Explore how Davidson's approaches the acutely unwell patient, from bedside monitoring and critical care examination to chest pain, breathlessness, anaphylaxis, and deterioration.
Highly regarded, trusted guidance on the principles and practice of medicine for 75 years – now fully revised Order your copy today at elsevierhealth.com/9780443287602 From Davidson’s Principles and Practice of Medicine, 25th Edition Exclusive preview: Acute medicine and critical illness 212 • Acute medicine And criticAl illness Clinical examination in critical care Airway Is the airway patent? Is the end-tidal CO2 trace normal? Are there any signs of airway obstruction? 1 2 Circulation Is the physiology normal (heart rate, blood pressure, peripheral temperature, lactate, urine output)? How much support is required (inotrope, vasopressor)? 3 4 5 Glucose What is the glucose level? Is insulin being administered? 7 7 4 Haematology What are the haemoglobin/ platelet levels? Are there any signs of bleeding? 8 Infection What is the temperature? Review recent infective markers and trend What antibiotics are being given and what is the duration of treatment? 9 Enteral/exposure Feeding regimen Stool frequency Abdominal tenderness/bowel sounds present? Disability Level of responsiveness Delirium screen Pupillary responses Doses of sedative drugs 6 Fluids, electrolytes and renal system What is the fluid balance? Urine volume and colour? Is there any oedema? Review the renal biochemistry and electrolyte levels Breathing Is the physiology normal ( Sp O2, respiratory rate, tidal volume)? What is the level of support? Are there any abnormal signs on chest examination? Review the ventilator settings, arterial blood gases and recent chest X-ray 6 5 3 2 1 monitoring • 213 10 Electrocardiography Heart rate, rhythm and QRS morphology Arterial line trace Size of the area under the curve is proportional to stroke volume Narrow peaks suggest low stroke volume as shown here Oxygen saturation Saturation of haemoglobin measured by plethysmography ( Sp O2). Gives an indication of adequacy of oxygenation, and the quality of tissue perfusion can also be inferred – a flat trace suggests poor peripheral perfusion Central venous pressure trace A non-specific guide to volume status and right ventricular function. Increased values in fluid overload and right ventricular failure Capnography Numerical value of end-tidal CO2 (ETCO2) is less than arterial P CO2 ( Pa CO2) by a variable amount. Shape of trace can signify airway displacement/obstruction, bronchospasm or a low cardiac output (as shown below) kPa mmHg Time (secs) 0 5 40 Normal Steep ‘upstroke’ in early expiration Bronchospasm Shallow ‘upstroke’ in early expiration Partial obstruction/displacement of airway device Decreasing cardiac output Decreasing size of ETCO2 waveform No ventilation (from any cause) Bedside physiological data commonly monitored in an intensive care unit setting. Monitoring Pulse oximetry ( Sp O 2 ) Basic principles • Uses the different red and infrared absorption profiles of oxyhaemoglobin and deoxyhaemoglobin to estimate arterial oxyhaemoglobin saturation ( Sa O 2 ) • Only pulsatile absorption is measured • A poor trace correlates with poor perfusion Sources of error • Race – Sp O 2 (vs Sa O 2 ) is overestimated in patients with darker skin. This is more pronounced at lower saturation levels. Desaturation can be under- estimated in patients with darker skin • Carboxyhaemoglobin – absorption profile is the same as oxyhaemoglobin: falsely elevated Sp O 2 • Methaemoglobinaemia – Sp O 2 will tend towards 85% regardless of oxygen content • Ambient light/poor application of probe/severe tricuspid regurgitation (pulsatile venous flow): falsely depressed Sp O 2 • Reduced accuracy below 80% saturation • Hyperbilirubinaemia does not affect Sp O 2 Presenting problems in acute medicine • 219 10 Anaphylaxis Anaphylaxis is a potentially life-threatening, systemic allergic reaction characterised by a variable combination of circulatory collapse, bron- chospasm, laryngeal stridor, angioedema and urticaria. The risk of death is increased in patients with pre-existing asthma, particularly if this is poorly controlled, and in situations where treatment with adrenaline (epi- nephrine) is delayed. Presentation Anaphylaxis occurs when an allergen binds to and cross-links mem- brane-bound IgE on mast cells in a susceptible individual, causing release of histamine, tryptase and other vasoactive mediators from mast cells. These mediators have a variety of effects, including vasodilatation, increased capillary permeability leading to hypotension, and broncho- constriction. It can be difficult to distinguish IgE-mediated anaphylaxis clinically from non-specific degranulation of mast cells on exposure to drugs, chemicals or other triggers where IgE is not involved, previously known as anaphylactoid reactions. Clinical assessment The clinical features of anaphylaxis are summarised in Figure 10.3. Several other conditions can mimic anaphylaxis and these are listed in Box 10.6. It is important to assess the severity of the reaction, and the time between allergen exposure and onset of symptoms provides a guide. Enquiry should be made about potential triggers. If a trigger is immedi- ately obvious, a detailed history of the previous 24 hours may be helpful. The most common triggers of anaphylaxis are foods, latex, insect venom and drugs. A history of previous local allergic responses to the offending agent is common. The route of allergen exposure may influence the prin- cipal clinical features of a reaction; for example, if an allergen is inhaled, the major symptom is frequently wheezing. Features of anaphylaxis may overlap with the direct toxic effects of drugs and venoms (Chs 11 and 12). Potentiating factors, such as exercise, alcohol, nonsteroidal anti-in- flammatory medications or fatigue, can lower the threshold for an ana- phylactic event. It is important to identify precipitating factors so that appropriate avoidance measures may be taken in the longer term. Investigations and management Measurement of serum mast cell tryptase concentrations is useful to confirm the diagnosis. It is important to measure tryptase in serial tests to demonstrate the temporal relationship to the triggering event. Specific IgE tests may be useful in confirming hypersensitivity and may be prefer- able to skin-prick tests when investigating patients with a history of ana- phylaxis. The cornerstone of management of a severe case is the early administration of adrenaline (epinephrine), which supports the cardiovas- cular system, reduces bronchospasm and has some disease-modifying effects. Secondary management depends upon which organs are most affected. The emergency management of anaphylaxis is summarised in Box 10.7. If present, angioedema of the orofacial area requires careful observation and timely intervention, possibly with endotracheal intuba- tion. The investigation and management of angioedema is discussed further on page 81. Individuals who have recovered from an anaphylactic event should be referred for specialist assessment. The aims are to identify the trig- ger, educate the patient regarding avoidance and management of sub- sequent episodes, and to establish whether specific treatment, such as immunotherapy, is indicated. If the trigger factor cannot be identi- fied or avoided, recurrence is common. Patients who have previously experienced an anaphylactic event should be prescribed self-injectable Itching of palms, soles of feet and genitalia Feeling of impending doom, loss of consciousness Conjunctival injection Flushing Sweating Hypotension Urticaria Wheeze, bronchoconstriction Angioedema of lips and mucous membrane Abdominal pain Diarrhoea Cardiac arrhythmias Laryngeal obstruction Stridor Wasp sting Fig. 10.3 Clinical manifestations of anaphylaxis. In this example, the response is to an insect sting containing venom to which the patient is allergic. This causes release of histamine and other vasoactive mediators, which lead to the characteristic features of anaphylaxis that are illustrated. 10.6 Differential diagnosis of anaphylaxis Causes of hypotension • Vasovagal syncope • Cardiac arrhythmia • Cardiogenic shock Causes of respiratory distress • Status asthmaticus • Pulmonary embolus Causes of laryngeal obstruction • C1 inhibitor deficiency • Idiopathic angioedema Causes of generalised flushing • Systemic mastocytosis • Carcinoid syndrome 214 • Acute medicine And criticAl illness Hospital medicine is becoming ever-more specialised and people are living longer while accruing increasing numbers of chronic disease diag- noses. Rather than diminishing the role of the generalist, these factors paradoxically create a need for experts in the undifferentiated presenta- tion. In the UK such physicians are known as ‘general physicians’, while in the United States they are referred to as ‘hospitalists’. Acute illness can present in a large variety of ways, depending on the nature of the illness, the underlying health of the individual, and their cul- tural and religious background. The skills of prompt diagnosis formation and provision of appropriate treatment rely on the integration of infor- mation from all the available sources, along with careful consideration of underlying chronic health problems. Patients who deteriorate while in hospital make up a small but impor- tant cohort. If they are well managed, in-hospital cardiac arrest rates will be low. This can be achieved through the combined effects of prompt resuscitation and appropriate end-of-life decision-making. Early recog- nition of deterioration by ward teams and initial management by health- care professionals operating within a functioning rapid response system are the central tenets of any system designed to improve the outcomes of deteriorating ward patients. Intensive care medicine has developed into a prominent specialty, central to the safe functioning of a modern acute hospital. Scientific endeavour has resulted in a much better understanding of the molecu- lar pathophysiology of processes such as sepsis and acute respiratory distress syndrome, which account for much premature death worldwide. Acute medicine Acute medicine is the part of general medicine that is concerned with the immediate and early management of medical patients who require urgent care. As a specialty, it is closely aligned with emergency medicine and intensive care medicine, but is firmly rooted within general medicine. Acute physicians manage the adult medical take and lead the develop- ment of acute care pathways that aim to reduce variability, improve care and cut down hospital admissions. In order to achieve these aims, acute physicians must use their knowledge, combined with high-level clinical reasoning and decision-making skills, to minimise both diagnostic error and the risks of over-investigation. These concepts are explained more fully in Chapter 1. The decision to admit to hospital Every patient presenting to hospital should be assessed by a clinician who is able to determine whether or not admission is required. The requirement for admission is determined by many factors, including the severity of illness, the patient’s physiological reserve, the need for urgent investigations, the nature of proposed treatments and the patient’s social circumstances. In many cases, it is clear early in the assessment pro- cess that a patient requires admission. In such cases, a move into a medical receiving unit – often termed a medical admissions unit (MAU) or acute medical unit (AMU) – should be facilitated as soon as the initial assessment has been completed and urgent investigations and/or treat- ments have been instigated. In hospitals where such units do not exist, patients will need to be moved to a downstream ward once treatment has been commenced and they have been deemed sufficiently stable. In suspected cases of airborne-transmissible infectious diseases, patients should be isolated initially and may require cohorting in specific areas of the hospital once diagnoses have been confirmed. Following the ini- tial assessment, it may be possible to discharge stable patients home with a plan for early follow-up (such as a rapid-access specialist clinic appointment). Ambulatory care In some hospitals, it is increasingly possible for patient care to be coordi- nated in an ambulatory setting, negating the need for a patient to remain in hospital overnight. In the context of acute medicine, ambulatory care can be employed for conditions that are perceived by either the patient or the referring practitioner as requiring prompt clinical assessment by a competent decision-maker with access to appropriate diagnostic resources. The patient may return on several occasions for investigation, observation, consultation or treatment. Some presentations, such as a unilateral swollen leg (p. 224), lend themselves to this type of manage- ment (Box 10.1). If indicated, a Doppler ultrasound can be arranged, and patients with confirmed deep vein thrombosis can be anticoagulated on an outpatient basis. Successful ambulatory care requires careful patient selection; while many patients may cherish the opportunity to sleep at home, others may find frequent trips to hospital or clinic too difficult due to frailty, poor mobility or transport difficulties. Presenting problems in acute medicine This section details some of the most common presentations to acute medicine. However, many people present to hospital with physical com- plaints that do not appear to be the symptoms of a medical condition, referred to as ‘medically unexplained’ or ‘functional’ symptoms (see Chs 22, 27 and 29). It is thought that such symptoms may account for up to half of all new visits to hospital in the UK. Rather than providing reassur- ance, a lack of understanding of the cause of the symptoms can result in more distress for patients. When the unexplained symptoms relate to the nervous system (such as limb weakness, numbness, shaking or black- outs), the term ‘functional neurological disorder’ is used (see p. 1183). Medically unexplained symptoms are more common in women, younger people, those who have previously suffered from depression or anxiety, recently bereaved people and those recovering from a recent physical illness. For every acute medical presentation, there will be a cohort of patients for whom the diagnosis remains elusive. In such circumstances, consideration should be given to the potential harm of over-investiga- tion and the alternative approaches required to manage medically unex- plained symptoms. 