- Email: [email protected]
Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient With Intraoperative Oxygenator Thrombosis
Author’s Accepted Manuscript Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient with Intraoperative Oxygenator Thrombosis Ian Grant, Max Breidenstein, Ana Parsee, Charles Krumholz, Jacob Martin www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1053-0770(17)30751-6 http://dx.doi.org/10.1053/j.jvca.2017.09.012 YJCAN4326
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Ian Grant, Max Breidenstein, Ana Parsee, Charles Krumholz and Jacob Martin, Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient with Intraoperative Oxygenator Thrombosis, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2017.09.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title: Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient with Intraoperative Oxygenator Thrombosis Authors: Grant, Ian; Breidenstein, Max; Parsee, Ana MD; Krumholz, Charles; Martin, Jacob MD Corresponding Author: Ian Grant BS, 4th year medical student at The Robert Larner, M.D. College of Medicine at The University of Vermont. Phone: (603) 204-8070 Email: [email protected] Address: 102 Centennial Ct. Burlington, VT 05401 Max Breidenstein BS, Research Assistant, Dept. of Anesthesia, University of Vermont Medical Center. Dr. Ana Parsee MD, Cardiothoracic Surgeon, Dept. of Cardiothoracic Surgery, University of Vermont Medical Center. Charles Krumholz CCP/MSA, Chief Perfusionist, Dept. of Cardiothoracic Surgery, University of Vermont Medical Center. Dr. Jacob Martin MD, Cardiothoracic Anesthesiologist, Dept. of Anesthesia, University of Vermont Medical Center. Funding: none Conflicts of interest: none Acknowledgements: none
1
Introduction: The incidence of oxygenator thrombosis during cardiopulmonary bypass (CPB) has significantly decreased with the advent of modern heparin-coated bypass circuits, but rare failures continue to be reported at a rate of 50-133 cases per year in the US.1,2,3 Oxygenator thrombosis is considered to be a serious, and potentially lethal, complication that requires CPB cessation and subsequent membrane oxygenator change-out.2
Mild operative hypothermia (32-34C) and controlled rewarming gradients are commonplace practices in modern CPB that afford a degree of neuroprotection from ischemic damage by avoiding perioperative hyperthermia, but the potential benefits of slow rewarming rates and hypothermic CPB weaning remain controversial.4-7 We report a case of CPB membrane oxygenator failure managed with rapid oxygenator replacement, operative hypothermia, and prolonged postoperative rewarming.
Case Report: A 51 year-old man with a medical history significant for obesity, untreated hypertension, hyperlipidemia, heavy tobacco use, poor dentition, and chronic intermittent dental abscesses was scheduled for a four-vessel coronary artery bypass graft (CABGx4) of his left anterior descending artery (LAD), posterior descending artery (PDA), 2nd obtuse marginal artery (OM2), and 1st diagonal artery (Diag1). The patient initially presented 5 days prior to surgery with an acute non ST-elevation myocardial infarction (NSTEMI) and concurrent bacteremia, thrombocytopenia, and leukocytosis secondary to a dental infection. He was treated with Augmentin for Parvimonas micra bacteremia and underwent surgical dental extraction of 5 teeth
2
2 days prior to surgery. On the day prior to surgery the patient’s thrombocytopenia and leukocytosis had resolved.
After induction of general anesthesia there were no significant intraoperative events prior to initiating CPB. The patient was loaded with a cumulative 45000 units of heparin, and at the time of bypass initiation his activated clotting time (ACT) was 440 seconds. An initial ε-aminocaproic acid (EACA) bolus of 7.5 grams was administered followed by an infusion of 1.5 grams per hour. The aorta was cross-clamped and CPB was initiated with a pump prime consisting of 700 mL PlasmaLyte, 5000 units of heparin, 25 meq of bicarbonate, and 6 grams of mannitol. Following successful initiation of CPB, cardioplegia was administered. 15 minutes after the start of bypass, the perfusionist reported difficulty maintaining sufficient mean arterial pressure (MAP). Over the next 6 minutes MAPs continued to decline despite progressively increasing doses of phenylephrine. TEE ruled out the presence of an aortic dissection, and the surgeon verified the cannula sites to be intact.
After thorough inspection of the entire CPB circuit, a clot was identified in the Turemo Capiox FX15 membrane oxygenator. At that time CPB was stopped and clamped, mechanical ventilation was initiated, a fluid bolus was administered, multiple bolus doses of phenylephrine were given, the aortic cross-clamp was removed, and the surgeon performed cardiac massage. The patient’s head was packed in ice, oxygenator change-out was completed in 9 minutes. As can be seen in Figure 1 (points C, D, and E), after stopping CPB and initiating resuscitative efforts, the patient’s MAP was maintained at >50 mmHg while the oxygenator was replaced. CPB was subsequently reinitiated at 50% bypass, at which point an arterial blood gas confirmed the integrity of the CPB
3
circuit (pO2 of 297 mmHg), and the patient was then transitioned to 100% bypass. The decision was made thereafter to complete the remainder of the CABG x4 based on the severity of the patient’s underlying coronary artery disease, the fact that graft harvesting and cannulation had already been completed, effective return of circulation and temperature management via CPB had been reestablished, and the diagnosis of any brain injury would have been delayed by controlled rewarming regardless of CABG completion.
