Over the past 20 years, critical care has matured in a myriad of ways resulting in dramatically higher survival rates for our sickest patients. For millions of new survivors comes de novo suffering and disability called "the postintensive care syndrome." Patients with postintensive care syndrome are robbed of their normal cognitive, emotional, and physical capacity and cannot resume their previous life. The ICU Liberation Collaborative is a real-world quality improvement initiative being implemented across 76 ICUs designed to engage strategically the ABCDEF bundle through team- and evidence-based care. This article explains the science and philosophy of liberating ICU patients and families from harm that is both inherent to critical illness and iatrogenic. ICU liberation is an extensive program designed to facilitate the implementation of the pain, agitation, and delirium guidelines using the evidence-based ABCDEF bundle. Participating ICU teams adapt data from hundreds of peer-reviewed studies to operationalize a systematic and reliable methodology that shifts ICU culture from the harmful inertia of sedation and restraints to an animated ICU filled with patients who are awake, cognitively engaged, and mobile with family members engaged as partners with the ICU team at the bedside. In doing so, patients are "liberated" from iatrogenic aspects of care that threaten his or her sense of self-worth and human dignity. The goal of this 2017 plenary lecture at the 47th Society of Critical Care Medicine Congress is to provide clinical ICU teams a synthesis of the literature that led to the creation of ICU liberation philosophy and to explain how this patient- and family-centered, quality improvement program is novel, generalizable, and practice changing.

The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families.

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH—early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.

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Comfort and patient-centred care without excessive sedation: the eCASH concept.

Background
Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used increasingly in neonatal intensive care units (NICUs). However, its effectiveness as a sedative in neonates has not been systematically evaluated.

Objectives
Primary objecive

To assess the effectiveness of intravenous midazolam infusion for sedation, as evaluated by behavioural and/or physiological measurements of sedation levels, in critically ill neonates in the NICU.

Secondary objectives

To assess effects of intravenous midazolam infusion for sedation on complications including the following.

1. Incidence of intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL).

2. Mortality.

3. Occurrence of adverse effects associated with the use of midazolam (hypotension, neurological abnormalities).

4. Days of ventilation.

5. Days of supplemental oxygen.

6. Incidence of pneumothorax.

7. Length of NICU stay (days).

8. Long-term neurodevelopmental outcomes.

Search methods
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), MEDLINE via PubMed (1966 to 16 June 2016), Embase (1980 to 16 June 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 June 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria
We selected for review randomised and quasi-randomised controlled trials of intravenous midazolam infusion for sedation in infants aged 28 days or younger.

Data collection and analysis
We abstracted data regarding the primary outcome of level of sedation. We assessed secondary outcomes such as intraventricular haemorrhage, periventricular leukomalacia, death, length of NICU stay and adverse effects associated with midazolam. When appropriate, we performed meta-analyses using risk ratios (RRs) and risk differences (RDs), and if the RD was statistically significant, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), along with their 95% confidence intervals (95% CIs) for categorical variables, and weighted mean differences (WMDs) for continuous variables. We assessed heterogeneity by performing the I-squared (I2) test.

Main results
We included in the review three trials enrolling 148 neonates. We identified no new trials for this update. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared with the placebo group. However, none of the sedation scales used have been validated in preterm infants; therefore, we could not ascertain the effectiveness of midazolam in this population. Duration of NICU stay was significantly longer in the midazolam group than in the placebo group (WMD 5.4 days, 95% CI 0.40 to 10.5; I2 = 0%; two studies, 89 infants). One study (43 infants) reported significantly lower Premature Infant Pain Profile (PIPP) scores during midazolam infusion than during dextrose (placebo) infusion (MD -3.80, 95% CI -5.93 to -1.67). Another study (46 infants) observed a higher incidence of adverse neurological events at 28 days' postnatal age (death, grade III or IV IVH or PVL) in the midazolam group compared with the morphine group (RR 7.64, 95% CI 1.02 to 57.21; RD 0.28, 95% CI 0.07 to 0.49; NNTH 4, 95% CI 2 to 14) (tests for heterogeneity not applicable). We considered these trials to be of moderate quality according to GRADE assessment based on the following outcomes: mortality during hospital stay, length of NICU stay, adequacy of analgesia according to PIPP scores and poor neurological outcomes by 28 days' postnatal age.

Authors' conclusions
Data are insufficient to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.

Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.

Sedation in the intensive care unit.

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Chronic pain after COVID-19: implications for rehabilitation.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) – short version

Hartmut Buerkle

Papers

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) – short version