Pulmonary Function after Emergence on 100% Oxygen in Patients with Chronic Obstructive Pulmonary Disease A Randomized, Controlled Trial Axel T. Kleinsasser, M.D., Iris Pircher, M.D., Suzan Truebsbach, M.D., Hans Knotzer, M.D., Alexander Loeckinger, M.D., Benedict Treml, M.D. ABSTRACT Background: During emergence from anesthesia, breathing 100% oxygen is frequently used to provide a safety margin toward hypoxemia in case an airway problem occurs. Oxygen breathing has been shown to cause pulmonary gas exchange disorders in healthy individuals. This study investigates how oxygen breathing during emergence affects lung function specifically whether oxygen breathing causes added hypoxemia in patients with chronic obstructive pulmonary disease. Methods: This trial has been conducted in a parallel-arm, case-controlled, open-label manner. Fifty-three patients with chronic obstructive pulmonary disease were randomly allocated (computer-generated lists) to breathe either 100 or 30% oxygen balanced with nitrogen during emergence from anesthesia. Arterial blood gas measurements were taken before induction and at 5, 15, and 60 min after extubation. Results: All participants tolerated the study well. Patients treated with 100% oxygen had a higher alveolar–arterial oxygen pressure gradient (primary outcome) compared with patients treated with 30% oxygen (25 vs. 20 mmHg) and compared with their baseline at the 60-min measurement (25 vs. 17 mmHg). At the 60-min measurement, arterial partial pressure of oxygen was lower in the 100% group (62 vs. 67 mmHg). Arterial partial pressure of carbon dioxide and pH were not different between groups or measurements. Conclusions: In this experiment, the authors examined oxygen breathing during emergence—a widely practiced maneuver known to generate pulmonary blood flow heterogeneity. In the observed cohort of patients already presenting with pulmonary blood flow disturbances, emergence on oxygen resulted in deterioration of oxygen-related blood gas parameters. In the perioperative care of patients with chronic obstructive pulmonary disease, oxygen breathing during emergence from anesthesia may need reconsideration. (Anesthesiology 2014; 120:1146-51)
A
CCORDING to the World Health Organization, chronic obstructive pulmonary disease (COPD) reflects a disease characterized by obstruction of airflow which interferes with normal breathing and is not fully reversible. In 2007, COPD was the fifth leading cause of death worldwide but will become the third leading cause by 2030.1 Patients with COPD often present with increased blood flow to lung units with subnormal ventilation—perfusion ratio.2,3 Loeckinger et al.4 documented the underlying modifications in pulmonary gas exchange: With oxygen breathing during emergence, pulmonary blood flow is redistributed to lung units with a subnormal ventilation–perfusion ratio. The consequence of oxygen breathing on postanesthetic pulmonary function in COPD patients remains uncertain and may involve changes in ventilation–perfusion ratios. On insertion and removal of artificial airways, the patients’ lungs are routinely ventilated with 100% oxygen. This is done to widen the safety margin toward hypoxemia in case airway problems occur. The gain in safety comes at a price: Oxygen breathing may cause alveolar instability and atelectasis formation. Hedenstierna et al.5 demonstrated
What We Already Know about This Topic • One hundred percent oxygen is frequently administered to emerging patients to prevent hypoxia after anesthesia
What This Article Tells Us That Is New • In a case-controlled, open-labeled study of 53 chronic obstructive pulmonary disease patients, patients breathing 100% oxygen during emergence had lower arterial oxygen levels after 60 min compared with patients breathing 30% oxygen balanced with nitrogen
atelectasis formation after induction. Benoît et al.6 showed that oxygen breathing during emergence from anesthesia equally results in atelectasis. Amazingly, there is no evidence base for oxygen breathing,7 and despite long-standing controversies,8,9 this routine remains a confirmed habit. Oxygen is also used in patients with COPD particularly because these frequently present with impaired oxygenation. Little is known about the pulmonary gas exchange after emergence on oxygen in COPD patients; however, a deterioration of pulmonary gas exchange is likely.
Submitted for publication April 22, 2013. Accepted for publication December 27, 2013. From the Department of Anesthesiology, Innsbruck Medical University, Innsbruck, Austria (A.T.K., I.P., S.T., B.T.); Department of Anesthesiology and CCM II, Klinikum Wels, Wels, Austria (H.K.); and Department of Anesthesiology and CCM, Hanusch Hospital, Vienna, Austria (A.L.). Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2014; 120:1146-51
Anesthesiology, V 120 • No 5 1146
May 2014
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For examining this theory, we hypothesized that in COPD patients, emergence on 100% oxygen leads to lower arterial oxygen pressures compared with the arterial oxygen pressures with emergence on 30% of oxygen.
Materials and Methods In Brief In this study, we examined COPD patients after general anesthesia. All patients were treated with 30% of oxygen at induction and during anesthesia. One group was treated with 100% of oxygen during emergence, and the other group remained on 30% of oxygen in this period. After the anesthetic, all patients were continued on room air so that the only difference between groups was the oxygen concentration during emergence from anesthesia. This is of course not the usual practice but was performed in this trial under supervision and with special attention. Pulse oxymetry was monitored continuously and arterial blood gas (ABG) analyses were performed before and 15 and 60 min after anesthesia. Overview This single-site study was performed from May 2007 to May 2008 at the hospital of the Medical University in Innsbruck, Austria. The type of the study is two-group, parallel arm. An overview of the study protocol is outlined in figure 1. Taken together, patients listed for elective carotid endarterectomy with general anesthesia were asked to participate in this study. Participants were thus recruited at the preanesthetic visit. After the visit on the day before surgery, informed consent was obtained and spirometry was performed on potential participants. Those with spirometry results positive for COPD (see Spirometry) were then further enrolled for pre- and postoperative ABG analyses and randomly allocated (see Statistical Analysis) to either emergence on 100% oxygen (100%, n = 26) or to emergence on 30% oxygen (30%, n = 27). The duration of emergence was measured. After extubation, patients were breathing room air. The study was approved by the local ethical committee and conducted in accordance to their guidelines. The ethics committee also served as a data-safety monitoring board (Innsbruck, Tirol, Austria). Spirometry After informed consent was obtained, potential participants were given 400 μg of salbutamol by inhalation. Fifteen minutes later, patients completed spirometry using a hand-held spirometer (Micro Spirometer; CareFusion, Basingstoke, United Kingdom). The best of three attempts was recorded. Parameters obtained included the forced expiratory volume in 1 s (FEV1, liters per second), the forced vital capacity (FVC, Liters), and the FEV1/FVC ratio calculated by the device (FEV1/FVC). Percent-of-predicted value of FEV1 (FEV1%) was calculated thereafter.
Fig. 1. Study outline with regard to enrollment, group allocation to treatment or control, and time points of measurements. ABG = arterial blood gas; BL = baseline; COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; OR = operation theater; PACU = postanesthesia care unit.
Definition of COPD Chronic obstructive pulmonary disease was defined as a FEV1/FVC ratio of less than 0.7 and an FEV1 of 80% or less 15 min after inhalation of 400 μg of salbutamol.10 Anesthesia General anesthesia with intubation was performed. Positive end-expiratory pressure (PEEP) was set 5 cm H2O. Patients enrolled in this study received no premedication. In terms of drugs, anesthesia was performed in a total intravenous manner using fentanyl (0.005 mg/kg), propofol (2.5 mg/kg), and rocuronium (0.6 mg/kg) for induction and continuous remifentanil (0.25 μg kg−1 min−1) and propofol (50 to 100 μg kg−1 min−1) for maintenance. Additional dosing of the listed drugs or higher infusion rates was left at the discretion of the anesthetist. Before intubation, lungs were ventilated using 30% oxygen balanced with nitrogen. This gas mixture was then used until emergence where—depending on group allocation—patients were kept on 30% oxygen or switched to 100% oxygen. Duration of emergence (from stopping the propofol infusion to extubation) was recorded. Before extubation, relaxometry was performed. A train-of-four ratio of greater than 0.9 was accepted for extubation otherwise neostigmine (25 μg/kg) and atropine (0.01 mg/kg) were given.11 Measurements Arterial blood gas samples were taken using an indwelling radial arterial catheter before induction and at 5, 15, and 60 min after extubation and immediately analyzed using a Chiron RapidLab 860 (Chiron, Fernwald, Germany). The 15 and 60 min measurements were taken in the postanesthesia care unit (fig. 1). Samples were immediately analyzed for Pao2, Paco2, pH, fraction of oxyhemoglobin, bicarbonate, and lactate. Other variables recorded included heart rate and blood pressure.
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Alveolar–Arterial Oxygen Partial Pressure Difference Calculation Aado2 (alveolar–arterial oxygen partial pressure difference) was calculated using the common alveolar gas equation: PA = FIO 2 ⋅ (Patm − PH2 O) −
PaCO 2 0.8
where PA reflects the alveolar pressure of oxygen, Fio2 is the fraction of the inspiratory oxygen, Patm is the atmospheric pressure, PH2O is water vapor pressure, Paco2 is the arterial partial pressure of carbon dioxide, and 0.8 is the respiratory quotient. Statistical Analysis This trial was registered in a national database. The analytical framework was to identify superiority when using 30% oxygen instead of 100% during emergence. The estimation of the sample size was based on the comparison of arterial oxygen tension because Aado2 is difficult to attain. The calculation was based on a two-treatment, parallel design. Assuming that the alternative hypothesis is a reduction in arterial oxygen tension of 8%, we a priori estimated that we needed to enrol 25 patients in each group (totalling 50) to reach a power of 80% with a type I error rate of 0.05 if the true difference between treatments is 0.8 times the standard derivation. The nature of the randomization scheme was blocking. Randomization was performed by using Research Randomizer,* a long-standing on-line tool. Randomization to the 30% or the 100% group (1:1 ratio) was prepared for 60 patients before the study using opaque envelopes labeled with the sequential number of the patient enrolled and containing the allocation information (100 or 30%). Randomization and envelope preparation were performed by a colleague who was not involved in perioperative care or in data acquisition. Analyses were performed using the Statistical Package for the Social Sciences (SPSS 15.0; IBM, Armonk, NY). Ahead of the main statistical analysis, results were tested for normal distribution using Pearson chi-square test. A two-way repeated-measures ANOVA was then used to detect inter- and intragroup differences. The hypothesis was tested two-tailed. Significant results were post hoc examined using the Newman–Keuls test. Primary outcome was a difference in Aado2 at the 60 min measurement. Secondary outcomes included Pao2, Paco2, pH, fraction of oxyhemoglobin, bicarbonate and lactate, heart rate, and blood pressure. Results are presented as mean ± SD of the mean. P values less than 0.05 were rendered significant.
Results Overview The presented data sets are complete. This study involved hypoxemia to a certain degree; however, all participants tolerated the study well. Data are displayed in tables 1 and 2 and figure 2. In this study, we examined 53 patients with COPD listed for elective * Available at: www.randomizer.org. Accessed February 3, 2014.
carotid endarterectomy. The patients we examined were in their sixties, had almost normal weight, and all had a smoking history greater than 50 pack-years. Spirometric findings in the examined cohort revealed COPD at Global Initiative for Obstructive Lung Disease stage 2.10 Our main findings were that Pao2 was lower after general anesthesia and this drop was more pronounced in those who had oxygen during emergence from anesthesia. Enrollment A total of 76 patients were screened. Fifty-three of 76 recruited patients had an FEV1/FVC of less than 0.7 together with an FEV1 of less than 80% of predicted and were further enrolled and examined for pre- and postoperative ABGs. Patients allocated to the 100% (n = 26) and to the 30% groups (n = 27) had similar anthropomorphic characteristics and spirometric findings (table 1). Physiological Data and ABG Results Physiological data and ABG results are given in table 2. Aado2 is presented in figure 2. Emergence on 100% oxygen leads to decrease in Pao2 (table 1) based on an increase in Aado2 when compared with emergence on 30% (intergroup) and when compared with baseline (intragroup) at 15 and 60 min after emergence from anesthesia. Paco2 was comparable between groups at all measurements. Other parameters including time-to-extubation and circulatory variables were not different between groups. Distribution of the Demographic Data and of the Results All demographic data and all results were normally distributed; hence, a parametric test (ANOVA) was adequate. When testing for a correlation between the drop amplitude in Aado2 and FEV1% (reduction from 100%), we could not detect a dependence (Pearson correlation = 0). Aado2: ANOVA-specific Results and 60-min Measurement Point Estimate In the ANOVA results, group effect had a P value of 0.02, time effect and group × time interaction had a P value of less Table 1. Demographic Characteristics
No. of patients (male:female) Age (yr) Body mass index Smoking history (pack-years) SpO2 at presentation (%) FVC (l) FEV1 (liters in 1 s) FEV1/FVC (ratio) FEV% (of predicted)
Extubation on 100%
Extubation on 30%
18:8 68 ± 13 26 ± 3 53 ± 5 94 ± 2 3.6 ± 1.1 1.9 ± 0.4 0.52 ± 0.10 61 ± 12
21:6 65 ± 10 25 ± 3 51 ± 4 94 ± 2 3.6 ± 0.9 2.0 ± 0.6 0.56 ± 0.14 60 ± 12
Results are reported as mean ± SD of the mean. FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; FEV% = the percentage of the predicted value; Spo2 = arterial oxygen saturation (pulse oxymetry).
