Renal Function and Cardiopulmonary Bypass: Effect of Perfusion Pressure Jorge Urzua, MD, Sergio Troncoso, MD, Guillermo Bugedo, MD, Roberto Canessa, MD, Hernan Mufioz, MD, Guillermo Lema, MD, And&s Valdivieso, MD, Manuel Irarrazaval, MD, Sergio Moran, MD, and Gladys Meneses, BSc Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine cl.2 mg/dL, creati- nine clearance >70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary sur- gery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to main- tain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were mea- sured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 + 36.7 in group 1 and 120.6 f 50.7 mL/min in group 2). In group 1, creatinine D ESPITE IMPROVEMENTS in cardiovascular anes- thesia, physiological monitoring, and cardiopulmo- nary bypass (CPB), postoperative renal dysfunction is still a frequent and potentially lethal complication following car- diac surgery.’ In this institution, its incidence exceeds 5% in adult patients. Extracorporeal circulation has been impli- cated as a possible etiology, because of the physiological alterations inherent to the technique.ie3 A hemodynamic abnormality frequently observed during CPB is arterial hypotension, more marked at the beginning of CPB, but often persisting during most of the perfusion period.4 It is known that hypotension may adversely affect renal func- tion1s3J; it has been suggested, therefore, that a low perfusion pressure during CPB could result in renal hypoperfusion, flow redistribution, and postoperative renal dysfunction5 This hypothesis remains controversial, and there has been a great deal of debate as to what is the minimal acceptable blood pressure during bypass.*,4 Therefore, this study was designed to see whether a low arterial pressure during CPB produced measurable changes in intraoperative renal func- tion, and whether postoperative renal function was better preserved if a relatively higher level of blood pressure was maintained. METHODS Following approval by the Medical School Research Committee and previous informed consent, 21 patients scheduled for elective coronary artery surgery were prospectively studied. Their preoper- ative renal function was normal, defined as a plasma creatinine < 1.2 mg/dL, creatinine clearance > 70 mlimin, and plasma urea < 60 mg/dL. All patients were between 50 and 70 years of age, with a normal ventricular ejection fraction and the absence of severe hypertension, diabetes, preoperative diuretic therapy, and clinical carotid or peripheral arterial disease. Patients with unstable angina, and those receiving inotropes or exposed to radiologic contrast medium in the previous 72 hours, were excluded. Patients were randomly assigned into one of two groups, according to the last digit of their clinical history number. Group 1 consisted of 14 patients whose arterial blood pressure during CPB was left clearance decreased during CPB to 88.7 * 39.7 mL/min, whereas in group 2 it increased to 157.6 f 79.5 mL/min; the difference between groups was significant. Early postopera- tively, there was no difference: 136.2 f 86.6 mL/min in group 1 and 100 f 21.4 mL/min in group 2. One week postopera- tively, values were 100.5 f 37.9 and 101.9 + 18.4, respec- tively. There was a significant correlation between the creat- inine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoper- ative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified. Copyright 0 1992 by W.B. Saunders Company KEY WORDS: extracorporeal circulation, cardiopulmonary bypass, pressure untreated. Group 2 comprised 7 patients who received phenyleph- rine to maintain their mean arterial pressure (MAP) > 70~mm Hg throughout bypass; the total dose required was between I and 20 mg. Except for this difference, the anesthetic and surgical manage- ment was uniform in both groups. Two thirds of the patients were randomized to group 1. because it had been planned to divide them into two groups with spontaneously occurring high or low MAPS; however, all of them remained hypotensive during most of bypass. All patients received 1 to 2 mg of oral flunitrazepam the night before surgery, and were premeditated with 0.1 mgikg of mor- phine, intramuscularly, 1 hour before transfer to the operating room. Following insertion of radial arterial, peripheral, and central venous catheters, anesthesia was induced with 25 to 30 Kg/kg of fentanyl and 0.12 mg/kg of pancuronium and maintained with isoflurane, 0.5% to 1.5%, in oxygen. Intraoperative and postopera- tive fluid intake and losses were measured. Loop diuretics or dopamine were not used intraoperatively or early in the postopera- tive period. All patients were mechanically ventilated until the following morning; intravenous morphine and diazepam were used for analgesia and sedation. The extracorporeal circulation system included nonpulsatile roller pumps and a disposable bubble oxygenator with an integral heat exchanger (BIO 10, Bentley Laboratories, Irvine, CA). It was primed with 1,500 mL of lactated Ringer’s solution and 500 mL of 15% mannitol. Cardiac index was maintained at 2.2 L/minim2 throughout CPB in all patients. Moderate hypothermia to 25°C was From the Departments of Anesthesiology, Cardiovascular Surgery, and Nephrology, Catholic University of Chile School of Medicine, Santiago de Chile. Supported in part by a grantfrom Abbott Laboratories de Chile, and by Grant No. 9OigSl from FONDECYT (G.M.). Present address: Setgto Troncoso, MD, Staff Anesthesiologist, The Army Hospital, Santiago de Chile. Address reprint requests to Jorge Urtua, MD, Department of Anesthesiology, Catholic University Medical School, PO Box 114-0, Santiago de Chile. Copyright 0 1992 by W.B. Saunders Company 1053-0770192/0603-0010$03.0010 Journalof Cardiothoracic and VascularAnesthesia, Vol6, No 3 (June), 1992: pp 299-303 299
Transcript
Renal Function and Cardiopulmonary Bypass: Effect of Perfusion Pressure
Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine cl.2 mg/dL, creati- nine clearance >70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary sur- gery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to main- tain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were mea- sured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 + 36.7 in group 1 and 120.6 f 50.7 mL/min in group 2). In group 1, creatinine
D ESPITE IMPROVEMENTS in cardiovascular anes- thesia, physiological monitoring, and cardiopulmo-
nary bypass (CPB), postoperative renal dysfunction is still a frequent and potentially lethal complication following car- diac surgery.’ In this institution, its incidence exceeds 5% in adult patients. Extracorporeal circulation has been impli- cated as a possible etiology, because of the physiological alterations inherent to the technique.ie3 A hemodynamic abnormality frequently observed during CPB is arterial hypotension, more marked at the beginning of CPB, but often persisting during most of the perfusion period.4 It is known that hypotension may adversely affect renal func- tion1s3J; it has been suggested, therefore, that a low perfusion pressure during CPB could result in renal hypoperfusion, flow redistribution, and postoperative renal dysfunction5 This hypothesis remains controversial, and there has been a great deal of debate as to what is the minimal acceptable blood pressure during bypass.*,4 Therefore, this study was designed to see whether a low arterial pressure during CPB produced measurable changes in intraoperative renal func- tion, and whether postoperative renal function was better preserved if a relatively higher level of blood pressure was maintained.
METHODS
Following approval by the Medical School Research Committee and previous informed consent, 21 patients scheduled for elective coronary artery surgery were prospectively studied. Their preoper- ative renal function was normal, defined as a plasma creatinine < 1.2 mg/dL, creatinine clearance > 70 mlimin, and plasma urea < 60 mg/dL. All patients were between 50 and 70 years of age, with a normal ventricular ejection fraction and the absence of severe hypertension, diabetes, preoperative diuretic therapy, and clinical carotid or peripheral arterial disease. Patients with unstable angina, and those receiving inotropes or exposed to radiologic contrast medium in the previous 72 hours, were excluded. Patients were randomly assigned into one of two groups, according to the last digit of their clinical history number. Group 1 consisted of 14 patients whose arterial blood pressure during CPB was left
clearance decreased during CPB to 88.7 * 39.7 mL/min, whereas in group 2 it increased to 157.6 f 79.5 mL/min; the difference between groups was significant. Early postopera- tively, there was no difference: 136.2 f 86.6 mL/min in group 1 and 100 f 21.4 mL/min in group 2. One week postopera- tively, values were 100.5 f 37.9 and 101.9 + 18.4, respec- tively. There was a significant correlation between the creat- inine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoper- ative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified. Copyright 0 1992 by W.B. Saunders Company
untreated. Group 2 comprised 7 patients who received phenyleph- rine to maintain their mean arterial pressure (MAP) > 70~mm Hg throughout bypass; the total dose required was between I and 20 mg. Except for this difference, the anesthetic and surgical manage- ment was uniform in both groups. Two thirds of the patients were randomized to group 1. because it had been planned to divide them into two groups with spontaneously occurring high or low MAPS; however, all of them remained hypotensive during most of bypass.
