Issues in Pulmonary Anesthesiology

¹Salbutamol Prevents the Increase of Respiratory Resistance Caused by Trachial Intubation During Sevoflurane Anesthesia in Asthmatic Children

¹Scalfaro, P, Sly, PD, Sims, C, Habre, W., , Salbutamol Prevents the Increase of Respiratory Resistance Caused by Trachial Intubation During Sevoflurane Anesthesia in Asthmatic Children Anesth Analg 2001; 93: 898-902

• ¹Summary:

  • Based on previous work, the authors have concluded that asthmatic children undergoing endotracheal intubation with sevoflurane will exhibit an increase in respiratory system resistance, Rrs.

  • The present study is described as a randomized, placebo-controlled, double-blinded study to assess whether or not salbutamol (aerosolized) will protect against sevoflurane-induced Rrs.

    • Accordingly, either a placebo or salbutamol was administered 30-60 minutes prior to anesthesia to 30 mildly to moderately asthmatic children.

      • These patients were undergoing elective surgery.

        • Induction utilized sevoflurane in a mixture of 50% nitrous oxide in oxygen and maintained at 3%-the children spontaneously breathing using a face mask with the Jackson-Rees modification of the T- piece.

    • Before and following endotracheal tube insertion, airway opening pressure and flow were determined.

    • Rrs and respiratory system compliance were calculated.

      • Groups were considered similar in terms of age, as the history, breathing pattern, and weight.

    • Intubation under this circumstance resulted in different Rrs responses in the two groups: children pretreated with salbutamol showed about a 6% decrease in Rrs; whereas, a placebo group exhibited about a 17% increase in Rrs.

    • The authors conclude that the data supports the idea that sevoflurane-induced increases in Rrs can be blunted by previous administration of salbutamol, a β₂ adrenergic agonist.

   

• ¹Introduction:

  • The authors provide a brief introduction concerning asthma, noting that bronchospasm can be induced by different stimuli associated with the perioperative timeframe.

    • Endotracheal intubation probably  induces acetylcholine release from postganglionic parasympathetic cholinergic nerve terminals, thus producing bronchospasm via a vagel reflex mechanism.

    • If asthmatic children did not receive their routine asthma medication before anesthesia, increased Rrs occurred when intubation involved sevoflurane.

      • Assessment of  pre-existing asthmatic inflammatory state severity is an important issue.

    • There is a marker of eosinophil activation called the eosinophilic cationic protein (ECP). Eosinophil activation is important in respiratory epithelial stimulation as well as induction of factors promoting bronchial smooth muscle contraction.

    • Accordingly,  ECP levels may be used to assess severity of asthma as well as the response of the condition to treatment.

    • The reason this point is introduced is that ECP levels were measured in the present study to determine if increased ECP levels correlated with Rrs increases following intubation.

  • The hypothesis in the study was that inhaled salbutamol would prevent Rrs increases following tracheal intubation under sevoflurane in asthmatic patients (children).

• ¹Methods

  • Asthmatic children used in the study had an age range of 2-13 years. The surgery was elective, requiring general anesthesia and endotracheal intubation.

    • ASA classification was either I or II.

    • Patients exhibited episodic asthma with wheezing over the preceding 12 months, had been clinically diagnosed and treated using inhaled drugs.

    • In order to detect possible bias within the groups, patient history for asthma symptoms, asthma medications, and smoking exposure were determined.

    •  Exclusion criteria included: recent (two weeks) upper respiratory infection, symptomatic presentations at enrollment time, and children with obstructive apnea.

  • Patients did not receive their anti-asthma medication on the surgical day and were randomly assigned to receive 30-60 minutes prior to anesthesia either 200 μg salbutamol or placebo.

  • Randomization was based on the table generated at the beginning of the study; the table utilizing a normal random function generator.

  • The pressure metered-dose inhalation canister was double blinded -- i.e. made available through the respiratory department.

    • The placebo canister contained only propellant; canisters were similar to those routinely used in patient education.

    • All subjects had anesthesia induced with sevoflurane (up-to-8%) in a mixture of 50% nitrous oxide in oxygen (total fresh gas flow was 6 L/min.) until an IV line was secured and a blood sample for ECP assay drawn.

    • Maintenance anesthesia utilized 3% sevoflurane; breathing was spontaneous vis face mask, utilizing Jackson-Rees modification of the T- piece.

    • The first set of measurements of airway opening pressure (Pao) and flow (V') was obtained upon achieving steady-state end-tidal sevoflurane concentration of 3%.

      • At that point sevoflurane concentration was increased to 5% and end-tidal anesthetic concentration monitored until 95% ED (effective dose) for endotracheal intubation was obtained. This turned out to be 4.68% at 95% confidence interval [3.91%-12.74%].

    • Following oral endotracheal tube insertion, spontaneous respiration was re-established during 3% sevoflurane administration [corresponding to 1.2 MAC]; sevoflurane anesthesia was provided in a mixture of 50% nitrous oxide in oxygen.

      • At this point respiratory mechanic measurements were repeated.

      • These measurements were obtained under the same concentration of carrier gas, 50% nitrous oxide in oxygen.

    • The pressure port transducer was used to measure Pao with a heated screen pneumotachograph used to measure V', (see ref 1 for equipment details);  the system was placed between the patients face mask or endotracheal tube and the Jackson Rees modification of the T- piece.

