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Background: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested.Methods: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients.Results: We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31).Conclusions: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. Methods/Design: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. Discussion: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified. [ABSTRACT FROM AUTHOR]

Background: Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients. Methods: We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL and uNGAL] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L. Measurements and main results: Bland-Altman analysis demonstrated that, despite correlating well ( r = 0.988), uNGAL and uNGAL were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03-450.44 ng/mg creatinine; limits of agreement: −1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction. Conclusions: uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker. [ABSTRACT FROM AUTHOR]

Abstract: Background: Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. Methods and results: Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 <35mmHg), 6705 (40.5%) into the normo- (35–45mmHg) and 6827 (41.3%) into the hypercapnia (>45mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p =0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p <0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p <0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p =0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p =0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p =0.52]). Cox-proportional hazards modelling supported these findings. Conclusions: Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors. [Copyright &y& Elsevier]

Abstract: Objectives: To measure the triage performance of the efferent arm of a rapid response system (RRS) by assessing the 24h outcome of patients triaged to remain on the ward after rapid response team (RRT) review. Methods: We performed a retrospective observational study of all consecutive RRS activations between August 2005 and December 2011 in a university-affiliated hospital. Calls involving patients with documented limitations of medical therapy (LOMT) orders were excluded. We determined patients who were triaged to stay on the ward at the end of their first (index) call and analyzed their vital status and location 24h later. Finally, we reviewed medical charts of patients triaged to remain on the ward and had a cardiac arrest and/or died within 24h of RRT review. Results: We studied 8304 RRT calls. We excluded 1794 calls involving patients with LOMT, 2165 that were repeat calls, 20 where data was missing, 650 where patients were immediately transferred to a high dependency (HDU) or an intensive care unit (ICU) and 92 where calls were rapidly upgraded to cardiac arrest calls. Thus, we identified 3583 index calls at the end of which patients were triaged to remain on the ward. Within 24h, 454 (12.7%) of those had a repeat RRT activation and 378 were transferred to HDU/ICU. 12 (0.3%) suffered a cardiac arrest on the ward. Altogether, 14 (0.4%) patients died within 24h of the index RRT activation. Of those 6 had LOMT applied after the call, 4 had been admitted to ICU in a further call and 6 (0.2%) patients had unexpected cardiac arrest on the ward. Conclusions: The rate of unexpected cardiac arrest in the 24h following RRT activation is very low for patients triaged to stay on the ward. Major triage errors by the RRT appear uncommon. [Copyright &y& Elsevier]

Abstract: Introduction: Use of non-invasive ventilation (NIV) is normally limited to the Emergency Department, Intensive Care Unit (ICU), Coronary Care Unit (CCU) or High Dependency Unit (HDU). However, NIV is sometimes used by the Medical Emergency Team (MET) as respiratory support for ward patients. Objectives: We reviewed the characteristics and outcome of ward patients treated with NIV in the setting of a MET Call and determined the clinical and prognostic significance of such treatment. Methods: We used our MET database to assess the characteristics and outcome of patients treated with NIV and compared them to a control group of patients with similar MET diagnoses but not treated with NIV. Results: We studied 5389 calls in 3880 patients. NIV was delivered during 483 (9.0%) calls to 426 patients (11% of the total). The four most common MET diagnoses associated with NIV were acute pulmonary edema (156 calls, 32.3%), pneumonia (84 calls, 17.4%), acute respiratory failure of unclear origin (59 calls, 12.2%) and exacerbation of chronic obstructive pulmonary disease (32 calls, 6.6%). Limitations of medical therapy (LOMT) were documented in 151 (35.4%) patients. Among NIV patients without LOMT, 115 (41.8%) were transferred to ICU and 50 (18.2%) to the coronary care or high dependency unit (CCU/HDU) compared with only 50 (18.0%) and 16 (5.8%) respectively in the control group (p <0.001). Overall, 76 NIV patients (27.6%) received endotracheal intubation (ETT) compared with 61 (21.9%) in controls. Mortality was 23.6% in the NIV group versus 18.8% in the control group. Conclusion: One in ten MET call patients received NIV. In those without LOMT, two thirds were transferred to ICU/HDU/CCU, one in four received ETT, and one in four died. NIV use at the time of a MET call identified high risk patients for whom admission to ICU/HDU/CCU should be strongly considered. [Copyright &y& Elsevier]