This simple physiological scoring system (Table 1.1) can be used at the bedside in a medical admission unit. It identifies patients at risk of deterioration who will require a higher level of care in either an HDU or an ICU.

Table 1.1 Modified Early Warning Score (MEWS)

A nurse or healthcare worker can record six vital signs on a chart (heart rate, respiratory rate, blood pressure, conscious level, temperature and hourly urine output for the previous 2 hours). A score of between 1 and 3 is recorded for each vital sign. The sum of all the scores determines the MEWS score. A score of 4 and above will prompt the nurse to call the patient’s doctor, and scores of 5 or more are associated with an increased risk of death and immediate admission to HDU or ICU.

Communication between handing-over teams can also be a problem in busy clinical environments. A suggested proforma that covers the essential factors in transferring patient care is SBAR (situation, background, assessment, recommendation — NHS Institute for Innovation and Improvement).

Pre- and peri-operative care and assessment

The aim of these assessments is to reduce the morbidity and mortality of patients undergoing surgery. Most units run pre-operative clinics prior to admission for surgery. Many procedures are performed as day cases, with local or spinal anaesthesia or short general anaesthetics.

The general condition of the patient is reviewed; cardiovascular and respiratory problems can often be addressed and treated prior to surgery. A commonly used five-point grading system has been developed by the American Society of Anesthesiologists (ASA):

• ASA I Healthy patient

• ASA II Mild systemic disease, no functional disability

• ASA III Moderate systemic disease, functional disability

• ASA IV Severe systemic disease, life-threatening

• ASA V Moribund, unlikely to survive 24 hours with or without an operation.

Anaemia, malnutrition, and electrolyte and metabolic disturbances should also all be corrected prior to surgery, if possible. Evaluation by the anaesthetist is performed in patients with chronic disorders and in those who are at high risk, e.g. the acutely ill.

History and examination

A full history with co-morbidities (particularly in the elderly) should be documented and an examination performed.

Co-morbidities

• Diabetes mellitus. Management is described on p. 595.

• Ischaemic heart disease. The incidence of myocardial infarctions in patients with previous heart attacks is >25%, compared to 0.2% in the healthy. Elective procedures should be delayed for at least 6 months (urgent surgery for 3 months) after an infarct. Unstable angina constitutes a very high risk.

• Hypertension. This should be controlled, as untreated hypertension carries a higher risk for myocardial infarctions and cerebrovascular disorders.

• Liver disorders. The risks depend on the aetiology of the disorder. Defer surgery in jaundiced patients with abnormal coagulation until the jaundice has resolved; relieve any biliary obstruction by stenting and give vitamin K (10 mg slow IV injection). The Child–Pugh classification can be used for patients with chronic liver disease to predict their operative mortality: class A (up to 10%) to class C (50–70%). Drugs that are metabolized by the liver are contraindicated in these patients and should only be prescribed if absolutely essential. The nursing and medical staff should be informed if the patient is hepatitis B- or C-positive, or HIV-positive.

• Respiratory problems. Pre-operative evaluation will require an assessment of lung function — spirometry with ABGs if the spirometry is abnormal and patients have long-term respiratory problems.

• Current medication. This should be noted and decisions made about continuation of therapy, particularly if the patient is on anticoagulants or antiplatelet therapy.

• Drug allergies/sensitivities. These should be noted with the reaction to the drug in the clinical record and a red (instead of a white) armband attached to the patient’s wrist.

• Smoking. Patients should be informed of the risks associated with smoking, and the benefits of stopping smoking prior to surgery must be emphasized. These include decreased sputum production, improved sputum clearance by cilia (often within 1–2 days of stopping smoking), increased oxygen-carrying capacity of the blood, reduced concentration of circulating nicotine (can cause vasoconstriction) and less bronchospasm.

• Alcohol. An assessment of alcohol intake should be made when taking the history. Patients may have alcohol-related chronic liver disease or develop acute alcohol withdrawal in the early post-operative period. Alcohol also causes an induction of the liver enzymes involved in the metabolism of some of anaesthetic drugs.

Elective surgery carries less risk of peri-operative problems than emergency surgery, in which there are often many co-morbidities and the patient is seriously ill.

Routine pre-operative tests

These are often not necessary in a patient undergoing minor or elective surgery.

• FBC — not unless there are co-morbidities or if more than a very small amount of blood is expected to be lost

• Coagulation tests — not necessary unless there is a bleeding disorder, the patient is on anticoagulants, or epidural anaesthesia is planned

• LFTs, biochemistry and U&E — not unless there are co-morbidities

• CXR — only for those with cardio-respiratory problems

• ECG — for the elderly or patients with a history of heart disease, or if examination revealed a cardio-respiratory problem

• Blood group and cross-matching — depending on the nature of the operation.

Prophylaxis for deep vein thrombosis

Anti-DVT/VTE measures include early ambulation, which reduces the risk of DVT/PE. Graduated compression stockings (unless patient has peripheral arterial disease) and low-molecular-weight heparin or oral anti-thrombotic agents e.g. dabigatran or rivaroxaban should be used. See p. 245 for details.

Beta-blockers

The current evidence supporting β-blocker therapy in non-cardiac surgery is poor and it should not be used, apart from in very ‘high-risk’ patients.

Specific interviews

Obtaining consent

Doctors seeking consent for a particular procedure must have proper knowledge of how the procedure is performed and its possible complications.

• Consent must be ‘informed’ to an adequate standard.

• Patients must be competent to consent to treatment.

• Patients must not be coerced into accepting treatment against their wishes.

• The doctor and patient should both sign the consent form before the procedure.

Patients need to weigh up the pros and cons of proposed treatments. They cannot do so without the basic ability to reason about information concerning what is wrong with them, what their doctors propose to do about it, and what potential benefits and risks are involved in treatment. Common and serious potential adverse events should be discussed with the patient.

Breaking bad news

These interviews are often difficult. The aim is to make sure that the patient is enabled to understand and make the best of even very bad circumstances. These interviews should always be carried out in a quiet place and without interruption; if possible, patients should have someone with them. Explain your status and your responsibility to them.

