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1 제89차종합학술대회프로그램및초록 소아마취의최신지견 1) Anesthesia for neonate and ex-premature infants 141 인제의대방시라 2) 소아를위한심폐소생술 145 서울의대김진태

2 세부전공학회발표 Anesthesia for neonate and ex-premature infants 인제대학교의과대학해운대백병원마취통증의학과 방시라 산과학과신생아학의발전은신생아생존, 특히 preterm neonate의생존증가에많은기여를하였다. 많은수의생존미숙아들은생애초기에크고작은수술이필요한경우가많아이에마취과의사들은다양한신생아수술을경험하게되어신생아생리와미숙아들의합병증등에대한이해와주의가필요하게되었다. Neonatal physiology Pulmonary A. Transition phase and persistent pulmonary hypertension of the neonate At birth - 대략 35 ml의양수가폐에서배출되며폐확장이이루어지며호흡이시작됨. 초기에폐는매우 stiff (compliance very low): first breath require negative forces > 70 cm H 2O. Pulmonary vascular resistance (PVR) 이빠르게감소하며 ductus arteriosus가출생후 1 15 hours 사이에닫힘. PVR 정상화는점진적인과정이며 3 4일정도가소요. ductus arteriosus와 foramen ovale의해부학적폐쇄는몇달이소요. 출생후 normal tidal ventilation은 10분내에 normal FRC 는 20분내에도달하게됨. Persistent pulmonary hypertension of the neonate (PPHN): hypoxia, hypercarbia, or acidosis can cause a sudden increase in PVR and a return to a fetal circulatory pattern. PPHN is an acute, life-threatening condition, as shunt fraction increases to 70% to 80%, and profound cyanosis results. Many factors during anesthesia can affect this transitional state. Anesthetic agents can markedly diminish systemic vascular resistance (SVR), resulting in right-to-left shunt. Hypoxia or hypercarbia and acidosis from inadequate ventilation can increase PVR, with similar effects on shunt. Summary of Pulmonary differences with adults 1. Higher O 2 Consumption 2. Higher closing volume 3. Higher MV:FRC 4. Compliant ribs and less Type 1 muscle in the diaphragm B. Airway anatomy Head: much larger compared with body size than that of older children Short neck, larger tongue Higher and anterior larynx: cords located at C4 in the infant compared with C5 or C6 in an adult. Epiglottis: soft and folded At the cricoids ring, 1 mm of edema results in a 60% reduction in the cross-sectional area of the airway, causing increased airway resistance and increased work of breathing. Laryngomalacia is also common in premature infants and can result in obstruction. Cardiovascular Reduced ventricular compliance and less ability to increase contractility relatively dependent on heart rate to increase cardiac output. According to Barash, the neonatal heart is only capable of increasing CO by about 30% (the adult, by contrast, can increase CO by 300%). Bradycardia: particularly dangerous in the neonate. Hypoxemia, which can precipitate bradycardia, should be vigorously avoided. Diminished baroreceptor response to hypotension, and have difficulty mounting a tachycardiac response. Renal Nephronogenesis: complete at 34 weeks gestation Term neonate: as many nephrons as an adult, although they are immature, with a glomerular filtration rate (GFR) approximately 30% of the adult s GFR. 141

3 With increasing cardiac output and decreasing renal vascular resistance, renal blood flow and GFR increase rapidly over the first few weeks of life, and reach adult levels by about 1 year of life. The diminished function over the first year is well balanced to the infant s needs because much of the neonate s solute load is incorporated into body growth, and excretory load is smaller. Temperature regulation Given a large surface area, small body volume, and minimal insulation, neonates are extremely prone to heat loss. Any degree of cold stress is detrimental and increases metabolic demands in the neonate. Preterm mortality Intensive medical care should be initiated at 26 weeks of gestation, aggressive resuscitation: not widely recommended for infants born before 23 weeks gestation grey zone : gestational age - play a role in influencing outcome. Infants born at weeks gestation : in addition to gestational age, four factors as important in the outcome of extreme prematurity. Higher birth weight, Female sex, Use of antenatal steroids, Singleton birth B. long-term morbidity neurodevelopmental sequelae [cerebral palsy (CP), cognitive delay, blindness, deafness, chronic lung disease, feeding difficulties, subglottic stenosis following prolonged endotracheal intubation. Brain development: particularly vulnerable during the second and third trimesters. Infants born at weeks gestation : high risk for hypoxic/ischemic brain injury intraventricular hemorrhage, frequently result in subsequent neurodevelopmental sequelae. Anesthetics and neurodevelopment The current controversy can perhaps be summarized in several points, as follows: A. Exposure to anesthetic agents, at clinically appropriate doses, at the peak of synaptogenesis can cause widespread neuroapoptosis in several species of animals, including primates. A clinically appropriate dose is the minimum necessary to induce anesthesia in the species. In some species, and with some agents, this dose also results in significant mortality, increasing the difficulty of interpreting the significance. Morbidity and mortality: remains high (one study estimating a mortality rate of 89% for infants weighing g) Almost all the survivors in this extremely low birth weight group suffered from considerable morbidity Preterm morbidity A. short-term morbidity respiratory distress syndrome, bronchopulmonary dysplasia, persistent patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis. B. Synaptogenesis in rats occurs postnatally over the first 2 weeks of life. An analogous period in humans would range from the third trimester of pregnancy through the first 3 years of life. Whether the child might be susceptible to anesthetic toxicity during this entire period is unknown. Other studies looking specifically at neurodevelopment suggest that a postnatal 7-day-old rat more closely corresponds to the human fetus between 17 and 22 weeks of gestation. Elucidation of the critical period is of prime importance in anesthetic management. C. The animal studies of apoptosis involve anesthesia without surgery. There is some indication that the presence of surgical stress may alter the response to anesthetics. D. Abnormal behaviors and learning have also been shown in animal studies after anesthetic exposure. 142

