of rich and organised vascular networks with visually apparent abnormal vessels, even in LGG.ConclusionsThis unique case series revealed in vivo insights about the microvascular architecture in both LGGs and HGGs. Ultrafast Doppler ultrasound revealed rich vascularisation, also in tumours with low perfusion at DSC MRI. These findings warrant further investigations using advanced MRI postprocessing, in particular for characterising adult-type diffuse glioma.Relevance statementOur findings challenge the current assumption behind the estimation of relative cerebral blood volume that the distribution of blood vessels in a voxel is random.Key points• Ultrafast Doppler ultrasound revealed rich vascularity irrespective of perfusion dynamic susceptibility contrast MRI state.• Rich and organised vascularisation was also observed even in low-grade glioma.• These findings challenge the assumptions for cerebral blood volume estimation with MRI.Graphical

Hidden blood loss and bleeding characteristics in children with congenital scoliosis undergoing spinal osteotomies.

Spinal osteotomies are often essential in the treatment of congenital scoliosis. Risk factors for bleeding in these patients needing extracavitatory approaches, especially hidden blood loss, are sparsely investigated. We aimed to investigate the bleeding characteristics and hidden blood loss in paediatric patients undergoing spinal osteotomies for congenital scoliosis. A retrospective analysis identified all patients with congenital scoliosis were retrospectively identified from the prospectively collected spine register from 2010 to 2022. Operative technique, perioperative laboratory results and imaging studies were extracted. The primary outcome was total blood loss including intraoperative, drain output and hidden blood loss. Fifty-seven children (32 boys) with a mean age of 8.3 years underwent spinal osteotomy for congenital scoliosis. Posterolateral hemivertebrectomy was sufficient in 34 (59%) patients, while vertebral column resection (VCR) was required in 23 patients. Total bleeding averaged 792 (523) ml accounting for 42% of the estimated blood volume. Hidden blood loss accounted for 40% of total bleeding and 21% of estimated blood volume with a mean of 317 (256) ml. VCR was associated with greater intraoperative and total bleeding than hemivertebrectomies (p = 0.001 and 0.007, respectively). After adjusting for patient weight and fusion levels, hidden blood loss was larger in hemivertebrectomies (4.18 vs. 1.77 ml/kg/fused level, p = 0.049). In multivariable analysis, intraoperative blood loss was inversely correlated with preoperative erythrocyte levels. Younger age was associated with significantly greater drain, hidden and total blood loss. Hidden blood loss constitutes a significant portion (40%) of total bleeding in congenital scoliosis surgery. Younger age is a risk factor for bleeding and the hidden blood loss should be taken into consideration in their perioperative management.

Proton-FLASH: effects of ultra-high dose rate irradiation on an in-vivo mouse ear model

FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

Calcium trafficking and gastrointestinal physiology following an acute lipopolysaccharide challenge in pigs.

The influence of systemic immune activation on whole-body calcium (Ca) trafficking and gastrointestinal tract (GIT) physiology is not clear. Thus, the study objectives were to characterize the effects of lipopolysaccharide (LPS) on Ca pools and GIT dynamics to increase understanding of immune-induced hypocalcemia, ileus, and stomach hemorrhaging. Twelve crossbred pigs [44 ± 3kg body weight (BW)] were randomly assigned to 1 of 2 intramuscular treatments: (1) control (CON; 2mL saline; n = 6) or (2) LPS (40 µg LPS/kg BW; n = 6). Pigs were housed in metabolism stalls to collect total urine and feces for 6h after treatment administration, at which point they were euthanized, and various tissues, organs, fluids, and digesta were weighed, and analyzed for Ca content. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature and respiration rate increased in LPS relative to CON pigs (1.4 °C and 32%, respectively; P ≤ 0.05). Inflammatory biomarkers such as circulating alkaline phosphatase, aspartate aminotransferase, and total bilirubin increased in LPS compared with CON pigs whereas albumin decreased (P ≤ 0.02). Plasma glucose and urea nitrogen decreased and increased, respectively, after LPS (43% and 80%, respectively; P < 0.01). Pigs administered LPS had reduced circulating ionized calcium (iCa) compared to CON (15%; P < 0.01). Considering estimations of total blood volume, LPS caused an iCa deficit of 23mg relative to CON (P < 0.01). Adipose tissue and urine from LPS pigs had reduced Ca compared to CON (39% and 77%, respectively; P ≤ 0.05). There did not appear to be increased Ca efflux into GIT contents and no detectable increases in other organ or tissue Ca concentrations were identified. Thus, while LPS caused hypocalcemia, we were unable to determine where circulating Ca was trafficked. LPS administration markedly altered GIT dynamics including stomach hemorrhaging, diarrhea (increased fecal output and moisture), and reduced small intestine and fecal pH (P ≤ 0.06). Taken together, changes in GIT physiology suggested dyshomeostasis and alimentary pathology. Future research is required to fully elucidate the etiology of immune activation-induced hypocalcemia and GIT pathophysiology.

Explaining the Elusive Nature of a Well-Defined Threshold for Blood Transfusion in Advanced Epithelial Ovarian Cancer Cytoreductive Surgery.

There is no well-defined threshold for intra-operative blood transfusion (BT) in advanced epithelial ovarian cancer (EOC) surgery. To address this, we devised a Machine Learning (ML)-driven prediction algorithm aimed at prompting and elucidating a communication alert for BT based on anticipated peri-operative events independent of existing BT policies. We analyzed data from 403 EOC patients who underwent cytoreductive surgery between 2014 and 2019. The estimated blood volume (EBV), calculated using the formula EBV = weight × 80, served for setting a 10% EBV threshold for individual intervention. Based on known estimated blood loss (EBL), we identified two distinct groups. The Receiver operating characteristic (ROC) curves revealed satisfactory results for predicting events above the established threshold (AUC 0.823, 95% CI 0.76-0.88). Operative time (OT) was the most significant factor influencing predictions. Intra-operative blood loss exceeding 10% EBV was associated with OT > 250 min, primary surgery, serous histology, performance status 0, R2 resection and surgical complexity score > 4. Certain sub-procedures including large bowel resection, stoma formation, ileocecal resection/right hemicolectomy, mesenteric resection, bladder and upper abdominal peritonectomy demonstrated clear associations with an elevated interventional risk. Our findings emphasize the importance of obtaining a rough estimate of OT in advance for precise prediction of blood requirements.

Development and validation of a scoring system to predict vasovagal reaction upon whole-blood donation.

Risk factors for vasovagal reaction (VVR) have been extensively studied. With knowledge of the relative importance of these risk factors for VVR, collection staff could take care of blood donors from the same standpoint, leading to improved donor safety. We therefore developed a scoring system to predict VVR, which incorporates registration information. Pre-syncopal and syncopal symptoms, as well as on- and off-site reactions, are included in this analysis as VVR. We defined the donor status as follows: first-time donors, repeat donors with no history of reaction and repeat donors with a history of reaction. We prepared two datasets: whole-blood donations at a blood donation site in Tokyo between January 2019 and December 2019 were included in training data (n = 361,114), and whole-blood donations between January 2020 and August 2020 were included in testing data (n = 216,211). The most important variable was the donor status, followed by age, estimated blood volume and height. We integrated them into a scoring system. Training and testing datasets were combined (n = 577,325), and VVR rates in groups with scores of 0, 1, 2, 3, 4 and 5 or more were 0.09% (95% CI: 0.081%-0.10%), 0.33% (95% CI: 0.31%-0.36%), 0.87% (95% CI: 0.78%-0.96%), 1.17% (95% CI: 1.05%-1.30%), 2.15% (95% CI: 1.98%-2.32%) and 3.11% (95% CI: 2.90%-3.34%), respectively. The scoring system enables staff to significantly predict VVR and may help them to identify donors at increased risk of experiencing syncope, thereby mitigating the negative impact of VVR on donor safety and return by paying close attention to high-risk donors.

Results of posterior spinal fusion after failed anterior vertebral body tethering.

In patients with adolescent idiopathic scoliosis (AIS) undergoing anterior vertebral tethering (AVBT), some will subsequently require posterior spinal fusion (PSF). Limited data exist on clinical and radiographic outcomes of fusion after tether failure. 490 patients who underwent AVBT were retrospectively analyzed. Twenty patients (4.1%) subsequently underwent conversion to PSF. A control group of patients with primary PSF (no previous AVBT) was matched for comparison. Data were compared using paired t-tests and Fisher Exact Tests. There was a significant increase in estimated blood loss (EBL) (p = 0.002), percent estimated blood volume (%EBV) (p = 0.013), operative time (p = 0.002), andincreased amount of fluoroscopy (mGy) (p = 0.04) as well as number of levels fused (p = 0.02) in the AVBT conversion group compared to primary fusion. However, no difference was found in implant density (p = 0.37), blood transfusions (p = 0.11), or intraoperative neuromonitoring events (p > 0.99). Both groups attained similar thoracic and lumbar percent correction (major coronal curve angle) from pre-op to the latest follow-up (thoracic p = 0.507, lumbar p = 0.952). A subset of patients with AVBT will require conversion to PSF. Although technically more challenging, revision surgery can be safely performed with similar clinical and radiographic outcomes to primary PSF.

Post-occlusive reactive hyperemia variables can be used to diagnose vascular dysfunction in hemorrhagic shock

IntroductionLaser doppler flowmetry (LDF) allows non-invasive assessment of microvascular functions. The combination of LDF with an occlusion functional test enables study of post-occlusive reactive hyperemia (PORH), providing additional information about vasomotor function, capillary blood flow reserve, and the overall reactivity of the microvascular system. AimTo identify early alterations of PORH variables in the skin of a rat in hemorrhagic shock (HS). Material and methodsMale Wistar rats (n = 14) weighing 400–450 g were anesthetized with a combination of tiletamine/zolazepam (20 mg/kg) and xylazine (5 mg/kg). The animals breathed on their own, and were placed on a heated platform in the supine position. A PE-50 catheter was inserted into the carotid artery to measure the mean arterial pressure (MAP). The optical probe of the Laser Doppler device was installed on the plantar surface of the hind limb of a rat; a pneumatic cuff was applied proximal to the same limb. The occlusion time was 3 min. The following physiological variables were measured at baseline and 30 min after blood loss: MAP, mmHg; mean cutaneous blood flow (M, PU); cutaneous vascular conductance (CVC = M/MAP); peak hyperemia (Mmax, PU) and maximum cutaneous vascular conductance (CVCmax) during PORH. In the HS group (n = 7), 30 % of the estimated blood volume was taken within 5 min. There was no blood loss in the group of sham-operated animals (Sham, n = 7). The results are presented as Me [25 %;75 %]. The U-Mann-Whitney criterion was used to evaluate intergroup differences. Differences were considered statistically significant at p < 0.05. ResultsThe groups did not differ at baseline. Blood loss led to a significant decrease in MAP (43 [31;46] vs. 94 [84;104] mmHg), M (11.5 [16.9;7.8] vs 16.7 [20.2;13.9]) and Mmax (18.1 [16.4;21.8] vs. 25.0 [23.0;26.2]) in the HS group compared to the Sham group, respectively. At the same time, both CVC (0.25 [0.23;0.30] vs. 0.16 [0.14;0.21]) and CVCmax (0.55 [0.38;0.49] vs 0.24 [0.23; 0.29]) increased after blood loss in the HS group compared to the Sham group. Arterial blood gas analysis revealed metabolic lactic acidosis in the HS group. ConclusionIn this rat model of HS, alterations in cutaneous blood flow are manifested by a decrease in perfusion (M) and the intensity of PORH (Mmax) with a simultaneous increase in vascular conductance (CVC and CVCmax).

NIMG-41. ASSOCIATION BETWEEN PERFUSION IMAGING METRICS AND RADIO-PATHOMIC MAPS OF TUMOR PROBABILITY WITHIN AND BEYOND THE CONTRAST-ENHANCING VOLUME IN GLIOMA PATIENTS

Abstract Perfusion MRI, using both contrast-based techniques such as dynamic susceptibility imaging (DSC) and non-contrast-based techniques like arterial spin labeling (ASL) have been used to monitor blood flow as a marker of angiogenic glioma presence, and showed substantial potential in the differentiation of true progression from pseudoprogression post-treatment. This study uses radio-pathomic maps of cellularity sensitive to areas of non-enhancing tumor to test the hypothesis that perfusion-derived markers of tumor probability will associate with tumor presence within contrast-enhancement but not beyond the enhancing margin. This study included pre-surgical relative cerebral blood volume (rCBV) estimates derived from DSC perfusion data from the PENN-GBM dataset (n=456) and presurgical ASL images from the UCSF-PDGM dataset (n=426) for analyses. The T1, T1C, FLAIR, and ADC images from each patient were used to generate radio-pathomic cell density maps using a previously validated model that excels at accurate detection of non-enhancing tumor presence. Mean cell density, rCBV, and ASL were computed for each corresponding patient within included segmentations for contrast-enhancement (excluding necrotic core) and FLAIR hyperintensity (excluding both necrotic core and enhancement). Pearson’s correlations were then used to quantify the association between perfusion-derived estimates and mean cell density within each region of interest. Both rCBV and ASL showed positive associations with cell density within contrast enhancement (rCBV: R=0.280, p&amp;lt; 0.001; ASL: R=0.117, p=0.016). However, both perfusion metrics also showed no association with cell density within the non-enhancing, FLAIR hyperintense region (rCBV: R=0.0162, p=0.731; ASL: R=-0.213, p=0.634). These results suggest that perfusion imaging successfully identifies angiogenic tumor but may be less efficacious in detecting non-enhancing tumor presence. Future studies should examine how perfusion’s relationship with hypercellular tumor presence evolves in the presence of treatment, as well as in relation to other advanced imaging metrics such as MR spectroscopy and CEST imaging.

Abstract 376: Comparison of Pre and Post Conditioning With Poloxamer 188 in Rat Model of Severe Hemorrhagic Shock

Background: Hemorrhagic shock remains a leading cause of morbidity and mortality after trauma. Poloxamer (P) 188, an FDA-approved copolymer-based cell membrane stabilizer, is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. While post conditioning may be used in a broad range of scenarios, pre-conditioning may add improved efficacy in scenarios where hemorrhage can be expected, the peri-operative period. We have previously demonstrated prolonged survival with P188 post-conditioning however without complete rescue, here we hypothesize pre-conditioning would further improve survival. Methods: 35 male Sprague Dawley rats (564+/-73 g) were anesthetized, ventilated and instrumented. All rats underwent rapid controlled blood loss of 40% estimated blood volume over 30 min, followed by prolonged permissive hypotension for 60 min before re-transfusion of the lost blood to euvolemia and up to 6 hrs of monitoring under general anesthesia. Rats were then randomized to 3 groups: 10 rats received a 0.8 cc iv bolus of 250mg/kg P188 15min before hemorrhage (pre), 12 rats received the same dose of P188 after hemorrhage (post), and 13 control rats only received 0.8 cc vehicle. Primary endpoint was survival time from the start of hemorrhage. Data are median and IQ range; statistics: Kruskal-Wallis and Chi-Square tests, *p&lt;0.05. Results: P188 administration immediately after hemorrhage significantly improved median survival time compared to both the pre and control groups [post *245 (49, 314) min vs. control group; 53 (32-60), vs pre; 59 (24-70) min, p = 0.0174, 0.00045, respectively]. However, there was no significant differences in survival time between pre and control grouyps and there were no differences in survival rate at 6 hours (pre; 0% vs post; 8% vs control; 7%). Conclusion: A bolus of P188 given immediately after a severe hemorrhagic insult prolonged survival time significantly. However, administration of P188 15 min before hemorrhage did not produce a significant prolongation of survival time.P188 is a highly promising compound whose dose, application timing and application duration in severe hemorrhagic shock require more research.

Abstract 370: Oral-Mucosal PCO 2 During Hemorrhagic Shock Closely Monitors Its Time Course, Severity, and Reversal Outperforming Blood Lactate Measurement

Objective: Oral-Mucosal PCO 2 (P OM CO 2 ) has been shown to closely correlate with the splanchnic mucosal PCO 2 and provide information on its microcirculation. We used a swine model of controlled hemorrhagic shock to assess the potential clinical relevance of monitoring P OM CO 2 to assess its clinical course, severity, and treatment effect. Methods: The study was performed on six male domestic pigs (37.9±1.4 kg). P OM CO 2 was measured using a non-invasive disposable sensor clipped to the cheek, developed by ExoStat Medical. Blood was removed over 120 minutes from the right atrium using a LabVIEW-controlled pump according to a mono-exponential decay curve modeling spontaneous bleeding and reinfused in 20 minutes observing the animal for a total of 180 minutes. Results: A total of 1,491±193 ml corresponding to 65.5% of the estimated blood volume were removed inducing the characteristic hemodynamic features of hemorrhagic shock including tachycardia, hypotension, reduced cardiac output, and reduced systemic oxygen delivery with increased systemic oxygen extraction. P OM CO 2 closely paralleled the time course of blood removal showing an early and steady increase from 85±5 mmHg at baseline to 144±32 mmHg after 120 minutes. Blood reinfusion rapidly reduced the P OM CO 2 to 130±17 mmHg after 20 minutes and 96±14 mmHg at the end of 180 minutes, coincident with reversal of hemorrhagic shock. P OM CO 2 also closely tracked changes in systemic oxygen extraction. Concurrent measurements of blood lactate demonstrated a slower increase during the hemorrhagic shock period (from 1.1±0.3 to 3.0±0.3 mmol/l) with further increase (not decrease) to 5.4±2.0 mmol/l after blood reinfusion, remaining at 4.3±0.8 mmol/l by the end of the 180-minute observation period. Conclusions: The study demonstrated capability of P OM CO 2 to closely and non-invasively track hemodynamic and metabolic changes occurring during hemorrhagic shock. P OM CO 2 outperformed blood lactate which exhibited a slower and delayed response. Thus, P OM CO 2 may provide a clinically practical and non-invasive means to monitor hemorrhagic shock assessing its severity, clinical course, and treatment effect.

Insights into the diversity of blood donation practice across Asia: How blood collection agencies adapt donor criteria and processes to their population.

Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up-to-date information on blood donors and donation practices in Asia to assist planning and strategy development. Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed. Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume. The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world.

Quantification of P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET

IntroductionP-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer’s disease and Parkinson’s disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[11C]verapamil PET. (R)-[11C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [18F]MC225 was developed to measure both increases and decreases in P-gp function.AimThe aim of this study was (1) to identify the pharmacokinetic model that best describes [18F]MC225 kinetics in the human brain and (2) to determine test-retest variability.MethodsFive (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [18F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (VT), Ki, and the rate constants K1 and k2). In addition, a reversible two-tissue compartment model with fixed k3/k4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility.ResultsSixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (VB) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the VT for [18F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model.Conclusion[18F]MC225 VT, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%.Trial registrationEudraCT 2020-001564-28. Registered 25 May 2020.

Elevated preoperative blood pressure and its relationship to intraoperative mean arterial pressure and blood loss in posterior spinal fusion for adolescent idiopathic scoliosis.

The relationship between preoperative blood pressure (BP) and intraoperative mean arterial pressure (MAP) and estimated blood loss (EBL) in pediatric spine surgery is currently unknown. The objectives of this study were to determine if elevated preoperative BP is associated with elevated intraoperative MAP, EBL, and percentage estimated blood volume (EBV) lost, and to determine if intraoperative MAP is associated with percentage of EBV lost during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). This is a retrospective cohort analysis of 209 patients undergoing PSF for AIS between 2016 and 2019 by a single surgeon. Data extracted included demographic characteristics, preoperative systolic and diastolic BP, continuous intraoperative MAP measured by arterial line, EBL, radiographic, and surgical characteristics. Time points of interest for MAP included incision and exposure. Elevated BP was defined as > 1 standard deviation above the mean BP of patients included in the study, and elevated MAP was defined as > 65mmHg. Elevated preoperative systolic BP was associated with elevated MAP at incision (p = 0.002). Patients with elevated preoperative diastolic BP had significantly higher MAP at exposure and throughout the procedure (p = 0.04). MAP > 65 at incision was associated with a 5% increase in EBV lost (p < 0.001). Patients with elevated preoperative BP parameters have increased MAPs at incision, exposure, and throughout surgery. Elevated MAP at incision is associated with an increased percentage of EBV lost in a small number of patients undergoing PSF for AIS.

Assessment of Ethynylestradiol-3-sulfate on Coagulation, Metabolism and Survival in Pigs with Traumatic Hemorrhage.

The beneficial effects of estrogens on survival from hemorrhage have been suggested in some preclinical models. This study investigated the effects of ethynylestradiol-3-sulfate (EE-3-S) on coagulation, metabolism and survival in pigs following traumatic hemorrhage. Twenty-six pigs were randomized into: normal saline group (NS, n = 10), EE-3-S group (EE-3, n = 11) groups, and no resuscitation group (NR, n = 5). Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and a 10 min shock period. Afterwards, pigs were resuscitated with a small volume of either NS alone (4 ml/kg) or EE-3-S with NS (1 ml/kg at concentration of 1 mg/ml, plus NS solution of 3 ml/kg). Pigs in NR group were not resuscitated with any fluid. All pigs were then monitored for 6 hours or until death, with hemodynamics and survival times recorded. Blood samples were taken during the study for measurements of oxygen metabolism (oxygen delivery, extraction, and consumption) and coagulation function (using Rotem® with Extem reagents). All baseline measurements were similar among the 3 groups. In the NS group, femur fracture and hemorrhage immediately reduced mean arterial pressure (MAP, 74 ± 3 mmHg to 44 ± 4 mmHg) and increased heart rate (97 ± 5 bpm to 218 ± 14 bpm, both p < 0.05). Similar changes in MAP and heart rate were observed in the EE-3 and NR groups. There were no differences observed in changes of Rotem® measurements or oxygen metabolism among the groups during the study. At 6-hour, 4 pigs in NS, 4 pigs in EE-3-S, and 2 pigs in the NR group survived to the end of the study. The mean survival times were similar among the NS (212 ± 43 min), EE-3 (212 ± 39 min) and NR (223 ± 63 min) groups (p = 0.9845). Following severe traumatic hemorrhage, hypotensive resuscitation with EE-3-S did not impact coagulation, metabolism, or survival in pigs.Study type: laboratory animal study. N/A.

