Co_exist1

Anesthesia Pharmacology Chapter 34: Anesthesia in the Asthmatic Patient and Related Issues

³Interaction of Sympathomimetic Drugs with other Agents Used in Anesthesia
³- adrenergic agonists used in management of asthma, drugs that include terbutaline, aminophylline, and theophylline are. sympathomimetic agents that can interact with volatile anesthetics. A consequence of this interaction may be induction of cardiac arrhythmias. Halothane is one example of a volatile anesthetic that sensitizes the heart to exogenous catecholamines. In this context, sensitization means that a reduced amount of epinephrine (IV) would be required to induce a premature ventricular contraction (PVC) in the presence of halothane compared to that in a normal, unanesthetized individual. If halothane is used, a dosage of 0.15 ml/kg of a 1:100000 epinephrine solution over a 10 minute. (Not to exceed 0.45 ml/kg of a 1:100000) is thought to be safe. Furthermore, lidocaine given in combination with epinephrine provides additional safety margin. Enflurane and isoflurane appear to cause less myocardial sensitization compared to halothane. Halothane is a potent bronchodilator and accordingly may be the best choice for anesthetizing asthmatic patients. However, if the asthmatic patient is already taking exogenous catecholamines or xanthines, halothane might not be most appropriate. ³The mechanism of action by which xanthines promote bronchodilation appear to include xanthine-mediated endogenous norepinephrine release as well as possible inhibition of phosphodiesterase, which breaks down cAMP. This latter mechanism may be questionable because of the high concentrations required for xanthine-mediated phosphodiesterase inhibition. However perhaps 40% of aminophylline's positive inotropic effect may be due to promotion of endogenous norepinephrine release. ³Plasma theophylline concentrations of 5 mg/L is required to decrease the high airway resistance; furthermore, if levels exceed 20 mg/L, toxicity may occur. Theophylline is metabolized by the liver, exhibiting a half-life of about four h in adults with a clearance of 1.2 ml/min./kg. [Aminophylline is composed of 85% theophylline and 15% ethylenediamine]. Because of toxicity concerns, factors that reduce clearance become important. Such factors include liver disease or pulmonary edema which can reduce theophylline clearance by 50% (liver) and 33% (pulmonary edema). In the laboratory setting, aminophylline and halothane interaction has been documented. The administration of 1% halothane with high dose, bolus aminophylline resulted in a significant number of ventricular arrhythmias in dogs (12/16) with 8/16 exhibiting ventricular tachycardia fibrillation. Based on this analysis, it would appear reasonable to wait three drug half-lives following the last aminophylline dose prior to administering anesthesia to an asthmatic patient. An alternative to halothane for those patients who require aminophylline or other sympathomimetic agents might be the substitution of halothane by enflurane or isoflurane which either of which is less likely to sensitize myocardium to catecholamines.

