Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

OBJECTIVE: Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy. DESIGN: Prospective observational study. SETTING: Emergency Department and Intensive Care Unit. PARTICIPANTS: Septic patients with systolic blood pressure <90 mmHg despite intravenous fluids or lactate >or=4.0 mM/L treated with early goal-directed therapy (EGDT). MEASUREMENTS AND RESULTS: We performed Sidestream Dark Field (SDF) videomicroscopy of the sublingual microcirculation <3 h from EGDT initiation and again within a 3-6 h time window after initial. We imaged five sites and determined the mean microcirculatory flow index (MFI) (0 no flow to 3 normal) blinded to all clinical data. We calculated the Sequential Organ Failure Assessment (SOFA) score at 0 and 24 h, and defined improved SOFA a priori as a decrease >or=2 points. Of 33 subjects; 48% improved SOFA over 0-24 h. Age, APACHE II, and global hemodynamics did not differ significantly between organ failure groups. Among SOFA improvers, 88% increased MFI during EGDT, compared to 47% for non-improvers (P = 0.03). Median change in MFI was 0.23 for SOFA improvers versus -0.05 for non-improvers (P = 0.04). CONCLUSIONS: Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics. These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.

Differing prevalence estimates of elevated blood pressure in ED patients using 4 methods of categorization.

OBJECTIVE: This study examined the variability of blood pressure measurements and prevalence estimates of elevated blood pressure in emergency department (ED) patients using 4 different methods of categorization. METHODS: A prospective, observational study was conducted on adult ED patients with elevated triage blood pressures (systolic > or = 140 or diastolic > or = 90 mm Hg). Three blood pressure measurements were obtained on all subjects and categorized as follows: (1) triage measurement only, (2) the mean of the triage and second measurement, (3) the mean of the 3 measurements, and (4) the mean of the second and third measurements. RESULTS: Of 2192 screened patients, 326 were included in the final analysis with mean triage systolic and diastolic blood pressures of 160 and 90 mm Hg, respectively. Prevalence estimates of elevated blood pressure in this sample ranged from 100% (reference standard: mean triage blood pressure) to the most conservative estimate of 67% (fourth method). CONCLUSION: Determination of elevated blood pressure in ED patients is largely dependent on the method of blood pressure categorization.

Characteristics and referral of emergency department patients with elevated blood pressure.

OBJECTIVES: To assess the prevalence, characteristics, and referral to health care of emergency department (ED) patients with elevated blood pressure (BP) and to compare those without a history of hypertension (HTN) with suboptimally controlled, known-hypertensive patients. METHODS: A prospective, observational study was conducted in non-critically ill adults with a triage systolic blood pressure (sBP) of > or =140 or with a diastolic blood pressure (dBP) of > or =90 mmHg. Two additional measurements were obtained, and a standardized questionnaire recorded demographics, medical history, and ED staff referrals. RESULTS: Of 1,719 nonpregnant adults, 991 agreed to participate, of whom 455 had elevated triage BP values. Using the mean of three measurements, 305 (67%) had an sBP of > or =140 or a dBP of > or =90 mm Hg (mean sBP = 157 and mean dBP = 89 mm Hg). Subjects with no prior history of HTN (n = 105) were predominantly male, younger, and more likely to smoke and consume alcohol than were known-hypertensive patients (n = 200). Three quarters of all subjects had access to primary health care; however, time elapsed since the last BP assessment was greater (155 vs. 53 d, p = 0.03) in subjects with no previous history. These subjects were also less likely to be informed of their elevated BP (33% vs. 50%, p = 0.02) or to be instructed by ED staff to obtain a repeat measurement (13% vs. 31%, p = 0.001). CONCLUSIONS: Of ED patients with elevated BP, one third had no prior history, and the remainder were suboptimally controlled hypertensive patients. Both groups were inadequately informed of their elevated BPs, and the group with no prior history of HTN, the population likely to obtain the greatest health benefit, had the lowest referral rate.

Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival.

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.

Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department.

OBJECTIVE: Early goal-directed therapy (EGDT) has been shown to decrease mortality in patients with severe sepsis and septic shock. Consensus guidelines now advocate EGDT for the first 6 h of sepsis resuscitation. However, EGDT has not yet been widely adopted in practice. A need for effective collaboration between emergency medicine and critical care medicine services has been identified as an obstacle for implementation. We aimed to determine if EGDT end points could reliably be achieved in real-world clinical practice. METHODS: EGDT was implemented as a collaborative emergency medicine/critical care quality improvement initiative. EGDT included the following: i.v. fluids (IVF) targeting central venous pressure > or = 8 mm Hg, vasopressors targeting mean arterial pressure > or = 65 mm Hg, and (if necessary) packed RBCs (PRBCs) and/or dobutamine targeting central venous oxygen saturation > or = 70%. A retrospective analysis was performed of emergency department (ED) patients with persistent sepsis-induced hypotension (systolic BP < 90 mm Hg despite 1.5 L of IVF) treated with EGDT during the first year of the initiative. Primary outcome measures included successful achievement of EGDT end points and time to achievement. A secondary analysis was performed comparing EGDT cases to historical control cases (nonprotocolized control subjects without invasive monitoring). RESULTS: All end points were achieved in 20 of 22 cases (91%). The median time to reach each end point was < or = 6 h. In the secondary analysis, patients (n = 38; EGDT, n = 22; pre-EGDT, n = 16) had similar age, do-not-resuscitate status, severity scores, hypotension duration, and vasopressor requirement (p = not significant). In the ED, EGDT used more IVF and included PRBC/dobutamine utilization, without any impact on the overall use of these therapies through the first 24 h in the ICU. EGDT was associated with decreased ICU pulmonary artery catheter (PAC) utilization (9.1% vs 43.7%, p = 0.01). CONCLUSIONS: With effective emergency medicine/critical care collaboration, we demonstrate that EGDT end points can reliably be achieved in real-world sepsis resuscitation. ED-based EGDT appears to decrease ICU PAC utilization.