Impact of the inspiratory oxygen fraction on the cardiac output during jugulo-femoral venoarterial extracorporeal membrane oxygenation in the rat.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) with femoral access has gained wide acceptance in the treatment of critically ill patients. Since the patient´s cardiac output (CO) can compete with the retrograde aortic ECMO-flow, the aim of this study was to examine the impact of the inspiratory oxygen fraction on the cardiac function during V-A ECMO therapy. METHODS: Eighteen male Lewis rats (350-400 g) received V-A ECMO therapy. The inspiratory oxygen fraction on the ventilator was randomly set to 0.5 (group A), 0.21 (group B), or 0 in order to simulate apnea (group C), respectively. Each group consisted of six animals. Arterial blood pressure, central venous saturation (ScvO2), CO, stroke volume, left ventricular ejection fraction (LVEF), end diastolic volume, and pressure were measured. Cardiac injury was determined by analyzing the amount of lactate dehydrogenase (LDH). RESULTS: During anoxic ventilation the systolic, mean and diastolic arterial pressure, CO, stroke volume, LVEF and ScvO2 were significantly impaired compared to group A and B. The course of LDH values revealed no significant differences between the groups. CONCLUSION: Anoxic ventilation during V-A ECMO with femoral cannulation leads to cardiogenic shock in rats. Therefore, awake V-A ECMO patients might be at risk for hypoxia-induced complications.

Comparison of the effect of membrane sizes and fibre arrangements of two membrane oxygenators on the inflammatory response, oxygenation and decarboxylation in a rat model of extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has gained widespread acceptance for the treatment of critically ill patients suffering from cardiac and/or respiratory failure. Various animal models have been developed to investigate the adverse effects induced by ECMO. Different membrane oxygenators have been used with varying priming volumes and membrane surfaces (Micro-1, small animal membrane oxygenator (SAMO)). METHODS: Sixteen male Lewis rats (350-400 g) were randomly assigned to receive ECMO with Micro-1 or SAMO (n = 8, respectively). Venoarterial ECMO was established after cannulation of the femoral artery and the jugular vein. The cardiac output was measured using a left-ventricular conductance catheter. The oxygen fraction of the ECMO was set to 1.0, 0.75, 0.5 and 0.21 after a stabilisation period of 15 min. Further, arterial blood gas analyses were performed at baseline, and during the first hour every 15 min after commencing the ECMO, and subsequently every 30 min. Dilutional anaemia was calculated using haemoglobin concentration at baseline, and 15 min after the start of ECMO therapy. Moreover, inflammation was determined by measuring tumour necrosis factor alpha, interleukin-6 and -10 at baseline and every 30 min. RESULTS: Animals of the Micro-1 group showed a significantly lower dilutional anaemia (ΔHaemoglobin t0 - t0.25: SAMO 6.3 [5.6-7.5] g/dl vs. Micro-1 5.6 [4.6-5.8] g/dl; p = 0.028). Further, significantly higher oxygen partial pressure was measured in the SAMO group, at an oxygen fraction of 0.75, 0.5 and 0.21 (380 [356-388] vs. 314 [263-352] mmHg, p = 0.002; 267 [249-273] mmHg vs. 197 [140-222] mmHg, p = 0.002; 87 [82-106] mmHg vs. 76 [60-79] mmHg, p = 0.021, respectively). However, no differences were found regarding the oxygen fraction of 1.0, in terms of carbon-dioxide partial pressure and cardiac output. Moreover, in the Micro-1 group tumour necrosis factor alpha was increased after 60 min and interleukin-6 after 120 min. CONCLUSION: While the dilutional anaemia was increased after commencing the ECMO, the oxygenation was augmented in the SAMO group. The inflammatory response was elevated in the Micro-1 group.

New noninvasive methodology to measure cardiac output in veno-venous extracorporeal membrane oxygenation patients.

INTRODUCTION: Cardiac output (CO) measurement is vital in veno-venous extracorporeal membrane oxygenation patient population to evaluate oxygen delivery and to early identify right heart failure. Standard clinical methods like pulmonary artery thermodilution and transpulmonary thermodilution are known to be inaccurate in the veno-venous extracorporeal membrane oxygenation setting, especially at high levels of recirculation. OBJECTIVE: The aim of the study was to develop a simple noninvasive method to measure CO in patients during veno-venous extracorporeal membrane oxygenation. METHODS: A mathematical model was developed where CO was analyzed as a combination of two flows: oxygenated blood from extracorporeal membrane oxygenation and less oxygenated mixed venous blood. The system of two mass balance equations for oxygen saturations was introduced to calculate CO. The procedure included measurement of recirculation (ELSA Monitor Transonic Systems Inc. Ithaca, USA) and arterial saturation at two extracorporeal membrane oxygenation flows after temporary pump flow decrease. Mathematic modeling that utilized a crude Monte Carlo method was used to analyze theoretical errors in CO calculations from unknown behavior of venous saturation. The developed concept was retrospectively applied to clinical data archive of 17 adult patients on veno-venous extracorporeal membrane oxygenation that included 52 measurement sessions. RESULTS: Mathematical modeling suggests that proportion of results with error ⩽10% was between 86% and 100% if pre-oxygenated saturation was available and it was between 78% and 86% if pre-oxygenated saturation was not available. Application of two mass balance equation concept to clinical data suggests that as the decrease of the arterial saturation reaches 6% due to flow decrease, then CO calculations becomes highly reliable as 96% (2 standard deviations) of the results has a reproducibility within 6.4%. CONCLUSION: The mathematical model and clinical retrospective analysis demonstrates that the new methodology has the potential to accurately measure CO in veno-venous extracorporeal membrane oxygenation patients. The next step is validation in animal and clinical settings.

International survey on the perioperative management of pulmonary endarterectomy: the perfusion perspective.

INTRODUCTION: Pulmonary endarterectomy (PEA) is the most effective treatment available for chronic thromboembolic pulmonary hypertension (CTEPH). Patient selection, surgical technique and perioperative management have improved patient outcomes, which are traditionally linked to surgical and center experience. However, optimal perfusion care has not been well defined. The goal of the international survey was to better characterize the contemporary perfusion management of PEA and highlight similarities and controversies. METHOD: The combined caseload of 15 participating centers was 5,066 cases. Topics queried included materials and types of cardiopulmonary bypass (CPB) equipment, choice of prime, fluid management, deep hypothermia strategy, temperature management, treatment of acid-base abnormalities and intraoperative hematocrit as well as anticoagulation management for heparin-induced thrombocytopenia. CONCLUSION: Our assessment could provide a base for further advancement and may help design future studies to elucidate the impact of perfusion in this challenging field.

The Impact of Recirculation on Extracorporeal Gas Exchange and Patient Oxygenation during Veno-Venous Extracorporeal Membrane Oxygenation-Results of an Observational Clinical Trial.

Background: Recirculation during veno-venous extracorporeal membrane oxygenation reduces extracorporeal oxygen exchange and patient oxygenation. To minimize recirculation and maximize oxygen delivery (DO2) the interaction of cannulation, ECMO flow and cardiac output requires careful consideration. We investigated this interaction in an observational trial. Methods: In 19 patients with acute respiratory distress syndrome and ECMO, we measured recirculation with the ultrasound dilution technique and calculated extracorporeal oxygen transfer (VO2), extracorporeal oxygen delivery (DO2) and patient oxygenation. To assess the impact of cardiac output (CO), we included CO measurement through pulse contour analysis. Results: In all patients, there was a median recirculation rate of approximately 14−16%, with a maximum rate of 58%. Recirculation rates >35% occurred in 13−14% of all cases. In contrast to decreasing extracorporeal gas exchange with increasing ECMO flow and recirculation, patient oxygenation increased with greater ECMO flows. High CO diminished recirculation by between 5−20%. Conclusions: Extracorporeal gas exchange masks the importance of DO2 and its effects on patients. We assume that increasing DO2 is more important than reduced VO2. A negative correlation of recirculation to CO adds to the complexity of this phenomenon. Patient oxygenation may be optimized with the direct measurement of recirculation.

Anesthetic Management During Pediatric Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy With Cisplatin in a Small Child: A Case Report and Systematic Literature Review.

Cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) present a challenging task for anesthesia providers. Anesthesia management may be complicated by hyperthermia, fluid shifts, and distinct inflammatory response. Only a few reports dealing with the anesthesia management of pediatric CS and HIPEC have been published. We report a case of a 2-year-old child with a relapse of an alveolar rhabdomyosarcoma of the uterus and peritoneal carcinomatosis treated with CS and HIPEC. For children, careful temperature measurement, intraoperative prevention of hyperthermia, and sufficient volume management are important, as well as postoperative pediatric intensive care with experience CS and HIPEC patients.

Watershed phenomena during extracorporeal life support and their clinical impact: a systematic in vitro investigation.

AIMS: Extracorporeal life support (ECLS) during acute cardiac failure restores haemodynamic stability and provides life-saving cardiopulmonary support. Unfortunately, all common cannulation strategies and remaining pulmonary blood flow increase left-ventricular afterload and may favour pulmonary congestion. The resulting disturbed pulmonary gas exchange and a residual left-ventricular action can contribute to an inhomogeneous distribution of oxygenated blood into end organs. These complex flow interactions between native and artificial circulation cannot be investigated at the bedside: only an in vitro simulation can reveal the underlying activities. Using an in vitro mock circulation loop, we systematically investigated the impact of heart failure, extracorporeal support, and cannulation routes on the formation of flow phenomena and flow distribution in the arterial tree. METHODS AND RESULTS: The mock circulation loop consisted of two flexible life-sized vascular models (aorta and vena cava) driven by two paracorporeal assist devices, resistance elements, and compliance reservoirs to mimic the circulatory system. Several large-bore antegrade and retrograde access ports allowed connection to an ECLS system for extracorporeal support. With four degrees of extracorporeal support-that for cardiac failure, early recovery, late recovery, and weaning-we investigated aortic blood flow velocity, blood flow, and mixing zones using colour-coded Doppler ultrasound in the aorta and its corresponding branches. Full retrograde extracorporeal support (3-4 L/min) perfused major portions of the aorta but did not reach the supra-aortic branches and ascending aorta, resulting in an area in the thoracic aorta demonstrating nearly stagnant blood flow velocities during cardiogenic shock and early recovery (0 ± 4 cm/s; -10 ± 15 cm/s, respectively) confined by two watersheds at the aortic isthmus and renal artery origin. Even increased ECLS flow was unable to shift the watershed towards the aortic arch. Antegrade support resulted in homogeneous flow distribution during all stages of cardiac failure but created a markedly negative flow vector in the ascending aorta during cardiogenic shock and early recovery with increased afterload. CONCLUSIONS: Our systematic fluid-mechanical analysis confirms the clinical assumption that despite restoring haemodynamic stability, extracorporeal support generates an inhomogeneous distribution of oxygenated blood with an inadequate supply to end organs and increased left-ventricular afterload with absent ventricular unloading. End-organ supply may be monitored by near-infrared spectroscopy, but an obviously non-controllable watershed emphasizes the need for additional measures: pre-pulmonary oxygenation with a veno-arterial-venous ECLS configuration can allow a transpulmonary passage of oxygenated blood, providing improved end-organ supply.

Cannula position and Bernoulli effect contribute to leg malperfusion during extracorporeal life support with femoral arterial cannulation-an in silico simulation study†.

