Thoracotomy is associated with severe postoperative pain, which is one of several factors causing postoperative impairment of ventilatory mechanics and gas exchange (1). This especially endangers patients who have preoperative pulmonary impairment, such as those with severe chronic obstructive pulmonary disease (COPD) (2). Atelectasis, shunt, and ventilation-perfusion mismatch, augmented by the influences of residual anesthesia, immobilization, and administration of analgesic and sedative drugs, may adversely affect perioperative ventilation and oxygenation (3,4). Thoracic epidural anesthesia (TEA) might beneficially influence postoperative ventilatory impairment and thus reduce postoperative pulmonary complications (5). Nevertheless, the results available to date are conflicting. Some reports suggest that postoperative analgesia with TEA may attenuate some of those deleterious perturbations in perioperative pulmonary function (6,7). Other authors found no change in the frequency of postoperative pulmonary complications when comparing postoperative epidural analgesia with the systemic administration of opioids (8). However, these studies were performed in patients with normal preoperative lung function.
TEA may cause a decrease in ventilatory reserve, peak negative and positive airflow, inspiratory capacity, expiratory reserve volume, and vital capacity (9,10). Patients suffering from severe COPD actively use abdominal and intercostal muscles for generation of sufficient flow (11). Potential motor block of the abdominal and intercostal musculature after TEA is presumably associated with decreased peak inspiratory and expiratory flow rates (PIFR, PEFR). A decrease in flow rates might limit ventilatory reserve and thus lead to insufficient spontaneous ventilation in end-stage emphysema patients. Furthermore, potential motor block might negatively affect the ability to cough sufficiently after thoracic surgery.
It is well established that the pattern of breathing, ventilatory mechanics, and respiratory muscle function is impaired after thoracotomy as a result of functional disruption of respiratory muscles, postoperative pain, and stimulation of viscera leading to decreased motoneuron output (1). TEA is without doubt beneficial for postoperative pain control (5,7). Nevertheless, it could have several adverse effects on postoperative spontaneous breathing and removal of secretions by means of sufficient cough as discussed above. In previous studies, TEA did not adversely affect ventilatory mechanics in patients with normal lung function and in patients who have mild COPD (12). However, the effect of TEA on ventilatory mechanics in patients with end-stage COPD could vary considerably from the effect of TEA on healthy subjects. Therefore, we performed a study to test the effect of TEA with bupivacaine 0.25% on ventilatory mechanics, breathing pattern, gas exchange, and maximal inspiratory pressure (MIP) in patients who have severe COPD.
We studied 12 patients (6 women and 6 men, all ASA physical status III) with severe COPD, defined as forced expiratory volume in 1 s percentage of predicted value (FEV1%) below 40%, after approval of our IRB. Written, informed consent was obtained from each subject. All subjects were scheduled for lung volume reduction surgery, which was performed after study measurements.
Patients were monitored by using an electrocardiogram (ECG) lead II and a pulse oximeter. A catheter was inserted into a peripheral vein for fluid administration and into the radial artery for invasive blood pressure monitoring and blood gas analysis. After the administration of 10 mL/kg lactated Ringer’s solution, an epidural catheter was inserted at the T4-5 level, and correct positioning was confirmed by an injection of 4 mL of 2% lidocaine with 1:200,000 epinephrine.
Baseline measurements of ventilatory mechanics were performed before insertion of the epidural catheter. After local anesthesia of the nasopharynx with lidocaine spray and administration of three puffs of salbutamol to avoid bronchospasm, an esophageal balloon catheter was inserted via the nose into the esophagus for measurements of ventilatory mechanics. Thereafter, a resting period of 15 min was allowed before baseline measurements of ventilatory mechanics and assessment of arterial blood gas values.
For assessment of ventilatory mechanics, airflow (&OV0312;) was measured by a flow sensor (Varflex, Bicore CP-100 monitor; Bicore Monitoring Systems Inc., Irvine, CA), connected to a tightly adjusted face mask. The fit of the face mask was evaluated by comparing inspiratory and expiratory volumes. A difference of <5% was regarded as sufficiently tight. Our patients were advised to breathe with their mouth closed and to let the entire airflow pass through the nose. They were constantly watched by one of the investigators during measurements via a transparent face mask. Tidal volume was obtained by integration of the flow signal. Airway pressure (Paw) was measured through a catheter attached to the flow sensor and the esophageal pressure (Pes) by a 7 FR nasogastric tube (Varflex; Bicore Monitoring Systems Inc.) incorporating an esophageal balloon (noncompliant polyethylene, 0.8-mL filling volume). The correct position of the balloon catheter was verified by using the occlusion test (13). The esophageal balloon and the flow sensor were connected to a portable monitor that provided a real-time display of &OV0312;, volume (V), Paw, and Pes tracings. Loops of Pes versus &OV0312; and Paw versus &OV0312; relationships were derived from this device.
Minute ventilation (Ve) and breathing pattern, i.e., tidal volume (Vt), respiratory frequency (Rf), the duration of inspiration (TI) and expiration (TE), and the duty cycle (Ti/Ttot) were analyzed from the flow signal.
Total resistive work of breathing (WOB) values were provided directly by the monitor, which calculated the area under the Pes versus lung volume curve (14). The monitoring system provides WOB for each breath. WOB is obtained by integrating the area subtended by Pes and lung volume during a complete respiratory cycle (14,15). Chest wall compliance was not included in our WOB calculations, because the subjects were breathing spontaneously during the entire measuring period.
Pulmonary resistance (RL) was calculated by the Bicore CP-100 monitor as the difference in transpulmonary pressure divided by the difference in flow taken at the same volume during both inspiration and expiration. Four recordings were taken during each breath (16).
Dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) was measured, whereby PEEPi,dyn is equal to the absolute change in Pes from the onset of inspiratory effort to the onset of inspiratory &OV0312;(17). Pes tracings were reviewed before and after TEA to detect activation of expiratory muscles which could influence the results of the measurements. Maximal change of Pes during an entire respiratory cycle (ΔPes) was evaluated for 39 breaths before and after TEA. All measurements were performed in patients quietly breathing room air in a 30° head-up position. During resting conditions, WOB, PEEPi,dyn, and RL were calculated from 39 breaths, after excluding values that differed from the mean by more than two standard deviations. These extreme values are most likely artifacts caused by coughing or swallowing. In addition, the evaluation of the Bicore CP-100 measurements and the calculations performed by the software of the device were satisfactory in end-stage COPD patients (18). An arterial blood gas was drawn and was immediately analyzed during assessment of ventilatory mechanics.
After the above described baseline measurements of ventilatory mechanics, the MIP measured by the flow sensor during a maximal inspiratory effort (Mueller maneuver) against the occluded inspiratory limb was measured. The highest value from three consecutive Mueller maneuvers was used for further data analysis. Patients were allowed a resting period of at least 2 min between maneuvers.
Immediately after the baseline measurements and confirmation of the position of the catheter with lidocaine 2% + epinephrine 1:200,000, 10–12 mL of bupivacaine 0.25% was administered via the epidural route. Spread of anesthesia was tested by means of pinprick test and warm/cold discrimination 45 min after the injection of bupivacaine 0.25%. If spread of anesthesia was found to be satisfactory, i.e., a minimum extension of blockade from T2-8, an arterial blood gas sample was drawn and ventilatory mechanics were measured as described above.
