CASE REPORTS
`
`Hypoxemia After Intraluminal Oxygen Line
`Obstruction During Cardiopulmonary Bypass
`James A. Robblee, MD, Edward Crosby, MD, and Wilbert J. Keon, MD
`Departments of Anaesthesia and Surgery, University of Ottawa Heart Institute, Ottawa Civic Hospital, Ottawa, Ontario, Canada
`
`A patient sustained an episode of hypoxemia during
`cardiopulmonary bypass. Investigation of the extracor-
`poreal circuit after successful resolution of the problem
`showed that a white, crystalline substance later identi-
`fied as mannitol occluded the oxygen supply line to a
`bubble oxygenator. The management and subsequent
`investigation of the problem are presented.
`(Ann Thoruc Surg 1989;48:575-6)
`
`T real cardiopulmonary bypass techniques constitute a
`
`he development and clinical utilization of extracorpo-
`
`major advance in modern medicine. In 50 years, proce-
`dures have advanced from the experimental laboratory to
`early clinical trials fraught with hazard and complexity to
`procedures that are common, generally safe, and effec-
`tive. Clinical techniques have improved, as has the design
`of circuits and devices. The biomaterials in contact with
`the blood of the patient have also improved. At present,
`clinical use of blood oxygenators is generally safe. Al-
`though many different blood oxygenators are currently
`available, design defects do not appear to constitute a
`serious threat to patient safety. The incidence of harmful
`effects, errors, failures, or problems attributable to blood
`oxygenators is difficult to ascertain, but life-threatening
`complications are rare and episodic in nature. Consider-
`ing the fundamental complexity of an extracorporeal
`circuit, the frequency of life-threatening complications is
`surprisingly low [l] .
`We present a case report, management, and subse-
`quent investigation of a patient who developed a life-
`threatening complication during cardiopulmonary by-
`pass; hypoxemia occurred because of obstruction of gas
`flow to a bubble oxygenator.
`
`A 54-year-old man weighing 86 kg with triple-vessel
`coronary artery disease and left ventricular aneurysm
`underwent aortocoronary bypass grafting, left ventricular
`aneurysm resection, and insertion of intraaortic balloon
`pump. A Bentley BEN-10 B bubble oxygenator was used
`in the extracorporeal circuit. After an uneventful bypass,
`the patient was weaned at 70 minutes elapsed time. One
`gram of calcium chloride was administered to facilitate
`separation. Bypass had to be reinstituted to permit repair
`of a distal graft anastomosis. At 50 minutes elapsed time
`
`Accepted for publication Feb 15, 1989
`Address reprint requests to Dr Robblee, University of Ottawa Heart
`Institute, Ottawa Civic Hospital, 1053 Carling Ave, Ottawa, Ontario, K1Y
`4E9 Canada.
`
`0 1989 by The Society of Thoracic Surgeons
`
`of the second bypass, the venous oxygen saturation
`suddenly decreased from 70% to 58%. The arterial blood
`was dark. Oxygen flow was increased from 2.5 to 6 Umin
`without improvement in color or saturation. The sound of
`gas being released through the pressure relief valve of the
`oxygen source was clearly audible. A decision was made
`to terminate bypass, and mechanical ventilation of the
`lungs with oxygen was started. Epinephrine (100 pg) was
`administered, and an infusion of dopamine (10 pglkgl
`min) was started. The patient was separated from bypass,
`and adequate cardiac output was maintained with
`dopamine (10 pgkg) and intraaortic balloon counterpul-
`sation.
`The oxygenator was examined after the procedure. A
`white crystalloid substance was obstructing the oxygen
`inlet port of the oxygenator. The length of the occlusion
`was 1 cm. Scattered deposits of the same material were
`visible on the walls of the oxygenator gas chamber and on
`the undersurface of the gas sparger plate. A sample of the
`material was subjected to infrared analysis and mass
`spectroscopy. A sagittal section of the oxygenator was
`obtained. Infrared analysis determined that the occlusive
`material was mannitol. This was confirmed by mass
`spectroscopy. Sagittal section of the oxygenator revealed
`that all gas and fluid chambers were intact and all fluid
`paths were patent.