It is always best to start off by finding out how much patients know about their condition and how they feel about their illness. Some indication should then be given by the clinician that the news is bad and possibly more serious than initially thought. Pause here to allow the patient to think. It might be worthwhile going through the results of investigations and explaining how the diagnosis has been confirmed. Give information in small chunks, being honest and not hedging about the diagnosis. Avoid technical terms and check that patients understand what you are telling them. Diagrams may be helpful.

Watch for the patient’s reactions; if the patient is too upset, it may be that you will have to return to continue the interview. Talk about the treatments that are available to provide a good quality of life, e.g. dealing with pain and some other symptoms. Always provide some positive information and hope but do not be overly optimistic.

Responding to the patient’s emotions can be very difficult. The patient may become very upset but the clinician may also be upset. Empathize as much as possible. Answer their questions. The patient might ask about the time frame of the illness. This is very difficult to give so do not provide a figure.

End with a date and time for a further interview (preferably soon) to answer questions and also to see other members of the family that the patient wishes you to see. Give a contact name and number, and also supply contact addresses of good support organizations. Write what you have told the patient and the patient’s wishes clearly in the clinical records.

Patient safety and infection control

Patients admitted to hospitals are in unfamiliar surroundings, are incapacitated and are susceptible to infections due to their illness, e.g. because of poor nutrition, as well as being exposed to hospital-acquired infections.

Approximately 10% of patients contract healthcare-acquired infections (HCAIs; previously called nosocomial infections). Risk factors for HCAIs include being on mechanical ventilation, trauma, prolonged length of stay in hospital and the presence of catheters (IV, urinary, naso-gastric tubes). Cross-infection is a problem, particularly with MRSA.

A safety culture must be fostered amongst all healthcare professionals, as preventable harm in healthcare is nearly always caused by medical errors and system failures. To do this, the awareness of possible problems must be raised and a safety culture of openness and learning ensured, along with sustained good risk management.

• Infection control measures. Poor infection control practice in hospitals and other healthcare environments can cause the transfer of infection from person to person. Transfer may be airborne, via fomites, or via a direct contact route. It is essential that all healthcare workers wash or clean their hands before and after patient contact; whenever necessary, they should wear gloves, aprons and other personal protective equipment. This is particularly necessary when performing invasive procedures or manipulating indwelling devices, such as cannulae. Indwelling lines must be checked regularly for signs of infection and this observation should be documented in the notes. Alcohol-based hand washes, which are freely available in the hospital, are a quick and easy alternative to hand washing but they do not prevent the spread of Clostridium difficile, which requires formal hand washing for physical removal of spores from the hands.

• Air-borne transmission prevention again relies on hand washing and also on the use of masks by patient and healthcare worker. Positive pressure isolation is used for patients having cancer chemotherapy treatments.

• Isolation facilities should always be available, e.g. for MRSA infection.

• Antibiotics. Antibiotics, particularly broad-spectrum ones, e.g. cephalosporins, should only be used when absolutely necessary, as hospital-acquired infections (particularly C. difficile and MRSA) have been linked to hospital over-prescribing. Many hospitals have their own antibiotic prescription policies based on local sensitivities and a reduction in the use of cephalosporins.

• Reduction of medical and procedural errors. Most hospitals have guidelines and protocols to avoid errors. All new personnel should be given an induction about the procedures to maintain patient safety and this should be followed up with continuing education.

• Patient nutrition. The Malnutrition Universal Screening Tool (MUST) has been used to assess the nutrition of patients entering hospitals (p. 123). Many hospital inpatients are malnourished. Patients should be provided with protected mealtimes, good hydration and good nutritional care with fact sheets. These are outlined in the Council of Europe’s ten key characteristics of good nutritional care in hospital (www.bapen.org.uk).

• Radiation from medical imaging. The ordering of imaging procedures is increasing as technology advances. Document all exposures to ionizing radiation. For example, a patient undergoing myocardial perfusion imaging receives 15.6 millisieverts (mSv), CT abdomen 8–10 mSv and percutaneous coronary intervention 15 mSv, compared with a CXR, which is only 0.02 mSv. These doses of radiation may, in the long term, present a small risk for the development of cancer.

Prescribing

Good prescribing requires a diversity of skills. Medicines should only be prescribed if they are really necessary and if the risks of not giving the drug outweigh the side-effects/harmful effects of the drug itself.

• Drugs should only be prescribed if an accurate diagnosis has been made. Exceptions would include pain relief and ‘blind’ antibiotics for severe sepsis.

• Co-morbidities should be documented, as some diseases may have an effect on the drug itself, e.g. its elimination.

• Polypharmacy should be avoided as far as possible and drug interactions checked before a new drug is added to the regimen.

• The decisions on therapy must be made with patients and they should be told exactly which drugs they are going to be given and why. This increases the likelihood of patients taking the drugs as prescribed, as they feel they are equal partners in the decision-making (concordance).

• Always look up the drug and its dosages and effects. This can either be done online, e.g. www.bnf.org, or from information in local hospital pharmacy booklets.

• The side-effects of treatment should be explained to patients in a language they understand prior to starting the medication.

• Allergies: Always document these fully in the notes with actual clinical reaction. A red name band should replace the usual white band on the patient’s wrist.

The WHO Guide to Good Prescribing is a useful training programme to assist in prescribing medicines (http://whqlibdoc.who.int/hq/1994/WHO_DAP_94.11.pdf).

Drug metabolism

Pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body)

Note that absorption, distribution, metabolism, and hepatic and renal elimination of drugs or their metabolites differ from person to person. Therefore the route of administration and the dose of the drug should be tailored to the patient’s needs. This may involve changing the drug, increasing/decreasing the dosage or choosing another route of administration.

Many drugs are metabolized by the liver. The metabolism varies between individuals, often because of changes in the cytochrome p450 family of enzymes. Inhibition or induction of cytochrome p450 isoenzymes is a major cause of drug interaction. Some examples are given in Box 1.1. Thus, for example, warfarin is metabolized by CYP2C9. Between 2 and 10% of people are homozygous for an allele that results in low enzyme activity and this leads to higher plasma warfarin levels.

The variability of a drug’s action within the body is partly due to the drug receptor and the polymorphism of this receptor.

The interplay between pharmacokinetics and pharmacodynamics will influence drug selection and drug dosage.

