Evaluation of the Maquet Neonatal and Pediatric Quadrox I with an integrated arterial line filter during cardiopulmonary bypass

Abstract

Background:

Perfusion equipment has evolved since its introduction into clinical practice more than fifty years ago to include smaller cardiopulmonary bypass (CPB) circuits and components. Perfusionists are now exploring the function of new oxygenators with an integrated arterial line filter (IALF). The purpose of this trial was to examine the Maquet Quadrox-I Neonatal and Pediatric oxygenators with IALF in a clinical setting, with respect to gas transfer, heat exchange co-efficiency (HEC), trans-membrane pressure (TMP) gradient and clinical experience.

Methods:

The Maquet Quadrox-I Neonatal oxygenator was used on 30 patients ranging from 2.2-13.1 kg. The Maquet Quadrox-I Pediatric oxygenator was used on 15 patients ranging from 12.7-24.5 kg. Arterial and venous blood gases were taken once the patient was stable on CPB and, subsequently, every 30 minutes afterwards, as per institution protocol. The values for gas transfer rates, HEC and TMP gradient were stratified into three main categories with each oxygenator: normothermia, cooling and re-warming.

Results:

During all conditions, the gas transfer rate with both oxygenators was efficient. The HEC values showed efficient heat exchanger performance during all conditions with both oxygenators. While maintaining CPB flow within the manufacturer’s recommended flow rate for each oxygenator, the TMP gradient range for the Neonatal Quadrox-I was 10-40 mmHg and the Pediatric Quadrox-I was 10-60 mmHg. During the clinical trial, foam was shown to break through the cardiotomy on several occasions when high sucker return was required.

Conclusion:

This new line of oxygenators performed well with regards to gas transfer, HEC and TMP gradient, but there were clinical experiences that did not meet expectations. There were repeated incidences with the venous reservoir which ultimately cast a negative light on the design of this new product from Maquet. In the future, the authors would like to evaluate updated versions of this product from Maquet and any other pediatric perfusion devices that could help the patient in the clinical arena.

Keywords

integrated arterial line filter pediatric perfusion oxygenator cardiopulmonary bypass gas transfer heat exchange co-efficiency trans-membrane pressure gradient

Introduction

Perfusion equipment has evolved since its introduction into clinical practice more than fifty years ago to include smaller bypass circuits and components. Historically, the prime volume of the cardiopulmonary bypass (CPB) circuit far exceeded the neonatal and pediatric patient’s circulating blood volume (CBV). The ratio of surface area and prime volume of the circuit to the neonatal and pediatric patient’s CBV exacerbates their inflammatory response during cardiac surgery.¹ A reduction in prime volume directly correlates to the use of allogenic blood products during pediatric cardiac surgery.¹ Therefore, concentrating on reducing the prime volume of the circuit decreases the patient’s hemodilution and helps reduce the negative effects of CPB on a neonate’s immature organ function.² One current challenge that is now being examined is the feasibility of combining an oxygenator with an integrated arterial line filter (IALF) while maintaining patient safety. There have been many studies that have investigated IALF in the in vitro setting^3-5 and there have been several studies performed in the clinical arena with respect to prime volume,¹ inflammatory response⁶ and gaseous microemboli (GME).^7,8

The most recent line of pediatric oxygenators to be approved by the FDA (Food and Drug Administration) for CPB support in the operating room is the Maquet Quadrox-I Neonatal and Pediatric oxygenators. These oxygenators contain a polypropylene, hollow-fiber membrane with a heat exchanger made of polyurethane fiber. Both oxygenators have an option of Softline or Bioline coating and/or the inclusion of an IALF. Each oxygenator has the ability for pre and post de-airing of the IALF. The venous reservoir has a unique funnel-shaped design and has a new defoamer coating to prevent silicone washout. The specifications of each oxygenator are shown in Tables 1 and 2.⁹

Table 1.

Quadrox-I Neonatal and Pediatric oxygenator specifications

	Quadrox-I Neonatal	Quadrox-I Pediatric
Maximum Blood Flow Rate	1.5 l/min	2.8 l/min
Static Prime Volume with Filter	40 ml	99 ml
Arterial Filter Pore Size	33 µm	33 µm
Oxygenator Membrane Surface Area	0.38 m²	0.8 m²
Maximum Oxygen Transfer (1:1)	90 ml/O₂/min	180 ml/O₂/min
Maximum Carbon Dioxide Transfer (1:1)	73 ml/min	140 ml/min
Heat Exchanger Surface Area	0.07 m²	0.15 m²

Table 2.

Quadrox-I venous reservoir specifications

	Quadrox-I Neonatal (VHK 11000)	Quadrox-I Pediatric (VHK 31000)
Venous Reservoir Volume Capacity	800 ml	1700 ml
Maximum Venous Cardiotomy Inflow	1.0 l/min	1.8 l/min
Minimum Operating Level	15 ml	30 ml
Venous Reservoir Volume Filter Pore Size	40 µm	40 µm
Venous Reservoir Screen Filter Pore Size	33 µm	40 µm

The authors’ interest in the Maquet Quadrox-I oxygenators was due to the models’ IALF, gas transfer rate, heat exchange performance, low surface area and prime volume. The purpose of this trial was to examine the Maquet Quadrox-I Neonatal and Pediatric oxygenators with an IALF in a clinical setting with respect to gas transfer, heat exchange co-efficiency (HEC), trans-membrane pressure (TMP) gradient and clinical experience.

Methods

The Maquet Quadrox-I Neonatal oxygenator was used on 30 patients ranging from 2.2 kg to 13.1 kg. The CPB circuit for all cases when containing the Maquet Quadrox-I Neonatal oxygenator with IALF, was accompanied by the following: VHK 11000 reservoir, the arterial-venous loop size corresponding with the patient size, and 1/4” pump boot. The Quadrox-I Pediatric oxygenator was used on 15 patients ranging from 12.7 kg to 24.5 kg. The CPB circuit for all cases involving the Quadrox-I Pediatric oxygenator with IALF was accompanied by the following: VHK 31000 reservoir, 1/4” arterial line, 1/4” or 3/8” venous line, dependent on patient size, and 1/4” pump boot. The prime volume for each CPB circuit ranged from 185 – 350 ml, dependent on the circuit selection, which correlated to patient size. The Sorin CSC 14 cardioplegia device (Sorin Group USA Inc., Arvada, CO), a Terumo HC05 hemoconcentrator (Terumo Inc., Ann Arbor, MI) with a 3/16” modified ultra filtration circuit, and a Jostra HL-20 (JOSTRA Medizintechnik AG, Hirrlingen, Germany) or Sorin S5 heart-lung machine (Stockert, Munich, Germany) with a roller head pump were used for all patients. The Stockert Heater-Cooler System 3T (Stockert, Munich, Germany) was utilized in each of the cases. All CPB circuit pressures were measured using Edwards Lifesciences pressure transducers (Edwards Lifesciences, Irvine, CA) and an analog signal transmitted the values of the pressure monitoring system. As is customary with institution protocol, pressure transducers for the pre- and post-membrane positions were zeroed prior to CPB initiation. Vacuum-assisted venous drainage (VAVD) was used if necessary for optimizing venous return.

The prime volume for all circuits consisted of Plasmalyte-A, whole blood if necessary to reach the target hematocrit (quantity calculated from the baseline hematocrit), sodium bicarbonate 1 mEq/kg, heparin 2 units/ml of prime solution, lasix 1 mg/kg, methyl prednisolone 30 mg/kg, cefazolin 25 mg/kg, and 50 ml of albumin 25%. When using blood in the prime, an additional 5 mEq of sodium bicarbonate was added along with 450 mg calcium gluconate and the prime volume was hemoconcentrated to remove excess volume. The hematocrit was maintained between 25-33% in all cases. All current institution CPB protocols were followed during the trial.

Arterial and venous blood gases were taken once stable on CPB and, subsequently, every 30 minutes or when indicated, as per institution protocol. The TMP gradient was determined by measuring the pre-membrane pressure on the pre-oxygenator Luer port and post membrane at the arterial filter de-airing port. Gas transfer, TMP, and HEC values were recorded after each blood gas measurement. Each measurement was categorized using the nasopharyngeal temperature of the patient. The values for gas transfer rates, HEC and TMP gradients were stratified into three main sections; normothermia, cooling and re-warming. In cases where the patients were not cooled, all values were recorded at normothermia (34-37°C). During cases when hypothermia was required, values were recorded at the initiation of CPB (34-37°C), at moderate hypothermia (24-28°C), during rewarming at moderate hypothermia (24-28°C) and once the patient reached normothermia (34-37°C) prior to the discontinuation of CPB. The inclusion of data points of 34ºC in the normothermia category were due to the patients starting body temperature registering less than 35ºC. After CPB initiation, these patients were re-warmed to above 35ºC for the normothermic cases or cooled for cases that required hypothermia. The calculations to determine gas transfer, HEC and TMP are shown in Table 3.

Table 3.

