Kumar&ClarkICU.pdf

25 Critical care medicine Michael J O'Dwyer, Rupert M Pearse, Charles J Hinds Introduction 1139 Clinical approach to the critically ill patient 1139 Recognition and diagnosis of critical illness 1139 General aspects of managing the critically ill 1141 Discharge from the ICU/HDU 1141 Applied cardio...

25 Critical care medicine Michael J O'Dwyer, Rupert M Pearse, Charles J Hinds Introduction 1139 Clinical approach to the critically ill patient 1139 Recognition and diagnosis of critical illness 1139 General aspects of managing the critically ill 1141 Discharge from the ICU/HDU 1141 Applied cardiorespiratory physiology 1142 Oxygen delivery and consumption Cardiovascular assessment and monitoring of critically ill patients 1145 Less invasive techniques for assessing cardiac function and guiding volume replacement 1148 Disturbances of acid–base balance 1149 Shock, sepsis and acute disturbances of haemodynamic function 1150 Respiratory failure 1161 Acute respiratory distress syndrome 1167 Acute kidney injury 1169 Neurocritical care 1170 Outcomes 1171 Withholding and withdrawing treatment 1171 Brain death and organ donation 1172 Introduction Critical care medicine (or ‘intensive care medicine’) is concerned predominantly with the management of patients with acute life-threatening conditions (‘the critically ill’) in specialized units. In addition to emergency cases, intensive care units (ICUs) admit high-risk patients electively after major surgery (Box 25.1). Frequently, ICU staff provide care throughout the hospital in the form of medical emergency teams and outreach care. These teams are trained to recognize and provide resuscitation to patients who become critically ill on the ward and transport them safely to an ICU. Another role for these teams is to identify patients who are deteriorating on the ward and to intervene early, perhaps thereby preventing the need for intensive care admission. Intensive care medicine also encompasses the resuscitation and transport of those who become acutely ill or are injured in the community. Teamwork and a multidisciplinary approach are central to the provision of intensive care and this functions most effectively when directed and coordinated by committed specialists. Box 25.1 So me c o mmo n indic a t io ns f o r a dmissio n t o int e nsive c a re Surgical emergencies • Acute intra-abdominal catastrophe – Perforated viscus, especially with faecal soiling of peritoneum (often complicated by sepsis/septic shock) – Ruptured/leaking abdominal aortic aneurysm • Trauma (often complicated by hypovolaemic and later sepsis/septic shock) – Multiple injuries – Massive blood loss – Severe head injury Medical emergencies • Respiratory failure – Exacerbation of chronic obstructive pulmonary disease (COPD) – Acute severe asthma – Severe pneumonia (often complicated by sepsis/septic shock) • Meningococcal infection • Status epilepticus • Severe diabetic ketoacidosis • Coma Elective surgical admissions • Extensive/prolonged procedure (e.g. oesophagogastrectomy) • Cardiothoracic surgery • Major head and neck surgery • Coexisting cardiovascular or respiratory disease Obstetric emergencies • Severe pre-eclampsia/eclampsia • Haemorrhage • Amniotic fluid embolism ICUs are usually reserved for patients with established or impending organ failure and provide facilities for the diagnosis, prevention and treatment of multiple organ dysfunction. They are fully equipped with monitoring and technical facilities, including an adjacent laboratory and ‘near-patient testing’ devices for the rapid determination of blood gases and simple biochemical data such as serum potassium, blood glucose and serum lactate levels. Technological advances have led to the development of more compact and complex mechanical ventilators that are adaptable to individual patient demands. Portable ultrasound and echocardiography equipment is commonly available. Patients receive continuous expert nursing care and the constant attention of appropriately trained medical staff. High-dependency units (HDUs) offer a level of care intermediate between that available on the general ward and that provided in an ICU. They provide monitoring and support for patients with acute (or acute-on-chronic) single-organ failure and for those who are at risk of developing organ failure. They can also provide a ‘step-down’ facility for patients being discharged from intensive care. The proportion of a hospital's resources dedicated to intensive care varies widely internationally. For example, the UK provides 6.6 ICU and HDU beds per 100 000 population, whereas Germany provides 29.2 such beds per 100 000 population. Clinical Approach to the Critically Ill Patient Recognition and diagnosis of critical illness Early recognition, immediate resuscitation and stabilization are fundamental to the successful management of the critically ill. Previously stable ward patients may deteriorate rapidly. In order to facilitate identification of ‘at-risk’ patients on the ward and early referral to the critical care team, a number of early warning systems have been devised (e.g. the Modified Early Warning Score, MEWS; Box 25.2). 