Critical illness

Critical illness

G.R. Nimmo

T. Walsh

Clinical examination of the critically ill patient

A critically ill patient is at imminent risk of death. Recognition, assessment and management of critical illness are thus fundamental to clinical care in any area of medicine. The principle underpinning intensive care is the simultaneous assessment of illness severity and stabilisation of life-threatening physiological abnormalities. The goal is to prevent deterioration and effect improvements as the diagnosis is established, and treatment of the underlying definitive disease process(es) is initiated. Blinkered attention to either resuscitation or diagnosis in isolation results in worse outcomes and increased mortality; the two processes are inextricably interlinked. Appropriate physiological monitoring is required to allow continuing assessment and re-assessment of response to therapy, wherever the clinical environment.

Physiology of critical illness

Oxygen transport

The principal function of the heart, lungs and circulation is the provision of oxygen (and other nutrients) to the various organs and tissues of the body. During this process, carbon dioxide and other metabolic waste products are removed. The rate of supply and removal should match the specific metabolic requirements of the individual tissues. This requires adequate oxygen uptake in the lungs, global matching of delivery and consumption, and regional control of the circulation. Failure to supply sufficient oxygen to meet the metabolic requirements of the tissues is the cardinal feature of circulatory failure or ‘shock’, and optimisation of tissue oxygen delivery and consumption is the goal of resuscitation.

Atmospheric oxygen moves down a partial pressure gradient from air, through the respiratory tract, from alveoli to arterial blood and then to the capillary beds and cells, diffusing into the mitochondria, where it is utilised at cytochrome a3 (Fig. 8.1). The movement of oxygen from the left ventricle to the systemic tissue capillaries is known as oxygen delivery (DO2), and is the product of cardiac output (flow) × arterial oxygen content (CaO2) The latter is the product of haemoglobin (Hb) × arterial oxygen saturation of haemoglobin (SaO2) × 1.34. By increasing cardiac output, arterial oxygen saturation or haemoglobin concentration, DO2 will be increased.

The regional distribution of oxygen delivery is important. If skin and muscle receive high blood flows but the splanchnic bed does not, the gut will become hypoxic even if overall DO2 is high.

The movement of oxygen from tissue capillary to cell occurs by diffusion and depends on the gradient of oxygen partial pressures, diffusion distance and the ability of the target cell to take up and use oxygen. Microcirculatory, tissue diffusion and cellular factors thus also influence the oxygen status of the cell.

Cardiovascular component of oxygen delivery: flow

A key determinant of DO2 is cardiac output, which is determined by the ventricular ‘preload’ and ‘afterload’, myocardial contractility and heart rate.


The atrial filling pressures, or preload, determine the end-diastolic ventricular volume, which, according to Starling’s Law and depending on myocardial contractility, defines the force of cardiac contraction and the stroke volume (see Fig. 18.22, p. 547). The principal determinant of preload is venous return, determined by the intravascular volume, venous ‘tone’ and intrathoracic pressure. This can be measured as the central venous pressure (CVP), as described on page 185 (Box 8.1).

When volume is lost (e.g. in major haemorrhage), venous ‘tone’ increases and this helps to offset the consequent fall in atrial filling pressure and stroke volume. If the equivalent volume is restored gradually by intravenous fluid administration, the right atrial pressure will return to normal as the intravascular volume is normalised and the reflex increase in venous tone abates. However, if fluid is infused too rapidly, there is insufficient time for the venous and arteriolar tone to fall and pulmonary oedema may occur, even though the intravascular volume has only been restored to the pre-morbid level.

If the preload is low, volume loading with intravenous fluids is the priority and is the most appropriate means of improving cardiac output and tissue perfusion. The choice of fluid for volume loading is controversial, but as there is no clear advantage of colloid over crystalloid, sodium chloride is used. Fluid challenges of 200–250 mL should be administered rapidly over a couple of minutes, and titrated against heart rate, blood pressure (BP), peripheral circulation, and measurements of CVP (Fig. 8.2). Red cells have traditionally been transfused to achieve and maintain a haemoglobin concentration of 100 g/L, but in the absence of significant heart disease, the target is 70–90 g/L (p. 184).

When the preload is high due to excessive intravascular volume or impaired myocardial contractility, removing volume from the circulation by using diuretics or haemofiltration, or increasing the capacity of the vascular bed by using venodilator therapy (glyceryl trinitrate, morphine) often improves stroke volume.


Afterload is the tension in the ventricular myocardium during systole, and is determined by the resistance to ventricular outflow, which is a function of the peripheral arteriolar resistance.

Understanding the reciprocal relationship between pressure, flow and resistance is crucial for appropriate circulatory management. High resistances produce lower flows at higher pressures for a given amount of ventricular work. Therefore, a systemic vasodilator (see below) will allow the same cardiac output to be maintained for less ventricular work but with a reduced arterial BP. In hyperdynamic sepsis, the peripheral arteriolar tone and BP are low but the cardiac output is often high; therefore the vasoconstrictor noradrenaline (norepinephrine) is appropriate to restore BP, usually at the price of some reduction in cardiac output.

Myocardial contractility

This determines the stroke volume that the ventricle can generate against a given afterload for a particular preload. The ventricular stroke work is the external work performed by the ventricle with each beat. The relationship between stroke work and filling pressure is shown in Figure 18.22 (p. 547). Myocardial contractility is frequently reduced in critically ill patients due to pre-existing cardiac disease (usually ischaemic), drugs (e.g. β-blockers, verapamil) or to the disease process itself (particularly sepsis, as the associated low diastolic BP may compromise coronary arterial perfusion). It is thus important to maintain satisfactory perfusion and oxygen delivery to all organs at maximum cardiac efficiency, to minimise myocardial ischaemia.

Oxygenation component of oxygen delivery: content

The major determinants of the oxygen content of arterial blood (CaO2) are the arterial oxygen saturation of haemoglobin (SaO2) and the haemoglobin concentration. Over 95% of oxygen carried in the blood is bound to haemoglobin.

The oxyhaemoglobin dissociation curve (Fig. 8.3) describes the relationship between the saturation of haemoglobin (SO2) and the partial pressure (PO2) of oxygen in the blood. A shift in the curve will influence the uptake and release of oxygen by the haemoglobin molecule. If the curve moves to the right, the haemoglobin saturation will be lower for any given oxygen tension: less oxygen will be taken up in the lungs but more will be released to the tissues. As capillary PCO2 rises, the curve moves to the right, increasing the unloading of oxygen in the tissues – a phenomenon known as the Bohr effect. Thus a shift to the right increases capillary PO2 and hence cellular oxygen supply.

Due to the shape of the curve, a small drop in arterial PO2 (PaO2) below 8 kPa (60 mmHg) will cause a marked fall in SaO2.. Its position and the effect of various physicochemical factors are defined by the PO2 at which 50% of the haemoglobin is saturated (P50), which is normally 3.5 kPa (26 mmHg). The shape of the curve also means that increases in PaO2 beyond the level that ensures SaO2 is greater than 90% produce relatively small additional increases in CaO2 (Fig. 8.3). Thus, in a patient who is both anaemic (Hb 60 g/L or 6 g/dL) and hypoxaemic (SaO2 75%) when breathing air (fractional inspired oxygen concentration (FiO2) 20%), supplementary oxygen at FiO2 40% will increase SaO2 to 93% and CaO2 by 24%. However, further increases in FiO2, while raising PaO2, cannot produce any further useful increases in SaO2 or CaO2. However, increasing haemoglobin to 90 g/L (9 g/dL) by blood transfusion will result in a further 50% increase in CaO2.

Traditionally, the optimum haemoglobin concentration for critically ill patients was considered to be approximately 100 g/L (10 g/dL), representing a balance between maximising the oxygen content of the blood and avoiding regional microcirculatory problems due to increased viscosity. However, improved outcomes have been demonstrated when the haemoglobin is maintained between 70 and 90 g/L (7–9 g/dL). A target haemoglobin of 100 g/L remains appropriate in the elderly and in patients with coronary artery disease, cardiogenic shock, significant aortic stenosis or acute brain trauma.

