Adjunctive Hydrocortisone Improves Hemodynamics in Critically Ill Patients with Septic Shock: An Observational Study Using Transpulmonary Thermodilution
Leonie JochheimDavid JochheimLivia HabenichtAlexander HernerJörg UlrichJohannes R. WießnerMarkus HeilmaierSebastian RaschRoland M. SchmidTobias LahmerUlrich Mayr
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Introduction: Septic shock is associated with high mortality and hemodynamic impairment. The use of corticoids is a common therapeutic tool in critically ill patients. However, data on the mechanisms and prognostic ability of hemodynamic improvement by adjunctive steroids are rare. This study primarily aimed to evaluate short-term effects of hydrocortisone therapy on catecholamine requirement and hemodynamics derived from transpulmonary thermodilution (TPTD) in 30 critically ill patients with septic shock and a 28 days mortality rate of 50%. Methods: Hydrocortisone was administered with an intravenous bolus of 200 mg, followed by a continuous infusion of 200 mg per 24 h. Hemodynamic assessment was performed immediately before as well as 2, 8, 16, and 24 h after the initiation of corticoids. For primary endpoint analysis, we evaluated the impact of hydrocortisone on vasopressor dependency index (VDI) and cardiac power index (CPI). Results: Adjunctive hydrocortisone induced significant decreases of VDI from 0.41 (0.29-0.49) mmHg-1 at baseline to 0.35 (0.25-0.46) after 2 h (P < .001), 0.24 (0.12-0.35) after 8 h (P < .001), 0.18 (0.09-0.24) after 16 h (P < .001) and 0.11 (0.06-0.20) mmHg-1 after 24 h (P < .001). In parallel, we found an improvement in CPI from 0.63 (0.50-0.83) W/m2 at baseline to 0.68 (0.54-0.85) after 2 h (P = .208), 0.71 (0.60-0.90) after 8 h (P = .033), 0.82 (0.6-0.98) after 16 h (P = .004) and 0.90 (0.67-1.07) W/m2 after 24 h (P < .001). Our analyses revealed a significant reduction in noradrenaline requirement in parallel with a moderate increase in mean arterial pressure, systemic vascular resistance index, and cardiac index. As a secondary endpoint, our results showed a significant decrease in lung water parameters. Moreover, changes in CPI (ΔCPI) and VDI (ΔVDI) after 24 h of hydrocortisone therapy revealed accurate prognostic ability to predict 28 days mortality (AUC = 0.802 vs 0.769). Conclusion: Adjunctive hydrocortisone leads to a rapid decrease in catecholamine requirement and a substantial circulatory improvement in critically ill patients with septic shock.Keywords:
Cardiac index
Bolus (digestion)
Clinical endpoint
The hemodynamic changes on the course of septic multiorgan failure (s-MOF), and the effects of norepinephrine administrated at septic shock state were evaluated in thirteen patients who died of s-MOF in ICU. The course in ICU was divided into following three stages. Stage I was for a few days after admission in ICU. Stage II was severe infected state. Stage III was the terminal state, i.e., a few days before death. Norepinephrine was administrated when conventional catecholamines (dopamine and/or dobutamine) could not maintain the blood pressure level in the shift from stage II to III, and the hemodynamic changes were evaluated before and after the administration. The following results were obtained: 1) Hemodynamic changes: The stage I was characterized as a moderately hyperdynamic state. The stage II exhibited a typical hyperdynamic state distinguished by a decrease in systemic vascular resistance (SVR). The stage III was distinguished as a normodynamic shock state, because of fall of cardiac output within normal control level. 2) Norepinephrine increased cardiac index, heart rate, and right ventricular stroke work index, but mean arterial pressure, stroke index and SVR did not exhibit any change. However, norepinephrine was useful aid to maintain the circulation in hypotensive state, when conventional catecholamines could not maintain blood pressure any more.
Dobutamine
Cardiac index
Mean arterial pressure
Hyperdynamic circulation
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Hemodynamics is monitoring a series of physiological and pathological parameter changes such as blood flow,the chamber pressure of the heart,pressure or resistance of cardiovascular and cardiopulmonary system.Traditional hemodynamic monitoring in septic shock manily includes central venous pressure,cardiac index,blood lactate and pH.In recent years,expanded non-invasive or invasive monitoring technologies include central venous or mixed venous oxygen saturation,continuous ultrasound associated with underlying cardiac output monitoring and pulse indicator continuous cardiac output.Macro-hemodynamic,metabolic and microcirculatory parameters constitute a new hemodynamics network.In order to properly assess the patient's blood volume and circulation function and to overcome the limitations of a single parameter,it is need to emphasize analysis and integration of the various parameters.
Key words:
Septic shock; Hemodynamics; Circulation function
Cardiac index
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Cardiac index
Bolus (digestion)
Endorphins
Mean arterial pressure
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Hyperdynamic circulation
Cardiac index
Venous return curve
Coronary circulation
Oxygen transport
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Determination was made of cardiac output (using the stain dilution technique), gases in blood and serum lactate levels in eight infants with hypovolemic shock and sixteen with septic shock. The data were carried to indexes (values per square meter of body surface). In children with hypovolemic shock the cardiac index was 1.88 +/- 0.031/min/m,2 while in septic patients it was 4.02 +/- 1.011/min/m2. The peripheral resistances were 3,079 din/min/cm.5 in hypovolemic cases and 907 din/min in the septic. In both groups serum lactante levels rised close to 4 mM 61. Oxigen consumption was found low in hypovolemic patients and slightly high in the septic. It is concluded that our data are similar to those reported in similar studies in adults and hypodynamic shock is shown in hypovolemic patients, while hyperdynamic shock appears in septic cases.
Cardiac index
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The relationship between cardiac output, total peripheral resistance index (TPRI) treatment, and prognosis was evaluated in 151 patients studied by the Shock Unit of the Detroit General Hospital. Although the hemodynamic values did not correlate with the severity of the shock and did not have a significant effect on the outcome of the patients, the drugs used and the response to treatment were critical. Drugs which maintained or increased any hemodynamic abnormality were detrimental. There was a significant increase in mortality when vasoconstrictor drugs were used in patients who had a low cardiac output (less than 2.5 liters/min/sq m) and were vasoconstricted (TPRI above 2,200 dyne-sec/cm5/sq m). Likewise, the use of vasodilators in septic patients, especially those with the highest cardiac outputs (above 3.5 liters/min/sq m) and most vasodilation (TPRI less than 1,300 dyne-sec/cm5/sq m), was also associated with a significantly increased mortality.
Cardiac index
Haemodynamic response
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The relationship between cardiac output, total peripheral resistance index (TPRI) treatment, and prognosis was evaluated in 151 patients studied by the Shock Unit of the Detroit General Hospital. Although the hemodynamic values did not correlate with the severity of the shock and did not have a significant effect on the outcome of the patients, the drugs used and the response to treatment were critical. Drugs which maintained or increased any hemodynamic abnormality were detrimental. There was a significant increase in mortality when vasoconstrictor drugs were used in patients who had a low cardiac output (less than 2.5 liters/min/sq m) and were vasoconstricted (TPRI above 2,200 dyne-sec/cm 5 /sq m). Likewise, the use of vasodilators in septic patients, especially those with the highest cardiac outputs (above 3.5 liters/min/sq m) and most vasodilation (TPRI less than 1,300 dyne-sec/cm 5 /sq m), was also associated with a significantly increased mortality.
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That a decline in oxygen consumption (VO2) might herald onset of septic shock prior to hemodynamic collapse is suggested by previous observations in humans and animals in which VO2 appeared to be suppressed in systemic sepsis, despite normal or supranormal cardiac output, and in cellular and mitochondrial preparations exposed to endotoxin, despite adequate flow of perfusate. That a supranormal VO2 might be one of the best predictors of ultimate survival is suggested by data collected from humans during various stages of septic shock. To evaluate VO2 as an early indicator of sepsis, the effect of endotoxemia was observed in 20 rhesus monkeys divided into groups according to hypodynamic, normodynamic, and hyperdynamic blood flow states; the effect of sepsis was observed in seven preterminal septic humans during the final hours of their lives. VO2 was measured using a new device that evaluates expired gases by means of a relatively simple feedback-controlled gas replenishment technique. In neither the primates nor the humans was it possible to demonstrate a flow-independent depression of VO2. VO2 was distinctly elevated in each of the humans over some interval during the final day of life. These observations, plus an in-depth review of the literature, suggest that other variables, particularly peripheral vascular resistance, systemic and regional blood flow, and oxygen extraction fraction attempt to accommodate in an effort to sustain VO2. Probability of survival in sepsis appears to be enhanced by VO2 and cardiac output that are supranormal; yet even when VO2 is elevated, death can ensue within minutes to hours. Significant decline in VO2 is a grave prognostic sign, almost always preceded by a relatively easily detected hemodynamic change. Systemic VO2 appears to represent neither a specific early indicator of sepsis nor a certain prognosticator of survival outcome; it might provide useful information regarding adequacy of resuscitation.
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The hemodynamic effect of dobutamine infusion (DI) was studied in 19 patients with septic shock. DI resulted in hemodynamic improvement as indicated by a significant increase in cardiac index (+36%, p less than 0.001), stroke index (+15%, p less than 0.01), mean arterial pressure (+20%, p less than 0.01), and a significant decrease in aVDO2 (-27%, p less than 0.01). This hemodynamic improvement occurred concomitantly with a fall in both right and left filling pressures. Mean systemic arterial resistance remained unchanged with a scatter of individual responses depending on other factors, such as infusion rate, initial vascular resistance, and underlying hemodynamic setting. In patients mechanically ventilated, venous admixture in the lung (Qs/Qt) during DI increased significantly (+30%, p less than 0.001) and insignificantly reduced PaO2, but this adverse effect was not observed when PEEP was used in patients mechanically ventilated. It is concluded that dobutamine can be useful in management of septic shock, particularly when filling pressures are high because of fluid overload or cardiac failure.
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Cardiac index
Mean arterial pressure
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Many animal studies have attempted to simulate the circulatory responses to Gram-negative septicemia (iv infusion of live bacteria, fecal inoculation into body cavities, and administration of purified endotoxins by various routes), but the contribution of the heart to the adverse hemodynamic derangements and thus to the pathogenesis of shock is difficult to determine because of peripheral vascular events that influence cardiac performance. When blood pools in the periphery, venous return decreases and cardiac output can decrease without a primary myocardial defect being present. However, early heart dysfunction has been recognized in sepsis. Hemodynamic monitoring has not reduced overall mortality, but it has been helpful in guiding fluid administration and evaluating response to vasopressor therapy.
Circulatory collapse
Venous return curve
CIRCULATORY FAILURE
Pathogenesis
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