Inotropes, Vasopressors, and Cardiovascular Medications

Inotropes and Vasopressors - March 2025 - KKH presentation

Populational-based blood pressure by EPIQ-CNN

Calculator here: https://neopeds.academy/bp/ 

Treatment of “isolated hypotension” of the very low birth weight (VLBW) infant is controversial as some studies indicate increase intraventricular hemorrhage (IVH) and no change in mortality (Dempsey et al. 2009). HIP trial (Dempsey et al. 2021) did not show any difference with the use dopamine but was terminated prematurely. As such, to avoid iatrogenic and without any indication that this leads to tissue ischemia, we do not recommend active interventions, but rather watchful assessments of ongoing perfusion.

Figure on cardiovascular medications (English)

Figure sur les médications cardiovasculaires (français)

Hemodynamic Considerations in Prematurity

Cardiovascular Medications in Prematurity

A big thanks to Louis Chartier - Pharmacist at the Montreal Children's Hospital for contributing his expertise in reviewing the half-life of each medications in the literature. 

Please find in french some references here regarding pharmacology in the NICU: Guide pratique des médicaments en néonatologie au CHU Sainte-Justine

Infusion rates

How to prepare certain dilutions

Adrenergic receptors (G-protein coupled)

• α1: Located on arterial and venous smooth muscle cells, cardiac myocytes. Smooth muscle (vascular) contraction leading to vasoconstriction (increasing calcium entry), increases contractility (inotrope), decreases insulin relase, increases gluconeogenesis.

• α2:  Sympathetic nerves and central nervous system. Blocks norepinerphine release, inhibits sympathetic output and leads to vascular smooth muscle relaxation. 

• β1: Sino atrial and atrio-ventricular node, atrial and ventricular muscle, conduction cells (Purkinje, sinoatrial, AV node). Increases heart rate (chronotropy) by acting on the SA node, increases conduction velocity by acting on the AV node, increases contractility and increases renin secretion. 

• β2: Arterial / venous smooth muscle cells, bronchial smooth muscle cells. Leads to smooth muscle relaxation (vasodilation), bronchial relaxation, increases heart rate and contractility, decreased intestinal motility, induces glycogenolysis, increases insulin secretion. 

Physiology reminders

• Blood pressure = Cardiac Output (Flow) x Vascular resistance 

• Cardiac Output = Heart rate x Stroke Volume

• Cardiac output = Systemic Blood pressure / Total peripheral vascular resistance

• Stroke volume is dependent on the preload, afterload and contractility

  • Preload: depends on volume in ventricle at end of diastole (impacted by blood volume, venous tone, intrapleural pressure, atrial contractility and capacity to fill - diastolic function)

  • Afterload: depends on resistance/pressure that ventricle confronts during contraction. Determined by the end diastolic aortic/pulmonary pressure and aortic/pulmonary resistance. 

  • Stroke volume = End diastolic volume - End systolic volume of the ventricle (volume ejected from the respective ventricle). 

• Stroke work = Work performed by the ventricle during a heartbeat leading to a rise in blood pressure = Stroke Volume x Mean Arterial Pressure.

• Frank Starling: Heart may adapt to different volumes (preload) - as the muscle is stretched with increasing amount of volume, there is increased forced in the contraction to pump extra blood. 

• Poiseuille´s law: The resistance of a vessel (R) is directly proportional to its length (L) and to the blood viscosity (η), and inversely proportional to the radius to the fourth power (r4).

• Great resource for Pressure-Volume Loop and relationship between Pressure-Volume-ECG, Frank-Starling Curve, Cardiac Work

Epinephrine 

α1 and β1 (slight β2)) - Vasoconstriction (α); Inotropy (β)

Side effects: Induces hyperglycemia (insulin suppression, ↑ glycogenolysis and in gluconeogenesis) and hyperlactatemia (increase in oxygen consumption)

In piglets: epinephine ↑ cardiac index with no effect on systolic arterial pressure or systemic vascular resistance

• Starting dose: 0.05 à 0.1 mcg/kg/min

• Range of treatment: 0.01 à 1 mcg/kg/min

• Continuous IV or intraosseous infusion: Initial: 0.02 to 0.1 mcg/kg/minute (usual range: 0.05 to 0.5 mcg/kg/minute); maximum recommended dose: 1 mcg/kg/minute; doses up to 2.6 mcg/kg/minute have been reported

  • Davis AL, Carcillo JA, Aneja RK, et al. American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med. 2017;45(6):1061-1093.doi: 10.1097/CCM.0000000000002425. [PubMed 28509730] 

  • Domonoske C. Appendix A: Common neonatal intensive care unit (NICU) medication guidelines. In: Eichenwald EC, Hansen AR, Martin CR, Stark AR. Cloherty and Stark's Manual of Neonatal Care. 8th edition. Lippincott Williams & Wilkins; 2017. 

