Maximal 0 genation of

Size: px

Start display at page:

Download "Maximal 0 genation of"

Buddy Butler
5 years ago
Views:

Maximal 0 genation of Dilute Bloo 7 Cardioplegic Solution William G. Hendren, M.D., Dennis D. OKeefe, M.D., Gillian A. Geffin, M.B., B.S., Alvin G. Denenberg, M.S., Tim R. Love, M.D., and Willard M.

1 Maximal 0 genation of Dilute Bloo 7 Cardioplegic Solution William G. Hendren, M.D., Dennis D. OKeefe, M.D., Gillian A. Geffin, M.B., B.S., Alvin G. Denenberg, M.S., Tim R. Love, M.D., and Willard M. Daggett, M.D. ABSTRACT The content of dissolved O2 (the major source of O2 for the myocardium) of dilute blood cardioplegic solution IdBCS) varied widely when oxygenated at 4'C by surface flow of O2 in a Bentley BCR-3500 cardiotomy reservoir. We have modified the system to consistently deliver maximally oxygenated dbcs to the heart. Laboratory studies indicated that bubbling O2 through a 16-gauge intravenous catheter in a central Luer-Lok port of the cardiotomy reservoir provided contents of dissolved O2 that were consistently near maximal. We then studied 17 patients in the operating room. The first 6 patients received dbcs oxygenated with 100% O2 with a high dissolved O2 content of 3.2 * 0.2 mydl. However, the ph of the dbcs became highly alkaline (7.83 & 0.11 at 37 C). Therefore, in the remaining 11 patients, 2% C02 was added to the 02. The dissolved O2 content remained high (3.3 & 0.1 mudl), and the ph was in a more physiological range ( at 37 C). We conclude that consistently maximal oxygenation of a dbcs at a more physiological ph can be achieved by this method. It has been demonstrated both in laboratory models [l- 31 and more recently in human beings [Z, 41 that oxygenation of cardioplegic solutions markedly improves myocardial preservation. However, we found both in the laboratory and in the operating room that if 0 2 flow was simply delivered across the surface of a crystalloid cardioplegic solution (CS) in the closed cardiotomy reservoir, there was slow and inconsistent oxygenation of the solution. The addition of pump blood to make a dilute blood cardioplegic solution (dbcs) further decreased the oxygenation of the solution. In complex operations in which multiple cardioplegic infusions were required and thus in which the cardiotomy reservoir had to be refilled and the solution reoxygenated quickly, there was even less oxygenation of the solution before it was infused into the patient. In the laboratory we found that if 0 2 was actively bubbled through the solution, there was From the Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA. Accepted for publication Nov 26, Address reprint requests to Dr. Daggett, Department of Surgery, Massachusetts General Hospital, Boston, MA rapid and consistent maximal oxygenation. Further, it was found that bubble oxygenating a cardioplegic solution buffered with 27 meq/l of bicarbonate with 100% O2 resulted in a highly alkaline ph. Addition of a small amount of CO2 to the O2 decreased the ph of the solution to a more physiological range. In light of these laboratory findings, we studied our system for consistency and adequacy of oxygenation and the maintenance of a more physiological ph in a dilute blood cardioplegic solution administered to 17 patients undergoing cardioplegic arrest during cardiac operation. Material and Methods Cardioplegic lnfusion System The system for delivery of the cardioplegic solution is illustrated in Figure 1. A commercially available cardiotomy reservoir (Bentley BCR-3500, Irvine, CA) was fitted with a 16-gauge, cm (8 inch) intravenous catheter (Deseret Medical Inc., Sandy Bay, VT) placed inside the inner defoamer, the 20-(1, depth filter and the outer defoamer through a central Luer-Lok port. Two liters of CS titrated with 0.1N HC1 to ph 7.6 to 7.7 measured at room temperature (about 20 C) was placed in the reservoir. One hundred percent O2 or a mixture of 98% O2 and 2% C02 was delivered from a commercially available tank (Yankee Oxygen Inc., Hingham, MA), passed through a 0.2-(1, 0 2 line filter (Pall Biomedical Products Corp., Glen Grove, NY), and then passed through the catheter at a rate of 10 L/min. Oxygenation of the CS resulted from the bubbling of O2 within the inner defoamer. The defoamed, filtered CS was taken from the bottom of the reservoir and recirculated in the delivery system at 600 mumin by a roller pump, both to rapidly oxygenate and to cool the solution to 4 C by circulating it through a stainless steel coil in an ice bath. After cardiopulmonary bypass had begun, 500 ml of pump blood, already hemodiluted with lactated Ringer's solution to a hematocrit of about 20%, was shunted through a stopcock from a filter in the arterial perfusion line and added to the 2 liters of oxygenated CS to make dbcs. The recirculating flow rate was decreased to 300 mllmin to minimize the possibility of hemolysis by the roller pump. The cardiotomy reservoir was refilled with CS and remixed with pump blood as needed during the course of the operation. The composition of the resulting dbcs follows. 48 Ann Thorac Surg 44:48-52, July 1987

2 49 Hendren, OKeefe, Geffin, et al: Maximal Oxygenation of Dilute Blood Cardioplegia - - Blood Shunt Gar Line from Art~riol Filtei Filter 98%02+ 2%C02, 10 11min to Patient Bentley BCR-3500 with 20rnicron Filter Fig 1. The delivery system for the cardioplegic solution. 0, is delivered through the catheter and bubbles in the solution inside a coarse defoamer, a 20-p depth filter, and a fine defoamer in the cardiotomy reservoir. The bubble-oxygenated dilute blood cardioplegic solution passes through all three layers before delivery. Oxygenated blood from the systemic pump is added to the cardiotomy reservoir as needed through fhe shunf from the arterial fiifer. Na+ (meq/l) K' (meql) C1- (meq/l) HC03 (meq/l) Glucose (mg/dl) Osmolality (mosdkg) Mannitol (gm/l) Hematocrit (%) & 1.2 Protocol Prior to these studies, 100% O2 had been delivered to the surface of the CS with variable oxygenation but with good clinical results [4]. Desiring to improve the system because of laboratory studies that showed enhanced recovery of cardiac function with improved oxygenation of the cardioplegic solution [3], we chose to use 100% 0 2 to bubble oxygenate the dbcs in the first 6 patients (Group 1). When marked alkalinity of the CS and dbcs was observed in Group 1, we changed to a mixture of 98% 0 2 and 2% CO2 in the next 11 patients (Group 2). Partial pressure of 0 2 PO^), partial pressure of C02 (Pcoz), ph, and O2 content were measured in the CS before oxygenation and at 20 minutes and 60 minutes during oxygenation. The same measurements were made 2 and 7 minutes after blood was added to the solution and just before each cardioplegic infusion to the patient. Partial pressure of O2 was measured at 10 C on a Radiometer blood gas analyzer (Copenhagen, Denmark), thermostatically controlled and calibrated at 10 C. We chose to measure Po2 at 10 C because this was the approximate mean temperature of the heart during cardioplegic arrest [4]. Measurement at 10 C was also necessary because the higher solubility of O2 at a cold temperature (the CS was oxygenated at 4 C) produces a Poz that is hyperbaric and higher than the range of the instrument if the solution is warmed to the standard 37 C. Pco2 was measured at 37 C because the very high solubility of C02 at 4 C makes its partial pressure lower than the range of the instrument at the lower temperature. The ph was also measured at 37 C so as to be at a comparable temperature with the measurement of Pc02 and to make ph changes interpretable at the usual blood gas temperature. 0 2 contents were measured with a Lex- 02-Con Oxygen Analyzer (Lexington Instruments, Lexington, MA). Total O2 content of the dbcs was first measured; the red cells were then separated by centrifugation, and dissolved O2 content of the supernatant was measured. To compare the actual ph of CS cooled to and measured at 10 C with the ph of the same sample measured at 37"C, we conducted the following experiment in vitro. CS was prepared and titrated with 0.1N HC1 to ph 7.6 to 7.7 at room temperature. Freshly drawn human blood was heparinized and diluted with an equal volume of lactated Ringer's solution and added to the CS in a 1 :4 ratio to prepare the dbcs (see preceding composition of this cardioplegic solution). The ph at lo", 20, and 37 C was measured with a KCl glass ph electrode (Radiometer, Copenhagen, Denmark). The ph electrode was calibrated at each temperature using a ph 7 buffer and adjusting the ph meter to the appropriate value for that temperature as calibrated by the manufacturer (National Bureau of Standards specifications).

50 The Annals of Thoracic Surgery Vol 44 No 1 July 1987 1 0 0 0 7 - - - 6 0 7 r - 1 CRYSTALLOID MLUTION mrdi/opleglc INFUSION Fig 2.

3 50 The Annals of Thoracic Surgery Vol 44 No 1 July r - 1 CRYSTALLOID MLUTION mrdi/opleglc INFUSION Fig 2. Partial pressure of O2 (PO,) and dissolved Oz content of the crystalloid cardioplegic solutions at 0, 20, and 60 minutes of oxygenation. The arrows indicate the addition of pump blood. Cardioplegic infusions (1, 2, 3, and 4) were analyzed just before infusion or 7 minutes after addition of pump blood if mixing preceded the infusion. Oxygenation was maximal regardless of which mixture, 100% Oz or 98% 0212% C02, was used. Po2 was measured at 10 C. Measurement of 0 2 content from sealed syringes is not dependent on temperature. 0 Gmuv I 1100% O>I Gavp 2 198% 0,, 2% GO* 1 I! h I ph [ : I 70 MINUTES OF O2 CARDIOPLEGIC SOLUTION Blond INFUSION Fig 3. Partial pressure of COz (PC02) and ph of the cardioplegic solutions in the same format as Figure 2. Shown is the detrimental effect of decreasing Pcoz, causing an increase in ph when 100% Or was used to oxygenate. Adding 2% CO, provided physiological PCO~ and ph values. The addition of pump blood had minor effects. Pcq and ph were measured at 3PC. Table 1. Po2, O2 Content, Pcq, and ph of Cardioplegic Solutions Variable Group 1 (100%02) Group 2 (98% 02/2% CO,) CS" dbcsb CS" dbcsb Poz at 10 C (mm Hg)' 754 * rt t 21 Dissolved O2 content (ml/dl) 3.4 t % * 0.1 Total O2 content (mlldl) 3.4 t f * * 0.2 Pco2 at 37 C (mm Hg) f 5 32 * ph at 37 C 7.89 t f * 0.09 "The reported values are those after 60 minutes of oxygenation. bthe reported values are those of the first infusion. 'Some Po2 values are hyperbaric because the solution was maximally oxygenated at 4 C and when warmed to 10 C for measurement, Po2 increased. Poz = partial pressure of oxygen; Pcoz = partial pressure of carbon dioxide; CS = crystalloid cardioplegic solution; dbcs = dilute blood cardioplegic solution. Results This cardioplegic infusion system provided rapid and complete oxygenation of the cardioplegic solutions, which was maintained throughout cardioplegic arrest (Fig 2). There was virtually complete oxygenation of CS at 4 C as evidenced by a Po2 of greater than 700 mm Hg and a dissolved O2 content of more than 3 mudl after oxygenation for 20 minutes with either 100% O2 in Group 1 or 98% OZ/2% C02 in Group 2. There was no significant difference in the Po2 or 0 2 contents between Groups 1 and 2, which indicated that the addition of a small amount of COz to the equilibrating 0 2 did not alter oxygenation. The addition of pump blood to the fully oxygenated CS did not significantly alter the Po2 or dissolved 0 2 content of the supernatant in the resulting dbcs (Table 1). There was a small initial drop in the oxygenation of the solution 2 minutes after the addition of pump blood (Po2 at 37 C about 300 mm Hg), but by 7 minutes, which was several minutes before the initial infusion, the dbcs bad a Poz and a dissolved Oz content comparable to those in the fully oxygenated CS. This degree of oxygenation was maintained in subsequent infusions throughout cardioplegic arrest (see Fig 2). In 9 of the 17 patients included in Figure 2, the cardiotomy reservoir had to be refilled with CS. Then this had to be remixed with pump blood and the new dbcs rapidly reoxygenated. The Po2 in the next cardioplegic infusion following refilling was 767 * 21 mm Hg and the dissolved O2 content was 3.2? 0.1 mvdl, indicating

4 51 Hendren, O'Keefe, Geffin, et al: Maximal Oxygenation of Dilute Blood Cardioplegia Table 2. ph at 10 C Compared with Measurement at 37 C Variable 100% % O2/2% CO2 CS dbcs CS dbcs Temperature ("C) 10 C C Pco2 (mm Hg)a <8 < Oxygenating time (min) Hematocrit (%) ap~02 was measured at 37 C on the Radiometer gas analyzer, the solution oxygenated at 1oOC. Duplicate determinations were made and averaged. 0 2 flow was approximately three times that of the clinical delivery system, and consequently ph was increased more. CS = crystalloid cardioplegic solution; dbcs = dilute blood cardioplegic solution; Pcol = partial pressure of C02. excellent reoxygenation despite the short time of oxygenation, which averaged 14 minutes (range, 5 to 30 minutes). Figure 3 shows that oxygenation of the CS containing bicarbonate with 100% O2 (Group 1) resulted in a solution that was excessively alkaline and that became more alkaline with time. The addition of 2% COz (Group 2) resulted in a less alkaline solution with a ph more physiological for human blood at 37 C and remaining stable with time. Table 1 shows that the addition of pump blood to CS in Group 1 lowered the ph slightly but the final dbcs still remained excessively alkaline. After the addition of pump blood in Group 2, the ph remained in a more physiological range. The ph measurements were reflected by the measurements of Pcoz (see Fig 3). The ph increased as Pc02 decreased in Group 1; ph and Pc02 were more physiological and stable in Group 2. Table 1 shows a small increase in Pco2 with addition of pump blood and a small decrease in ph in Group 1. These changes were more marked in Group 2. There were no technical problems with the delivery system. Although the system creates mild foaming within the defoamers of the cardiotomy reservoir with the addition of blood and the bubbling of the 02, there is defoaming and filtering before delivery. No hemolysis was encountered at recirculating flow rates of 300 ml/ min. The results of the measurements of ph at hypothermic temperatures in vitro appear in Table 2. When oxygenated with 100% 02, the ph of dbcs was very alkaline, whether measured at 10" (8.60) or 37 C (8.50). This degree of alkalinity was far outside the range for blood in vertebrates-7.9 to 8.0 at 10 C or 7.40 to 7.50 at 37 C-as determined by Rahn [5]. When 98% 02/2% C02 was used, the ph of dbcs at 10 C was 7.68, just below the physiological range, and when measured at 37T, was within the physiological range at Comment Our results indicate that bubbling 0 2 through a catheter inside the defoamers and filter of a cardiotomy reservoir can consistently maximize the dissolved O2 in a dbcs as shown by a Po2 of more than 700 mm Hg at 10 C and a dissolved O2 content of more than 3.0 ddl. The first cardioplegic infusion is always fully oxygenated and even when long cross-clamp times are encountered and the remixing and reoxygenation of the dbcs becomes necessary, there is no compromise of 0 2 delivery in subsequent infusions. Maximal 0 2 delivery by cold cardioplegic solutions appears to be dependent predominantly on the dissolved O2 content in the solution, rather than on the content of O2 bound to hemoglobin. Red cell hemoglobin can bind additional 02 but this may be poorly released because of the shift to the left of the oxyhemoglobin dissociation curve related to decreased temperature and increased ph IS]. Digerness and co-workers [7] showed that little O2 bound to hemoglobin can be released in vitro during hypothermia at 10 C; dissolved 0 2 is readily released. However, it is uncertain how much 02 is released from red cells in vivo during hypothermic arrest. When maximally oxygenated at 4OC, the greater part of the dissolved 0 2 will be delivered before the Po2 is sufficiently low for release of 0 2 bound to hemoglobin. Some blood cardioplegic solutions have been reported to provide better myocardial preservation compared with certain asanguineous solutions [8]. This effect may be related to better dissolved O2 content in the blood cardioplegic solutions, better capillary perfusion by a particulate solution [9-121, better buffering of myocardial ph, provision of a small concentration of calcium, or as yet unknown factors. In regard to dissolved 02, the Po2 of crystalloid solutions equilibrated with room air is about 155 mm Hg at room temperature (20 C). The Po2 of blood from the cardiopulmonary bypass oxygenator for cardioplegic solutions is about 350 mm Hg at hypothermic body temperature (25 C). The Po2 of both decreases with cooling, but the Po2 of the blood remains higher. Therefore, blood cardioplegic solutions would contain more dissolved 02, a finding that may explain better myocardial preservation than with asanguineous solutions. However, these cardioplegic solutions do not contain maximal dissolved O2 content and without further oxygenation at low temperature, there will be suboptimal delivery of 02. The oxygenating system that we use ensures maximal dissolved O2 content to optimize 0 2 delivery during dbcs infusion. Our results indicate that including 2% CO2 with the O2 prevents excessive alkalinity of the dbcs, as suggested by Digerness and co-workers [7]. Oxygenating with 100% 0 2 displaces CO2 from a solution containing bicarbonate, thereby resulting in a highly alkaline ph. Since the ph of this dilute blood solution containing bicarbonate increases with decreasing temperature, the ph at the temperature of the solution when delivered is even more alkaline [5]. We have recently shown in an isovolumic rat heart preparation that oxygenation of an

52 The Annals of Thoracic Surgery Vol 44 No 1 July 1987 acalcemic crystalloid cardioplegic solution with 100% O2 resulted in severe alkalinity and the calcium paradox on reperfusion, despite profound

