Neutrophil activation during acute human anaphylaxis: analysis of MPO and sCD62L.

BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the emergency department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time-points. Traditional anaphylaxis biomarkers, histamine and mast cell tryptase, were measured by ELISA and ImmunoCAP, respectively. Plasma myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L concentrations by cytometric bead array, and both compared to healthy controls. RESULTS: In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine positive, and 47 (70%) were mast cell tryptase positive. At enrolment, myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4, 10.5) fold higher in moderate and severe patients, respectively, compared with healthy controls, and remained stable over the first 5 h following symptom onset. At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower in moderate and severe patients, respectively, than healthy controls, and was stable over the first 5 h. There were no associations between myeloperoxidase or soluble CD62L concentrations and either histamine or mast cell tryptase concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide compelling evidence for the involvement of neutrophils during acute human anaphylaxis, suggesting they are activated early in the reaction, regardless of mast cell activation. This important finding increases our understanding of the basic mechanisms of anaphylaxis, a necessary precursor to improving treatment and prevention.

Near-infrared spectroscopy-based microcirculatory assessment in acute atrial fibrillation.

Near-infrared spectroscopy is a means of assessing microcirculatory function, but has not been studied in atrial fibrillation (AF). We evaluated the effect of acute AF on thenar eminence near-infrared spectroscopy-derived microcirculatory variables. Stable patients presenting to the emergency department with acute onset AF underwent dynamic near-infrared spectroscopy assessment with a three minute vascular occlusion test (VOT). This was repeated after cardioversion to sinus rhythm (SR). Each assessment included baseline tissue oxygen saturation (StO2), slope of StO2 decrease during VOT, slope of StO2 increase post VOT, minimum and maximum StO2, amplitude of StO2 response and post-ischaemic hyperperfusion. Pre and post cardioversion values were compared by Wilcoxon signed-rank test. Twelve participants (seven male, five female) with a median age of 63 years (interquartile range 52 to 70 years) were enrolled. Median baseline StO2 was 74% before and 77% after cardioversion (P=0.03). The median slope of StO2 decrease during VOT was -0.19%/second and -0.16%/second (P=0.018) and the median slope of StO2 increase post VOT was 3.03%/second and 2.56%/second (P=0.002), pre and post cardioversion, respectively. Minimum StO2 was lower (39% versus 52%, P=0.002) and the amplitude of StO2 response greater (49% versus 40%, P=0.005) in AF, but there was no significant difference in maximum StO2 or the degree of reperfusion hyperaemia. In summary, baseline and minimum StO2 were lower with a greater ischaemic decrease in StO2 during AF, reflecting reduced tissue perfusion, compared with sinus rhythm. Recovery after ischaemia was higher in AF, suggesting normalisation of capillary recruitment during ischaemia.

Spontaneous pneumothorax; a multicentre retrospective analysis of emergency treatment, complications and outcomes.

BACKGROUND: Spontaneous pneumothorax can be managed initially by observation, aspiration or chest drain insertion. AIMS: To determine the clinical features of spontaneous pneumothorax in patients presenting to the emergency department (ED), interventions, outcomes and potential risk factors for poor outcomes after treatment. METHODS: Retrospective chart review from ED of three major referral and two general hospitals in Australia of presentations with primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP). Main outcomes were prolonged air leak (>5 days) and pneumothorax recurrence within 1 year. RESULTS: We identified 225 people with PSP and 98 with SSP. There were no clinical tension pneumothoraces with hypotension. Hypoxaemia (haemoglobin oxygen saturation measured by pulse oximetry ≤92%) occurred only in SSP and in older patients (age >50 years) with PSP. Drainage was performed in 150 (67%) PSP and 82 (84%) SSP. Prolonged air leak occurred in 16% (95% confidence interval 10-23%) of PSP and 31% (21-42%) of SSP. Independent risk factors for prolonged drainage were non-asthma SSP and pneumothorax size >50%. Complications were recorded in 11% (7.5-16%) of those having drains inserted. Recurrences occurred in 5/91 (5%, 1.8-12%) of those treated without drainage versus 40/232 (17%, 13-23%) of those treated by drainage, of which half occurred in the first month after drainage. CONCLUSION: Pneumothorax drainage is associated with substantial morbidity including prolonged air leak. As PSP appears to be well tolerated in younger people even with large pneumothoraces, conservative treatment in this subgroup may be a viable option to improve patient outcomes, but this needs to be confirmed in a clinical trial.

Is comorbid status the best predictor of one-year mortality in patients with severe sepsis and sepsis with shock?

Understanding longer term outcomes in critically ill patients will assist treatment decisions, allocation of scarce resources and clinical research in that population. The aim of this study was to compare a well-validated means of determining comorbidity, the Charlson Comorbidity Score, to other verified risk stratification models in predicting one-year mortality and other outcomes in emergency department patients with severe sepsis and sepsis with shock. We conducted a planned subgroup analysis of a prospective observational study, the Critical Illness and Shock Study, in adult patients with sepsis meeting study criteria for critical illness. From emergency department arrival, patients were prospectively enrolled with data collected for a minimum of one year post-enrolment. Scoring systems were derived from this data and compared using receiver-operating characteristic curves. One hundred and four patients were enrolled. The 28-day mortality was 18% and one-year mortality 40%. For predicting one-year mortality, the area under the receiver-operating characteristic curve for age-weighted Charlson Comorbidity Score (0.71, 95% confidence interval 0.61 to 0.81) was at least as good or superior to other scoring systems analysed. The intensive care unit admission rate was 45% and the median hospital length-of-stay was eight days. We conclude that in patients who present to the emergency department with severe sepsis or sepsis with shock, age-weighted Charlson Comorbidity Score is a predictor of one-year mortality that is simple to calculate and at least as accurate as other validated scoring systems.