OBJECTIVES: Limb ischaemia during extracorporeal life support (ECLS) using femoral artery cannulation is frequently observed even in patients with regular vessel diameters and without peripheral arterial occlusive disease. We investigated underlying pathomechanisms using a virtual fluid-mechanical simulation of the human circulation. METHODS: A life-sized model of the human aorta and major vascular branches was virtualized using 3-dimensional segmentation software (Mimics, Materialise). Steady-state simulation of different grades of cardiac output (0-100%) was performed using Computational Fluid Dynamics (CFX, ANSYS). A straight cannula [virtualized 16 Fr (5.3 mm)] was inserted into the model via the left common femoral artery. The ECLS flow was varied between 1 and 5 l/min. The pressure boundary conditions at the arterial outlets were selected to demonstrate the downstream vascular system. Qualitative and quantitative analyses concerning flow velocity and direction were carried out in various regions of the model. RESULTS: During all simulated stages of reduced cardiac output and subsequently adapted ECLS support, retrograde blood flow originating from the ECLS cannula was observed from the cannulation site up to the aortic bifurcation. Analysis of pressure showed induction of zones of negative pressure close to the cannula tip, consistent with the Bernoulli principle. Depending on cannula position and ECLS flow rate, this resulted in negative flow from the ipsilateral superficial femoral artery or the contralateral internal iliac artery. The antegrade flow to the non-cannulated side was generally greater than that to the cannulated side. CONCLUSIONS: The cannula position and ECLS flow rate both influence lower limb perfusion during femoral ECLS. Therefore, efforts to optimize the cannula position and to avoid limb malperfusion, including placement of a distal perfusion cannula, should be undertaken in patients treated with ECLS.

Development and Validation of a Life-Sized Mock Circulatory Loop of the Human Circulation for Fluid-Mechanical Studies.

Mock circulatory loops (MCLs) are usually developed for assessment of ventricular assist devices and consist of abstracted anatomical structures represented by connecting tubing pipes and controllable actuators which could mimic oscillating flow processes. However, with increasing use of short-term peripheral mechanical support (extracorporeal life support [ECLS]) and the upcoming evidence of even counteracting flow processes between the failing native circulation and ECLS, MCLs incorporating the peripheral vascular system and preserved anatomical structures are becoming more important for systematic assessment of these processes. For reproducible and standardized fluid-mechanical studies using magnetic resonance imaging, Doppler ultrasound, and computational fluid dynamics measurements, we developed a MCL of the human circulation. Silicon-based life-sized dummies of the human aorta and vena cava (vascular module) were driven by paracorporeal pneumatic assist devices. The vascular module is placed in a housing with all arterial branches merging into peripheral resistance and compliances modules, and blood-mimicking fluid returns to the heart module through the venous dummy. Compliance and resistance chambers provide for an adequate simulation of the capillary system. Extracorporeal life support cannulation can be performed in the femoral and subclavian arteries and in the femoral and jugular veins. After adjusting vessel diameters using variable Hoffmann clamps, physiologic flow rates were achieved in the supraaortic branches, the renal and mesenteric arteries, and the limb arteries with physiologic blood pressure and cardiac output (4 L/min). This MCL provides a virtually physiologic platform beyond conventional abstracted MCLs for simulation of flow interactions between the human circulation and external circulation generated by ECLS.

RNase1 as a potential mediator of remote ischaemic preconditioning for cardioprotection†.

OBJECTIVES: Remote ischaemic preconditioning (RIPC) is a non-invasive and virtually cost-free strategy for protecting the heart against acute ischaemia-reperfusion injury (IRI). We have recently shown that the inhibition of extracellular RNA (eRNA) using non-toxic RNase1 protected the heart against acute IRI, reduced myocardial infarct (MI) size and preserved left ventricular systolic function in rodent animal MI models. Based on this previous work in animals, the role of the eRNA/RNase1 system in cardiac RIPC in humans should be defined. METHODS: Fourteen patients underwent cardiac surgery without RIPC; from each patient, six separate 5 ml blood specimens from radial artery and two blood specimens from coronary sinus at different time points during heart surgery were taken. Six healthy donors received RIPC (4 × 5 min upper limb ischaemia); blood parameters were quantified before and after RIPC. Twelve patients underwent cardiac surgery of which 6 received RIPC, whereas the remaining 6 were exposed to sham procedure. Circulating eRNA was quantified in plasma from arterial and coronary sinus blood obtained from patients undergoing cardiac by standard procedures. Tumour necrosis factor-α (TNF-α) production by heart tissue was assessed by enzyme-linked immuno-sorbent assay; RNase activity was quantified by an enzymatic assay. RESULTS: Before surgery, eRNA levels were similar in both groups (14 ± 6 vs 13 ± 5 ng/ml; P = 0.9967). In patients without RIPC, arterial eRNA levels rose during surgery (87 ± 12 ng/ml) and peaked after (127 ± 11 ng/ml) aortic declamping; accordingly, eRNA levels in coronary sinus blood were significantly higher (206 ± 32 ng/ml; P = 0.0129) than that in radial artery. Moreover, significant elevation of TNF-α (36 ± 6 ng/ml; P = 0.0059) particularly in coronary sinus blood after opening of the aortic clamping was observed. Interestingly, applying a RIPC protocol significantly increased levels of plasma endogenous vascular RNase1 by >7-fold, and the levels of arterial (31 ± 7 ng/ml; P = 0.0024) and coronary sinus (37 ± 9 ng/ml; P < 0.0001) circulating eRNA, as well as circulating TNF-α (20 ± 4 ng/ml; P = 0.0050) levels were significantly reduced. CONCLUSIONS: Upon RIPC, the level of cardioprotective RNase1 increased, while the concentration of damaging eRNA and TNF-α decreased. The present findings imply a significant contribution of the RIPC-dependent (endothelial) RNase1 for improving the outcome of cardiac surgery. However, the exact mechanism of RNase1-induced cardioprotection still remains to be explored.

Interference between pacemakers/implantable cardioverter defibrillators and video capsule endoscopy.

Our Letter to the Editor, related to the article "Small bowel capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter defibrillators: Outcome analysis using telemetry" by Cuschieri et al, comments on some small errors, that slipped into the authors discussions. The given informations concerning the pacemaker- and implantable cardioverter defibrillators modes were inaccurate and differ between the text and the table. Moreover, as 8 of 20 patient's pacemakers were programmed to VOO or DOO ("interference mode") and one patient was not monitored by telemetry during capsule endoscopy, 9 of 20 patients (45%) lack the informations of possible interference between capsule endoscopy their implanted device. Another objection refers to the interpretation of an electrocardiogram (figure 1, trace B) presented: in contrast to the author's opinion the marked spike should be interpreted as an artefact and not as "undersensing of a fibrillatory wave". Finally, three comments to cited reviews were not complete respectively not quoted correctly.

rFVIIa in the treatment of persistent hemorrhage in pediatric patients on ECMO following surgery for congenital heart disease.

BACKGROUND: Patients who require extracorporeal membrane oxygenation (ECMO) postsurgery for congenital heart disease (CHD) frequently experience severe bleeding episodes. Whereas recombinant-activated factor VII (rFVIIa) has proven efficacy in counteracting intractable hemorrhage in various scenarios, its use in patients on ECMO is limited by the increased risk for thrombotic events. METHODS: Between December 2004 and January 2006, ECMO was used in 10 pediatric patients following cardiac surgery, of whom seven were treated with rFVIIa because of intractable hemorrhage. Their medical records were reviewed with respect to variations in chest tube output and transfusion requirements, occlusion of or thrombus formation in the ECMO circuit and the occurrence of thromboembolic events. Outcome and rate of ECMO circuit occlusion were compared with historic controls. RESULTS: Three patients died, and four survived (none of the deaths was attributable to thrombus formation or bleeding). All patients were treated with aprotinin prior to and during rFVIIa therapy. Two patients developed an occlusion of the oxygenator, one after receiving co-medication with a FXIII concentrate, another after RBC transfusion in the ECMO system. In two patients, thrombus formation was observed in the ECMO system on inspection after discontinuation. Thromboembolic events were not observed. CONCLUSIONS: Recombinant-activated factor VII in a median dosage of 90 microg.kg(-1) was used in seven pediatric patients on ECMO. Rates of ECMO system occlusions and mortality did not differ from historic controls. Neither the reduction of chest tube output nor the blood product transfusion requirements did reach statistical significance.