A narrative review of historic and current approaches for patients with difficult venous access: considerations for the emergency department.

INTRODUCTION: Timely placement of vascular access devices is critical during emergent clinical situations; however, challenges in peripheral access can be a common occurrence. Historically, emergency teams have used various approaches to gain peripheral vascular access in situations where traditional means were not feasible; these options have included peripheral venous cutdown, ultrasound-guided peripheral intravenous catheters (PIVs), longer PIVs, central catheters, and intraosseous devices. Each of these options have associated strengths and limitations depending on the clinical situation. AREAS COVERED: This narrative review reports on the burden of difficult venous access situations and discusses the evidence, and strengths and limitations of vascular access options to help address this challenge. Although first puncture success rates can be high when using alternative methods, significant challenges can include increased procedure time and greater risk of complications. The Easy-Internal Jugular (Easy-IJ) technique is a newer alternative option for patients with difficult venous access that is demonstrated to be safe and effective in emergency care. EXPERT OPINION: Moving forward, additional clinical studies are required to fully characterize the outcomes associated with the Easy-IJ technique and guidewire-assisted intravenous catheters, as well as to inform guideline development for more comprehensive recommendations on managing challenging or difficult peripheral access situations.

Alcohol-use disorders in the critically ill patient.

Alcohol abuse and dependence, referred to as alcohol-use disorders (AUDs), affect 76.3 million people worldwide and account for 1.8 million deaths per year. AUDs affect 18.3 million Americans (7.3% of the population), and up to 40% of hospitalized patients have AUDs. This review discusses the development and progression of critical illness in patients with AUDs. In contrast to acute intoxication, AUDs have been linked to increased severity of illness in a number of studies. In particular, surgical patients with AUDs experience higher rates of postoperative hemorrhage, cardiac complications, sepsis, and need for repeat surgery. Outcomes from trauma are worse for patients with chronic alcohol abuse, whereas burn patients who are acutely intoxicated may not have worse outcomes. AUDs are linked to not only a higher likelihood of community-acquired pneumonia and sepsis but also a higher severity of illness and higher rates of nosocomial pneumonia and sepsis. The management of sedation in patients with AUDs may be particularly challenging because of the increased need for sedatives and opioids and the difficulty in diagnosing withdrawal syndrome. The health-care provider also must be watchful for the development of dangerous agitation and violence, as these problems are not uncommonly seen in hospital ICUs. Despite studies showing that up to 40% of hospitalized patients have AUDs, relatively few guidelines exist on the specific management of the critically ill patient with AUDs. AUDs are underdiagnosed, and a first step to improving patient outcomes may lie in systematically and accurately identifying AUDs.

Hypoxia inducible factor-1: regulation by nitric oxide in posthypoxic microvascular endothelium.

Microvascular endothelial cells provide a critical regulatory interface between blood constituents and tissue. Hypoxia inducible factor-1 (HIF-1) is a key transcription factor required for expression of hypoxia-dependent genes. We employed a model of hypoxia and reoxygenation (H/R) using the dermal microvascular endothelial cell line HMEC-1 to examine the effects of altered oxygen concentrations on microvascular HIF-1 expression and nitric oxide (NO) formation. Hypoxia increased inducible NO synthase (iNOS) mRNA in a time-dependent manner in HMEC-1. However, endothelial NO synthase mRNA progressively declined during hypoxia. H/R promoted significant increases in cellular nitrite levels that were significantly abrogated by the specific iNOS inhibitor N6-(1-iminoethyl)-L-lysine, di hy drochloride. Exogenous NO promoted stabilization of the alpha subunit of HIF-1 and produced functional DNA binding. Exposure of HMEC-1 to H/R resulted in previously unrecognized biphasic HIF-1alpha stabilization during reoxygenation. When the iNOS gene was silenced through the use of iNOS-specific small interfering RNA, HIF-1alpha stabilization and HIF-1 activation were dramatically diminished, suggesting that inducible NOS-derived NO is a key factor sustaining HIF-1 activation during both hypoxia and reoxygenation.

Atypical mechanism of NF-kappaB activation during reoxygenation stress in microvascular endothelium: a role for tyrosine kinases.

The transcription factor nuclear factor kappaB (NF-kappaB) regulates genes that contribute to acute inflammatory reactions in cytokine-activated endothelium. Tumor necrosis factor activates NF-kappaB through serine phosphorylation, induced by inhibitor kappaB kinases (IKK), and subsequent degradation of inhibitor kappaB (IkappaB). In contrast to cytokine stress, our studies show that oxidative stress, generated by exposure to hypoxia followed by reoxygenation (H/R), failed to activate IKK in human microvascular endothelial cells (HMEC-1). We report an alternative mechanism for NF-kappaB activation during H/R stress without IkappaBalpha degradation. This mechanism involves activation of protein tyrosine kinases (PTK) that phosphorylate IkappaBalpha with peak phosphorylation occurring after 30 min of reoxygenation. Involvement of PTK was reinforced by the demonstration that the PTK inhibitor, herbimycin A, prevented H/R-mediated NF-kappaB activation. Tyrosine phosphorylation alters the association between IkappaBalpha and NF-kappaB with sufficient intensity to allow transient NF-kappaB translocation to the cell nuclei within 45 min of onset of reoxygenation stress. Immunofluorescence imaging of NF-kappaB protein reveals it to be shuttled between the nucleus and cytoplasm within 90 min of reoxygenation. Furthermore, IkappaBalpha appears to be associated with NF-kappaB during the nucleo-cytoplasmic shuttling and is thus protected from degradation. Overall, these studies suggest that tyrosine phosphorylation of IkappaBalpha represents a proteolysis-independent mechanism of NF-kappaB activation that can be targeted for preventing H/R-mediated injury without affecting normal inflammatory responses.

Reoxygenating microvascular endothelium exhibits temporal dissociation of NF-kappaB and AP-1 activation.

Alterations of cellular redox balance in microvascular endothelium results in changes of essential cell functions. These alterations may arise, in part, due to modifications in the pattern of gene expression produced by transcription factor activation. Endothelium subjected to hypoxia/reoxygenation becomes redox imbalanced, thereby leading to activation and perhaps production of a proinflammatory state. A human dermal microvascular endothelial cell line (HMEC-1) was exposed to 6 h of hypoxia (3% O(2)) followed by return to normoxia atmospheric conditions. Reactive oxygen species (ROS) generation (dichlorofluoroscein epifluorescence) was immediate and significant following reoxygenation. Electrophoretic mobility shift assays revealed activation of the oxidant sensitive transcription factors NFkappaB and AP-1, though importantly, peak activation of each factor was separated temporally by greater than 60 min. NFkappaB activation occurred without degradation of the inhibitory protein IkappaBalpha. Reoxygenating HMEC-1 exhibited a greater than 500-fold increase in polymorphonuclear neutrophil (PMN) adhesion when compared to normoxic controls. Exposure of reoxygenating HMEC-1 to the antioxidant pyrrolidine dithiocarbamate produced complete abrogation of NFkappaB activation and the intensive PMN adhesion observed in untreated, posthypoxic HMEC-1. Though rexoygenation stress induced significant upregulation of PMN adhesion, no upregulation of interleukin-8 production was observed. Our results suggest that ROS generation occurring in endothelium following onset of reoxygenation stress signals activation of key transcription factors and that their activation takes place in a temporal fashion. The temporal feature of transcription factor activation may be key to production of a postischemic proinflammatory state.