Postoperative respiratory complications are common,1 and they may increase morbidity and mortality.2,3 Obesity may increase the risk of developing perioperative hypoxia and respiratory dysfunction.4–7 An increased body mass index (BMI) is associated with a reduced pharyngeal area and a tendency for upper airway collapse.8–10
The choice of anesthetic may influence postoperative lung dysfunction. Propofol decreases upper airway tone,11 unlike the volatile anesthetics. This may lead to more significant postoperative effects in overweight and obese patients who are already at increased risk of respiratory complications.
Desflurane and propofol have the most favorable pharmacokinetic profile for rapid recovery from inhaled and IV approaches to anesthesia.12,13 Obesity does not seem to greatly affect the rate of anesthetic elimination.14–16 One would thus not expect that any postoperative respiratory effects of these 2 drugs in obese patients, beyond those that might occur immediately after anesthesia, would be due to slower elimination and the continued presence of the drug. The aim of this study was to investigate whether desflurane and propofol have different effects on postoperative impairment of respiratory function up to 24 hours after minor surgery in overweight and obese patients.
The Ethics Committee of the University of Marburg approved this study, and each patient gave informed written consent. We prospectively recruited 134 overweight to obese adult patients (BMI 25–35 kg/m2, ASA physical status II–III) from a pool of 159 patients scheduled for minor peripheral surgery expected to last 40 to 120 minutes that did not require head-down tilt (Table 1). We excluded patients who had gastroesophageal reflux or hiatus hernia, or who had an airway suggested by physical examination to indicate a difficult intubation. We excluded pregnant patients, patients with bronchial asthma requiring therapy, those with cardiac disease associated with dyspnea more than New York Heart Association II, and those with a severe psychiatric disorder.
In the evening before surgery, patients were premedicated with oral chlorazepate 20 mg. After administering oxygen by facemask, we induced anesthesia with fentanyl 2 to 3 μg · kg−1 and propofol 2 mg · kg−1. Patients' lungs were manually ventilated with 100% oxygen via a facemask. A single dose of rocuronium (0.5 mg · kg−1 ideal body weight [height − 100 cm]) facilitated orotracheal intubation; no additional neuromuscular blocking drug was given. Ventilatory settings were standardized. After intubation, the lungs were mechanically ventilated with a tidal volume of 8 mL · kg−1 of ideal body weight. Respiratory rate was adjusted to maintain an end-tidal CO2 pressure of 30 to 35 mm Hg. A maximum peak pressure of 30 cm H2O was permitted, and the inspiratory/expiratory ratio was adjusted to 1:1.5. A positive end-expiratory pressure of 10 cm H2O was used throughout anesthesia. The cuff pressure was continuously adjusted to 30 cm H2O. During maintenance of anesthesia, 50% oxygen in nitrogen was administered.
We maintained anesthesia with either continuous infusion of propofol 3 to 6 mg · kg−1 · h−1 (kilograms ideal body weight) or desflurane (patients assigned on a random basis). A bispectral index (BIS)-electroencephalogram electrode strip (BIS Quatro™; Aspect Medical Systems, Norwood, MA) was positioned on the forehead as recommended by the manufacturer. Remifentanil (0.1–0.2 μg · kg−1 · min−1, ideal body weight) and propofol infusions or desflurane concentration were adjusted according to hemodynamic variables and to BIS values ranging from 40 to 60. The overall desflurane concentration was maintained within a range of 3 to 6 vol%. Peripheral arterial oxygen saturation was monitored continuously by pulse oximetry. The train-of-four ratio was measured with a peripheral nerve stimulator (TOF-Watch; Organon Teknika, Eppelheim, Germany), and we did not extubate the trachea unless the train-of-four ratio exceeded 0.90.17 Fifteen minutes before extubation, the propofol infusion or desflurane concentration was reduced and each patient received dolasetron (25 mg IV) and dexamethasone (4 mg IV) as prophylaxis against postoperative nausea and vomiting. When sufficient spontaneous breathing was established and the patient responded adequately to instructions, the trachea was extubated without suction, with the patient in a head-up position with a positive pressure of 10 cm H2O and an oxygen concentration of 100%. Thereafter, each patient was transported to the postanesthesia care unit (PACU), breathing room air. Peripheral arterial oxygen saturation was continuously monitored by pulse oximetry. Each patient remained in a 30° head-up position in the PACU. All patients received supplemental oxygen delivered via a Venturi mask with an adjusted oxygen flow of 6 L−1 during the PACU stay. Signs of respiratory insufficiency (dyspnea, severe reduction of pulse oximetry saturation <90%) were not present in any patient.
Postoperative Pain Management
Both groups received non-opioid analgesia with IV acetaminophen 1 g and metamizole 1 g IV as soon as they arrived in the PACU. If necessary, analgesia was supplemented with the synthetic opioid piritramide IV when the visual analog scale (with a maximum of 10) value exceeded 4. Cumulative piritramide consumption was recorded for the first 24 hours postoperatively.
Spirometry and Pulse Oximetry
The potential for bias was minimized by the support of anesthesiologists not involved in the study, who were responsible for giving patients preoperative information. Additionally, postoperative spirometry was performed by trained nurses who were unaware of the study hypothesis and were not otherwise involved in this study. Spirometry and pulse oximetry measurements were obtained by a blinded investigator after each patient had breathed air for 5 minutes while in a 30° head-up position.18 After thorough demonstration to the patient of the maneuvers to be performed, baseline spirometry and pulse oximetry measurements were obtained at the preanesthetic visit (T0). For this purpose, we used the self-calibrating “Easy One CS Spirometer” (GE Healthcare, Munich, Germany). To produce reliable measurements, a minimum-quality, degree “C” had to be attained. Vital capacity, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), midexpiratory flow (MEF) (25–75), peak expiratory flow, peak inspiratory flow (PIF), and the forced inspiratory vital capacity were measured, and the FEV1/FVC ratio was calculated. At each assessment time, spirometry was performed at least 3 times as needed to meet the criteria of the European Respiratory Society, and the best measurement was recorded.19 In the PACU (approximately 5–10 minutes after extubation), we repeated spirometry measurements (T1) as soon as the patient was alert and fully cooperative (fast track score exceeding 10; maximum score 14)20; pain and dyspnea were assessed during coughing at a fast track score exceeding 10 before and, if necessary, after analgesic therapy. All study patients had fast track scores exceeding 10 within 20 minutes of extubation.
Spirometry and pulse oximetry assessments were repeated in the PACU at 0.5 hour (T2), 2 hours (T3), and at 24 hours (T4) after extubation. Before each assessment, as soon as the patients were free from pain during coughing, piritramide requirements were documented. Factors that interfered with breathing (e.g., pain, shivering) were minimized to produce reliable measurements.
A prospective power analysis performed with the PASS 2002 software (Number Cruncher Statistical Systems, Kaysville, UT) revealed that 63 patients per group provided >80% chance to detect an absolute improvement of 1% (e.g., 94% SaO2 to 95% SaO2) with an expected standard deviation of 2 in both groups using the Student t test with a type I error of 5%. To compare postoperative respiratory data and pulse oximetry between the 2 groups, we used repeated-measures analysis of variance (ANOVA) followed by t test analysis at each time point with an adjusted P < 0.0125 due to multiple testing (Bonferroni correction). The impact of BMI on postoperative deterioration of lung function and oxygenation was analyzed using regression analysis. For a more detailed characterization of the interaction of BMI and anesthesia maintenance, we performed a multifactorial ANOVA (MANOVA) at different time points. Statistical significance was considered to be P < 0.05. Overall, 134 patients were included with 5 values each (1 preoperative value = baseline, 4 postoperative values as percentage of preoperative baseline). All values for BIS, remifentanil, propofol consumption, and desflurane concentration were collected through an online documentary system (Medlinq Easy Software, Hamburg, Germany). Statistical analysis was performed with the JMP 7.0 statistical package for Windows (SAS Institute, Cary, NC).