5 52 The Annals of Thoracic Surgery Vol 44 No 1 July 1987 acalcemic crystalloid cardioplegic solution with 100% O2 resulted in severe alkalinity and the calcium paradox on reperfusion, despite profound hypothermia [13]. For these reasons, we have added 2% CO2 to the 0 2 to maintain the final ph of the dbcs in a more physiological range for blood measured at 37 C. The physiological range for ph at 10 C may be more alkaline than that obtained by oxygenating the CS with 98% 02/2% COz [5]. However, the major factor affecting ph when oxygenating the CS with 100% 02 is the loss of C02, thereby producing severe alkalinity, which we have shown to be detrimental to the heart, even at 10 C [13]. The optimal ph for cardioplegic solutions is also uncertain and may be more acid than the observed physiological ph for blood at temperatures used during hypothermic cardioplegic arrest [14]. In conclusion, we use a cold dbcs fully oxygenated at a physiological ph by bubbling 98% O2 and 2% C02 for preservation of the arrested ischemic heart. Maximal oxygenation of the solution is achieved with this delivery system by maintaining the cardioplegic solution at 4 C to provide maximal solubility of 02. Rapid recirculation is necessary to maintain the low temperature. Rapid recirculation also increases the rate of oxygenation by exposing the cardioplegic solution more frequently to the 02. C02 is necessary to prevent extreme alkalinity of the solution containing bicarbonate to maintain a near physiological ph under these hypothermic conditions. With these techniques, excellent 0 2 delivery and myocardial preservation can be achieved during hypothermic cardioplegic arrest. Supported in part by Grant HL from the National Institutes of Health. We gratefully acknowledge the cooperation and assistance of pump technicians Jack Higgins, Chris Coughlin, Ken Griffin, Raymond Hawkins, Linda McFarland, and Gerry Pelligrini. We thank Carmelo Bondi and Dominic Misiano for assistance with measurements of blood gases and O2 contents. We are particularly indebted to Mary Chasse for the preparation of the manuscript. References 1. Bodenhamer RM, DeBoer LWV, Geffin GA, et a1 Enhanced myocardial protection during ischemic arrest: oxygenation of a crystalloid cardioplegic solution. J Thorac Cardiovasc Surg 85769, Guyton RA, Dorsey LMA, Craver JM, et al: Improved myocardial recovery after cardioplegic arrest with an oxygenated crystalloid solution. J Thorac Cardiovasc Surg 89:877, Randolph JD, Toal KW, Geffin GA, et al: Improved myocardial preservation with oxygenated cardioplegic solutions as reflected by on-line monitoring of intramyocardial ph during arrest. J Vasc Surg 3:216, Daggett WM, Randolph JD, Jacobs M, et al: The superiority of cold oxygenated dilute blood cardioplegia. Ann Thorac Surg 43:397, Rahn H: Body temperature and acid-base regulation. Pneumonologie 151:87, Severinghaus JW: Oxyhemoglobin dissociation curve correction for temperature and ph variation in human blood. J Appl Physiol 12485, Digemess SB, Vanin V, Wideman FE: In vitro comparison of oxygen availability from asanguineous and sanguineous cardioplegic media. Circulation 64:Suppl 2:80, Fremes SE, Christakis GT, Weisel RD, et al: A clinical trial of blood and crystalloid cardioplegia. J Thorac Cardiovasc Surg 88726, Zweifach BW. The distribution of blood perfusates in capillary circulation. Am J Physiol 130:512, Berkowitz HD, Mendham J, Miller LD: Importance of circulating microparticles for optimal renal perfusion. Surg Forum 24293, Suaudeau J, Shaffer B, Daggett WM, et al: Role of procaine and washed red cells in the isolated dog heart perfused at 5 C. J Thorac Cardiovasc Surg 84:886, Heitmiller RF, DeBoer LWV, Geffin GA, et al: Myocardial recovery after hypothermic arrest: a comparison of oxygenated crystalloid to blood cardioplegia: the role of calcium. Circulation 72Suppl2:241, Hendren WG, Love TR, Geffin GA, et al: Oxygenation of cardioplegia: potential for the calcium paradox. J Thorac Cardiovasc Surg (in press, 1987) 14. Nugent WC, Levine FH, Liapis CD, et al: Effect of the ph of cardioplegic solution on post-arrest myocardial preservation. Circulation 66.Suppl 1:68, 1982

Clinical Engineering. Equipment (Heart-lung machines)

Clinical Engineering. Equipment (Heart-lung machines) Clinical Engineering Clinical Engineering Equipment (Heart-lung machines) Syed Mohd Nooh Bin Syed Omar Open Heart Surgery Coronary artery bypass grafting (CABG) Repair or replace valves (Stenosis @ Regurgitation)