Prescribing for the elderly

This may require changes in drug dosages in the presence of co-morbidities. It should be remembered that concordance diminishes as the number of prescribed drugs increases and also in the face of cognitive impairment.

• Rates of hepatic drug metabolism and renal excretion decline with age. Extrapolation of dosage regimens from younger adults could therefore lead to drug toxicity.

• Predisposition to toxicity can also occur with changes in drug distribution, a reduction of body mass, changes in body composition, and the preferential distribution of the cardiac output to the brain.

• Co-morbidity (and therefore often polypharmacy too) can lead to increased opportunities for drug interactions.

• Exaggerated pharmacodynamic effects of drugs acting on the cardiovascular system, CNS and gastrointestinal tract occur more commonly (Table 1.2).

Table 1.2 Common adverse effects of drugs in the elderly

Drug	Effect
β-Blockers (including eye drops) Digoxin	_Bradycardia
Nitrates α-Adrenoceptor-blockers Diuretics	_{Postural hypotension}
Diuretics (thiazides)	Glucose intolerance, gout
Antimuscarinic drugs Tricyclic antidepressants Neuroleptics Minor tranquillizers Anticonvulsants Hypnotics Opioids	_{Confusion, cognitive dysfunction}
Bisphosphonates (mainly alendronic acid)	Oesophageal ulceration and stricture formation
NSAIDs	Gastric erosions Upper gastrointestinal bleeding Perforated peptic ulcer Renal impairment

Prescribing in pregnancy/breast feeding

Clinicians should be very cautious of prescribing any drug to pregnant women. Always consult the relevant literature for any drug prescribed to check its effects in women of childbearing age, in pregnancy and in nursing mothers.

Never prescribe a drug to pregnant women unless it is absolutely necessary and you have checked for possible teratogenic effects on the fetus. Appendix A gives websites for drug use. If a known teratogenic drug is required during pregnancy (e.g. an anticonvulsant), always discuss the adverse effects on the fetus with the parents, preferably prior to conception.

Most drugs can be detected in breast milk, albeit in small amounts. A few drugs, e.g. aspirin and carbimazole, can cause harm to the infant if ingested in breast milk.

Writing a prescription

International non-proprietary names (INNs) of drugs should always be prescribed, as proprietary names can cause confusion and can be more expensive. There are rare exceptions where it is necessary to prescribe proprietary preparations, e.g. mesalazine (mesalamine), as the delivery characteristics of the product may vary.

• Write legibly (or use a computer).

• Give the name and address of the patient (if writing an outpatient prescription).

• Name the drug. Do not use abbreviations, e.g. GTN.

• State the dose required as mg or ml (or mL). Write ‘micrograms’ or ‘units’ out in full. Avoid decimal points, if possible, or write 0.5 mg rather than .5 mg, as this can lead to mistakes.

• State which route of administration you want the drug to be given by. The abbreviations IV (for intravenous), IM (for intramuscular) or SC (subcutaneous) are usually recognized. Write ‘orally’ rather than p.o. (by mouth).

• To state frequency, do not use Latin abbreviations, as many doctors do not learn Latin. Write once daily (or ×1 daily), twice daily (or ×2 daily), three times daily (×3 daily), four times daily (×4 daily), when required (but also spell out the minimum dose interval), or immediately (not stat).

• Give special information, if required, e.g. ‘with food’, ‘on an empty stomach’ or ‘at night’. You must be familiar with the way certain drugs are given, e.g. bisphosphonates cause oesophageal damage and must be taken sitting or standing with plenty of water.

• State the amount you want dispensed. Drugs often come in packages to last days, weeks or months. Prescribe these, if possible, as fewer mistakes will be made in dispensing.

• Sign, write your name in capitals and date the prescription.

Prescribing controlled drugs

• Prescriptions must be written out in full, in legible hand-writing and in ink. Computer-based prescriptions should still be signed in ink. Write out the patient’s name and address (or hospital ward). Do not use a sticker with the patient’s name.

• State the name and strength of the formulation.

• State the type of formulation (e.g. oral liquid, suppository, modified-release capsule or tablet).

• State dose and frequency, e.g. twice daily.

• Write the total amount to be supplied in words as well as figures.

• Sign and date the prescription, e.g.

Patient: Mr AN Other, Ward 21. DOB 01-01-1950. Hospital no. 123456

Please dispense ten (10) times ten milligram (10 mg) MORPHINE SULPHATE modified release capsules to TOTAL one hundred milligrams (100 mg) only.

Dr J BLOGGS Day, month, year

Adverse drug reactions (ADRs)

The unwanted effects of drugs occurring under normal conditions of use are a significant cause of morbidity and mortality. About 5% of acute medical emergencies are admitted with ADRs. Between 10 and 20% of hospital inpatients suffer an ADR during their inpatient stay. Unwanted effects of drugs occur more frequently in the elderly, and the risk of an ADR rises sharply with polypharmacy.

Classification

Two types of ADR are recognized (Table 1.3):

• Type A (augmented) reactions, which are common, predictable, usually dose-dependent but occasionally serious. They can occur after a single dose (e.g. hypotension with ACE inhibitors) or can take place after months (e.g. amiodarone causing pulmonary fibrosis) or years (catatonic drugs causing cancer).

• Type B (idiosyncratic) reactions, which bear no resemblance to the recognized pharmacological or toxicological effects of the drug. They are therefore unpredictable, usually dose-independent, often serious but fortunately rare.

Table 1.3 Examples of adverse drug reactions

Drug	Adverse reaction
Type A (augmented)
Anticoagulants	Bleeding
Insulin	Hypoglycaemia
ACE inhibitors/antagonists	Hypotension
Antipsychotics	Acute dystonia and dyskinesia Parkinson’s disease Tardive dyskinesia
Tricyclic antidepressants	Dry mouth
Amiodarone	Hyperthyroidism Hypothyroidism Pulmonary fibrosis
Cytotoxic agents	Bone marrow dyscrasias Cancer
Glucocorticoids	Osteoporosis
Type B (idiosyncratic)
Benzylpenicillin	_Anaphylaxis
Radiological contrast media	Anaphylaxis Nephrogenic systemic fibrosis, e.g. gadolinium
Amoxicillin	Maculopapular rash
Sulphonamides Lamotrigine	_{Toxic epidermal necrolysis}
Volatile anaesthetics Suxamethonium	Malignant hyperthermia
Diclofenac Isoflurane, sevoflurane Isoniazid Rifampicin Phenytoin	_{Hepatotoxicity}

The following six characteristics can help distinguish an adverse reaction from an event due to some other cause:

• Time interval. E.g. minutes (acute anaphylaxis), months (aplastic anaemia) or years (drug-induced malignancy).

• Nature of the reaction. Some are typically iatrogenic, e.g. maculopapular rashes, angio-oedema, fixed drug eruptions, toxic epidermal necrolysis.

• Plausibility. An event may be a manifestation of a known pharmacological property of the drug (type A). Recognition of type B reactions may be very difficult unless there is a previous report in the literature.

• Exclusion of other possible causes

• Laboratory tests e.g. plasma concentration, diagnostic histopathological features.

• De-/rechallenge. Results of dechallenge (withdrawal of the drug) and rechallenge (giving the drug again). The latter may be very hazardous and is seldom justified.

Management

• Type A reactions. Reduction in dosage usually helps.

• Type B reactions. The drug should be withdrawn (and never re-instituted).

• Specific therapy. This is sometimes required for ADRs such as bleeding with warfarin (vitamin K), acute dystonias (benzatropine) or acute anaphylaxis. See Emergencies in Medicine p.000.

Any adverse or unexpected drug reaction should be reported to a national authority. In the UK, this is done via a Yellow Card system to the Medicines and Healthcare Regulatory Authority (MHRA).

Clinical trials

Evidence-based medicine is the systematic approach to justify the administration of a drug or treatment. Treatments should be used in routine clinical care only if they have been demonstrated to be effective in formal clinical trials. These trials need to be well designed with proper control groups, be properly randomized and have proper end-points. There should be similarity between groups that are being compared with defined entry criteria.

Randomized controlled trials (RCTs)

These can be performed as a ‘parallel group design’ study where patients with a particular condition are given one of two treatments, usually allocated randomly (randomized controlled trial).

• A ‘single blind’ trial is where the patient is unaware of the drug and a ‘double blind’ is where both the patient and the doctor are unaware — reducing the bias of both patient and doctor.

• Recruitment can be from several locations (‘multicentre’ trial).

• In a ‘crossover trial’ the patient receives both the active and the comparator drug in a random fashion.

Although a large, well-designed, double-blind RCT is the gold standard for obtaining best evidence, it is very expensive and other trials can also be useful.

Controlled observational trials can also be used to test the clinical effectiveness of therapeutic interventions; historical controlled trials, case-control studies and before-and-after studies can be used. The case-controlled trials compare patients who have a particular condition (the ‘cases’) with those who do not have that condition (‘controls’). They are used to identify the ‘risk factors’ for specific conditions by the estimation of the odds ratio.

Odds/risk ratios and number needed to treat

The odds ratio (OR) is the probability of an event occurring, as opposed to the probability of the event not occurring. Thus, for an adverse event, the OR can be calculated as the number with the event (a), divided by the number without the event (b), divided by the odds of the event occurring in the placebo group, i.e. the number of controls with an adverse event (c), divided by the number without (d). Thus:

The risk ratio or relative risk (RR) is calculated by dividing the number with the adverse event (a) by the total number of the cases (a + b). This sum is then divided by the number of people in the placebo group who have an adverse event (c) by the total number in the placebo group (c + d).

If, for example, the total was 4, it would mean there was 4 times the risk.

The relative risk reduction would then be 1−RR.

The benefits or harm of drug therapy can be expressed as the number needed to treat (NNT) in order to prevent one adverse clinical event, e.g. a myocardial infarct, thus (NNTB) (benefit), or as the number needed to treated for harm to occur (NNTH) (harm). This is calculated as for relative risk but by subtracting instead of dividing. Thus:

Interpretation of diagnostic tests

Diagnostic tests are interpreted according to their sensitivities and specificities and their predictive values. For example, if:

a = patients with disease who have a positive test

b = patients with no disease who have a positive test

c = patients with disease who have a negative test

d = patients with no disease who have a negative test

• Sensitivity is the proportion of patients with a particular disease who have a positive test, i.e. a/(a + c).

• Specificity is the proportion of patients who do not have the disease and have a negative test, i.e. d/(c + d).

• Positive predictive value is the proportion of people with the disease who have a positive test, i.e. a/(a + b).

• Negative predictive value is the proportion of people who do not have the disease and have a negative test, i.e. d/(c + d).

Thus, when reviewing the results of a test, we can assess the likelihood of whether a test result (symptom or sign) would be expected in a patient with the disease compared to a patient without the disease. This likelihood ratio (LR) can be calculated from the equation

A high LR indicates that a particular disorder is more likely in people with a given result.

The receiver operator characteristic (ROC) curve also uses the sensitivity and specificity results to plot the discriminating power of a test. The opposite ends of the curve will show either high sensitivity and low specificity, or high specificity and low sensitivity. The area under the ROC curve also has the ability to discriminate between patients with and without a disease when two different tests are compared.

Statistical analysis

The average

The ‘average’ value (or ‘central tendency’) can be expressed as follows:

• Mean — the average of a distribution of values that are grouped symmetrically around the central tendency

• Median — the middle value of a sample, used where the values in a sample are asymmetrically distributed around the average

• Mode — the interval that contains more values than any other in a frequency distribution of values.

In a symmetrically distributed population the mean, median and mode are the same.

In clinical studies the value of a particular variable (e.g. height, weight, BP, haemoglobin) may be described, quantitatively, in a sample of a defined population.

Confidence interval (CI)

This is the confidence that can placed on a sample ‘average’ truly reflecting the average value of a population. The CI describes the probability of a sample mean being a certain distance away from the population mean. If, for example, the mean systolic BP of 100 students is 124 mmHg with a CI of 95% of ± 15, then if one replicates the study 100 times, the value of the mean will be within the range of 109–139 mmHg on 95 occasions. Thus, the larger the sample is, the smaller will be the CI.

