By the end of this module you should:
1. Know the definition of shock and its types.
2. Know the basics of CVS physiology and the pathophysiology of shock.
3. Be able to apply your knowledge of pathophysiology to explain common symptoms and signs of shock.
4. Have the theoretic background to enable you to make informed decisions when managing shock.
5. Understand the mode of action and indications for commonly used inotropes/vasopressors.
There are many physiological pathways and mechanisms that regulate the cardiovascular system. One of the most important of these is the autonomic nervous system. The sympathetic outflow originates from preganglionic neurons located in the lateral horns of the spinal cord (T1-L2). These neurons connect through synapses to postganglionic neurons. These synapses are located in the two sympathetic chains that lie on either side of the vertebral column. The postganglionic neurons form the sympathetic nerves supply the effector organs.
The vagus nerve supplies the only important parasympathetic nerve fibres to the cardiovascular system. Parasympathetic ganglia are embedded in the heart, mainly on the SA and AV nodes. Postganglionic parasympathetic fibres are very short.
ß2 receptors are present on other organs, stimulation causes relaxation e.g. of bronchial and uterine smooth muscle.
Noradrenaline (norepinephrine) is the sympathetic neurotransmitter in the effector organs. It is released from postganglionic fibres and activates both α and ß receptors.
Adrenaline (epinephrine) also activates the sympathetic receptors. It is synthesised in the adrenal glands and reaches the sympathetic receptors via the circulation, figure 1.
Figure 1. Summary of effects of sympathetic nervous system on the cardiovascular system.
Drugs that activate the sympathetic receptors, hence mimicking the activity of the sympathetic nervous system, are called sympathomimetics.
The neurotransmitter for the parasympathetic system is acetylcholine. This activates two types of acetylcholine receptors, nicotinic and muscarinic receptors. The receptors on effector organs are of the muscarinic type.
The neurotransmitter in sympathetic and parasympathetic ganglia is acetylcholine and the receptors are of the nicotinic variety.
Shock is a serious, often life-threatening condition which merits prompt intervention. It can be defined as circulatory insufficiency with inadequate oxygen delivery resulting in hypoperfusion and tissue hypoxia
In order to understand the pathophysiology, and the subsequent management, of shock two physiological equations are extremely useful (A + B).
(A) Blood pressure (BP) = Cardiac output (CO) X systemic vascular resistance (SVR)
This informs us that in order to maintain an adequate perfusion pressure (BP) we need an adequate flow of blood (CO) and adequate vascular tone (SVR). A useful analogy for this is to consider the pressure generated from water flowing through a pipe. One can increase the pressure in the pipe (analogous to the BP) by one of two ways:
(i) increasing the flow of water through the pipe (increasing the CO).
(ii) maintaining the same flow but increasing the resistance to flow by decreasing the pipe diameter (increasing the SVR through vasoconstriction).
We can therefore see that hypotension (and resultant hypoperfusion) can be caused by either a low cardiac output (cardiogenic shock, outflow obstruction, hypovolaemic shock) or a low SVR (neurogenic or septic shock) or both (septic shock).
For low cardiac output states we must also remember that:
CO = Stroke volume (SV) x Heart rate (HR).
Heart rate is easy to measure, stroke volume is not. However we can consider the variables that determine stroke volume:
1. Pre-load: If we have two identical elastic bands and fire the first one at the wall, how do we make the second one hit the wall harder? We pull it back more before releasing. I.e. the more we stretch it the more “ping” we achieve. The heart muscle is very similar. The more we stretch it the more it pings back. How do we stretch the heart muscle? We increase end-diastolic volume by filling the heart. This will lead to an increase in the stroke volume, see figure 2.
Figure 2. The Starling curve.
In the critically ill patient, low pre-load from either hypovolaemia or relative hypovolaemia is probably the most common cause of a low SV and subsequent low CO and reduced perfusion. Fortunately, it can normally be easily rectified by fluid resuscitation. The hypovolaemic patient will attempt to maintain CO and perfusion by mounting a tachycardia. You’ll also see from figure 2 that it is possible to over stretch the heart. This is why reducing preload (and/or afterload) with vasodilators or diuretics in patients with heart failure improves myocardial function.
