With the recently approved IEC 61511 and ANSI/ISA‐84.00.01 standards, process industry companies are being challenged to determine the level of performance required from their safety instrumented functions (SIF) and to verify that the design, installation, operation, and maintenance employed is sufficient to ensure that the required performance is sustained until the SIF is decommissioned. As a practical matter, user companies must self‐certify or user approve their SIF equipment, since they are responsible for the correct operation of the SIF in the operating environment, not just individual components as manufactured. To accomplish this, user companies need lifecycle assistance from equipment manufacturers, irrespective of hardware or software certification status related to IEC 61508. One of the best means to communicate the necessary information is via a safety manual for those involved in instrument system design installation and operation. IEC 61508 requires that equipment manufacturers provide a safety manual with any product claimed to comply with IEC 61508. Although required for product certification, it is the authors' current experience that quality and consistency in safety manuals is lacking. Part of this is due to IEC 61508 not providing a clear concise template with minimum requirements. The safety manual requirements are scattered throughout the rather complex standard. This article seeks to provide a user's perspective of what essential information is needed from equipment manufacturers to not only comply with IEC 61508, but also to provide enough information to the user of the product to allow the essential balance of reliability and safety in both SIF and instrumented protective function applications. © 2007 American Institute of Chemical Engineers Process Saf Prog 2007

Endogenous release of epinephrine after stress as well as exogenous epinephrine infusion are known to result in impaired glucose tolerance. Previous studies of man and animals have demonstrated that this effect of epinephrine results from inhibition of insulin secretion and augmentation of hepatic glucose production. However, the effect of epinephrine on tissue sensitivity to insulin, and the relative contributions of peripheral vs. hepatic resistance to impaired insulin action, have not been defined. Nine young normal-weight subjects were studied with the insulin clamp technique. Plasma insulin was raised by approximately 100 muU/ml while plasma glucose concentration was maintained at basal levels by a variable glucose infusion. Under these conditions of euglycemia, the amount of glucose metabolized equals the glucose infusion rate and is a measure of tissue sensitivity to insulin. Subjects received four studies: (a) insulin (42.6 mU/m(2).min), (b) insulin plus epinephrine (0.05 mug/kg.min), (c) insulin plus epinephrine plus propranolol (1.43 mug/kg.min), and (d) insulin plus propranolol. During insulin administration alone, glucose metabolism averaged 5.49+/-0.58 mg/kg.min. When epinephrine was infused with insulin, glucose metabolism fell by 41% to 3.26 mg/kg.min (P < 0.001). After insulin alone, hepatic glucose production declined by 92% to 0.16+/-0.08 mg/kg.min. Addition of epinephrine was associated with a delayed and incomplete suppression of glucose production (P < 0.01) despite plasma insulin levels >100 muU/ml. When propranolol was administered with epinephrine, total glucose metabolism was restored to control values and hepatic glucose production suppressed normally. Propranolol alone had no effect on insulin-mediated glucose metabolism. These results indicate that epinephrine, acting primarily through a beta-adrenergic receptor, markedly impairs tissue sensitivity to an increase in plasma insulin levels, and that this effect results from both peripheral and hepatic resistance to the action of insulin.

We studied the effect of physical training on in vivo tissue sensitivity to insulin and insulin binding to monocytes in six previously untrained healthy adults. Physical training (one hour of cycle-ergometer exercise four times per week for six weeks) failed to alter body weight but resulted in a 20 per cent increase (P less than 0.02) in maximal aerobic power (VO2 max) and a 30 per cent increase (P less than 0.01) in insulin-mediated glucose uptake (determined by the insulin clamp technique). The increase in insulin sensitivity correlated directly with the rise in VO2 max (P less than 0.05). Binding of [125I]insulin to monocytes also rose by 35 per cent after physical training (P less than 0.02), primarily because of an increase in the concentration of insulin receptors. Our data indicate that physical training increases tissue sensitivity to insulin in proportion to the improvement in physical fitness. Physical training may have a role in the management of insulin-resistant states, such as obesity and maturity-onset diabetes, that is independent of its effects on body weight.

Tissue sensitive to insulin and insulin binding to monocytes were evaluated in 15 nonobese maturity-onset diabetics and in 16 healthy controls. Insulin sensitivity was determined by the insulin clamp technique in which the plasma insulin is acutely raised and maintained 100 muU/ml above the fasting level and plasma glucose is held constant at fasting levels by a variable glucose infusion. The amount of glucose infused is a measure of overall tissue sensitivity to insulin. In the diabetic group, the fasting plasma glucose concentration (168+/-4 mg/dl) was 85% greater than controls (P < 0.01) whereas the plasma insulin level (15+/-1 muU/ml) was similar to controls. During the insulin clamp study, comparable plasma insulin levels were achieved in the diabetics (118+/-5) and the controls (114+/-5 muU/ml). However, the glucose infusion rate in the diabetics (4.7+/-0.4 mg/kg.min) was 30% below controls (P < 0.01). Among the diabetics, the glucose infusion rate correlated directly with the fasting plasma glucose level (r = 0.57, P < 0.05). In five diabetic subjects, glucose metabolism was similar to controls, and these diabetics had the highest fasting glucose levels. When they were restudied after prior normalization (with insulin) of the fasting plasma glucose (100+/-1 mg/dl), the glucose infusion rate during the insulin clamp was 30% lower than observed in association with hyperglycemia (P < 0.01). Studies that employed tritiated glucose to measure endogenous glucose production indicated comparable 90-95% inhibition of hepatic glucose production during hyperinsulinemia in the diabetic and control subjects.(125)I-insulin binding to monocytes in the diabetics (5.5+/-0.6%) was 30% below that in controls (P < 0.01). Insulin binding to monocytes and insulin action as determined with the insulin clamp were highly correlated in both control (r = 0.67, P < 0.01), and diabetic subjects (r = 0.88, P < 0.001). We conclude that (a) tissue sensitivity to physiologic hyperinsulinemia is reduced in most maturity-onset diabetics; (b) this decrease in sensitivity is located, at least in part, in extrahepatic tissues; (c) the resistance to insulin may be mediated by a reduction in insulin binding; and (d) in maturity-onset diabetics with normal tissue sensitivity to insulin, hyperglycemia may be a contributing factor to the normal rates of insulin-mediated glucose uptake.