In critically ill patients, it is frequently challenging to identify who will benefit from admission to the intensive care unit and life-sustaining interventions when the chances of a meaningful outcome are unclear. In addition, the acute illness not only affects the patients but also family members or surrogates who often are overwhelmed and unable to make thoughtful decisions. In these circumstances, a time-limited trial (TLT) of intensive care treatment can be helpful. A TLT is an agreement to initiate all necessary treatments or treatments with clearly delineated limitations for a certain period of time to gain a more realistic understanding of the patient's chances of a meaningful recovery or to ascertain the patient's wishes and values. In this article, we discuss current research on different aspects of TLTs in the intensive care unit. We propose how and when to use TLTs, discuss how much time should be taken for a TLT, give an overview of the potential impact of TLTs on healthcare resources, describe ethical challenges concerning TLTs, and discuss how to evaluate a TLT.

Renal denervation (RDN) is a promising novel treatment for resistant hypertension. Effectiveness of treatment is, however, highly variable and unpredictable. Incomplete denervation of the renal nerves is a plausible explanation for the variable blood pressure lowering effect of RDN. Here, we present for the first time a histopathological evaluation of the effects of RDN on perivascular nerves of the renal arteries in a human patient. Our findings potentially have important implications for future directions with RDN.

Chronic elevation of sympathetic nervous system is a key factor in metabolic syndrome. Because renal denervation (RDN) is thought to modulate sympathetic activity, we performed the Denervation of the Renal Arteries in Metabolic Syndrome (DREAMS)–study to investigate the effects of RDN on insulin sensitivity and blood pressure (BP) in patients with metabolic syndrome. Twenty-nine patients fulfilling the criteria for metabolic syndrome and who used a maximum of 1 antihypertensive or 1 antidiabetic drug or 1 of both gave informed consent and were treated by RDN. Glucose tolerance tests and 24-hour ambulatory BP measurements were performed at baseline, at 6 and 12 months of follow-up. Moreover, we performed self-monitored BP measurements at home every month. To assess sympathetic activity, we performed muscle sympathetic nerve activity and heart rate variability measurements at baseline and follow-up. The majority of the included patients was men (57%), mean body mass index was 31±5 kg/m 2 . Median insulin sensitivity as assessed by the Simple Index assessing Insulin Sensitivity oral glucose tolerance test did not change at 6- and 12-month follow-up ( P =0.60 and P =0.77, respectively). Mean 24-hour BP decreased by 6±12/5±7 mm Hg 12 months after RDN ( P =0.04/0.01). However, self-monitored BP measurements data showed no reduction over time. Measurements of sympathetic activity showed no reduction in systemic sympathetic activity. In conclusion, RDN did not lead to a significant improvement of insulin sensitivity ≤12 months after treatment. Although a significant reduction in ambulatory BP was observed in this nearly drug-naïve population, the self-monitored BP measurements data suggest that this may be explained by regression to the mean. Moreover, no effect in systemic sympathetic activity was observed.

Depending on populations studied and applied methods and definitions, the prevalence of treatment-resistant hypertension varies from 3% to 30%. 1,2 The SYMPLICITY studies [3][4][5] demonstrated that in this indication catheter-based endovascular sympathetic renal denervation (RDN) by means of low-frequency energy is feasible. It entails a 25-to 30-mm Hg decrease in office systolic blood pressure, 84% of patients achieving a decrease in office systolic blood pressure of ≥10 mm Hg with a rate of procedural adverse events <5% assessed 6 months after RDN. 4 However, as reviewedAbstract-Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center's criteria was 42.5% (95% confidence interval, 38.0%-47.0%) and 39.7% (36.2%-43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Accordingly, several national and international consensus papers 16,17 have proposed guidelines for evaluation and management of patients with resistant hypertension before considering RDN. The proportion of patients with truly resistant hypertension eligible for RDN and the reasons of noneligibility after thorough screening and optimization of drug treatment in expert centers remain elusive. In this study, we reviewed the reasons for noneligibility at 11 hypertension expert centers performing RDN for treatment-resistant hypertension and collaborating within the European Network COordinating research on Renal Denervation (ENCOReD). 8 Methods PatientsWe performed systematic reviews of the literature published elsewhere 6,7 and identified ENCOReD centers engaging in RDN. At the fourth ENCOReD network meeting, held...