Methylthioninium chloride: pharmacology and clinical applications with special emphasis on nitric oxide mediated vasodilatory shock during cardiopulmonary bypass.

Vasodilatory shock after cardiopulmonary bypass is a common complication requiring treatment with high doses of inotropes and prolonged stays in the intensive care unit. The vasodilatory shock is initiated by an inflammatory response to the extracorporeal circuit. The inflammatory response results in endothelial synthesis and release of nitric oxide resembling the clinical features observed in vasodilatory shock caused by septicaemia. During vasodilatory shock, the inhibition of nitric oxide synthase and the nitric oxide/cyclic guanylyl monophosphate pathway is an attractive adjunct to therapy with traditional inotropes. Methylthioninium chloride inhibits nitric oxide/cyclic guanylyl monophosphate mediated vasodilation and can successfully be used as a supplement in the treatment of vasodilatory shock associated with cardiopulmonary bypass. The application of methylthioninium chloride in septicaemia has not produced comparable positive clinical results.

Analysis of intensive care populations to select possible candidates for high dependency care.

OBJECTIVES: To identify the proportion, and range across intensive care units, of intensive care patients who might potentially be managed on a high dependency unit (HDU) using three different classification systems. METHODS: 8095 adult patients admitted to 15 intensive care units in the south of England between 1 April 1993 and 31 December 1994 were studied. Patients were identified as potential HDU admissions if their APACHE III derived risk of hospital mortality was < or =10%, if they were categorised as a low risk monitor (LRM) patient using the Wagner risk stratification method, or if they did not require advanced respiratory support (ARS). RESULTS: 4146 patients (51.2%) had an APACHE III derived risk of hospital death of < or =10%, 1687 (20.8%) were classified as LRM, and 3860 (47.7%) did not receive ARS. The values for each intensive care unit ranged from 32.8-63.3% (APACHE III group), 7.2-29.9% (LRM group), and 14.4-68.2% (ARS group). No matter which of the three methods was used, there were significant differences between the 15 units (p<0.0001) with regard to the number of potential HDU patients identified within the scored population. CONCLUSIONS: The percentage of intensive care patients who might be more appropriately managed in a HDU varies considerably between hospitals, and depends upon both local circumstances and the method used to define a high dependency patient. However, whichever method is used, it appears that significant numbers of patients of low dependency status currently fill intensive care beds in the units studied. If these analyses are correct, the perceived national shortage in intensive care beds might be improved by the development of HDUs.

The effect of lead time bias on severity of illness scoring, mortality prediction and standardised mortality ratio in intensive care--a pilot study.

The effect of lead time bias on severity of illness scoring, mortality prediction and standardised mortality ratios was examined in a pilot study of 76 intensive care (ICU) patients using APACHE II, APACHE III and SAPS II scoring systems. The inclusion of data collected in the period prior to ICU admission increased severity of illness scores and estimated risk of hospital mortality significantly for all three scoring systems (p < 0.01) by up to 14 points and 42.7% (APACHE II), 50 points and 26.3% (APACHE III) and 23 points and 33.4% (SAPS II), respectively. Standardised mortality ratios fell from 0.99 to 0.79 (APACHE II), 0.96 to 0.84 (APACHE III) and 0.75 to 0.64 (SAPS II), but these changes failed to reach statistical significance. Lead time bias had most effect in medical patients and on emergency admissions, and least effect in patients admitted from the operating theatre. These trends suggest that mortality ratios may not necessarily reflect intensive care unit performance and indicate that a larger study of the effect of lead time bias, case mix, pre-ICU care or post-ICU management on standardised mortality ratios is indicated.

Gallbladder function and fasting enterogastric bile reflux.

The relationship between gallbladder function and duodenogastric reflux of bile has been investigated in the fasting phase by 99Tcm-EHIDA biliary scintigraphy in 370 patients with abdominal pain. This isotope is cleared from the blood-pool by hepatocellular function and is excreted into the biliary tract. Obstruction of the common bile duct was found in 79 patients, leaving 291 who were evaluable for duodenogastric bile reflux. Gallblader function was present in 169 and absent in 122 patients. Duodenogastric reflux of bile was observed in 82 patients, 10 of whom had had previous gastric surgery. Only 298 of 169 (17%) patients with a functioning gallbladder showed evidence of enterogastric bile reflux compared to 43 of 122 (35%) with absent gallbladder function (p less than 0.005 by Chi Square). These results suggest that continuous bile flow into the duodenum in the absence of a functioning gallbladder facilitates duodenogastric reflux.

Polymorphonuclear leucocyte chemotaxis in response to leukotriene B4 in treated and untreated psoriatics.

Various chemoattractants have been implicated in the aetiology of the polymorphonuclear leucocyte (PMN) migration into the epidermis seen in early lesions of psoriasis. Using an under-agarose technique, the in vitro chemotactic responses of PMN to the arachidonic acid lipoxygenase product leukotriene B4 (LTB4) were assayed in five groups of subjects: normal healthy volunteers (n = 12), untreated psoriatics (n = 11) and psoriatics treated with topical tar (n = 12), PUVA (n = 11) and UVB phototherapy (n = 10). No significant difference was observed between the responses of control subjects and of untreated psoriatics, nor between the untreated psoriatic group and the PUVA- and UVB-treated groups, respectively. However, comparison of the tar-treated and untreated groups revealed a significantly increased chemotactic response to LTB4 in the tar-treated group (p less than 0.01).

Dapsone and human polymorphonuclear leucocyte chemotaxis in dermatitis herpetiformis.

Polymorphonuclear leucocyte chemotaxis was investigated in 6 patients with active dermatitis herpetiformis in the untreated state and when under control with Dapsone. Control studies were undertaken in 7 healthy volunteers. No significant difference in chemotaxis was demonstrated between the active, treated and control groups. Furthermore, when Dapsone in physiological concentrations was added separately in all three groups there was no additional effect on chemotaxis. These results clearly show that polymorphonuclear leucocytes from active untreated dermatitis herpetiformis have normal chemotactic activity compared with those from the same patients in the treated state and controls. Additional Dapsone did not alter these findings.