      • The following equation was used in the calculation of respiratory mechanical values, where V is  tidal volume and P_A,EE is the end-expiratory alveolar pressure. Multiple linear regression was used to estimate the coefficients Crs (dynamic compliance) and Rrs. The directly measured values again were Pao and V' (flow).

•  Unpaired two-tailed Mann-Whitney U-test was implemented to compare demographic data.  Kruskal-Wallis nonparametic analysis of variance was used for respiratory variable assessment.  Fisher's exact test was implemented for categorical data analysis.  Dunn's multiple comparison correction was used as needed. Significance was defined at 0.05; Data presented as the mean +/- standard error of the mean (SEM)

• Results:

  • The number of participants took into account a number of individuals who either refused participation or who were excluded for methodological reasons.

    • For example, 5 of the 35 consecutive eligible patients refused to participate.

    • Data from an additional 6 patients were discarded for methodological reasons, that is 3 salbutamol and 2 placebo patients exhibited evidence of active expiration and therefore results from these patients could not be fit to the mathematical model; furthermore, one patient exhibited laryngospasm prior to measurements.

  • The two groups were considered comparable with respect to height, weight, age, gender, and size of endotracheal tube.

    • Furthermore, no difference between groups were noted with respect to asthma history or in terms of previous/current asthma management.

  • Four patients in the placebo group and three in the salbutamol group had been hospitalized for asthma during the preceding year, although none had been admitted to ICU.

    • With respect to frequency of symptoms, symptom occurrence at night or morning, and symptoms associated with exercise or infection, these endpoints were similar between groups.

  • The mean ECP (eosinophilic cationic protein) was 15 +/- 2.8 /L in the placebo group and 16.9 +/- 3.6 /L in the salbutamol group.

    • Three patients in each group exhibited ECP levels > 20 /L corresponding to the 97 percentile in a normal pediatric population distribution.

    • No correlation was noted between ECP levels and Rrs before after intubation within groups or for the two groups combined.

• Baseline and ventilation variables and associated respiratory mechanics were not different between groups (+/- salbutamol) during spontaneous face mask breathing at 3% sevoflurane in a mixture of 50% nitrous oxide in oxygen.

• Following intubation no difference in tidal volume (V), respiration rate, or expiratory time within or between groups was noted.

• Percentage change in Rrs between groups was noted, despite similarity in mean Rrs.

  • Rrs increased by about 17% (95% confidence interval, + 4.4% to + 3.9%) in the placebo group; Rrs decreased by 6% (- 25.2% to + 13.2%) in the salbutamol group.

  • A larger proportion of patients in the placebo group increased their Rrs following tracheal intubation compared to salbutamol pretreated patients. [placebo: 11 of 12; pretreated 6 of 13]

  • Single history items or ECP values were not helpful in predicting Rrs increases in either group.

    • No change in dynamic compliance (Crs) was noted in either group.

• ¹Discussion:

  • The study indicates that salbutamol appears effective in preventing increase in total Rrs following endotracheal intubation under sevoflurane and mild-to-moderate asthmatic children.

    • These results are consistent with other results indicating that in adults +/- asthma, inhaled ₂ adrenergic agonists given prior to surgery prevents increases in lung resistance following endotracheal intubation.

  • In this study patient asthma was well-controlled and the children received inhaled medication until the surgical day.

    • A significantly larger proportion of patients who received salbutamol (compared to placebo patients) exhibited the Rrs decrease following endotracheal intubation; however, this effect was only noted in about 50% of treated patients.

    • Respiratory mechanics can be divided into two components-an airway component and a parenchymal component.

      • Salbutamol would affect the airway component but presumably would not affect the tissue "visco-elastic" component (parenchymal).

        • Increases in resistance therefore caused by this parenchymal component could explain why all members of the salbutamol group did not exhibit reduced Rrs.

  • Preoperative assessment might be useful in identifying specific asthmatic children and particularly those at high risk for bronchospasm.

    • However, this study suggests difficulty in identifying an individual patient' s risk.

    • Clinical history was not useful in determining ahead of time which children would exhibit increased Rrs on intubation.

      • In this study serum ECP levels were also not useful in predicting Rrs response to endotracheal intubation, although ECP, in general, has been suggested to be a useful marker for airway responsiveness in mild asthmatic children and ECP determination might be (become) an objective asthma severity measurement approach.

  • Another possibility for predicting bronchial hyperreactivity would be direct preanesthetic lung function tests.

    • However, such lung function measurements might be difficult to obtain in all children, according to these researchers.

    • They did apply a technique to assess respiratory mechanical properties. The multilinear regression technique (MLR) results in a weighted average for Rrs and dynamic compliance (Crs) through the respiratory cycle.

      • Since expiration is considered entirely passive, Pao (airway opening pressure) would be the driving pressure applied to the respiratory system to overcome combined resistive and visco-elastic forces of the lung-thorax system, following from equations of motion.

    • In this study respiratory mechanic parameters were calculated without measurement of esophageal pressure; moreover, use of data collected during only passive expiration avoids possible leak effects around the endotracheal tube.

  • This study concludes that since salbutamol prevents increases in Rrs in asthmatic children having tracheal intubation under sevoflurane induction,  use of inhaled  β₂ adrenergic agonists before anesthesia with endotracheal intubation may be generally beneficial.

  • A larger trial was thought necessary to evaluate potential clinical benefits of this intervention with outcomes such as reduced perioperative respiratory adverse events being assessed. Further study of the possible effectiveness of serum ECP level determinations was also considered warranted.