Impact of regional differences and neighborhood socioeconomic deprivation on the outcomes of patients with lower extremity wounds evaluated by a limb-preservation service.

OBJECTIVE: Management of lower extremity (LE) wounds has evolved with the establishment of specialized limb preservation services. Although clinical factors contribute to limb outcomes, socioeconomic status and community factors also influence the risk for limb loss. The Distressed Community Index (DCI) score is a validated index of social deprivation created to provide an objective measure of economic well-being in United States communities. Few studies have examined the influence of geographic deprivation on outcomes in patients with LE wounds. We examined relationships between socioeconomic deprivation and outcomes of inpatients evaluated by a dedicated limb preservation service (Functional Limb Extremity Service [FLEX]). METHODS: Inpatients referred to FLEX over a 5-year period were included. Wound, Ischemia, foot Infection (WIfI) staging was collected. DCI scores were determined using seven indices based on ZIP Code. Outcomes included any minor or major amputations, any endovascular or open LE revascularization, or wound care procedures. Disease etiology, demographic, and anthropometric data were collected. Associations between neighborhood deprivation and limb-specific outcomes were evaluated in models for the DCI and each of its components separately. RESULTS: A total of 677 patients were included. Thirty-eight percent were female, with a mean age of 64 years. Sixty percent had WIfI stage 3 or 4 risk of amputation, and 43% had WIfI stage 3 or 4 risk of revascularization. Mean ankle-brachial index and toe pressure were 0.96 (standard deviation [SD], 0.43) and 80 (SD, 57) mmHg. Thirty-five percent were non-White. Amputation was performed in 31% of patients, whereas 17% underwent revascularization. The mean distress score was 64 (SD, 24). Mean DCI scores did not differ across WIfI scores. Likewise, overall DCI distress score was not related to any of the outcomes in univariable or multivariable linear regression models. In univariable linear regression models for amputation, higher poverty rate (odds ratio for SD increase 1.20; 95% confidence interval, 1.02-1.42; P = .025) was significantly associated with the outcome. In multivariable models, neither DCI distress score nor any of its components remained significantly associated with the outcome. CONCLUSIONS: Despite known racial disparities in limb-specific outcomes, an aggregate measure of community level distress was not found to be related to outcomes. Although the poverty rate demonstrated a significant relationship with amputation in univariable analysis, this association was not found in multivariable models. Notably, non-White race emerged as a predictor of amputation, underscoring the importance of addressing racial disparities in LE outcomes. Further investigation of potential determinants of LE outcomes is needed, particularly the interaction of such factors with race.

Dynamic Aortic Pressure Augmentation as a Novel Method of Swine Terminal Blood Extraction.

INTRODUCTION: Uncontrolled hemorrhage models require sufficient quantities of donor blood products to support resuscitation. To that end, we describe a novel method of whole blood extraction from donor swine using resuscitative endovascular balloon occlusion of the aorta (REBOA) to support hemodynamics during terminal blood extraction and its impact on the quality of banked blood. METHODS: Ten adult Yorkshire-cross swine were anesthetized and instrumented with an REBOA catheter, femoral multistage venous cannula, and proximal/distal blood pressure monitoring. Hemodynamics during terminal blood extraction was supported with hand-titrated partial REBOA. Blood samples were taken at set time points for analysis. RESULTS: The median collected blood volume was 3912 mL, with all animals surviving through the planned blood collection of 60% estimated total blood volume (ETBV). Median lactate and potassium levels remained within normal limits for swine through collection of 40% of the ETBV. Median hemoglobin through collection of 40% ETBV did not significantly change from values measured at the start of hemorrhage. CONCLUSIONS: This method of whole blood extraction provided sufficient blood volume and blood quality appropriate for transfusion through 40% ETBV, with remaining collected blood likely still acceptable for allogeneic transfusion despite increased lactate levels. This method of whole blood extraction can efficiently provide a large volume of quality blood to support resuscitation for subsequent uncontrolled hemorrhage models.

Endovascular Perfusion Augmentation After Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Renal Perfusion and Decreases Vasopressors.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes a severe ischemia-reperfusion injury. Endovascular Perfusion Augmentation for Critical Care (EPACC) has emerged as a hemodynamic/mechanical adjunct to vasopressors and crystalloid for the treatment of post-REBOA ischemia-reperfusion injury. The objective of the study is to examine the impact of EPACC as a tool for a wean from complete REBOA compared to standard resuscitation techniques. METHODS: Nine swine underwent anesthesia and then a controlled 30% blood volume hemorrhage with 30 min of supraceliac total aortic occlusion to create an ischemia-reperfusion injury. Animals were randomized to standardized critical care (SCC) or 90 min of EPACC followed by SCC. The critical care phase lasted 270 min after injury. Hemodynamic markers and laboratory values of ischemia were recorded. RESULTS: During the first 90 min the intervention phase SCC spent 60% (54%-73%) and EPACC spent 91% (88%-92%) of the time avoiding proximal hypotension (<60 mm Hg), P = 0.03. There was also a statistically significant decrease in cumulative norepinephrine dose at the end of the experiment between SCC (80.89 mcg/kg) versus EPACC (22.03 mcg/kg), P = 0.03. Renal artery flow during EPACC was similar compared to SCC during EPACC, P = 0.19. But during the last hour of the experiment (after removal of aortic balloon) the renal artery flow in EPACC (2.9 mL/kg/min) was statistically significantly increased compared to SCC (1.57 mL/min/kg), P = 0.03. There was a statistically significant decrease in terminal creatinine in the EPACC (1.7 mg/dL) compared to SCC (2.1 mg/dL), P = 0.03. CONCLUSIONS: The 90 min of EPACC as a weaning adjunct in the setting of a severe ischemia-reperfusion injury after complete supraceliac REBOA provides improved renal flow with improvement in terminal creatinine compared to SCC with stabilized proximal hemodynamics and decreased vasopressor dose.

Evaluation of Neuropathy, Glycemic Control, and Revascularization as Risk Factors for Future Lower Extremity Amputation among Diabetic Patients.

BACKGROUND: Diabetes mellitus is a major risk factor for progression to lower extremity amputation (LEA) due to progressive neuropathy and glycemia-induced vasculopathy. In this study, we evaluated risk factors for incident LEA type 2 diabetics during a randomized controlled trial and extended post-trial follow-up. METHODS: The Action to Control Cardiovascular Risk in Diabetes trial randomized 10,251 type 2 diabetics to intensive glycemic control (Hemoglobin A1c (HbA1c) target <6.0%) versus standard glycemic control (HbA1c target 7.0-7.9%). Using backward elimination logistic regression models, we examined relationships between neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) and glycemic control and incident LEA during the clinical trial and subsequent follow-up. RESULTS: 9,746 patients were followed for a mean of 7.9 +/-3.1 (median 8.9) years after randomization. Ninety-eight (1%) participants underwent an incident LEA during the trial or post-trial follow-up period. Baseline demographics and traditional risk factors were examined by incident amputation status. Multivariable models revealed that abnormal 10 gm filament test (HR 4.50, 95% CI 2.92-6.95, P < 0.0001), presence of ulceration (HR 4.22, 95% CI 1.65-10.8, P = 0.0004), abnormal appearance on foot examination (HR 4.75, 95% CI 2.30-9.83, P < 0.0001), and mean postrandomization HbA1c (HR 1.65, 95% CI 1.35-2.00, P < 0.0001) were strongly predictive of LEA when accounting for other common risk factors for amputation. CONCLUSIONS: In this post hoc analysis of a large randomized controlled population of diabetic patients, we found that components of the MNSI score including presence of ulceration, abnormal appearance of the foot, and 10 gm filament monofilament scoring were strongly predictive of LEA. This adds a valuable clinical tool in the risk stratification of diabetic patients for LEA.

A novel model of highly lethal uncontrolled torso hemorrhage in swine.

INTRODUCTION: A reproducible, lethal noncompressible torso hemorrhage model is important to civilian and military trauma research. Current large animal models balancing clinical applicability with standardization and internal validity. As such, large animal models of trauma vary widely in the surgical literature, limiting comparisons. Our aim was to create and validate a porcine model of uncontrolled hemorrhage that maximizes reproducibility and standardization. METHODS: Seven Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver tourniquet was applied before injury to prevent unregulated hemorrhage while creating a traumatic amputation of 30% of the liver. Release of the tourniquet and rapid abdominal closure following injury provided a standardized reference point for the onset and duration of uncontrolled hemorrhage. At the moment of death, the liver tourniquet was quickly reapplied to provide accurate quantification of intra-abdominal blood loss. Weight and volume of the resected and residual liver segments were measured. Hemodynamic parameters were recorded continuously throughout each experiment. RESULTS: This liver injury was rapidly and universally lethal (11.2 ± 4.9 min). The volume of hemorrhage (35.8% ± 6% of total blood volume) and severity of uncontrolled hemorrhage (100% of animals deteriorated to a sustained mean arterial pressure <35 mmHg for 5 min) were consistent across all animals. Use of the tourniquet effectively halted preprocedure and postprocedure blood loss allowing for accurate quantification of amount of hemorrhage over a defined period. In addition, the tourniquet facilitated the creation of a consistent liver resection weight (0.0043 ± 0.0003 liver resection weight: body weight) and as a percentage of total liver resection weight (27% ± 2.2%). CONCLUSIONS: This novel tourniquet-assisted noncompressible torso hemorrhage model creates a standardized, reproducible, highly lethal, and clinically applicable injury in swine. Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage. Recorded blood loss was similar across all animals. Improving reproducibility and standardization has the potential to offer improvements in large animal translational models of hemorrhage. LEVEL OF EVIDENCE: Level I.

Technical and early outcomes using ultrasound-guided reentry for chronic total occlusions.

BACKGROUND: Subintimal angioplasty is a common treatment for chronic total occlusions (CTOs) in the iliac and infrainguinal arteries. Although technical success has been described using intravascular ultrasound-guided reentry devices (IVUS-RED), outcomes are still not well defined. This report describes the technical aspects and longitudinal follow-up after intravascular ultrasound-guided reentry of iliac and infrainguinal CTOs. METHODS: A retrospective review was performed of 20 patients with lower extremity CTO treated with IVUS-RED from 2011 to 2013. A matched cohort of patients who underwent lower extremity interventions without the use of IVUS-RED was also identified. Procedural success, patency estimates, ankle-brachial indices (ABIs), complications, and limb salvage were analyzed. RESULTS: Twenty patients (mean age, 69 ± 13 years), including 11 men and 9 women, underwent attempted IVUS-RED-guided recanalization. Median follow-up was 4.3 months (range, 0.4-24). Eleven patients presented with critical limb ischemia (CLI), and 9 presented with claudication. Technical success was achieved in 18 (90%) patients. Ten common iliac arteries, 3 external iliac arteries, and 5 superficial femoral arteries (SFA) were treated. No intraoperative complications resulted from device use. After procedure, ABIs significantly increased (0.5-0.9; P < 0.01) in the 13 patients with follow-up. Primary patency for the entire cohort was 62% at 12 months. No patient treated for claudication required reintervention, whereas 3 (27%) of those treated for CLI required repeat interventions. During follow-up, 2 patients died unrelated to the procedure, 1 patient required an amputation, and 1 patient eventually required open revascularization. When the IVUS-RED group was compared with a cohort matched on Trans-Atlantic Inter-Society Consensus and age, no difference was found in runoff scores and patency between the 2 groups during follow-up (P > 0.05). CONCLUSIONS: Recanalization of CTO using IVUS-RED is safe and effective. Use of IVUS-RED does not adversely impact outcomes in conjunction with other endovascular techniques. Early follow-up demonstrates acceptable patency, especially in patients with claudication, and freedom from reintervention.

Improving the precision of shock resuscitation by predicting fluid responsiveness with machine learning and arterial blood pressure waveform data.

Fluid bolus therapy (FBT) is fundamental to the management of circulatory shock in critical care but balancing the benefits and toxicities of FBT has proven challenging in individual patients. Improved predictors of the hemodynamic response to a fluid bolus, commonly referred to as a fluid challenge, are needed to limit non-beneficial fluid administration and to enable automated clinical decision support and patient-specific precision critical care management. In this study we retrospectively analyzed data from 394 fluid boluses from 58 pigs subjected to either hemorrhagic or distributive shock. All animals had continuous blood pressure and cardiac output monitored throughout the study. Using this data, we developed a machine learning (ML) model to predict the hemodynamic response to a fluid challenge using only arterial blood pressure waveform data as the input. A Random Forest binary classifier referred to as the ML fluid responsiveness algorithm (MLFRA) was trained to detect fluid responsiveness (FR), defined as a ≥ 15% change in cardiac stroke volume after a fluid challenge. We then compared its performance to pulse pressure variation, a commonly used metric of FR. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), confusion matrix metrics, and calibration curves plotting predicted probabilities against observed outcomes. Across multiple train/test splits and feature selection methods designed to assess performance in the setting of small sample size conditions typical of large animal experiments, the MLFRA achieved an average AUROC, recall (sensitivity), specificity, and precision of 0.82, 0.86, 0.62. and 0.76, respectively. In the same datasets, pulse pressure variation had an AUROC, recall, specificity, and precision of 0.73, 0.91, 0.49, and 0.71, respectively. The MLFRA was generally well-calibrated across its range of predicted probabilities and appeared to perform equally well across physiologic conditions. These results suggest that ML, using only inputs from arterial blood pressure monitoring, may substantially improve the accuracy of predicting FR compared to the use of pulse pressure variation. If generalizable, these methods may enable more effective, automated precision management of critically ill patients with circulatory shock.

MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK.

ABSTRACT: Background: Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). We hypothesized that PACC-MAN would achieve equivalent resuscitation outcomes to PDM while maintaining normotension with lower fluid and vasopressor requirements. Methods : Twelve swine underwent 30% controlled hemorrhage over 30 min, followed by 45 min of aortic occlusion to generate a vasoplegic shock state, transfusion to euvolemia, and randomization to PACC-MAN or PDM for 4.25 h. Primary outcomes were total crystalloid volume, vasopressor administration, total time spent at hypotension (mean arterial blood pressure <60 mm Hg), and total number of interventions. Results : Weight-based fluid volumes were similar between PACC-MAN and PDM; median and IQR are reported (73.1 mL/kg [59.0-78.7] vs. 87.1 mL/kg [79.4-91.8], P = 0.07). There was no statistical difference in cumulative norepinephrine (PACC-MAN: 33.4 µg/kg [27.1-44.6] vs. PDM: 7.5 [3.3-24.2] µg/kg, P = 0.09). The median percentage of time spent at hypotension was equivalent (PACC-MAN: 6.2% [3.6-7.4] and PDM: 3.1% [1.3-6.6], P = 0.23). Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg, P = 0.13). Conclusion : Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.

Investigating the Relationship between Bleeding, Clotting, and Coagulopathy During Automated Partial REBOA Strategies in a Highly Lethal Porcine Hemorrhage Model.

BACKGROUND: Death due to hemorrhagic shock, particularly, non-compressible truncal hemorrhage (NCTH), remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer (EGL). In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared to pREBOA due to more oscillatory flow. METHODS: Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 minutes of automated partial REBOA (pREBOA), intermittent REBOA (iREBOA), or no balloon support (Control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., 8 key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 minutes). Citrated kaolin heparinase (CKH) assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. RESULTS: As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R-time: p < 0.001; K-time: p < 0.001) and clot strength (MA: p = 0.01; G: p = 0.02) over the duration of the experiment. CONCLUSIONS: Despite observing acute differences in peak proximal pressures between iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R-times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.

Disparities in outcomes for Hispanic patients undergoing endovascular and open abdominal aortic aneurysm repair.

