Implementation of an Early Extubation Protocol in Cardiac Surgical Patients Decreased Ventilator Time But Not Intensive Care Unit or Hospital Length of Stay.

OBJECTIVE: The optimal timing of extubation following cardiac surgery is currently unknown. Protocols implemented in order to achieve a rapid extubation may achieve this goal, but not prove beneficial in terms of outcomes. DESIGN: A prospective clinical trial. SETTING: Tertiary care cardiac surgical intensive care unit. PARTICIPANTS: Adult cardiac surgical patients. INTERVENTIONS: Implementation of an 8-tier multidisciplinary rapid weaning protocol. MEASUREMENTS AND MAIN RESULTS: Ventilator times 6 months prior to and 6 months after implementation of the protocol were measured. Outcomes associated with ventilator times were measured by dividing the patients into tertiles (<6 hours, 6-12 hours, >12 hours). Primary outcomes were intensive care unit (ICU) and hospital length of stay. Secondary outcomes included mortality at 30 days and other major morbidities. In all, 459 patients were included in the study. With implementation of the protocol, median ventilation times decreased from 7.4 hours (interquartile range, IQR = 3rd quartile - 1st quartil e= 6.72 hours) to 5.73 hours (IQR = 5.51 hours) (p < 0.0001). However, median ICU length of stay in patients who achieved extubation within 6 hours increased to 49.45 hours (IQR = 44.4) from 40.3 (IQR = 25.6) (p = 0.0017). Median hospital length of stay was not significantly changed due to the protocol in any ventilation tertile (p = 0.650). CONCLUSIONS: Decreasing intubation times to <6 hours in postsurgical cardiac patients is obtainable with implementation of a multidisciplinary rapid weaning protocol. However, patients extubated within 6 hours had increased ICU length of stay and no difference in hospital length of stay with this intervention.

Opioid Overdose Deaths and Florida's Crackdown on Pill Mills.

OBJECTIVES: We examined the effect on opioid overdose mortality of Florida state laws and law enforcement operations targeting "pill mills." METHODS: We collected 2003 to 2012 mortality data from the Florida Department of Health and the North Carolina State Center for Health Statistics (the comparison state) to estimate changes in the rates of death from prescription opioid, heroin, or any opioid overdose. RESULTS: Florida's actions were associated with an estimated 1029 lives saved from prescription opioid overdose over a 34-month period. Estimated reductions in deaths grew over the intervention period, with rates per 100,000 population that were 0.6 lower in 2010, 1.8 lower in 2011, and 3.0 lower in 2012 than what would have been expected had the changes in mortality rate trends in Florida been the same as changes in trends in North Carolina. Florida's mortality rates from heroin and total opioid overdose were also lower than anticipated relative to changes in trends in North Carolina. CONCLUSIONS: Findings from this study indicate that laws regulating pain clinics and enforcement of these laws may, in combination, reduce opioid overdose deaths.

Rapid transepithelial transport of prions following inhalation.

Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa via M cells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrP(d)). Infected or uninfected brain homogenate was identified adhering to M cells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrP(d) was identified within a limited number of M cells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results support M cell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity.

Early Extubation Without Increased Adverse Events in High-Risk Cardiac Surgical Patients.

BACKGROUND: Previous reports of early extubation after cardiac surgical procedures vary in the definition of "early" and may limit findings to patients with less preoperative risk. This study sought to determine whether an eight-tier multidisciplinary early extubation protocol with the goal of extubating within 6 hours postoperatively would be successful without increasing adverse events in patients with increased preoperative risk. METHODS: Postoperative adult cardiac surgical patients in a tertiary care intensive care unit (n = 459) were analyzed 6 months before and 6 months after implementation of the protocol. The Society of Thoracic Surgeons (STS) risk scores were used as surrogate markers of risk. Patients with STS scores (n = 333) were stratified into four equal groups from lowest to highest score. A composite of acute renal failure, reintubation, stroke, and mortality was the primary outcome. Secondary outcomes included intensive care unit and hospital lengths of stay, reoperation, and sternal wound infection. RESULTS: In all patients, ventilation times were significantly decreased from a median of 7.4 hours to 5.7 hours after protocol implementation. When stratified by STS scores, higher-risk patients (groups 3 and 4) had the largest reduction in ventilation times from a median of 9.2 hours to 5.7 hours (p < 0.0001) without a significant increase in adverse events. The highest-risk patients (STS score >40%; n = 14) all had extubation times shorter than 6 hours after the protocol with no significant increase found in adverse events (p = 0.138). CONCLUSIONS: A prudent and diligent multifaceted early extubation protocol may be successful in high-risk cardiac surgical patients without an increase in adverse outcomes. A larger study is needed in the future to confirm the finding.

Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules.

In HIV infection, CD8+ cells show cytotoxic and noncytotoxic anti-HIV activity. The latter function is mediated, at least in part, by a secreted antiviral protein, the CD8+ cell antiviral factor (CAF). Because antiviral effector molecules, such as perforin and granzymes, reside in the exocytic granules of CD8+ T cells, we examined the possibility that granules contain CAF-like activity. CD8+ cells from HIV-infected individuals showing strong CAF-mediated antiviral activity were induced to release their granule constituents into culture media. Within 1 hour of stimulation, high levels of granzyme B (a primary granule constituent) were found in the culture fluids of previously activated CD8+ cells. The same culture fluids contained no or very low amounts of CAF activity, as measured with HIV-infected CD4+ cells. Maximal levels of CAF activity were not observed until 5 or 7 days after stimulation, consistent with typical CAF production kinetics. In addition, extracts of granules purified from antiviral CD8+ cells did not show any CAF activity, whereas the cytoplasmic fraction of these cells showed substantial levels of antiviral activity. These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells.