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Beta-blockade in experimental fluid-resuscitated sepsis: acute haemodynamic effects of esmolol differ in predicted survivors and non-survivors


Beta-blockade therapy during sepsis has a sound rationale in view of its cardiac, metabolic, inflammatory and other effects [1]. Whether it is safe and efficacious in both good prognosis and poor prognosis patients is yet to be ascertained. We have developed a 72-h fluid-resuscitated rat model of faecal peritonitis, where prognosis can be accurately predicted as early as 6 h post-insult based on the degree of myocardial depression (low stroke volume, high heart rate)[2]. This model offers a useful means of testing safety and efficacy.


To compare dose-related haemodynamic effects of esmolol at 6 hours in predicted survivors and non-survivors from faecal peritonitis.


Instrumented male Wistar rats (350 ± 16 g) had sepsis induced with intraperitoneal injection of faecal slurry. Fluid resuscitation (10 ml/kg/h) was begun 2 h later. At 6 h, animals were divided into predicted survivors or non-survivors depending on a stroke volume cut-off of 0.20 ml. After an additional 10-ml/kg fluid bolus, esmolol was administered as a 500- µg/kg loading dose followed by an increasing stepwise infusion (50 to 200 µg/kg/min in 25- µg/kg/min increments 5 minutes apart). Heart rate, stroke volume and mean arterial pressure were recorded just prior to each dose increase. Repeated measures ANOVA and post-hoc Holm-Sidak test were used to seek statistically significant differences.


Baseline stroke volume at 6h was significantly lower in poor prognosis animals (0.27 ± 0.07 vs. 0.18 ± 0.02 ml, p < 0.05). Stroke volume increased with low dose esmolol in predicted non-survivors, and this offset the reduction in heart rate (Figure 1). Cardiac output was thus maintained in predicted non-survivors but fell significantly in predicted survivors. Mean BP fell in parallel in both groups, though significant changes were seen earlier in predicted survivors.

Figure 1
figure 1

*p < 0.05 vs. baseline (good prognosis group, dark blue bars, N = 4). # p < 0.05 vs. baseline (poor prognosis group, light blue bars, N = 4).


Depending on their prognosis, septic rats show different haemodynamic responses to a short-term esmolol infusion at 6 h post-septic insult. Whether longer-term infusion is beneficial or harmful to these subgroups will be the subject of future study.

Grant Acknowledgement

ESICM Basic Science Award, UK Intensive Care Society Young Investigator Award, NIHR.


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  2. Rudiger A, et al: Clin Sci. 2013, 124: 391-401. 10.1042/CS20120334.

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Khaliq, W., Andreis, D. & Singer, M. Beta-blockade in experimental fluid-resuscitated sepsis: acute haemodynamic effects of esmolol differ in predicted survivors and non-survivors. ICMx 3 (Suppl 1), A801 (2015).

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  • Stroke Volume
  • Esmolol
  • Haemodynamic Effect
  • Faecal Peritonitis
  • Poor Prognosis Patient