2. Contractility: Going back to elastic bands, if we have a range of elastic bands to fire at the wall but can only pull them back a fixed distance how can we pick an elastic band that will hit the wall harder? We pick a thicker one. This will give us more “ping” per unit stretch. In the heart this can be achieved by administration of an inotrope. The effect of an inotrope on the Starling curve is demonstrated in figure 3.
Figure 3. The Starling curve. Effect of inotropes on contractility and stroke volume.
We can see that an inotrope generates a greater SV for a given preload. One important point to note is that an inotrope is more effective with an adequately filled heart giving substance to the statement that “a sick heart has as much right to be full as a healthy one”.
3. After load: If you fire an elastic band through air it will hit the wall harder than if fired through water. A high SVR will tend to reduce CO. This has further implications as we will see later.
However, one must also remember that perfusion pressure (BP) is not the only important factor in ensuring adequate oxygen delivery. In order to understand why an “adequate” BP is not always reassuring we must look at a second equation.
Oxygen Delivery = Blood flow X oxygen content of blood
In other words:
DO2 = CO X [oxygen content]
(B) DO2 = CO X ([Hb x arterial oxygen saturations x constant] + a small amount dissolved in plasma)
Here we see that oxygen delivery is dependant on blood flow NOT pressure. We can now look back at equation A and see that it could be possible to be in a situation where the blood pressure was in the normal range but this was generated by an extremely high SVR and very low CO. Although “perfusion” pressure was adequate a low CO would result in very low oxygen delivery (see B) and tissue hypoxia.
You can be shocked with a “normal” blood pressure.
We will come back to these formulae when we consider diagnosis and treatment.
Inadequate circulation volume. The most common causes of this type of shock being any cause of fluid loss; haemorrhage, salt and water loss, sepsis, burns, etc.
A poor venous return to the heart will decrease the stroke volume and cardiac output (see Starling curve on previous page). The patient will attempt to compensate by tachycardia and increased systemic vascular resistance (SVR). They become cold peripherally (shut down).
Figure 4. Pathophysiological changes in hypovolaemic shock.
Pump failure. The patient will have a poor cardiac output and will therefore attempt to maintain a blood pressure by increasing SVR. Blood pressure can be low, normal or high, but organ perfusion is compromised, peripheries are cold and the patient is prone to pulmonary oedema.
Early echocardiography is important to assess contractility, valve function and exclude significant pericardial effusion.
Figure 5. Pathophysiological changes in cardiogenic shock.
Peripheral vasodilatation and subsequent maldistribution of blood flow. This leads to a relative hypovolaemia. (There is more space in which to put the same volume of fluid). Common examples of this type being septic, anaphylactic and neurogenic shock.
Septic shock is the commonest of these you will see in the ICU and frequently includes vasodilatation, high cardiac output, and loss of intravascular volume due to ‘leaky capillaries’. The patient may start with a low cardiac output due to the leaky capillaries with loss of fluid and because the vasodilated arterial tree requires a larger blood volume to fill it (relative hypovolaemia).
With appropriate fluid volume replacement the heart will pump against lower resistance and therefore there will often be an increase in cardiac output in order to compensate for the reduction in SVR. The patient may remain hypotensive but will have warm peripheries and a bounding pulse. The bounding pulse is a reflection of the wide pulse pressure which is due to a low diastolic pressure. However it is possible, due to toxins and acidosis, for sepsis to have a negative inotropic affect on the heart as well as causing vasodilatation and the patient can therefore have a low cardiac output and a low SVR.
Neurogenic shock occurs when there is damage to the spinal cord and a subsequent loss of the sympathetic tone. Features of this shock are hypotension, bradycardia, warm peripheries, venous pooling and sometimes priapism. Seek senior help if this type of shock is suspected. Please note that bradycardia is an important feature of this shock; if hypotension and tachycardia are present, e.g. in an RTA victim, look for other causes of shock like external or internal haemorrhage.
Figure 6. Pathophysiological changes in distributive shock.
Caused by extra-cardiac obstruction to blood flow. For example, in pulmonary embolism, aortic stenosis, pericardial effusion and tension pneumothorax.
