Effects of Halothane P. Colson,

and Isoflurane With Infrarenal

MD, X. Capdevilla,

MD, H. Barlet,

on Transient Renal Dysfunction Aortic Cross-Clamping

MD, J.R. SBguin,

Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = IO). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamits were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (‘%hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 2 25.8 and lg.7 + 5.2 mL/min, respectively) than in the isoflurane group (253.4 + 51.5 and 44.9 f 8.4 mL/min) (P < 0.05 for both). During cross-clamping, the

T

HE SYSTEMIC HEMODYNAMIC effects of infrarenal aortic cross-clamping during abdominal aortic surgery have been documented.1-3 In contrast, the consistent reductions in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) related to renal vasoconstriction, during and after aortic cross-clamping, remain unexplained. 4~5Nevertheless, postoperative renal failure, which is the most frequent complication after aortic reconstruction6y7 might be explained by these renal hemodynamic alterations.4*5 Whether blunting of the intraoperative changes in renal hemodynamics associated with clamping and unclamping of the aorta might prevent the perioperative renal dysfunction is unknown. Both halothane and isoflurane have been shown to have either a vasodilating effects-l0 or a vasoconstricting effect”J2 on the renal circulation by different authors. The purpose of this study was to further assess the effects of isoflurane or halothane anesthesia on renal hemodynamics during infrarenal aortic surgery. METHODS

Cardiothoracic

and

VascularAnesthesia,

Vol6,

No 3

(June),

MD, and B. Roquefeuil,

MD

renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 f 47.1 and 49.5 + 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 + 31.8and 14.8 + 3.7 mL/min,respectively) (P c 0.05). After aortic unclamping, ERPF increased markedly in both groups (487.8 f 122 and 362.5 f 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 + 22 and 71.8 + 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment. Copyright o 1992 by WA Saunders Company KEY WORDS: anesthesia, aortic surgery

isoflurance, halothane,

abdominal

controlled using 50% nitrous oxide and oxygen to maintain normal arterial blood gases. In all patients, a peripheral vein was cannulated before anesthesia, then a 7-Fr thermodilution pulmonary artery catheter was inserted via the internal jugular vein; a radial artery catheter and a Foley urinary bladder catheter were inserted after the induction of anesthesia. The aorta was approached via a midline laparotomy incision. When the mean arterial blood pressure (MAP) exceeded 105 mmHg, additional doses of fentanyl(lO0 or 200 pg) and increased concentrations of the volatile anesthetic were given. Intravenous fluid (crystalloid, colloid, or blood) was infused to maintain the MAP, pulmonary capillary wedge pressure (PCWP), and hematocrit above 60 mmHg, 10 mmHg, and 28%, respectively. Systemic and renal hemodynamics were measured at three study periods as follows: during the surgical approach to the aorta (preclamp period), during aortic cross-clamping (cross-clamp period), and after unclamping and distal revascularization (postclamp period). Heart rate (HR), MAP, PCWP, and cardiac output (CO) were recorded and blood samples were withdrawn at the midpoint of each period (20 to 30 minutes each). GFR and ERPF were estimated from the clearances of 99Tc-DTPA, and ‘311-hippuran, respectively, using a continuous infusion technique previously described by this laboratoryr3J4 ( a ft er a loading dose, a continuous infusion was maintained for 60 minutes before the first measure-

