Association of Milrinone Dosing with Efficacy

Despite the fact that for most admissions (80.3%) the patient started milrinone before admission to the CCU, low cardiac output syndrome during the CCU stay was common (76.1%). This frequency was nearly twice the 45% reported in the Prophylactic Intravenous Use of Milrinone after Cardiac Operation in Pediatrics (PRIMACORP) study. Both studies defined low cardiac output syndrome as AVO2 difference of 30% or more, but the PRIMACORP study also counted those with doubling of inotropes. We excluded the inotrope compo­nent of the definition, and many of the patients in our study were receiving additional inotropes. The observed mortality rate of 6.1 % was well above that observed in the PRIMACORP study (0.8%, with no deaths during milrinone therapy), which suggests that the population in the current study had a higher severity of illness.

The population in the current study differed in other respects from previous study populations. The age range was wider (from less than 1 day old to 18 years), and the patients had greater severity of illness and underwent more complex surgeries (including single-ventricle repair). This high­lights the paucity of literature assessing milrinone use in an “expanded population” that includes patients with a single functional ventricle and children with septic shock. kamagra oral jelly 100mg

There appeared to be a trend between milrinone therapy involving greater average infusion rate and longer duration and greater likelihood of low cardiac output syndrome (Table 3). This suggests that sicker patients may require more milrinone, although the retrospective nature of the study prevents more definitive conclusions on this point. The complexity of the patient population (e.g., patients with a single ventricle) may explain the duration of milrinone use (up to 928.6 h or nearly 39 days), although this cannot be confirmed. It was interesting that type of surgery (single-ventricle versus biventricular) was not significantly associated with low cardiac output syndrome in the regression model. There was a trend toward an associa­tion between AVO2 difference of 30% or more and a greater average dose rate of milrinone (p = 0.053) (Table 3). A lactate difference greater than 2 mmol/L was positively associated with a longer duration of infusion (p < 0.001). However, the odds ratio was close to 1, so the clinical significance is questionable, even though the result was statistically significant. Use of a pacemaker and dose of dopamine were positively associated with AVO2 difference of 30% or more (Table 3). These 2 factors may indicate the acuity of illness, with sicker patients having a greater likelihood of low cardiac output syndrome. The number of nephrotoxins was negatively associated with AVO2 difference or 30% or above. One explanation for this may be that antibiotics coded as nephrotoxins (i.e., aminogly- cosides) were used for prophylaxis in cases of delayed sternal closure, and this delayed closure may have reduced the likeli­hood of low cardiac output syndrome. However, we did not determine the incidence of sternal opening, and this explana­tion remains purely speculative.

Association of Milrinone Dosing Regimen with Adverse Effects

Thrombocytopenia and arrhythmias are well documented adverse effects of milrinone. The reported incidence of throm- bocytopenia among children receiving milrinone has ranged from 10% to 58%. The extent of this range is partly due to the various methods of assessing platelet function and to confounders, such as cardiac surgery, that can also cause thrombocytopenia. Various types of arrhythmias have been documented in 6% to 29% of patients receiving milrinone. We found no statistically significant associations between milrinone dose and adverse effects. Adverse events were frequent (thrombocytopenia in 12.7% of admissions, arrhythmia in 38.5%). There was a trend toward greater likelihood of thrombocytopenia with greater milrinone loading doses, but this was neither statistically significant (p = 0.53) nor clinically significant (odds ratio 0.997) (Table 3). Determining the incidence of milrinone-induced thrombocytopenia might be difficult because of potential confounding factors in the intra- operative and postoperative periods. Viagra Super Active

Regression analysis revealed a significant association between the adverse effects of milrinone and the following factors: need for inotropes, length of stay, use of a pacemaker, body temperature on day 1 of milrinone therapy, and number of anti-arrhythmic medications. This indicates the diversity of factors that could confound the incidence of arrhythmias and thrombocytopenia.