Acta zyxwvutsrqpo Anaesthesiol Scand zyxwvutsrqp 1989: 33: 4 13-4 15 Adverse effects on the brain in connection with isoflurane-induced hypotensive anaesthesia M. ENLUND, B. AHLSTEDT, B. REVENAS, L. KREKMANOV and G. RONQUIST Departments of Anesthesia and Intensive Care and Oral Surgery, Central Hospital, Vasterls and Department of Clinical Chemistry, University Hospital, Uppsala, Sweden As a marker of brain cell injury, adenylate kinase (AK) was measured in cerebrospinal fluid (CSF) in 10 patients given anaesthesia with isoflurane-induced hypotension for corrective surgery of dentofacial deformit- ies. Nine out of 10 patients displayed a marked increase in CSF-AK postoperatively compared with preoperative values. The postoperative mean value displayed a zyxwv 400% increase compared to the corresponding preoperative value. This difference was statistically significant zyxw (P= 0.001). The rise in CSF-AK was most probably the result of an enhanced efflux of AK into CSF subsequent to a presumed hypoxic injury to brain cells. Received 27 34 1988, accepted for publication 20 February 1989 Key words: Adenylate kinase; brain hypoxia; cerebrospinal fluid; induced hypotension; isoflurane anesthesia; maxillofacial surgery. Anaesthesia with induced and controlled hypotension has been employed for about 40 years with the inten- tion of minimizing bleeding and creating better oper- ative conditions (1). Records of focal damages as well as total cerebral catastrophes have been published (2-8). On the other hand, several studies have failed to show signs of cerebral hypoxia after induced hypo- tension !9-11). Hypotension may reach a point where the blood supply to brain cells becomes critical, with harmful metabolic effects in the cells. When cerebral blood flow was reduced below about 50% of control in rats, there were changes in cerebral metabolism similar to those observed in hypoxia with relative ischemia (12-14). Hence, a dysmetabolic state in brain cells may be expected following hypotension, provided this has been sufficiently profound. In two studies with patients undergoing open-heart surgery, the release of adenylate kinase (AK) into cerebrospinal fluid (CSF) correlated well with changes in an index of intellectual function (15, 16). From those and other studies (17-19), CSF-AK is regarded as a sensitive marker of brain hypoxia. When ATP- production is lowered in brain cells, regardless of underlying mechanisms, the electrochemical potential of the cell membrane decreases. This would lead to increased permeability, resulting in a leakage of AK into the extracellular space. Since brain interstitial fluid is in diffusion equilibrium with CSF, any change in CSF-AK activity may reflect such metabolic dys- function of the brain cells (18). Adenylate kinase is an enzyme of low molecular weight (about 22000 daltons), and it catalyzes a dis- mutation reaction between 2 moles of ADP giving rise to 1 mole of AMP and 1 mole ATP. The aim of the present study was to investigate whether any change took place in CSF-AK activity in connection with isoflurane-induced hypotensive anaes- thesia. PATIENTS AND METHODS Ten patients, all in ASA class I, admitted for corrective surgery of dentofacial deformities were studied. The mean age of the six women and four men was 43.7 years (range 24-66). Each patient gave consent after being given detailed information concerning the study and the extra-lumbar punctures. The study was approved by the Ethical Committee of the University of Uppsala. Samples of 3 ml of CSF were taken by lumbar puncture under local anaesthesia the evening before operation and about 20 h post- operatively. The specimens were immediately placed in ice-water and centrifuged twice. The supernatants were stored at zyx - 70°C until analysed according to a previously described method (19). The ac- tivity was expressed in units per litre (19). Premedication of morphine 0.1-0.2 mg kg-' and scopolamine 4-8 pg kg-l was given 6&90 min before induction of anaesthesia. Fentan- yl 68 pg kg-', thiopentone sodium 4-5 mg kg-' and pancuronium 0.1 mg kg-l were used for induction. For half the number of patients, suxamethonium 1 mg kg-' was considere4 necessary for nasal intu- bation. By addition ofisoflurane 0.5-2( - zy 3)%, a mean arterial press- ure of 5 5 4 5 mmHg (7.3-8.6 kPa) was maintained for a maximum of 170 min (Table 1). Intra-arterial pressure monitoring was commenced after induction but before the start of hypotension. A naso-gastric tube was passed. A Penlon NuEeld 200 ventilator was used with a Penlon-Bain system. The minute ventilation was adjusted to 120 ml kg-lmin-' and the