Bolus Of Milrinone Research Articles

Dynamic assessment of left ventricular coupling and myocardial reserve in patients with cardiogenic shock.

Pulmonary artery catheter haemodynamics are associated with improved survival in cardiogenic shock (CS). We investigated the utility of aortic pulsatility index (API) and cardiac power output (CPO) as surrogates for left ventricular (LV) coupling and myocardial reserve, respectively, in patients with CS undergoing dynamic assessment after a milrinone bolus. Patients with SCAI Stage C CS underwent a milrinone drug study (50 mcg/kg bolus infused over 10 min) to assess inotropic response. Haemodynamic measurements were obtained at baseline and following the bolus. Aortic pulsatility index and CPO were used to risk-stratify patients with the incidence of LV assist device (LVAD), orthotopic heart transplantation (OHT), or death at 1 year as the primary composite endpoint. Two hundred and twenty-four patients in SCAI Stage C CS underwent haemodynamics prior to milrinone bolus, and 117 patients had low baseline API < 1.45. Of the 117 patients, 88 had a final API < 2.2 after milrinone load, consistent with LV decoupling, in which 73% met the composite endpoint. The remaining 29 patients had a final API ≥ 2.2 consistent with LV recoupling, and only 55% met the composite endpoint (P = 0.046). Of the 117 patients, 40 patients had low myocardial reserve (final CPO < 0.77 W), in which 78% met the composite endpoint. Of the 77 patients who demonstrated myocardial reserve (final CPO ≥ 0.77 W), only 64% met the composite endpoint (P = 0.039). The use of API and CPO in a dynamic assessment after provocative testing led to improved risk stratification in patients with SCAI Stage C CS for clinical outcomes including LVAD, OHT, or death at 1 year.

Abstract 15585: Myocardial Reserve After Milrinone to Predict Right Ventricular Failure After LVAD Implantation

Introduction: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a common complication associated with increased morbidity and mortality. Identifying patients at risk for RVF remains challenging. We sought to assess pre-operative right ventricular myocardial reserve after milrinone loading as a risk predictor for post-LVAD RVF. Methods: Adult patients implanted with LVADs from 2013-2019 at a single center who had right heart catherization with milrinone drug study within 30-days preoperatively were included. In addition to standard hemodynamic variables, pulmonary artery pulsatility index (PAPI), right atrial to pulmonary capillary wedge pressure ratio (RA/PCWP), right ventricular stroke work index (RVSWI), pulmonary vascular resistance index (PVRi), and stroke volume index (SVI) were recorded before and after milrinone bolus (50 mcg/kg over ten minutes). Incidence of RVF defined by MCS-ARC criteria within one-year post LVAD were recorded. Student’s unpaired t-tests were used to compare mean of hemodynamic markers to RVF outcome. Results: A total 34 patients were included; 38% women, 50% African American, 68% had non-ischemic cardiomyopathy, 47% implanted with HeartMate 3 LVAD, 20.5% with HeartMate 2, and 32% with HeartWare HVAD. Final right atrial pressure (RAP) after milrinone was higher in those with post-LVAD RVF (15.5 + 7.8mmHg vs 9.2 + 3.9mmHg, p=0.005), as was final diastolic PA pressure (34.3 + 9.2mmHg vs 25.6 + 7.7mmHg, p=0.006). SVI post-milrinone was numerically higher in those without post-LVAD RVF (32.3 + 9.2 vs 26.0 + 7.9mL/m 2 , p=0.06). Percent change in PAPI (p=0.26), RA/PCWP (p=0.35), RVSWI (p=0.10), or PVRi (p=0.92) after milrinone were not associated with RVF. Conclusions: Persistently elevated RAP and diastolic PA pressure, despite milrinone infusion, are associated with RVF after LVAD implantation. Continued reduction in SVI post milrinone may also identify patients at risk for post-LVAD RVF.

Management of cerebral vascular spasm in posttraumatic subarachnoid hemorrhage using a combination therapy of oral nimodipine and intravenous milrinone

Background Intravenous milrinone has been investigated for management of vasospasm after aneurysmal subarachnoid hemorrhage (SAH); however, its role in vasospasm after traumatic SAH is still under evaluation. Patients and methods A total of 30 patients with cerebral vascular spasm after traumatic SAH were randomly divided into two equal groups. Group H was given nimodipine (60 mg/4 h) orally or via nasogastric tube and then combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy). Group M was given nimodipine (60 mg/4 h) orally or in the nasogastric tube and then intravenous milrinone bolus of 0.1–0.2 mg/kg followed by intravenous infusion of 0.75–1.25 μg/k/min. The infusion was continued for 72 h before gradual discontinuation at a rate of 0.25 μg/kg/min every 24 h until complete weaning. For refractory cases in both groups, emergency angioplasty was done. Primary outcome was the transcutaneous cerebral regional oxygen saturation 14 days after starting treatment. Secondary outcomes were the Glasgow coma score 14 days after starting treatment, infarction rate, ICU and hospital stays, and modified Rankin scale and Glasgow outcome scale at 3 and 6 months after starting treatment. Results Group M showed significant increase in regional oxygen saturation and Glasgow coma score; decrease in infarction rate, ICU stay, and hospital stay; and improvement in modified Rankin scale and Glasgow outcome scale. Significance was set at P value less than 0.05. Conclusion The combination of oral nimodipine and intravenous milrinone improves the outcome of vasospasm in posttraumatic SAH.

Assessment of the effect of two regimens of milrinone infusion in paediatric patients with pulmonary artery hypertension undergoing corrective cardiac procedure: A prospective observational study.

The aim of the study was to compare the effect of two different regimens of milrinone in pediatric patients with pulmonary artery hypertension (PAH) undergoing corrective procedure. This randomized prospective study included 100 pediatric patients undergoing corrective cardiac surgeries. Group E: Milrinone was started as infusion 0.5 μg/kg/min without a loading dose after induction of anesthesia and continued as infusion 0.5-0.75 μg/kg/min in the pediatric cardiac surgical intensive care unit (PSICU). Group L: Milrinone was started as a loading dose 50 μg/kg over 10 min before weaning from cardiopulmonary bypass (CPB) followed by infusion 0.5-0.75 μg/kg/min in the PSICU. We compared heart rate, mean arterial blood pressure, central venous pressure, cardiac index (CI), mean pulmonary arterial pressure (MPAP), serum lactate level, urine output, vasoactive inotropic score, mechanical ventilation duration, and intensive care unit (ICU)- and hospital length of stay between the groups. There was an increase in mean arterial blood pressure, CI, and urine output in Group E compared to Group L (P < 0.05). MPAP, serum lactate level, and requirement of inotropes and vasopressors were lower in Group E compared to Group L (P < 0.05). Mechanical ventilation duration, ICU, and hospital length of stay were shorter in Group E than Group L (P < 0.05). Early use of milrinone in patients with PAH undergoing corrective cardiac surgeries improved CI and mean arterial pressure, decreased MPAP, improved urine output, decreased serum lactate level, and decreased requirement of inotropes and vasopressors after weaning from CPB compared to the milrinone bolus group.

Acute Right Ventricular Failure in Cardiac Surgery During Cardiopulmonary Bypass Separation: A Retrospective Case Series of 12 Years’ Experience With Intratracheal Milrinone Administration

To report the authors' 12 years of experience with intratracheal milrinone administration and to assess the efficacy and limitations of intratracheal milrinone bolus administration for the treatment of unexpected acute right ventricular (RV) failure in patients undergoing cardiac surgery. Retrospective analysis. Single-center university hospital. One hundred seventy-six patients (4.6%) undergoing on-pump cardiac surgery. Endotracheal tube administration of milrinone (5-mg bolus) after unexpected acute RV failure during separation from cardiopulmonary bypass (CPB) weaning. RV failure was defined as the simultaneous presence of all of the following criteria: (1) hemodynamic instability or difficult separation from CPB with associated elevated central venous pressure or abnormal RV pressure waveform, (2)>20% reduction of RV fractional area change from baseline evaluated by transesophageal echocardiography, and (3) anatomical visualization of impaired or absent RV wall motion by direct intraoperative visual inspection. Intratracheal milrinone administration was found to improve RV failure in 109 patients (61.9%) whereas RV failure persisted in 67 patients (38.1%). Using a multiple logistic regression model, severely decreased left ventricular ejection fraction (<35% v >50%) (adjusted odds ratio [OR] 3.72; 95% confidence interval [CI] 1.2-11.3; p = 0.012), longer CPB time (adjusted OR 1.014; CI 1.01-1.02; p = 0.001) and elevated postoperative fluid balance (adjusted OR 1.39; CI 1.1-1.8; p = 0.02) were found to be significant predictors of persistent RV failure. Intratracheal instillation of milrinone was associated with clinical improvement of RV failure occurring during separation from CPB in almost two-thirds of patients. Factors limiting its therapeutic efficacy include severe left ventricular dysfunction, increased fluid balance, and long CPB time.