Demographic variables did not differ between groups (Table 1). The duration of surgery was 80 ± 20 minutes (mean ± SD), with a range of 40 to 120 minutes. All patients received ventilation as planned. Of the 159 recruited patients, 4 declined to continue; measurements were unsatisfactory in a further 14 (8 in the desflurane group; 6 in the propofol group). All unsatisfactory measurements were the result of missed fast track criteria (a modified fast track score of ≤10) within 20 minutes after surgery. Three patients in the propofol group and 4 in the desflurane group were excluded because of adverse events. Laryngospasm or bronchospasm occurred in 2 patients in each study group. Unexpected difficulties in intubation occurred in 3 patients who were also excluded. Antagonism of neuromuscular block was not necessary in any patient. Thus, we present data for 134 patients with 67 individuals per group.
Baseline (preoperative) pulse oximetry values were within the normal range and did not differ between groups before or after premedication (Table 2). In both groups, the lowest values were found directly after extubation, in the PACU, after achieving a fast track value exceeding 10. The propofol group had a small (average difference <1%) but significantly larger decrease in postoperative oxygenation than the desflurane group (Fig. 1, ANOVA P = 0.0024) at the first 3 measurement points by t test (Table 3, P < 0.01) but did not differ 24 hours after surgery.
Preoperative (baseline) spirometry values were normal and did not differ between groups (Table 2). Postoperative spirometry and peak flow values showed a pattern qualitatively similar to the values for pulse oximetry (Figs. 2 and 3 , Table 3). Postoperative values decreased more after propofol than after desflurane anesthesia. Both groups showed a recovery with the passage of time, but even 24 hours after surgery, some measures of lung function were significantly decreased, by up to 25% from baseline values. Patients given desflurane had less average impairment at all measurement points within the first 2 postoperative hours, with a difference of 10 to 20 percentage points between study groups (Fig. 3). At 24 hours, MEF 25 and FVC did not differ significantly between desflurane and propofol groups, but FEV1, peak expiratory flow, MEF 75, MEF 50, PIF, and forced inspiratory vital capacity continued to differ (Table 3; t test).
No patient experienced untreatable postoperative pain. The maximum postoperative pain score on a visual analog scale before analgesia was 6 in both groups. The 2 groups had comparable opioid consumption for the first 24 hours (Table 1). At each measurement point, every patient had an acceptable vigilance level, and none had pain, shivering, or nausea that might have interfered with spirometry.
Spirometry Measurements Related to BMI
At the first PACU assessment, within 20 minutes of extubation, the desflurane group had better lung function results than the propofol group. Inspiratory lung function values displayed a significant relationship between BMI and lung function in both study groups, whereas peak inspiratory values did not correlate with increasing BMI (Fig. 4). At discharge from the PACU, 2 hours after surgery, a linear decrease of lung function with BMI was evident in the propofol group, but not in the desflurane group for FEV1, MEF 25, and PIF (Fig. 5). However, the correlation coefficients ranged from 0.2 to 0.45 for propofol and 0.04 to 0.15 for desflurane. Two factorial MANOVA analyses confirmed an interaction between propofol and BMI for the change in FEV1 and MEF 25 at 0.5 hour and at 2 hours. This effect ceased at 24 hours after surgery.
Pulmonary complications can occur in the immediate postoperative period.21 The lowest spirometry and pulse oximetry values are observed immediately after extubation.22 Our findings confirm the notion that surgery, general anesthesia and/or the associated procedures, and drugs can impair postoperative respiratory mechanics and decrease oxyhemoglobin saturation. Given that the surgery in our patients was minor and peripheral, that pain was minimal, and that wakefulness appeared to be adequate, we believe that anesthesia contributed a major share of the impairment. The finding that impairment differed between desflurane and propofol contributes further to this notion of an anesthetic contribution because the groups otherwise did not differ in surgery. Other researchers similarly have shown that the choice of anesthetic may contribute to pulmonary impairment: impairment may be greater immediately (a few to 90 minutes) after anesthesia in which thiopental rather than propofol is used for induction,21 or isoflurane rather than propofol.23
Others have found that obesity can contribute to impairment of postoperative respiratory mechanics.24–26 In addition, we find that the impairment with obesity may be dependent on the anesthetic drug used.
