Use of microalbuminuria as a predictor of outcome in critically ill patients.

We have investigated the use of microalbuminuria as a predictor of outcome in a pilot study involving 50 critically ill patients in a six-bed hospital intensive care unit (ICU). Urinary microalbumin:creatinine (M:Cr) ratios measured only 6 h after admission to the ICU demonstrated a significant difference (P = 0.01) between survivors and non-survivors, allowing rapid identification of patients at increased risk of developing organ failure and at greater risk of death. This work suggests that earlier identification of these patients using a rapid, simple, inexpensive biochemical test is possible; if confirmed in a larger study, it may be that clinical interventions can be targeted at those most likely to benefit.

Measures of total free radical activity in critically ill patients.

OBJECTIVES: To examine the role played by free radicals during the initial phase of critical illness in patients on an Intensive Care Unit (ICU). DESIGN AND METHODS: Serum total antioxidant status (TAS) and uric acid (UA) levels were measured in 50 patients over 18 hours to represent the initial stage of critical illness. Clinical scoring systems (APACHE II and multiple organ dysfunction scores) were used to assess the degree of organ dysfunction. Outcome was assessed according to patient survival (survivors, n = 36; non-survivors, n = 14). RESULTS: Serum TAS was higher in non-survivors; a similar finding was demonstrated for serum UA. Levels of both biochemical markers were associated with the degree of organ function and with higher antioxidant and UA levels present in patients with more severe organ dysfunction. In addition, serum UA was significantly correlated to serum TAS and probably accounted for much of the antioxidant activity observed. CONCLUSIONS: The increased TAS and UA levels observed may simply be a response to the degree of renal dysfunction observed as those patients with worse renal function had higher TAS and UA levels. In conclusion, measurement of serum TAS appears to be a reflection of UA concentration and results should be interpreted with caution particularly in patients who have renal dysfunction.

The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients.

OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) when given as an early treatment to critically ill patients on the serum total anti-oxidant potential (TAP) and urine micro-albumin:creatinine (M:Cr) ratio. DESIGN: Prospective, placebo controlled double blinded clinical trial. SETTING: General intensive care unit in a teaching hospital. PATIENTS: Sixty critically ill patients were recruited but ten were withdrawn due to less than 48 h of ICU stay. INTERVENTIONS: After envelope randomisation, patients received either NAC (n = 23): a bolus of 150 mg/kg in 250 ml of 5% dextrose followed by a continuous infusion of 12 mg/kg per h in 500 ml of 5% dextrose over 24 h or, as controls (n = 27), the equal volume of placebo. Treatment lasted for a minimum of 3, up to a maximum of 5, days. Blood and urine samples were collected on admission (0 h) and then 6 hourly up 18 h. MEASUREMENTS AND RESULTS: There was no significant difference between NAC and placebo groups regarding the required length of inotropic support, mechanical ventilation and ICU stay. There was no significant difference in TAP or M:Cr ratio over 18 h or between the groups. CONCLUSIONS: Our results suggest that NAC had no significant effects on the progress of the TAP and the urinary albumin excretion in our patients, which may suggest that NAC at the given dose has no clinical relevance as an early treatment in the critically ill.

Hepatic inactivation of Leu-enkephalin.

Leu-enkephalin radiolabelled at the N-terminal tyrosine by two different methods was presented to isolated perfused rat livers. Approximately 10% of a pulse of tritiated Leu-enkephalin was taken up first-pass; this was increased to 62% when the peptide was iodinated with Bolton and Hunter reagent. Uptake of both forms of radiolabelled Leu-enkephalin was inhibited by taurocholate in a concentration-dependent manner. The proportion of internalised radioactivity secreted into bile also differed but in both cases showed a very rapid time-course similar to that of [24-(14)C]taurocholate and suggestive of non-endocytic transfer via membrane transport proteins. Pre-perfusion with the aminopeptidase inhibitor bestatin increased uptake of 3H-labelled Leu-enkephalin from 10% to 23%; no further increase occurred when the endopeptidase 24.11 inhibitor thiorphan was also present. On infusion of the native peptide into rat livers, 80% of Leu-enkephalin immunoreactivity was lost between the pre- and post-hepatic perfusate; this was reduced to 65% in the presence of 10(-5) M bestatin. The almost total release of the N-terminal tyrosine from 3H-labelled Leu-enkephalin which escaped first-pass uptake confirmed that substantial sinusoidal metabolism had occurred. Low levels of aminopeptidase N were visualised in the sinusoidal membrane using a specific monoclonal antibody coupled to peroxidase staining. Thus, hepatic inactivation of Leu-enkephalin is primarily via hydrolysis mediated by cell surface peptidase (including aminopeptidases) whilst uptake of the intact peptide, probably by a bile salt transport protein, is quantitatively minor unless the N-terminus is blocked by Bolton and Hunter reagent or peptidase inhibitors are present.