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When SC was admitted to AE, she was diagnosed with moderate AEBA secondary to community-acquired pneumonia. Nebulized Combivent which is a combination product of 0.5mg ipratropium bromide and 2.5mg salbutamol was administered 2 hourly initially to manage her acute asthma attack.1 Clinical trials revealed that a single dose of Combivent was recommended for the treatment of acute asthma as 0.5g nebulized ipratropium bromide significantly enhanced the bronchodilator response of 2.5mg salbutamol (p<0.05).1 According to the British Guideline on the Management of Asthma, addition of ipratropium bromide to salbutamol significantly provokes greater bronchodilating effects over salbutamol alone, resulting in faster recovery and shorter hospital admission period.2 Rodrigo GJ et al. presented that the use of Combivent decreased the risk of hospitalization by 49%.3 Besides, substantial evidence showed that patients on combined treatment produced a 21% larger improvement in PEFR as compared to patients on salbutamol alone.4 According to the Clinical Practice Guideline for Management of Adult Asthma, patients with acute asthma should undergo immediate treatment with inhaled salbutamol in combination with ipratropium bromide via oxygen-driven nebulizer.5 Therefore, the use of Combivent in treating acute asthma exacerbation for SC was advocated and justified by the current evidences.
Corticosteroids like hydrocortisone, prednisolone and budesonide were given to manage SC's asthma exacerbation. Recent evidences have suggested that corticosteroids significantly decreased mortality, frequency of relapses requiring additional care and hospitalization.6 Systemic corticosteroid was recommended to be given within the first hour of treatment for acute asthma in emergency setting, as recently supported by a prospective study revealed that the earlier the systemic corticosteroid administered, the lower the need for hospitalization.2,7 A Cochrane review in 2008 demonstrated that a short course of corticosteroids significantly diminished the requirement for short-acting Î²2-agonist therapy without a marked increase in adverse effects.6
Firstly, IV hydrocortisone 200mg was commenced immediately when SC was admitted to A&E with presenting complaints of marked shortness of breath. Then, prednisolone tablet 30mg once daily was prescribed during hospitalization. Based on the Clinical Practice Guideline for Management of Adult Asthma, prednisolone tablet 30-60mg should be given immediately to patients with acute asthma.5 However, if patients unable to tolerate orally, IV hydrocortisone 200mg should then be administered instantaneously.5 A 2008 Cochrane Review reported that low dose corticosteroids (â‰¤ 80mg/day prednisolone or â‰¤400mg/day intravenous hydrocortisone) were adequate in the early treatment of acute asthma.8 In addition, higher doses of corticosteroids did not show any additional therapeutic benefits.2 Manser and colleagues presented that no significant difference was observed between low and high doses of corticosteroids in term of adverse effects and respiratory failure rate.8 On the other hand, a recent review evaluated the effectiveness of oral versus intravenous corticosteroids demonstrated that both oral and intravenous routes exhibited similar efficacy in treating acute asthma exacerbation.7 However, the intravenous route is preferred at the beginning for patients who had difficulty in swallowing due to marked breathlessness.7 Hence, the use of both corticosteroids in managing SC's asthma attack was appropriate based on the recent guideline and reviews.
In addition, SC was prescribed with MDI budesonide 200Î¼g twice daily to reduce her airway inflammation. The use of inhaled budesonide in the management of asthma was strongly supported by a 2008 Cochrane review.9 Data from the review showed that budesonide significantly improved FEV1 (force expiratory volume in one second), PEFR in the morning and asthma exacerbation as compared to placebo.9 Current meta-analysis concluded that most of the therapeutic advantage of inhaled budesonide was obtained with doses of 400Î¼g/day and the maximum achievable benefits ensued with doses of 1000Î¼g/day.10 Chanez et al. proposed that both standard initial doses (400Î¼g/day) and high initial dose (1600 Î¼g/day) of budesonide had equivalent efficacy in improving pulmonary function and controlling mild-to-moderate asthma symptoms.11 Since SC has been using MDI budesonide for the past 2 years and she claimed that budesonide works well on her asthma, MDI budesonide should be continued indefinitely during hospitalization and after discharge.
