Recognition and diagnosis of critical illness

Early recognition and immediate resuscitation are fundamental to the successful management of the critically ill. In order to facilitate identification of ‘at risk’ patients on the ward and early referral to the critical care emergency or outreach team a number of early warning systems have been devised (e.g. the Modified Early Warning Score, MEWS; see Box 16.1). These are based primarily on bedside recognition of deteriorating physiological variables and can be used to supplement clinical intuition. A MEWS score of ≥5 is associated with an increased risk of death and warrants immediate admission to ICU. Another example of a system used to trigger referral to a Medical Emergency Team (MET) is also shown in Box 16.1 (see also ‘Management of shock and sepsis’ and ‘Clinical assessment of respiratory failure’, below).

In some of the most seriously ill patients, the precise underlying diagnosis is initially unclear but in all cases, the immediate objective is to preserve life and prevent, reverse or minimize damage to vital organs such as the lungs, brain, kidneys and liver. This involves a rapid assessment of the physiological derangement followed by prompt institution of measures to support cardiovascular and respiratory function in order to restore perfusion of vital organs, improve delivery of oxygen to the tissues and encourage the removal of carbon dioxide and other waste products of metabolism (following the ABC approach: Airway, Breathing, Circulation, see Fig. 16.25, below). The patient’s condition and response to treatment should be closely monitored throughout. The underlying diagnosis may only become clear as the results of investigations become available, a more detailed history is obtained and a more thorough physical examination is performed. In practice resuscitation, assessment and diagnosis usually proceed in parallel.

Critically ill patients require multidisciplinary care with:

Discharge of patients from intensive care should normally be planned in advance and should ideally take place during normal working hours. Planned discharge often involves a period in a ‘step-down’ intermediate care area. Premature or unplanned discharge, especially during the night, has been associated with higher hospital mortality rates. A summary including ‘points to review’ should be included in the clinical notes and there should be a detailed handover to the receiving team (medical and nursing). The intensive care team should continue to review the patient, who might deteriorate following discharge, on the ward and should be available at all times for advice on further management (e.g. tracheostomy care, nutritional support). In this way, deterioration and readmission to intensive care (which is associated with a particularly poor outcome) or even cardiorespiratory arrest might be avoided.

This chapter concentrates on cardiovascular and respiratory problems. Many patients also have failure of other organs such as the kidney and liver; treatment of these is dealt with in more detail in the relevant chapters.

Oxygen delivery and consumption

Oxygen delivery (DO₂) (Fig. 16.1) is defined as the total amount of oxygen delivered to the tissues per unit time. It is dependent on the volume of blood flowing through the microcirculation per minute (i.e. the total cardiac output, ) and the amount of oxygen contained in that blood (i.e. the arterial oxygen content, C_aO₂). Oxygen is transported both in combination with haemoglobin and dissolved in plasma. The amount combined with haemoglobin is determined by the oxygen capacity of haemoglobin (usually taken as 1.34 mL of oxygen per gram of haemoglobin) and its percentage saturation with oxygen (SO₂), while the volume dissolved in plasma depends on the partial pressure of oxygen (PO₂). Except when hyperbaric oxygen is administered, the amount of dissolved oxygen in plasma is insignificant.

Figure 16.1 Tissue oxygen delivery and consumption in a normal 70 kg person breathing air. Oxygen delivery (DO₂) = cardiac output × (haemoglobin concentration × oxygen saturation (S_aO₂) × 1.34). In normal adults, oxygen delivery is roughly 1000 mL/min, of which 250 mL is taken up by tissues. Mixed venous blood is thus 75% saturated with oxygen. , mixed venous oxygen content; , mixed venous oxygen saturation; CaO₂, arterial oxygen content.

Clinically, however, the utility of this global concept of oxygen delivery is limited because it fails to account for changes in the relative flow to individual organs and the distribution of flow through the microcirculation (i.e. the efficiency with which oxygen delivery is matched to the metabolic requirements of individual tissues or cells). Furthermore, some organs (such as the heart) have high oxygen requirements relative to their blood flow and will receive insufficient oxygen, even if the overall oxygen delivery is apparently adequate. Lastly, microcirculatory flow is influenced by blood viscosity.

Oxygenation of the blood

Oxyhaemoglobin dissociation curve

The saturation of haemoglobin with oxygen is determined by the partial pressure of oxygen (PO₂) in the blood, the relationship between the two being described by the oxyhaemoglobin dissociation curve (Fig. 16.2). The sigmoid shape of this curve is significant for a number of reasons:

Modest falls in the partial pressure of oxygen in the arterial blood (P_aO₂) may be tolerated (since oxygen content is relatively unaffected) provided that the percentage saturation remains above 92%.

Increasing the P_aO₂ to above normal has only a minimal effect on oxygen content unless hyperbaric oxygen is administered (when the amount of oxygen in solution in plasma becomes significant).

Once on the steep ‘slippery slope’ of the curve (percentage saturation below about 90%), a small decrease in P_aO₂ can cause large falls in oxygen content, whereas increasing P_aO₂ only slightly, e.g. by administering 28% oxygen to a patient with chronic obstructive pulmonary disease (COPD), can lead to a useful increase in oxygen saturation and content.

Figure 16.2 The oxyhaemoglobin dissociation curve. a, arterial point; v, venous point; x, arteriovenous oxygen content difference. HbO₂ (%) is the percentage saturation of haemoglobin with oxygen. The curve will move to the right in the presence of acidosis (metabolic or respiratory), pyrexia or an increased red cell 2,3-DPG concentration. For a given arteriovenous oxygen content difference, the mixed venous PO₂ will then be higher. Furthermore, if the mixed venous PO₂ is unchanged, the arteriovenous oxygen content difference increases and more oxygen is off-loaded to the tissues (see p. 374). P₅₀ (the PO₂ at which haemoglobin is half saturated with O₂) is a useful index of these shifts – the higher the P₅₀ (i.e. shift to the right), the lower the affinity of haemoglobin for O₂.

The P_aO₂ is in turn influenced by the alveolar oxygen tension (P_AO₂), the efficiency of pulmonary gas exchange, and the partial pressure of oxygen in mixed venous blood .

Alveolar oxygen tension (P_AO₂)

The partial pressures of inspired gases are shown in Figure 16.3. By the time the inspired gases reach the alveoli they are fully saturated with water vapour at body temperature (37°C), which has a partial pressure of 6.3 kPa (47 mmHg) and contain CO₂ at a partial pressure of approximately 5.3 kPa (40 mmHg); the P_AO₂ is thereby reduced to approximately 13.4 kPa (100 mmHg).

Figure 16.3 The composition of inspired and alveolar gas (partial pressures in kPa).

The clinician can influence P_AO₂ by administering oxygen or by increasing the barometric pressure.

Pulmonary gas exchange

In normal subjects there is a small alveolar-arterial oxygen difference (P_A–aO₂). This is due to:

a small (0.133 kPa, 1 mmHg) pressure gradient across the alveolar membrane

a small amount of blood (2% of total cardiac output) bypassing the lungs via the bronchial and thebesian veins

a small degree of ventilation/perfusion mismatch.

Pathologically, there are three possible causes of an increased P_A–aO₂ difference:

Diffusion defect. This is not a major cause of hypoxaemia even in conditions such as lung fibrosis, in which the alveolar-capillary membrane is considerably thickened. Carbon dioxide is also not affected, as it is more soluble than oxygen.

Right-to-left shunts. In certain congenital cardiac lesions or when a segment of lung is completely collapsed, a proportion of venous blood passes to the left side of the heart without taking part in gas exchange, causing arterial hypoxaemia. This hypoxaemia cannot be corrected by administering oxygen to increase the P_AO₂, because blood leaving normal alveoli is already fully saturated; further increases in PO₂ will not, therefore, significantly affect its oxygen content. On the other hand, because of the shape of the carbon dioxide dissociation curve (Fig. 16.4), the high PCO₂ of the shunted blood can be compensated for by over-ventilating patent alveoli, thus lowering the CO₂ content of the effluent blood. Indeed, many patients with acute right-to-left shunts hyperventilate in response to the hypoxia and/or to stimulation of mechanoreceptors in the lung, so that their P_aCO₂ is normal or low.