Our data do not reveal what may have caused postoperative pulmonary impairment or the different effects of the 2 anesthetics. A lack of cooperation seems an unlikely cause, since all patients in this study were alert and fully compliant within 20 minutes of extubation. Pain had been treated, with no difference in the amount of pain or pain medication given each group. Additionally, any lack of cooperation and insufficient pain management should affect each group to a comparable degree. A difference in anesthetic “depth” of the patients included in our study seems unlikely. The operation time did not exceed 120 minutes, propofol dosage and desflurane concentration were titrated to the same BIS values, and recovery times did not differ between the 2 groups. One might postulate a difference in immediate effects of one as opposed to the other anesthetic on bronchial tone, but it is difficult to envision that the small amounts of either anesthetic that would remain 2 hours, much less 24 hours, after surgery could have pharmacological effects.
Anesthetics may have long-term effects. Inhaled anesthetics can produce extended periods of genetic upregulation and downregulation.27 Such changes form the basis of some of the protective effects of inhaled anesthetics against episodes of myocardial ischemia (anesthetic preconditioning). Regardless of the cause, it seems that desflurane has subtly fewer detrimental effects on postoperative pulmonary function than does propofol.
Are the modest differences between our study groups of clinical relevance? All of our measurements are but surrogates for hard measures of untoward effects such as pneumonia that require large numbers of patients to reveal. Still, moderately obese patients are at increased risk of early postoperative respiratory complications, so even small improvements in early or intermediate recovery may be beneficial.
Finally, our study has selection limitations. We recruited relatively healthy (see exclusions) overweight patients (BMI between 25 and 35 kg/m2), scheduled for minor peripheral surgery. Morbidly obese patients, or patients with respiratory (e.g., chronic obstructive pulmonary disease or asthma) or heart disease (e.g., heart failure or cardiovascular disease) might show responses different from those we found. Similarly, we excluded patients having abdominal insufflation (laparoscopy) or head-down tilt, and these might have altered our findings. Our findings do not allow us to state that desflurane is preferred as the standard maintenance anesthetic for these cases, nor can we draw any conclusions about respiratory complications. As indicated above, such a determination requires large-scale outcomes studies using “gold standards” such as the incidence of untoward pulmonary complications. Our data do suggest that such studies might produce clinically important results.
We thank Prof. Edmond I Eger, II, for his expertise and his advisory support concerning the manuscript. For statistical support, we thank Prof. Helge Müller.
1. Moller JT, Johannessen NW, Berg H, Espersen K, Larsen LE. Hypoxaemia during anaesthesia: an observer study. Br J Anaesth 1991;66:437–44
2. Qaseem A, Snow V, Fitterman N, Hornbake ER, Lawrence VA, Smetana GW, Weiss K, Owens DK, Aronson M, Barry P, Casey DE Jr, Cross JT Jr, Sherif KD, Weiss KB. Risk assessment for and strategies to reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from the American College of Physicians. Ann Intern Med 2006;144:575–80
3. Thomas EJ, Goldman L, Mangione CM, Marcantonio ER, Cook EF, Ludwig L, Sugarbaker D, Poss R, Donaldson M, Lee TH. Body mass index as a correlate of postoperative complications and resource utilization. Am J Med 1997;102:277–83
4. Eichenberger A, Proietti S, Wicky S, Frascarolo P, Suter M, Spahn DR, Magnusson L. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg 2002;95:1788–92
5. Damia G, Mascheroni D, Croci M, Tarenzi L. Perioperative changes in functional residual capacity in morbidly obese patients. Br J Anaesth 1988;60:574–8
6. Pelosi P, Croci M, Ravagnan I, Cerisara M, Vicardi P, Lissoni A, Gattinoni L. Respiratory system mechanics in sedated, paralyzed, morbidly obese patients. J Appl Physiol 1997;82:811–8
7. von Ungern-Sternberg BS, Regli A, Schneider MC, Kunz F, Reber A. Effect of obesity and site of surgery on perioperative lung volumes. Br J Anaesth 2004;92:202–7
8. Schwartz AR, Patil SP, Laffan AM, Polotsky V, Schneider H, Smith PL. Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches. Proc Am Thorac Soc 2008;5:185–92
9. Busetto L, Calo E, Mazza M, De Stefano F, Costa G, Negrin V, Enzi G. Upper airway size is related to obesity and body fat distribution in women. Eur Arch Otorhinolaryngol 2009;266:559–63
10. Mortimore IL, Marshall I, Wraith PK, Sellar RJ, Douglas NJ. Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects. Am J Respir Crit Care Med 1998;157:280–3
11. Eastwood PR, Platt PR, Shepherd K, Maddison K, Hillman DR. Collapsibility of the upper airway at different concentrations of propofol anesthesia. Anesthesiology 2005;103:470–7
12. La Colla G, La Colla L, Turi S, Poli D, Albertin A, Pasculli N, Bergonzi PC, Gonfalini M, Ruggieri F. Effect of morbid obesity on kinetic of desflurane: wash-in wash-out curves and recovery times. Minerva Anestesiol 2007;73:275–9
13. Juvin P, Servin F, Giraud O, Desmonts JM. Emergence of elderly patients from prolonged desflurane, isoflurane, or propofol anesthesia. Anesth Analg 1997;85:647–51
14. Juvin P, Vadam C, Malek L, Dupont H, Marmuse JP, Desmonts JM. Postoperative recovery after desflurane, propofol, or isoflurane anesthesia among morbidly obese patients: a prospective, randomized study. Anesth Analg 2000;91:714–9
15. Blouin RA, Kolpek JH, Mann HJ. Influence of obesity on drug disposition. Clin Pharm 1987;6:706–14
16. Servin F, Farinotti R, Haberer JP, Desmonts JM. Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide: a clinical and pharmacokinetic study. Anesthesiology 1993;78:657–65
17. Eikermann M, Groeben H, Hüsing J, Peters J. Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology 2003;98:1333–7
18. Gudmundsson G, Cerveny M, Shasby DM. Spirometric values in obese individuals: effects of body position. Am J Respir Crit Care Med 1997;156:998–9
19. Standardized lung function testing. Official statement of the European Respiratory Society. Eur Respir J Suppl 1993;16:1–100
20. White PF, Song D. New criteria for fast-tracking after outpatient anesthesia: a comparison with the modified Aldrete's scoring system. Anesth Analg 1999;88:1069–72
21. Rose DK, Cohen MM, Wigglesworth DF, DeBoer DP. Critical respiratory events in the postanesthesia care unit: patient, surgical, and anesthetic factors. Anesthesiology 1994;81:410–8
22. von Ungern-Sternberg BS, Regli A, Reber A, Schneider MC. Effect of obesity and thoracic epidural analgesia on perioperative spirometry. Br J Anaesth 2005;94:121–7
23. Speicher A, Jessberger J, Braun R, Hollnberger H, Stigler F, Manz R. Postoperative pulmonary function after lung surgery: total intravenous anesthesia with propofol in comparison to balanced anesthesia with isoflurane [in German]. Anaesthesist 1995;44:265–73
24. Warner DO. Preventing postoperative pulmonary complications: the role of the anesthesiologist. Anesthesiology 2000;92:1467–72
25. Eichenberger A, Proietti S, Wicky S, Frascarolo P, Suter M, Spahn DR, Magnusson L. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg 2002;95:1788–92
26. Rampil IJ, Moller DH, Bell AH. Isoflurane modulates genomic expression in rat amygdala. Anesth Analg 2006;102:1431–8
27. Zaugg M, Lucchinetti E, Garcia C, Pasch T, Spahn DR, Schaub MC. Anaesthetics and cardiac preconditioning. Part II. Clinical implications. Br J Anaesth 2003;91:566–76