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MANAGEMENT OF ASTHMA IN PREGNANCY

DR HALIMATUN MANSOR

PHYSIOLOGY ADAPTATION DURING PREGNANCY


Oxygen consumption rises about 45ml/mnt Or 18 % which 1/3 for fetus and others for mothers metabolisme. Little increased in PaO2. Tidal volume increased from 500 ml to 700ml ( 20 % ) occurs early in pregnancy. Effective alveolar ventilation further increased by reduction of 20 % in Residual volume. Ventilation increased by 40 %

Stimulus to ventilation is probably due to progesterone which may act via several mechanism.
Lower respiratory centre threshold to CO2. Increased sensitivity of CO2 therefore increased ventilation by 5 l/mnt compared to 1.5 l/mnt in non pregnancy state. Increased carbonic anhydrase B in RBC which facilitates CO2 transfer.

Vital capacity does not change Anatomical changes showed


Level of diaphragm rises by 4 cm in early pregnancy and also by the enlarging uterus. And so with reduction of residual volume.

Gas transfer or pulmonary diffusing capacity is markedly decrease. Therefore the ventilation will be increased in order to compensate the reduce O2 defusions.

BRONCHIAL ASTHMA IN PREGNANCY


Chronic disease sustained with an inflammatory process and many triggering factor can intervene at different levels and time Common condition affecting the pregnancy which more than 1- 7 %. Life threatening event = 0.05 2 %. Serious complications maternal and fetal hypoxemia; increased risks of perinatal death, preterm birth, low birth weight and may increased risks of PIH or PE.

Maternal Deaths From medical conditions CEMD 1991-2000

18 16 14 12 10 8 6 4 2 0 1991 1993 1995 1997 1999 % Maternal Deaths

Medical conditions in Pregnancy 800


700 600 500 400 300 200 100 0 Hosp A Hosp B Hosp C Hosp D Hosp E Hosp F Anaemia Cardiac Asthma Thyroid Infections

Effects of pregnancy on Asthma


Most common respiratory disorder complicating pregnancy. Affecting in variable conditions
Severity depends on exposure to allergens, chest infection or seasons. Turner et al reviewed 1054 cases reported in 9 different publications showed
No changed = 48 % Improved = 29 % Deteriorate = 23 %

Effects of pregnancy on Asthma


Williams et al, 37 % of 63 patient with asthma react differently in different pregnancy.. Not depends on sex of fetus. Pregnancy does not change in airway rsistance due to
Bronchodilator influence
Increased progesterone secretion as a bronchodilator effect and increased B adrenergic activity. Increased free cortisol

Bronchoconstrictor influence
Reduced residual volume Reduced PaCO2 Increased Prostaglandin F 2a secretion

Effects of pregnancy on Asthma


The deterioration in pregnancy due to under treatment probably mistaken belief treatment will harmful fetus.

Effects of pregnancy on Asthma


Statistically no significant extra risks to fetus for mother with asthma.
Templeton suggested hypoxic was a cause of recurrent growth retardation in bronchitis patient In acute attack , hyperventilation also lead to hypocapnea and respiratory alkolosis which lead to fetal hypoxia( reduction maternal placenta perfusion)

3.7 % newborn baby of asthmatic mother will have transient tachypnea compared 0.3 % to non asthmatic mother.

Management of Atsthma
Golds of asthma management during pregnancy
Optimal control of resp symptoms including nocturnal exacerbations Achiving normal or near normal respiratory fx Allowing to perform usual activities of every days life Avoiding or minimizing asthma exacerbations Preventing / avoiding side effects dt

CEMD and Respiratory Disease


Respiratory disease contribute significantly to indirect maternal deaths during pregnancy In the 4 years review(1997-2000), majority of the death was due to bronchial asthma, followed by pneumonia and non-cardiogenic acute pulmonary oedema Among these respiratory conditions, asthma was the disease that already existed prior to pregnancy The course of the disease is predictable, death is preventable and the trend seems to be decreasing Majority of deaths occurred in the postpartum period

Ten asthmatic deaths in pregnancy were reported in 1997-2000 The deaths were highest in 1997 and decreasing towards 2000 Most of the deaths were due to status asthmaticus Deaths mostly occur during the second trimester and 4 of them died during postpartum period

