Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

OBJECTIVES: To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. DESIGN: An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. SETTING: Tertiary medical center and school of medicine laboratory. PARTICIPANTS: Laboratory animals-rabbits. INTERVENTIONS: Balloon obstruction of infrarenal aorta introduced via femoral artery incision. RESULTS: Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). CONCLUSIONS: In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord.

Antimicrobial use in the ICU: indications and accuracy--an observational trial.

BACKGROUND: In intensive care unit (ICU) patients, signs of infection and inflammation are similar, making diagnosis of bacterial infections difficult. Antimicrobials may therefore be overused, contributing to development of antimicrobial-resistant bacteria. OBJECTIVES: To measure the accuracy of clinician decisions to start antimicrobials; to correlate clinician certainty with the presence of infection; and to examine whether physiological variables correlate with clinician certainty. DESIGN: Prospective observational study. SETTING AND PATIENTS: Patients staying >48 hours in a general ICU of a tertiary care hospital. MEASUREMENTS: The ICU clinician's certainty for the presence of infection was recorded when starting antimicrobials. An independent infectious diseases (ID) specialist determined if antimicrobials were required and if infection was present. Clinician antibiotic start decisions were tested for accuracy according to the ID determination for the presence of infection. RESULTS: Empirical antimicrobial therapy was justified by the presence of infection on 67/125 (54%) occasions. Clinician certainty for infection correlated well with the presence of defined infection (r(2) = 0.78), however, infection was defined on 6/19 (31%) occasions when ICU clinician certainty was low (≤2), and antimicrobials were prescribed even when clinician certainty was minimal. Antimicrobial course length was similar whether infection was defined or not (11.5 ± 9.2 vs 10.7 ± 9.1 days; P = 0.65). Physiological variables were not associated with clinician certainty of infection. CONCLUSIONS: Antimicrobial therapy is probably overused in the ICU, possibly resulting from difficulties in diagnosis and the perceived greater risk of untreated infection when compared to the risks of potentially unnecessary antimicrobial therapy. Efforts to improve antimicrobial-related decision-making should be mandatory.