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Anaesthesia is extensively used worldwide and in Denmark alone more than 400,000 anaesthesias are performed each year. In spite of that the molecularly mechanism of anaesthesia has not been proven. Hypotheses have been suggested (lipid versus protein theory), but none has yet been able to explain the whole mechanism. Molecular targets for volatile anaesthetics (e.g. potassium and calcium channels) affected areas in the central nervous system and the impact on the cerebral metabolism versus the cerebral blood flow are discussed.

Erythropoietin (EPO) is a cytokine which is commonly associated with its central role in erythropoiesis. The clinical applications of the recombinant hormone are currently restricted to the treatment of anemia in renal failure and cancer. Recent studies, however, have suggested a new role for EPO as an anti-inflammatory and neuroprotective drug. EPO and its receptor are expressed in neurons, glial cells and brain capillary endothelial cells, and the system is upregulated in conditions of cerebral ischaemia and hypoxia. Animal studies have now established that intracerebroventricular administration of recombinant EPO exerts neuroprotection in models of stroke. The mechanisms appear to involve an upregulation of specific anti-apoptotic and anti-inflammatory pathways. In addition, neurotrophic and angiogenetic effects of EPO may contribute in a long latency protection. Interestingly, also systemic administration of recombinant EPO ameliorates neuronal damage after brain ischaemia, and prevents the loss of autoregulation of cerebral blood flow following experimental subarachnoid haemorrhage. Recombinant human EPO is a safe and non-toxic drug, and clinical studies are currently investigating the neuroprotective potential of EPO in humans.

Non-steroidal anti-inflammatory drugs (NSAID) are now commonly used in the treatment of postoperative pain. In normovolaemic conditions, prostaglandins do not seem to play a substantial role in maintaining renal function. However, numerous studies have shown that during activation of vasoconstrictor systems the synthesis of renal prostaglandins counteracts the vasoconstrictor effects and thereby maintains renal function. In animals, renal blood flow and GFR are markedly decreased when an NSAID is administered in the presence of renal hypoperfusion. Major surgery decreases renal function secondary to stimulation of the adrenosympathetic system and the renin-angiotensin system, and it has previously been demonstrated that maintenance of renal blood flow during laparotomy in dogs depends on an intact prostaglandin synthesis. Perioperative effects of NSAIDs are only sparsely investigated in humans, and studies on the effect on renal haemodynamics have not been presented. As in unanaesthetized volunteers, NSAID have been found to decrease the postoperative excretion of water, sodium and potassium. It therefore still remains unclarified whether general anaesthesia and surgery increase the risk of renal side effects of NSAIDs. Because of the potential risk of peri- and postoperative complications that may further deteriorate renal function, NSAIDs should not be used preoperatively, and not in patients in unstable haemodynamic states.

Dopamine is an endogenic catecholamine which, in addition to being the direct precursor of noradrenaline, has also an effect on peripheral dopaminergic receptors. These are localized mainly in the heart, splanchnic nerves and the kidneys. Dopamine is produced in the kidneys and the renal metabolism is closely associated with the renal treatment of water and salt but the mechanism is not yet elucidated. In low doses (1-5 micrograms/kg/min), dopamine increases renal blood flow (RBF) and the glomerular filtration rate (GFR). In addition, pronounced diuretic and natriuretic effects are observed which are possible not exclusively secondary to alterations in the renal haemodynamics but may also be due to specific tubular effects. Recent investigations have revealed that dopamine does not increase RBF and GFR in patients with chronic renal failure if GFR is less than 60 ml/minute. Dopamine in low doses is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render dialysis unnecessary in a number of patients on account of increased diuresis and natriuresis. The effect of GFR and the significance for the prognosis are not known.

Cimetidine lowers secretion of creatinine in the renal tubuli in healthy individuals and persons with chronic renal disease. The conditions in patients with renal transplants have hitherto been unknown. The renal clearance of endogenic creatinine (CKrea) was investigated prior to and after an intravenous bolus injektion of cimetidine (5 mg/kg) in nine patients with renal transplants. The rate of glomerular filtration (GFR) was determined by clearance investigation of 125I-thalamate (CTh). CKrea fell 29% from 65 ml/min (median) to 46 ml/min (p less than 0.01), whereas GFR remained unchanged. The fractionated creatinine clearance (CKrea/CTh) fell therefore from 1.43 (median) to 1.03 (p less than 0.01). It is concluded that cimetidine reduces creatinine secretion in patients with renal transplants and this should be borne in mind when the function of the graft is assessed solely with CKrea.

Beta-2-microglobulin (beta 2M) is a low-molecular protein which is filtered freely over the glomeruli. Under normal circumstances, more than 99.9% is resorbed in the proximal tubuli of the kidneys and is metabolized there. In renal disease with damage to this segment of the nephron, eg acute tubulo-interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant diseases and reflects the size of the tumour mass. During cytostatic treatment of myelomatosis and chronic lymphatic leukaemia, the serum-beta 2M levels decrease on remission and increase on relapse. In acute leukaemia and malignant lymphoma with infiltration of the CNS, similar conditions prevail for CSF-beta 2M. beta 2M is a sensitive but non-specific parameter in inflammation and infection. Determination of beta 2M in saliva has been found to be of value in Sjögren's syndrome. In HIV-positive patients, a high serum-beta 2M level is a poor prognostic sign. Determinations of CSF-beta 2M in AIDS patients must be presumed to be of value not only in the diagnosis of cerebral AIDS and other (latent) CNS infections but also to demonstrate complicating cerebral malignant lymphomata at an early stage.