This thesis is based on the following studies:

Abstract

Induced hypotension to a mean arterial pressure, MAP, of 50 mmHg is considered safe, even for a highly oxygen‐dependent organ like the brain. The original aim was to confirm this consideration by measuring a sensitive marker of neuronal injury in CSF, the enzyme adenylate kinase, AK. However, the CSF‐AK activity was pathologically increased in 9 of 10 patients (90%), indicating leakage of the marker from the intracellular to the extracellular compartment when exposed to orthognathic surgery and isoflurane‐induced hypotension. The brain cell injury implied was supposed to be originated from hypoxia. Low cerebral perfusion, in turn secondary to hypotension, was hypothesised to be the triggering event.The unexpected result initiated a randomised trial in which patients were anaesthetised to hypotension or normotension. Twenty‐four out of 37 patients (65%) expressed pathological CSF‐AK activity postoperatively. There was no correlation between CSF‐AK and MAP level. Four out of 17 (24%) neuropsy‐chologically examined patients performed less well postoperatively. The extent of deterioration was considered clinically significant, as compared with the preoperative results, but it was not addressed at this stage whether or not these changes in performance were reversible.The proportion of pathological CSF‐AK values was the same in a third clinical study as in the second, 20 of 29 (69%). Again, there was no correlation between CSF‐AK results and MAP level. Ten of 30 patients (33%), who were investigated neuropsy‐chologically, deteriorated significantly between preoperative and postoperative examinations. Three of 5 patients, who accepted to be reexamined 12–30 months later, seemed to suffer from long‐lasting memory deficit. The 10 deteriorated patients differed statistically significantly from the others in several demographic variables, of which some indicated anaesthetic drug sensitivity. But, there was also a statistical relation with surgical variables. However, there will be no strong conclusions drawn from these post hoc findings. They will only serve as starting points for further investigations beyond the scope of this thesis.In another group of patients, admitted for hysterectomy, in which strict normotension was kept peroperatively, 4 out of 19 (21%) presented moderately pathological CSF‐AK results.Positron emission tomography (PET) was used to measure regional cerebral oxygenation and blood flow in Rhesus monkeys kept hypotensive with isoflurane or propofol. A previously known difference in blood flow pattern was confirmed. The cerebral blood flow was regionally uneven, and the metabolism‐flow relationship was uncoupled in isoflurane anaesthesia, while with propofol it was regionally uniform and with intact metabolism‐flow coupling. However, no hypoxia was detected in this limited study.The clinical benefits of induced hypotension were found doubtful in orthognathic surgery in terms of blood loss reduction, increased quality of the surgical field, reduction of surgical time and the final surgical result.In conclusion, adverse effects on the brain were found, using a sensitive biochemical method and a battery of standard psychometric examinations. Arterial hypotension was not shown to have a direct causal relationship to the adverse effects found, and therefore further efforts have to be made in order to find and eliminate the causal mechanism(s). No obvious benefits of the hypotensive technique were demonstrated in connection with orthognathic surgery.