10.1 Groups of patients who are potentially suitable for ambulatory care Group Example(s) Quality and safety issues Diagnostic exclusion group Chest pain – possible myocardial infarction; breathlessness – possible pulmonary embolism Even when a specific condition has been excluded, there is still a need to explain the patient’s symptoms through the diagnostic process Low-risk stratification group Non-variceal upper gastrointestinal bleed with low Blatchford score (Box 22.17); community-acquired pneumonia with low CURB-65 score (see Fig. 17.32) Appropriate treatment plans should be in place Specific procedure group Replacement of percutaneous endoscopic gastrostomy (PEG) tube; drainage of pleural effusion/ascites The key to implementation is how ambulatory care for this group of patients can be delivered when they present out of hours Outpatient group with supporting infrastructure Deep vein thrombosis (DVT); cellulitis These are distinct from the conditions listed above because the infrastructure required to manage them is quite different
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 Acute medicine and critical illness 10 Victoria R Tallentire Michael J MacMahon Clinical examination in critical care 212 Monitoring 213 Acute medicine 214 The decision to admit to hospital 214 Ambulatory care 214 Presenting problems in acute medicine 214 Chest pain 215 Acute breathlessness 217 Anaphylaxis 219 Syncope/presyncope 220 Headache 222 Confusion 224 Unilateral leg swelling 224 Acute abdomen 226 Identification and assessment of deterioration 228 Early warning scores and the role of the medical emergency team 228 Immediate assessment of the deteriorating patient 228 Selecting the appropriate location for ongoing management and anticipatory care planning 228 Common presentations of deterioration 229 Tachypnoea 229 Hypoxaemia 229 Tachycardia 229 Hypotension 232 Hypertension 234 Decreased conscious level 234 Decreased urine output/deteriorating renal function 235 Disorders causing critical illness 235 Sepsis and the systemic inflammatory response 235 Acute respiratory distress syndrome 238 Acute circulatory failure (cardiogenic shock) 239 Cardiac arrest 240 Post cardiac arrest 241 Other causes of multi-organ failure 241 Critical care medicine 243 Decisions around intensive care admission 243 Stabilisation and institution of organ support 244 Respiratory support 244 Cardiovascular support 246 Renal support 249 Neurological support 249 Daily clinical management in intensive care 250 Clinical review 250 Infection surveillance 250 Sedation and analgesia 250 Delirium in intensive care 250 Weaning from respiratory support 251 Extubation 251 Tracheostomy 251 Nutrition 251 Other essential components of intensive care 251 Complications and outcomes of critical illness 252 Adverse neurological outcomes 252 Airway complications 252 Micro- and macrovascular complications 253 Other complications 253 The older patient 254 Withdrawal of active treatment and death in intensive care 254 Discharge from intensive care 255 Critical care scoring systems 255
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 212 • Acute medicine And criticAl illness Clinical examination in critical care Airway Is the airway patent? Is the end-tidal CO2 trace normal? Are there any signs of airway obstruction? 1 2 Circulation Is the physiology normal (heart rate, blood pressure, peripheral temperature, lactate, urine output)? How much support is required (inotrope, vasopressor)? 3 4 5 Glucose What is the glucose level? Is insulin being administered? 7 7 4 Haematology What are the haemoglobin/ platelet levels? Are there any signs of bleeding? 8 Infection What is the temperature? Review recent infective markers and trend What antibiotics are being given and what is the duration of treatment? 9 Enteral/exposure Feeding regimen Stool frequency Abdominal tenderness/bowel sounds present? Disability Level of responsiveness Delirium screen Pupillary responses Doses of sedative drugs 6 Fluids, electrolytes and renal system What is the fluid balance? Urine volume and colour? Is there any oedema? Review the renal biochemistry and electrolyte levels Breathing Is the physiology normal ( Sp O2, respiratory rate, tidal volume)? What is the level of support? Are there any abnormal signs on chest examination? Review the ventilator settings, arterial blood gases and recent chest X-ray 6 5 3 2 1
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 monitoring • 213 10 Electrocardiography Heart rate, rhythm and QRS morphology Arterial line trace Size of the area under the curve is proportional to stroke volume Narrow peaks suggest low stroke volume as shown here Oxygen saturation Saturation of haemoglobin measured by plethysmography ( Sp O2). Gives an indication of adequacy of oxygenation, and the quality of tissue perfusion can also be inferred – a flat trace suggests poor peripheral perfusion Central venous pressure trace A non-specific guide to volume status and right ventricular function. Increased values in fluid overload and right ventricular failure Capnography Numerical value of end-tidal CO2 (ETCO2) is less than arterial P CO2 ( Pa CO2) by a variable amount. Shape of trace can signify airway displacement/obstruction, bronchospasm or a low cardiac output (as shown below) kPa mmHg Time (secs) 0 5 40 Normal Steep ‘upstroke’ in early expiration Bronchospasm Shallow ‘upstroke’ in early expiration Partial obstruction/displacement of airway device Decreasing cardiac output Decreasing size of ETCO2 waveform No ventilation (from any cause) Bedside physiological data commonly monitored in an intensive care unit setting. Monitoring Pulse oximetry ( Sp O 2 ) Basic principles • Uses the different red and infrared absorption profiles of oxyhaemoglobin and deoxyhaemoglobin to estimate arterial oxyhaemoglobin saturation ( Sa O 2 ) • Only pulsatile absorption is measured • A poor trace correlates with poor perfusion Sources of error • Race – Sp O 2 (vs Sa O 2 ) is overestimated in patients with darker skin. This is more pronounced at lower saturation levels. Desaturation can be under- estimated in patients with darker skin • Carboxyhaemoglobin – absorption profile is the same as oxyhaemoglobin: falsely elevated Sp O 2 • Methaemoglobinaemia – Sp O 2 will tend towards 85% regardless of oxygen content • Ambient light/poor application of probe/severe tricuspid regurgitation (pulsatile venous flow): falsely depressed Sp O 2 • Reduced accuracy below 80% saturation • Hyperbilirubinaemia does not affect Sp O 2
