LBM 3 Farmakologi tentang Gangguan Hemodinamik Akut 7 Nop 2024 PDF

Modul : Konsep Patomekanisme 1 & Konsep Dasar Penatalaksanaan Masalah Kesehatan Pokok Bahasan : “TATALAKSANA PADA GANGGUAN HEMODINAMIK AKUT” dr. Kinanti Narulita Dewi, M.Si, Sp.An-TI FAKULTAS KEDOKTERAN UNIVERSITAS ISLAM SULTAN AGUNG Capaian Pembelajaran 1...

Modul : Konsep Patomekanisme 1 & Konsep Dasar Penatalaksanaan Masalah Kesehatan Pokok Bahasan : “TATALAKSANA PADA GANGGUAN HEMODINAMIK AKUT” dr. Kinanti Narulita Dewi, M.Si, Sp.An-TI FAKULTAS KEDOKTERAN UNIVERSITAS ISLAM SULTAN AGUNG Capaian Pembelajaran 1. Menjelaskan definisi dan komponen / parameter hemodinamik 2. Menjelaskan fisiologi sistem saraf simpatis sebagai target / titik tangkap kerja obat hemodinamik 3. Menjelaskan penanganan farmakologi pada komplikasi akut gangguan hemodinamik 4. Menjelaskan penanganan non farmakologi pada komplikasi akut gangguan hemodinamik Hemodynamics, a word derived from the Greek meaning blood power. peripheral vascular cardiac function physiology and the physical laws → control blood flow  HEMODYNAMIC Hemodynamics ultimately begins with the heart which supplies the driving force for all blood flow in the body. Cardiac output propels blood through the arteries and veins as a function of ventricular contraction. Ventricular motion results from the shortening of cardiac myocytes concentrically. This squeezing motion is translated into the cardiac output. HEMODYNAMIC PARAMETERS The primary hemodynamic parameters include : heart rate (HR) and blood pressure (BP) The advanced hemodynamic parameters include : stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR)  PHYSIOLOGY Most causes of circulatory shock are characterized by low CO. CO is the product of stroke volume (SV) and heart rate (HR) and is a major determinant of MAP and the delivery of oxygen (DO2). MAP = CO × DO2 = CaO2 × CO = SV × HR SVR CO (in dL/min) CaO2 (oxygen content) = (Hb x 1,34 x SaO2) + (PaO2 x 0,0031)  PHYSIOLOGY 1. Optimizing SV and HR will improve CO, MAP, and DO2 2. SV and overall myocardial performance is determined by five other factors in addition to inotropy (contractility) that requires consideration: a. HR and rhythm (atrioventricular synchrony) b. Myocardial blood flow c. Preload d. Afterload e. Diastolic function  CIRCULATORY SHOCK Decreased venous return Inadequate cardiac output Myocardial depression → inadequate tissue flow Inadequate tissue blood flow Generalized deterioration of cellular Inadequate oxygen delivery to and organ function. cells  CIRCULATORY SHOCK Inadequate oxygen delivery to the tissues, typically in the setting of hypotension. HYPOTENSION Systolic arterial blood pressure 60–65 determinant of product of CO and SVR, mmHg to both MAP and therefore transiently maintain DO2, further increasing the SVR with vital resuscitation vasopressors to achieve an cerebral and focused on MAP >60–65 mmHg is coronary augmenting CO is acceptable while secondary perfusion. preferred. resuscitation is ongoing.  SECONDARY RESUSCITATION First ensuring adequate volume status (correcting hypovolemia) Subsequently administering other vasoactive agents if necessary Monitoring the resuscitation endpoints proved in goal-directed therapy (GDT) OVERVIEW OF VASOACTIVE AGENTS PHYSIOLOGY OF SYMPATHETIC SYSTEM SYMPATHETIC DRUGS Neurochemical Transmission Synthesis, Storage, and Termination of the Action of Norepinephrine  EPINEPHRINE VS NOREPINEPHRINE Adrenergic neurons release norepinephrine as the primary neurotransmitter. These neurons are found in the central nervous system (CNS) and in the sympathetic nervous system, where they serve as links between ganglia and the effector organs. Adrenergic drugs act on adrenergic receptors, located either presynaptically on the neuron or postsynaptically on the effector organ. Primary tissue locations of α-adrenoceptors and β- adrenoceptors. Effects of catecholamines on vascular smooth muscle Cardiac effects of catecholamines ADRENOCEPTOR ACTIONS  VASOACTIVE AGENTS No agent is superior. In the general population of critically ill patients : agent selection is based on clinical experience and preference. Meta-analysis of 23 RCT : comparing commonly used vasoactive agents (dopamine, norepinephrine, epinephrine, phenylephrine, vasopressin, and terlipressin), either alone or in combination with dobutamine or dopexamine → showed no difference in mortality.  VASOPRESSORS Primarily used : CPR & treatment of circulatory shock. Main clinical benefit : raising the MAP → restore rapidly organ perfusion. Some vasopressors have inotropic properties as well, and the predominant effect is usually dose-dependent. In CPR, vasopressors cause profound systemic vasoconstriction that preferentially increases coronary perfusion pressure in an attempt to restore myocardial blood flow, oxygen delivery, and the return of spontaneous circulation. In circulatory shock with refractory hypotension → enhanced clinical recovery by restoring & maintaining normal organ perfusion pressure. Distributive shock : vasopressors correct the underlying deficit in SVR → restoring organ perfusion pressure.  VASOPRESSORS Vasopressor actions Arterial & venous vascular smooth muscle are mediated via → increase in systemic & pulmonary alpha-1 receptors vascular resistance & venous return.  VASOPRESSORS (1) Pure vasoconstrictors Vasopressor (2) Inoconstrictors classified by their (vasoconstrictors clinical effect : with inotropic properties) ADRENERGIC AGENTS = SYMPATHOMIMETIC Mimic sympathetic nervous system Catecholamines : contain a Noncatecholamines : catechol group & are rapidly longer durations of metabolized by action (5–15 min), not catechol-O-methyltransferase & metabolized by monoamine oxidase, short catechol-O-methyl- duration of action (1–2 min) → transferase ideal for titration  INOTROPES Inotropes differ from Inotropy (contractility) Inotrope = drug that vasopressors, which refers to : FORCE & produces positive primarily produce VELOCITY of cardiac inotropy (increased vasoconstriction and a muscle contraction contractility). subsequent rise in MAP. Some inotropes have vasopressor properties (the predominant effect is usually dose-dependent).  INOTROPES DO2 = CaO2 × CO (in dL/min) In cardiogenic & obstructive shock : Increase characterized by SV Restore low CO → adequate increasing DO2 to vital contractility with Increase organs inotropes CO In cardiogenic shock, the failing ventricle is very sensitive to afterload, so inotropes that produce systemic vasodilation (inodilators) should be first-line agents as long as systemic hypotension does not occur.  INOTROPES All inotropes increase CO by increasing the force of contraction of cardiac muscle. Some inotropes directly increase HR, some indirectly decrease HR, while others have no effect. Some inotropes increase venous tone (venoconstriction) and arterial tone (afterload) while others decrease these through vasodilation, and some improve diastolic function.  INOTROPES Inotropes are broadly classified below by their clinical effects as : (1) (2) Inodilators agents Inoconstrictors agents that produce inotropy that produce inotropy and vasodilation and vasoconstriction COMMON VASOACTIVE AGENTS  PURE VASOCONSTRICTORS Stimulates only α receptors → arterial & Phenylephrine → correct hypotension, improve venous vasoconstriction → increase SVR, venous return, & decrease the HR in patients MAP, venous return, & with various cardiac conditions (treatment of baroreceptor-mediated reflex bradycardia. hypotension caused by tachyarrhythmias) PHENYLEPHRINE Increase in SVR (afterload) & reflex Phenylephrine is considered a first-line bradycardia → decrease CO, so phenylephrine agent in hyperdynamic (normal CO) septic should only be used with caution in patients shock as it restores SVR and organ with preexisting cardiac dysfunction (low CO). perfusion pressure.  PURE VASOCONSTRICTORS VASOPRESSIN Vasopressin (antidiuretic hormone) levels are increased in response to early shock to maintain organ perfusion, but levels fall dramatically as shock progresses. Vasopressin does not stimulate adrenergic receptors and is not associated with their adverse effects. Vasopressin improves the vascular response to adrenergic agents → reduction in their dosing → reduce adverse effects seen with adrenergic agents (adrenergic sparing effect). Compared to adrenergic agents such as norepinephrine, vasopressin produces selective systemic vasoconstriction, with minimal effect on the pulmonary vasculature.  PURE VASOCONSTRICTORS VASOPRESSIN Coupled to phospholipase C and increased intracellular Ca2+ concentration → vascular smooth muscle contraction Vasopressin through V1 receptor Methylene blue scavenges nitric oxide and inhibits NO synthesis → reversing vasodilatory effects on the endothelium & vascular smooth muscle.  inoconstrictors Epinephrine In low doses : increases CO because beta-1 inotropic and chronotropic effects predominate, while the minimal alpha-1 vasoconstriction is offset by beta-2 vasodilation, resulting in increased CO with decreased SVR and variable effects on the MAP. At higher doses : alpha-1 vasoconstrictive effects predominate, producing increased SVR, MAP, and CO. Thus, in the acutely failing ventricle (e.g., low CO syndrome after cardiac surgery), epinephrine maintains coronary perfusion pressure and CO. It is a second-line agent in septic or refractory circulatory shock and is the drug of choice in anaphylaxis because of its efficacy to maintain MAP, partly due to its superior recruitment of splanchnic reserve (about 800 mL), compared to other vasoactive agents, which helps to restore venous return and CO.  inoconstrictors Norepinephrine Norepinephrine has potent alpha-1, modest beta-1, and minimal beta-2 activity. Thus, norepinephrine produces powerful vasoconstriction and a reliable increase in SVR and MAP, but a less pronounced increase in HR and CO, compared to epinephrine.  inodilators Dobutamine Primarily stimulates beta-1 and beta-2 receptors resulting in increased chronotropy, inotropy, and systemic and pulmonary vasodilation.  NON PHARMACOLOGY MANAGEMENT OF CIRCULATORY SHOCK SECONDARY RESUSCITATION  SECONDARY RESUSCITATION First ensuring adequate volume status (correcting hypovolemia) Subsequently administering other vasoactive agents if necessary Monitoring the resuscitation endpoints proved in goal-directed therapy (GDT) VOLUME OF BODY FLUIDS EXAMPLE Total body fluid accounts for about 60% of the lean body weight in males (600 mL/kg) and 50% of the lean body weight in females (500 mL/kg). Total body fluid : Adult male 75 kg will thus have 0.6 × 75 = 45 liters Adult female 60 kg will have 0.5 × 60 = 30 liters INTRAVENOUS FLUIDS FOR RESUSCITATION The clinical determination of the intravascular volume can be extremely difficult in critically ill and injured patients. Fluid loading is considered the first step in the resuscitation of hemodynamically unstable patients. Under-resuscitation → inadequate organ perfusion. Over-resuscitation → increases the morbidity and mortality of critically ill patients. FLUID CHALLANGES There is no standard protocol for fluid challenges. The principal concern is to ensure that the fluid challenge will increase ventricular preload (i.e., end-diastolic volume). The fluid challenge favored in clinical studies is 500 mL of isotonic saline infused over 10 – 15 minutes. Fluid responsiveness is evaluated by the response of the cardiac output (which can be measured noninvasively using Doppler ultrasound techniques). An increase in cardiac output of at least 12 –15% after a fluid challenge is used as evidence of fluid responsiveness.  EXTRACELLULAR FLUID 40% of the total body fluid, composed of extravascular (interstitial) & intravascular (plasma) fluid compartments. Comparison of interstitial fluid and plasma volumes = plasma volume is about 25% of interstitial fluid volume. Since sodium equilibrates throughout the extracellular fluid, 75% of infused saline solutions will distribute in the interstitial fluid, and 25% will distribute in the plasma. COLLOID & CRYSTALLOID RESUSCITATION Crystalloid fluids are sodium-rich electrolyte solutions that distribute throughout the extracellular space, and these fluids expand the extracellular volume (small molecules that can diffuse freely from intravascular to interstitial fluid compartments) Colloid fluids are sodium-rich electrolyte solutions that contain large molecules that do not pass readily out of the bloodstream. The retained molecules hold water in the intravascular compartment; as a result, colloid fluids primarily expand the intravascular (plasma) volume.  COLLOID & CRYSTALLOID RESUSCITATION The principal component of crystalloid fluids is sodium chloride. Sodium is the principal determinant of extracellular volume, and is distributed uniformly in the extracellular fluid. The sodium in crystalloid fluids also distributes uniformly in the extracellular fluid. Because the plasma volume is only 25% of the interstitial fluid volume, only 25% of an infused crystalloid fluid will expand the plasma volume, while 75% of the infused volume will expand the interstitial fluid. COLLOID & CRYSTALLOID RESUSCITATION Crystalloids passed readily through the membrane, whereas colloids did not. Intravenous fluids are similarly classified based on their ability to pass through capillary walls that separate the intravascular and interstitial fluid compartments. Colloid fluids have large molecules that do not readily escape from the bloodstream, and these retained molecules hold water in the intravascular compartment. As a result, as much as 100% of the infused volume of colloid fluids will remain in the vascular space and add to the plasma volume at least in the first few hours after infusion. Abbreviations: D5LR, 5% dextrose in lactated Ringer; D5NS, 5% dextrose in normalsaline; D5 1/2NS, 5% dextrose in 1/2 normalsaline; LR, lactated Ringer; NS, normalsaline.  ISOTONIC SALINE Variety of names = normal saline, physiologic saline, isotonic saline, but none of which is appropriate. This solution is neither chemically nor physiologically normal. Normal Saline is Not Normal Influence of acute hemorrhage and fluid resuscitation on blood volume and hematocrit The immediate goal of resuscitation for acute blood loss is to support oxygen delivery (DO2) to vital organs. The determinants of DO2 are identified in the following equation : Acute blood loss affects two components of this equation : CO and hemoglobin concentration in blood. Therefore, the immediate goals of resuscitation are to promote cardiac output and maintain an adequate Hb.  KASUS RESUSITASI CAIRAN Seorang perempuan berusia 45 tahun, BB 60 dibawa ke IGD karena mengalami kecelakaan lalu lintas. Pada paha kanan tampak adanya patah tulang terbuka. Dari hasil pemeriksaan fisik didapatkan : kesadaran somnolen, akral teraba dingin dan pucat, frekuensi nadi 128x/menit teraba kecil dan lemah, TD 90/50 mmHg, RR 34x/menit, SpO2 95%. Dokter jaga IGD mendiagnosis pasien mengalami syok hipovolemik derajat III dan segera melakukan resusitasi cairan pada pasien tersebut. 1. Berapa EBV (Estimated Blood Volume) pasien tersebut ? 2. Berapa perkiraan kehilangan darah pasien ? 3. Berapa perkiraan kehilangan volume plasma pasien ? 4. Bagaimanakah pemberian resusitasi cairan yang tepat pada pasien tersebut ?  KASUS RESUSITASI CAIRAN Seorang perempuan berusia 45 tahun, BB 60 dibawa ke IGD karena mengalami kecelakaan lalu lintas. Pada paha kanan tampak adanya patah tulang terbuka. Dari hasil pemeriksaan fisik didapatkan : kesadaran somnolen, akral teraba dingin dan pucat, frekuensi nadi 128x/menit teraba kecil dan lemah, TD 90/50 mmHg, RR 34x/menit, SpO2 95%. Dokter jaga IGD mendiagnosis pasien mengalami syok hipovolemik derajat III dan segera melakukan resusitasi cairan pada pasien tersebut. 1. Berapa EBV (Estimated Blood Volume) pasien tersebut ? ± 3900 ml 2. Berapa perkiraan kehilangan darah pasien ? 30 – 45 % dari EBV = 1200 – 1750 ml 3. Berapa perkiraan kehilangan volume plasma pasien ? 720 – 800 ml (± 750 ml) 4. Bagaimanakah pemberian resusitasi cairan yang tepat pada pasien tersebut ? Kristaloid = 3 x 750 ml = 2250 ml Koloid = 1 x 750 ml = 750 ml R E F E R E N S I REFERENSI