The use of remifentanil in clinical practice offers several advantages and it is used for a wide range of procedures, ranging from day-surgery anesthesia to more complex procedures. Nonetheless, remifentanil has been consistently linked with development of opioid-induced hyperalgesia (OIH), which is described as a paradoxical increase in sensitivity to painful stimuli that develops after exposure to opioid treatment. The development of OIH may cause several issues, delaying recovery after surgery and preventing timely patient’s discharge. Moreover, it causes patient’s discomfort with higher pain scores, greater use of analgesics, and associated side effects. Remifentanil is the opioid most convincingly associated with OIH, and hereby we provide a review of remifentanil-induced hyperalgesia, describing both the underlying mechanisms involved and the available studies investigating experimental and clinical pharmacologic approaches aiming at reducing its incidence and degree.

Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan. We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion. Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05). Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Millions of critically ill patients are discharged from intensive care units (ICUs) every year. These ICU survivors may suffer from a condition known as post-intensive care syndrome (PICS) which includes a wide range of cognitive, psychological, and physical impairments. This article will provide an extensive review of PICS. ICU survivors may experience cognitive deficits in memory and attention, with a slow-down of mental processing and problem-solving. From psychological perspectives, depression, anxiety, and post-traumatic stress disorder are the most common issues suffered after ICU discharge. These psycho-cognitive impairments might be coupled with ICU-acquired weakness (polyneuropathy and/or myopathy), further reducing the quality of life, the ability to return to work, and other daily activities. The burden of ICU survivors extends to families too, leading to the so-called PICS-family (or PICS-F), which entails the psychological impairments suffered by the family and, in particular, by the caregiver of the ICU survivor. The development of PICS (and PICS-F) is likely multifactorial, and both patient- and ICU-related factors may influence it. Whilst the prevention of PICS is complex, it is important to identify the patients at higher risk of PICS, and clinicians should be aware of the tools available for diagnosis. Stakeholders should implement strategies to achieve PICS prevention and to support its effective treatment during the recovery phase with dedicated pathways and supporting care.