Oxygen consumption

The sum of the oxygen consumed by the various organs represents the global oxygen consumption (VO2), and is approximately 250 mL/min for an adult of 70 kg undertaking normal daily activities.

The oxygen saturation in the pulmonary artery, or ‘mixed venous oxygen saturation’ (SvO2), is a measure of the oxygen not consumed by the tissues (DO2VO2). The saturation of venous blood from different organs varies considerably; the hepatic venous saturation usually does not exceed 60% but the renal venous saturation may reach 90%, reflecting the difference in the metabolic requirements of these organs, and the oxygen content of the blood delivered to them. The SvO2 is a flow-weighted average measured in the mixed effluent blood from all perfused tissues, and is influenced by changes in both oxygen delivery (DO2) and consumption (VO2). Provided the microcirculation and the mechanisms for cellular oxygen uptake are intact, it can be used to monitor whether global oxygen delivery is adequate to meet overall demand, so its measurement is particularly useful in low-flow situations such as cardiogenic shock. Central venous oxygen saturation (ScvO2) is used in the same way, but as it does not reflect hepatosplanchnic oxygen consumption, it may be less helpful than SvO2.

The re-oxygenation of the blood that returns to the lungs and the resulting arterial saturation (SaO2) will depend on how closely pulmonary ventilation and perfusion are matched. If part of the pulmonary blood flow perfuses non-ventilated parts of the lung (‘shunting’), the blood entering the left atrium will be desaturated in proportion to the size of the shunt and the level of SvO2.

Relationship between oxygen consumption and delivery

The tissue oxygen extraction ratio (OER) is 20–25% in a normal individual at rest, but rises as consumption increases or supply diminishes. The maximum OER is approximately 60% for most tissues; at this point, no further increase in extraction can occur and any further increase in oxygen consumption or decline in oxygen delivery will cause tissue hypoxia, anaerobic metabolism and increased lactic acid production. This ultimately results in multiple organ failure and an increased risk of death.

In practice, if there is a metabolic acidosis, hyperlactataemia and/or oliguria that could be due to inadequate oxygen delivery, a therapeutic trial of increased oxygen delivery (while maintaining an adequate BP) may be helpful clinically. If oxygen consumption rises, it can indicate an oxygen debt that is being repaid.

Pathophysiology of the inflammatory response

The mediators and clinical manifestations of the inflammatory response are described on page 82. In critically ill patients, these have important consequences (Box 8.2).

Fever, tachycardia with warm peripheries, tachypnoea and a raised white cell count prompt a diagnosis of sepsis, with the presentation caused by invading microorganisms and their breakdown products. Other conditions, such as pancreatitis, trauma, malignancy, tissue necrosis (e.g. burns), aspiration syndromes, liver failure, blood transfusion and drug reactions, can also present in this way in the absence of infection.

Local inflammation

The body’s initial response to a noxious local insult is to produce a local inflammatory response, with sequestration and activation of white blood cells and the release of a variety of mediators to overcome the primary ‘insult’ and prevent further damage locally or in distant organs.

Normally, a delicate balance is achieved between pro- and anti-inflammatory mediators. However, if the response is excessive, a large array of pro-inflammatory mediators may be released into the circulation (p. 74). The inflammatory and coagulation cascades are intimately linked, as the latter cause not only platelet activation and fibrin deposition, but also activation of leucocytes and endothelial cells. Conversely, leucocyte activation induces tissue factor expression and initiates coagulation pathways. The natural anticoagulants, antithrombin (AT III), activated protein C (APC) and tissue factor pathway inhibitor (TFPI), inhibit pro-inflammatory cytokines. Deficiency of AT III and APC (features of disseminated intravascular coagulation (DIC), p. 1056) facilitates thrombin generation and promotes further endothelial cell dysfunction.