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 shown in Box 25.3 (see also pp. 1156–1161). Box 25.2 M o dif ie d Ea rly Wa rning Sc o re ( M EWS) f o r re f e rra l o f ‘ a t risk’ pa t ie nt s t o t he c rit ic a l c a re t e a m Score Parameter 3 Systolic blood pressure (mmHg) <70 2 1 71– 81– 8 0 Heart rate (b.p.m.) <40 Respiratory rate (breaths/min) Temperature (°C) 10 0 41–50 <9 <34 0 34– 1 101– 199 2 3 200 51–100 101–110 111–129 130 9–14 15–20 21–29 30 35–38.4 38.5 3 5 AVPU score (Alert, Volume, Pain, Unresponsive) Alert Reacting to voice Reacting to pain Unresponsive Box 25.3 C a lling c rit e ria f o r t he M e dic a l Eme rg e nc y Te a m Parameter Description Airway If threatened Breathing All respiratory arrests Respiratory rate <5 breaths/min Respiratory rate >36 breaths/min Circulation All cardiac arrests Pulse rate <40 b.p.m. Pulse rate >140 b.p.m. Systolic blood pressure <90 mmHg Neurology Sudden fall in level of consciousness (fall in Glasgow Coma Scale score of >2 points) Repeated or prolonged seizures Other Any patient who does not fit the criteria above but who seriously worries you (From Hillman K, Chen J, Cretikos M et al. Introduction of the medical emergency team (MET) system: a clusterrandomized controlled trial. Lancet 2005; 365:2091–2097, with permission.) These early warning systems are not infallible and have not been universally implemented. It is therefore imperative that clinicians are trained to recognize critically ill patients at the bedside. The initial assessment may elicit obvious signs. The patient may be unduly agitated or, perhaps more worryingly, unresponsive. Of particular concern is the obtunded patient who is unable to protect their own airway from aspiration of gastric or oral contents. Snoring, grunting or other respiratory sounds may indicate an obstructed airway, which can be caused by posterior displacement of the tongue due to lax oropharyngeal musculature in a comatose patient, or perhaps by secretions pooling in the oropharynx in a patient with a depressed cough reflex. Obvious use of the accessory respiratory muscles and a tracheal tug are sensitive signs of impending respiratory decompensation. Patients in severe respiratory distress frequently sit forwards, grip the sides of the bed and cannot complete sentences in a single breath. Review of the nursing observations may reveal a sudden deterioration in recorded variables, such as a sharp rise in temperature, increasing heart rate, a fall in blood pressure or decreased urine output. On examination, cool peripheries in conjunction with diaphor​esis indicate increased sympathetic drive and may be a sign of cardiogenic shock, hypovolaemia or hypoglycaemia. In contrast, flushed, warm peripheries may be a sign of a hyperdynamic circulation consistent with sepsis. Abdominal catastrophes are a common cause of an acute deterioration; an abdominal examination should always be performed and may reveal a distended, tender abdomen and often absent or altered bowel sounds consistent with a perforated viscus or ischaemic bowel. Blood gas analysis is usually readily available and should be performed as soon as possible. Acid–base status, haemoglobin concentration, blood glucose and electrolyte levels obtained from an arterial blood gas sample can all be helpful when assessing the cause and severity of an acute illness. Increased lactate levels usually indicate severe illness. An electrocardiogram (ECG) can allow the rapid diagnosis of treatable conditions, as can a portable chest X-ray. Frequently, 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. A systematic approach to the recognition and initial treatment of acute illness should be adopted, as well as performance of investigations to search for the underlying cause. A rapid assessment of the physiological derangement should be carried out, followed by prompt institution of measures to support cardiovascular and respiratory function (following the ABC approach: Airway, Breathing, Circulation; see Fig. 25.23). The patient's condition and response to treatment should be closely monitored throughout. In practice, resuscitation, assessment and diagnosis usually proceed in parallel. General aspects of managing the critically ill Critically ill patients require multidisciplinary care with: • Intensive skilled nursing care (in the UK, usually with a 1 : 1 nurse/patient ratio in an ICU (level 3 care) or 1 : 2 in a HDU (level 2 care)). Frequent clinical observations are required. • Specialized physiotherapy. This should include chest physiotherapy, mobilization and rehabilitation. • Management of pain and distress. There should be judicious administration of analgesics and sedatives (see p. 1164). • Constant reassurance and support. Critically ill patients easily become disorientated; delirium (a transient alteration in consciousness, attention, orientation, perception or behaviour) is common. Delirium may be hypoactive, agitated (hyperactive) or a combination of the two. Pain, advanced age, sleep/sensory deprivation, sedative administration (especially benzodiazepines), alcohol/drug withdrawal, neurological injury, severe illness and medical comorbidities all play a role. Patients with delirium are more difficult to wean from ventilation, are at greater risk of self-extubation and require larger doses of sedatives. Delirium has been associated with increased