‘p’ value

An alternative to the CI is the probability (p value), which is used if the population has a normal distribution. The basic assumption is that there is no difference between two groups (i.e. the Null Hypothesis). Statistical tests are used to determine the probability that an observed difference is due to chance. By convention, if it is less than 1 in 20 (p < 0.05), it is described as being ‘statistically significant’ and is unlikely to be due to chance (i.e. rejecting the Null Hypothesis). If the p value is >0.05, there is no statistical difference between the two groups and the Null Hypothesis cannot be rejected.

Standard deviation (SD) v standard error (SE)

The SD gives an estimate of the variability of the population from which the sample was taken. If the population has a ‘normal’ distribution, i.e. exhibits a Gaussian ‘bell-shaped curve’, then 95% of people will have values within 2 SD above and below the mean.

The SE of the sample mean depends on both the SD and also the sample size, i.e.

The SE will fall as the sample size is increased, but the SD will not change.

The 95% confidence interval (see above) is:

Correlation

• The degree of correlation between two ordinal variables can be investigated by calculating the correlation coefficient (‘r’), which may range from 1 to −1. If r is 1, there is complete and direct concordance between the two variables; if r = −1, there is complete but inverse concordance; and where r = 0 there is no concordance. The correlation coefficient measures the degree of association between the two variables.

• Statistical tables can inform investigators as to the probability that ‘r’ is due to chance. If the probability is less than 1 in 20 (p < 0.05), then it is regarded as ‘statistically significant’. However, it must be emphasized that the 1 in 20 rule does not exclude the possibility that a presumed association is due to chance. Also, the fact that there is an association between two variables does not necessarily mean that it is causal.

Do not attempt resuscitate (DNAR) orders

• The resuscitation status of every patient should be discussed by senior doctors at the time of admission and the decision documented in the notes.

• Many hospitals have specific DNAR forms. Deciding a person’s resuscitation status is a careful balance of risk versus benefit. The patient’s co-morbidities and pre-morbid quality of life should be taken into account.

• Involve the patient and family in this discussion, and explain the medical reasoning behind the decision. If the patient requests that CPR is not performed in the event of cardio-pulmonary arrest, those wishes should be respected.

Remember that a decision not to resuscitate a patient is not the same as the decision to withhold other treatments. A patient who is not for resuscitation may still be eligible for antibiotics, fluids, endoscopy and even surgery. Management should remain positive, allowing the patient to die free of distress and with dignity.

Care of the dying

A decision by a multidisciplinary that a patient is dying is agreed and should be recorded in the clinical record. This decision must be discussed with the carers and relatives of the patient. The National Institute for Health and Clinical Excellence (2004) guidance on improving supportive and palliative care for adults is shown in Box 1.2.

Box 1.2

Source: National Institute for Clinical Excellence 2004 Guidance on Cancer Services. Improving Supportive and Palliative Care for Adults with Cancer.

Best practice in the last hours and days of life

• Current medications are assessed and non-essentials discontinued

• ‘As required’ subcutaneous medication is prescribed according to an agreed protocol to manage pain, agitation, nausea and vomiting and respiratory tract secretions

• Decisions are taken to discontinue inappropriate interventions, including blood tests, intravenous fluids and observation of vital signs

• The ability of the patient, family and carers to communicate is assessed

• The insights of the patient, family and carers into the patient’s condition are identified

• Religious and spiritual needs of the patient, family and carers are assessed

• Means of informing family and carers of the patient’s impending death are identified

• The family and carers are given appropriate written information

• The GP practice is made aware of the patient’s condition

• A plan of care is explained and discussed with the patient, family and carers

The Liverpool Care pathway for the dying patient has been widely adopted and used in many general healthcare settings to support clinicians to make decisions about care of the dying.

Confirmation of death

Verification of death can be daunting. Ask relatives to leave the ward while you confirm the death.

There are a number of steps that should be carried out during this final examination in order to avoid mistakes. The approach is similar to any critically ill patient, with assessments of the A, B, C and D.

1 Check that the patient is unresponsive and that there are no signs of life. Look at the chest for movements, and at the throat for signs of swallowing.

2 Auscultate for breath sounds for 2 mins.

3 Check for absence of the carotid pulse.

4 Auscultate for heart sounds for 1 min.

5 Using a pen-torch, ensure that the pupils are not reactive, i.e. are fixed in diameter.

6 Some advocate checking the fundi for ‘trucking’ — the segmentation of the blood vessels.

Findings should be clearly documented in the medical notes, with the exact time of pronouncement of death. The presence or absence of a pacemaker and radioactive implant should be noted, as this may cause explosions if the body is cremated. The presence of other medical devices, such as cannulae, should be documented; these should not be removed. A death certificate should be filled out as soon as practicable.

Inform the nursing staff, the next of kin and the patient’s primary care physician. Ensure that the patient’s family are looked after and that they also have the opportunity to ask any questions.

Diagnostic tests for the confirmation of brainstem death

These are performed in intensive care situations when the patient is on a ventilator. (See page 561.)

Specific clinical problems

Allergy

• Atopy. Approximately one-third of the population is atopic, i.e. produce an exaggerated IgE response to normal environmental allergens. Clinically this response may manifest with eczema, hay fever or asthma (p. 496).

• Allergic reactions. These are increased in atopic persons but also occur in the rest of the population following sensitization to a particular allergen, e.g. drugs, blood transfusions, bee stings and other environmental factors. They are due to an IgE-mediated degranulation of the mast cells releasing mediators, e.g. histamine, which cause leakage of dermal and sub-dermal capillaries.

Clinical features of allergic reactions

Severe symptoms include urticaria, angio-oedema and anaphylaxis. Allergic reactions usually occur within minutes of exposure to an antigen, although sometimes this can be delayed. Establish the time lag between the exposure to a particular allergen and the onset of symptoms. A history of previous allergic symptoms, drugs taken (including complementary), possible allergens in the home or workplace (occupation), and a family history of allergic disorders may be helpful.

• Urticaria (hives, ‘nettle rash’) is common. Itchy weals or swellings develop acutely in the skin due to leaky dermal vessels. Acute urticaria lasts < 6 weeks but chronic persists longer than this. The ‘trigger’ can be food (e.g. strawberries, seafoods, food colourings), insect venom, a drug, physical factors (e.g. heat, cold, pressure) or vigorous exercise. Drugs include aspirin, NSAIDs, ACE inhibitors, opiates, antibiotics or radio-contrast media. Occasionally, urticaria can be secondary to viral or parasitic infections or may rarely occur with SLE. Often the cause is not found.

