Rethinking the Doses of Tissue Plasminogen Activator and Deoxyribonuclease Administrated Concurrently for Intrapleural Therapy for Complicated Pleural Effusion and Empyema.

Background Complicated parapneumonic effusions empyema (CPEE) is fairly common and associated with increased morbidity and mortality. The Multicenter Intrapleural Sepsis Trial 2 (MIST 2) established the combination of intrapleural deoxyribonuclease (DNase) and tissue plasminogen activator (tPA) as an effective treatment for CPEE, thereby avoiding surgery and decreasing the length of hospitalization. MIST 2, however, used a labor-intensive protocol with some risk of bleeding. We hypothesize the simpler regimen of concurrent administration of intrapleural tPA and DNase (lower dose of tPA and a higher DNAse dose) to be equally effective with a decreased risk of bleeding. Methods Retrospective analysis of the concurrent administration of intrapleural tPA and DNase for CPEE during November 2014 to February 2016 was done at a tertiary care center. The inclusion criteria included 1) pleural fluid with any of the following: (a) exudative and loculated effusion in a patient with pneumonia, (b) gram stain/culture positive, (c) macroscopically purulent 2) chest tube placement during current hospitalization 3) concurrent administration of intrapleural tPA and DNase (4mg and 10mg per instillation respectively). The exclusion criteria was 1) chest tube placement prior to current hospitalization and 2) age < eighteen. Results Seventeen patients received concurrent tPA and DNase therapy for CPEE in the study period. Two had chest tubes placed prior to current hospitalization and were excluded. Twelve patients (80%) were successfully discharged with clinical resolution of CPEE with medical therapy. One (7%) patient required surgery. No mortality due to pleural sepsis was noted. The median number of concurrent tPA and DNase treatment was two. Median cumulative tPA dose was 8 mg (mean: 14.1±17 mg) and median cumulative DNase dose was 20mg (mean: 19.7 ± 12.2 mg). The median dwell time for the chest tubes was 8.5 days. Our regimen had similar success when compared to MIST 2 and allowed for lesser treatments and cumulative doses. No complication of intrapleural therapy with hemorrhagic conversion of CPEE, or worsening pain leading to discontinuation of therapy was noted. Conclusion The concurrent administration of intrapleural therapy at lower doses than the current standard MIST 2 protocol is practical, efficient and effective. We suggest a higher DNase dose with a lower tPA dose which may further decrease hemorrhagic complications. Further randomized trials are required to establish the optimal dose of intrapleural therapy for CPEE.

Role of inferior vena cava diameter in assessment of volume status: a meta-analysis.

BACKGROUND AND OBJECTIVE: Hypovolemic shock is an important cause of death in the emergency department (ED). We sought to conduct a meta-analysis to quantify existing evidence on sonographic measurement of inferior vena cava (IVC) diameter in assessing of volume status adult ED patients. METHODS: A search of 5 major databases of biomedical publication, EMBASE, Ovid Medline, evidence-based medicine (EBM) Reviews, Scopus, and Web of Knowledge, was performed in first week of March 2011. Studies meeting the following criteria were included: (1) prospectively conducted, (2) measured IVC diameter using ultrasonography, (3) inpatients under spontaneous ventilation, and (4) reported IVC diameter measurement with volume status or shock. Article search, study quality assessment, and data extraction were done independently and in duplicate. Mean difference in IVC diameter was calculated using RevMan version 5.5 (Cochrane collaboration). RESULTS: A total of 5 studies qualified for study eligibility from 4 different countries, 3 being case-control and 2 before-and-after design, studying 86 cases and 189 controls. Maximal IVC diameter was significantly lower in hypovolemic status compared with euvolemic status; mean difference (95% confidence interval) was 6.3 mm (6.0-6.5 mm). None of the studies blinded interpreters for volume status of participants. CONCLUSION: Moderate level of evidence suggests that the IVC diameter is consistently low in hypovolemic status when compared with euvolemic. Further blinded studies are needed before it could be used in the ED with confidence.

Diagnostic accuracy of pulmonary embolism rule-out criteria: a systematic review and meta-analysis.

STUDY OBJECTIVE: To perform a systematic review and meta-analysis to define the diagnostic performance of pulmonary embolism rule-out criteria (PERC) in deferring the need for D-dimer testing to rule out pulmonary embolism in the emergency department (ED). METHODS: We searched EMBASE, MEDLINE, Scopus, Web of Knowledge, and all the evidence-based medicine reviews that included the Cochrane Database of Systematic Reviews through August 14, 2011, and hand searched references in potentially eligible articles and conference proceedings of major emergency medicine organizations for the previous 2 years. We selected studies that reported diagnostic performance of PERC, reported original research, and were conducted in the ED, with no language restrictions. Two investigators independently identified eligible studies and extracted data. We used contingency tables to calculate sensitivity, specificity, and likelihood ratios. RESULTS: We found 12 qualifying cohorts (studying 13,885 patients with 1,391 pulmonary embolism diagnoses), 10 prospective and 2 retrospective, from 6 countries. Pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios for 10 included studies were 0.97 (95% confidence interval [CI] 0.96 to 0.98), 0.23 (95% CI 0.22 to 0.24), 1.24 (95% CI 1.18 to 1.30), and 0.17 (95% CI 0.13 to 0.23), respectively. Significant heterogeneity was observed in specificity (I(2)=97.2%) and positive likelihood ratio (I(2)=84.2%). CONCLUSION: The existing literature suggests consistently high sensitivity and low but acceptable specificity of the PERC to rule out pulmonary embolism in patients with low pretest probability.