John H. J. M. Meertens

Bench-to-bedside review: Angiopoietin signalling in critical illness – a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and – despite many unanswered questions – therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.

Cardiac dysfunction after aneurysmal subarachnoid hemorrhage: Relationship with outcome

Objective: To assess whether cardiac abnormalities after aneurysmal subarachnoid hemorrhage (aSAH) are associated with delayed cerebral ischemia (DCI) and clinical outcome, independent from known clinical risk factors for these outcomes. Methods: In a prospective, multicenter cohort study, we performed echocardiography and ECG and measured biochemical markers for myocardial damage in patients with aSAH. Outcomes were DCI, death, and poor clinical outcome (death or dependency for activities of daily living) at 3 months. With multivariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals. We used survival analysis to assess cumulative percentage of death in patients with and without echocardiographic wall motion abnormalities (WMAs). Results: We included 301 patients with a mean age of 57 years; 70% were women. A wall motion score index ≥1.2 had an adjusted RR of 1.2 (0.9–1.6) for DCI, 1.9 (1.1–3.3) for death, and 1.8 (1.1–3.0) for poor outcome. Midventricular WMAs had adjusted RRs of 1.1 (0.8–1.4) for DCI, 2.3 (1.4–3.8) for death, and 2.2 (1.4–3.5) for poor outcome. For apical WMAs, adjusted RRs were 1.3 (1.1–1.7) for DCI, 1.5 (0.8–2.7) for death, and 1.4 (0.8–2.5) for poor outcome. Elevated troponin T levels, ST-segment changes, and low voltage on the admission ECGs had a univariable association with death but were not independent predictors for outcome. Conclusion: WMAs are independent risk factors for clinical outcome after aSAH. This relation is partly explained by a higher risk of DCI. Further study should aim at treatment strategies for these aSAH-related cardiac abnormalities to improve clinical outcome.

Efficacy of Magnesium-Amiodarone Step-Up Scheme in Critically Ill Patients With New-Onset Atrial Fibrillation: A Prospective Observational Study

Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO 4) has shown to be effective for both rate and rhythm control, to act synergistically with antiarrhythmic drugs, and to prevent proarrhythmia. Treatment with MgSO4 may reduce the need for antiarrhythmic drugs such as amiodarone in critically ill patients with new-onset atrial fibrillation. The efficacy of a new institutional protocol was evaluated. Patients were treated with a new institutional protocol for new-onset atrial fibrillation in critically ill patients. An MgSO4 bolus (0.037 g/kg body weight in 15 minutes) was followed by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given to those not responding to MgSO4 within 1 hour. Clinical response was defined as conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of the 29 patients responded to MgSO4 monotherapy, whereas the addition of amiodarone was needed in 13 patients. Median (range) time until conversion to sinus rhythm after MgSO4 was 2 (1-45) hours. Median (range) conversion time in patients requiring amiodarone was 4 (2-78) hours, and median (range) conversion time in all patients was 3 (1-78) hours. The 24-hour conversion rate was 90%. Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step-up scheme reduces the need for amiodarone, effectively converts new-onset atrial fibrillation into a sinus rhythm within 24 hours, and seems to be safe in critically ill patients.

Multicentric, Randomized, Controlled Trial to Evaluate Blood Glucose Control by the Model Predictive Control Algorithm Versus Routine Glucose Management Protocols in Intensive Care Unit Patients: Response to Plank et al.

In the February issue of Diabetes Care , Plank et al. (1) reported the results of their computer-assisted model predictive control (MPC) algorithm versus routine glucose management in 60 postoperative thoracosurgical patients in three different hospitals. We agree that better glycemic control is worth …

Lung transplantation for acute respiratory failure in rapidly progressive idiopathic pulmonary fibrosis

Lung transplantation is a well-established therapy for patients with progressive respiratory failure after having been screened for inand exclusion criteria [1]. Mechanical ventilation, especially invasive ventilation has long been considered a strong relative contraindication. However, a limited number of patients have received a lung transplant while on the ventilator. These patients either passed the screening program, or developed primary graft failure. The outcome for these patients seems to be somewhat less favourable than for nonventilated patients [2,3]. We believe this is the first report of successful lung transplantation for patients developing ventilator dependent acute respiratory failure who were not previously screened. Some of the diseases considered suitable for lung transplantation may go unrecognised for some time or may develop very rapidly, and may present as acute respiratory failure, e.g. idiopathic pulmonary fibrosis (IPF). Also, such patients may become ventilator dependent after diagnostic procedures. We describe three patients (Table 1) with histologically proven IPF with ventilator-dependent acute respiratory failure that underwent bilateral lung transplantation after a limited screening; these patients had their diagnostic work-up while ventilated. Lung transplantation for acute respiratory failure is feasible. This preliminary report does not allow firm conclusions but the postoperative course was comparable with that of patients in our regular lung transplant programme. Patients transplanted in this emergency setting were less well-evaluated and prepared, both physically and emotionally. The urgent need for a transplant might have influenced the team to accept donor organs that would not have been accepted for elective transplant purposes. These considerations might conceivably compromise outcome. On the contrary, patients on the ventilator receive immunosuppressants in an attempt to treat their alveolitis, and because of the acute onset and short duration of respiratory failure, their alimentary and general condition may still be relatively favourable. These patients might not yet have developed right ventricular, hepatic or renal failure. Also, they are less likely to be colonized with resistant pathogens. These factors might improve outcome. The net effect of the ventilator-dependent setting is uncertain and many more patients need to be evaluated to draw conclusions. However, the immediate survival advantage for IPF patients is clear because nontransplanted ventilated patients have an ICU mortality of 100% [4]. Survival advantage is more obvious than for those in regular transplant programmes [5]. While we report here on a beneficial outcome of ventilated patients suffering from rapidly progressive IPF, one wonders if these results can be extrapolated to other diagnoses for which presently only elective transplantation is offered. Maybe conditions, for which transplantation is presently not deemed feasible, like acute respiratory distress syndrome (ARDS) with single organ failure or inhalation trauma, should also be offered lung transplantation. The scarcity of available donor organs urges a robust evaluation of costs and outcome. For fulminant hepatic failure, transplantation has become a standard treatment for patients meeting the Table 1. Patient characteristics and outcome.