Ahmed Zaky

Characterization of cardiac dysfunction in sepsis: an ongoing challenge.

ABSTRACT Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs in patients with severe sepsis and septic shock. The clinical characterization of SIC has been largely concept-driven. Heart function has traditionally been evaluated according to two basic conceptual models: a hydraulic pump system, whereby the output from the heart is entirely dependent on its input, or a hemodynamic pump, whereby the cardiac output is a function of preload, global ventricular performance, and afterload. Minimal attention has been given to the intrinsic contractile function of the heart or to the interaction between the peripheral circulation and the intrinsic myocardial function in sepsis. Currently, SIC is assumed to be the result of the interaction of microorganisms that activate the physiopathological pathways and cellular signaling mechanisms that lead to intrinsic myocardial dysfunction. However, the animal models used to study SIC exhibit multiple limitations. This review addresses the conceptual background, historical perspectives, physiologic mechanisms, current evidence, and limitations of SIC characterization. It also highlights potential future directions for the hemodynamic assessment of the intrinsic contractile function of the heart to overcome current methodological limitations. Finally, the present review recommends the exploration of additional potential mechanisms underlying SIC.

Cirrhosis-Associated Cardiomyopathy

Liver cirrhosis is the 12 th leading cause of death in the US. The heart is one of the most adversely affected organs in liver cirrhosis. Cirrhosis-induced cardiomyopathy describes the cardiac dysfunction in patients with cirrhosis characterized by impaired contractile response to stress and/or altered diastolic relaxation with electrophysiologic abnormalities in the absence of other known cardiac disease. The current definition of cirrhosis-induced cardiomyopathy does not take into account recent evidence of resting contractile and relaxation dysfunction that can be appreciated by advanced imaging tools such as Doppler tissue imaging and cardiac magnetic resonance imaging. Cirrhosis-induced cardiomyopathy is caused by cellular as well as physiological mechanisms including but not limited to: beta adrenergic receptor dysfunction, calcium channelopathy, elevated levels of catecholamines, elevated levels of nitric oxide, carbon monoxide and hydrogen sulphide and stimulation of endogenous cannabinoid pathways capable of producing negative inotropic, relaxation, and electrophysiological defects. Currently there is no specific therapy for cirrhosis-induced cardiomyopathy. There is some evidence that short courses of beta blockers may restore prolonged QT interval to normal values. Also, there is an emerging evidence for a role of aldosterone antagonists in reducing myocardial hypertrophy. Liver transplantation may revert cardiac dysfunction, but surgery and shunt insertion may also aggravate the condition. More standardized tools are needed to screen for and treat cirrhosis-induced cardiomyopathy.

Towards a better characterization of cirrhosis-associated cardiomyopathy?

Diagnostic criteria: Systolic dysfunction • Blunted increase in cardiac output with exercise, volume challenge or pharmacological stimuli • Resting EF <55% Diastolic dysfunction • E/A <1 • Prolonged deceleration time (>200 msec) • Prolonged isovolumetric relaxation time (<80 msec) Supportive criteria • Electrophysiological abnormalities • Chronotropic incompetence • Electromechanical uncoupling • Prolonged QTc interval • Enlarged left atrium • Increased myocardial mass • Increased BNP, pro-BNP • Increased Troponin I To the Editor: ‘Cirrhotic cardiomyopathy’ arose as a separate clinical entity when characterized by Lee and colleagues in 1989 [1]. According to the World Congress of Gastroenterology [2], cirrhotic cardiomyopathy describes ‘cardiac dysfunction in patients with cirrhosis characterized by impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in the absence of known cardiac disease’ (Table 1). It is known that patients with cirrhotic cardiomyopathy have high mortality and morbidity [3]. Thus, there is a need that this entity be more accurately described. Impaired contractile responsiveness to stress originated from reports of failure to increase one or more measures of cardiac performance including: cardiac output, ejection fraction, and stroke volume in response to stress, with elevation of left ventricular filling pressures. The changes in cardiac afterload have been reported inconsistently among studies; with afterload being elevated in some [4,5] and reduced in others [6]. Based on these observations, the consistent response of left ventricular output and filling pressures to varying stress-related changes in afterload was coined as stress-related contractile dysfunction. As a consequence, normal ventricular filling pressures coupled with an elevated output during resting conditions were perceived as appropriate function. In other words, left ventricular stroke volume, cardiac output, and ejection fraction have all been regarded as presumptive surrogates of intrinsic contractile function as a function of filling pressures. Several physiological considerations would argue against such interpretation of cardiac output and ejection fraction. First, cardiac output is the product of stroke volume and heart rate. Therefore, a hyperdynamic state characterized by an elevated heart rate may mask an intrinsic contractile dysfunction. Second, cardiac output and stroke volume are load-dependent indices that show mutually inverse proportionality with venous return and afterload. Therefore, reduction in afterload may mask both an intrinsic contractile dysfunction, as well as mild hypovolemia, during resting conditions. On the other hand, marked hypovolemia secondary to dehydration may mask an increase in cardiac output resulting from afterload reduction, as occurs in exercise. The same limitations apply to ejection fraction as a surrogate of ventricular contractility. An elevated resting left ventricular end diastolic volume, coupled with a decrease in end systolic volume due to a reduction in afterload, might explain the increase in resting ejection fraction that is unrelated to intrinsic contractile dysfunction [7]. Third, ejection fraction is a marker of the more circularly arranged myocardial fibers, which are less vulnerable than the longitudinally arranged subendocardial fibers to ischemia and fibrosis [7]. Therefore, a normal resting ejection fraction may not necessarily represent normal intrinsic ventricular contractile function. Fourth, there are multiple technical limitations in the measurement of ejection fraction by echocardiography such as: less accurate border detection in postoperative and mechanically ventilated patients, and underestimation of end diastolic volumes [8]. Fifth, elevated ventricular

Shiver Yes, Die No

This case discusses the interaction between an unsuspected source of selegiline in a transdermal patch and meperidine, resulting in serotonin syndrome.

The use of intraoperative positive end expiratory pressure

General anesthesia is associated with impaired gas exchange mainly because of increased shunt due to atelectasis in the dependent regions of the lung. Postoperative atelectasis is associated with adverse clinical outcomes in terms of hypoxic respiratory failure requiring endotracheal intubation and pneumonia secondary to impairment of ciliary and lymphatic functions. Prevention of atelectasis and/or airway closure could be a mechanism by which positive end expiratory pressure (PEEP) improves oxygenation. Positive end expiratory pressure has been used intraoperatively as a part of open lung and protective lung ventilation strategies. However, it is unclear at the present time whether the intraoperative use of PEEP is associated with a decrease in mortality or in the incidence of other important clinical surrogates of outcome such as postoperative respiratory failure. The aim of this review is to review the physiologic effects and history of PEEP, to present some of the current uses in specific surgical populations and comment on potential benefits on postoperative mortality and pulmonary complications that may be ascribed to intraoperative PEEP use.