mortality and length of hospital stay. Treatment focuses on effective pain control, minimizing sensory deprivation and early mobilization. Avoid benzodiazepines and limit sedative administration. The use of newer sedative agents, such as the α2 agonist dexmedetomidine, may reduce the incidence of delirium and time on the ventilator. • H2-receptor antagonists or proton pump inhibitors. These agents should be given in selected cases to reduce gastric acidity and prevent stress-induced ulceration. They may, however, encourage bacterial overgrowth in the upper gastrointestinal tract and predispose patients to ventilator-associated pneumonia (VAP) if these bacteria are aspirated. • Compression stockings (full-length and graduated), pneumatic compression devices and subcutaneous low-molecular-weight heparin. These help to prevent venous thrombosis. • Mouth care. Mouth care, particularly the use of chlorhexidine mouth washes, helps to reduce hospital-acquired infections and VAP by reducing the burden of pathogenic oral flora that may be aspirated into the respiratory tree. The recent introduction of chlorhexidine body washes may reduce the total carriage of resistant microorganisms. • Prevention of constipation and pressure ulcers. • Organ support. For example, inotropes and vasopressors may be required for cardiovascular support, invasive and non-invasive ventilation for respiratory failure, and dialysis for renal failure. Specialized units may provide extracorporeal membrane oxygenation (ECMO) for severe respiratory failure, mechanical support of the circulation for cardiac failure, and advanced liver support in the form of liver dialysis (e.g. the molecular adsorbent recirculation system, MARS). • Nutritional support (see pp. 212–216). Protein energy malnutrition is common in critically ill patients and is associated with muscle wasting, weakness, delayed mobilization, difficulty weaning from ventilation, immune compromise and impaired wound healing. Enteral nutrition, usually delivered via a fine-bore nasogastric tube, is preferred because it is less expensive, preserves gut mucosal integrity, is more physiological and is associated with fewer complications. However, the value of enteral nutrition early in the course of an acute illness remains uncertain, apart from giving small amounts of enteral feed to preserve gut viability. If enteral feeding is not possible due to the gut dysmotility and malabsorption associated with critical illness, the alternative is intravenous (parenteral) nutrition (see p. 214). This is more invasive and expensive, and can be complicated by deranged liver function tests, hypertriglyceridaemia, hyperglycaemia and an increased susceptibility to hospital-acquired infections. Usually, hypocaloric enteral nutrition is continued for up to a week in previously well-nourished patients prior to considering parenteral nutrition. Administering parenteral nutrition early in order to maintain caloric input and prevent an energy deficit may be detrimental. Although all nutrition should contain carbohydrate, protein, lipids and some micronutrients, the precise optimal formulation is unclear. Supplementation with the amino acid glutamine has theoretical advantages and is recommended in some guidelines. The omega-3 fatty acids derived from fish oils also have potentially beneficial antioxidant activity but have not been convincingly shown to improve outcome, as has been the case for micronutrient supplementation with selenium, copper, manganese, zinc, iron and vitamins. Many critically ill patients are at risk of developing a ‘re-feeding syndrome’ (see p. 194) when nutritional support is first initiated. Critically ill patients commonly require intravenous insulin infusions, often in high doses, to combat insulin resistance and hyperglycaemia (which is associated with hospital-acquired infections, renal impairment and poor wound healing; see p. 1249). Although the use of intensive insulin therapy to achieve ‘tight glycaemic control’ (blood glucose level between 4.4 and 6.1 mmol/L) was initially shown to improve outcome, subsequent studies found that this approach is associated with an unacceptably high incidence of hypoglycaemia, and possibly increased mortality. Current recommendations suggest that blood glucose levels should be maintained below 8–10 mmol/L. Discharge from the ICU/HDU Discharge of patients from intensive care should normally be planned in advance and should ideally take place during normal working hours. Assessment with a quick SOFA is helpful (see p. 1154). Frequently, when the condition of critically ill patients improves, they are initially ‘stepped down’ to HDU (level 2) care. Premature or unplanned discharge from the ICU or HDU, especially during the night, has been associated with higher hospital mortality rates and should be avoided where possible. 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, respiratory, renal and neurological problems. Many patients also have failure of other organs, such as the liver; treatment of these is dealt with in more detail in the relevant chapters. F urt he r re a ding Adhikari NKJ, Fowler RA, Bhagwanjee S et al. Critical care and the global burden of critical illness. Lancet 2010; 376:1339–1341. Arabi YM, Aldawood AS, Haddad SH et al. Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med 2015; 372:2398–2408. Casaer MP, Mesotten O, Hermans G et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011; 365:506–517. Casaer MP, Van den Berghe G. Nutrition in the acute phase of critical illness. N Engl J Med 2014; 370:1227–1236. Frost PJ, Wise MP. Early management of acutely ill ward patients. BMJ 2012; 345:e5677. Fullerton JN, Perkins GD. Who to admit to intensive care? Clin Med 2011; 11:601–604. NICE–SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1293–1297. Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med 2014; 370:444–454. Vincent JL. Critical care – where have we been and where are we going? Crit Care 2013; 17(Suppl 1):S2. Applied Cardiorespiratory Physiology Oxygen delivery and consumption Oxygen delivery (DO2) (Fig. 25.1) 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, CaO2). 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). 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 25.1 Tissue oxygen delivery and consumption in a normal 70 kg person breathing air. Oxygen delivery (DO2) = cardiac output × (haemoglobin concentration × oxygen saturation (SaO2) × 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. CaO2, arterial oxygen content; content; , mixed venous oxygen , mixed venous oxygen saturation. 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 may receive insufficient oxygen, even if the overall oxygen delivery is apparently adequate. Lastly, microcirculatory flow can be impaired by an increase in 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. 25.2). 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 (PaO2) may be tolerated (since oxygen content is relatively unaffected), provided that the percentage saturation remains above about 92%. • Increasing the PaO2 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 slope of the curve (percentage saturation below about 90%), a small decrease in PaO2 can cause large falls in oxygen content, whereas increasing PaO2 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 25.2 The oxyhaemoglobin dissociation curve. 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-diphosphoglycerate (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. 520). 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. a, arterial point; v, venous point; x, arteriovenous oxygen content difference. If the PCO2 increases, the oxyhaemoglobin curve moves to the right, facilitating oxygen unloading to the tissues (Bohr effect). The PaO2 is influenced, in turn, by the alveolar oxygen tension (PAO2), the efficiency of pulmonary gas exchange, and the partial pressure of oxygen in mixed venous blood ( ). Alveolar oxygen tension (PAO2) The partial pressures of inspired gases are shown in Figure 25.3. 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 PAO2 is thereby reduced to approximately 13.4 kPa (100 mmHg). FIGURE 25.3 The composition of inspired and alveolar gas. (Partial pressures in kPa.) The clinician can influence PAO2 by administering oxygen or by increasing the barometric pressure (hyperbaric therapy). Pulmonary gas exchange In normal subjects, there is a small alveolar–arterial oxygen difference (PA–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 PA–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 PAO2 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. 25.4), 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 PaCO2 is normal or low. FIGURE 25.4 The carbon dioxide dissociation curve. Note that, in the physiological range, the curve is essentially linear. • Ventilation/perfusion (see pp. 1063–1064). Diseases of the lung parenchyma (e.g. pneumonia, pulmonary oedema, acute lung injury) result in mismatch, producing an increase in alveolar dead space and hypoxaemia. The increased dead space 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 PAO2, even in poorly ventilated areas of lung. Oxygen cascade Oxygen levels fall further as oxygen is unloaded into the tissues and diffuses to the mitochondria. Tissue oxygen content varies, depending on the distance travelled from the local capillary network. Some mitochondria continue to function at a PO2 as low as 0.07 kPa (0.5 mmHg) (Fig. 25.5). FIGURE 25.5 The oxygen cascade. Oxygen levels decrease (shown in graph) as oxygen is unloaded into the tissues and diffuses to the mitochondria. Mb, myoglobin. 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 PaO2 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 abnormalities) 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 (SCVO2), rather than pulmonary artery blood is less invasive and may be a useful guide to the resuscitation of some critically ill patients (see p. 1161). Adaptation to hypoxia Acute exposure to severe hypoxia may lead to sudden death if the immediate adaptive responses fail to maintain mitochondrial oxygen delivery. Chronic exposure to low oxygen tension, on the other hand, allows time for compensatory mechanisms to develop. Amongst the first is an acute increase in cardiac output, achieved primarily by increasing heart rate. Given the reciprocal relationship between the partial pressures of oxygen and carbon dioxide in the alveoli, as defined by the alveolar gas equation (PAO2 = PIO2 − PACO2/R), an