MDR-TB will become a serious problem to maintain the sustainable success of National TB Program (NTP) in declining TB prevalence in Indonesia. Since the main cause of MDR due to inappropriate medication or treatment failure, obviously the most important strategy for controlling MDR-TB only by curing each TB patients on the first place, because to treat MDR TB patients will be extremely expensive far beyond the patient affordability as well as government capability.
WHO (2003) declared the increasing incidence of MDR TB gradually by 2% per year.
MDR-TB prevalence in developing countries are predicted between 4.6% to 22.2% .
Preliminary data from the first drug-resistance survey in Java suggests low rates of MDR-TB in new cases (1-2%), but elevated rates of MDR-TB in NTP patients reporting previous treatment (15%). Limited and unrepresentative hospital data (2006) show the reality of MDR-TB and XDR-TB, with one third of MDR-TB cases resistant to Ofloxacin and one documented XDR-TB case (among 24 MDR-TB cases). MDR-TB cases in Indonesia do not yet have access to adequate treatment of MDR-TB, as not all relevant drugs are available in the country.
From 2005 to 2007, 3727 total number TB patients in Persahabatan Hospital 554 (15%) patients confirmed as MDR-TB by culture.
The biggest problems lies in private sectors that is private practicing physicians and most hospitals which are not covered NTP.
Past and current use of second line drugs.
Currently there only two categories of second line drugs avalailable in Indonesia: Kanamycin (KM) and Fluoroquinolones (FQ). Kanamycin is almost exclusively used for TB and short treatment of STI.
The other four categories of second line drugs: Capreomycin, Ethionamide Prothionamid and PAS are not registered in Indonesia. Cycloserine is registered but not avalailable in the market.
Kanamycin and streptomycin were widely used exclusively for treating TB patients before the era of short course therapy Rifampicin containing regiment.
FQs are regarded as the most cost effective drugs for the treatment of MDR-TB, unfortunately the FQs are already being widely used for almost all kind infectious diseases mainly respiratory infections regardless of true or false infections, bringing this class of drugs to rapid resistance including to M tuberculosis in the near future, furthermore it also known to be highly cross resistance with other FQs.
Our previous study (1997) with FQ namely Ofloxacin for the treatment of MDR-TB (58 pts) showed promising even with lower than recommended dosage(400 mg/day) in combination with Pyrazinamide, Ethambutol and Streptomycin for 9-12 months plus 12 months follow up period with smear conversion up to 72% at the end of therapy, relapse rate 11.2% on 12 months follow up. Those who were resistance with only two drugs (RH) and duration of resistance less than 3 years showed better cure rate (90%) and lower relapse rate than those who were more than two drug resistance (8%) and more than 3 years duration of resistance. The resistance pattern of Oflo for Mtb in that study showed 20% (MIC>2mcg), clearly it should be higher rate by now.
Yew WW et al in retrospective comparison study effectiveness of Ofloxacin versus Levofloxacin in patients wih MDR-TB showed that Levo was more effective than oflo by 90 to 79% respectively
Limitation towards successful treatment of MDR-TB patients includes: substandard diagnostics and drug therapy, high cost of therapy, no government support, long duration (24 months), adverse reactions.
Current management of MDR-TB patients will be following WHO Guidelines os DOTS Plus Program.
Conclusions.
The top priority is not how to manage MDR-TB, but how to prevent MDR-TB.
Acute asthma or acute asthma exacerbation is a very common condition that can be found in emergency department (ED) in most hospitals world wide ranging from mild attacks to nearly fatal, even death can be occurred. In many countries, asthma mortality increased from the 1960s to the second half of the 1980s, due to better management of acute asthma in primary health care and hospitals, a recent downward trend was observed, overall asthma has a low mortality rate compared to other lung diseases. In PersahabatanHospital only 2.0 % death occurred in hospital admitted patients.
However death still occur typically in patients with poorly controlled disease whose condition gradually deteriorates over a period of days or even weeks before the fatal attack. Infrequently, death occurs suddenly. Accordingly, most deaths are preventable, and a useful practice is to assume that every exacerbation is potentially fatal
The majority of deaths occur at home, work, or during transport to the hospital as also shown by data from PersahabatanHospital in which 2.7% ( 6/2209) death on arrival occurred in ED.