BACKGROUND: Previous studies have demonstrated racial and ethnic disparities associated with the outcomes of abdominal aortic aneurysm (AAA) repair, although little is known about the influence of race and ethnicity on the costs associated with these disparities. The current study was undertaken to examine the influence of race and ethnicity on the outcomes of endovascular (EVAR) and open repair (open AAA) of unruptured AAA and its effect on costs in contemporary practice. METHODS: The Nationwide Inpatient Sample (2005 to 2008) was queried using ICD-9-CM codes for unruptured AAA (441.4). The primary outcomes were mortality and total hospital charges. Multivariate analyses were performed adjusting for age, gender, race, comorbidities (Charlson index), year, insurance type, and hospital characteristics. RESULTS: A total of 62,728 patients underwent EVAR and 24,253 patients underwent open AAA. White patients (72%) were more likely to undergo EVAR than Hispanic (69%) or black patients (69%; P = 0.02). On univariate analysis, in-hospital mortality after EVAR was increased in Hispanic patients compared with white patients (1% vs 2%; P = 0.02). There were no differences in mortality after EVAR between white and black patients, and there were no racial or ethnic differences in mortality after open AAA. Hispanic ethnicity remained an independent risk factor for increased mortality after AAA repair on multivariate analysis (RR 1.64; 95% CI [1.05 to 2.57]; P = 0.03). Hispanic ethnicity was associated with increased hospital charges compared with white ethnicity after both EVAR ($108,886 vs $77,748; P < 0.001) and open AAA ($134,356 vs $85,536; P < 0.001) and for black patients after open AAA ($101,168 vs $85,536; P = 0.04). CONCLUSIONS: Hispanic ethnicity is an independent risk factor for mortality after AAA repair independent of insurance type or hospital characteristics. There were dramatic disparities in hospital costs for Hispanic patients undergoing either EVAR or open AAA and for black patients after open AAA compared with white patients. This observation seems unrelated to length of stay, postoperative complications, and admission status. Further studies are needed to determine whether these disparities extend beyond the primary hospitalization.

Investigating the variability in pressure-volume relationships during hemorrhage and aortic occlusion.

Introduction: The pressure-volume (P-V) relationships of the left ventricle are the classical benchmark for studying cardiac mechanics and pumping function. Perturbations in the P-V relationship (or P-V loop) can be informative and guide the management of heart failure, hypovolemia, and aortic occlusion. Traditionally, P-V loop analyses have been limited to a single-beat P-V loop or an average of consecutive P-V loops (e.g., 10 cardiac cycles). While there are several algorithms to obtain single-beat estimations of the end-systolic and end-diastolic pressure-volume relations (i.e., ESPVR and EDPVR, respectively), there remains a need to better evaluate the variations in P-V relationships longitudinally over time. This is particularly important when studying acute and transient hemodynamic and cardiac events, such as active hemorrhage or aortic occlusion. In this study, we aim to investigate the variability in P-V relationships during hemorrhagic shock and aortic occlusion, by leveraging on a previously published porcine hemorrhage model. Methods: Briefly, swine were instrumented with a P-V catheter in the left ventricle of the heart and underwent a 25% total blood volume hemorrhage over 30 min, followed by either Zone 1 complete aortic occlusion (i.e., REBOA), Zone 1 endovascular variable aortic control (EVAC), or no occlusion as a control, for 45 min. Preload-independent metrics of cardiac performance were obtained at predetermined time points by performing inferior vena cava occlusion during a ventilatory pause. Continuous P-V loop data and other hemodynamic flow and pressure measurements were collected in real-time using a multi-channel data acquisition system. Results: We developed a custom algorithm to quantify the time-dependent variance in both load-dependent and independent cardiac parameters from each P-V loop. As expected, all pigs displayed a significant decrease in the end-systolic pressures and volumes (i.e., ESP, ESV) after hemorrhage. The variability in response to hemorrhage was consistent across all three groups. However, upon introduction of REBOA, we observed significantly high levels of variability in both load-dependent and independent cardiac metrics such as ESP, ESV, and the slope of ESPVR (Ees). For instance, pigs receiving REBOA experienced a 342% increase in ESP from hemorrhage, while pigs receiving EVAC experienced only a 188% increase. The level of variability within the EVAC group was consistently less than that of the REBOA group, which suggests that the EVAC group may be more supportive of maintaining healthier cardiac performance than complete occlusion with REBOA. Discussion: In conclusion, we successfully developed a novel algorithm to reliably quantify the single-beat and longitudinal P-V relations during hemorrhage and aortic occlusion. As expected, hemorrhage resulted in smaller P-V loops, reflective of decreased preload and afterload conditions; however, the cardiac output and heart rate were preserved. The use of REBOA and EVAC for 44 min resulted in the restoration of baseline afterload and preload conditions, but often REBOA exceeded baseline pressure conditions to an alarming level. The level of variability in response to REBOA was significant and could be potentially associated to cardiac injury. By quantifying each P-V loop, we were able to capture the variability in all P-V loops, including those that were irregular in shape and believe that this can help us identify critical time points associated with declining cardiac performance during hemorrhage and REBOA use.

Precision Automated Critical Care Management: Closed-loop critical care for the treatment of distributive shock in a swine model of ischemia-reperfusion.