Systemic inflammation

In a severe inflammatory response, systemic release of cytokines and other mediators triggers widespread interaction between the coagulation pathways, platelets, endothelial cells and monocytes, tissue macrophages, and neutrophils. Activated neutrophils express adhesion factors, which make them adhere to and initially roll along the endothelium, before adhering firmly and migrating through the damaged and disrupted endothelium into the extravascular interstitial space (together with fluid and proteins), resulting in tissue oedema and inflammation. A vicious circle of endothelial injury, intravascular coagulation, microvascular occlusion, tissue damage and further release of inflammatory mediators ensues. This can occur in all organs, manifesting in the lungs as acute lung injury and in the kidneys as acute tubular necrosis (ATN). Similar processes probably account for damage to other organs, including the heart.

The endothelium itself produces mediators that control local blood vessel tone. The profound vasodilatation that characterises septic shock and some other acute systemic inflammatory states, such as pancreatitis, results from excessive production of nitric oxide (NO, p. 82), due to activation of inducible NO synthase enzymes.

Systemic inflammatory processes also have important effects on mitochondrial function, resulting in impaired oxidative phosphorylation and aerobic energy generation. This block to oxygen utilisation by cells is sometimes called cytopathic hypoxia. Patients typically have a reduced arteriovenous oxygen difference, a low oxygen extraction ratio, a raised plasma lactate and a paradoxically high mixed venous oxygen saturation (SvO2), despite normal or supranormal oxygen delivery. This is associated with the development of multiple organ failure (MOF) and reduced survival.


Monitoring in intensive care includes a combination of clinical and automated recordings. Electrocardiogram (ECG), SpO2 (oxygen saturation), BP and usually CVP recordings are taken at least hourly, using either a 24-hour chart or a computerised system. Urine output measurement requires early catheterisation. All invasive haemodynamic monitoring should be referenced to the mid-axillary line as ‘zero’. Clinical monitoring of physical signs, such as respiratory rate, the appearance of the patient, restlessness, conscious level and indices of peripheral perfusion (pale, cold skin; delayed capillary refill in the nailbed), is just as important as a set of blood gases or monitor readings.

Monitoring the circulation

Central venous pressure

CVP or right atrial pressure (RAP) is monitored using a catheter inserted via either the internal jugular or the subclavian vein, with the distal end sited in the upper right atrium. The CVP may help in assessing the need for intravascular fluid replacement and the rate at which this should be given (see Box 8.1, p. 182). If the CVP is low in the presence of a low MAP or cardiac output, fluid resuscitation is necessary. However, a raised level does not necessarily mean that the patient is adequately volume-resuscitated. Right heart function, pulmonary artery pressure, intrathoracic pressure and venous ‘tone’ also influence CVP, and may lead to a raised CVP even when the patient is hypovolaemic (Box 8.3). In addition, positive pressure ventilation raises intrathoracic pressure and causes marked swings in atrial pressures and systemic BP in time with respiration. Pressure measurements should be recorded at end-expiration.

In severe hypovolaemia, the RAP may be sustained by peripheral venoconstriction, and transfusion may initially produce little or no change in the CVP (see Fig. 8.3, p. 183).

Pulmonary artery catheterisation and pulmonary artery ‘wedge’ pressure

The CVP is usually an adequate guide to the filling pressures of both sides of the heart. However, certain conditions, such as pulmonary hypertension or right ventricular dysfunction, may lead to raised CVP levels even in the presence of hypovolaemia. In these circumstances, it may be appropriate to insert a pulmonary artery flotation catheter (Fig. 8.4) so that pulmonary artery pressure and pulmonary artery ‘wedge’ pressure (PAWP), which approximates to left atrial pressure, can be measured.

The mean PAWP normally lies between 6 and 12 mmHg (measured from the mid-axillary line) but in left heart failure it may be grossly elevated, exceeding 30 mmHg. Provided the pulmonary capillary membranes are intact, the optimum PAWP when managing acute circulatory failure in the critically ill patient is generally 12–15 mmHg, because this will ensure good left ventricular filling without risking hydrostatic pulmonary oedema.

Pulmonary artery catheters also allow measurement of cardiac output and sampling of blood from the pulmonary artery (‘mixed venous’ samples), permitting continuous monitoring of the mixed venous oxygen saturation (SvO2) by oximetry. Measurement of SvO2 gives an indication of the adequacy of cardiac output (and hence DO2) in relation to the body’s metabolic requirements. It is especially useful in low cardiac output states.

Cardiac output

Measurement of cardiac output is important, particularly when large doses of a vasopressor are being administered, when there is underlying cardiac disease (acute or chronic), and when volume resuscitation and vasoactive drug therapy are not achieving resolution of lactic acidosis or oliguria. It is most accurately measured by indicator dilution methods. Most PA catheters incorporate a heating element, which raises blood temperature at frequent intervals, and the resultant temperature change is detected by a thermistor at the tip of the catheter.

Oesophageal Doppler ultrasonography provides a rapid and useful assessment of volume status and cardiac performance to guide early fluid and vasoactive therapy. A 6 mm probe is inserted into the distal oesophagus, allowing continuous monitoring of the aortic flow signal from the descending aorta (Fig. 8.5). Using the stroke distance (area under the velocity/time waveform) and a correction factor that incorporates the patient’s age, height and weight, an estimate of left ventricular stroke volume and hence cardiac output can be made. Peak velocity is an indicator of left ventricular performance, while flow time is an indicator of left ventricular filling and peripheral resistance.

Analysis of arterial pressure waveform is another means of continuously estimating cardiac output, and can be calibrated either by transpulmonary thermodilution (PiCCO) or lithium dilution methods (LidCO). The Vigileo/Flotrac system derives cardiac output from arterial pressure waveform analysis with no external calibration.

Blood lactate, hydrogen ion and base excess/deficit

Acid–base balance is discussed on page 443. Base excess or deficit is calculated as the difference between the patient’s bicarbonate and the normal bicarbonate after the PCO2 has been maintained in a blood gas machine at 5.33 kPa (40 mmHg). This is particularly useful, as it describes patients’ underlying metabolic status independently of their current respiratory status. A metabolic acidosis with base deficit of more than 5 mmol/L requires investigation (p. 445). It often indicates increased lactic acid production in poorly perfused, hypoxic tissues, and impaired lactate metabolism and clearance due to poor hepatic perfusion. Serial lactate measurements may therefore be helpful in monitoring tissue perfusion and response to treatment. Other conditions, such as acute renal failure, ketoacidosis and poisoning, may be the cause, and infusions of large volumes of fluids containing sodium chloride may lead to a hyperchloraemic acidosis.

Monitoring respiratory function

Oxygen saturation

Oxygen saturation (SpO2) is measured by a probe attached to a finger or earlobe. Spectrophotometric analysis determines the relative proportions of saturated and desaturated haemoglobin. It is unreliable if peripheral perfusion is poor, in the presence of nail polish, excessive movement or high ambient light. It is not useful in carbon monoxide poisoning, as it does not detect carboxy-haemoglobin. If this is suspected, PO2 must be measured in an arterial blood gas sample. In general, arterial oxygenation is safe if SpO2 is above 90%. Box 8.4 lists the causes of sudden falls in SpO2.


The CO2 concentration in inspired gas is zero, but during expiration, after clearing the physiological dead space, it rises progressively to reach a plateau that represents the alveolar or end-tidal CO2 concentration. This cyclical change in CO2 concentration, or capnogram, is measured using an infrared sensor inserted between the ventilator tubing and the endotracheal tube (Fig. 8.6). In normal lungs, the end-tidal CO2 closely mirrors PaCO2, and can be used to assess the adequacy of alveolar ventilation. However, its use is limited as there may be marked discrepancies in the presence of lung disease or impaired pulmonary perfusion (e.g. due to hypovolaemia). In combination with the gas flow and respiratory cycle data from the ventilator, CO2 production and hence metabolic rate may be calculated. In clinical practice, end-tidal CO2 is used to confirm correct placement of an endotracheal tube, in the management of head injury, and during the transport of ventilated patients. Continuous measurement of end-tidal CO2 is important in the minute-to-minute monitoring of any patient ventilated through an endotracheal tube or tracheostomy in the acute setting.