There are two different pathogenic scenarios involved in the asthma attack progression, type 1 or slow-onset acute asthma and type 2 or asphyxic or hyperacute asthma. Type 1 characterized predominantly by airway inflammation .patients show a progressive (over many hours, days, or even weeks) clinical and functional deterioration prevalence of this type of asthma progression is between 80% and 90% of adults with acute asthma in ED. In the less common asthma progression scenario, bronchospasm is predominant and patients presenting with a sudden-onset asthma attack characterized by rapid development of airway obstruction (< 3 to 6 h after the onset of the attack).
Acute asthma is a medical emergency that must be diagnosed and treated urgently. The assessment of an asthma exacerbation constitutes a process with two different dimensions: (1) a static assessment to determine the severity of attack, and (2) a dynamic assessment to evaluate the response to treatment. Overall, it requires an analysis of several factors.
The severity of asthma exacerbations determines the treatment. The goals of treatment may be summarized as maintenance of adequate arterial oxygen saturation with supplemental oxygen, relieve airflow obstruction with repetitive administration of rapid-acting inhaled bronchodilators (β-agonists and anticholinergics), and reduce airway inflammation and to prevent future relapses with early administration of systemic corticosteroids. Controversies exist among different delivery on drug administration, combination therapy, inhaled versus oral or systemic drugs administration, including the benefit of i.v Mg.3
The patient should be hospitalized if, despite 2 to 3 hours of intensive treatment in the ED he or she still has significant wheezing, accessory muscle use, permanent requirement for oxygen to maintain SpO2 ≥ 92%, and a persistent reduction in lung function (FEV1 or PEF ≤ 40% of predicted), in much the same way that the presence of factors indicating high risk of asthma-related would lead to a decision to hospitalize the patient.
Patients with findings of severe airflow obstruction who improve minimally or deteriorate despite therapy should be admitted to an ICU. Clinical markers for this include respiratory distress, high pulse pressure or a falling pulsus in a patient with fatigue, or the patient’s subjective sense of impending respiratory failure. Other indications for ICU admission include respiratory arrest, altered mental status, SpO2 < 90% despite supplemental oxygen, and a rising PaCO2 coupled to clinical evidence of non resolution
Many patients admitted to the ICU with acute asthma simply require additional time for the therapies instituted in the ED to be continued and for respiratory function to improve. These patients often require a relatively brief period of time in the ICU; when improvement is clear, they can be discharged to the regular ward.
A few patients will require positive pressure ventilatory support because of progression to respiratory failure in advance of response to treatment or prior to treatment, and these challenging patients require specific ventilator strategies to be employed to optimize outcome.
Among patients sent home from the ED following acute asthmatherapy, 17% will have a relapse and PEFR does not predict who will develop this outcome.The rate was slightly higher (21.7% ) in PersahabatanHospital .2,4
Another study from Persahabatan Hospital demonstrated a significant advantage in overall maximal bronchodilator response when repeated high doses nebulized steroid or intravenous steroid combined with b2 agonist in treatment of acute severe asthma5
References
1.Rodrigo and Rodrigo. Acute Asthma in Adults. A review. Chest 2004;3:s
2.Emerman CL et al. Prospective Multicenter Study of Relapse Following Treatment for Acute Asthma Among Adult Presenting to the Emergency Department. Chest. 1999; 115:919-927
3.Fitzgerald M. Clinical Review Extracts from “Clinical Evidence” Acute Asthma”. BMJ 2001;323:841-845
4.Husain B, Yunus Fet al. Relapse rate post asthma exacerbation treated with oral methyl prednisolon and other related factors. J Respir Indo 2004; 24:52-64
5.Febrina S, Yunus F. The efficacy of nebulized versus systemic steroid in acute severe asthma. Paper presented at the Asia Pacific Society of Respirology. Kyoto Japan 2007
Respiratory failure is a syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygenation and carbon dioxide elimination. In practice, respiratory failure is defined as a PaO2 value of less than 60 mm Hg while breathing air or a PaCO2 of more than 50 mm Hg. Furthermore, respiratory failure may be acute or chronic. While acute respiratory failure is characterized by life-threatening derangements in arterial blood gases and acid-base status, the manifestations of chronic respiratory failure are less dramatic and may not be as readily apparent.
Classification of respiratory failure
Respiratory failure may be classified as hypoxemic or hypercapnic and may be either acute or chronic and it is sub-classified into one of two types of respiratory failure based on the level of PaCO2 :
Type 1 Hypoxemic respiratory failure:
PaCO2 is normal or low
PaO2 less than 60 mmHg
Type 2 Hypercapnic respiratory failure:
PaCO2 is greater than 50 mmHg
PaO2 is less than 60 mmHg
Aetiology type 1 Hypoxemic respiratory failure
The causes of type 1 Hypoxemic respiratory failure :
diseases that damage lung tissue
conditions where there is a V/Q mismatch
conditions where there is hypoxaemia due to right to left shunts
It may be acute or chronic.
Acute type 1 Hypoxemic respiratory failure
Acute type 1 respiratory failure may occur in conditions such as:
asthma - in the acute phase the cause of respiratory failure in asthma is not the bronchoconstriction but rather the intense inflammation and oedema of the lungs which results in impaired oxygenation of the blood
pulmonary embolus
pulmonary oedema
adult respiratory distress syndrome
Chronic type 1 Hypoxemic respiratory failure
Causes of chronic type 1 respiratory failure include:
emphysema
respiratory muscle disease, e.g. myasthenia gravis
kyphoscoliosis
thromboembolic pulmonary hypertension
lymphangitis carcinomatosa
pulmonary alveolar fibrosis
Aetiology of type 2 Hypercapnic respiratory failure
Type 2 Hypercapnic respiratory failure occurs in conditions which cause alveolar hypoventilation, for example, where there is:
a reduced ventilatory effort
increased dead space
increased carbon dioxide production
a combination of these
Type 2 Hypercapnic respiratory failure may be acute or chronic.
Acute type 2 Hypercapnic respiratory failure
Possible causes include:
severe acute asthma - as the patient becomes exhausted type 2 hypercapnic respiratory failure occurs
acute epiglottitis
respiratory muscle paralysis; a number of aetiologies including Guillain-Barre syndrome
Chronic type 2 Hypercapnic respiratory failure
Possible causes include:
chronic bronchitis
primary alveolar hypoventilation
motor neurone disease
Clinical features
Clinical features of respiratory failure may include:
clinical features of the underlying cause of the respiratory failure
hypoxia - restlessness, confusion and ultimately, coma
hypercapnia causing:
drowsiness
flapping tremor
warm peripheries
headaches
bounding pulse
papilloedema
Investigations
Initial patient assessment:
·assess the patient's previous disability
·are there signs of deterioration?
Screening investigations:
·chest radiology
·blood gases
·peak expiratory flow rate
·ECG
·full blood count
·biochemistry
·sputum and blood culture
·store a blood sample for serology
Blood gases and acid-base disorders in respiratory failure
Type 1 Hypoxemic respiratory failure:
·acute - PaO2 low, PaCO2 normal, pH normal, bicarbonate normal
·acute - PaO2 low, PaCO2 high, pH low, bicarbonate normal
·chronic - PaO2 low PaCO2 high, pH low/high, bicarbonate high
Blood gases
Blood gases are commonly measured, and with a logical, systematic approach they may be easily interpreted.
Blood gases provide information about:
·ventilation
·oxygenation and alveolar-arterial O2 gradient
·acid-base status
Blood gases and oxygenation
The normal range for PaO2 is 80-100 mmHg. A partial pressure less than 60 mmHg defines respiratory failure.
Arterial hypoxaemia is commonly due to pulmonary disease:
·poor gas transfer:
otype I respiratory failure
oPaCO2 is typically low
·hypoventilation:
otype II respiratory failure
oPaCO2 is typically raised
Arterial hypoxaemia may occur when the lungs are normal :
·low inspired partial pressure of oxygen e.g. altitude
·ventilation-perfusion mismatch
·right to left shunts:
ocongenital heart disease
oarteriovenous malformation of the pulmonary vessels
The alveolar-arterial oxygen gradient
Measurement of the alveolar-arterial (A-a) gradient is useful in hypoxic patients and may help to distinguish hypoxaemia due to pulmonary disease from other causes of hypoxaemia.
The Alveolar : arterial oxygen gradient is an index of the efficiency of gas transfer across the alveolar membrane. It is the difference in oxygen tension across the alveolar membrane.
This difference is calculated by the following equation:
PaO2 = FIO2 x (PB – PH2 O) – PaCO2/R
For the above equation, PaO2 = alveolar PO2, FIO2 = fractional concentration of oxygen in inspired gas, PB = barometric pressure, PH2 O = water vapor pressure at 37°C, PaCO2 = alveolar PCO2, assumed to be equal to arterial PCO2, and R = respiratory exchange ratio. R depends on oxygen consumption and carbon dioxide production. At rest, VCO2/VO2 is approximately 0.8.
Even normal lungs have some degree of V/Q mismatching and a small quantity of right-to-left shunt, alveolar PO2 is slightly higher than arterial PO2. However, an increase in alveolar-to-arterial PO2 above 15-20 mm Hg indicates pulmonary disease as the cause of hypoxemia.