BACKGROUND: Goal-directed blood pressure management in the intensive care unit can improve trauma outcomes but is labor-intensive. Automated critical care systems can deliver scaled interventions to avoid excessive fluid or vasopressor administration. We compared a first-generation automated drug and fluid delivery platform, Precision Automated Critical Care Management (PACC-MAN), to a more refined algorithm, incorporating additional physiologic inputs and therapeutics. We hypothesized that the enhanced algorithm would achieve equivalent resuscitation endpoints with less crystalloid utilization in the setting of distributive shock. METHODS: Twelve swine underwent 30% hemorrhage and 30 minutes of aortic occlusion to induce an ischemia-reperfusion injury and distributive shock state. Next, animals were transfused to euvolemia and randomized into a standardized critical care (SCC) of PACC-MAN or an enhanced version (SCC+) for 4.25 hours. SCC+ incorporated lactate and urine output to assess global response to resuscitation and added vasopressin as an adjunct to norepinephrine at certain thresholds. Primary and secondary outcomes were decreased crystalloid administration and time at goal blood pressure, respectively. RESULTS: Weight-based fluid bolus volume was lower in SCC+ compared with SCC (26.9 mL/kg vs. 67.5 mL/kg, p = 0.02). Cumulative norepinephrine dose required was not significantly different (SCC+: 26.9 µg/kg vs. SCC: 13.76 µg/kg, p = 0.24). Three of 6 animals (50%) in SCC+ triggered vasopressin as an adjunct. Percent time spent between 60 mm Hg and 70 mm Hg, terminal creatinine and lactate, and weight-adjusted cumulative urine output were equivalent. CONCLUSION: Refinement of the PACC-MAN algorithm decreased crystalloid administration without sacrificing time in normotension, reducing urine output, increasing vasopressor support, or elevating biomarkers of organ damage. Iterative improvements in automated critical care systems to achieve target hemodynamics in a distributive-shock model are feasible.

Automated partial resuscitative endovascular balloon occlusion of the aorta reduces blood loss and hypotension in a highly lethal porcine liver injury model.

BACKGROUND: Partial and intermittent resuscitative endovascular balloon occlusion of the aorta (pREBOA and iREBOA, respectively) are lifesaving techniques designed to extend therapeutic duration, mitigate ischemia, and bridge patients to definitive hemorrhage control. We hypothesized that automated pREBOA balloon titration compared with automated iREBOA would reduce blood loss and hypotensive episodes over a 90-minute intervention phase compared with iREBOA in an uncontrolled liver hemorrhage swine model. METHODS: Twenty-four pigs underwent an uncontrolled hemorrhage by liver transection and were randomized to automated pREBOA (n = 8), iREBOA (n = 8), or control (n = 8). Once hemorrhagic shock criteria were met, controls had the REBOA catheter removed and received transfusions only for hypotension. The REBOA groups received 90 minutes of either iREBOA or pREBOA therapy. Surgical hemostasis was obtained, hemorrhage volume was quantified, and animals were transfused to euvolemia and then underwent 1.5 hours of automated critical care. RESULTS: The control group had significantly higher mortality rate (5 of 8) compared with no deaths in both REBOA groups, demonstrating that the liver injury is highly lethal ( p = 0.03). During the intervention phase, animals in the iREBOA group spent a greater proportion of time in hypotension than the pREBOA group (20.7% [16.2-24.8%] vs. 0.76% [0.43-1.14%]; p < 0.001). The iREBOA group required significantly more transfusions than pREBOA (21.0 [20.0-24.9] mL/kg vs. 12.1 [9.5-13.9] mL/kg; p = 0.01). At surgical hemostasis, iREBOA had significantly higher hemorrhage volumes compared with pREBOA (39.2 [29.7-44.95] mL/kg vs. 24.7 [21.6-30.8] mL/kg; p = 0.04). CONCLUSION: Partial REBOA animals spent significantly less time at hypotension and had decreased transfusions and blood loss. Both pREBOA and iREBOA prevented immediate death compared with controls. Further refinement of automated pREBOA is necessary, and controller algorithms may serve as vital control inputs for automated transfusion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Endovascular procedures in patients with Ehlers-Danlos syndrome: a review of clinical outcomes and iatrogenic complications.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a hereditary connective tissue disorder caused by mutations in genes involved with collagen matrix formation that results in weakened blood vessels. Endovascular therapy on patients with EDS is fraught with concerns of vessel dissection and access site complications. We describe the technical and clinical outcomes of patients with EDS who have undergone a range of endovascular procedures. METHODS: Patients with EDS undergoing endovascular procedures at a single-institution academic center between 1994 and 2010 were retrospectively reviewed. Perioperative data, including details of the procedure, hospital course, complications, and in-hospital mortality, were evaluated using nonparametric tests. RESULTS: In all, 26 patients (8 with classic EDS, 15 with hypermobile EDS, and 3 with vascular EDS) who underwent 48 endovascular procedures (5 diagnostic, 43 interventional; 13 arterial, 35 venous) were identified. The indications for endovascular therapy included pelvic venous varices, visceral aneurysms/pseudoaneurysms, visceral/peripheral occlusive disease, coronary artery disease, and others. Median length of hospital stay was 2 days (range: 0-21 days). The rate of perioperative vascular injury and access site complications was low (2%), and it was not found to be associated with the type of vascular access technique, arterial versus venous procedures, target vessel site, sheath size, or method of closure (all: p > 0.1). Median follow-up period was 7.5 years. There were no late complications from the initial endovascular procedure. CONCLUSIONS: Certain endovascular procedures for patients with EDS can be safely performed with a low rate of dissections and access site complications. However, some indications (particularly aortic interventions) still remain to be determined.

