The impact of hypovolemia and PEEP on recirculation in venovenous ECMO: an experimental porcine model.

BACKGROUND: Recirculation is a common problem in venovenous extracorporeal membrane oxygenation (VV ECMO) and may limit the effect of ECMO treatment due to less efficient blood oxygenation or unfavorable ECMO and ventilator settings. The impact of hypovolemia and positive end expiratory pressure (PEEP) on recirculation is unclear and poorly described in guidelines, despite clinical importance. The aim of this study was to investigate how hypovolemia, autotransfusion and PEEP affect recirculation in comparison to ECMO cannula distance and circuit flow. METHODS: In anesthetized and mechanically ventilated pigs (n = 6) on VV ECMO, we measured recirculation fraction (RF), changes in recirculation fraction (∆RF), hemodynamics and ECMO circuit pressures during alterations in PEEP (5 cmH2O vs 15 cmH2O), ECMO flow (3.5 L/min vs 5.0 L/min), cannula distance (10-14 cm vs 20-26 cm intravascular distance), hypovolemia (1000 mL blood loss) and autotransfusion (1000 mL blood transfusion). RESULTS: Recirculation increased during hypovolemia (median ∆RF 43%), high PEEP (∆RF 28% and 12% with long and short cannula distance, respectively), high ECMO flow (∆RF 49% and 28% with long and short cannula distance, respectively) and with short cannula distance (∆RF 16%). Recirculation decreased after autotransfusion (∆RF - 45%). CONCLUSIONS: In the present animal study, hypovolemia, PEEP and autotransfusion were important determinants of recirculation. The alterations were comparable to other well-known factors, such as ECMO circuit flow and intravascular cannula distance. Interestingly, hypovolemia increased recirculation without significant change in ECMO drainage pressure, whereas high PEEP increased recirculation with less negative ECMO drainage pressure. Autotransfusion decreased recirculation. The findings are interesting for clinical studies.

Fibrocartilaginous embolism as a cause of anterior spinal artery syndrome? / Fibrocartilaginøs emboli som årsak til arteria spinalis anterior-syndrom?

BACKGROUND: Fibrocartilaginous embolism (FCE) is a rare cause of spinal cord infarction. Most spinal cord infarctions are due to aortic pathologies and aortic surgeries. One theory is that material from the intervertebral discs follows a retrograde route to the anterior spinal artery. Fibrocartilaginous embolism and spinal cord infarction have also been described in veterinary literature. Spinal cord MRI diffusion-weighted imaging is of great help in finding the right diagnosis. CASE PRESENTATION: A young man was admitted to hospital after he woke up due to a sudden pain between his shoulders. He developed paresis in both his arms and legs within three hours. A neurological examination uncovered urinary retention, sensory deficits and paresis. The clinical picture was consistent with an infarction in the anterior spinal arterial distribution area. MRI of the patient's spine revealed an infarction in the anterior medulla. INTERPRETATION: Fibrocartilaginous embolism is probably more common than previously presumed.

Esmolol for cardioprotection during resuscitation with adrenaline in an ischaemic porcine cardiac arrest model.

BACKGROUND: The effectiveness of adrenaline during resuscitation continues to be debated despite being recommended in international guidelines. There is evidence that the ß-adrenergic receptor (AR) effects of adrenaline are harmful due to increased myocardial oxygen consumption, post-defibrillation ventricular arrhythmias and increased severity of post-arrest myocardial dysfunction. Esmolol may counteract these unfavourable ß-AR effects and thus preserve post-arrest myocardial function. We evaluated whether a single dose of esmolol administered prior to adrenaline preserves post-arrest cardiac output among successfully resuscitated animals in a novel, ischaemic cardiac arrest porcine model. METHODS: Myocardial infarction was induced in 20 anaesthetized pigs by inflating a percutaneous coronary intervention (PCI) balloon in the circumflex artery 15 min prior to induction of ventricular fibrillation. After 10 min of untreated VF, resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated and the animals were randomized to receive an injection of either 1 mg/kg esmolol or 9 mg/ml NaCl, prior to adrenaline. Investigators were blinded to allocation. Successful defibrillation was followed by a 1-h high-flow VA-ECMO before weaning and an additional 1-h stabilization period. The PCI-balloon was deflated 40 min after inflation. Cardiac function pre- and post-arrest (including cardiac output) was assessed by magnetic resonance imaging (MRI) and invasive pressure measurements. Myocardial injury was estimated with MRI, triphenyl tetrazolium chloride (TTC) staining and serum concentrations of cardiac troponin T. RESULTS: Only seven esmolol and five placebo-treated pigs were successfully resuscitated and available for post-arrest measurements (p = 0.7). MRI revealed severe but similar reductions in post-arrest cardiac function with cardiac output 3.5 (3.3, 3.7) and 3.3 (3.2, 3.9) l/min for esmolol and control (placebo) groups, respectively (p = 0.7). The control group had larger left ventricular end-systolic and end-diastolic ventricular volumes compared to the esmolol group (75 (65, 100) vs. 62 (53, 70) ml, p = 0.03 and 103 (86, 124) vs. 87 (72, 91) ml, p = 0.03 for control and esmolol groups, respectively). There were no other significant differences in MRI characteristics, myocardial infarct size or other haemodynamic measurements between the two groups. CONCLUSIONS: We observed similar post-arrest cardiac output with and without a single dose of esmolol prior to adrenaline administration during low-flow VA-ECMO in an ischaemic cardiac arrest pig model.