Acid base balance
To ensure an acid-base balance the body has to deal with the following:
·the daily fixed acid load of 50 to 100 mmoles
·the daily carbon dioxide production of 13,000 to 15,000 mmoles
Homeostatic mechanisms maintain the following normal range of pH by regulation of the pCO2 and bicarbonate:
·pH: 7.35 to 7.45
·pCO2: 35 to 45 mmHg (regulated by ventilation)
·bicarbonate: 22 to 24 mEq (regulated by the kidneys)
Blood gases and ventilatory efficiency
The arterial partial pressure of carbon dioxide, PaCO2 reflects alveolar ventilation and in most cases may be used as an index of ventilatory efficiency.
It is raised i.e. greater than 45 mmHg, with hypoventilation and decreased i.e. less than 35 mmHg, during hyperventilation.
Respiratory acidosis
This is characterised by a raised PaCO2, a normal or slightly elevated serum bicarbonate, and a low pH.
A respiratory acidosis may be pure, or it may be complicated by a metabolic derangement (i.e. a mixed acidosis). Measurement of the serum bicarbonate permits definitive diagnosis:
·acute respiratory acidosis:
oserum bicarbonate increases by 1 mmol/l for each 10 mmHg increase in PaCO2
·chronic respiratory acidosis:
oserum bicarbonate increases by 3.5 mmol/l for every 10 mmHg increase in PaCO2
·if the bicarbonate is lower than expected then the condition is likely to be a mixed respiratory acidosis and metabolic acidosis
·if the bicarbonate is higher than expected then the condition is likely to be a mixed respiratory acidosis and metabolic alkalosis
Metabolic acidosis
This is characterised by a primary decrease in serum bicarbonate and a slight decrease in paCO2. Serum pH may be reduced or normal.
Causes are distinguished on the basis of the anion gap. In acidosis with a normal anion gap, plasma chloride is increased in order to maintain electrical neutrality - hyperchloraemic acidosis.
Metabolic acidosis (increased anion gap)
·diabetic ketoacidosis
·starvation ketoacidosis
·lactic acidosis (types A and B)
·acidosis of renal failure
·salicylate poisoning
·methanol poisoning
·ammonium chloride
Metabolic acidosis (normal anion gap)
Normal anion gap / hyperchloraemic acidosis:
·bicarbonate loss in the gut, e.g. pancreatic fistula, diarrhoea, utero-enterostomy
·renal tubular acidosis:
oproximal - bicarbonate loss
odistal - failure of acidification - proton pump failure
otreatment with excessive carbonic anhydrase inhibitors
Features of a metabolic acidosis
The classical clinical finding in the patient with metabolic acidosis is the deep, sighing breathing pattern which is termed Kussmaul respiration.
The physiological consequences of metabolic acidosis include:
·impaired myocardial contractility:
othe effect is independent of hypoxia
ocardiac failure may induce lactic acidosis
·increased risk of ventricular fibrillation
·pulmonary vasoconstriction
Anion gap
The anion gap is a method of assessing the contribution of unmeasured anions to acidosis. It is calculated as a difference between the total of sodium and potassium ion concentration, minus the total of chloride and bicarbonate concentration. Some people omit the potassium. Thus:
The normal range for the anion gap is 6 - 16 mmol/l. The anion gap provides a measure of the difference between unestimated anions - phosphate, acetate and ketones - and cations.
Reference:
1.Joint Pathology Services Royal Liverpool & Broadgreen University Hospitals (September 2006)
2.Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 1998. pp849-856
3.Franco D’Alessio, et al. Acute RespiratoryFailure. Piccini & Nilsson: The Osler Medical Handbook, 2nd ed. Johns Hopkins University. 2006
4.Sat Sharma, MD, FRCPC. Respiratory Failure.emedicine.medscape.com. Updated: Jun 29, 2006
5.Richard M. Effros,M.D.Jeffrey A. Wesson,M.D., Ph.D.Acid-Base Balance. Mason: Murray & Nadel's Textbook of Respiratory Medicine, 4th ed.2005 Saunders, An Imprint of Elsevier
7.Kurt A. Wargo, PharmD, BCPS,* and Robert M. Centor, MD. ABCs of ABGs: A Guide to Interpreting Acid-Base Disorders. Hospital Pharmacy, Volume 43, Number 10, pp 808–815; 2008 Wolters Kluwer Health, Inc
8.Dr. Praveen Kumar Neema. RESPIRATORY FAILURE. Indian J. Anaesth. 2003; 47 (5) : 360-366