All patients received 1 to 2 mg of oral flunitrazepam the night before surgery, and were premeditated with 0.1 mgikg of mor- phine, intramuscularly, 1 hour before transfer to the operating room. Following insertion of radial arterial, peripheral, and central venous catheters, anesthesia was induced with 25 to 30 Kg/kg of fentanyl and 0.12 mg/kg of pancuronium and maintained with isoflurane, 0.5% to 1.5%, in oxygen. Intraoperative and postopera- tive fluid intake and losses were measured. Loop diuretics or dopamine were not used intraoperatively or early in the postopera- tive period. All patients were mechanically ventilated until the following morning; intravenous morphine and diazepam were used for analgesia and sedation.
The extracorporeal circulation system included nonpulsatile roller pumps and a disposable bubble oxygenator with an integral heat exchanger (BIO 10, Bentley Laboratories, Irvine, CA). It was primed with 1,500 mL of lactated Ringer’s solution and 500 mL of 15% mannitol. Cardiac index was maintained at 2.2 L/minim2 throughout CPB in all patients. Moderate hypothermia to 25°C was
From the Departments of Anesthesiology, Cardiovascular Surgery, and Nephrology, Catholic University of Chile School of Medicine, Santiago de Chile.
Supported in part by a grantfrom Abbott Laboratories de Chile, and by Grant No. 9OigSl from FONDECYT (G.M.).
Present address: Setgto Troncoso, MD, Staff Anesthesiologist, The Army Hospital, Santiago de Chile.
Address reprint requests to Jorge Urtua, MD, Department of Anesthesiology, Catholic University Medical School, PO Box 114-0, Santiago de Chile.
Copyright 0 1992 by W.B. Saunders Company 1053-0770192/0603-0010$03.0010
Journalof Cardiothoracic and VascularAnesthesia, Vol6, No 3 (June), 1992: pp 299-303 299
300 URZUA ET AL
used. Cold St. Thomas cardioplegic solution was intermittently infused in the aortic root for myocardial preservation; part of it was returned to the oxygenator. Potassium supplementation, other than that present in the cardioplegic solution, was not given. Isoflurane, l%, was added to the oxygenator. The hematocrit was allowed to decrease to 20%; larger decreases were corrected with 1 to 2 U of packed red blood cells in three patients in group 1. No other homologous blood products were used intraoperatively. The alpha-stat technique was used for blood gas management. Sodium bicarbonate (25-75 mEq) was used to correct metabolic acidosis in two patients in group 1 and one patient in group 2. The MAP was recorded every 2 minutes during CPB, and was not allowed to increase above 100 mmHg in either group; sodium nitroprusside was used to prevent hypertension during rewarming in five patients in group 1 and six patients in group 2.
Plasma creatinine, sodium, potassium, and osmolality were measured in venous blood preoperatively on the day of surgery, after 30 minutes of CPB, and on the morning of the second postoperative day. Urine was collected for 24 hours preoperatively; throughout the period of CPB, injecting filtered air in order to displace any urine remaining in the bladder or tubing; and, for 24 hours postoperatively. Urinary creatinine, sodium, potassium, and osmolality were measured and creatinine, osmolal and free water clearances, and the fractional excretion of sodium were calculated. Intraoperative clearances were calculated based on the volume of urine collected throughout the duration of CPB. Laboratory personnel were unaware in which group the patients belonged. Techniques and formulae used were standard for this institution and have been previously reported.s Plasma creatinine and creati- nine clearance were also measured 1 week postoperatively.
Each patient’s preoperative measurements were considered the control values. The significance of differences, both sequential and between groups, was ascertained by a two-way analysis of variance (ANOVA) using a statistical package (Statview, Brainpower, Calabasas, CA). Exact P values were determined by Student’s paired or unpaired t tests and by a one-way ANOVA with Fisher’s least significant difference and Scheffe F tests. Correlation be- tween variables was determined by linear regression. Unless specified otherwise, all results are expressed as means 2 1 SD. The level of significance was selected at P = 0.05.