Comparison of quantitative and calculated postpartum blood loss after vaginal delivery

Because there is no consensus on the method of assessing postpartum blood loss, the comparability and relevance of the postpartum hemorrhage-related literature are questionable. Quantitative blood loss assessment using a volumetric technique with a graduated collector bag has been proposed to overcome limitations of intervention-based outcomes but remains partly subjective and potentially biased by amniotic fluid or missed out-of-bag losses. Calculated blood loss based on laboratory parameters has been studied and used as an objective method expected to reflect total blood loss. However, few studies have compared quantitative with calculated blood loss. This study aimed to compare the distribution of postpartum blood loss after vaginal delivery assessed by 2 methods-quantitative and calculated blood loss-and the incidence of abnormal blood loss with each method. Data were obtained from the merged database of 3 multicenter, randomized controlled trials, all testing different interventions to prevent postpartum blood loss in individuals with a singleton live fetus at ≥35 weeks of gestation, born vaginally. All 3 trials measured blood loss volume by using a graduated collector bag. Hematocrit was measured in the eighth or ninth month of gestation and on day 2 postpartum. The 2 primary outcomes were: quantitative blood loss, defined by the total volume of blood loss measured in a graduated collector bag, and calculated blood loss, mathematically defined from the peripartum hematocrit change (estimated blood volume × [(antepartum hematocrit-postpartum hematocrit)/antepartum hematocrit], where estimated blood volume [mL]=booking weight [kg] × 85). We modeled the association between positive quantitative blood loss and positive calculated blood loss with polynomial regression and calculated the Spearman correlation coefficient. Among the 8341 individuals included in this analysis, the median quantitative blood loss (100 mL; interquartile range, 50-275) was significantly lower than the median calculated blood loss (260 mL; interquartile range, 0-630) (P<.05). The incidence of abnormal blood loss was lower with quantitative blood loss than calculated blood loss for all 3 thresholds: for ≥500 mL, it was 9.6% (799/8341) and 32.3% (2691/8341), respectively; for ≥1000 mL, 2.1% (176/8341) and 11.5% (959/8341); and for ≥2000 mL, 0.1% (10/8341) and 1.4% (117/8341) (P<.05). Quantitative blood loss and calculated blood loss were significantly but moderately correlated (Spearman coefficient=0.44; P<.05). The association between them was not linear, and their difference tended to increase with blood loss. Negative calculated blood loss values occurred in 23% (1958/8341) of individuals; among them, >99% (1939/1958) had quantitative blood loss ≤500 mL. Quantitative and calculated blood loss were significantly but moderately correlated after vaginal delivery. However, clinicians should be aware that quantitative blood loss is lower than calculated blood loss, with a difference that tended to rise as blood loss increased.

Evaluation of an Association Between Enoxaparin Dose per Estimated Blood Volume and Clinically Relevant Bleeding in Low-Weight Trauma Patients.

The optimal dosing for enoxaparin venous thromboembolism (VTE) prophylaxis in low-weight trauma patients is unknown. Estimated blood volume (EBV) has shown promise as a dose modifier. To characterize the association of enoxaparin dose per EBV with the prevalence of VTE and bleeding in low-weight trauma patients. This was a retrospective study of trauma patients admitted over a 4-year period. Included patients were adults weighing <60 kg who received a minimum of 3 consecutive doses of enoxaparin. The primary endpoint was a comparison of enoxaparin dose per EBV in patients experiencing bleeding and VTE. Secondary endpoints included comparisons of dose per body mass index (BMI) and total body weight (TBW) and the ability of dose per EBV to predict clinical endpoints. Subgroup analyses for patients weighing <50 kg were performed for all endpoints. A total of 189 patients were included. Statistical comparisons for VTE were not performed because of low prevalence. The dose of enoxaparin per EBV was not statistically different between patients who did and did not bleed in all analyses. Doses per BMI and TBW were also not statistically different between the groups. In patients weighing <50 kg, numerically higher doses per EBV, BMI, and TBW were noted in patients that bled versus those that did not. Enoxaparin dose per EBV was not a statistically significant predictor of bleeding in logistic regression models. No significant associations between enoxaparin dose per EBV, BMI, or TBW and bleeding were noted in the study. Future analyses of EBV and other dose modifiers should consider inclusion of patients weighing <50 kg.

