Dexmedetomidine and paralytic exposure after damage control laparotomy: risk factors for delirium? Results from the EAST SLEEP-TIME multicenter trial.

PURPOSE: To evaluate factors associated with ICU delirium in patients who underwent damage control laparotomy (DCL), with the hypothesis that benzodiazepines and paralytic infusions would be associated with increased delirium risk. We also sought to evaluate the differences in sedation practices between trauma (T) and non-trauma (NT) patients. METHODS: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry admitted from January 1, 2017 to December 31, 2018. We included all adults undergoing DCL, regardless of diagnosis, who had completed daily Richmond Agitation Sedation Score (RASS) and Confusion Assessment Method-ICU (CAM-ICU). We excluded patients younger than 18 years, pregnant women, prisoners and patients who died before the first re-laparotomy. Data collected included age, number of re-laparotomies after DCL, duration of paralytic infusion, duration and type of sedative and opioid infusions as well as daily CAM-ICU and RASS scores to analyze risk factors associated with the proportion of delirium-free/coma-free ICU days during the first 30 days (DF/CF-ICU-30) using multivariate linear regression. RESULTS: A 353 patient subset (73.2% trauma) from the overall 567-patient cohort had complete daily RASS and CAM-ICU data. NT patients were older (58.9 ± 16.0 years vs 40.5 ± 17.0 years [p < 0.001]). Mean DF/CF-ICU-30 days was 73.7 ± 96.4% for the NT and 51.3 ± 38.7% in the T patients (p = 0.030). More T patients were exposed to Midazolam, 41.3% vs 20.3% (p = 0.002). More T patients were exposed to Propofol, 91.0% vs 71.9% (p < 0.001) with longer infusion times in T compared to NT (71.2 ± 85.9 vs 48.9 ± 69.8 h [p = 0.017]). Paralytic infusions were also used more in T compared to NT, 34.8% vs 18.2% (p < 0.001). Using linear regression, dexmedetomidine infusion and paralytic infusions were associated with decreases in DF/CF-ICU-30, (- 2.78 (95%CI [- 5.54, - 0.024], p = 0.040) and (- 7.08 ([- 13.0, - 1.10], p = 0.020) respectively. CONCLUSIONS: Although the relationship between paralytic use and delirium is well-established, the observation that dexmedetomidine exposure is independently associated with increased delirium and coma is novel and bears further study.

Trauma and nontrauma damage-control laparotomy: The difference is delirium (data from the Eastern Association for the Surgery of Trauma SLEEP-TIME multicenter trial).

BACKGROUND: Damage-control laparotomy (DCL) has been used for traumatic and nontraumatic indications. We studied factors associated with delirium and outcome in this population. METHODS: We reviewed DCL patients at 15 centers for 2 years, including demographics, Charlson Comorbidity Index (CCI), diagnosis, operations, and outcomes. We compared 30-day mortality; renal failure requiring dialysis; number of takebacks; hospital, ventilator, and intensive care unit (ICU) days; and delirium-free and coma-free proportion of the first 30 ICU days (DF/CF-ICU-30) between trauma (T) and nontrauma (NT) patients. We performed linear regression for DF/CF-ICU-30, including age, sex, CCI, achievement of primary fascial closure (PFC), small and large bowel resection, bowel discontinuity, abdominal vascular procedures, and trauma as covariates. We performed one-way analysis of variance for DF/CF-ICU-30 against traumatic brain injury severity as measured by Abbreviated Injury Scale for the head. RESULTS: Among 554 DCL patients (25.8% NT), NT patients were older (58.9 ± 15.8 vs. 39.7 ± 17.0 years, p < 0.001), more female (45.5% vs. 22.1%, p < 0.001), and had higher CCI (4.7 ± 3.3 vs. 1.1 ± 2.2, p < 0.001). The number of takebacks (1.7 ± 2.6 vs. 1.5 ± 1.2), time to first takeback (32.0 hours), duration of bowel discontinuity (47.0 hours), and time to PFC were similar (63.2 hours, achieved in 73.5%). Nontrauma and T patients had similar ventilator, ICU, and hospital days and mortality (31.0% NT, 29.8% T). Nontrauma patients had higher rates of renal failure requiring dialysis (36.6% vs. 14.1%, p < 0.001) and postoperative abdominal sepsis (40.1% vs. 17.1%, p < 0.001). Trauma and NT patients had similar number of hours of sedative (89.9 vs. 65.5 hours, p = 0.064) and opioid infusions (106.9 vs. 96.7 hours, p = 0.514), but T had lower DF/CF-ICU-30 (51.1% vs. 73.7%, p = 0.029), indicating more delirium. Linear regression analysis indicated that T was associated with a 32.1% decrease (95% CI, 14.6%-49.5%; p < 0.001) in DF/CF-ICU-30, while achieving PFC was associated with a 25.1% increase (95% CI, 10.2%-40.1%; p = 0.001) in DF/CFICU-30. Increasing Abbreviated Injury Scale for the head was associated with decreased DF/CF-ICU-30 by analysis of variance (p < 0.001). CONCLUSION: Nontrauma patients had higher incidence of postoperative abdominal sepsis and need for dialysis, while T was independently associated with increased delirium, perhaps because of traumatic brain injury. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Management and Challenges of Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients, and can be classified into mild, moderate, and severe by the Glasgow coma scale (GCS). Prehospital, initial emergency department, and subsequent intensive care unit (ICU) management of severe TBI should focus on avoiding secondary brain injury from hypotension and hypoxia, with appropriate reversal of anticoagulation and surgical evacuation of mass lesions as indicated. Utilizing principles based on the Monro-Kellie doctrine and cerebral perfusion pressure (CPP), a surrogate for cerebral blood flow (CBF) should be maintained by optimizing mean arterial pressure (MAP), through fluids and vasopressors, and/or decreasing intracranial pressure (ICP), through bedside maneuvers, sedation, hyperosmolar therapy, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or decompressive craniectomy (DC). While controversial, direct ICP monitoring, in conjunction with clinical examination and imaging as indicated, should help guide severe TBI therapy, although new modalities, such as brain tissue oxygen (PbtO2) monitoring, show great promise in providing strategies to optimize CBF. Optimization of the acute care of severe TBI should include recognition and treatment of paroxysmal sympathetic hyperactivity (PSH), early seizure prophylaxis, venous thromboembolism (VTE) prophylaxis, and nutrition optimization. Despite this, severe TBI remains a devastating injury and palliative care principles should be applied early. To better affect the challenging long-term outcomes of severe TBI, more and continued high quality research is required.

