Journal of Pediatric Surgery VOL 35, NO 10
Quantification of Recirculation by Thermodilution During Venovenous Extracorporeal Membrane Oxygenation By Con Sreenan, Horacio Osiovich, Po-Yin Cheung, and Robert P. Lemke Edmonton, Alberta
Purpose: The aim of this study was to determine whether recirculation could be quantified by a thermodilution technique during venovenous (VV) extracorporeal membrane oxygenation (ECMO) in a rabbit model. Methods: Five New Zealand white rabbits, mean weight, 4.5 (range, 3.7 to 5.7) kg, were anesthetized, instrumented, cannulated with a double-lumen catheter, and placed on VV ECMO. Serial injections of ice-cold saline were performed at the arterial arm of the circuit, and the resultant temperature change at various pump flows was measured at the venous arm of the circuit using a thermistor-tipped catheter and a cardiac output computer. Results were compared with the respective 100% recirculation measured with all the circuit flow passing through the bridge. Results: Using linear regression, recirculation percentage
XTRACORPOREAL membrane oxygenation (ECMO) is an effective treatment for severe respiratory failure in neonates.1,2 Venoarterial bypass has been the traditional mode of ECMO support, but in recent years double-lumen (DL) venovenous (VV) ECMO has been used with increasing frequency.3,4 In contrast to venoarterial ECMO, during VV ECMO there always is some degree of recirculation, which may lead to ineffective oxygenation of systemic blood. Recirculation occurs because a variable proportion of arterial blood from the ECMO circuit passes via the venous drainage holes of the DL catheter back to the ECMO circuit instead of passing through the tricuspid valve to the pulmonary circulation. Using a DL catheter for VV ECMO, recirculation has been found to be 65% at a flow of 500 mL/min.5 Currently, there is no convenient noninvasive way to measure recirculation. If recirculation could be quantified accurately it might be possible to reduce it and optimize oxygen delivery by various maneuvers such as adjusting the position of the doublelumen catheter.
Journal of Pediatric Surgery, Vol 35, No 10 (October), 2000: pp 1411-1414
could be calculated as: 19 ⫹ 0.1 ⫻ pump flow (R2 ⫽ 0.81, P ⬍ .005). Recirculation correlated positively with pump flow. Variability between results at each flow was less than 10%.
Conclusions: Recirculation can be quantified during VV ECMO by measuring the change in temperature in the venous arm using a cardiac output computer after injection of a known quantity of ice-cold saline in the arterial side of the circuit. The effect of interventions to reduce recirculation can be assessed conveniently and reliably. J Pediatr Surg 35:1411-1414. Copyright © 2000 by W.B. Saunders Company. INDEX WORDS: Extracorporeal membrane oxygenation, venovenous, thermodilution, recirculation, double-lumen catheter.
Cardiac output measurement by thermodilution was described originally in anesthetized dogs in 1954.6 Since the development of balloon-tipped catheters by Ganz and Swan7 the technique has been used widely in adults and critically ill infants and children.8 Thermodilution involves the injection of room temperature or ice-cold saline into the right atrium and the derivation of cardiac output from the resulting temperature-time curve recorded in the main pulmonary artery. We have shown previously, using 2 ECMO circuits in series joined by a mixing chamber, that recirculation during experimental
From the Division of Neonatology, Royal Alexandra Hospital, and the Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Address reprint requests to Robert P. Lemke, MD, FRCPC, FAAP, Neonatal Intensive Care Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada T5H 3V9. Copyright © 2000 by W.B. Saunders Company 0022-3468/00/3510-0001$03.00/0 doi:10.1053/jpsu.2000.16402
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perfusion can be quantified accurately using a modified thermodilution technique.9 Because the specific use of thermodilution to quantify recirculation during ECMO has not been evaluated, we designed this study to determine whether in vivo recirculation could be quantified by thermodilution during VV ECMO in rabbits. We assumed that by detecting the temperature change in the venous arm of the ECMO circuit after injecting a known quantity of ice-cold saline into the arterial side of the circuit, the recirculation flow could be measured using a cardiac output computer.
lines unclamped and the bridge clamped. The ventilatory support was reduced to pressures of 15/4 cm H2O, FIO2 0.3 at a rate of 15 breaths per minute.
