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CV Pharmacology-
Pathophysiology and Treatment of Shock
Recommended Reading:
Autonomic pharmacology
Formatives:
Practice Question Set #1
Clinical:
E-Medicine Articles
Shock, Cardiogenic
Shock, Hypovolemic
Shock, Septic
Prepared and presented by:
Marc Imhotep Cray, M.D.
BMS / CK-CS Teacher
http://www.imhotepvirtualmedsch.com/
2
Shock (circulatory) See: Shock (circulatory)
Effects of inadequate perfusion on cell function
From: http://en.wikipedia.org/wiki/Shock_%28circulatory%29
3
Shock, Circulatory Defined
 Circulatory shock, commonly known as just shock, is a
serious, life-threatening medical condition where insufficient
blood flow reaches body tissues
 As blood carries oxygen and nutrients around body,
reduced flow hinders delivery of these components to
tissues, and can stop tissues from functioning properly
 The process of blood entering tissues is called perfusion, so
when perfusion is not occurring properly this is called a
hypoperfusional (hypo = below) state
See: Shock: An Overview PDF by Michael L. Cheatham, MD, Ernest F.J. Block, MD, Howard G. Smith, MD,
John T. Promes, MD, Surgical Critical Care Service, Department of Surgical Education, Orlando
Regional Medical Center Orlando, Florida
4
The problem in shock
 Altered circulatory parameters
 Compromised microcirculation
 Persistent severe hypoxia
 Multiple organ failure
From: http://www.cvpharmacology.com/clinical
topics/hypotension.htm
5
Main types of Shock
 Vasoconstrictive
 Trauma, bleeding, burning, ileus (volumen loss)
 Pulmonary embolism (impaired cardiac filling)
 Myocardial infarction (impaired cardiac contraction)
 Vasodilatative
 Anaphylaxis, sepsis (maldistribution of blood flow)
 Spinal medullary injury (venous pooling)
 Hypothermia
6
Classification
 In 1972 Hinshaw and Cox suggested
the following classification which is
still used today
 It uses four types of shock:
1. hypovolemic,
2. cardiogenic,
3. distributive and
4. obstructive shock
7
Classification
(based on cardiovascular characteristics, which was
initially proposed in 1972 by Hinshaw and Cox)
 Hypovolaemic
 Hemorrhagic, Fluid
depletion, Increased
vascular capacitance
 Cardiogenic
 Myopathic,
Mechanical,
Arrhythmic
 Distributive
 Septic, etc.
 Obstructive
 PE, pericarditis,
pnumothorax etc.
8
Hypovolemic shock
Hypovolemic shock –
 This is the most common type of shock and
based on insufficient circulating volume.
 Its primary cause is loss of fluid from the
circulation from either an internal or external
source.
 An internal source may be haemorrhage.
 External causes may include extensive
bleeding, high output fistulae or severe
burns.
9
Cardiogenic shock
Cardiogenic shock –
 This type of shock is caused by the failure of
the heart to pump effectively.
 This can be due to damage to the heart
muscle, most often from a large myocardial
infarction.
 Other causes of cardiogenic shock include
arrhythmias, cardiomyopathy, congestive
heart failure (CHF), and cardiac valve
problems.
10
Distributive shock
Distributive shock –
 As in hypovolaemic shock there is an insufficient
intravascular volume of blood.
 This form of "relative" hypovolaemia is the result of
dilation of blood vessels which diminishes
systemic vascular resistance. Examples of
this form of shock are:
1. Septic shock
2. Anaphylactic shock
3. Neurogenic shock
11
Obstructive shock
Obstructive shock –
 In this situation the flow of blood is
obstructed which impedes circulation and can
result in circulatory arrest.
 Several conditions result in this form of
shock.
1. Cardiac tamponade
2. Tension pneumothorax
3. pulmonary embolism
4. Aortic stenosis
12
Endocrine shock
based on endocrine disturbances.
