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Performance of closed-loop resuscitation in a pig model of haemorrhagic shock with fluid alone or in combination with norepinephrine, a pilot study

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We evaluated the performance of a new device to control the administration of fluid alone or co-administration of fluid and norepinephrine in a pig model of haemorrhagic shock in two sets of experiments. In the first one, resuscitation was guided using continuous arterial pressure measurements (three groups: resuscitation with fluid by a physician, CL resuscitation with fluid, and CL resuscitation with fluid and norepinephrine). In the second one, resuscitation was guided using discontinuous arterial pressure measurements (three groups: CL resuscitation with fluid alone, CL resuscitation with fluid and moderate dose norepinephrine, and CL resuscitation with fluid and a high dose of norepinephrine). Pigs were resuscitated for 1 h. In the first set of experiments, proportion of time spent in the target area of 78–88 mmHg of systolic arterial pressure was not statistically different between the three groups: manual, 71.2% (39.1–80.1); CL with fluid, 87.8% (68.3–97.4); and CL with fluid and norepinephrine, 78.1% (59.2–83.6), p = 0.151. In the second set of experiments, performance of CL resuscitation with fluid or with combination of fluid and high or moderate dose of norepinephrine was not significantly different (p = 0.543 for time in target). Pigs resuscitated with norepinephrine required less fluid and had less haemodilution than pigs resuscitated with fluid alone. Performance of CL resuscitation using continuous arterial pressure measurement was not significantly different than optimised manual treatment by a dedicated physician. Performance of CL resuscitation was reduced with discontinuous arterial pressure measurements in comparison with continuous arterial pressure measurements.
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Journal of Clinical Monitoring and Computing (2021) 35:835–847
Performance ofclosed‑loop resuscitation inapig model
ofhaemorrhagic shock withfluid alone orincombination
withnorepinephrine, apilot study
NicolasLibert1,2 · GuillaumeChenegros3· AnatoleHarrois1,4· NathalieBaudry1· BenoitDecante5·
GillesCordurie3· RyadBenosman3· OlafMercier6,7· EricVicaut1,8· JacquesDuranteau1,4
Received: 12 December 2019 / Accepted: 28 May 2020 / Published online: 12 June 2020
© Springer Nature B.V. 2020
We evaluated the performance of a new device to control the administration of fluid alone or co-administration of fluid and
norepinephrine in a pig model of haemorrhagic shock in two sets of experiments. In the first one, resuscitation was guided
using continuous arterial pressure measurements (three groups: resuscitation with fluid by a physician, CL resuscitation with
fluid, and CL resuscitation with fluid and norepinephrine). In the second one, resuscitation was guided using discontinuous
arterial pressure measurements (three groups: CL resuscitation with fluid alone, CL resuscitation with fluid and moderate
dose norepinephrine, and CL resuscitation with fluid and a high dose of norepinephrine). Pigs were resuscitated for 1h. In
the first set of experiments, proportion of time spent in the target area of 78–88mmHg of systolic arterial pressure was not
statistically different between the three groups: manual, 71.2% (39.1–80.1); CL with fluid, 87.8% (68.3–97.4); and CL with
fluid and norepinephrine, 78.1% (59.2–83.6), p = 0.151. In the second set of experiments, performance of CL resuscitation
with fluid or with combination of fluid and high or moderate dose of norepinephrine was not significantly different (p = 0.543
for time in target). Pigs resuscitated with norepinephrine required less fluid and had less haemodilution than pigs resuscitated
with fluid alone. Performance of CL resuscitation using continuous arterial pressure measurement was not significantly
different than optimised manual treatment by a dedicated physician. Performance of CL resuscitation was reduced with
discontinuous arterial pressure measurements in comparison with continuous arterial pressure measurements.
Keywords Closed-loop· Resuscitation· Haemorrhagic shock· Fluid· Norepinephrine
1 Introduction
Trauma remains an important cause of morbidity and mor-
tality worldwide, particularly among young people. Haem-
orrhagic shock is the major mechanism leading to death
Electronic supplementary material The online version of this
article (https :// 7-020-00542 -7) contains
supplementary material, which is available to authorized users.
