EVERYDAY PRACTICE

Oral preparations are available as single drug, short act-ing tablets; sustained release tablets (retard) and fixed dosecombinations with beta agonists (ephedrine or salbutamol).Sustained release tablets are useful in the management ofnocturnal bronchospasm. Combinations with beta agonistshave the advantage of providing an additive effect withlower doses of both.

SIDE EFFECTSWhile using theophylline it is essential to remember thatthere are many drugs which interact with it (Table I).

Side effects are dose related. Early effects includenausea and vomiting (irrespective of route), tremor andanxiety. When serum levels exceed 30 mgIL theophyllinecauses arrhythmias, convulsions and coma. The convulsionsneed to be controlled with intravenous diazepam orthiopentone sodium. Theophylline potentiates the cardiaceffects of beta agonists and cardiac arrhythmias are morelikely when these drugs are combined. Repeated rectaladministration can cause proctitis.

TABLE I. Drug interactionsof theophylline

Drugs which potentiate theophyllineAllopurinol-long term Oral contraceptives ErythromycinCimetidine Ciprofloxacin Propranolol

Drugs which decrease theophylline levelsBarbiturates Rifampicin CarbamazepineSulfinpyrazone Phenytoin'Piggyback' infusions with the following drugs are incompatible.Chlorpromazine . Gentamicin Pencillin GCimetidine Hydrallazine ProcainamideCephotaxime Insulin PhosphateDobutamine Nitroprusside.

Oxygen therapy in clinical practice

Oxygen therapy is used to increase the oxygen content ofthe arterial blood in hypoxaemic patients. Common indica-tions for oxygen therapy are acute or chronic respiratoryfailure, acute pulmonary oedema and peripheral circulatoryfailure. The therapy is also useful in" 'anoxic spells' inpatients with cyanotic heart disease, and in congestiveheart failure, severe anaemia and carbon monoxidepoisoning. It is most beneficial in patients who have arterialunsaturation due to an underlying pulmonary disorder.

Oxygen therapy increases the arterial oxygen content inpatients with cyanotic heart disease only marginally,because the blood flowing through the lungs is alreadysaturated with oxygen. In several conditions where thearterial oxygen saturation is almost normal, inhalation of

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CLINICAL USETheophylline is useful in the management of

Reversible airways obstruction. For relieving broncho-spasm and in combination with beta agonists and steriodsfor bronchial asthma or chronic obstructive airwaysdisease.

Left ventricular failure and pulmonary oedema. Inpreventing left ventricular failure and also in managingpatients with acute left ventricular failure in pulmonaryoedema.

Cheyne-Stokes' respiration. It can be treated withaminophylline, the active moiety being ethylenediamine.

SUMMARYTheophylline is a methyl xanthine which is useful in themanagement of reversible airways obstruction, left ven-tricular failure and pulmonary oedema. Since there aremany factors influencing the clearance rate of theophyllineit should be used with caution. While oral theophylline isused in the management of bronchial asthma and chronicobstructive airways disease, long acting preparations helpin the management of nocturnal bronchospasm. Combi-nation preparations are useful for their additive effect andparenteral preparations are beneficial in the managementof status asthmaticus and acute pulmonary oedema.Suitable dose modifications are needed depending on theclinical profile of the patient and the use of other drugs.

GEORGE JOHNChristian Medical College

Vellore

high concentrations of oxygen may result in a slightincrease in the arterial oxygen content because of anincrease in physically dissolved oxygen in the plasma. Thismay, however, be of considerable benefit in a patient witha very low cardiac output whose tissue oxygen tension hasdropped to critically low levels.

Normal arterial blood contains 20 ml of oxygen per100 ml. Most of it is in combination with haemoglobin,which is almost fully saturated. The solubility of oxygenin the plasma is low (0.0031 ml/lOOml of plasma/mm Hgoxygen tension). If a person were to breath 100% oxygenand had no haemoglobin in the blood, the arterial oxygencontent would be only 2 ml per 100 ml. The inspiredoxygen tension in a person breathing room air at sea levelis 48 mm Hg. The cascade of oxygen tension in the humanbody is shown in Table I. Tissue oxygen tensions are closeto those in the venous blood. Mitochondrial oxygen ten-

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TABLE I. Oxygen cascade from inspired air to tissues cells

Inspired airAlveolar airArterial bloodCapillary bloodVenous blood

mmHg150100905140

(kPa)20.013.718.36.85.5

sion is approximately 20 mm Hg. Mixed venous or tissueoxygen tensions less than 20 mm Hg are not compatiblewith prolonged survival.

The relationship between oxygen tension and haemoglo-bin saturation is given by the oxyhaemoglobin dissociationcurve (Fig. 1). P50 is the oxygen tension required toachieve 50% saturation of haemoglobin at given reactionconditions of pH, temperature. etc. An increase in thenormal value of P50 (approximately 30 mm Hg) meansthat oxygen is relatively loosely bound to haemoglobin orthe affinity of haemoglobin for oxygen is low. This wouldfavour peripheral unloading of oxygen at the tissue level.

