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Hepatic blood flow during cardiopulmonary bypass operations: The effect of temperature and pulsatility
292
The Journal of Thoracic and Cardiovascular Surgery August 1997
Brief communications
HEPATIC BLOOD FLOW DURING CARDIOPULMONARYBYPASSOPERATIONS:THE EFFECTOF TEMPERATURE AND PULSATILITY R. T. Mathie, PhD, a S. K. Ohri, MD, FRCS, a J. J. Batten, PhD, a A. M. Peters, M D , b and B. E. Keogh, MD, FRCS, a
London, United Kingdom Hepatic dysfunction after cardiopulmonary bypass (CPB) is widely recognized. Hypoperfusion of the liver during surgery is a probable cause, but until now few clinical hemodynamic studies have been performed to support or refute this hypothesis. Using the galactose clearance technique to measure liver blood flow, Hampton and associates a observed a mean decrease in blood flow of 19% during hypothermic nonpulsatile CPB at perfusion rates of 2.1 to 2.8 L • min -~ • m -2. In a more recent study, however, color Doppler measurements reveaRd maintenance of portal venous blood flow during a similar hypothermic CPB protocol. 2 Experimental support for the latter observation is available from studies in a canine model3; these experiments also demonstrated better preservation of liver blood flow during pulsatile than nonpulsatile flow under normothermic conditions of CPB, but only when a low flow rate (1.2 L . min -1 • m -2) was used. The hepatic hemodynamic effect of normothermic or pulsatile perfusion at fixed flow rate and blood pressure in human beings has not, however, previously been reported. The present study was therefore carried out to examine the effect of different regimens of high-flow CPB on the hepatic circulation in human beings, with a view to establishing the optimum hemodynamic conditions for preserving liver blood flow during and immediately after CPB. Twenty-four nondiabetic patients undergoing elective CPB (2.4 L • min • m - z ) for coronary artery bypass grafting were randomized into four groups: 37°C with pulsatile flow, 37°C with nonpulsatile flow, 28°C with pulsatile flow, and 28 ° C with nonpulsatile flow (n = 6 per group). The groups did not differ with respect to age (mean for 24 patients, 59.3 years), number of arteries grafted (median for all groups, 3), crossclamp time (mean for 24 patients, 33.9 minutes), or smoking habits. The mean body weight of the patient groups did not differ significantly. Informed written consent was obtained from all patients on the day before the investigation. The same anesthetic regimen (methohexitone/fentanyl/midazolam/ enflurane) was used for all subjects. Preoperative use of /3-blockers, calcium antagonists, and aspirin did not differ among the groups. Cardiac output (thermal dilution) and arterial blood pressure were measured and peripheral vascular resistance was calculated in each patient. Mean From the Departments of Surgerya and Diagnostic Radiology, b Royal Postgraduate Medical School, London, United Kingdom. Received for publication Jan. 20, 1997; accepted for publication Jan. 30, 1997. J Thorac Cardiovasc Surg 1997;114:292-3
arterial pressure during CPB was controlled in the range 50 to 70 mm Hg with methoxamine or phentolamine as appropriate. The clearance of indocyanine g r e e n (ICG) 4 was measured at three time points: 20 to 30 minutes before thoracotomy, during CPB, and 20 to 30 minutes after CPB. A n I C G dose of 0.25 m g • kg x was introduced intravenously before and after CPB or (during CPB) directly into the pump-oxygenator. Blood samples (3 to 4 ml) were obtained from the peripheral arterial line before and after CPB or (during CPB) directly from the pump-oxygenator 5 minutes before and then at the following times after ICG injection: 4, 7, 10, 13, 16, 19, 22, 25, and 28 minutes. Cardiac output measurements (in triplicate) were made at 10-minute intervals during the pre-CPB and post-CPB sampling periods. Blood was immediately transferred to lithium-heparin tubes and centrifuged for 15 minutes at 1700g. The absorbance of the plasma samples was read spectrophotometrically at 805 and 900 nm, the absorbance at 900 nm being used to correct for turbidity. 4 The concentration of I C G was calculated from the corrected absorbance at 805 nm by means of a standard curve constructed from human plasma containing known concentrations of ICG. Over the duration of ICG sampling, the concentration-time curve was monoexponential, and I C G
Table I. Cardiac output (L . min -1) in patients
undergoing CPB 37°C 37°C 28°C 28°C Pulsatile Nonpulsatile Pulsatile Nonpulsatile Before CPB 4.4 _+0.3 During CPB 4.7 ± 0.2 After CPB 5.6 ± 0.4
4.1 ± 0.4 4.7 ± 0.2 5.9 ± 0.3*
4.3 _+0.4 4.6 _+0.1 5.5 +_0.3*
4.3 _+0.5 4.6 _+0.1 4.9 ± 0.4
Values are presented as mean -+ standard error of the mean. *Significant difference from 'Before CPB' measurement in the same group
(p < 0.05).
