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Ann Thorac Surg 1995;59:46-51
© 1995 The Society of Thoracic Surgeons

Clinical Study of Normothermic Cardiopulmonary Bypass in 100 Patients With Coronary Artery Disease

Departments of Cardiovascular Surgery and Anesthesiology, Hôpital Bichat, Paris, France

Accepted for publication June 10, 1994.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
During normothermic cardiopulmonary bypass (CPB), the body temperature is maintained at 37°C. Since 1987, it has been our standard practice to use normothermic CPB in our patients undergoing a cardiac operation, and our experience now consists of more than 3,000 consecutive patients. Myocardial protection is achieved through the combination of cold intermittent antegrade blood cardioplegia, no topical cooling, and a terminal ``hot shot'' of blood cardioplegia. We disagree with the stance of the Toronto group that normothermic CPB requires the administration of large volumes of cardioplegic and crystalloid solutions and the frequent use of phenylephrine hydrochloride to ensure a low systemic vascular resistance. To establish a routine technique of cold heart-warm body bypass, we conducted a clinical study in 100 consecutive patients with coronary artery disease. We found that the total cardioplegia volume needed in our patients was 1,946 ± 257 mL, versus 4,700 ± 1,900 mL in the Toronto study, and an additional crystalloid volume loading of 400 ± 141 mL during CPB was needed in 26% of our patients, versus a total volume of 3,650 ± 800 mL in the Toronto series. Phenylephrine (250 µg) was used in 16% of our patients, versus 88% of the patients in the Toronto study (mean dose, 1.3 mg). During normothermic CPB, the mean radial arterial pressure was 57.3 ± 9.4 mm Hg. In our experience, normothermic CPB in combination with cold intermittent cardioplegia and a terminal hot shot has the following advantages: it facilitates the conduct of surgical procedures because it produces a clear operative field, it is easy for the perfusionist to manage, and it is associated with no adverse side effects.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 51.

There is growing interest in the performance of warm heart surgical procedures since the introduction of the normothermic technique by Salerno [1] and Lichtenstein [z2] and their colleagues. Acceptance of this technique among surgeons has grown despite insufficient data concerning the systemic effects of warm heart procedures. Continuing debate now seems to be even more focused on the accepted standard of the cardiopulmonary bypass (CPB) technique itself: should CPB also be normothermic, should the temperature just be allowed to drift to 33°C during the procedure, or should it be deliberately kept hypothermic? The innocuousness of normothermic CPB has been questioned. The work of Christakis and associates [3] pointed up the importance of fluid overload and the significantly higher phenylephrine hydrochloride requirements during and after CPB, with the same requirements during the first 3 postoperative hours. Other complaints voiced by discussants of their paper include the greater risks of pancreatitis, acute tubular necrosis, jaundice, and multiorgan failure. Stone heart and myocardial necrosis in hypertrophied hearts have also been reported (Fifth European Meeting of the Society of Cardiopulmonary Bypass. Arles, France, June 1993). Our experience with normothermic CPB in combination with cold heart myocardial preservation in more than 3,000 patients has given us a different insight into the complications attributed to normothermic CPB. The intention of this study was to compare our prospective data with those data reported by Christakis and associates [3].

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
A clinical study of the systemic effects of normothermic CPB was started in January 1993, and the patient population consists of 100 consecutive patients undergoing coronary artery bypass grafting. Patients undergoing any additional cardiac or noncardiac procedures were excluded. Patients with chronic renal failure being treated with dialysis were also excluded.

Data Collection
Data regarding volume requirements were collected in the operating room during and after bypass. Hemodynamic variables (pressures, calculated systemic vascular resistance (SVR = [mean arterial pressure - right atrial pressure/cardiac output] x 80), flow, and venous saturation) were determined and recorded at 10-minute intervals throughout the procedure. Results were expressed as the mean ± the standard deviation. Data were also collected in the intensive care unit regarding the initial SVR, hematocrit value, renal function, the maximum myocardial bound creatine kinase (from blood sampled every 4 hours for 24 hours), the appearance of new Q waves, and the duration of assisted ventilation.

Anesthesia and Cardiopulmonary Bypass Technique
Anesthesia was induced with high doses of fentanyl (100 µg/kg) and pancuronium bromide (0.1 mg/kg). At the onset of bypass, midazolam (1 to 5 mg) and fentanyl were administered to promote and maintain anesthesia. No gas anesthetic agents were used. Monitoring with a Swan-Ganz thermodilution catheter and a radial artery pressure catheter was performed in all patients. The central core temperature was monitored continuously with an endourinary bladder catheter (Hi-Lo Temp Foley Catheter; Mallinckrodt, St. Louis, MO).

Patients were continuously warmed to maintain a central body temperature of 37° ± 0.5°C.

Ascending aortic and two-stage single venous cannulation techniques were employed. Only membrane oxygenators were used. Moderate hemodilution was accomplished with a pump prime (total volume, 1,400 mL) consisting of the following: 600 mL of Ringer's lactate, 500 mL of a colloid solution (Plasmion), 300 mL of bicarbonate, and 6,000 IU of heparin. A pump pressure of 35 to 90 mm Hg was considered adequate with a flow rate of 2.4 L • min^-1 • m^-2. When the pump pressure decreased below 35 mm Hg, a bolus of phenylephrine (250 µg) was administered. When the pump pressure exceeded 90 mm Hg, a bolus of nicardipine (1 mg) was administered.

After initiating CPB and cross-clamping the aorta, all patients received cold antegrade blood cardioplegia; this was administered every 30 minutes, or earlier in the event of ventricular activity. After discontinuation of CPB, all patients received blood from the Cell Saver III (Haemonetics, Braintree, MA), which recovered shed blood from the operating field and from the residual volume left in the oxygenator and circuit at the end of the procedure.

Cardioplegia Techniques
The blood cardioplegic solution was composed of equal volumes of St. Thomas' solution (magnesium, 16 mmol/L; sodium, 147 mmol/L; potassium, 20 mmol/L; calcium, 2 mmol/L; and chloride, 203 mmol/L, prepared by Aguettant Laboratory, Lyon, France) and oxygenated blood obtained from the CPB circuit after the onset of bypass. Cardioplegia was delivered through a coil cooled in ice (CCAS-R; Bentley Laboratories, Irvine, CA). The temperature at the pump was 4.9° ± 0.96°C and the temperature at delivery was 6.5° ± 0.6°C. The mean values of the various characteristics of the cardioplegia at delivery were as follows: hematocrit, 11% ± 0.02%; potassium, 19.6 ± 0.8 mmol/L; oxygen tension, 50.5 ± 6.13 kPa; and pH, 7.42 ± 0.05.

All proximal anastomoses were performed before aortic cross-clamping was done using a partial occluding clamp. After aortic cross-clamping, 825 ± 107 mL of cold cardioplegic solution was infused through the ascending aorta. The infusion pressure and myocardial temperatures were not measured. No topical cooling was used. Cold blood cardioplegia (300 mL) was administered every 30 minutes, or earlier if myocardial activity occurred. Before the release of the aortic cross-clamp, 1 L of warm antegrade blood cardioplegia was infused at a rate of 200 mL per minute for 5 minutes. The composition of this warm blood shot was the same as that of the cold blood cardioplegia.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Patients
Patients were predominantly male (84%) and the mean age was 62 ± 10.6 years. The distribution of the coronary lesions was as follows: left main coronary artery, 21%; three-vessel disease, 46%; two-vessel disease, 23%; and one-vessel disease, 10%. Thirty-five percent of the patient had suffered a myocardial infarction. The left internal mammary artery was used in 98% of the patients. Two arterial grafts (mammary arteries) were used in 31% of the patients; three-artery anastomosis was performed sequentially in 7%. Veins were used as the only grafts in 2% of the patients. Six percent of the procedures were redo operations. Spontaneous defibrillation occurred as a rule (94%) after the aortic cross-clamp was removed despite episodes of recurrent electrical activity during cross-clamping in 52% of the patients. One patient was reoperated on for the control of bleeding. There were no instances of mediastinitis, sternal instability, or postoperative phrenic palsy.

Volume Requirements During and After Cardiopulmonary Bypass
The patients received 946 ± 257 mL of cold blood cardioplegia and 1,000 mL (delivered over 5 minutes at a rate of 200 mL/min) of warm blood cardioplegia before aortic unclamping (which corresponds to a crystalloid loading dose of 1 L). No additional volumes were added during CPB in 66% of the patients. In 18%, 250 ± 353 mL of homologous banked blood was added to the pump. In 26% of the patients, an additional 400 ± 141 mL of crystalloid was needed. After discontinuation of CPB, all the patients received 758 ± 158 mL of blood from the Cell Saver, and this blood had a hematocrit of 56% ± 8%. After discontinuation of bypass, all patients received a drip infusion of 300 to 500 mL of colloid. In 5% of the patients, 250 mL of banked blood was added.

Hemodynamic Variables
PERFUSION PRESSURES.
The range of perfusion pressures is depicted in Figure 1 and summarized in Table 1. The mean highest pressure recorded was 77 ± 12 mm Hg and the mean lowest pressure was 44.6 ± 8.6 mm Hg. In 61% of the patients, at some time during CPB the perfusion pressure was less than 50 mm Hg. The mean overall perfusion pressure was 57 ± 9 mm Hg.

View larger version (13K): [in this window] [in a new window]   Fig 1. . Perfusion pressure, showing highest and lowest values.

View larger version (14K): [in this window] [in a new window]   Fig 2. . Pump flow, showing highest and lowest values.

View larger version (15K): [in this window] [in a new window]   Fig 3. . Systemic vascular resistance, showing highest and lowest values.

Indicators of Adequate Perfusion
Adequate perfusion was evaluated in the first 20 patients. The mean arteriovenous oxygen difference was 2.54 ± 0.45 and the mean lactate level was 3.96 ± 0.80 mmol/L at the beginning of CPB and 2.52 ± 0.45 mmol/L during CPB. The higher initial lactate values are attributed to the 600 mL of Ringer's lactate crystalloid solution contained in the priming volumes. Acidosis was not encountered, with a pH of 7.45 ± 0.08 recorded on the arterial catheter. The venous saturation during CPB was 75% ± 4.8% at the lowest flow rates and 78% ± 5% at the highest flow rates. Saturations were continuously monitored on the venous catheter. When the venous saturation tended to be less than 70%, an increase in the flow rate would restore the saturation to a normal level.

Postoperative Findings
Upon arrival in the intensive care unit, the patients' SVR averaged a mean of 1,411 ± 433 dynes • s^-1 • cm^-5. The hematocrit was 32.7% ± 4.1%. Renal function was not altered (Fig 4): the creatinine values in 98% of our patients varied between less than 30% to greater than 10% of the preoperative values. Two patients had a decrease in renal function: 1 patient had a high preoperative creatinine level (>15 mg/dL) and 1 patient suffered a perioperative myocardial infarction necessitating intraaortic balloon counterpulsation. Assisted ventilation was maintained for less than 24 hours in 86% of the patients. The myocardial bound creatine kinase titer (Fig 5) during the patients' stay in the intensive care unit was usually less than 20 units. The maximum titers in 92% of the patients were less than 60 units (this being considered the borderline value between infarction and noninfarction at our institution). Three patients showed new Q waves: the first was an acute case involving a recently occluded left anterior descending coronary artery; the second patient had undergone a redo procedure because of incomplete revascularization; and the third had undergone an extensive right coronary artery endarterectomy. Two patients died, one from pulmonary infection and the other, despite a thorough postmortem examination, showed no evidence of lung disease, hepatitis, or pancreatitis. Neurologic complications were unusual: 1 patient suffered a stroke due to a cerebral atheroma embolism that migrated from the ascending aorta, with multiple defects seen on a computed tomographic scan of the brain. The 5 patients with a tight asymptomatic carotid stenosis remained asymptomatic.

View larger version (17K): [in this window] [in a new window]   Fig 4. . Renal function.

View larger version (12K): [in this window] [in a new window]   Fig 5. . Maximum titers of myocardial bound creatinine kinase (CK-MB).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

In the study conducted by Christakis' group, a low SVR was found to result in the infusion of significantly greater volumes of crystalloid solution (3.650 ± 800 mL under normothermic conditions versus 3,100 ± 700 mL under hypothermic conditions). The large volume overload is due to the increased volume of continuous blood cardioplegia delivered and the additional crystalloid solution added to the bypass circuit because of the low SVR. The total cardioplegia volume delivered in their normothermic group (4,700 ± 1,900 mL) was higher than that delivered to their hypothermic group (2,600 ± 1,900 mL). The total crystalloid volume (975 ± 125 mL) and total cardioplegia volume (1,946 ± 257 mL) administered to our patients during normothermic bypass are considerably less.

The low SVR observed in Christakis and associates' study was responsible for the large doses of phenylephrine hydrochloride required during and after CPB. They used phenylephrine hydrochloride to keep the systemic pressure above 50 mm Hg. The cumulative dose of phenylephrine administered during normothermic CPB in their patients averaged 1.3 mg. They state that 88% of their patients on normothermic CPB required phenylephrine. An infusion drip for more than 20 minutes was necessary in 5%. The requirements for phenylephrine remained the same for the first 3 hours postoperatively. In their hypothermic group, 64% of the patients received phenylephrine, whereas, in our study, only 18% of the patients received phenylephrine during normothermic CPB. This was always administered in a bolus of 250 µg, and a second bolus was needed in 2% of the patients. No permanent infusion drip was necessary. Nicardipine (0.5 to 2 mg) was administered in 20% of the patients to lower the SVR during normothermic bypass. More patients in our study needed hypotensive drugs to lower perfusion pressure than they needed hypertensive drugs to raise the pressure. Although the perfusion pressure in 61% of our patients declined at some time during CPB to below 50 mm Hg, we did not think this was a mandatory indication for phenylephrine. It is generally agreed that a minimal perfusion pressure of 35 to 40 mm Hg is necessary to maintain capillary patency [4] and that neurologic impairment is precipitated by low flow [6] and not by low pressure.

INDICATORS OF ADEQUATE PERFUSION.
Poor peripheral perfusion may be revealed by a wide arteriovenous oxygen difference, a low venous oxygen saturation, increased lactate production, and acidosis. Poor perfusion with a high venous oxygen saturation is found in the setting of septic shock. Normal or high venous oxygen saturation such as that encountered in our study indicates correct peripheral perfusion. Regional perfusion may still be questioned, but we did not encounter increased lactate production. The initial higher-than-normal values were related to the Ringer's lactate in the priming solution. There was no alteration in renal function. This has also been reported by other teams of investigators [1, 7]. If one accepts impairment of renal function as being significant when the postoperative creatinine level exceeds the preoperative values by 50% [8], then only 2 of our patients met this criteria. One had a high preoperative creatinine level (>15 mg/dL) and 1 suffered a perioperative myocardial infarction necessitating intraaortic balloon counterpulsation.

NEUROLOGIC INJURY.
Controversy exists as to whether normothermic CPB has an effect on the neuropsychologic outcome in patients undergoing heart procedures [8]. Higher stroke rates have also been reported in this context [9]. Only 1 of our patients had a stroke, and this was related to an atheromatous embolism, with multiple bilateral defects seen on the computed tomographic scan of the brain. This neurologic episode was not related to the bypass temperature.

