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Digoxin
Digoxin is used to treat heart failure and atrial fibrillation. It works by inhibiting the sodium-potassium pump in cardiac cells, increasing intracellular calcium levels and strengthening heart muscle contractions. The optimal serum concentration is 0.5-0.9 ng/mL. Adverse effects include nausea, vomiting, arrhythmias, and can be caused by electrolyte imbalances or drug interactions. Digoxin is primarily excreted unchanged in urine and its half-life is increased in renal impairment. It is indicated to treat heart failure with reduced ejection fraction or atrial fibrillation with a rapid ventricular response.
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Digoxin
- 1. الرحيم الرحمن الرحمنهللا بسم PEDIATRIC WAD MEDANI TEACHING HOSPITAL UNIT: PROF AHMED ALNOUR DR HISHAM ALUMDA DR ABDALSALAM PHARMACOLOGICAL BASIS AND PEDIATRICS USES OF DIGOXIN Presented by Dr ; Mogahed.I.H.Hussein
- 2. OBJECTIVES • Understanding normalphysiological mechanisms implicated in cardiac muscle contraction and relaxation. • Know the mechanisms by which digoxin alter cardiac contractility • Know the pharmacokinetics of the drug • Know the uses of digoxin and its potential adverse effects
- 9. Mechanism of Action Digoxin’s primary mechanism of action is the ability to inhibit membrane-bound alpha subunits of sodium- potassium ATPase (sodium pump), mainly but not exclusively located in the human myocardium. This inhibition promotes sodium-calcium exchange, which increases the intracellular calcium concentration that is available to the contractile proteins, resulting in an increase in the force of myocardial contraction.2,3
- 10. Mechanism of Action In the human myocardium, there is no evidence of up- regulation of the sodium pump during chronic digoxin therapy.4 The inhibition of the sodium pump may also improve baroreceptor sensitivity in HF and may explain some of the neurohormonal effects of digoxin.5 Digoxin also has important parasympathetic effects, particularly on the atrioventricular node.
- 11. Mechanism of Action In patients with reduced systolic function and abnormal central hemodynamics who are in sinus rhythm, digoxin improves left ventricular ejection fraction (LVEF) and reduces pulmonary capillary wedge pressure while increasing cardiac output both at rest and during exercise.
- 12. Mechanism of Action In HF, however, when hemodynamics are normalized first with diuretics and vasodilators, no further improvement in pulmonary capillary wedge pressure or cardiac output is achieved after the acute administration of digoxin.6,7 The improvement in hemodynamics is sustained during chronic therapy.8
- 14. Hemodynamic Effects Digitalisadministration does not alter cardiac output in normal subjects, although it does cause significant increase in contractility. This lack of effect on cardiac output is likely due to an increase in systemic vascular resistance produced by digitalis that prevents the increase in contractility from translating into increased cardiac output.
- 15. Neurohormonal Effects (1)Baroreceptor function: In low-output HF models, there is attenuation of carotid sinus baroreceptor discharge sensitivity. Administration of digoxin produces improvement in baroreceptor function that results in decreased activation of the sympathetic nervous system.5 (2) Vagomimetic effect: Digoxin at therapeutic doses increases vagal tone (ie, decreases sinoatrial and atrioventricular conduction).10
- 16. Neurohormonal Effects (3)Sympathoinhibitory effects: Digoxin has a direct sympathoinhibitory effect that does not appear to be related to an increase in the cardiac output produced by the drug. Although dobutamine and digoxin cause a similar increase in cardiac output in HF, only the latter decreases sympathetic nerve discharge.11 (4) Circulating neurohormones: Therapeutic doses of digoxin decrease the serum norepinephrine concentrations and plasma renin activity.12
- 17. Neurohormonal Effects (5)Dose related effects on neurohormones: A low dose of digoxin that has no effect on cardiac contractility or hemodynamics decreases cardiac norepinephrine spillover in severe HF.13 Increasing the dose within therapeutic range continues to improve the hemodynamics without further improvement of the neurohormonal profile.14 (6) Antifibrotic effects: Patients with HF often have chronically high levels of aldosterone. Aldosterone stimulation of the sodium pump may lead to perivascular fibrosis that experimentally may be prevented by digoxin administration.15
- 18. Electrophysiological Effects Therapeuticdoses of digoxin have a predominantly parasympathomimetic action on atrial myocardium, slowing conduction, and prolonging atrioventricular node refractory period. There are practically no electrophysiological effects on the Purkinje system. Although digoxin intoxication may produce lethal arrhythmias, therapeutic doses do not appear to increase arrhythmias in the absence of ischemia.16
- 19. Electrophysiological Effects ventricularresponse. Irrespective of the indication, a low dose of 0.125 mg should be used. Digoxin should be avoided or used with extreme caution in the very elderly or in patients with severe conduction abnormalities, acute coronary syndromes, or renal failure.
- 22. Pharmacokinetics Sixty to80 percent of digoxin is absorbed from the tablets and over 90% from the capsules in 1 to 3 hours. This is followed by a 6- to 8-hour tissue distribution phase. In some patients, oral digoxin is partial inactivated by colonic bacteria; as a result, certain antibiotics may increase digoxin absorption. Only 16% of the absorbed digoxin is metabolized, whereas the rest is excreted unchanged in the urine.
- 23. Pharmacokinetics The half-lifeof digoxin is 36 to 48 hours in patients with normal renal function and 3.5 to 5 days in anuric patients. Digoxin is not removed by exchange transfusions or peritoneal dialysis or hemodialysis, or during cardiopulmonary bypass. In patients with normal renal function, an oral daily maintenance dose without a loading dose results in a steady-state blood concentration in approximately 7 days.
- 24. Digoxin Dose/ SerumConcentration Low dose digoxin, resulting in a serum concentration (SDC) less than 1 ng/mL, has beneficial hemodynamic, neurohormonal, and clinical effects.26,27 Retrospective analysis of the DIG trial suggests that digoxin has a bidirectional effect, with a possible decrease in mortality when SDC is 0.5 to 0.9 ng/mL and an increase in mortality when SDC is above 1 ng/mL.28
- 25. Digoxin Dose/ SerumConcentration Additional data from the DIG trial suggest that in patients with normal renal function who are not receiving medications that tend to increase SDC, a dose of 0.125 mg daily will result in SDC of approximately 0.8 ng/mL.21 Determination of SDC is not routinely necessary because it is predictable based on dose used. Only the post- distribution phase (12 to 24 hours after the dose) is useful to evaluate whether the dose of digoxin is acceptable.29
- 26. Factors predisposing todigitalis toxicity: Electrolytic disturbances Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics, and this usually can be prevented by use of a potassium-sparing diuretic or supplementation with potassium chloride. Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity.
- 27. Drugs: Quinidine, verapamil,and amiodarone, to name a few, can cause digoxin intoxication, both by displacing digoxin from tissue protein-binding sites and by competing with digoxin for renal excretion. As a consequence, digoxin plasma levels may increase by 70 to 100 percent, requiring dosage reduction. Potassium- depleting diuretics, corticosteroids, and a variety of other drugs can also increase digoxin toxicity . Hypothyroidism, hypoxia, renal failure, and myocarditis are also predisposing factors to digoxin toxicity.