Table II. Liver blood flow (ml. min-1) measured
by ICG clearance in patients undergoing CPB 37°C Pulsatile
37°C Nonpulsatile
28°C Pulsatile
28°C Nonpulsatile
BeforeCPB 723±69 During CPB 621 _+57 After CPB 621 _+58
586-+45 550 ± 53 753 ± 65*
641--44 448 -- 20* 634 ± 78
535_+52 465 ± 45 601 _+82
Copyright © 1997 by Mosby-Year Book, Inc.
Values are presented as mean -+ standard error of the mean. *Significant difference from 'Before CPB' measurement in the same group
0022-5223/97 $5.00 + 0
(p < 0.05).
12/54/80941
The Journal of Thoracic and Cardiovascular Surgery Volume 114, Number 2
clearance (milliliters per minute) was calculated as dose • o~ • 103/A, where dose is expressed in milligrams, A is the intercept of the clearance curve on the concentration axis (expressed in milligrams per liter), and a (per minute) = log2/TV2, where T1/2 is the clearance halftime (expressed in minutes). This calculation assumes that the hepatic extraction efficiency of I C G is essentially 100%. 4 Mean cardiac output was just above baseline levels during CPB in all four groups of patients, and it increased by a further 6% to 25% after CPB (Table I). During normothermic CPB, mean liver blood flow did not change significantly in either the pulsatile group (14% mean decrease) or the nonpulsatile group (6% mean decrease); immediately after CPB, liver blood flow was significantly higher than baseline only in the patients receiving nonpulsatile perfusion (Table II). During hypothermic CPB, mean liver blood flow decreased significantly compared with baseline in the pulsatile group (30% mean decrease) but not in the nonpulsatile group (13% mean decrease). We conclude that hepatic blood flow is well maintained by both pulsatile and nonpulsatile flow during normothermic CPB at 2.4 L • min -1 • m -2. However, a decrease in liver blood flow during hypothermic perfusion is associated more with pulsatile than with nonpulsatile flow. These data support the previously published reports from clinical2 and animal 3 investigations, which noted preservation of liver blood flow during hypother-
Brief communications
293
mic, nonpulsatile flow, together with loss of benefit owing to pulsatility at 2.4 compared with 1.2 L • min -1 • m -2. They are also consistent with our recent clinical report of reduced gastric mucosal perfusion during hypothermic CPB. 5 The present findings thus support the view that an optimum CPB protocol for preserving the hepatic circulation requires a high perfusion rate with pulsatile or nonpulsatile flow at 37 ° C; if hypothermia is used, a nonpulsatile protocol appears to be preferable to a pulsatile one.
REFERENCES 1. Hampton WW, Townsend, MC, Schirmer WJ, Haybron DM, Fry DE. Effective hepatic blood flow during cardiopulmonary bypass. Arch Surg 1989;124:458-9. 2. Yamada T, Nomoto S, Aota M, Nishimura K, Matsuda K, Ban T. Hepatic circulation during nonpulsatile cardiopulmonary bypass. ASAIO J 1995;41:M294-7. 3. Desai JB, Mathie RT, Taylor KM. Hepatic blood flow during cardiopulmonary bypass in the dog: the effect of temperature, flow rate and pulsatility. Perfusion 1993;8:149-58. 4. Grainger SL, Keeling PW, Brown IM, Marigold JH, Thompson RP. Clearance and non-invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin Sci 1983;64:207-12. 5. Mathie RT, Ohri SK, Keogh BE, Williams J, Siney L, Grilfith TM. Nitric oxide activity in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;112:1394-5.
