Impact of Telemonitoring of Critically Ill Emergency Department Patients Awaiting ICU Transfer.

OBJECTIVES: Because of overcrowding and limited critical care resources, critically ill patients in the emergency department may spend hours to days awaiting transfer to the ICU. In these patients, often termed "ICU boarders," delayed ICU transfer is associated with poor outcomes. We implemented an emergency department-based, electronic ICU monitoring system for ICU boarders. Our aim was to investigate the effect of this initiative on morbidity, mortality, and ICU usage. DESIGN: Single-center, retrospective cohort study. SETTING: Nonprofit, tertiary care, teaching hospital with greater than 100,000 emergency department visits per year. PATIENTS: Emergency department patients with admission orders for the medical ICU, who spent more than 2 hours boarding in the emergency department after being accepted for admission to the medical ICU, were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, a total of 314 patients were admitted to the medical ICU from the emergency department, 214 of whom were considered ICU boarders with a delay in medical ICU transfer over 2 hours. Of ICU boarders, 115 (53.7%) were enrolled in electronic ICU telemonitoring (electronic ICU care), and the rest received usual emergency department care (emergency department care). Age, mean illness severity (Acute Physiology and Chronic Health Evaluation IVa scores), and admitting diagnoses did not differ significantly between ICU boarders receiving electronic ICU care and emergency department care. Forty-one electronic ICU care patients (36%) were ultimately transitioned to a less intensive level of care in lieu of ICU admission while still in the emergency department, compared with zero patients in the emergency department care group. Among all ICU boarders transferred to the ICU, in-hospital mortality was lower in the electronic ICU care cohort when compared with the emergency department care cohort (5.4% vs 20.0%; adjusted odds ratio, 0.08). CONCLUSIONS: In critically ill patients awaiting transfer from the emergency department to the medical ICU, electronic ICU care was associated with decreased mortality and lower ICU resource utilization.

Clinical Outcomes in Patients Taking Inhaled Loxapine, Haloperidol, or Ziprasidone in the Emergency Department.

OBJECTIVES: Our objective was to compare outcomes of discharge disposition, need for additional medications, and restraint use for patients who received inhaled loxapine compared with patients receiving traditional antipsychotic drugs in the emergency department (ED). METHODS: A retrospective chart review was conducted on all patients who presented to the ED with agitation and received antipsychotic therapy, including loxapine, ziprasidone, or haloperidol from December 1, 2014, through October 31, 2016. RESULTS: The mean time from physician assignment to medical clearance was 7.9 hours for patients treated with inhaled loxapine versus 10.3 hours for controls (P < 0.01). Those who received inhaled loxapine were given significantly less benzodiazepines as additional rescue medications as compared with other antipsychotic medications (P < 0.01, 35.2% vs 65.1%). Additionally, restraints were utilized less frequently in the loxapine group (P < 0.01, 1.8% vs 19.8%). CONCLUSIONS: Treating patients with agitation due to psychotic episodes in an ED setting with inhaled loxapine versus haloperidol or ziprasidone was associated with significantly improved treatment outcomes, suggesting that inhaled loxapine may be a more effective and rapid treatment option.

A Novel Approach for the Administration of Medications and Fluids in Emergency Scenarios and Settings.

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or intraosseous routes, but in many patients, particularly in the emergency or critical care settings, these routes are often unavailable or time-consuming to access. A novel device is now available that offers an easy route for administration of medications or fluids via rectal mucosal absorption (also referred to as proctoclysis in the case of fluid administration and subsequent absorption). Although originally intended for the palliative care market, the utility of this device in the emergency setting has recently been described. Specifically, reports of patients being treated for dehydration, alcohol withdrawal, vomiting, fever, myocardial infarction, hyperthyroidism, and cardiac arrest have shown success with administration of a wide variety of medications or fluids (including water, aspirin, lorazepam, ondansetron, acetaminophen, methimazole, and buspirone). Device placement is straightforward, and based on the observation of expected effects from the medication administrations, absorption is rapid. The rapidity of absorption kinetics are further demonstrated in a recent report of the measurement of phenobarbital pharmacokinetics. We describe here the placement and use of this device, and demonstrate methods of pharmacokinetic measurements of medications administered by this method.

Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful?

Objective The objective of this study was to evaluate whether trimester-specific D-dimer levels or the modified Wells score (MWS) is a useful risk stratification tool to exclude pregnant women at low risk of pulmonary embolism (PE) from diagnostic imaging. Study Design This is a prospective and retrospective cohort study. Pregnant women who underwent diagnostic imaging for suspected PE were prospectively enrolled. D-dimer serum levels were drawn, and a MWS was assigned. Pregnant women diagnosed with a PE before study launch who underwent diagnostic imaging and had a D-dimer level drawn were also evaluated. Results In this study, 17 patients were diagnosed with a PE and 42 patients had no PE on diagnostic imaging. Sixteen out of 17 patients with a PE versus 11 out of 42 without PE had an abnormal D-dimer level (p = 0.001). Four patients with a PE versus zero without a PE had an abnormal MWS (p = 0.005). The combination of a trimester-specific D-dimer level along with the MWS was abnormal in all 17 patients with a documented PE versus 11/42 (26.2%) patients without a documented PE (p = 0.001). Conclusion A combination of trimester-specific D-dimer levels along with a MWS can be used in pregnancy to triage women into a low-risk category for PE and thereby avoid radiation exposure in a majority of pregnant patients.

Regulation of the HIF-system in human macrophages--differential regulation of HIF-α subunits under sustained hypoxia.

Macrophages are often associated to pathophysiological processes and were found at hypoxic areas. However, cell adaption greatly depends on hypoxia-inducible factors (HIF). Activation of these transcription factors is induced by heterodimerization of an α-(HIF-1α, -2α, -3α) and HIF-1ß subunit. The main regulatory pathway is represented by α-subunit stability. Beside, little is known about the exact mechanisms of fine-tuning in Hif-regulation. The present study characterizes the hypoxia-induced regulation of HIF-1α and -2α in human macrophages. The hypoxic increase of both subunits is initially mediated by protein stabilization. Sustained hypoxia caused a distinct regulation of HIF-1α and -2α. The striking increase of HIF-2α protein expression was contrasted by a dramatic decrease of HIF-1α. The long-term downregulation of HIF-1α is due to downregulation of its mRNA. This decrease was accompanied by increased expression of ahif, a natural cis-antisense transcript of HIF-1α. The ahif-transcript was strongly inducible by hypoxia and rapidly degraded under reoxygenation. Using an adenoviral overexpression and siRNA silencing approach revealed that the targeted regulation of ahif is mediated by the HIF-system itself. Furthermore it could be shown that ahif indeed is able to modulate the hypoxic expression of HIF-1α and influences the expression of the HIF-target gene Enolase-2. Taken together, this study characterizes a new regulation process of the HIF-transcription factor-system in human macrophages under hypoxia. For the first time evidence is provided that ahif is regulated by the HIF-system and influences HIF-1α expression in primary human macrophages.

Local inhibition of hypoxia-inducible factor reduces neointima formation after arterial injury in ApoE-/- mice.

OBJECTIVE: Hypoxia plays a pivotal role in development and progression of restenosis after vascular injury. Under hypoxic conditions the hypoxia-inducible factors (HIFs) are the most important transcription factors for the adaption to reduced oxygen supply. Therefore the aim of the study was to investigate the effect of a local HIF-inhibition and overexpression on atherosclerotic plaque development in a murine vascular injury model. METHODS AND RESULTS: After wire-induced vascular injury in ApoE-/- mice a transient, local inhibition of HIF as well as an overexpression approach of the different HIF-subunits (HIF-1α, HIF-2α) by adenoviral infection was performed. The local inhibition of the HIF-pathway using a dominant-negative mutant dramatically reduced the extent of neointima formation. The diminished plaque size was associated with decreased expression of the well-known HIF-target genes vascular endothelial growth factor-A (VEGF-A) and its receptors Flt-1 and Flk-1. In contrast, the local overexpression of HIF-1α and HIF-2α further increased the plaque size after wire-induced vascular injury. CONCLUSIONS: Local HIF-inhibition decreases and HIF-α overexpression increases the injury induced neointima formation. These findings provide new insight into the pathogenesis of atherosclerosis and may lead to new therapeutic options for the treatment of in stent restenosis.