The study population consisted of 19 patients (18 men, one woman; aged 36 to 76 years) scheduled for infrarenal aortic surgery because of either an aortic aneurysm (n = 12) or aorto-occlusive disease (n = 7). Patients with prior renal dysfunction (serum creatinine > 1.8 mg/dL), cardiac failure, aortic thrombosis, or emergency surgery were not included. No renal artery stenosis was detectable on angiograms. Preoperative therapy was maintained until the day before surgery, except for antianginal medications, of which the last dose was given at the time of premeditation. The protocol was approved by the Committee for Ethics in Clinical Research of the institution and informed consent was obtained from each patient. Preanesthetic medication consisted of flunitrazepam (1 mg orally). Anesthesia was induced with fentanyl (6 pg/kg), midazolam (0.15 mg/kg), and pancuronium (0.1 mgikg). Patients were allocated in a randomized fashion to either the halothane group (n = 9) or isoflurane group (n = 10). Halothane and isoflurane were administered using a Drager (Liibeck, Germany) vaporizer. End-tidal halothane or isoflurane concentrations were measured at the proximal end of the endotracheal tube using an infrared analyzer (Capnomag, Datex, Helsinki, Finland). Ventilation was

Journalof

MD, Ch. Marty-An&,

Associated

This article is accompanied by an editorial. Please see: Gelman S: Halothane or Isoflurane for Infrarenal Aortic

From the Dtpatiments d’Anesth&ie et de Chirurgie Cardiovasculake, Centre Hospitalier Universitaire, Hopital St-Eloi et Laboratoire de Physiologic Cardiovasculaire, Institut de Biologie, Montpellier, France. Address reprint requests to P. Cohort, MD, Depattement d ‘Anesthbie, Hopital St-Eloi, Avenue Bertin-Sans, 34059 Montpellier, France. Copyright 0 1992 by WB. Saunders Company 1053-0770/92/0603-0009$3.00/0

1992:

pp 295-298

295

COLSON ET AL

296

ment period to allow equilibration). Fractional excretion of sodium (FEN.) was calculated as: Na clearance/DTPA clearance x 100. Data are expressed as the mean 2 SEM. Two-way analysis of variance (ANOVA) for repeated measures and Student’s t test with Bonferroni’s correction were used to assess significance between and within groups. P < 0.05 was considered level of significance.

the minimum

Table 2. Systemic Hemodynamic Halothane

Data lsoflurane

Heart Rate (beats/min) Preclamp

81.5 + 5.9

71.7 + 3.5

Crossclamp

67.7 + 5.1

61.9 + 4.5

Postclamp

68.0 + 6.3

62.8 -t 3.4

Preclamp

76.9 + 2.5

83.5 + 3.1

Crossclamp

83.4 + 4.0

86.5 I+_4.5

Postclamp

83.9 i 2.6

77.2 2 3.3

Preclamp

15.4 -t 1.4

13.9 + 0.7

Crossclamp

15.9 t 1.1

16.7 -t 1.4

Postclamp

16.1 * 1.4

15.8 -t 1.3

MAP (mm Hg)

RESULTS

The two groups of patients were similar with regard to demographic characteristics and preoperative serum creatinine, creatinine clearance, and MAP (Table 1). Anesthesia was maintained with similar doses of fentanyl and mean end-tidal concentrations of volatile anesthetics at preclamp, cross-clamp, and postclamp periods were 0.67% ~fr 0.06%, 0.64% +- 0.05%, and 0.62% ? 0.07% for halothane, and 0.81% ? O.ll%, 0.77% * 0.06%, and 0.65 t 0.08% for isoflurane, respectively. Volume infusion requirements for the entire procedure were the same for the two groups, and no vasopressors were given to any patient. Effect of Aortic Cross-clamping on Systemic Hemodynamic Data During the preclamp period, systemic hemodynamic parameters were similar in both groups (Table 2). During aortic cross-clamping, HR, MAP, and PCWP were not significantly altered in either group. The CO decreased significantly in the halothane and isoflurane groups by 30.2% and 24.5%, respectively (P < 0.05 from baseline for both). Systemic vascular resistance (SVR) increased in both groups by 47% and 34.9% (P < 0.05 for both) in the Table 1. Demographic and Perioperative Data Halothane

lsoflurane

Patients NO.

9

10

Age (vr) Weight (kg)

60.3 2 4.0

60.2 r 2.9

66.4 2 2.3

70.3 2 2.5

Serum creatinine (mg/dL)

1.14 2 0.06

1.24 + 0.09

Creatinine clearance (mL/min/ m2) MAP (mm Hg)

91.0 t-11.0

79.8 r 8.6

94.3 r 2.9

95.1 f 3.4

Preoperative treatment Calcium antagonists

619

2110

ACE inhibitors

519

2110

Nitrates

219

l/IO

Methyldopa

o/9

2/10

319

4110

Surgery Aorto-occlusive diseases Aortic aneurysms

619 31.3 2 2.5

Cross-clamping time (min)

6/10 30.1 it 3.6

Anesthesia 6.4 2 0.3

6.6 2 0.4

E,C (%.)

0.64 ? 0.06

0.74 + 0.08

VOL, (L/h)

0.91 * 0.05

1.19 2 0.09

Fentanyl (pg/h)

NOTE. Data are expressed as the mean & SEM.

PCWP (mm Hg)

CO (L/min) Preclamp

5.3 + 0.4

5.3 2 0.3

Crossclamp

3.7 f 0.2*

4.0 It 0.2*

Postclamp

4.6 t 0.5

5.2 t 0.5

SVR (dynes.sec.cm-5) Preclamp

1,080 -t 111

1,208 + 114

Crossclamp

1,590 +- 95”

1,630 t 123*

Postclamp

1,360?

1,153 + 142

GO,

113

(%)

Preclamp

82.4 + 2.5

83.8 + 4.3

Crossclamp

75.1 t- 3.3

81.0 + 2.9

Postclamp

74.2 + 2.7

80.0 + 2.9

NOTE. Data are expressed as the mean 2 SEM.

?? P < 0.05 within groups from previous period.

halothane and isoflurane groups, respectively. Clamp removal was followed by no changes in HR, MAP, or PCWP in either group. The CO increased, while the SVR decreased in both groups, but they did not reach the preclamp values in the halothane-anesthetized patients. Venous oxygen saturation (SvOZ) was not significantly altered in either group at any time during the study in either group. During the preclamp period, ERPF and GFR were significantly lower in the halothane group than in the isoflurane group (P < 0.05) (Table 3). During crossclamping, ERPF and GFR changes from preclamp values did not reach statistical significance in either group, despite a further decrease in GFR (24.9%) in the halothane group; GFR remained significantly lower in the halothane group than in the isoflurane group (P < 0.05). Urine flow decreased from baseline in the halothane group (by 56.7%, P < 0.05), but not in the isoflurane group. After aortic unclamping, renal variables improved in both groups. ERPF, GFR, and urine flow markedly increased in the halothane group from the cross-clamp values (by 253%, 405%, and 596%, respectively; P < 0.05 for all). There was no further significant difference in any renal variable between the groups. FEN, was not altered in the groups at any time during the study. None of the patients developed acute postoperative renal failure. DISCUSSION

Abbreviations: MAP, preoperative mean arterial blood pressure; ACE inhibitors, angiotensin-converting

enzyme inhibitors; E,C, mean end-

tidal concentration of volatile anesthetic during the study; VOL,, total volume infused per hour of surgery.

This study shows that halothane anesthesia during infrarenal aortic surgery is associated with low ERPF and GFR before and during aortic cross-clamping. On the contrary,

RENAL DYSFUNCTION

297

DURING AORTIC SURGERY

Table 3. Renal Hemodynamic

Data

Halothane

lsoflurane

ERPF (mL/min) Preclamp

118.4 +- 24.6t

Crossclamp

132.4 2 31.6

253.4 + 51.5 232.9 + 47.1

Postclamp

467.8 2 122*

362.5 2 57.7

GFR (mL/min) Preclamp

19.7 -’ 5.2t

44.9 2 8.4

Crossclamp

14.8 z 3.7t

49.5 +- 1.2

Postclamp

74.8 -’ 22*

71.8 2 13.1

Urine flow (mL/min) Preclamp

0.6 f 0.1

1.0 + 0.2

Crossclamp

0.3 f 0.1*t

0.9 * 0.3

Postclamp

1.8 f 0.5’