- 29. Digoxin Intoxication Traditionallydivided into extra cardiac and cardiac ‘Definite’ Toxicity defined as Nausea/Vomiting with Cardiac effects with Resolution of side effects on discontinuation SDC not a necessary criterion – but SDC > 2.0 ng/ml helpful
- 30. Extracardiac SEs Nonspecificbut more common Gastrointestinal (60-80%) Nausea / Vomiting Anorexia, Abdominal Pain, Diarrhoea Malaise (30-40%) Lethargy, Fatigue
- 31. Neurological (20-30%) Dizziness, Confusion Headache Visual changes (flashing lights, halos, colour disturbances in green – yellow spectrum, blurred vision)
- 32. Cardiac SEs Morespecific but less common Almost any permutations and combinations of heart block, brady- and tachydysrhythmias are possible. The only dysrhythmia not assumed to be due to Digoxin toxicity – Mobitz Type 2 Heart block
- 33. Inverse check mark:Digoxin effect
- 35. Digoxin toxicitysigns Inverse check mark with proximal ST segment depressed In leads other than those with tall R waves With T wave not rising above baseline (Inverted T) With shortened Qtc
- 37. Note that Digoxin does not affect the QRS Maximal therapeautic effect of digoxin is usually present befoe the ECG effects appear
- 38. Management If theevidence of toxicity is relatively minor with, for example, symptoms of nausea, withdrawal of the drug is often the only specific treatment required. If there is no evidence of serious cardiac problems, such as heart block or significant dysrhythmias, then following the withdrawal of the drug and the correction of electrolyte imbalance, symptomatic measures will usually suffice.
- 39. More seriousevidence of toxicity, particularly with cardiac involvement, dysrhythmias, is potentially life threatening, and requires admission to hospital. Measures Hypokalemia correction - intravenous supplementation of no more than 20 mmol/h of potassium, to reduce digitalis binding to Na/K ATPase. More rapid infusion may lead to asystole. Heart blocks – Atropine and Temporary cardiac pacing
- 40. Malignant ventricular arrhythmias Phenytoin(100 mg intravenously, repeated after 5 minutes if required) is a useful antidysrhythmic as it opposes digitalis binding and may improve atrioventricular conduction by its anticholinergic properties.‘
- 41. Malignant ventricular arrhythmias Ultrashortacting beta blockers – Esmolol Cardioversion should be avoided wherever possible, due to the risk of precipitating asystole, and when necessary should be attempted using the lowest energy possible.
- 42. Digoxin-specific antibody fragments Digoxin-specificfab antibody fragments (Digibind) are the most effective treatment available. However, this therapy is expensive and therefore should be reserved for treatment of serious toxicity, especially in the presence of malignant cardiac dysrhythmias.
- 43. Digoxin-specific antibody fragments Theseantibodies have a high affinity and specificity for cardiac glycosides and have been shown to reverse digoxin toxicity and reduce the risk of death. In several large studies, approximately 80% of patients had complete resolution of all evidence of toxicity, 10% improved whilst 0% showed no response. They appear effective for all age groups and also in patients with poor renal reserve (despite eventual renal elimination).
- 44. Digoxin-specific antibody fragments Pharmacokinetics Half life 12-20 hrs Vd 0.4 L/kg After administration, SDC cannot be measured without complete elimination from the body
- 45. Special Considerations inthe Use of Digoxin Acute Heart Failure Syndrome In patients hospitalized for HF and systolic dysfunction, oral or intravenous administration of digoxin will increase the cardiac output, reduce pulmonary capillary wedge pressure and heart rate, and improve the neurohormonal profile.7
- 46. Acute Heart FailureSyndrome These beneficial hemodynamic effects have not been correlated with symptoms. Rapid intravenous administration of digoxin as a bolus may result in worsening HF through an early predominant vasoconstrictor effect.36
- 47. Special Considerations inthe Use of Digoxin Advanced Heart Failure Digoxin may be particularly beneficial in patients with a LVEF less than 25%, symptoms with minimal exertion or at rest, and/or cardiomegaly on chest x-ray.21 Isolated Right-Sided Heart Failure Digoxin increases cardiac output and decreases norepinephrine concentration in patients with right ventricular failure due to cor pulmonale.37 There are no clinical data supporting the use of digoxin for isolated right- sided failure.
- 48. Digoxin in theMultidrug Approach of Heart Failure Diuretics Because digoxin affects potassium homeostasis, combination therapy with non-potassium sparing diuretics may induce serious arrhythmias. In these patients, high normal concentration of potassium and magnesium should be maintained. The arrhythmogenic effects of digoxin may be lessened by potassium sparing diuretics.
- 49. Beta-Blockers Although chronicbeta-blocker therapy is highly beneficial in HF, during its initiation, hemodynamic deterioration may occur, particularly in patients with very severe HF.38 Beta-blocker use may also increase the safety of digoxin therapy, because experimentally they can abolish the digoxin-induced life-threatening arrhythmias in ischemic HF.39
- 50. Precautions in UsingDigoxin Digoxin should not be used in patients with sinoatrial or second/third degree atrioventricular block unless a functioning pacemaker is present. Digoxin should also not be used in Wolff-Parkinson-White syndrome, hypertrophic or restrictive cardiomyopathy, and amyloid heart disease.
- 51. Precautions in UsingDigoxin It should be used with caution in patients with impaired renal function, electrolyte disorders, thyroid disorders, and acute coronary syndromes. It is preferable to discontinue digoxin a few days before electrical cardioversion. If cardioversion is performed in patients receiving digoxin, potassium levels should be corrected, and the lowest energy possible should be used.
- 52. Indications for DigoxinTherapy Digoxin is indicated in patients with HF and impaired systolic function who are in sinus rhythm and continue to have signs and symptoms despite standard therapy that includes angiotensin-converting enzyme inhibitors and beta- blockers.40
- 53. Indications for DigoxinTherapy Digoxin may be particularly useful in patient therapies. Digoxin is indicated in patients with atrial fibrillation, with or without HF, and a rapid with severe symptoms, LVEF less than 25%, or cardiomegaly on chest x-ray. In patients with diastolic HF, digoxin should be used for atrial fibrillation with a rapid ventricular response and/or severe symptoms not responding after optimization of all other
- 54. Digoxin in children Despitethe lack of data regarding its use in children, digoxin continues to be used by most clinicians in the management of pediatric heart failure. Primary Myocardial disease HF is most acceptable indication of Digoxin in Pediatric HF.
- 55. Digoxin in children Leftto right shunts and Valvular heart disease patients are treated with digoxin only after they become symptomatic. Also, any HF due to digoxin responsive Tachyarrhythmia is a strong indication – needs Rapid digitalisation Lower starting dose (½ to ¾ maintenance) is indicated in acute phase of myocarditis, renal failure, and with drugs which increase SDC.
- 56.
- 57. OBJECTIVES IN UNDERSTANDING SHOCK Know the general principles that aid well recognition of CVS pathology Understands the primary disturbances, compensatory responses, decompensatory processes, and possible therapeutic interventions that pertain to various abnormal cardiovascular situations: Identifies the primary disturbances that can account for cardiogenic, hypovolemic, anaphylactic, septic, and neurogenic shock states.
- 58. OBJECTIVES Lists thecompensatory processes that may arise during various types of circulatory shock. Identifies the decompensatory processes that may arise during shock and describes how these lead to irreversible shock states Defines circulatory shock.
- 60. General Principles • PA,mean arterial pressure; • CO, cardiac output; • TPR, total peripheral resistance; • SV, stroke volume;
- 61. General Principles • HR,heart rate • ESV, end-systolic volume • EDV, end-diastolic volume • PcV' central venous pressure
- 62. General Principles • NE,norepinephrine • ACh, acetylcholine • P P' arterial pulse pressure • CA, arterial compliance • SA, sinoatrial.
- 63. General Principles • PA=COxTPR • CO=SVxHR • SV=EDV-ESV • Ejection fraction = SV/EDV
- 64.
- 65. General Principles NO &MUSCLE RELAXATION
- 66.
- 67.
- 68. General Principles IMMUNOLOGICAL RESPONSETHAT LEAD TO SHOCK
- 69. General Principles Requirements forEffective Operation • For effective efficient ventricular pumping action, the heart must be functioning properly in five basic respects: 1. The contractions of individual cardiac muscle cells must occur at regular intervals and be synchronized (not arrhythmic). 2. The valves must open fully (not stenotic).
- 70. General Principles Requirements forEffective Operation 3- The valves must not leak (not insufficient or regurgitant). 4- The muscle contractions must be forceful (not foiling). 5- The ventricles must fill adequately during diastole.
- 72.
- 73. Demand Supply
- 74. Introduction • A stateof circulatory "shock" exists whenever there is a generalized, severe reduction in blood supply to the body tissues and the metabolic needs of the tissues are not met. • Even with all cardiovascular compensatory mechanisms activated, arterial pressure is usually (though not always) low in shock.
- 75. Introduction • In severeshock states of any etiology, inadequate brain blood flow leads to loss of consciousness often with sudden onset (called syncope). • The approach to understanding the causes and selecting an appropriate treatment depends on determination of the underlying primary disturbance.
- 76. Introduction • Recall thatarterial pressure is determined by cardiac output and total peripheral resistance, so any loss in blood pressure is a result of a decrease in either one or both of these variables
- 77. Primary Disturbances • Ingeneral, the shock state is precipitated by one of three cardiovascular crises: (1) severely depressed myocardial functional ability. (2) grossly inadequate cardiac filling due to low mean circulatory filling pressure.
- 78. Primary Disturbances (3) profoundsystemic vasodilation either due to the abnormal presence of powerful vasodilators or due to the absence of neurogenic tone normally supplied by the sympathetic nervous system. The consequences of these primary disturbances are represented in the five categories of shock summarized in the next Figure .
- 79. Primary Disturbances Cardiogenic shock •Cardiogenic shock occurs whenever cardiac pumping ability is compromised (eg, as a result of severe arrhythmias, abrupt valve malfunction, coronary occlusions, or myocardial infarction). • The direct consequence of any of these abnormalities is a significant fall in cardiac output.
- 80. Primary Disturbances Hypovolemic shock •Accompanies significant hemorrhage (usually greater than 20% of blood volume), or fluid loss from severe burns, chronic diarrhea, or prolonged vomiting. • These situations can induce shock by depleting body fluids and thus circulating blood volume. • The direct consequence of hypovolemia is inadequate cardiac filling and reduced stroke volume.
- 81. Primary Disturbances Hypovolemic shock •There are some situations that may result in reduced cardiac filling that are not related to hypovolemia. • For example, cardiac tamponade, associated with fluid accumulation in the pericardial sac, prevents adequate diastolic filling as does the occurrence of a pulmonary embolus (a clot mobilized from systemic veins lodging in a pulmonary vessel).
- 82. Primary Disturbances Anaphylactic shock •Anaphylactic shock occurs as a result of a severe allergic reaction to an antigen to which the patient has developed a sensitivity (eg, insect bites, antibiotics, and certain foods).
- 83. Primary Disturbances Anaphylactic shock •This immunological event, also called an "immediate hypersensitivity reaction," is mediated by several substances (such as histamine, prostaglandins, leukotrienes, and bradykinin) that, by multiple mechanisms, results in substantial arteriolar vasodilation, increases in microvascular permeability, and loss of peripheral venous tone. • These combine to reduce both total peripheral resistance and cardiac output
- 84. Primary Disturbances Septic shock •Septic shock is also caused by profound vasodilation but specifically from substances released into the circulating blood by infective agents. One of the most common is endotoxin, a lipopolysaccharide released from bacteria.
- 85. Primary Disturbances Septic shock •This substance induces the formation of a nitric oxide synthase (called inducible nitric oxide synthase to distinguish it from the normally present comtitutive nitric oxide synthase) in endothelial cells, vascular smooth muscle, and macrophages that then produce large amounts of the potent vasodilator nitric oxide. • The term distributive shock is sometimes used to describe both the anaphylactic and septic shock states.
- 86. Primary Disturbances Neurogenic shock •Neurogenic shock is produced by loss of vascular tone due to inhibition of the normal tonic activity of the sympathetic vasoconstrictor nerves and often occurs with deep general anesthesia or in reflex response to deep pain associated with traumatic injuries.