General Considerations
Why did we switch to using normothermic CPB at a time when hypothermia was the standard? Our department of cardiac surgery opened in 1982. In the first few years, we used hypothermic CPB with cold crystalloid cardioplegia and topical cooling with crushed ice. We began using cold blood cardioplegia in 1985, but this did not confer any obvious advantages. We began to administer a terminal warm shot of blood cardioplegia in 1986 in patients undergoing heart transplantation. The results in these patients were so convincing that the warm shot was soon used routinely for all open heart operations. The use of crushed ice was abandoned because of the high prevalence of phrenic palsy. The incidence of phrenic palsy of 5% when crushed ice was used for topical cooling declined to 1% with the use of a phrenic protecting pad [10]. The incidence then declined to zero when all forms of topical cooling were abandoned. The hearts were proving to rewarm more without topical cooling (septal myocardial temperature was monitored until 1987), but no disadvantages appeared. We then questioned the necessity of using hypothermic CPB as a source of collateral cooling. As a result, normothermic bypass has been our standard practice since March 1987.

In conclusion, normothermic CPB ensures adequate perfusion, as demonstrated by normal renal function, no increased lactate production, normal pH, and the high venous saturation during bypass. Normothermic bypass does not precipitate volume overload and high doses of adrenergic drugs are not needed during and after CPB. We have not encountered the general systemic complications reported for warm heart surgical procedures. Finally, normothermic bypass at 37°C with cold intermittent cardioplegia and a terminal hot shot confers the following advantages: it facilitates a clear operative field, there is a high rate of spontaneous defibrillation, it is easy for perfusionists to manage, and, in our experience, it has produced no adverse effects.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Hvass, Chirurgie Cardiaque, Hôpital Bichat, 46 rue Henri Huchard, Paris 75877, France.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Salerno TA, Houk JP, Borrozo CAM, et al. Retrograde continuous warm blood cardioplegia. A new concept in myocardial protection. Ann Thorac Surg 1991;51:245–7.[Abstract]
2. Lichtenstein SV, Asche KA, El Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1991;101:269–74.[Abstract]
3. Christakis GT, Koch JP, Deemar KA, et al. A randomized study of the systemic effects of warm heart surgery. Ann Thorac Surg 1992;54:449–59.[Abstract]
4. Robicsek F, Masters TN, Niedluchowski W, Yearger JC, Duncan GD. Vasomotor activity during cardiopulmonary bypass. In: Utley JR, ed. Pathophysiology and techniques of cardiopulmonary bypass (Vol 2, Cardiothoracic surgery series).
5. Lehot JJ, Villard J, Piriz H. Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1992;6:132–9.[Medline]
6. Brusino FG, Reves JG, Prough DS, Stump DA. Cerebral blood flow during cardiopulmonary bypass in a patient with occlusive cerebrovascular disease. J Cardiothorac Anesth 1989;3:87–90.
7. Corwin HL, Sprague SM, DeLaria GA, Norusis MJ. Acute renal failure associated with cardiac operations. A case control study. J Thorac Cardiovasc Surg 1989;98:1107–12.[Abstract]
8. Mora CT, Henson MB, Weintraub WS, et al. Neuropsychological functions following cardiopulmonary bypass. Does warm bypass adversely affect central nervous system outcome? [Abstract]. In: Proceedings of the Eighth Annual Meeting of the European Association of Cardiothoracic Anesthesiologists, Zurich, April 1993.
9. Nussmeier N, Fish KJ. Neuropsychological dysfunction after cardiopulmonary bypass: a comparison of two institutions. J Cardiothorac Vasc Anesth 1991;5:584–8.[Medline]
10. Debrux JL, Popoff G, Hvass U, et al. Paralysies phreniques après chirurgie cardiaque: rôle du froid, intérêt d'un nouveau protège phrénique isolant. Ann Chir 1991;45:117–21.[Medline]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hvass, U. Articles by Depoix, J.-P. Search for Related Content PubMed PubMed Citation Articles by Hvass, U. Articles by Depoix, J.-P.