Overall the patient spent ~24 minutes with MAPs below 50 mmHg, with nadir of 10 mmHg, while at temperatures ranging from 33.4-33.7C as measured by both nasopharyngeal and arterialinflow temperature probes. This period of cerebral hypoperfusion and global ischemia was not monitored as cerebral oximetry was not utilized during the case. After CPB was reinitiated, cooling of the patient was continued to a nadir of 25.1C. Neurology was consulted intraoperatively, and they encouraged slow rewarming at a rate of no greater than 1 degree per hour which was extrapolated from temperature management and rewarming protocols used in cardiac arrest. The patient was separated from the CPB circuit after rewarming to 34C and transferred to the SICU where his initial temperature was 33.5C. Intraoperative mean arterial pressure and temperature are summarized in Figure 1.
In the SICU the patient remained intubated and sedated via Propofol throughout the rewarming process with his temperature controlled by an Arctic Sun temperature management system. After slow controlled rewarming to 37.6C per the recommendations of Neurology (Figure 2), sedation was stopped, and a neurologic examination was completed demonstrating intact cortical and brainstem function, purposeful movements to painful stimuli, and eye opening to verbal stimuli.
4
The patient required low dose epinephrine and norepinephrine infusions (4 micrograms and 3 micrograms per minute respectively) for postoperative cardiogenic shock. No brain MRI or CT was obtained in light of the absence of neurologic symptoms. On post-op day 2 the patient was transferred to the intermediate cardiac care unit where he remained hemodynamically stable and neurologically intact. He was discharged home on post-op day 5 without any objective or subjective neurologic deficits compared to his preoperative baseline.
Discussion: In the 1990s, studies demonstrated significantly reduced rates of abnormal oxygenator pressure gradients in CPB that utilized heparin-coated oxygenators as compared to their uncoated counterparts.3,8 Retrospective surveys were conducted to assess the incidence of uncoated oxygenator failure, with results ranging from 1/773 cases to 1/4375-4539 cases.9-11 Despite almost universal use of coated oxygenators, from 2009-2011 rare failures continued to be reported to oxygenator manufacturers at a rate of 50-133 cases per year in the US.1 The differential for oxygenator failure during CPB is broad, but retrospective analyses have proposed high pressure drop, oxygenator debris, oxygenator leakage, oxygenator thrombosis, and material failure are among the more common etiologies.10,12 This is complicated by the fact that the underlying cause of oxygenator failure is often unclear or indeterminate, and the categories for reporting failures are vague, subject to change, and often overlapping.13 However, it has been proposed that the definitive means for identifying oxygenator failure is via the monitoring of oxygenator inlet and outlet pressures, with any subsequent refinement of causality provided by later inspection and analysis of the oxygenator itself.10,12
5
Oxygenator failure secondary to oxygenator thrombosis despite adequate heparinization is considered to be indicative of an underlying hypercoagulable state.13 The potential causes of such a state are numerous; commonly including infection, cancer, tobacco use, age, and genetic coagulopathies.13 Furthermore, hypothermia has been associated with increased coagulability, and low-volume CPB priming has been found to be associated with increased incidence of oxygenator thrombosis.13 In this particular case, numerous risk factors for a hypercoagulable state were present including the patient’s pre-op septicemia and chronic tobacco use, as well as the utilization of hypothermic CPB and a low-volume prime solution. No retrospective genetic testing to rule out any possible coagulopathies was performed in this case.
Regardless of the etiology of CPB oxygenator failure, the time required for detection and subsequent oxygenator change-out can result in ischemic injury or death.2,8 The continuing occurrence of oxygenator failure, and its substantial risk to patients, has led to the development of written protocols, simulations, and training exercises for oxygenator change-out.3,11,14 The change-out method utilized in this case is displayed in Table 1. Novel protocols have been developed which incorporate the emergent installation of a 2nd oxygenator in parallel with the original failed oxygenator, thus theoretically eliminating the need to remove the oxygenator or stop CPB.15 There are numerous case reports published detailing quick detection and change-out of failed oxygenators over the past 10 years, but these reports have primarily focused on CPB circuit interventions, oxygenator change-out protocols, and staff training.3,14 This case is different from other case reports of oxygenator failure or thrombosis because this case involved the use of intentional hypothermic CPB weaning and prolonged postoperative rewarming.
