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ACUTE SEVERE
ASTHMA: Status Asthmaticus - in the ER and the OR Objectives [He}
presents with a distressing sense of want of breath and a feeling of great
oppression in the chest. Soon the respiratory efforts become violent,
and all of the accessory muscles are brought into play. In a few minutes
the patient is in a paroxysm of the most intense dyspnea. Introduction In
this review, the management of patients with acute severe asthma will
be discussed. The review will not discuss the preparation of the stable
asthmatic for elective surgery. For reviews of this topic the reader is
referred elsewhere.(2) Epidemiology Over
reliance on inhaled beta2 adrenergic agents, underuse of anti-inflammatory
medi- cations, environmental conditions, and lack of appreciation of disease
severity by both patient and physician are often cited as reasons for
increasing morbidity and mortality. Population studies suggest that older
age, black ethnicity, poor socioeconomic status, and psychological problems
are risk factors for developing life threatening asthma.(5) Factors associated
with those at risk for developing severe asthma include: previous severe
attacks (i.e. previous intubation or respiratory acidosis without intubation),
multiple or recent hospital admissions, recent steroid use, and deterioration
while on steroids.(5) Identification
of High Risk Asthmatics Clinical
Features Clinical
Features The degree of wheezing and dyspnea are not reliable indicators of the degree of obstruction.(6) Some patients will have minimal symptoms of dyspnea despite severe airflow reduction. The perception of breathlessness may be more related to the rate of change in airflow than the absolute degree of obstruction (temporal adaptation). Symptoms and signs of airflow obstruction may diminish after treatment despite minimal gains in FEV1 and PEFR. Spirometry is easy to do at the bedside and should be performed on all patients except those that are clearly life threatened. One of the frequently cited avoidable factors in asthma mortality is physician (and patient) underestimation of the degree of airflow obstruction!!! It has been estimated that anywhere between 25% and 89%(5, 7) of asthma deaths are avoidable!!! ABG's usually show a respiratory alkalosis.(8) Normal or increased CO2 implies severe disease although the converse is not necessarily true. Hypercarbia is unlikely unless marked airflow obstruction exists (FEV1 < 20% OR 1 LPM, OR PEFR < 150 LPM).(5) Lactic acidosis is due to hypoxia, overworked respiratory muscles, and intracellular alkalosis from decreased CO2 and should be considered a marker of severe disease. However, beta2 agonists can induce lactic acidosis without the presence of cellular hypoxia. A
chest radiograph is rarely helpful.(5) However, an uncertain diagnosis,
the question of barotrauma or pneumonia, and severe disease warrant that
one be taken. The
differential diagnosis of wheezing includes: pulmonary edema, aspiration,
pneumothorax, anaphylactic / anaphylactoid reactions, mechanical airway
obstruction or compression (tumors, secretions, foreign bodies, laryngeal
dysfunction, tracheal stenosis, tracheomalacia, congenital causes i.e.
vascular ring), pulmonary embolism, and in the intubated patient, misplaced
or obstructed ETT, and surgical compression. Pathophysiology Acute severe asthma may develop rapidly over a few hours (i.e. in response to ASA), or, more commonly, it develops over a number of days.(9) It is only the patients and physicians recognition of the severity of the attack that is acute! Prolonged attacks are more likely to have mucous plugging and bronchial edema. In
asthma, inspiratory muscles hold the lung at high volumes so as to maintain
airway patency and to overcome increased resistance to airflow. Bronchial
obstruction creates areas with low V/Q ratios (hypoxia). In other areas
alveolar distension causes high V/Q zones and increased deadspace (hypercarbia).
The respiratory muscles will have increased oxygen consumption and may
eventually tire, leading to loss of lung volume, more obstruction, and
frank respiratory failure. Alveolar distension and hypoxic pulmonary vasoconstriction
increase pulmonary artery pressures which may impair RV function. Intraventricular
septal shift to the left may impair LV function. Treatment In
some severe cases however, there is so little airflow that inhaled therapy
does not work. Parenteral therapy may be given SC, IV, or, in an emergency,
via the ETT. Salbutamol or epinephrine are the most commonly used parenteral
beta2 agonists Epinephrine may be given as an infusion (2-8 mg/min.),
subcutaneously (0.3-0.5 mg q20-30 min.), or via the ETT (5 ml of 1:10,000).