Recently a fifth form of shock has been introduced:
 Hypothyroidism, in critically ill patients, reduces cardiac output and
can lead to hypotension and respiratory insufficiency
 Thyrotoxicosis may induce a reversible cardiomyopathy
 Acute adrenal insufficiency is frequently the result of discontinuing
corticosteroid treatment without tapering the dosage
 However, surgery and intercurrent disease in patients on
corticosteroid therapy without adjusting the dosage to accommodate
for increased requirements may also result in this condition
 Relative adrenal insufficiency in critically ill patients where present
hormone levels are insufficient to meet the higher demands
13
Comparison of types of shock
(Early stage)
Vasoconstrictive Vasodilatative
Hypovolamic Cardiogenic Circulatory Septic
Cardiac
index
Cardiac
index
Peripheral
resistance
Peripheral
resistance
Blood
Volume
Blood
Volume
Malperfusion and organ dysfunction are the ultimate end point of any shock stage
14
Decreased cardiac output
Decreased blood pressure
Decreased tissue perfusion
Decreased coronary perfusion
Decreased myocardial function
Microcirculatory
obstruction
Cellular aggregation
Microcirculatory demage
Cell hypoxia
Metabolic
acidosis
Decreased
myocardial
contraction
Inracellular
fluid
loss
Decreased
venous return
BP = CO x SVR
Pathophysiology Concept Map
15
Hypovolemic Shock
loss in circulatory volume
 Decreased venous return
 Decreased filling of the cardiac chambers
 Decreased cardiac output
 increase in the systemic vascular resistance (SVR).
low central venous pressure (CVP), a low pulmonary capillary wedge pressure (PCWP), low
cardiac output (CO) and cardiac index (CI), and high SVR. The arterial blood pressure may be
normal or low.
16
HYPOVOLEMIC (oligemic)
SHOCK
 Hemorrhagic
 - Trauma
 - Gastrointestinal
 - Retroperitoneal
 • Fluid depletion (nonhemorrhagic)
 External fluid loss
 Dehydration
 Vomiting
 Diarrhea
 Polyuria
 Interstitial fluid redistribution
 Thermal injury
 Trauma
 Anaphylaxis
 • Increased vascular
capacitance (venodilatation)
 - Sepsis
 - Anaphylaxis
 - Toxins/Drugs
17
Cardiogenic Shock
 dependent on poor pump function
 acute catastrophic failure of left
ventricular pump function
high PCWP, low CO and CI, and generally a high SVR
18
CARDIOGENIC
 Myopathic
 -Myocardial infarction (Left
ventricle, Right ventricle)
 -Myocardial contusion
(trauma)
 -Myocarditis
 -Cardiomyopathy
 -Post ischemic
myocardial stunning
 -Septic myocardial
depression
 -Pharmacologic
Anthracycline
cardiotoxicity Calcium
channel blockers
19
 Mechanical
 -Valvular failure Regurgitant Obstructive
 -Hypertropic cardiomyopathy
 -Ventricular septal defect
 Arrhythmic
 -Bradycardia Sinus (e.g.,vagal
syncope)Atrioventricular blocks
 -Tachycardia SupraventricularVentricular
CARDIOGENIC (2)
20
DISTRIBUTIVE
 Septic (bacterial, fungal, viral, rickettsial)
 Toxic shock syndrome
 Anaphylactic, anaphylactoid
 Neurogenic (spinal shock)
 Endocrinologic
 Adrenal crisis
 Toxic (e.g., nitroprusside, bretyllium)
21
Extracardiac obstructive shock
Impaired diastolic filling (decreased
ventricular preload)
 a physical impairment to adequate forward circulatory flow involving
mechanisms (different than primary myocardial or valvular dysfunction)
 Frank decrease in filling pressures (as in mediastinal compressions of
great veins) or
 trends towards equalization of pressures in the case of cardiac
tamponade or
 markedly increased right ventricular filling pressures
High CVP, low PCWP Cardiac output is usually decreased with increased SVR.
22
Symptoms
 Narrowing of
pulse pressure
 Tachycardia,
hypotension
 Restlessnes
 Disphoria
 Decreased urine
output
 Anxiety
 Cool, clammy skin
 Obtundation
 Dyspnea
 Unconsciousness
23
Treatment of
shock
Generalities:
 Positioning, avoiding
hypothermia
 Maintaining adequate
oxygenization
 Fluid resuscitation
 Pain relief ?
 (inotropic treatment?)
24
Enhance compensatory phase
of the shock
 Maintenance of mean circulatory pressure
 Maximizing cardiac function
 Redistributing perfusion to vital organs
 Optimizing unloading of oxygen at tissues
25
Maintain Volume
 -Fluid redistribution to
vascular space
 From interstitium
(Starling effect)
 From intracellular
space (Osmotic
effect)
 -Decreased renal fluid
losses
 Decreased
glomerular filtration
rate (GFR) Increased
aldosterone
 Increased
vasopressin
26
Mintain Pressure
 Decreased venous capacitance
 Increased sympathetic activity
 Increased circulating (adrenal) epinephrine
 Increased angiotensin
 Increased vasopressin
27
Maximize Cardiac Performance
 Increased contractility
 Sympathetic stimulation
 Adrenal stimulation
28
Early mechanical ventilation
 allows blood flow to be redistributed
 tends to reverse lactic acidosis
 supports the patient until other
therapeutic measures can be effective
Tidal volumes in the order of 7-10 mlkg-1 of lean body mass, an O2
concentration that results in arterial saturation not less than 92%, adequate
ventilator rate and sedation to minimize the work of breathing.
29
Fluid resuscitation
 IV line
 Large bore cannula
 More iv line
 Choice of infusion
 Lactated Ringer's
solution (initial
bolus: 10-25 ml/kg
/ 10 min.)
 Colloids
 Dextrane
 Hydroethylstrach
 Gelatine
 Small volume resuscitation
 Rate, amount
 General conditions
 parameters ( BP, Pulse,
CVP, SatO2 etc)
30
Dextrane
 Molecular weight: 40K - 60/70K Dalton
 Concentration: 10% (40K)*; 6% (60/70K)**
 Water binding: 25 ml/g -- 4 - 6 h
 Plasma expanding effect: * 180-200; ** 150%
 Elimination:
 metabolic
 kidney
31
Hydroxyethylstrach
 Molecular weight: 450K - 200K - 40K Dalton
 Substitution: 0,5 - 0,62 - 0,7
 Water binding: 15 - 20 ml/g -- 3 - 6 h
 6% HES (200K/0,5) -- plasma substitution (100%)
 10%HES (200K/0,5) -- plasma expanding (140%)
 Elimination:
 kidney
 12 - 24 h (65 - 70 %) --- 168 h
32
Inotropic drugs
Inotropie Heart rate SVR Kidney
Blood flow
Cornarry
Blood flow
Cardiac
Output
Dose
Epinephrin ++ + + - + + 10-30
mcg/min
Norepinephrin ++ 0 ++ -- + + 2-8
mcg/min
Dopamin ++ + - ++ + ++ 2-5
mcg/min/kg
Dobutamin +++ (+) -- + + ++ 5-15
mcg/min/kg
Isoproterenol ++ ++ - + + ++ 5 mcg/mi
Amrinon +++ 0 -- + + ++
Bolus 0.5 -
1.5 mg/kg
Cont.: 2 to
10
mcg/kg/min
33
Reference Resource
Joynt, Gavin (April 2003). "Introduction to
management of shock for junior ICU trainees and
medical students". The Chinese University of
Hong Kong. Retrieved on 9 October, 2006.

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Pathophysiology, Pharmacology and Treatment of Shock

  • 1. CV Pharmacology- Pathophysiology and Treatment of Shock Recommended Reading: Autonomic pharmacology Formatives: Practice Question Set #1 Clinical: E-Medicine Articles Shock, Cardiogenic Shock, Hypovolemic Shock, Septic Prepared and presented by: Marc Imhotep Cray, M.D. BMS / CK-CS Teacher http://www.imhotepvirtualmedsch.com/
  • 2. 2 Shock (circulatory) See: Shock (circulatory) Effects of inadequate perfusion on cell function From: http://en.wikipedia.org/wiki/Shock_%28circulatory%29
  • 3. 3 Shock, Circulatory Defined  Circulatory shock, commonly known as just shock, is a serious, life-threatening medical condition where insufficient blood flow reaches body tissues  As blood carries oxygen and nutrients around body, reduced flow hinders delivery of these components to tissues, and can stop tissues from functioning properly  The process of blood entering tissues is called perfusion, so when perfusion is not occurring properly this is called a hypoperfusional (hypo = below) state See: Shock: An Overview PDF by Michael L. Cheatham, MD, Ernest F.J. Block, MD, Howard G. Smith, MD, John T. Promes, MD, Surgical Critical Care Service, Department of Surgical Education, Orlando Regional Medical Center Orlando, Florida
  • 4. 4 The problem in shock  Altered circulatory parameters  Compromised microcirculation  Persistent severe hypoxia  Multiple organ failure From: http://www.cvpharmacology.com/clinical topics/hypotension.htm
  • 5. 5 Main types of Shock  Vasoconstrictive  Trauma, bleeding, burning, ileus (volumen loss)  Pulmonary embolism (impaired cardiac filling)  Myocardial infarction (impaired cardiac contraction)  Vasodilatative  Anaphylaxis, sepsis (maldistribution of blood flow)  Spinal medullary injury (venous pooling)  Hypothermia
  • 6. 6 Classification  In 1972 Hinshaw and Cox suggested the following classification which is still used today  It uses four types of shock: 1. hypovolemic, 2. cardiogenic, 3. distributive and 4. obstructive shock
  • 7. 7 Classification (based on cardiovascular characteristics, which was initially proposed in 1972 by Hinshaw and Cox)  Hypovolaemic  Hemorrhagic, Fluid depletion, Increased vascular capacitance  Cardiogenic  Myopathic, Mechanical, Arrhythmic  Distributive  Septic, etc.  Obstructive  PE, pericarditis, pnumothorax etc.
