Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.

In this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia.

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

Prospective randomized trials are required to investigate this important topic further. Several are currently ongoing. Until the results of these are available for scrutiny, there is currently insufficient evidence to recommend any changes to current clinical practice. Opioids continue to play an important role in the perioperative period.

The standard spinal preparation of bupivacaine contains a high concentration of glucose (80 mg ml(-1)). However, the addition of only a small amount of glucose (8 mg ml(-1)) to plain solutions of bupivacaine results in a solution which, although no more than marginally hyperbaric, produces a more predictable block when used for spinal anaesthesia in non-pregnant patients. However, bupivacaine 5 mg ml(-1) in glucose 8 mg ml(-1) has a density [1.00164 (SD 0.00008) at 37 degrees C] which is relatively greater than that of the cerebrospinal fluid (CSF) of the pregnant patient at term (1.0003 at 37 degrees C) because CSF density decreases during pregnancy. Therefore, a double-blind, randomized, controlled study was carried out to compare intrathecal bupivacaine (glucose 8 mg ml(-1)) with bupivacaine (glucose 80 mg ml(-1)) in 40 pregnant patients at term. Although there was no difference between groups in onset of sensory block, dose of ephedrine or patient satisfaction, patients receiving bupivacaine (5 mg ml(-1)) with glucose (8 mg ml(-1)) had persistently higher sensory blocks between 60 and 120 min after intrathecal injection, suggesting that the spread of spinal solutions in the pregnant patient at term is not dependent on density.

Two groups of 12 patients had a sciatic nerve block performed with 20 ml of either ropivacaine 7.5 mg ml(-1) or bupivacaine 5 mg ml(-1). There was no statistically significant difference in the mean time to onset of complete anaesthesia of the foot or to first request for post-operative analgesia. The quality of the block was the same in each group. Although there was no statistically significant difference in the mean time to peak plasma concentrations the mean peak concentration of ropivacaine was significantly higher than that of bupivacaine. There were no signs of systemic local anaesthetic toxicity in any patient in either group.

Intrathecal drug spreadT HIS year sees the one hundredth anniversary of the first deliberate spinal (i.e., intrathecal) anaesthetic by August Bier in Kiel in Germany. 1 The subsequent century, since this first direct pharmacological assault on the central nervous system, has seen a number of swings in the popularity of the technique. These swings have been associated with (and perhaps driven by) three common themes. On the negative side have been concerns about the risk of neurological damage and frustration at the variability between patients in the effect of a standard injection. Conversely, increased popularity has often been associated with the availability of a new drug preparation. This is certainly relevant to the current popularity which, to a degree at least, stems from the interest there was in evaluating bupivacaine for this purpose in the early 1980s. 2 Other factors include the challenges produced by changes in surgical practice, particularly in elderly patients, and greater understanding of the causes of complications of all kinds. The recent FDA announcement regarding the possible risk of vertebral canal bleeding in association with the use of the new heparin type drugs shows that concerns about safety remain, although they have been explored by a number of authors, s,4However, the topic of this contribution is the more frequent problem: the causes of variability in effect. The problem was recognised from the beginning, even Bier referring to the "lauenhaft" or waywardness of the technique. Since then there has been a progressive, almost exponential growth of research in this field, but a clear understanding of the mechanism(s) of spread of drugs through the subarachnoid space has remained elusive. The variability between patients relates to both extent and duration of block, and occurs even when technically identical injection techniques are used. The search to identify and control the factors influencing this variability began shortly after Bier's pioneering work. Barker, a London based surgeon, was the first to examine the problem systematically using a glass model of the spinal column as well as clinical observation, s-7 He deduced that gravity and the curves of the vertebral column could be used to influence the spread of a solution with a density which differed from that of cerebrospinal fluid. As a result he devised a solution that was hyperbaric and could be used with predictable effects. Babcock, meanwhile, took the opposite approach using a solution that was less dense than cerebrospinal fluid so that it would "float. ''sSince then a huge amount of information has been generated, allowing Greene to identify, in a major review, 25 factors that affect spread of a solution through the CSF. 9 This is a daunting prospect for the clinician trying to develop a technique, particularly because there are still some unknowns. However, two papers in this issue add some useful information to our knowledge of the CSF and local anaesthetic components of the equation. The latter, at least, is under our ...

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