ABSTRACT
BACKGROUND: Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200â mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48â h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24â h. This did not reduce myocardial injury over 48â h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6â h in elafin-treated patients (median 2.4 vs 4.1â µg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499â mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238â ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58, ISRCTN82061264).
Subject(s)
Coronary Artery Bypass/adverse effects , Coronary Artery Disease/surgery , Elafin/administration & dosage , Intraoperative Complications/drug therapy , Myocardial Reperfusion Injury/drug therapy , Double-Blind Method , Follow-Up Studies , Humans , Infusions, Intravenous , Intraoperative Complications/etiology , Intraoperative Period , Magnetic Resonance Imaging, Cine , Myocardial Reperfusion Injury/diagnosis , Myocardial Reperfusion Injury/etiology , Protease Inhibitors/administration & dosage , Recombinant Proteins , Retrospective StudiesSubject(s)
Databases, Factual , Faculty, Nursing , Information Services/organization & administration , Internet/organization & administration , Interprofessional Relations , Nurse Administrators , Nursing Staff/education , Nursing Staff/supply & distribution , Communication , Employment , Forecasting , Humans , Kansas , Leadership , Models, Nursing , Nurse Administrators/psychology , Nursing Staff/trends , Organizational Objectives , Program EvaluationABSTRACT
The purposes of this qualitative study were to describe behaviors of infants and toddlers when in acute pain and to describe changes in those behaviors across the 3-yr span. With the use of naturalistic observation, 32 children, birth to 36 mo of age, were observed following surgery, fractures, or burns. Purposeful sampling of children, who were inpatients of a private midwestern hospital, was used. Data sources included child observations, parent interviews, and patient records. The research method used was grounded theory. Three pain behavior categories were developed, and characteristics of each category were identified. Pain categories included motor movement, communication, and facial expression. Theoretic implications were proposed. It is concluded that predictable changes in pain behaviors occur within infancy and toddlerhood. A matrix of pain behavior is presented.