OP36 - Tracheal milrinone bolus administration as an alternative therapy in right ventricular dysfunction during cardiovascular surgery

OP36 - Tracheal milrinone bolus administration as an alternative therapy in right ventricular dysfunction during cardiovascular surgery

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass

To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings.

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy.

Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

Transesophageal Echocardiography in Ross Procedure

Ross procedure is one of the surgical procedures for correction of severe congenital aortic insufficiency. Intraoperative transesophageal echocardiography is essential for optimal surgical evaluation. Furthermore, it is able to assess the blood volume profile and the need for administration of vasoactive drugs during surgery. This is a 15-year old teenager with severe congenital aortic insufficiency scheduled for corrective surgery with the Ross procedure. In the operating room, the patient was monitored with electrocardiography and pulse oximeter, and he was premedicated with midazolam. After the administration of premedication, the left radial artery and right subclavian vein were punctured. Anesthetic induction was accomplished with etomidate, cisatracurium, and fentanyl while maintenance was achieved with sevoflurane. The probe of the transesophageal echocardiography equipment was introduced immediately after tracheal intubation, showing increased left ventricle; severe aortic insufficiency due to coaptation failure of the three leaflets; and competent pulmonary valve without anatomical and physiological changes. Intercurrences were not observed during surgery, with 120 minutes of extracorporeal circulation (ECC) and 8 hours of surgery. Immediately after removal from ECC the transesophageal echocardiography showed good function of both the auto- and homograft; however, the right ventricle presented hypocontractility, which was corrected with a bolus of milrinone followed by continuous infusion. The patient was transferred to the postanesthetic recovery unit intubated and hemodynamically stable with infusion of milrinone and sodium nitroprusside. Ross procedure is one of the techniques for correction of congenital aortic insufficiency in which transesophageal echocardiography guides the surgeon precisely on the physiological and anatomical status of vascular grafts.

Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation

The incidence of porto-pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP]>45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT.

Anti‐ischemic effects of inotropic agents in experimental right ventricular infarction

Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised hemodynamics. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury. IR injury was induced by temporary ligation of the distal right coronary artery for 90 min, followed by 120 min of reperfusion. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n=12; 50 microg/kg) and levosimendan (n=10; 24 microg/kg) was applied in different groups, followed by continuous infusion of the drugs at 0.5 and 0.2 microg/kg/min, respectively. The effects on myocardial injury and inflammation were compared with a control (n=12) and a dobutamine group (n=10), where treatment was started with an infusion of 5 microg/kg/min. Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7+/-10.2%, 45.7+/-8.1%) when compared with the control group (58.3+/-6.1%). In contrast, dobutamine had no effect (55.8+/-7.7%). All drugs reduced the number of neutrophils infiltrating into the different myocardial regions and the circulating levels of interleukin-6. Increased levels of tumor necrosis factor alpha during reperfusion were only abated by milrinone and levosimendan. Cardioprotective properties of milrinone and levosimendan were demonstrated for the first time in a clinically relevant model of RV infarction.

Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

The reversibility of elevated pulmonary vascular resistance in heart failure bears an important relation to outcome after cardiac transplantation. The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation. PDE3 inhibitors also have direct inotropic effects. We contrasted the acute hemodynamic responses to intravenous PDE3 and PDE5 inhibitors in patients with congestive cardiac failure to assess their relative suitability for reversibility testing in this setting. Thirty patients undergoing assessment for cardiac transplantation underwent right heart catheterization. Patients were randomized to receive an intravenous bolus of milrinone (0.05 mg/kg) or sildenafil citrate at a high (0.43 mg/kg) or low dose (0.05 mg/kg). Differences between low- and high-dose sildenafil were not significant. Both agents caused similar reductions in systemic and pulmonary vascular resistance. Milrinone caused significantly greater reductions in pulmonary artery wedge and mean pulmonary artery pressure, and increases in heart rate. In all study groups, greater increases in cardiac index (>25%) were seen in patients with a higher pulmonary artery wedge pressure at baseline (29 +/- 1 vs 20 +/- 2 mm Hg; p < 0.001). In end-stage congestive cardiac failure, intravenous milrinone and sildenafil both cause similar reductions in systemic and pulmonary vascular resistance; however, milrinone has more cardiac selective effects on left ventricular filling and heart rate. Both agents appear to have a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure. Larger studies are needed to confirm these results.

Milrinone Increases Flow in Coronary Artery Bypass Grafts After Cardiopulmonary Bypass: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

To compare the effects of a bolus of milrinone, 50 microg/kg, versus placebo on flow in coronary artery bypass grafts after cardiopulmonary bypass (CPB). A prospective, randomized, double-blind study. A university hospital. Forty-four patients with stable angina and left ventricular ejection fraction >30% scheduled for elective coronary artery bypass graft (CABG) surgery were included. Patients were randomized to receive 50 microg/kg of milrinone (n = 22) or placebo (n = 22) after aortic declamping. The flow in coronary artery bypass grafts was measured with a transit time flow meter at 10 minutes and 30 minutes after termination of CPB. The hemodynamic evaluation included transesophageal echocardiography, mean arterial pressure (MAP), heart rate, and intracavitary measurement of left ventricular end-diastolic pressure (LVEDP). The flow in the saphenous vein grafts was significantly higher in the milrinone group when compared with the placebo group both at 10 and 30 minutes after termination of CPB (p < 0.001). At 10 minutes, the flow was 64.5 +/- 37.4 mL/min (mean +/- standard deviation) and 43.6 +/- 25.7 mL/min in nonsequential vein grafts for milrinone and placebo, respectively. Corresponding values at 30 minutes were 54.8 +/- 29.9 mL/min and 35.3 +/- 22.4 mL/min. The left internal thoracic artery (LITA) flow was higher in the milrinone group but did not reach statistical significance. The fractional area change was higher, and the MAP and calculated pressure gradient (MAP-LVEDP) were lower at 10 minutes in the milrinone group. Milrinone significantly increases the flow in anastomosed saphenous vein grafts after CPB, and has beneficial effects on left ventricular function.

Milrinone Does Not Improve Free Flap Survival in Microvascular Surgery

Free flap microvascular surgery involves the transfer of a mobilised tissue flap with complete vascular re-anastomosis at the new site. Ischaemia frequently threatens flap survival and may require a return to the operating theatre for anastomotic revision. Arterial spasm and hypoperfusion are recognised as factors in flap ischaemia. Phosphodiesterase inhibitors such as milrinone may improve flap blood flow and possibly flap survival by arterial dilation and increasing cardiac output. To investigate the role of milrinone in this type of surgery, a double-blinded randomised controlled trial was conducted with 88 patients receiving either a milrinone bolus and infusion throughout surgery or placebo (normal saline). We found that milrinone did not improve graft survival, return to theatre rate, or surgically graded arterial spasm, but did require more vasopressor support. We conclude that intraoperative milrinone did not improve flap outcomes in microvascular surgery.

Milrinone Combined with Vasopressin Improves Cardiac Index after Cardiopulmonary Resuscitation in a Pig Model of Myocardial Infarction

Milrinone used for acute cardiac insufficiency could be of interest during cardiopulmonary resuscitation because of its positive inotropic effects. In this study, the combination of milrinone-vasopressin was compared with epinephrine and vasopressin, as well as with the combination of epinephrine-vasopressin, in reference to hemodynamics. Thirty-two pigs underwent ligation of the circumflex coronary artery and induction of ventricular fibrillation lasting for 4 min. Cardiopulmonary resuscitation was performed after randomization to one of four groups: epinephrine (30-microg/kg bolus), vasopressin (0.4-U/kg bolus), epinephrine-vasopressin (15-microg/kg epinephrine bolus, 0.2-U/kg vasopressin bolus), or milrinone-vasopressin (0.4-U/kg vasopressin bolus, 50-microg/kg milrinone bolus over 5 min and a continuous infusion of 0.4 microg.kg.min). The hemodynamic variables were measured before cardiopulmonary resuscitation as well as 4, 8, 15, and 30 min after return of spontaneous circulation. All animals were resuscitated successfully. The animals of the milrinone-vasopressin group displayed significantly (P<0.05) higher cardiac index values (30 min after return of spontaneous circulation: epinephrine, 65.8+/-13.2; vasopressin, 70.7+/-18.3; epinephrine-vasopressin, 69.1+/-36.2; milrinone-vasopressin, 120.7+/-34.8 ml.min.kg) without a decrease in mean arterial pressure or coronary perfusion pressure. The combination of vasopressin-milrinone as compared with epinephrine during cardiopulmonary resuscitation leads to an improved cardiac index without relevant decrease of mean arterial pressure or coronary perfusion pressure.

This Month in Anesthesiology

This Month in Anesthesiology

Does Milrinone Improve Hemodynamic Variables in Patients with Pulmonary Hypertension Due to Valvular Heart Disease?

Background: Milrinone is a bipyridine phosphodiesterase III inhibitor that exerts both positive inotropic and direct vasodilatory effects. The efficacy and safety of intravenous milrinone in heart failure has been evaluated in a number of clinical studies. In addition, performance of the right ventricle is improved primarily in reduced right ventricular afterload, and pulmonary vascular resistence as milrinone produces minimal inotropic effects on the right ventricle. Most clinical studies have been performed in left ventricular failure patients. Therefore, we investigated whether intravenous milrinone improves the hemodynamics in patients with pulmonary hypertension due to valvular heart disease. Methods: This study included 33 patients undergoing a valvular replacement with pulmonary hypertension (mean pulmonary artery pressure 30 mmHg after induction). Patients were randomly divided into two groups, normal saline group (N) and milrinone group (M). In group N, normal saline was infused. In group M, a single intravenous bolus of milrinone (50/kg body weight) was injected over 10 min. Hemodynamic data were measured at preinjection, 5, 10, and 20 min after injection. Results: There was no significant difference in systemic mean arterial pressure and central venous pressure between both groups. In group M, systemic vascular resistance was reduced at 5 min after injection and cardiac index was improved at 10 min after injection. There was no significant difference in pulmonary mean arterial pressure and vascular resistance between both groups. Conclusions: Milrinone had no effect on pulmonary artery pressure and pulmonary vascular resistance in patients with pulmonary hypertension due to valvular heart disease. However, it increased cardiac index and decreased systemic vascular resistance.

Pharmacodynamic effects of milrinone with and without a bolus loading infusion

Background Milrinone is a positive inotropic agent with vasodilatory and lusitropic activity. Milrinone dosed as a 50 μg/kg bolus followed by a continuous infusion provides an immediate and sustained hemodynamic response. The comparative pharmacodynamics of a placebo bolus and a milrinone bolus followed by a continuous milrinone infusion in patients with decompensated heart failure are unknown. Methods Nineteen patients with decompensated heart failure underwent right heart catheterization and were randomized to receive an intravenous infusion of milrinone at a rate of 0.50 μg/kg/min with (n = 9) or without (n = 10) a preceding 50 μg/kg bolus. Pulmonary capillary wedge pressure, cardiac index, and plasma milrinone levels were measured serially over 24 hours. Results In the milrinone bolus group, maximal effects on plasma concentration (352.3 ng/mL), cardiac index (+0.97 L/min/m2, P =.02), and pulmonary capillary wedge pressure (–11.25 mm Hg, P <.001) were seen after the loading dose. In the placebo loading dose group, significant hemodynamic effects were observed starting at 30 minutes after the start of the continuous infusion. Changes in pulmonary capillary wedge pressure (placebo –8.6 vs milrinone –8.78 mm Hg, P not significant [NS]) were similar in both groups at 2 hours, whereas changes in cardiac index (placebo loading +0.81 vs milrinone loading +0.78 L/min/m2, P NS) and milrinone levels (placebo loading 168.0 vs milrinone loading 165.6 ng/mL, P NS) were similar at 3 hours. One patient randomized to a milrinone bolus demonstrated a marked decrease in blood pressure and was discontinued from therapy. Conclusions A milrinone infusion without a bolus appears to be a rapidly effective inotropic strategy that may have an improved safety profile during the initiation of therapy compared with a continuous infusion strategy initiated with a bolus. (Am Heart J 2000;141:e6.)

Milrinone improves arterial oxygenation in dogs with acute lung injury induced by oleic acid.

The aim of the study was to investigate effects of milrinone on pulmonary permeability in dogs with acute lung injury induced by oleic acid. To induce acute lung injury, we administered 0.08 mg/kg of oleic acid to 19 adult mongrel dogs and then measured hemodynamic parameters and performed blood gas analysis. An injection of oleic acid depressed the mean arterial pressure, cardiac index, and arterial oxygenation. Dogs were divided into three groups: six received a bolus of milrinone (50 microg/kg) followed by a continuous (0.5 microg/kg/min, low-dose), seven received a bolus (100 microg/kg) followed by a continuous (1.0 microg/kg/min; i.e., a low-dose twice; high-dose), and six no milrinone (control). Milrinone administration improved the cardiac index and arterial oxygenation and simultaneously depressed the intrapulmonary shunt fraction and the extravascular thermal lung water as extravascular water content of the lung. These changes produced by milrinone are different according to the doses. In conclusion, milrinone acts on the capillary endothelium and inhibits an accumulation in the extravascular water content of the lung, which may induce an improvement in arterial oxygenation. Milrinone may also improve arterial oxygenation through an inhibition of platelet aggregation and chemical mediators that are released from platelets. The latter mechanism also may improve arterial oxygenation, and the exact property responsible for causing the effect of milrinone has not yet been identified.

Effect of Bolus Milrinone on Hemodynamic Variables and Pulmonary Vascular Resistance in Patients With Severe Left Ventricular Dysfunction: A Rapid Test for Reversibility of Pulmonary Hypertension

To examine the feasibility of using milrinone to test pulmonary vascular reactivity in patients before heart transplantation, we tested the hypothesis that milrinone would lower pulmonary vascular resistance (PVR) in patients with severe heart failure. Fixed pulmonary hypertension is a risk factor for right heart failure and death after orthotopic heart transplantation. Sodium nitroprusside, the agent used most commonly to test for reversibility of pulmonary hypertension before transplantation, requires dose titration and is frequently limited by hypotension. Milrinone is an intravenously active phosphodiesterase inhibitor that acts rapidly and exerts both positive inotropic and direct vasodilator effects in patients with heart failure. The ability of milrinone to lower PVR in patients with heart failure has not been tested. In 27 patients with New York Heart Association functional class III or IV heart failure referred for heart transplantation with a PVR > or = 200 dynes-s-cm-5, we measured the hemodynamic response to a single intravenous bolus of milrinone (50 micrograms/kg body weight) infused over 1 min. Milrinone decreased PVR in all patients. The effect was maximal 5 to 10 min after the bolus and persisted for at least 20 min. The reduction in PVR at 5 min ([mean +/- SEM] 31 +/- 4%) was associated with a 42 +/- 4% increase in cardiac output and decreases of 12 +/- 4% and 16 +/- 5% in mean pulmonary artery and pulmonary artery wedge pressures, respectively, but no change in transpulmonary pressure gradient. Milrinone had no effect on heart rate or systemic arterial pressure. The magnitude of the decrease in PVR correlated inversely with the milrinone-induced increase in cardiac output. Bolus milrinone consistently decreases PVR in patients with pulmonary hypertension secondary to severe heart failure. This effect is rapid in onset and well tolerated, even by patients with low systemic arterial pressure. An intravenous bolus of milrinone can be used to test for the reversibility of pulmonary hypertension in patients with heart failure undergoing evaluation for heart transplantation.