6
The risk of negative neurological outcomes following cardiopulmonary bypass is well recognized, and the gradient of the resultant neurological damage is very broad.15,17 It has been estimated that patients experience some form of cognitive dysfunction compared to pre-op baseline at a rate of 45-88% at discharge and 30-65% at 1 month post-op.5,17 While adequate patient anticoagulation and the use of heparin-coated circuits function to decrease risk of thromboembolic events, further interventions, including the use of mild intraoperative hypothermia, have also been developed to limit the extent of any potential global or focal ischemic damage. The neuroprotective effect of mild hypothermia to 32-34C is considered to be derived from a reduction in both structural and functional cerebral metabolic rate (CMRO2), with a proportional decrement of cerebral blood flow (CBF), thus preserving the CBF-CMRO2 ratio.5,17 Hypothermia may also exert neuroprotective effects by limiting free radical damage, inhibiting excitatory neurotransmitter release, and slowing enzymatic reactions.5,17
It has been hypothesized that prolonged rewarming may improve neurologic outcomes by minimizing patient exposure to detrimental perioperative hyperthermia and limiting intravascular gas desaturation and subsequent gaseous-microemboli formation.5-7,18 Hyperthermia during or following an ischemic event has been found to cause accelerated brain cell necrosis and may lead to worse patient outcomes and larger infarct areas.18,19 In the study conducted by Thong et al, hyperthermia (>38.5C) following hypothermic CPB was found to be common, occurring in 38% of patients in the first 48 hour post-op period.20 Furthermore, it was noted by Grocott et al that 6 weeks after undergoing CABG, the patients who had experienced the highest temperature peaks within the first 24 hours post-op were more likely to experience worse cognitive dysfunction.21
7
The most recent 2016 CPB Thermal Guidelines recommend accurate temperature monitoring strategies, limiting rewarming gradients between arterial outlet and venous inflow to <10C, and avoidance of cerebral hyperthermia.4 Limiting rewarming temperature gradients results in an inherent slowing of the rewarming rate, a regimen which has itself been correlated in some studies with better cognitive performance after CPB.22 Based on these studies, Grigore et al have proposed that patients with high preoperative risk of neurologic dysfunction be either cooled to 28-32C and slowly rewarmed, or cooled to 32-34C and weaned cold from CPB at 34-35C.5 Furthermore, they have reported results that indicate patients subjected to slower rewarming protocols display better cognitive outcomes at 6 weeks post-op.5 Both prolonged rewarming and weaning cold may lower the risk of perioperative hyperthermia, but there are potential limitations to both interventions.5,6 Prolonged rewarming may require longer CPB times, a factor independently correlated with worse patient outcomes.7 Similarly, hypothermic CPB weaning has been shown to decrease cardiac output, increase systemic vascular resistance, and increase the risk of bleeding.5 However, these considerations do not address hypothermic management of potential intraoperative complications such as CPB failure and resultant patient ischemia.
The 2015 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) recommend that comatose adult patients who experience return of spontaneous circulation following cardiac arrest be treated with targeted temperature management to 32-36C and maintained at that temperature for 24 hours.22 The patient described in this case report experienced ~24 minutes of limited circulation with MAPs less than 50 mmHg following thrombosis of the CPB membrane oxygenator. Maintenance of hypothermia and resuscitative measures were undertaken for the duration of the oxygenator
8
change-out, but effective return of circulation only occurred following successful reinitiation of CPB. Given that the patient experienced circulatory arrest while anesthetized it was not possible to assess his mental status or perform an accurate neurologic exam. After consulting with Neurology, the decision was made to slowly rewarm the patient through a protocol extrapolated from the AHA Guidelines. Furthermore, the decision was made to wean the patient cold from CPB because the avoidance of hyperthermia following CPB failure was deemed to outweigh the potential risks of hypothermic weaning.
In summary, oxygenator thrombosis during CPB is a rare event that is reported to the FDA Manufacturer and User Facility Device Experience Database at a rate of 50-133 cases per year in the US,1,2,3 and it has the potential to result in significant circulatory insufficiency, ischemic injury, and death. In this case report the authors discuss the utilization of rapid oxygenator change-out, hypothermic CPB weaning, and prolonged postoperative rewarming in a case of intraoperative CPB membrane oxygenator thrombosis.
References: 1. Soo, A., Booth, K., Parissis, H., 2012. Successful Management of Membrane Oxygenator Failure during Cardiopulmonary Bypass—The Importance of Safety Algorithm and Simulation Drills. J Extra Corpor Technol 44, 78–80. 2. Wendel, H.P., Philipp, A., Weber, N., Birnbaum, D.E., Ziemer, G., 2001. Oxygenator thrombosis: worst case after development of an abnormal pressure gradient - incidence and pathway. Perfusion 16, 271–278.
9
3. Webb, D.P., Deegan, R.J., Greelish, J.P., Byrne, J.G., 2007. Oxygenation Failure During Cardiopulmonary Bypass Prompts New Safety Algorithm and Training Initiative. J Extra Corpor Technol 39, 188–191. 4. Engelman, R., Baker, R.A., Likosky, D.S., Grigore, A., Dickinson, T.A., ShoreLesserson, L., Hammon, J.W., Society of Thoracic Surgeons, Society of Cardiovascular Anesthesiologists, American Society of ExtraCorporeal Technology, 2015. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass. Ann. Thorac. Surg. 100, 748–757. 5. Grigore, A.M.M., Murray, C.F.B., Ramakrishna, H.M., Djaiani, G.M., 2009. A Core Review of Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Review]. Anesthesia & Analgesia 109, 1741– 1751. 6. Grocott, H.P.M., 2009. PRO: Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Editorial]. Anesthesia & Analgesia 109, 1738–1740. 7. Cook, D.J., 2009. CON: Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Editorial]. Anesthesia & Analgesia 109, 1733–1737. 8. Palanzo, D.A., 2005. Perfusion safety: defining the problem. Perfusion 20, 195–203.