Recognition of critical illness

The immediate appearance of the patient yields a wealth of information. Introducing yourself, shaking hands and asking ‘How are you?’ allow assessment of:

Tachypnoea is often the earliest abnormality to appear and the most sensitive sign of a worsening clinical state, but it is the least well documented. In the UK, the use of early warning scores, such as the Standard Early Warning System chart (SEWS, p. 181), has been adopted to improve the recognition of critical illness. These alert staff to severely ill patients, complement clinical judgement and facilitate the prioritisation of clinical care. A patient with a SEWS score of 4 or more requires urgent review and appropriate interventions. An elevated score correlates with increased mortality.

Assessment and initial resuscitation of the critically ill patient

Airway and breathing

If the patient is talking, the airway is clear and breathing is adequate. A rapid history should be obtained whilst initial assessment is undertaken.

Assess breathing as described above. Supplemental oxygen should be administered to patients who are breathless, tachypnoeic or bleeding, or who have chest pain or reduced conscious level. The clinical status of the patient determines how much oxygen to give, but the critically ill should receive at least 60% oxygen initially. High-concentration oxygen is best given using a mask with a reservoir bag, which, at 15 L/min, can provide nearly 90% oxygen. ABGs should be checked early to assess oxygenation, ventilation (PaCO2) and metabolic state (pH or H+, HCO3 and base deficit). Oxygen therapy should be adjusted in light of the ABGs, remembering that oxygen requirements may subsequently increase or decrease. Early application of pulse oximeter monitoring is ideal, although this may not be reliable if the patient is peripherally shut down. Intubation, while often essential, may be hazardous in a patient with cardiorespiratory failure, and full monitoring and resuscitation facilities must be available.


The carotid pulse should be sought in the collapsed or unconscious patient, but peripheral pulses checked in the conscious. The radial, brachial, foot and femoral pulses may disappear as shock progresses, and this indicates the severity of circulatory compromise.

Venous access for the administration of drugs and/or fluids is vital but often difficult in sick patients. The gauge of cannula needed is dictated by its purpose. Wide-bore cannulae are required for rapid fluid administration. Ideally, two 16G or larger cannulae should be inserted, one in each arm, in the severely hypovolaemic patient. If the two cannulae are of different sizes, the pulse oximeter should be placed on the same side as the larger one, and the BP cuff on the same side as the smaller one. This facilitates unimpeded volume resuscitation and uninterrupted oxygen saturation monitoring. Pressure infusors and blood warmers should be utilised for rapid, high-volume fluid resuscitation, particularly of blood products. An 18G cannula is adequate for drug administration.

Machine-derived cuff BP measurement is inaccurate at extremes of BP and in tachycardia, especially atrial fibrillation. Manual sphygmomanometer BP readings tend to be more accurate in hypotension. If severe hypotension is not readily corrected with fluid, early consideration should be given to arterial line insertion and vasoactive drug therapy.


Conscious level should be assessed using the Glasgow Coma Scale (GCS; see Box 26.15, p. 1160). Best eye, verbal and motor responses should be assessed and documented. Appropriate painful stimuli include supra-orbital pressure and trapezius pinch. A score of 8 or less denotes coma with associated airway compromise and loss of airway protection, which necessitates intervention. Focal neurological signs may indicate unilateral cerebral pathology. Abnormal pupil size, symmetry or reaction to light may indicate primary cerebral disease or global cerebral insults induced by drugs (e.g. opioids), hypoxia or hypoglycaemia.

Clinical decision-making and referral to critical care

During the initial assessment and resuscitation, several decisions must be made (Box 8.5), but particularly whether referral to the critical care service is necessary. This requires local knowledge about the clinical areas providing enhanced care, whether intermediate high-dependency or advanced intensive care, and the mechanism of referral.

• Intensive care units allow management of the sickest patients who require invasive ventilation, multimodal monitoring and multiple organ system support (Box 8.6).

• High-dependency care allows a greater degree of monitoring, physiological support and nursing/medical input than the standard ward, for patients following major surgery, or for the septic patient requiring invasive haemodynamic monitoring and circulatory support alone, or for the patient with respiratory failure manageable with non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP).

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Apr 9, 2017 | Posted by in GENERAL SURGERY | Comments Off on Critical illness

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