Ventilation/perfusion mismatch (see p. 796). Diseases of the lung parenchyma (e.g. pulmonary oedema, acute lung injury) result in mismatch, producing an increase in alveolar deadspace and hypoxaemia. The increased deadspace can be compensated for by increasing overall ventilation. In contrast to the hypoxia resulting from a true right-to-left shunt, that due to areas of low can be partially corrected by administering oxygen and thereby increasing the P_AO₂ even in poorly ventilated areas of lung.

Figure 16.4 The carbon dioxide dissociation curve. Note that in the physiological range the curve is essentially linear.

Mixed venous oxygen tension and saturation ()

The is the partial pressure of oxygen in pulmonary arterial blood that has been thoroughly mixed during its passage through the right heart. Assuming P_aO₂ remains constant, and will fall if more oxygen has to be extracted from each unit volume of blood arriving at the tissues. A low therefore indicates either that oxygen delivery has fallen or that tissue oxygen requirements have increased without a compensatory rise in cardiac output. If falls, the effect of a given degree of pulmonary shunting on arterial oxygenation will be exacerbated. Thus, worsening arterial hypoxaemia does not necessarily indicate a deterioration in pulmonary function but might instead reflect a fall in cardiac output and/or a rise in oxygen consumption.

Conversely, a rise in and may reflect impaired tissue oxygen extraction (due to microcirculatory dysfunction) and/or reduced oxygen utilization (e.g. due to mitochondrial dysfunction) as seen in severe sepsis (see below).

Monitoring the oxygen saturation in central venous (), rather than pulmonary artery blood is less invasive and has been shown to be a valuable guide to the resuscitation of critically ill patients (see p. 891).

Cardiac output

Cardiac output is the product of heart rate and stroke volume, and is affected by changes in either of these (see Fig. 16.5).

Figure 16.5 The determinants of cardiac output.

Stroke volume

The volume of blood ejected by the ventricle in a single contraction is the difference between the ventricular end-diastolic volume (VEDV) and end-systolic volume (VESV) (i.e. stroke volume = VEDV – VESV). The ejection fraction describes the stroke volume as a percentage of VEDV (i.e. ejection fraction = (VEDV − VESV)/VEDV × 100%) and is an indicator of myocardial performance.

Three interdependent factors determine the stroke volume (see p. 671).

Preload

This is defined as the tension of the myocardial fibres at the end of diastole, just before the onset of ventricular contraction, and is therefore related to the degree of stretch of the fibres. As the end-diastolic volume of the ventricle increases, tension in the myocardial fibres is increased and stroke volume rises (Fig. 16.6). Myocardial oxygen consumption () increases only slightly with an increase in preload (produced, for example, by a ‘fluid challenge’, see below) and this is therefore the most efficient way of improving cardiac output.

Figure 16.6 The Frank–Starling relationship: as preload is increased, stroke volume rises. If the ventricle is overstretched, stroke volume will fall (x). In myocardial failure, the curve is depressed and flattened. Increasing contractility, e.g. due to sympathetic stimulation, shifts the curve upwards and to the left (z).

Myocardial contractility

This refers to the ability of the heart to perform work, independent of changes in preload and afterload. The state of myocardial contractility determines the response of the ventricles to changes in preload and afterload. Contractility is often reduced in critically ill patients, as a result of either pre-existing myocardial damage (e.g. ischaemic heart disease), or the acute disease process itself (e.g. sepsis). Changes in myocardial contractility alter the slope and position of the Starling curve; worsening ventricular performance is manifested as a depressed, flattened curve (Fig. 16.6 and Fig. 14.5). Inotropic drugs can be used to increase myocardial contractility (see below).

Afterload

This is defined as the myocardial wall tension developed during systolic ejection. In the case of the left ventricle, the resistance imposed by the aortic valve, the peripheral vascular resistance and the elasticity of the major blood vessels are the major determinants of afterload. Ventricular wall tension will also be increased by ventricular dilatation, an increase in intraventricular pressure or a reduction in ventricular wall thickness.

Decreasing the afterload (exercise, sepsis, vasodilator agents) can increase the stroke volume achieved at a given preload (Fig. 16.7), while reducing . The reduction in wall tension also leads to an increase in coronary blood flow, thereby improving the myocardial oxygen supply/demand ratio. Excessive reductions in afterload will cause hypotension.

Figure 16.7 The effect of changes in afterload on the ventricular function curve. At any given preload, decreasing afterload increases the stroke volume.

Increasing the afterload (increased sympathetic activity, vasoconstrictor agents), on the other hand, can cause a fall in stroke volume and is a potent cause of increased . Right ventricular afterload is normally negligible because the resistance of the pulmonary circulation is very low but is increased in pulmonary hypertension.

Monitoring critically ill patients

As well as allowing immediate recognition of changes in the patient’s condition, monitoring can also be used to establish or confirm a diagnosis, to gauge the severity of the condition, to follow the evolution of the illness, to guide interventions and to assess the response to treatment. Invasive monitoring is generally indicated in the more seriously ill patients and in those who fail to respond to initial treatment. These techniques are, however, associated with a significant risk of complications, as well as additional costs and patient discomfort and should therefore only be used when the potential benefits outweigh the dangers. Likewise, invasive devices should be removed as soon as possible.

Blood pressure

Alterations in blood pressure are often interpreted as reflecting changes in cardiac output. However, if there is vasoconstriction with a high peripheral resistance, the blood pressure may be normal, even when the cardiac output is reduced. Conversely, the vasodilated patient may be hypotensive, despite a very high cardiac output.

Hypotension jeopardizes perfusion of vital organs. The adequacy of blood pressure in an individual patient must always be assessed in relation to the premorbid value. Blood pressure is traditionally measured using a sphygmomanometer but if rapid alterations are anticipated, continuous monitoring using an intra-arterial cannula is indicated (Practical Box 16.1; Fig. 16.8).

 Practical Box 16.1

Radial artery cannulation

Technique

1. The procedure is explained to the patient and, if possible, consent obtained.

2. The arm is supported, with the wrist extended, by an assistant. (Gloves should be worn.)

3. The skin should be cleaned with chlorhexidine.

4. The radial artery is palpated where it arches over the head of the radius.

5. In conscious patients, local anaesthetic is injected to raise a weal over the artery, taking care not to puncture the vessel or obscure its pulsation.

6. A small skin incision is made over the proposed puncture site.

7. A small parallel-sided cannula (20 gauge for adults, 22 gauge for children) is used in order to allow blood flow to continue past the cannula.

8. The cannula is inserted over the point of maximal pulsation and advanced in line with the direction of the vessel at an angle of approximately 30°.

9. ‘Flashback’ of blood into the cannula indicates that the radial artery has been punctured.

10. To ensure that the shoulder of the cannula enters the vessel, the needle and cannula are lowered and advanced a few millimetres into the vessel.

11. The cannula is threaded off the needle into the vessel and the needle withdrawn.

12. The cannula is connected to a non-compliant manometer line filled with saline. This is then connected via a transducer and continuous flush device to a monitor, which records the arterial pressure.

Complications

Thrombosis

Loss of arterial pulsation

Distal ischaemia, e.g. digital necrosis (rare)

Infection

Accidental injection of drugs – can produce vascular occlusion

Disconnection – rapid blood loss.

Figure 16.8 Percutaneous cannulation of the radial artery.

Central venous pressure (CVP)

This provides a fairly simple, but approximate method of gauging the adequacy of a patient’s circulating volume and the contractile state of the myocardium. The absolute value of the CVP is not as useful as its response to a fluid challenge (the infusion of 100–200 mL of fluid over a few minutes) (Fig. 16.9). The hypovolaemic patient will initially respond to transfusion with little or no change in CVP, together with some improvement in cardiovascular function (falling heart rate, rising blood pressure, increased peripheral temperature and urine output). As the normovolaemic state is approached, the CVP usually rises slightly and reaches a plateau, while other cardiovascular values begin to stabilize. At this stage, volume replacement should be slowed, or even stopped, in order to avoid overtransfusion (indicated by an abrupt and sustained rise in CVP, often accompanied by some deterioration in the patient’s condition). In cardiac failure, the venous pressure is usually high; the patient will not improve in response to volume replacement, which will cause a further, sometimes dramatic, rise in CVP.

Figure 16.9 The effects on the central venous pressure (CVP) of a rapid administration of a ‘fluid challenge’ to patients with a CVP within the normal range.

(From Sykes MK. Venous pressure as a clinical indication of adequacy of transfusion. Annals of Royal College of Surgeons of England 1963; 33:185–197.)

Central venous catheters are usually inserted via a percutaneous puncture of the subclavian or internal jugular vein using a guidewire technique (Practical Box 16.2; Figs 16.10, 16.11). The guidewire techniques can also be used in conjunction with a vein dilator for inserting multilumen catheters, double lumen cannulae for haemofiltration or pulmonary artery catheter introducers. The routine use of ultrasound to guide central venous cannulation reduces complication rates.

 Practical Box 16.2

Internal jugular vein cannulation

Technique

1. The procedure is explained to the patient and, if possible, consent obtained.

2. The patient is placed head-down to distend the central veins (this facilitates cannulation and minimizes the risk of air embolism but may exacerbate respiratory distress and is dangerous in those with raised intracranial pressure).

3. The skin is cleaned with an antiseptic solution such as chlorhexidine. Sterile precautions are taken throughout the procedure.

4. Local anaesthetic (1% plain lidocaine) is injected intradermally to raise a weal at the apex of a triangle formed by the two heads of sternomastoid with the clavicle at its base.

5. A small incision is made through the weal.

6. The cannula or needle is inserted through the incision and directed laterally downwards and backwards in the direction of the nipple until the vein is punctured just beneath the skin and deep to the lateral head of sternomastoid.

Ultrasound-guided puncture is recommended to reduce the incidence of complications.

7. Check that venous blood is easily aspirated.

8. The cannula is threaded off the needle into the vein or the guidewire is passed through the needle (see Fig. 16.11).

9. The CVP manometer line is connected to a manometer/transducer.

10. A chest X-ray should be taken to verify that the tip of the catheter is in the superior vena cava and to exclude pneumothorax.

Possible complications

Haemorrhage

Accidental arterial puncture (carotid or subclavian)

Pneumothorax

Damage to thoracic duct on left

Air embolism

Thrombosis

Catheter-related sepsis.

Figure 16.10 Cannulation of the right internal jugular vein.

Figure 16.11 Seldinger technique – insertion of a catheter over guidewire. (1) Puncture vessel; (2) advance guidewire; (3) remove needle; (4) dilate vessel; (5) advance catheter over guidewire; (6) remove guidewire; (7) catheter in situ.

The CVP should be read intermittently using a manometer system or continuously using a transducer and bedside monitor. It is essential that the pressure recorded always be related to the level of the right atrium. Various landmarks are advocated (e.g. sternal notch with the patient supine, sternal angle or mid-axilla when the patient is at 45°), but which is chosen is largely immaterial provided it is used consistently in an individual patient. Pressure measurements should be obtained at end-expiration.

The following are common pitfalls in interpreting central venous pressure readings:

Blocked catheter. This results in a sustained high reading, with a damped or absent waveform, which often does not correlate with clinical assessment.

Transducer wrongly positioned. Failure to level the system is a common cause of erroneous readings.

Catheter tip in right ventricle. If the catheter is advanced too far, an unexpectedly high pressure with pronounced oscillations is recorded. This is easily recognized when the waveform is displayed.

FURTHER READING

Ortega R, Song M, Hansen CJ et al. Ultrasound-guided internal jugular vein cannulation. Videos in Medicine. N Engl J Med 2010; 362:e57.

Left atrial pressure

In uncomplicated cases, careful interpretation of the CVP provides a reasonable guide to the filling pressures of both sides of the heart. In many critically ill patients, however, there is a disparity in function between the two ventricles. Most commonly, left ventricular performance is worse, so that the left ventricular function curve is displaced downward and to the right (Fig. 16.12). High right ventricular filling pressures, with normal or low left atrial pressures, are less common but occur with right ventricular dysfunction and in cases where the pulmonary vascular resistance (i.e. right ventricular afterload) is raised, such as in acute respiratory failure and pulmonary embolism.

Figure 16.12 Left ventricular (LV) and right ventricular (RV) function curves in a patient with left ventricular dysfunction. Since the stroke volume of the two ventricles must be the same (except perhaps for a few beats during a period of circulatory adjustment), left atrial pressure (LAP) must be higher than right atrial pressure (RAP). Moreover, an increase in stroke volume (x) produced by expanding the circulatory volume may be associated with a small rise in RAP (y) but a marked increase in LAP (z).

Pulmonary artery pressure

A ‘balloon flotation catheter’ enables reliable catheterization of the pulmonary artery. These ‘Swan–Ganz’ catheters can be inserted centrally (Fig. 16.10) or through the femoral vein, or via a vein in the antecubital fossa. Passage of the catheter from the major veins, through the chambers of the heart, into the pulmonary artery and into the wedged position is monitored and guided by the pressure waveforms recorded from the distal lumen (Practical Box 16.3; Fig. 16.13). A chest X-ray should always be obtained to check the final position of the catheter. In difficult cases, screening with an image intensifier may be required.

 Practical Box 16.3

Passage of a pulmonary artery balloon flotation catheter through the chambers of the heart into the ‘wedged’ position

Consent should be obtained if possible from the patient after explanation of the procedure.

Note: (a), (b), (c), (d) refer to Figure 16.13.

1. A balloon flotation catheter is inserted through a large vein (see text).

2. Once in the thorax, respiratory oscillations are seen. The catheter should be advanced further towards the lower superior vena cava/right atrium (a), where pressure oscillations become more pronounced. The balloon should then be inflated and the catheter advanced.

3. When the catheter is in the right ventricle (b), there is no dicrotic notch and the diastolic pressure is close to zero. The patient should be returned to the horizontal, or slightly head-up, position before advancing the catheter further.

4. When the catheter reaches the pulmonary artery (c) a dicrotic notch appears and there is elevation of the diastolic pressure. The catheter should be advanced further with the balloon inflated.

5. Reappearance of a venous waveform indicates that the catheter is ‘wedged’. The balloon is deflated to obtain the pulmonary artery pressure. The balloon is inflated intermittently to obtain the pulmonary artery occlusion (also known as pulmonary artery, or capillary, ‘wedge’) pressure (d).

Figure 16.13 Passage of pulmonary artery balloon flotation catheter through the chambers of the heart into the ‘wedged’ position to measure the pulmonary artery occlusion pressure. (See Practical Box 16.3.)

Once in place, the balloon is deflated and the pulmonary artery mean, systolic and end-diastolic pressures (PAEDP) can be recorded. The pulmonary artery occlusion pressure (PAOP, previously referred to as the pulmonary artery or capillary ‘wedge’ pressure) is measured by reinflating the balloon, thereby propelling the catheter distally until it impacts in a medium-sized pulmonary artery. In this position there is a continuous column of fluid between the distal lumen of the catheter and the left atrium, so that PAOP is usually a reasonable reflection of left atrial pressure.

The technique is generally safe – the majority of complications such as ‘knotting’, valve trauma and pulmonary artery rupture (which can be fatal) are related to user inexperience. Pulmonary artery catheters should preferably be removed within 72 h, since the incidence of complications, especially infection, then increases progressively

Cardiac output

Cardiac output can be continuously monitored using a modified pulmonary artery catheter which transmits low heat energy into the surrounding blood and constructs a ‘thermodilution curve’. These catheters also optically measure and continuously display .

In general, pulmonary artery catheters enable the clinician to optimize cardiac output and oxygen delivery, while minimizing the risk of volume overload. They can also be used to guide the rational use of inotropes and vasoactive agents and are particularly helpful in patients with pulmonary hypertension. There is, however, a considerable body of evidence to suggest that the unselective use of this monitoring device in the absence of evidence-based haemodynamic goals does not lead to improved outcomes and less invasive techniques are increasingly preferred.