  • Heckmann M, Trotter A, Pohlandt F, Lindner W. Epinephrine treatment of hypotension in very low birthweight infants. Acta Paediatr. 2002;91(5):566-570. [PubMed 12113327]

Biventricular dysfunction before Epinephrine initiation:

Significant improvement after epinephrine initiation:

Dopamine

No neonatal data showing different dosages have different cardiovascular impact in newborns.

• DA1 receptors (theoretical vasodilation at renal, mesenteric, cerebral and coronary level)

• β1 (chronotropy, inotropy)

• α1 (peripheral vasoconstriction)

Adrenergic by degradation in Norepinephrine and Epinephrine (in adrenal medulla – can be immature in premature or injured in those with asphyxia).

Theoretical impact on thyroid hormonal secretion. May increase pulmonary vascular resistance.

Initial dosage : 5-10 mcg/kg/min; Usual range: 1 à 20 mcg/kg/min

• Increases pulmonary vascular resistance

• Increased Pulmonary/Systemic pressure ratio

• β1 (slightly β2): Inotropy and chronotropy (arrhythmias / tachycardia).

• Meta-analysis have been done on dopamine in the context of HIE and did not find any differences in mortality or neurodevelopmental outcomes

• Dopamine associated in observational studies with a rise in BP numbers, but no link with improved outcomes

• Few animal studies done: Apoptotic cell death ↓ in cerebral white matter of (dopamine treated fetal sheep) brains vs NS.

• Dopamine dose-dependent effect unproven in the newborn. Theoretically, has been described to have, at low doses (<5 mcg/kg/minute), increase renal blood flow and urine output effect; at intermediate doses (5 to 15 mcg/kg/minute) increase renal blood flow, heart rate, cardiac contractility, cardiac output, and blood pressure; and high doses (>15 mcg/kg/minute) leads to vasoconstriction and increased blood pressure. However, these effects have largely not been proven in the neonate. There are concerns regarding its effect on the brain (dopamine receptors) and in the pulmonary vasculature (increase PVR). 

Dobutamine

• Synthetic agonist of β1 (slightly β2): Inotropy and chronotropy (may induce arrhythmias).

• Theoretical benefit in cardiogenic shock but can disturb diastolic function as heart rate increases (less filling time)

  • ↑ cardiac O2 consumption. Can induce tachycardia and eventually arrhytmias. 

• Initial dosage : 5-10 mcg/kg/min

• Usual range: 1 à 20 mcg/kg/min (we locally rarely go above 15). 

  • Dempsey E, Rabe H. The use of cardiotonic drugs in neonates. Clin Perinatol. 2019;46(2):273-290. doi:10.1016/j.clp.2019.02.010 [PubMed 31010560] 

  • Domonoske C. Appendix A: Common neonatal intensive care unit (NICU) medication guidelines. In: Eichenwald EC, Hansen AR, Martin CR, Stark AR. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Lippincott Williams & Wilkins; 2017. 

  • Joynt C, Cheung PY. Treating hypotension in preterm neonates with vasoactive medications. Front Pediatr. 2018;6:86. doi:10.3389/fped.2018.00086 [PubMed 29707527]

• Some data from animal models: dose-dependent increase in cardiac index by ↑ in HR, with no effect on stroke volume. SVR ↓ but not PVR

Norepinephrine

• Mostly vasoconstriction: α>β1>β2

• May lead to mesenteric / cutaneous ischemia by vasoconstriction.

• ↑ afterload (beware if poor LV function).

• Observational animal and human: may have some advantageous effect in pulmonary hypertension (observational studies). Better Pulmonary to Systemic pressure ratio. To consider in acute pulmonary hypertension by decreasing the Pulmonary:Systemic ratio. Some inotropic effect but mostly vasoconstrictive. 

• To consider in severe diabetic hypertrophic cardiomyopathy with septal hypertrophy to stent the left ventricular outflow tract. To avoir too much chronotropic effect (which decreases filling time), one may also consider phenylephrine (pure alpha-agonist). Some infants with this disease may need beta-blocker (such as Esmolol, which has a rapid half-life and easy to titrate), in order to promote filling time by decreasing heart rate when the infant is tachycardic. 