* Jacques Duranteau
1 Laboratoire d’Étude de la Microcirculation, UMR 942,
Université Paris, 7-11-13, Paris, France
2 Service d’Anesthésie-Réanimation, Hôpital d’instruction des
armées Percy, Clamart, France
3 Institut de la Vision UMR-S 968, Sorbonne Université,
Université Pierre et Marie Curie UPMC, Paris, France
4 Service d’Anesthésie-Réanimation Chirurgicale, Hôpital
de Bicêtre, Université Paris-Sud, Hôpitaux Universitaires
Paris-Sud, Assistance Publique-Hôpitaux de Paris,
LeKremlinBicêtre, France
5 Unité de Recherche et d’innovation, Hôpital Marie
Lannelongue, LePlessisRobinson, France
6 École de médecine, Université Paris-Sud et Paris-Saclay,
Kremlin-Bicêtre, France
7 Département de Chirurgie Thoracique et Vasculaire et
Transplantation cœur-Poumon, DHU Thorax Innovation,
INSERM UMR-S 999, LabEx LERMIT, Hôpital Marie
Lannelongue, LePlessisRobinson, France
8 Unité de Recherche Clinique, Université Paris 7, Hôpitaux
Saint Louis Lariboisière, Assistance Publique-Hôpitaux de
Paris, Paris, France
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... While there are other CLV systems that have been described in the literature [16][17][18][19][20][21][22], to our knowledge there have been limited clinical studies performed using SAP as the main variable to guide norepinephrine titration. Personalizing intraoperative SAP by maintaining values within 10% of baseline has been shown to improve outcomes [14]. ...
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Introduction: Vasopressor infusions are essential in treating and preventing intraoperative hypotension. Closed-loop vasopressor therapy outperforms clinicians when the target is set at a mean arterial pressure (MAP) baseline, but little is known on the performance metrics of closed-loop vasopressor infusions when systolic arterial pressure (SAP) is the controlled variable. Methods: Patients undergoing intermediate- to high-risk abdominal surgery were included in this prospective cohort feasibility study. All patients received norepinephrine infusion through a computer controlled closed-loop system that targeted SAP at 130 mmHg. The primary objective was to determine the percent of case time in hypotension or under target defined as SAP below 10% of the target (SAP < 117 mmHg). Secondary objectives were the percent of case time “above target” (SAP > 10% of the target or >143 mmHg) and “in target” (within 10% of the SAP target or SAP between 117 and 143 mmHg). Results: A total of 12 patients were included. The closed-loop system infused norepinephrine for a median of 94.6% (25–75th percentile: 90.0–98.0%) of case time. The percentage of case time in hypotension or under target was only 1.8% (0.9–3.6%). The percentages of case time “above target” and “in target” were 4.7% (3.2–7.5%) and 92.4% (90.1–96.3%), respectively. Conclusions: This closed-loop vasopressor system minimizes intraoperative hypotension and maintains SAP within 10% of the target range for >90% of the case time in patients undergoing intermediate- to high-risk abdominal surgery.
... In this study we compared four controller types, each configured two ways, for a total of eight controller configurations. These four controller types, decision table [12,13], single-input fuzzy logic [14], dual-input fuzzy logic [15][16][17], and proportional-integralderivative [18][19][20], have been previously used in PCLC applications but not compared head-to-head. The goal for this effort was to determine, as objectively as possible, which of the many possible controllers demonstrate the best performance, making it favorable for further development. ...
