Infectious disease/original research
Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: Relationship to hemodynamics, oxygen transport, and survival

Presented in part at the American College of Emergency Physicians Scientific Assembly, October 2005, Washington, DC; the Society of Critical Care Medicine Congress, January 2006, San Francisco, CA; and the Society for Academic Emergency Medicine Annual Meeting, May 2006, San Francisco, CA.
https://doi.org/10.1016/j.annemergmed.2006.08.021Get rights and content

Study objective

To study early microcirculatory perfusion indices in patients with severe sepsis/septic shock, compare early microcirculatory indices in sepsis survivors versus nonsurvivors, and identify systemic hemodynamic/oxygen transport variables that correlate with early microcirculatory perfusion indices.

Methods

This prospective observational study used orthogonal polarization spectral imaging to directly visualize the sublingual microcirculation in patients with severe sepsis/septic shock treated with early goal-directed therapy. We performed initial imaging within 6 hours of early goal-directed therapy initiation and late follow-up studies at 24-hour intervals until death or resolution of organ dysfunction. We imaged 5 sublingual sites and analyzed the data offline in a blinded fashion. We calculated 3 microcirculatory perfusion indices: flow velocity score, flow heterogeneity index, and capillary density. We analyzed early data to compare survivors versus nonsurvivors and examine correlations with systemic hemodynamic measurements. We used a linear mixed-effects model for longitudinal analyses.

Results

We performed 66 orthogonal polarization spectral studies in 26 sepsis patients. Early microcirculatory indices were more markedly impaired (lower flow velocity and more heterogeneous perfusion) in nonsurvivors compared with survivors. These same early indices, flow velocity and heterogeneity, were also more markedly impaired with increasing severity of systemic cardiovascular dysfunction (lower arterial pressure or increasing vasopressor requirement).

Conclusion

Early microcirculatory perfusion indices in severe sepsis and septic shock are more markedly impaired in nonsurvivors compared with survivors and with increasing severity of global cardiovascular dysfunction.

Introduction

Microcirculatory dysfunction is a pivotal element of the pathogenesis of severe sepsis and septic shock.1, 2, 3 Using intravital videomicroscopy, experimental models of sepsis have demonstrated impaired microcirculatory flow velocity, “stopped-flow” microvessels, increased heterogeneity of regional perfusion, and low density of perfused capillaries.4, 5, 6, 7 With new imaging modalities such as orthogonal polarization spectral imaging, it is now possible to visualize the microcirculatory network in human subjects.1, 2

Derangement of microcirculatory perfusion in sepsis can occur independent of arterial pressure.1, 3, 8, 9 In fact, the precise relationship between global (ie, macrocirculatory) hemodynamics and microcirculatory blood flow is considered one of the key pathophysiologic questions in sepsis but remains incompletely understood. Practice parameters for the cardiovascular support of patients with septic shock advocate maintaining a mean arterial pressure greater than 65 mm Hg.10, 11 However, it is unclear whether arterial pressure above this threshold ensures adequacy of tissue perfusion.

Derangement of microcirculatory flow appears to be one of the critical pathogenic events in sepsis1 and has been associated and with acute multiorgan failure and mortality.3, 12 However, microcirculatory flow has not been studied in concert with a resuscitation protocol that helps ensure early optimization of global tissue perfusion. Effective resuscitation with early goal-directed therapy13 is considered a critical component of sepsis management.11, 14 We therefore undertook a study of microcirculatory blood flow in sepsis in the context of a practice setting that has implemented an early goal-directed therapy protocol.15, 16, 17 We studied the microcirculation in early sepsis because organ failure is hypothesized to be a perfusion-mediated phenomenon in early-phase sepsis,13 perhaps to a greater extent than the organ failure of late-phase sepsis, which may result from mitochondrial dysfunction18 and bioenergetic failure.19

All patients treated with early goal-directed therapy had physiologic data derived from invasive monitoring, allowing us to investigate correlations between microcirculatory indices and a full range of systemic hemodynamic indices. Although previous studies of orthogonal polarization spectral imaging in sepsis reported no predictable relationship between microcirculatory flow and systemic hemodynamics,1, 3 neither study was designed to focus on early time points nor a protocol targeting specific endpoints of resuscitation. Characterizing the nature of this relationship could be an initial step toward a better understanding of the role of the microcirculation in sepsis-associated cardiovascular dysfunction, as well as the microcirculatory response to conventional hemodynamic support.

Using the early goal-directed therapy phase of therapy as a marker to identify an early point in sepsis, we performed an investigation of orthogonal polarization spectral imaging in early severe sepsis/septic shock to test our hypotheses that early indices of microcirculatory perfusion would be more severely impaired in sepsis nonsurvivors compared to survivors and early microcirculatory perfusion indices would correlate with systemic hemodynamic and oxygen transport indices.

Section snippets

Study Design

This was a single-center prospective observational study.

Setting

The emergency department (ED) and ICU of an urban academic medical center (Cooper University Hospital, Camden, NJ) were used for the study.

Selection of Participants

The subjects were sepsis patients meeting criteria for early goal-directed therapy (defined below) during 12 months. We enrolled sepsis patients nonconsecutively, with enrollment depending on investigators’ ability to obtain orthogonal polarization spectral images at an early point (as defined below).

Characteristics of the Study Subjects

Twenty-six sepsis patients and 5 controls were enrolled. Baseline characteristics for sepsis subjects are shown in Table 1. Ten of 26 sepsis patients had early goal-directed therapy initiated and early images obtained in the ED. Sixteen of 26 sepsis patients originated on the inpatient ward and had early goal-directed therapy initiated and early images obtained on ICU arrival. When the early orthogonal polarization spectral images were obtained, sepsis patients were captured in various stages

Limitations

We recognize limitations in interpreting our findings. This was a study of early microcirculatory perfusion derangements in patients with severe sepsis/septic shock, and we used the early goal-directed therapy period as a marker to identify an early time point in sepsis management. We designed the study to obtain orthogonal polarization spectral images as soon as possible after initiating early goal-directed therapy; however, images were not obtained at a predefined step in the goal-directed

Discussion

Circulatory shock is defined as a failure of the cardiovascular system to maintain effective tissue perfusion, causing cellular dysfunction and acute organ system failure if not promptly restored. Although it is the macrocirculation (ie, heart and large arteries) that distributes blood flow globally throughout the body, the microcirculation is a critical component of the cardiovascular system that is necessary for blood flow to individual tissues. In the earliest phases of incipient shock, it

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    Supervising editor: David A. Talan, MD

    Author contributions: ST, RPD, JEP, and SMH conceived and designed the study. ST and SMH obtained research funding. ST and JSB performed microvideoscopic data acquisition. SMH supervised all aspects of image analysis. ST, RPD, MG, JB, NLA, RCA, SZ, and SMH analyzed the data. JB and NLA managed the data. ST, RPD, JEP, MG, NLA, RCA, SZ, and SMH interpreted results. SC contributed to study design and performed statistical analyses. ST drafted the article, and all authors contributed substantially to its revision. ST supervised all aspects of the conduct of the study and takes responsibility for the paper as a whole.

    Funding and support: This study was supported by Career Development grants from the Emergency Medicine Foundation and the National Program of the American Heart Association (0530152N) to Dr. Trzeciak.

    Reprints not available from the authors.

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