Calculations used for O₂ and CO₂ transfer and HEC and TMP gradients

Oxygen Transfer	{[(Arterial-Venous Saturation) × 1.34 × Actual Hemoglobin × Blood Flow] / 100} / FiO² = O² Transfer (ml/O₂/min)
Carbon Dioxide Transfer	(PaCO² × Gas Flow Rate) / 0.863 = CO₂ Transfer (ml/min).
Heat Exchanger Coefficient	[(Temperature of Blood Entering Heat Exchanger) – (Temperature of Blood Exiting Heat Exchanger)] / [(Temperature of Blood Entering Heat Exchanger) – (Temperature of Water Entering Heat Exchanger)] = HEC
Trans-membrane Pressure Gradient	(Pre-Oxygenator Membrane Pressure) – (Post-Oxygenator Membrane Pressure) = TMP Gradient (mmHg)

Results

During cases where patients remained normothermic, gas transfer was efficiently maintained with both the Quadrox-I Neonatal and Pediatric oxygenators (Figures 2 -5). The majority of oxygen transfer with the Quadrox-I Neonatal while at normothermia was maintained between 20-60 ml/O₂/min during all cases. The Quadrox-I Pediatric ranged from 58-123 ml/O₂/min for oxygen transfer during all conditions.The Quadrox-I Neonatal carbon dioxide transfer rate ranged from 5-88 ml/min during all conditions. The range for carbon dioxide transfer during all conditions with the Quadrox-I Pediatric was 45-145 ml/min (Table 4). The HEC measurements were taken during normothermia cases, as well as during cooling and re-warming phases of cases requiring hypothermia. The HEC values showed efficient heat exchanger performance during all conditions with both oxygenators (Table 5). The average TMP gradient for normothermia cases with both oxygenators was low during all conditions (Figure 6). The Quadrox-I Neonatal TMP gradient ranged from 10-45 mmHg while CPB flows were within the manufacturer’s recommended flow rates. The TMP gradient of the Quadrox-I Pediatric ranged from 10-60 mmHg during all conditions when maintaining the manufacturer’s recommended flow rates. As to be expected, an increasing TMP gradient directly correlated with increased CPB Flow (Figure 6).

Table 4.

O₂ and CO₂ Transfer Rate Measurements classified by Age and Category

		Normothermia	Warming
		34-37°C	24-28°C	34-37°C
O₂	Neonatal: mean (sd)	49.8 (20.7)	23.7 (11.0)	36.6 (21.1)
	Pediatric: mean (sd)	90.7 (32.7)	35.4 (4.4)	105.8 (17.8)
CO₂	Neonatal: mean (sd)	37.8 (29.6)	51.3 (38.0)	23.1 (22.7)
	Pediatric: mean (sd)	66.4 (20.4)	121.5 (24.3)	68.1 (18.1)

Table 5.

HEC measurements classified by age and category

	Normothermia	Cooling		Warming
	34-37°C	24-28°C	34-37°C	24-28°C	34-37°C
Neonatal: mean (sd)	0.3 (0.4)	0.7 (0.3)	0.7 (1.2)	0.3 (0.8)	0.5 (0.2)
Pediatric: mean (sd)	0.0 (0.8)	0.7 (n/a)	0.8 (0.5)	0.5 (n/a)	0.4 (0.4)

n/a indicates too small of a sample size to provide sufficient calculations

Averages and standard deviations (sd) were calculated for oxygen transfer, carbon dioxide transfer and HEC measurements. Each variable is shown for each category of CPB and sub-category of temperature (Tables 4, 5). The values of the calculations are shown for oxygen transfer, carbon dioxide transfer, TMP and HEC measurements (Figures 2 -6). Further statistical analysis was not performed due to the intent of this trial.

Clinical Observations

Of the 30 neonatal and 15 pediatric oxygenators used during our trial, we saw foam break through the cardiotomy on several occasions. With each of these foam incidents, it must be noted that the case required higher sucker and vent return per surgeon request. This large amount of sucker and vent return, consisting of blood and air, exceeded the inflow rating of the cardiotomy. While foam did occur and GME were noticed in the post-membrane toggle of the de-airing port, the Jostra HL20 bubble detector was never triggered during any CPB procedure. The Jostra HL20 bubble sensor detects any emboli that are larger than 300 μm, therefore, no air emboli larger than 300 μm was shown to pass the sensor.

Discussion

The use of arterial line filters in CPB has been considered a standard of practice to as many as 96% of clinical perfusionists since the 1980s.¹⁰ As technology has advanced so has the availability of perfusion products for pediatric patients. The introduction of the Maquet Quadrox-I Neonatal and Pediatric oxygenators with IALF brings many unique new design features to evaluate.

The Maquet Quadrox-I line utilizes an innovative funnel-shaped reservoir design. This allows for venous return to flow directly into the venous reservoir while all other return from the CPB circuit passes through channels of the exterior portion and into the cardiotomy filter located in the center of the reservoir. The Maquet VHK 11000 and VHK 31000 are the hard-shell cardiotomy reservoirs that are affiliated with the Quadrox-I oxygenators (Figure 1).

One concern with the design of the Quadrox-I Neonatal oxygenator was related to the venous reservoir capacity (Figure 1). When this oxygenator was utilized with patients who required the upper end of the recommended flow rates, the reservoir volume was not large enough to hold the patient’s blood volume, let alone any additional volume such as cardioplegia or saline flush when utilizing deep hypothermic circulatory arrest. A perfusionist could choose the VHK 31000 reservoir, which is used as the Quadrox-I Pediatric oxygenator reservoir, for the Quadrox-I Neonatal, but the authors felt the original design of the Quadrox-I Neonatal venous reservoir should have allowed for a larger size neonate, instead of adaptation by the clinician.

Along with the issue of reservoir volume capacity, the design of each venous reservoir can be criticized for the maximum inflow of the cardiotomy reservoir. The maximum inflow to the cardiotomy portion of the VHK 11000 reservoir is 1.0 l/min, while the total maximum outflow rate of the Quadrox-I Neonatal oxygenator is 1.5 l/min. Similarly, the maximum inflow to the cardiotomy portion of the VHK 31000 reservoir is 1.8 l/min, while the total maximum outflow rate of the Quadrox-I Pediatric oxygenator is 2.8 l/min (Table 2). This becomes a concern when maximum sucker and vent return is required, as the limited inflow capacity can, potentially, over-pressurize the cardiotomy and allow foam to break through to the reservoir. When foam is shown to be in the venous reservoir without a generous reservoir level, GME can be dispersed to the rest of the circuit. While there is an integrated pressure relief valve located on the reservoir portion which will function as a safety device for VAVD, it will not indicate or relieve pressure in the cardiotomy.

The Maquet VHK 11000 and VHK 31000 reservoirs are diethylexyl-phthalate (DEHP) free for biocompatibility and the defoamer is silicone free to eliminate the risk of silicone washout.⁹ The new high-molecular copolymer, anchor silicon coating (ASC) is the substance that coats the defoamer. The incidence of air emboli being generated during CPB has been documented more frequently than silicone emboli.^11-13 While high amounts of silicone in the bloodstream can result in an embolic event,¹⁴ most reported events involving silicone emboli and CPB were with the use of bubble oxygenators.^15,16 With technological advancement of the CPB circuitry, there is a relatively low risk of silicone embolization from the cardiotomy defoamer. However, the known detrimental effects of GME made the visualization of foam in the CPB circuit alarming. Even the standard cardiotomy venous reservoirs today utilize a silicone particle coating on the defoamer, making the Quadrox-I line a unique reservoir which is completely silicone free.

A clinical review of the other design features with the Maquet Quadrox-I Neonatal and Pediatric oxygenators showed various positives and negatives. The incorporation of the IALF allowed for a low prime volume for the CPB circuit. The IALF has a unique feature which allows de-airing within the pre- and/or post-filter areas. The oxygenator has a convenient vent cap that can be removed during use to purge air pre oxygenator, but this feature could be considered a safety hazard with the use of VAVD. The high efficiency of oxygenation and temperature control is due to the unique arrangement of the oxygenator sheets that optimize the function of gas transfer and heat exchange. Ultimately, the IALF reduced the prime volume of the CPB circuit without compromising the function or efficiency expected of a neonatal or pediatric oxygenator.

Limitations

There were particular limitations with this study. The authors would like to have seen a larger sample size for all conditions with regard to the Quadrox-I Pediatric oxygenator. The trial was discontinued due to the incidences with the venous reservoir, which limited the number of Quadrox-I Pediatric oxygenators.

Gas transfer was not calculated during the cooling phase of hypothermic cases. pH-stat gas management introduces CO₂ into the CPB circuit, which alters the results with the O₂/CO₂ gas transfer calculation.

The clinical perfusionists at Children’s Hospital of Philadelphia utilize a minimally sized shunt (1/16”) for the arterial purge line during CPB. Clinical CPB flow is determined by using all other patient and CPB parameters during clinical cases and is shown to be more than adequate. The idea of “stolen blood flow” due to the arterial purge line during bypass is irrelevant for this study. The results of the calculations are not affected by the shunt flow. All values were taken before the outlet of the oxygenator and the purge line.