METHEMOGLOBINEMIACOMPLICATINGTOPICALANESTHESIADURING BRONCHOSCOPIC PROCEDURES Bryan Clary, MD, a Lynne Skaryak, MD, a Mark Tedder, MD, a Andrew Hilton, MD, b Gregory Botz, MD, b and David Harpole, MD, a Durham, N.C.
Methemoglobinemia is a potential complication of topical anesthesia during bronchoscopic procedures. If unrecognized, it can lead to death. The presentations and management of two patients in whom methemoglobinemia developed after topical anesthesia with benzocaine during treatment with a flexible bronchoscope are presented, followed by a brief review of the literature. From the Departments of Surgerya and Anesthesiology, u Duke University Medical Center, Durham, N.C. Received for publication Dec. 20, 1996; accepted for publication Jan. 30, 1997. Address for reprints: Bryan M. Clary, MD, Box 3324 DUMC, Durham, NC 27710. J Thorac Cardiovasc Surg 1997;114:293-5 Copyright © 1997 by Mosby-Year Book, Inc. 0022-5223/97 $5.00 + 0 12/54/80777
Clinical summaries PATIENT 1. A 67-year-old man underwent resection of a posterior mediastinal mass. On postoperative day 2 a chest roentgenogram showed complete opacification of the left lung field and a leftward shift of the mediastinal structures, consistent with a collapse of the left lung. A fiberoptic bronchoscope was inserted at the bedside with the aid of topical anesthesia. The nasopharynx was lubricated with viscous lidocaine and the oropharynx was sprayed twice with a 20% benzocaine solution (Hurricain e Spray). Bronchoscopic examination revealed significant mucus plugging of the left main-stem bronchus. Twenty minutes into the procedure the patient was noticed to be cyanotic. The oxygen saturation by pulse oximetry (Spo2) had dropped gradually from 94% at the beginning of the procedure to 60% to 65%. The patient became disoriented and was promptly intubated. The initial arterial blood gas value immediately after intubation with the
The Journal of Thoracic and Cardiovascular Surgery August 1997
Brief communications
HEPATIC BLOOD FLOW DURING CARDIOPULMONARYBYPASSOPERATIONS:THE EFFECTOF TEMPERATURE AND PULSATILITY R. T. Mathie, PhD, a S. K. Ohri, MD, FRCS, a J. J. Batten, PhD, a A. M. Peters, M D , b and B. E. Keogh, MD, FRCS, a
London, United Kingdom Hepatic dysfunction after cardiopulmonary bypass (CPB) is widely recognized. Hypoperfusion of the liver during surgery is a probable cause, but until now few clinical hemodynamic studies have been performed to support or refute this hypothesis. Using the galactose clearance technique to measure liver blood flow, Hampton and associates a observed a mean decrease in blood flow of 19% during hypothermic nonpulsatile CPB at perfusion rates of 2.1 to 2.8 L • min -~ • m -2. In a more recent study, however, color Doppler measurements reveaRd maintenance of portal venous blood flow during a similar hypothermic CPB protocol. 2 Experimental support for the latter observation is available from studies in a canine model3; these experiments also demonstrated better preservation of liver blood flow during pulsatile than nonpulsatile flow under normothermic conditions of CPB, but only when a low flow rate (1.2 L . min -1 • m -2) was used. The hepatic hemodynamic effect of normothermic or pulsatile perfusion at fixed flow rate and blood pressure in human beings has not, however, previously been reported. The present study was therefore carried out to examine the effect of different regimens of high-flow CPB on the hepatic circulation in human beings, with a view to establishing the optimum hemodynamic conditions for preserving