What does cardiac output determine?
Blood pressure, hence tissue perfusion
How is cardiac output calculated?
Heart rate x stroke volume
What can control of cardiac output be divided into?
- Intracardiac
- Extracardiac
What does the intracardiac mechanism of controlling CO depend on?
Physical properties of the cardiac muscle
What happens when the cardiac muscle fibres are stretched?
They respond with more forceful contraction until the sarcomeres become overstretched
What is the relationship between cardiac muscle fibres stretching and contraction described by?
The Frank-Starling curve
What initially happens in the Frank-Starling curve?
Increases in ventricular end-diastolic volume result in an increase in stroke volume, and hence cardiac output
What is the increase in cardiac output with increased ventricular end-diastolic volume the rationale for?
Volume resuscitation in shock
What happens to the Frank-Starling curve as there is stretching beyond the optimal sarcomere length?
There is reduction in stroke volume
What is the clinical relevance of stroke volume decreasing as sarcomeres become overstretched?
It means that excessive volume resuscitation has a negative effect
What does the intracardiac mechanism of control of cardiac output ensure?
The right and left ventricles perform equally, and fluid does not accumulate in the lungs
What is the extracardiac mechanism of control of cardiac output?
The autonomous nervous system
What effect does the SNS have on cardiac output?
Increases heart rate and contractility, increasing CO
What effect does the PNS have on CO?
Reduces heart rate and contractility, reducing CO
How does the SNS increase cardiac output?
The SNS causes a release of adrenaline from the adrenal glands, and noradrenaline from sympathetic nerve fibres innervating the heart and blood vessels. This causes vasoconstriction of arterioles and veins, and increase heart rate and contractility via stimulation of alpha and beta adrenergic receptors
How does the parasympathetic nervous system affect CO?
Fibres innervate the blood vessels of the head, viscera, and heart. They release ACh, which causes vasodilation and reduction in heart rate and contractility via muscarinic M3 and M2 receptors respectively.
Where are baroreceptors located?
In the carotid sinus and aortic arch
What do baroreceptors respond to?
Stretch
Where do baroreceptors send impulses to?
They send impulses to the autonomic vasomotor centre in the brainstem
What does baroreceptor stimulation result in?
Vasoconstriction and and increases in HR, BP, and CO
Via what system do baroreceptors lead to an increase in HR, BP, and CO?
The SNS
Where are chemoreceptors located?
Carotid body and aortic arch
What do chemoreceptors respond to?
- Hypoxaemia
- CO2
- Acidosis
What do chemoreceptors stimulate?
- Vasoconstrictor response
- Respiratory rate
What does chemoreceptor stimulation of the vasoconstrictor response result in?
Increase in arterial pressure
What does chemoreceptor stimulation of the respiratory rate result in?
Provides respiratory compensation of metabolic acidosis
What is the vasomotor centre?
An intense controller of BP
When is the strongest response by the vasomotor centre seen?
When it is subjected to ischaemia, i.e. cerebral ischaemia
What secretes renin?
The juxtaglomerular cells of the kidney
When is renin secreted?
In response to a fall in BP
What does renin do?
Converts angiotensinogen to angiotensin I in the plasma
What happens to angiotensin I?
It is converted to angiotensin II in the lung
What is the effect of angiotensin II?
- Vasoconstrictor
- Causes kidney to retain salt and water
How does angiotensin II cause the kidney to retain salt and water?
It stimulates the adrenal to secrete aldosterone, causing more salt and water retention
Where is aldosterone secreted from?
Adrenal cortex
How long does aldosterone take to be stimulated?
2-3 hours
How long does aldosterone take to reach peak effect?
Almost a week
Where is ADH secreted?
Hypothalamus
What is ADH secreted in response to?
Reduced atrial stretch receptor response
What does ADH act on?
Kidney
What does ADH action on the kidney do?
Promotes water reabsorption
What effect does ADH have in high concentrations?
Causes strong vasoconstriction
What is ADH also known as?
Vasopressin
What does the atrial stretch receptor produce?
Atrial natriuretic peptide (ANP)
What does ANP do?
Promote salt and water excretion, and counteracts effects of aldosterone and ADH
What is shock?
A clinical syndrome of inadequate tissue perfusion
What is the physiological description of shock?
When DO2 (delivery of oxygen) is less than VO2 (tissue uptake of oxygen)
How is delivery of oxygen calculated?
Cardiac output x arterial oxygen content
How is arterial oxygen content calculated?
Oxyhaemoglobin + dissolved oxygen
What is HR influenced by?
- Drugs
- Conduction system
What is stroke volume influenced by?
Ventricular compliance
What is ventricular compliance influenced by?
- End diastolic volume
- End systoliv volume
What is end diastolic volume influenced by?
- CVP
- Venous volume
- Venous tone
What is contractility influenced by?
- Metabolic milieu
- Ions
- Acid base
- Temperature
- Drugs
- Toxins
- Afterload
- Temperature
- Drugs
- Blockers
- Competitors
- Autonomic tone
What is the final pathway in shock?
A state of acute cellular oxygen deficiency
What does the acute cellular oxygen deficiency in the end stages of shock lead to?
Anaerobic metabolism and tissue acidosis
What does anaerobic metabolism and tissue acidosis in shock culminate in?
- Loss of normal cellular function
- Cell death
- Organ dysfunction
- Death
What are the types of shock?
- Hypovolaemic
- Cardiogenic
- Distributive
- Obstructive
- Dissociative
What is the problem in distributive shock
Abnormalities of vessels
What is the problem in dissociative shock?
Inadequate oxygen releasing capacity of the blood
Give 7 causes of hypovolaemic shock?
- Haemorrhage
- Gastroenteritis
- Stomal losses
- Intussusception
- Volvulus
- Burns
- Peritonitis
Give 4 causes of distributive shock?
- Sepsis
- Anaphylaxis
- Vasodilating drugs
- Spinal cord injury
Give 5 causes of cardiogenic shock
- Arrhythmias
- Cardiomyopathy
- Heart failure
- Valvular disease
- Myocardial contraction
Give 6 causes of obstructive shock
- Congenital cardiac
- Tension pneumothorax
- Haemopneumothorax
- Flail chest
- Cardiac tamponade
- Pulmonary embolism
Give 3 causes of dissociative shock
- Profound anaemia
- Carbon monoxide poisoning
- Methaemoglobinaemia
What is the problem with categorising shock?
In many cases, several mechanisms may coexist
What are the stages of shock?
- Compensated
- Uncompensated
- Irreversible
What is compensated shock?
When vital organ function is maintained
What are the clinical signs of compensated shock?
- Mild agitation
- Skin pallor
- Increased HR
- Cold peripheral skin with decreased CRT
- Reduced urine output
How is compensation achieved in shock?
The SNS increases systemic arterial resistance, diverts blood away from non-essential tissues, constricts the venous reservoir, and increases HR to maintain CO
What happens to the systolic BP in compensated shock?
It remains normal
How is BP maintained in compensated shock?
Increased secretion of angiotensin and vasopressin causes the kidneys to conserve water and salt
Why is urine output reduced in compensated shock?
Reduced renal perfusion leads to reduced urine output
What happens in uncompensated shock?
Microvascular perfusion is impaired, organ and cellular function deteriorate and anaerobic metabolism becomes the major source of energy
What does anaerobic metabolism produce?
Lactate
What does the lactate produced in anaerobic metabolism cause?
Lactic acidosis
What effect does the acidosis have in uncompensated shock?
- Reduces myocardial contractility
- Impairs response to circulating catecholamines
Is shock reversible at the uncompensated stage?
Yes, if recognised
What happens to the BP in uncompensated shock?
Normal or low
How does uncompensated shock present?
- Tachycardia
- Prolonged CRT
- Cold peripheries
- Acidotic breathing
- Depressed mental state
- Reduced urine output
What is irreversible shock?
Tissue damage has already occurred, and even if cardiovascular pathology is restored, the patient will still develop multiple organ failure and die
What is the most common cause of shock in children?
Sepsis
What is the clinical relevance of sepsis being the most common cause of shock in children?
Unless an alternative diagnosis is obvious, broad spectrum antibiotics should be given ASAP (ideally after doing blood culture)
What is the antibiotic of choice for community acquired sepsis of unknown origin outside the neonatal period?
Third generation cephaloporins e.g. ceftriaxone
Why are third generation cephalosporins e.g. ceftriaxone the antibiotics of choice in community-acquired sepsis of unknown origin?
- Cover the most frequently encountered organisms in the UK, including pneumococcus and meningococcus
- Have good penetration of the blood-brain barrier
- Can be used to treat both meningitis and septicaemia
What may be needed to treat hypovolaemia in sepsis?
Fluid resuscitation
What may be needed to treat myocardial depression in shock?
Inotropes
What may be needed to treat inappropriate vasodilation in shock?
Vasopressors
How should exsanguinating haemorrhage in trauma be treated?
- Urgent replacement of circulating volume with blood and plasma
- Surgical management of bleeding
How should cardiogenic shock be managed in terms of fluid resuscitation?
Some fluid resuscitation may be needed, but fluid should be given judiciously
What may be required alongside fluid resuscitation in the management of cardiogenic shock?
Inotopic support
How should shock caused by arrhythmias be treated?
Drugs or DC cardioversion
What must be considered as a potential cause in cardiogenic shock in the neonatal period?
Duct dependent congenital cardiac lesions
What should be done in cardiogenic shock caused by duct dependent congenital cardiac lesions?
Consider prostaglandin to maintain ductal patency
How should shock caused by anaphylaxis be managed?
- IM adrenaline
- Antihistamines
- Steroids
What is the problem with targeted management of shock?
It may be difficult to distinguish the underlying cause at the point of presentation
What should the priority be in the management of shock at initial presentation?
Physiological goals to maximise tissue oxygenation
How can oxygen delivery be increased in shock?
- Supplemental oxygen therapy
- Blood transfusion to maintain haemoglobin concentration within physiological range
- Optimisation of cardiac preload with fluid therapy
- Optimisation of cardiac pump function with inotropes
How can oxygen demand be decreased in shock?
- Intubation and mechanical ventilation to avoid work of breathing
- Maintenance of normotherapy
- Treating underlying cause of the problem
How much fluid is given in resuscitation in shock?
20mg/kg bolus
What kind of fluid in resuscitation in shock?
Crystalloid
By what route can fluid resuscitation be given in shock?
IV or IO
How much fluid resuscitation may be needed in the first 24-48 hours in sepsis?
Up to 200ml/kg
What situations require cautious fluid resuscitation?
- Cardiogenic shock
- Raised ICP
How much fluid should be given in boluses in situations that require cautious fluid resuscitation? Q
10ml/kg
Why is cautious fluid resuscitation required in raised ICP?
Hypotension is detrimental for cerebral perfusion, but excessive fluids may be cerebral oedema
What should be looked for after each fluid bolus to show improvement?
- Fall in HR
- Improvement in skin perfusion and urine output
- Improved conscious level
- Increase in BP
- Improvement in metabolic acidosis and lactate
How should renal perfusion be monitored?
Urinary catheter and measurement of hourly urine output
What is considered to be ‘fluid refractory shock’?
Signs of ongoing shock after receiving more than 40-60ml/kg
What should be considered in patients with fluid refractory shock?
- Intubation and mechanical ventilation
- Starting inotropes
How does intubation and ventilation help in fluid refractory shock?
- Mechanical ventilation, sedation, and paralysis decrease tissue oxygen uptake
- Allow delivery of adequate concentrations of oxygen
- Reduce pulmonary oedema
- Facilitate placement of arterial and central venous catheters
What inotropes are commonly used in paediatric critical care?
- Noradrenaline
- Adrenaline
- Dopamine
- Dobutamine
- Milrionone
What is the mechanism of action of noradrenaline?
Alpha-adrenergic receptor agonist
What is the action of noradrenaline?
Increases SVR
What is the dose of adrenaline?
0.05-1.0µg/kg/min
What is the mechanism of action of adrenaline?
Alpha/beta adrenergic receptor agonist
What is the action of adrenaline?
Increases HR, SVR, contractility
What is the dose of adrenaline?
0.05-1.5µg/kg/min
What is the mechanism of action of dopamine?
DA (dopamine) receptor, alpha/beta adrenergic receptor agonist
What is the action of low dose dopamine?
Increases renal and splanchnic blood flow
What is ‘low dose’ dopamine?
2-5µg/kg/min
Through what receptor dose low dose dopamine exert its actions?
Dopamine
What is the action of medium dose dopamine?
Increases HR
What is ‘medium dose’ dopamine?
5-12µg/kg/min
Through what receptor does medium dose dopamine exert its actions?
Beta
What is the action of high dose dopamine?
Increases SVR
What is ‘high dose’ dopamine?
12-20µg/kg/min
Through what receptor does high dose dopamine exert its actions?
Alpha
What is the mechanism of action of dobutamine?
Beta adrenergic receptor agonist
What is the action of dobutamine?
- Increases contractility
- May reduced SVR
What is the dose of dobutamine?
1-20µg/kg/min
What is the mechanism of action of milrinone?
- Phosphodiesterase 3 inhibitor in cardiac myocytes and vascular smooth muscle
- Increases intracellular calcium
What is the action of milrinone?
Increases contractility and vasodilator
What is the dose of milrinone?
0.3-1µg/kg/min
What inotrope is usually given initially in fluid refractory shock?
Dopamine
Can dopamine be given via a peripheral IV catheter?
Yes
What is ‘cold shock’?
When myocardial depression and vasoconstriction predominate
What inotrope can be given in addition to dopamine in cold shock?
Adrenaline
What other inotrope may be useful in cold shock?
Milrinone
What is warm shock?
When vasodilation is the predominant cardiovascular response
What inotrope may be useful in addition to dopamine in warm shock?
Noradrenaline
What is ‘goal directed therapy’ in septic shock?
Optimisation of preload by titrating fluid bolus therapy to a CVP of 8-12mmHg, and aiming for a normal arterial pressure for age, urine output of >0.5ml/kg/hour, and central venous (superior vena cava) or mixed venous oxygen saturation of 70% or greater
What does central venous oxygen saturation reflect?
Tissue uptake of oxygen from arterial blood into tissues
What are central venous oxygen saturation values of <70% suggestive of?
Inadequate oxygen delivery and excessive oxygen uptake, which are the hallmarks of the shock state
Is goal directed therapy in septic shock proven to work?
No
When might ECMO be useful in shock?
In some cases, particularly cardiomyopathy and myocarditis
What is the clinical relevance of delivery of oxygen to the tissues being critically dependent on cardiac output and arterial oxygen concentration?
Therapies designed to treat shock aim to improve these factors via a variety of different mechanism
What factors influence the oxygenation of blood?
- A-a gradient
- DPG
- Acid base balance
- Blockers
- Competitors
- Temperature
