Gerald T. Mikesell

Improved oxygenation with reduced recirculation during venovenous ECMO: comparison of two catheters

Objectives: To determine whether the new double-lumen catheter made by OriGen Biomedical (Austin, TX) for venovenous (VV) extracorporeal membrane oxygenation (ECMO) would reduce recirculation and improve oxygenation during VV ECMO when compared with the Kendall double-lumen catheter (Kendall Healthcare Products, Mansfield, MA). Design: Prospective intervention study. Setting: The animal research laboratory at Children’s National Medical Center, Washington, DC. Subjects: Nine newborn lambs one to seven days old and weighing 4.4± 0.8 kg. Intervention: Animals were anesthetized, intubated, and ventilated. The ductus arteriosus was ligated. Femoral arterial and venous, cephalic jugular vein, and pulmonary artery catheters were placed. After systemic heparinization, the catheter to be tested, an OriGen catheter, was placed in the right internal jugular vein and advanced into the right atrium. The animal was placed on ECMO and stabilized, with the ventilator settings decreased to a peak inspiratory pressure of 15-20 cmH2O, peak end-expira-tory pressure of 5 cmH2O, rate of 15-25 breaths/min, and a fractional inspired oxygen concentration of 0.21-0.30. ECMO flows were increased in 100-ml increments from 200 to 600 ml/min with measurements taken 15 min after each change. The OriGen catheter was removed, the Kendall catheter was placed, and the studies were repeated. Measurements and Main Results: Heart rate, mean blood pressure, paO2, jugular cerebral oxygen saturation, pulmonary artery oxygen saturation, pump venous oxygen saturation, and postmembrane circuit pressures were measured at each study period. The OriGen catheter improved oxygenation, with higher systemic paO2, higher pulmonary artery and cerebral oxygen saturations, and lower pump venous oxygen saturations (indicating less recirculation). With the OriGen catheter, paO2 levels ranged from 69± 18 mmHg [9.2± 2.4 kPa] to 114 ± 45 mmHg [15.2± 6.0 kPa], compared range from 61± 15 mmHg [8.1± 2.0 kPa] to 87± 34 mmHg [11.5± 4.5 kPa] for the Kendall catheter. These findings indicate that, at all flow rates studied, less recirculation occurred with the OriGen catheter than with the Kendall catheter. The postmembrane pressures were significantly lower for the OriGen catheter at any given flow (from 30 ± 5 to 122 ± 18 mmHg) when compared with the Kendall catheter (from 77± 16 to 330 ± 78 mmHg). Conclusions: These findings indicate that the OriGen catheter resulted in a reduction of recirculation, thereby resulting in an improvement in oxygenation while on VV ECMO. The lower postmembrane pressure potentially could reduce the risk of ECMO circuit complications such as tubing rupture, bleeding complications, as well as hemolysis. This new catheter makes VV ECMO more effective and represents a design that could be used for neonatal and/or pediatric ECMO.

Improved oxygenation with reduced recirculation during venovenous extracorporeal membrane oxygenation: evaluation of a test catheter.

OBJECTIVE To determine whether modifications of the original design of a double-lumen, venovenous, extracorporeal membrane oxygenation (ECMO) catheter would reduce recirculation and improve oxygenation during venovenous ECMO. DESIGN Prospective, interventional study. SETTING The animal research laboratory at The Childrens National Medical Center. SUBJECTS Six newborn lambs, 1 to 7 days old and weighing 4.7 +/- 0.9 kg. INTERVENTIONS Animals were anesthetized, intubated and ventilated. The ductus arteriosus was ligated. Femoral artery and vein, cephalic jugular vein, and pulmonary artery catheters were placed. After systemic heparinization, the test catheter (with venous drainage holes moved away from the arterial return holes) was placed in the right internal jugular vein and advanced into the right atrium. The animal was placed on ECMO and stabilized, with the ventilator settings decreased to a peak inspiratory pressure of 15 cm H2O, peak positive end-expiratory pressure of 5 cm H2O, respiratory rate of 15 breaths/min, and an FIO2 of 0.21. ECMO flows were increased in 100-mL increments from 200 to 600 mL/min, with measurements taken 15 mins after each change. The test catheter was removed, the double-lumen, venovenous ECMO catheter was placed, and the studies were repeated. MEASUREMENTS AND MAIN RESULTS Heart rate, mean arterial pressure, PaO2, jugular cerebral oxygen saturation, pulmonary artery oxygen saturation, mixed venous oxygen saturation, and postmembrane circuit pressures were measured at each study period. The test catheter improved oxygenation significantly, with higher systemic PaO2, higher pulmonary artery and cerebral oxygen saturations, and lower mixed venous oxygen saturations (indicating less recirculation). With the test catheter, PaO2 levels ranged from 62 +/- 6 torr (8.3 +/- 0.8 kPa) to 112 +/- 12 torr (14.9 +/- 1.6 kPa), compared with 46 +/- 4 torr (6.1 +/- 0.5 kPa) to 59 +/- 2 torr (7.9 +/- 0.3 kPa) for the double-lumen, venovenous ECMO catheter (p < or = .001). These findings indicate that at all flow rates studied, less recirculation occurred with the test catheter than with the double-lumen, venovenous ECMO catheter. CONCLUSIONS These findings indicate that the redesign of the double-lumen, venovenous ECMO catheter, as outlined in this study, resulted in a significant reduction of recirculation, thereby resulting in a significant improvement in oxygenation while on venovenous ECMO. This newly designed catheter makes venovenous ECMO more effective, and represents a design that could be used for pediatric and/or adult ECMO.

Continuous Blood Gas Monitoring Using an In-Dwelling Optode Method: Comparison to Intermittent Arterial Blood Gas Sampling in ECMO Patients

INTRODUCTION: The ability to measure postmembrane arterial blood gases is essential in the management of critically ill neonates treated with extracorporeal membrane oxygenation (ECMO). A new technology using, the Paratrend 7 system (Diametrics Medical, High Wycombe,UK) allows for continuous measurement of pH, PCO2 and PO2, and calculates oxygen saturation, bicarbonate, and base excess.OBJECTIVE: To evaluate and compare the results of continuous blood gas measurement using the Paratrend 7 system with a standard system of blood gas analysis in our intensive care unit.DESIGN: Prospective, controlled, interventional study.SETTING: The neonatal intensive care unit of a tertiary referral center.PATIENTS: Neonates who required extracorporeal life support and were expected to have frequent postmembrane arterial blood sampling during the testing period.RESEARCH DESIGN AND METHOD: To enable Paratrend 7 sensor access to the ECMO circuit, the postmembrane access port extension set that is routinely used for blood drawn for blood gas analysis was used. The study began with the insertion of the Paratrend 7 sensor. Subjects remained on the study until the ECMO was discontinued and/or frequent blood gases were no longer needed. The blood gas results from the Paratrend 7 system were not used in clinical management of the patient.BLOOD GAS MEASUREMENT: During the study period, with each blood sample drawn for laboratory analysis, a printout from the Paratrend 7 monitor was recorded for comparison.RESULTS: A total of 242 pairs of blood gas samples were collected from 10 neonates. The mean bias/precision for pH was −0.02/0.04; for PO2 68.35/93.44 mm Hg; and for PCO2 1.75/4.23 mm Hg. The correlation (r value) between the sensor reading and the blood gases were 0.89 for pH, 0.96 for PO2, and 0.73 for PCO2 (Table 1).CONCLUSION: The blood gases compared in the two methods had a strong correlation for pH, PCO2 and PO2.Results of this study indicate that this technology provides an accurate means of monitoring continuous blood gas parameters in neonatal ECMO patients. Use of the Paratrend 7 should allow reduced health-care provider exposure to blood and decreased patient iatrogenic blood loss.

Continuous Blood Gas Monitoring Using an In-Dwelling Optode Method: Clinical Evaluation of the Neotrend Sensor Using a Luer Stub Adaptor to Access the Umbilical Artery Catheter

INTRODUCTION: Arterial blood gases are essential in the management of critically ill neonates. A new technology using the Neotrend system (Diametrics Medical) allows for continuous measurement of pH, PaCO2, and PaO2, and calculates oxygen saturation, bicarbonate, and base excess.OBJECTIVE: To evaluate and compare the results of continuous blood gas measurement using the Neotrend system with a standard system of blood gas analysis in our intensive care unit.DESIGN: Prospective, controlled, interventional study.SETTING: The neonatal intensive care unit of a tertiary referral center.PATIENTS: Neonates with respiratory distress who required respiratory support and frequent arterial blood gas sampling and had a UAC.RESEARCH DESIGN AND METHOD: To enable Neotrend sensor access to an existing Argyle umbilical artery catheter (UAC) the catheter was cut at the 25-cm mark and connected to an 18-gauge blunt needle luer stub adaptor (Vygon 95440). The study began with the insertion of the Neotrend sensor. Subjects remained on the study until the UAC was discontinued and/or frequent blood gases were no longer needed. The blood gas results from the Neotrend system were not used in clinical management of the patient.BLOOD GAS MEASUREMENT: During the study period, with each blood sample drawn for laboratory analysis, a printout from the Neotrend monitor was recorded for comparison.RESULTS: A total of 217 pairs of blood gas samples were collected from seven neonates. The mean bias/precision for pH was 0.01/0.04; for PaO2 0.72/18.5 mm Hg; and for PaCO2 3.96/2.63 mm Hg. The correlation (r value) between the sensor reading and the blood gases were 0.85 for pH, 0.96 for PaO2, and 0.92 for PaCO2.CONCLUSION: The blood gases compared in the two methods had a strong correlation for pH, PaCO2, PaO2, and oxygen saturation. Although the bicarbonate and base excess values showed suboptimal statistical correlation, the difference was not clinically relevant. Results of this study indicate that this technology provides an accurate means of monitoring continuous blood gas parameters in neonatal patients. It also allows reduced healthcare provider exposure to blood and decreased patient iatrogenic blood loss.

