Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.

Septic Shock in Humans: Advances in the Understanding of Pathogenesis, Cardiovascular Dysfunction, and Therapy

Marked abnormalities in cardiovascular function accompany septic shock, and bacterial endotoxin is believed to be one of the principal mediators of these abnormalities. To evaluate the cardiovascular effects of endotoxemia in humans, we measured hemodynamic variables in nine normal subjects given an intravenous bolus dose of endotoxin (Escherichia coli, 4 ng per kilogram of body weight) and in six normal subjects given a bolus dose of saline, before and three hours after administration. All the subjects then underwent volume loading with normal saline (mean, 2217 ml) during the fourth and fifth hours after administration of the bolus, and the measurements were repeated. Three hours after the administration of endotoxin and before volume loading, the cardiac index had increased by 53 percent and the heart rate by 36 percent (both changes were significant; P less than or equal to 0.008), and the systemic vascular-resistance index had decreased by 46 percent (P = 0.004). After volume loading (five hours after the administration of endotoxin), the left ventricular ejection fraction decreased by 1 percent of the base-line value in the subjects given endotoxin, but increased by 14 percent in the controls (P = 0.008). The left ventricular end-diastolic and end-systolic volume indexes increased by 18 percent (P = 0.07) and 24 percent (P = 0.042), respectively. Left ventricular performance, as measured by the ratio of the peak systolic pressure to the end-systolic volume index, was depressed (a decrease of 0.90 in the subjects given endotoxin vs. an increase of 0.76 in the controls; P = 0.024). We conclude that the administration of endotoxin to normal subjects causes a depression of left ventricular function that is independent of changes in left ventricular volume or vascular resistance. The changes in function are similar to those observed in septic shock and suggest that endotoxin is a major mediator of the cardiovascular dysfunction in this condition.

https://www.nejm.org/doi/pdf/10.1056/NEJM198908033210503?listPDF=true

The cardiovascular response of normal humans to the administration of endotoxin

The adult respiratory distress syndrome (ARDS) is an important and common medical emergency and is likely to occur in all hospitals dealing in respiratory care. The syndrome occurs from a variety of diffuse pulmonary injuries which are either direct or indirect attacks on the lung parenchyma. Once lung damage occurs, exudation of fluid and loss of surfactant activity leads to impaired gas exchange and reduced pulmonary compliance. The syndrome presents clinically as marked respiratory distress, tachypnea, cyanosis, refractory hypoxemia, high inflation pressure requirements during ventilatory support, diffuse alveolar infiltrates on chest roentgenograms and postmortem pulmonary congestion, hyperemia and hyaline membrane formation. Principles of management include adequate support of oxygen transport, ventilation and circulation employing volume respirators with positive end-expiratory pressure (PEEP). During the support phase, further pulmonary injury in terms of fluid overload, oxygen toxicity or infection, must be prevented or treated. When these principles of management are followed, recovery often occurs in spite of severe pulmonary injury as indicated by the first two illustrative cases.

https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1739&context=mcvq

The Adult Respiratory Distress Syndrome: Clinical Features, Factors Influencing Prognosis and Principles of Management

Objectives:To review mechanisms underlying sepsis-induced cardiac dysfunction in general and intrinsic myocardial depression in particular.Data Source:MEDLINE database.Data Synthesis:Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis. Due to the lack of a general

Mechanisms of sepsis-induced cardiac dysfunction

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur. A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others. Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Sepsis and the Heart

To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 +/- 47 vs 130 +/- 21 ml/min in the control group, p less than .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p less than .005), while that of lactate was increased (36% vs 12%, p less than .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41% of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Respiratory pressure-volume (PV) curves are commonly obtained in paralyzed patients by relating airway pressure to volume changes of a syringe (Vsyr). This is based on the implicit assumption that changes in thoracic volume (Vtho) and Vsyr are equal. We undertook to verify this assumption through simultaneous measurements of Vtho by respiratory inductive plethysmography and Vsyr in six comatose, paralyzed, intubated patients. At any constant Vsyr, Vtho fell and was smaller on deflation than on inflation during inflation-deflation (ID) cycle. The rate of fall was 110 +/- 64 (SD) ml/min. During ID cycles lasting 76 +/- 7 s, thoracic PV curves showed less hysteresis and a larger compliance on deflation than PVsyr curves (12 +/- 2 vs. 18 +/- 6% and 73 +/- 13 vs. 67 +/- 12 ml/cmH2O, P less than 0.05). With PVsyr curves, hysteresis increased and compliance on deflation decreased with increasing rate of fall of Vtho. We submit that the difference between changes in Vsyr and Vtho is best explained by gas exchange and should be taken into account when performing PV curves with a syringe in paralyzed patients.

Causes of error of respiratory pressure-volume curves in paralyzed subjects

The Coronary Circulation and the Myocardial Oxygen Supply/Uptake Relationship: A Short Review

Respiratory inductive plethysmography (RIP), first used in research has progressively become a routine respiratory monitoring technique, by the fact that the latest generation of equipment is especially designed for the intensive care environment. Now easy to use and reliable, RIP allows close monitoring of the respiratory function of patients before, during and after mechanical ventilation. It is therefore part of the decision-making process in the ICU [1].

Respiratory Inductive Plethysmography for Assessing Risk of Pulmonary Barotrauma

The mortality of the adult respiratory distress syndrome (ARDS) remains high, but patients who survived the acute phase of the syndrome generally resume productive lives with no serious pulmonary limitations [1–3]. Specific treatments of ARDS should ideally be directed to limit the initial abnormal inflammatory response. However, ARDS therapy is essentially supportive with a central role for mechanical ventilation. Conventional mode of ventilation aimed to obtain “normal” pulmonary function as reflected by arterial blood gases, and some lung injury was accepted as an inevitable consequence [4, 5]. Positive-end expiratory pressure (PEEP) has been early proposed to achieve adequate arterial oxygenation while decreasing FiO2 to limit oxygen toxicity [4, 5]. This type of ventilatory support is frequently associated with high airway pressures and volumes for effective ventilation which, in turn, may worsen the lung injury [7–11]. Optimal ventilation would be the mode achieving adequate gas exchange without increasing the risk of ventilator-induced barotrauma [7, 12]. New strategies have been developed to prevent the lungs exposure to high pressures and to lower minute ventilation [13–15]. All these modes of ventilation introduce a new concept of ventilation which allows “abnormal” respiratory function with hypercapnia [12, 16]. There are no convincing data indicating that any ventilatory mode is superior to others for ARDS patients, both in terms of reduction of morbidity and mortality.

J. F. Dhainaut

Papers

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Causes of error of respiratory pressure-volume curves in paralyzed subjects

The Coronary Circulation and the Myocardial Oxygen Supply/Uptake Relationship: A Short Review

Respiratory Inductive Plethysmography for Assessing Risk of Pulmonary Barotrauma

Mechanical Ventilation should be Individually Optimized in Patients with ARDS