4 방시라 :Anesthesia for neonate and ex-premature infants E. Initial extremely limited studies of children after anesthetic exposure as infants are suggestive, but difficult to interpret. It is impossible to separate the effects of anesthesia from the effects of surgery; the fact that in Wilder and colleagues study an effect was seen only with multiple anesthetics might be related to dose, but could be related to other confounding effects, such as more severe illness. F. The effects under examination are subtle, and difficult to categorize and measure. The effects of fetal ethanol exposure were first elucidated because of marked craniofacial abnormalities, rather than more subtle developmental problems. G. As has been proposed, the careful multicenter FDA initiative may be needed to determine the clinical impact of the problem. 결론적으로신생아마취에대해신경학적손상을최소화하기위한방안을고려해보면, A. The benefits versus the risk of delay in surgical procedures, particularly if performed in premature infants, should be carefully considered. Similar concerns could be raised in older children if the procedure is elective. B. It seems reasonable to perform a simple anesthetic. There is virtually no extensive experience with many anesthetic agents in neonates. This lack of extensive experience is not unusual in neonates or pediatrics in general, but may be of increased importance given the small therapeutic margin of most anesthetics. There would seem to be little utility in the combination of agents, such as midazolam, propofol, and isoflurane, when a single agent could be as easily used. Whether the use of multiple agents could decrease the required dose of each, and whether this would be beneficial is impossible to answer. One preference is to use a predominant narcotic technique in premature infants who may be most at risk, when appropriate. Fentanyl has little, if any, activity as either an NMDA antagonist or GABA agonist. It is well tolerated hemodynamically, and effective at preventing the surgical stress reaction. This particular technique may prevent extubation, but in this generally ill population, this is not usually a consideration. The possibility of recall with a pure narcotic technique can be raised, but with a dose adequate to prevent the stress response, this may not be important. Summary of recommendations for the anesthetic care of the expremature patient ㆍDelay nonessential surgery until apnea risk is reduced: Post-pone surgery until PCA _ 60 weeks ㆍWhen surgery cannot be delayed, plan for overnight admission and monitoring (at least 18 hours (?) in those still at risk for apnea. ㆍOptimize medical conditions, including reactive airway disease and gastroesophageal reflux, prior to surgery. ㆍRecognize limitations of all expremies, even those that are not obvious (pulmonary function, developmental): Assessment of comorbidity or anaemia. ㆍConsult with the patient s physicians regarding ongoing medical problems. Fig. 1. Post-operative monitoring of the former preterm infant with a post-conceptual age (PCA) < 60 weeks. Acta Anaesthesiol Scand. 2006; 50(7):

5 ㆍ Choose appropriate anaesthesia technique ㆍ Plan for intraoperative bronchospasm. ㆍConsider postoperative intensive care unit admission prior to surgery to ensure availability, should it become necessary. ㆍDecide level of post-operative monitoring (see Fig. 1) References 1. Martin RJ, Fanaroff AA, Michele C. WalshFanaroff and Martin s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, 9th ed. pp Laura S. Seminars in Anesthesia, Perioperative Medicine and Pain (2006) 25, Walther-Larsen S, Rasmussen LS. The former preterm infant and risk of post-operative apnoea: recommendations for management. Acta Anaesthesiol Scand. 2006; 50(7): Davis P, Cladis F, Motoyama E. Smith s Anesthesia for infancts and children, 8th ed Wilder RT, et al: Early exposure to anesthesia and learning disabilities in a population-based birth cohort, Anesthesiology 110: 796,

