The basic principles of anesthesia for the neonate | Colombian Journal of Anesthesiology

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Source: Authors." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Edgar Cortés-Reyes, Katherine Parrado-Bermúdez, Franklin Escobar-Córdoba" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Edgar" "apellidos" => "Cortés-Reyes" ] 1 => array:2 [ "nombre" => "Katherine" "apellidos" => "Parrado-Bermúdez" ] 2 => array:2 [ "nombre" => "Franklin" "apellidos" => "Escobar-Córdoba" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S012033471630079X" "doi" => "10.1016/j.rca.2016.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S012033471630079X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2256208716300475?idApp=UINPBA00004N" "url" => "/22562087/0000004500000001/v1_201701060057/S2256208716300475/v1_201701060057/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2256208716300736" "issn" => "22562087" "doi" => "10.1016/j.rcae.2016.11.003" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "320" "copyright" => "Sociedad Colombiana de Anestesiología y Reanimación" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-sa/4.0/" "subdocumento" => "ssu" "cita" => "Rev Colomb Anestesiol. 2017;45:48-53" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1099 "formatos" => array:3 [ "EPUB" => 113 "HTML" => 730 "PDF" => 256 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Hypothermia in elective surgery: The hidden enemy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "48" "paginaFinal" => "53" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipotermia en cirugía electiva. El enemigo oculto" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jorge Enrique Bayter-Marín, Jorge Rubio, Arnaldo Valedón, Álvaro Andrés Macías" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Jorge Enrique" "apellidos" => "Bayter-Marín" ] 1 => array:2 [ "nombre" => "Jorge" "apellidos" => "Rubio" ] 2 => array:2 [ "nombre" => "Arnaldo" "apellidos" => "Valedón" ] 3 => array:2 [ "nombre" => "Álvaro Andrés" "apellidos" => "Macías" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0120334716301174" "doi" => "10.1016/j.rca.2016.08.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0120334716301174?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2256208716300736?idApp=UINPBA00004N" "url" => "/22562087/0000004500000001/v1_201701060057/S2256208716300736/v1_201701060057/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "The basic principles of anesthesia for the neonate" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "54" "paginaFinal" => "61" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lynn D. Martin" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Lynn D." "apellidos" => "Martin" "email" => array:1 [ 0 => "lynn.martin@seattlechildrens.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Professor, Departments of Anesthesiology & Pain Medicine and Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Correspondence to: Seattle Children's Hospital, Anesthesiology & Pain Medicine, 4800 Sand Point Way, N.E. Seattle, WA 98105, USA." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Principios básicos de la anestesia neonatal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Reproduced with permission from LeDez and Lerman.<a class="elsevierStyleCrossRef" href="#bib0495">41</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1333 "Ancho" => 1464 "Tamanyo" => 72438 ] ] "descripcion" => array:1 [ "en" => "The minimum alveolar concentration (MAC) of isoflurane and post-conceptual age." ] ] ] "textoCompleto" => "IntroductionOne of the most challenging tasks an anesthesiologist will ever face is the provision of safe and effective anesthesia care of a newborn for surgery. Neonatal anesthesia demands a thorough understanding of the rapidly changing physiology and pathology of the neonate and both the pharmacokinetics and pharmacodynamics of the medications used to provide anesthesia. This knowledge is then incorporated into a well planned anesthetic plan of care. Furthermore, great manual skills and continuous experience with these unique challenges presented by neonates are essential for optimal clinical outcome for these vulnerable patients. This selective review aims to provide a brief summary of theoretical aspects of neonatal anesthesia and present some practical guidelines of care for this patient population.Physiology of the neonateThe respiratory system has to undergo major physiologic changes in function in seconds when transitioning from the fetal to neonatal environment. To facilitate easier passage through the birth canal, the neonate's chest wall (rib cage) is flexible with little calcification of the bones.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> In contrast, the newborns lungs are populated with immature alveoli that contain little elastin; thereby making them stiff and difficult to inflate.<a class="elsevierStyleCrossRef" href="#bib0300">2</a> This combination of flexible chest wall and stiff lung increases the closing volume of the lung and promotes lung collapse.<a class="elsevierStyleCrossRef" href="#bib0305">3</a> Functional residual capacity (FRC) when normalized by body weight is relatively constant from birth through adult life.<a class="elsevierStyleCrossRef" href="#bib0310">4</a> Spontaneously breathing neonates will dynamically compensate for their immature respiratory mechanics with rapid breathing without expiratory pauses and expiratory air breaking through the larynx.<a class="elsevierStyleCrossRef" href="#bib0315">5</a> To overcome these developmental challenges under passive conditions, pediatric anesthesiologists will routinely recruit alveoli after each brief period of apnea and will use positive end-expiratory pressure (PEEP) when mechanically ventilating a neonate to maintain normal lung volumes.In spite of equivalent FRCs, neonates will rapidly desaturate with apnea even with effective pre-oxygenation with 100% inspired oxygen.<a class="elsevierStyleCrossRef" href="#bib0320">6</a> This principally is due to a doubling of the rate of oxygen consumption when normalized by body weight in comparison to an adult.<a class="elsevierStyleCrossRef" href="#bib0325">7</a> To compensate for this high oxygen consumption, neonates also have twice the alveolar ventilation of an adult. Pediatric anesthesiologists routinely take advantage of this during inhalational induction of anesthesia where the rapid wash in of anesthetics leads to a more rapid induction of anesthesia in the young compared to an adult.<a class="elsevierStyleCrossRef" href="#bib0330">8</a>Anesthesiologists also must understand that neonates are obligate nose breathers and more easily experience airway obstruction under anesthesia due to the relatively larger tongue and more compliant (collapsible) airway soft tissue.<a class="elsevierStyleCrossRef" href="#bib0335">9</a> Similarly, practitioners in neonates realize the importance of the artificial airway diameter because airway resistance increases by the fourth power as radius decreases.<a class="elsevierStyleCrossRef" href="#bib0340">10</a>During the neonatal period the control of breathing varies significantly from that seen in older children and adults. The increase in ventilation to hypercapnia is less in a neonate compared to an adult; however, it is the response to hypoxemia that differs dramatically. While an adult will have a sustained increase in ventilation when exposed to hypoxia, neonates will demonstrate a brief increase follow by a sustained depression of ventilator drive when exposed to hypoxemia.<a class="elsevierStyleCrossRef" href="#bib0345">11</a> The immaturity of the respiratory centers in the central nervous system in neonates are likely responsible in part of the pronounced affect anesthetics have in this population. In the only published systematic review of studies evaluating perioperative apnea in this population, general anesthesia increased the risk for postoperative apnea in premature infants less than 60 weeks postconceptional age.<a class="elsevierStyleCrossRef" href="#bib0350">12</a> This risk is further increased by anemia (Hct<30%). Even at 56 postconceptional weeks the risk for postoperative apnea remains approximately 1% (see <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>); therefore, most textbooks and leaders in the field of pediatric anesthesia recommend that patients under this threshold should be admitted to the hospital for monitoring for 12–24h.<a class="elsevierStyleCrossRef" href="#bib0355">13</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Following birth the circulatory system undergoes dramatic changes from a fetal parallel system characterized by both ventricles pumping the majority of their output into the system circulation to an extra-uterine series system with the right and left ventricles assuming responsibility for the pulmonary and the systemic circulations respectively.