John A. Henry

Clinical review: Major consequences of illicit drug consumption

Because illicit drugs are now widely consumed, every doctor needs to know their acute medical consequences and complications. Here, we review the problems associated with the different drugs from a systems-based viewpoint. Apart from the respiratory depressant effect of opioids, crack cocaine is the most common cause of respiratory complications, mainly linked with its mode of use, with airway burns, pneumothorax, pneumomediastinum, and lung syndromes being well-recognised sequelae. Because of its marked cardiovascular effects, cocaine is also a major cause of coronary syndromes and myocardial infarction. Amphetamines may produce similar effects less commonly. Hyperthermia may occur with cocaine toxicity or with 3,4-methylenedioxymethamphetamine (MDMA) due to exertion or from serotonin syndrome. Cerebral haemorrhage may result from the use of amphetamines or cocaine. Hallucinations may follow consumption of LSD, amphetamines, or cocaine. MDMA is a major cause of acute severe hyponatraemia and also has been linked with hepatic syndromes. Collapse, convulsions, or coma may be caused in different circumstances by opioids, MDMA, or gamma hydroxybutyrate and may be aggravated by other sedatives, especially alcohol and benzodiazepines. Recognition of these acute complications is urgent, and treatment must be based on an understanding of the likely underlying problem as well as on basic principles of supportive care.

Epidemiology and relative toxicity of antidepressant drugs in overdose

SummaryAntidepressant drugs are currently the mainstay of treatment for all but the mildest forms of depression. Their effectiveness in the management of depressive illness is undisputed and their effectiveness in preventing suicide, while not proven, may be assumed. Nevertheless, of all the drugs that are taken in lethal overdose, prescribed antidepressants are among the most common.Epidemiological studies from several countries have provided evidence of marked differences in overdose toxicity between drug classes and, in some cases, between individual drugs within a class, with some of the older tricyclic anti-depressants (TCAs) being the most toxic.Over 80% of all deaths arising from overdose of antidepressant medication in the UK between 1987 and 1992 were caused by 2 drugs: amitriptyline and dothiepin. Taken alone, this figure conveys little information about the toxicity of either drug. However, when considered within an epidemiological context, the evidence suggests that both drugs are highly toxic in overdose, a conclusion that is supported by animal studies of the toxicity of TCAs and by clinical evidence of overdose toxicity.This paper reviews the epidemiological evidence concerning the acute toxicity of antidepressant drugs and considers the interplay of factors that contribute to the toxicity which occurs when they are taken in acute overdose. The inherent toxicity of the drug appears to be the crucial factor and, although less well researched, prescribing practices and perception of toxicity are probable contributory factors.

Detection of hypertension in the emergency department

Objectives: To assess whether an emergency department (ED) is a suitable location for the targeted screening of hypertension. Methods: This was a prospective targeted screening study based at the ED of an inner city teaching hospital. Non-acute subjects over 18 years were recruited consecutively from the “minors” section of the ED and invited to participate. All subjects had their blood pressure measured twice. A verbal numerical pain score (PS) out of 10 using a visual analogue scale was obtained. Those with a mean systolic blood pressure >140 mmHg or a mean diastolic blood pressure >90 mmHg (WHO JNC stage 1 hypertension) were invited for a subsequent follow up measurement. The primary outcome measure was the proportion of subjects with hypertension at follow up. The secondary outcome measure was the correlation between a subject’s mid blood pressure (MBP) and their PS. Results: In total, 765 subjects were tested, of whom 213 subjects were hypertensive at presentation (28.7%). After excluding those on anti-hypertensive medication (nu200a=u200a43; 5.6%) and those who were non-UK residents (nu200a=u200a44; 5.8%), 126 subjects were invited for follow up, of whom 51 subjects actually attended (40% attendance, 6.6% of study population). The MBP of those who re-attended was significantly lower than at presentation (p<0.001); 39 subjects (5% of the study population, 76.4% of those attending follow up) remained hypertensive. There was no correlation between a subject’s PS and their MBP (Pearson correlation coefficient u200a=u200a−0.02). A 10/10 PS was associated with an 8.4 mmHg rise in MBP compared to the mean MBP of subjects with PS 0–9 (p<0.1). Of those originally presenting with PS>5/10, 62% still had hypertension at follow up when the painful stimulus was significantly reduced (mean PSu200a=u200a0.6). Conclusion: The ED provides an opportunity for identifying those individuals with hypertension who may otherwise remain undiagnosed. Caution is advised when diagnosing hypertension in those individuals suffering from anxiety and/or acute severe pain on presentation.

Constraints on Antidepressant Prescribing and Principles of Cost-Effective Antidepressant Use

SummaryCost-effectiveness studies are a useful tool in drug-choice decisions. They are appropriate when alternative therapies have different levels of effectiveness, as with antidepressants. The calculation of cost effectiveness is similar to that used by some authors to determine whether a drug should be included in a formulary, so it clearly has immediate practical application and potential acceptability.However, the actual acceptability of cost-effectiveness studies has been hampered by a lack of conformity over study objectives, methodology and use of available data, and this significantly affects results. Studies that focus on the same location and setting, and conducted at the same time, frequently provide different results in their conclusions, depending on the assumptions and viewpoints, and the effects of sampling error. For example, dosage can affect purchase price calculations, but also compliance and efficacy, which are important considerations. Moreover, conclusions based on cost disadvantages of new drugs are not appropriate for planning for the future, since a drug’s market price tends to fall with time and increasing demand.Appropriate use of outcome measures is important, and treatment failures, as well as successes, should be considered. Cost-effectiveness analysis has been used to demonstrate an important point: even when the appropriate use of antidepressants and speciality care increases medical costs, it improves value for money. A variety of drugs for one indication should be available to the prescriber, as the most cost-effective one may differ between patient subpopulations.Many costs of morbidity, adverse effects and secondary effects of antidepressants remain to be properly quantified, but are likely to have an important influence on cost effectiveness. These costs are likely to be higher for tricyclic antidepressants than the newer reversible inhibitors of monoamine oxidase and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors.Costing in some areas of health is relatively straightforward. Depression is among the most difficult areas to cost because of its gradation in severity, its chronic and recurrent nature, and its subtle effects on working capacity. Quantification of differences resulting from the use of different drugs has many pitfalls. Until now, each cost analysis of depression has differed from the last, and most have placed excessive reliance on poorly substantiated and hypothetical assumptions. More in-depth studies are required to define the most cost-effective policies for recommendation to healthcare decision-makers and antidepressant drug prescribers. Compliance, adverse effects, and safety in overdose are important factors. The impact of indirect costs also needs to be addressed.

Constraints on antidepressant prescribing and principles of cost-effective antidepressant use. Part 1: Depression and its treatment.

SummaryDepression is a common, recurrent, disabling and potentially fatal disorder. Its effect on quality of life is more severe than that of some other chronic medical conditions. Its cost burden (direct and indirect) has been estimated at

Increase in alcohol related deaths: is hepatitis C a factor?

US26 billion to

Carbon monoxide: not gone, not to be forgotten.

US43.7 billion in the US (in 1990), and 3.4 billion pounds sterling in the UK (in 1992).With contemporary levels of diagnosis and treatment, and of treatment failure, the indirect economic losses to society from depression-associated morbidity and mortality may be up to 7 times the direct costs, with 69 to 98% of these costs related to morbidity. Impaired capacity while at work may equal absenteeism in terms of costs. Depression carries an increased risk of suicide and suicide attempts, both of which are costly. It is ironic, then, that the drugs used to treat depression account for 9% of poisoning deaths in England and Wales. The newer antidepressants are less toxic than the tricyclic antidepressants (TCAs).The physician’s choice of antidepressant should be motivated primarily by clinical considerations, but cost implications are of increasing importance. In some healthcare systems, the expenditure associated with prescribing by doctors has been successfully modified, at least temporarily, by drug formularies, audit and feedback. This may be to the disadvantage of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors; they have higher acquisition costs than the TCAs, since they are newer and lack cheaper generic forms, and definitive evidence of benefits may be inadequate or equivocal. However, market price is only one of many factors that should affect the prescriber, and the increasing trend towards cost containment policies is liable to lead to false economies.

Prevalence of cocaine use among patients attending the emergency department with chest pain

Aim: To evaluate recent trends in alcohol related deaths in the UK and to consider possible causative factors. Design: Observational retrospective study of the database of the Office for National Statistics, alcohol consumption data reported by the General Household Survey, and other published data. Setting: England, 1993–9. Results: Deaths for each million of the population from alcohol related illness increased by 59% in men and 40% in women over the years 1993 to 1999. One subgroup of alcohol related deaths, ICD 571.3 (alcoholic liver damage unspecified), showed a 243% increase in men aged 40 to 49 years over the same period. Figures for younger men, and women in all age groups, showed less pronounced increases. There has been no associated rise in alcohol intake. There has been an increase in the incidence of hepatitis C virus (HCV) infection in recent years, and alcohol consumption in HCV positive individuals accelerates the progression to cirrhosis. Circumstantial evidence links the rise in HCV infection to the use of illicit drugs in the 1970s and 1980s, among those currently aged 40 to 59 years. Conclusions: The recent increase in alcohol related deaths cannot be solely explained by a change in drinking habits. It is suggested that this probably results from the rapid progression of alcoholic cirrhosis in people who have acquired HCV infection through intravenous drug use. Alcohol consumption in HCV positive individuals is firmly linked with a poor outcome.

IPCS/CEC evaluation of antidotes series. Volume 1: Naloxone, flumazenil and dantrolene as antidotes

Carbon monoxide is a remarkable poison. Because of the non-specific manner in which it may present, and the consequent multiplicity of possible diagnoses, it has been described as the silent killer. This issue of the journal contains three publications on the topic, and if that were not enough, the Chief Medical Officer has recently written to all the general practitioners in Britain warning them of the problems associated with carbon monoxide poisoning. Another useful reference document has also appeared from the Health and Safety Executive outlining the diagnosis and management of carbon monoxide toxicity with an emphasis on the industrial aspects. It is necessary for all those working in accident and emergency departments to be aware of the diagnosis, the management, the pitfalls, and the science of carbon monoxide poisoning. Some may ask why there is such concern about carbon monoxide. The reason is that, apart from being the commonest cause of fatal poisoning in Britain and many other countries, it is now well recognised as a cause of neurotoxicity. There may be clearly evident damage, such as parkinsonian syndromes, cortical blindness, and dementia, or there may be more subtle problems, such as apathy, fatigue, irritability, minor memory disturbances, difficulty with decisions, and personality change.4 5 It is not necessary for the patient to have suffered severe or life threatening poisoning for these effects to occur. Carbon monoxide is also unusual in that delayed neurotoxicity may occur days or even weeks after apparent recovery from the episode of poisoning. The most immediate problem is that of diagnosis. The clinical assessment of the patient may reveal very few clues. Headache, dizziness, fatigue, and nausea are common symptoms. Tachycardia, tachypnoea, postural hypotension, and signs of central nervous system depression occur in more severe cases. One should always suspect carbon monoxide when people present with non-specific symptoms, particularly in cold weather; unfortunately, this is precisely the time when viral and bacterial infections are more common. When more than one person has suffered typical symptoms, or if a pet animal has also become ill or died, the clinician should actively consider the diagnosis.7 If everyone in the premises has suffered from headache and vomiting, then carbon monoxide poisoning is by far the most likely diagnosis. The carboxyhaemoglobin (COHb) concentration is the most important diagnostic test, and blood should be taken as early as possible after the patient presents, as the blood COHb declines rapidly, especially if the patient is being given oxygen by facemask. The paper by Turner, Esaw, and Clark (p96),8 which investigates the importance of metabolic acidosis, helps to confirm that acidosis is a significant feature of carbon monoxide poisoning and also that initial acidosis is a good predictor of severity and of treatment requirements. It is clear that the initial assessment of the patient should include a full history and clinical examination, a COHb concentration, and also an arterial pH estimation. However, this publication also shows us that better markers of intracellular hypoxia are needed. What is currently being measured reflects whole body hypoxia, but it is mainly cerebral hypoxia that is responsible for the acute presentation and long term sequelae. The update by Turner, Hamilton-Farrell, and Clark (p92) is a useful review of a range of new concepts in carbon monoxide poisoning.9 Ideas about the mechanism of toxicity have developed markedly. The original simplistic picture put forward by Haldane is no longer accepted. He believed that the toxicity of carbon monoxide was secondary to its high affinity for haemoglobin, and that the resulting decrease in the oxygen carrying capacity of the blood caused end organ hypoxia. Other mechanisms are much stronger candidates for causing symptomatology and toxicity. These include combination of carbon monoxide with cytochromes and with myoglobin, inhibition of mitochondrial metabolism, competition with nitrous oxide, promotion of free radical damage and inflammatory mechanisms; their precise contributions remain to be elucidated. However, these mechanisms are not easy to detect or identify in clinical practice, and because of its ease of measurement, blood COHb remains the most important diagnostic test despite its poor predictive value. The authors have posed questions about the roles of glucose and ethanol, but the relationship of these two to acute and chronic human poisoning is not clear. Therapeutic interventions are limited to supportive care and normobaric or hyperbaric Accident and Emergency Department, St Marys Hospital, Queen Elizabeth the Queen Mother Wing, South WharfRoad, London W2 lNY

Cannabis as a precipitant of cardiovascular emergencies

Introduction Cocaine is the only drug to show a rise in misuse between 1996 and 2007 in England and Wales. It can cause chest pain and myocardial infarction. This study assessed the prevalence of cocaine use in patients presenting with chest pain, and determined the association between cocaine use and chest pain. Methods Patients presenting with chest pain had a urine sample collected at presentation. Each patient with chest pain was matched with a non-chest pain control. Demographic detail, drug history and clinical outcome was recorded, samples anonymised and subsequently tested for cocaine and metabolites. Results Of the 1469 patients, 101 (6.9%) tested positive for cocaine compared with 3.8% of controls (p<0.001). Men (8%) were more likely than women (5.1%) to test positive for cocaine. Two patients developed a myocardial infarction. Cocaine use was highest in those aged 18–30u2005years for both sexes and decreased with age. Cocaine-positive patients with chest pain were more likely to present in the evening, after midnight or at the weekend. Only 18% of all patients presenting with chest pain had a specific drug history recorded in their notes. Conclusions As many patients do not admit to use of an illegal drug, routine testing would enable cocaine-related ischaemic events to be identified more easily but this remains controversial. As management of cocaine-induced chest pain is different from other causes of chest pain, doctors should routinely question patients with chest pain about cocaine use in addition to well recognised risk factors.