Surgeon Estimated Blood Loss is Discordant with Calculated Blood Loss in Acetabular and Pelvic Fracture Surgery.

To compare blood loss as estimated by surgeon estimated blood loss (EBL), the Gross formula, and the HB equation in open pelvic and acetabular surgery. Retrospective cohort study. Single Level I academic trauma center. We included 710 patients 18-89 years of age who underwent acetabular or pelvic surgery for management of fracture between 2008 and 2018. Surgical treatment for management of acetabular or pelvic fracture and blood transfusion when deemed clinically appropriate in the perioperative setting. Surgeon EBL, calculated blood loss (using the Gross formula, a Gross formula derivative, and the HB equation with both Moore and Nadler blood volume estimations). 192 patients (27%) received intraoperative blood transfusions. Surgeon EBL significantly differed from all formulas except the Gross/ Nadler and the modified Gross/ Nadler calculations. Gross and HB calculation methods yielded similar results in the overall cohort, but yielded significantly different results in the subgroup analysis. Use of a corrective transfusion factor mildly improved correlation of the Gross equation with EBL. At high levels of blood loss, surgeon EBL predictions became more discordant with calculated blood loss values. When assessing only patients who did not receive transfusions, concordance improved. Blood loss in pelvic and acetabular surgery is challenging to quantify, and this study demonstrates discordance between formula predictions and surgeon estimated blood loss. At higher levels of blood loss, this discrepancy worsens. This exploratory study highlights the need for the development of improved methods of quantifying blood loss in orthopaedic trauma surgery. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Review and assessment of the donor safety among plasma donors.

Review and assessment of the donor safety among plasma donors.

Peripheral Intravenous Waveform Analysis Responsiveness to Subclinical Hemorrhage in a Rat Model.

Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers. Eleven male Sprague Dawley rats were anesthetized and mechanically ventilated. A total of 20% of the EBV was removed over ten 5 minute-intervals. The peripheral intravenous pressure waveform was continuously transduced via a 22-G angiocatheter in the saphenous vein and analyzed using MATLAB. Mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored. Cardiac output (CO), right ventricular diameter (RVd), and left ventricular end-diastolic area (LVEDA) were evaluated via transthoracic echocardiogram using the short axis left ventricular view. Dynamic markers such as pulse pressure variation (PPV) were calculated from the arterial waveform. The primary outcome was change in the first fundamental frequency (F1) of the venous waveform, which was assessed using analysis of variance (ANOVA). Mean F1 at each blood loss interval was compared to the mean at the subsequent interval. Additionally, the strength of the association between blood loss and F1 and each other marker was quantified using the marginal R2 in a linear mixed-effects model. PIVA derived mean F1 decreased significantly after hemorrhage of only 2% of the EBV, from 0.17 to 0.11 mm Hg, P = .001, 95% confidence interval (CI) of difference in means 0.02 to 0.10, and decreased significantly from the prior hemorrhage interval at 4%, 6%, 8%, 10%, and 12%. Log F1 demonstrated a marginal R2 value of 0.57 (95% CI 0.40-0.73), followed by PPV 0.41 (0.28-0.56) and CO 0.39 (0.26-0.58). MAP, LVEDA, and systolic pressure variation displayed R2 values of 0.31, and the remaining predictors had R2 values ≤0.2. The difference in log F1 R2 was not significant when compared to PPV 0.16 (95% CI -0.07 to 0.38), CO 0.18 (-0.06 to 0.04), or MAP 0.25 (-0.01 to 0.49) but was significant for the remaining markers. The mean F1 amplitude of PIVA was significantly associated with subclinical blood loss and most strongly associated with blood volume among the markers considered. This study demonstrates feasibility of a minimally invasive, low-cost method for monitoring perioperative blood loss.