Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial.

OBJECTIVES: Microcirculatory alterations have been associated with morbidity and mortality in human sepsis. Such alterations occur despite pressure-guided resuscitation. Earlier data suggested that impaired microcirculatory blood flow could be corrected with intravenous nitroglycerin in these patients. We tested this concept after fulfillment of preset systemic hemodynamic resuscitation end points in the early phase of sepsis. DESIGN: Prospective, single center, randomized, placebo-controlled, double-blind clinical trial. SETTING: Closed-format 22-bed mixed intensive care unit in a tertiary teaching hospital. PATIENTS: Patients > or =18 yrs with sepsis, according to international criteria, and at least one early sign of organ dysfunction, as the principal reason for intensive care unit admission, were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive nitroglycerin (n = 35) or placebo (n = 35) after fulfillment of protocol-driven resuscitation end points. This trial is registered with ClinicalTrials.gov as NCT00493415. MEASUREMENTS AND MAIN RESULTS: Primary outcome was sublingual microcirculatory blood flow of small vessels, as assessed by side-stream dark field imaging. After protocolized resuscitation, we observed recruitment of sublingual microcirculation in both groups, as indicated by a significant improvement in the microcirculatory flow index after 24 hrs, in comparison to baseline. However, no difference in the sublingual microvascular flow index was observed between groups. The median microvascular flow index in sublingual small-sized vessels was 2.71 (1.85-3) in the nitroglycerin group and 2.71 (1.27-3), p = .80, in the placebo group. In medium-sized vessels, the respective values were 3 (2.75-3) vs. 2.86 (2.19-3), p = .21, and in large-sized vessels, 3 (3-3) vs. 3 (2.89-3), p = .06. In-hospital mortality, as a secondary outcome, was 34.3% in the nitroglycerin group and 14.2% in the placebo group, p = .09. CONCLUSIONS: In the context of a strict resuscitation protocol, based upon fulfillment of systemic hemodynamic end points in patients with early-phase severe sepsis or septic shock, we conclude that intravenous nitroglycerin does not promote sublingual microcirculatory blood flow.

The step length-frequency relationship in physically active community-dwelling older women.

This study evaluated the step length-frequency relationship in physically active community-dwelling older women in order to investigate whether the relationship between these two spatio-temporal gait parameters changes with increasing age. Forty older women in four age groups, i.e. 64-69, 70-74, 75-79 and 80-85 year olds, participated in the study. Subjects walked at five different self-selected speeds and while simultaneously performing an additional cognitive and/or upper-extremity motor task. Gait parameters were determined from forward accelerations measured by a tri-axial accelerometer on the lower back. All subjects demonstrated a strong linear relationship between step length and step frequency for walking at different speeds. No evidence for a change in the step length-frequency relationship with age was found, suggesting that there are no differences between physically active older women of different age groups regarding the adoption of a "cautious gait", i.e. a gait pattern characterized by a reduced step length.