Diuretic Resistance in Heart Failure.

Decompensated heart failure accounts for approximately 1 million hospitalizations in the United States annually, and this number is expected to increase significantly in the near future. Diuretics provide the initial management in most patients with fluid overload. However, the development of diuretic resistance remains a significant challenge in the treatment of heart failure. Due to the lack of a standard definition, the prevalence of this phenomenon remains difficult to determine, with some estimates suggesting that 25-30% of patients with heart failure have diuretic resistance. Certain characteristics, including low systolic blood pressures, renal impairment, and atherosclerotic disease, help predict the development of diuretic resistance. The underlying pathophysiology is likely multifactorial, with pharmacokinetic alterations, hormonal dysregulation, and the cardiorenal syndrome having significant roles. The therapeutic approach to this common problem typically involves increases in the diuretic dose and/or frequency, sequential nephron blockade, and mechanical fluid movement removal with ultrafiltration or peritoneal dialysis. Paracentesis is potentially useful in patients with intra-abdominal hypertension.

Cardiogenic Pulmonary Edema.

The initial events in cardiogenic pulmonary edema involve hemodynamic pulmonary congestion with high capillary pressures. This causes increased fluid transfer out of capillaries into the interstitium and alveolar spaces. High capillary pressures can also cause barrier disruption which increases permeability and fluid transfer into the interstitium and alveoli. Fluid in alveoli alters surfactant function and increases surface tension. This can lead to more edema formation and to atelectasis with impaired gas exchange. Patients with barrier disruption have increased levels of surfactant protein B in the circulation, and these levels often remain high after the initial clinical improvement. Routine clinical assessment may not identify patients with increased extravascular fluid in the lungs; pulmonary ultrasound can easily detect pulmonary edema in patients with acute decompensation and in patients at risk for decompensation. Studies using serial pulmonary ultrasound could help characterize patients with cardiogenic pulmonary edema and help identify subgroups who need alternative management. The conventional management of cardiogenic pulmonary edema usually involves diuresis, afterload reduction and in some cases noninvasive ventilation to reduce the work of breathing and improve oxygenation. Patients with persistent symptoms, abnormal chest x-rays and diuretic resistance might benefit from alternative approaches to management. These could include beta agonists and pentoxifylline which warrant more study in patients with cardiogenic pulmonary edema.

Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review.

The conventional analysis of acute cardiogenic pulmonary edema involves the development of high pulmonary capillary pressures resulting in hydrostatic gradients for fluid flux out of capillaries into the interstitial space and alveolar spaces. However, some patients respond poorly to diuretic management. The PubMed database was searched to identify experimental studies on pulmonary edema in animals, experimental studies on surfactant function, including patients with pulmonary edema, and clinical studies reporting barrier dysfunction and/or injury in patients with acute pulmonary edema. Studies with animal models demonstrate that high capillary pressures can cause barrier disruption in alveolar capillary units which increases permeability and the transfer of fluid and protein into lung parenchyma. Fluid in alveolar spaces alters surfactant function which increases fluid flux out of capillaries into the lung parenchyma secondary to larger transcapillary hydrostatic gradients. Patients with acute cardiogenic pulmonary edema have increased levels of surfactant protein B in their plasma which reflect barrier disruption and increased levels of tumor necrosis factor alpha which reflect acute tissue injury. Increased surfactant protein B plasma levels are associated with abnormal gas exchange in patients with chronic heart failure. Patients with exercise-induced left ventricular dysfunction have increased levels of surfactant protein B after short periods of exercise. Pathology studies in patients with chronic heart failure have found increased connective tissue in alveolar capillary units and increased numbers of type II alveolar cells, and these changes represent an adaptive response in these patients. Clinicians need to consider the possibility of barrier dysfunction and disruption in patients with both acute and chronic pulmonary edema and understand that diuresis may have a limited effect on symptoms in some patients.

Assessment of the impact of oxandrolone on outcomes in burn injured patients.

The purpose of this study is to use a retrospective cohort of burn patients to evaluate the contribution of oxandrolone on burn care outcomes. Longitudinal clinical data is used to analyze outcomes from a new perspective. Our random-effects longitudinal regression analysis model used temporal clinical data to evaluate oxandrolone's impact on outcomes (oxandrolone/non-oxandrolone n=50/11, median length of stay [LOS]=42.2/39.3, mean weight (kg)=192.2/207.6, mean initial prealbumin (mg/dL) 10.1/7.5). The resultant predictive models (p<0.001) described how certain factors influence clinically significant outcomes via a robust data analysis method. LOS was predicted and extended by a greater magnitude of 3rd-degree versus 2nd-degree burns (1.01 versus 0.85 additional days for each %TBSA, p<0.001). Weight was decreased by LOS (145.2g lost per day, p<0.001). Oxandrolone improved prealbumin (3.503mg/dL increase, p<0.001) but instead did not influence patient weight (p>0.05) nor LOS (5.27days shortening, p=0.361). Prealbumin over time was also influenced by initial value (0.293mg/dL, p=0.003), LOS (0.072mg/dL increase per additional day, p<0.001), and the presence of inhalation injury (2.652mg/dL decrease if present, p=0.009). Oxandrolone appears to benefit anabolic protein production. It is difficult to isolate the role of oxandrolone on major outcomes due to the concomitant influence of other variables.