A GDP strategy is effective in reducing AKIN stage 1 AKI. Further studies are needed to define perfusion interventions that may reduce more severe levels of renal injury (AKIN stage 2 or 3).

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The QT interval occupies a pivotal role in drug development as a surface biomarker of ventricular repolarization. The electrophysiologic substrate for QT prolongation coupled with reports of non-cardiac drugs producing lethal arrhythmias captured worldwide attention from government regulators eventuating in a series of guidance documents that require virtually all new chemical compounds to undergo rigorous preclinical and clinical testing to profile their QT liability. While prolongation or shortening of the QT interval may herald the appearance of serious cardiac arrhythmias, the positive predictive value of an abnormal QT measurement for these arrhythmias is modest, especially in the absence of confounding clinical features or a congenital predisposition that increases the risk of syncope and sudden death. Consequently, there has been a paradigm shift to assess a compound’s cardiac risk of arrhythmias centered on a mechanistic approach to arrhythmogenesis rather than focusing solely on the QT interval. This entails both robust preclinical and clinical assays along with the emergence of concentration QT modeling as a primary analysis tool to determine whether delayed ventricular repolarization is present. The purpose of this review is to provide a comprehensive understanding of the QT interval and highlight its central role in early drug development.

Day-case anaesthesia requires rapidly eliminated anaesthetics which are relatively expensive. This multinational, multicentre European study assessed the relative costs of propofol or sevoflurane anaesthesia in 211 patients. Anaesthesia was induced and maintained with propofol in group 1, with propofol and sevoflurane in group 2, and with sevoflurane in group 3. Drug and delivery costs were calculated in US$. Induction of anaesthesia was fastest in groups 1 and 2, although spontaneous ventilation resumed earliest in group 3. Emergence times and times at which patients were fit for discharge were similar in all groups. Group 2 had the lowest costs based on actual drug use (mean $14.2 (SEM 0.8) vs $18.7 (0.8) and $17.3 (0.8) in groups 1 and 3, respectively). Anaesthetic drug wastage and disposable costs were highest in group 1 and lowest in group 3. Consequently, total costs were highest in group 1 ($31.9 (0.9)) compared with groups 2 ($19.7 (0.9)) and 3 ($18.8 (0.9)). Although we observed increased nausea and vomiting in groups 2 and 3 and reduced patient satisfaction in group 3, these differences should be balanced against the greater cost of propofol anaesthesia.

SummaryEight patients were given a propofol infusion until they no longer responded to loud verbal stimuli, a sedation score of two (modified Observer Assessment of Alertness and Sedation Scale). After receiving 15 mg of intravenous epinephrine, changes in sedation score and bispectral index (BIS) were observed. Mean pulse rate increased from 68 to 96 (SD 10) beat.min 21 , mean blood pressure increased from 107/60 (SD 10/8) mmHg to 140/70 (SD 27/14) mmHg, and mean BIS level rose from 63 to 76 (p , 0.005). Sedation scores increased in six of the eight patients. Exogenous catecholamines seem to have an arousal effect on lightly anaesthetised patients. This could be due to changes in neurotransmitter levels in the brain, or due to the effects consequent on increased cardiac output.