Mark W. Rolfe

Clinical Investigations in Critical CareSignificant Tracheal Obstruction Causing Failure to Wean in Patients Requiring Prolonged Mechanical Ventilation: A Forgotten Complication of Long-term Mechanical Ventilation

INTRODUCTION Modern low-pressure, high-volume cuffed tracheotomy tubes have been shown to decrease tracheal injury. However, injury still occurs in patients requiring prolonged mechanical ventilation and prevents weaning, delays decannulation, prolongs hospitalization, and may totally obstruct the airway. We describe 37 patients, including the first reported case of failure to wean due to tracheal obstruction. METHODS Over a 3-year period, from September 1994 to August 1997, the hospital records of 37 patients requiring prolonged mechanical ventilation (> 4 weeks) and found to have tracheal obstruction were reviewed retrospectively. They were a subgroup of 756 patients admitted to hospitals during the same period. The average endotracheal/tracheostomy cannulation time was 3 weeks/12 weeks (range 2 to 4 weeks/8 to 14 weeks). Average age was 76 years (range, 34 to 81). Underlying diseases included COPD, postcoronary artery bypass graft surgery, postpneumonectomy, severe pneumonia, acute lung injury, and ischemic heart disease. RESULTS All 37 patients who initially failed to wean had difficulty in breathing and developed intermittent high peak airway pressures either early or during the weaning process or just on being ventilated. The insertion of a longer tracheal tube bypassed the obstruction, reestablished the airway, decreased peak airway pressures, and allowed the patient to breathe more easily. The obstruction was confirmed on bronchoscopy. Treatment consisted of either placement of a longer tracheal tube (34 of 37 patients) or placement of a tracheal stent. All but two of the patients (5.4%) were able to be weaned within a week. The two patients who still failed to be weaned were subsequently diagnosed as having amyotrophic lateral sclerosis. CONCLUSION Tracheal obstruction in patients requiring prolonged mechanical ventilation prevented weaning. Reestablishment of the airway with a longer tracheal tube or tracheal stent allowed most of the patients to be weaned.

Extraocular Muscle Involvement in Sarcoldosis

BACKGROUND Sarcoidosis is a granulomatous inflammatory disease that may have a variety of ocular and orbital manifestations. The most common ocular manifestation is uveitis, and the most common orbital manifestation is dacryoadenitis. Extraocular muscle involvement in sarcoidosis has rarely been reported. The authors report a case of sarcoidosis involving the extraocular muscles of a 15-year-old boy with bilateral, painful, external ophthalmoplegia and enlargement of all extraocular muscles on computed tomography (CT) scan. RESULTS Lateral rectus muscle biopsy and transbronchial lung biopsy showed noncaseating granulomas characteristic of sarcoidosis. Cultures and serologic studies excluded fungal and mycobacterial diseases. Treatment with oral corticosteroids improved symptoms and signs. CONCLUSIONS The authors report the first case of sarcoidosis in a patient with symptomatic extraocular muscle involvement, and only the third case in which extraocular muscle involvement has been shown histologically.

Chemotactic Cytokine (IL-8 and MCP-1) Gene Expression by Human Whole Blood

The salient features of systemic or local inflammation are the myriad of cellular and humoral interactions that result in elicitation of inflammatory leukocytes. In this study using specialized connective tissue, intact whole blood, we demonstrate the gene expression of two novel chemotactic factors. The buffy-coat cellular expression of neutrophil chemotactic/activating factor/interleukin 8 (IL-8) and monocyte chemotactic/activating protein (MCP-1) mRNA were time and dose-dependent in response to either lipopolysaccharide or zymosan stimulation. This system with the complexity of tissue provides a unique model for the determination of chemotactic cytokine gene expression.

The Role of Cytokine Networks Mediating Inflammation and Ischemia-Reperfusion Injury

Acute inflammation constitutes the host’s response to a variety of insults, including infection, multiorgan failure associated with sepsis, cancer, trauma, shock, allograft rejection, and ischemia-reperfusion injury. The salient inflammatory reaction that accompanies these states is often related to severe microvascular injury. The consequence of this vascular injury is diffuse endothelial cell damage resulting in 1) increased vascular permeability and extravascular fluid accumulation, 2) enhanced activation of the intrinsic and extrinsic coagulation pathways and inhibition of plasminogen activation favoring a procoagulant state, 3) release of reactive oxygen metabolites, cytokines, vasoactive mediators including kinins, 4) arachidonate metabolites, culminating in augmented intravascular aggregation and transendothelial leukocyte emigration. Although, the principal leukocyte effector cell associated with the above conditions is the neutrophil, other immune and non-immune cells can become active participants in the inflammatory responses. Thus humoral mediators leading to interactions between immune and non-immune cells are important to the full development of the pathogenesis of the acute inflammatory response. In this chapter, we will focus our attention on mediators of inflammation that are potentially critical to the inflammatory response associated with ischemia-reperfusion injury.