increase in respiratory rate serves to decrease alveolar PCO2 and thereby increase alveolar PO2 (see also Fig. 25.3). Over time, increased erythropoietin production stimulates haemoglobin synthesis, leading to a marked increase in haematocrit. Over the longer term, capillary bed density in specific tissues adjusts to the physiological demand. In those residing at altitude over generations, the hypoxic ventilatory drive and pulmonary vasoconstrictor response evolve to maximize oxygen uptake. In 2007, a series of arterial blood samples were obtained by a group of critical care doctors on the summit of Mount Everest (see more online). The project included a 4-month acclimatization period at altitude and the samples were eventually obtained at an altitude of 8400 m whilst breathing air. The average PaO2 was 3.2 kPa (24.6 mmHg). These figures neatly demonstrate features of both acute (hyperventilation) and chronic (increased haematocrit) acclimatization to hypobaric hypoxia. F urt he r re a ding Grocott MPW, Martin DS, Levett DZH et al. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009; 360:140–149. Box e25.1 Art e ria l blo o d g a s me a sure me nt s a nd c a lc ula t e d va lue s f o r pulmo na ry g a s e xc ha ng e f ro m f o ur subje c t s a t a n a lt it ude o f 8 4 0 0 m, during de sc e nt f ro m t he summit o f M o unt Eve re st Variable Subject no. 1 2 Group mean 3 4 pH 7.55 7.45 7.52 7.60 7.53 PaO2 (mmHg) 29.5 19.1 21.0 28.7 24.6 PaCO2 (mmHg) 12.3 15.7 15.0 10.3 13.3 Bicarbonate (mmol/Litre) 10.5 10.67 11.97 9.87 10.8 Base excess of blood −6.3 −9.16 −6.39 −5.71 −6.9 Lactate concentration (mmol/Litre) 2.0 2.0 2.9 1.8 2.2 SaO2 (%) 68.1 34.4 43.7 69.7 54.0 Haemoglobin (g/dL) 20.2 18.7 18.8 19.4 19.3 PAO2 – mmHg 32.4 26.9 27.4 33.2 30.0 Alveolar–arterial oxygen difference (mmHg) 2.89 7.81 6.44 4.51 5.41 Cardiac output Cardiac output is the product of heart rate and stroke volume, and is affected by changes in either of these (Fig. 25.6). FIGURE 25.6 The determinants of cardiac output. Heart rate When heart rate increases, the duration of systole remains essentially unchanged, whereas diastole, and thus the time available for ventricular filling, becomes progressively shorter and the stroke volume eventually falls. In the normal heart, this occurs at rates greater than about 160 beats per minute, but in those with cardiac pathology, especially when ventricular filling is restricted (e.g. mitral stenosis), stroke volume may fall at much lower heart rates. Furthermore, tachycardias cause a marked increase in myocardial oxygen consumption ( ) and this may precipitate ischaemia in areas of the myocardium with restricted coronary perfusion. When the heart rate falls, a point is reached at which the increase in stroke volume is insufficient to compensate for bradycardia, and again cardiac output falls. Alterations in heart rate are often caused by disturbances of rhythm (e.g. atrial fibrillation, complete heart block) in which ventricular filling is not augmented by atrial contraction, exacerbating the fall in stroke volume. 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 ventricular 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. 935). 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. 25.7). 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 25.7 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, such as that 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 (Figs 25.7 and 23.5). 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 (through vasodilatation due to exercise, sepsis or vasodilating agents) can increase the stroke volume achieved at a given preload (Fig. 25.8), 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 25.8 The effect of changes in afterload on the ventricular function curve. At any given preload, decreasing afterload increases the stroke volume. Increasing the afterload (vasoconstriction due to increased sympathetic activity, vasoconstrictor agents), on the other hand, can cause a fall in stroke volume and an increase in . Right ventricular afterload is normally negligible because the resistance of the pulmonary circulation is very low but is increased in pulmonary hypertension. Cardiovascular assessment and monitoring of 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, gauge the severity of the condition, follow the evolution of the illness, guide interventions and 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. Assessment of tissue perfusion • Pale, cold skin, delayed capillary refill and the absence of visible veins in the hands and feet indicate poor perfusion. Although peripheral skin temperature measurements can help clinical evaluation, the earliest compensatory response to hypovolaemia or a low cardiac output, and the last to resolve after resuscitation, is vasoconstriction in the splanchnic region. • Metabolic acidosis with raised lactate concentration suggests that tissue perfusion is sufficiently compromised to cause cellular hypoxia and anaerobic glycolysis. Persistent, severe lactic acidosis is associated with a very poor prognosis. In addition to being used as a screen for cardiovascular insufficiency and poor tissue perfusion, lactate levels are frequently used to guide resuscitation. Extremely high lactate levels that do not respond to resuscitation are suggestive of reduced splanchnic blood flow and bowel ischaemia. In many critically ill patients, especially those with sepsis, lactic acidosis can also be caused by metabolic disorders unrelated to tissue hypoxia and can be exacerbated by reduced clearance owing to hepatic or renal dysfunction, as well as the administration of adrenaline (epinephrine). • Urinary flow is a sensitive indicator of renal perfusion and haemodynamic performance. 