Internal Medicine

Prevalence and Pattern of Self Medication use in coastal regions of South India

Balamurugan E and Ganesh K
Article Citation and PDF Link
BJMP 2011;4(3):a428
Abstract / Summary

Aim:Self medication (SM) is proportionately increasing in both urban and rural communities. The prevalence and pattern of SM use is not well established, hence a cross sectional survey was undertaken which recruited a sample size of 200 participants randomly from the coastal regions of south India.
Method: Each participant underwent a face to face interview with the help of a structured questionnaire; data collected was analyzed using descriptive and inferential statics in SPSS.
Result: SM use was reported by 71% of the subjects, which ranged from a frequency of at least one time to a maximum of 5 times and above. Lack of time (41.5%), minor illness (10.5%) and quick relief (10%) was cited as the most common reason for SM use. The majority of the participants (93.5%) were not aware about the side effects of SM. Findings revealed females and people living in urban areas are more likely to use SM than males and people in rural areas (P<0.001). 
Conclusion: there maybe a larger role for a training programme to empower people about safety and side effects of SM use, to achieve a greater sense of self control

Self-medication, Rural, Urban, over the counter drug, Medicines


William Osler has said that "A desire to take medicine is perhaps the great feature which distinguishes man from animals" This desire, however may play havoc when a person starts taking medicines on their own (i.e. self-medicating), forgetting that all drugs are toxic and their justifiable use in therapy is based on a calculable risk 1.

Self-medication (SM) can be defined as obtaining and consuming drugs without the advice of a physician2. There is a lot of public and professional concern about the irrational use of drugs in SM. In developing countries like India, easy availability of a wide range of drugs coupled with inadequate health services result in increased proportions of drugs used as SM compared to prescribed drugs2. Although, over-the-counter (OTC) drugs are meant for SM and are of proved efficacy and safety, their improper use due to lack of knowledge of their side effects and interactions could have serious implications, especially in extremes of ages (children and old age) and special physiological conditions like pregnancy and lactation 3, 4. There is always a risk of interaction between active ingredients of hidden preparations of OTC drugs and prescription medicines, as well as increased risk of worsening of existing disease pathology 5 . As very few studies have been published in our community regarding usage of self medication we conducted this cross-sectional study in the coastal region of Pudhucherry, South India, t assess the prevalence and pattern of SM use.

Materials and methods:

The present study was a cross-sectional survey conducted in coastal region of pudhucherry, south India. For this study we recruited 200 patients randomly from both urban and rural communities (100 each) for a period of six months during 2009. Patients who were = 18 years of age and who were able to read and write the local language (Tamil) or English were included in the study after informed consent explaining the purpose of the study. Participants with intellectual, psychiatric and emotional disturbances that could affect the reliability of their responses were excluded from the study. To collect data regarding SM usage a structured questionnaire was prepared, after an extensive literature review.. The structured questionnaire contained 25 items in the form of closed and open ended questions. Initially the tool was validated by a panel of experts in the field of public health for the appropriateness of each item and assessment of content validity (0.91) and re-test reliability coefficient (0.89). Approval to conduct the study was granted by the Institute ethics committee prior to data collection. Each participant underwent a face to face interview to collect data followed by an informal educational counseling about potential adverse effects of consuming common SM. Data collected was analyzed using SPSS for windows statistical software version 14 (SPSS Inc., Chicago, Il, USA). Data was presented using descriptive statistics (i.e. numbers, percentage) and inferential statistics (i.e. Chi-square). A probability value of < 0.05 was considered to be significant.


Basic demographic details:

The majority of the participants were female (56%). Most of the participants (60%) were between 26-45 years of age. There were an equal number of participants from the rural and urban community. Among the total 200 participants 70% were literate.

Findings related to usage of SM:

Overall, out of 200 participants, 71 % of them reported that they have used SM in the past. The frequency of SM use varied among the subjects with a minimum of at least one time to maximum of 5 times and above See Figure 1. When the participants were asked about the reasons for SM use, the majority of them - 41.5% - stated lack of time to visit a doctor as the main reason followed by minor illness and quick relief. See Table 1.   The major source through which the participants learned to use SM were as follows, directly from pharmacist (57.3%), prescription of previous illness (21.5%), friends (12.5%), television (5.5%) and books (3%).See Table 2. The main indications for SM use were fever (36%), headache (35%), then cough/cold/sore throat (20%). See Table 3 for detailed data.

Figure 1: Frequency of self medication Use

Table 1: Reasons for Self Medication Use

Reasons Number (%)
Lack of time 41.5
Minor illness 10.5
Economical 14
Quick relief 10
Learning opportunity 2
Ease and convenience 10.5
Avoiding crowd in visiting doctor 6
Unavailability of doctor 5.5

Table 2: Sources of Self Medication Use

Sources for self medication use Number (%)
Directly from pharmacy without prescription 57.3
Prescription of previous illness 21.5
Friends prescription 12.5
Television media 5.5
Book 3

Table 3: Indications for Self Medication Use

Indications for self medication use Number (%)
Headache 35
Stomach ache 3
Vomiting 1
Eye symptoms 0.73
Diarrhoea 2
Cough, cold, sore throat 20
Fever 36
Skin symptoms 0.27
Ear symptoms 2

While calculating chi-square to find out the association between usage of SM and selected demographic variables we found an association between residence (i.e. rural or urban) and gender; urban people were more likely to use SM than rural people (urban, 60/100 vs. rural 82/100, p value = .006). In relation to gender females were more likely to use SM in comparison to males (female, 78/112 vs. 43/88, p value= .002). Other variables were not significantly associated with SM use. Finally, when the subjects were asked about the side effects of their used self medications 93.5% of them said that they are not aware of the side effects and only the remaining 6.5% of them said they are aware of the side effects.


The current study examined the prevalence and pattern of SM use in a coastal region of South India. The study findings revealed 71% of the people reporting SM use in the past,  this prevalence rate in our study is consistent with previous finding3,6,7,8,9,10,11 The figure of participants who use SM is very high, which requires immediate attention. The frequency of self medication use in our study ranged from a minimum of one time to a maximum of 5 times and above, this finding was in line with the findings of a study by Nalini (2010)12.

Participants cited multiple reasons for use of SM like lack of time , quick relief from illness and ease and convenience, a similar reasons were cited  in an another Indian study13. In the current study participants reported SM use in a variety of conditions like headache, stomach ache, cough and fever, this these finding are comparable with those of Sontakke et al (2011) 14. The reason for SM use may be mufti-factorial, in our study an association was found between gender and residence, i.e. female and rural people reporting more  SM use, this finding was similar to two previous studies15,16 To establish the reasons why requires further research. One potential limitation of this study is the limited sample size, which we tried to overcome by adopting a random sampling method so as to generalize findings.


Factors influencing SM include patient satisfaction with the healthcare provider, cost of the drugs, educational level, socioeconomic factors, age and gender 17. Interactions between prescribed drugs and the drugs taken for SM is an important risk factor of which healthcare providers must be aware of.17,2

Easy availability of wide range of drugs without a prescription is the major factor responsible for irrational use of drugs in SM as, thus resulting in impending health problems (antimicrobial resistance, increased load of mortality and morbidity) and economic loss. The need for promoting appropriate use of drugs in the health care system is not only for financial reasons, with which policy makers and manager are usually most concerned, but also for health and medical care of patients and the community. There is need for authorities to strengthen existing laws regarding OTC drugs to ensure their rational sale and use. Also, specific pharmacovigilance is needed and the patient, pharmacist and physician must be encouraged to report any adverse events. Periodic studies on the knowledge, attitude about and practice of SM may give insight into the changing pattern of drug use in societies.

Acknowledgements / Conflicts / Author Details
The author is grateful to all study participants who willingly participated in the study.
Competing Interests: 
None declared
Details of Authors: 
BALAMURUGAN E. (R.N, R.M, M.Sc.), Research Scholar, College of Nursing, All India Institute of Medical Science, New Delhi, India. GANESH K. (R.N, R.M, M.Sc), Research Scholar, College of Nursing, All India Institute of Medical Science, New Delhi, India
Corresponding Author Details: 
Balamurugan E., Research Scholar, College of Nursing, All India Institute of Medical Science, Ansari Nagar, New Delhi -110029, India
Corresponding Author Email:


  1. Phalke VD, Phalke DB, Durgawale PM. Self-medication practices in rural Maharashtra. Indian J Community Med .2006; 31:34-5.
  2. Montastruc JL, Bagheri H, Geraud T, Lapeyre MM. Pharmacovigilance of self-medication. Therapie 1997;52:105-10
  3. Shankar PR, Partha P, Shenoy N. Self-medication and non-doctor prescription practices in Pokhara valley, Western Nepal; a questionnaire based study. BMC Fam Pract. 2002;3:17
  4. Murray MD, Callahan CM. Improving medication use for older Adults: An integrated research agenda. Ann Intern Med 2003;139:2425-9
  5. Choonara I, Gill A, Nunn A. Drug toxicity and surveillance in children. Br J Clin Pharmacol. 1996;42:407-10
  6. Sharma R, Verma U, Sharma CL, Kapoor B. Self-medication among urban population of Jammu city. Indian J Pharmacol. 2005;37:40-3
  7. Kasilo OJ, Nhachi CF, Mutangadura EF. Epidemiology of household medications in urban Gweru and Harare. Cent Afr J Med. 1991;37:167-71
  8. Awad A, Eltayeb I, Matowe L, Thalib L. Self-medication with antibiotics and antimalarials in the community of Khartoum State, Sudan. J Pharm Pharm Sci. 2005 Aug 12;8(2):326-31.
  9. Al-Azzam SI, Al-Husein BA, Alzoubi F, Masadeh MM, Al-Horani MA. Self-medication with antibiotics in Jordanian population. Int J Occup Med Environ Health. 2007;20(4):373-80.
  10. Richman PB, Garra G, Eskin B, Nashed AH, Cody R. Oral antibiotic use without consulting a physician: a survey of ED patients. Am J Emerg Med. 2001 Jan;19(1):57-60.
  11. Cagri Buke A, Ermertcan S, Hosgor-Limoncu M, Ciceklioglu M, Eren S. Rational antibiotic use and academic staff. Int J Antimicrob Agents. 2003 Jan;21(1):63-6.
  12. Berzanskyte A, Valinteliene R, Haaijer-Ruskamp FM, Gurevicius R, Grigoryan L. Self-medication with antibiotics in Lithuania. Int J Occup Med Environ Health. 2006;19(4):246-53.
  13. Nalini GK. Self Medication Use Among allopathic Medical Doctors in Karnataka, India. British Journal of Medical Practioner. 2010; 3(2):325.
  14. Kayalvizhi S, Senapathi R. International Journal of Enterprise and Innovation Management Studies.2010; 1(3): 40-44.
  15. Sontakke SD , Bajait CS , Pimpalkhute SA, Jaiswal KM, Jaiswal SR. International Journal of Biological & Medical Research. Int J Biol Med Res. 2011; 2(2): 561-564
  16. Figueiras A, Caamano F, Gestal OJJ. Sociodemographic factors related to self-medication in Spain. Eur J Epidemiol. 2000;16:19–26
  17. Hebeeb GE, Gearhart JG. Common patient symptoms: patterns of self-treatment and prevention. J Miss State Med Assoc. 1993; 34:179–181.

‘Well the doctors should check the side-effects shouldn’t they?’ A case of Nitrofurantoin-induced liver injury

Louise Macdougall, Kate Armitage, Richard Thomson and Robert Stirling
Article Citation and PDF Link
BJMP 2011;4(3):a429
Abstract / Summary

This case report discusses an interesting case of drug- induced autoimmune hepatitis following the long term use of nitrofurantoin for recurrent urinary tract infections (UTIs).  Recurrent UTIs are common and the evidence for long term antibiotics are discussed along with the difficulty in deciding whether drugs are implicated as the cause of deranged liver function tests. 

An 80-year old lady was referred to a gastroenterology clinic in August 2009 with deranged liver function tests; alkaline phosphatase 180 IU/L (35-120), alanine transferase 147 IU/L (<40), gamma glutamyl transferase 384 IU/L (<45) and globulins 45 g/L (20-35).  She had initially presented to her general practitioner with symptoms of lethargy and malaise four months previously. She denied any symptoms of obstructive jaundice and there were no risk factors for hepatitis; she seldom consumed alcohol. 

Past medical history included osteoarthritis, migraines and recurrent urinary tract infections; these had been investigated by urology and the patient had undergone cystoscopy and urethral dilatation in September 2003; despite this she continued to experience urinary tract infections and was therefore commenced on prophylactic nitrofurantion by her General Practitioner with approval by the Urologist.  This was initially commenced at 50mg at night.  This regime was continued for approximately three years however during this time she had a further three treatment courses of nitrofurantoin.  In October 2005 her prophylactic dose was therefore increased to 100mg at night. Other medication included lansoprazole 30mg daily, pizotifen 500 micrograms at night, metoprolol 100mg twice daily, simvastatin 10mg at night, senna 15mg at night and furosemide 40mg daily.

On examination there was evidence of palmar erythema and Dupuytren’s contractures but no other stigmata of chronic liver disease.  The liver was tender and palpable 4 cm below the costal margin. A liver ultrasound was performed which was normal.  Liver screen and autoimmune profile are shown in table 1; notably a positive nuclear antibody was found (1 in 1280 IgG) with Hep 2 cell staining showing a homogenous (ANA) pattern at 1:320 IgG, and a nuclear lamin pattern at 1:1280 IgG;.  Due to the positive ANA and raised globulins a suspected diagnosis of nitrofurantoin-induced autoimmune hepatitis was made and a liver biopsy performed.

Test Result
Hepatitis C antibody Negative
Hepatitis B surface antigen Negative
Ferritin 85 ug/L (15-300)
Caeruloplasmin 0.33g/L (0.19-0.71)
Double-stranded DNA antibody 4.44 IU/ml (<10)
Nuclear antibody 1 in 1280 IgG
Mitochondrial antibody Negative
Smooth muscle antibody Negative
Reticulin antibody Negative
ENA- Ro/La/RNP/Sm/Jo-1/Scl-70 Negative
Liver kidney microsomal antibody Negative
Soluble liver antigen antibody Borderline
Liver cytosol antibody Negative

Table 1: liver screen and autoimmune profile

Figure 1a. Liver biopsy showing portal-based interface hepatitis


Figure 1b. Liver biopsy showing portal-based interface hepatitis

Figure 2. Serial LFTs over time

Liver biopsy (figure 1) indicated a moderate hepatitis which was mainly portal based with multifocal interface hepatitis; these morphological appearances were consistent with those of an autoimmune hepatitis. The patient was advised to immediately stop nitrofurantoin and was commenced on prednisolone 30mg which caused a rapid improvement in LFTs (figure 2). This improvement was maintained following a step-wise reduction in steroid dose and prednisolone was discontinued after eight months of treatment. LFTs are currently normal one month following cessation of steroids


This case raises two points of discussion.   The first is whether the long term use of nitrofurantoin as prophylaxis for urinary tract infections is appropriate and based on solid evidence. Nitrofurantoin has many side effects and is well documented to cause liver derangement1,2,3. The patient described in this case had been taking nitrofurantoin for seven years and had received a large cumulative dose, on the basis that this was effective prophylaxis. The continuous, long term use of antibiotics as prophylaxis for urinary tract infections is debatable.  Madersbacher et al4 recommend the use of prophylactic antibiotics  but only after or alongside additional measures including behavioural change, the use of topical oestrogens and the use of alternative therapies; this view is supported by the European Association of Urology5.A Cochrane Review6  in 2004 found that antibiotic use did decrease the number of urinary tract infections compared to placebo but only for the duration of treatment; antibiotics  do not alter the natural history of the underlying condition7. There is no clear evidence for duration of treatment and any trials have only been continued for six or twelve months6.  It has been noted that all antibiotics had a worse adverse event profile compared to placebo. There was no consensus as to which antibiotic should be used although nitrofurantoin has been associated with a greater withdrawal rate6. One study8 comparing nitrofurantoin and trimethoprim revealed no significant difference in recurrence rates or side effects between the two antibiotics, although this involved a lower dose of nitrofurantoin than was used in this case, and a treatment duration of just 6 months. We would argue that due to the side effect profile of nitrofurantoin and the evidence base available, it is not appropriate to continue it for a duration beyond 6 months.

The second discussion point is whether nitrofurantoin was actually the cause for liver derangement in this case. As documented in a recent review article on the diagnosis of drug-induced liver injury, establishing with any certainty whether liver injury is drug induced can be very difficult3.   The key issues are whether there is a temporal relationship between the drug and the onset of liver injury, and whether other causes have been excluded.  In this case the patient had negative viral serology and a normal ferritin and caeruloplasmin but her positive autoantibodies raise the possibility of autoimmune hepatitis.  Guidelines from the American Association for Liver Diseases9 suggests that the diagnosis of autoimmune hepatitis should be made on the following criteria

  • laboratory abnormalities (serum AST or ALT,  and increased serum total IgG or gamma-globulins)
  • positive serological markers including ANA,SMA, anti-LKM1 or anti- LC1
  • histological changes consistent with autoimmune hepatitis i.e. interface hepatitis

This case meets these above criteria for autoimmune hepatitis however the presence of nitrofurantoin does confound the issue. Other case reports10  have reported nitrofurantoin to have caused autoimmune hepatitis based on the relationship between the timing of the drug and the onset of biochemical abnormalities.  Bjornsson et al11 performed a comparative study of patients with autoimmune hepatitis and found drugs, particularly nitrofurantoin and minocycline were causally implicated in 9% of cases.  When they compared the two groups no significant differences were found in the diagnostic parameters of biochemical, serological and histological abnormalities.  In fact the only difference was that no drug-induced cases relapsed on withdrawal of steroids whereas nearly two third of those with non-drug-induced hepatitis relapsed. Bjornsson et al therefore argue in favour of autoimmune immune hepatitis being induced by drugs such as nitrofurantoin; rather than particular drugs simply unmasking sporadic cases based on these management differences. 

The patient in this case so far has shown no signs of relapse following steroid withdrawal.  We believe that this case does represent one of nitrofurantoin-induced autoimmune hepatitis. In view of the above we would urge readers to consider their use of nitrofurantoin for recurrent urinary-tract infection prophylaxis.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
LOUISE MACDOUGALL, Teaching and Research Fellow, North Tyneside General Hospital, UK. KATE ARMITAGE, Teaching and Education Fellow, North Tyneside General Hospital, UK. RICHARD THOMSON, Consultant Gastroenterologist and Clinical Subdean, North Tyneside General Hospital, UK. ROBERT STIRLING, Consultant Histopathologist, North Tyneside General Hospital, UK.
Corresponding Author Details: 
LOUISE MACDOUGALL, Teaching and Research Fellow, Northumbria Healthcare NHS Trust, North Tyneside General Hospital, Rake Lane, North Shields, Tyne and Wear, NE29 8NH
Corresponding Author Email:
  1. Haukekeete ML Hepatoxicity of antibiotics. Act Gastroenterologica Belgica 2003 ; 58 (3): 290-6
  2. Chalasani N, Fontana R. Causes, clinical features and outcomes from a prospectve study of drug-induced liver injury in the United States 2008;135:1924-34
  3. Verma S, Kaplowitz Diagnosis, management and prevention of drug-induced liver injury 2009;58: 1555-1564
  4. Madersbacher S, Thalhammerb F and Marbergera MPathogenesis and management of recurrent urinary tract infection in women Current opinion in Urology 2000; 10:29-33
  5. Grabe M., Bjerkland-Johansen T.E., Botto H. Guidelines on Urological Infections. European Association of Urology 2010.  Available at December 2010)
  6. Albert X, Huertas I, Pereiro II et al. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev 2004(3):CD001209
  7. Madersbacher S, Thalhammerb F and Marbergera MPathogenesis and management of recurrent urinary tract infection in women Current opinion in Urology 2000; 10:29-33
  8. Vahlensick W Jr, Westenfelder M Nitrofurantoin versus trimethoprim for low dose long-term prophlaxis in patients with recurrent urinary tract infections.  A prospective randomized study. International Journal of Urology and Nephrology 1992; 24(1): 3-10
  9. Manns M.P., Czaja A.J., Gorham J.D. et al Diagnosis and Management of Autoimmune Hepatitis. Hepatology 2010; 51(6): 1-31
  10. Koulaouzidis A., Bhat S., Moshos J. et al. Nitrofurantoin-induced lung and hepatotoxicity. Annals of Hepatology 2007; 6(2): 119-121
  11. Bjornsson E., Talwalkar J, Treeprasertsuk S. et al Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology 2010; 51 (6): 2040-8

Diagnosis and Management of Stable COPD

Katerina M Achilleos and Duncan J Powrie
Article Citation and PDF Link
BJMP 2011;4(3):a427

Chronic obstructive pulmonary disease (COPD) is a debilitating condition resulting in significant morbidity and mortality. It is the fifth leading cause of death in the UK 1, estimated to be the third by 2020 2.


  1. COPD is a preventable and treatable disease with some extra-pulmonary effects that may contribute to the severity in individual patients Its pulmonary component is characterised by airflow limitation that is progressive and not fully reversible. There is an abnormal inflammatory response of the lung to noxious gases and particles, most commonly cigarette smoke 3.
  2. Airflow obstruction is defined as post-bronchodilator FEV1/FVC ratio (where FEV1 is the forced expiratory volume in one second and FVC is the forced vital capacity) of less than 0.7 If FEV1 is ≥ 80% predicted, a diagnosis of COPD should only be made in the presence of respiratory symptoms 4.

Incidence/ Prevalence:

Within the UK it is estimated that 3 million people are affected with COPD 4. However, only 900,000 are diagnosed -4An estimated two million people who have COPD remain undiagnosed 4.


90% of cases are smoking related 4, particularly those with >20 pack year smoking histories 5. Environmental and occupational factors can also play a role, including exposure to biomass fuels such as: coal, straw, animal dung, wood and crop residue which are used to cook in some countries and heat poorly ventilated homes COPD occurs in 10-20% of smokers, suggesting there is an element of genetic susceptibility 2-3, 5.


To make a diagnosis of COPD an obstructive deficit must be demonstrated on spirometry in patients over the age of 35 years with risk factors (mainly smoking) and signs and symptoms of the disease 4.

Signs and Symptoms:

  1. Progressive dyspnoea on exertion
  2. Chronic cough
  3. Chronic sputum production
  4. Wheeze
  5. Frequency of exacerbations – particularly during winter months 4
  6. Functional status – bearing in mind gradual progression of disability, effort intolerance and fatigue.
  7. Features suggestive of Cor pulmonale 5:
    1. Peripheral oedema
    2. Elevated jugular venous pressure
    3. Hepatomegaly
    4. Right ventricular heave
    5. Tricuspid regurgitation

Investigations/ Tests to consider:

  1. Post-bronchodilator Spirometry – essential in confirming the diagnosis of COPD.
    1. Demonstrating an obstructive picture.
    2. FEV1 is used to assess the progression and severity of COPD, but correlates poorly with the degree of dyspnoea 3-6. (Table 1)
  1. Pulmonary functions tests – Markers suggesting the presence of emphysema include:
    1. Reduced TLCO and KCO due to a reduced surface area for gaseous exchange 5.
    2. Raised Total lung capacity, residual volume and functional residual capacity due to air trapping 5.
  1. Chest radiograph – Is not required for the diagnosis, but is recommended to exclude other conditions such as interstitial lung disease, pleural effusions or pneumothorax. It may demonstrate features of the condition, such as 3, 5:
    1. Hyperinflated lung fields
    2. Flattened diaphragms
    3. Bullous changes, particularly at the apices
  1. BODE index prognostic indicator – This is grading system shown to be better than FEV1 at predicting the risk of hospitalisation and death in patients with COPD. Patients are scored between 0 and 10, with higher scores having an increased risk of death. It encompasses 3, 5-7: (Table 2)
    1. BMI
    2. Airflow Obstruction – taking into account the FEV1
    3. Dyspnoea – in accordance with the Medical Research Council (MRC) scale 5.
    4. Exercise capacity – measured by the distance walked in 6 minutes. (Table 3)

Table 1. Severity of airflow obstruction 4

Stage Severity post-bronchodilator FEV1 (%) Predicted Comments
1 Mild ≥ 80% Only diagnosed in the presence of symptoms
2 Moderate 50- 79% Managed within the community
3 Severe 30-49% TLCO usually Low
Hospitalization may be needed only with exacerbations
4 Very Severe <30% Or FEV1 <50% with respiratory failure

Table 2. BODE Index 3, 5-8

  1 2 3  
FEV1 Predicted (%) ≥ 65 50- 64 36- 49 ≤ 35
Distance walked in 6 minutes (meters) ≥ 350 250- 349 150- 249 ≤ 149
MRC dyspnoea scale 0-1 2 3 4
BMI ≥ 21 ≤ 21    

Table 3. Medical research council (MRC) Dyspnoea scale 5, 8

1 Dyspnoeic only on strenuous activity
2 Dyspnoeic on walking up a slight incline or when hurrying
3 Walks slower than contemporaries on the flat, or has to stop for breath, or has to stop for breath when walking at own pace
4 Stops for breath on walking 100m or after a few minutes on walking on the flat
5 Breathless on minimal exertion e.g. dressing/ undressing. To breathless to leave the house

Differential Diagnosis:

  1. Asthma – the most important differential diagnosis to consider.
    1. This is steroid and bronchodilator responsive
    2. Indicative of reversible airway obstruction.
    3. It is not associated with smoking.
    4. Patients with asthma may exhibit 3, 9: chronic non-productive cough, variability in breathlessness, diurnal /day-to-day variation, nocturnal wheeze and dyspnoea
    5. However both conditions may coexist creating diagnostic uncertainty.
  1. Alpha1 antitrypsin deficiency is an autosomal dominant condition associated with an increased risk of developing emphysema at an early age 3, 5, 9.
    1. It can occur in non-smokers
    2. Can be asymptomatic and thus under-diagnosed with an estimated 1 in 2000-5000 individuals being affected 5.
    3. The disease is worse in smokers
    4. COPD can develop in patients < 35years of age
    5. It is associated with liver cirrhosis.
    6. All patients with COPD should be screened.
    7. Emphasis should be made to avoid smoking, including passive smoking.
  1. Other conditions to consider include:
    1. Bronchiectasis
    2. Interstitial lung disease
    3. Cardiac failure.


Goals of management include:

  1. Early and accurate diagnosis
  2. Improve symptoms and quality of life
  3. Reduce the number of exacerbations
  4. Improve mortality

Non-pharmacological management:

  1. Smoking cessation – an accurate smoking history should be obtained, including the number of pack years smoked. All current smokers with COPD should be encouraged to stop at every opportunity, and offered smoking cessation advice. Advising the patient alone will help a certain proportion to stop, whilst referral to smoking cessation services has been shown to further increase in quit rates. There are a range of nicotine and other pharmacological therapies available such as Bupropion (Zyban®) and Varenicline (Champix®) 3-4, 7, 8.
  2. Vaccinations – A once off Pneumococcal and annual Influenza vaccine should be offered.
  3. Pulmonary rehabilitation – Should be offered to patients who have had a recent exacerbation requiring hospitalisation and those that have an MRC score of ≥ 3, but are still able to mobilise and thus have the potential for further rehabilitation. It is not suitable for those patients that are immobile or limited in their mobility due to symptoms of unstable angina or a recent cardiac event. Benefits are seen in terms of reduced hospital admission, improved quality of life and exercise tolerance Commitment to the programme should be relayed to the patient, and each programme should be tailored to their individual needs. This usually includes 3-5:
    1. Disease education – which can improve the ability to manage their illness.
    2. Exercise – tailored programmes to prevent de-conditioning and improve functional exercise capacity, dyspnoea and quality of life 4. This includes strength and endurance training of upper limbs and respiratory muscles Benefits may be seen even after 6 months.
    3. Physiotherapy – to teach active cycle breathing techniques or to use positive expiratory pressure masks in patients with excessive sputum production.
    4. Nutritional support – in the form of supplementation or dietician advice in patients with a suboptimal BMI. A low BMI is associated with increased mortality as it is associated with poor exercise capacity, reduced diaphragmatic mass and impaired pulmonary status. Alternatively, weight loss is recommended in patients who are in the obese range.
    5. Psychological – Assessment for support at home, introduction of patients to day centres, assessing for features of depression and anxiety, and aiding in the obtainment of a car disability badges may require referral to occupational therapy and social services.
  1. Travel advice – Patients who are planning air travel and have FEV1 <50%, Sa02 < 93%, or are on long term oxygen therapy (LTOT) should undergo formal assessment -4Patients with bullous disease should be informed that they are at increased risk of pneumothorax during high altitude flights 4.

Pharmacological management:

  1. Bronchodilators – Provide long term benefit in reducing dyspnoea. This is not reflected in improvements in FEV1 as it may not show reversibility 4.
    1. Start with an inhaled SABA (short-acting beta2-agonist) or a SAMA (short-acting muscarinic antagonist) on an as required basis for symptomatic relief. If symptoms remain despite regular SABA therapy (i.e. four times a day), then treatment will need to be stepped up.
    2. If symptoms persist or if the patient is having recurrent exacerbations add in a LABA (long-acting beta2 agonist) or a LAMA (long acting muscarinic antagonist).
    3. If symptoms continue, add in a LAMA if already on a LABA (or vice versa).
    4. If FEV1 <50% add in an inhaled corticosteroid (ICS). This can be offered as a combination inhaler.

Inhaled therapy should offer sufficient bronchodilator response. A spacer can be used for those with poor technique. Nebulisers are reserved for patients who demonstrate respiratory distress despite maximal inhaled therapy, and for those that show an improvement in symptoms or exertional capacity 4.

Diagram 1: Summary of step-by-step management 4

  1. Corticosteroids – A short course of oral steroids may be used during exacerbations. A maintenance course however is not recommended Any patients on long term steroids should be weaned off.
  2. Mucolytic agents – May be considered in patients with a chronic cough who have difficulty expectorating. They should only be continued if symptomatic benefit is evident, otherwise they can be stopped. There is no evidence to show that they reduce the exacerbation frequency.
  3. Theophylline – Should only be offered in people that are unable to use inhaled therapy or after trials of SA and LA bronchodilators 4. The same generic brand should be prescribed as individual brands will have different efficacy. It is usually used as an adjunct to beta2-agonists and muscarinic antagonists. Interactions with macrolides and fluroquinolones and other drugs are also common, and as such the theophylline dose should be reduced if interactions are known. Caution should be taken in prescribing theophylline in the polypharmacy patient 3, 5. Little evidence has been shown to support theophylline usage in COPD (compared to asthma), however it is used for its anti-inflammatory effects As such levels are only performed if toxicity is suspected and should not be adjusted if in the sub-therapeutic range.
  4. Oxygen therapy – Patients should be assessed for long-term oxygen therapy (LTOT) if they exhibit 4:
    1. Severe airflow obstruction
    2. Features of Cor pulmonale
    3. Hypoxaemia (Sa02 ≤ 90%)
    4. Cyanosis
    5. Polycythaemia

Patients with stable COPD who are receiving maximum medical therapy are assessed by measuring arterial blood gases taken on two separate occasions at least 3 weeks apart. To meet the criteria patients must have 4:

  1. A Pa02 < 7.3 kPa when stable, or
  2. A Pa02 >7.3 but < 8.0 kPa when stable and:
    1. Pulmonary hypertension or
    2. Peripheral oedema or
    3. Secondary polycythaemia or
    4. Nocturnal hypoxaemia

LTOT should be used for a minimum of 15L per day, including during sleep 3-4.

Patients who continue to smoke should be made aware of the serious risk of facial injuries due to the highly flammable nature of oxygen.

When to refer:

Referrals for specialist advice or specialist investigations may be appropriate at any stage of the disease.

Other possible reasons for referral 4

§ Diagnostic uncertainty § Suspected severe COPD
§ Onset of Cor pulmonale § Rapid decline in FEV1
§ Assessment for LTOT, home nebulisers or oral corticosteroid therapy § Symptoms that do not correlate to lung function deficit
§ Pulmonary rehabilitation assessment § Frequent infective exacerbations
§ Family history of alpha-1-antitrypsin deficiency § Haemoptysis
§ Onset of symptoms < 40 years § Bullous lung disease
§ Assessment for lung volume reduction surgery/ lung transplantation § Dysfunctional breathing


Patients with stable mild-moderate COPD should be reviewed by their general practitioner at least once a year and those with severe COPD twice yearly.

At each visit 4:

  1. An opportunity should be taken to ask about their current smoking status and the desire to stop.
  2. Assessment of adequate control of symptom: dyspnoea, exercise tolerance and the estimated number of exacerbations per year.
  3. Assessment of inhaler technique.
  4. To assess the effects/side effects of each drug treatment.
  5. The need for pulmonary rehabilitation.

For those patients with very severe airflow obstruction (FEV1 < 30%), the above still remains, in addition to the assessment of 4:

  1. Features of Cor pulmonale
  2. Nutritional status
  3. The need for LTOT
  4. Signs of depression
  5. The need for occupational therapy and social services input
  6. Referral to specialist and their services
  7. Measurements of:
    1. FEV1 and FVC
    2. BMI
    3. MRC dyspnoea scale
    4. Sa02 via pulse oximetry

Those patients requiring long term non-invasive ventilation will be reviewed by a specialist on a regular basis.

Patient Information:


Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
KATERINA M ACHILLEOS, MBBS BSc (Hons), Southend University Hospital, Prittlewell chase, Westcliff-on-sea, SS0 0RY DUNCAN J POWRIE, MB ChB, Consultant Respiratory Physician, Heart and chest clinic, Southend University Hospital, Prittlewell chase, Westcliff-on-sea, SS0 0RY
Corresponding Author Details: 
KATERINA M ACHILLEOS, ST1 Respiratory Medicine, Southend University Hospital, Prittlewell chase, Westcliff-on-sea, SS0 0RY
Corresponding Author Email:

1.      National statistics (2006) Health Statistics Quarterly 29.

2.      European Respiratory society (2003) European White Lung Book.

3.      Global Strategy for Diagnosis, Management, and Prevention of COPD.  Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2010.

4.      Chronic obstructive pulmonary disease. Management of chronic obstructive pulmonary disease in adults in primary and secondary care. NICE guidelines 2010.

5.      Chapman S, Robinson G, Straddling J, West S. Oxford handbook of  respiratory medicine, 2e, Oxford university press, 2009

6.      Celli BR.  Update on the management of COPD. Chest 2008;133:1451-1462.

7.      Celli BR, et al. The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease. NEJM 2004; 350: 1005-12.

8.      Todd DC et al. Approach to chronic obstructive pulmonary disease in primary care. Can Fam Physician 2008; 54:706-11.

9.      Celli BR, MacNee W et al. Standards for the diagnosis and treatment of patients with COPD. A summary of the ATS/ESR position paper.Eur Respir J 2004; 23: 932–946

10.  Barnes PJ. Theophylline for COPD. Thorax 2006; 61: 742-743.

Dabigatran: A look before we leap

Naseer A Masoodi and Bilal Ahmad
Article Citation and PDF Link
BJMP 2011;4(2):a423

Warfarin is the most commonly used oral anticoagulant and has established efficacy for more than 50 years for the prevention of thromboembolic events, but its use is limited by fear of bleeding, drug-drug and drug-food interactions, and routine monitoring of international normalized ratio (INR). In patients with atrial fibrillation (AF), warfarin prevents 64% of strokes in research studies but the real-world effectiveness drops to 35% because of various factors leading to its suboptimal use.1 In October 2010 the United States (US) Food and Drug Administration (FDA) approved Pradaxa capsules (dabigatran etexilate) as the first new agent to prevent stroke and systemic emboli in patients with non-valvular AF. In this article we will discuss some of the evidence for and against the use of dabigatran.

In the RE-LY study2 (Randomized Evaluation of Long-term Anticoagulant Therapy), high-dose dabigatran (150mg twice a day) was found to be superior to warfarin for the prevention of stroke and systemic emboli, required no routine INR monitoring, and had few food and drug interactions. James Freeman and colleagues,3 using data from the RE-LY trial, found that high-dose dabigatran (150mg twice a day) was the most efficacious and cost-effective strategy compared with adjusted-dose warfarin among adults older than 65 with AF.

Dabigatran has been shown to specifically and reversibly inhibit thrombin, the key enzyme in the coagulation cascade. Studies in healthy volunteers4 and in patients undergoing orthopaedic surgery have indicated that dabigatran has a predictable pharmacokinetic/pharmacodynamic profile, allowing for a fixed-dose regimen. Peak plasma concentrations of dabigatran are reached approximately two hours after oral administration in healthy volunteers, with no unexpected accumulation of drug concentrations upon multiple dosing. Excretion is predominantly via the renal route as unchanged drug. Dabigatran is not metabolized by cytochrome P450 isoenzymes. Though use of dabigatran for non-valvular AF and venous thromboembolism (VTE) is gaining practice,5 it remains far from being the standard of care. 

What are the concerns with use of dabigatran? In the RE-LY study the INR control was relatively poor (64% TTR (time in the therapeutic range)) but, probably more importantly, the relationship between events and individual’s INR control was not reported. The use of centre’s time in therapeutic range (cTTR) in the RE-LY study as a surrogate for INR control may not truly reflect TTRs for individual patients. Also in RE-LY study, randomization was stratified for centre and by the centre-based analyses, and the quality of oral anticoagulant services was the basis for the comparisons in this report. A subgroup analysis6 concluded that relative effectiveness of dabigatran versus warfarin was mainly seen at centres with poorer INR control. For example, Swedish centres had good TTR and the relative effectiveness and safety of dabigatran was virtually the same as with warfarin; thus, it is only the price difference that counts. It also highlights how local standards of care affect the benefits of use of new treatment alternatives and hence further limits the generalizability of any ‘overall average’ cost-effectiveness of dabigatran,  raising the question that if an intervention does not do more, why should a payer pay more for it? There are several other factors that could impact on the cost-effectiveness7 of dabigatran such as patient medication adherence, dosing frequency, and the potential effect of new efficient methods of warfarin management improving INR control by patient self-testing.

The other shortcomings of dabigatran include lack of antidotes when patients do bleed and lack of any alert to physicians that patients are not compliant with dabigatran (INR serves this purpose for warfarin). Additionally, in the RE-LY trial, dabigatran was used twice daily thus raising compliance issues compared to once daily warfarin (the rates of discontinuation of dabigatran were higher at 15% and 21% at one and two years, respectively); 11.3% reported dyspepsia (twice the rate of warfarin group); high rate of gastrointestinal bleed compared with warfarin; patients in the dabigatran cohort were at slightly higher risk of myocardial infarction (not sure how it will translate in real world practice); and contraindication of dabigatran in severe renal dysfunction raises some more questions about its use and cost effectiveness. In addition, the RE-LY trial excluded patients who had: contraindications to anticoagulation, severe heart-valve disorder, stroke within 14 days or severe stroke within six months before screening, a condition that increased risk of haemorrhage, creatinine clearance of less than 30ml per minute, active liver disease, and pregnancy.  Clinicians will need to use their judgement to weigh and balance the risk for bleeding with this new agent in a setting of an acute stroke versus the risk of having another ischaemic stroke in someone with AF if not given anti-coagulation therapy immediately. Safety and efficacy at extremes of body weight is not well established with current FDA approved doses of dabigatran either.

In summary dabigatran is a very exciting new agent with significant advantages over warfarin. However, in view of dabigatran’s higher non-adherence rate and greater risk of non-haemorrhagic side effects, patients already taking warfarin with excellent INR control have little to gain by switching to dabigatran.1 Until more studies and post-marketing data become widely available, we should advocate tight INR control for which there is a wealth of evidence for benefits, and promote strategies to improve the management of therapy with warfarin.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None Declared
Details of Authors: 
NASSEER A MASOODI MD, MBA, FACP, CMD, CPE, Associate Professor Clinical Sciences, FSU College of Medicine, Tallahassee, FL-32060, USA; Medical Director Health Services, ACV Inc., Dowling Park, FL-USA BILAL AHMAD MD, Clinical Instructor, Internal Medicine/Geriatrics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA
Corresponding Author Details: 
NASSEER A MASOODI, Associate Professor Clinical Sciences, FSU College of Medicine, Tallahassee, FL-32060, USA


  1. Gage BF. Can we rely on RE-LY? N Engl J Med. 2009; 361:1200-1202.
  2. Connolly SJ, Ezekowitz MD, Yusuf S et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361:1139-1151.
  3. Freeman JV, Zhu RP , Owens DK , Garber AM , Hutton DW , Go AS , Wang PJ , Turakhia MP. Ann Intern Med. 2011 Jan 4;154(1):1-11.
  4. Stangier J, Rathgen K et al. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007 September; 64(3):292-303.
  5. Clayville LR, Anderson KV et al. New options in anticoagulation for the prevention of venous thromboembolism and stroke. P T. 2011 February; 36(2):86-88, 93-99.
  6. Wallentin L, Yusuf S, Ezekowitz MD et al; RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalized ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010; 376:975-83.
  7. Masoodi NA. Compared with warfarin, high-dose dabigatran might be cost-effective for preventing stroke in older patients with nonvalvular AF (Comment). ACP Journal Club. 2011 Jun 21; 154:JC6-12.

An unusual case of Lactic Acidosis

Muhammad Badar Ganaie and Rodney Hughes
Article Citation and PDF Link
BJMP 2011;4(2):a420
Abstract / Summary
Lactic Acidosis, Metabolic Acidosis, Severe Asthma, Salbutamol, Albuterol


Lactic acidosis is an important cause of metabolic acidosis in hospitalised patients. This usually occurs either due to over production or under utilisation of lactate1 . Most cases of lactic acidosis are due to marked tissue hypoperfusion or hypoxia in systemic shock.

Asymptomatic lactic acidosis has been reported previously during acute severe asthma and attributed to fatiguing respiratory muscles, hypoxaemia and liver ischaemia. It has also been linked to β2 agonist therapy in asthma, although lactic acidosis causing increasing dyspnoea in the asthmatic patient has only been recorded rarely.

Case presentation

We present a case of lactic acidosis in a patient with acute severe asthma who did not have any overt signs of sepsis or tissue hypoperfusion.

Mr IL was a 49 years old male who was known to have moderate asthma. He had multiple previous admissions to hospital with exacerbation of asthma but had never required an intensive care admission and had never been intubated. His other comorbidities included atrial fibrillation, ischaemic heart disease and depression.

His usual medications included salbutamol, budesonide and salmeterol inhalers, aspirin, atorvastatin and digoxin. He was a mechanic by trade with no obvious occupational sensitisation. He had no pets at home. He was a smoker with a 20 pack year history. Recent lung function tests showed an FEV1/FVC of 0.68 with a post bronchodilator FEV1 of 4.17 L (95% predicted).

He was admitted with a 1 week history of worsening shortness of breath, dry cough and wheeze. His baseline blood tests including full blood count, C reactive protein, liver and renal function were normal. Chest radiograph was unremarkable. Arterial blood gas showed no evidence of hypoxia or acidosis.He was treated as acute severe asthma with back to back nebulisers, intravenous hydrocortisone and magnesium sulphate resulting in gradual improvement in bronchospasm and peak expiratory flow rate.

Despite optimal treatment, his breathing started to deteriorate. Arterial blood gas at this time showed lactic acidosis with normal oxygenation (Table 1). There was no clinical or biochemical evidence of haemodynamic compromise or sepsis. A presumptive diagnosis of lactic acidosis secondary to salbutamol was made. The nebulisers were withheld and he has transferred to high dependency unit for closer monitoring. The acidosis completely resolved in the following 12 hours on stopping salbutamol and the patient made an uneventful recovery.

Table 1: Serial Arterial Blood Gases (On admission, 4 hours later and on stopping salbutamol)





07:42 *

















pH (7.35-7.45)










pCO2 (4.5-6.0 kPa)










pO2 (11-14 kPa)










HCO3 (22-28 mmol/L)










BE (2- -2)










Lactate (0.5-2 mEq/L)










* Salbutamol witheld


Lactate is a product of anaerobic glucose metabolism and is generated from pyruvate. Normal plasma lactate concentration is 0.5-2 meq/L. Most cases of lactic acidosis are due to marked tissue hypoperfusion or hypoxia in systemic shock2 .

Lactic acidosis can occur in acute severe asthma due to inadequate oxygen delivery to the respiratory muscles to meet an elevated oxygen demand3 or due to fatiguing respiratory muscles4 . A less recognised cause of lactic acidosis is treatment with salbutamol. The mechanism of this complication is poorly understood.

Salbutamol is the most commonly used short acting βagonist. Stimulation of β adrenergic receptors leads to a variety of metabolic effects including increase in glycogenolysis, gluconeogenesis and lipolysis5 thus contributing to lactic acidosis.

Table 2 shows an assortment of previously published case reports and case series of lactic acidosis in the context of acute asthma.

Table 2: Details of etiology and consequences of lactic acidosis in previously published case reports 




Suggested etiology of lactic acidosis

Effect of lactic acidosis

Roncoroni et al, 1976 [6]


Uncertain: increased respiratory muscle production, decreased muscle or liver metabolism

None observed

Appel et al, 1983 [7]


Increased respiratory muscle production, decreased muscle or liver metabolism

8 out of 12 developed respiratory acidosis, 6 required invasive ventilation

Braden et al, 1985 [8]


β2 agonist, steroid and theophylline therapy


O’Connell & Iber, 1990 [9]


Uncertain: intravenous β2 agonist versus severe asthma


Mountain et al, 1990 [10]


Hypoxia and increased respiratory muscle production


Maury et al, 1997 [11]


β2 agonist therapy

Inappropriate intensification of β2 agonist therapy

Prakash and Mehta, 2001 [2]


β2 agonist therapy

Contributed to hypercapneic respiratory failure

Manthous, 2001 [12]


β2 agonist therapy


Stratakos et al, 2002 [3]


β2 agonist therapy


Creagh-Brown and Ball, 2008 [13]


β2 agonist therapy

Patient required invasive ventilation

Veenith and Pearce, 2008 [14]


β2 agonist therapy


Saxena and Marais, 2010 [15]


β2 agonist therapy



In this case, the patient developed lactic acidosis secondary to treatment with salbutamol nebulisers. The acidosis resolved spontaneously without any specific treatment.

Lactic acidosis secondary to β agonist administration may be a common scenario which can be easily misinterpreted and confuse the clinical picture. Acidosis itself results in hyperventilation which could be mistaken for failure to treat the  response. This may in turn lead to inappropriate intensification of treatment.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
MUHAMMAD BADAR GANAIE, LAT Specialist Registrar, Blackpool Victoria Hospital, UK RODNEY HUGHES, Consultant Respiratory Physician, Northern General Hospital, Sheffield, UK
Corresponding Author Details: 
MUHAMMAD BADAR GANAIE, LAT Specialist Registrar, Blackpool Victoria Hospital, UK
Corresponding Author Email:


  1. Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest 2000; 117:260–267
  2. Prakash S, Mehta S: Lactic acidosis in asthma: Report of two cases and review of the literature. Canadian Respiratory Journal. 2002, 9(3):203-208
  3. Stratakos G, Kalomenidis J, Routsi C, Papiris S, Roussos C. Transient lactic acidosis as a side effect of inhaled salbutamol. Chest. 2002 Jul;122(1):385-6
  4. Mountain RD, Heffner JE, Brackett NC Jr, Sahn SA. Acid-base disturbances in acute asthma. Chest. 1990 Sep;98(3):651-5
  5. Haffner CA, Kendall MJ. Metabolic effects of β2 agonists. J Clin Pharm Ther 1992; 17:155–164
  6. Roncoroni AJ, Adrougué HJ, De Obrutsky CW, Marchisio ML, Herrera MR. Metabolic acidosis in status asthmaticus. Respiration. 1976;33(2):85–94
  7. Appel D, Rubenstein R, Schrager K, Williams MH., Jr. Lactic acidosis in severe asthma. Am J Med. 1983 Oct;75(4):580–584 
  8. Braden GL, Johnston SS, Germain MJ, Fitzgibbons JP, Dawson JA. Lactic acidosis associated with the therapy of acute bronchospasm. N Engl J Med. 1985 Oct 3;313(14):890-1
  9. O'Connell MB, Iber C. Continuous intravenous terbutaline infusions for adult patients with status asthmaticus. Ann Allergy. 1990 Feb;64(2 Pt 2):213-8
  10. Mountain RD, Heffner JE, Brackett NC, Jr, Sahn SA. Acid-base disturbances in acute asthma.Chest. 1990 Sep;98(3):651–655
  11. Maury E, Ioos V, Lepecq B, Guidet B, Offenstadt G. A paradoxical effect of bronchodilators.Chest. 1997 Jun;111(6):1766–1767
  12. Manthous CA. Lactic acidosis in status asthmaticus : three cases and review of the literature.Chest. 2001 May;119(5):1599–1602
  13. Creagh-Brown BC, Ball J. An under-recognized complication of treatment of acute severe asthma. Am J Emerg Med. 2008 May;26(4):514.e1-3
  14. Veenith TV, Pearce A. A case of lactic acidosis complicating assessment and management of asthma. Int Arch Med. 2008 Apr 15;1(1):3
  15. R Saxena, G Marais. Salbutamol: beware of the paradox! BMJ Case Reports 2010; doi:10.1136/bcr.01.2010.2665

Tumefactive Multiple sclerosis

Potjana Jitawatanarat, Bhatraphol Tingpej and Paul Deringer
Article Citation and PDF Link
BJMP 2011;4(2):a419
Abstract / Summary
Multiple sclerosis, Tumefactive multiple sclerosis


Tumefactive multiple sclerosis (MS) is a rare variant of MS.  This form of MS can masquerade as neoplasm or infectious etiology.  Understanding of the disease is limited to case report but it is associated with high morbidity and mortality.

Case report

A 44 year old man presented with a 2-month history of progressive right upper extremity weakness, confusion and visual change.  Physical exam revealed weakness, hyperreflexia on the right side and right homonymous hemianopia.  MRI of the brain showed multiple ring-enhancing lesions located in both cerebral hemispheres.  CSF analysis disclosed elevated protein with positive oligoclonal bands and myelin basic protein.  Stains and cultures for bacteria and mycobacteria were negative.  Serologies including HIV, Toxoplasmosis, and Lyme were all negative.  Patient was treated with high-dose IV corticosteroid and clinically improved.  One month later, he presented with increasing confusion, aphasia and progressive weakness.  Repeat MRI of the brain revealed worsening multiple ring-enhancing lesions with surrounding vasogenic edema in most lesions.  High-dose corticosteroid was promptly started.  There was also concern about infection, especially brain abscess; hence, intravenous ceftriaxone, vancomycin, and metronidazole were empirically given.  Due to uncertainty of diagnosis, first brain biopsy at right frontal lobe lesion yielded non-specific gliosis.  Repeat MRI brain showed increasing number of ring-enhancing lesions in both cerebral hemispheres.  As a result, a second brain biopsy was performed, which showed an active demyelinating process consistent with multiple sclerosis.  Patient experienced severe disability and was discharged to long-term facility with slowly tapered schedule of corticosteroid. He was readmitted several times and eventually family decided hospice care.


Multiple sclerosis is diagnosed by demonstrating clinical and/or radiographic evidence of dissemination of disease in time and space1.  Tumefactive MS is a term used when the clinical presentation and/or MRI findings are indistinguishable from a brain tumor2.  Not all case of tumefactive MS are fulminant.  Marburg variant MS is an acute rare variant of MS which has a rapidly progressive course with frequent, severe relapses leading to death or severe disability within weeks to months3.  The tumefactive demyelinating lesions are defined as large (>2 cm.) white matter lesions with little mass-like effect or vasogenic edema, and post-gadolinium magnetic resonance imaging (MRI) typically showing an incomplete ring enhancement2,4.  The clinical and imaging characteristics of these demyelinating lesions may mimic primary and secondary brain tumors, brain abscess, tuberculoma, and other inflammatory disorders e.g. sarcoidosis, primary sjogren’s syndrome5. As a result, tumefactive MS is frequently misdiagnosed. There are some MRI characteristics that are more suggestive of tumefactive demyelinating lesions than of other etiologies.  These include incomplete ring enhancement, mixed T2-weighted iso-and hyperintensity of enhanced regions, absence of a mass effect and absence of cortical involvement2,6.   Differential diagnosis of rapidly progressive neurological deficit with ring-enhancing lesions include brain abscess, primary brain neoplasm or brain metastasis, acute disseminated encephalomyelitis (ADEM) and tumefactive multiple sclerosis.  Careful clinical history, CSF study, serial MRI evaluation and follow-up are usually sufficient to make a diagnosis. Some cases pose considerable diagnostic difficulty owing to clinical and radiographical resemblance to brain tumor, for which biopsy may be warranted.  Pathologically, the lesions are characterized by massive macrophage infiltration, acute axonal injury, and necrosis.  No specific histological features distinguished specimens derived from patients developing classic multiple sclerosis from those who had tumefactive form7.  A limited number of cases of Marburg’s variant MS have been reported in the literature whereby most patients died within a period of weeks to months.  Only two cases survived after one year7,8.  There is no current standard treatment for this condition.  Plasma exchange and Mitoxantrone are reportedly showed some promising options9,10.

Figure A: FLAIR imaging at first presentation showed lesion in both hemisphere. Figure B: FLAIR imaging at one month later showed progression of multiple lesion in both hemisphere. Figure C: T1 Post contrast imaging showed intense ring enhancement pattern in almost all lesions  with mild edema and minimal mass effect. Figure D: Showed lesion view as sagittal section.

Our patient presented somewhat like a stroke with visual field defect and right hemiparesis which is unusual in MS, but MRI and CSF exam yielded a diagnosis of probable MS.  Because of his abrupt clinical deterioration and impressive worsening of his MRI, concern was raised about possibility of infection or neoplasm.  Hence, he received two brain biopsies, the second of which showed active demyelination, confirming the diagnosis of severe tumefactive multiple sclerosis and can be consider as a Marburg variant multiple sclerosis.


Marburg variant multiple sclerosis carries a high morbidity and mortality.  This disease notoriously mimics other conditions leading to delay diagnosis and treatment.  Absence of definitive diagnosis test apart from brain biopsy makes diagnosis, prognosis and treatment decisions difficult. 

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
POTJANA JITAWATANARAT, MD Internal Medicine Resident, Bassett Medical Center, Cooperstown, NY BHATRAPHOL TINGPEJ, MD Internal Medicine Resident, Bassett Medical Center, Cooperstown, NY PAUL DERINGER, MD Neurology Attending, Bassett Medical Center, Cooperstown, NY
Corresponding Author Details: 
POTJANA JITAWATANARAT, MD Internal Medicine resident, Bassett Medical Center, Cooperstown, NY
Corresponding Author Email:


1.  McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of multiple sclerosis. Ann Neurol.2001; 50: 121–7.2.  Dagher AP, Smirniotopoulos J. Tumefactive demyelinating lesions. Neuroradiology. 1996; 38: 560–5.3.  Canellas AR, Gols AR, Izquierdo JR, et al. Idiopathic inflammatory-demyelimating disease of central nervous system. Neuroradiology.2007; 49:393-409.4.  Lucchinetti CF, et al. Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain.2008; 131:1759-75.5.  Sanahuja J, Ordonez-Palau S, Beque R, Brieva L, Boquet D. Primary Sjogren syndrome with tumefactive central nervous system involvement. Am J Neuroradiol.2008 Nov; 29(10):1878-79.6.  Kim DS, et al. Distinguishing tumefactive demyelinating lesions from glioma or central nervous system lymphoma: Added value of unenhanced CT compared with conventional contrast-enhanced MR imaging. Radiology. 2009; 251:467-75.7.  Turatti M, Gajofatto A, Rossi F, et al. Long survival and clinical stability in Marburg variant multiple        sclerosis. Neurol Sci. 2010; 31(6):807-11.8.  Giubilei F, Sarrantonio A, Teisei P, et al. Four-year follow-up of a case of acute multiple sclerosis of the Marburg type. Ital J Neurol Sci.1997; 18:163-166.9.  Jeffery DR, Lefkowitz DS, Crittenden JP. Treatment of Marburg variant multiple sclerosis with mitoxanthrone. J Neuroimaging. 2004; 14:58-6210.  Rodriguez M, Karnes WE, Bartleson JD, Pineda AA Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology.1993; 43 (6):1100-4.

Malignant Hypertension Masquerading as Thrombotic Thrombocytopenic Purpura

Muhammad Zohaib Bawany, Zeeshan Tariq, Thomas Sodeman and Anand Mutgi
Article Citation and PDF Link
BJMP 2011;4(2):a418
Abstract / Summary

Hypertension is common, but with early detection and treatment, it is rare to see malignant hypertension.  Malignant hypertension is a medical emergency with an incidence of 1% in hypertensive patients.  We report on a patient who presented with signs suggestive of Thrombotic Thrombocytopenic Purpura and severe hypertension, which resolved with the treatment of hypertension.

Malignant Hypertension, Thrombotic Thrombocytopenic Purpura


Hypertension is common but, with early detection and treatment, it is rare to see malignant hypertension. We report a patient who presented with signs suggestive of thrombotic thrombocytopenic purpura and severe hypertension, which resolved with the treatment of hypertension.


A 34 year old African American male presented to the emergency department (ED) having experienced nausea, vomiting and diarrhoea for two days.  He denied haematochezia, meleana or sick contacts at home.  He complained of blurred vision without photophobia, headache and mild chest discomfort.  His past medical history was unremarkable.  The patient did not have any significant family history. Smoking history was significant for a pack of cigarettes daily for seven years.  He reported occasional alcohol intake, and denied use of recreational drugs.  On presentation, this patient’s blood pressure was 201/151 mmHg, with a mean of 168 mmHg.  Pulse 103 beats per minute, respirations 20 per minute and temperature 98.4F.  Physical examination was otherwise unremarkable, including absence of focal neurological deficits.

Blood tests showed: Haemoglobin 12.6 g/dl, White cell count 13.9 g/dl, Platelets 67000, Sodium 136, Potassium 3.4, BUN 24, Creatinine 2.56 and LDH 556. Chest x-ray showed cardiomegaly.  A non-contrast computed tomography scan of the brain did not show any sign of stroke (haemorrhage).  Urinalysis was positive for proteins 4+, a large amount of blood, 0-2 white blood cells/high power field (HPF) and 0-2 red blood cells/HPF.

Figure 1

The patient’s initial treatment whilst in the ER consisted of a Labetalol drip.  His mean arterial pressure decreased to approximately 115 mmHg during the first hour, and his chest pain and headache improved with the control of elevated mean arterial pressure.  Furthermore, over the next 24 - 48 hours, the patient’s blood pressure was brought down to 138/86 mmHg and his blurred vision improved significantly.  Subsequently, intravenous medications were switched to an oral regimen.  Blood peripheral smear from the day of admission was significant for the schistocytes (Figure 1) suggesting ongoing haemolysis.  Renal ultrasound was unremarkable.  His cardiac ultrasound revealed an enlarged left ventricle, however no valvular abnormality was seen.  Serum calcium and thyroid stimulating hormone levels were normal, as were urine catecholamines and vanillylmandelic acid level.  On two week follow up in the outpatient clinic, the patient’s platelet count and creatinine had returned back to baseline and peripheral smear did not reveal any schistocytes as the blood pressure came under better control. [Table 1]

Variable On day 1 Day 3 Day 5 Day 6 Follow-up in 2 weeks
Haemoglobin 12.6 9.3 9.3 10.3 11.4
Platelets 67, 000 65,000 90,000 125,000 204,000
Retic. count 3.9 -- -- 4.3 --
Creatinine 3.06 2.86 2.69 2.4 2.3
BUN 29 27 28 27 27
LDH 556 370 333 240 --
Troponin 0.10 0.08 0.06 0.05 --
Peripheral Smear Schistocytes -- -- -- No Schistocytes

Table 1


Malignant hypertension is a medical emergency with an incidence of 1% in hypertensive patients1and is more common in the African American population2.  Depending on the clinical presentation, it must be differentiated from thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), glomerulonephritis and vasculitis.

Suspicion for TTP was initially high in this patient because of haemolysis, thrombocytopaenia, central nervous system (CNS) manifestations and renal insufficiency.  However, TTP did not explain the presence of elevated blood pressure3,4nor the improvement in symptoms and signs with the management of this, which clearly supports our diagnosis.  Rapidly progressive glomerulonephritis did not explain the CNS symptoms, and a normal prothrombin time and activated partial thromboplastin time ruled against disseminated intravascular coagulation5.  The patient did not have a history of preceding diarrhoea6, which could possibly direct towards haemolytic uraemic syndrome (HUS)4.  There was no history of prosthetic valves, nor clinical evidence of vasculitis. The patient’s symptoms of severe hypertension, haemolysis, thrombocytopaenia and renal failure were consistent with malignant hypertension, and treating the hypertension7gradually resolved the thrombocytopaenia, haemolysis and renal failure8


This case report highlights that malignant hypertension is a medical emergency which can present with features resembling a wide variety of diseases, including TTP and HUS.  Using appropriate management to control the elevation in blood pressure can help reveal the underlying diagnosis.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
Muhammad Zohaib Bawany MD, Zeeshan Tariq MD, Thomas Sodeman MD FACP, Anand Mutgi MD FACP, University of Toledo Medical Center, Toledo, OH
Corresponding Author Details: 
Muhammad Zohaib Bawany, University of Toledo Medical Center, 3000 Arlington Ave Mail stop 1150, Toledo OH, USA 43614
Corresponding Author Email:


1.    Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol 1998;9:133-42.2.    Khanna A, McCullough PA. Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal failure. Rev Cardiovasc Med 2003;4:255-9.3.    Patel A, Patel H. Thrombotic thrombocytopenic purpura: the masquerader. South Med J 2009;102:504-9.4.    Shibagaki Y, Fujita T. Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate one from the other? Hypertens Res 2005;28:89-95.5.    Kitchens CS. Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC). Hematology Am Soc Hematol Educ Program 2009:240-6.6.    Hertig A, Ridel C, Rondeau E. [Hemolytic uremic syndrome in adults]. Nephrol Ther 2010;6:258-71.7.    Varon J, Marik PE. The diagnosis and management of hypertensive crises. Chest 2000;118:214-27.8.    Gassanov N, Pollok M, Er F. Acute renal failure associated with malignant hypertension. Dtsch Med Wochenschr 2009;134:2224-7.

MRSA infection of a Primary TKA following an infected IV cannula site complicated by Stevens-Johnson Syndrome- A Case Report

SKM Annamalai, SS Raju and VG Langkamer
Article Citation and PDF Link
BJMP 2011;4(2):a415
Abstract / Summary

We present here a 63 year old lady who had a primary total knee arthroplasty( TKA) for  osteoarthritis of knee. She developed methicillin resistant staphylococcus aureus( MRSA )infection of the primary  prosthesis following an intravenous(IV) cannula site infection with MRSA bacteraemia. This was complicated by Stevens-Johnson syndrome following vancomycin therapy for the infection, which was confirmed by clinical features including typical skin rashes and skin biopsy. She was treated with alternative antibiotics and was referred to a specialist orthopaedic unit where she had a two- stage revision.

In retrospect, the infection could have been avoided if the IV cannula was not left in for so long. She also unfortunately had an adverse reaction to the vancomycin which complicated the situation, making management difficult. A team consisting of orthopaedic surgeons, microbiologists, dermatologists and physiotherapists was essential for successful management of this difficult and complicated  situation.

MRSA (methicillin resistant staphylococcus aureus), IV( intravenous), TKA (total knee arthroplasty), DM( diabetes mellitus)


Infection of a prosthetic total knee joint is a serious complication1 and should be diagnosed promptly2 and treated aggressively. We present an interesting case of MRSA infection of a primary total knee replacement following  an IV cannula infection leading to bacteremia and subsequent infection of  the knee prosthesis, complicated by stevens- Johnson syndrome .

There were many challenging issue which are outlined including diagnosis and management.

Case Report

A 63-year- old lady had an elective total knee arthroplasty for severe osteoarthritis of the knee. She had a background history of well-controlled type 2 diabetes mellitus and was on warfarin for a previous pulmanory embolism. As per the hospital protocol her warfarin was stopped before surgery until her INR was <1.5 and she was heparinised with a view of

warfarinizing after the surgery. She had an uneventful knee arthoplasty, but unfortunately one of her IV cannula site became cellulitic. She was empirically started on oral flucloxacillin after taking blood cultures and sending the cannula tip for microscopic culture and sensitivity (which is routinely done has hospital protocol for infected cannula sites).

Surprisingly the tip grew MRSA and also had MRSA bacteraemia. She became systemically unwell and septic, and was treated aggressively with parentral vancomycin for MRSA bacteraemia. She had a transeosphageal echocardiogram to rule out cardiac vegetation. She gradually improved but developed typical papular rashes over her palm, dorsum of hand, extensor surface of arm and forearm and trunk and buccal mucosa (Fig 1 and 2) .

Fig 1: Rash over the dorsum hands

Fig 2: Rash over the extensor aspects of forearm

She had a severe allergic reaction to vancomycin and the skin biopsy of the lesion confirmed that she had developed Stevens-Johnson syndrome. An alternative antibiotic was started following discussion with the specialist bone infection unit. She gradually improved over the next few weeks without any problem in her prosthetic replaced knee. At about 6 weeks post- operatively she developed severe pain and hot swelling of her replaced knee with decrease range of motion. Her inflammatory markers were markedly raised and the knee aspirate confirmed MRSA infection of the total knee replacement. She was referred to a specialist bone infection unit due to the complexity of the case, where she successfully underwent two- stage revision.


Infection of  a Knee replacement is a serious complication that requires significant hospital-based recourse for successful management3. The rate of infection of a primary knee replacement varies from 0.5- 12%1. Rheumatoid arthritis , previous surgery , diabetes mellitus are all associated with an increased risk of infection 4. Although there is no absolute diagnostic test for peri-prosthetic infection2 , a high index of clinical suspicion is essential. There has been a case report on MRSA cervical epidural abscess following IV cannulation 5, but to the best of our knowledge there has been no previous report of MRSA- infected knee arthroplasty following complications of IV cannulation. Stevens-Johnson syndrome involves rare but severe cutaneous adverse reactions related to a variety of medications including antibiotics6. Parenteral vancomycin is the first line treatment for MRSA bacteraemia. It is recognised that vancomycin is indicated in inducing Stevens -Johnson syndrome, mortalitiy being 30-100%7. It is vital that Stevens- Johnson syndrome is recognised early so that offending agents are stopped and supportive treatment commenced. Early dermatological consultation, skin biopsy and direct immunofluorescence7 are essential to confirm diagnosis  so that effective treatment can be instituted.The diagnosis and management of this serious complication is complex and requires considerable recourse allocation by the patient, the hospital, the infectious disease specialist, and the orthopaedic surgeon1,5.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
SKM Annamalai, MBBS MRCS, Orthopaedic Registrar, Peterborough City Hospital, UK SS Raju, F2 Trainee, Western General Hospital Western Super Mare, UK VG Langkamer, Consultant Orthopaedic Surgeon, Western General Hospital Weston Super Mare, UK
Corresponding Author Details: 
SKM Annamalai, MBBS MRCS, 2, Boulton Court, Oadby, Leicester, LE2 4XA
Corresponding Author Email:
  1. Blom AW, Brown J, Taylor AH, Pattison G, Whitehouse S, Bannister GC. Infection after total knee arthroplasty. J Bone Joint surgery Br 2004 Jul;86(5):688-91.
  2. Elie Ghanem et al. Cell Count and Differential of the Aspirated fluid in the Diagnosis of the Infection at the Site of Total Knee Arthroplasty.  J Bone Joint Surg Am. 2008;09: 1637-43.
  3. Buechel F F, Femino FP, D’Alessio J. Primary Exchange Revision Arthroplasty for Infected Total Knee Arthroplasty: A Long-Term study The Americal journal Of Orthopaedics .2004;April.190-98.
  4. Bengtson S, Knutson K. The infected Knee arthoplasty. A 6 year follow-up of 357 cases. Acta Orthop Scand 1991 Aug;62(4):310-11.
  5. Burgess CM, Wolverson AS, Dale MT.Cervical epidural abscess: a rare complication of intravenous cannulation. Anaesthesia. 2005 Jun;60(6):605-8.
  6. Mockenhaupt-Maja et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The Euro SCAR- study: J-Invest- Dermatol, Jan2008, vol128, no. 1, p 35-44.
  7. Jones DH, Todd M, Craig TJ. Early diagnosis is key in vancomycin-induced linear IgA bullous dermatosis and stevens- Johnson syndrome. J Am Osteopath Assoc. 2004 Apr;10494):157-63

Interview with Prof. Robert Moots

Article Citation and PDF Link
BJMP 2011;4(2):a414


Robert Moots is Professor of Rheumatology at the University of Liverpool and Director for Research and Development at the University Hospital, Aintree. He is also a Consultant Rheumatologist at the hospital.

He graduated from St Mary’s Hospital, London University in 1985 and also worked at Harvard Medical School. He became a Consultant Rheumatologist at University Hospital Aintree in 1997 and the youngest full-time professor of Rheumatology and Head of Department in 2003.

Professor Moots has published extensively in rheumatology, winning the prestigious Michael Mason prize for rheumatology research. He advises the UK Department of Health and NICE. His research interests are inflammatory rheumatic diseases, in particular innate cellular immunity in rheumatoid arthritis, immunotherapy, new therapeutic targets and clinical trials.

How long have you been working in your speciality?

I’ve been working as a consultant in rheumatology since1997, when I returned to the UK from the USA. Of course I was a trainee in rheumatology for a few years before then.

Which aspect of your work do you find most satisfying?

Its hard to single out any one thing. The great fun of being Professor is that no two days are the same. My job varies so much from looking after patients, to teaching, running research and also communicating and sharing research findings with other clinicians and scientists throughout the world – giving me the opportunity to visit countries, where I would not normally have visited.

What achievements are you most proud of in your medical career?

Clinically, I often deal with rare rheumatic diseases, or situations where normal treatments have failed and other doctors have said there is “no more that can be done”. Each patient that I see in this situation, who then goes on to recover and have a normal happy life, gives me a great satisfaction. Academically, building up a successful research team of talented individuals in Liverpool, the first academic rheumatology unit in that city, has been a great privilege.

Which part of your job do you enjoy the least?

Trying to balance the demands of patient care with the many other calls on my time can be rather wearing. But nothing is worse than the ever expanding administration tasks and bureaucracy!

What are your views about the current status of medical training in your country and what do you think needs to change?

When I visit other countries to lecture, I always try to see how medicine runs there. I attend clinics and hospitals, see patients and learn how practice compares to the UK. I am pleased to note that the standard in the UK remains amongst the highest of all countries.

How would you encourage more medical students into entering your speciality?

Its hard to image why students and doctors could consider any specialty other than Rheumatology! Rheumatology provides the opportunity to see patients of all ages, develop a close rapport with patients as the diseases tend to be chronic and prevalent, perform cutting edge research to understand pathophysiological process underlying the diseases and access drugs that can make a revolution to lives with great outcomes.

What qualities do you think a good trainee should possess?

Be keen to learn, open, honest and bright. I also like trainees to challenge accepted wisdom – a considered critical approach is needed to move things forward and to keep us on our toes.

What is the most important advice you could offer to a new trainee?

Don’t accept non-evidence based dogma. Don’t learn bad habits. Be critical and try to improve things. Try to spend some time away from your unit and ideally out of your country – seeing how medicine works in other environments to get life and work in a better perspective.

What qualities do you think a good trainer should possess?

Good trainers should be excellent clinicians, inspirational leaders and listeners with patience. If you know someone like this, you should really treasure them!

Do you think doctors are over-regulated compared with other professions?

No – but I fear that we are getting there in the UK.

Is there any aspect of current health policies in your country that are de-professionalising doctors? If yes what shouldbe done to counter this trend?

With a recent change in government in the UK and major changes to the Health Service planned, it’s a little too early to tell. We have to be vigilant though.

Which scientific paper/publication has influenced you the most?

For much of my working life, I was focused on the T cell as the major driver for diseases such as rheumatoid arthritis. The paper that changed that was: Edwards SW, Hallett MB. Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid arthritis. Immunol Today.1997 Jul;18(7):320-4. This crucial paper from Steve Edwards, the world leader in neutrophil biology opened my eyes to a whole new field of work. I didn’t know at the time that I would eventually have the privilege of working with Steve.

What single area of medical research in your specialty should be given priority?

That’s an easy one – it should be whatever my group are working on at the time.(I just wish that were the case!)

What is the most challenging area in your specialty that needs further development?

Many rheumatic diseases such as rheumatoid arthritis can be treated extremely successfully (with patients enjoying a full remission) if they can access the right drugs at the right time. There is still much variability in time to diagnosis and in provision of appropriate medications – the challenge is to ensure that best practice can be rolled out more effectively.

Which changes would substantially improve the quality of healthcare in your country?

There needs to be a greater understanding of the importance of rheumatic diseases in the UK. These conditions are prevalent, may cause significant morbidity (and indeed mortality), cost the nation considerably in reduced productivity and in disability payments – yet many of these conditions can be treated most effectively.

Do you think doctors can make a valuable contribution to healthcare management?  If so how?

Its crucial that doctors are fully engaged in management. We are in the best position to be advocates for our patients but cannot do this effectively without understanding the health care system and take the lead in ensuring this works for the best.

How has the political environment affected your work?

The consequences of the recent change in Government in the UK are likely to be considerable for the National Health Service. This will involve major changes to the work of staff at all levels. It is too early to know the full extent of this – but we all wait with trepidation

What are your interests outside of work?

With so much to do, its hard to find the time for much else apart from relaxing with my family. I travel a lot and especially enjoy taking my children with me. My 10 year old has heard me lecture so much that I suspect she can give my talk for me (and do it better). She has also taken to asking questions at the end of my lecture, which always scares the chairperson of the meeting!

If you were not a doctor, what would you do?

I’m not sure that I would be fit for anything else!

An Unusual Cause of Chronic Dyspnoea

Fadi Seif and Lamia H. Ibrahim
Article Citation and PDF Link
BJMP 2011;4(1):a408

A 73 year old lady presented for assessment of her recurrent right sided pleural effusion. She had a history of gallstones and underwent open cholecystectomy.  One month after surgery the patient had recurrent pleural effusion requiring thoracocentesis on a monthly basis. On the chest x-ray, the pleural effusion was seen exclusively on the right side occupying the whole right hemithorax. 

The pleural fluid was transudative on multiple occasions and there was no evidence of malignant cells. Her echocardiography revealed preserved cardiac function. An abdominal ultrasound showed findings of cirrhosis and splenomegaly consistent with portal hypertension.

Image 1

Computerised tomography (CT) of the chest and abdomen revealed a large right-sided pleural effusion and minimal ascites (Image 1). An ultrasound guided paracentesis was performed with difficulty and only 17cc of fluid.was obtained.  The abdominal fluid showed similar consistency as the pleural fluid. The blood workup at the same time was unremarkable.

Image 2

Intra-peritoneal administration of 99mTc-sulphur colloid was attempted but failed in the absence of ascites. Computed tomography with three dimensional reconstruction at the diaphragmatic level revealed a defect in the posterior aspect of the right hemidiaphragm (Image 2 black arrow) and also revealed irregular contours of the liver, an indirect sign of diaphragmatic defect (Image 2 white arrow).

The patient declined any surgical intervention at that point including the option of pleurodesis. She was started on diuretics and a low salt diet with significant improvement. 


Pleural effusion due to hepatic cirrhosis and ascites is well known, but hepatic hydrothorax in the absence of ascites is a rare complication. We report a case of liver cirrhosis with a large and recurring right sided pleural effusion that had an apparent abdominal source in the absence of ascites. We review the characteristics and treatment for hepatic hydrothorax in the absence of ascites.

Hepatic hydrothorax is defined as the presence of significant pleural effusion in a cirrhotic patient without primary pulmonary or cardiac disease1. Postulated mechanisms for the development of pleural effusions in patients with hepatic cirrhosis include: hypoalbuminemia and decreased oncotic pressure leakage of the plasma from the hypertensive azygos vein, lymphatic leak from the thoracic duct, passage of ascitic fluid to the pleural space by way of lymphatic channels in the diaphragm, and transfer of peritoneal fluid directly via diaphragmatic defects2.

The usual unilaterality of hepatic hydrothorax could be attributed to a congenital factor, but not to physiologic mechanisms3. The most likely explanation appears to be that ascitic fluid passes through congenital or acquired fenestrations in the diaphragm directly into the pleural space2. The description of hepatic hydrothorax in the absence of ascites is very rare1. The flow of the ascitic fluid into the pleural space equaled the rate of ascites production in patients with this entity3.

The composition of pleural fluid from hepatic hydrothorax is similar to that of ascitic fluid. Pleural effusions associated with portal hypertension are always transudative1. Nuclear scans can be performed to establish the diagnosis of hepatic hydrothorax with fairly high accuracy. Intra-peritoneal administration of 99mTc-human serum albumin or 99mTc-sulphur colloid can be used to demonstrate the communication between the peritoneal and pleural space. Recent advances in radiological imaging have enabled investigators to examine in detail the diaphragmatic defects responsible for the development of hepatic hydrothorax1.

The management is challenging and frequently associated with poor outcomes in most cases. Dietary restriction of sodium intake and the addition of diuretics is the initial approach. Thoracocentesis can be performed in patients with dyspnoea due to hepatic hydrothorax for immediate relief of symptoms. When thoracocentesis is required too frequently in patients on maximal sodium restriction and optimal diuretics, alternative treatment options must be considered1, 3.

Over the last few years, new insights into the pathogenesis of this entity have lead to improved treatment modalities such as portosystemic shunts (TIPS) and video-assisted thoracoscopy (VATS) for closure of diaphragmatic defects. Both, though temporary  measures, are perhaps the best available bridging to liver transplantation in selected patients with refractory hepatic hydrothorax2, 3.

Acknowledgements / Conflicts / Author Details
Competing Interests: 
None declared
Details of Authors: 
Fadi Seif, M.D. Fellow, Pulmonary Critical Care and Sleep Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine Lamia H. Ibrahim, M.D., FCCP, Director of Asthma Center, Director of Medical Student and Resident Pulmonary Education, Division of Pulmonary, Critical Care and Sleep, University Hospitals Case Medical Center. Assistant Professor of Medicine, Case Western Reserve University School of Medicine, Louis Stokes Cleveland VAMC
Corresponding Author Details: 
Fadi Seif, M.D. Fellow, Pulmonary Critical Care and Sleep Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine
Corresponding Author Email:
  1. Kiafar C, Gilani N. Hepatic hydrothorax: Current concepts of pathophysiology and treatment options. Annals of Hepatology 2008; 7(4): 313-320
  2. Mentese BB, Kayhan B,  Görgül A, et al. Hepatic Hydrothorax in the Absence of Ascites. Report of Two Cases and Review of the Mechanism. Digestive Diseases and Sciences 1997; 42(4): 781-788
  3. Gur C,  Ilan Y, Shibolet O. Hepatic hydrothorax – pathophysiology, diagnosis and treatment – review of the literature. Liver International 2004; 24(4): 281-284

Syndicate content