Assisted Fluid Management and Sublingual Microvascular Flow During High-Risk Abdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: Implementation of goal-directed fluid therapy (GDFT) protocols remains low. Protocol compliance among anesthesiologists tends to be suboptimal owing to the high workload and the attention required for implementation. The assisted fluid management (AFM) system is a novel decision support tool designed to help clinicians apply GDFT protocols. This system predicts fluid responsiveness better than anesthesia practitioners do and achieves higher stroke volume (SV) and cardiac index values during surgery. We tested the hypothesis that an AFM-guided GDFT strategy would also be associated with better sublingual microvascular flow compared to a standard GDFT strategy. METHODS: This bicenter, parallel, 2-arm, prospective, randomized controlled, patient and assessor-blinded, superiority study considered for inclusion all consecutive patients undergoing high-risk abdominal surgery who required an arterial catheter and uncalibrated SV monitoring. Patients having standard GDFT received manual titration of fluid challenges to optimize SV while patients having an AFM-guided GDFT strategy received fluid challenges based on recommendations from the AFM software. In all patients, fluid challenges were standardized and titrated per 250 mL and vasopressors were administered to maintain a mean arterial pressure >70 mm Hg. The primary outcome (average of each patient's intraoperative microvascular flow index (MFI) across 4 intraoperative time points) was analyzed using a Mann-Whitney U test and the treatment effect was estimated with a median difference between groups with a 95% confidence interval estimated using the bootstrap percentile method (with 1000 replications). Secondary outcomes included SV, cardiac index, total amount of fluid, other microcirculatory variables, and postoperative lactate. RESULTS: A total of 86 patients were enrolled over a 7-month period. The primary outcome was significantly higher in patients with AFM (median [Q1-Q3]: 2.89 [2.84-2.94]) versus those having standard GDFT (2.59 [2.38-2.78] points, median difference 0.30; 95% confidence interval [CI], 0.19-0.49; P < .001). Cardiac index and SVI were higher (3.2 ± 0.5 vs 2.7 ± 0.7 l.min-1.m-2; P = .001 and 42 [35-47] vs 36 [32-43] mL.m-2; P = .018) and arterial lactate concentration was lower at the end of the surgery in patients having AFM-guided GDFT (2.1 [1.5-3.1] vs 2.9 [2.1-3.9] mmol.L-1; P = .026) than patients having standard GDFT strategy. Patients having AFM received a higher fluid volume but 3 times less norepinephrine than those receiving standard GDFT (P < .001). CONCLUSIONS: Use of an AFM-guided GDFT strategy resulted in higher sublingual microvascular flow during surgery compared to use of a standard GDFT strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.

Restrictive versus Decision Support Guided Fluid Therapy During Major Hepatic Resection Surgery: A Randomized Controlled Trial.

BACKGROUND: Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure (CVP), retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen™ Assisted Fluid Management system uses novel decision support software whose algorithm helps clinicians optimize fluid therapy. We tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy. METHODS: This two-arm, prospective, randomized controlled, assessor-and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1-2 ml.kg-1.h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure >65mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure). RESULTS: Ninety patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median[Q1-Q3] 2.5[1.9-3.7]mmol.L-1 vs 4.6[3.1-5.4]mmol.L-1, median difference -2.1, 95%CI(-2.7,-1.2), p<0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median[Q1-Q3] 450[300-600]ml vs 500[300-800]ml, p=0.727) although CVP was higher in the decision support group (mean (SD) of 7.7(2.0)mmHg vs 6.6(1.1)mmHg, p<0.002). CONCLUSION: Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.

Effects of Hemorrhagic Shock and Rhabdomyolysis on Renal Microcirculation, Oxygenation, and Function in a Female Swine Model.

