Refractory septic shock: efficacy and safety of very high doses of norepinephrine

The aim of this study was to evaluate the safety, efficacy, and effects of administration of very high doses of norepinephrine (> 4 microg kg(-1) min(-1)) in catecholamine-resistant septic shock. We reviewed the charts of all patients with nonresponding to commonly used norepinephrine doses (< or = 4 microg kg(-1) min(-1)) septic shock from January 1999 to December 2002 in our Surgical Intensive Care Unit. All patients were treated with high norepinephrine doses (> 4 microg kg(-1) min(-1)), after initial resuscitation, so as to achieve a mean arterial pressure higher than or equal to 65 mmHg. During this 4-year period, 12 consecutive patients with catecholamine-resistant septic shock were included in our study. When compared with the values obtained prior to the administration of very high norepinephrine doses, the values of mean arterial pressure (p = 0.003) and systemic vascular resistance (p = 0.002) significantly increased after the administration of such doses, and additionally, lactate concentrations (p = 0.003) decreased. In contrast, no significant changes were observed regarding mean central venous pressure, pulmonary capillary wedge pressure, and pulmonary arterial pressure. Administration of high norepinephrine doses in our patients resulted in a survival rate of 33.4%. Management of catecholamine-resistant septic shock patients poses a challenging problem. Administration of very high norepinephrine doses is safe and effective and may improve survival of these patients with otherwise extremely high mortality rates.