Acta anaesth. stand. 1979, 23, 444-452

Renal Function and Fluoride Formation and Excretion During Enflurane Anaesthesia P.-0. JARNBERG, J. EKSTRAND, L. IRESTEUT and J. SANTESSON Department of Anaesthesiology and Urological Research Laboratory, Karolinska Sjukhuset and Department of Cardiology, Karolinska Institutet, Stockholm, Sweden

Central circulation, renal function, and fluoride formation and excretion were studied in nine patients during enflurane anaesthesia and surgery. Cardiac output and mean systemic arterial pressure remained unchanged compared with prroperative control values. During anaesthesia and surgery, urine flow rate, inulin clearance, PAH clearance and fractional sodium excretion were 60, 65, 55, and 45% of control values, respectively. Mean peak plasma levrl of fluoride was 20.0 pM. It was reached 4 hours after termination of anaesthesia. Fluoridc clearance (C,) decreased from 23.9 ml . min-' to 2.7 ml . min-' during anaesthesia. Postoperative, CF increased to 41.6 and 76.0 ml . min- I , rrspectively, during two consecutive measurement periods. There was no correlation betwrrn plasma fluoride levrls and depression of any renal function variablr. Received 8 February, accepted,for publication 3 March 1.979

Enflurane is partly metabolized to inorganic renal function prior to anaesthesia (HARTNETT fluoride ions in man (CHASEet al. 1971, et al. 1974, LOEHNINC & MAZZE 1974, COUSINS & MAZZE1974, MADUSKA 1974). EICHHORN et al. 1976). A transient decrease Fluoride ions are potentially nephrotoxic in urine-concentrating ability after proand another fluorinated inhalation anaes- longed anaesthesia in healthy volunteers thetic, methoxyflurane causes dose-related was, however, found by MAZZE et al. (1977). pitressin-resistant polyuric renal failure after Since compromise of renal function only anaesthesia, due to its metabolism to in- becomes apparent after anaesthesia, most organic fluoride (TAVES et al. 1970, MAZZE investigators have limited their interest in et al. 1972, COUSINS & MAZZE1973, COUSINSthe influence of enflurane on renal function et al. 1974). to the postanaesthetic period. Thus, little Plasma fluoride concentrations are usually information seems to exist concerning fluoride below the nephrotoxic threshold (approxi- metabolism and its influence on renal function mately 50 pM) during and after enflurane during enflurane anaesthesia in man. Thc anaesthesia in man (MADUSKA 1974, COUSINSaim of the present investigation was, thereet al. 1976, CORALL et al. 1977), but occa- fore, to study renal function and the formasionally values in the toxic range have been tion and excretion of fluoride during and et al. 1974, MADUSKAafter enflurane anaesthesia and surgery. measured (COUSINS 1974). Polyuric renal failure following prolonged enflurane anaesthesia has been reported in rats (BARR et al. 1974). In man, MATERIAL AND METHODS clinical polyuric renal failure after enflurane Nine patients, four males and five females, age range anaesthesia has been described in only three 25-60 years (mean age 42 years), undergoing gallpatients, all of whom had impairment of bladder or gastric surgery, were investigated. 'IIIIP 0001-5172/79/050444-09$02.50/0

0 1979 The Scandinavian Society of Anaesthesiologists

FLUORIDE METABOLISM AND ENFLURANE ANAESTHESIA

patients had no known histories of renal or cardiopulmonary disease. Preoperative chest films, ECG, serum-creatinine and electrolyte values were normal. The Ethical Committee of Karolinska Sjukhuset liad given its consent to the study, the scope of which was explained to the patients, and their informed consent was obtained. There were no complications during the investigation. :f iiaeslliesia 'The patients were premedicated with oxicon 10-15 mg and scopolamine 0.4-0.6 mg s.c. according to age and weight. Anaesthesia was induced about 2 h later with thiopentone 4 m g . kg-' b.w. and intubation was carried out under muscle relaxation with pancuronium bromide 0.1 mg . kg-' b.w. Anaesthesia was maintained with enflurane vaporized by a specially calibrated vaporizer (Cyprane Ltd, Keighley, U.K.) and administered together with nitrous oxide and oxygen, 2: 1. Ventilation was controlled (Engstrom 300, LKB Medical, Stockholm, Sweden) and adjusted to maintain a normal Paco, based on repeated arterial hlood gas determinations. End-tidal enflurane concentration was continuously measured with the aid of a mass-spectrometer (MGA 200, Centronic Ltd, Croydon, U.K.). T h e vaporizer was set at 1.5% in all patients, which gave an end-tidal enflurane concentration of 1.25 k 0.06% during surgery, equivalent to approximately 1.5 MAC when nitrous oxide is used in the proportion described above (TORRI et al. 1974). The average duration of anaesthesia was 150 min. Calheterizativri The pulmonary artery was catheterized with a flowdirected thermodilution catheter (Swan-Ganz, Edwards Laboratories, Irvine, California, U.S.A.) under pressure-tracing guidance. A teflon catheter was inserted into a radial artery, and the nrinary bladder was also catheterizrd. Circulatory analysis Cardiac output (QT) was determined by a thermodilution technique with the aid of a cardiac output computer (Model 95 10, Edwards Laboratories). T h e reproducibility of this computer model using a 10 ml & GANZ1976). cold injection is 4.0% (BUCHBINDER Daterminations were repeated five times within 5 min, and the corresponding thermodilution curves were recorded (Mingograf 81, Siemens-Elema, Stockholm, Sweden). Systemic arterial (SBP), pulmonary arterial (PAP), right atrial (RAP) and pulmonary capillary wedge pressures (PCWP) were measured with pressure transducers (E 840, Micro Electronic AS, Oslo, Norway) and recorded (Mingograf 81, SiemensElema). Mean pressures were obtained by electronic integration. As a reference for zero pressure, the midpoint of a sagittal plane of the thorax was used. Heart rate (HR) was determined from ECG standard leads.

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Systemic vascular resistance (SVR) was calculated from SBP, RAP and QT. A more detailed account of the central circulation was given in a previous article (SANTESSON et al. 1978). Renal furrctioii A standard clearance technique was used. Values for inulin (GI") and PAH clearance ((IPAII) were correlated to 1.73 m* body surface. 0.5 ml . kg-l b.w. of a solution containing 85 mg . ml-' of inulin (inutesto) and 30 mg . ml-I of para-amino hippurate (PAH, Merck, Sharp & Dohme) in 5.5% glucose was given intravenously as a priming dose. This solution was then infused a t a constant rate of 0.5 ml . ml-' by a motor pump (Infusomat, B. Braun, Melsungen, W. Germany) and allowed to equilibrate 60 min before tlie start of the study. Urine was collected through the intravesical catheter. The bladder was emptied by rinsing with 30 ml of sterile water, aspiration, air insumation and gentle suprapubic pressure. Arterial blood samples were drawn midperiod. Fluid therapy The patients received 5 ml . k g - ' b.w. . h - ' of a balanced electrolyte solution during surgery. The infusion was started at the beginning of the equilibration period. Blood losses u p to 500 ml were compensated by infusion of the balanced electrolyte solution in an amount three times that of the measured loss. Blood losses over 500 ml were compensated with whole blood primed with PAH and inulin. Analyses arid calculations Inulin was analyzed according to HEYROVSKY (1956), and PAH according to BRUN (1951). Sodium concentrations in plasma and urine were measured in a flame photometer (IL-143, Instrumentation Laboratories, Lexington, Mass., U.S.A.). Osmolality was measured cryoscopically in a Knauer osmometer. (Kriauer A.G., Berlin, W. Germany). Free water reabsorption (T;,O) was calculated from the equation : TE20 = C,,,-UF, where U F is urine flow in m l . min-' and C,,, is osmolal clearance in ml . min-'. Fluoride concentrations in plasma and urine were analysed in duplicate for the fluoride content, using a fluoride-sensitive electrode (96-09, Orion Research, Massachusetts, U.S.A.). T o all samples 1/10 vol. F-free 7.5 M acetate buffer pH 5.0 containing 2% CDTA (trans-l.2-diaminocyclohexane-N,N, N1, N'tetra-acetic acid) was added. T h e accuracy of the method has been shown to be &5.6% (rel. s.d. %) in the range 10-20 ng F - . min-', 3.9% in the range 20-50 ng F- . ml-', and less than 2.4% between 40 and 300 ng F- . ml-' (EKSTRAND 1977). Clearance rates and fractional excretions of fluoride, inulin, PAH, sodium, chloride and osmoles were calculated. Arterial oxygen and carbon dioxide tensions were measured with a conventional electrode technique (IL-413, Instrumentations Laboratories).

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P.-0.JARNBERC ET AL.

Procedure All examinations commenced with the patient premedicated and in a supine position. Blank samples of blood and urine were obtained. The priming dose was given and the constant infusion started. Catheterizations were carried out during the equilibration period. After equilibration, renal function was evaluated during two 15-min periods. T h e patient was then anaesthetized. Thirty minutes after institution of anaesthesia, the end-tidal enflurane concentration had reached a steady state. Renal function was then measured during 30-60-min periods throughout the duration of anaesthesia and surgery. Cardiac output measurements were performed and pressure recordings obtained preoperatively before induction of anaesthesia and approximately 30 min after commencement of surgery. Fluoride plasma and urine levels were determined preoperatively. Plasma fluoride concentrations were then followed every 30 min during anaesthesia, every 60 min postoperatively for 6 h, and then every 24 h until they reached the basal level. Fluoride concentrations were determined in the urine collected during the different periods of investigation. The renal function study was terminated at the end of surgery. Fluoride clearance was, however, calculated in the immediate postoperative period during a 4-h period and a second 12-11 period.

Statistics Means and standard deviations (Xks.d.) of different groups of data were calculated. Regression analysis was performed according to the least square method. Student's t-test was used to assess the significance of differences between data. Differences with a random probability of 5% or less were considered significant.

RESULTS

All data are presented as means+s.d. The data on renal function represent mean values of the different clearance periods pre- and interoperatively. Comparisons, unless other-

wise stated, are made between data obtained preoperatively before induction of anaesthesia and data obtained during anaesthesia and surgery. Urineflow and renal haeniodynamics (Table 1 ) Urine flow (UF) decreased during surgery by 40% from 0.93k0.19 ml amin-' to 0.5610.20 ml * min-' (P

Renal function and fluoride formation and excretion during enflurane anaesthesia.

Acta anaesth. stand. 1979, 23, 444-452 Renal Function and Fluoride Formation and Excretion During Enflurane Anaesthesia P.-0. JARNBERG, J. EKSTRAND,...
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