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Trauma and hemorrhage are leading causes of death and disability worldwide in both civilian and military contexts. The delivery of life-saving goal-directed fluid resuscitation can be difficult to provide in resource-constrained settings, such as in forward military positions or mass-casualty scenarios. Automated solutions for fluid resuscitation could bridge resource gaps in these austere settings. While multiple physiological closed-loop controllers for the management of hypotension have been proposed, to date there is no consensus on controller design. Here, we compare the performance of four controller types—decision table, single-input fuzzy logic, dual-input fuzzy logic, and proportional–integral–derivative using a previously developed hardware-in-loop test platform where a range of hemorrhage scenarios can be programmed. Controllers were compared using traditional controller performance metrics, but conclusions were difficult to draw due to inconsistencies across the metrics. Instead, we propose three aggregate metrics that reflect the target intensity, stability, and resource efficiency of a controller, with the goal of selecting controllers for further development. These aggregate metrics identify a dual-input, fuzzy-logic-based controller as the preferred combination of intensity, stability, and resource efficiency within this use case. Based on these results, the aggressively tuned dual-input fuzzy logic controller should be considered a priority for further development.
... Due to the scope of this review, systems that were meant for vasopressor infusion control were not included, and only the fluid management component was addressed in the cases where both fluid management and vasopressor control were described. Two exceptions were the systems described by Libert et al. [27,28] and by Markevicius et al. [29,30], where these two components were essentially inseparable. ...
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Physiological Closed-Loop Controlled systems continue to take a growing part in clinical practice, offering possibilities of providing more accurate, goal-directed care while reducing clinicians’ cognitive and task load. These systems also provide a standardized approach for the clinical management of the patient, leading to a reduction in care variability across multiple dimensions. For fluid management and administration, the advantages of closed-loop technology are clear, especially in conditions that require precise care to improve outcomes, such as peri-operative care, trauma, and acute burn care. Controller design varies from simplistic to complex designs, based on detailed physiological models and adaptive properties that account for inter-patient and intra-patient variability; their maturity level ranges from theoretical models tested in silico to commercially available, FDA-approved products. This comprehensive scoping review was conducted in order to assess the current technological landscape of this field, describe the systems currently available or under development, and suggest further advancements that may unfold in the coming years. Ten distinct systems were identified and discussed.
... In 2021, JCMC also published a highly interesting study investigating closed-loop (CL) resuscitation in an experimental animal (pig) model of hemorrhagic shock [32]. Anesthetized pigs were bled to a mean arterial pressure level between 30 and 35 mmHg and maintained there for 90 min, after which interventions were made. ...
Anesthesiology and intensive care medicine provide fertile ground for innovation in automation, but to date we have only achieved preliminary studies in closed-loop intravenous drug administration. Anesthesiologists have yet to implement these tools on a large scale despite clear evidence that they outperform manual titration. Closed-loops continuously assess a predefined variable as input into a controller and then attempt to establish equilibrium by administering a treatment as output. The aim is to decrease the error between the closed-loop controller’s input and output. In this editorial we consider the available intravenous anesthesia closed-loop systems, try to clarify why they have not yet been implemented on a large scale, see what they offer, and propose the future steps towards automation in anesthesia.
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Purpose of Review This review provides an overview of the rapidly evolving field of computer-assisted fluid management systems, aimed at familiarizing clinicians with its key concepts and advancements. Recent Findings Over the past two decades, several attempts have been made to develop computerized systems to support clinicians with the complicated task of patient fluid management. These systems vary in their purpose, logic, evaluation methods, and more, but they share the principle of utilizing closed-loop control mechanisms. Summary Computer-assisted fluid management systems (CAFMs) provide automated tools to support the task of fluid management, promoting precise fluid therapy that is continuously adjusted to meet the set goal. As advanced physiological sensors and algorithms continue to evolve and mature, the implementation of CAFMs within the realm of anesthesia and critical care will continue to grow.
Physiological closed-loop control (PCLC) systems are a key enabler for automation and clinician support in medicine, including, but not limited to, patient monitoring, diagnosis, clinical decision making, and therapy delivery. Existing body of work has demonstrated that PCLC systems hold promise to advance critical care as well as a wide range of other domains in medicine bearing profound implications in quality of life, quality of care, and human wellbeing. However, the state-of-the-art PCLC technology in critical care is associated with long-standing limitations related to its development and assessment, including (i) isolated and loop-by-loop PCLC design without sufficient account for multi-faceted patient physiology, (ii) suboptimal choice of therapeutic endpoints, (iii) concerns related to collective safety originating from multi-PCLC interferences, and (iv) premature PCLC assessment methodology. Such limitations motivate research to generate new knowledge and create innovative methods. In this perspective, we propose possible high-reward opportunities that can accelerate the advances in PCLC systems, which may be explored by deep fusion and collaboration among multiple disciplines including physiological systems and signals analysis, control and estimation, machine learning and artificial intelligence, and wearable sensing and embedded computing technologies.
Rationale: Norepinephrine (NE) is commonly used in combination with fluid during resuscitation of hemorrhagic shock, however its impact on kidney microcirculation, oxygenation and function is still unknown in this setting. Objectives: During hemorrhagic shock resuscitation, does a combination of fluid and norepinephrine affect kidney oxygenation tension, kidney microcirculatory perfusion and 48-hour kidney function, as compared to fluid alone? Methods: Hemorrhagic shock was induced in 24 pigs and 8 pigs were included as sham. Resuscitation of hemorrhagic shock was performed, using a closed-loop device, either by fluid alone (0.9% NaCl, Fluid group) or associated with the administration of NE at two doses (moderate dose: mean rate of 0.64 µ and high dose: mean rate of 1.57 µ in order to obtain SAP (systolic arterial pressure) target of 80-90 mmHg. Resuscitation was followed by transfusion of the withdrawn blood. Measurements and main results: The amount of fluid required to reach SAP target was lower in NE groups than in Fluid group with subsequent less hemodilution. Norepinephrine restored kidney microcirculation, oxygenation, and function in a manner comparable to that achieved with fluid resuscitation alone. There were no histological differences among animals resuscitated with Fluid or with NE. Conclusion: In pigs with hemorrhagic shock, resuscitation with a combination of NE and fluid restored kidney microcirculation and oxygenation, as well as renal function, in a manner comparable to fluid resuscitation alone and without differences between the two NE doses. NE administration led to a fluid volume sparing effect with subsequently less hemodilution.
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The Yorkshire-cross swine model is a valuable translational model commonly used to study cardiovascular physiologyand response to insult. Although the effects of vasoactive medications have been well described in healthy swine, the effects of these medications during hemorrhagic shock are less studied. In this study, we sought to expand the utility of the swine model by characterizing the hemodynamic changes that occurred after the administration of commonly available vasoactive medications during euvolemic and hypovolemic states. To this end, we anesthetized and established femoral arterial,central venous, and pulmonary arterial access in 15 juvenile Yorkshire-cross pigs. The pigs then received a series of rapidlymetabolized but highly vasoactive medications in a standard dosing sequence. After completion of this sequence, each pigunderwent a 30-mL/kg hemorrhage over 10 min, and the standard dosing sequence was repeated. We then used standard statisticaltechniques to compare the effects of these vasoactive medications on a variety of hemodynamic parameters betweenthe euvolemic and hemorrhagic states. All subjects completed the study protocol. The responses in the hemorrhagic state wereoften attenuated or even opposite of those in the euvolemic state. For example, phenylephrine decreased the mean arterialblood pressure during the euvolemic state but increased it in the hemorrhagic state. These results clarify previously poorlydefined responses to commonly used vasoactive agents during the hemorrhagic state in swine. Our findings also demonstratethe need to consider the complex and dynamic physiologic state of hemorrhage when anticipating the effects of vasoactivedrugs and planning study protocols.