As a result of the low cardiac output the patient will be tachycardic and have an increase in SVR to compensate. The patient becomes cold and shut down. They may demonstrate raised JVP and venous congestion of the face and body due to the obstruction.
Figure 7. Pathophysiological changes in obstructive shock.
Inotropes are drugs that increase contractility of the heart, while vasopressors are drugs that lead to vasoconstriction. These drugs are sometimes used in combination to achieve an improvement in contractility and vasoconstriction (increase in SVR).
All of these drugs should be infused centrally through a dedicated port. They should be given centrally because they are irritant drugs and extravasation can cause skin necrosis. They should be given through a dedicated port because these are very potent drugs and should never be given as a bolus (unless patient in cardiac arrest, in which case adrenaline 1 mg should be given as per ALS guidelines).
Acts on both ß and α adrenoreceptors. In a low dose infusion the ß effects predominate, leading to an increase in heart rate, contractility and cardiac output. In high doses the α effects predominate, leading to vasoconstriction and an increase in blood pressure.
Disadvantages – excessive tachycardia, dysrhythmias, myocardial ischaemia, hyperglycaemia, lactic acidosis (which is usually transient).
Uses – as a positive inotrope to increase cardiac output and provide vasoconstriction at higher doses. Due to its dual action it is sometimes used in the moribund shocked patient until further investigations/monitoring ascertain the cause of shock.
It has a role in anaphylaxis due to its ability to stabilise mast cells and prevent further histamine release as well as treat hypotension.
Concentration – There are many ways to prepare all inotropes and each unit will have a agreed policy which must be followed carefully due to the high potency of these drugs.
If you want to establish an average (50-100 Kg) adult patient on adrenaline and do not have access to your local policy, then dilute 3mg of adrenaline in 50ml of saline and start an infusion at 5ml/hr. You should notice an effect within a few minutes. Then change rate to achieve target BP or cardiac output.
All inotropes/vasopressors work within 1-2 minutes and their effect wears off within minutes.
Acts mainly on α1 receptors causing vasoconstriction and increasing SVR. This leads to an increase in the BP (perfusion pressure) which leads to an improvement in organ perfusion (provided the patient is adequately fluid resuscitated). It also acts on ß1receptors causing an increase in contractility and heart rate.
Disadvantages – excessive vasoconstriction seen as blue/ black peripheries, dysrhythmias, myocardial ischaemia.
Uses – it is many intensivists’ drug of choice for improvement of BP in septic shock. Used in neuro ICU patients to increase BP to maintain cerebral perfusion pressure.
Stimulates α, ß, and dopamine receptors to varying degrees. It is therefore a non specific inotrope/vasopressor that can be used to increase cardiac output and SVR.
Disadvantages – excessive tachycardia and dysrhythmias
Uses – as a positive inotrope to increase cardiac output and provide vasoconstriction at higher doses. Used in septic shock in some centres.
Note: there is no role for “renal dose” dopamine in modern intensive care medicine.
Mainly acts on the ß receptors leading to an increase in heart rate and contractility together with vasodilatation mediated via the ß2 receptors. The net effect is an increase in cardiac output.
Disadvantages – hypotension, tachycardia
Uses – low cardiac output states especially cardiogenic shock.
Is a nitrate vasodilator that is commonly used in cardiogenic shock. In a low dose it acts as a venodilator, thus offloading the heart and reducing preload. In higher doses it acts as an arterial dilator, thus reducing afterload. The net effect is to improve the function of the myocardium and cardiac output by reducing both preload and afterload.
It also causes relaxation of the coronary arteries and is therefore useful in angina.
Further information on inotropes is available from the following website:
Inotropes/vasopressors to treat shock, should only be considered after adequate fluid resuscitation.
The administration of inotropes/vasopressors to a patient who is under filled is not only futile, but is potentially harmful.
After adequate fluid resuscitation:
For shock of unknown cause use adrenaline.
For septic shock use noradrenaline.
For cardiogenic shock use dobutamine.
Inotropes/vasopressors are very potent and potentially lethal drugs.
You should not use these drugs if you are unfamiliar with them.
You should NEVER administer these drugs as a bolus, with the exception of adrenaline in a cardiac arrest situation.
You should infuse them through a central line via a dedicated port.
Make sure you adhere to the local policy for dilution in your unit.
If in doubt ask a senior member fob your team.
When we attempt to diagnose shock what we are really looking for are signs of failing organs due to inadequate perfusion. In other words, organ dysfunction. We can start this process from the end of the bed.
Respiratory rate: Tissue hypoxia will result in a metabolic acidosis. This will normally stimulate hyperventilation to create a compensatory respiratory alkalosis. If the respiratory rate is normal and there are no signs of respiratory distress (or other factors that could compromise the hyperventilatory response like head injury or opiates) then tissue hypoperfusion will be less likely.
On the flip site of this, a patient with a high respiratory rate does not necessarily have a respiratory problem (which is often the first assumption made in clinical practice). It may merely be a sign of metabolic distress and respiratory compensation.
Level of consciousness: If the patient is awake and lucid then brain function is probably OK suggesting adequate brain perfusion and oxygen delivery.
Skin colour: Pink would be reassuring, grey or mottled would be less so, suggesting poor perfusion.
We can then go onto gain information from touching the patient:
Peripheral temperature: If the patient is peripherally warm it would tend to suggest that skin perfusion is adequate and that marked vasoconstriction was absent. This would be reassuring. Capillary refill of less than 2 seconds would provide similar reassurance. As with all these signs, this should not be used in isolation. A patient with septic shock may well have warm peripheries.
Heart Rate: Tachycardia may signify an attempt to maintain CO in the face of decreasing SV.
Then we can look at other things:
Urine output: A healthy urine output of >0.5ml/kg/hr suggests adequate renal perfusion. It is a late sign of shock and can take some time to improve even after adequate resuscitation.
Blood pressure: Commonly measured before all the indices above but as we have seen, not necessarily always reassuring in isolation.
So, if the patient is alert, looks a normal colour, has a normal respiratory rate, is warm peripherally, has a normal heart rate and is passing adequate amounts of urine their oxygen delivery is most probably adequate and shock unlikely. If one or more of these signs are present then it is safer to assume shock than ignore it.
If suspicious, the next steps would be to observe closely for further deterioration and hunt for more evidence of inadequate perfusion. An excellent “next step” investigation would be to perform an arterial blood gas (ABG) looking for a metabolic acidosis (even better if the ABG included a lactate). A metabolic, and particularly a lactic acidosis would provide further evidence of organ failure and inadequate oxygenation. Making a diagnosis early is vital for survival. Indifying the source of sepsis, for example, allow early treatment with appropriate emperic antibiotics or source control (e.g. incision of abscess, debridement of infected tissues).
Classically there are 4 stages of shock:
1. Initial: Hypoperfusion causes hypoxia. This leads to mitochondrial dysfunction. The cells become leaky and switch to anaerobic metabolism. This switch produces lactic acid and a resultant metabolic acidosis.
2. Compensatory: During this phase the body employs several mechanisms in an attempt to correct the metabolic upset of shock:
3. Progressive: The mechanisms listed above can only compensate for worsening shock for so long. Eventually they will begin to fail. At this point cellular dysfunction begins to spiral out of control, metabolic acidosis worsens and the arteriolar and precapillary sphincters constrict such that blood remains in the capillaries. The pressure within the capillaries will increase. This, combined with membrane dysfunction, will lead to fluid loss into the extravascular interstitial spaces. This will further worsen the intravascular volume status.
4. Refractory: At this stage organs fail and the shock can no longer be reversed. Death normally occurs rapidly.
When shock is present, tissue oxygen demand is higher than oxygen delivery. The management of shock therefore, aims at improving oxygen delivery and reducing oxygen demand.
These should be done at the same time as trying to provide definitive treatment of the underlying cause, e.g. thrombolysis of massive pulmonary embolism or laporotomy for perforated large bowel.
It is also important to appreciate that the worse the degree of shock, the quicker we have to act to improve the situation.
The basis of managing the shocked patient is similar to the approach to any sick patient – ABCDE.