Less invasive techniques for assessing cardiac function and guiding volume replacement

Arterial pressure variation as a guide to hypovolaemia

Systolic arterial pressure decreases during the inspiratory phase of intermittent positive pressure ventilation (p. 894). The magnitude of this cyclical variability has been shown to correlate more closely with hypovolaemia than other monitored variables, including CVP. Systolic pressure (or pulse pressure) variation during mechanical ventilation can therefore be used as a simple and reliable guide to the adequacy of the circulatory volume. The response to fluid loading can also easily be predicted by observing the changes in pulse pressure during passive leg raising.

Oesophageal Doppler

Stroke volume, cardiac output and myocardial function can be assessed non-invasively using Doppler ultrasonography. A probe is passed into the oesophagus to continuously monitor velocity waveforms from the descending aorta (Fig. 16.14). Although reasonable estimates of stroke volume, and hence cardiac output can be obtained, the technique is best used for trend analysis rather than for making absolute measurements. Oesophageal Doppler probes can be inserted quickly and easily and are particularly valuable for perioperative optimization of the circulating volume and cardiac performance in the unconscious patient. They are contraindicated in patients with oropharyngeal/oesophageal pathology.

Figure 16.14 Doppler ultrasonography. Velocity waveform traces are obtained using oesophageal Doppler ultrasonography.

(Reproduced from Singer et al (1991) with permission © 1991 The Williams & Wilkins Co., Baltimore.)

Pulse contour analysis

Lithium dilution/pulse contour analysis does not require pulmonary artery catheterization or instrumentation of the oesophagus and is suitable for use in conscious patients. A bolus of lithium chloride is administered via a central venous catheter and the change in arterial plasma lithium concentration is detected by a lithium-sensitive electrode. This sensor can be connected to an existing arterial cannula via a three-way tap. A small battery-powered peristaltic pump is used to create a constant blood flow through the sensor and over the electrode tip. The cardiac output determined in this way can be used to calibrate an arterial pressure waveform (‘pulse contour’) analysis programme that will continuously monitor changes in cardiac output. Devices that use uncalibrated pulse contour analysis to estimate cardiac output are also available. As with pulse pressure variation, stroke volume variation using these devices can accurately predict fluid replacements.

Echocardiography

Echocardiography is being used increasingly often to provide immediate diagnostic information about cardiac structure and function (myocardial contractility, ventricular filling) in the critically ill patient. Transoesophageal echocardiography (TOE) is preferred because of its superior image clarity (Fig. 16.15).

Figure 16.15 Aortic dissection (transoesophageal echocardiography, TOE). (a) Mid-oesophageal, long axis view showing Type A aortic dissection. (b) Short axis view of descending aorta showing intimal flap with false and true lumen.

(From Hinds CJ, Watson JD. Intensive Care: A Concise Textbook, 3rd edn. Edinburgh: Saunders; 2008. Courtesy of Dr C. Rathwell.)

If there is disagreement between clinical signs and a monitored variable, it should be assumed that the monitor is incorrect until all sources of potential error have been checked and eliminated. Changes and trends in monitored variables are more informative than a single reading.

Disturbances of acid–base balance

The physiology of acid–base control is discussed on page 660. Acid–base disturbances can be described in relation to the diagram illustrated in Figure 13.13, p. 663 (which shows P_aCO₂ plotted against arterial [H⁺]).

Both acidosis and alkalosis can occur, each of which are either metabolic (primarily affecting the bicarbonate component of the system) or respiratory (primarily affecting P_aCO₂). Compensatory changes may also be apparent. In clinical practice, arterial [H⁺] values outside the range 18–126 nmol/L (pH 6.9–7.7) are rarely encountered.

Blood gas and acid–base values (normal ranges) are shown in Table 16.2. (For blood gas analysis, see p. 891.)

Table 16.2 Arterial blood gas and acid–base values (normal ranges)

Respiratory acidosis. This is caused by retention of carbon dioxide. The P_aCO₂ and [H⁺] rise. A chronically raised P_aCO₂ is compensated by renal retention of bicarbonate, and the [H⁺] returns towards normal. A constant arterial bicarbonate concentration is then usually established within 2–5 days. This represents a primary respiratory acidosis with a compensatory metabolic alkalosis (see p. 666). Common causes of respiratory acidosis include ventilatory failure and COPD (type II respiratory failure where there is a high P_aCO₂ and a low P_aO₂, see p. 814).

Respiratory alkalosis. In this case, the reverse occurs and there is a fall in P_aCO₂ and [H⁺], often with a small reduction in bicarbonate concentration. If hypocarbia persists, some degree of renal compensation may occur, producing a metabolic acidosis, although in practice this is unusual. A respiratory alkalosis may be produced, intentionally or unintentionally, when patients are mechanically ventilated; it may also be seen with hypoxaemic (type I) respiratory failure (see Ch. 15, p. 817), spontaneous hyperventilation and in those living at high altitudes.

Metabolic acidosis (p. 664). This may be due to excessive acid production, most commonly lactate and H⁺ (lactic acidosis) as a consequence of anaerobic metabolism during an episode of shock or following cardiac arrest. A metabolic acidosis may also develop in chronic renal failure or in diabetic ketoacidosis. It can also follow the loss of bicarbonate from the gut or from the kidney in renal tubular acidosis. Respiratory compensation for a metabolic acidosis is usually slightly delayed because the blood–brain barrier initially prevents the respiratory centre from sensing the increased blood [H⁺]. Following this short delay, however, the patient hyperventilates and ‘blows off’ carbon dioxide to produce a compensatory respiratory alkalosis. There is a limit to this respiratory compensation, since in practice values for P_aCO₂ less than about 1.4 kPa (11 mmHg) are rarely achieved. Spontaneous respiratory compensation cannot occur if the patient’s ventilation is controlled or if the respiratory centre is depressed, for example by drugs or head injury.

Metabolic alkalosis. This can be caused by loss of acid, for example from the stomach with nasogastric suction, or in high intestinal obstruction, or excessive administration of absorbable alkali. Overzealous treatment with intravenous sodium bicarbonate is sometimes implicated. Respiratory compensation for a metabolic alkalosis is often slight, and it is rare to encounter a P_aCO₂ above 6.5 kPa (50 mmHg), even with severe alkalosis.

The sympatho-adrenal response to shock (Fig. 16.16)

Hypotension stimulates the baroreceptors, and to a lesser extent the chemoreceptors, causing increased sympathetic nervous activity with ‘spill-over’ of noradrenaline (norepinephrine) into the circulation. Later this is augmented by the release of catecholamines (predominantly, adrenaline (epinephrine)) from the adrenal medulla. The resulting vasoconstriction, together with increased myocardial contractility and heart rate, help to restore blood pressure and cardiac output.

Figure 16.16 The sympatho-adrenal response to shock showing the effect of increased catecholamines on the left of the diagram and the release of angiotensin and aldosterone on the right. Both mechanisms help to maintain the cardiac output and blood pressure in shock.

Reduction in perfusion of the renal cortex stimulates the juxtaglomerular apparatus to release renin. This converts angiotensinogen to angiotensin I, which in turn is converted in the lungs and by the vascular endothelium to the potent vasoconstrictor angiotensin II. Angiotensin II also stimulates secretion of aldosterone by the adrenal cortex, causing sodium and water retention (p. 566). This helps to restore the circulating volume (see p. 639).

Neuroendocrine response

Although absolute adrenocortical insufficiency (e.g. due to bilateral adrenal haemorrhage or necrosis) is rare, there is evidence that patients with septic shock have a blunted response to exogenous ACTH (so-called ‘relative’ or ‘occult’ adrenocortical insufficiency) and that this could be associated with an impaired pressor response to noradrenaline (norepinephrine) and a worse prognosis. The diagnosis, causes and clinical significance of this phenomenon remain unclear.

Release of pro- and anti-inflammatory mediators

Severe infection (often with bacteraemia or endotoxaemia), the presence of large areas of damaged tissue (e.g. following trauma or extensive surgery), hypoxia or prolonged/repeated episodes of hypoperfusion can trigger an exaggerated inflammatory response with systemic activation of leucocytes and release of a variety of potentially damaging ‘mediators’ (see also Ch. 3). Although beneficial when targeted against local areas of infection or necrotic tissue, dissemination of this ‘innate immune’ response can produce shock and widespread tissue damage. Characteristically the initial episode of overwhelming inflammation is followed by a period of immune suppression, which in some cases may be profound and during which the patient is at increased risk of developing secondary infections. It also seems that pro- and anti-inflammatory elements of the host response may co-exist.

