Hypercapnia has been used in conjunction with hyperventilation to provide a more rapid return of responsiveness after inhaled anesthesia with more soluble drugs (1–3). In a recent clinical study with isoflurane, we confirmed that the time from turning off the vaporizer to opening of eyes was shortened by an average of 62% when the minute ventilation was increased and the end-tidal CO2 (Etco2) was kept at 52 mm Hg rather than 28 mm Hg during emergence (4). The current study was conducted to see if hypercapnia with hyperventilation accelerates recovery proportionately for less soluble anesthetics such as sevoflurane and desflurane. A proportional decrease might be anticipated and would mean that the absolute decrease would be less because recovery is more rapid with desflurane and sevoflurane than with isoflurane.
After IRB approval, we obtained written consent from 32 ASA Class I or II patients scheduled to have elective surgery (Table 1). When we assumed that recovery times would change by the same proportion for desflurane as they did for isoflurane, a power analysis suggested that a sample size of six patients in each desflurane group would have 99% power to detect a difference in means of 5 min (the difference between a Group 1 mean, μ1, of 3 min and a Group 2 mean, μ2, of 8 min) assuming that the common standard deviation is 1.64 min using a two group t-test with a 0.05 two-sided significance level (nQuery advisor 6.0). We took a conservative approach and enrolled eight patients in each group.
All patients underwent general anesthesia lasting more than 1 h. Each patient was premedicated with 1–2 mg of midazolam. Anesthesia was induced with propofol and maintained with 2% sevoflurane or 6% desflurane in oxygen (Table 1). After tracheal intubation, the respiratory rate was set at 8 breaths/min and the tidal volume was adjusted to keep the Etco2 concentration at 33 mm Hg (Narkomed II, North American Dräger, Telford, PA). A gas analyzer measured the inspired and Etco2 and anesthetic concentrations continuously (Datex AS/3, Datex-Ohmeda, Helsinki, Finland). A continuous infusion of remifentanil was used as an adjunct to the inhaled anesthetic, so that the same level of sevoflurane and desflurane could be used in all groups despite differing levels of surgical stimulus. Remifentanil infusions were discontinued at least 10 min before turning off the vaporizer. Opioids (fentanyl, morphine and/or dilaudid), titrated to meet the patient’s need for analgesia, were not administered during the hour before turning off the vaporizer at the end of surgery. The total amount of opioid given is reported in Table 1 as fentanyl equivalents. Pressors and fluids were used as needed to maintain adequate hemodynamics when decreased surgical stimulus would otherwise require the tapering of anesthetic.
When the surgeon applied the first adhesive wound closure strip, we turned off the vaporizer and increased the oxygen flow to 10 L/min. A coin was tossed at the beginning of the study to determine which of the next six patients were alternatively hyperventilated and kept hypercapnic during emergence. For the hyperventilated patients, we increased the respiratory rate to 16 breaths/min, increased the tidal volume as needed to double the minute ventilation (as measured by the Narkomed II), and inserted the device (shown in Fig. 1) between the endotracheal tube and the breathing circuit “Y” piece, with the rebreathing hose fully extended to 822 mL. We shortened the length of the rebreathing hose as needed to prevent the Etco2 concentration from increasing >55 mm Hg. In the patients who were not hyperventilated, we left the respiratory rate and tidal volume unchanged. However, the increase in oxygen flow to 10 L/min resulted in a slight increase in tidal volume delivered by the Narkomed II ventilator and a modest decrease in the Etco2, as reported in Table 1.
We recorded the time from when the vaporizer was turned off until the patients first opened their eyes or their mouths, after calling them by name every 30 s and making the request to open their eyes. Once the eyes were open, the patients were asked to open their mouths every 15 s. The effect of the method of emergence on time to eye and mouth opening were compared using a two-way ANOVA with SigmaStat version 2.03 (SPSS Inc.). Post hoc Bonferroni tests were performed when interaction effects were found to be significant.
Table 1 shows that for both anesthetics the two groups (with and without hypercapnia–hyperventilation) were not statistically significantly different with respect to demographics, the duration of anesthesia, or the total amount of IV drugs administered. The table shows that differences in the Etco2 (hypercapnia) and minute ventilation (hyperventilation) were statistically significant during the recovery period. Table 2 shows that the times to open eyes and open mouth after turning off the vaporizer were shorter with hypercapnia and hyperventilation, which proves our initial hypothesis. Both differences were statistically significant (P < 0.05).
In this study we found that hypercapnia with hyperventilation shortened the recovery time by 6.4 ± 0.8 min after sevoflurane and by 5.2 ± 0.3 min after desflurane. In an earlier study, we found a 10.2 ± 2.0 min shorter recovery after isoflurane (4). The decrease in recovery time (time to open eyes after turning off the vaporizer) was proportionately the same, and appears to be independent of solubility: 52% after sevoflurane, 64% after desflurane, and 62% after isoflurane. The absolute recovery times remained shorter for the less soluble anesthetics, sevoflurane, and desflurane.
Our findings confirm previous results with other anesthetics showing that hypercapnia with hyperventilation accelerates recovery (2,5). Anesthesiologists who use hypercapnia with hyperventilation after 1 MAC of isoflurane can expect recovery times (time to open eyes) of 6.2 ± 2.1 min, which are faster than that expected by those who use normocapnia and normal ventilation after desflurane (8.2 ± 1.3 min). Those who use 1 MAC of desflurane and choose to also use hypercapnia with hyperventilation can expect recovery times of 2.9 ± 1.0 min. Return of responsiveness normally occurs when the cerebral concentration of the inhaled anesthetic decreases to <0.34 MAC (6,7). If the desflurane concentration can safely be reduced near the end of a surgical procedure to 0.6 MAC, the transition from 0.6 to 0.34 MAC and return of responsiveness might occur within 1.5 min.
Hyperventilation without rebreathing of anesthetic rapidly removes anesthetic from the lungs, keeps the alveolar concentration low, and maintains a high anesthetic concentration gradient between pulmonary capillary blood and alveolar gas. Hypercapnia causes cerebral arterial smooth muscle to dilate and cerebral blood flow to increase by as much as 6% per mm Hg change in Paco2 (8,9). If the concentration of anesthetic in the arterial blood is less than the brain concentration, the higher cerebral blood flow will cause more rapid clearance of volatile anesthetic from the cerebral tissue. Theoretically, hypercapnia may shorten recovery time by a slightly smaller percentage for sevoflurane than for the other two anesthetics because the change in cerebrovascular resistance with a change in Paco2 is less for sevoflurane than for isoflurane and desflurane (10). A smaller percent increase in cerebral blood flow with hypercapnia and sevoflurane might lead to slower clearance of sevoflurane from the cerebral tissue and a proportionately slower recovery. In our study, hypercapnia seemed to shorten recovery time by a smaller percentage with sevoflurane (52%) than it did with desflurane (64%) and isoflurane (62%); however, this difference was not statistically significant. Differences in the brain/blood partition coefficient will also play a role in the rate of recovery (11).
Our study has several limitations. The observer who recorded the time when the patients opened their eyes and mouths was not blinded to the presence or absence of hypercapnia, hyperventilation, or the rebreathing hose. However, the observations of eye and mouth opening are objective measures. In addition, the randomization procedure was done by a coin toss at the very beginning of the case. It would have been better to have waited to alert the anesthesiologist to the allocation until just before emergence. The decision as to the type of supplemental opioid and the amount to give could have been biased because of the group allocation. However, administration of longer-acting opioids was discontinued 1 h before the anticipated end of the procedure, administration of remifentanil was discontinued 10 min before, and similar amounts of opioid were administered in both groups (Table 1).
The present study with sevoflurane and desflurane and our previous study with isoflurane show that hypercapnia with hyperventilation shortens the time to awakening (time to reach MACawake). However, we did not measure whether there are sustained differences as a result of the shorter recovery times. Future studies might look to other indices of recovery to see if perhaps the return to normal judgment or the ability to reason is similarly shortened.
The impact of hyperventilation with hypercapnia on recovery time will be less if the anesthesiologist decreases the anesthetic vapor concentration before the procedure ends (tapering). Although tapering can accelerate recovery, hypercapnia with hyperventilation may be preferred when sustained anesthetizing concentrations might be useful to reduce the risk of intraoperative awareness, inadequate analgesia, or patient movement.
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