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 214 • Acute medicine And criticAl illness Hospital medicine is becoming ever-more specialised and people are living longer while accruing increasing numbers of chronic disease diag- noses. Rather than diminishing the role of the generalist, these factors paradoxically create a need for experts in the undifferentiated presenta- tion. In the UK such physicians are known as ‘general physicians’, while in the United States they are referred to as ‘hospitalists’. Acute illness can present in a large variety of ways, depending on the nature of the illness, the underlying health of the individual, and their cul- tural and religious background. The skills of prompt diagnosis formation and provision of appropriate treatment rely on the integration of infor- mation from all the available sources, along with careful consideration of underlying chronic health problems. Patients who deteriorate while in hospital make up a small but impor- tant cohort. If they are well managed, in-hospital cardiac arrest rates will be low. This can be achieved through the combined effects of prompt resuscitation and appropriate end-of-life decision-making. Early recog- nition of deterioration by ward teams and initial management by health- care professionals operating within a functioning rapid response system are the central tenets of any system designed to improve the outcomes of deteriorating ward patients. Intensive care medicine has developed into a prominent specialty, central to the safe functioning of a modern acute hospital. Scientific endeavour has resulted in a much better understanding of the molecu- lar pathophysiology of processes such as sepsis and acute respiratory distress syndrome, which account for much premature death worldwide. Acute medicine Acute medicine is the part of general medicine that is concerned with the immediate and early management of medical patients who require urgent care. As a specialty, it is closely aligned with emergency medicine and intensive care medicine, but is firmly rooted within general medicine. Acute physicians manage the adult medical take and lead the develop- ment of acute care pathways that aim to reduce variability, improve care and cut down hospital admissions. In order to achieve these aims, acute physicians must use their knowledge, combined with high-level clinical reasoning and decision-making skills, to minimise both diagnostic error and the risks of over-investigation. These concepts are explained more fully in Chapter 1. The decision to admit to hospital Every patient presenting to hospital should be assessed by a clinician who is able to determine whether or not admission is required. The requirement for admission is determined by many factors, including the severity of illness, the patient’s physiological reserve, the need for urgent investigations, the nature of proposed treatments and the patient’s social circumstances. In many cases, it is clear early in the assessment pro- cess that a patient requires admission. In such cases, a move into a medical receiving unit – often termed a medical admissions unit (MAU) or acute medical unit (AMU) – should be facilitated as soon as the initial assessment has been completed and urgent investigations and/or treat- ments have been instigated. In hospitals where such units do not exist, patients will need to be moved to a downstream ward once treatment has been commenced and they have been deemed sufficiently stable. In suspected cases of airborne-transmissible infectious diseases, patients should be isolated initially and may require cohorting in specific areas of the hospital once diagnoses have been confirmed. Following the ini- tial assessment, it may be possible to discharge stable patients home with a plan for early follow-up (such as a rapid-access specialist clinic appointment). Ambulatory care In some hospitals, it is increasingly possible for patient care to be coordi- nated in an ambulatory setting, negating the need for a patient to remain in hospital overnight. In the context of acute medicine, ambulatory care can be employed for conditions that are perceived by either the patient or the referring practitioner as requiring prompt clinical assessment by a competent decision-maker with access to appropriate diagnostic resources. The patient may return on several occasions for investigation, observation, consultation or treatment. Some presentations, such as a unilateral swollen leg (p. 224), lend themselves to this type of manage- ment (Box 10.1). If indicated, a Doppler ultrasound can be arranged, and patients with confirmed deep vein thrombosis can be anticoagulated on an outpatient basis. Successful ambulatory care requires careful patient selection; while many patients may cherish the opportunity to sleep at home, others may find frequent trips to hospital or clinic too difficult due to frailty, poor mobility or transport difficulties. Presenting problems in acute medicine This section details some of the most common presentations to acute medicine. However, many people present to hospital with physical com- plaints that do not appear to be the symptoms of a medical condition, referred to as ‘medically unexplained’ or ‘functional’ symptoms (see Chs 22, 27 and 29). It is thought that such symptoms may account for up to half of all new visits to hospital in the UK. Rather than providing reassur- ance, a lack of understanding of the cause of the symptoms can result in more distress for patients. When the unexplained symptoms relate to the nervous system (such as limb weakness, numbness, shaking or black- outs), the term ‘functional neurological disorder’ is used (see p. 1183). Medically unexplained symptoms are more common in women, younger people, those who have previously suffered from depression or anxiety, recently bereaved people and those recovering from a recent physical illness. For every acute medical presentation, there will be a cohort of patients for whom the diagnosis remains elusive. In such circumstances, consideration should be given to the potential harm of over-investiga- tion and the alternative approaches required to manage medically unex- plained symptoms. 10.1 Groups of patients who are potentially suitable for ambulatory care Group Example(s) Quality and safety issues Diagnostic exclusion group Chest pain – possible myocardial infarction; breathlessness – possible pulmonary embolism Even when a specific condition has been excluded, there is still a need to explain the patient’s symptoms through the diagnostic process Low-risk stratification group Non-variceal upper gastrointestinal bleed with low Blatchford score (Box 22.17); community-acquired pneumonia with low CURB-65 score (see Fig. 17.32) Appropriate treatment plans should be in place Specific procedure group Replacement of percutaneous endoscopic gastrostomy (PEG) tube; drainage of pleural effusion/ascites The key to implementation is how ambulatory care for this group of patients can be delivered when they present out of hours Outpatient group with supporting infrastructure Deep vein thrombosis (DVT); cellulitis These are distinct from the conditions listed above because the infrastructure required to manage them is quite different