BACKGROUND: Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors for acute kidney injury after severe trauma; however, the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion, and morphology in a pig model. METHODS: Forty-seven female pigs were divided into five groups: sham, RM, HS, HS and moderate RM (RM4/HS), and HS and severe RM (RM8/HS). Rhabdomyolysis was induced by intramuscular injection of glycerol 50% with a moderate dose (4 ml/kg for the RM4/HS group) or a high dose (8 ml/kg for the RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 h. Macro- and microcirculatory parameters measurements were performed. RESULTS: RM alone induced a decrease in creatinine clearance at 48 h (19 [0 to 41] vs. 102 [56 to 116] ml/min for RM and sham, respectively; P = 0.0006) without alteration in renal perfusion and oxygenation. Hemorrhagic shock alone impaired temporarily renal microcirculation, function, and oxygenation that were restored with fluid resuscitation. The RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that was not improved by fluid resuscitation. Mortality was increased in the RM8/HS and RM4/HS groups in the first 48 h (73% vs. 56% vs. 9% for the RM8/HS, RM4/HS, and HS groups, respectively). CONCLUSIONS: The combination of HS and RM induced an early deleterious effect on renal microcirculation, function, and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone.

Development of an ultrafast PCR to detect clinically relevant acquired vancomycin-resistance genes from cultured enterococci.

BACKGROUND: VRE are increasingly described worldwide. Screening of hospitalized patients at risk for VRE carriage is mandatory to control their dissemination. Here, we have developed the Bfast [VRE Panel] PCR kit, a rapid and reliable quantitative PCR assay for detection of vanA, vanB, vanD and vanM genes, from solid and liquid cultures adaptable to classical and ultrafast real-time PCR platforms. METHODS: Validation was carried out on 133 well characterized bacterial strains, including 108 enterococci of which 64 were VRE. Analytical performances were determined on the CFX96 Touch (Bio-Rad) and Chronos Dx (BforCure), an ultrafast qPCR machine. Widely used culture plates and broths for enterococci selection/growth were tested. RESULTS: All targeted van alleles (A, B, D and M) were correctly detected without cross-reactivity with other van genes (C, E, G, L and N) and no interference with the different routinely used culture media. A specificity and sensitivity of 100% and 99.7%, respectively, were determined, with limits of detection ranging from 21 to 238 cfu/reaction depending on the targets. The Bfast [VRE Panel] PCR kit worked equally well on the CFX and Chronos Dx platforms, with differences in multiplexing capacities (five and four optical channels, respectively) and in turnaround time (45 and 16 minutes, respectively). CONCLUSIONS: The Bfast [VRE Panel] PCR kit is robust, easy to use, rapid and easily implementable in clinical microbiology laboratories for ultra-rapid confirmation of the four main acquired van genes. Its features, especially on Chronos Dx, seem to be unmatched compared to other tools for screening of VRE.

Control of mean arterial pressure using a closed-loop system for norepinephrine infusion in severe brain injury patients: the COMAT randomized controlled trial.

Brain injury patients require precise blood pressure (BP) management to maintain cerebral perfusion pressure (CPP) and avoid intracranial hypertension. Nurses have many tasks and norepinephrine titration has been shown to be suboptimal. This can lead to limited BP control in patients that are in critical need of cerebral perfusion optimization. We have designed a closed-loop vasopressor (CLV) system capable of maintaining mean arterial pressure (MAP) in a narrow range and we aimed to assess its performance when treating severe brain injury patients. Within the first 48 h of intensive care unit (ICU) admission, 18 patients with a severe brain injury underwent either CLV or manual norepinephrine titration. In both groups, the objective was to maintain MAP in target (within ± 5 mmHg of a predefined target MAP) to achieve optimal CPP. Fluid administration was standardized in the two groups. The primary objective was the percentage of time patients were in target. Secondary outcomes included time spent over and under target. Over the four-hour study period, the mean percentage of time with MAP in target was greater in the CLV group than in the control group (95.8 ± 2.2% vs. 42.5 ± 27.0%, p < 0.001). Severe undershooting, defined as MAP < 10 mmHg of target value was lower in the CLV group (0.2 ± 0.3% vs. 7.4 ± 14.2%, p < 0.001) as was severe overshooting defined as MAP > 10 mmHg of target (0.0 ± 0.0% vs. 22.0 ± 29.0%, p < 0.001). The CLV system can maintain MAP in target better than nurses caring for severe brain injury patients.