Hardware and software implementation of POCT1-A for integration of point of care testing in research.

Point of care testing (POCT) is increasingly utilized in clinical medicine. Small, portable testing devices can now deliver reliable and accurate diagnostic results during a patient encounter. With these increases in POCT, the issue of data and results management quickly emerges. Results need to be cataloged accurately and efficiently while the providers/support staff are simultaneously managing patient encounters. The integration of electronic medical records (EMR) as data repositories requires that point of care testing data imports automatically into the EMR. POCT1-A was developed as a standard communication language for POCT device manufacturers to streamline automatic data import integration. While all modern POCT devices are built with this connectivity, the systems that provide the integration layer are often proprietary and require a fee for service. In the research environment, there is not enough throughput to justify the practical investment in these data management architectures. Moreover, researcher needs are different and unique compared to data management systems for clinicians. To meet this need, we developed a novel hardware and software connectivity solution using commercially available components to automate data management from a point-of-care blood biochemical analyzer during a critical care study in the preclinical research environment.

The physiology of aortic flow and pressures during partial resuscitative endovascular balloon occlusion of the aorta in a swine model of hemorrhagic shock.

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown promise as a method to extend REBOA, but there lacks a standard definition of the technique. The purpose of this study was to investigate the relationships between distal and proximal mean arterial pressure (MAP) and distal aortic flow past a REBOA catheter. We hypothesize that a relationship between distal aortic flow and distal MAP in Zone 1 partial REBOA (pREBOA) is conserved and that there is no apparent relationship between aortic flow and proximal MAP. METHODS: A retrospective data analysis of swine was performed. Cohort 1 underwent 20% controlled hemorrhage and then randomized to aortic flow of 400 mL/min or complete occlusion for 20 minutes (n = 11). Cohort 2 underwent 30% controlled hemorrhage followed by complete aortic occlusion for 30 minutes (n = 29). Then, they all underwent REBOA wean in a similar stepwise fashion. Blood pressure was collected from above (proximal) and below (distal) the REBOA balloon. Aortic flow was measured using a surgically implanted supraceliac aortic perivascular flow probe. The time period of balloon wean was taken as the time point of interest. RESULTS: A linear relationship between distal MAP and aortic flow was observed ( R2 value, 0.80), while no apparent relationship appeared between proximal MAP and aortic flow ( R2 value, 0.29). The repeated-measures correlation coefficient for distal MAP (0.94; 95% confidence interval, 0.94-0.94) was greater than proximal MAP (-0.73; 95% confidence interval, -0.74 to -0.72). CONCLUSION: The relationship between MAP and flow will be a component of next-generation pREBOA control inputs. This study provides evidence that pREBOA techniques should rely on distal rather than proximal MAP for control of distal aortic flow. These data could inform future inquiry into optimal flow rates and parameters based on distal MAP in both translational and clinical contexts.