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Table 2. Physiologic Data and Blood Gas Results
Heart rate (bpm) MAP (mmHg) Pao2 (mmHg) Paco2 (mmHg) apH Sao2
Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30%
BL
5’
15’
60’
73 ± 15 75 ± 14 104 ± 17 110 ± 17 81 ± 12 78 ± 11 37 ± 3 37 ± 3 7.42 ± 0.02 7.42 ± 0.02 94 ± 2 94 ± 2
87 ± 16 85 ± 21 107 ± 20 109 ± 21 125 ± 7 61 ± 7 48 ± 6 47 ± 4 7.31 ± 0.04 7.34 ± 0.03 94 ± 4 89 ± 3
90 ± 22 85 ± 16 112 ± 23 107 ± 22 61 ± 7*† 68 ± 7† 44 ± 5 41 ± 3 7.35 ± 0.04 7.37 ± 0.03 89 ± 4 92 ± 3
77 ± 19 75 ± 16 100 ± 14 99 ± 19 62 ± 6*† 67 ± 7† 41 ± 3 41 ± 3 7.37 ± 0.03 7.38 ± 0.03 89 ± 2* 92 ± 3
Results are reported as mean ± SD of the mean. 5’ reflects 5 min, 15’ is 15 min, and 60’ is 60 min after extubation. *P < 0.05 in intergroup comparison; †P < 0.01 in comparison to baseline. apH = arterial pH; BL = baseline; MAP = mean arterial pressure; Paco2 = arterial carbon dioxide partial pressure; Pao2 = arterial partial pressure of oxygen; Sao2 = arterial saturation of hemoglobin.
patients to develop shunt has been first noted by Wagner et al.2 Previous work from our group where emergence on oxygen has been examined in anesthetized animals also indicates blood flow heterogeneity as the leading cause of decreases in Pao2; however, these have been healthy animals.4
Fig. 2. Aado2 refers to alveolar arterial partial pressure difference where *P < 0.05 in intergroup comparison, †P < 0.01 in intergroup comparison, and ‡P < 0.01 in comparison to the preanesthetic value.
than 0.001. A point estimate was calculated for the difference between the two conditions at the 60-min measurement, where the mean difference was 5.32 (95% CI, 1.05 to 9.98).
Discussion This investigation showed that in COPD patients subjected to surgery for carotid artery stenosis, general anesthesia impaired postoperative oxygenation in all patients. Those who received 100% oxygen during emergence showed a statistically significant increase in Aado2 and hence lower Pao2 as compared with patients receiving 30% oxygen during emergence. Comparison of Our Results with Previous Work The findings by Gunnarsson et al.12 using the multiple inert gas technique showed that COPD patients develop an increase in pulmonary blood flow heterogeneity—but no increase in shunt. This means that our observed changes in Aado2 are interpretable as changes in heterogeneity rather than increases in shunt. The relative inability of COPD
Implications of the Changes in Aado2 In the observed setting, increases in Aado2 suggest changes in diffusion, ventilation–perfusion ratio, or in shunt. Shunt, however, has been shown to be of little importance in patients with COPD.2,12 In the absence of shunt and with no changes in diffusion, Aado2 reflects the heterogeneity of pulmonary blood flow. An increase in Aado2 as in our results indicates increased ventilation–perfusion heterogeneity or—put differently—an intensification of the pre-existing pathology. Oxygen Breathing in Normal Subjects and in COPD With oxygen breathing in normal subjects, a shunt usually develops within 30 min and is also readily reversible.13 The mechanism behind is alveolar denitrogenation. In lung units, where oxygen uptake into the blood exceeds the delivery of fresh gas, atelectasis occurs.13 In terms of anesthesia, oxygen is not the sole source of atelectasis formation: supine posture, reduction in the functional residual capacity, and airway closure all contribute to the formation of atelectasis.5,14 In COPD patients, lungs may show clinically significant pulmonary blood flow to lung units with normal and low ventilation–perfusion ratios.8 In awake oxygen breathing, COPD patients rarely develop intrapulmonary rightto-left shunt, which might be associated with collateral ventilation, where alveoli ventilate other alveoli distal of an airway obstruction.2 Some of the observed changes during oxygen breathing may also be attributed to the hypoxic pulmonary vasoconstriction (HPV). HPV is a vascular reflex, where airway
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hypoxia causes pulmonary arteries to constrict, diverting blood flow from poorly to better-oxygenated lung units.15 Although HPV is of little importance in the healthy lung (because there are no poorly ventilated units), it is critical for maintaining a balanced distribution of ventilation and perfusion in the lungs of COPD patients.16,17 Oxygen breathing obviously dampens the HPV as nifedipine does.17 In the classic experiments performed by Mélot et al., the difference in Pao2 with a vigorous HPV compared with a dampened HPV response is approximately 20 mmHg—roughly the same as in our comparison between 100 and 30% oxygen during emergence from anesthesia. Concept: Oxygen Breathing before Removal of PEEP: An Unfortunate Sequence? From the alveolus, oxygen moves into the pulmonary capillary blood. This uptake is usually completed in a quarter of a second. Alveolar nitrogen does not readily move into the blood because there is only a negligible partial pressure gradient and because it has a low solubility in blood. Nitrogen helps to keep an alveolus open. Also, our perioperative treatment helps to keep the alveoli open: PEEP is an airway and alveolar pressure above the atmospheric pressure at the end of expiration. PEEP is considered to keep alveoli open. When oxygen breathing (partially) washes the nitrogen out of the alveoli, the alveolus may become increasingly critical and eventually collapses.13 This occurs when all nitrogen is washed out and all oxygen is taken up by the blood. When oxygen breathing is applied during emergence from anesthesia, ventilated alveoli first have their nitrogen washed out and then after extubation also have the PEEP taken away. In contrast to anesthetic induction, this sequence is now inverted leaving oxygen-filled alveoli suddenly unpressurized and thus prone to become partially emptied by the blood flow. Regional ventilation will be impaired as alveoli become critical and ventilation–perfusion ratios become lower. So in this concept, extubation on oxygen may particularly help to develop lung units with subnormal ventilation–perfusion ratios. The latter partly explains the observed increases in Aado2. Postoperative Oxygen in the COPD Patient In this experiment, we examined a widely practiced maneuver that generates pulmonary blood flow heterogeneity in a cohort of patients already presenting with such a heterogeneity. Our patients presented with Pao2 values of approximately 80 mmHg which is at the lower end of the normal range (80 to 105 mmHg). After extubation on either 100 or 30% oxygen, we observed a consistent difference in Pao2. The observed values (table 2) are all relatively low, and given that a Pao2 of 60 mmHg is generally considered as an indication for intubation, this issue deserves attention, because oxygen breathing leads to Pao2 values of approximately 60 mmHg. Furthermore, these Pao2 values are on the steep section of the oxygen dissociation curve, where a small decrease in oxygen partial pressure results in a large drop in saturation. Anesthesiology 2014; 120:1146-51
The decrease in Pao2 between preanesthetic values and those measured at 15 and 60 min after extubation is very large in both groups (P = 0.0001; table 2) and reflects why we need to be cautious with general anesthesia in COPD patients. In a survey performed in the United Kingdom and Ireland in 2005, 54% of the anesthetists claim to always use pure oxygen during emergence, 32% say, they mostly use it and 10% state, they occasionally use oxygen on extubation.18 And recently, Mackintosh et al.19 published that high intraoperative concentrations of oxygen do not alter the postoperative oxygen requirements in those with healthy lungs. Emergence on oxygen is still a common practice and it seems to be harmful for only those with a pre-existing pulmonary problem. A recommendation or guideline for those presenting with COPD for general anesthesia might help to establish an adapted and adequate treatment. When we give thought to postoperative care of a COPD patient with a low Pao2, we come across the nurse in the postanesthesia care unit. As in the observed cohort, such low Pao2 values indicate that supplemental oxygen is required. It is uncertain how supplemental oxygen affects pulmonary function of the already compromised COPD lung. Research may thus also be directed on the postoperative care of the COPD patient after general anesthesia. Noninvasive ventilation via face mask may be a strategy to keep the airways open, compensate for the work of breathing and avoid dynamic hyperinflation. Positive end-inspiratory pressure could be set to values at the patient’s intrinsic PEEP,20 and delivering low oxygen concentrations may help to avoid further redistributions in pulmonary blood flow. Strengths and Limitations In our study, we examined a homogenous cohort, with individuals similar in terms of demographics, spirometry results, and treatment received. Postoperative oxygenation deficits are thus attributable to the only difference between the two groups: oxygen breathing during emergence. Some limitations should also be mentioned: First, the anesthetist was not blinded in terms of group allocation; however, this is impossible due to patient safety. Second, we examined predominantly men, however, fewer women with a smoking history present for carotid endarterectomy. Another limitation is our failure to perform measurements later than 60 min after extubation. This is in part due to the fact that we did not expect such long-term changes. Last, it has to be noted that induction at 30% of oxygen is uncommon, and some may even consider it dangerous. However, having done proper airway assessment (i.e., anesthetic history and Mallampati score), we were able to induce anesthesia with 30% safely. It also needs to be mentioned that omitting supplemental oxygen after general anesthesia is not the usual practice in the European Union.
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Summary After emergence on oxygen sustained alterations in pulmonary gas exchange could be observed in patients with COPD. Emergence on 30% oxygen also caused gas exchange disorders in these patients, but to a lesser extent. The mechanism can be attributed to an increase in pulmonary blood flow heterogeneity because COPD patients show a relative inability to develop shunt. The routine use of 100% oxygen during emergence might need reconsideration in the treatment of COPD patients.
7. Gordon RJ: Anesthesia dogmas and shibboleths: Barriers to patient safety? Anesth Analg 2012; 114:694–9
Acknowledgments
11. Kopman AF, Yee PS, Neuman GG: Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology 1997; 86:765–71
Support was provided solely from institutional and/or departmental sources.
9. Lumb AB: Just a little oxygen to breathe as you go off to sleep: Is it always a good idea? Br J Anaesth 2007; 99:769–71 10. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187:347–65
12. Gunnarsson L, Tokics L, Lundquist H, Brismar B, Strandberg A, Berg B, Hedenstierna G: Chronic obstructive pulmonary disease and anaesthesia: Formation of atelectasis and gas exchange impairment. Eur Respir J 1991; 4:1106–16
Competing Interests The authors declare no competing interests.
Correspondence Address correspondence to Dr. Kleinsasser: Department of Anesthesiology, Innsbruck Medical University, Anichstreet 35, 6020 Innsbruck, Austria. [email protected]. Information on purchasing reprints may be found at www. anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
References 1. Mannino DM, Buist AS: Global burden of COPD: Risk factors, prevalence, and future trends. Lancet 2007; 370:765–73 2. Wagner PD, Dantzker DR, Dueck R, Clausen JL, West JB: Ventilation-perfusion inequality in chronic obstructive pulmonary disease. J Clin Invest 1977; 59:203–16 3. Rodríguez-Roisin R, Drakulovic M, Rodríguez DA, Roca J, Barberà JA, Wagner PD: Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity. J Appl Physiol 2009; 106:1902–8 4. Loeckinger A, Kleinsasser A, Keller C, Schaefer A, Kolbitsch C, Lindner KH, Benzer A: Administration of oxygen before tracheal extubation worsens gas exchange after general anesthesia in a pig model. Anesth Analg 2002; 95:1772–6 5. Hedenstierna G: Oxygen and anesthesia: What lung do we deliver to the post-operative ward? Acta Anaesthesiol Scand 2012; 56:675–85 6. Benoît Z, Wicky S, Fischer JF, Frascarolo P, Chapuis C, Spahn DR, Magnusson L: The effect of increased FIO2 before tracheal extubation on postoperative atelectasis. Anesth Analg 2002; 95:1777–81
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8. Lindahl SG, Mure M: Dosing oxygen: A tricky matter or a piece of cake? Anesth Analg 2002; 95:1472–3
13. Wagner PD, Laravuso RB, Uhl RR, West JB: Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2. J Clin Invest 1974; 54:54–68 14. Lumb AB, Greenhill SJ, Simpson MP, Stewart J: Lung recruitment and positive airway pressure before extubation does not improve oxygenation in the post-anaesthesia care unit: A randomized clinical trial. Br J Anaesth 2010; 104:643–7 15. Von Euler US, Liljestrand G: Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 1946; 12:301–20 16. Mélot C, Naeije R, Rothschild T, Mertens P, Mols P, Hallemans R: Improvement in ventilation-perfusion matching by almitrine in COPD. Chest 1983; 83:528–33 17. Melot C, Hallemans R, Naeije R, Mols P, Lejeune P: Deleterious effect of nifedipine on pulmonary gas exchange in chronic obstructive pulmonary disease. Am Rev Respir Dis 1984; 130:612–6 18. Rassam S, Sandbythomas M, Vaughan RS, Hall JE: Airway management before, during and after extubation: A survey of practice in the United Kingdom and Ireland. Anaesthesia 2005; 60:995–1001 19. Mackintosh N, Gertsch MC, Hopf HW, Pace NL, White J, Morris R, Morrissey C, Wilding V, Herway S: High intraoperative inspired oxygen does not increase postoperative supplemental oxygen requirements. Anesthesiology 2012; 117:271–9 20. Marini JJ: Dynamic hyperinflation and auto-positive end-expiratory pressure: Lessons learned over 30 years. Am J Respir Crit Care Med 2011; 184:756–62
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A
CCORDING to the World Health Organization, chronic obstructive pulmonary disease (COPD) reflects a disease characterized by obstruction of airflow which interferes with normal breathing and is not fully reversible. In 2007, COPD was the fifth leading cause of death worldwide but will become the third leading cause by 2030.1 Patients with COPD often present with increased blood flow to lung units with subnormal ventilation—perfusion ratio.2,3 Loeckinger et al.4 documented the underlying modifications in pulmonary gas exchange: With oxygen breathing during emergence, pulmonary blood flow is redistributed to lung units with a subnormal ventilation–perfusion ratio. The consequence of oxygen breathing on postanesthetic pulmonary function in COPD patients remains uncertain and may involve changes in ventilation–perfusion ratios. On insertion and removal of artificial airways, the patients’ lungs are routinely ventilated with 100% oxygen. This is done to widen the safety margin toward hypoxemia in case airway problems occur. The gain in safety comes at a price: Oxygen breathing may cause alveolar instability and atelectasis formation. Hedenstierna et al.5 demonstrated
What We Already Know about This Topic • One hundred percent oxygen is frequently administered to emerging patients to prevent hypoxia after anesthesia
What This Article Tells Us That Is New • In a case-controlled, open-labeled study of 53 chronic obstructive pulmonary disease patients, patients breathing 100% oxygen during emergence had lower arterial oxygen levels after 60 min compared with patients breathing 30% oxygen balanced with nitrogen
atelectasis formation after induction. Benoît et al.6 showed that oxygen breathing during emergence from anesthesia equally results in atelectasis. Amazingly, there is no evidence base for oxygen breathing,7 and despite long-standing controversies,8,9 this routine remains a confirmed habit. Oxygen is also used in patients with COPD particularly because these frequently present with impaired oxygenation. Little is known about the pulmonary gas exchange after emergence on oxygen in COPD patients; however, a deterioration of pulmonary gas exchange is likely.
Submitted for publication April 22, 2013. Accepted for publication December 27, 2013. From the Department of Anesthesiology, Innsbruck Medical University, Innsbruck, Austria (A.T.K., I.P., S.T., B.T.); Department of Anesthesiology and CCM II, Klinikum Wels, Wels, Austria (H.K.); and Department of Anesthesiology and CCM, Hanusch Hospital, Vienna, Austria (A.L.). Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2014; 120:1146-51
Anesthesiology, V 120 • No 5 1146
May 2014
PERIOPERATIVE MEDICINE
For examining this theory, we hypothesized that in COPD patients, emergence on 100% oxygen leads to lower arterial oxygen pressures compared with the arterial oxygen pressures with emergence on 30% of oxygen.
Materials and Methods In Brief In this study, we examined COPD patients after general anesthesia. All patients were treated with 30% of oxygen at induction and during anesthesia. One group was treated with 100% of oxygen during emergence, and the other group remained on 30% of oxygen in this period. After the anesthetic, all patients were continued on room air so that the only difference between groups was the oxygen concentration during emergence from anesthesia. This is of course not the usual practice but was performed in this trial under supervision and with special attention. Pulse oxymetry was monitored continuously and arterial blood gas (ABG) analyses were performed before and 15 and 60 min after anesthesia. Overview This single-site study was performed from May 2007 to May 2008 at the hospital of the Medical University in Innsbruck, Austria. The type of the study is two-group, parallel arm. An overview of the study protocol is outlined in figure 1. Taken together, patients listed for elective carotid endarterectomy with general anesthesia were asked to participate in this study. Participants were thus recruited at the preanesthetic visit. After the visit on the day before surgery, informed consent was obtained and spirometry was performed on potential participants. Those with spirometry results positive for COPD (see Spirometry) were then further enrolled for pre- and postoperative ABG analyses and randomly allocated (see Statistical Analysis) to either emergence on 100% oxygen (100%, n = 26) or to emergence on 30% oxygen (30%, n = 27). The duration of emergence was measured. After extubation, patients were breathing room air. The study was approved by the local ethical committee and conducted in accordance to their guidelines. The ethics committee also served as a data-safety monitoring board (Innsbruck, Tirol, Austria). Spirometry After informed consent was obtained, potential participants were given 400 μg of salbutamol by inhalation. Fifteen minutes later, patients completed spirometry using a hand-held spirometer (Micro Spirometer; CareFusion, Basingstoke, United Kingdom). The best of three attempts was recorded. Parameters obtained included the forced expiratory volume in 1 s (FEV1, liters per second), the forced vital capacity (FVC, Liters), and the FEV1/FVC ratio calculated by the device (FEV1/FVC). Percent-of-predicted value of FEV1 (FEV1%) was calculated thereafter.
Fig. 1. Study outline with regard to enrollment, group allocation to treatment or control, and time points of measurements. ABG = arterial blood gas; BL = baseline; COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; OR = operation theater; PACU = postanesthesia care unit.
Definition of COPD Chronic obstructive pulmonary disease was defined as a FEV1/FVC ratio of less than 0.7 and an FEV1 of 80% or less 15 min after inhalation of 400 μg of salbutamol.10 Anesthesia General anesthesia with intubation was performed. Positive end-expiratory pressure (PEEP) was set 5 cm H2O. Patients enrolled in this study received no premedication. In terms of drugs, anesthesia was performed in a total intravenous manner using fentanyl (0.005 mg/kg), propofol (2.5 mg/kg), and rocuronium (0.6 mg/kg) for induction and continuous remifentanil (0.25 μg kg−1 min−1) and propofol (50 to 100 μg kg−1 min−1) for maintenance. Additional dosing of the listed drugs or higher infusion rates was left at the discretion of the anesthetist. Before intubation, lungs were ventilated using 30% oxygen balanced with nitrogen. This gas mixture was then used until emergence where—depending on group allocation—patients were kept on 30% oxygen or switched to 100% oxygen. Duration of emergence (from stopping the propofol infusion to extubation) was recorded. Before extubation, relaxometry was performed. A train-of-four ratio of greater than 0.9 was accepted for extubation otherwise neostigmine (25 μg/kg) and atropine (0.01 mg/kg) were given.11 Measurements Arterial blood gas samples were taken using an indwelling radial arterial catheter before induction and at 5, 15, and 60 min after extubation and immediately analyzed using a Chiron RapidLab 860 (Chiron, Fernwald, Germany). The 15 and 60 min measurements were taken in the postanesthesia care unit (fig. 1). Samples were immediately analyzed for Pao2, Paco2, pH, fraction of oxyhemoglobin, bicarbonate, and lactate. Other variables recorded included heart rate and blood pressure.
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Alveolar–Arterial Oxygen Partial Pressure Difference Calculation Aado2 (alveolar–arterial oxygen partial pressure difference) was calculated using the common alveolar gas equation: PA = FIO 2 ⋅ (Patm − PH2 O) −
PaCO 2 0.8
where PA reflects the alveolar pressure of oxygen, Fio2 is the fraction of the inspiratory oxygen, Patm is the atmospheric pressure, PH2O is water vapor pressure, Paco2 is the arterial partial pressure of carbon dioxide, and 0.8 is the respiratory quotient. Statistical Analysis This trial was registered in a national database. The analytical framework was to identify superiority when using 30% oxygen instead of 100% during emergence. The estimation of the sample size was based on the comparison of arterial oxygen tension because Aado2 is difficult to attain. The calculation was based on a two-treatment, parallel design. Assuming that the alternative hypothesis is a reduction in arterial oxygen tension of 8%, we a priori estimated that we needed to enrol 25 patients in each group (totalling 50) to reach a power of 80% with a type I error rate of 0.05 if the true difference between treatments is 0.8 times the standard derivation. The nature of the randomization scheme was blocking. Randomization was performed by using Research Randomizer,* a long-standing on-line tool. Randomization to the 30% or the 100% group (1:1 ratio) was prepared for 60 patients before the study using opaque envelopes labeled with the sequential number of the patient enrolled and containing the allocation information (100 or 30%). Randomization and envelope preparation were performed by a colleague who was not involved in perioperative care or in data acquisition. Analyses were performed using the Statistical Package for the Social Sciences (SPSS 15.0; IBM, Armonk, NY). Ahead of the main statistical analysis, results were tested for normal distribution using Pearson chi-square test. A two-way repeated-measures ANOVA was then used to detect inter- and intragroup differences. The hypothesis was tested two-tailed. Significant results were post hoc examined using the Newman–Keuls test. Primary outcome was a difference in Aado2 at the 60 min measurement. Secondary outcomes included Pao2, Paco2, pH, fraction of oxyhemoglobin, bicarbonate and lactate, heart rate, and blood pressure. Results are presented as mean ± SD of the mean. P values less than 0.05 were rendered significant.
Results Overview The presented data sets are complete. This study involved hypoxemia to a certain degree; however, all participants tolerated the study well. Data are displayed in tables 1 and 2 and figure 2. In this study, we examined 53 patients with COPD listed for elective * Available at: www.randomizer.org. Accessed February 3, 2014.
carotid endarterectomy. The patients we examined were in their sixties, had almost normal weight, and all had a smoking history greater than 50 pack-years. Spirometric findings in the examined cohort revealed COPD at Global Initiative for Obstructive Lung Disease stage 2.10 Our main findings were that Pao2 was lower after general anesthesia and this drop was more pronounced in those who had oxygen during emergence from anesthesia. Enrollment A total of 76 patients were screened. Fifty-three of 76 recruited patients had an FEV1/FVC of less than 0.7 together with an FEV1 of less than 80% of predicted and were further enrolled and examined for pre- and postoperative ABGs. Patients allocated to the 100% (n = 26) and to the 30% groups (n = 27) had similar anthropomorphic characteristics and spirometric findings (table 1). Physiological Data and ABG Results Physiological data and ABG results are given in table 2. Aado2 is presented in figure 2. Emergence on 100% oxygen leads to decrease in Pao2 (table 1) based on an increase in Aado2 when compared with emergence on 30% (intergroup) and when compared with baseline (intragroup) at 15 and 60 min after emergence from anesthesia. Paco2 was comparable between groups at all measurements. Other parameters including time-to-extubation and circulatory variables were not different between groups. Distribution of the Demographic Data and of the Results All demographic data and all results were normally distributed; hence, a parametric test (ANOVA) was adequate. When testing for a correlation between the drop amplitude in Aado2 and FEV1% (reduction from 100%), we could not detect a dependence (Pearson correlation = 0). Aado2: ANOVA-specific Results and 60-min Measurement Point Estimate In the ANOVA results, group effect had a P value of 0.02, time effect and group × time interaction had a P value of less Table 1. Demographic Characteristics
No. of patients (male:female) Age (yr) Body mass index Smoking history (pack-years) SpO2 at presentation (%) FVC (l) FEV1 (liters in 1 s) FEV1/FVC (ratio) FEV% (of predicted)
Extubation on 100%
Extubation on 30%
18:8 68 ± 13 26 ± 3 53 ± 5 94 ± 2 3.6 ± 1.1 1.9 ± 0.4 0.52 ± 0.10 61 ± 12
21:6 65 ± 10 25 ± 3 51 ± 4 94 ± 2 3.6 ± 0.9 2.0 ± 0.6 0.56 ± 0.14 60 ± 12
Results are reported as mean ± SD of the mean. FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; FEV% = the percentage of the predicted value; Spo2 = arterial oxygen saturation (pulse oxymetry).
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Table 2. Physiologic Data and Blood Gas Results
Heart rate (bpm) MAP (mmHg) Pao2 (mmHg) Paco2 (mmHg) apH Sao2
Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30% Extubation on 100% Extubation on 30%
BL
5’
15’
60’
73 ± 15 75 ± 14 104 ± 17 110 ± 17 81 ± 12 78 ± 11 37 ± 3 37 ± 3 7.42 ± 0.02 7.42 ± 0.02 94 ± 2 94 ± 2
87 ± 16 85 ± 21 107 ± 20 109 ± 21 125 ± 7 61 ± 7 48 ± 6 47 ± 4 7.31 ± 0.04 7.34 ± 0.03 94 ± 4 89 ± 3
90 ± 22 85 ± 16 112 ± 23 107 ± 22 61 ± 7*† 68 ± 7† 44 ± 5 41 ± 3 7.35 ± 0.04 7.37 ± 0.03 89 ± 4 92 ± 3
77 ± 19 75 ± 16 100 ± 14 99 ± 19 62 ± 6*† 67 ± 7† 41 ± 3 41 ± 3 7.37 ± 0.03 7.38 ± 0.03 89 ± 2* 92 ± 3
Results are reported as mean ± SD of the mean. 5’ reflects 5 min, 15’ is 15 min, and 60’ is 60 min after extubation. *P < 0.05 in intergroup comparison; †P < 0.01 in comparison to baseline. apH = arterial pH; BL = baseline; MAP = mean arterial pressure; Paco2 = arterial carbon dioxide partial pressure; Pao2 = arterial partial pressure of oxygen; Sao2 = arterial saturation of hemoglobin.
patients to develop shunt has been first noted by Wagner et al.2 Previous work from our group where emergence on oxygen has been examined in anesthetized animals also indicates blood flow heterogeneity as the leading cause of decreases in Pao2; however, these have been healthy animals.4
Fig. 2. Aado2 refers to alveolar arterial partial pressure difference where *P < 0.05 in intergroup comparison, †P < 0.01 in intergroup comparison, and ‡P < 0.01 in comparison to the preanesthetic value.
than 0.001. A point estimate was calculated for the difference between the two conditions at the 60-min measurement, where the mean difference was 5.32 (95% CI, 1.05 to 9.98).
Discussion This investigation showed that in COPD patients subjected to surgery for carotid artery stenosis, general anesthesia impaired postoperative oxygenation in all patients. Those who received 100% oxygen during emergence showed a statistically significant increase in Aado2 and hence lower Pao2 as compared with patients receiving 30% oxygen during emergence. Comparison of Our Results with Previous Work The findings by Gunnarsson et al.12 using the multiple inert gas technique showed that COPD patients develop an increase in pulmonary blood flow heterogeneity—but no increase in shunt. This means that our observed changes in Aado2 are interpretable as changes in heterogeneity rather than increases in shunt. The relative inability of COPD
Implications of the Changes in Aado2 In the observed setting, increases in Aado2 suggest changes in diffusion, ventilation–perfusion ratio, or in shunt. Shunt, however, has been shown to be of little importance in patients with COPD.2,12 In the absence of shunt and with no changes in diffusion, Aado2 reflects the heterogeneity of pulmonary blood flow. An increase in Aado2 as in our results indicates increased ventilation–perfusion heterogeneity or—put differently—an intensification of the pre-existing pathology. Oxygen Breathing in Normal Subjects and in COPD With oxygen breathing in normal subjects, a shunt usually develops within 30 min and is also readily reversible.13 The mechanism behind is alveolar denitrogenation. In lung units, where oxygen uptake into the blood exceeds the delivery of fresh gas, atelectasis occurs.13 In terms of anesthesia, oxygen is not the sole source of atelectasis formation: supine posture, reduction in the functional residual capacity, and airway closure all contribute to the formation of atelectasis.5,14 In COPD patients, lungs may show clinically significant pulmonary blood flow to lung units with normal and low ventilation–perfusion ratios.8 In awake oxygen breathing, COPD patients rarely develop intrapulmonary rightto-left shunt, which might be associated with collateral ventilation, where alveoli ventilate other alveoli distal of an airway obstruction.2 Some of the observed changes during oxygen breathing may also be attributed to the hypoxic pulmonary vasoconstriction (HPV). HPV is a vascular reflex, where airway
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hypoxia causes pulmonary arteries to constrict, diverting blood flow from poorly to better-oxygenated lung units.15 Although HPV is of little importance in the healthy lung (because there are no poorly ventilated units), it is critical for maintaining a balanced distribution of ventilation and perfusion in the lungs of COPD patients.16,17 Oxygen breathing obviously dampens the HPV as nifedipine does.17 In the classic experiments performed by Mélot et al., the difference in Pao2 with a vigorous HPV compared with a dampened HPV response is approximately 20 mmHg—roughly the same as in our comparison between 100 and 30% oxygen during emergence from anesthesia. Concept: Oxygen Breathing before Removal of PEEP: An Unfortunate Sequence? From the alveolus, oxygen moves into the pulmonary capillary blood. This uptake is usually completed in a quarter of a second. Alveolar nitrogen does not readily move into the blood because there is only a negligible partial pressure gradient and because it has a low solubility in blood. Nitrogen helps to keep an alveolus open. Also, our perioperative treatment helps to keep the alveoli open: PEEP is an airway and alveolar pressure above the atmospheric pressure at the end of expiration. PEEP is considered to keep alveoli open. When oxygen breathing (partially) washes the nitrogen out of the alveoli, the alveolus may become increasingly critical and eventually collapses.13 This occurs when all nitrogen is washed out and all oxygen is taken up by the blood. When oxygen breathing is applied during emergence from anesthesia, ventilated alveoli first have their nitrogen washed out and then after extubation also have the PEEP taken away. In contrast to anesthetic induction, this sequence is now inverted leaving oxygen-filled alveoli suddenly unpressurized and thus prone to become partially emptied by the blood flow. Regional ventilation will be impaired as alveoli become critical and ventilation–perfusion ratios become lower. So in this concept, extubation on oxygen may particularly help to develop lung units with subnormal ventilation–perfusion ratios. The latter partly explains the observed increases in Aado2. Postoperative Oxygen in the COPD Patient In this experiment, we examined a widely practiced maneuver that generates pulmonary blood flow heterogeneity in a cohort of patients already presenting with such a heterogeneity. Our patients presented with Pao2 values of approximately 80 mmHg which is at the lower end of the normal range (80 to 105 mmHg). After extubation on either 100 or 30% oxygen, we observed a consistent difference in Pao2. The observed values (table 2) are all relatively low, and given that a Pao2 of 60 mmHg is generally considered as an indication for intubation, this issue deserves attention, because oxygen breathing leads to Pao2 values of approximately 60 mmHg. Furthermore, these Pao2 values are on the steep section of the oxygen dissociation curve, where a small decrease in oxygen partial pressure results in a large drop in saturation. Anesthesiology 2014; 120:1146-51
The decrease in Pao2 between preanesthetic values and those measured at 15 and 60 min after extubation is very large in both groups (P = 0.0001; table 2) and reflects why we need to be cautious with general anesthesia in COPD patients. In a survey performed in the United Kingdom and Ireland in 2005, 54% of the anesthetists claim to always use pure oxygen during emergence, 32% say, they mostly use it and 10% state, they occasionally use oxygen on extubation.18 And recently, Mackintosh et al.19 published that high intraoperative concentrations of oxygen do not alter the postoperative oxygen requirements in those with healthy lungs. Emergence on oxygen is still a common practice and it seems to be harmful for only those with a pre-existing pulmonary problem. A recommendation or guideline for those presenting with COPD for general anesthesia might help to establish an adapted and adequate treatment. When we give thought to postoperative care of a COPD patient with a low Pao2, we come across the nurse in the postanesthesia care unit. As in the observed cohort, such low Pao2 values indicate that supplemental oxygen is required. It is uncertain how supplemental oxygen affects pulmonary function of the already compromised COPD lung. Research may thus also be directed on the postoperative care of the COPD patient after general anesthesia. Noninvasive ventilation via face mask may be a strategy to keep the airways open, compensate for the work of breathing and avoid dynamic hyperinflation. Positive end-inspiratory pressure could be set to values at the patient’s intrinsic PEEP,20 and delivering low oxygen concentrations may help to avoid further redistributions in pulmonary blood flow. Strengths and Limitations In our study, we examined a homogenous cohort, with individuals similar in terms of demographics, spirometry results, and treatment received. Postoperative oxygenation deficits are thus attributable to the only difference between the two groups: oxygen breathing during emergence. Some limitations should also be mentioned: First, the anesthetist was not blinded in terms of group allocation; however, this is impossible due to patient safety. Second, we examined predominantly men, however, fewer women with a smoking history present for carotid endarterectomy. Another limitation is our failure to perform measurements later than 60 min after extubation. This is in part due to the fact that we did not expect such long-term changes. Last, it has to be noted that induction at 30% of oxygen is uncommon, and some may even consider it dangerous. However, having done proper airway assessment (i.e., anesthetic history and Mallampati score), we were able to induce anesthesia with 30% safely. It also needs to be mentioned that omitting supplemental oxygen after general anesthesia is not the usual practice in the European Union.
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Summary After emergence on oxygen sustained alterations in pulmonary gas exchange could be observed in patients with COPD. Emergence on 30% oxygen also caused gas exchange disorders in these patients, but to a lesser extent. The mechanism can be attributed to an increase in pulmonary blood flow heterogeneity because COPD patients show a relative inability to develop shunt. The routine use of 100% oxygen during emergence might need reconsideration in the treatment of COPD patients.
7. Gordon RJ: Anesthesia dogmas and shibboleths: Barriers to patient safety? Anesth Analg 2012; 114:694–9
Acknowledgments
11. Kopman AF, Yee PS, Neuman GG: Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology 1997; 86:765–71
Support was provided solely from institutional and/or departmental sources.
9. Lumb AB: Just a little oxygen to breathe as you go off to sleep: Is it always a good idea? Br J Anaesth 2007; 99:769–71 10. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187:347–65
12. Gunnarsson L, Tokics L, Lundquist H, Brismar B, Strandberg A, Berg B, Hedenstierna G: Chronic obstructive pulmonary disease and anaesthesia: Formation of atelectasis and gas exchange impairment. Eur Respir J 1991; 4:1106–16
Competing Interests The authors declare no competing interests.
Correspondence Address correspondence to Dr. Kleinsasser: Department of Anesthesiology, Innsbruck Medical University, Anichstreet 35, 6020 Innsbruck, Austria. [email protected]. Information on purchasing reprints may be found at www. anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
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