By ensuring a patent airway, adequate breathing and oxygenation, and optimising cardiovascular performance one would hope to avoid shock, stop its progression or reverse it. Once we have diagnosed shock clinically, the exact cause of shock is not vital to determine in the initial stages. More important is to embark on a generic “shocked” patient treatment pathway that will ensure prompt reversal of the shocked state.
Lets go back to formula A & B:
DO2 = CO x ([Hb x saturations x constant]
If oxygen delivery is failing then this can really only be due to one or more of three things:
The management of shock starts with ensuring a patent Airway and adequate Breathing to ensure optimum oxygenation.
BP = CO x SVR
We must also optimise perfusion pressure. This we can do by ensuring adequate CO as above and SVR. Sepsis is probably the most common shocked state with a low SVR. Noradrenaline is frequently used to increase SVR and maintain an adequate BP.
A useful word of caution regarding noradrenaline: Noradrenaline has become the first line drug for hypotension in many ICUs. One has to remember that it is not an inotrope but a vasopressor. It will increase the SVR generating a “normal” blood pressure, but this may be at the expense of increasing after load and reducing the CO and hence oxygen delivery. A great example of a “normal” blood pressure being misleading and flow being equally important to pressure.
2) Reducing oxygen consumption
Another important strategy to address the imbalance in oxygen demand and delivery which is present in shock, is to reduce oxygen consumption. E.g. a patient who suffers cardiogenic shock immediately after an MI. Here intubation and ventilation might form part of the management strategy, as this reduces work of breathing (which can be significant) and therefore oxygen consumption.
Adequate sedation, especially if the patient is agitated, is another way to reduce oxygen consumption.
Figure 8. Management of shock.
|Optimise oxygenation by ensuring patent Airway and adequate Breathing of high oxygen concentration and flow|
|Replace Hb if low|
|Use vasopressors to improve BP e.g. septic shock|
|Use inotrope to improve contractility if required e.g. dobutamine for cardiogenic shock|
|Adrenaline is a vasopressor and inotrope and can be used if cause of shock is unknown|
|Vasodilators are also used to reduce afterload and offload the heart in cardiogenic shock|
|Reduce oxygen demand|
|Call for HELP sooner rather than later if you are unsure|
|Adhere to you local ICU policy for inotrope/vasopressor dilutions|
The bleeding patient: Acute blood loss leads to a loss of circulating volume. This will reduce venous return and therefore end-diastolic volume (pre-load). The Starling curve then dictates that the patient will move from right to left with a resultant drop in SV.
The Starling curve
The patient will attempt to compensate for this. The priorities is to maintain oxygen delivery and perfusion pressure.
To maintain flow the patient must maintain CO.
CO = HR x SV
As SV is dropping due to volume loss the only way to maintain CO is to increase the HR.
To maintain perfusion pressure the patient must maintain flow (as above) and resistance (vascular tone).
As CO will tend to fall as the HR compensation reaches its maximum the only way then to maintain BP is to increase SVR. This will result in peripheral vasoconstriction; cold peripheries.
So the bleeding patient will become tachycardic with cold peripheries! The other signs of increased respiratory rate, decreased urine output, grey skin colour, confusion will also become apparent if the problem is not corrected.
To reverse these effects we need to restore normal physiology. Fluid will increase pre-load, move us back towards the right of the Starling curve, SV will therefore increase. If the SV increases we will need less of a HR to maintain a similar CO. HR will therefore decrease (a good marker of improving volume status), Fig 8.
Of course giving fluid other than blood may increase flow but it will not increase oxygen carrying capacity. If a large amount of fluid is required (normally greater than 30% circulating volume) one should consider administering blood to maintain oxygen carrying capacity.
As CO improves, BP will be maintained with a lesser SVR. The patient will become warmer peripherally. In fact it is often useful to document at which point the patient becomes peripherally warm before you start resuscitation (wrist, elbow, mid humerus, shoulder). The improvement in this point can be used as a useful yardstick of adequate resuscitation.
Oxygen Delivery = CO x Oxygen content (Hb x SpO2 x c)
BP = CO x SVR