Automated aortic endovascular balloon volume titration prevents re-arrest immediately after return of spontaneous circulation in a swine model of nontraumatic cardiac arrest.

Objectives: Endovascular aortic occlusion as an adjunct to cardiopulmonary resuscitation (CPR) for non-traumatic cardiac arrest is gaining interest. In a recent clinical trial, return of spontaneous circulation (ROSC) was achieved despite prolonged no-flow times. However, 66% of patients re-arrested upon balloon deflation. We aimed to determine if automated titration of endovascular balloon volume following ROSC can augment diastolic blood pressure (DBP) to prevent re-arrest. Methods: Twenty swine were anesthetized and placed into ventricular fibrillation (VF). Following 7 minutes of no-flow VF and 5 minutes of mechanical CPR, animals were subjected to complete aortic occlusion to adjunct CPR. Upon ROSC, the balloon was either deflated steadily over 5 minutes (control) or underwent automated, dynamic adjustments to maintain a DBP of 60 mmHg (Endovascular Variable Aortic Control, EVAC). Results: ROSC was obtained in ten animals (5 EVAC, 5 REBOA). Sixty percent (3/5) of control animals rearrested while none of the EVAC animals rearrested (p = 0.038). Animals in the EVAC group spent a significantly higher proportion of the post-ROSC period with a DBP > 60 mmHg [median (IQR)] [control 79.7 (72.5-86.0)%; EVAC 97.7 (90.8-99.7)%, p = 0.047]. The EVAC group had a statistically significant reduction in arterial lactate concentration [7.98 (7.4-8.16) mmol/L] compared to control [9.93 (8.86-10.45) mmol/L, p = 0.047]. There were no statistical differences between the two groups in the amount of adrenaline (epinephrine) required. Conclusion: In our swine model of cardiac arrest, automated aortic endovascular balloon titration improved DBP and prevented re-arrest in the first 20 minutes after ROSC.

Closed-loop automated critical care as proof-of-concept study for resuscitation in a swine model of ischemia-reperfusion injury.

BACKGROUND: Volume expansion and vasopressors for the treatment of shock is an intensive process that requires frequent assessments and adjustments. Strict blood pressure goals in multiple physiologic states of shock (traumatic brain injury, sepsis, and hemorrhagic) have been associated with improved outcomes. The availability of continuous physiologic data is amenable to closed-loop automated critical care to improve goal-directed resuscitation. METHODS: Five adult swine were anesthetized and subjected to a controlled 30% estimated total blood volume hemorrhage followed by 30 min of complete supra-celiac aortic occlusion and then autotransfusion back to euvolemia with removal of aortic balloon. The animals underwent closed-loop critical care for 255 min after removal of the endovascular aortic balloon. The closed-loop critical care algorithm used proximal aortic pressure and central venous pressure as physiologic input data. The algorithm had the option to provide programmatic control of pumps for titration of vasopressors and weight-based crystalloid boluses (5 ml/kg) to maintain a mean arterial pressure between 60 and 70 mmHg. RESULTS: During the 255 min of critical care the animals experienced hypotension (< 60 mmHg) 15.3% (interquartile range: 8.6-16.9%), hypertension (> 70 mmHg) 7.7% (interquartile range: 6.7-9.4%), and normotension (60-70 mmHg) 76.9% (interquartile range: 76.5-81.2%) of the time. Excluding the first 60 min of the critical care phase the animals experienced hypotension 1.0% (interquartile range: 0.5-6.7%) of the time. Median intervention rate was 8.47 interventions per hour (interquartile range: 7.8-9.2 interventions per hour). The proportion of interventions was 61.5% (interquartile range: 61.1-66.7%) weight-based crystalloid boluses and 38.5% (interquartile range: 33.3-38.9%) titration of vasopressors. CONCLUSION: This autonomous critical care platform uses critical care adjuncts in an ischemia-reperfusion injury model, utilizing goal-directed closed-loop critical care algorithm and device actuation. This description highlights the potential for this approach to deliver nuanced critical care in the ICU environment, thereby optimizing resuscitative efforts and expanding capabilities through cognitive offloading. Future efforts will focus on optimizing this platform through comparative studies of inputs, therapies, and comparison to manual critical care.