liver blood flow during and immediately after CPB. Twenty-four nondiabetic patients undergoing elective CPB (2.4 L • min • m - z ) for coronary artery bypass grafting were randomized into four groups: 37°C with pulsatile flow, 37°C with nonpulsatile flow, 28°C with pulsatile flow, and 28 ° C with nonpulsatile flow (n = 6 per group). The groups did not differ with respect to age (mean for 24 patients, 59.3 years), number of arteries grafted (median for all groups, 3), crossclamp time (mean for 24 patients, 33.9 minutes), or smoking habits. The mean body weight of the patient groups did not differ significantly. Informed written consent was obtained from all patients on the day before the investigation. The same anesthetic regimen (methohexitone/fentanyl/midazolam/ enflurane) was used for all subjects. Preoperative use of /3-blockers, calcium antagonists, and aspirin did not differ among the groups. Cardiac output (thermal dilution) and arterial blood pressure were measured and peripheral vascular resistance was calculated in each patient. Mean From the Departments of Surgerya and Diagnostic Radiology, b Royal Postgraduate Medical School, London, United Kingdom. Received for publication Jan. 20, 1997; accepted for publication Jan. 30, 1997. J Thorac Cardiovasc Surg 1997;114:292-3
arterial pressure during CPB was controlled in the range 50 to 70 mm Hg with methoxamine or phentolamine as appropriate. The clearance of indocyanine g r e e n (ICG) 4 was measured at three time points: 20 to 30 minutes before thoracotomy, during CPB, and 20 to 30 minutes after CPB. A n I C G dose of 0.25 m g • kg x was introduced intravenously before and after CPB or (during CPB) directly into the pump-oxygenator. Blood samples (3 to 4 ml) were obtained from the peripheral arterial line before and after CPB or (during CPB) directly from the pump-oxygenator 5 minutes before and then at the following times after ICG injection: 4, 7, 10, 13, 16, 19, 22, 25, and 28 minutes. Cardiac output measurements (in triplicate) were made at 10-minute intervals during the pre-CPB and post-CPB sampling periods. Blood was immediately transferred to lithium-heparin tubes and centrifuged for 15 minutes at 1700g. The absorbance of the plasma samples was read spectrophotometrically at 805 and 900 nm, the absorbance at 900 nm being used to correct for turbidity. 4 The concentration of I C G was calculated from the corrected absorbance at 805 nm by means of a standard curve constructed from human plasma containing known concentrations of ICG. Over the duration of ICG sampling, the concentration-time curve was monoexponential, and I C G
Table I. Cardiac output (L . min -1) in patients
undergoing CPB 37°C 37°C 28°C 28°C Pulsatile Nonpulsatile Pulsatile Nonpulsatile Before CPB 4.4 _+0.3 During CPB 4.7 ± 0.2 After CPB 5.6 ± 0.4
4.1 ± 0.4 4.7 ± 0.2 5.9 ± 0.3*
4.3 _+0.4 4.6 _+0.1 5.5 +_0.3*
4.3 _+0.5 4.6 _+0.1 4.9 ± 0.4
Values are presented as mean -+ standard error of the mean. *Significant difference from 'Before CPB' measurement in the same group
(p < 0.05).
Table II. Liver blood flow (ml. min-1) measured
by ICG clearance in patients undergoing CPB 37°C Pulsatile
37°C Nonpulsatile
28°C Pulsatile
28°C Nonpulsatile
BeforeCPB 723±69 During CPB 621 _+57 After CPB 621 _+58
586-+45 550 ± 53 753 ± 65*
641--44 448 -- 20* 634 ± 78
535_+52 465 ± 45 601 _+82
Copyright © 1997 by Mosby-Year Book, Inc.
Values are presented as mean -+ standard error of the mean. *Significant difference from 'Before CPB' measurement in the same group
0022-5223/97 $5.00 + 0
(p < 0.05).