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 (Box 25.4 and Fig. 25.9). Box 25.4 R a dia l a rt e ry c a nnula t io n Technique 1. Explain the procedure to the patient and, if possible, obtain consent. 2. Ask an assistant to support the patient's arm, with the wrist extended. (Gloves should be worn.) 3. Clean the skin with chlorhexidine. Take sterile precautions throughout the procedure. 4. Palpate the radial artery where it arches over the head of the radius. 5. In conscious patients, inject local anaesthetic to raise a weal over the artery, taking care not to puncture the vessel or obscure its pulsation. 6. Make a small skin incision over the proposed puncture site. 7. Use a small, parallel-sided cannula (20 gauge for adults, 22 gauge for children) in order to allow blood flow to continue past the cannula. 8. Insert the cannula over the point of maximal pulsation and advance it in line with the direction of the vessel at an angle of approximately 30°. 9. Look for ‘flashback’ of blood into the cannula, which indicates that the radial artery has been punctured. 10. To ensure that the shoulder of the cannula enters the vessel, lower the needle and cannula and advance them a few millimetres into the vessel. 11. Thread the cannula off the needle into the vessel and withdraw the needle. 12. Connect the cannula to a non-compliant manometer line filled with saline. Then connect this 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 25.9 Percutaneous cannulation of the radial artery. Central venous pressure Assessment of central venous pressure (CVP) provides a fairly simple, but approximate, method of gauging the adequacy of a patient's circulating volume and may reflect the contractile state of the myocardium. The absolute value of the CVP is not as informative as its response to a fluid challenge (the infusion of 100–200 mL of fluid over a few minutes; Fig. 25.10). 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 may rise slightly and reach a plateau, while other cardiovascular values begin to stabilize. At this stage, volume replacement should be slowed, or even stopped, in order to avoid excessive transfusion (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 25.10 The effects on the central venous pressure (CVP) of rapid administration of a ‘fluid challenge’ to patients with a CVP within the normal range. The use of CVP to assess cardiovascular function, and the relationship between the response of the CVP to fluid challenge and the intravascular volume, are controversial. Many studies have failed to confirm this relationship and the use of CVP for this purpose is beginning to be supplanted by newer methods, particularly pulse contour analysis and oesophageal Doppler techniques (see below). Central venous catheters are usually inserted via a percutaneous puncture of the subclavian or internal jugular vein using a guidewire technique (Box 25.5 and Figs 25.11 and 25.12). The objective is to place the tip of the catheter approximately at the junction of the superior vena cava and the right atrium. Usually, these catheters consist of more than one lumen, some of which may be used for drug or fluid administration. Central venous cannulae may also be inserted via the femoral vein; when this route is used, the tip of the cannula will lie in the inferior vena cava and pressure measurements will not be a reliable guide to the circulating volume. Guidewire techniques can also be used for inserting double-lumen cannulae for haemofiltration or pulmonary artery catheter introducers. The routine use of ultrasound to guide central venous cannulation reduces complication rates. Box 25.5 Int e rna l jug ula r ve in c a nnula t io n Technique 1. Explain the procedure to the patient and, if possible, obtain consent. 2. Place the patient 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. Clean the skin with an antiseptic solution such as chlorhexidine. Take sterile precautions throughout the procedure. 4. Inject local anaesthetic (1% plain lidocaine) 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. Make a small incision through the weal. 6. Insert the cannula or needle through the incision and direct it 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. Thread the cannula off the needle into the vein or pass the guidewire through the needle (see Fig. 25.12). 9. Connect the central venous pressure manometer line to a manometer/transducer. 