• Often use in the context of vasoplegic septic shock / NEC (with release of LPS leading to systemic vasodilation and hypotension - "warm shock"). 

• One factor to consider when choosing a vasopressor (increasing SVR) is that norepinephrine may increase heart rate through its β₁-adrenergic effects. Phenylephrine would not because it is a pure alpha-agonist (synthetic) but has barely been studies in the neonatal population. Vasopressin, on the other hand, typically does not increase heart rate and may help preserve ventricular filling time. If the goal is to enhance chronotropy (i.e. low heart rate, or bradycardia), norepinephrine may be more suitable. Conversely, if it's important to limit the impact on filling time, such as in a tachycardic infant, vasopressin could be a better option. 

• Dose: Usual initial dose: 0.02 to 0.1 mcg/kg/minute; titrate to desired effect; usual maximum dose: 1 to 3 mcg/kg/minute

  • Ref: Dempsey E, Rabe H. The use of cardiotonic drugs in neonates. Clin Perinatol. 2019;46(2):273-290. doi:10.1016/j.clp.2019.02.010 [PubMed 31010560]; 

  • Domonoske C. Appendix A: Common neonatal intensive care unit (NICU) medication guidelines. In: Eichenwald EC, Hansen AR, Martin CR, Stark AR. Cloherty and Stark's Manual of Neonatal Care. 8th edition. Lippincott Williams & Wilkins; 2017.

  • Sasse S, Kribs A, Vierzig A, Roth B. A staged protocol for the treatment of persistent pulmonary hypertension of the newborn. Klin Padiatr. 1997;209(5):301-307. doi:10.1055/s-2008-1043968 [PubMed 9342718] 

  • Tourneux P, Rakza T, Bouissou A, Krim G, Storme L. Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension. J Pediatr. 2008b;153(3):345-349. [PubMed 18534241]

Phenylephrine

• Phenylephrine is a selective alpha-1 adrenergic receptor agonist primarily used for its vasoconstrictive properties. In newborns, its application is generally limited due to safety concerns and the availability of alternative treatments.

• When administered, phenylephrine induces vasoconstriction, leading to increased systemic vascular resistance and elevated blood pressure. However, in neonates, especially those with low birth weight or preexisting conditions, phenylephrine can cause significant adverse effects, including: 

  • Reflex Bradycardia: The sudden increase in blood pressure can trigger a baroreceptor-mediated reflex, resulting in a decreased heart rate. 

  • Tissue Ischemia: Excessive vasoconstriction may reduce blood flow to vital organs, potentially leading to ischemic complications. 

  • Hypertension: Neonates are particularly sensitive to blood pressure changes, and even small doses can cause significant hypertension. This may lead to IVH.

• Phenylephrine eye drops are commonly used to dilate pupils during retinopathy of prematurity (ROP) examinations. However, systemic absorption can occur, potentially leading to hemodynamic effects such as increased blood pressure. To minimize these risks, lower concentrations, such as 0.5% or 1%, are recommended. Studies have shown that using a combination of phenylephrine 0.5% and cyclopentolate 0.1% in microdrop form (approximately 7 μL) is effective for pupil dilation and reduces the likelihood of systemic side effects.operties.

  • Reference: Kremer LJ, Medlicott N, Sime MJ, Broadbent R, Edmonds L, Berry MJ, et al. Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial. Arch Dis Child Fetal Neonatal Ed. 2023;108(4):380-6.

• Usual initial range for a continuous intravenous infusion is 0.1 to 0.5 mcg/kg/minute. However, doses up to 2 mcg/kg/minute have been reported but not necessarily in the newborn period. 

  • Wessel DL. Managing low cardiac output syndrome after congenital heart surgery. Crit Care Med. 2001;29(10)(suppl):S220-S230. [PubMed 11593065]

  • Kliegman RM, St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Saunders Elsevier; 2020. 

  • Shaddy RE, Viney J, Judd VE, McGough EC. Continuous intravenous phenylephrine infusion for treatment of hypoxemic spells in tetralogy of Fallot. J Pediatr. 1989;114(3):468-470. [PubMed 2921691]

• In the context of an infundibular spasm in Tetralogy of Fallot (commonly called: Tet spell), phenylephrine is part of the management strategy to acutely raise SVR to promote pulmonary blood flow. Dose are typically 5 to 20 mcg/kg IV bolus and followed by a continuous infusion of 0.1 to 0.4 mcg/kg/minute. Extreme doses up to 5 mcg/kg/minute have been described but based on case reports.