10
9. Wahba, A., Philipp, A., Behr, R., Birnbaum, D.E., 1998. Heparin-Coated Equipment Reduces the Risk of Oxygenator Failure. The Annals of Thoracic Surgery 65, 1310– 1312. 10. Fisher, A.R., 1999. The incidence and cause of emergency oxygenator changeovers. Perfusion 14, 207–212. 11. Mejak, B.L., Stammers, A., Rauch, E., Vang, S., Viessman, T., 2000. A retrospective study on perfusion incidents and safety devices. Perfusion 15, 51–61. 12. Svenmarker, S., Häggmark, S., Jansson, E., Lindholm, R., Appelblad, M., Åberg, T., 1997. The relative safety of an oxygenator. Perfusion 12, 289–292. 13. Schaadt, J., 1999. Oxygenator thrombosis: an international phenomenon. Perfusion 14, 425–435. 14. Darling, E., Searles, B., 2010. Oxygenator change-out times: the value of a written protocol and simulation exercises. Perfusion 25, 141–143. 15. Groom, R.C., Forest, R.J., Cormack, J.E., Niimi, K.S., Morton, J., 2002. Parallel replacement of the oxygenator that is not transferring oxygen: the PRONTO procedure. Perfusion 17, 447–450. 16. Roach, G.W., Kanchuger, M., Mangano, C.M., Newman, M., Nussmeier, N., Wolman, R., Aggarwal, A., Marschall, K., Graham, S.H., Ley, C., Ozanne, G., Mangano, D.T., Herskowitz, A., Katseva, V., Sears, R., 1996. Adverse Cerebral Outcomes after Coronary Bypass Surgery. New England Journal of Medicine 335, 1857–1864. 17. Hogue, C.W.J., Palin, C.A.F., Arrowsmith, J.E.F., 2006. Cardiopulmonary Bypass Management and Neurologic Outcomes: An Evidence-Based Appraisal of Current Practices. [Review]. Anesthesia & Analgesia 103, 21–37.
11
18. Coselli, J.S., LeMaire, S.A., 2002. Temperature management after hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 123, 621–623. 19. Grocott, H.P., Mackensen, G.B., Grigore, A.M., Mathew, J., Reves, J.G., Phillips-Bute, B., Smith, P.K., Newman, M.F., Neurologic Outcome Research Group (NORG), Cardiothoracic Anesthesiology Research Endeavors (CARE) Investigators’ of the Duke Heart Center, 2002. Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery. Stroke 33, 537–541. 20. Thong, W.Y., Strickler, A.G., Li, S., Stewart, E.E., Collier, C.L., Vaughn, W.K., Nussmeier, N.A., 2002. Hyperthermia in the forty-eight hours after cardiopulmonary bypass. Anesth. Analg. 95, 1489–1495, table of contents. 21. Grigore, A.M., Grocott, H.P.M., Mathew, J.P., Phillips-Bute, B., Stanley, T.O., Butler, A.M., Landolfo, K.P., Reves, J.G., Blumenthal, J.A., Newman, M.F., Center, the N.O.R.G. of the D.H., 2002. The Rewarming Rate and Increased Peak Temperature Alter Neurocognitive Outcome After Cardiac Surgery. Anesthesia & Analgesia 94, 4–10. 22. Callaway, C.W., Donnino, M.W., Fink, E.L., Geocadin, R.G., Golan, E., Kern, K.B., Leary, M., Meurer, W.J., Peberdy, M.A., Thompson, T.M., Zimmerman, J.L., 2015. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 8: Post–Cardiac Arrest Care. Circulation 132, S465–S482.
12
Figure Descriptions: figure 1: Patient body temperature and MAP recorded for the duration of the procedure. Time points A-E represent the following: A. surgery start time; B. CPB on; C. clot identified; D. CPB off; E. oxygenator replaced in circuit, CPB restart. figure 2: Post-operative patient body temperature recorded in the ICU during prolonged rewarming following cold wean from CPB.
Sequence for Membrane Oxygenator Change-out 1. Place a blanket on floor under the failed oxygenator 2. Clamp the inlet and outlets 3. Cut the inlet and outlets with sterile scissors while leaving sufficient tubing to attach onto the new oxygenator 4. Disconnect the oxygen line and place onto the new oxygenator 5. Clamp and subsequently disconnect the water lines 6. Disconnect the temperature probes and sampling lines 7. Remove the failed oxygenator and place the new oxygenator into its holder 8. Connect the inlet and outlets lines 9. Connect the sampling line to the outlet 10. Prime the new oxygenator through the re-circulation line 11. De-air the arterial outlet 12. Return to bypass 13. Reconnect the water lines and temperature probes
13
14
PII: DOI: Reference:
S1053-0770(17)30751-6 http://dx.doi.org/10.1053/j.jvca.2017.09.012 YJCAN4326
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Cite this article as: Ian Grant, Max Breidenstein, Ana Parsee, Charles Krumholz and Jacob Martin, Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient with Intraoperative Oxygenator Thrombosis, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2017.09.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title: Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming in a Patient with Intraoperative Oxygenator Thrombosis Authors: Grant, Ian; Breidenstein, Max; Parsee, Ana MD; Krumholz, Charles; Martin, Jacob MD Corresponding Author: Ian Grant BS, 4th year medical student at The Robert Larner, M.D. College of Medicine at The University of Vermont. Phone: (603) 204-8070 Email: [email protected] Address: 102 Centennial Ct. Burlington, VT 05401 Max Breidenstein BS, Research Assistant, Dept. of Anesthesia, University of Vermont Medical Center. Dr. Ana Parsee MD, Cardiothoracic Surgeon, Dept. of Cardiothoracic Surgery, University of Vermont Medical Center. Charles Krumholz CCP/MSA, Chief Perfusionist, Dept. of Cardiothoracic Surgery, University of Vermont Medical Center. Dr. Jacob Martin MD, Cardiothoracic Anesthesiologist, Dept. of Anesthesia, University of Vermont Medical Center. Funding: none Conflicts of interest: none Acknowledgements: none
1
Introduction: The incidence of oxygenator thrombosis during cardiopulmonary bypass (CPB) has significantly decreased with the advent of modern heparin-coated bypass circuits, but rare failures continue to be reported at a rate of 50-133 cases per year in the US.1,2,3 Oxygenator thrombosis is considered to be a serious, and potentially lethal, complication that requires CPB cessation and subsequent membrane oxygenator change-out.2
Mild operative hypothermia (32-34C) and controlled rewarming gradients are commonplace practices in modern CPB that afford a degree of neuroprotection from ischemic damage by avoiding perioperative hyperthermia, but the potential benefits of slow rewarming rates and hypothermic CPB weaning remain controversial.4-7 We report a case of CPB membrane oxygenator failure managed with rapid oxygenator replacement, operative hypothermia, and prolonged postoperative rewarming.
Case Report: A 51 year-old man with a medical history significant for obesity, untreated hypertension, hyperlipidemia, heavy tobacco use, poor dentition, and chronic intermittent dental abscesses was scheduled for a four-vessel coronary artery bypass graft (CABGx4) of his left anterior descending artery (LAD), posterior descending artery (PDA), 2nd obtuse marginal artery (OM2), and 1st diagonal artery (Diag1). The patient initially presented 5 days prior to surgery with an acute non ST-elevation myocardial infarction (NSTEMI) and concurrent bacteremia, thrombocytopenia, and leukocytosis secondary to a dental infection. He was treated with Augmentin for Parvimonas micra bacteremia and underwent surgical dental extraction of 5 teeth
2
2 days prior to surgery. On the day prior to surgery the patient’s thrombocytopenia and leukocytosis had resolved.
After induction of general anesthesia there were no significant intraoperative events prior to initiating CPB. The patient was loaded with a cumulative 45000 units of heparin, and at the time of bypass initiation his activated clotting time (ACT) was 440 seconds. An initial ε-aminocaproic acid (EACA) bolus of 7.5 grams was administered followed by an infusion of 1.5 grams per hour. The aorta was cross-clamped and CPB was initiated with a pump prime consisting of 700 mL PlasmaLyte, 5000 units of heparin, 25 meq of bicarbonate, and 6 grams of mannitol. Following successful initiation of CPB, cardioplegia was administered. 15 minutes after the start of bypass, the perfusionist reported difficulty maintaining sufficient mean arterial pressure (MAP). Over the next 6 minutes MAPs continued to decline despite progressively increasing doses of phenylephrine. TEE ruled out the presence of an aortic dissection, and the surgeon verified the cannula sites to be intact.
After thorough inspection of the entire CPB circuit, a clot was identified in the Turemo Capiox FX15 membrane oxygenator. At that time CPB was stopped and clamped, mechanical ventilation was initiated, a fluid bolus was administered, multiple bolus doses of phenylephrine were given, the aortic cross-clamp was removed, and the surgeon performed cardiac massage. The patient’s head was packed in ice, oxygenator change-out was completed in 9 minutes. As can be seen in Figure 1 (points C, D, and E), after stopping CPB and initiating resuscitative efforts, the patient’s MAP was maintained at >50 mmHg while the oxygenator was replaced. CPB was subsequently reinitiated at 50% bypass, at which point an arterial blood gas confirmed the integrity of the CPB
3
circuit (pO2 of 297 mmHg), and the patient was then transitioned to 100% bypass. The decision was made thereafter to complete the remainder of the CABG x4 based on the severity of the patient’s underlying coronary artery disease, the fact that graft harvesting and cannulation had already been completed, effective return of circulation and temperature management via CPB had been reestablished, and the diagnosis of any brain injury would have been delayed by controlled rewarming regardless of CABG completion.
Overall the patient spent ~24 minutes with MAPs below 50 mmHg, with nadir of 10 mmHg, while at temperatures ranging from 33.4-33.7C as measured by both nasopharyngeal and arterialinflow temperature probes. This period of cerebral hypoperfusion and global ischemia was not monitored as cerebral oximetry was not utilized during the case. After CPB was reinitiated, cooling of the patient was continued to a nadir of 25.1C. Neurology was consulted intraoperatively, and they encouraged slow rewarming at a rate of no greater than 1 degree per hour which was extrapolated from temperature management and rewarming protocols used in cardiac arrest. The patient was separated from the CPB circuit after rewarming to 34C and transferred to the SICU where his initial temperature was 33.5C. Intraoperative mean arterial pressure and temperature are summarized in Figure 1.
In the SICU the patient remained intubated and sedated via Propofol throughout the rewarming process with his temperature controlled by an Arctic Sun temperature management system. After slow controlled rewarming to 37.6C per the recommendations of Neurology (Figure 2), sedation was stopped, and a neurologic examination was completed demonstrating intact cortical and brainstem function, purposeful movements to painful stimuli, and eye opening to verbal stimuli.
4
The patient required low dose epinephrine and norepinephrine infusions (4 micrograms and 3 micrograms per minute respectively) for postoperative cardiogenic shock. No brain MRI or CT was obtained in light of the absence of neurologic symptoms. On post-op day 2 the patient was transferred to the intermediate cardiac care unit where he remained hemodynamically stable and neurologically intact. He was discharged home on post-op day 5 without any objective or subjective neurologic deficits compared to his preoperative baseline.
Discussion: In the 1990s, studies demonstrated significantly reduced rates of abnormal oxygenator pressure gradients in CPB that utilized heparin-coated oxygenators as compared to their uncoated counterparts.3,8 Retrospective surveys were conducted to assess the incidence of uncoated oxygenator failure, with results ranging from 1/773 cases to 1/4375-4539 cases.9-11 Despite almost universal use of coated oxygenators, from 2009-2011 rare failures continued to be reported to oxygenator manufacturers at a rate of 50-133 cases per year in the US.1 The differential for oxygenator failure during CPB is broad, but retrospective analyses have proposed high pressure drop, oxygenator debris, oxygenator leakage, oxygenator thrombosis, and material failure are among the more common etiologies.10,12 This is complicated by the fact that the underlying cause of oxygenator failure is often unclear or indeterminate, and the categories for reporting failures are vague, subject to change, and often overlapping.13 However, it has been proposed that the definitive means for identifying oxygenator failure is via the monitoring of oxygenator inlet and outlet pressures, with any subsequent refinement of causality provided by later inspection and analysis of the oxygenator itself.10,12
5
Oxygenator failure secondary to oxygenator thrombosis despite adequate heparinization is considered to be indicative of an underlying hypercoagulable state.13 The potential causes of such a state are numerous; commonly including infection, cancer, tobacco use, age, and genetic coagulopathies.13 Furthermore, hypothermia has been associated with increased coagulability, and low-volume CPB priming has been found to be associated with increased incidence of oxygenator thrombosis.13 In this particular case, numerous risk factors for a hypercoagulable state were present including the patient’s pre-op septicemia and chronic tobacco use, as well as the utilization of hypothermic CPB and a low-volume prime solution. No retrospective genetic testing to rule out any possible coagulopathies was performed in this case.
Regardless of the etiology of CPB oxygenator failure, the time required for detection and subsequent oxygenator change-out can result in ischemic injury or death.2,8 The continuing occurrence of oxygenator failure, and its substantial risk to patients, has led to the development of written protocols, simulations, and training exercises for oxygenator change-out.3,11,14 The change-out method utilized in this case is displayed in Table 1. Novel protocols have been developed which incorporate the emergent installation of a 2nd oxygenator in parallel with the original failed oxygenator, thus theoretically eliminating the need to remove the oxygenator or stop CPB.15 There are numerous case reports published detailing quick detection and change-out of failed oxygenators over the past 10 years, but these reports have primarily focused on CPB circuit interventions, oxygenator change-out protocols, and staff training.3,14 This case is different from other case reports of oxygenator failure or thrombosis because this case involved the use of intentional hypothermic CPB weaning and prolonged postoperative rewarming.
6
The risk of negative neurological outcomes following cardiopulmonary bypass is well recognized, and the gradient of the resultant neurological damage is very broad.15,17 It has been estimated that patients experience some form of cognitive dysfunction compared to pre-op baseline at a rate of 45-88% at discharge and 30-65% at 1 month post-op.5,17 While adequate patient anticoagulation and the use of heparin-coated circuits function to decrease risk of thromboembolic events, further interventions, including the use of mild intraoperative hypothermia, have also been developed to limit the extent of any potential global or focal ischemic damage. The neuroprotective effect of mild hypothermia to 32-34C is considered to be derived from a reduction in both structural and functional cerebral metabolic rate (CMRO2), with a proportional decrement of cerebral blood flow (CBF), thus preserving the CBF-CMRO2 ratio.5,17 Hypothermia may also exert neuroprotective effects by limiting free radical damage, inhibiting excitatory neurotransmitter release, and slowing enzymatic reactions.5,17
It has been hypothesized that prolonged rewarming may improve neurologic outcomes by minimizing patient exposure to detrimental perioperative hyperthermia and limiting intravascular gas desaturation and subsequent gaseous-microemboli formation.5-7,18 Hyperthermia during or following an ischemic event has been found to cause accelerated brain cell necrosis and may lead to worse patient outcomes and larger infarct areas.18,19 In the study conducted by Thong et al, hyperthermia (>38.5C) following hypothermic CPB was found to be common, occurring in 38% of patients in the first 48 hour post-op period.20 Furthermore, it was noted by Grocott et al that 6 weeks after undergoing CABG, the patients who had experienced the highest temperature peaks within the first 24 hours post-op were more likely to experience worse cognitive dysfunction.21
7
The most recent 2016 CPB Thermal Guidelines recommend accurate temperature monitoring strategies, limiting rewarming gradients between arterial outlet and venous inflow to <10C, and avoidance of cerebral hyperthermia.4 Limiting rewarming temperature gradients results in an inherent slowing of the rewarming rate, a regimen which has itself been correlated in some studies with better cognitive performance after CPB.22 Based on these studies, Grigore et al have proposed that patients with high preoperative risk of neurologic dysfunction be either cooled to 28-32C and slowly rewarmed, or cooled to 32-34C and weaned cold from CPB at 34-35C.5 Furthermore, they have reported results that indicate patients subjected to slower rewarming protocols display better cognitive outcomes at 6 weeks post-op.5 Both prolonged rewarming and weaning cold may lower the risk of perioperative hyperthermia, but there are potential limitations to both interventions.5,6 Prolonged rewarming may require longer CPB times, a factor independently correlated with worse patient outcomes.7 Similarly, hypothermic CPB weaning has been shown to decrease cardiac output, increase systemic vascular resistance, and increase the risk of bleeding.5 However, these considerations do not address hypothermic management of potential intraoperative complications such as CPB failure and resultant patient ischemia.
The 2015 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) recommend that comatose adult patients who experience return of spontaneous circulation following cardiac arrest be treated with targeted temperature management to 32-36C and maintained at that temperature for 24 hours.22 The patient described in this case report experienced ~24 minutes of limited circulation with MAPs less than 50 mmHg following thrombosis of the CPB membrane oxygenator. Maintenance of hypothermia and resuscitative measures were undertaken for the duration of the oxygenator
8
change-out, but effective return of circulation only occurred following successful reinitiation of CPB. Given that the patient experienced circulatory arrest while anesthetized it was not possible to assess his mental status or perform an accurate neurologic exam. After consulting with Neurology, the decision was made to slowly rewarm the patient through a protocol extrapolated from the AHA Guidelines. Furthermore, the decision was made to wean the patient cold from CPB because the avoidance of hyperthermia following CPB failure was deemed to outweigh the potential risks of hypothermic weaning.
In summary, oxygenator thrombosis during CPB is a rare event that is reported to the FDA Manufacturer and User Facility Device Experience Database at a rate of 50-133 cases per year in the US,1,2,3 and it has the potential to result in significant circulatory insufficiency, ischemic injury, and death. In this case report the authors discuss the utilization of rapid oxygenator change-out, hypothermic CPB weaning, and prolonged postoperative rewarming in a case of intraoperative CPB membrane oxygenator thrombosis.
References: 1. Soo, A., Booth, K., Parissis, H., 2012. Successful Management of Membrane Oxygenator Failure during Cardiopulmonary Bypass—The Importance of Safety Algorithm and Simulation Drills. J Extra Corpor Technol 44, 78–80. 2. Wendel, H.P., Philipp, A., Weber, N., Birnbaum, D.E., Ziemer, G., 2001. Oxygenator thrombosis: worst case after development of an abnormal pressure gradient - incidence and pathway. Perfusion 16, 271–278.
9
3. Webb, D.P., Deegan, R.J., Greelish, J.P., Byrne, J.G., 2007. Oxygenation Failure During Cardiopulmonary Bypass Prompts New Safety Algorithm and Training Initiative. J Extra Corpor Technol 39, 188–191. 4. Engelman, R., Baker, R.A., Likosky, D.S., Grigore, A., Dickinson, T.A., ShoreLesserson, L., Hammon, J.W., Society of Thoracic Surgeons, Society of Cardiovascular Anesthesiologists, American Society of ExtraCorporeal Technology, 2015. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass. Ann. Thorac. Surg. 100, 748–757. 5. Grigore, A.M.M., Murray, C.F.B., Ramakrishna, H.M., Djaiani, G.M., 2009. A Core Review of Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Review]. Anesthesia & Analgesia 109, 1741– 1751. 6. Grocott, H.P.M., 2009. PRO: Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Editorial]. Anesthesia & Analgesia 109, 1738–1740. 7. Cook, D.J., 2009. CON: Temperature Regimens and Neuroprotection During Cardiopulmonary Bypass: Does Rewarming Rate Matter? [Editorial]. Anesthesia & Analgesia 109, 1733–1737. 8. Palanzo, D.A., 2005. Perfusion safety: defining the problem. Perfusion 20, 195–203.
