The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases ...per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.
Differential hypoxaemia (DH) is common in patients supported by femoral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and can cause cerebral hypoxaemia. To date, no models have studied ...the direct impact of flow on cerebral damage. We investigated the impact of V-A ECMO flow on brain injury in an ovine model of DH. After inducing severe cardiorespiratory failure and providing ECMO support, we randomised six sheep into two groups: low flow (LF) in which ECMO was set at 2.5 L min
ensuring that the brain was entirely perfused by the native heart and lungs, and high flow (HF) in which ECMO was set at 4.5 L min
ensuring that the brain was at least partially perfused by ECMO. We used invasive (oxygenation tension-PbTO
, and cerebral microdialysis) and non-invasive (near infrared spectroscopy-NIRS) neuromonitoring, and euthanised animals after five hours for histological analysis. Cerebral oxygenation was significantly improved in the HF group as shown by higher PbTO
levels (+ 215% vs - 58%, p = 0.043) and NIRS (67 ± 5% vs 49 ± 4%, p = 0.003). The HF group showed significantly less severe brain injury than the LF group in terms of neuronal shrinkage, congestion and perivascular oedema (p < 0.0001). Cerebral microdialysis values in the LF group all reached the pathological thresholds, even though no statistical difference was found between the two groups. Differential hypoxaemia can lead to cerebral damage after only a few hours and mandates a thorough neuromonitoring of patients. An increase in ECMO flow was an effective strategy to reduce such damages.
Abstract Background Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with ...relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. Methods In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Results The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays ( P < . 001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 95% confidence interval {CI}, 0.97-0.99; hs-cTnI, Beckman Coulter Inc, 0.97 95% CI, 0.96-0.99; hs-cTnI, Siemens, 0.96 95% CI, 0.93-0.99) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Conclusions Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI.
During the last decade, the incidence and mortality rates of ST-elevation myocardial infarction (STEMI) has been steadily increasing in young women but not in men. Environmental variables that ...contribute to cardiovascular events in women remain ill-defined.
A total of 2199 consecutive patients presenting with acute ST-elevation myocardial infarction (STEMI, 25.8% women, mean age 62.6±12.4 years) were admitted at the Montreal Heart Institute between June 2010 and December 2014. Snow fall exceeding 2cm/day was identified as a positive predictor for STEMI admission rates in the overall population (RR 1.28, 95% CI 1.07-1.48, p = 0.005), with a significant effect being seen in men (RR 1.30, 95% CI 1.06-1.53, p = 0.01) but not in women (p = NS). An age-specific analysis revealed a significant increase in hospital admission rates for STEMI in younger women ≤55 years, (n = 104) during days with higher outside temperature (p = 0.004 vs men ≤55 years) and longer daylight hours (p = 0.0009 vs men ≤55 years). Accordingly, summer season, increased outside temperature and sunshine hours were identified as strong positive predictors for STEMI occurrence in women ≤55 years (RR 1.66, 95% CI 1.1-2.5, p = 0.012, RR 1.70, 95% CI 1.2-2.5, p = 0.007, and RR 1.67, 95% CI 1.2-2.5, p = 0.011, respectively), while an opposite trend was observed in men ≤55 years (RR for outside temperature 0.8, 95% CI 0.73-0.95, p = 0.01).
The impact of environmental variables on STEMI is age- and sex-dependent. Higher temperature may play an important role in triggering such acute events in young women.
To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay.
...The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers.
In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts.
This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
Abstract Background The incremental value of copeptin, a novel marker of endogenous stress, for rapid rule-out of non-ST-elevation myocardial infarction (NSTEMI) is unclear when sensitive or even ...high-sensitivity cardiac troponin cTn (hs-cTn) assays are used. Methods In an international multicenter study we evaluated 1929 consecutive patients with symptoms suggestive of acute myocardial infarction (AMI). Measurements of copeptin, three sensitive and three hs-cTn assays were performed at presentation in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists using all clinical information including coronary angiography and levels of hs-cTnT. The incremental value in the diagnosis of NSTEMI was quantified using four outcome measures: area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), sensitivity and negative predictive value (NPV). Early presenters (< 4 h since chest pain onset) were a pre-defined subgroup. Results NSTEMI was the adjudicated final diagnosis in 358 (18.6%) patients. As compared to the use of cTn alone, copeptin significantly increased AUC for two (33%) and IDI (between 0.010 and 0.041 (all p < 0.01)), sensitivity and NPV for all six cTn assays (100%); NPV to 96–99% when the 99th percentile of the respective cTnI assay was combined with a copeptin level of 9 pmol/l (all p < 0.01). The incremental value in early presenters was similar to that of the overall cohort. Conclusion When used for rapid rule-out of NSTEM in combination with sensitive or hs-cTnI assays, copeptin provides a numerically small, but statistically and likely also clinically significant incremental value.
