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Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

ABSTRACT: 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.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.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.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.

SUBMITTER: Uemura K

PROVIDER: S-EPMC5654105 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

Uemura Kazunori K Kawada Toru T Zheng Can C Li Meihua M Sugimachi Masaru M

BMC anesthesiology 20171023 1

<h4>Background</h4>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 ...[more]

PMID: 29061119

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Project description:BackgroundClosed-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.MethodWe 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.ResultsGroups 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.ConclusionsThis 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.

Project description:BackgroundVolume 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.MethodsFive 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.ResultsDuring 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.ConclusionThis 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.

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Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

Publications

Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

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