  • Drugs for pediatric emergencies. Committee on Drugs, Committee on Drugs, 1996 to 1997, Liaison Representatives, and AAP Section Liaisons. Pediatrics. 1998;101(1):E13. [PubMed 9734990] 

  • Shaddy RE, Viney J, Judd VE, McGough EC. Continuous intravenous phenylephrine infusion for treatment of hypoxemic spells in tetralogy of Fallot. J Pediatr. 1989;114(3):468-470. [PubMed 2921691]

• This medication should be used with the utmost caution and only under the guidance of a local expert or within the framework of a study protocol. Their use requires careful consideration and strict monitoring.

Hydrocortisone

• Appropriate glucocorticoid response to stress is essential for maintenance of hemodynamic stability.

• Glucocorticosteroids improve adrenergic receptors in smooth muscles, inhibits NO synthase expression and ↓ reuptake of norepinephrine leading to an increase in vascular tone and support of myocardial function.

• Effective in increasing BP and decreasing inotropic support.

• No study showing improved clinical outcomes with steroids in newborn shock

• Hydrocortisone normalizes PDE-5 activity in pulmonary artery smooth muscle cells from lambs with PPHN (Perez, M., Wedgwood, S., Lakshminrusimha, S., Farrow, K. N., & Steinhorn, R. H. (2014). Hydrocortisone normalizes phosphodiesterase-5 activity in pulmonary artery smooth muscle cells from lambs with persistent pulmonary hypertension of the newborn. Pulmonary circulation, 4(1), 71-81.)

Vasopressin

• Patient started on Vasopressin – up to 0.3 milliunits/kg/minute with good response in BP and presence of adequate urine output.

• Usual dosage: 0.1 to 0.3 milliunits/kg/min, to increase by steps of 0.1 to 0.2 milliunits/kg/min q60 min (avoid increasing faster than q20minutes). Beware of the units. 

  • Hypotension - range: 0.17 to 0.67 milliunits/kg/minute (0.01 to 0.04 units/kg/hour); initiated at low end and titrated q20 minutes in 0.17 milliunits/kg/minute (0.01 units/kg/hour) increments. Reference: Rios DR, Moffett BS, Kaiser JR. Trends in pharmacotherapy for neonatal hypotension. J Pediatr. 2014;165(4):697-701. [PubMed 25039051]

  • Persistent pulmonary hypertension of the newborn (PPHN): Initial: 0.1 milliunits/kg/minute, increase in 0.1 milliunits/kg/minute increments every hour as needed for clinical response to a maximum dose of 1.2 milliunits/kg/minute. Reference: Mohamed A, Nasef N, Shah V, McNamara PJ. Vasopressin as a rescue therapy for refractory pulmonary hypertension in neonates: case series. Pediatr Crit Care Med. 2014;15(2):148-154. [PubMed 24141655]

• In animal model: vasopressin increases BP numbers. Act by increasing systemic vascular resistance (vasoconstriction). Does not have inotropic effect on the ventricles.

• Will increase LV afterload - to avoid if there are signs of significant LV dysfunction

• More evidence in context of acute PH with great response. To consider if significant PPHN with adequate LV function since it seems to decreases the Pulmonary:Systemic pressure ratio

• Half life of 6 minutes - Reference: Article: Agakidou E, Chatziioannidis I, Kontou A, Stathopoulou T, Chotas W, Sarafidis K. An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication. Children (Basel). 2024 Apr 19;11(4):490. doi: 10.3390/children11040490. PMID: 38671707; PMCID: PMC11049273.

• Beware of Syndrome of inappropriate antidiuretic hormone secretion (SiADH), often present in HIE or with hyponatremia - vasopressin may lead to significant hyponatremia if no adequate urine output. May also be associated with natriuresis and require Na supplementation. 

• One advantage is that adrenergic medications are sensitive to pH. Vasopressin seem to act regardless of underlying pH (such as in profound acidosis) 

• Reference on Vasopressin in the newborn

• One factor to consider when choosing a vasopressor (increasing SVR) is that norepinephrine may increase heart rate through its β₁-adrenergic effects. Phenylephrine would not because it is a pure alpha-agonist (synthetic) but has barely been studies in the neonatal population. Vasopressin, on the other hand, typically does not increase heart rate and may help preserve ventricular filling time. If the goal is to enhance chronotropy (i.e. low heart rate, or bradycardia), norepinephrine may be more suitable. Conversely, if it's important to limit the impact on filling time, such as in a tachycardic infant, vasopressin could be a better option. 

• Some infants develop hyponatremia on vasopressin, but vasopressin may also help achieve better renal perfusion pressure by increasing systemic vascular resistance (SVR) and restoring adequate pressure in the systemic vascular compartment. This improvement in renal perfusion can promote diuresis and help rebalance sodium levels by facilitating water excretion.

• Other references: 

  • Al-Saadi A, Sushko K, Bui V, van den Anker J, Razak A, Samiee-Zafarghandy S. Efficacy and Safety of Vasopressin and Terlipressin in Preterm Neonates: A Systematic Review. Int J Environ Res Public Health. 2022 Oct 22;19(21):13760. doi: 10.3390/ijerph192113760. PMID: 36360641; PMCID: PMC9658127.

  • Masarwa R, Paret G, Perlman A, Reif S, Raccah BH, Matok I. Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis. Crit Care. 2017 Jan 5;21(1):1. doi: 10.1186/s13054-016-1589-6. PMID: 28057037; PMCID: PMC5217634.

Terlipressin

• Similar mechanism of action than Vasopressin. Non-selective synthetic analogue of arginine vasopression. It acts on V1 (vascular), V2 (renal), and V3 (pituitary) receptors.

• Very limited data in the newborn period. Higher affinity to V1 receptors than vasopressin, and a longer half-life (6 hours compared to 6 minutes)

  • Reference: Agakidou E, Chatziioannidis I, Kontou A, Stathopoulou T, Chotas W, Sarafidis K. An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication. Children (Basel). 2024 Apr 19;11(4):490. doi: 10.3390/children11040490. PMID: 38671707; PMCID: PMC11049273.

• One study used: "1 mg of the active ingredient terlipressin (TP) acetate with 5 mL solution solvent; Ferring Pharmaceuticals, Saint-Prex, Switzerland), which was diluted in 10 mL normal saline and administered as an IV loading dose (2 g/kg bolus) followed by continuous IV infusion (2–20 g/kg/h; TP group)."

  • Reference: Study: Ismail R, Awad H, Allam R, Youssef O, Ibrahim M, Shehata B. Methylene blue versus vasopressin analog for refractory septic shock in the preterm neonate: A randomized controlled trial. J Neonatal Perinatal Med. 2022;15(2):265-273. doi: 10.3233/NPM-210824. PMID: 34719443. - Table 2 and Figure 2 outlined here.

  • In that study, Methylene Blue was more efficient and achieving normalization of blood pressure and reduction in norepinephrine load. Of note - this study was very small (n=15 participants per group) and single centre, with short term outcomes only. 

  • One study mentioned: Bolus of 5–20 mcg/kg IV, followed by maintenance doses of 5–20 mcg/kg every 4 hours

    • Reference: Nilsson G., Lindblom P., Ohlin M., Berling R., Vernersson E. Pharmacokinetics of Terlipressin after Single i.v. Doses to Healthy Volunteers. Drugs Exp. Clin. Res. 1990;16:307–314.

  • This medication should be used with the utmost caution and only under the guidance of a local expert or within the framework of a study protocol. Their use requires careful consideration and strict monitoring.

  • Other references: 

    • Al-Saadi A, Sushko K, Bui V, van den Anker J, Razak A, Samiee-Zafarghandy S. Efficacy and Safety of Vasopressin and Terlipressin in Preterm Neonates: A Systematic Review. Int J Environ Res Public Health. 2022 Oct 22;19(21):13760. doi: 10.3390/ijerph192113760. PMID: 36360641; PMCID: PMC9658127.

    • Masarwa R, Paret G, Perlman A, Reif S, Raccah BH, Matok I. Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis. Crit Care. 2017 Jan 5;21(1):1. doi: 10.1186/s13054-016-1589-6. PMID: 28057037; PMCID: PMC5217634.

    • Chen Q, Huang Z, Chen Y. Terlipressin in the treatment of neonatal refractory hypotension caused by septic shock: a case report. Turk J Pediatr. 2020;62(4):668-672. doi: 10.24953/turkjped.2020.04.019. PMID: 32779422.