Statistical Analysis and Sample Size
All continuous data are presented as mean and sd. The Kolmogorov-Smirnov goodness-of-fit test indicated that none of the continuous outcome variables showed a significant departure from a normal distribution. Therefore, paired t- tests were used to evaluate mean differences pre- and post-TEA. In addition, repeated-measures analysis of variance was used to determine whether changes in ventilatory mechanics or breathing pattern were independent of patients’ age, height, and weight. A power analysis indicated that a sample size of 13 end-stage COPD patients would provide 90% power to detect a difference of 1 sd (effect size of 1.0) in each outcome variable between pre- and post-TEA (α = 0.05; β = 0.10). Thirteen patients were enrolled although one patient had to be excluded because the spread of anesthesia was insufficient after 45 min. The remaining 12 patients exhibited at least a spread of anesthesia from T2-8. The final sample size of 12 patients decreased the power to 88%, although this was still considered adequate (version 3.0, nQuery Advisor; Statistical Solutions, Boston, MA). All reported P values are two-tailed. Statistical analysis was performed by using SPSS software package (version 10.0, SPSS Inc., Chicago, IL).
Age, preoperative values of vital capacity, FEV1, and residual volume are presented in Table 1. The mean spread of blockade was 8.2 ± 1.3 segments. The minimum caudal extension of blockade was T8 (one patient). One subject had a spread of 5 segments and was therefore excluded from data analysis.
Changes in the pattern of breathing, characterized by Vt, Rf, Ve, and Ti/Ttot, are shown in Table 2. While Vt (P = 0.003) and Ve (P = 0.04) increased significantly after TEA (Table 2), mean RL was 20.7 ± 9.9 cm H2O · L-1 · s-1 pre-TEA and decreased to 16.6 ± 8.1 cm H2O · L-1 · s-1 (P = 0.02) post-TEA (Table 3). PIFR increased significantly from 0.48 ± 0.17 L/s to 0.55 ± 0.14 L/s (P = 0.02) after TEA, whereas PEFR remained unchanged. Table 3 depicts changes in PIFR and PEFR. Repeated-measures analysis of variance indicated that the changes in PIFR and RL were independent of age, height, or weight. PEEPi,dyn, WOB, and Δ Pes (Table 3) demonstrated no significant differences between pre- and post-TEA (all P > 0.50). Whereas Pao2 was not affected by TEA, Paco2 decreased slightly (P = 0.04;Table 2). MIP was 81.7 ± 25.5 cm H2O pre-TEA compared with 76.8 ± 32.0 cm H2O post-TEA (P = 0.79).
The purpose of this study was to test the effects of TEA with bupivacaine 0.25% in patients with end-stage COPD. TEA did not adversely affect ventilatory mechanics, breathing pattern, gas exchange, and inspiratory muscle force generation in these patients.
Ventilatory mechanics were assessed in severe COPD patients before and after TEA with 0.25% bupivacaine; thus, all subjects served as their own control. This approach was chosen to overcome interindividual differences. Bupivacaine 0.25% was preferred over bupivacaine 0.5%, because the later is more likely to cause paralysis of the expiratory muscles (19), and thus, bupivacaine 0.25% seemed preferable for achieving adequate sensory block. After baseline measurements, bupivacaine was administered via the thoracic epidural catheter and “TEA measurements” were performed approximately 45–60 min thereafter. This sequence was used in all subjects to avoid differences in the time course of the experiment.
The accuracy of the measurements provided by the Bicore monitoring system has been found satisfactory in patients suffering from severe COPD (14,18). Nevertheless, changes in respiratory muscle activity during expiration were not assessed directly by means of electromyogram because of ethical concerns. Changes in expiratory muscle activity can markedly influence variables characterizing ventilatory mechanics such as PEEPi,dyn, RL, and WOB (15,17). To eliminate artifacts , original tracings (Pes, Paw, V, and &OV0312;) of 6–10 consecutive breaths were reviewed in addition to the calculation of ΔPes for 39 consecutive breaths (Table 3). No significant difference in ΔPes could be observed between pre-TEA and post-TEA measurements (Table 3). Unchanged PEEPi,dyn and ΔPes values at the two measuring time points indirectly indicate that changes in expiratory muscle activation did not influence our results. Additionally, we observed increased Vt and Ve after TEA (Table 2), which can hardly be achieved during inactivation of respiratory muscles. Furthermore, inspiratory muscle activity evaluated by MIP measurements remained unchanged. Although it seems unlikely that our results were influenced by changes in expiratory muscle activity, we cannot completely eliminate this possibility without direct electromyogram measurements.