Comparison of the effect of venovenous versus venoarterial extracorporeal membrane oxygenation on renal blood flow in newborn lambs

Venovenous extracorporeal membrane oxygenation (VV ECMO) using double lumen catheters is an alternative to venoarterial (VA) ECMO and allows for total blood flow using the patient’s cardiac output in comparison to partial blood flow provided during VA ECMO. Objective: To compare the effects of VV versus VA ECMO on renal blood flow. Design: Prospective study. Setting: Research laboratory in a hospital. Subject: Newborn lambs 1-7 days of age (n=15). Interventions: In anesthetized, ventilated lambs, fe-moral artery and vein were cannulated for monitoring and renal venous blood sampling. An ultrasonic flow probe was placed on the left renal artery for continuous renal blood flow measurements. Animals were randomly assigned to control (non-ECMO), VV ECMO and VA ECMO groups. After systemic heparinization, the animals were cannulated and studied at bypass flows of 120 mL-kg/min (partial bypass) for two hours in both ECMO groups and 200 mL/kg/min (full bypass) for an additional 30 min in the VA group. Changes in blood pressure and renal flow on ECMO and during ECMO bridge unclamping were recorded continuously. Plasma renin activity (PRA) levels were sequentially sampled. Results: Systemic blood pressure was not different in VV or VA ECMO at partial bypass flow. However, systemic blood pressure increased significantly at maximal bypass flow in the VA ECMO group. There was no change in renal flow in either VV or VA ECMO groups. PRA levels did not correlate with bypass flow change. During unclamping of the ECMO bridge, blood pressure and renal flow drop significantly in the VA group, but not in the VV group. Conclusion: VV and VA ECMO at partial bypass flows had comparable effect on blood pressure, renal blood flow and PRA level in this short-term study. However, unclamping of the ECMO bridges did differentially affect blood pressure and renal blood flow between VV and VA groups. We speculate that this repeated acute change in long-run VA ECMO support may play a role in the persistent hypertension seen in some patients.

Techniques for Warming Red Blood Cells Packaged in Different Containers for Neonatal Use

Essential to the management of the sick, low birth weight infant is maintenance of a neutral thermal environment by use of convection incubators and radiant warmers. Manipulation of the infant in preparation for transfusion and the transfusion of cold blood could theoretically lower the infants body temperature, subsequently contribute to cold stress, and concomitantly increase metabolic demands and oxygen requirements. The authors evaluated different pretransfusion ma nipulations of syringe aliquots and bags of blood in an effort to provide a clinically acceptable product for transfusion to sick, very low birth weight infants.

Evaluation of the new generation dual-lumen catheter for neonatal ECMO

Objectives: The purpose of this study was to compare the newly designed dual-lumen venovenous catheter (VR13, OriGen Biomedical, Austin, TX) with the current dual-lumen catheter (VV12, OriGen Biomedical). Methods: Five newborn lambs, 1 to 5 days old and weighing 4.2 ± 0.5 kg, were cannulated with the VV13 OriGen catheter and placed on extracorporeal membrane oxygenation (ECMO). ECMO flows were increased from 200 to 600 ml/min, with measurements taken after the changes. The experiment was then repeated using the VV12 catheter. Results: Recirculation values were equal for both catheters. The pressure drop at the reinfusion port was equal for both catheters at 200 ml/min, increasing to 275 mmHg at 500 ml/min for the VR13 vs. 240 mmHg for the VV12 catheter. Conclusion: These findings indicate that the VR13 catheter resulted in levels of recirculation equal to the VV12. Based on resistance measurements, we do not recommend the use of this new catheter beyond 400 ml/min until minor design changes are made.

In vitro evaluation of the Mera Silox-S 0.5 and 0.8 m2 silicone hollow-fibre membrane oxygenator for use in neonatal ECMO

The Mera Silox-S is a silicone hollow-fibre membrane oxygenator made up of thousands of fibres in a clear polycarbonate housing. Being a silicone membrane it does not have the plasma leakage problem associated with conventional microporous hollow fibres when used in a long-term application. This device (Mera Senko Medical Instrument Co., Japan) is made in three sizes: 0.3, 0.5 and 0.8 m2. The performance of the 0.5 m2 and 0.8 m2 Silox-S membrane oxygenators was tested in vitro using filtered ovine blood and a customized test circuit designed to provide a continuous source of de-oxygenated, CO2-laden blood, according to the AAMI standard for oxygenator performance. The 0.8 m2 membrane provided excellent oxygenation, with a transfer rate of 13.0-43.5 ml/min for blood flows of 200-800 ml/min. CO2 transfer over the same range of flows measured 32.3-40.8 ml/min. Flow rates of 100-500 ml/min for the 0.5 m2 membrane provided an oxygen transfer of 6.8-28.3 ml/min and would probably not be suited for the existing neonatal ECMO population. A matter of concern with both oxygenators was an increased pressure drop for blood flow through the devices. The ΔPfor the 0.5 m2 for flows of 100-500 ml/min ranged from 155 ± 7 mmHg to 516 ± 6 mmHg. For the 0.8 m2, ΔP was 194 ± 39 mmHg to 492 ± 53 mmHg for flows of 200-800 ml/min. Overall, favourable results support further long-term evaluation for potential use in neonatal ECMO.

Influence of central hemodynamics on VV ECMO oxygen delivery in neonatal animal model.

BACKGROUND Recirculation of oxygenated blood in venovenous extracorporeal membrane oxygenation (VV ECMO) can decrease the oxygen delivery provided by the ECMO support. This study investigated the influence of central hemodynamics and catheter position on the amount of recirculation and oxygen delivery during VV ECMO. METHODS Recirculation was measured in seven newborn lambs (mean weight 4.7 kg) during VV ECMO using the ELSA Monitor (Transonic Systems, Inc., Ithaca, NY) and using the central venous line (CVL) method. The ECMO pump was set at the prescribed flow of 110-120 mL/kg/min for a targeted oxygen delivery rate of 6cc/kg/min without recirculation. Hemodynamic status before and during ECMO was also measured by the COstatus Monitor (Transonic Systems, Inc.,Ithaca, NY). RESULTS Lambs with a higher cardiac index (>160 ml/min/kg), had a tendency to have higher percent oxygen delivery (65-94%, at prescribed flow) while lambs with lower cardiac index (<150 ml/min/kg), tended to have lower percent oxygen delivery (39-62%, at prescribed flow). ELSA recirculation measurements had a squared correlation coefficient R2 = 0.8 with the CVL method. CONCLUSIONS The ELSA monitor provides an easy to use, non-invasive method to measure recirculation in VV ECMO. The data suggests that cardiac function may play an important prognostic role in achieving effective VV ECMO support.

In vitro and in vivo assessment of oxygenator blood volume for the prediction of clot formation in an ECMO circuit (theory and validation)

Introduction: Clotting is one of the major causes of mortality and morbidity during extracorporeal membrane oxygenation (ECMO). A large meta-analysis study suggests that 29% of patients require the oxygenator to be replaced during ECMO. As clots usually form in the oxygenator, the oxygenator blood volume (OXBV) decreases over time. The currently used pressure gradient as a predicator of clot formation is unreliable. Objective: The aim of this study was to develop and validate ultrasound dilution technology in a quantitative assessment of clotting, using measurements of OXBV. Methods: OXBV was measured using the ELSA monitor (Transonic Systems Inc., Ithaca, NY, USA) from the transit time of a saline bolus passing through the oxygenator as recorded by a sensor placed after the oxygenator. The accuracy and reproducibility (coefficient of variation [CV]) of OXBV measurement and its independence from ECMO flow was assessed in vitro in lambs and from a clinical data archive. Results: The in vitro accuracy compared with volumetric measurements of OXBV of 22-134 ml at flows of 300-700 ml/min was −0.8±6.6%. For an OXBV of 355 ml at flows of 1020-7000 ml/min, accuracy was −0.4±1.6%. In 88 animal OXBV measurements, the CV was 1.49±1.12%. For an OXBV of 153 (range 42-387 ml), clinical measurements at flow ranged from 210-5960 ml/min, with a CV of 3.20±2.44 %. Conclusion: Dilution technology has the ability to accurately and reproducibly assess the clotting process in the oxygenator. Larger studies are needed to establish guidelines for the prediction of imminent clotting and may help to avoid unnecessary circuit changes.