Delirium in the intensive care unit

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients, occurring in up to 80% of the sickest intensive care unit (ICU) populations. Critically ill patients are subject to numerous risk factors for delirium. Some of these, such as exposure to sedative and analgesic medications, may be modified to reduce risk. Although dysfunction of other organ systems continues to receive more clinical attention, delirium is now recognized to be a significant contributor to morbidity and mortality in the ICU, and it is recommended that all ICU patients be monitored using a validated delirium assessment instrument. Patients with delirium have longer hospital stays and lower 6-month survival than do patients without delirium, and preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge. Little evidence exists regarding the prevention and treatment of delirium in the ICU, but multicomponent interventions reduce the incidence of delirium in non-ICU studies. Strategies for the prevention and treatment of ICU delirium are the subjects of multiple ongoing investigations

Delirium and mortality risk prediction: a story in evolution

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Neural Correlates of Attention Bias to Threat in Post-traumatic Stress Disorder

Attention bias has been proposed to contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD), although the neural correlates of these processes have not been well defined. When engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions such as the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (vlPFC), and amygdala; however, few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and included emotionally-salient information, which was the goal of the present study. We administered a modified attention bias task, the dot probe, which is equipped to measure direction and magnitude of bias, to a sample of 37 (19 trauma control, 18 PTSD+) traumatized African-American adults during functional magnetic resonance imaging. Compared to traumatized participants without PTSD, PTSD+ participants demonstrated increased activation in the dlPFC in response to trials including angry/threatening expressions. In addition, attentional avoidance of threat cues corresponded with increased vlPFC and dorsal ACC (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide some evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation to threat cues in the context of heightened attentional demands represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

Abstract Introduction Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients. Methods In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis. Results Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11). Conclusions In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results. Trial Registration NCT00095251

Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

Both childhood trauma and a functional COMT genetic polymorphism have been associated with PTSD and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n=38, Met carriers, n=35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms, and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met-carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk, and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes

Episodic memory after trauma exposure: Medial temporal lobe function is positively related to re-experiencing and inversely related to negative affect symptoms

Hippocampal structure is particularly sensitive to trauma and other stressors. However, previous findings linking hippocampal function with trauma-related psychopathology have been mixed. Heterogeneity in psychological responses to trauma has not been considered with respect to hippocampal function and may contribute to mixed findings. To address these issues, we examined associations between data-driven symptom dimensions and episodic memory formation, a key function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were defined using principal components analysis (PCA) in 3881 trauma-exposed African-American women recruited from primary care waiting rooms of a large urban hospital. Hippocampal and amygdala function were subsequently investigated in an fMRI study of episodic memory formation in a subset of 54 women. Participants viewed scenes with neutral, negative, and positive content during fMRI, and completed a delayed cued recall task. PCA analysis produced five symptom dimensions interpreted as reflecting negative affect, somatic symptoms, re-experiencing, hyper-arousal, and numbing. Re-experiencing was the only symptom type associated with hippocampal function, predicting increased memory encoding-related activation in the hippocampus as well as the amygdala. In contrast, the negative affect component predicted lower amygdala activation for subsequently recalled scenes, and lower functional coupling with other important memory-related regions including the precuneus, inferior frontal gyrus, and occipital cortex. Symptom dimensions were not related to hippocampal volume. The fMRI findings for re-experiencing versus negative affect parallel differences in behavioral memory phenomena in PTSD versus MDD, and highlight a need for more complex models of trauma-related pathology

Atomic Resonance and Scattering

Contains reports on nine research projects.U.S. Energy Research and Development Administration (Contract EG-77-S-02-4370)U. S. Air Force - Office of Scientific Research (Contract F44620-72-C-0057)Joint Services Electronics Program (Contract DAAB07-76-C-1400)National Science Foundation (Grant PHY75-15421-AO1)National Science Foundation (Grant PHY77-09155)National Science Foundation (Grant CHE76-81750)U. S. Air Force - Office of Scientific Research (Grant AFOSR-76-2972A