Numbers of maternal deaths from causes of respiratory diseases(19972000)


causes
Bronchial asthma Pneumonia

1997 1998 (n=5) (n=7) 5 3


-

1999 (n=3) -

2000 (n=4) 2 2 -

3 1

Emphysema

Pulmonary oedema

Asthma is a chronic inflammatory disorder of the airways. This inflammation causes recurrent episodes of wheezing Breathlessness Chest tightness Cough particularly at night and early morning Airflow obstruction that is often reversible

Acute inflammation Bronchospasm mucosal oedema Vasodilation Mucus hypersecretion Persistent Chronic Inflammation Subepithelial fibrosis Smooth muscle hyperplasia / hypertrophy Mucus hyperplasia New vessel formation

Diagnosis
Consider asthma if any of the following signs and symptoms are present: Wheezing cough night/early morning recurrent difficulty in breathing recurrent chest tightness

Asthma may improve, deteriorate or remain unchanged during pregnancy Women with only mild disease are unlikely to experience problems, whereas severe asthmatics are at greater risk of deterioration, particularly in late pregnancy Those women whose symptoms improve during the last trimester of pregnancy may experience postnatal deterioration Deterioration in disease control is commonly caused by reduction or even complete cessation of treatment due to fear of its safety

In most women there are no adverse effects of asthma Severe, poorly controlled asthma, associated with chronic or intermittent maternal hypoxia, may adversely affect the fetus Some association(mostly retrospective, uncontrolled or small studies) between asthma and following : Pregnancy-induced hypertension/PE : Preterm birth and premature labour : Low birth weight infants : IUGR

Neonatal morbidity : transient tachypnoea of newborn : neonatal hypoglycaemia : neonatal seizure : admission to NICU

In general, adverse effects on pregnancy outcome are small and related to the severity and control of asthma Women should be advised that their asthma is unlikely to adversely affect their pregnancy and any small risks may be minimized by maintaining good control of asthma throughout pregnancy

Goals of Therapy
To abolish day and night symptoms of asthma To maintain normal activity levels To prevent acute exacerbations of asthma To deliver healthy infant

Approach to Therapy
Assessment of severity and response to treatment Education of patient and family Avoidance of precipitating factors Use of the lowest effective dose of convenient medications minimising short and long term side effects

Management
Prepregnancy Prenatal Intrapartum Postnatal

Prepregnancy
Overall it should be anticipated that pregnancy will be well tolerated Baseline pulmonary function study may be of benefit in the moderate to severe asthmatics Medication should be adjusted appropriately to stabilize respiratory function Reassurance should be given regarding safety and importance of continuation of maintenance pharmacologic drugs into pregnancy

Nature of asthma Preventive measures/ avoidance of triggers Drugs used and side effects Proper use of inhaled medications Peak flow meter monitoring Knowledge of difference between relieving and preventive medications Recognition of features of worsening asthma Self-management plan Danger of non-prescribed self medication.

Prenatal
Current emphasis is prevention rather treatment of acute attacks Regular inhaled anti-inflammatory medication is considered first-line maintenance treatment for all but those with infrequent attacks Aim of treatment is achieve virtual total freedom from symptoms, such that the lifestyle of the individual is not affected

Subsequent follow up
Review of symptoms PEF monitoring at every visit. PEF > 80% of best suggests good control Regular visits
compliant to medication Avoiding triggers meet expected goals Any concern

Home peak flow monitoring and personalized self management plans should be encouraged An increase in the dose or frequency of inhaled steroid should be the first line steps if symptoms are not optimally controlled on the current dose of inhaled steroid Women should be counselled about the indications for an an increase in inhaled steroid dosage and if appropriate given emergency supply of oral steroid

All drugs in widespread use to treat asthma including systemic steroids are safe during pregnancy and lactation Ensure adequate preconceptual or early pregnancy counselling so that women do not stop important anti-inflammatory inhaled therapy

treatment should be inhalational rather than oral, since reduce systemic effects Inhalation technique should be checked Avoid precipitating factor

Medications used in BA
1) Anti-inflammatory medications 2) Long-acting bronchodilators 3) Short-acting bronchodilators

Use beclomethasone or budesonide if required during pregnancy If the pt is already on other ICS and well controlled, continue rather than switch. Consideration of inhaled salmeterol if asthma is not controlled by ICS Avoid oral decongestants during first trimester Leukotriene modifiers montelukast, zafirlukast, zileuton. No human gestational data available but no problems detected during animal studies. Should only be considered in pts with recalcitrant asthma who have shown a uniquely favorable response prior to becoming pregnant