Sonorheometry Device Thresholds in Liver Transplantation: An Observational Retrospective Study.

BACKGROUND: Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors' deficit. METHODS: In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft. RESULTS: Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87-0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76-0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77-094, p < 0.001), 0.82 (95% CI 0.74-0.91, p < 0.001) and 0.88 (95% CI 0.82-0.95, p < 0.001), respectively. CONCLUSION: Quantra® provides a rapid assessment of haemostasis during LT.

Perioperative Fluid and Vasopressor Therapy in 2050: From Experimental Medicine to Personalization Through Automation.

Intravenous (IV) fluids and vasopressor agents are key components of hemodynamic management. Since their introduction, their use in the perioperative setting has continued to evolve, and we are now on the brink of automated administration. IV fluid therapy was first described in Scotland during the 1832 cholera epidemic, when pioneers in medicine saved critically ill patients dying from hypovolemic shock. However, widespread use of IV fluids only began in the 20th century. Epinephrine was discovered and purified in the United States at the end of the 19th century, but its short half-life limited its implementation into patient care. Advances in venous access, including the introduction of the central venous catheter, and the ability to administer continuous infusions of fluids and vasopressors rather than just boluses, facilitated the use of fluids and adrenergic agents. With the advent of advanced hemodynamic monitoring, most notably the pulmonary artery catheter, the role of fluids and vasopressors in the maintenance of tissue oxygenation through adequate cardiac output and perfusion pressure became more clearly established, and hemodynamic goals could be established to better titrate fluid and vasopressor therapy. Less invasive hemodynamic monitoring techniques, using echography, pulse contour analysis, and heart-lung interactions, have facilitated hemodynamic monitoring at the bedside. Most recently, advances have been made in closed-loop fluid and vasopressor therapy, which apply computer assistance to interpret hemodynamic variables and therapy. Development and increased use of artificial intelligence will likely represent a major step toward fully automated hemodynamic management in the perioperative environment in the near future. In this narrative review, we discuss the key events in experimental medicine that have led to the current status of fluid and vasopressor therapies and describe the potential benefits that future automation has to offer.

Mastering the brain in critical conditions: an update.

Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events-vascular damage in strokes and biomechanical damage in traumatic brain injuries-they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Tight control of mean arterial pressure using a closed loop system for norepinephrine infusion after high-risk abdominal surgery: a randomized controlled trial.

Intensive care unit (ICU) nurses frequently manually titrate norepinephrine to maintain a predefined mean arterial pressure (MAP) target after high-risk surgery. However, achieving this task is often suboptimal. We have developed a closed-loop vasopressor (CLV) controller to better maintain MAP within a narrow range. After ethical committee approval, fifty-three patients admitted to the ICU following high-risk abdominal surgery were randomized to CLV or manual norepinephrine titration. In both groups, the aim was to maintain MAP in the predefined target of 80-90 mmHg. Fluid administration was standardized in the two groups using an advanced hemodynamic monitoring device. The primary outcome of our study was the percentage of time patients were in the MAP target. Over the 2-hour study period, the percentage of time with MAP in target was greater in the CLV group than in the control group (median: IQR25-75: 80 [68-88]% vs. 42 [22-65]%), difference 37.2, 95% CI (23.0-49.2); p < 0.001). Percentage time with MAP under 80 mmHg (1 [0-5]% vs. 26 [16-75]%, p < 0.001) and MAP under 65 mmHg (0 [0-0]% vs. 0 [0-4]%, p = 0.017) were both lower in the CLV group than in the control group. The percentage of time with a MAP > 90 mmHg was not statistically different between groups. In patients admitted to the ICU after high-risk abdominal surgery, closed-loop control of norepinephrine infusion better maintained a MAP target of 80 to 90 mmHg and significantly decreased postoperative hypotensive when compared to manual norepinephrine titration.