Our results were derived from 12 end-stage COPD patients scheduled for lung volume reduction surgery. These patients have extreme respiratory limitation and suffer frequently from attacks of anxiety. Thus, it seemed important to choose the smallest possible sample size for detection of clinically relevant differences. The power of the final sample size to detect a difference of 1 sd in each outcome variable between pre- and post-TEA (α = 0.05; β = 0.10) was 88%. Therefore, a sample size of 12 subjects was deemed to be sufficient for detection of clinically relevant differences.
Vt increased significantly after TEA associated with a significant increase in Ve (Table 2). Several factors may be responsible for this. Patients could have felt increasing discomfort caused by the esophageal balloon catheter, which was kept in place between mea-surements in our study. However, discomfort would more likely lead to an increase in Rf in healthy and especially in severe COPD patients, but Rf was unchanged in our subjects (Table 2). No other reports are available testing the influence of TEA on Vt and Ve without surgical intervention in patients suffering from end-stage COPD. Sakura et al. (20) found a significant decrease in Vt and Ve after TEA in elderly patients with normal lung function. The pattern of breathing is extremely variable in healthy subjects (21), whereas variability decreases with mechanical loading (22). Therefore, it is possible that decreased Vt and &OV0312;e after TEA were coincidentally in the article of Sakura et al. (20).
PIFR (Table 3) and RL (Table 3) increased significantly in our patients after TEA, and PEFR remained unchanged. Our findings of unchanged PEFR agree with those of Yuan et al. (23) who showed that epidural anesthesia with neural sympathetic blockade had no influence on airway resistance in healthy dogs. Groeben et al. (24) also noted that high TEA did not alter airway resistance in patients with bronchial hyper-reactivity. We even found reduced RL after TEA in our end-stage COPD patients, suggesting a beneficial effect of epidural blockade in our patients with severely impaired lung function. However, the mechanism causing the decrease in RL cannot be assessed by the data available.
PEEPi,dyn and WOB remained unchanged (Table 3) in the presence of increased Vt and Ve (Table 2). This is remarkable, because an increase in Ve regularly leads to dynamic pulmonary hyperinflation and an increase in WOB in patients who have severe COPD (11,15,18). Changes in PEEPi,dyn have to be interpreted very cautiously, because active use of expiratory muscles can artificially increase PEEPi,dyn values (23). However, changes in activation of expiratory muscles seem unlikely in our patients, because ΔPes did not change before and after TEA (Table 3). The precondition for unchanged WOB during increased &OV0312;e is decreased RL (Table 3) enabling increased PIFR (Table 3). WOB is an overall variable of ventilatory mechanics. Thus, unchanged WOB in the presence of increased Ve after TEA lead to the conclusion that ventilatory mechanics were not negatively influenced by TEA with 0.25% bupivacaine in our patients who had severe COPD.
A significant decrease in MIP and Vt was observed by Capdevila et al. (25) after cervical epidural analgesia with 0.25% bupivacaine. This would be a potentially dangerous side effect in patients who have end-stage COPD. MIP was unchanged after TEA which suggests that inspiratory muscle force is unaltered after TEA with 0.25% bupivacaine in end-stage COPD patients.
In summary, we observed a significant decrease in RL accompanied by an increase in PIFR and Ve in the presence of unchanged dynamic pulmonary hyperinflation and WOB in end-stage COPD patients after TEA. Inspiratory muscle force was not influenced by TEA. Therefore we conclude, that TEA with bupivacaine 0.25% does not lead to unfavorable changes in ventilatory mechanics, inspiratory muscle force generation, and gas exchange in severely limited COPD patients. Thus, TEA with bupivacaine 0.25% can be used safely in this especially endangered patient subpopulation.
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© 2001 International Anesthesia Research Society
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