Musculoskeletal symptoms among female garment factory workers in Sri Lanka.

OBJECTIVES: To assess the prevalence of musculoskeletal symptoms and their association with sociodemographic risk factors among female garment factory workers in Sri Lanka. METHODS: 1058 randomly selected female garment factory workers employed in the free trade zone of Kogalla, Sri Lanka were recruited to complete two interviewer-administered questionnaires assessing musculoskeletal symptoms and health behaviors. DISCUSSION: Musculoskeletal complaints among female garment workers in the FTZ of Kogalla are less common than expected. Sociocultural factors may have resulted in underreporting and similarly contribute to the low rates of healthcare utilization by these women. RESULTS: 164 (15.5%) of workers reported musculoskeletal symptoms occurring more than 3 times or lasting a week or more during the previous 12-month period. Back (57.3%) and knee (31.7%) were the most common sites of pain. Although most symptomatic women reported that their problems interfered with work and leisure activities, very few missed work as a result of their pain. Prevalence correlated positively with increased age and industry tenure of less than 12 months. Job type, body mass index, and education were not significant predictors of musculoskeletal symptoms.

Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro.

ATPases and histone chaperones facilitate RNA polymerase II (pol II) elongation on chromatin. In vivo, the coordinated action of these enzymes is necessary to permit pol II passage through a nucleosome while restoring histone density afterward. We have developed a biochemical system recapitulating this basic process. Transcription through a nucleosome in vitro requires the ATPase remodels structure of chromatin (RSC) and the histone chaperone nucleosome assembly protein 1 (NAP1). In the presence of NAP1, RSC generates a hexasome. Despite the propensity of RSC to evict histones, NAP1 reprograms the reaction such that the hexasome is retained on the template during multiple rounds of transcription. This work has implications toward understanding the mechanism of pol II elongation on chromatin.

Multimodal communication and spatial binding in pied currawongs (Strepera graculina).

To make accurate assessments about their environment, animals must integrate a variety of sensory cues into a single unified percept. The effects of redundant multimodal signaling may be equivalent to the responses elicited by each individual cue, or enhanced when cues are combined. Binding of two seemingly coupled cues can persist despite small spatial and temporal discrepancies in signal presentation, a phenomenon termed the ventriloquist effect. Our study had two aims: first, to test the cognitive ability of a territorial, forest-dwelling bird to bind two spatially disparate cues; and second, to define the processing of the acoustic and visual cues as having either equivalent or enhanced effects when presented together. We broadcasted pied currawong (Strepera graculina) vocalizations alone or in the presence of a model currawong situated either adjacent to, or far away from a speaker, to free-living currawongs. The number of locomotive events and the average standard deviation in the distance from the speaker maintained by the focal currawong were greater in response to "far" than "close" treatments. Additionally, the average standard deviation of the distance to speaker for the uni-modal, speaker only treatment was similar to "far" responses. These findings support our hypothesis that currawongs cognitively bind two stimuli in close spatial proximity. In nature, this would result in an enhanced level of response toward territorial intruders. Our study was novel in its attempt to assess cognitive processes involved in the integration of spatially disparate bimodal signaling events in free-living birds.

A mechanism for coordinating chromatin modification and preinitiation complex assembly.

Transcription of eukaryotic genes within a chromatin environment requires the sequential recruitment of histone modification enzymes and the general transcription factors (GTFs) by activators. However, it is unknown how preinitiation complex assembly is coordinated with chromatin modification. Here, we show that the model activator GAL4-VP16 directs the ordered assembly of Mediator, histone acetyltransferases (HATs), and GTFs onto immobilized chromatin and naked DNA templates in vitro. Using purified proteins, we found that the Mediator regulates this assembly process by binding to p300 and TFIID. An acetyl-CoA-dependent catalytic switch causes p300 to acetylate chromatin and then dissociate. Dissociation of p300 enhances TFIID binding and active transcription. The dissociation is caused by an autoacetylation-induced conformational change in the catalytic domain of p300. We conclude that autoacetylation-induced dissociation of p300 acts as a catalytic switch, which allows TFIID binding and subsequent preinitiation complex assembly.