Marsh, Herbert W.

Abstract The sections in this article are: Effects of Anesthesia on the Chest Wall Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Effects of Anesthesia on FRC Effects of Anesthesia on Pressure‐Volume Relationships Total Respiratory System Lungs Chest Wall Mechanisms for Changes in Pressure‐ Volume Relationships Effects of Anesthesia on Pressure‐Flow Relationships Effects of Anesthesia on Intrapulmonary Inspired‐Gas Distribution Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Conclusions

The use of a differential quantitative blood culture technique (Isolator) to diagnose intravascular-device-related bacteremia (IDRB) was studied prospectively. During septic episodes in 44 patients, blood was obtained simultaneously through the suspected infected device and from a peripheral venipuncture. The blood samples were processed by the Isolator technique, which enables easy quantification of microorganisms. The cannula was removed, and its tip was cultured semiquantitatively. Of the 52 cannulas studied, 15 were the cause of IDRB, but only 7 of these showed a significantly higher bacterial count in blood obtained through the device compared with peripheral blood. The bacterial count was higher in blood drawn through the device than in peripheral blood in four of six cases that did not fulfill the definition of IDRB. Some blood cultures obtained through the device were positive despite negative cultures of peripheral blood and cannula tips (six cannulas). Quantitative blood cultures were not useful in diagnosing IDRB in this study.

Pyridostigmine without atropine, pyridostigmine with atropine or neostigmine with atropine were used to antagonise neuro-muscular blockade induced by d-tubocurarine in forty otherwise healthy, female patients recovering from gynaecological surgery. Pulse rates fell significantly (P < 0.01 control heart rate 72 ± 18 beats/min (M ± SD) to 55 ± 13 beats/min) at ten minutes after pyridostigmine (10 mg/70 kg), necessitating administration of atropine (1.25 mg/70 kg) by fifteen minutes after pyridostigmine. After an initial rise in rate, pulse rates also fell significantly (P < 0 01 control heart rate 70 ± 12 beats/min to 44 ± 11 beats/min) at fifteen minutes after injection of neostigmine (2.5 mg/70 kg) with atropine (1.25 mg/70 kg) By contrast when pyrdostigmine and atropine were used together, pulse rates rose and then fell, but mean values never fell below control during a twenty-minute observation period. It was concluded that pyridostigmine should not be given alone, but requires the use of atropine to prevent bradycardia. This combination may, however, provide a more stable heart rate than that seen with neostigmine and atropine in usual doses, when these drugs are used to antagonise d-tubocurarine.

High-dose glucocorticoid treatment results in protein wasting. To determine whether such therapy affects leucine oxidation in the postabsorptive state and the disposal of dietary amino acids, eight normal subjects were studied twice in random order, once after 5 days of prednisone (20 mg three times daily) and on a second occasion without prednisone as a control. In the postabsorptive state prednisone therapy increased (P less than 0.05) plasma concentrations of leucine, alpha-ketoisocaproate, glucose, insulin, and C-peptide, as well as leucine carbon flux and oxidation calculated by means of isotope dilution techniques and [1-13C]leucine. During infusion of a chemically defined meal, total leucine carbon flux and oxidation increased similarly on both study days, but leucine oxidation was greater (P less than 0.01) during prednisone treatment; net leucine balance became positive on the control day but remained negative or zero on the prednisone study day despite higher (P less than 0.05) plasma insulin concentrations. These studies demonstrate that high-dose glucocorticoid treatment impairs the balance of the essential amino acid leucine in both the postabsorptive and absorptive states in humans.

Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg · kg−1 · day−1), prednisone (0.8 mg · kg−1 · day−1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P &lt; 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 ± 57 pmol/ml, P &lt; 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 ± 2.1 mM, P &lt; 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 ± 72 and 564 ± 65 pmol/ml, respectively, P &lt; 0.001) compared with placebo (226 ± 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 ± 54 pmol/ml, P &lt; 0.01). Protein oxidation ([14C]leucine) increased (P &lt; 0.001) with prednisone therapy, decreased (P &lt; 0.001) with rhGH treatment, and was normal during the combined treatment. By indirect calorimetry, glucose oxidation was similar in all groups; fasting fat oxidation was decreased by prednisone (P &lt; 0.001) and increased by rhGH, although only significantly in the fed state (P &lt; 0.01). In summary, insulin antagonism of rhGH and prednisone are probably caused by independent mechanisms in which rhGH and prednisone may reciprocally regulate the oxidation of protein and fat while decreasing the efficiency of glucose disposal.

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 ± 1 vs. 14 ± 2 g) and postprandial hepatic glucose release (51 ± 5 vs. 24 ± 3 g) were greater (P &lt; .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 ± 2 vs. 35 ± 5%), the absolute rate was greater in the diabetic patients (13 ± 1 vs. 8 ± 1 g; P &lt; .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P &lt; .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 ± 22 to 144 ± 21 mg/dl; P &lt; .01) and integrated postprandial glycemic response (from 814 ± 68 to 621 ± 72 min · mg· ml−1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P &lt; .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P &lt; .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P &lt; .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance, hepatic glucose release, and new glucose synthesis, as well as extrahepatic substrate metabolism, are altered in NIDDM after ingestion of a mixed meal. Basal insulin supplementation improves but does not normalize postprandial glucose metabolism.