⁴Case Study: Management of Status Asthmatics in a Parturient
⁴Que, JC and Lusaya, VO Sevoflurane Induction for Emergency Cesarean Section in a Parturient in Status Asthmaticus, Anesthesiology, 1999; 90: 1475-1476. This case report considers the use of sevoflurane for induction of anesthesia in a parturient with status asthmaticus. The context is emergency cesarean section. This circumstance is considered complex because the patient probably has received various medications and because of additional medical complications having to do with preterm labor and asthma. Sevoflurane is considered in view of its non-irritating character as well as its low blood-gas partition coefficient. The patient is a 41-year-old multiparous woman and 33-34 weeks gestation. Admission occurred following an acute asthmatic attack, bronchopneumonia, as well as labor pains. This patient had childhood-onset asthma and had experienced acute worsening during the fifth month of pregnancy. At that time and endoracheal intubation had been required. As a result of previous experience, the patient had indicated an "allergy" to salbutamol, aminophylline, and theophylline indicating that these agents caused palpitations, confusion and headache. At the time of admission, the patient was described as dyspneic, with a respiratory rate of 24, productive cough (greenish phlegm) and intercostal retractions. Oxygen was administered (nasal cannula; 32% inspired fraction). Also, the patient received nebulized terbutaline alternated with fenoterol-ipratropium bromide every four hours and the patient was also started on 100 mg IV hydrocortisone every 6 hours, 750 mg cefuroxime every eight hours as well as terbutaline drip at 15 mcg/min. for tocolysis. Laboratory data: hemoglobin 9g/dl, hematocrit 0.29 serum sodium: 139 mEq/l, serum potassium 2.2 mEq/l arterial blood gases; pH 7.51, P_CO244 mmHg, P_O2 88.9 mmHg, HCO₃ 35.3 mEq/l, SpO₂ 97% At this point the terbutaline infusion rate was reset to 10 mcg/min. and 35 mEq KCL was added to the IV fluid. On the fourth day following admission, respiratory rate increased to 32/min. and the patient could not tolerate the supine position. Following transferred to the ICU, continuous hydrocortisone (0.4 mg/kg/min.) infusion was initiated and enoxaparin (2000U; daily) started. The individual became refractory to all medication and began active labor on the fifth hospital day; at this point, serum sodium was 139 mEq/l and potassium and decreased to 2.0 mEq/l. Terbutaline was discontinued and vaginal delivery was planned; therefore, oxytocin was started slowly (drip). Shortly thereafter, spontaneous membrane rupture revealed meconium-stained amniotic fluid; moreover, fetal heart rate monitoring indicated periods of deceleration. Emergency cesarean section was planned in the patient prepared. At this point, the patient was in a sitting position with orthopnea and was exhibiting both inspiratory and expiratory wheezes. Gasping between each word was noted and supraclavicular and intercostal retractions also noted. Given both the absence of a pre-existing epidural catheter and the extent of fetal maternal distress, general anesthesia was considered. General anesthesia with sevoflurane 7% (6 l/min oxygen.) following fentanyl 15 mcg IV was induced while the patient was in a sitting position. Within 30 seconds of slow, deep breathing, the patient no longer responded to verbal commands yet spontaneous ventilation continued. Oxygen saturation remained at 98% during induction. Vecuronium 0.1 mg/kg [succinylcholine was not available] and lidocaine 1.5 mg/kg were administered intravenously while cricoid pressure was applied. Intubation occurred atraumatically after 2.5 minutes; the patient having been ventilated by mask and bag before that point. Tube depth was considered appropriate based on auscultation; some expiratory wheezing was also noted. At the time of surgical incision, the sevoflurane concentration was reduced to 2%. Four minutes after induction and within 90 seconds of incision, the baby was delivered with Apgar scores of 5,8, 9 and 1,5, and 10 minutes respectively. Following placental delivery, uterine bleeding of 1.5 l was noted along with declining blood pressure from 1 20/70 mm Hg to 60/40 mm Hg. Sevoflurane was temporarily discontinued eliminating the possibility of its role in promoting blood loss. Oxytocin infusion was re-initiated lactated Ringer's solution infused rapidly and IV ephedrine (20 mg) was given. Uterine contraction improved with bleeding eventually controlled and blood pressure stabilized at 100/70 mm Hg. At this point, sevoflurane was administered again, maintained at 2%. The patient was discharged four days later following an uneventful recovery. The authors raise the following points in their discussion of the case: This patient was both dyspneic and restless in the sitting position and as such was not considered a good candidate for regional block. Regional block could worsen oxygen delivery to the mother and the fetus; furthermore, the hypokalemia secondary to terbutaline administration could be worsened. Enoxaparin administration represents a relative contraindication for regional block. For cesarean section, local infiltration analgesia might be used; the problem here is that the amount of local anesthetic required might induce systemic toxicity. Furthermore, the patient and the fetus were in distress and given the above considerations, emergency cesarean section was considered the best course of action. Another consideration has to do with choice of induction agents. With respect intravenous agents: Thiopental has been found to not reliably protect against reflex-induced bronchospasms at the dosage typically used clinically for induction. Propofol possibly results in less wheezing than thiopental; however, the particular study which reached this conclusion included patients who were not wheezing before induction-- thus complicating analysis and interpretation. . Another alternative is ketamine which does reduce airway resistance in asthma patients and has been recommended for general anesthesia induction for cesarean section at a dosage of 1 mg/kg. A problem here is that the ketamine concentration required for bronchodilation is above 1 mg/kg dosage; furthermore, in patients that have already received sympathomimetic agents (hypokalemia and increased sympathetic tone), the addition of ketamine may lead to hypertension and arrhythmias during induction. In the absence of IV access, sevoflurane has been suggested to be an appropriate emergency cesarean section inhalational agent. The rationale includes the drug's low blood-gas solubility (0.69), increased min. ventilation, and reduced functional residual capacity and MAC associated with pregnancy-all factors which speed induction. Sevoflurane is also noted to have limited or no airway irritation and itself may promote bronchodilation. By comparison to halothane, sevoflurane is less likely to promote arrhythmias and more likely to ensure hemodynamic stability even though adrenergic agonists action may still be present secondary to drugs given earlier. In this case uterine bleeding and hypotension noted following placental delivery could occur as a result of enoxaparin administration. Enoxaparin is a low molecular weight heparin form; however, causal relationship has been difficult to establish. In general surgery, low molecular weight heparin may be associated with more bleeding. Sevoflurane (as well as other volatile agents) will in a dose-dependent manner depress uterine contraction and might contribute to increased blood loss. In this study 2% sevoflurane (vaporizer concentration) did not apparently interfere with uterine response to oxytocin which allowed maintenance of a contracted uterus. This case study indicates the possibility that sevoflurane inhalational anesthesia in a parturient also in status asthmaticus may be a reasonable choice in support of cesarean section, also noting that fetal distress was present.