Before placing the animal on ECMO, 100% recirculation was studied by injecting 3 mL of ice-cold saline into a port 6 cm from the bridge in the arterial arm of the ECMO circuit, with the inflow and outflow lines clamped and the bridge unclamped. Serial measurements of the 100% recirculation flow based on the temperature change at the venous arm of the circuit, using the thermistor-tipped catheter, were computed from a cardiac output computer (American Edward Laboratories, Santa Ana, CA). Triplicate measurements were made at ECMO pump flows from 100 to 450 mL/min in increments of 50 mL. If an individual measurement at each flow differed from the other measurements by 10%, that result was discarded, and another measurement was made. The results were averaged for subsequent analysis. Once the animal was stabilized on ECMO for 20 minutes, triplicate measurements of bypass recirculation flow were repeated at the same flow rates. Subsequently, the animal was killed with pentobarbital, and when the heart had stopped, measurements were repeated again at each flow to confirm 100% recirculation measurements.
Five female New Zealand white rabbits, with a mean weight of 4.5 (range, 3.7 to 5.7) kg, were used for this study.
MATERIALS AND METHODS This study conforms with the guidelines for the care and use of experimental animals of the Canadian Council on Animal Care and was approved by the Health Sciences Animal Policy and Welfare Committee of the University of Alberta.
ECMO Circuit The ECMO circuit used was identical to that used in our Neonatal Intensive Care Unit: a 0.8-m2 silicone membrane oxygenator (Avecor Cardiovascular Inc, Plymouth, MN) connected to a heat exchanger (Avecor Cardiovascular Inc) and then via Tygon tubing to the arterial inflow line. The venous return line leads to a silicone bladder, which controls pump flow, and then via a Sarns roller pump (S10 KII, 3M Healthcare, Irvine, CA) back to the membrane oxygenator. The ECMO circuit was primed with anticoagulated rabbit blood (Pel-Freez, Rogers, AK), and venous drainage from the rabbit was provided through the venous channel of a 12F DL catheter (Origen Biomedical, Austin, TX), which was connected to the venous return limb of the ECMO circuit. The arterial inflow line of the circuit was connected to the arterial channel of the DL catheter. To study recirculation by thermodilution, a 5F thermistor-tipped catheter (Argyll, Sherwood Medical, St Louis, MO) was inserted into the venous arm of the circuit 6 cm from the bridge with the catheter directed against the flow of returning blood.
Data were expressed as mean ⫾ SEM. The flow measured by thermodilution when all the flow passed through the bridge of the circuit was considered as 100% recirculation flow. With the bridge clamped and VV ECMO started, the bypass recirculation flow as measured by thermodilution at each pump rate was compared with the respective 100% recirculation and used to calculate recirculation percentage by the equation: bypass recirculation flow (mL/min) ⫼ 100% recirculation flow (mL/min) ⫻ 100. Recirculation percent (dependent variable) and pump flow (independent variable) were then studied by linear regression (Sigma Stat, Version 2.0, Jandel Corp, San Rafael, CA). A P value of less than .05 was considered statistically significant.
Recirculation correlated positively with pump flow (r ⫽ 0.9, P ⬍ .005). Figure 1 shows the percent recirculation against pump flow: recirculation (%) ⫽ 19 ⫹ 0.1 ⫻ pump flow (mL/min); (R2 ⫽ 0.81, P ⬍ .005).
Surgical Procedure The animals were premedicated with intramuscular ketamine (40 mg/kg), rompun (8 mg/kg), and acepromazine (0.5 g/kg), and then received inhalational anesthesia using halothane (initially 5% reduced to 0% to 2% for maintenance as needed). Arterial and central venous catheters (Argyll, Sherwood Medical), 3.5F or 5F as appropriate, were inserted via the femoral vessels. An intravenous bolus of 10 g/kg fentanyl was given followed by an infusion of 4 g/kg/h for the duration of the experiment. A tracheotomy then was performed, and the animals were ventilated artificially, after muscle relaxation with intravenous pancuronium bromide (0.1 mg/kg every 60 to 90 minutes) to maintain normal blood gases (PaO2, 60 to 80 mm Hg, PaCO2, 35 to 45 mm Hg, pH 7.35 to 7.45). Throughout the experiment, heart rate, mean arterial blood pressure, central venous pressure, and pulse oximetry (Nellcor Inc, Hayward, CA) were monitored continuously. After a 30-minute stabilization period, an intravenous bolus of heparin (50 U/kg) was given and the DL catheter was inserted into the right atrium via the external jugular vein and the position confirmed by fluoroscopy. VV ECMO then was started with the inflow and outflow
Fig 1. Calculated recirculation percentage using thermodilution during VV ECMO in rabbits; Recirculation % ⴝ 19 ⴙ 0.1 ⴛ pump flow (mL/min).
RECIRCULATION DURING VV ECMO
Table 1. Flow Measured by Thermodilution with 100% Recirculation Compared With Postmortem Flow for Rabbits Undergoing DoubleLumen Venovenous ECMO Pump Flow (mL/min)
100% Recirculation Flow (mL/min, mean ⫾ SEM)
Postmortem Flow (mL/min, mean ⫾ SEM)
100 150 200 250 300 350 400 450
105 ⫾ 3 152 ⫾ 3 190 ⫾ 5 241 ⫾ 7 291 ⫾ 11 348 ⫾ 9 394 ⫾ 9 443 ⫾ 6
108 ⫾ 2 149 ⫾ 3 193 ⫾ 3 255 ⫾ 8 300 ⫾ 13 359 ⫾ 8 405 ⫾ 8 449 ⫾ 6
.57 .61 .75 .37 .57 .46 .49 .55
NOTE. Flow measured with bridge unclamped compared with flow after the animal was killed and the heart stopped.
There was no difference between 100% recirculation flow and the respective bypass recirculation flow after the animal was killed (Table 1). Baseline physiologic parameters were heart rate, 184 ⫾ 18 beats per minute (mean ⫾ SD); mean arterial pressure, 111 ⫾ 12 mm Hg; central venous pressure, 12 ⫾ 0 mm Hg; and pH, 7.44 ⫾ 0.09 and were stable throughout the experiment. DISCUSSION
The results of this study show that recirculation can be quantified conveniently and accurately during VV ECMO using a thermodilution technique with measurement of the temperature changes in the venous arm of the ECMO circuit after injection of a known quantity of ice-cold saline into the arterial side of the circuit. In this study recirculation increased with increasing pump flow. Using this rabbit model of VV ECMO at flow rates of more than 350 mL/min, recirculation was greater than 50%, indicating the ineffectiveness of bypass at higher flows. Recirculation is a frequent problem during VV ECMO and leads to less efficient oxygen delivery. If recirculation becomes excessive, effective flow and thus oxygenation of systemic blood will be reduced. Increasing flows further to try and remedy the situation paradoxically can lead to further recirculation and a further decrease in oxygenation. Factors affecting recirculation include catheter position and design, hypovolemia, venous return, degree of pulmonary hypertension, and use of a cephalad catheter.10,11 Malpositioning of the catheter is the most common problem causing recirculation during VV ECMO.11 Currently there is no convenient noninvasive way to measure recirculation. The thermodilution technique used in this study provides a safe and convenient method for quantifying recirculation during VV ECMO. In addition, it provides a method to assess and trend the effect of various interventions that may be used to reduce recirculation, eg, catheter manipulation. The fact that there was no difference 100% recirculation flow and bypass recirculation flow after the animal was killed and
the heart stopped confirms the accuracy and reproducibility of this technique. Because the heart is not beating at this point all the flow delivered to the right atrium should be recirculated back to the circuit confirming the measurement of 100% recirculation. Previous evaluations could only be performed by measuring mixed venous saturation, which requires a temporary discontinuation of bypass support.5 This is not practical in the clinical situation with neonates critically dependent on ECMO support. Use of a 14F DL catheter in human neonates, as opposed to the 12F DL catheter used in this study, may result in less recirculation. This may explain why the degree of recirculation found in this study is greater than previously reported in human neonates.5 However, we feel that the actual estimate of the recirculation itself is less important than the opportunity that this technique offers to trend recirculation conveniently. There are several possible limitations in this model. First, it is possible that transient alterations in right atrial hemodynamics, induced after injection of cold injectate into the right atrium, might result in a modestly different measurement of the amount of recirculation. However, we had a variance of less than 10% in triplicate measurements. Second, the percent recirculation increased again as pump flows were decreased to less than 150 mL/min. This may be related to technical limits at such low pump flows in both the cardiac output