- 87. Primary Disturbances Neurogenic shock •It may also be accompanied by an increase in vagal activity, which significantly slows the cardiac beating rate. • This type of shock is often referred to a vasovagal syncope. The transient syncope evoked by strong emotions is a mild form of neurogenic shock and is usually quickly reversible.
- 89. Primary Disturbances • Asshown in the top half of previous Figure, the common primary disturbances in all forms of shock are decreased cardiac output and/or total peripheral resistance leading to decreased mean arterial pressure. • Generally, the reduction in arterial pressure is substantial, and so therefore, is the influence on the cardiovascular centers from reduced arterial baroreceptor discharge rate.
- 90. Primary Disturbances • Inaddition, in the case of hypovolemic, anaphylactic, and septic shock, diminished activity of the cardiopulmonary baroreceptors due to a decrease in central venous pressure and/or volume acts on the medullary cardiovascular centers to stimulate sympathetic output.
- 91. Primary Disturbances • Inthe case of cardiogenic shock, central venous pressure will increase; and in the case of neurogenic shock, central venous pressure cannot be predicted because both cardiac output and venous return are likely to be depressed. • Thus, in these instances, it is not clear how the cardiopulmonary baroreceptors affect autonomic output
- 92.
- 94. Compensatory Mechanisms • CompensatoryMechanisms in general, the various forms of shock evoke the compensatory responses in the autonomic nervous system that we would expect from a fall m blood pressure.
- 95. Compensatory Mechanisms • Twoprimary exceptions to this statement include (I) neurogenic shock, where reflex responses may be absent or lead to further depression of blood pressure (II) certain instances of cardiogenic shock associated with inferoposterior myocardial infarctions, which elicit a reflex bradycardia and decrease sympathetic drive (the Bezold-Jarisch reflex).
- 96. Compensatory Mechanisms • Theseincreases in sympathetic activity and decreases in parasympathetic activity are indicated in the bottom half of the previous Figure. • Cardiac and peripheral vascular compensatory responses to shock, however, may be much more intense than those that accompany more ordinary cardiovascular disturbances.
- 97. Compensatory Mechanisms • Manyof the commonly recognized symptoms of shock (eg, pallor, cold clammy skin, rapid heart rate, muscle weakness, and venous constriction) are a result of greatly increased sympathetic nerve activity. • When the immediate compensatory processes are inadequate, the individual may also show signs of abnormally low arterial pressure and reduced cerebral perfusion, such as dizziness, confusion, or loss of consciousness.
- 98. Compensatory Mechanisms • Additionalcompensatory processes initiated during the shock state may include the following: 1. Rapid and shallow breathing occurs, which promotes venous return to the heart by action of the respiratory pump. 2. Increased renin release from the kidney as a result of sympathetic stimulation promotes the formation of the hormone, angiotensin II, which is a potent vasoconstrictor and participates in the increase in total peripheral resistance even in mild shock states.
- 99. Compensatory Mechanisms 3. Increasedcirculating levels of vasopressin (also known as antidiuretic hormone) from the posterior pituitary gland contribute to the increase in total peripheral resistance. This hormone is released in response to decreased firing of the cardiopulmonary and arterial baroreceptors. 4. Increased circulating levels of epinephrine from the adrenal medulla in response to sympathetic stimulation contribute to systemic vasoconstriction.
- 100. Compensatory Mechanisms 5. Reducedcapillary hydrostatic pressure resulting from intense arteriolar constriction, promotes fluid movement from the interstitial space into the vascular space. 6. Increased glycogenolysis in the liver induced by epinephrine and norepinephrine results in a release of glucose and a rise in blood (and interstitial) glucose levels and, more importantly, a rise in extracellular osmolarity by as many as 20 mOsm. This will induce a shift of fluid from the intracellular space into the extracellular (including intravascular) space.
- 101. Compensatory Mechanisms • Thelatter two processes result in a sort of "autotransfusion" that can move as much as a liter of fluid into the vascular space in the first hour after the onset of the shock episode. • This fluid shift accounts for the reduction in hematocrit that is commonly observed in hemorrhagic shock.
- 102. Compensatory Mechanisms • Theextent of fluid shift may be limited by a reduction in colloid osmotic pressure. • In addition to the immediate compensatory responses, fluid retention mechanisms are evoked by hypovolemic states that affect the situation in the long term.
- 103. Compensatory Mechanisms • Theproduction and release of the antidiuretic hormone (vasopressin) from the posterior pituitary promote water retention by the kidneys. • Furthermore, activation of the renin-angiotensin-aldosterone pathway promotes renal sodium retention {via aldosterone) and the thirst sensation and drinking behavior {via angiotensin II). These processes contribute to the replenishment of extracellular fluid volume within a few days of the shock episode.
- 104. Decompensatory Processes • Oftenthe strong compensatory responses during shock evoked by the intense sympathetic activation are capable of preventing drastic reductions in arterial pressure. • However, because the compensatory mechanisms involve overwhelming arteriolar vasoconstriction, perfusion of tissues other than the heart and the brain may be inadequate despite nearly normal arterial pressure.
- 105. Decompensatory Processes • Forexample, blood flow through vital organs such as the liver, gastrointestinal tract, and kidneys may be reduced nearly to zero by intense sympathetic activation. • The possibility of permanent renal, hepatic, or GI tract ischemic damage is a very real concern even in seemingly mild shock situations. • Patients who have apparently recovered from a state of shock may die several days later because of renal failure, uremia, or sepsis due to bacterial penetration of the weakened mucosal barrier in the GI tract.
- 106. Decompensatory Processes • Theimmediate danger with shock is that it may enter the progressive stage, wherein the general cardiovascular situation progressively degenerates, or, worse yet, enter the irreversible stage, where no intervention can halt the ultimate collapse of cardiovascular system that results in death. The mechanisms behind progressive and irreversible shock are not completely understood. • However, it is clear from the mechanisms shown in the next Figure, that bodily homeostasis can progressively deteriorate with prolonged reductions in organ blood flow. • These homeostatic disturbances, in turn, adversely affect various components of the cardiovascular system so that arterial pressure and organ blood flow are further reduced.
- 107. Decompensatory Processes • Notethat the events shown in the Figure are decompensatory mechanisms. • Reduced arterial pressure leads to alterations that further reduce arterial pressure rather than correct it {ie, a positive feedback process). • These decompensatory mechanisms that are occurring at the tissue level to lower blood pressure are eventually further compounded by a reduction in sympathetic drive and a change from vasoconstriction to vasodilation with a further lowering of blood pressure.
- 108. Decompensatory Processes • Thefactors that lead to this unexpected reduction in sympathetic drive from the medullary cardiovascular centers are not clearly understood. • If the shock state is severe enough and/or has persisted long enough to enter the progressive stage, the self-reinforcing decompensatory mechanisms progressively drive arterial pressure down. Unless corrective measures are taken quickly, death will ultimately result.
- 109.
- 110.
- 111. KEY CONCEPTS Circulatoryshock is defined as a generalized, severe reduction in tissue blood flow so that metabolic needs are not met. The primary disturbances that can lead to shock can be categorized as those that directly interfere with pump function, those that interfere with ventricular filling, or those that cause sustained vascular dilation.
- 112. KEY CONCEPTS Shockis usually accompanied by a compensatory increase in sympathetic activity aimed at maintaining arterial pressure via augmented cardiac output and vascular resistance. Decompensatory processes precipitated by the shock state are generally caused by inadequate tissue blood flow, loss of local homeostasis, and tissue damage leading to a progressive and irreversible fall in arterial pressure.
- 113. MANAGMENT The mostcommon error in treating shock is underestimating the severity of the condition. If compensated shock is suspected, treat promptly and aggressively to prevent progression to hypovolemic shock. All patients require a secure vascular access, oxygen therapy, and cardiopulmonary monitoring.
- 114. MANAGMENT The goalsof initial management are to restore normal mental status, heart rate and blood pressure, good peripheral perfusion, and adequate urine output.
- 115. ED 1. Position: allowa conscious patient to assume a position of comfort. 2. Oxygen: give 100% supplemental oxygen by nonrebreather mask to spontaneously breathing patients. Consider the use of noninvasive positive-pressure ventilation (BiPAP, CPAP) as an alternative to intubation in selected cases (awake and cooperative patients).
- 116. ED 3. Assisted ventilation:if there is evidence of airway compromise, assist ventilation with either a bag-mask device or tracheal intubation.
- 117. ED 4. Intravenous access:establish two large-bore peripheral IV lines or place a central catheter. If venous access is not possible or delayed, use an IO needle. In critically ill or injured patients, do not spend more than 1–2 minutes attempting to establish peripheral vascular access. The effort may be resumed after the IO line is secured.
- 118. ED 5. Fluid: infusea fluid bolus of 20 mL/kg of isotonic crystalloid (lactated Ringer’s or normal saline) as rapidly as possible. Several boluses may be required; large volumes of fluid for resuscitation in previously healthy children do not increase the risk of developing acute respiratory distress syndrome or cerebral edema. Trauma victims may require blood (10 mL/kg) to replace ongoing losses; use cross-matched, type-specific or O-negative blood.
- 119. ED Trauma patients whoremain hypotensive after fluid resuscitation may require immediate operative intervention. 6. Reassess: after each intervention, look for improvement in vital signs, skin perfusion, and level of consciousness. Insert a Foley catheter and monitor urine output; the goal is 1–2 mL/kg/h or 30 mL/h in adolescents.
- 120. ED 7.Inotropic infusion: ifthe patient remains hypotensive after initial fluid resuscitation of 40–60 mL/kg, an inotropic agent, or a combination of several agents, may be necessary to stabilize blood pressure . Titrate the dose to the desired effect. Monitor the patient carefully and switch to a less potent agent once the blood pressure has improved.
- 121. ED 8.Septic shock: administerantibiotic therapy as soon as possible. Send the appropriate cultures, but do not delay therapy if cultures are not readily obtained.
- 122. ED Empiric antibiotics includevancomycin plus cefotaxime or ceftriaxone for the possibility of resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. Consider adding acyclovir for HSV in neonates and cefepime for Pseudomonas aeruginosa in immunocompromised patients.
- 123. ED 9.Anaphylactic shock: managementinvolves early recognition of symptoms of anaphylaxis and anticipating need for advanced airway techniques .
- 124. Cardiogenic shock 10. Givefluid boluses judiciously, at volumes of 5–10 mL/kg, to patients with a history of cardiomyopathy or congenital heart disease. Reassess frequently for signs of cardiac failure. Give patients in congestive heart failure supplemental oxygen, diuretics (furosemide 1 mg/kg), and inotropic agents (dobutamine, dopamine), and consult with a pediatric cardiologist.
- 125. Cardiogenic shock Treat pediatricdysrhythmias according to the PALS Guidelines . a. Asystole and PEA: epinephrine b. Symptomatic bradycardia: epinephrine and atropine c. Supraventricular tachycardia : i. Stable: adenosine ii. Unstable: synchronized cardioversion (0.5–1 J/kg)
- 126. Cardiogenic shock d. Ventriculartachycardia (with pulses) i. Stable: amiodarone or procainamide (not concurrently) or lidocaine ii. Unstable: synchronized cardioversion (0.5–1 J/kg)
- 127. Cardiogenic shock e. Ventricularfibrillation and pulseless ventricular tachycardia: CPR followed by defibrillation, one shock,(2J/kg)and immediate resumption of CPR, epinephrine, and/or amiodarone, and/or lidocaine. Alternate drugs with defibrillation (4J/kg: single shock each time).
- 128. Cardiogenic shock Always resumeCPR immediately after shock for 2 minutes or 5 cycles of 30:2 or 10 cycles of 15:2, then reassess rhythm. Once defibrillation isS successful, many patients will required additional CPR before they regain a perfusing rhythm.
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