Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

Abstract

Introduction: The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function.

Methods: This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 +/- 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis.

Results: Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 +/- 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%.

Conclusion: Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.

Figure 1

Institutional hemodynamic protocol. *Fluid resuscitation using crystalloids to cover basal fluid demands (~30 mL/kg per day) and colloids for further fluid loading (guided by responses in stroke volume and cardiac index, arterial and central venous pressure, heart rate, and clinical signs). Colloids hydroxyethyl starch (molecular weight, 130.000; Voluven^® 130/0.4; Fresenius Kabi, Graz, Austria) with a dose limitation of 30 mL/kg per day based on the manufacturer's instructions and gelatine (molecular weight, 22.600; Gelofusin^®; B. Braun, Melsungen, Germany) without a dose limitation were used. ^#New-onset tachyarrhythmias, progressive tachycardia of greater than 110 beats per minute despite adequate fluid resuscitation, pulmonary arterial hypertension with new signs of right heart dysfunction, new-onset hyperglycemia (blood sugar of greater than 130 mg/dL) resistant to insulin dosages of greater than 5 IU/hour, new increase in troponin serum concentrations, or progressive deterioration of diastolic or systolic ventricular function. CI, cardiac index; MAP, mean arterial blood pressure; NE, norepinephrine; RBC, red blood cell; ScvO₂, central venous oxygen saturation.