Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial.

BACKGROUND: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation. METHODS: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality. RESULTS: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01). CONCLUSIONS: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.

A Different Approach to Dependence Analysis.

This article focuses on a statistical tool for dependence analysis in scientific research. Starting from a recent index of concordance for a multiple linear regression model, a coefficient suitable in catching any monotonic dependence relationship between a dependent variable and an independent variable is derived and discussed. Given its interpretation in terms of monotonic dependence, it is called monotonic dependence coefficient (MDC). It is appropriate to all contexts where the dependent variable is quantitative (continuous or discrete) and the independent variable is at least of ordinal nature; tied data are also allowed. MDC's adequacy is validated through Monte Carlo simulations led by taking into account different scenarios of dependence. Finally, an application to real data is provided to stress MDC's capability of detecting dependence relationships between two variables, even if some pieces of information about original data are lost.

Simulating Ordinal Data.

The increasing use of ordinal variables in different fields has led to the introduction of new statistical methods for their analysis. The performance of these methods needs to be investigated under a number of experimental conditions. Procedures to simulate from ordinal variables are then required. In this article, we deal with simulation from multivariate ordinal random variables. We propose a new procedure for generating samples from ordinal random variables with a prespecified correlation matrix and marginal distributions. Its features are examined and compared with those of its main competitors. A software implementation in R is also provided along with examples of its application.

Thyroid dysfunction in women with systemic sclerosis.

Hypothyroidism has been frequently reported in systemic sclerosis (SSc), but whether SSc itself increases the risk of thyroid dysfunction is still controversial. The aim of the present study was to determine whether routine thyroid function screening in SSc should be warranted. Serum levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone, and the presence of thyroid-specific autoantibodies (antithyroid peroxidase and antithyreoglobulin) were measured in 79 women with SSc and 81 age-matched women with osteoarthritis (OA) serving as controls. Hyperthyroidism was found in 2 of 79 (2.5%) SSc and in 4 of 81 (5%) OA cases. Hypothyroidism was found in 16 of 79 (20%) patients with SSc (subclinical in 14/16 cases) and in 9 of 81 (11%) patients with OA (subclinical in all cases; P = 0.131). Antithyreoglobulin antibodies were present in 14% versus 13% patients (SSc versus OA, P = NS), whereas antithyroid peroxidase antibodies were present in 23% versus 11% patients (SSc versus OA, P = 0.057). The risk of hypothyroidism was significantly higher in antithyroid peroxidase-positive patients (P < 0.0001), irrespective of the primary diagnosis, and greater in women with OA (OR = 24.6, 95% CI 4.3-141.9, P < 0.0001) than SSc (OR = 4.2, 95% CI 1.2-14.3, P = 0.035). SSc is not independently associated with an increased risk of thyroid dysfunction, but antithyroid peroxidase antibodies may identify a subset of patients at risk of developing thyroid dysfunction.