Microorganisms and their toxic products (Fig. 16.17)

In sepsis/septic shock the innate immune response and inflammatory cascade are triggered by the recognition of pathogen-associated molecular patterns (PAMPs), including cell wall components (e.g. endotoxin) and/or exotoxins (antigenic proteins produced by bacteria such as staphylococci, streptococci and Pseudomonas).

Figure 16.17 Induction of the innate immune response by the lipopolysaccharide–lipopolysaccharide-binding protein (LPS-LBP) complex. This simplified figure illustrates the intracellular events initiated by Gram-negative and Gram-positive bacteria, which eventually lead to bacterial killing. LPS, lipopolysaccharide; LBP, lipopolysaccharide binding protein; LTA, lipoteichoic acid; NFκB, nuclear factor kappa B; IκB, inhibitory factor kappa B; PEPG, peptidoglycan-N; TLR, toll-like receptors; MSR, macrophage scavenger receptor; MyD88, myeloid differentiation factor 88; TIR, toll-interleukin receptor; TIRAP, toll-interleukin 1 receptor adaptor protein; MD2 is a secreted protein involved in binding liposaccharide with TLR4; TIRAP/Mal, an adaptor protein for TLR2 and TLR4.

Endotoxin is a lipopolysaccharide (LPS) derived from the cell wall of Gram-negative bacteria and is a potent trigger of the inflammatory response. The lipid A portion of LPS can be bound by a protein normally present in human serum known as lipopolysaccharide binding protein (LBP). The LBP/LPS complex attaches to the cell surface marker CD14 and, combined with a secreted protein (MD2), this complex then binds to a member of the toll-like receptor family (TLR4), which transduces the activation signal into the cell. These receptors act through a critical adaptor molecule, myeloid differentiation factor 88 (MyD 88), to regulate the activity of NFκB pathways. Intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD) 1 may also be involved. Another mechanism in this complex area involves TREM-I (triggering receptor expressed in myeloid cells, see p. 54), which triggers secretion of pro-inflammatory cytokines.

Specific kinases then phosphorylate inhibitory kappa B (IκB), releasing the nuclear transcription factor NFκB, which passes into the nucleus where it binds to DNA and promotes the synthesis of a wide variety of inflammatory mediators. Gram-positive bacteria have cell wall components which are similar in structure to LPS (e.g. lipoteichoic acid), and can also trigger a systemic inflammatory response, probably through similar (TLR2) but not identical pathways (Fig. 16.17). Following traumatic or surgical tissue injury, inflammatory pathways may be triggered by damage-associated molecular patterns (DAMPS) such as DNA fragments.

Endothelium-derived vasoactive mediators

Endothelial cells synthesize a number of mediators which contribute to the regulation of blood vessel tone and the fluidity of the blood; these include nitric oxide, prostacyclin and endothelin (a potent vasoconstrictor). Nitric oxide (NO) is synthesized from the terminal guanidino-nitrogen atoms of the amino acid L-arginine under the influence of nitric oxide synthase (NOS). NO inhibits platelet aggregation and adhesion and produces vasodilatation by activating guanylate cyclase in the underlying vascular smooth muscle to form cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP) (Fig. 16.18). There are several distinct NOS enzymes.

Constitutive or endothelial NOS (cNOS or eNOS) present in endothelial cells is responsible for the basal release of NO and is involved in the physiological regulation of vascular tone, blood pressure and tissue perfusion.

Neuronal NOS (nNOS). The role of nerves containing nNOS is uncertain but they probably provide neurogenic vasodilator tone. In the central nervous system nNOS may be a regulator of local cerebral blood flow as well as fulfilling a number of other physiological functions, such as the acute modulation of neuronal firing behaviour.

Inducible NOS (iNOS) is induced in vascular endothelial smooth muscle cells and monocytes within 4–18 h of stimulation with endotoxin and certain cytokines, such as TNF. The resulting prolonged increase in NO formation is believed to be a cause of the sustained vasodilatation, hypotension and reduced reactivity to adrenergic agonists (‘vasoplegia’) that characterizes septic shock. This mechanism is also involved in severe prolonged haemorrhage/traumatic shock. The NO generated by macrophages contributes to their role as highly effective killers of intracellular and extracellular pathogens, in part as a consequence of its ability to bind to cytochrome oxidase and inhibit electron transport, but also via the production of the highly reactive radical peroxynitrite.

Figure 16.18 Synthesis and biochemical action of nitric oxide. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate.

Haemodynamic and microcirculatory changes

The dominant haemodynamic feature of severe sepsis/septic shock is peripheral vascular failure with:

Figure 16.19 Still side-stream dark field (SDF) image of the microcirculation in (a) a normal subject and (b) septic shock.

Although these vascular and microvascular abnormalities may partly account for the reduced oxygen extraction often seen in septic shock, there is also a primary defect of cellular oxygen utilization caused by mitochondrial dysfunction (see above). Initially, before hypovolaemia supervenes, or when therapeutic replacement of the circulating volume has been adequate, cardiac output is usually high and peripheral resistance is low. These changes may be associated with impaired oxygen consumption, a reduced arteriovenous oxygen content difference, an increased and a lactic acidosis (so-called ‘tissue dysoxia’). Vasodilatation and increased vascular permeability also occur in anaphylactic shock.

In the initial stages of other forms of shock, and sometimes when hypovolaemia and myocardial depression supervene in sepsis and anaphylaxis, cardiac output is low and increased sympathetic activity causes vasoconstriction. This helps to maintain the systemic blood pressure.

Activation of the coagulation system

The inflammatory response to shock, tissue injury and infection is frequently associated with systemic activation of the clotting cascade, leading to platelet aggregation, widespread microvascular thrombosis and inadequate tissue perfusion.

Initially the production of PGI₂ by the capillary endothelium is impaired. Cell damage (e.g. to the vascular endothelium) leads to exposure to tissue factor (p. 416), which triggers coagulation. In severe cases these changes are compounded by elevated levels of plasminogen activation inhibitor type 1, which impairs fibrinolysis, as well as by deficiencies in physiological inhibitors of coagulation (including antithrombin, proteins C and S and tissue factor-pathway inhibitor). Antithrombin and protein C have a number of anti-inflammatory properties, whereas thrombin is pro-inflammatory.

Plasminogen is converted to plasmin, which breaks down thrombus, liberating fibrin/fibrinogen degradation products (FDPs). In some cases there is increased fibrinolysis. Circulating levels of FDPs are therefore increased, the thrombin time, PTT and PT are prolonged and platelet and fibrinogen levels fall. Activation of the coagulation cascade can be confirmed by demonstrating increased plasma levels of D-dimers. The development of disseminated intravascular coagulation (DIC) often heralds the onset of multiple organ failure. Because clotting factors and platelets are consumed in DIC, they are unavailable for haemostasis elsewhere and a coagulation defect results – hence the alternative name for DIC is ‘consumption coagulopathy’. DIC presents with microvascular bleeding or generalized ‘oozing’ of blood, e.g. from surgical or traumatic wounds and skin puncture sites. In some cases, a microangiopathic haemolytic anaemia develops. DIC is relatively uncommon but is particularly associated with septic shock, especially when due to meningococcal infection (see p. 127). Management of the underlying cause is most urgent. Supportive treatment may include infusions of fresh frozen plasma, platelets, cryoprecipitate when fibrinogen levels are low and occasionally factor VIII concentrates.

Reperfusion injury

Restoration of flow to previously hypoxic tissues can exacerbate cell damage through the generation of large quantities of reactive oxygen species and activation of polymorphonuclear leucocytes (see above) (Fig. 16.20). The gut mucosa seems to be especially vulnerable to this ‘ischaemia-reperfusion injury’.

Figure 16.20 Generation of reactive oxygen species following ischaemia and reperfusion. ATP, ADP, AMP, adenosyl tri, di- and monophosphate, respectively. IMP, inositol monophosphate.