Abstract Objective Coronary angiography is considered to be a safe tool for the evaluation of coronary artery disease and performed in approximately 12 million patients each year worldwide. The aim ...of our study was to investigate the frequency and predictors of cardiomyocyte injury in patients undergoing elective coronary angiography. Methods A total of 749 consecutive patients who were scheduled to undergo elective coronary angiography were prospectively analyzed. High-sensitivity cardiac troponin T concentrations were measured both before and after elective coronary angiography (without intervention). Acute cardiomyocyte injury was predefined as an absolute increase in high-sensitivity cardiac troponin T of at least 7 ng/L (if also fulfilling a relative change of >20%). Results Acute cardiomyocyte injury was observed in 101 patients (13.5%, 95% confidence interval CI, 11.1-16.2). It was independently associated with aortic valve stenosis (odds ratio OR, 5.4; 95% CI, 3.0-9.8; P <.001), age (OR, 1.05; 95% CI, 1.02-1.08; P <.001), female sex (OR, 3.5; 95% CI, 1.8-6.8; P <.001), contrast volume (OR, 1.006; 95% CI, 1.001-1.012; P = .019 per 10 mL of contrast volume), documented cardiomyopathy (OR, 2.5; 95% CI, 1.0-6.0; P = .045), and mitral regurgitation (OR, 2.3; CI, 1.0-4.9; P = .033). In contrast, operator experience and extent of coronary artery disease were not found to be associated with acute cardiomyocyte injury. Conclusions Cardiomyocyte injury accompanies elective coronary angiography in 1 of 8 patients. Sex, age, contrast agent volume, and ventricular disease, rather than the extent of coronary artery disease, independently predict cardiomyocyte injury. Further research aiming to reduce the incidence of cardiomyocyte injury seems warranted.
Background
The impact of obesity on the incidence of perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery is not well understood.
Methods
We performed a ...prospective diagnostic study enrolling consecutive patients undergoing non-cardiac surgery, who were considered at increased cardiovascular risk. All patients were screened for PMI, defined as an absolute increase from preoperative to postoperative sensitive/high-sensitivity cardiac troponin T (hs-cTnT) concentrations. The body mass index (BMI) was classified according to the WHO classification (underweight< 18 kg/m
2
, normal weight 18–24.9 kg/m
2
, overweight 25–29.9 kg/m
2
, obesity class I 30–34.9 kg/m
2
, obesity class II 35–39.9 kg/m
2
, obesity class III > 40 kg/m
2
). The incidence of PMI and all-cause mortality at 365 days, both stratified according to BMI.
Results
We enrolled 4277 patients who had undergone 5413 surgeries. The median BMI was 26 kg/m
2
(interquartile range 23–30 kg/m
2
). Incidence of PMI showed a non-linear relationship with BMI and ranged from 12% (95% CI 9–14%) in obesity class I to 19% (95% CI 17–42%) in the underweight group. This was confirmed in multivariable analysis with obesity class I. showing the lowest risk (adjusted OR 0.64; 95% CI 0.49–0.83) for developing PMI. Mortality at 365 days was lower in all obesity groups compared to patients with normal body weight (e.g., unadjusted OR 0.54 (95% CI 0.39–0.73) and adjusted OR 0.52 (95% CI 0.38–0.71) in obesity class I).
Conclusion
Obesity class I was associated with a lower incidence of PMI, and obesity in general was associated with a lower all-cause mortality at 365 days.
Background
Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore ...haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.
Methods
A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.
Results
Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (
p
> 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (
p
< 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (
p
< 0.0001). The novel crystalloid supported rapid peripheral vasodilation (
p
= 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (
p
= 0.012) but delayed peripheral perfusion (
p
= 0.034).
Conclusions
Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.
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