RESULTS
The two groups were comparable in age, sex, weight, height, duration of CPB, number of bypasses, and intraop- erative and postoperative fluid intake and losses (Table 1). As designed, group 2 had a significantly higher MAP and fewer episodes of hypotension throughout CPB (Table 2). Ah patients completed their operations and postoperative
Table 1. Patient Demographics
Group 1 Group 2 P
Age (~4 Height (cm)
Weight (kg) Sex (M/F) CPB duration (min)
Range (min) Hematocrit on CPB No. of grafts lntraop fluids in (mL) lntraop fluids out (mL) Postop fluids in (mL)
*TM-50 index = the magnitude of MAP readings <50 mm Hg during
bypass times the duration of these low-pressure episodes.7
courses uneventfully. There was no clinical or laboratory evidence of renal dysfunction in any patient throughout the study period.
Group 1 and group 2 patients had similar urine outputs preoperatively (1.29 5 0.37 ml/kg/h and 1.31 t 0.31 ml/kg/h, respectively). This increased during CPB to 4.18 * 2.78 ml/kg/h (P = 0.0026) in group 1 and 7.75 f 4.78 ml/kg/h (P = 0.0089) in group 2, significantly higher in the phenylephrine group (P = 0.042). Urine output dc- creased postoperatively to 1.15 2 0.50 ml/kg/h in group 1 and to 0.84 + 0.38 ml/kg/h in group 2 (P = 0.0036 and 0.0203, respectively, compared with intraoperative values; P > 0.05 in both groups, compared with control) (Fig 1). Free water clearance decreased during CPB from - 16.5 2 34.6 mL/h to -62.2 + 29.7 mL/h in group 1 (P = O.OOll), and from -20.9 ? 31.4 mL/h to -54.9 + 36.3 mL/h in group 2 (P > 0.05). It remained negative postoperatively (-84.6 2 42.5 mL/h in group 1 and -64.5 + 12 mL/h in group 2); there was no significant difference between groups (Fig 1).
Plasma sodium was normal before surgery (group 1, 141.3 2 1.49 mEq/L; group 2, 141.5 2 1.67 mEq/L). However, it decreased significantly (P = 0.0001 in group 1 and P = 0.0002 in group 2) during CPB, to 131.9 2 2.77 mEq/L and 132.4 ? 2.93 mEq/L, respectively (Fig 2).
PREOP lNTRAOP POSTOP
Fig 1. Urine output (upper) increased in both groups during CPB, returning to control values early postoperatively. Free water clear- ance (lower) decreased in both groups intraoperatively and remained negative postoperatively.
RENAL FUNCTION AND PERFUSION PRESSURE 301
A* 160
-L v URINARY
‘20 SODIUM
Fig 2. Significant decreases in plasma sodium concentration were found during CPB in both groups (upper). However, urinary sodium concentration did not decrease (middle). The excreted sodium frac- tion (lower) increased markedly during bypass. All values returned to control postoperatively.
Postoperatively, plasma sodium returned to normal (group 1, 140.8 +- 2.8 mEq/L; group 2, 138.8 ? 1.91 mEq/L, P > 0.05 compared with control and P = 0.0001 and 0.0009 compared with intraoperative values). There was no signifi- cant difference between groups. Urinary sodium concentra- tion did not change significantly in either group during bypass (from 58.1 * 28.13 mEq/L to 87.4 -I- 50.4 mEq/L in group 1 and from 55.7 * 18.76 mEq/L to 82.0 ? 21.35 mEq/L in group 2) (Fig 2). Postoperatively, it was 62.3 + 48.27 mEq/L in group 1 and 52.5 ? 30.25 mEq/L in group 2. There was no significant difference between groups. Ex- creted sodium fraction increased markedly during CPB, from 0.627 ? 0.281 to 3.38 ? 2.08 in group 1 (P = 0.0006), and from 0.572 + 0.262 to 5.50 ? 5.10 in group 2 (P = 0.038) (Fig 2). After surgery, it decreased to 0.58 ? 0.52 in group 1 (P = 0.0003) and to 0.42 ? 0.41 in group 2 (P = 0.064). There was no significant difference between groups.