Salbutamol may given by metered dose inhaler (MDI) with a spacer (4-20
puffs/hour), by wet nebulization (WN) (5-10 mg q 15 min. prn), or intravenously
(4 mg/kg load then 0.1-0.2 mg/kg/min. infusion).(1,5,9,10) Considerable drug is wasted with WN as the predominant part of respiration is expiration hence as little as 1% of drug may actually reach the lungs. A large amount of drug (5-10 mg salbutamol) should be therefore be given frequently (q 15-30 min.).(10) Salbutamol may be given continuously by WN although this may increase risk for toxicity.(10) The optimal delivery technique and appropriate dosing in ventilated patients has not been clearly established as considerable amount of drug is probably lost. If using MDI, use a spacer and increase the dose (? 6-15 puffs/treatment). Higher doses of WN drug are probably appropriate.(12) Whether intubated or not, the dosing of beta2 agonists should be "titrated to effect" using objective and clinical signs of airflow limitation. Dosing cannot be standardized due to the heterogeneity of the disease process (spasm vs inflammation), and the heterogeneity of individual patients responses (? down regulation of beta2 receptors). Overaggressive dosing can cause severe side effects. Anticholinergic agents, although not first line therapy may be of benefit in mild to moderate asthma, and should be used, in addition to beta2 agonists in severe asthma.(1,5,10) In the severely obstructed patient drug deposition tends to be in the more proximal airways which is where cholinergic receptors are located. Ipratropium may be given by MDI (4-8 puffs q15 min.) or by WN (0.25-0.5 mg). The maximum effect is probably reached with 0.5 mg, although more may be required in ventilated patients.(12) Glycopyrrolate and atropine both produce bronchodilation if given IV (atropine 20 mg/kg, glycopyrrolate 10 mg/kg), although there is a high incidence of side effects.(13) They may also be nebulized (glycopyrrolate 1.0 mg, atropine 1.2-2.0 mg) which diminishes the incidence of side effects, particularly with glycopyrrolate.(14) Corticosteroids are invaluable in acute asthma but take 6-12 hours to show an effect - so give early! Methylprednisolone has less mineralocorticoid activity and is cheaper than hydrocortisone. Dexamethasone is cheaper again. Doses shown to be effective are 10-15 mg/kg/day of hydrocortisone or its equivalent (120-180 mg methylprednisolone/day, i.e. 40mg q6h).(15,16) There may be slight improvements with 125 mg q6-8h. Smaller doses may be as effective although firm data is not available.(15,16) There is no role for inhaled steroids during an acute severe asthma attack. Aminophylline is second line therapy.(1,5,10) It is a weak bronchodilator, has a low therapeutic index, and a high incidence of potentially serious side effects. A recent meta anlaysis (17) and several subsequent studies (5,10) have not shown significant improvement in PFT's when aminophylline is added to conventional treatment (beta2 agents plus steroids). Although it has little additive bronchodilatory effect, its other possible actions including increased diaphragm contractility, diuresis, mucociliary clearance, and antiinflammatory action may offer some benefit.(18) If other first line therapy has been unsuccessfully tried, some clinicians will add aminophylline (loading dose of 3-6 mg/kg, infusion of 0.2-0.9 mg/kg/hr). Magnesium Sulfate: There are several small studies that demonstrate improved bronchodilation with the addition of intravenous magnesium to conventional therapy.(19,20) Overall, most studies show only modest improvements in PFT's, and there are also some negative studies.(21) In the doses given (10-12 mmol/20 min) it appears to be a relatively safe agent and can be considered in those not responding to conventional treatment. Magnesium inhibits catecholamine induced arrhythmias.(41) In theory it may not only improve the efficacy of beta2 agonists, but also their safety. Cromolyn
and Nedocromil prevent the release of mediators from mast cells. They
are of no benefit during an acute asthma attack although they may be of
use in the preoperative preparation of a known asthmatic. They are devoid
of any significant cardiovascular effects.(2) Emergency
Drug Doses EPINEPHRINE
(1:1000) IPRATROPIUM CORTICOSTEROIDS AMINOPHYLLINE Intubation The decision as to who and when to intubate is more of an art than a science. Progressive exhaustion, respiratory arrest, decreased level of consciousness, persistent respiratory acidosis (pH<7.2), AND UNREMITTING HYPOXEMIA (SATS<90) ARE CLEAR INDICATIONS FOR INTUBATION.(5,9,12,23) Hypercarbia, although a marker of severe disease, is not an indication for intubation and ventilation. Studies show that the majority of patients with hypercarbia will improve with aggressive use of bronchodilators.(5,24) Recommendations vary regarding the optimum route and technique of intubation. Intubation can be a marked stimulus for bronchospasm. This may be diminished with "deep" anesthesia rather than just "light" sedation. When positive pressure is initiated the markedly negative pleural pressures seen during spontaneous inspiration will become positive, venous return drops, and precipitous hypotension may occur. This can be aggravated by induction agents. Large bore IV's should be in place (some advocate fluid bolusing prior to intubation) and vasopressors should be immediately available. It would seem reasonable to avoid agents that may release histamine. A large ETT is preferred to facilitate suctioning and possible bronchoscopy. Once intubated, many patients will require sedation and paralysis. Thiopental: Controversy exists over the ability of thiopental to constrict the airways when given in lower doses.(2) Large doses may block bronchospasm induced by an irritating ETT but increase the risk of hypotension. Although perhaps suitable for the elective intubation of a stable asthmatic, it may not be appropriate for a patient with severe status. Ketamine: Ketamine causes bronchodilation predominantly due to its sympathomimetic effects. Inhibition of vagal pathways and direct relaxation of smooth muscle are other possible mechanisms of action. It has been used successfully for intubation of asthmatic patients and to improve bronchospasm in ventilated and non ventilated patients.(25,26,27) Exercise caution with regards to its cardiovascular effects when used with other sympathomimetics. Many would consider this the induction agent of choice. Lidocaine: Intravenous lidocaine can reduce irritant induced bronchospasm by blocking airway reflexes (1-2 mg/kg). IV infusions of 1-4 mg/min. may also be helpful.(2) Topical application may induce bronchospasm. Propofol: Propofol's effect on airway tone and reactivity are not clear. There are case reports of its successful use in decreasing bronchospasm in ventilated COPD patients (28) (? direct smooth muscle relaxation). It may be preferable to thiopental for induction and a good choice for sedation of the ventilated asthmatic patient. Anticholinergics: As discussed above the anticholinergic agents (ipratropium and glycopyrrolate) may help block irritant induced bronchospasm via either the IV or inhaled routes (less side effects). Benzodiazepines: Benzodiazepines are commonly used for intubation and sedation and appear to be safe. Narcotics: With the usual caveat of avoiding histamine release there appears to be no major concern with the use of narcotics as an adjunct to intubation or sedation. Neuromuscular Blocking Agents: NMBs can theoretically induce bronchospasm by inducing histamine release or by reacting with muscarinic receptors. It has been suggested that those NMBs that cause histamine release (dtc, atracurium), or that block M2 muscarinic receptors be avoided in the treatment of the acute asthmatic.(2) There has been recent concern over profound muscle weakness developing in asthmatic patients who have received both NMBs and corticosteroids. Although guidelines do not exist, it would be prudent to monitor CPKs, and to minimize the dose and duration of administered NMBs.(5) Cholinesterase
inhibitors may provoke bronchospasm by increasing acetylcholine at
parasympathetic nerve terminals.(2) Muscarinic receptor antagonists can
prevent this, although it may be advisable to avoid using cholinesterase
inhibitors if possible. Ventilation Darioli and Perret (29) achieved 100% survival in their series of 34 patients using the concept of "controlled hypoventilation". Their goals of treatment were to keep peak inspiratory pressures (PIP) < 50 CM H2O (TO AVOID BARO/VOLUTRAUMA), MAINTAIN NORMAL OXYGENATION, AND TO ACCEPT HYPERCARBIA IF NECESSARY. THE SUCCESS OF THIS APPROACH HAS LED TO MANY RECOMMENDATIONS TO KEEP PIP BELOW 50 CM H2O.(9,23) Others feel that due to high airway resistance PIP was a poor predictor of alveolar pressures and of subsequent barotrauma, (5,22) and that controlled hypoventilation decreases barotrauma due to it's effect on DHI rather than PIP. If this is true, attention should therefore be paid to measures of DHI rather than PIP. Hypercarbia and subsequent acidosis are usually well tolerated.(5,9,12,23) In theory, respiratory acidosis may cause myocardial depression and increased CBF (which may be inappropriate in a patient suffering from hypoxia brain injury). The acidosis can be treated with bicarbonate (? treat pH < 7.2). BICARBONATE ADMINISTRATION UNFORTUNATELY INCREASES CO2 PRODUCTION (? CLINICAL SIGNIFICANCE), INCREASES INTRACELLULAR ACIDOSIS, AND CAN POSSIBLY CAUSE METABOLIC ALKALOSIS WHEN THE CO2 IS CORRECTED. Tuxen et al (30) have described a relatively simple way of estimating DHI. They measured the volume of gas that was exhaled during a prolonged apnea (40-60 sec) following a normal ventilator delivered tidal breath. This "volume at end inspiration" (VEI) appears to reflect the severity of DHI (composed of tidal volume and trapped gas). They found that VEI was more predictive of barotrauma than PIP. The most critical factor in determining DHI was minute ventilation (VE). Decreasing the inspiratory flow rate (VI) decreased PIP, but the subsequent obligatory shortening of expiratory time caused an increase in Pplat, VEI, and DHI. Slowing the respiratory rate, or increasing VI prolonged expiratory time (TE) and decreased DHI.(31) It can be misleading to focus on I:E ratios rather than TE. For example, a patient with a VE of 15 lpm (VT1000 x 15) and VI of 60 lpm has an I:E ratio of 1:3. Increasing VI to 120 lpm will impressively increase the I:E ratio to 1:7 but only increase TE from 3 to 3.5 seconds. Decreasing the respiratory rate to 12 and maintaining the VI at 60 will "only" improve the I:E to 1:4 but will increase TE to 4 seconds.(5) PEEP: The role of PEEP in acute asthma is controversial. There are both positive and negative case reports.(9,32) In theory PEEP will splint open airways during exhalation. If the applied external PEEP is less than auto-PEEP there should be little increase in alveolar pressure, and obstructed units could empty due to decreased dynamic airway compression. The risk is increased DHI. Overall there is little evidence to support use of PEEP in the sedated, paralyzed, mechanically ventilated patient. There may be an advantage to using low to moderate levels of PEEP in spontaneously breathing patients as it decreases WOB.(9,23,32) Initial
respirator settings may be as follows: On occasion profound hypotension will occur with ventilated asthmatic patients. This may be a result of barotrauma (pneumothorax) or volutrauma. If due to the latter, disconnecting the patient from the ventilator (apnea) may reduce the DHI and the BP should improve. After
intubation it may be physically impossible to ventilate a patient. The
position and patency of the ETT should be determined and pneumothorax
ruled out. If severe bronchospasm is the likely problem then adrenaline
can be administered via IV or ETT. If related to extreme hyperinflation
then repeated intermittent chest compression during expiration may increase
exhaled gas volume and decrease DHI.(33) Alternative
Treatments Heliox: Due to its low density, high kinematic viscosity, and low Reynolds number, Heliox should decrease airway resistance, flow resistive work, and hyperinflation. A recent report describes dramatic improvements in pCO2 and PIP in 7 patients ventilated with Heliox.(37) There are some logistical (type of ventilator, FiO2 delivered) and financial constraints to using Heliox. ECMO: There are successful case reports of ECMO and ECO2R in severe intractable asthma.(38,39) However, as asthma will likely improve in a few days and hypercapnia is usually well tolerated there are few patients who would require this treatment. Pulmonary lavage: Pulmonary lavage via a flexible bronchoscope has been used to remove mucous plugs in severe unremitting asthma. This is not without risk as DHI may increase during bronchoscopy due to the effects of diminished inspiratory and expiratory flows created by the bronchoscope; obviously a large ETT is required (> 8.0 mm) There is also a risk of hypoxemia, pneumothorax, and infection associated with pulmonary lavage.(40) Suggested
reading: Bibliography
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