The Systemic and Regional Hemodynamic Effects of Phenylephrine in Sheep Under Normal Conditions and During Early Hyperdynamic Sepsis

Department of Intensive Care, Austin Health, Melbourne, Victoria, Heidelberg, Victoria 3084, Australia.
Anesthesia and analgesia (Impact Factor: 3.47). 05/2012; 115(2):330-42. DOI: 10.1213/ANE.0b013e31825681ab
Source: PubMed


Phenylephrine treatment of hypotension in sepsis raises concern because it may decrease vital organ bloodflow. Accordingly, we investigated the effects of phenylephrine on systemic and regional bloodflow in normal and septic sheep.
Responses to phenylephrine or vehicle infusion for 6 hours were determined in conscious normal sheep and sheep with early sepsis induced by administration of live Escherichia coli. Cardiac output and coronary, mesenteric, and renal bloodflow were measured with implanted flow probes.
In normal sheep, phenylephrine decreased cardiac output and heart rate (HR) but increased stroke volume and mean arterial blood pressure (MAP) (84 ± 6 to 108 ± 6 mm Hg, magnitude of mean difference [diff.] 19 [22.6%]; 95% confidence intervals [CI], 17-21). There were significant decreases in regional conductance values with a transient decrease in mesenteric bloodflow, no change in coronary bloodflow, and increased renal bloodflow (222 ± 53 to 271 ± 55 mL/min; diff. 31 [13.9%]; 95% CI, 26-36). During hyperdynamic sepsis, vasodilatation and increased bloodflow occurred in all vascular beds. Phenylephrine restored MAP and stroke volume to baseline values, but HR, cardiac output, and total peripheral conductance progressively decreased. Phenylephrine decreased mesenteric and coronary conductance, with no sustained reduction in flows, but renal conductance was significantly decreased and overall renal bloodflow increased (293 ± 22 vs 347 ± 100 mL/min; diff. 55 [18.8%]; 95% CI, 47-65).
In sheep with early hyperdynamic sepsis, phenylephrine, at a dose that restored MAP, increased stroke volume and renal bloodflow while decreasing HR and coronary bloodflow but not mesenteric bloodflow. Similar responses were seen in normal animals.

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    • "Furthermore, given the complex and heterogeneous nature of the renal vasculature, some pathophysiological processes might be associated with increased global RBF [11,12] despite loss of function suggesting intra-renal shunting [13]. Therefore, techniques allowing the study of microcirculatory parameters might be more valuable in increasing our understanding of the pathophysiology of AKI. "
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    ABSTRACT: Contrast-enhanced ultrasound (CEUS) is a new technique that might enable portable and non-invasive organ perfusion quantification at the bedside. However, it has not yet been tested in critically ill patients. We sought to establish CEUS's feasibility, safety, reproducibility and potential diagnostic value in the assessment of renal cortical perfusion in the peri-operative period in cardiac surgery patients. We recruited twelve patients deemed at risk of acute kidney injury (AKI) planned for elective cardiac surgery. We performed renal CEUS with destruction-replenishment sequences before the operation, on ICU arrival and the day following the admission. Enhancement was obtained with Sonovue(R) (Bracco, Milano, Italy) at an infusion rate of 1 ml/min. We collected hemodynamic parameters before, during and after contrast agent infusion. At each study time, we obtained five video sequences, which were analysed using dedicated software by two independent radiologists blinded to patient and time. The main output was a perfusion index (PI), corresponding to the ratio of relative blood volume (RBV) over mean transit time (mTT). All 36 renal CEUS studies, including 24 in the immediate post-operative period could be performed and were well tolerated. Correlation between readers for PI was excellent (R2=0.96, p<0.0001). Compared with baseline, there was no overall difference in median PI's on ICU admission. However, the day after surgery, median PI's had decreased by 50% (p<0.01) [22% decrease in RBV (p=0.09); 48% increase in mTT (p=0.04), both suggestive of decreased perfusion]. These differences persisted after correction for haemoglobin; vasopressors use and mean arterial pressure. Four patients developed AKI in the post-operative period. CEUS appears feasible and well tolerated in patients undergoing cardiac surgery even immediately after ICU admission. CEUS derived-parameters suggest a decrease in renal perfusion occurring within 24 hours of surgery.
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    ABSTRACT: Purpose of review: Global renal blood flow is considered pivotal to renal function. Decreased global renal blood flow (decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rate responsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinary biochemical tests are widely taught to allow the differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidence regarding these two key clinical paradigms. Recent findings: Recent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonance technology are not consistent with the decreased perfusion paradigm. They suggest instead that changes in the intra-renal circulation including modification in efferent arteriolar function and intra-renal shunting are much more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicate the urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker and microscopic evidence of tubular injury. Summary: Intra-renal microcirculatory changes are likely more important than changes in global blood flow in the development of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in critically ill patients at risk of or with AKI.
    Full-text · Article · Sep 2012 · Current opinion in critical care
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