10
9. Wahba, A., Philipp, A., Behr, R., Birnbaum, D.E., 1998. Heparin-Coated Equipment Reduces the Risk of Oxygenator Failure. The Annals of Thoracic Surgery 65, 1310– 1312. 10. Fisher, A.R., 1999. The incidence and cause of emergency oxygenator changeovers. Perfusion 14, 207–212. 11. Mejak, B.L., Stammers, A., Rauch, E., Vang, S., Viessman, T., 2000. A retrospective study on perfusion incidents and safety devices. Perfusion 15, 51–61. 12. Svenmarker, S., Häggmark, S., Jansson, E., Lindholm, R., Appelblad, M., Åberg, T., 1997. The relative safety of an oxygenator. Perfusion 12, 289–292. 13. Schaadt, J., 1999. Oxygenator thrombosis: an international phenomenon. Perfusion 14, 425–435. 14. Darling, E., Searles, B., 2010. Oxygenator change-out times: the value of a written protocol and simulation exercises. Perfusion 25, 141–143. 15. Groom, R.C., Forest, R.J., Cormack, J.E., Niimi, K.S., Morton, J., 2002. Parallel replacement of the oxygenator that is not transferring oxygen: the PRONTO procedure. Perfusion 17, 447–450. 16. Roach, G.W., Kanchuger, M., Mangano, C.M., Newman, M., Nussmeier, N., Wolman, R., Aggarwal, A., Marschall, K., Graham, S.H., Ley, C., Ozanne, G., Mangano, D.T., Herskowitz, A., Katseva, V., Sears, R., 1996. Adverse Cerebral Outcomes after Coronary Bypass Surgery. New England Journal of Medicine 335, 1857–1864. 17. Hogue, C.W.J., Palin, C.A.F., Arrowsmith, J.E.F., 2006. Cardiopulmonary Bypass Management and Neurologic Outcomes: An Evidence-Based Appraisal of Current Practices. [Review]. Anesthesia & Analgesia 103, 21–37.
11
18. Coselli, J.S., LeMaire, S.A., 2002. Temperature management after hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 123, 621–623. 19. Grocott, H.P., Mackensen, G.B., Grigore, A.M., Mathew, J., Reves, J.G., Phillips-Bute, B., Smith, P.K., Newman, M.F., Neurologic Outcome Research Group (NORG), Cardiothoracic Anesthesiology Research Endeavors (CARE) Investigators’ of the Duke Heart Center, 2002. Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery. Stroke 33, 537–541. 20. Thong, W.Y., Strickler, A.G., Li, S., Stewart, E.E., Collier, C.L., Vaughn, W.K., Nussmeier, N.A., 2002. Hyperthermia in the forty-eight hours after cardiopulmonary bypass. Anesth. Analg. 95, 1489–1495, table of contents. 21. Grigore, A.M., Grocott, H.P.M., Mathew, J.P., Phillips-Bute, B., Stanley, T.O., Butler, A.M., Landolfo, K.P., Reves, J.G., Blumenthal, J.A., Newman, M.F., Center, the N.O.R.G. of the D.H., 2002. The Rewarming Rate and Increased Peak Temperature Alter Neurocognitive Outcome After Cardiac Surgery. Anesthesia & Analgesia 94, 4–10. 22. Callaway, C.W., Donnino, M.W., Fink, E.L., Geocadin, R.G., Golan, E., Kern, K.B., Leary, M., Meurer, W.J., Peberdy, M.A., Thompson, T.M., Zimmerman, J.L., 2015. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 8: Post–Cardiac Arrest Care. Circulation 132, S465–S482.
12
Figure Descriptions: figure 1: Patient body temperature and MAP recorded for the duration of the procedure. Time points A-E represent the following: A. surgery start time; B. CPB on; C. clot identified; D. CPB off; E. oxygenator replaced in circuit, CPB restart. figure 2: Post-operative patient body temperature recorded in the ICU during prolonged rewarming following cold wean from CPB.
Sequence for Membrane Oxygenator Change-out 1. Place a blanket on floor under the failed oxygenator 2. Clamp the inlet and outlets 3. Cut the inlet and outlets with sterile scissors while leaving sufficient tubing to attach onto the new oxygenator 4. Disconnect the oxygen line and place onto the new oxygenator 5. Clamp and subsequently disconnect the water lines 6. Disconnect the temperature probes and sampling lines 7. Remove the failed oxygenator and place the new oxygenator into its holder 8. Connect the inlet and outlets lines 9. Connect the sampling line to the outlet 10. Prime the new oxygenator through the re-circulation line 11. De-air the arterial outlet 12. Return to bypass 13. Reconnect the water lines and temperature probes
13
14