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 Presenting problems in acute medicine • 215 10 Chest pain Chest pain is a common symptom in patients presenting to hospital. The differential diagnosis is wide (Box 10.2), and a detailed history and thor- ough clinical examination are paramount to ensure that the subsequent investigative pathway is appropriate. Presentation Chest ‘pain’ is clearly a subjective phenomenon and may be described by patients in a variety of different ways. Whether the patient describes ‘pain’, ‘discomfort’ or ‘pressure’ in the chest, there are some key features that must be elicited from the history. Site and radiation Pain secondary to myocardial ischaemia is typically located in the centre of the chest. It may radiate to the neck, jaw and upper or even lower arms. Occasionally, it may be experienced only at the sites of radiation or in the back. The pain of myocarditis or pericarditis is characteristically felt retrosternally, to the left of the sternum, or in the left or right shoulder. The severe pain of aortic dissection is typically central with radiation through to the back. Central chest pain may also occur with tumours affecting the mediastinum, oesophageal disease (p. 824) or disease of the thoracic aorta (p. 479). Pain situated over the left anterior chest and radiating laterally is unlikely to be due to cardiac ischaemia and may have many causes, including pleural or lung disorders, musculoskeletal problems or anxiety. Rarely, sharp, left-sided chest pain that is suggestive of a mus- culoskeletal problem may be a feature of mitral valve prolapse (p. 491). Characteristics Pleurisy, a sharp or ‘catching’ chest pain aggravated by deep breathing or coughing, is indicative of respiratory pathology, particularly pulmonary infection or infarction. However, the pain associated with myocarditis or pericarditis is often also described as ‘sharp’ and may ‘catch’ dur- ing inspiration, coughing or lying flat. It typically varies in intensity with movement and the phase of respiration. A malignant tumour invading the chest wall or ribs can cause gnawing, continuous local pain. The pain of myocardial ischaemia is typically dull, constricting, choking or ‘heavy’, and is usually described as squeezing, crushing, burning or ach- ing. Patients often emphasise that it is a discomfort rather than a pain. Angina occurs during (not after) exertion and is promptly relieved (in less than 5 minutes) by rest. It may also be precipitated or exacerbated by emotion but tends to occur more readily during exertion, after a large meal or in a cold wind. In crescendo or unstable angina, similar pain may be precipitated by minimal exertion or at rest. The increase in venous return or preload induced by lying down may also be sufficient to provoke pain in vulnerable patients (decubitus angina). Patients with reversible airways obstruction, such as asthma, may also describe exertional chest tightness that is relieved by rest. This may be difficult to distinguish from myocardial ischaemia. Bronchospasm may be associated with wheeze, atopy and cough (p. 537). Musculoskeletal chest pain is variable in site and intensity but does not usually fall into any of the patterns described above. The pain may vary with posture or movement of the upper body, or be associated with a specific movement (bending, stretching, turning). Many minor soft tissue injuries are related to everyday activities, such as driving, manual work and sport. Onset The pain associated with myocardial infarction (MI) typically takes sev- eral minutes or even longer to develop to its maximal intensity; similarly, angina builds up gradually in proportion to the intensity of exertion. Pain that occurs after, rather than during, exertion is usually musculoskele- tal or psychological in origin. The pain of aortic dissection (severe and ‘tearing’), massive pulmonary embolism (PE) or pneumothorax is usually very sudden in onset. Other causes of chest pain tend to develop more gradually, over hours or even days. Associated features The pain of MI, massive PE or aortic dissection is often accompanied by autonomic disturbance, including sweating, nausea and vomiting. Some patients describe a feeling of impending death, referred to as ‘angor animi’. Breathlessness, due to pulmonary congestion arising from tran- sient ischaemic left ventricular dysfunction, is often a prominent feature of myocardial ischaemia. Breathlessness may also accompany any of the respiratory causes of chest pain and can be associated with cough, wheeze or other respiratory symptoms. Patients with myocarditis or peri- carditis may describe a prodromal viral illness. Gastrointestinal disorders, such as gastro-oesophageal reflux or peptic ulceration, may present with chest pain that is hard to distinguish from myocardial ischaemia; it may even be precipitated by exercise and be relieved by nitrates. However, it is usually possible to elicit a history relating chest pain to supine pos- ture or eating, drinking or oesophageal reflux. The pain of gastro-oe- sophageal reflux often radiates to the interscapular region and dysphagia may be present. Severe chest pain arising after retching or vomiting, or following oesophageal instrumentation, should raise the possibility of oesophageal perforation. Anxiety-induced chest pain may be associated with breathlessness (without hypoxaemia), throat tightness, perioral tingling and other evi- dence of emotional distress. It is important to remember, however, that chest pain itself can be an extremely frightening experience, and so psy- chological and organic features often coexist. Anxiety may amplify the effects of organic disease and a confusing clinical picture may result. A detailed and clear history is key to narrowing the differential diagno- sis of chest pain. Figure. 10.1 shows how certain features of the history, particularly when combined, can tip the balance of evidence towards or away from ischaemic cardiac chest pain. 10.2 Differential diagnosis of chest pain Central Cardiac • Myocardial ischaemia (angina) • Myocardial infarction • Myocarditis • Pericarditis • Mitral valve prolapse syndrome Aortic • Aortic dissection • Aortic aneurysm Oesophageal • Oesophagitis • Oesophageal spasm • Mallory–Weiss syndrome • Oesophageal perforation (Boerhaave syndrome) Pulmonary embolus Mediastinal • Malignancy Anxiety/emotion 1 Peripheral Lungs/pleura • Pulmonary infarct • Pneumonia • Pneumothorax • Malignancy • Tuberculosis • Connective tissue disorders Musculoskeletal 2 • Osteoarthritis • Rib fracture/injury • Acute vertebral fracture • Costochondritis (Tietze syndrome) • Intercostal muscle injury • Epidemic myalgia (Bornholm disease) Neurological • Prolapsed intervertebral disc • Herpes zoster 1 May also cause peripheral chest pain. 2 Can sometimes cause central chest pain.
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 216 • Acute medicine And criticAl illness Ischaemic cardiac chest pain Non-cardiac chest pain Relieving factors Respiratory, gastrointestinal, locomotor or psychological Rest Quick response to nitrates Precipitation Spontaneous, not related to exertion, provoked by posture, respiration or palpation Precipitated by exertion and/or emotion Character Sharp, stabbing, catching Tight, squeezing, choking Radiation Other or no radiation Jaw/neck/shoulder/arm (occasionally back) Location Peripheral, localised Central, diffuse Associated features Not relieved by rest Variable or no response to nitrates Breathlessness Fig. 10.1 Identifying ischaemic cardiac pain: the ‘balance’ of evidence. Clinical assessment Cardiorespiratory examination may detect clinical signs that help guide ongoing investigation. Patients with a history compatible with myocardial ischaemia should have a 12-lead electrocardiogram (ECG) performed while clinical examination proceeds. Ongoing chest pain with clinical fea- tures of shock or pulmonary oedema, or ECG evidence of ventricular arrhythmia or complete heart block, should prompt urgent cardiology review and referral to a higher level of care. Chest pain that is accompanied by clinical evidence of increased intra- cardiac pressure (especially a raised jugular venous pressure) increases the likelihood of myocardial ischaemia or massive PE. The legs should be examined for clinical evidence of deep vein thrombosis. A large pneumothorax should be evident on clinical examination, with absent breath sounds and a hyper-resonant percussion note on the affected side. Other unilateral chest signs, such as bronchial breathing or crackles, are most likely to indicate a respiratory tract infection, and a chest X-ray should be expedited. Pericarditis may be accompanied by a pericardial friction rub. In aortic dissection, syncope or neurological deficit may occur. Examination may reveal asymmetrical pulses, features of undiagnosed Marfan syndrome (p. 481) or a new early diastolic murmur representing aortic regurgitation. Any disease process involving the pleura may restrict rib movement and a pleural rub may be audible on the affected side. Local tenderness of the chest wall is likely to indicate musculoskeletal pain but can also be found in pulmonary infarction. Subdiaphragmatic inflammatory pathology, such as a liver abscess, cholecystitis or ascending cholangitis, can mimic pneumonia by causing fever, pleuritic chest pain and a small sympathetic pleural effusion, usu- ally on the right. Likewise, acute pancreatitis can present with thoracic symptoms, and an amylase or lipase level should be requested where appropriate. It is imperative that the abdomen is examined routinely in all patients presenting with pleuritic chest pain. Initial investigations Chest X-ray, ECG and biomarkers (e.g. troponin, D-dimer) play a pivotal role in the evaluation of chest pain. However, indiscriminate ordering of such investigations may result in diagnostic confusion and over-inves- tigation. The choice of investigation(s) is intimately linked to the history and examination findings. A chest X-ray and 12-lead ECG should be per- formed in the vast majority of patients presenting to hospital with chest pain. Pregnancy is not a contraindication to chest X-ray, but particular consideration should be given to whether the additional diagnostic infor- mation justifies breast irradiation. The chest X-ray may confirm the suspected diagnosis, particularly in the case of pneumonia. Small pneumothoraces are easily missed, as are rib fractures or small metastatic deposits, and all should be considered individually during chest X-ray review. A widened mediastinum suggests acute aortic dissection, but a normal chest X-ray does not exclude the diagnosis. Provided it has been more than 1 hour since the onset of pain, chest X-ray in oesophageal rupture may reveal subcutaneous emphy- sema, pneumomediastinum or a pleural effusion. Patients with a history compatible with myocardial ischaemia require an urgent 12-lead ECG. Acute chest pain with ECG changes indicating an ST segment elevation myocardial infarction (STEMI) suggests that the patient is likely to benefit from immediate reperfusion therapy. Specific information relating to cocaine or amphetamine use should be sought, particularly in younger patients. In the context of a compatible history, an ECG showing ischaemic changes that do not meet STEMI criteria should prompt regular repeat ECGs and treatment for non-ST segment elevation myocardial infarction (NSTEMI)/unstable angina. Measurement of serum troponin concentration on admission is often helpful in cases where there is diagnostic doubt, but a negative result should always prompt a repeat sample 6–12 hours after maximal pain. Acute coronary syndrome may be diagnosed with confidence in patients with a convincing history of ischaemic pain (see Fig. 10.1) and either ECG evidence of ischaemia or an elevated serum troponin. If an elevated serum troponin is found in a patient who has an atypical history or is at low risk of ischaemic heart disease, then alternative causes of raised troponin should be considered (Box 10.3). Further management of acute coronary syndromes is dis- cussed on page 468. In the absence of convincing ECG evidence of myocardial ischaemia, other life-threatening causes of chest pain, such as aortic dissection, massive PE and oesophageal rupture, should be considered. Suspicion of aortic dissection (background of hypertension, trauma, pregnancy or previous aortic surgery) should prompt urgent thoracic computed tomography (CT) or transoesophageal echocardiography. An ECG in the context of massive PE most commonly reveals only a sinus tachycardia, but may show new right axis deviation, right bundle branch block or a dominant R wave in V 1 . The classical finding of S 1 Q 3 T 3 (a deep S wave in lead I, with a Q wave and T wave inversion in lead III) is rare. If massive PE is suspected and the patient is haemodynamically unstable, a transtho- racic echocardiogram, to seek evidence of right heart strain and exclude alternative diagnoses such as tamponade, is extremely useful.
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 Presenting problems in acute medicine • 217 10 B A Fig. 10.2 Inhaled foreign body. A Chest X-ray showing a tooth lodged in a main bronchus. B Bronchoscopic appearance of inhaled foreign body (tooth) with a covering mucous fi lm. 10.3 Causes of elevated serum troponin other than acute coronary syndrome Cardiorespiratory causes • Pulmonary embolism • Acute pulmonary oedema • Tachyarrhythmias • Myocarditis/myopericarditis • Aortic dissection • Cardiac trauma • Cardiac surgery/ablation Non-cardiorespiratory causes • Prolonged hypotension • Severe sepsis • Severe burns • Stroke • Subarachnoid haemorrhage • End-stage renal failure If the patient is deemed to be at low risk of PE, a D-dimer test can be informative, as a negative result effectively excludes the diagnosis. The D-dimer test should be performed only if there is clinical suspicion of PE, as false-positive results can lead to unnecessary investigations. If the D-dimer is positive, there is high clinical suspicion, or there is other convincing evidence of PE (such as features of right heart strain on the ECG), prompt imaging should be arranged (p. 586 and Fig. 17.66). Acute breathlessness In acute breathlessness, the history, along with a rapid but careful exam- ination, will usually suggest a diagnosis that can be confi rmed by routine investigations including chest X-ray, 12-lead ECG and arterial blood gas (ABG) sampling. Presentation A key feature of the history is the speed of onset of breathlessness. Acute severe breathlessness (over minutes or hours) has a distinct differential diagnosis list to chronic exertional breathlessness. The presence of asso- ciated cardiovascular (chest pain, palpitations, sweating and nausea) or respiratory (cough, wheeze, haemoptysis, stridor) symptoms can narrow the differential diagnosis yet further. A previous history of left ventricular dysfunction, asthma or exacerbations of chronic obstructive pulmonary disease (COPD) is important. A high temperature, cough (productive or non-productive) and/or viral prodrome may indicate respiratory infection and, if so, relevant infection control precautions should be taken from initial assessment. In the severely ill patient, it may be necessary to obtain the history from accompanying witnesses. In children, the possibility of inha- lation of a foreign body (Fig. 10.2) or acute epiglottitis should always be considered. There is often more than one underlying diagnosis; a thorough assessment should continue, even after a possible diagnosis has been reached, particularly if the severity of symptoms does not seem to be ade- quately explained. The causes of acute severe breathlessness are covered here; chronic exertional dyspnoea is discussed further on page 528. Clinical assessment Airway obstruction, anaphylaxis and tension pneumothorax require immediate identifi cation and treatment. If any of these is suspected, treatment should not be delayed while additional investigations are per- formed, and anaesthetic support is likely to be required. In the absence of an immediately life-threatening cause, the following should be assessed and documented: • level of consciousness • degree of central cyanosis • work of breathing (rate, depth, pattern, use of accessory muscles) • adequacy of oxygenation ( Sp O 2 ) • ability to speak (in single words or sentences) • cardiovascular status (heart rate and rhythm, blood pressure (BP) and peripheral perfusion). Pulmonary oedema is suggested by a raised jugular venous pres- sure and bi-basal crackles or diffuse wheeze, while asthma or COPD is characterised by wheeze and prolonged expiration. A hyper-resonant hemithorax with absent breath sounds raises the possibility of pneu- mothorax, while severe breathlessness with normal breath sounds may indicate PE. Leg swelling may suggest cardiac failure or, if asymmetrical, venous thrombosis. The presence of wheeze is not always indicative of bronchospasm. In acute left heart failure, an increase in the left ventricular diastolic pressure causes the pressure in the left atrium, pulmonary veins and pulmonary capillaries to rise. When the hydrostatic pressure of the pulmonary capil- laries exceeds the oncotic pressure of plasma (about 25–30 mmHg), fl uid moves from the capillaries into the interstitium. This stimulates respira- tion through a series of autonomic refl exes, producing rapid respiration, and congestion of the bronchial mucosa may cause wheeze (sometimes known as cardiac asthma). Sitting upright or standing may provide some relief by helping to reduce congestion at the apices of the lungs. The patient may be unable to speak and is typically distressed, agitated, sweaty and pale. Respiration is rapid, with recruitment of accessory muscles, coughing and wheezing. Sputum may be profuse, frothy and blood-streaked or pink. Extensive crepitations and rhonchi are usually audible in the chest, and there may also be signs of right heart failure. Any arrhythmia may cause breathlessness, but usually does so only if the heart is structurally abnormal, such as with the onset of atrial fi brilla- tion in a patient with mitral stenosis. In such cases, the classic mid-dias- tolic rumbling murmur may be heard. Patients sometimes describe chest tightness as ‘breathlessness’. However, myocardial ischaemia may also induce true breathlessness by provoking transient left ventricular dys- function. When breathlessness is the dominant or sole feature of myo- cardial ischaemia, it is known as ‘angina equivalent’. A history of chest tightness or close correlation with exercise should be sought. Initial investigations As shown in Box 10.4, amalgamation of a clear history and thor- ough clinical examination with chest X-ray, ECG and ABG findings
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 218 • Acute medicine And criticAl illness 10.4 Clinical features in acute breathlessness Condition History Signs Chest X-ray ABG ECG Pulmonary oedema Chest pain, palpitations, orthopnoea, cardiac history* Central cyanosis, ↑ JVP, sweating, cool extremities, basal crackles* Cardiomegaly, oedema/ pleural effusions* ↓ Pa O 2 ↓ Pa CO 2 Sinus tachycardia, ischaemia*, arrhythmia Massive pulmonary embolus Risk factors, chest pain, pleurisy, syncope*, dizziness* Central cyanosis, ↑ JVP*, absence of signs in the lung*, shock (tachycardia, hypotension) Often normal Prominent hilar vessels, oligaemic lung fields* ↓ Pa O 2 ↓ Pa CO 2 Sinus tachycardia, RBBB, S 1 Q 3 T 3 pattern ↑ T(V 1 –V 4 ) Acute severe asthma History of asthma, asthma medications, wheeze* Tachycardia, pulsus paradoxus, cyanosis (late), silent chest/ cyanosis (late)*, ↓ peak flow, wheeze* Hyperinflation only (unless complicated by pneumothorax)* ↓ Pa O 2 Normal Pa CO 2 ( ↑ Pa CO 2 in extremis) Sinus tachycardia (bradycardia in extremis) Acute exacerbation of COPD Previous episodes*, smoker. If in type II respiratory failure, may be drowsy Cyanosis, hyperinflation*, signs of CO 2 retention (flapping tremor, bounding pulses)* Hyperinflation*, bullae, complicating pneumothorax or ↓↓ Pa O 2 ↑ Pa CO 2 in type II failure ± ↑ H + , ↑ − HCO3 in chronic type II failure Normal, or signs of right ventricular strain Pneumonia/lower respiratory tract infection Prodromal illness*, fever*, rigors*, pleurisy* Fever, delirium, pleural rub*, consolidation*, cyanosis (if severe) Pneumonic consolidation* ↓ Pa O 2 ↓ Pa CO 2 ( ↑ in extremis) Tachycardia Metabolic acidosis Evidence of diabetes mellitus or renal disease, aspirin or ethylene glycol overdose Fetor (ketones), hyperventilation without heart or lung signs*, dehydration*, air hunger Normal Pa O 2 normal ↓↓ Pa CO 2 , ↑ H + ↓ − HCO3 Psychogenic Previous episodes, digital or perioral dysaesthesia No cyanosis, no heart or lung signs, carpopedal spasm Normal Pa O 2 normal* ↓↓ Pa CO 2 , ↓ H + * *Valuable discriminatory feature. (ABG = arterial blood gas; COPD = chronic obstructive pulmonary disease; JVP = jugular venous pressure; RBBB = right bundle branch block) will usually indicate the primary cause of breathlessness. In cases of suspected infection, a viral throat swab should be obtained early in the course of the assessment; increasingly, point-of-care testing of viral throat swabs is available, providing important and rapid diag- nostic information. If available, sputum should be sent for culture. If bronchospasm is suspected, measurement of peak expiratory flow will assist in the assessment of severity and should be performed whenever possible. An ABG will often provide additional information to Sp O 2 meas- urement alone, particularly if there is clinical evidence (drowsiness, delirium, asterixis) or a strong likelihood of hypercapnia. An acute rise in Pa CO 2 will increase the HCO 3 − by only a small amount, resulting in inadequate buffering and acidaemia. Renal compensation and a large rise in HCO 3 − will take at least 12 hours. In acute type II respira- tory failure (p. 535), the rate of rise of Pa CO 2 is a better indicator of severity than the absolute value. An ABG can also give a carboxy- haemoglobin level after smoke inhalation (although this can also be measured on a venous sample), and is central to the identification of metabolic acidosis or the diagnosis of psychogenic hyperventilation (see Box 10.4). If pulmonary embolism is suspected, calculating pre-test probability (see Ch. 1) is key. In a patient with a pre-test probability of less than 15%, the pulmonary embolism rule-out criteria (PERC) can exclude pulmonary embolism clinically, negating the need for further imaging, if none of the criteria listed in Box 10.5 are met. Further detail on the investigation and management of pulmonary embolus is given on page 586. Procalcitonin (PCT) and N-terminal pro-hormone brain natriuretic protein (NT-proBNP) can be measured in venous blood. While these biomarkers can give an indication of aetiology in shortness of breath, they are probably of more value in tracking clinical progression and response to treatment. Elevated PCT is a biomarker for bacterial infec- tion and may be useful, in addition to clinical assessment, in helping decide the need for and duration of antibiotic therapy in patients with confirmed viral respiratory disease (such as COVID-19) who may have 10.5 PERC rule for pulmonary embolism Rules out PE if none of the eight criteria is present and pre-test probability is less than or equal to 15% * • Age ≥ 50 • Heart rate ≥ 100 • Oxygen saturation on room air < 95% • Unilateral leg swelling • Haemoptysis • Recent surgery or trauma ( ≤ 4 weeks ago requiring hospitalisation) • Prior venous thromboembolism (VTE) • Hormone use (oral contraceptives), hormone replacement or oestrogenic hormone use in male or female patients additional bacterial super-infection. Elevated NT-proBNP is suggestive of underlying left ventricular failure (p. 429), although it can be elevated in other conditions such as renal failure, COPD, pulmonary hyperten- sion and pulmonary embolism. Measurement of NT-proBNP may be considered if there is no clear-cut evidence of pulmonary oedema on a chest X-ray and can be particularly useful as a ‘rule-out’ test, as a normal NT-proBNP has high negative predictive value for heart failure. Individuals with suspected heart failure should undergo early echocardiography. CT imaging (with or without pulmonary angiography) is a useful investigation in many respiratory conditions as interstitial changes, tumours or consolidation may not be evident on chest X-ray. If breathlessness is suspected to be an ‘angina equivalent’, objective evidence of myocardial ischaemia from stress testing may help to establish the diagnosis, although coronary artery angiography (either by CT or cardiac catheterisation) is often performed early in the inves- tigation pathway. * A false-negative level of <1.8% was chosen as the point of equipoise between the benefits and risks of further investigations for PE, and the benefits and risks of not investigating further .
Order your copy of Davidson’s Principles and Practice of Medicine, 25th Edition at elsevierhealth.com/9780443287602 Presenting problems in acute medicine • 219 10 Anaphylaxis Anaphylaxis is a potentially life-threatening, systemic allergic reaction characterised by a variable combination of circulatory collapse, bron- chospasm, laryngeal stridor, angioedema and urticaria. The risk of death is increased in patients with pre-existing asthma, particularly if this is poorly controlled, and in situations where treatment with adrenaline (epi- nephrine) is delayed. Presentation Anaphylaxis occurs when an allergen binds to and cross-links mem- brane-bound IgE on mast cells in a susceptible individual, causing release of histamine, tryptase and other vasoactive mediators from mast cells. These mediators have a variety of effects, including vasodilatation, increased capillary permeability leading to hypotension, and broncho- constriction. It can be difficult to distinguish IgE-mediated anaphylaxis clinically from non-specific degranulation of mast cells on exposure to drugs, chemicals or other triggers where IgE is not involved, previously known as anaphylactoid reactions. Clinical assessment The clinical features of anaphylaxis are summarised in Figure 10.3. Several other conditions can mimic anaphylaxis and these are listed in Box 10.6. It is important to assess the severity of the reaction, and the time between allergen exposure and onset of symptoms provides a guide. Enquiry should be made about potential triggers. If a trigger is immedi- ately obvious, a detailed history of the previous 24 hours may be helpful. The most common triggers of anaphylaxis are foods, latex, insect venom and drugs. A history of previous local allergic responses to the offending agent is common. The route of allergen exposure may influence the prin- cipal clinical features of a reaction; for example, if an allergen is inhaled, the major symptom is frequently wheezing. Features of anaphylaxis may overlap with the direct toxic effects of drugs and venoms (Chs 11 and 12). Potentiating factors, such as exercise, alcohol, nonsteroidal anti-in- flammatory medications or fatigue, can lower the threshold for an ana- phylactic event. It is important to identify precipitating factors so that appropriate avoidance measures may be taken in the longer term. Investigations and management Measurement of serum mast cell tryptase concentrations is useful to confirm the diagnosis. It is important to measure tryptase in serial tests to demonstrate the temporal relationship to the triggering event. Specific IgE tests may be useful in confirming hypersensitivity and may be prefer- able to skin-prick tests when investigating patients with a history of ana- phylaxis. The cornerstone of management of a severe case is the early administration of adrenaline (epinephrine), which supports the cardiovas- cular system, reduces bronchospasm and has some disease-modifying effects. Secondary management depends upon which organs are most affected. The emergency management of anaphylaxis is summarised in Box 10.7. If present, angioedema of the orofacial area requires careful observation and timely intervention, possibly with endotracheal intuba- tion. The investigation and management of angioedema is discussed further on page 81. Individuals who have recovered from an anaphylactic event should be referred for specialist assessment. The aims are to identify the trig- ger, educate the patient regarding avoidance and management of sub- sequent episodes, and to establish whether specific treatment, such as immunotherapy, is indicated. If the trigger factor cannot be identi- fied or avoided, recurrence is common. Patients who have previously experienced an anaphylactic event should be prescribed self-injectable Itching of palms, soles of feet and genitalia Feeling of impending doom, loss of consciousness Conjunctival injection Flushing Sweating Hypotension Urticaria Wheeze, bronchoconstriction Angioedema of lips and mucous membrane Abdominal pain Diarrhoea Cardiac arrhythmias Laryngeal obstruction Stridor Wasp sting Fig. 10.3 Clinical manifestations of anaphylaxis. In this example, the response is to an insect sting containing venom to which the patient is allergic. This causes release of histamine and other vasoactive mediators, which lead to the characteristic features of anaphylaxis that are illustrated. 10.6 Differential diagnosis of anaphylaxis Causes of hypotension • Vasovagal syncope • Cardiac arrhythmia • Cardiogenic shock Causes of respiratory distress • Status asthmaticus • Pulmonary embolus Causes of laryngeal obstruction • C1 inhibitor deficiency • Idiopathic angioedema Causes of generalised flushing • Systemic mastocytosis • Carcinoid syndrome