Considering all patients, there was no risk reduction of in-hospital death for those receiving beta-blockers. If the revised cardiac risk index score was 0 or 1, the patients had an increase in the risk of death (43% and 13%, respectively). However, those patients whose scores were 2, 3, or 4 or higher had a reduction in the risk of death (from 10% to 43% as their score increased).
How are we to account for these results? In the high-risk patients we see benefit in treatment with beta-blockers. We suspect this drug class improves coronary filling time during diastole and/or prevents dangerous arrhythmias. In patients at low and intermediate risk, the results may be surprising. The study group did not have patient charts available. It is possible that these patients were given betablockers not for prophylaxis but in response to a postoperative ischemic event or infarction. If this misclassification took place, then the effectiveness of beta-blockers is underestimated and the suggestion that these drugs are harmful in this situation would be erroneous.
Given the data gleaned from this study and considering previous publications, we are justified—even obligated—in using betablockers in high-risk patients, without contraindications, who undergo major noncardiac surgery. Before using these drugs in patients at low or intermediate risk we need more information. Two large ongoing randomized trials (POISE and DECREASE–IV) should bring clarity to this issue. We expect results from these in the next four years.
A NEW CLINICAL ENTITY: THE HEPATOADRENAL SYNDROME
Marik PE, Gayowski T, Starzl TE, et al. The hepatoadrenal syndrome: a common yet unrecognized clinical condition. Crit Care Med. 2005;33:1254-1259.
It is not uncommon to see the temporary dysfunction of the hypothalamic-pituitary-adrenal axis while someone is critically ill. Many physicians who suspect this condition attempt to make a diagnosis using either a random total cortisol level or perform a cosyntropin stimulation test. End-stage liver disease and sepsis share some elements of their pathophysiology, such as endotoxemia and increased levels of mediators that influence inflammation.
A liver transplant intensive care unit has produced data on what they have coined the “hepatoadrenal syndrome.” Due to emerging evidence that severe liver disease is associated with adrenal insufficiency, this liver transplant intensive care unit began routinely testing all patients admitted to their unit for this condition. They presented their findings for 340 patients. This review will focus only on those patients with chronic liver failure and fulminant hepatic failure because transplant patients are often cared for by a multidisciplinary team. Patients were labeled as having adrenal insufficiency if the random total cortisol level was <20 micrograms (mcg)/dL in patients who were “highly stressed” (i.e., hypotension, respiratory failure). In all other patients a random total cortisol level of <15 mcg/dL or a 30-minute level <20 mcg/dL post-low-dose (1 mcg) cosyntropin established the diagnosis. Lipid profiles were also obtained from each patient. Those receiving glucocorticoids were excluded. It was left to the discretion of the treating physician whether or not to treat patients with steroids.
Eight patients (33%) with fulminant hepatic failure and 97 patients (66%) with chronic liver disease met their criteria for adrenal insufficiency. Of the patients with adrenal insufficiency the mortality rate was 46% for those not treated with glucocorticoids compared with 26% for those receiving glucocorticoid therapy. The HDL level was the only variable predictive of adrenal insufficiency (p<.0001).
The association between HDL levels and cortisol is as follows: The adrenal glands do not store cortisol. Cholesterol is a precursor for the synthesis of steroids—80% of cortisol arises from it. The lipoprotein of choice to use as substrate in steroid production is HDL. Because a major protein component of HDL is synthesized by the liver, those with liver disease have low levels of serum HDL.