Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O<sub>2</sub> extraction during septic shock

Ospina-Tascón, Gustavo Adolfo; Marín, Alberto Federico García; Echeverri, Gabriel J.; Bermúdez, William; Madriñán-Navia, Humberto; Valencia, Juan D.; Quiñones, Edgardo; Rodríguez, Fernando; Marulanda, Ángela; Arango-Dávila, César Augusto; Bruhn, Alejandro; Hernández, Glenn; Backer, Daniel De

doi:10.1152/japplphysiol.00886.2016

Cited by 28 publications

(16 citation statements)

References 46 publications

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“…In contrast, DOB may facilitate vasodilation of the spinal cord vasculature directly via β 2 -adrenergic receptor stimulation 21 and indirectly via shear-mediated vasodilation 22 , to ultimately optimize blood flow distribution and reduce hemorrhage in the injured cord. Such DOB-mediated improvements in microvascular blood flow have been reported in septic shock 23 – 25 , and coincide with restored local oxygen delivery and mitigated tissue acidosis, all of which are in line with the SCO 2 and microdialysis findings in the current study. A study by De Backer et al 24 notably highlighted that DOB-mediated improvements in capillary perfusion were not related to changes cardiac index, MAP, or total peripheral resistance, indicating that DOB may improve local microvascular flow and oxygen delivery independent of its effects on cardiac or arterial hemodynamics.…”

Section: Discussionsupporting

confidence: 90%

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

et al. 2020

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Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the β-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.

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Section: Discussionsupporting

confidence: 90%

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

et al. 2020

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“…We found only a weak correlation between PPV and arterial elastance. Similarly, other studies showed a weak, and often transitory, correlation between PPV and macrohemodynamic parameters (e.g., cardiac output, oxygen delivery, and venous oxygen saturation) in septic patients [20, 21]. It could be also speculated that arterial elastance may be more influenced by the arteriolar tone, while other factors, such as tissue edema, neural perivascular activity, and changes in red blood cells deformability, may impact on capillary density and perfusion.…”

Section: Discussionmentioning

confidence: 63%

Relationship between Microcirculatory Perfusion and Arterial Elastance: A Pilot Study

Bond

Santis

Iesu

et al. 2019

Critical Care Research and Practice

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Background. Arterial elastance (Ea) represents the total afterload imposed on the left ventricle, and it is largely influenced by systemic vascular resistance (SVR). Although one can expect that Ea is influenced by peripheral endothelial function, no data are available to support it in patients. The aim of this study was to investigate the relationship between Ea, SVR, and microvascular perfusion in critically ill patients undergoing the fluid challenge (FC). Methods. A prospective study in patients receiving a fluid challenge. A pulse wave analysis system (MostCare, Vygon, France) was used to estimate Ea and an incident dark field (IDF) handheld device (Braedius Medical BV, The Netherlands) to evaluate the sublingual microcirculation. Microvascular perfusion was assessed using the proportion of small-perfused vessels (PPV). Relative changes in each variable were calculated before and after FC; fluid responsiveness was defined as an increase in the cardiac index by at least 10% from baseline. Results. We studied 20 patients requiring a fluid challenge (n=10 for hypotension; n=5 for oliguria; n=3 for lactate values greater than 2 mmol/l; n=2 for tachycardia), including 12 fluid responders. There was a strong correlation between Ea and SVR (r2 = 0.75; p<0.001) and only a weak correlation between Ea and PPV at baseline (r2 = 0.22; p=0.04). Ea decreased from 1.4 [1.2–1.6] to 1.2 [1.1–1.4] mmHg/mL (p=0.01), SVR from 1207 [1006–1373] to 1073 [997–1202] dyn ∗ s/cm5 (p=0.06), and PPV from 56 [51–64] % to 59 [47–73] % (p=0.25) after fluid challenge. Changes in Ea were significantly correlated with changes in SVR, but not with changes in PPV. Conclusions. The correlation between Ea and indexes of microvascular perfusion in the sublingual region is weak. The impact of microcirculatory perfusion on the arterial load is probably limited.

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“…Any recruitment maneuver targeting the microcirculation will comprise two aspects, i.e., the “ (re-)opening ” of the capillary network (e.g., using fluid resuscitation, ino-dilation and restriction of vasoconstriction) and the subsequent attenuation of flow heterogeneity (summarized in Figure 2A ) ( 2 ). Based on this rationale, fluid resuscitation ( 30 – 34 ), dobutamine ( 35 ), levosimendan ( 36 ), milrinone ( 37 ), nitric oxide (NO) donors ( 38 – 40 ), and prostacyclin (PGI 2 ) ( 40 – 42 ) have all been tested. In experimental settings, this approach was often successful but the majority of animal studies were only of short duration and/or did not include standard intensive care measures, which may limit transferability into clinical practice ( 43 ).…”

Section: Does “Microvascular Resuscitation” Help?mentioning

confidence: 99%

Microcirculation vs. Mitochondria—What to Target?

et al. 2020

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Circulatory shock is associated with marked disturbances of the macro- and microcirculation and flow heterogeneities. Furthermore, a lack of tissue adenosine trisphosphate (ATP) and mitochondrial dysfunction are directly associated with organ failure and poor patient outcome. While it remains unclear if microcirculation-targeted resuscitation strategies can even abolish shock-induced flow heterogeneity, mitochondrial dysfunction and subsequently diminished ATP production could still lead to organ dysfunction and failure even if microcirculatory function is restored or maintained. Preserved mitochondrial function is clearly associated with better patient outcome. This review elucidates the role of the microcirculation and mitochondria during circulatory shock and patient management and will give a viewpoint on the advantages and disadvantages of tailoring resuscitation to microvascular or mitochondrial targets.

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Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O₂ extraction during septic shock

Cited by 28 publications

References 46 publications

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

Relationship between Microcirculatory Perfusion and Arterial Elastance: A Pilot Study

Microcirculation vs. Mitochondria—What to Target?

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Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock

Cited by 28 publications

References 46 publications

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

Relationship between Microcirculatory Perfusion and Arterial Elastance: A Pilot Study

Microcirculation vs. Mitochondria—What to Target?

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Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O₂ extraction during septic shock