Drugs delivery
The inhaled route is preferred for beta2 agonist and steroids Pressurised MDI is suitable for most patients as long as the inhalation technique is correct. For patients with poor coordination, alternative methods include spacer devices, dry powder inhalers, breath-actuated pressurised MDI Nebulised route is preferred in the management of acute attacks

If inhaled betasympathomimetic drugs are necessary for symptomatic relief more than once daily, start regular inhalational antiinflammatory drugs either glucocorticoid(beclomethasone 100-400 mcg bid) or chromoglycate switching to beclomethasone if chromiglycate fail The next step is high dose inhalational steroids(beclomethasone 800-2000mcg daily in divided doses) or additional long acting betaagonists

Corticosteroid
Both oral and inhaled steroids are safe in pregnancy Only minimal amount of inhaled corticosteroid preparations are systematically absorbed There is no evidence for an increased incidence of congenital malformations or adverse fetal effects attributable to the use of inhaled beclomethasone(Becotide) in pregnancy There is less information of budesonide(Pulmicort) but it is widely used and appear safe Fluticasone propionate(Flixotide) is a newer inhaled corticosteroid and experience is growing with its use in pregnancy. Its too appear safe

The addition of systemic corticosteroids to control exacerbation of asthma is safe and these must not be withheld if current medications are inadequate Prednisolone is metabolized by the placenta and very little (10%) active drugs reach the fetus There is no evidence of an increased risk of abortion, stillbirth, congenital malformations, adverse fetal effects or neonatal death attributable to maternal steroid therapy Although suppression of of the fetal hypothalamopituitary-adrenal axis is a theoritical possibility with maternal systemic steroid therapy, there is only trivial anecdotal evidence from clinical practice to support this

However, oral steroids will increase the risk of GDM, and cause a deterioration in blood-glucose control in those womwn with established impairment of glucose tolerance in pregnancy Blood glucose should be checked regularly, and the hyperglycaemia is amenable to treatment with diet and if required, insulin and is reversible on cessation or reduction of steroid dose The requirement should be determined by the asthma status

Inhahaled corticosteroid
Most effective antiinflammatory medication in asthma Reduce airway inflammation in asthma Reduce bronchial hyperresponsiveness greater stimulus required to provoke symptoms

Beta2 Agonist
B2 agonist from the systemic circulation cross the placenta rapidly, but very little of inhaled dose reaches the lungs and only a minute fraction of this reaches the systemic circulation Studies showed no difference in perinatal mortality, congenital malformations, birth weight, Apgar scores or delivery complications when pregnant asthmatics treated with inhaled B2 agonist are compared with asthmatics not using B2 agonist and non asthmatic controls

Experience with the use of the inhaled long acting B2 agonist, salmeterol(Serevant) in pregnancy is growing and it too appear safe No adverse fetal effects have been reported with the use of the following inhaled disodium cromoglycate(Intal), nedocromil(Tilade) or anti-cholinergic drus eg Atrovent

There is no conclusive evidence of ill effect or malformation in human fetus Some studies have noted transient tachycardia, jaundice or irritability in neonates of mothers receiving xanthines but this may relate to disease severity rather the drugs itself

Acute Severe Asthma


A dangerous situation Should be managed in hospital with a respiratory physician in an intensive care environment The treatment is no different from the emergency management of acute severe asthma in non pregnant women Management should in combination with medical team +/- anaethetic team

Management
High concentration of O2 (>40%) . Inhaled B2 agonist ( salbutamol 5 mg or terbutaline 5 mg or fenoterol 5 mg) in combination with anticholinergic ( ipratropium bromide 0.5 mg) via nebuliser driven by oxygen.If compressed air nebuliser is used, administer supplemental oxygen. *Alternatively multiple actuations of MDI into a large spacer device(2-5 mg i.e 20-50 puffs) preferably in combination with anticholinergic

Nebulised beta2agonist 2-4 hourly (up to every 15 minutes) preferably in combination with anticholinergics IV hydrocortisone 100-200 mg 6 hourly or prednisolone 30-60 mg daily If poor response, s.c terbutaline or salbutamol 0.25-0.50 mg Note : No sedatives. Antibiotics are indicated only if there is evidence of a bacterial infection.Do a CXR if pneumothorax or pneumonia is suspected.
If life threatening features present : Intravenous aminophylline 250 mg slowly over 20 minutes or iv terbutaline or salbutamol 250 mcg over 10 minutes. (Bolus aminophylline should not be given to patients already taking oral theophylline). Pts with features of life threatening asthma require admission preferably to ICU.