<a class="elsevierStyleCrossRef" href="#bib0360">14</a> In addition, the three embryological shunts (foramen ovale, ductus venosus, and ductus arteriosus) will functionally close in the early postnatal period.Certain neonatal conditions (i.e., birth asphyxia, meconium aspiration, septicemia, and congenital diaphragmatic hernia) may prevent this normal transition in circulation from occurring due to persistent elevation in pulmonary vascular resistance and blood pressure. This persistent fetal circulation (PFC), also known as pulmonary hypertension of the newborn, is characterized by profound hypoxia due to right-to-left shunting through the fetal extra-pulmonary shunts combined with right ventricular strain and circulatory compromise.<a class="elsevierStyleCrossRef" href="#bib0365">15</a> Conventional treatment for this condition includes tracheal intubation and mechanical ventilation to restore normal lung volume without excessive distention, correction of metabolic acidosis, induction of mild alkalosis via hyperventilation, restoration of circulatory volume and inotropic support. Over the last decade the selective pulmonary vasodilatation by means of inhalation of nitric oxide (iNO) has become one the principle treatments for PFC.<a class="elsevierStyleCrossRef" href="#bib0370">16</a> The effective dose range appears to be between 1 and 30 parts per million (ppm). Abrupt withdrawal of iNO can result in sudden severe rebound of pulmonary hypertension so this therapy needs to weaned slowly once initiated. For the few patients that failed to respond to iNO, the short-term use of extracorporeal life support for several days has been shown to achieve 90% survival in patients with a predicted mortality of 50%.<a class="elsevierStyleCrossRef" href="#bib0375">17</a>The neonatal cardiac myocyte contains more non-contractile elements, has a disorganized intracellular arrangement of contractile proteins, and is less elongated than in the adult.<a class="elsevierStyleCrossRef" href="#bib0380">18</a> This leads to a reduction in the force generation capability of the neonatal myocardium. In addition, the sarcoplasmatic reticulum and the T-tubular system are also immature, leading to an increased dependence on extracellular calcium for contraction.<a class="elsevierStyleCrossRef" href="#bib0385">19</a> Developmental changes in the cytoskeleton and the extracellular matrix make the neonatal myocardium less compliant with reduced early and late diastolic filling compared to adults.<a class="elsevierStyleCrossRef" href="#bib0390">20</a> The parasympathetic innervation of the neonatal heart is considered to be more mature compared to the sympathetic system, leading to reduction in heart rate with stimulation. While slow heart rates can reduce cardiac output, the rapid heart rate of the neonate can also limit diastolic filling and stroke volume. After optimizing filling pressures via administration of crystalloid fluid, heart rated between 120 and 180 beats per minute should be the target for neonates.The central nervous system is incompletely developed at birth. However, pain pathways are integrated with somatic, neuroendocrine, and autonomic changes early in gestation. The hormonal responses to pain and stress may be exaggerated in newborns,<a class="elsevierStyleCrossRef" href="#bib0395">21</a> although the clinical importance of this has not yet been defined. Recent studies suggest the cerebral blood flow responses to oxygen and carbon dioxide as well as the autoregulation of blood flow are present in the newborn<a class="elsevierStyleCrossRefs" href="#bib0400">22,23</a>; however, the range of autoregulation is narrow and very close to the limits of normal blood pressure (see <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The lower threshold of autoregulation remains somewhat uncertain. Although an association between the incidence of intraventricular hemorrhage and fluctuations in blood pressure has been noted,<a class="elsevierStyleCrossRef" href="#bib0410">24</a> there has been no confirmation of a causal relationship.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Immaturity of the central nervous system also contributes to the development of retinopathy of the premature (ROP). This condition begins as retinal vascular narrowing and obliteration followed by neovascularization, hemorrhage and in the most severe cases retinal detachment and blindness. Infants suffering from ROP frequently require anesthetics for ocular examination and potential laser treatment for hemorrhage and retinal detachment. While the etiology of ROP is likely multifactorial<a class="elsevierStyleCrossRef" href="#bib0415">25</a>; oxygen toxicity (perhaps from short-term exposure during brief surgical procedures) contributes to this common complication of prematurity.Thermoregulation in the neonate differs markedly from the older child and adult. Heat loss is favored by the comparatively larger body surface-to-body weight relationship, the poorly developed insulating subcutaneous tissues, and the inability to use shivering thermogenesis. These limitations are partially compensated for by the unique thermal capacity for non-shivering thermogenesis via brown fat. Both volatile and intravenous anesthetics have been shown to inhibit non-shivering thermogenesis,<a class="elsevierStyleCrossRefs" href="#bib0420">26,27</a> potentially contributing to heat loss in the perioperative period. Hypothermia can reduce metabolism of medications, slow emergence from anesthesia and subject neonate to cardiovascular stress. Maintaining a neutral thermal environment (36–37°C) via warming of the operative suite, use of radiant warmers, force air heating units, and warmed intravenous and irrigation fluids are beneficial.<a class="elsevierStyleCrossRef" href="#bib0430">28</a>The total body water is significantly higher in a preterm infant (>80%), term neonate (75%) compared to an adult (60%).<a class="elsevierStyleCrossRef" href="#bib0435">29</a> Extracellular water represents in excess of 50% of a premature infant's body weight. Similarly the blood volume is higher in premature infants (90–100mL/kg) compared to term neonates (85mL/kg) compared to adults.<a class="elsevierStyleCrossRef" href="#bib0440">30</a> Fluid requirements increase the first several days of life (60, 80, 100, 120mL/kg/day at day 1, 2, 3, and 4 respectively), and then remain stable the remainder of the neonatal period (approximately 150mL/kg/day).<a class="elsevierStyleCrossRef" href="#bib0445">31</a> Glomerular filtration rate is low in the term infant, then doubles within the first 2 weeks of life, but does not reach adult levels until 2 years of age.<a class="elsevierStyleCrossRef" href="#bib0450">32</a> Glycogen stores develop in the last several weeks of gestation. Therefore, premature infants are susceptible to hypoglycemia if they are deprived from a source of continuous glucose administration.<a class="elsevierStyleCrossRef" href="#bib0455">33</a>Developmental pharmacologyThe major routes of elimination by which drugs and their metabolites leave the body are the hepatobiliary, renal and respiratory systems; all of which undergo significant maturation after birth.<a class="elsevierStyleCrossRef" href="#bib0460">34</a> Hepatobiliary clearance via the P450 iso-enzymes is present at term and reaches approximately 85% of adult levels by 44 weeks postmenstrual age.<a class="elsevierStyleCrossRef" href="#bib0465">35</a> Protein binding to albumen and α1-acid glycoprotein is reduced in neonates due to lower concentrations of these proteins in the serum.<a class="elsevierStyleCrossRef" href="#bib0470">36</a> This lower protein binding leads to larger amounts of free (unbound) drug which potentiates the risk for adverse side-effects in neonates (particularly local anesthetics).<a class="elsevierStyleCrossRef" href="#bib0475">37</a> These proteins reach approximate adult concentrations at 6 months of age.Renal elimination of drugs and their metabolites is determined by glomerular filtration, tubular secretion and tubular reabsorption. Glomerular filtration rate (GFR) is only 10% of the mature value at 25 weeks, 35% at term and 90% of the adult value at 1 year of age.<a class="elsevierStyleCrossRef" href="#bib0450">32</a> This reduction has significant implications on dosing intervals of drugs principally eliminated via renal clearance (i.e. aminoglycosides). The same factors that determine anesthetic absorption through the lung (i.e., alveolar ventilation, functional residual capacity, cardiac output, and blood/gas solubility) also contribute to their elimination kinetics.The pharmacokinetic variables important to anesthesiologists are known. Clearance (CL) is the most important, as it determines maintenance dosing or drug infusion rates. Volume of distribution (V) has relatively minor importance except in relation to loading doses. These parameters determine the shape of the time-concentration curve. The three major sources of pharmacokinetic variability in neonates have been identified (size, age, and organ function).<a class="elsevierStyleCrossRef" href="#bib0480">38</a> Size is the most common co-variable used to determine dose in children even though normal variation in weight with age is large. Size alone is insufficient to predict CL in neonates and infants, the addition of a maturation effect (age) is required. The cause for the slower drug clearance seen in newborns is not limited to just the normal developmental changes in hepatic and renal organ function; compromised organ function due to critical illness in the newborn may also play a significant role in slowing drug CL in neonates.<a class="elsevierStyleCrossRef" href="#bib0485">39</a>As described earlier, the increase in metabolic rate (i.e. oxygen consumption) leads to an increase in alveolar ventilation and volatile anesthetic uptake in neonates when compared to adults. In addition, an increase percentage of the cardiac output is delivered to vessel rich groups (brain and other vital organs) and the solubility of volatile anesthetics is reduced, both factors contributing to an increase in volatile anesthetic uptake.<a class="elsevierStyleCrossRef" href="#bib0490">40</a> Minimum alveolar concentration (MAC) is commonly used to express anesthetic vapor potency. The MAC typically is reduced in pre-terms and peak at 1–6 months of age before decreasing to adult values in adolescence (see <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<a class="elsevierStyleCrossRef" href="#bib0495">41</a> These agents tend to have more myocardial depression in the newborn compared to adults. Contrary to other volatile anesthetic agents, the MAC of sevoflurane is not reduced in pre-term and newborn infants compared to older children (see <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<a class="elsevierStyleCrossRef" href="#bib0500">42</a> Thus, the MAC for sevoflurane in the neonate is approximately 3.2%, which is similar to the MAC values for the 1–6 month old infants. The safety of these agents is potentially compromised by the ability to deliver multiple MAC concentrations from the vaporizer and to further increase uptake via excessive minute ventilation with mechanical ventilator support. This problem has been significantly reduced by the elimination of halothane production in developed countries.<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Intravenous agents play a significant part in the delivery of modern anesthesia care to a neonate. It goes without saying the delivery of any intravenous medications requires patient stable access to the circulatory system. Practitioners of anesthesia for neonates must be able to safely establish peripheral and occasionally central venous access for medication delivery.Unfortunately data regarding the dose-response relationship of most medications is well known in adults and frequently not well understood in neonates. Thus, it is common practice to extrapolate dose guidelines for neonates from adult data. As described previously, neonates generally have reduced serum protein levels which lead to higher concentrations of free (unbound) drug. In addition, reductions in hepatic metabolism and renal elimination generally increase the interval between doses necessary for therapeutic effect.Because of their more frequent use, the pharmacology and side-effects of narcotics in neonates are more thoroughly understood.<a class="elsevierStyleCrossRef" href="#bib0505">43</a> Morphine has been associated with more hypotension and the development of a prolonged elimination half-life due to its dependence on renal elimination. It was the release of potent, synthetic narcotic fentanyl in the 1980s with its minimum affect on the cardiovascular system that allowed the first safe and effective treatment of surgical pain in the neonate. Larger doses were able to partially suppress the neonatal surgical stress response and improve outcomes (survival) following neonatal surgery.<a class="elsevierStyleCrossRef" href="#bib0510">44</a> The wide spread use of propofol for the induction of anesthesia and facilitation in placement of an endotracheal tube for adults has filtered into neonatal practice as well. Propofol has been shown to more commonly cause adverse hemodynamic effects (hypotension) when administered for placement of endotracheal tubes in critically ill neonates.<a class="elsevierStyleCrossRef" href="#bib0515">45</a> In addition, propofol has delayed redistribution and clearance which lead to prolonged action in neonates. Lastly the long-term continuous infusion of propofol (hours to days) has been associated with the development of metabolic acidosis, organ failure and death in neonates and young children<a class="elsevierStyleCrossRef" href="#bib0520">46</a>; therefore, the dose and duration of infusions for sedation should be limited or prohibited to avoid this serious complication.It is very common to use neuromuscular blocking agents to facilitate patient relaxation during neonatal surgery. The use of a depolarizing neuromuscular agent (succinylcholine) is now typically reserved for emergency placement of an endotracheal tube. Because of its very large volume of distribution, the recommended dose for intubation in a neonate (2mg/kg) is twice that recommended in an adult patient (1mg/kg). In spite of this large dose, the duration of action in not prolonged due to rapid clearance by plasma esterase's. The similarity of structure between succinylcholine and acetylcholine along with the fully mature parasympathetic nervous system of the neonate commonly results in the development of a relative bradycardia with succinylcholine administration. For this reason, many authorities recommend pre-treatment with an anticholinergic agent (atropine or glycopyrrolate).The response to non-depolarizing neuromuscular agents in neonates is quite variable and more difficult to predict. All of these agents have an increase in their volume of distribution and decrease in their clearance. In addition, the neonatal myoneural junction appears to demonstrate an increased sensitivity to this class of agents. Pancuronium historically has been popular for this patient population due to its vagal lytic (increase in heart rate) properties. However, this use is significantly limited by the long duration of action in neonates. Vecuronium and rocuronium have fewer vagal lytic properties and are reported to by shorter in duration; however, their duration of action remains longer than 60min in most infants.Perioperative care of the neonateThe anesthesiologist scheduled to care for a newborn must have a reliable comprehensive system to assess the stability of the patient and use this information in the development of their anesthetic plan of care. Important historical information that can be gathered from the medical record includes gestational age, weight, and birth events (including Apgar scores at 1, 5, and 10min). The anesthesiologist should consult with their neonatal and surgical colleagues to ascertain the presence of congenital anomalies. Ultrasound examinations are frequently used to non-invasively identify these anomalies. Finally the anesthesiologist must closely inspect the care requirements of the neonate of the last 24h to ascertain the likely starting point for support in the operative suite.Physical examination of the infants is required to assess the stability and patency of the neonate's airway and gas exchange. If mechanical ventilator support is needed, close inspections of the placement of the airway on chest X-ray, current ventilator settings and the result of the most recent blood gas are needed. The anesthesia provider must perform a careful assessment for signs or symptoms of cardiovascular abnormalities and stability. Hydration (volume) status should be assessed via vital signs (heart rate, blood pressure), capillary refill and urine output. Any evidence of dehydration should be fully corrected before the induction of anesthesia except in true life-threatening emergent situations. Lastly the anesthesiologist must assess the safety of the current vascular access and associated infusions and determine if the access will be sufficient for the perioperative care.The last task in the pre-operative assessment is the review of available laboratory studies. Typically complete blood counts are available to assess the risk for anemia associated with significant blood loss and platelet counts to look for evidence of disseminated intravascular coagulopathy. Low platelets counts (less than 100,000) likely indicate intravascular consumption and should prompt further work-up for coagulopathy. Serum electrolytes will assist with acid-base assessment and possible risk for hyperkalemia with rapid blood transfusion. In addition, the serum glucose level during current therapy will help the anesthesia provider lessen the risk for intraoperative hypoglycemia.Common anesthesia practices in neonates include the routine use of physiologic monitors (ECG, non-invasive blood pressure, temperature, pulse oximetry and end-tidal carbon dioxide). Care must be taken to preserve normal temperature during transport to and from the operative suites and well has heating the operative environment. Continuous glucose delivery throughout the duration of the procedure is required with potential to monitor intermittent serum glucose levels. General anesthesia with placement of endotracheal tubes is generally required for the safe care of the neonate. Anesthesia typically consists of balanced combination of volatile agent supplemented with narcotic (typically fentanyl) for hemodynamic stability. This fentanyl-based anesthetic frequently leads to delayed awakening and the need for post-operative mechanical ventilation. Lung recruitment maneuvers are applied after each period of apnea at ambient pressure to restore normal lung volumes. Mechanical ventilator support routinely includes delivery of PEEP to maintain normal lung volumes with sufficient intermittent positive pressure to maintain normal alveolar ventilation and carbon dioxide clearance.With these modern advances in anesthesia practice multiple studies over the last 3 decades have shown that the risk of anesthesia-related mortality has decreased significantly over time for both adult and pediatric patients<a class="elsevierStyleCrossRefs" href="#bib0525">47–50</a>; however, neonates continue to have the highest risk for perioperative cardiac arrest of any age group.<a class="elsevierStyleCrossRefs" href="#bib0545">51,52</a> In addition, the risk of mortality following cardiac arrest is much higher in the vulnerable group of patients. It is primarily this evidence of increased anesthesia-related risk that led first to formal (certified) advanced pediatric anesthesia fellowship training programs in the United States and more recently the development of board certification in pediatric anesthesiology by the American Board of Anesthesiology.Controversies in neonatal anesthesiaIn spite of the dramatic improvements in care for the neonate in the perioperative environment of the last decade there remains many issues without clear evidence for best practice. What is clear is that there remain many opportunities for clinical investigators to closely evaluate current practice options in efforts to further reduce the risk of anesthesia for the vulnerable neonate.Over the last 15 years many investigators have produced evidence in the laboratory setting that exposure to many different anesthetic agents can potentially induce injury to the developing nervous system with long lasting effects.<a class="elsevierStyleCrossRef" href="#bib0555">53</a> These theoretical concerns regarding anesthesia-related neurotoxicity in infants along with dramatic technical improvements in portable ultrasound has led to a resurgence in the interest and application of regional anesthesia in the neonate. The potential advantages and disadvantages of regional anesthesia as compared to systemic analgesia in a neonate have been debated (see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0560">54</a> While there is no clear consensus on the preferred option, it is clear that many anesthesiologists caring for neonates increasingly value the benefits of regional anesthesia in neonates based on the increasing use of this care option.<a class="elsevierStyleCrossRef" href="#bib0565">55</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>A comprehensive review summarizes the growing body of evidence that the use of high concentrations of oxygen during neonatal resuscitation is associated with oxidative stress, adverse effects on breathing physiology and cerebral circulation, and potential tissue damage from oxygen free radicals.<a class="elsevierStyleCrossRef" href="#bib0570">56</a> This same evidence has been used to suggestion that short exposures to excessive oxygen in the perioperative period could also lead to adverse outcomes.<a class="elsevierStyleCrossRef" href="#bib0575">57</a> Indeed, some investigators now recommend avoidance of excess oxygen for even brief periods in the perioperative setting with an upper limit of oxygen saturation of 95%.<a class="elsevierStyleCrossRef" href="#bib0580">58</a>FundingThe author did not receive sponsorship to undertake this article.Conflicts of interestThe author has no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres785821" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec784536" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres785820" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec784537" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Physiology of the neonate" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Developmental pharmacology" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Perioperative care of the neonate" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Controversies in neonatal anesthesia" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-22" "fechaAceptado" => "2016-07-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec784536" "palabras" => array:4 [ 0 => "Infant, newborn" 1 => "Anesthesia, general" 2 => "Pharmacology" 3 => "Anesthesia, conduction Pharmacokinetics" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec784537" "palabras" => array:4 [ 0 => "Recién, nacido" 1 => "Anestesia, general" 2 => "Farmacología" 3 => "Anestesia de conducción Farmacocinética" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionThere are significant developmental differences in physiology and pharmacology in neonates that make the conduct of a safe anesthetic much more challenging in a neonate. ObjectivesComplete a focused review of the current knowledge of the physiological and pharmacologic differences seen in newborns that impact the safe administration of anesthesia. MethodsA selective review of literature in developmental changes in physiology and pharmacology was completed. ResultsThis knowledge acquired in the review was used to establish common principles for the safe administration of anesthesia to newborn patients. ConclusionIn spite of the persistence of large gaps in our knowledge in this physiology and pharmacology, common modern anesthetic management principles for neonatal surgery have significantly improved clinical outcomes." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónExisten diferencias significativas de desarrollo en la fisiología y la farmacología de los neonatos que hacen que sea mucho más difícil llevar a cabo una anestesia segura. ObjetivosCompletar una revisión focalizada del conocimiento actual sobre las diferencias fisiológicas y farmacológicas observadas en recién nacidos que tienen un impacto en la administración segura de la anestesia. MétodosSe llevó a cabo una revisión selectiva de la literatura sobre cambios en el desarrollo fisiológico y farmacológico. ResultadosEl conocimiento adquirido en esta revisión fue usado para establecer principios comunes para la administración segura de la anestesia en pacientes recién nacidos. ConclusiónA pesar de la persistencia de grandes lagunas en nuestro conocimiento en esta fisiología y la farmacología, los principios modernos y comunes del manejo de la anestesia en cirugía neonatal han mejorado significativamente los resultados clínicos." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Martin LD. Principios básicos de la anestesia neonatal. Rev Colomb Anestesiol. 2017;45:54–61." ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Reproduced with permission from Cote et al.<a class="elsevierStyleCrossRef" href="#bib0350">12</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 946 "Ancho" => 1473 "Tamanyo" => 71630 ] ] "descripcion" => array:1 [ "en" => "Predicted probability of apnea by postconceptional weeks (solid line) with 95% upper confidence limit (broken line). The 1% risk for postoperative apnea reaches 95% confidence at approximately 56 weeks postconceptional age." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Reproduced with permission from Cayabyab et al.<a class="elsevierStyleCrossRef" href="#bib0405">23</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 767 "Ancho" => 1658 "Tamanyo" => 115231 ] ] "descripcion" => array:1 [ "en" => "A schematic drawing of the blood flow/mean arterial pressure relation of the normal cerebral circulation in the preterm newborn baby. The flat portion represents the autoregulatory plateau. The lower blood pressure autoregulation threshold is 30mm Hg or less." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Reproduced with permission from LeDez and Lerman.<a class="elsevierStyleCrossRef" href="#bib0495">41</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1333 "Ancho" => 1464 "Tamanyo" => 72438 ] ] "descripcion" => array:1 [ "en" => "The minimum alveolar concentration (MAC) of isoflurane and post-conceptual age." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Reproduced with permission from Lerman et al.<a class="elsevierStyleCrossRef" href="#bib0500">42</a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1018 "Ancho" => 1490 "Tamanyo" => 47752 ] ] "descripcion" => array:1 [ "en" => "The mean (± standard deviation) end-tidal concentration of sevoflurane in oxygen for each of the six age groups from neonates to older children up to 12 years of age." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Source: author." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Technique \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pros \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cons \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">Regional analgesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Blockade of surgical stress • No hemodynamic instability • Avoid systemic opioids • No post-operative ventilation • Anesthesia-related neurotoxicity? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Difficulty in placement • Risks of dural puncture and spinal cord trauma • Limited system familiarity • Benefits in neonates not proven \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">Systemic analgesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Widely used and extensively studied in neonates • Short-term post-op ventilation safe and widely available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Post-op ICU care required • Surgical stress response ablated not blocked • Tolerance and withdrawal • Opioid induced hyperalgesia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1306387.png" ] ] ] ] "descripcion" => array:1 [ "en" => "A comparison of the pros and cons of regional anesthesia and systemic analgesia in neonates." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:58 [ 0 => array:3 [ "identificador" => "bib0295" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung and chest wall compliance of apneic paralyzed infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.C. 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The basic principles of anesthesia for the neonate

Principios básicos de la anestesia neonatal

Lynn D. Martin

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lynn.martin@seattlechildrens.org

Correspondence to: Seattle Children's Hospital, Anesthesiology & Pain Medicine, 4800 Sand Point Way, N.E. Seattle, WA 98105, USA.

Professor, Departments of Anesthesiology & Pain Medicine and Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">One of the most challenging tasks an anesthesiologist will ever face is the provision of safe and effective anesthesia care of a newborn for surgery&#46; Neonatal anesthesia demands a thorough understanding of the rapidly changing physiology and pathology of the neonate and both the pharmacokinetics and pharmacodynamics of the medications used to provide anesthesia&#46; This knowledge is then incorporated into a well planned anesthetic plan of care&#46; Furthermore&#44; great manual skills and continuous experience with these unique challenges presented by neonates are essential for optimal clinical outcome for these vulnerable patients&#46; This selective review aims to provide a brief summary of theoretical aspects of neonatal anesthesia and present some practical guidelines of care for this patient population&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Physiology of the neonate</span><p id="par0010" class="elsevierStylePara elsevierViewall">The respiratory system has to undergo major physiologic changes in function in seconds when transitioning from the fetal to neonatal environment&#46; To facilitate easier passage through the birth canal&#44; the neonate&#39;s chest wall &#40;rib cage&#41; is flexible with little calcification of the bones&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> In contrast&#44; the newborns lungs are populated with immature alveoli that contain little elastin&#59; thereby making them stiff and difficult to inflate&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a> This combination of flexible chest wall and stiff lung increases the closing volume of the lung and promotes lung collapse&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">3</span></a> Functional residual capacity &#40;FRC&#41; when normalized by body weight is relatively constant from birth through adult life&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a> Spontaneously breathing neonates will dynamically compensate for their immature respiratory mechanics with rapid breathing without expiratory pauses and expiratory air breaking through the larynx&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> To overcome these developmental challenges under passive conditions&#44; pediatric anesthesiologists will routinely recruit alveoli after each brief period of apnea and will use positive end-expiratory pressure &#40;PEEP&#41; when mechanically ventilating a neonate to maintain normal lung volumes&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In spite of equivalent FRCs&#44; neonates will rapidly desaturate with apnea even with effective pre-oxygenation with 100&#37; inspired oxygen&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">6</span></a> This principally is due to a doubling of the rate of oxygen consumption when normalized by body weight in comparison to an adult&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a> To compensate for this high oxygen consumption&#44; neonates also have twice the alveolar ventilation of an adult&#46; Pediatric anesthesiologists routinely take advantage of this during inhalational induction of anesthesia where the rapid wash in of anesthetics leads to a more rapid induction of anesthesia in the young compared to an adult&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Anesthesiologists also must understand that neonates are obligate nose breathers and more easily experience airway obstruction under anesthesia due to the relatively larger tongue and more compliant &#40;collapsible&#41; airway soft tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">9</span></a> Similarly&#44; practitioners in neonates realize the importance of the artificial airway diameter because airway resistance increases by the fourth power as radius decreases&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">During the neonatal period the control of breathing varies significantly from that seen in older children and adults&#46; The increase in ventilation to hypercapnia is less in a neonate compared to an adult&#59; however&#44; it is the response to hypoxemia that differs dramatically&#46; While an adult will have a sustained increase in ventilation when exposed to hypoxia&#44; neonates will demonstrate a brief increase follow by a sustained depression of ventilator drive when exposed to hypoxemia&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a> The immaturity of the respiratory centers in the central nervous system in neonates are likely responsible in part of the pronounced affect anesthetics have in this population&#46; In the only published systematic review of studies evaluating perioperative apnea in this population&#44; general anesthesia increased the risk for postoperative apnea in premature infants less than 60 weeks postconceptional age&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a> This risk is further increased by anemia &#40;Hct<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37;&#41;&#46; Even at 56 postconceptional weeks the risk for postoperative apnea remains approximately 1&#37; &#40;see <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#59; therefore&#44; most textbooks and leaders in the field of pediatric anesthesia recommend that patients under this threshold should be admitted to the hospital for monitoring for 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Following birth the circulatory system undergoes dramatic changes from a fetal parallel system characterized by both ventricles pumping the majority of their output into the system circulation to an extra-uterine series system with the right and left ventricles assuming responsibility for the pulmonary and the systemic circulations respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">14</span></a> In addition&#44; the three embryological shunts &#40;foramen ovale&#44; ductus venosus&#44; and ductus arteriosus&#41; will functionally close in the early postnatal period&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Certain neonatal conditions &#40;i&#46;e&#46;&#44; birth asphyxia&#44; meconium aspiration&#44; septicemia&#44; and congenital diaphragmatic hernia&#41; may prevent this normal transition in circulation from occurring due to persistent elevation in pulmonary vascular resistance and blood pressure&#46; This persistent fetal circulation &#40;PFC&#41;&#44; also known as pulmonary hypertension of the newborn&#44; is characterized by profound hypoxia due to right-to-left shunting through the fetal extra-pulmonary shunts combined with right ventricular strain and circulatory compromise&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">15</span></a> Conventional treatment for this condition includes tracheal intubation and mechanical ventilation to restore normal lung volume without excessive distention&#44; correction of metabolic acidosis&#44; induction of mild alkalosis via hyperventilation&#44; restoration of circulatory volume and inotropic support&#46; Over the last decade the selective pulmonary vasodilatation by means of inhalation of nitric oxide &#40;iNO&#41; has become one the principle treatments for PFC&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">16</span></a> The effective dose range appears to be between 1 and 30 parts per million &#40;ppm&#41;&#46; Abrupt withdrawal of iNO can result in sudden severe rebound of pulmonary hypertension so this therapy needs to weaned slowly once initiated&#46; For the few patients that failed to respond to iNO&#44; the short-term use of extracorporeal life support for several days has been shown to achieve 90&#37; survival in patients with a predicted mortality of 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The neonatal cardiac myocyte contains more non-contractile elements&#44; has a disorganized intracellular arrangement of contractile proteins&#44; and is less elongated than in the adult&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">18</span></a> This leads to a reduction in the force generation capability of the neonatal myocardium&#46; In addition&#44; the sarcoplasmatic reticulum and the T-tubular system are also immature&#44; leading to an increased dependence on extracellular calcium for contraction&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> Developmental changes in the cytoskeleton and the extracellular matrix make the neonatal myocardium less compliant with reduced early and late diastolic filling compared to adults&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> The parasympathetic innervation of the neonatal heart is considered to be more mature compared to the sympathetic system&#44; leading to reduction in heart rate with stimulation&#46; While slow heart rates can reduce cardiac output&#44; the rapid heart rate of the neonate can also limit diastolic filling and stroke volume&#46; After optimizing filling pressures via administration of crystalloid fluid&#44; heart rated between 120 and 180 beats per minute should be the target for neonates&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The central nervous system is incompletely developed at birth&#46; However&#44; pain pathways are integrated with somatic&#44; neuroendocrine&#44; and autonomic changes early in gestation&#46; The hormonal responses to pain and stress may be exaggerated in newborns&#44;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> although the clinical importance of this has not yet been defined&#46; Recent studies suggest the cerebral blood flow responses to oxygen and carbon dioxide as well as the autoregulation of blood flow are present in the newborn<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">22&#44;23</span></a>&#59; 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While the etiology of ROP is likely multifactorial<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a>&#59; oxygen toxicity &#40;perhaps from short-term exposure during brief surgical procedures&#41; contributes to this common complication of prematurity&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Thermoregulation in the neonate differs markedly from the older child and adult&#46; Heat loss is favored by the comparatively larger body surface-to-body weight relationship&#44; the poorly developed insulating subcutaneous tissues&#44; and the inability to use shivering thermogenesis&#46; These limitations are partially compensated for by the unique thermal capacity for non-shivering thermogenesis via brown fat&#46; Both volatile and intravenous anesthetics have been shown to inhibit non-shivering thermogenesis&#44;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">26&#44;27</span></a> potentially contributing to heat loss in the perioperative period&#46; Hypothermia can reduce metabolism of medications&#44; slow emergence from anesthesia and subject neonate to cardiovascular stress&#46; Maintaining a neutral thermal environment &#40;36&#8211;37<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; via warming of the operative suite&#44; use of radiant warmers&#44; force air heating units&#44; and warmed intravenous and irrigation fluids are beneficial&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">28</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The total body water is significantly higher in a preterm infant &#40;&#62;80&#37;&#41;&#44; term neonate &#40;75&#37;&#41; compared to an adult &#40;60&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">29</span></a> Extracellular water represents in excess of 50&#37; of a premature infant&#39;s body weight&#46; Similarly the blood volume is higher in premature infants &#40;90&#8211;100<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#41; compared to term neonates &#40;85<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#41; compared to adults&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">30</span></a> Fluid requirements increase the first several days of life &#40;60&#44; 80&#44; 100&#44; 120<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;day at day 1&#44; 2&#44; 3&#44; and 4 respectively&#41;&#44; and then remain stable the remainder of the neonatal period &#40;approximately 150<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;day&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">31</span></a> Glomerular filtration rate is low in the term infant&#44; then doubles within the first 2 weeks of life&#44; but does not reach adult levels until 2 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a> Glycogen stores develop in the last several weeks of gestation&#46; Therefore&#44; premature infants are susceptible to hypoglycemia if they are deprived from a source of continuous glucose administration&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Developmental pharmacology</span><p id="par0065" class="elsevierStylePara elsevierViewall">The major routes of elimination by which drugs and their metabolites leave the body are the hepatobiliary&#44; renal and respiratory systems&#59; all of which undergo significant maturation after birth&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a> Hepatobiliary clearance via the P450 iso-enzymes is present at term and reaches approximately 85&#37; of adult levels by 44 weeks postmenstrual age&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a> Protein binding to albumen and &#945;<span class="elsevierStyleInf">1</span>-acid glycoprotein is reduced in neonates due to lower concentrations of these proteins in the serum&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> This lower protein binding leads to larger amounts of free &#40;unbound&#41; drug which potentiates the risk for adverse side-effects in neonates &#40;particularly local anesthetics&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> These proteins reach approximate adult concentrations at 6 months of age&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Renal elimination of drugs and their metabolites is determined by glomerular filtration&#44; tubular secretion and tubular reabsorption&#46; Glomerular filtration rate &#40;GFR&#41; is only 10&#37; of the mature value at 25 weeks&#44; 35&#37; at term and 90&#37; of the adult value at 1 year of age&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a> This reduction has significant implications on dosing intervals of drugs principally eliminated via renal clearance &#40;i&#46;e&#46; aminoglycosides&#41;&#46; The same factors that determine anesthetic absorption through the lung &#40;i&#46;e&#46;&#44; alveolar ventilation&#44; functional residual capacity&#44; cardiac output&#44; and blood&#47;gas solubility&#41; also contribute to their elimination kinetics&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The pharmacokinetic variables important to anesthesiologists are known&#46; Clearance &#40;CL&#41; is the most important&#44; as it determines maintenance dosing or drug infusion rates&#46; Volume of distribution &#40;V&#41; has relatively minor importance except in relation to loading doses&#46; These parameters determine the shape of the time-concentration curve&#46; The three major sources of pharmacokinetic variability in neonates have been identified &#40;size&#44; age&#44; and organ function&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> Size is the most common co-variable used to determine dose in children even though normal variation in weight with age is large&#46; Size alone is insufficient to predict CL in neonates and infants&#44; the addition of a maturation effect &#40;age&#41; is required&#46; The cause for the slower drug clearance seen in newborns is not limited to just the normal developmental changes in hepatic and renal organ function&#59; compromised organ function due to critical illness in the newborn may also play a significant role in slowing drug CL in neonates&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">As described earlier&#44; the increase in metabolic rate &#40;i&#46;e&#46; oxygen consumption&#41; leads to an increase in alveolar ventilation and volatile anesthetic uptake in neonates when compared to adults&#46; In addition&#44; an increase percentage of the cardiac output is delivered to vessel rich groups &#40;brain and other vital organs&#41; and the solubility of volatile anesthetics is reduced&#44; both factors contributing to an increase in volatile anesthetic uptake&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> Minimum alveolar concentration &#40;MAC&#41; is commonly used to express anesthetic vapor potency&#46; The MAC typically is reduced in pre-terms and peak at 1&#8211;6 months of age before decreasing to adult values in adolescence &#40;see <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">41</span></a> These agents tend to have more myocardial depression in the newborn compared to adults&#46; Contrary to other volatile anesthetic agents&#44; the MAC of sevoflurane is not reduced in pre-term and newborn infants compared to older children &#40;see <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">42</span></a> Thus&#44; the MAC for sevoflurane in the neonate is approximately 3&#46;2&#37;&#44; which is similar to the MAC values for the 1&#8211;6 month old infants&#46; The safety of these agents is potentially compromised by the ability to deliver multiple MAC concentrations from the vaporizer and to further increase uptake via excessive minute ventilation with mechanical ventilator support&#46; This problem has been significantly reduced by the elimination of halothane production in developed countries&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Intravenous agents play a significant part in the delivery of modern anesthesia care to a neonate&#46; It goes without saying the delivery of any intravenous medications requires patient stable access to the circulatory system&#46; Practitioners of anesthesia for neonates must be able to safely establish peripheral and occasionally central venous access for medication delivery&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Unfortunately data regarding the dose-response relationship of most medications is well known in adults and frequently not well understood in neonates&#46; Thus&#44; it is common practice to extrapolate dose guidelines for neonates from adult data&#46; As described previously&#44; neonates generally have reduced serum protein levels which lead to higher concentrations of free &#40;unbound&#41; drug&#46; In addition&#44; reductions in hepatic metabolism and renal elimination generally increase the interval between doses necessary for therapeutic effect&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Because of their more frequent use&#44; the pharmacology and side-effects of narcotics in neonates are more thoroughly understood&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">43</span></a> Morphine has been associated with more hypotension and the development of a prolonged elimination half-life due to its dependence on renal elimination&#46; It was the release of potent&#44; synthetic narcotic fentanyl in the 1980s with its minimum affect on the cardiovascular system that allowed the first safe and effective treatment of surgical pain in the neonate&#46; Larger doses were able to partially suppress the neonatal surgical stress response and improve outcomes &#40;survival&#41; following neonatal surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a> The wide spread use of propofol for the induction of anesthesia and facilitation in placement of an endotracheal tube for adults has filtered into neonatal practice as well&#46; Propofol has been shown to more commonly cause adverse hemodynamic effects &#40;hypotension&#41; when administered for placement of endotracheal tubes in critically ill neonates&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a> In addition&#44; propofol has delayed redistribution and clearance which lead to prolonged action in neonates&#46; Lastly the long-term continuous infusion of propofol &#40;hours to days&#41; has been associated with the development of metabolic acidosis&#44; organ failure and death in neonates and young children<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a>&#59; therefore&#44; the dose and duration of infusions for sedation should be limited or prohibited to avoid this serious complication&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">It is very common to use neuromuscular blocking agents to facilitate patient relaxation during neonatal surgery&#46; The use of a depolarizing neuromuscular agent &#40;succinylcholine&#41; is now typically reserved for emergency placement of an endotracheal tube&#46; Because of its very large volume of distribution&#44; the recommended dose for intubation in a neonate &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; is twice that recommended in an adult patient &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; In spite of this large dose&#44; the duration of action in not prolonged due to rapid clearance by plasma esterase&#39;s&#46; The similarity of structure between succinylcholine and acetylcholine along with the fully mature parasympathetic nervous system of the neonate commonly results in the development of a relative bradycardia with succinylcholine administration&#46; For this reason&#44; many authorities recommend pre-treatment with an anticholinergic agent &#40;atropine or glycopyrrolate&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The response to non-depolarizing neuromuscular agents in neonates is quite variable and more difficult to predict&#46; All of these agents have an increase in their volume of distribution and decrease in their clearance&#46; In addition&#44; the neonatal myoneural junction appears to demonstrate an increased sensitivity to this class of agents&#46; Pancuronium historically has been popular for this patient population due to its vagal lytic &#40;increase in heart rate&#41; properties&#46; However&#44; this use is significantly limited by the long duration of action in neonates&#46; Vecuronium and rocuronium have fewer vagal lytic properties and are reported to by shorter in duration&#59; however&#44; their duration of action remains longer than 60<span class="elsevierStyleHsp" style=""></span>min in most infants&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Perioperative care of the neonate</span><p id="par0110" class="elsevierStylePara elsevierViewall">The anesthesiologist scheduled to care for a newborn must have a reliable comprehensive system to assess the stability of the patient and use this information in the development of their anesthetic plan of care&#46; Important historical information that can be gathered from the medical record includes gestational age&#44; weight&#44; and birth events &#40;including Apgar scores at 1&#44; 5&#44; and 10<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; The anesthesiologist should consult with their neonatal and surgical colleagues to ascertain the presence of congenital anomalies&#46; Ultrasound examinations are frequently used to non-invasively identify these anomalies&#46; Finally the anesthesiologist must closely inspect the care requirements of the neonate of the last 24<span class="elsevierStyleHsp" style=""></span>h to ascertain the likely starting point for support in the operative suite&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Physical examination of the infants is required to assess the stability and patency of the neonate&#39;s airway and gas exchange&#46; If mechanical ventilator support is needed&#44; close inspections of the placement of the airway on chest X-ray&#44; current ventilator settings and the result of the most recent blood gas are needed&#46; The anesthesia provider must perform a careful assessment for signs or symptoms of cardiovascular abnormalities and stability&#46; Hydration &#40;volume&#41; status should be assessed via vital signs &#40;heart rate&#44; blood pressure&#41;&#44; capillary refill and urine output&#46; Any evidence of dehydration should be fully corrected before the induction of anesthesia except in true life-threatening emergent situations&#46; Lastly the anesthesiologist must assess the safety of the current vascular access and associated infusions and determine if the access will be sufficient for the perioperative care&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The last task in the pre-operative assessment is the review of available laboratory studies&#46; Typically complete blood counts are available to assess the risk for anemia associated with significant blood loss and platelet counts to look for evidence of disseminated intravascular coagulopathy&#46; Low platelets counts &#40;less than 100&#44;000&#41; likely indicate intravascular consumption and should prompt further work-up for coagulopathy&#46; Serum electrolytes will assist with acid-base assessment and possible risk for hyperkalemia with rapid blood transfusion&#46; In addition&#44; the serum glucose level during current therapy will help the anesthesia provider lessen the risk for intraoperative hypoglycemia&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Common anesthesia practices in neonates include the routine use of physiologic monitors &#40;ECG&#44; non-invasive blood pressure&#44; temperature&#44; pulse oximetry and end-tidal carbon dioxide&#41;&#46; Care must be taken to preserve normal temperature during transport to and from the operative suites and well has heating the operative environment&#46; Continuous glucose delivery throughout the duration of the procedure is required with potential to monitor intermittent serum glucose levels&#46; General anesthesia with placement of endotracheal tubes is generally required for the safe care of the