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Inotropes in Neonates HYPOTENSION © 2009 SNL All rights reserved Inotropes in term neonates Systemic hypotension is common in infants requiring intensive care. This article covers the pathophysiology of this condition and the importance of treating it. The article outlines management plans for the rational use of inotropes in these hypotensive newborns and suggests which further options are available in refractory cases. Kiran Patwardhan etween one third to a half of all babies preloading of the left ventricle thereby MBBS, DCH, DNB, MRCP, FRCPCH Badmitted for neonatal intensive care increasing left ventricular output. If Paediatric Intensive Care Unit, Royal become hypotensive within 24 hours of complications occur during this transition, Hospital for Sick Children, Edinburgh admission. This systemic hypotension is a blood pressure may be affected. [email protected] relatively common complication of preterm birth but also affect full term sick Blood pressure measurement neonates with a range of medical and Direct, invasive measurement obtained surgical conditions. Increasingly, more from a well-positioned, unobstructed intra- neonates are admitted to the paediatric arterial catheter is the gold standard. Mean intensive care unit peri-operatively needing blood pressure is minimally affected by the circulatory support. This article is written mechanical properties of the intra-arterial from the perspective of a paediatric catheter and the transducer system, micro intensivist, who often faces the challenge of air bubbles and site (central versus treating low blood pressure in the face of peripheral)2. If direct measurements are not poor evidence to support any treatment available, a Doppler probe with an approp- options. It will review the use of vasoactive riate sized cuff gives a similar degree of drugs in hypotensive newborn infants and accuracy, although it tends to overestimate suggest what further options may be the blood pressure in the hypotensive available in refractory cases. ranges. It would appear that oscillometric Circulatory adaptation at birth systems are inaccurate when the systolic blood pressure is less than 40mmHg. The time immediately after birth is a critical period for the newborn, as Definition of hypotension transition is made from fetal to neonatal A number of studies have looked at the life. This transition is a complex multi- blood pressure ranges in the newborns.2-5 organ system process1. The ability to make Perhaps the best data on normal values can Keywords these adjustments may be more difficult be found in a study done in the northern for a premature infant. Fetal circulation is newborn; blood pressure; inotropes; region in the UK. After four hours and characterised by a low systemic vascular hypotension before 24 hours of age, the systolic blood resistance due to the presence of a low pressure should not be lower than the Key points resistance placental vascular bed. In gestational age in weeks. The commonly contrast, the pulmonary vascular resistance Patwardhan K. Inotropes in neonates. cited ‘rule of thumb’ defines hypotension is high, allowing only 6-12% of the cardiac Infant 2009; 5(1): 12-17. as mean blood pressure below an infants’ 1. Systemic hypotension is a common output to travel to the lungs. After birth, gestational age in weeks6. However it must complication in infants on the with contraction of the umbilical arteries be stressed that blood pressure alone paediatric intensive care unit and and separation from the placenta, systemic remains an unreliable measure of either requires an individualised approach. vascular resistance rises rapidly. Pulmonary 2. Treatment is unnecessary for those who vascular resistance falls progressively as cardiac output or of systemic oxygen have adequate perfusion and no signs lungs expand. The ductus arteriosus shunts delivery (see below) and should not be of shock. blood predominantly from right to left in treated in isolation. 3. Although most term newborns will utero, but changes to shunt predominantly Physiology of blood pressure respond to standard treatment, several from left to right after birth, as a result of other options are available to treat the the changes in systemic and pulmonary regulation refractory cases. vascular resistance. Pulmonary blood flow Blood pressure is the product of cardiac 4. Clinical assessment and supportive increases resulting in increased pulmonary output and systemic vascular resistance. measures are equally important. venous return. This increases the Cardiac output is the product of heart rate 12 VOLUME 5 ISSUE 1 2009 infant HYPOTENSION primary cause of neonatal hypotension in I. HYPOVOLAEMIA Preload Contractility Afterload a full term neonate with a medical or • Massive pulmonary haemorrhage surgical