A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes.</p> <p>Methods/Design</p> <p>A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates.</p> <p>Discussion</p> <p>Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic.</p> <p>Trial Registration Number</p> <p><a href="http://www.controlled-trials.com/ISRCTN45190901">ISRCTN45190901</a></p

Broncho-pleuropericardial fistula complicating staphylococcal sepsis

This is a rare case of broncho-pleuropericardial fistula in a 12-year-old female who presented with fever, painful joint swelling, and pleural and pericardial effusion secondary to disseminated methicillin-sensitive Staphylococcus aureus infection. The pleural and pericardial effusion were drained, however, air leak was observed from both tubes and was synchronous with mechanical inspiration. A broncho-pleuropericardial fistula was suspected and confirmed with computed tomography. This case report demonstrated that disseminated S. aureus bacteremia could result in broncho-pleuropericardial fistula. The ability of disseminated staphylococcal infection to produce pnemopericardium should be added to the list of other complications associated with disseminated staphylococcal sepsis

Continuous cardiac output measurement by un-calibrated pulse wave analysis and pulmonary artery catheter in patients with septic shock

Septic shock is a serious medical condition. With increased concerns about invasive techniques, a number of non-invasive and semi-invasive devices measuring cardiac output (CO) have become commercially available. The aim of the present study was to determine the accuracy, precision and trending abilities of the FloTrac and the continuous pulmonary artery catheter thermodilution technique determining CO in septic shock patients. Consecutive septic shock patients were included in two centres and CO was measured every 4 h up to 48 h by FloTrac (APCO) and by pulmonary artery catheter (PAC) using the continuous (CCO) and intermittent (ICO) technique. Forty-seven septic shock patients with 326 matched sets of APCO, CCO and ICO data were available for analysis. Bland and Altman analysis revealed a mean bias ±2 SD of 0.0 ± 2.14 L min−1 for APCO–ICO (%error = 34.5 %) and 0.23 ± 2.55 L min−1 for CCO–ICO (%error = 40.4 %). Trend analysis showed a concordance of 85 and 81 % for APCO and CCO, respectively. In contrast to CCO, APCO was influenced by systemic vascular resistance and by mean arterial pressure. In septic shock patients, APCO measurements assessed by FloTrac but also the established CCO measurements using the PAC did not meet the currently accepted statistical criteria indicating acceptable clinical performance