Left Ventricle Function During Therapeutic Hypothermia with Beta1-Adrenergic Receptor Blockade.

Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated. We hypothesized that beta1-adrenergic receptor blockade (esmolol infusion) exacerbates the negative effects of hypothermia on active myocardial motions, affecting both systolic and diastolic LV function. A pig (n = 10) study was performed to evaluate the myocardial effects of esmolol during hypothermia (33°C) and during normothermia, at spontaneous and pacing-increased heart rates (HRs). LV function was assessed by a LV pressure transducer, an epicardial ultrasonic transducer (wall thickness, wall thickening/thinning velocity) and an aortic ultrasonic flow-probe (stroke volume, cardiac output). The data were compared using a paired two-tailed Students t-test, and also analyzed using a linear mixed model to handle dependencies introduced by repeated measurements within each subject. The significance level was p ≤ 0.05. The effects of hypothermia and beta blockade were distinct and additive. Hypothermia reduced myocardial motion velocities and increased diastolic filling restrictions, but end-systolic wall thickness increased, and stroke volume and dP/dtmax (pumping function) were maintained. In contrast, esmolol predominantly affected systolic pumping function, by a negative inotropic effect. In combination, hypothermia and esmolol reduced myocardial velocities in systole and diastole by ∼40%, compared with normothermia without esmolol, inducing in combination both systolic and diastolic LV function impairment. The cardiac dysfunction deteriorated at increased HRs during hypothermia. Beta1-adrenergic receptor blockade (esmolol) exacerbates the negative effects of hypothermia on active myocardial contraction and relaxation. The combination of hypothermia with beta-blockade induces both systolic and diastolic LV function impairment.

Does therapeutic hypothermia during extracorporeal cardiopulmonary resuscitation preserve cardiac function?

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury. METHODS: After a 15-min untreated ventricular fibrillation, the pigs (n = 20) were randomized to either normothermic (38 °C) or hypothermic (32-33 °C) E-CPR. Defibrillation terminated ventricular fibrillation after 5 min of E-CPR, and extracorporeal support continued for 2 h, followed by warming, weaning and a stabilization period. Magnetic resonance imaging and left ventricle pressure measurements were used to assess left ventricular function pre-arrest and 5 h post-arrest. Myocardial injury was estimated by serum concentrations of cardiac TroponinT and Aspartate transaminase (ASAT). RESULTS: E-CPR resuscitated all animals and the hypothermic strategy induced therapeutic hypothermia within minutes without impairment of the resuscitation success rate. All animals suffered a severe global systolic left ventricular dysfunction post-arrest with 50-70% reductions in stroke volume, ejection fraction, wall thickening, strain and mitral annular plane systolic excursion. Serum concentrations of cardiac TroponinT and ASAT increased considerably post-arrest. No significant differences were found between the two groups. CONCLUSIONS: Two-hour therapeutic hypothermia during E-CPR offers an equal resuscitation success rate, but does not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR. Trial registration FOTS 4611/13 registered 25 October 2012.

Successful ECMO-cardiopulmonary resuscitation with the associated post-arrest cardiac dysfunction as demonstrated by MRI.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO-CPR) is a life-saving rescue for selected patients when standard cardiopulmonary resuscitation fails. The use is increasing although the treatment modality is not fully established. Resuscitated patients typically develop a detrimental early post-arrest cardiac dysfunction that also deserves main emphasis. The present study investigates an ECMO-CPR strategy in pigs and assesses early post-arrest left ventricular function in detail. We hypothesised that a significant dysfunction could be demonstrated with this model using magnetic resonance imaging (MRI), not previously used early post-arrest. METHODS: In eight anaesthetised pigs, a 15-min ventricular fibrillation was resuscitated by an ECMO-CPR strategy of 150-min veno-arterial ECMO aiming at high blood flow rate and pharmacologically sustained aortic blood pressure and pulse pressure of 50 and 15 mmHg, respectively. Pre-arrest cardiac MRI and haemodynamic measurements of left ventricular function were compared to measurements performed 300-min post-arrest. RESULTS: All animals were successfully resuscitated, weaned from the ECMO circuit, and haemodynamically stabilised post-arrest. Cardiac output was maintained by an increased heart rate post-arrest, but left ventricular ejection fraction and stroke volume were decreased by approximately 50 %. Systolic circumferential strain and mitral annular plane systolic excursion as well as the left ventricular wall thickening were reduced by approximately 50-70 % post-arrest. The diastolic function variables measured were unchanged. CONCLUSIONS: The present animal study demonstrates a successful ECMO-CPR strategy resuscitating long-lasting cardiac arrest with adequate post-arrest haemodynamic stability. The associated severe systolic left ventricular dysfunction could be charted in detail by MRI, a valuable tool for future cardiac outcome assessments in resuscitation research. TRIAL REGISTRATION: Institutional protocol number: FOTS 4611/13 .