Is myocardial adrenergic responsiveness depressed in human septic shock?

Objective To assess left ventricular (LV) contractile function and adrenergic responsiveness in septic patients. Methods We used echocardiographically defined fractional area of contraction (FAC), and LV area to end-systolic arterial pressure estimates of end-systolic elastance (E'es) and its change in response to dobutamine (5 μg/kg/min) in 10 subjects in septic shock admitted to an intensive care unit of an academic medical center. Subjects were studied on admission and again at both 5 days and 8–10 days after admission. Results Three of the 10 subjects died as a result of their acute process, while the others were discharged from hospital. Nine out of 10 subjects required intravenous vasopressor therapy on day 1, while only 1 of 9 subjects required vasopressor support at day 5. LV end-diastolic area (EDA) increased from day 1 to day 5 and days 8–10 (p < 0.05), but neither FAC nor E'es was altered by time (EDA 15.7 ± 5.8, 21.4 ± 5.1, and 19.4 ± 5.6 cm²; FAC 0.46 ± 0.19, 0.50 ± 0.20, and 0.48 ± 0.15%; E'es 21.6 ± 12.6, 23.2 ± 8.5, and 19.2 ± 6.3 mmHg/cm², mean ± SD, for days 1, 5 and 8–10 respectively). Although dobutamine did not alter E'es on day 1 or day 5, E'es increased in all of the 5 subjects studied on days 8–10 (p < 0.05). Conclusions Adrenergic hyporesponsiveness is present in septic shock and persists for at least 5 days into recovery, resolving by days 8–10 in survivors. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Dr. Pinsky was a Professeur Associé at Cochin Hospital and Paris Descartes University.     

Bench-to-bedside review: Is there a place for epinephrine in septic shock?

The use of epinephrine in septic shock remains controversial. Nevertheless, epinephrine is widely used around the world and the reported morbidity and mortality rates with it are no different from those observed with other vasopressors. In volunteers, epinephrine increases heart rate, mean arterial pressure and cardiac output. Epinephrine also induces hyperglycemia and hyperlactatemia. In hyperkinetic septic shock, epinephrine consistently increases arterial pressure and cardiac output in a dose dependent manner. Epinephrine transiently increases lactate levels through an increase in aerobic glycolysis. Epinephrine has no effect on splanchnic circulation in dopamine-sensitive septic shock. On the other hand, in dopamine-resistant septic shock, epinephrine has no effect on tonometric parameters but decreases fractional splanchnic blood flow with an increase in the gradient of mixed venous oxygen saturation (SVO₂) and hepatic venous oxygen saturation (SHO₂). In conclusion, epinephrine has predictable effects on systemic hemodynamics and is as efficient as norepinephrine in correcting hemodynamic disturbances of septic shock. Moreover, epinephrine is cheaper than other commonly used catecholamine regimens in septic shock. The clinical impact of the transient hyperlactatemia and of the splanchnic effects are not established.     

Is there a place for N-acetylcysteine in the treatment of septic shock?

Excessive inflammatory responses and impaired oxygen utilization because of microcirculatory failure are implicated in septic shock. Recent studies have pointed out some beneficial effects in the treatment of septic shock of several vasodilators that exert anti-inflammatory properties. In particular, the antioxidant N-acetylcysteine has been demonstrated to enhance cardiac performance, and to improve hepatosplanchnic perfusion and liver function in patients with established septic shock. These clinical observations may lead us to examine further the role of antioxidant agents in developing novel therapies for septic shock.     

Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: Time to aim higher?

Purpose

Septic patients with hyperlactatemia have increased mortality rates, irrespective of hemodynamic and oxygen-derived variables. The aims of the study are the following: (1) to ascertain whether lactate clearance (LC) (percentage change in lactate over unit time) predicts mortality in septic patients admitted to intensive care directly from the emergency department and (2) to calculate the optimal “cut-off” value for mortality prediction.

Methods

Three-year retrospective observational study of consecutive patients with severe sepsis and septic shock admitted to intensive care from the emergency department of a tertiary UK hospital. We calculated 6-hour LC, performed receiver operating characteristic analyses to calculate optimal cut-off values for initial lactate and LC, dichotomized patients according to the LC cut-off, and calculated hazard ratios using a Cox proportional hazards model.

Results

One hundred six patients were identified; 78, after exclusions. Lactate clearance was independently associated with 30-day mortality (P < .04); optimal cut-off, 36%. Mortality rates were 61.1% and 10.7% for patients with 6-hour LC 36% or less and greater than 36%, respectively. Hazard ratio for death with LC 36% or less was 7.33 (95% confidence interval, 2.17-24.73; P < .001).

Conclusions

Six-hour LC was independently associated with mortality, and the optimal cut-off value was 36%, significantly higher than previously reported. We would support further research investigating this higher LC as a distinct resuscitation end point in patients with severe sepsis and septic shock.     

Fever control in septic shock: beneficial or harmful?

The beneficial effects of interventions to control fever in sepsis are controversial. We investigated whether the use of acetaminophen and external cooling is beneficial to control fever in septic shock. We studied 24 fasted, anesthetized, invasively monitored, mechanically ventilated female sheep (27.0 +/- 4.6 kg) that received 0.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Ringer's lactate (RL) was titrated to maintain pulmonary artery occlusion pressure (PAOP) at baseline levels throughout the experimental period. During the 2 h after the surgical operation, animals were placed in the hypothermia group if their temperature fell below 36.0 degrees C; the other animals were randomized to three groups: high fever (T > 39.0 degrees C), mild fever (37.5 degrees C < T < 38.5 degrees C), and normothermia (36.0 degrees C < T < 37.0 degrees C). The administration of 25 mg/kg acetaminophen every 4 to 6 h combined with external cooling (ice pad) was used to control core temperature in these three groups. The PaO2/FiO2 ratio was higher and blood lactate concentration was lower in the high fever than in the other groups (P < 0.01 and 0.05, respectively). Survival time was longer in the high fever group (25.2 +/- 3.0 h) than in the mild fever (17.7 +/- 3.5 h), normothermia (16.0 +/- 1.9 h), and hypothermia (18.5 +/- 2.5 h) groups (P < 0.05 for all). Plasma heat shock protein (HSP) 70 levels were higher in the two fever groups than in the other groups (P < 0.05). In this clinically relevant septic shock model, the febrile response thus resulted in better respiratory function, lower blood lactate concentration, and prolonged survival time. Antipyretic interventions including acetaminophen and external cooling were associated with lower circulating HSP70 levels. These data challenge the temperature control practices often used routinely in acutely ill patients.     

How much fluid resuscitation is optimal in septic shock?

ABSTRACT: Smith and Perner report an observational cohort study of 164 patients with septic shock. For patients still alive on day 3, higher compared with lower fluid volume resuscitation was associated with lower 90-day mortality. This association of a relationship between fluid intake and decreased mortality aligns with the randomized controlled trial of early goal-directed therapy and later observational studies. I suggest careful individualization of fluid resuscitation to achieve adequate mean arterial pressure (about 60 to 70 mmHg) and normalization of arterial lactate levels in septic shock. TRIAL REGISTRATION: ISRCTN94845869.