A middle aged man developed septic shock secondary to community acquired pneumonia. He was ventilated and commenced on noradrenaline therapy. He had an echo on admission that showed a structurally normal heart with normal biventricular function. He remained statically unwell for several days and had a further deterioration on day 4 with further bilateral consolidation seen on CXR. Repeat echocardiography showed a well filled, but globally impaired heart with an ejection fraction of 10-20%. He was commenced on additional inotropic support, but continued to deteriorate, developed multiorgan failure and died.
Is septic cardiomyopathy reversible? What is the current best treatment?
Reversible myocardial depression in patients with septic shock has been described since the 1980s (1) in both animal models and patient case series. Its prevalence was underestimated for many years due to the widespread use of the pulmonary artery catheter which is unsuitable for establishing the diagnosis (see below). The pathogenesis of cardiac depression in sepsis is likely multifactorial. In vitro exposure of myocardial cells to the serum of septic patients leads to reduced shortening. Several cytokines have been implicated, including TNF-α, IL-1β and NO. Direct alteration in cellular respiration with mitochondrial dysfunction and phosphorylation of troponin I may also play a role.
Septic cardiomyopathy can occur in the acute stages of the illness. Several case series describing the condition were performed in patients in the first 6 hours of resuscitation. It is reversible, providing that the patient recovers. In a case series of 90 patients Jardin et al (2) reported that left ventricular (LV) ejection fraction normalised within a few days. Unlike cardiogenic shock (where the LV filling pressures are elevated) the LV filling pressures are normal or low. This results from the frequent association with right ventricular (RV) dysfunction (secondary to pulmonary hypertension) or circulating cytokines. It also occurs from an increase in LV compliance. These two mechanisms result in pulmonary capillary wedge pressures of around 11mmHg (3), explaining why the historical widespread use of pulmonary artery catheters led to the underestimation of the incidence of the LV dysfunction.
Incidence is currently reported as 18% – 65% (4). This large disparity is likely as a result of changes in LV afterload in patients with sepsis, as ejection fraction reflects the LV afterload rather than the intrinsic contractility. A patient whose LV contractility remains constant will have an increase in ejection fraction if the afterload decreases (as often seen in sepsis) and a decrease in ejection fraction if the afterload increases (such as a noradrenaline infusion). The association of LV dysfunction in sepsis with mortality is poorly understood as most studies are small in size. A meta-analysis published in 2013 (5) included 14 studies, with >700 patients available for LV analysis and >400 for RV analysis. It found no significant differences in left ventricular ejection fractions and right ventricular ejection fractions between the survivor and non-survivor groups.
Although septic cardiomyopathy has been described since the 1980s uncertainty persists over best treatment options. Massive fluid infusion has been proposed to maintain a normal cardiac index when faced with impaired LV contractility through LV pre-load adaptation (1). This effect is however limited as these patients have a flat Frank-Starling curve. Additionally it is now known that fluid overload is deleterious for survival (6). Inotropic drugs such as dobutamine can increase LV ejection fraction and cardiac index (7). It is well established that the cardiovascular response to dobutamine stress predicts outcome in sepsis, patients with an increased oxygen consumption in response to a dobutamine infusion have a much higher survival rate (8). It is not however known if dobutamine improves survival. Levosimendan (a calcium channel sensitizer) may improve both LV and RV function, with preliminary animal models showing restoration of LV elastance. Further work is needed however to see if this translates into clinical benefit. The majority of patients with septic shock are currently treated with norepinephrine. As mentioned above it may unmask an LV with impaired contraction, but it may also increase cardiac output through an increase in both cardiac preload and cardiac contractility (9).
Septic cardiomyopathy is an acutely reversible condition. Cardiac performance evaluated by echocardiography reflects both intrinsic contractility and the degree of vasoplegia. Current data does not indicate an association between septic cardiomyopathy and mortality. The haemodynamic response to a dobutamine challenge has prognostic value, but further studies are needed to establish whether inotropic drugs have a role to play in the treatment of this condition.
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