problem13. If there is an • Acute surgical emergencies identifiable volume loss, ideally the same Heart rate Stroke • Intracranial/subgaleal haemorrhage kind of fluid should be replaced. For volume • Disseminated intravascular example, in cases of blood loss, blood coagulation transfusion should be given. If bleeding Cardiac Systemic vascular • Dehydration: insensible water occurs secondary to disseminated output resistance losses/polyuria intravascular coagulation, fresh frozen • Third space losses, e.g. sepsis due to plasma, cryoprecipitate or platelet rich necrotising enterocolitis Blood pressure plasma should be used. This serves a dual • Decreased venous return purpose of treatment of the underlying TABLE 1 Physiology of blood pressure7. – Air leak syndromes problem and as volume replacement. In – High positive end expiratory cases of greater transepidermal water losses and stroke volume. Stroke volume is pressure (PEEP)/high frequency or polyuria, administration of saline with dependent on the amount of blood oscillation more free water is indicated. returning to the heart (preload), strength II. CARDIOGENIC SHOCK If the cause of hypovolaemia or of hypo- of myocardial contractility (the pump) and • Birth asphyxia tension is unclear, isotonic saline should be the resistance against which the heart must used. A bolus of 10mL/kg (5mL/kg in case • Congenital heart disease pump (after load). Newborns have a of perioperative cardiac newborn) over 20- – Duct dependant lesions with limited ability to increase the stroke 30 minutes may bring about a sustained closure of the duct volume. Hence, neonatal cardiac output is increase in blood pressure. In such a case a more dependent on heart rate. – Total anomalous pulmonary venous connection further bolus can be repeated, if necessary. The strength of myocardial contractility However, if the central venous pressure • Postoperative cardiac surgery depends on the filling volume and pressure, (CVP) increases without appreciable • Cardiomyopathy as well as on the maturity and integrity of increase in blood pressure, hypovolaemia is the myocardium. Thus hypovolaemia, • Myocarditis unlikely. In such a situation treatment with arrhythmias, extreme prematurity, hypoxia, • Arrhythmias an inotrope is indicated. The rationale for acidosis, electrolyte imbalances (especially III. SEPTIC SHOCK administration of an inotrope to a hypocalcaemia) and infections will affect hypotensive newborn unresponsive to the myocardial contractility, which may IV. ENDOCRINE volume therapy is to increase systemic lead to a fall in cardiac output. If systemic • Adrenal haemorrhage perfusion pressure, and thereby systemic vascular resistance (after load) is too high, • Congenital adrenal hyperplasia blood flow and oxygen delivery. the ability of the myocardium to pump against the increased resistance may V. DRUGS: Sedation on the ICU Inotropes become compromised and the cardiac TABLE 2 Causes of neonatal hypotension8. Drugs that improve myocardial output will fall. contractility are called inotropes. They In the clinical settings, it is difficult to increase the peak force of contraction Significance of hypotension in sick assess the adequacy of blood flow to the under isometric conditions. Drugs that neonates organs as it depends (among other things) increase the heart rate are called Systemic hypotension may reduce the on cardiac output and end organ vascular chronotropes. Generally, they accelerate blood flow to the vital organs and make resistance. Therefore, blood pressure is the heart and may also have inotropic them vulnerable to ischaemic injury. used as an indirect measure of perfusion. properties. The action of these drugs on Hypotension is independently associated When the oxygen delivery to the tissues is the myocardium can be due to an effect on with adverse neurodevelopmental compromised, shock ensues. Shock the calcium transit (up-stream outcome9. In addition, the duration and remains a major cause of neonatal regulation)14 or on the sensitivity of the severity of hypotension may be morbidity and mortality. contractile proteins to calcium (down- important10,11. In a recent article, stream regulation). No inotrope currently Barrington12 has emphasised the concept of Treatment of hypotension used in clinical practice increases the force ‘permissive hypotension’. Treatment of The most common pathological factors for of contraction by a direct effect on the systemic hypotension in infants with good neonatal hypotension are: myofibrils. A group of drugs known as perfusion and no signs of shock is probably 1. Inappropriate peripheral vasoregulation calcium sensitizers is currently under unnecessary and could be potentially resulting in vasoconstriction (usually investigation. Certain drugs (calcium
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