• Angio-oedema is a localized swelling of the subcutaneous tissues, presenting as a soft-tissue swelling around the eyes, mouth, lips and hands; it is rarely itchy. When it affects the larynx and tongue it can be a life-threatening emergency, as it causes obstruction of the airways. It can also affect the intestine and cause abdominal pain. It usually occurs with urticaria. Severe angio-oedema can lead to anaphylaxis (see below).

• Hereditary angio-oedema is usually not associated with urticaria. It is recurrent and lasts from hours to days. It can be precipitated by trauma, even dental procedures.

• Acute hereditary angio-oedema is treated with C1 esterase concentrates or fresh frozen plasma. For maintenance treatment, anabolic steroids (e.g. stanozol or danazol) are used, as they stimulate an increase in hepatic synthesis of C1 esterase.

Investigations

History is usually the most useful factor in diagnosing urticaria. Investigations are unnecessary unless there are factors suggesting an underlying cause. The following can be useful in doubtful cases and for cases of angio-oedema:

• Blood tests include FBC (looking for non-specific eosinophilia — an absolute count of > 1.5 × 10⁹/L suggests an atopic cause), C1 esterase inhibitor deficiency (<50% of normal) and complement (C3, C4, C1) inhibitor levels.

• Serum mast cell tryptase can be useful, as it peaks within 2 hours and remains raised for 24 hours or so.

• For some food allergies

• Serum IgE and an IgE to a specific allergen (radioallergosorbent test, RAST).

• Skin prick tests using a droplet of diluted standardized allergen on the forearm.

• Challenge tests to allergens, e.g. food challenge; these should only be performed by specialists.

Treatment

• Antihistamines. Antihistamines, e.g. cetirizine 10 mg daily or 5 mg twice daily, desloratadine 5 mg daily, fexofenadine 120–180 mg (for chronic urticaria) daily, or loratadine 10 mg daily. Chlorphenamine 4 mg 4–6-hourly to a maximum of 24 mg daily is also used. Patients should be advised that drowsiness may occur with these drugs and affect their performance, e.g. in driving. Other rarer side-effects include hypotension, palpitations, arrhythmias, dizziness, extrapyramidal effects and sleep disturbances.

• Corticosteroids. See p. 584.

• Cysteinyl leukotriene receptor antagonists e.g. montelukast are used in aspirin-induced asthma.

• Monoclonal antibodies. Monoclonal antibodies against IgE, e.g. omalizumab SC injection, dose varies with IgE concentration and body weight. These inhibit the binding of IgE to basophils and mast cells, and are used in severe peanut allergy.

• Antigen-specific monotherapy (desensitization). Increasing sequential amounts of diluted antigen are given over prolonged periods in specialized centres. The exact mechanism of action is unknown. It is used in the prevention of insect venom anaphylaxis.

• Sublingual. For grass and tree pollen-induced conjunctivitis or rhinitis, a daily sublingual grass pollen extract is given four months before the start of the pollen season.

• Avoidance of allergen. If the allergen is known, an attempt should be made to avoid it with the help of dietitians.

Anaphylaxis

This life-threatening emergency is due to a systemic allergic reaction, which is rapid in onset. This reaction requires ‘priming’ by an antigen followed by re-exposure and the allergen must be systemically absorbed (ingestion or parenteral injection). Serum platelet-activating factor (PAF) levels have been found to correlate directly with the severity of anaphylaxis, whereas PAF acetylhydrolase (the enzyme that inactivates PAF) correlates inversely.

Causes

Allergens include:

• Foods: Nuts — peanuts (protein-arachis hypogaea Ara h 1–3), Brazil nuts, cashew nuts. Shellfish—shrimp (allergen Met e 1), lobster. Dairy products, egg and, more rarely, citrus fruits, mango, strawberry, tomato.

• Venoms: wasps, bees, yellow-jackets, hornets.

• Medications: antisera (tetanus, diphtheria), dextran, latex, some antibiotics and blood products.

Clinical features

The clinical features are shown in Box 1.3. Symptoms range from widespread urticaria and angio-oedema (laryngeal oedema, airway obstruction) to cardiovascular collapse, respiratory arrest and death. Initially there may only be tingling, warmth and itchiness. This is followed by a generalized flush, hypotension, bronchospasm, laryngeal oedema and cardiac arrhythmias; myocardial infarction can follow. Death can occur within minutes.

Box 1.3 Acute anaphylaxis

Clinical features

• Bronchospasm

• Facial and laryngeal oedema

• Hypotension

• Nausea, vomiting and diarrhea

• For Management, see Fig. 20.3.

Emergency treatment

Treatment for acute anaphylaxis is shown in Emergencies in Medicine Fig. 20.3.

Non-emergency treatment

• Prevention by avoidance of triggering foods, particularly nuts and shellfish.

• Patient education in the self-administration of adrenaline (epinephrine); patients should always carry pre-loaded syringes.

• Desensitization, particularly if exposure is unavoidable or unpredictable, as in insect stings; this is carried out in specialist centres only.

Anxiety

Anxiety is common in the sick and hospitalized patient. Discussion of the cause of the anxiety with the patient, along with reassurance, is often sufficient to relieve the anxiety. Hyperventilation, which is a feature of anxiety, is described in Box 1.4

Box 1.4 The hyperventilation syndrome

Cause

• Overbreathing leading to a decrease in PaCO₂ and a decrease in bicarbonate and therefore an increase in arterial pH (respiratory alkalosis), causing a decrease in ionised calcium and a relative hypocalcaemia

Diagnosis

• A provocation test — voluntary overbreathing for 2 mins — provokes similar symptoms

• Rebreathing from a large paper bag relieves them

• Blood gases to exclude severe asthma

Management

• Explanation and reassurance are given

• The patient is trained in relaxation techniques and slow controlled breathing

• The patient is asked to breathe into a closed paper bag

Benzodiazepines

These are used for the short-term relief of severe anxiety; their action is described on p. 22. Agents used are:

• Diazepam 2 mg 3 times daily, increased if necessary to 15–30 mg in divided doses per day

• Chlordiazepoxide 10 mg 3 times daily, increased if necessary to 100 mg in divided doses

• Oxazepam 15–30 mg (10–20 mg in the elderly) 3–4 times daily.

