Sedation, sleep-promotion, and non-verbal and verbal communication techniques in critically ill intubated or tracheostomized patients: results of a survey.

BACKGROUND: The aim of this survey was to describe, on a patient basis, the current practice of sedation, pharmacologic and non-pharmacologic measures to promote sleep and facilitation of communication in critically ill patients oro-tracheally intubated or tracheostomized. METHODS: Cross-sectional online-survey evaluating sedation, sleep management and communication in oro-tracheally intubated (IP) or tracheostomized (TP) patients in intensive care units on a single point. RESULTS: Eighty-one intensive care units including 447 patients (IP: n = 320, TP: n = 127) participated. A score of ≤ -2 on the Richmond Agitation Sedation Scale (RASS) was prevalent in 58.2% (IP 70.7% vs. TP 26.8%). RASS -1/0 was present in 32.2% (IP 25.9% vs. TP 55.1%) of subjects. Propofol and alpha-2-agonist were the predominant sedatives used while benzodiazepines were applied in only 12.1% of patients. For sleep management, ear plugs and sleeping masks were rarely used (< 7%). In half of the participating intensive care units a technique for phonation was used in the tracheostomized patients. CONCLUSIONS: The overall rate of moderate and deep sedation appears high, particularly in oro-tracheally intubated patients. There is no uniform sleep management and ear plugs and sleeping masks are only rarely applied. The application of phonation techniques in tracheostomized patients during assisted breathing is low. More efforts should be directed towards improved guideline implementation. The enhancement of sleep promotion and communication techniques in non-verbal critically ill patients may be a focus of future guideline development.

An Inverse Relationship Between c-Kit/CD117 and mTOR Confers NK Cell Dysregulation Late After Severe Injury.

Major trauma-induced tissue injury causes a dysregulation of the immune system. Severe systemic inflammation occurs early after the insult. Later on, an enhanced risk for life-threatening opportunistic infections develops that culminates at the end of the first week after trauma. CD56bright Natural killer (NK) cells play a key role in the defense against infection due to their rapid release of Interferon (IFN) γ in response to Interleukin (IL) 12. NK cells are impaired in IFN-γ synthesis after severe injury due to a disturbed IL-12/IFN-γ axis. Thereby, a circulating factor mediates extrinsic suppression of NK cells. Yet unknown cell-intrinsic mechanisms manifest by day 8 after trauma and render NK cells unresponsive to stimulatory cytokines. In the present study, we investigated the origin of such late NK cell-intrinsic suppression after major trauma. Peripheral blood mononuclear cells (PBMC) were isolated from patients 8 day after severe injury and from healthy control subjects and were stimulated with inactivated Staphylococcus aureus. The expression of diverse cytokine receptors, intracellular signaling molecules, and the secretion of IFN-γ by CD56bright NK cells were examined. After stimulation with S. aureus, NK cells from patients expressed enhanced levels of c-kit/CD117 that inversely correlated with IFN-γ synthesis and IL-12 receptor (IL-12R) ß2 expression. Supplementation with IL-15 and inhibition of the transforming growth factor receptor (TGF-ßR) I reduced CD117 expression and increased the level of IL-12Rß2 and IFN-γ. NK cells from patients showed reduced phosphorylation of mammalian target of rapamycin (mTOR). Addition of IL-15 at least partly restored mTOR phosphorylation and increased IL-12Rß2 expression. The reduced mTOR phosphorylation after severe injury was cell-intrinsic as it was not induced by serum factors. Inhibition of mTOR in purified NK cells from healthy donors by rapamycin decreased the synthesis of IFN-γ. Thus, impaired mTOR phosphorylation in response to a microbial challenge contributes to the cell-intrinsic mechanisms that underlie NK cell dysregulation after trauma. Restoration of the mTOR phosphorylation capacity along with inhibition of the TGF-ßRI signaling in NK cells after severe injury might improve the immune defense against opportunistic infections.

Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation.

BACKGROUND: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. METHODS: NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. FINDINGS: During systemic inflammation, the expression of the IL-12 receptor ß2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor ß receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor ß2 expression on NK cells and was enhanced in patients who later acquired septic complications. INTERPRETATION: GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. FUND: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen.