Infectious disease/original researchEarly microcirculatory perfusion derangements in patients with severe sepsis and septic shock: Relationship to hemodynamics, oxygen transport, and survival
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
References (46)
- et al.
Nitroglycerin in septic shock after intravascular volume resuscitation
Lancet
(2002) - et al.
Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis
J Surg Res
(1996) - et al.
Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department
Chest
(2006) Cytopathic hypoxia: mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis
Crit Care Clin
(2001)- et al.
Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation
Lancet
(2004) - et al.
Comparisons between sublingual and gastric tonometry during hemorrhagic shock
Chest
(2000) The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome
Blood
(2003)- et al.
Microvascular blood flow is altered in patients with sepsis
Am J Respir Crit Care Med
(2002) - et al.
Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock
Crit Care Med
(2004) - et al.
Bench-to-bedside review: microvascular dysfunction in sepsis: hemodynamics, oxygen transport, and nitric oxide
Crit Care
(2003)
Microvascular perfusion is impaired in a rat model of normotensive sepsis
J Clin Invest
Increases in tissue PCO2 during circulatory shock reflect selective decreases in capillary blood flow
Crit Care Med
Effects of perfusion pressure on tissue perfusion in septic shock
Crit Care Med
Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function
Crit Care Med
Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update
Crit Care Med
Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock
Crit Care Med
Microcirculatory alterations are an independent outcome predictor in patients with severe sepsis and septic shock
Crit Care Med
Early goal-directed therapy in the treatment of severe sepsis and septic shock
N Engl J Med
Severe sepsis and septic shock: review of the literature and emergency department management guidelines
Ann Emerg Med
Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol
Crit Care Med
Early goal-directed therapy, corticosteroid, and recombinant human activated protein C for the treatment of severe sepsis and septic shock in the emergency department
Acad Emerg Med
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis
Crit Care Med
Orthogonal polarization spectral imaging: a new method for study of the microcirculation
Nat Med
Cited by (521)
Microcirculatory effects of rewarming in experimental hemorrhagic shock
2023, Microvascular ResearchSepsis, septic shock, and its treatment
2023, Current Therapy of Trauma and Surgical Critical CareA new convolutional neural network-construct for sepsis enhances pattern identification of microcirculatory dysfunction
2023, Intelligence-Based MedicineEvaluation of the impact of blood donation on tissue perfusion and sublingual microcirculation in dogs: A pilot study
2022, Research in Veterinary ScienceEvaluation of pimobendan effect on sublingual microcirculation in an experimental pharmacology induced hypotension porcine model
2022, Research in Veterinary Science
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.