10. Take a chest X-ray 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 25.11 Cannulation of the right internal jugular vein. FIGURE 25.12 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 is usually displayed continuously using a transducer and bedside monitor but, in the absence of such equipment, can be recorded intermittently using a manometer system. It is essential for the recorded pressure always to 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 the choice is largely immaterial, provided the landmark is used consistently in an individual patient. Left atrial pressure In uncomplicated cases, careful interpretation of the CVP may provide 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 downwards and to the right (Fig. 25.13). High right ventricular filling pressures, with normal or low left atrial pressures, are less common but occur with right ventricular dysfunction and with raised pulmonary vascular resistance (i.e. right ventricular afterload), such as in acute respiratory failure and pulmonary embolism. FIGURE 25.13 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 pressures A ‘balloon flotation catheter’ enables reliable catheterization of the pulmonary artery. These ‘Swan–Ganz’ catheters can be inserted centrally (see Fig. 25.11) 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 (Box 25.6 and Fig. 25.14). A chest X-ray should always be obtained to check the final position of the catheter (Fig. 25.15). Box 25.6 P a ssa g e o f a pulmo na ry a rt e ry ba llo o n f lo t a t io n c a t he t e r The catheter is passed through the chambers of the heart into the ‘wedged’ position. 1. Explain the procedure to the patient and, if possible, obtain consent. 2. Insert a balloon flotation catheter through a large vein (see text). 3. Look for respiratory oscillations once the catheter is in the thorax. Advance it further towards the lower superior vena cava/right atrium (see Fig. 25.14A), where pressure oscillations become more pronounced. Then inflate the balloon and advance the catheter. 4. When the catheter is in the right ventricle (see Fig. 25.14B), there is no dicrotic notch and the diastolic pressure is close to 0. Return the patient to the horizontal, or slightly head-up, position before advancing the catheter further. 5. When the catheter reaches the pulmonary artery (see Fig. 25.14C), a dicrotic notch appears and there is elevation of the diastolic pressure. Advance the catheter further with the balloon inflated. 6. Reappearance of a venous waveform indicates that the catheter is ‘wedged’. Deflate the balloon to obtain the pulmonary artery pressure. Inflate the balloon intermittently to obtain the pulmonary artery occlusion pressure (also known as pulmonary artery or capillary ‘wedge’ pressure; see Fig. 25.14D). FIGURE 25.14 Passage of pulmonary artery balloon flotation catheter through the chambers of the heart. The catheter is passed into the ‘wedged’ position to measure the pulmonary artery occlusion pressure (see Box 25.6). PA, pulmonary artery; RA, right artery; RV, right ventricle. FIGURE 25.15 Chest X-ray of a critically ill, mechanically ventilated patient. The X-ray shows (a) endotracheal tube; (b) end of central venous line seen here medial to the proximal end of the pulmonary artery catheter; (c) double-lumen catheter for continuous renal replacement therapy placed via the left internal jugular vein; (d) tip of the intra-aortic balloon pump travelling superiorly from a femoral artery; and (e) pulmonary artery catheter. Note that the tip of the catheter is too distal; it was therefore subsequently withdrawn by a few centimetres. Once in place, the balloon is deflated and the pulmonary artery mean, systolic and enddiastolic 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 re-inflating 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 the 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. Cardiac output Cardiac output can be continuously monitored using a modified pulmonary artery catheter that transmits low-energy heat from a heating element in the catheter into the surrounding blood. A ‘thermodilution curve’ is constructed by measuring dissipation of the heat using a thermistor located distal to the heating coil. The dissipation of heat is directly proportional to the cardiac output. These catheters also optically measure and continuously display . In general, pulmonary artery catheters may help 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. The unselective use of this monitoring device in the absence of evidence-based haemodynamic goals does not, however, lead to improved outcomes and less invasive techniques are preferred, except in the most complex cases (e.g. high-risk cardiac surgery). 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 (see p. 1163). 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 be predicted simply 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 monitor velocity waveforms from the descending aorta continuously (Fig. 25.16). 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 25.16 Doppler ultrasonography. Velocity waveform traces are obtained using oesophageal Doppler ultrasonography. (Reproduced from Singer et al (1991), with permission. © 1991 The W illiams & W ilkins Co., Baltimore.) Arterial waveform 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. Other devices utilize a thermodilution technique, where a small volume of cold fluid is injected into a large central vein and a temperature washout curve is detected via a sensor in a modified arterial line. Following this calibration, beat-to-beat cardiac output is generated by computer-based analysis of the arterial pressure waveform. As with pulse pressure variation, stroke volume variation, determined by oesophageal Doppler or arterial waveform analysis, can be used to guide fluid replacement. 