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OBJECTIVE:: To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia. DESIGN:: Prospective observational study during a 36-month period. SETTING:: Medical-surgical intensive care unit of a university hospital. PATIENTS:: One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p = .04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria. CONCLUSIONS:: A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To determine the effect of vasodilatory septic shock–like conditions on vasoconstricting responses to vasopressin and norepinephrine in isolated resistance arteries. DESIGN:: Prospective, randomized animal study.SETTING:: University research laboratory. SUBJECTS:: Male adult Sprague-Dawley rats. INTERVENTIONS:: Small mesenteric arteries (outside diameter, 50–150 μm) were cannulated and studied in vitro under physiologic conditions. A vasodilatory septic shock–like state was produced by treatment with the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Vasoconstricting concentration-response relationships were determined for norepinephrine and vasopressin before and after application of SNAP or SNAP+ IBMX. Synergism between low-dose vasopressin and norepinephrine and between low-dose norepinephrine and vasopressin was determined before and after SNAP or SNAP+IBMX. MAIN RESULTS:: Norepinephrine and vasopressin produced concentration-dependent contractions (half-maximal effective concentration [EC50] = 2.5 μM and 3.9 nM, respectively) that were significantly inhibited by 1 μM SNAP (EC50 = 3.6 μM and 8.1 nM, respectively) or 100 μM SNAP + 10 μM IBMX (EC50 = 10 μM and 8.2 nM, respectively). Low-dose vasopressin significantly increased the responsiveness to norepinephrine (EC50 = 0.5 μM) just as a low-dose norepinephrine significantly enhanced the vasopressin response (EC50 = 2.3 nM). The synergistic effects of low-dose vasopressin and norepinephrine, or low-dose norepinephrine and vasopressin, were also significantly inhibited by 1 μM SNAP (EC50 = 2.5 μM and 4.2 nM, respectively) or 100 μM SNAP + 10 μM IBMX (EC50 = 9 μM and 8.4 nM, respectively). CONCLUSIONS:: Vasoconstriction produced by vasopressin or norepinephrine, and the synergistic vasoconstriction produced by the combinations, was inhibited in vasodilatory septic shock–like conditions. Thus, in addition to the well-described vasopressin deficiency in vasodilatory septic shock, these studies indicate that decreased vasopressin responsiveness further contributes to a state of relative vasopressin insufficiency in this condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. DESIGN:: Prospective, open-label, randomized, controlled study. SETTING:: Medical-surgical intensive care unit of a tertiary care teaching hospital. PATIENTS:: Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure =60 mm Hg. INTERVENTIONS:: Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. MEASUREMENTS AND MAIN RESULTS:: Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.86.0) to 5.8 (4.36.9) Lminm. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14127) and 70 (15121) mL; serum creatinine, 170 (117333) and 153 (112310) molL; and creatinine clearance, 50 (1277) and 67 (1389) mLmin1.73 m. CONCLUSIONS:: Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function. [ABSTRACT FROM AUTHOR]