'too

~ 800

z0

~ 60a:::J 50f-«(j) 40zwC.9>-x0 20

Pso = Tension at 50% saturation

~~~(H+ 1= 40 nmOI/L

II+- Pso a.t pH 7•.•II (H+):;: 40 nmol/L1<I

o~--~-L~--~--~-,---,---,---,12 14 16 kPa2 4 8 10

i6

40 60Pao2

80 100 120 mmHgo 20

FIG. 1 Oxygen dissociation curve-normal curve and shifts

Acidosis, increase in 2,3 diphosphoglycerate concentrationand hyperthermia favour an increase in P50 (Table II).

Prolonged inhalation of high concentrations of oxygenmay result in pulmonary damage. Moreover, use of highconcentrations of oxygen in patients with chronic hyper-capnia may produce serious respiratory depression.Hence oxygen should be administered only in patientswho are likely to benefit from this form of treatment.Monitoring of arterial gas tensions is mandatory, particu-larly in critically ill patients.

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 2, NO.4

TABLE II. Factors which influence the oxygen dissociation curve

Factors increasing P50(shift curve to the right)

t temperature!pH

t Pco2

t 2,3,DPG

Factors decreasing P50(shift curve to the left)

t temperature

t pHt Pco2

t 2,3,DPG

DPO Diphosphoglycerate P50 Oxygen tension at 50% saturation

DEVICES FOR OXYGEN THERAPYRequirements of an ideal device are:

1. control of fractional inspired oxygen concentration(Fi02),

2. prevention of CO2 accumulation,3. minimal resistance to breathing,4. acceptance of patients, and5. efficient and economical use of oxygen.

Present devices can be classified into fixed or variableperformance systems. Variable .performance devices arecommonly used, inexpensive and convenient but areincapable of delivering constant oxygen concentrations.Fixed performance systems, on the other hand, are accu-rate and constant delivery systems (Table III).

TABLE III. Oxygen therapy devices

Device Oxygen flowUmin.

Concentrations%

Nasal cathetersSemi-rigid masksSemi-plastic masksVenturi masksVentilatorsAnaesthetic circuitsIncubator

2---{j

4-124-84-8

VariableVariable

3-8

30-5035-6540-80

24,28,35,40,50,6021-10021-100

Upt040

Variable performance devicesThese may be divided into three types.

1. No capacity systems-nasal catheters (Fig. 2)2. Small capacity systems-any device which consists of a

mask shell only3. Large capacity systems-any device with a bag

Variable performance systems give uncontrollable oxygentherapy as they function only in relation to the patientwho 'creates' the inspired mixture by the act of breathing.Several factors influence performance; these include theinspiratory flow rate (which not only varies within eachbreath but attains a variable peak from breath to breath),the duration of expiration, the expiratory pause, the oxygenflow rate and the vent resistance. The subtle interplay ofthese factors results in unpredictable oxygen dosage in agiven patient at a given time. Oxygen therapy may bestarted using a basic device and if Pa02 remains low (<60mm Hg), fixed performance systems may have to beresorted to.

EVERYDAY PRACTICE

FIG. 2 Patient inhaling oxygen through anasal cannula

Fixed performance devicesThese allow a controlled (known, fixed and selectable)oxygen dosage. To supply a patient with a constantinspired mixture the device must either be capable ofexactly following the inspiratory flow waveform as insome ventilators and anaesthetic machines or supply the gasmixture as a continuous flow in excess of peak inspiratoryflow rate. This is referred to as high air flow with oxygenenrichment (HAFOE). HAFOE (Fig. 3) operates on the

FIG. 3 Ventimask with colour coded regulators

Venturi principle in which a jet of pure oxygen draws aconstant ratio of room air to produce a fixed concentra-tion mixture which is independent of patient factors. Awide range of oxygen concentrations with varying flowrates is possible and humidification is optional since roomair is entrained. The advent of fixed performance oxygendevices in the management of hypoxaemia has veeredaway from control of ventilation to measures supportingoxygenation.

197

Domiciliary oxygen therapyPatients with chronic respiratory failure and chronic corpulmonale have been shown to have better survival andamelioration of congestive heart failure, if they areadministered oxygen at a low concentration for 12 to 15hours every day for the rest of their lives (this requiresoxygen inhalation at home). Simple nasal catheters aretolerated best for this form of prolonged treatment.Humidified oxygen is given at a rate of 1 to 2 Llminute,usually at night.

An oxygen concentrator is a device which absorbsatmospheric nitrogen so that the concentration of oxygenis increased. It can be installed in a patient's home. Theinitial cost is high (approximately Rs 40 000), but there islittle recurring cost. It is an effective method for providingoxygen at low concentrations for prolonged periods.

Effort tolerance of patients with respiratory failure mayimprove during oxygen inhalation. Light-weight portableoxygen cylinders with shoulder straps permit oxygeninhalation during ambulation (Fig. 4). The oxygen supplyfrom these cylinders, however, is adequate for 2 to 3 hoursonly.

,

FIG. 4 Patient using a portable oxygen cylinder

HAZARDS OF OXYGEN THERAPYCarbon dioxide narcosis can be precipitated in patientswith respiratory failure who are dependent on their hypoxicdrive for ventilation. If CO2 narcosis occurs despite carefuloxygen administration then ventilation must be supported.

Prolonged use of oxygen (more than 6 hours cf 100%O2) can cause pulmoary changes. A decrease in com-pliance is followed by interstitial and alveolar oedema.The capillary endothelial and alveolar damage is a direct

198

toxic effect of oxygen-free radicals (hyperoxic damage).Retrolental fibroplasia has occurred in premature babiesexposed to high oxygen concentrations for prolongedperiods of time. It is therefore suggested that oxygen beused in concentrations of 50% or less and if in spite of thishypoxaemia (Pa02 <60 mm Hg) persists, other measuresof ventilatory support with oxygen delivered under a cons-tant positive airway pressure (CPAP) or positive endexpiratory pressure (PEEP) may be instituted. Thesemeasures increase the functional residual capacity andthereby improve oxygenation. Simple CPAP circuits with amask are available for use on spontaneously breathingpatients. These can be extremely useful, at times obviatingthe need for intubation.

Management of asthma

Asthma is a common disease characterized by reversibleairways obstruction caused by hyperreactivity of thebronchial musculature to different stimuli.

PATHOPHYSIOLdGYWhen an atopic individual is exposed to an allergen,antibodies of the IgE class are formed. These moleculesattach. themselves to mast cells. At the second and sub-sequent encounters the offending allergen becomesattached to the IgE-mast cell complex. This results indegranulation of the mast cell and liberation of many sub-stances with potent bronchoconstrictor properties.Thesesubstances also attract many inflammatory cells and causemucosal oedema.

Bronchial muscle tone is controlled via intracellularlevels of cAMP .(cyclic adenosine monophosphate) andcGMP (cyclic guanidine monophosphate). A decrease incAMP in relation to cGMP also results in bronchocons-triction. The autonomic nervous system controls bron-chomotor tone through this pathway. Sympathetic ~receptor stimulation causes bronchodilatation by increasingcAMP levels while sympathetic ex receptor and vagal stimu-lation increase cGMP levels causing bronchoconstriction.

,CLINICAL FIJIATURESThe presen~~ bronchospasm is obvious when wheezesare audible. It is important to remember that all wheezesare not due to asthma. In acute bronchitis, mucosaloedema and secretions can cause wheezing. However,cough and purulent sputum are prominent features ofbronchitis. In children, bronchitis and asthma are oftendifficult to differentiate; hence the necessity for making adiagnosis of 'wheezy' or 'asthmatic' bronchitis. Left

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL.2, NO.4

SUMMARYOxygen therapy may be used in a wide variety of conditionsand with the increased understanding of its indicationsand hazards and the development of portable devices ithas improved the quality of lives of many patients withhypoxia.

SUGGESTED READING1 Oh TE. Intensive care manual. London:Butterworths, 1985.2 Nunn JF. Applied respiratoryphysiology. London:Butterworths, 1987.

N.KORULA

Christian Medical CollegeVellore

ventricular failure should be considered in adults whohave had no previous attacks of asthma. Wheezes can alsobe heard in patients with chronic obstructive airwaysdisease, with chronic bronchitis as a major component.Signs of cor pulmonale, pulmonary hypertension and thecontinuous nature of the respiratory symptoms help indifferentiating bronchitis from asthma. Tropical pulmo-nary eosinophilia may also simulate asthma. An absoluteeosinophil count above 2000 per cumm is an importantdistinguishing feature in patients with tropical pulmonaryeosinophilia.

CLINICAL TYPESAmong asthmatic subjects various clinical subgroups canbe identified.

Extrinsic asthmaThis term is applied to patients who usually have an onsetof disease in childhood, a strong family history of asthmaand atopy, and in whom serum IgE levels are usuallyelevated. On skin sensitivity testing many such patientsmay be found to react to one or more external allergens.

Intrinsic asthmaThis term denotes patients who also have an onset inadulthood, but in whom a family history of asthma is lessevident. IgE levels are usually normal and these patientsdo not react to allergens on skin testing.

Drug induced asthmaIn this type of asthma certain drugs such as acetylsalicylicacid (but not sodium salicylate) and dyes such as tatrazineprovoke asthma by altering the synthesis of prostaglan-dins. Nasal polyps are often an associated finding. Someauthors believe that 10% of asthmatics belong to thisgroup. These patients are worth identifying as avoidanceof the provoking agents can prevent attacks of asthma.