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. Although transoesophageal echocardiography (TOE) may be preferred because of its superior image clarity (Fig. 25.17), trans​thoracic probes are increasingly used on general ICUs. FIGURE 25.17 Aortic dissection (transoesophageal echocardiography, TOE). A. Mid-oesophageal, longaxis view showing type A aortic dissection. B. Short-axis view of descending aorta showing intimal flap with false and true lumen. (From Hinds CJ, W atson JD. Intensive Care: A Concise Textbook, 3rd edn. Edinburgh: Saunders; 2008. Courtesy of Dr C. Rathwell.) Key points in monitoring cardiac function These are shown in Box 25.7. F urt he r re a ding Lamperti M, Bodenham AR, Pittiruti M et al. International evidence-based recommendations on ultrasound-guided vascular access. Intensive Care Med 2012; 38:1105–1117. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care 2011; 1:1. Box 25.7 Ke y po int s in mo nit o ring c a rdia c f unc t io n • 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 • Use non-invasive monitoring where possible • Remove invasive devices as soon as possible Disturbances of Acid–Base Balance The physiology of acid–base control is discussed on pages 174–176. Acid–base disturbances can be described in relation to Figure 9.14 (which shows PaCO2 plotted against arterial [H+]). Both acidosis and alkalosis can occur, each of which is either metabolic (primarily affecting the bicarbonate component of the system) or respiratory (primarily affecting PaCO2). 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 Box 25.8. (For blood gas analysis, see pp. 1161–1162.) Box 25.8 Art e ria l blo o d g a s a nd a c id– ba se va lue s Analyte Normal reference range H+ 35–45 nmol/L (pH 7.35–7.45) PO2 (breathing room air) 10.6–13.3 kPa (80–100 mmHg) PCO2 4.8–6.1 kPa (36–46 mmHg) Base deficit ± 2.5 Plasma HCO3− 22–26 mmol/L O2 saturation 95–100% Respiratory acidosis This is caused by retention of carbon dioxide. The PaCO2 and [H+] rise. A chronically raised PaCO2 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. 177). Common causes of respiratory acidosis include ventilatory failure and COPD (type II respiratory failure, where there is a high PaCO2 and a low PaO2; see p. 1161). Respiratory alkalosis In this case, the reverse occurs and there is a fall in PaCO2 and [H+], often with a small reduction in bicarbonate concentration. If hypo​carbia 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 in patients with hypoxaemic (type I) respiratory failure (see p. 1161), those with spontaneous hyperventilation, and those living at high altitudes (see online, ‘Adaptation to hypoxia’, for an example of a partly compensated respiratory alkalosis secondary to extreme hypoxaemia). Metabolic acidosis Metabolic acidosis (see p. 177) may be due to excessive acid production, often lactate and H+ (lactic acidosis), as a consequence of anaerobic metabolism during an episode of shock or following cardiac arrest. A metabolic acidosis may develop as a consequence of 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 PaCO2 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 PaCO2 above 6.5 kPa (50 mmHg), even with severe alkalosis. Shock, Sepsis and Acute Disturbances of Haemodynamic Function Shock is the term used to describe acute circulatory failure with inadequate or inappropriately distributed tissue perfusion, resulting in generalized cellular hypoxia and/or an inability of the cells to utilize oxygen. Aetiology of shock Abnormalities of tissue perfusion can result from: • failure of the heart to act as an effective pump • mechanical impediments to forward flow • loss of circulatory volume • abnormalities of the peripheral circulation. The causes of shock are shown in Box 25.9; see also page 1154 for definitions of sepsis. Often, shock can result from a combination of these factors (e.g. in sepsis, distributive shock is frequently complicated by hypovolaemia and myocardial depression). Box 25.9 C a use s o f sho c k Hypovolaemic • Exogenous losses (e.g. haemorrhage, burns) Cardiogenic • ‘Myocardial failure’ (e.g. ischaemic myocardial injury) Obstructive • Obstruction to cardiac outflow (e.g. pulmonary embolus) • Restricted cardiac filling (e.g. cardiac tamponade, tension pneumothorax) Distributive • (e.g. sepsis, anaphylaxis) • Vascular dilatation • Sequestration • Arteriovenous shunting • Maldistribution of flow • Myocardial depression Pathophysiology The sympatho-adrenal response to shock 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 (Fig. 25.18). FIGURE 25.18 The sympatho-adrenal response to shock. The effect of increased catecholamines is shown 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. Reduced perfusion of the renal cortex stimulates the juxtaglomerular apparatus to release renin. This converts angiotensin​ogen to angiotensin I, which, in turn, is converted in the lungs and by the vascular endothelium to the potent vasoconstrictor angio​tensin II. Angiotensin II also stimulates secretion of aldosterone by the adrenal cortex, causing sodium a