Conclusion

This evaluation of the Maquet Quadrox-I Neonatal and Pediatric oxygenators and reservoirs analyzed particular areas of its design and performance in the clinical arena. This new line of oxygenators performed exceptionally well with regards to gas transfer, HEC and TMP gradient, but there were clinical experiences which did not meet expectations. There were repeated experiences with foam breaking through the cardiotomy within the venous reservoir with both the neonatal and pediatric models which, ultimately, cast a negative light on the design of this new Maquet product. With advancement in technology, there can be great improvements with design and function; however, some advancement can challenge safety standards. The pediatric perfusion community welcomes the latest advancement in perfusion technology with the hope to improve clinical outcomes. Patient safety needs to be a primary concern when designing new technology in healthcare.¹⁷ In the future, the authors would like to evaluate updated versions of this product from Maquet and any other pediatric perfusion devices that could help the patient in the clinical arena.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest Statement

None declared

References

Deptula

Valleley

Glogowski

Detwiler

Hammel

Duncan

. Clinical evaluation of the Terumo Capiox FX05 Hollow Fiber Oxygenator with integrated arterial line filter. J Extra Corpor Technol 2009; 41: 220–225.

Golab

Takkenberg

JJM

Bogers

AJJC

. Specific requirements for bloodless cardiopulmonary bypass in neonates and infants; a review. Perfusion 2010; 25: 237–243.

Qiu

Guan

Kunselman

Undar

. Evaluation of neonatal membrane oxygenators with respect to gaseous microemboli capture and transmembrane pressure gradients. Artif Organs 2010; 34: 923–929.

Salavitabar

Qiu

Kunselman

Ündar

. Evaluation of the Quadrox-I neonatal oxygenator with an integrated arterial filter. Perfusion 2010; 25: 409–415.

Guan

Palanzo

Kunselman

Undar

. Evaluation of membrane oxygenators and reservoirs in terms of capturing gaseous microemboli and pressure drops. Artif Organs 2009; 33: 1037–1043.

Kiessling

Khalil

Assaf

Isgro

Kretz

Saggau

. Blood-air interface during cardiopulmonary bypass. Heartcenter Ludwigshafen, Cardiac Surgery, Klinikum Ludwigshafen, Germany. Asian Cardiovasc Thorac Ann 2004; 12: 198–201.

Preston

Gomez

Olshove

Jr Phillips

Galantowicz

. Clinical gaseous microemboli assessment of an oxygenator with integral arterial filter in the pediatric population. J Extra Corpor Technol 2009; 41: 226–30.

Gomez

Preston

Olshove

Phillips

Galantowicz

. Evaluation of air handling in a new generation neonatal oxygenator with integral arterial filter. Perfusion 2009; 24: 107–112.

Maquet Cardiovascular. Maquet Quadrox-I Neonatal and Pediatric Oxygenator Brochure. http://www.maquet.com/content/Cardiopulmonary/Documents/Brochures/QUADROX-i_Neo-Ped_brochure-low_res_US.pdf . January 2012.

10.

Groom

Froebe

Martin

. Update on pediatric perfusion practice in North America. J Extra Corpor Technol 2005; 37: 343–350.

11.

Kurusz

Butler

. Bubbles and bypass: an update. Perfusion 2004; 19 Suppl 1: S49–55.

12.

Wang

Woitas

Clark

Myers

Undar

. Clinical real-time monitoring of gaseous microemboli in pediatric cardiopulmonary bypass. Artif Organs 2009; 33: 1026–1030.

13.

Lou

Liu

Long

. Generation, detection and prevention of gaseous microemboli during cardiopulmonary bypass procedure. Int J Artif Organs 2011; 34: 1039–1051.

14.

Lindberg

DAB

Lucas

Sheagren

Malm

. Silicone embolization during clinical and experimental heart surgery employing a bubble oxygenator. Am J Pathol 1961; 39: 129–144.

15.

Orenstein

Sato

Aaron

Buchholz

Bloom

. Microemboli observed in deaths following cardiopulmonary bypass surgery: silicone antifoam agents and polyvinyl chloride tubing as sources of emboli. Hum Pathol 1982; 13: 1082–1090.

16.

Suchil Bernal

Hernandez Rondriguez

Hurtado

Orsornio Vargas

. Antifoaming agent microembolism in patients undergoing extracorporeal circulation. Its frequency in post mortem material and its pathogenic potential in vitro. Rev Esp Cardiol 1992; 45: 578–583.

17.

Bonow

Douglas

Buxton

. ACCF/AHA methodology for the development of quality measures for cardiovascular technology: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol 2011 27; 58: 1517–1538.