The hepatoadrenal syndrome: A common yet unrecognized clinical condition

Objective: Adrenal failure is common in critically ill patients, particularly those with sepsis. As liver failure and sepsis are both associated with increased circulating levels of endotoxin and proinflammatory mediators and reduced levels of apoprotein-1/ high-density lipoprotein, we postulated that adrenal failure may be common in patients with liver disease. Design: Clinical study. Setting: Liver transplant intensive care unit. Patients: The study cohort included 340 patients with liver disease. Interventions: Based on preliminary observational data, all patients admitted to our 28-bed liver transplant intensive care unit (LTICU) undergo adrenal function testing. An honest broker system was used to extract clinical, hemodynamic, medication, and laboratory data on patients admitted to the LTICU from March 2002 to March 2004. A random (stress) cortisol level <20 μg/dL in a highly stressed patient (respiratory failure, hypotension) was used to diagnose adrenal insufficiency. In all other patients, a random cortisol level <15 μg/dL or a 30-min level <20 μg/dL post-low-dose (1 μg) cosyntropin was considered diagnostic of adrenal insufficiency. Patients were grouped as follows: a) chronic liver failure; b) fulminant hepatic failure; c) patients immediately status post-orthotopic liver transplantation receiving a steroid-free protocol of immunosuppression; and d) patients status post-remote liver transplant (≥6 months). The decision to treat patients with stress doses of hydrocortisone was at the discretion of the treating intensivist and transplant surgeon. Measurements and Main Results: Two-hundred and forty-five (72%) patients met our criteria for adrenal insufficiency (the hepatoadrenal syndrome). Eight (33%) patients with fulminant hepatic failure, 97 (66%) patients with chronic liver disease, 31(61%) patients with a remote history of liver transplantation, and 109 (92%) patients who had undergone liver transplantation under steroid-free immunosuppression were diagnosed with adrenal insufficiency. The high-density lipoprotein level at the time of adrenal testing was the only variable predictive of adrenal insufficiency (p < .0001). In vasopressor-dependent patients with adrenal insufficiency, treatment with hydrocortisone was associated with a significant reduction (p = .02) in the dose of norepinephrine at 24 hrs, whereas the dose of norepinephrine was significantly higher (p = .04) in those patients with adrenal failure not treated with hydrocortisone. In vasopressor-dependent patients without adrenal insufficiency, treatment with hydrocortisone did not affect vasopressor dose at 24 hrs. One hundred and forty-one patients (26.4%) died during their hospitalization. The baseline serum cortisol was 18.8 ± 16.2 μg/dL in the nonsurvivors compared with 13.0 ± 11.8 μg/dL in the survivors (p < .001). Of those patients with adrenal failure who were treated with glucocorticoids, the mortality rate was 26% compared with 46% (p = .002) in those who were not treated. In those patients receiving vasopressor agents at the time of adrenal testing, the baseline cortisol was 10.0 ± 4.8 μg/dL in those with adrenal insufficiency compared with 35.6 ± 21.2 μg/dL in those with normal adrenal function. Vasopressor-dependent patients who did not have adrenal failure had a mortality rate of 75%. Conclusions: Patients with liver failure and patients post-liver transplantation have an exceedingly high incidence of adrenal failure, which may be pathophysiologically related to low levels of high-density lipoprotein. Treatment of patients with adrenal failure may improve outcome. High baseline serum cortisol levels may be a maker of disease severity and portend a poor prognosis. Copyright © 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

The diagnosis of adrenal insufficiency in the critically ill patient: does it really matter?

The definition of what constitutes a \u27normal\u27 adrenal response to critical illness is unclear. Consequently, published studies have used a variety of biochemical criteria to define \u27adrenal insufficiency\u27. These criteria have been based on the baseline cortisol level or the increment in cortisol following corticotropin administration. However, in critically ill patients there are a number of confounding factors that make interpretation of these tests difficult. Furthermore, in those patients who are most likely to benefit from treatment with low-dose glucocorticoids, there is no evidence that treatment should be based on adrenal function testing. In those patients in whom the diagnosis of adrenal insufficiency may be important, this diagnosis may best be made based on the free cortisol level or the total cortisol level stratified by serum albumin

Echocardiographic Assessment of Preload Responsiveness in Critically Ill Patients

Fluid challenges are considered the cornerstone of resuscitation in critically ill patients. However, clinical studies have demonstrated that only about 50% of hemodynamically unstable patients are volume responsive. Furthermore, increasing evidence suggests that excess fluid resuscitation is associated with increased mortality. It therefore becomes vital to assess a patient's fluid responsiveness prior to embarking on fluid loading. Static pressure (CVP, PAOP) and echocardiographic (IVC diameter, LVEDA) parameters fails to predict volume responsiveness. However, a number of dynamic echocardiographic parameters which are based on changes in vena-caval dimensions or cardiac function induce by positive pressure ventilation or passive leg raising appear to be highly predictive of volume responsiveness

Perioperative hypertension management

Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension

Surviving sepsis: going beyond the guidelines

The Surviving Sepsis Campaign is a global effort to improve the care of patients with severe sepsis and septic shock. The first Surviving Sepsis Campaign Guidelines were published in 2004 with an updated version published in 2008. These guidelines have been endorsed by many professional organizations throughout the world and come regarded as the standard of care for the management of patients with severe sepsis. Unfortunately, most of the recommendations of these guidelines are not evidence-based. Furthermore, the major components of the 6-hour bundle are based on a single-center study whose validity has been recently under increasing scrutiny. This paper reviews the validity of the Surviving Sepsis Campaign 6-hour bundle and provides a more evidence-based approach to the initial resuscitation of patients with severe sepsis

Bench-to-bedside review: Rhabdomyolysis – an overview for clinicians

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration