Preliminary Experience With Combined Inhaled Milrinone and Prostacyclin in Cardiac Surgical Patients With Pulmonary Hypertension

doi:10.1053/j.jvca.2014.06.012

Journal of Cardiothoracic and Vascular Anesthesia

Volume 29, Issue 1, February 2015, Pages 38-45

https://doi.org/10.1053/j.jvca.2014.06.012 Get rights and content

Objective

To retrospectively evaluate the effects of combined inhaled prostacyclin and milrinone to reduce the severity of pulmonary hypertension when administered prior to cardiopulmonary bypass.

Design

Retrospective case control analysis of high-risk patients undergoing cardiac surgery.

Setting

Single cardiac center.

Participants

Sixty one adult cardiac surgical patients with pulmonary hypertension, 40 of whom received inhalation therapy.

Intervention

Inhaled milrinone and inhaled prostacyclin were administered before cardiopulmonary bypass (CPB).

Measurements and Main Results

Administration of both inhaled prostacyclin and milrinone was associated with reductions in central venous pressure, and mean pulmonary artery pressure, increases in cardiac index, heart rate, and the mean arterial-to-mean pulmonary artery pressure ratio (p < 0.05), with no significant change in mean arterial pressure. The rate of difficult and complex separation from CPB was 51% in the inhaled group and 70% in the control group (p = 0.1638). Postoperative vasoactive requirement was reduced at 12 hours (35.9 v 73.7% p<0.01) and 24 hours (25.6 v 57.9% p<0.05) postoperatively in the combined inhaled agent group. Hospital length of stay and mortality were similar between the groups.

Conclusion

Preemptive treatment of pulmonary hypertension with a combination of inhaled prostacyclin and milrinone before CPB was associated with a reduction in the severity of pulmonary hypertension. In addition, a significant reduction in vasoactive support in the intensive care unit during the first 24 hours after cardiac surgery was observed. The impact of this strategy on postoperative survival needs to be determined.

Section snippets

Methods

After approval from the local ethics and research committee, the authors retrospectively reviewed the files of 600 consecutive patients operated from December 2003 to October 2009 using a transesophageal echocardiography (TEE) database of the Montreal Heart Institute.¹⁹ The inclusion criteria were patients with PH undergoing cardiac surgery with CPB in whom both inhaled PGI₂ and milrinone had been given before CPB. Patients were considered to have PH if systolic pulmonary artery pressure (SPAP)

Results

A total of 41 patients received both inhaled PGI₂ and milrinone before CPB. The preoperative, intraoperative and postoperative characteristics of the population are summarized in Table 1. There were no significant differences between the groups in terms of age, Parsonnet score, and risk factors such as recent myocardial infarction, unstable angina, dilated left ventricle, systemic arterial hypertension, diabetes, and peripheral vascular disease. These patients represent a very high-risk

Discussion

The aim of this study was to determine whether the combination of PGI₂ and milrinone, given by inhalation before CPB, was effective in reducing PH. In addition, the authors wanted to explore if the combination had a beneficial effect after CPB and in the ICU in high-risk patients with preoperative PH and RV dysfunction. The major findings of the present study were combined inhaled agents increased CI by reducing indices of RV afterload. The increase in CI with reduction in CVP was associated

Conclusion

Administration of both inhaled PGI₂ and inhaled milrinone significantly reduces the severity of PH without systemic hypotension. Combining inhaled therapy significantly reduced the prevalence of vasoactive requirement in the post-CPB period and in the ICU during the first 24 hours compared with a control group with PH. The importance of this advantage on survival remains to be studied in a larger group of patients using a randomized controlled trial.

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Cited by (40)

Inhaled Epoprostenol and Milrinone Effect on Right Ventricular Pressure Waveform Monitoring
2023, Canadian Journal of Cardiology
Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. This study aimed to evaluate the change in RV pressure waveform in patients receiving a combination of inhaled epoprostenol and inhaled milrinone (iE&iM) before cardiopulmonary bypass (CPB) and to assess the safety of this approach with a matched case-control group.
A prospective single-centre cohort study of adult patients undergoing cardiac surgery administered iE&iM through an ultrasonic mesh nebulizer. RV pressure waveform monitoring was obtained by continuously transducing the RV port of the pulmonary artery (PA) catheter.
The final analysis included 26 patients receiving iE&iM. There was a significant drop in mean PA pressure (MPAP) (–4.8 ± 8.7, P = 0.010), systolic PA pressure (SPAP) (–8.2 ± 12.8, P = 0.003), RV end-diastolic pressure (RVEDP) (–2.1 ± 2.8, P < 0.001) and RV diastolic pressure gradient (RVDPG) (–1.7 ± 1.4, P < 0.001) after 17 ± 9 minutes of iE&iM administration. Patients also had a significant increase in RV outflow tract (RVOT) gradient (3.7 ± 4.7, P < 0.001), RV maximal rate of pressure rise during early systole (dP/dt max) (68.3 ± 144.7, P = 0.024), and left ventricular (LV) dP/dt max (66.4 ± 90.1, P < 0.001). Change in RVOT gradient was only observed in those with a positive pulmonary vasodilator response to treatment. Treatment with iE&iM did not present adverse effects when compared with a matched case-control group.
Coadministration of iE&iM in cardiac surgery patients presenting with PH or signs of RV dysfunction is a safe and effective treatment approach in improving RV function. Appearance of a transient increase in RVOT gradient after iE&iM could be useful to predict response to treatment.
L’hypertension pulmonaire (HP) et la dysfonction du ventricule droit (VD) sont des complications majeures des interventions chirurgicales cardiaques. Notre étude visait à évaluer la variation de la forme d’onde de la pression dans le VD chez des patients recevant une combinaison d’époprosténol et de milrinone en inhalation (Ei+Mi) avant un pontage cardiopulmonaire et à déterminer l’innocuité de cette stratégie en comparant les résultats avec ceux obtenus dans un groupe de cas-témoins appariés.
Nous avons réalisé une étude de cohorte unicentrique prospective auprès de patients adultes subissant une intervention chirurgicale cardiaque, à qui on a administré une combinaison Ei+Mi au moyen d’un nébuliseur ultrasonique à mailles. La surveillance de la forme d’onde de la pression dans le VD a été effectuée par transduction continue du signal obtenu au port VD du cathéter de l’artère pulmonaire (AP).
L’analyse finale portait sur 26 patients ayant reçu la combinaison Ei+Mi. Nous avons observé une baisse significative de la pression moyenne dans l’AP (–4,8 ± 8,7, p = 0,010), de la pression systolique dans l’AP (–8,2 ± 12,8, p = 0,003), de la pression télédiastolique dans le VD (–2,1 ± 2,8, p < 0,001) et du gradient de la pression diastolique dans le VD (–1,7 ± 1,4, p < 0,001) après l’administration de la combinaison Ei+Mi pendant 17 ± 9 minutes. Nous avons aussi noté une augmentation significative du gradient dans la chambre de chasse du VD (3,7 ± 4,7, p < 0.001), de la vitesse maximale d’augmentation de la pression dans le VD au début de la systole ([dP/dt]_max) (68,3 ± 144,7, p = 0,024) et de la valeur (dP/dt)_max dans le ventricule gauche (66,4 ± 90,1, p < 0,001). Une variation du gradient de la chambre de chasse du VD n’a été observée que chez les patients présentant une réponse vasodilatatrice pulmonaire positive au traitement. Le traitement par la combinaison Ei+Mi n’a pas eu d’effets indésirables par rapport aux cas-témoins appariés.
L’administration de la combinaison Ei+Mi aux patients qui subissent une intervention chirurgicale cardiaque et qui présentent une HP ou des signes de dysfonction du VD est une stratégie thérapeutique sûre et efficace pour améliorer la fonction du VD. L’observation d’une augmentation transitoire du gradient dans la chambre de chasse du VD après l’administration de la combinaison Ei+Mi pourrait être un facteur de prédiction de la réponse au traitement.
Preliminary Experience Using Diastolic Right Ventricular Pressure Gradient Monitoring in Cardiac Surgery
2020, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
Inhaled vasodilators were used in 113 patients (44%) in the present retrospective study. These agents have been reported to reduce the reperfusion injury associated with CPB in animal studies33,34; furthermore, the authors have reported their experience in several retrospective studies35-38 and clinical trials.5,39,40 A meta-analysis has shown that these agents in cardiac surgery are superior to intravenous agents in terms of pulmonary selectivity.41
Right ventricular (RV) dysfunction in cardiac surgery is associated with increased mortality and morbidity and difficult separation from cardiopulmonary bypass (DSB). The primary objective of the present study was to describe the prevalence and characteristics of patients with abnormal RV diastolic pressure gradient (PG). The secondary objective was to explore the association among abnormal diastolic PG and DSB, postoperative complications, high central venous pressure (CVP), and high RV end-diastolic pressure (RVEDP).
Retrospective and prospective validation study.
Tertiary care cardiac institute.
Cardiac surgical patients (n=374) from a retrospective analysis (n=259) and a prospective validation group (n=115).
RV pressure waveforms were obtained using a pulmonary artery catheter with a pacing port opened at 19 cm distal to the tip of the catheter. Abnormal RV diastolic PG was defined as >4 mmHg. Both elevated RVEDP and high CVP were defined as >16 mmHg.
From the retrospective and validation cohorts, 42.5% and 48% of the patients had abnormal RV diastolic PG before cardiac surgery, respectively. Abnormal RV diastolic PG before cardiac surgery was associated with higher EuroSCORE II (odds ratio 2.29 [1.10-4.80] v 1.62 [1.10-3.04]; p = 0.041), abnormal hepatic venous flow (45% v 29%; p = 0.038), higher body mass index (28.9 [25.5-32.5] v 27.0 [24.9-30.5]; p = 0.022), pulmonary hypertension (48% v 37%; p = 0.005), and more frequent DSB (32% v 19%; p = 0.023). However, RV diastolic PG was not an independent predictor of DSB, whereas RVEDP (odds ratio 1.67 [1.09-2.55]; p = 0.018) was independently associated with DSB. In addition, RV pressure monitoring indices were superior to CVP in predicting DSB.
Abnormal RV diastolic PG is common before cardiac surgery and is associated with a higher proportion of known preoperative risk factors. However, an abnormal RV diastolic PG gradient is not an independent predictor of DSB in contrast to RVEDP.
A Practical Approach to Cerebro-Somatic Near-Infrared Spectroscopy and Whole-Body Ultrasound
2019, Journal of Cardiothoracic and Vascular Anesthesia
Near-infrared spectroscopy (NIRS) is an emerging noninvasive monitoring modality based on chromophore absorption of infrared light. Because NIRS provides instantaneous information on cerebral and somatic tissue oxygenation, it becomes mandatory to identify rapidly the etiology of impaired regional oxygenation and thus perfusion. To do so, the use of whole-body ultrasound (WHOBUS) represents a significant advance in the management of patients experiencing cerebral or somatic desaturation. This narrative review describes the authors’ experience since 2002 in the use of combined NIRS and WHOBUS. A practical approach in the use of both modalities and their respective limitations is described.
Perioperative Right Ventricular Pressure Monitoring in Cardiac Surgery
2019, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
For instance, preload reduction when initiating CPB will be associated with normalization of an oblique or square-root Prv waveform (Fig 13), and the opposite will be observed in excessive fluid administration. Inhaled agents such as milrinone or epoprostenol, alone or in combination, have been shown to reduce the mean Ppa without reducing the mean systemic arterial pressure21,61 and also may prevent post-CPB reperfusion injury.62,63 The advantage of Prv and Ppa waveform monitoring while using inhaled agents is that reduction of Ppa can be seen at the same time as the normalization of the early- to end-diastolic Prv waveform gradient (Fig 14), as a sign of improvement in RV diastolic function.
Right ventricular (RV) dysfunction is a cause of increased morbidity and mortality in both cardiac surgery and noncardiac surgery and in the intensive care unit. Early diagnosis of this condition still poses a challenge. The diagnosis of RV dysfunction traditionally is based on a combination of echocardiography, hemodynamic measurements, and clinical symptoms. This review describes the method of using RV pressure waveform analysis to diagnose and grade the severity of RV dysfunction. The authors describe the technique, optimal use, and pitfalls of this method, which has been used at the Montreal Heart Institute since 2002, and review the current literature on this method. The RV pressure waveform is obtained using a pulmonary artery catheter with the capability of measuring RV pressure by connecting a pressure transducer to the pacemaker port. The authors describe how RV pressure waveform analysis can facilitate the diagnosis of systolic and diastolic RV dysfunction, the evaluation of RV-arterial coupling, and help diagnose RV outflow tract obstruction. RV pressure waveform analysis also can be used to guide pharmacologic treatment and fluid resuscitation strategies for RV dysfunction.
Acute Right Ventricular Failure in Cardiac Surgery During Cardiopulmonary Bypass Separation: A Retrospective Case Series of 12 Years’ Experience With Intratracheal Milrinone Administration
2019, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
If a pulmonary artery catheter (Paceport, Edwards Lifesciences, Irvine, CA) was available, the authors used continuous RV pressure waveform monitoring as a supplemental marker of RV function. This has been described in small clinical trials5,28,36 and several review articles.37,38 Intraoperative fluid balance was calculated by subtracting documented urine output and blood loss (weight of the blood-soaked sponges during surgery and the amount of suctioned blood) from fluid replacement and transfusion products; insensible losses from surgery and preoperative fasting were excluded from the calculation.
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.
Intravenous and Inhaled Milrinone in Adult Cardiac Surgery Patients: A Pairwise and Network Meta-Analysis
2019, Journal of Cardiothoracic and Vascular Anesthesia
To summarize the evidence on the hemodynamic, echocardiographic, and clinical effects of inhaled and intravenous milrinone (iMil and IvMil) in adult cardiac surgery patients.
Systematic review, pairwise and network meta-analysis.
Multi-institutional.
Adult cardiac surgery patients.
Comparison between iMil and IvMil versus other agents or placebo.
The primary endpoints were mean pulmonary artery pressure (MPAP) and peripheral vascular resistance (PVR). Secondary endpoints included the following: (1) mean arterial pressure, heart rate, and cardiac index (CI); (2) echocardiographic data; and (3) clinical outcomes. Random model, leave-one-out-analysis, and meta-regression were used. Thirty studies (6 iMil and 24 IvMil) were included for a total of 1,438 patients (194 iMil and 521 IvMil). IvMil was associated with a lower MPAP, lower PVR, and higher CI compared to placebo (standardized mean difference [SMD] = –0.22 [95% CI = –0.48 to 0.05], SMD = –0.49 [95% CI = –0.71 to –0.27], and SMD = 0.94 [95% CI = 0.51 to 1.37]). No difference in any outcome was found between iMil and placebo. At network meta-analysis, significantly lower PVR and shorter hospital length of stay were found for IvMil compared to iMil (SMD = –0.82 [95% CI = –1.53 to –0.10] and SMD = –0.50 [95% CI = –0.95 to –0.05], respectively).
These results support the clinical use of IvMil in cardiac surgery patients. No evidence at present supports the adoption of iMil.

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: Supported by Fonds de la recherche du Québec en Santé, Montreal, Quebec, Canada and Montreal Heart Institute Foundation, Montreal, Quebec, Canada.

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Original ArticlesPreliminary Experience With Combined Inhaled Milrinone and Prostacyclin in Cardiac Surgical Patients With Pulmonary Hypertension

Objective

Design

Setting

Participants

Intervention

Measurements and Main Results

Conclusion

Section snippets

Methods

Results

Discussion

Conclusion

Ann Thorac Surg

J Cardiothorac Vasc Anesth

Ann Thorac Surg

J Cardiothorac Vasc Anesth

Chest

J Cardiothorac Vasc Anesth

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Cardiothorac Vasc Anesth

J Am Soc Echocardiogr

J Cardiothorac Vasc Anesth

J Cardiothorac Vasc Anesth

J Thorac Cardiovasc Surg

J Chromatogr B Analyt Technol Biomed Life Sci

J Cardiothorac Vasc Anesth

J Cardiothorac Vasc Anesth

J Heart Lung Transplant

J Heart Lung Transplant

J Cardiothorac Vasc Anesth

Original Articles
Preliminary Experience With Combined Inhaled Milrinone and Prostacyclin in Cardiac Surgical Patients With Pulmonary Hypertension