12/54/80941
The Journal of Thoracic and Cardiovascular Surgery Volume 114, Number 2
clearance (milliliters per minute) was calculated as dose • o~ • 103/A, where dose is expressed in milligrams, A is the intercept of the clearance curve on the concentration axis (expressed in milligrams per liter), and a (per minute) = log2/TV2, where T1/2 is the clearance halftime (expressed in minutes). This calculation assumes that the hepatic extraction efficiency of I C G is essentially 100%. 4 Mean cardiac output was just above baseline levels during CPB in all four groups of patients, and it increased by a further 6% to 25% after CPB (Table I). During normothermic CPB, mean liver blood flow did not change significantly in either the pulsatile group (14% mean decrease) or the nonpulsatile group (6% mean decrease); immediately after CPB, liver blood flow was significantly higher than baseline only in the patients receiving nonpulsatile perfusion (Table II). During hypothermic CPB, mean liver blood flow decreased significantly compared with baseline in the pulsatile group (30% mean decrease) but not in the nonpulsatile group (13% mean decrease). We conclude that hepatic blood flow is well maintained by both pulsatile and nonpulsatile flow during normothermic CPB at 2.4 L • min -1 • m -2. However, a decrease in liver blood flow during hypothermic perfusion is associated more with pulsatile than with nonpulsatile flow. These data support the previously published reports from clinical2 and animal 3 investigations, which noted preservation of liver blood flow during hypother-
Brief communications
293
mic, nonpulsatile flow, together with loss of benefit owing to pulsatility at 2.4 compared with 1.2 L • min -1 • m -2. They are also consistent with our recent clinical report of reduced gastric mucosal perfusion during hypothermic CPB. 5 The present findings thus support the view that an optimum CPB protocol for preserving the hepatic circulation requires a high perfusion rate with pulsatile or nonpulsatile flow at 37 ° C; if hypothermia is used, a nonpulsatile protocol appears to be preferable to a pulsatile one.
REFERENCES 1. Hampton WW, Townsend, MC, Schirmer WJ, Haybron DM, Fry DE. Effective hepatic blood flow during cardiopulmonary bypass. Arch Surg 1989;124:458-9. 2. Yamada T, Nomoto S, Aota M, Nishimura K, Matsuda K, Ban T. Hepatic circulation during nonpulsatile cardiopulmonary bypass. ASAIO J 1995;41:M294-7. 3. Desai JB, Mathie RT, Taylor KM. Hepatic blood flow during cardiopulmonary bypass in the dog: the effect of temperature, flow rate and pulsatility. Perfusion 1993;8:149-58. 4. Grainger SL, Keeling PW, Brown IM, Marigold JH, Thompson RP. Clearance and non-invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin Sci 1983;64:207-12. 5. Mathie RT, Ohri SK, Keogh BE, Williams J, Siney L, Grilfith TM. Nitric oxide activity in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;112:1394-5.
METHEMOGLOBINEMIACOMPLICATINGTOPICALANESTHESIADURING BRONCHOSCOPIC PROCEDURES Bryan Clary, MD, a Lynne Skaryak, MD, a Mark Tedder, MD, a Andrew Hilton, MD, b Gregory Botz, MD, b and David Harpole, MD, a Durham, N.C.
Methemoglobinemia is a potential complication of topical anesthesia during bronchoscopic procedures. If unrecognized, it can lead to death. The presentations and management of two patients in whom methemoglobinemia developed after topical anesthesia with benzocaine during treatment with a flexible bronchoscope are presented, followed by a brief review of the literature. From the Departments of Surgerya and Anesthesiology, u Duke University Medical Center, Durham, N.C. Received for publication Dec. 20, 1996; accepted for publication Jan. 30, 1997. Address for reprints: Bryan M. Clary, MD, Box 3324 DUMC, Durham, NC 27710. J Thorac Cardiovasc Surg 1997;114:293-5 Copyright © 1997 by Mosby-Year Book, Inc. 0022-5223/97 $5.00 + 0 12/54/80777
Clinical summaries PATIENT 1. A 67-year-old man underwent resection of a posterior mediastinal mass. On postoperative day 2 a chest roentgenogram showed complete opacification of the left lung field and a leftward shift of the mediastinal structures, consistent with a collapse of the left lung. A fiberoptic bronchoscope was inserted at the bedside with the aid of topical anesthesia. The nasopharynx was lubricated with viscous lidocaine and the oropharynx was sprayed twice with a 20% benzocaine solution (Hurricain e Spray). Bronchoscopic examination revealed significant mucus plugging of the left main-stem bronchus. Twenty minutes into the procedure the patient was noticed to be cyanotic. The oxygen saturation by pulse oximetry (Spo2) had dropped gradually from 94% at the beginning of the procedure to 60% to 65%. The patient became disoriented and was promptly intubated. The initial arterial blood gas value immediately after intubation with the