1.8 ‘- 0.5

FE,. W Preclamp

0.7 k 0.2

0.38 -t 0.1

Crossclamp

0.3 2 0.1

0.4 -t 0.1

Postclamp

0.5 + 0.2

0.5 2 0.1

NOTE. Data are expressed as the mean + SEM. *P < 0.05 within groups from previous period. tP < 0.05 between groups.

isoflurane anesthesia was associated with better renal hemodynamics. Systemic hemodynamic variations before and during aortic cross-clamping, as well as after unclamping, were identical in the two groups and were comparable to other studies.1-5J5 Most investigators agree that CO decreases and SVR increases during aortic cross-clamping, though the magnitude of reported changes varies widely from one study to another. Gelman et al3 hypothesized that the decrease in CO may reflect a metabolic and hemodynamic adaptation to the exclusion of the lower body rather than a deterioration in cardiac performance. In the present study, hemodynamic changes were associated with moderate changes in Si;O,, which suggests adaptation of cardiac function to metabolic demand throughout the study. Although ERPF and GFR were not measured before induction of anesthesia, both preoperative serum creatinine and creatinine clearance values were normal for the age group of the patients. ERPF and GFR measured during anesthesia and surgery in the isoflurane group are, therefore, considered moderately decreased, and comparable to a previous report.lz However, the very low ERPF and GFR observed before clamping in the halothane group suggest that severe renal vasoconstriction occurred. Previous studies of renal function during halothane or isoflurane anesthe-

sia have reported only moderate renal impairment.1**12 Because renal vasodilation appears to be the direct effect of halothane on experimentally isolated kidneys,8 the halothane-nitrous oxide concentrations used in this study may not have impeded sympathetic-induced renal vasoconstriction during surgery. l6 Conversely, Ostman et allo have shown that isoflurane blunts stress-related renal vasoconstriction in cats. An important finding of this study is that isoflurane anesthesia prevents renal hemodynamic impairment during infrarenal aortic cross-clamping. Renal preservation cannot be attributed to a beneficial effect of isoflurane on systemic hemodynamics, since neither MAP nor CO differed from the halothane-anesthetized patients. The observed decreases in ERPF and GFR associated with aortic crossclamping appear to be mediated by renal vasoconstriction.4,5 Isoflurane probably acts, therefore, at the renal level to alleviate renal vasoconstriction,9Jo but the mechanism is unknown. There is evidence against a blunting of increased renal sympathetic activity from studies showing that epidural anesthesia failed to alter aortic cross-clampinginduced changes in renal hemodynamics.5J0 Participation of the renin-angiotensin system was suspected by some authors because plasma renin activity was found to be increased at the time of cross-clamping.i5J7 However, extracellular fluid expansion, which is known to reduce renin dependency of blood pressure and renal function,ls failed to prevent perioperative renal impairment.15 Although PCWP is a poor index of extracellular fluid loading, relatively high values for the PCWP failed to prevent the decrease in GFR in the halothane group in the present study. Therefore, the renin-angiotensin system plays, at most, a minor role in renal alterations during infrarenal aortic surgery. After aortic unclamping, renal variables improved in the isoflurane group and, more strikingly, in the halothane group. The protective effect of halothane to ischemic kidneys associated with normalization of renal hemodynamits following unclamping may account for the improvement of renal function after partial ischemia.19 In conclusion, halothane anesthesia was associated with severe deterioration in renal hemodynamics before and during aortic cross-clamping. Although this effect was transient, isoflurane anesthesia, which produced a blunting of the effect of aortic clamping on renal hemodynamics, appears to be advantageous during reconstructive aortic surgery.

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COLSON ET AL

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