Metabolic response to trauma, major surgery and severe infection

This is initiated and controlled by the neuroendocrine system and various cytokines (e.g. IL-6) acting in concert, and is characterized initially by an increase in energy expenditure (‘hypermetabolism’) (see also p. 201). Gluconeogenesis is stimulated by increased glucagon and catecholamine levels, while hepatic mobilization of glucose from glycogen is increased. Catecholamines inhibit insulin release and reduce peripheral glucose uptake. Combined with elevated circulating levels of other insulin antagonists such as cortisol, and downregulation of insulin receptors, these changes mean that the majority of patients are hyperglycaemic (‘insulin resistance’). Later hypoglycaemia may be precipitated by depletion of hepatic glycogen stores and inhibition of gluconeogenesis. Free fatty acid synthesis is also increased, leading to hypertriglyceridaemia.

Protein breakdown is initiated to provide energy from amino acids, and hepatic protein synthesis is preferentially augmented to produce the ‘acute phase reactants’. The amino acid glutamine (which is indispensable in this situation) is mobilized from muscle for use as a metabolic fuel in rapidly dividing cells such as leucocytes and enterocytes. Glutamine is also required for hepatic production of the free radical scavenger glutathione. When severe and prolonged, this catabolic response can lead to considerable weight loss. Protein breakdown is associated with wasting and weakness of skeletal and respiratory muscle, prolonging the need for mechanical ventilation and delaying mobilization. Tissue repair, wound healing and immune function also are compromised.

Sepsis and multiple organ failure (MOF) (also known as multiple organ dysfunction syndrome, MODS)

Sepsis is being diagnosed with increasing frequency and is now the commonest cause of death in non-coronary adult intensive care units. The estimated incidence of severe sepsis has varied from 77 to 300 cases per 100 000 of the population. Mortality rates are high (between 20% and 60%) and are closely related to the severity of illness and the number of organs that fail. Those who die are overwhelmed by persistent or recurrent sepsis, with fever, intractable hypotension and failure of several organs (Fig. 16.22).

Figure 16.22 Bilateral pneumococcal pneumonia. Community acquired pneumonia is the commonest cause of sepsis requiring admission to intensive care.

(From Hinds CJ, Watson JD. Intensive Care: A Concise Textbook, 3rd edn. Edinburgh: Saunders; 2008. Courtesy of Dr SPG Padley.)

Sequential failure of vital organs occurs progressively over weeks, although the pattern of organ dysfunction is variable. In most cases the lungs are the first to be affected (acute lung injury, ALI; acute respiratory distress syndrome, ARDS; see below) in association with cardiovascular instability and deteriorating renal function. Damage to the mucosal lining of the gastrointestinal tract, as a result of reduced splanchnic flow followed by reperfusion, allows bacteria within the gut lumen, or their cell wall components, to gain access to the circulation. The liver defences, which are often compromised by poor perfusion, are overwhelmed and the lungs and other organs are exposed to bacterial toxins and inflammatory mediators released by liver macrophages. Some have therefore called the gut the ‘motor of multiple organ failure’. Secondary pulmonary infection, complicating ALI/ARDS, also frequently acts as a further stimulus to the inflammatory response. Later, kidney injury and liver dysfunction develop (see p. 884). Gastrointestinal failure, with an inability to tolerate enteral feeding and paralytic ileus, is common. Ischaemic colitis, acalculous cholecystitis, pancreatitis and gastrointestinal haemorrhage may also occur. Features of central nervous system dysfunction include impaired consciousness and disorientation, progressing to coma. Characteristically, these patients initially have a hyperdynamic circulation with vasodilatation and a high cardiac output, associated with an increased metabolic rate. Eventually, however, cardiovascular collapse supervenes. It is now often possible to support such patients for weeks or months; many now die following a decision to withdraw or not to escalate treatment (see p. 897).

Less common causes

Prognosis

Mortality from ALI/ARDS has fallen over the last decade, from around 60% to between 30% and 40%, perhaps as a consequence of improved general care, the increasing use of management protocols, and attention to infection control and nutrition, as well as the introduction of novel treatments and lung-protective strategies for respiratory support. Prognosis is, however, still very dependent on aetiology. When ARDS occurs in association with intra-abdominal sepsis, mortality rates remain very high, whereas much lower mortality rates are to be expected in those with ‘primary’ ARDS (pneumonia, aspiration, lung contusion). Mortality rises with increasing age and failure of other organs. Most of those dying with ARDS do so as a result of MODS and haemodynamic instability rather than impaired gas exchange.

Clinical assessment of respiratory failure

A clinical assessment of respiratory distress should be made on the following criteria (those marked with an asterisk* may be indicative of respiratory muscle fatigue):

Blood gas analysis should be performed to guide oxygen therapy and to provide an objective assessment of the severity of the respiratory failure. The most sensitive clinical indicator of increasing respiratory difficulty is a rising respiratory rate. Measurement of tidal volume is a less sensitive indicator.

Vital capacity is often a better guide to deterioration and is particularly useful in patients with respiratory inadequacy that is due to neuromuscular problems such as the Guillain–Barré syndrome or myasthenia gravis, in which the vital capacity decreases as weakness increases.

Monitoring of respiratory failure

Management of respiratory failure

Standard management of patients with respiratory failure includes:

The load on the respiratory muscles should be reduced by improving lung mechanics. Correction of abnormalities which may lead to respiratory muscle weakness, such as hypophosphataemia and malnutrition, is also necessary.

Oxygen therapy

Methods of oxygen administration

Oxygen is initially given via a facemask. In the majority of patients (except those with COPD and chronically elevated P_aCO₂) the concentration of oxygen given is not vital and oxygen can therefore be given by a ‘variable performance’ device such as a simple facemask or nasal cannulae (Fig. 16.26).

Figure 16.26 Methods of administering supplemental oxygen to the unintubated patient. (a) Simple facemask. (b) Nasal cannulae. (c) Mask with reservoir bag and non-rebreathing value.

With these devices, the inspired oxygen concentration varies from about 35% to 55%, with oxygen flow rates of between 6 and 10 L/min. Nasal cannulae are often preferred because they are less claustrophobic and do not interfere with feeding or speaking, but they can cause ulceration of the nasal or pharyngeal mucosa. Higher concentrations of oxygen can be administered by using a mask with a reservoir bag attached (Fig. 16.26c). Figure 16.26 should be compared with the fixed-performance mask shown in Figure 15.25, with which the oxygen concentration can be controlled. This latter type of mask is used in patients with COPD and chronic type II failure; the hazards of reducing hypoxic drive can be overemphasized and are less dangerous when the patient is in a critical care unit – remember, severe hypoxaemia is more dangerous than hypercapnia.

Oxygen toxicity

Experimentally, mammalian lungs have been shown to be damaged by continuous exposure to high concentrations of oxygen, but oxygen toxicity in humans is less well proven. Nevertheless, it is reasonable to assume that high concentrations of oxygen might damage the lungs, and so the lowest inspired oxygen concentration compatible with adequate arterial oxygenation should be used. Dangerous hypoxia should never be tolerated through a fear of pulmonary oxygen toxicity. There has been concern that in some circumstances (e.g. following myocardial infarction) routine administration of supplemental oxygen may be harmful, perhaps because of associated vasoconstriction.

Respiratory support

If, despite the above measures, the patient continues to deteriorate or fails to improve, the institution of some form of respiratory support is necessary (Table 16.7). Non-invasive ventilation via a mask or hood (see p. 895) can be used, particularly in respiratory failure due to COPD, but in critically ill patients invasive ventilation through an endotracheal tube or tracheostomy is more usual.

Table 16.7 Techniques for respiratory support

Intermittent positive pressure ventilation (IPPV) is achieved by intermittently inflating the lungs with a positive pressure delivered by a mechanical ventilator. Over the last few decades there have been a number of refinements and modifications to the manner in which positive pressure is applied to the airway and in the interplay between the patient’s respiratory efforts and mechanical assistance (p. 894).

Controlled mechanical ventilation (CMV), with the abolition of spontaneous breathing, rapidly leads to atrophy of respiratory muscles so that assisted modes that are triggered by the patient’s inspiratory efforts (see below) are preferred.