Milrinone

• PDE3 inhibitor leads to ↑ intra-cellular calcium in myocardial muscle.

• Theoretical effect: Inotropic, lusitropic (promotes filling), ↓ systemic and pulmonary vascular resistance, ↓ afterload of LV and/or RV to promote forward flow. May lead to significant hypotension. Excreted by kidneys and neonates may be intoxicated with no urine output. 

• Usual initial dosage : 0.2 to 0.5 mcg/kg/min (usually starts at 0.3 mcg/kg/min)

• Very limited neonatal data

• 9 cases described with early improvements in O2 with milrinone infusion after iNO

• BEWARE in HIE: renally excreted and can accumulate in blood, vasodilation and can induce distributive shock à refractory hypotension

• Can lead to V/Q mismatch (beware in meconium aspiration).

References:

Dietrichs ES, Kondratiev T, Tveita T. Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model. Cryobiology. 2014;69(3):361-6.

McNamara PJ, Laique F, Muang-In S, Whyte HE. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. Journal of critical care. 2006;21(2):217-22.

Tveita T, Sieck GC. Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model. Cryobiology. 2012;65(1):27-32.

Dietrichs ES, Kondratiev T, Tveita T. Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model. Cryobiology. 2014;69(3):361-6.

Levosimendan 

• Mechanism of Action: 

  • Calcium Sensitizer. It enhances cardiac contractility by sensitizing troponin C to calcium without increasing intracellular calcium levels, reducing the risk of arrhythmias. 

  • Vasodilatory Effects: Activates ATP-sensitive potassium (K-ATP) channels in vascular smooth muscle, leading to systemic and pulmonary vasodilation. 

  • Inflammatory modulation: May have anti-inflammatory and anti-apoptotic effects, providing myocardial and organ protection. 

• Off-label use in neonates due to limited studies in this population. Used for low cardiac output syndrome (LCOS) in neonates following cardiac surgery or severe cardiac dysfunction. May be considered in persistent pulmonary hypertension of the newborn (PPHN) to reduce pulmonary vascular resistance. 

• Dosage: Typically administered as an intravenous infusion. "Estimated dose regimen for neonates, small infants, and children up to 20 kg was a 24 h infusion dose of 0.2 mcg/kg/min"

  • Reference: Agakidou E, Chatziioannidis I, Kontou A, Stathopoulou T, Chotas W, Sarafidis K. An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication. Children (Basel). 2024 Apr 19;11(4):490. doi: 10.3390/children11040490. PMID: 38671707; PMCID: PMC11049273.

  • A cautious approach would be to start at a lower dose of 0.05 μg/kg/min and titrate for effect up to 0.2. A loading dose is avoided in neonates to minimize the risk of hypotension. 

  • Most evidence is extrapolated from pediatric and adult populations. Small case series and reports suggest potential benefits in improving cardiac output and reducing pulmonary artery pressures. Short-term improvements in hemodynamics observed, but long-term outcomes remain unclear. 

  • Adverse Effects: 

    • Hypotension: Due to vasodilatory properties, careful titration is needed. 

    • Tachycardia: May occur due to increased cardiac workload. 

    • Electrolyte Imbalances: Monitor potassium levels as hypokalemia may occur. 

    • Arrhythmias: Although less common, they can still occur and should be closely monitored. 

    • Considerations Use should be reserved for specialized centers with experience in neonatal cardiac care. Requires continuous hemodynamic monitoring during administration. Optimal dosing and safety profile in neonates remain undefined, emphasizing the need for further studies.

  • This medication should be used with the utmost caution and only under the guidance of a local expert or within the framework of a study protocol. Their use requires careful consideration and strict monitoring.

Hemodynamic instability in HIE

From: Ruoss JL, McPherson C, DiNardo J. Inotrope and vasopressor support in neonates. NeoReviews. 2015;16(6):e351-e61.

From: Giesinger RE, McNamara PJ. Hemodynamic instability in the critically ill neonate: An approach to cardiovascular support based on disease pathophysiology. Semin Perinatol. 2016 Apr;40(3):174-88. doi: 10.1053/j.semperi.2015.12.005. Epub 2016 Jan 14. PMID: 26778235.

Presentation on Approach to hypotension by Dr Carolina Macias Michel

Anti-Hypertensive Medications

Presentation at PAS 2024 - TARGET Shock - Targeted Agents Reducing Global hypoperfusion in Extreme preTerms