neonate&#46; Anesthesia typically consists of balanced combination of volatile agent supplemented with narcotic &#40;typically fentanyl&#41; for hemodynamic stability&#46; This fentanyl-based anesthetic frequently leads to delayed awakening and the need for post-operative mechanical ventilation&#46; Lung recruitment maneuvers are applied after each period of apnea at ambient pressure to restore normal lung volumes&#46; Mechanical ventilator support routinely includes delivery of PEEP to maintain normal lung volumes with sufficient intermittent positive pressure to maintain normal alveolar ventilation and carbon dioxide clearance&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">With these modern advances in anesthesia practice multiple studies over the last 3 decades have shown that the risk of anesthesia-related mortality has decreased significantly over time for both adult and pediatric patients<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">47&#8211;50</span></a>&#59; however&#44; neonates continue to have the highest risk for perioperative cardiac arrest of any age group&#46;<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">51&#44;52</span></a> In addition&#44; the risk of mortality following cardiac arrest is much higher in the vulnerable group of patients&#46; It is primarily this evidence of increased anesthesia-related risk that led first to formal &#40;certified&#41; advanced pediatric anesthesia fellowship training programs in the United States and more recently the development of board certification in pediatric anesthesiology by the American Board of Anesthesiology&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Controversies in neonatal anesthesia</span><p id="par0135" class="elsevierStylePara elsevierViewall">In spite of the dramatic improvements in care for the neonate in the perioperative environment of the last decade there remains many issues without clear evidence for best practice&#46; What is clear is that there remain many opportunities for clinical investigators to closely evaluate current practice options in efforts to further reduce the risk of anesthesia for the vulnerable neonate&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Over the last 15 years many investigators have produced evidence in the laboratory setting that exposure to many different anesthetic agents can potentially induce injury to the developing nervous system with long lasting effects&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a> These theoretical concerns regarding anesthesia-related neurotoxicity in infants along with dramatic technical improvements in portable ultrasound has led to a resurgence in the interest and application of regional anesthesia in the neonate&#46; The potential advantages and disadvantages of regional anesthesia as compared to systemic analgesia in a neonate have been debated &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> While there is no clear consensus on the preferred option&#44; it is clear that many anesthesiologists caring for neonates increasingly value the benefits of regional anesthesia in neonates based on the increasing use of this care option&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">A comprehensive review summarizes the growing body of evidence that the use of high concentrations of oxygen during neonatal resuscitation is associated with oxidative stress&#44; adverse effects on breathing physiology and cerebral circulation&#44; and potential tissue damage from oxygen free radicals&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">56</span></a> This same evidence has been used to suggestion that short exposures to excessive oxygen in the perioperative period could also lead to adverse outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a> Indeed&#44; some investigators now recommend avoidance of excess oxygen for even brief periods in the perioperative setting with an upper limit of oxygen saturation of 95&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">The author did not receive sponsorship to undertake this article&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Controversies in neonatal anesthesia"
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            1 => "Anesthesia&#44; general"
            2 => "Pharmacology"
            3 => "Anesthesia&#44; conduction Pharmacokinetics"
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            0 => "Reci&#233;n&#44; nacido"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There are significant developmental differences in physiology and pharmacology in neonates that make the conduct of a safe anesthetic much more challenging in a neonate&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Complete a focused review of the current knowledge of the physiological and pharmacologic differences seen in newborns that impact the safe administration of anesthesia&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A selective review of literature in developmental changes in physiology and pharmacology was completed&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This knowledge acquired in the review was used to establish common principles for the safe administration of anesthesia to newborn patients&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In spite of the persistence of large gaps in our knowledge in this physiology and pharmacology&#44; common modern anesthetic management principles for neonatal surgery have significantly improved clinical outcomes&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Existen diferencias significativas de desarrollo en la fisiolog&#237;a y la farmacolog&#237;a de los neonatos que hacen que sea mucho m&#225;s dif&#237;cil llevar a cabo una anestesia segura&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Completar una revisi&#243;n focalizada del conocimiento actual sobre las diferencias fisiol&#243;gicas y farmacol&#243;gicas observadas en reci&#233;n nacidos que tienen un impacto en la administraci&#243;n segura de la anestesia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo una revisi&#243;n selectiva de la literatura sobre cambios en el desarrollo fisiol&#243;gico y farmacol&#243;gico&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El conocimiento adquirido en esta revisi&#243;n fue usado para establecer principios comunes para la administraci&#243;n segura de la anestesia en pacientes reci&#233;n nacidos&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A pesar de la persistencia de grandes lagunas en nuestro conocimiento en esta fisiolog&#237;a y la farmacolog&#237;a&#44; los principios modernos y comunes del manejo de la anestesia en cirug&#237;a neonatal han mejorado significativamente los resultados cl&#237;nicos&#46;</p></span>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Technique&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="middle">Systemic analgesia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Post-op ICU care required<br>&#8226; Surgical stress response ablated not blocked<br>&#8226; Tolerance and withdrawal<br>&#8226; Opioid induced hyperalgesia&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 22562087
Original language: English

DOI:10.1016/j.rcae.2016.11.010

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	39	6	45
2024 October	266	24	290
2024 September	309	50	359
2024 August	291	46	337
2024 July	274	39	313
2024 June	197	31	228
2024 May	200	21	221
2024 April	210	22	232
2024 March	267	53	320
2024 February	411	51	462
2024 January	290	39	329
2023 December	230	29	259
2023 November	232	41	273
2023 October	224	33	257
2023 September	171	20	191
2023 August	155	29	184
2023 July	150	23	173
2023 June	131	27	158
2023 May	157	21	178
2023 April	140	26	166
2023 March	126	30	156
2023 February	84	23	107
2023 January	101	41	142
2022 December	83	16	99
2022 November	81	16	97
2022 October	82	33	115
2022 September	97	39	136
2022 August	102	20	122
2022 July	98	33	131
2022 June	73	22	95
2022 May	82	35	117
2022 April	74	26	100
2022 March	61	23	84
2022 February	74	12	86
2022 January	109	14	123
2021 December	31	14	45
2021 November	35	11	46
2021 October	63	21	84
2021 September	89	17	106
2021 August	247	14	261
2021 July	66	11	77
2021 June	42	10	52
2021 May	72	16	88
2021 April	122	17	139
2021 March	35	6	41
2021 February	13	6	19
2021 January	14	10	24
2020 December	22	4	26
2020 November	18	5	23
2020 October	12	6	18
2020 September	21	7	28
2020 August	39	8	47
2020 July	15	10	25
2020 June	15	8	23
2020 May	13	7	20
2020 April	17	4	21
2020 March	10	3	13
2020 February	13	2	15
2020 January	13	3	16
2019 December	8	6	14
2019 November	5	1	6
2019 October	5	5	10
2019 September	2	4	6
2019 July	2	3	5
2019 June	1	1	2
2019 May	2	12	14
2018 September	1	0	1
2018 June	8	1	9
2018 May	44	7	51
2018 April	69	10	79
2018 March	55	13	68
2018 February	34	12	46
2018 January	51	10	61
2017 December	34	15	49
2017 November	29	8	37
2017 October	35	9	44
2017 September	44	18	62
2017 August	35	9	44
2017 July	31	9	40
2017 June	52	12	64
2017 May	56	12	68
2017 April	72	21	93
2017 March	76	11	87
2017 February	36	9	45
2017 January	54	16	70
2016 December	9	14	23

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