Independent sector and peri-operative cardiac arrest as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest including those that occurred in the independent healthcare sector, which provides around 1 in 6 NHS-funded care episodes. In total, 174 (39%) of 442 independent hospitals contacted agreed to participate. A survey examining provider preparedness for cardiac arrest had a response rate of 23 (13%), preventing useful analysis. An activity survey with 1912 responses (from a maximum of 45% of participating hospitals) showed that, compared with the NHS caseload, the independent sector caseload was less comorbid, with fewer patients at the extremes of age or who were severely obese, and with a large proportion of elective orthopaedic surgery undertaken during weekday working hours. The survey suggested suboptimal compliance rates with monitoring recommendations. Seventeen reports of independent sector peri-operative cardiac arrest comprised 2% of NAP7 reports and underreporting is likely. These patients were lower risk than NHS cases, reflecting the sector's case mix, but included cases of haemorrhage, anaphylaxis, cardiac arrhythmia and pulmonary embolus. Good and poor quality care were seen, the latter including delayed recognition and treatment of patient deterioration, and poor care delivery. Independent sector outcomes were similar to those in the NHS, though due to the case mix, improved outcomes might be anticipated. Assessment of quality of care was less often favourable for independent sector reports than NHS reports, though assessments were often uncertain, reflecting poor quality reports. Overall, NAP7 is unable to determine whether peri-operative care relating to cardiac arrest is more, equally or less safe than in the NHS.

Dexamethasone-induced impairment in skeletal muscle glucose transport is not reversed by inhibition of free fatty acid oxidation.

Our previous studies suggested a possible role for the glucose-free fatty acid (FFA) cycle, ie, preferential utilization of FFA by muscle at the expense of glucose, in dexamethasone (DEX)-induced insulin resistance. To determine whether this resistance could be reversed by inhibiting FFA utilization, we used etomoxir, a potent inhibitor of mitochondrial FFA oxidation. Male Sprague-Dawley rats were injected subcutaneously with 1 mg/kg DEX or the vehicle every other day for 10 days, and half of each group was administered 10 mg/kg etomoxir by gavage once per day and 1 hour before the experiment. As expected, etomoxir treatment increased serum FFA levels and inhibited FFA oxidation by diaphragm in vitro. Administration of etomoxir decreased serum glucose and insulin concentrations under basal conditions in both control and DEX-treated animals, implying enhanced insulin sensitivity. DEX treatment significantly increased endogenous glucose production and decreased whole-body glucose disposal, as well as 2-deoxyglucose (2-DG) uptake by skeletal muscle during euglycemic-hyperinsulinemic clamps. Administration of etomoxir led to small but significant increases in glucose disposal rates of both control (14%) and DEX (23%) groups, but had no effect on residual endogenous glucose production. Thus, DEX-induced insulin resistance was marginally ameliorated but not completely reversed by etomoxir. Depressed 2-DG uptake by individual muscle tissues observed in the present study in conjunction with the absence of free intracellular glucose in muscle tissue following glucose-insulin infusion strongly suggests that the primary defect in glucose metabolism is at the level of transport. Neither overall abundance of the insulin-sensitive glucose transporter (GLUT-4) in skeletal muscle nor its distribution between intracellular stores and plasma membrane were modified by DEX treatment, either, under basal conditions or in response to acute insulin stimulus. These results suggest a defect(s) in the inherent activity of plasma membrane-bound GLUT-4 as the likely mechanism for DEX-induced insulin resistance.

Impaired glucose transport in skeletal muscle but normal GLUT-4 tissue distribution in glucose-infused rats.

This study was undertaken to determine if glucose toxicity in normal rats caused decreased whole body insulin-stimulated glucose disposal and in vivo impaired muscle glucose transport and, if so, whether it was mediated by changes in GLUT-4 content or tissue distribution. Rats were infused with 50% dextrose for 48 h after which they were clamped and injected with 2-deoxy-D-[3H]glucose. Hindlimb muscles were removed for measurement of uptake of radioactivity (glucose transport) and GLUT-4 levels in total, plasma and internal membrane fractions. Dextrose infusions caused significant hyperglycemia [15.5 +/- 1.4 vs. 6.7 +/- 0.3 (SE) mM], hyperinsulinemia [678 +/- 108 vs. 168 +/- 42 (SE) pM], and depressed insulin-mediated whole body glucose disposal [12.8 +/- 2.0 vs. 47.0 +/- 10.6 (SE) mg glucose.kg-1.min-1.pmol insulin-1.1(-1) x 10(3)]. Muscle glucose transport (ng.min-1.mg tissue-1) was significantly decreased in biceps (4.0 +/- 0.6 vs. 13.4 +/- 2.5), gastrocnemius (4.6 +/- 1.1 vs. 12.9 +/- 2.2), and plantaris (5.5 +/- 0.7 vs. 17.5 +/- 3.6) muscles compared with saline-infused rats. The difference in the soleus muscle (13.2 +/- 1.6 vs. 19.4 +/- 2.7) did not quite reach statistical significance. There were no differences in total, plasma, or internal membrane GLUT-4 content between the two groups. It is concluded that glucose toxicity causes impaired insulin-stimulated glucose transport, probably due to decreased activity of GLUT-4.