Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Abstract

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients’ response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes.

Pulse wave analysis as a tool for the evaluation of resuscitation therapy in septic shock

“…Previous results from our group have shown how, in several animal populations undergoing sepsis/septic shock and different resuscitation protocols, reduced arterial compliance, total peripheral resistance and pulse pressure amplification were still present even after standard resuscitation with fluids and vasopressors was evaluated to be successful according to recommended targets. Moreover, the morphological profile of the blood pressure waveform continued to exhibit changes upon completion of the resuscitation protocol, reinforcing the evidence for persistent alterations in the cardiovascular system involving blood pressure propagation and reflection (Carrara et al 2020a(Carrara et al , 2020b(Carrara et al , 2022.…”

“…However, morphological alterations of the arterial waveform are typically overlooked during resuscitation, despite they can be highly informative regarding the underlying cardiovascular functions and properties. Previous works on experimental septic shock have shown how the arterial waveform still exhibits an evident morphological alteration despite successful haemodynamic resuscitation, hinting that the of mean haemodynamic targets does not directly imply the return to a physiological condition (Carrara et al 2020a(Carrara et al , 2022.…”

Acoplamiento nervo-vascular como pronóstico de mortalidad del paciente con sepsis en la unidad de cuidados intensivos

“…Encontraron que la sepsis induce un desacoplamiento de la propagación de la onda del pulso arterial de los sitios centrales a los periféricos, sin resolución después de la reanimación óptima, atribuyéndolos como signos de disfunción autonómica, que ocasionan un desacoplamiento vascular persistente por horas después de una reanimación completa con fluidos y norepinefrina. 1,2,6,16,18…”

“…La factibilidad de realizar la evaluación al pie de cama del enfermo crítico contribuye a identificar oportunamente sujetos con riesgo de desarrollar complicaciones como resistencia vasopresora, persistencia de taquicardia a pesar de hipotensión e hipovolemia corregida, así como asociar a mayor riesgo de severidad y mortalidad. 1,2,6 MATERIAL Y MÉTODOS Tipo de estudio: retrospectivo, descriptivo, observacional y longitudinal.…”

“…Las endotoxinas en la sepsis y choque séptico activan mediadores inflamatorios que activan células glómicas quimiosensibles del cuerpo carotideo, lo que lleva a una actividad respiratoria aumentada. [6][7][8][9][10] El endotelio vascular regula el tono, la hemostasia y la permeabilidad vascular; la hiperactividad simpática y la disfunción vascular pueden estar íntima y causalmente relacionadas entre sí de una manera muy compleja, como aumento de la rigidez de las grandes arterias y esta rigidez altera la función barorrefleja, interfiriendo así con el control simpático del tono vascular del músculo liso. Los receptores adrenérgicos alfa 1 sufren un proceso de desensibilización y un mecanismo de retroalimentación para proteger al receptor contra la sobreestimulación; esto contribuye aún más al fracaso de la modulación autonómica del tono vascular y a una menor eficacia de los vasopresores.…”