`These conditions were simulated in an unused dis-
`carded cardiopulmonary bypass circuit with a Bentley
`BEN-10 B bubble oxygenator. The circuit was primed with
`crystalloid solution. Mannitol was then added from the
`cardiotomy reservoir. The oxygen supply was discon-
`nected at the source during the addition of mannitol.
`Mannitol flowed into the oxygen tubing. The line was
`reconnected, and oxygen flow was started. At five min-
`utes, a white precipitate began to form (Fig 1). At 25
`minutes, the precipitate was almost occlusive (Figs 2, 3).
`
`Comment
`Hypoxemia during cardiopulmonary bypass may be a
`life-threatening event. Light anesthesia and inadequate
`muscle relaxation cause mild hypoxemia because of in-
`creased peripheral oxygen consumption [2]. Leaks in the
`oxygen supply line are a potential cause of hypoxemia,
`which may be mild or severe (31. Oxygenator failure is a
`rare event, but design and manufacturing defects have
`been reported [l, 41. Gas line obstruction is a potential
`cause of hypoxemia. Hypoxemia secondary to intralumi-
`nal obstruction of the oxygen supply has not been re-
`ported.
`Mannitol is an osmotic diuretic commonly used in
`
`MYLAN INST. EXHIBIT 1114 PAGE 1
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`MYLAN INST. EXHIBIT 1114 PAGE 1
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`576
`
`ROBBLEE ET AL
`CASE REPORT
`HYPOXEMIA DURING CARDIOPULMONARY BYPASS
`
`Ann Thorac Surg
`1989;48:575-6
`
`Fig I . Flocculant precipitate formed five minutes after oxygen pow in
`tubing containing mannitol was started.
`
`association with cardiopulmonary bypass to enhance
`urine flow. Solutions of mannitol are chemically stable,
`but in concentrations of 15% or greater, mannitol may
`crystallize when exposed to low temperature or polyvinyl
`chloride surfaces. A heavy, white flocculant precipitate
`forms, acting as a nucleus for rapid rate crystallization. In
`our patient, 20% mannitol flowed into the oxygen tubing.
`This occurred at a time when the oxygen tubing was not
`connected to the oxygen source. The oxygen tubing was
`looped in such a way that the nadir of the tubing was
`lower than the cardiotomy return point of the oxygenator.
`The oxygen tubing was then properly connected, and gas
`
`Fig 2 . Near occlusion of oxygen tubing 25 minutes after oxygen flow
`was started.
`
`Fig 3. Cross-section of oxygen tubing at site of maximum precipitate
`formation,
`
`flow was started through the tubing. Several hours after
`mannitol was added to the prime, crystallization occurred
`and occluded the oxygen tubing.
`One may conclude from this near mishap that the
`routine preoperative check list of a cardiopulmonary
`bypass circuit should include a thorough examination of
`the oxygen supply line for leaks, disconnections, and the
`presence of substances in the tubing. Mannitol should be
`diluted before administration into the prime or should be
`administered into the circuit after cardiopulmonary by-
`pass is started.
`
`References
`1. Irish CL, Murkin JM, Cleland A, MacDonald JL, Mayer R. The
`influence of resting muscle tone on systemic oxygen consump-
`tion during hypothermic cardiopulmonary bypass. Can
`Anaesth SOC J 1988;35:S120.
`2. Mortensen JD. Safety and efficacy of extracorporeal blood
`oxygenators: a review. Med Instrum 1978;12:12&32.
`3. Gravlee GP, Wong AB, Charles DJ. Hypoxemia during cardio-
`pulmonary bypass from leaks in the gas supply system.
`Anesth Analg 1985;64:649-50.
`4. Warner SJ, Miller CD. Severe hypoxemia during cardiopulmo-
`nary bypass. Anaesthesiology 1986;41:12&7.
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`MYLAN INST. EXHIBIT 1114 PAGE 2
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