ABG
Should be measured if a patient has any of the severe or life threatening features. Markers of a severe, life threatening attack include : a normal (5-6 kPa or 36-45 mmHg) or high PaCO2 severe hypoxaemia : PaO2 < 8 kPa(60 mmHg) low pH

REQUIRED ICU MANAGEMENT


Deteriorating PEF Worsening hypoxaemia or hypercapnia Exhaustion or feeble respiration Confusion or drowsiness Coma or respiratory arrest

MONITORING
Hydration Maternal monitoring with pulse oximetry. Maintain arterial oxygen saturation above 95% Continuous fetal monitoring Repeat PEF 15-30 minutes after starting treatment Repeat ABG measurements if initial results are abnormal or if pt deteriorates Monitor PEF at least 4 times daily throughout hospital stay

DISCHARGE PLANNED
Start on inhaled steroids for at least 48 hours in addition to a short course of oral prednisolone and bronchodilators Stable on medication she is going to take outside the hospital for at least 24 hrs PEF > 75% predicted/best and PEF diurnal variability < 20% Able to use inhaler correctly / alternative inhaler devices Educate the patient

Give prednisolone 30-40 mg dly tapering over 7-14 days, + regular inhaled steroids + inhaled B2 agonist PRN. Ensure enough supply of medications Appointment within 2-4 weeks Advice to return if asthma worsens

INTRAPARTUM MANAGEMENT
Asthmatic attacks in labour are rare Women should not discontinue their prophylactic inhalers during labour No evidence to suggest that B2 agonist given via the inhaled route impair uterine contraction or delay the onset of labour Women receiving oral steroids(>7.5mg Prednisolone daily for 2 weeks prior to delivery) should receive parenteral hydrocortisone(100mg 3-4x/ day) to cover the stress of labour, and until oral medication is started

Prostaglandin E2 (Prostin) used to induce labour, to ripen the cervix or for early termination of pregnancy is a bronchodilator and is safe PGF2 alpha (Haemabate) to treat life threatening PPH may be unavoidable but it can cause bronchospasm and should be used with caution in asthmatics Ergometrine has been reported to cause broncospasm, in particular in association with general anesthesia, but this does not seem to be a practical problem when Syntometrine is used for the prophylaxis of PPH

MANAGEMENT PLAN INTRAPARTUM


Oxygen Continue daily treatment regimen IV hydrocortisone every 8 hrs as clinically indicated Avoid drugs that can cause histamine release and bronchospasm Epidural placement for labour analgesia Epidural and spinal anaesthesia preferred for caesarian section

ANALGESICS
All forms of pain relief in labour including epidural and Entonox can be safely used by asthmatic patients In acute severe asthmatic attacks, opiates for pain relief should be avoided Epidural rather than general anaesthesia, is preferable because of decreased risk of chest infection and atelectasis

BREASTFEEDING
The risk of atopic disease developing in the child of an asthmatic woman is about 1:10 or 1:3 if both parents are atopic There is some evidence that this risk may be reduced by breastfeeding Breast feeding between 1 to 6 months reduces the prevalence of atopy in 17 years old by about 30-50% All the drugs including oral steroids are safe to use in nursing mother Prednisolone is secreted in breast milk but there have been no reported clinical effects in infants breast fed by mothers receiving prednisolone. Concerns regarding neonatal adrenal function are unwarranted with doses below 30mg/day

RECOMENDATION
Asthmatic ladies should have good asthmatic control before becoming pregnant The therapy should be optimised in order to obtain good asthmatic control Patient should be educated on the predisposing factor/s for acute exacerbation of asthma.They should try to avoid exposure towards that Poorly controlled asthma should be managed in combined clinic.If the patient is in hospital, combined care should be given by both physician and obstetrician in order to achieve good asthmatic control and to ensure good pregnancy outcome

Genetic Counseling
Risks of child having asthma is 4% if one parent having asthma Increased 8-16% if parent is also atopy. Increased 30% if both parents having asthma and atopy Drugs treatment is not harmful.

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