Abstract
In this thesis, the role of venous return in organ perfusion is elucidated. Using experimental studies, we investigated this relationship in order to improve monitoring-guided therapies aimed at supporting organ function in patients with circulatory shock.
To this end, in chapter 2, we studied a bedside technique that estimated the mean systemic filling pressure (a potential marker of volume status). The clinical applicability of this method to guide volume therapy in its current form remains unclear. Moreover, chapter 3 revealed that the foundation, on which this mean systemic filling pressure is build, rattles. As a consequence, this exerts a major influence on the measured quantity, and consecutive interpretation and clinical relevance.
In Chapter 4 and 5 of this thesis we focus on a novel therapeutic strategy for patients with septic shock, namely heart rate control using β-blockers. We showed that it is effective to reduce myocardial oxygen consumption when its need outstrips the capacity. However, excessive β-blockade had negative inotropic effects and could put the cardiac output below the threshold that is needed to maintain organ and tissue perfusion. This implies that for safe application of β-blockers with maximum effect, one should focus on; moment of administration, type of β-blocker, resuscitation targets and patient characteristics.
Another therapy option for patients in septic shock is the use of vasopressors. In chapter 6, we investigated whether any vasopressor in particular (norepinephrine, phenylephrine, or vasopressin) holds an advantage when considering effects on both the micro- and macrocirculation. Hampered by the use of low dosages of vasopressors in healthy volunteers, we only saw exerted effects on macrocirculatory parameters compared to placebo. In the last chapter of this thesis, chapter 7, we showed–using extensive analysis of the renal autoregulation–that the dependency of flow to pressure could be attributed to the low perfusion pressures, rather than a damaged autoregulatory system of the kidneys.
Together, in this thesis we revealed that the role of venous return in organ blood flow depends on pathological conditions, therapeutic interventions, (right) ventricular function, ventilatory settings and autoregulatory mechanisms. Moreover, organ blood flow cannot be assessed by solely looking at the macrocirculation.
To this end, in chapter 2, we studied a bedside technique that estimated the mean systemic filling pressure (a potential marker of volume status). The clinical applicability of this method to guide volume therapy in its current form remains unclear. Moreover, chapter 3 revealed that the foundation, on which this mean systemic filling pressure is build, rattles. As a consequence, this exerts a major influence on the measured quantity, and consecutive interpretation and clinical relevance.
In Chapter 4 and 5 of this thesis we focus on a novel therapeutic strategy for patients with septic shock, namely heart rate control using β-blockers. We showed that it is effective to reduce myocardial oxygen consumption when its need outstrips the capacity. However, excessive β-blockade had negative inotropic effects and could put the cardiac output below the threshold that is needed to maintain organ and tissue perfusion. This implies that for safe application of β-blockers with maximum effect, one should focus on; moment of administration, type of β-blocker, resuscitation targets and patient characteristics.
Another therapy option for patients in septic shock is the use of vasopressors. In chapter 6, we investigated whether any vasopressor in particular (norepinephrine, phenylephrine, or vasopressin) holds an advantage when considering effects on both the micro- and macrocirculation. Hampered by the use of low dosages of vasopressors in healthy volunteers, we only saw exerted effects on macrocirculatory parameters compared to placebo. In the last chapter of this thesis, chapter 7, we showed–using extensive analysis of the renal autoregulation–that the dependency of flow to pressure could be attributed to the low perfusion pressures, rather than a damaged autoregulatory system of the kidneys.
Together, in this thesis we revealed that the role of venous return in organ blood flow depends on pathological conditions, therapeutic interventions, (right) ventricular function, ventilatory settings and autoregulatory mechanisms. Moreover, organ blood flow cannot be assessed by solely looking at the macrocirculation.
| Original language | English |
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| Qualification | Doctor of Philosophy |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 12 Feb 2020 |
| Place of Publication | Enschede |
| Publisher | |
| Print ISBNs | 978-90-365-4946-2 |
| DOIs | |
| Publication status | Published - 12 Feb 2020 |