6 세부전공학회발표 소아를위한심폐소생술 서울대학교의과대학마취통증의학교실 김진태 성공적인심폐소생술을위해가장효과적인방법은시뮬레인션을통한적절한교육이라고생각한다. 심폐소생술에는 basic life support (BLS), ACLS (advanced cardiovascular life support), PALS (pediatric advanced life support) 가있고, 미국심장협회 (American heart association) 에서는이를기초로교육을하고있다. 대한심폐소생협회에서도이를기초하여 provider와 instructor 배출에힘쓰고있고, PALS provider, instructor 과정도이에포함된다. PALS provider 과정은 BLS test, skill station (management of respiratory emergencies, rhythm disturbance/electrical therapy, vascular access), core case simulations and discussions로구성되어있다. Table 1은 BLS 정리표이다. 소아의경우적어도흉부앞뒤직경의 1/3 깊이로적어도 100회 / 분으로가슴압박을해야한다. 소아에서의료인이 2명일경우 15:2로압박과호흡을시행하고그이외의경우는모두 30:2로시행한다. 소아가반응을하지않을경우의료인의경우맥박을촉진할수있는데 (brachial artery in infant, carotid or femoral artery in a child), 10초이상넘지말아야한다. 맥박이 60회이상이고호흡계문제일경우분당 12 20회의호흡을시행한다. Fig. 1은소아에서 BLS algorithm이다. 이때주의할점은압박후완전히가슴이펴지도록해야하는것, 가슴압박이중단되는시간을최소화해야하는것, 그리고과환기를피하는것이다. 소아의경우는 hand-only CPR이 mouth-tomouth rescue breathing과가습압박을동반하는경우와비교했을때덜효과적이었다. 이는소아에서 asphyxia로인한심정지가많기때문이다. 소아심폐소생술을잘하기위해서는다음과같은체계적인평가가필요하다. Systematic approach to the seriously ill child 1.1 Initial impression 1) Consciousness - level of consciousness (unresponsive, irritable, alert) 2) Breathing - increased work of breathing, absent or decreased respiratory effort 3) color - abnormal skin color (cyanosis, pallor, mottling) 1.2 Evaluate 1) Primary assessment: A rapid ABCDE approach (airway, breathing, circulation, disability, exposure) to evaluate respiratory, cardiac, and neurologic function, this step Table 1. BLS 145

7 Fig. 1. Pediatric BLS algorithm. 146

8 김진태 : 소아를위한심폐소생술 Fig. 2. PALS pulseless arrest algorithm. 147

Fig. 3. PALS bradycardiac algorith. includes assessment of V/S and pulse oximeter 2)Secondary assessment: a focused medical history and focused P/E 3) Diagnostic test: 1.

9 Fig. 3. PALS bradycardiac algorith. includes assessment of V/S and pulse oximeter 2)Secondary assessment: a focused medical history and focused P/E 3) Diagnostic test: 1.3 indentify 1) Respiratory ㆍupper airway obstruction ㆍlower airway obstruction ㆍlung tissue disease ㆍdisordered control of breathing severity 에따라 respiratory distress 혹은 failure 2) Circulatory ㆍhypovolemic shock ㆍdistributive shock ㆍcardiogenic shock ㆍobstructive shock severity에따라 compensated shock 혹은 hypotensive shock 148

10 김진태 : 소아를위한심폐소생술 Fig. 4. PALS tachycardia algorithm. 성공적인심폐소생술을위해서는효과적인 resuscitation team dynamics가요구되는데다음과같다. Eight elements of effective team dynamics 1) Closed-loop communication 2) Clear messages 3) Clear roles and responsibilities 4) Knowing one s limitations 5) Knowledge sharing 6) Constructive intervention 7) Reevaluation and summarizing 8) Mutual respect PALS pulseless arrest algorithm, PALS bradycardia algorithm, PALS tachycardia algorithm, PALS 약제를 Fig. 2, 3, 4 와 Table 2에정리하였다. 성공적인소아심폐소생술을하기위해서는상기표와 algorithm을숙지하고평상시교육과훈련이필요하다. 또한수술장내에서심폐소생술은일반상황과다른면이있으므로이에대한이해가필요하겠다. 149

11 Table 2. 소아심폐소생술시약제 참고문헌 1. Berg MD, Schexnayder SM, Chameides L, Terry M, Donoghue A, Hickey RW, Berg RA, Sutton RM, Hazinski MF. Part 13: pediatric basic life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3): S Kleinman ME, Chameides L, Schexnayder SM, Samson RA, Hazinski MF, Atkins DL, Berg MD, de Caen AR, Fink EL, Freid EB, Hickey RW, Marino BS, Nadkarni VM, Proctor LT, Qureshi FA, Sartorelli K, Topjian A, van der Jagt EW, Zaritsky AL. Part 14: pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3): S

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract