Role of Autonomic Nervous System and Bronchial Hyperreactivity
Parasympathetic nervous system is the dominating neural system for the regulation of bronchial tone. Irritant receptors are stimulated and send signals via parasympathetic afferent fibres to the central nervous system, where the efferent response is expressed in cough and bronchoconstriction. At the level of the parasympathetic ganglia efferent impulses are passed on via vagal fibres and muscarinic receptors. Basically M1, M2 and M3 receptors are involved. M1 receptors are found at the corpus of the parasympathetic ganglionic cells and enhance parasympathetic activity, while M2 receptors located on the neural site of the parasympathetic synapses, serving a negative feedback mechanism. Thus, M2 receptor stimulation inhibits an overshoot of parasympathetic activity. A destruction of the M2 receptors, as occurs in the course of certain viral infections, can temporarily cause bronchial hyper-reactivity with asthma-like symptoms. Finally, M3 receptors are located mostly on smooth muscle cells and cause smooth muscle contraction.
Muscarinic antagonists like atropine ipratropium bromide and glycopyrrolate have been used to treat pathological bronchoconstriction. However, all three substances are nonselective and cause blockade of all three receptor types. Unfortunately, in low doses these substances can affect the function of M2 receptors more than the function of M1 or M3 receptors, with the effect of a paradoxical bronchoconstriction. In higher doses all three receptors are blocked and lead to bronchodilation. The development of more M2 and M3 receptor-specific agents like thiotropium may hopefully enhance the effectiveness of parasympatholytic agents.
The effect of direct sympathetic innervation is mediated via sympathetic fibres and β1-adrenergic receptors. In
contrast to the effect of parasympathetic innervation of bronchial tree, the effect of direct sympathetic innervation
seems to be negligible. A blockade of the pulmonary sympathetic innervation by thoracic epidural anesthesia
does not lead to increased bronchoconstriction, but is overridden by the systemic effect of the local anesthetic
and even attenuates bronchial reactivity. However, besides only a small number of β1-adrenergic receptors, the bronchial tissue is provided with a large number of β2 -adrenergic receptors; β2 -adrenergic receptors are stimulated not by direct sympathetic innervation but by circulating catecholamines. Therefore, blockade of β2-adrenergic receptors by nonspecific β-adrenergic receptor blockers can lead to increased airway resistance and acute bronchospasm, while β2-adrenergic agonists are a cornerstone of the treatment of obstructive airway diseases.
Effect of High Central Neuraxial Blockade on Bronchial Tone
There is a concern among many anesthesiologists that high thoracic sympathetic blockade of the bronchial tree may provoke bronchospasm. In a well-controlled study, Groeben, et al. assessed the effect of TEA (Thoracic Epidural Anesthesia) on airway resistance in patients with bronchial hyperactivity. Blockade of pulmonary sympathetics (T2- T7) with thoracic epidural local anesthetic not only did not change airway resistance, but actually attenuated the response to an inhalational provocation with acetylcholine, suggesting a therapeutic benefit of TEA. Interestingly, a control group of patients who received similar doses of local anesthetic intravenously also demonstrated attenuation of the response to the inhalational provocation, suggesting that the therapeutic benefit may be due to systemic levels of local anesthetic.
Stepped-Care Approach to Asthma Treatment
This simplified stepped-care approach to asthma treatment (Fig. 3.2) is constructed around the central role of inhaled corticosteroids. For each of the overlapping steps, the dose of the inhaled corticosteroid can be adjusted as needed to achieve the goal of well-controlled asthma while minimizing the long- term risks associated with high doses. LABA denotes long- acting β-agonist, LTM leukotriene modifier, LTRA leukotriene- receptor antagonist, and SABA short-acting β-agonist.
Classification of Severity of Bronchial Asthma Exacerbation
Table 3.7 describes the classification of the severity of bronchial asthma exacerbation with salient features.
Management of Asthma Exacerbations in the Emergency Department
Management of asthma exacerbations in the emergency department and hospital-based treatment, as recommended bytheNationalAsthmaEducationandPreventionProgram is given in Figure 3.3. (Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma).
Perioperative Steroid Coverage (Stress Dose)
Although the question is controversial, suppression is difficult to predict.
Patients with long-term steroid therapy
Most experts still recommend perioperative steroid coverage for patients who are receiving more than 5mg/day of prednisone or an equivalent and for patients who have recently stopped long-term steroid therapy.
The stress dose should be proportionate to the severity of surgical stress and should be given for no longer than 1 to 3 days perioperatively.
The physiologic rationale for steroid coverage is that long-term corticosteroid therapy for chronic autoimmune
or inflammatory diseases (such as rheumatoid arthritis, ulcerative colitis, or asthma) suppresses the hypothalamic- pituitary-adrenal (HPA) axis. In normal patients, severe illness, trauma, stress, and surgery are accompanied by activation of the HPA axis. Patients with HPA axis suppression from long-term corticosteroid therapy may be unable to produce this physiologic response to stress.
Patients with a history of steroid use
Some patients previously treated with glucocorticoids should also receive steroid coverage. The literature suggests that, in some patients, the HPA axis may not recover for up to a year after glucocorticoid therapy is stopped, so it would be reasonable to prescribe supplements for patients who have stopped long-term glucocorticoid use within the past year. On the other hand, stress doses are not required for patients who have recently received short bursts of corticosteroids (therapy lasting 1 week or less), because in these patients, HPA function recovers within 1 week.
Consensus Recommendations on Doses
Perioperative management of adrenal insufficiency is based on the anticipated glucocorticoid requirements for a given level of stress. Doses that have historically been given as “stress coverage” are often excessive when compared to studies of perioperative corticosteroid production by healthy patients. Maximal cortisol secretion is about 300 mg in the 24 hours following surgery. More typically, secretion is 75 to 150 mg in 24 hours following major surgery, and less for minor procedures. Although short term, high dose steroids are generally well tolerated, excess glucocorticoids could play a role in impaired wound healing, increased blood glucose or increased susceptibility to infection in the perioperative setting. Thus, adjusting steroid supplementation to the estimated level of physiologic stress is now routine, with doses ranging from simple maintenance of baseline medication for minor procedures to 300 mg hydrocortisone over 24 hours for major surgery and severe postoperative complications.
Currently, there is no evidence to support a single, definitive approach concerning the preoperative evaluation and perioperative management of the patient on steroids. The degree of risk for perioperative adrenal insufficiency, the optimal diagnostic test(s) for adrenal function, and the appropriate doses of perioperative steroid coverage are somewhat controversial. Preoperative consultation should include a clinical assessment of the patient’s risk for adrenal insufficiency under stress, based on underlying diseases and the prior use of therapeutic glucocorticoids. When uncertainty exists, options include preoperative testing with an ACTH stimulation test or empiric glucocorticoid
supplementation. Perioperative steroid doses should be based on the degree of physiologic stress and can be tapered rapidly with recovery. Even with a “normal” ACTH stimulation test, adrenal insufficiency should be considered in the surgical patient with unexplained or refractory hypotension.
Recommendation perioperative hydrocortisone dosage for patients on long-term steroid therapy
The guidelines are summarised as given in Table 3.8.
Steroid Equivalent Doses
The knowledge of the equivalent doses of steroids (Table 3.9) is necessary while assessing for adrenal suppression.
The term Cushing “syndrome” refers to the mani-festations of excessive corticosteroids, commonly due to supraphysiologic doses of corticosteroid drugs and rarely due to spontaneous production of excessive corticosteroids by the adrenal cortex. About 40% of cases are due to Cushing “disease,” by which is meant the manifestations of hypercortisolism due to ACTH hypersecretion by the pituitary. Cushing disease is caused by a benign pituitary adenoma that is typically very small (< 5 mm) and usually located in the anterior pituitary (98%) or in the posterior pituitary (2%). It is at least three times more frequent in women than men.
Patients with Cushing syndrome usually have central obesity with a plethoric “moon face,” “buffalo hump,”
supraclavicular fat pads, protuberant abdomen, and thin extremities; oligomenorrhea or amenorrhea (or impotence in the male); weakness, backache, and headache; hypertension; osteoporosis; avascular bone necrosis; and acne and superficial skin infections (Fig. 3.4). Patients may have thirst and polyuria (with or without glycosuria), renal calculi, glaucoma, purple striae (especially around the thighs, breasts, and abdomen), and easy bruisability. Wound healing is impaired. Mental symptoms may range from diminished ability to concentrate to increased lability of mood to frank psychosis. Patients are susceptible to opportunistic infections.