The rational use of mechanical ventilation depends on a clear understanding of its potential beneficial effects, as well as the dangers.

Beneficial effects of mechanical ventilation

Relief from exhaustion. Mechanical ventilation reduces the work of breathing, ‘rests’ the respiratory muscles and relieves the extreme exhaustion present in patients with respiratory failure. In some cases, if ventilation is not instituted, this exhaustion may culminate in respiratory arrest.

Effects on oxygenation. Application of positive pressure can prevent or reverse atelectasis. In those with severe pulmonary parenchymal disease, the lungs may be very stiff and the work of breathing is therefore greatly increased. Under these circumstances, the institution of respiratory support significantly reduces total body oxygen consumption; consequently and thus P_aO₂ may improve. Because ventilated patients are connected to a leak-free circuit, it is possible to administer high concentrations of oxygen (up to 100%) accurately and to apply a positive end-expiratory pressure (PEEP). In selected cases, the latter may reduce shunting and increase P_aO₂ (see below).

Improved carbon dioxide elimination. By increasing the volume of ventilation, the P_aCO₂ can be controlled.

Indications for mechanical ventilation

Acute respiratory failure, with signs of severe respiratory distress (e.g. respiratory rate >40/min, inability to speak, patient exhausted) persisting despite maximal therapy. Confusion, restlessness, agitation, a decreased conscious level, a rising P_aCO₂ (>8 kPa) and extreme hypoxaemia (<8 kPa), despite oxygen therapy, are further indications.

Acute ventilatory failure due, for example, to myasthenia gravis or Guillain–Barré syndrome. Mechanical ventilation should usually be instituted when the vital capacity has fallen to 10 mL/kg or less. This will avoid complications such as atelectasis and infection as well as preventing respiratory arrest. The tidal volume and respiratory rate are relatively insensitive indicators of respiratory failure in the above conditions and change late in the course of the disease. A high P_aCO₂ (particularly if rising) is an indication for urgent mechanical ventilation.

By no means all patients with respiratory failure and/or a reduced vital capacity require ventilation; clinical assessment of each individual case is essential. The patient’s general condition, degree of exhaustion, level of consciousness and ability to protect their airway are often more useful than blood gas values.

Other indications include:

Postoperative ventilation in high-risk patients

Head injury: to avoid hypoxia and hypercarbia, which increase cerebral blood flow and intracranial pressure

Trauma: chest injury and lung contusion

Severe left ventricular failure with pulmonary oedema

Coma with breathing difficulties, e.g. following drug overdose.

Institution of invasive respiratory support

This requires tracheal intubation. If the patient is conscious, the procedure must be fully explained and consent obtained before anaesthesia is induced. The complications of tracheal intubation are given in Table 16.8.

Table 16.8 Complications of endotracheal intubation

Complication	Comments
Immediate
Trauma to the upper airway  Tube in oesophagus	Lips, teeth, gums, trachea Gives rise to hypoxia and abdominal distension Detected by capnography Requires immediate removal, bag-mask ventilation with oxygen and re-insertion of the tracheal tube
Tube in one or other (usually the right) main bronchus	Avoid by checking both lungs are being inflated, i.e. both sides of the chest move and air entry is heard bilaterally on auscultation Obtain chest X-ray to check position of tube and to exclude lung collapse
Early
Migration of the tube out of the trachea  Leaks around the tube  Obstruction of tube because of kinking or secretions	Dangerous complications The patient becomes distressed, cyanosed and has poor chest expansion The following should be performed immediately:
	Manual inflation with 100% oxygen
	Tracheal suction
	Check position of tube
	Deflate cuff
	Check tube for ‘kinks’ or blockage with secretions or blood (common)
	If no improvement, remove tube, ventilate with facemask and then insert new endotracheal tube
Late
Sinusitis  Mucosal oedema and ulceration  Laryngeal injury  Tracheal narrowing and fibrosis  Tracheomalacia

Intubating patients in severe respiratory failure is a hazardous undertaking and should only be performed by experienced staff. In extreme emergencies, it may be preferable to ventilate the patient by hand using an oropharyngeal airway and a facemask with added oxygen until experienced help arrives. An alternative is insertion of a laryngeal mask airway.

The patient is usually hypoxic and hypercarbic, with increased sympathetic activity; the stimulus of laryngoscopy and intubation can precipitate dangerous arrhythmias, bradycardia and even cardiac arrest. Except in an extreme emergency, therefore, the ECG and oxygen saturation should be monitored, and the patient preoxygenated with 100% oxygen before intubation. Resuscitation drugs should be immediately available. If time allows, the circulating volume should be optimized and, if necessary, inotropes commenced before attempting intubation. In some cases, it is appropriate to establish intra-arterial and central venous pressure monitoring before instituting mechanical ventilation, although many patients will not tolerate the supine or head-down position. In some deeply comatose patients, no sedation is required, but in the majority of patients, a short-acting intravenous anaesthetic agent, usually with an opiate followed by muscle relaxation will be necessary. When available, capnography must be used to confirm tracheal intubation.

Sedation, analgesia and muscle relaxation

Most critically ill patients will require analgesia and many will receive sedatives. The combination of an opiate with a benzodiazepine or propofol is often used to facilitate mechanical ventilation and to obtund the physiological response to stress. Heavy sedation is indicated in those with severe respiratory failure, especially since ‘lung protective’ ventilatory strategies (see p. 895) are inherently uncomfortable. A few may require neuromuscular blockade, indeed evidence suggests that early administration of atracurium improves outcomes for mechanically ventilated patients with severe ARDS. It is now recognized, however, that minimizing sedation levels using ‘sedation scores’ and ‘daily wakening’, or even the avoidance of sedatives altogether, often in combination with spontaneous breathing modes of respiratory support (see p. 895) is associated with reductions in the duration of mechanical ventilation and more rapid discharge from the ICU and hospital. It is also now recognized that benzodiazepines predispose to the development of delirium (which is an independent predictor of increased mortality and length of hospital stay) in critically ill patients. The use of dexmedetomidine (an α₂ agonist) rather than a benzodiazepine has been shown to be associated with less delirium and reduced time on the ventilator.

FURTHER READING

Riker RR, Shehabi Y, Bokesch PM et al. Dexmedetomidine vs midazolam for sedation of critically ill patients. JAMA 2009; 301:489–499.

Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. Lancet 2010; 375:475–480.

Tracheostomy

Tracheostomy may be required for the long-term control of excessive bronchial secretions, particularly in those with a reduced conscious level, and/or to maintain an airway and protect the lungs in those with impaired pharyngeal and laryngeal reflexes. Tracheostomy is also performed when intubation is likely to be prolonged, for patient comfort, to reduce sedation requirements and to facilitate weaning from mechanical ventilation.

Tracheostomy can be performed in the ICU or in an operating theatre. A percutaneous dilatational approach, which is quick and can be performed at the bedside, is a suitable technique for most critically ill patients (and can be used in an emergency). The alternative surgical approach, opening the trachea vertically through the second, third and fourth tracheal rings via a transverse skin incision, involves transferring the patient to an operating theatre.

A life-threatening obstruction of the upper respiratory tract that cannot be bypassed with an endotracheal tube can be relieved by a cricothyroidotomy, which is safer, quicker and easier to perform than a formal tracheostomy.

Tracheostomy has a small but significant mortality rate. Complications of tracheostomy are shown in Table 16.9.

Table 16.9 Complications of tracheostomy
(As for tracheal intubation, see Table 16.8), plus:

Early Death Pneumothorax Haemorrhage Hypoxia Hypotension Cardiac arrhythmias Tube misplaced in pretracheal subcutaneous tissues Subcutaneous emphysema Intermediate Mucosal ulceration Erosion of tracheal cartilages (can cause tracheo-oesophageal fistula) Erosion of innominate artery (occasionally leads to fatal haemorrhage) Stomal infection Pneumonia Late Failure of stoma to heal Tracheal granuloma Tracheal stenosis at level of stoma, cuff or tube tip Collapse of tracheal rings at level of stoma Cosmetic

Complications associated with mechanical ventilation

Airway complications. There may be complications associated with tracheal intubation or tracheostomy (see above) (Tables 16.8, 16.9).

Disconnection, failure of gas or power supply, mechanical faults. These are unusual but dangerous. A method of manual ventilation, a facemask and oxygen must always be available by the bedside.

Cardiovascular complications. The application of positive pressure to the lungs and thoracic wall impedes venous return and distends alveoli, thereby ‘stretching’ the pulmonary capillaries and causing a rise in pulmonary vascular resistance. Both these mechanisms can produce a fall in cardiac output.

Respiratory complications. Mechanical ventilation can be complicated by a deterioration in gas exchange because of mismatch, fluid retention and collapse of peripheral alveoli. Traditionally, the latter was prevented by using high tidal volumes (10–12 mL/kg) but high inflation pressures, with overdistension of compliant alveoli, perhaps exacerbated by the repeated opening and closure of distal airways, can disrupt the alveolar–capillary membrane. There is an increase in microvascular permeability and release of inflammatory mediators leading to ‘ventilator-associated lung injury’. Extreme overdistension of the lungs during mechanical ventilation with high tidal volumes and PEEP can rupture alveoli and cause air to dissect centrally along the perivascular sheaths. This ‘barotrauma’ may be complicated by pneumomediastinum, subcutaneous emphysema, pneumoperitoneum, pneumothorax, and intra-abdominal air. The risk of pneumothorax is increased in those with destructive lung disease (e.g. necrotizing pneumonia, emphysema), asthma or fractured ribs.

A tension pneumothorax can be rapidly fatal in ventilated patients. Suggestive signs include the development or worsening of hypoxia, hypercarbia, respiratory distress, an unexplained increase in airway pressure, as well as hypotension and tachycardia, sometimes accompanied by a rising CVP. Examination may reveal unequal chest expansion, mediastinal shift away from the side of the pneumothorax (deviated trachea, displaced apex beat) and a hyperresonant hemithorax. Although breath sounds are often diminished over the pneumothorax, this sign can be misleading in ventilated patients. If there is time, the diagnosis can be confirmed by chest X-ray prior to definitive treatment with chest tube drainage.

Ventilator-associated pneumonia. Hospital-acquired pneumonia occurs in as many as one-third of patients receiving mechanical ventilation and this is associated with a significant increase in mortality. It can be difficult to diagnose. The measurement of serum procalcitonin, a specific marker of severe bacterial infections, can be helpful. Various organisms can be isolated, such as aerobic Gram-negative bacilli, e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Acinetobacter spp. and Staphylococcus aureus, including MRSA. Leakage of infected oropharyngeal secretions past the tracheal tube cuff is thought to be largely responsible. Bacterial colonization of the oropharynx may be promoted by regurgitation of colonized gastric fluid and the risk of ventilator-associated pneumonia can be reduced by nursing patients in the semi-recumbent, rather than the supine, position and by oropharyngeal decontamination.

FURTHER READING

Bonadma L et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units. Lancet 2010; 375:463–474.

Techniques for respiratory support (Table 16.7)

Controlled mechanical ventilation (CMV)

This technique is used in patients in whom respiratory efforts are absent or have been abolished.

Ventilation involves one of two types:

Volume controlled ventilation. The tidal volume and respiratory rate are preset on the ventilator. The airway pressure varies according to both the ventilator setting and the patient’s lung mechanics (airways resistance and compliance).

Pressure controlled ventilation. Both the inspiratory pressure and the respiratory rate are preset but the tidal volume varies according to the patient’s lung mechanics.

Positive end-expiratory pressure (PEEP)

A positive airway pressure can be maintained at a chosen level throughout expiration by attaching a threshold resistor valve to the expiratory limb of the circuit. PEEP re-expands underventilated lung units, and redistributes lung water from the alveoli to the perivascular interstitial space, thereby reducing shunt and increasing P_aO₂. The inevitable rise in mean intrathoracic pressure associated with the application of PEEP may, however, further impede venous return, increase pulmonary vascular resistance and reduce cardiac output. The fall in cardiac output can be ameliorated by expanding the circulating volume, although in some cases inotropic or vasopressor support is required. Thus, although arterial oxygenation is often improved by the application of PEEP, a simultaneous fall in cardiac output can lead to a reduction in total oxygen delivery.

Traditionally, the application of PEEP was only considered if it proved difficult to achieve adequate oxygenation of arterial blood despite raising the inspired oxygen concentration above 50%. Many now use low levels of PEEP (5–7 cmH₂O) in the majority of mechanically ventilated patients in order to maintain lung volume, as well as for those with basal atelectasis and in selected cases with airways obstruction.

Continuous positive airway pressure (CPAP)

The application of CPAP achieves for the spontaneously breathing patient what PEEP does for the ventilated patient. Oxygen and air are delivered under pressure via an endotracheal tube, a tracheostomy, a tightly fitting facemask or a hood (Fig 16.27). Not only can CPAP improve oxygenation, but the lungs become more compliant, and the work of breathing is reduced.

Figure 16.27 Use of a continuous positive airway pressure (CPAP) hood.

Pressure support ventilation (PSV)

Spontaneous breaths are augmented by a preset level of positive pressure (usually between 5 and 20 cmH₂O) triggered by the patient’s spontaneous respiratory effort and applied for a given fraction of inspiratory time or until inspiratory flow falls below a certain level. Tidal volume is determined by the set pressure, the patient’s effort and pulmonary mechanics. The level of pressure support can be reduced progressively as the patient improves.

Intermittent mandatory ventilation (IMV)

This technique allows the patient to breathe spontaneously between the ‘mandatory’ tidal volumes delivered by the ventilator. These mandatory breaths are timed to coincide with the patient’s own inspiratory effort (synchronized IMV or SIMV). SIMV can be used with or without CPAP, and spontaneous breaths may be assisted with pressure support ventilation.

‘Lung-protective’ ventilation

This is designed to avoid exacerbating or perpetuating lung injury by avoiding overdistension of alveoli, minimizing airway pressures and preventing the repeated opening and closure of distal airways. Alveolar volume is maintained with PEEP, and sometimes by prolonging the inspiratory phase, while tidal volumes are limited to 6–8 mL/kg ideal bodyweight. Peak airway pressures should not exceed 35–40 cmH₂O. An alternative is to deliver a constant preset inspiratory pressure for a prescribed time in order to generate a low tidal volume at reduced airway pressures (‘pressure-limited’ mechanical ventilation). Respiratory rate can be increased to improve CO₂ removal and avoid severe acidosis (pH <7.2), but hypercarbia is frequent and should be accepted (‘permissive hypercarbia’). Both techniques can be used with SIMV. Ventilation with low tidal volumes has been shown to improve outcome in patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) (see p. 884). Lung protective ventilation should now be used in almost all patients undergoing mechanical ventilation.

FURTHER READING

Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet 2009; 374:250–259.

Peek GJ, Mugford M, Tinwoipati R et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374:1351–1363.

High frequency oscillation (HFO)

With HFO, there is no bulk flow of gas; rather gas oscillates to and fro at rates of 60–3000 cycles/min with a V_T of 1–3 mL/kg. Both inspiration and expiration are actively controlled with a sine wave pump. The mechanism of gas exchange is not fully understood but lung volume is well maintained and oxygenation may be improved. There is some evidence to suggest that HFO is a safe and effective intervention for patients with severe ARDS.

FURTHER READING

Sud S, Sud M, Friedrich JP. High frequency oscillation in patients with acute lung injury and acute respiratory distress syndrome (ARDS): systematic review and meta-analysis. BMJ 2010; 340:C2327, doi:10.1136/bmj.c2327.

Extracorporeal gas exchange (ECGE)

In patients with severe refractory respiratory failure pumped veno-venous bypass through a membrane lung (extracorporeal membrane oxygenation, ECMO or extracorporeal carbon dioxide removal, ECCO₂-R) has been used to reduce ventilation requirements, thereby minimizing further ventilation-induced lung damage and encouraging resolution of the lung injury. A recent (2010) randomized controlled trial suggested that ECMO might improve outcome in adult patients with severe respiratory failure. There is also some indication that the technique is particularly valuable in young patients with acute respiratory distress syndrome caused by influenza.