The dose should be as small as possible to control symptoms.

• Side-effects (p. 23). Dependence and tolerance occur more frequently. Withdrawal symptoms are particularly severe after prolonged use and the drugs must be discontinued slowly. This period can range from 4 weeks to 1 year.

Beta-receptor adrenergic blockers

• Propranolol 20–40 mg 3 times daily is used to control the peripheral symptoms of anxiety such as palpitations, tremor and tachycardia. These drugs do not help control the underlying anxiety.

Management of the severely disturbed patient

Severely disturbed patients (see also p. 626) are usually seen in the accident and emergency department. The primary aims of management are the control of dangerous behaviour and establishment of a provisional diagnosis. The main causes are personality disorders, drug and alcohol abuse, and psychosis. For delirium tremens, see p. 627; hallucinations are desccribed in Box 1.5.

Box 1.5 Hallucination

A hallucination is defined as a perception in the absence of a stimulus. It is:

• a false perception and not a distortion

• perceived as inhabiting objective space

• perceived as having qualities of normal perception

• perceived alongside normal perceptions

• independent of the individual’s will

Three specific strategies are employed when dealing with the violent patient:

• Reassurance and explanation. Most disturbed patients are themselves frightened, as well as frightening, and may feel threatened by those around them. Staff should always explain the situation and their intentions.

• Physical restraint. Patients must be restrained from harming themselves and others. A sufficient number of trained staff must be available. At least one person per limb and two others are required if a sedating drug is to be given. Once brought under physical control, the patient should be held in the prone position to protect the airway and to allow an IM injection to be given. Care must be taken to ensure that neither the airway nor breathing is impeded, by having someone always present at the head of the patient. Patients should continue to be restrained until they have calmed down. If IM medications are given into the buttock, damage to the sciatic nerve is best avoided by injecting into the upper outer quadrant.

• Medication. Patients should be rapidly tranquillized if they have a psychosis.

• A deep IM injection of zuclopenthixol in a dose ranging from 50 to 150 mg, together with lorazepam 0.5–1 mg, is the treatment of choice for rapid effect. Used in combination, they have a synergistic action.

• Moderate doses of a neuroleptic, e.g. IM chlorpromazine 25–50 mg, 6–8-hourly, or a benzodiazepine can also be given at regular, comparatively short intervals (30–60 mins) IM.

• An alternative regimen is IM butyrophenone (haloperidol 2–10 mg) in patients under 60 years old. This dose should be reduced in the elderly and those with known cardiac or hepatic disease. The patient should be observed for up to 1 hour before a further dose is administered.

• In the case of continuing disturbance, it is preferable to administer an adjunctive IM benzodiazepine (lorazepam 2 mg) rather than a further dose of a neuroleptic.

Breathing, pulse rate and BP should be monitored for respiratory difficulty, arrhythmias and hypotension.

This procedure must be carefully documented and be within legal boundaries.

Falls

Falls are very common in older people, with about 15% resulting in serious injury. They are the commonest cause of fracture of the neck of femur in the elderly. Most hospitals have a ‘falls’ policy and patients are assessed for their risk of falling; this should be reviewed at regular intervals.

Assessment of risk

Assessment of the risk of falling should include: visual impairment, mobility (e.g. arthritis), impairment of activities of daily living, environment, nutrition, continence and cognitive status (confusion, agitation). The medication that patients are taking (particularly polypharmacy) should be reviewed (e.g. for any causing hypotension or sedation). Blackouts, muscle weakness, accidental trips and previous medical history should be ascertained.

Management

Investigations. Investigations to find an acute illness should include:

• FBC, U&E, LFTs, CRP, glucose, calcium

• CXR and urinary analysis for infection

• blood culture if pyrexial.

For chronic conditions:

• serum 25 hydroxy vitamin D

• cardiovascular assessment (ECG, e.g. for arrhythmias)

• neurological assessment (muscle weakness, gait disturbance, Parkinson’s disease).

Prevention. This usually involves a multidisciplinary approach. Any abnormality detected should be addressed and reversed, if possible. For example, poor vision should be corrected, medication rationalized, and environmental hazards at home removed or modified. Medical treatment for conditions such as osteoporosis or cardiovascular disorders (common in the elderly, e.g. postural hypotension) may be required. Exercise and balance training can be very helpful in preventing falls. The nutritional status of the patient should be assessed and a proper healthy diet advised. Bone protectors (e.g. hip protector pads) are helpful in reducing the number of fractures of the neck of femur. Aids, such as walking sticks, tripods or Zimmer frames, might be suitable for some.

Insomnia

Insomnia is difficulty in sleeping; it can be due to mood disorders such as anxiety; drug use — both prescribed drugs such as steroids and drugs of abuse, or analgesics for pain — as well as excess alcohol consumption. The causes should be addressed prior to using a hypnotic.

Benzodiazepines

These are frequently used. They act at the benzodiazepine receptors, which are linked to the GABA receptors:

• Nitrazepam and flurazepam have a prolonged action. Dosages are nitrazepam 5–10 mg (dose halved in the elderly) and flurazepam 15–30 mg (15 mg in the elderly).

• Lorazepam, lormetazepam and diazepam have a shorter action and so have fewer hangover effects on the following day. Dosages are lorazepam 1–2 mg, lormetazepam 0.5–1.5 mg (500 mcg in the elderly) and diazepam 5–15 mg. These drugs should not be given for more than 4 weeks to avoid dependence.

• Side-effects include drowsiness, confusion and ataxia. Both tolerance and dependence can develop. An increase in aggression and anxiety is sometimes seen. All side-effects are more prevalent in the elderly. A withdrawal syndrome occurs on stopping any benzodiazepine, even a short-acting one which should always be done gradually. Symptoms include insomnia, anxiety, loss of appetite, tremor, confusion and a psychosis.