  • 8. 8 Hypovolemic shock Hypovolemic shock –  This is the most common type of shock and based on insufficient circulating volume.  Its primary cause is loss of fluid from the circulation from either an internal or external source.  An internal source may be haemorrhage.  External causes may include extensive bleeding, high output fistulae or severe burns.
  • 9. 9 Cardiogenic shock Cardiogenic shock –  This type of shock is caused by the failure of the heart to pump effectively.  This can be due to damage to the heart muscle, most often from a large myocardial infarction.  Other causes of cardiogenic shock include arrhythmias, cardiomyopathy, congestive heart failure (CHF), and cardiac valve problems.
  • 10. 10 Distributive shock Distributive shock –  As in hypovolaemic shock there is an insufficient intravascular volume of blood.  This form of "relative" hypovolaemia is the result of dilation of blood vessels which diminishes systemic vascular resistance. Examples of this form of shock are: 1. Septic shock 2. Anaphylactic shock 3. Neurogenic shock
  • 11. 11 Obstructive shock Obstructive shock –  In this situation the flow of blood is obstructed which impedes circulation and can result in circulatory arrest.  Several conditions result in this form of shock. 1. Cardiac tamponade 2. Tension pneumothorax 3. pulmonary embolism 4. Aortic stenosis
  • 12. 12 Endocrine shock based on endocrine disturbances. Recently a fifth form of shock has been introduced:  Hypothyroidism, in critically ill patients, reduces cardiac output and can lead to hypotension and respiratory insufficiency  Thyrotoxicosis may induce a reversible cardiomyopathy  Acute adrenal insufficiency is frequently the result of discontinuing corticosteroid treatment without tapering the dosage  However, surgery and intercurrent disease in patients on corticosteroid therapy without adjusting the dosage to accommodate for increased requirements may also result in this condition  Relative adrenal insufficiency in critically ill patients where present hormone levels are insufficient to meet the higher demands
  • 13. 13 Comparison of types of shock (Early stage) Vasoconstrictive Vasodilatative Hypovolamic Cardiogenic Circulatory Septic Cardiac index Cardiac index Peripheral resistance Peripheral resistance Blood Volume Blood Volume Malperfusion and organ dysfunction are the ultimate end point of any shock stage
  • 14. 14 Decreased cardiac output Decreased blood pressure Decreased tissue perfusion Decreased coronary perfusion Decreased myocardial function Microcirculatory obstruction Cellular aggregation Microcirculatory demage Cell hypoxia Metabolic acidosis Decreased myocardial contraction Inracellular fluid loss Decreased venous return BP = CO x SVR Pathophysiology Concept Map
  • 15. 15 Hypovolemic Shock loss in circulatory volume  Decreased venous return  Decreased filling of the cardiac chambers  Decreased cardiac output  increase in the systemic vascular resistance (SVR). low central venous pressure (CVP), a low pulmonary capillary wedge pressure (PCWP), low cardiac output (CO) and cardiac index (CI), and high SVR. The arterial blood pressure may be normal or low.
  • 16. 16 HYPOVOLEMIC (oligemic) SHOCK  Hemorrhagic  - Trauma  - Gastrointestinal  - Retroperitoneal  • Fluid depletion (nonhemorrhagic)  External fluid loss  Dehydration  Vomiting  Diarrhea  Polyuria  Interstitial fluid redistribution  Thermal injury  Trauma  Anaphylaxis  • Increased vascular capacitance (venodilatation)  - Sepsis  - Anaphylaxis  - Toxins/Drugs
  • 17. 17 Cardiogenic Shock  dependent on poor pump function  acute catastrophic failure of left ventricular pump function high PCWP, low CO and CI, and generally a high SVR
  • 18. 18 CARDIOGENIC  Myopathic  -Myocardial infarction (Left ventricle, Right ventricle)  -Myocardial contusion (trauma)  -Myocarditis  -Cardiomyopathy  -Post ischemic myocardial stunning  -Septic myocardial depression  -Pharmacologic Anthracycline cardiotoxicity Calcium channel blockers
  • 19. 19  Mechanical  -Valvular failure Regurgitant Obstructive  -Hypertropic cardiomyopathy  -Ventricular septal defect  Arrhythmic  -Bradycardia Sinus (e.g.,vagal syncope)Atrioventricular blocks  -Tachycardia SupraventricularVentricular CARDIOGENIC (2)
  • 20. 20 DISTRIBUTIVE  Septic (bacterial, fungal, viral, rickettsial)  Toxic shock syndrome  Anaphylactic, anaphylactoid  Neurogenic (spinal shock)  Endocrinologic  Adrenal crisis  Toxic (e.g., nitroprusside, bretyllium)
  • 21. 21 Extracardiac obstructive shock Impaired diastolic filling (decreased ventricular preload)  a physical impairment to adequate forward circulatory flow involving mechanisms (different than primary myocardial or valvular dysfunction)  Frank decrease in filling pressures (as in mediastinal compressions of great veins) or  trends towards equalization of pressures in the case of cardiac tamponade or  markedly increased right ventricular filling pressures High CVP, low PCWP Cardiac output is usually decreased with increased SVR.
  • 22. 22 Symptoms  Narrowing of pulse pressure  Tachycardia, hypotension  Restlessnes  Disphoria  Decreased urine output  Anxiety  Cool, clammy skin  Obtundation  Dyspnea  Unconsciousness
  • 23. 23 Treatment of shock Generalities:  Positioning, avoiding hypothermia  Maintaining adequate oxygenization  Fluid resuscitation  Pain relief ?  (inotropic treatment?)
  • 24. 24 Enhance compensatory phase of the shock  Maintenance of mean circulatory pressure  Maximizing cardiac function  Redistributing perfusion to vital organs  Optimizing unloading of oxygen at tissues
  • 25. 25 Maintain Volume  -Fluid redistribution to vascular space  From interstitium (Starling effect)  From intracellular space (Osmotic effect)  -Decreased renal fluid losses  Decreased glomerular filtration rate (GFR) Increased aldosterone  Increased vasopressin
  • 26. 26 Mintain Pressure  Decreased venous capacitance  Increased sympathetic activity  Increased circulating (adrenal) epinephrine  Increased angiotensin  Increased vasopressin
  • 27. 27 Maximize Cardiac Performance  Increased contractility  Sympathetic stimulation  Adrenal stimulation
  • 28. 28 Early mechanical ventilation  allows blood flow to be redistributed  tends to reverse lactic acidosis  supports the patient until other therapeutic measures can be effective Tidal volumes in the order of 7-10 mlkg-1 of lean body mass, an O2 concentration that results in arterial saturation not less than 92%, adequate ventilator rate and sedation to minimize the work of breathing.
  • 29. 29 Fluid resuscitation  IV line  Large bore cannula  More iv line  Choice of infusion  Lactated Ringer's solution (initial bolus: 10-25 ml/kg / 10 min.)  Colloids  Dextrane  Hydroethylstrach  Gelatine  Small volume resuscitation  Rate, amount  General conditions  parameters ( BP, Pulse, CVP, SatO2 etc)
  • 30. 30 Dextrane  Molecular weight: 40K - 60/70K Dalton  Concentration: 10% (40K)*; 6% (60/70K)**  Water binding: 25 ml/g -- 4 - 6 h  Plasma expanding effect: * 180-200; ** 150%  Elimination:  metabolic  kidney
  • 31. 31 Hydroxyethylstrach  Molecular weight: 450K - 200K - 40K Dalton  Substitution: 0,5 - 0,62 - 0,7  Water binding: 15 - 20 ml/g -- 3 - 6 h  6% HES (200K/0,5) -- plasma substitution (100%)  10%HES (200K/0,5) -- plasma expanding (140%)  Elimination:  kidney  12 - 24 h (65 - 70 %) --- 168 h
  • 32. 32 Inotropic drugs Inotropie Heart rate SVR Kidney Blood flow Cornarry Blood flow Cardiac Output Dose Epinephrin ++ + + - + + 10-30 mcg/min Norepinephrin ++ 0 ++ -- + + 2-8 mcg/min Dopamin ++ + - ++ + ++ 2-5 mcg/min/kg Dobutamin +++ (+) -- + + ++ 5-15 mcg/min/kg Isoproterenol ++ ++ - + + ++ 5 mcg/mi Amrinon +++ 0 -- + + ++ Bolus 0.5 - 1.5 mg/kg Cont.: 2 to 10 mcg/kg/min
  • 33. 33 Reference Resource Joynt, Gavin (April 2003). "Introduction to management of shock for junior ICU trainees and medical students". The Chinese University of Hong Kong. Retrieved on 9 October, 2006.