Plasma potassium remained normal throughout the study period in both groups (group 1,4.1 ? 0.26 mEq/L preoper- atively, 4.0 f 0.52 mEq/L intraoperatively, and 3.95 ? 0.24 mEq/L postoperatively; group 2,4.0 ? 0.37 preoperatively, 4.3 * 0.42 mEq/L intraoperatively, and 4.2 f 0.23 mEq/L postoperatively). Urinary potassium showed large individ- ual variations, without significant differences between mea- surements or between groups (group 1,24.3 2 8.39 mEq/L preoperatively, 46.6 & 76.78 mEq/L intraoperatively, and 55.3 + 24.59 mEq/L postoperatively; group 2, 18.3 + 5.14 mEq/L preoperatively, 25.1 + 25.16 mEq/L intraopera- tively, and 48.8 +- 12.89 postoperatively).
Plasma creatinine was normal at all times in both groups (preoperatively, 1.04 * 0.13 mg/dL in group 1 and 0.94 * 0.15 mg/dL in group 2; intraoperatively, 0.99 2 0.2 mg/dL in group 1 and 0.91 + 0.18 mg/dL in group 2; early postoperatively, 1.08 ? 0.19 mg/dL in group 1 and 1.03 + 0.27 mg/dL in group 2; 1 week postoperatively, 1.0 ? .23 mg/dL in group 1 and 0.94 * .2 mg/dL in group 2; P > 0.1 for all comparisons) (Fig 3). Urinary creatinine decreased from 69 ? 27.5 mg/dL to 25.6 + 21.3 mg/dL in group 1 (P < 0.0001) and from 71.4 2 21.3 mg/dL to 19.2 2 13.8 mg/dL in group 2 (P < 0.0001) during bypass; postopera- tively, it increased to 113.5 ? 54.5 mg/dL in group 1 (P = 0.0056) and to 108 ? 39.2 mg/dL (P < 0.0002) in group 2 (Fig 3). There was no significant difference between groups. Creatinine clearances were comparable preopera- tively (101.9 ? 36.7 mL/min in group 1 and 120.6 f. 50.7 in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 ? 39.7 mL/min, whereas in group 2 it increased to 157.6 ? 79.5 mL/min; since the values changed in opposite directions, the difference between groups reached statistical significance (P = 0.0174). However, early postoperatively, there was no significant difference; creati- nine clearance was 136.2 ? 86.6 mL/min in group 1 and 100 ? 21.4 mL/min in group 2. One week postoperatively, values were 100.5 2 37.9 and 101.9 ? 18.4 ml/mitt, respectively; there was no significant difference from con- trol or between groups (Fig 3). Individual creatinine clear- ances correlated significantly with the MAP during CPB intraoperatively, but not postoperatively (Fig 4).
Plasma osmolality increased during CPB from 291.2 2 3.5 mOsm/L to 300.9 f 5.4 mOsm/L in group 1 (P = 0.0001) and from 291.9 * 4.3 mOsm/L to 301.5 2 3.3 mOsm/L in group 2 (P < 0.0001). It returned to normal (286.5 ? 4.7
Fig 3. Creatinine clearance (upper) decreased during CPB in group 1, while it increased in group 2; *indicates that intraoperative creatinine clearance was significantly higher in group 2. Plasma creatinine (middle) remained within normal limits in both groups. Urinary creatinine (lower) decreased intraoperatively and increased postoperatively in both groups.
302
Fig 4. Creatinine clearance correlated significantly with this MAP during bypass (upper left box), but not postoperatively [lower left box). A similar correlation was found for osmolal clearance (right boxes); however, statistical significance was marginal.
mOsm/L in group I and 287.5 * 7.9 mOsm/L in group 2) postoperatively; there was no significant difference between groups. Urine osmolality during CPB did not differ signifi- cantly from control (from 346.8 ? 111.9 mOsm/L to 385.4 t 49.4 mOsm/L in group 1 and from 361.7 4 103 mOsm/L to 342 +. 34.4 mOsm/L in group 2). It increased postoperatively to 620.3 5 184.7 mOsm/L in group 1 (P = 0.0098) and to 635.8 ? 139.6 mOsm/L in group 2 (P = 0.0047) (Fig 5). Osmolal clearances during CPB increased from 112.6 2 52.8 mL/h to 349.2 * 214.1 mL/h (P = 0.0021) in group 1 and from 114 ? 41.8 mL/h to 616.9 % 344.4 mL/h (P = 0.0118) in group 2. There was no significant difference between groups. Postoperatively, os-
Fig 5. There was a significant intraoperative increase in osmolal clearance in both groups, which returned toward normal postopera- tively (upper); *indicates that patients with lower pressure during bypass had significantly higher postoperative osmolal clearance than phenylephrlne-treated patients. Urine osmolallty (lower) did not change intraoperatively. but increased postoperatively in both groups.
URZUA ET AL
molal clearance decreased significantly to 166.7 + 44.3 mL/h in group 1 (P = 0.015) and to 123.4 +- 25.2 mL/h (P = 0.0405) in group 2; the difference between groups was significant (P < 0.05) (Fig 5).
DISCUSSION
Patients in whom the MAP during CPB was kept above 70 mmHg had a significantly higher intraoperative creati- nine clearance than patients in whom MAP was lower. Intraoperative creatinine clearance correlated significantly with average perfusion pressure. These findings are consis- tent with current knowledge; creatinine clearance is an indicator of glomerular filtration rate (GFR), which is a function of transglomerular filtration pressure, and is in part dependent on the MAP. Postoperatively, creatinine clearances were similar in the two groups.
Creatinine clearance measured during CPB may not reflect a steady state due to the large hemodynamic and metabolic changes that may occur at that time. Calculated clearance is a mean value, whereas GFR most likely changed substantially over time. To correct in part for this limitation, blood samples were taken after 30 minutes of CPB, once equilibrium had presumably been reached, and a precise urine collection technique was used to include all urine produced throughout bypass. Excellent correlation has been reported between creatinine clearance measured over 2 hours, compared with 22 hours, provided that all urine produced during the test period is included.6 There- fore, it is believed that the results reasonably reflect the situation that was most prevalent during bypass.
Urine output and osmolal clearance increased during bypass in both groups. At least in part, this resulted from the fluid and electrolyte load due to the crystalloid infusion and the osmolal load of mannitol. The higher MAP on CPB further increased intraoperative urine output and osmolal clearance. However, postoperatively, osmolal clearance was significantly greater in the group with a low MAP during bypass. It seems reasonable to speculate that the patients with a higher perfusion pressure during CPB increased their intraoperative GFR and osmolal diuresis more rapidly than patients who were hypotensive; the latter patients partly delayed water and osmolal excretion into the early postoperative period. It is not clear whether a higher urine output and creatinine clearance during CPB wet-c advantageous, since patients in the lower pressure group did not suffer any renal dysfunction and presented higher osmolal clearance postoperatively. A larger intraoperative GFR is desirable; however, postoperative renal function may be even more important, as renal failure most fre- quently develops after several hours or days postopera- tively.1,3a7
All patients in the low-pressure group had normal renal function after surgery and 1 week postoperatively. Hypoten- sion during CPB differs from other clinical situations, in which hypotension indicates a severely deranged circula- tion and is often associated with a low cardiac output, renal vasoconstriction, and impaired renal function.1,3,7 However, during CPB, cardiac output is mechanically secured at a constant value, no matter how low the MAP may be.4J It is
RENAL FUNCTION AND PERFUSION PRESSURE
perhaps comparable to controlled hypotension during anes- thesia, which rarely produces postoperative renal dysfunc- tion, even though GFR during the hypotension is reduced.9 Low pressure during CPB is not due to a low cardiac output, but to reduced resistance, mostly due to lowered blood viscosity associated with hemodilution.4JJ0J1 The lack of complications associated with hypotension during CPB7 may also be explained in part by the shift of auto- regulation associated with hemodilution4 and the reduced metabolic demands with hypothermia. The study size was not sufficiently large, nor was the patient population appro- priate, to decide that a higher perfusion pressure might benefit patients at increased risk for renal complications.
Patients in both groups did not decrease their urinary sodium concentration during CPB, despite significantly lowered plasma sodiums. To maintain homeostasis, the kidneys should have responded to hyponatremia by increas- ing tubular sodium reabsorption; urine sodium, therefore, should have been decreased. Low plasma sodium probably did not correspond to a total sodium deficit, but rather to the osmolal effect of mannitol, as plasma osmolality was increased despite the hyponatremia. Hyperosmolality due to mannitol promotes an osmotic diuresis, but it could also induce vasopressin release. Water and sodium excretion probably resulted from several mechanisms, rather than from a single cause, as it is known that antidiuretic hormone and aldosterone often increase during bypass.‘* It is also
303
possible that tubular and loop responses to aldosterone and vasopressin were impaired by hypothermia, as it decreases the speed of chemical reactions and enzyme function. Interpreting the results would have been simpler if manni- to1 had been avoided; however, the authors believe that mannitol is necessary in cardiac surgical patients to prevent an undesirably large positive fluid balance. Hyperosmolal solutions are effective in decreasing fluid requirements and promoting diuresis during cardiac surgery.r3 Moreover, mannitol may help preserve renal function, as it improves renal plasma flow, increases urine output, and possibly acts as a free radical scavenger.5 Furthermore, Thurner et al reported that avoidance of mannitol did not prevent osmo- la1 clearance increases similar to those found in the present study,14 perhaps due to the much larger amount of fluids that they had to infuse into their patients. They also reported that in hypertensive patients, MAPS <50 mmHg during CPB decreased the intraoperative, but not postoper- ative, creatinine clearance.r4
It is concluded that keeping the MAP above 70 mmHg during CPB may increase the intraoperative GFR. No deleterious effect of a low perfusion pressure on postopera- tive renal function could be identified in patients with normal preoperative renal function; on the contrary, the group of patients ,who did not receive vasoconstrictors during CPB had normal renal function and higher postoper- ative osmolal clearance.
REFERENCES
1. Hilberman M, Derby G, Spencer RN: Sequential pathophysi- ological changes characterizing the progression from renal dysfunc- tion to acute renal failure following cardiac operation. J Thorac Cardiovasc Surg 79:838+X44, 1980
2. Taylor KM, Morton IJ, Brown JJ, et al: Hypertension and the renin-angiotensin system following open heart surgery. J Thorac Cardiovasc Surg 74:840-845,1977
3. Moran SM, Myers BD: Pathophysiology of protracted acute renal failure in man. J Clin Invest 76:1440-1448, 1985
4. Urzua J: Cardiopulmonary bypass, in Estafanous FG (ed): Anesthesia and the Heart Patient, New York, NY, Butterworths, 1990, pp 151-156
5. Urzua J: Enfermedades Renales y Anestesia, in Aldrete A (ed): Tratado Teorico-Practice de Anestesiologia. Mexico City, Mexico, Salvat, 1988, pp 1333-1348
6. Sladen RN, Endo E, Harrison T: Two-hour versus twenty-two hour creatinine clearance in critically ill patients. Anesthesiology 67:1013-1016,1987
7. Slogoff S, Reul GJ, Keats AS: Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 50:911-918,199O
8. Urzua J: Low perfusion pressure or interruption of blood flow suppresses electroencephalographic activity? J Clin Monit 7:68, 1991
9. Lessard MR, Trtpanier CA: Renal function and hemodynam- its during prolonged isoflurane-induced hypotension in humans. Anesthesiology 74:860-865,199l
10. Urzua J, Zurick AM, Starr NJ, et al: Enhanced cardiac performance following cardiopulmonary bypass. J Cardiovasc Surg 26:53-58, 1985
11. Gordon RJ, Ravin MB: Rheology and anesthesiology. Anesth Analg 57:252-261,1978
12. Philbin DM, Levine FH, Emerson CW, et al: Plasma vasopressin levels and urinary flow during cardiopulmonary bypass in patients with valvular heart disease. J Thorac Cardiovasc Surg 78:779-783, 1979
13. Metz S, Keats AS: Benefits of a glucose-containing priming solution for cardiopulmonary bypass. Anesth Analg 72:428-434, 1991
14. Thurner F, Bottinger E, Pasch Th: Veranderungen von Wasserhaushalt und Nierenfunktion durch den kardiopulmonalen Bypass. Anasth Intensivther Notfallmed 21:5-8, 1986