Non-benzodiazepines

• Zaleplon, zolpidem and zopiclone all act at the benzodiazepine receptor and are used for insomnia. Dosages are zaleplon 10 mg, zolpidem 10 mg (5 mg in the elderly) and zopiclone 3.75–7.5 mg at night. They should not be used in patients with severe hepatic or renal disease.

• Side-effects include headache, diarrhea, nausea, confusion and daytime drowsiness. Non-benzodiazepines do not cause any withdrawal symptoms but dependence has been reported.

The red eye

This is a common condition and can be a medical emergency. It can be associated with pain, a sticky, watery eye, reduced vision/visual loss and photophobia.

• A painful red eye with visual problems is due to glaucoma (see below), severe inflammation, acute anterior uveitis, infective endophthalmitis, or central corneal ulcers or abscesses.

• A painful eye without visual problems is due to early anterior uveitis, peripheral corneal ulcers or erosions, keratitis or anterior scleritis.

• Non-painful eyes may be associated with a purulent discharge (bacterial, viral, chlamydial, infective conjunctivitis); a sticky, watery discharge (hay fever, acute allergy, allergic conjunctivitis); grittiness (e.g. blepharitis, sicca syndrome); and photophobia (e.g. keratitis, herpes simplex, early iritis, corneal abrasion). Other causes, e.g. episcleritis, marginal ulcers, pterygium or rosacea keratitis, can produce a sector of redness.

Box 1.6 gives the red flags for a red eye. URGENT REFERRAL TO EYE CLINIC IS MANDATORY.

Conjunctivitis

This is the commonest cause of a red eye. There is inflammation causing soreness and a discharge but the visual acuity is usually, but not always, good. It can arise from a number of causes:

• Viral conjunctivitis (e.g. adenovirus) may be associated with a watery discharge and a cold or sore throat. It is commonly associated with chemosis, lid oedema and a palpable pre-auricular lymph node. Viral conjunctivitis can cause deterioration in visual acuity owing to corneal involvement (focal areas of inflammation). In 50% of patients the conjunctivitis is unilateral.

• Treatment is usually self-limiting. Lubricants, together with a cold compress, can be soothing. Strict hygiene and keeping towels separate from the rest of the household reduce spread. Topical steroids are used in patients with corneal involvement or intense conjunctival inflammation.

• Bacterial conjunctivitis is uncommon (5%) and causes grittiness without visual problems. There is a mucopurulent discharge and conjunctivitis can be rapid in onset (e.g. gonococcus). Less acute inflammation can be due to Haemophilus influenzae and Streptococcus pneumoniae.

• Treatment should be given promptly with oral and topical penicillin in gonococcal conjunctivitis to reduce the rate of corneal perforation. A Gram stain of the conjunctival swab can quickly confirm the presence of diplococci. Gonococcal conjunctivitis is a notifiable disease in the UK.

• Empirical treatment for both subacute and chronic bacterial conjunctivitis involves a topical broad-spectrum antibiotic such as chloramphenicol. Swabs should be taken if these cases do not respond to this initial treatment.

• Allergic conjunctivitis causes an itchy, stringy discharge and can be due to various types viz. seasonal, perennial, vernal, atopic and giant papillary. Seasonal allergic conjunctivitis and perennial conjunctivitis affect 20% of the general population. The main symptoms include itching, redness, soreness, watering and a stringy discharge.

• Treatment reduces the allergen load (e.g. dust) and antihistamine drops are given, e.g. azelastine and emedastine, along with topical mast cell-stabilizing agents such as sodium cromoglicate and nedocromil. Olopatadine has a dual action and is both an antihistamine and a mast cell stabilising agent. Corticosteroid drops should be avoided. Oral antihistamines help the itching.

Acute angle-closure glaucoma (AACG)

This is an ophthalmic emergency, presenting with an acute red, painful eye and blurred vision. The patient is unwell, with nausea, vomiting and headache. The eye is injected and tender; the cornea is hazy and the pupil is semi-dilated.

AACG usually occurs in the older person when there is a sudden rise in intra-ocular pressure (IOP) to levels greater than 50 mmHg.

• Treatment must be prompt to preserve the sight.

• Give IV acetazolamide 500 mg (provided there are no contraindications) to reduce IOP. Instillation of pilocarpine 4% drops to constrict the pupil improves aqueous outflow and prevents iris adhesion to the trabecular meshwork.

• Other topical drops, such as β-blockers and prostaglandin analogues, can also be instilled if available, provided there are no contraindications.

• Give analgesia and antiemetics as required.

• Refer to an ophthalmologist immediately for reduction in IOP and monitoring. Other agents, e.g. oral glycerol or IV mannitol, can be administered to non-responding patients. Definitive treatment requires laser or surgery to make a hole in the periphery of the iris of both eyes.

Anterior uveitis (iritis)

The classical presentation is with a triad of redness, pain and photophobia. Vision is normal or blurred, depending on the degree of inflammation. Redness may be general or localized. On examination, keratic precipitates (KP) are seen on the corneal endothelium, with fibrin or hypopyon (pus), and the pupil may have adhered to the lens (posterior synechiae). The IOP may be normal or raised either due to cells clogging up the trabecular meshwork or because of posterior synechiae and reducing aqueous drainage.

• Treatment

• Reduce inflammation with topical steroids, e.g. dexamethasone 0.1% every 30–60 mins until the inflammation is controlled and then reduce to 4 times daily.

• Dilate the pupil with cyclopentolate 1% to prevent formation of posterior synechiae. Dilatation also allows fundoscopy to exclude posterior segment involvement.

• If the IOP is raised, treat with topical β-blockers, e.g. timolol 0.25%, prostaglandin analogues, e.g. latanoprost 50 mcg/mL once daily, or oral or IV acetazolamide 0.25 mg–1 g daily in divided doses.

• Refer to an ophthalmologist.

Pain management

Many patients complain of pain and require treatment, often without a precise diagnosis, e.g. non-specific headache. Before medication is prescribed, reassurance and explanation are often helpful.

Pain in palliative care is discussed on p. 292.

Analgesics, e.g. NSAIDs as used in rheumatic disorders, are discussed on p. 298. They (e.g. diclofenac 150 mg orally, IV, IM or rectally in 2–3 divided doses daily) are also useful in ureteric colic if renal function is normal and in post-operative musculoskeletal pain, for example.