When SC was diagnosed with CAP on day 1, IV cefuroxime 1.5g was given immediately and 750mg three times daily. Cefuroxime, a second generation cephalosporin is an empirical antibiotic therapy for the treatment of CAP.12 It has established antibacterial action against penicillin-resistant Streptococcus pneumonia.12 Although amoxicillin is the first line therapy for CAP, IV cefuroxime is recommended for use in patients intolerant of penicillins.13 A prospective study in Denmark presented that no significant difference was noticed between amoxicillin-treated group and cefuroxime-treated group in terms of clinical treatment failure.14 Yael Dinur-Schejter and colleagues reported that the clinical outcome of treatment with amoxicillin was comparable to treatment with cefuroxime.15 There was no statistically significant difference in hospitalization period, complications and duration of intravenous administration between both treatment groups.15 Since BK has penicillin allergy, the use of cefuroxime as the antibiotic for treating her CAP was strongly recommended, as presented in the evidences above.
Besides that, azithromycin 500mg tablet was given immediately and once daily to SC for treating her CAP. Azithromycin is a macrolide antibiotic with both anti-inflammatory and anti-bacterial properties.16 An open-label study in Japan demonstrated that azithromycin was well tolerated and had a good clinical outcome in the treatment of CAP with macrolide-resistant Streptococcus pneumonia.16 Sanchez et al. presented that patients treated with azithromycin significantly reduced both hospitalization period (p<0.01) and the mortality rate (p<0.05) as compared to patients treated with clarithromycin.17 A current study compared the effectiveness of azithromycin versus erythromycin therapy revealed that azithromycin was as well tolerated and as effective as erythromycin in treating CAP.18 Furthermore, the study found out that three day therapy with azithromycin was more cost-effective and more convenient than erythromycin.18 Since the level of evidence of supporting the use of azithromycin was strong, azithromycin was recommended as the first treatment choice for SC.
In conclusion, on the basis of much of the evidence as shown above, the use of nebulized Combivent, IV hydrocostisone, oral prednisolone and MDI budesonide in managing SC's moderate AEBA were strongly advocated. Furthermore, the evidences lead to the conclusion that cefuroxime and azithromycin were recommended for the treatment of CAP.
Critical analysis of management of patient
When BK was admitted to A&E department, subcutaneous Fondaparinux 2.5mg was administered immediately and given once daily during her hospitalization period. Fondaparinux is a synthetic pentasaccharide which selectively binds to antithrombim III to induce the neutralization of factor Xa.1 The use of subcutaneous Fondaparinux 2.5mg daily as a thromboprophylaxis for this patient was strongly recommended by the National Institute for Health and Clinical Excellence (NICE) guideline and Scottish Intercollegiate Guidelines Network (SIGN) guideline. According to the NICE guideline, Fondaparinux is recommended for the initial treatment of NSTEMI or unstable angina along with standard anti-platelet therapy for patients with low bleeding risk.2 SIGN guideline suggested that fondaparinux should be given immediately when there is an ischaemic electrocardiographic changes or increase in troponin levels in acute coronary syndrome (ACS) patients.3 In addition, it should be continued up to a maximum of 8 days or until hospital discharged.3 These recommendations are mainly due to the OASIS-5 (Fifth Organization to Assess Strategies in Acute Ischemic Syndromes) trial outcome.
In OASIS-5 trial, result showed that fondaparinux (2.5mg/day subcutaneously) had comparable clinical efficacy to enoxaparin (1mg/kg twice daily subcutaneously) in the treatment of NSTEMI but with lower major bleeding risk.4 The primary outcomes of myocardial infarction, refractory ischaemia or death at 9 days for both fondaparinux (5.8%) and enoxaparin (5.7%) were similar.1 Besides, the major bleeding risk at 9 days was significantly declined by fondaparinux (2.2%) when compared with enoxaparin (4.1%).4 Furthermore, Fondaparinux significantly decreased the risk of death at 30 days (2.9% for fondaparinux versus 3.5% for enoxaparin; p<0.05).1 Hence, the use of fondaparinux was advocated since BK was diagnosed with NSTEMI.
Besides that, aspirin and clopidogrel tablets were given to BK in both emergency setting and ward setting. Aspirin and clopidogrel are anti-platelet drugs which prevent thrombus formation by reducing platelet aggregation.5 The use of aspirin plus clopidogrel is recommended by the SIGN guideline for the treatment of NSTEMI.3 Based on the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study, aspirin (300mg stat and 75-150mg daily) in combination with clopidogrel (300mg stat and 75mg daily) was significantly more effective than aspirin alone.5 Combined therapy showed a statistically significant risk reduction rate of 20% in the combined end point of myocardial infarction (MI), cardiovascular death or stroke in high risk NSTEMI patients compared with aspirin alone (9.3% vs 11.4%).6 A Cochrane review in 2001 revealed that combined aspirin and clopidogrel therapy was associated with a fall in cardiovascular event risks but an increase in the major bleeding risk.7 Moreover, most benefits derived from clopidogrel was occured during the first 3 months but no evidence of benefits beyond 12 months has been found.5 On the basis of much of the evidence presented above, combining aspirin with clopidogrel was recommended for this patient as the benefits of combined therapy outweigh the risks.
Metoprolol, a cardioselective beta-blocker was given 50mg twice daily to reduce cardiovascular event and for secondary prevention.8 A randomized-controlled trial revealed that patients treated with beta-blocker had a higher risk of getting cardiogenic shock.9 However, evidence from SIGN guideline demonstrated that long-term treatment with a beta-blocker decreased the total mortality and risk of sudden death in post MI patients by 23% and 32% respectively.3 A study of patients with post MI aged 65 years or older showed that the rate of in-hospital mortality was significantly lower in patients on beta-blocker than those untreated.9 Howard PA et al. reported that initiation of beta-blocker treatment after MI reduced the total mortality, non-fatal MI and sudden death by 20-30% regardless of age or sex.10 Since the greatest benefits of beta-blocker therapy was seen in the patients who are at high risk (left ventricular dysfunction, larger anterior infarction and advanced age), the use of metoprolol for BK was recommended.8,10
In addition, atorvastatin tablet 40mg was taken at night by BK for controlling her blood cholesterol level and for secondary prevention.11 Findings from recent meta-analysis showed that statin therapy significantly decreased the risk of cardiovascular disease mortality (RR [Relative Risk] 0.75, 95% CI 0.68 to 0.83) and coronary heart disease mortality (RR 0.72, 95% CI 0.64 to 0.80).11 In addition, substantial evidences suggested that the risk of primary and secondary cardiovascular events was statistically reduced with the use of statin.12 According to the Acute Coronary Syndrome Guideline, atorvastatin 40-80mg once daily is recommended as the first line for secondary prevention of cardiovascular events in ACS patients.13 Schwartz GG et al. reported that atorvastatin (80mg/day) significantly decreased the incidence of recurrent myocardial ischemic events in the first 16 weeks in ACS patients.14 Hence, atorvastatin 40mg tablet should be continuously prescribed for BK as the level of evidence supporting the use of atorvastatin was robust.
Besides that, BK was prescribed with perindopril 2mg tablet once daily. Perindopril is an angiotensin converting enzyme (ACE) inhibitor licensed for secondary prevention in primary and secondary care for post MI patients.9 According to the SIGN guideline, long term ACE inhibitor should be given within the first 36 hours for patients with MI.3 A meta-analysis in 2006 showed found that the use of of ACE inhibitor in patients with coronary artery disease was associated with a decline in total mortality (RR 0.87, 95% CI 0.81 to 0.94) and cardiovascular mortality (RR 0.83, CI 0.72 to 0.96).15 Saha and his colleagues reported that there was a statistically significant reduction in the risk of mortality following MI in patients who treated with perindopril.16 In a randomized clinical trial, perindopril have demonstrated significant beneficial effects when used for secondary prevention.16 Moreover, NICE found evidences that long-term therapy with ACE inhibitor after an MI was cost-effective especially for patients with stable coronary artery disease, heart failure or left ventricular dysfunction.9 Hence, the use of perindopril for secondary prevention in this patient was strongly advocated.
In short, evidences shown above leads to the conclusion that fondaparinux and aspirin plus clopidogrel should be given to BK as thromboprophylaxis, as recommended in the NICE and SIGN guideline. Metoprolol, atorvastatin and perindopril were strongly recommended as the second prevention strategy in post MI patients.