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Most dynamic systems are controlled by discrete time controllers. One of the main challenges faced during the design of a digital control law is the selection of the appropriate sampling time. A small sampling time will increase the accuracy of the controlled output at the expense of heavy computations. In contrast, a large sampling time will decrease the computational power needed to update the control law at the expense of a smaller stability region. In addition, once the setpoint is reached, the controlled input is still updated, making the overall controlled system not energetically efficient. To be more efficient, one can update the control law based on a significant fixed change of the controlled signal (send-on-delta or event-based controller). Like for time-based discretization, the amplitude of the significant change must be chosen carefully to avoid oscillations around the setpoint (e.g., if the setpoint is in between two samples) or an unnecessary increase of the samples number needed to reach the setpoint with a given accuracy. This paper proposes a novel non-linear event-based discretization method based on inter-events duration. We demonstrate that our new method reaches an arbitrary accuracy independently of the setpoint amplitude without increasing the network data transmission bandwidth. The method decreases the overall number of samples needed to estimate the states of a dynamical system and the update rate of an actuator, making it more energetically efficient.
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Initial feasibility of a novel closed-loop controller created by our group for closed-loop control of vasopressor infusions has been previously described. In clinical practice, vasopressor potency may be affected by a variety of factors including other pharmacologic agents, organ dysfunction, and vasoplegic states. The purpose of this study was therefore to evaluate the effectiveness of our controller in the face of large variations in drug potency, where ‘effective’ was defined as convergence on target pressure over time. We hypothesized that the controller would remain effective in the face up to a tenfold variability in drug response. To perform the robustness study, our physiologic simulator was used to create randomized simulated septic patients. 250 simulated patients were managed by the closed-loop in each of 7 norepinephrine responsiveness conditions: 0.1 ×, 0.2 ×, 0.5 ×, 1 ×, 2 ×, 5 ×, and 10 × expected population response to drug dose. Controller performance was evaluated for each level of norepinephrine response using Varvel’s criteria as well as time-out-of-target. Median performance error and median absolute performance error were less than 5% in all response levels. Wobble was below 3% and divergence remained negative (i.e. the controller tended to converge towards the target over time) in all norepinephrine response levels, but at the highest response level of 10 × the value approached zero, suggesting the controller may be approaching instability. Response levels of 0.1 × and 0.2 × exhibited significantly higher time-out-of-target in the lower ranges (p < 0.001) compared to the 1 × response level as the controller was slower to correct the initial hypotension. In this simulation study, the closed-loop vasopressor controller remained effective in simulated patients exhibiting 0.1 to 10 × the expected population drug response.
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Background: Closed-loop resuscitation can improve personalization of care, decrease workload and bring expert knowledge in isolated areas. We have developed a new device to control the administration of fluid or simultaneous co-administration of fluid and norepinephrine using arterial pressure. Method: We evaluated the performance of our prototype in a rodent model of haemorrhagic shock. After haemorrhagic shock, rats were randomized to five experimental groups: three were resuscitated with fluid and two with co-administration of fluid and norepinephrine. Among groups resuscitated with fluid, one was resuscitated by a physician and two were resuscitated according to two different closed-loop algorithms. Among groups resuscitated with fluid and norepinephrine, one was resuscitated by a physician and the other one by the closed-loop device. The precision of arterial pressure during the resuscitation period was assessed using rising time, time passed in the target area and performance error calculations. Results: Groups resuscitated with fluid had similar performances and passed as much time in the target area of 80-90 mmHg as the manual group [manual: 76.8% (67.9-78.2), closed-loop: 64.6% (45.7-72.9) and 80.9% (59.1-85.3)]. Rats resuscitated with fluid and norepinephrine using closed-loop passed similar time in target area than manual group [closed-loop: 74.4% (58.4-84.5) vs. manual: 60.1% (46.1-72.4)] but had shorter rising time to reach target area [160 s (106-187) vs. 434 s (254-1081)] than those resuscitated by a physician. Rats resuscitated with co-administration of fluid and norepinephrine required less fluid and had less hemodilution than rats resuscitated with fluid alone. Lactate decrease was similar between groups resuscitated with fluid alone and fluid with norepinephrine. Conclusions: This study assessed extensively the performances of several algorithms for closed-loop resuscitation of haemorrhagic shock with fluid alone and with co-administration of fluid and norepinephrine. The performance of the closed-loop algorithms tested was similar to physician-guided treatment with considerable saving of work for the caregiver. Arterial pressure closed-loop guided algorithms can be extended to combined administration of fluid and norepinephrine.
