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Septic patients with myocardial depression are routinely treated with dobutamine. Whether this strategy is desirable is questionable, as catecholamines increase cardiac work, reduce myocardial efficiency, and are cardiotoxic. We can accurately predict mortality in a 72-hour fluid-resuscitated rat model of faecal peritonitis as early as 6 hours, based on the degree of myocardial depression (low stroke volume, high heart rate). This model offers a useful means of testing safety and efficacy of therapeutic interventions in predicted survivors and non-survivors.
To compare dose-related haemodynamic effects of dobutamine at 6 hours post-insult in predicted survivors and non-survivors from faecal peritonitis.
Male Wistar rats (341 ± 33 g) were instrumented with arterial and central venous lines. Sepsis was induced (ip injection of faecal slurry), and fluid resuscitation (10 ml/kg/h) started 2 hours later. At 6 hours, animals were assigned to good prognosis or poor prognosis groups - depending on echo-derived stroke volume (cutoff value 0.20 ml, based on previous experiments). An additional fluid bolus (10 ml/kg) was given, followed by dobutamine infusion, increasing from 5 to 20 µg/kg/min in 2.5-µg/kg/min increments every 5 minutes, with haemodynamic measures recorded just prior. Repeated measures ANOVA and post-hoc Holm-Sidak test were used to seek statistically significant. differences.
Stroke volume at 6 h was significantly lower in poor prognosis animals; good prognosis animals were more responsive than poor prognosis animals to dobutamine, with earlier rises in heart rate, stroke volume and cardiac output, and a fall in blood pressure (Figure (Figure11).
The early hypodynamic circulatory profile of poor prognosis septic rats is associated with catecholamine-hyporesponsiveness. This supports an underlying mechanism of impaired adrenergic signal transduction, and/or dysfunctional downstream pathways. Our data support the investigation of alternative agents for sepsis-induced myocardial depression.
ESICM Basic Science Award, UK Intensive Care Society Young Investigator Award, NIHR.