Subsequent infections in survivors of sepsis: epidemiology and outcomes.

PURPOSE: Sepsis is a devastating condition with considerable mortality. The causes of long-term mortality are poorly understood. To test the hypothesis that patients with sepsis are more susceptible to recurrent infections and death due to infectious complications, we investigated the outcomes of patients who survived sepsis, with regard to the incidence of recurrent infections and mortality. MATERIALS AND METHODS: A retrospective study of the patients admitted to the intensive care unit (ICU) for sepsis from 2001 to 2002 who achieved 30-day survival (sepsis survivors [SSs], N = 78) and a control group of patients admitted to the ICU for noninfectious conditions with a similar severity of illness (N = 50) was performed. The primary end point was the number of recurrent infections in the first year posthospitalization. RESULTS: The SSs group had higher rates of infections following hospital discharge compared to controls. Using a multivariable model, having survived sepsis was the strongest predictor of the development of subsequent infections (rate ratio [RR]: 2.83, P= .0006), the need for rehospitalization for infection in the year after the initial hospitalization (RR: 3.78, P = .0009), and postdischarge mortality (hazard ratio = 3.61, P = .003). CONCLUSIONS: Critically ill patients who survive sepsis have an increased risk of recurrent infections in the year following their septic episode that is associated with increased mortality.

Lung transplantation in patients with scleroderma.

PURPOSE OF REVIEW: Systemic sclerosis (SSc) is an autoimmune disorder that involves skin and internal organs. Pulmonary diseases, comprising interstitial lung disease and pulmonary arterial hypertension, are the leading causes of morbidity and mortality in patients with SSc. Lung transplantation in patients with SSc remains controversial owing to a presumed heightened risk in the postoperative period from SSc-related gastroesophageal reflux, renal impairment, and skin fibrosis. In this article, we review the indications and patient selection criteria for lung transplantation in patients with SSc, discuss the implications and recommendations related to single versus bilateral lung transplantation, and review postlung transplantation survival data. RECENT FINDINGS: Early aggressive surgical treatment of gastroesophageal reflux disease decreases the rate of bronchiolitis and improves survival in lung transplant patients. Heart transplantations remain rare owing to frequent involvement of other organ systems in SSc patients with cardiac manifestations. The procedure of choice in patients with SSc has not been determined, but given the dearth of donor lungs, single lung transplantation has become commonplace for most SSc patients without severe pulmonary hypertension. Carefully selected patients without extrapulmonary systemic disease experience similar survival after lung transplantation compared to those with other end-stage pulmonary diseases. Patients with SSc undergoing lung transplantation have similar rates of chronic rejection as patients transplanted for nonconnective tissue disease-related interstitial lung disease. SUMMARY: Lung transplantation represents a viable therapeutic option to consider for patients with end-stage lung disease due to SSc who have limited extrapulmonary manifestations.

Sleep disorders in chronic liver disease.

Sleep-related complaints and disturbances are increasingly recognized in the setting of chronic liver disease and have recently been shown to be an important prognostic factor in patients with advanced chronic liver disease. This article reviews the literature surrounding sleep disturbances and disorders in a variety of types of chronic liver disease. This includes the association of sleep disturbances with hepatitis C and antiviral therapy, primary biliary cirrhosis, and Wilson disease as well as the circadian rhythm abnormalities present in cirrhosis and hepatic encephalopathy. The association between chronic liver disease, particularly nonalcoholic fatty liver disease, and sleep-disordered breathing is also reviewed in detail.

A 38-Year-Old Man With Well Treated OSA on CPAP With Persistent Nocturnal Hypoxemia.

CASE PRESENTATION: A 38-year-old male with a prior diagnosis of severe OSA (apnea-hypopnea index [AHI] 99/h) presented for transfer of care. He was successfully titrated to CPAP of 10 cm H2O at an outside laboratory and was compliant with therapy with residual AHI 1.9/h. On presentation, he was polycythemic, with negative evaluation for primary polycythemia, and evaluation for hypoxemia was initiated.

A 67-Year-Old Man With Palpitations During Sleep.

CASE PRESENTATION: A 67-year-old man with a history of atrial fibrillation (AF) presented to his physician with symptoms of episodic, nighttime palpitations and excessive daytime sleepiness. Four years prior he underwent radiofrequency ablation after a confirmed diagnosis of AF with subsequent resolution of his palpitations. His palpitations returned approximately 1 year following the ablation. These events would occur only at night and awake him from sleep. Holter monitoring showed baseline sinus rhythm with multiple episodes of AF with rates of 75 to 169 beats/min. These events were all nocturnal and correlated with the symptom diary; episodes ranged from 45 min to 2 h. An echocardiogram showed normal left ventricular size and ejection fraction with a mildly enlarged right atrium (4.38 cm) and no evidence of pulmonary hypertension.

Evaluation of thiol-based antioxidant therapeutics in cystic fibrosis sputum: Focus on myeloperoxidase.

Neutrophil-dependent reactions catalysed by myeloperoxidase (MPO) are thought to play important roles in the pulmonary pathobiology of cystic fibrosis (CF). Aerosolized thiol antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC) are currently being utilized as therapeutics to modify CF respiratory tract oxidative processes. This study hypothesized that MPO in CF airway lining fluids may be a target of such therapeutics. MPO activity in sputum from 21 adult CF patients was found to be inversely associated with lung function (FEV(1)). In contrast, systemic inflammation (assessed by plasma C-reactive protein) was not correlated with lung function. Ex vivo studies revealed that GSH and NAC effectively scavenged N-chloramines in sputum and inhibited sputum MPO activity with potency exquisitely dependent upon MPO activity levels. Detailed kinetic analyses revealed that NAC and GSH inhibit MPO by distinct mechanisms. Activation of the key pro-inflammatory transcription factor NF-κB in cultured HBE1 cells was inhibited by GSH. The findings reveal that MPO activity and its reactive products represent useful predictors of the doses of inhaled thiol antioxidants required to ameliorate airway oxidative stress and inflammation in CF patients and provide mechanistic insight into the antioxidative/anti-inflammatory mechanisms of action of GSH and NAC when administered into the CF lung.

Bench-to-bedside review: the role of nitric oxide in sepsis.

Sepsis is a state of systemic inflammation directed at microbes or their toxins in blood or tissues. Nitric oxide (NO) is one of many vasoactive molecules released from a variety of cell types during sepsis. Almost two decades ago, NO emerged as a potential therapeutic target in sepsis. NO produced by the constitutive NO synthase (NOS) isoform (endothelial NOS and neuronal NOS) in the vascular endothelium and elsewhere acts as a nonadrenergic, noncholinergic neurotransmitter, an inhibitor of platelet aggregation and a vasodilator. During sepsis, activation of inducible NOS (iNOS) in the lung epithelium and other organs occurs, leading to NO overproduction. The result of excessive circulating NO is enhanced bacterial destruction, but also profound vasodilatation, activation of inflammatory cascades and depression of cardiac function. Trials of nonselective NOS inhibitors have shown increased mean arterial pressure, but also increased pulmonary artery pressure and reduced cardiac output. Small animal studies of iNOS selective inhibition have produced dichotomous results, but larger clinical studies assessing mortality are lacking. Inhaled NO has been touted as a therapeutic option to improve systemic oxygenation in the acute lung injury of sepsis (hypoxic pulmonary vasoconstriction and pulmonary hypertension); however, studies of inhaled NO in acute respiratory distress syndrome have not shown survival efficacy. Further investigation into the role of NO in human sepsis, and the development of methods to assess NO balance in patients with sepsis is essential in this field. In this review, we outline the effects of NO in sepsis, and summarize the therapeutic outcomes of NOS inhibitors, and inhaled NO in sepsis and acute respiratory distress syndrome.