computer that we used and the thermodilution method itself. However, it is possible that recirculation does increase again as pump flows are lowered because of increased dwell time within the right atrium allowing more recirculation. In the clinical situation this will not be of practical importance, because at such flows, flows are being weaned and preparations are being made for a trial off ECMO. Third, the temperature change in the venous arm of the circuit was measured by a thermistor-tipped catheter when icecold saline was injected into the arterial side of the circuit and not at the proximal port of the thermistor catheter. This might have resulted in some errors in the measurement of temperature change by the catheter. We cur-
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rently are developing a circuit into which thermistors are incorporated into the venous and arterial limbs of the circuit. With this circuit recirculation would be at a minimum when after a thermodilution injection the temperature difference between the venous and arterial thermistors is at a maximum. Finally, the DL catheter used in this experiment is not the one generally used in most centers. The degree of recirculation may be less with other catheter types. Because of the size of the neck vessels in the model we studied, we used a 12F catheter. Again, the degree of recirculation may well be different with a 14F or 16F catheter. The purpose of this study was not to provide a recirculation equation for each cannula type, size, and position, to be applied clinically but to
show the convenience of the technique in providing a “real-time” trend in recirculation. This technique can conveniently and accurately quantify recirculation during VV ECMO by measuring the temperature change in the venous arm of the ECMO circuit after the injection of a known quantity of iced saline into the arterial side of the circuit. Application to the clinical setting is planned with further studies to validate our method. ACKNOWLEDGMENTS The authors thank Origen biomedical for supplying the 12F doublelumen ECMO catheters. They also thank the staff of the Neonatal Research Laboratory of the Royal Alexandra Hospital and Wendy Ainsworth, ECMO Coordinator, for help with carrying out this study.
REFERENCES 1. Shanley CJ, Hirschl RB, Schumacher RE, et al: Extracorporeal life support for neonatal respiratory failure: A 20-year experience. Ann Surg 220:269-280, 1994 2. UK Collaborative ECMO trial group: UK collaborative randomized trial of neonatal extracorporeal membrane oxygenation. Lancet 348:75-82, 1996 3. Cornish D, Heiss K, Clark R, et al: Efficacy of venovenous extracorporeal membrane oxygenation for neonates with respiratory and circulatory compromise. J Pediatr 122:105-109, 1993 4. Osiovich HC, Peliowski A, Ainsworth W, et al: The Edmonton experience with venovenous extracorporeal membrane oxygenation. J Pediatr Surg 33:1749-1752, 1998 5. Anderson HL, Otsu T, Chapman RA, et al: Venovenous extracorporeal life support in neonates using a double lumen catheter. ASAIO Trans 35:650-653, 1989 6. Fegler G: Measurement of cardiac output in anaesthetized animals by a thermodilution method. Q J Exp Physiol 39:153-164, 1954
7. Ganz W, Swan HJC: Measurement of blood flow by thermodilution. Am J Cardiol 29:241-246, 1971 8. Wyse SD, Pfitzner J, Rees A, et al: Measurement of cardiac output by thermal dilution in infants and children. Thorax 30:262-265, 1973 9. Sreenan C, Osiovich HC, Lemke RP: Noninvasive quantification of recirculation during venovenous extracorporeal membrane oxygenation. Pediatr Res 45:46A, 1999 (abstract) 10. Rais-Bahrani R, Rivero O, Mikesell G, et al: Improved oxygenation with reduced recirculation during venovenous extracorporeal membrane oxygenation: Evaluation of a test catheter. Crit Care Med 23:1722-1725, 1995 11. Cornish JD, Clark RH: Principles and practice of venovenous extracorporeal membrane oxygenation, in Zwischenberger JB, Bartlett RH (eds): Extracorporeal Pulmonary Support in Critical Care. Extracorporeal Life Support Organization 1995, pp 87-109