Effect of intraoperative fluid optimisation on renal function in patients undergoing emergency abdominal surgery: a randomised controlled pilot study (ISRCTN 11799696).

BACKGROUND: Emergency abdominal surgery carries a high risk of postoperative morbidity and mortality. Goal directed therapy has been advocated to improve outcome in high-risk surgery. The aim of the present pilot study was to examine the effect of goal directed therapy using fluid alone on postoperative renal function and organ failure score in patients undergoing emergency abdominal surgery. METHODS: This prospective randomised pilot study included patients over the age of 50 undergoing emergency abdominal surgery. In the intervention group pulse pressure variation measurements were used to guide fluid boluses of 6% Hydroxyethylstarch 130/0.4. The control group received standard care. Serum urea, creatinine and cystatin C levels were measured prior to and at the end of surgery and postoperatively on day 1, day 3 and day 5. RESULTS: Thirty patients were recruited. One patient died prior to surgery and was excluded from the analysis. The intervention group received a median of 750 ml of hydroxyethylstarch. The peak values of postoperative urea were 6.9 (2.7-31.8) vs. 6.4 (3.5-11.5)mmol/l (p=0.425), creatinine 100 (60-300) vs. 85 (65-150) micromol/l (p=0.085) and cystatin C 1.09 (0.66-4.94) vs. 1.01 (0.33-2.29)mg/dl (p=0.352) in the control and intervention group, respectively. CONCLUSIONS: In the present pilot study replacing the identified fluid deficit was not associated with a change in renal function. These results do not preclude that goal directed therapy using fluid alone may have an effect on renal function but they would suggest that the effect size of fluid optimisation alone on renal function is small.

Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury.

Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal axolemma. By 4 h, there was novel labeling for Ca-ATPase membrane pump activity at the same site. There was loss of IMPs from the nodal axolemma extending over several hours after injury. There was loss of both membrane pump Ca-ATPase and p-nitro-phenylphosphatase (p-NPPase) activity of the node. There was loss of ecto-Ca-ATPase activity but increased labeling for p-NPPase activity at sites of dissociation of compacted myelin. Quantitative freeze-fracture demonstrated statistically significant changes in membrane structure. We provide support for the hypothesis that structural and functional changes occur in the axolemma and myelin sheath at nondisruptive axonal injury.

Cytochemical evidence for redistribution of membrane pump calcium-ATPase and ecto-Ca-ATPase activity, and calcium influx in myelinated nerve fibres of the optic nerve after stretch injury.

There has been controversy for some time as to whether a posttraumatic influx of calcium ions occurs in stretch/nondisruptively injured axons within the central nervous system in both human diffuse axonal injury and a variety of models of such injury. We have used the oxalate/pyroantimonate technique to provide cytochemical evidence in support of such an ionic influx after focal axonal injury to normoxic guinea pig optic nerve axons, a model for human diffuse axonal injury. We present evidence for morphological changes within 15 min of injury where aggregates of pyroantimonate precipitate occur in nodal blebs at nodes of Ranvier, in focal swellings within axonal mitochondria, and at localized sites of separation of myelin lamellae. In parallel with these studies, we have used cytochemical techniques for localization of membrane pump Ca(2+)-ATPase and ecto-Ca-ATPase activity. There is loss of labelling for membrane pump Ca(2+)-ATPase activity on the nodal axolemma, together with loss of ecto-Ca-ATPase from the external aspect of the myelin sheath at sites of focal separation of myelin lamellae. Disruption of myelin lamellae and loss of ecto-Ca-ATPase activity becomes widespread between 1 and 4 h after injury. This is correlated with both infolding and retraction of the axolemma from the internal aspect of the myelin sheath to form periaxonal spaces which are characterized by aggregates of pyroantimonate precipitate, and the development of myelin intrusions into invaginations of the axolemma such that the regular profile of the axon is lost. There is novel labelling of membrane pump Ca(2+)-ATPase on the cytoplasmic aspect of the internodal axolemma between 1 and 4 h after injury. There is loss of an organized axonal cytoskeleton in a proportion of nerve fibres by 4-6 h after injury. We suggest that these changes demonstrate a progressive pathology linked to calcium ion influx after stretch (non-disruptive) axonal injury to optic nerve myelinated fibres. We posit that calcium influx, linked to or correlated with changes in Ca(2+)-ATPase activities, results in dissolution of the axonal cytoskeleton and axotomy between 4 and 6 h after the initial insult to axons.