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Background Hemodynamic resuscitation in septic shock requires aggressive fluid replacement and appropriate use of vasopressors to optimize arterial pressure (AP) and cardiac output (CO). Because responses to these drugs vary between patients and within patient over time, strict monitoring of patient condition and repetitive adjustment of drug dose are required. This task is time and labor consuming, and is associated with poor adherence to resuscitation guidelines. To overcome this issue, we developed a computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in septic shock, and evaluated the performance of the system in a canine model of endotoxin shock. Methods Our system monitors AP, CO and central venous pressure, and computes arterial resistance (R), stressed blood volume (V) and Frank-Starling slope of left ventricle (S). The system controls R with noradrenaline (NA), and V with Ringer’s acetate solution (RiA), thereby controlling AP and CO. In 4 dogs, AP and CO were measured invasively. In another 4 dogs, AP and CO were measured less invasively using clinically acceptable modalities, aiming to make the system clinically feasible. In all 8 dogs, endotoxin shock was induced by injecting Escherichia coli lipopolysaccharide, which significantly decreased AP from 95 (91–108) to 43 (39–45) mmHg, and CO from 112 (104–142) to 62 (51–73) ml·min⁻¹·kg⁻¹. The system was then connected to the dogs, and activated. System performance was observed over a period of 4 h. Results Our system immediately started infusions of NA and RiA. Within 40 min, RiA increased V to target level, and NA maintained R at target level, while S was concomitantly increased. These resulted in restoration of AP to 70 (69–71) mmHg and CO to 130 (125–138) ml·min⁻¹·kg⁻¹. Median of absolute performance error, an index of precision of control, was small in AP [2.5 (2.1–4.5) %] and CO [2.4 (1.4–5.5) %], which were not increased even when the variables were measured less invasively. Conclusions In a canine model of endotoxin shock, our system automatically improved and maintained AP and CO at their target values with small performance error. Our system is potentially an attractive clinical tool for rescuing patients with septic shock. Electronic supplementary material The online version of this article (10.1186/s12871-017-0437-9) contains supplementary material, which is available to authorized users.
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Background Hemorrhagic shock is the leading cause of trauma-related death in the military setting. Definitive surgical treatment of a combat casualty can be delayed and life-saving fluid resuscitation might be necessary in the field. Therefore, improved resuscitation strategies are critically needed for prolonged field and en route care. We developed an automated closed-loop control system capable of titrating fluid infusion to a target endpoint. We used the system to compare the performance of a decision table algorithm (DT) and a fuzzy logic controller (FL) to rescue and maintain the mean arterial pressure (MAP) at a target level during hemorrhages. Fuzzy logic empowered the control algorithm to emulate human expertise. We hypothesized that the FL controller would be more effective and more efficient than the DT algorithm by responding in a more rigid, structured way. Methods Ten conscious sheep were submitted to a hemorrhagic protocol of 25 ml/kg over three separate bleeds. Automated resuscitation with lactated Ringer’s was initiated 30 min after the first hemorrhage started. The endpoint target was MAP. Group differences were assessed by two-tailed t test and alpha of 0.05. Results Both groups maintained MAP at similar levels throughout the study. However, the DT group required significantly more fluid than the FL group, 1745 ± 552 ml (42 ± 11 ml/kg) versus 978 ± 397 ml (26 ± 11 ml/kg), respectively (p = 0.03). Conclusion The FL controller was more efficient than the DT algorithm and may provide a means to reduce fluid loading. Effectiveness was not different between the two strategies. Automated closed-loop resuscitation can restore and maintain blood pressure in a multi-hemorrhage model of shock.
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Closed-loop feedback computer-controlled vasopressor infusion has been previously described for maintaining blood pressure during spinal anaesthesia for caesarean section but there are limited data available comparing the relative performance of different vasopressors. The aim of this study was to compare the performance of norepinephrine versus phenylephrine in this system. Data from a randomized, two-arm parallel group, double-blinded controlled trial were reanalyzed. 104 patients scheduled for elective caesarean section under spinal anaesthesia were randomized to receive computer-controlled closed-loop infusion of either norepinephrine 5 µg ml(-1) or phenylephrine 100 µg ml(-1). This was started immediately after induction of spinal anaesthesia and used an algorithm designed to maintain systolic blood pressure near baseline until fetal delivery. Performance error calculations were used to compare the performance of the two vasopressors. The primary outcome was defined as the median absolute performance error. Median performance error, wobble and divergence were also compared. Median absolute performance error was smaller in the norepinephrine group (median 3.79 [interquartile range 2.82-5.17] %) versus the phenylephrine group (4.70 [3.23-6.57] %, P = 0.028). In addition, median performance error was smaller (0.75 [-1.56-2.52] %) versus 2.61 [0.83-4.57] %, P = 0.002) and wobble was smaller (2.85 [2.07-5.17] %) versus 3.39 [2.62-4.90] %, P = 0.028) in the norepinephrine group versus the phenylephrine group. Divergence was similar between groups. The precision of the control of blood pressure was greater with norepinephrine compared with phenylephrine at the drug concentrations used.
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Background Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. Methods The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. ResultsThe guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. ConclusionsA multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.
Background: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. Methods: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. Results: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. Conclusions: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. Trial registry number: NCT03515161 (
What we already know about this topic: Intraoperative hypotension has been associated with adverse postoperative outcomes.A randomized controlled trial of individualized blood pressure management in patients undergoing major abdominal surgery found reduced postoperative adverse events in patients in the blood pressure management intervention group versus the standard of care group. What this article tells us that is new: In this study of pigs with normovolemic hypotension induced by administration of sodium nitroprusside, an automated closed-loop vasopressor administration device was able to maintain mean arterial pressure within 5 mmHg of 80 mmHg for 98% of the intraoperative period. This suggests that norepinephrine can be accurately titrated using an automated infusion device in order to maintain target blood pressure. Background: Multiple studies have reported associations between intraoperative hypotension and adverse postoperative complications. One of the most common interventions in the management of hypotension is vasopressor administration. This approach requires careful and frequent vasopressor boluses and/or multiple adjustments of an infusion. The authors recently developed a closed-loop controller that titrates vasopressors to maintain mean arterial pressure (MAP) within set limits. Here, the authors assessed the feasibility and overall performance of this system in a swine model. The authors hypothesized that the closed-loop controller would be able to maintain MAP at a steady, predefined target level of 80 mmHg for greater than 85% of the time. Methods: The authors randomized 14 healthy anesthetized pigs either to a control group or a closed-loop group. Using infusions of sodium nitroprusside at doses between 65 and 130 µg/min, we induced four normovolemic hypotensive challenges of 30 min each. In the control group, nothing was done to correct hypotension. In the closed-loop group, the system automatically titrated norepinephrine doses to achieve a predetermined MAP of 80 mmHg. The primary objective was study time spent within ±5 mmHg of the MAP target. Secondary objectives were performance error, median performance error, median absolute performance error, wobble, and divergence. Results: The controller maintained MAP within ±5 mmHg of the target for 98 ± 1% (mean ± SD) of the time. In the control group, the MAP was 80 ± 5 mmHg for 14.0 ± 2.8% of the time (P< 0.0001). The MAP in the closed-loop group was above the target range for 1.2 ± 1.2% and below it for 0.5 ± 0.9% of the time. Performance error, median performance error, median absolute performance error, wobble, and divergence were all optimal. Conclusions: In this experimental model of induced normovolemic hypotensive episodes in pigs, the automated controller titrated norepinephrine infusion to correct hypotension and keep MAP within ±5 mmHg of target for 98% of management time.
Background: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. Methods: In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. Results: The CLC maintained MAP within 5 mm Hg of the target for (mean ? standard deviation) 93.5% ? 3.9% of the time versus 72.4% ? 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ? 3.3% and 25.8% ? 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. Conclusions: The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.