Improvement of ‘dynamic analgesia’ does not decrease atelectasis after thoracotomy

N. Boisseau1, O. Rabary1, B. Padovani2, P. Staccini3, J. Mouroux4, D. Grimaud1 and M. Raucoules-Aimé1

1Department of Anesthesiology, 2Department of Radiology, 3Department of Clinical Statistics, and 4Department of Thoracic Surgery, Nice School of Medecine, University of Nice-Sophia Antipolis, Hôpital Pasteur, Avenue de la voie romaine, F-06000 Nice, CHU de Nice, France*Corresponding author

Accepted for publication: April 30, 2001


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
There is still controversy concerning the beneficial aspects of ‘dynamic analgesia’ (i.e. pain while coughing or moving) on the reduction of postoperative atelectasis. In this study, we tested the hypothesis that thoracic epidural analgesia (TEA) prevents these abnormalities as opposed to multimodal analgesia with i.v. patient controlled analgesia (i.v. PCA) after thoracotomy. Fifty-four patients undergoing thoracotomy (lung cancer) were randomly assigned to one of the two groups. Clinical respiratory characteristics, arterial blood gas, and pulmonary function tests (forced vital capacity and forced expiratory volume in 1 s) were obtained before surgery and on the next 3 postoperative days. Atelectasis was compared between the two groups by performing computed tomography (CT) scan of the chest at day 3. Postoperative respiratory function and arterial blood gas values were reduced compared with preoperative values (mean (SD) FEV1 day 0: 1.1 (0.3) litre; 1.3 (0.4) litre) but there was no significant difference between groups at any time. PCA and TEA provided a good level of analgesia at rest (VAS day 0: 21 (15/100); 8 (9/100)), but TEA was more effective for analgesia during mobilization (VAS day 0: 52 (3/100); 25 (17/100)). CT scans revealed comparable amounts of atelectasis (expressed as a percentage of total lung volume) in the TEA (7.1 (2.8)%) and in the i.v. PCA group (6.71 (3.2)%). There was no statistical difference in the number of patients presenting with at least one atelectasis of various types (lamellar, plate, segmental, lobar).

Br J Anaesth 2001; 87: 564–9

Keywords: complications, pulmonary; complications, morbidity; anaesthetics local; analgesics opioid, morphine; physiotherapy


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Postoperative analgesia may improve morbidity and clinical outcome.13 However, the influence of analgesic techniques on atelectasis formation is still a matter of debate. Because of diaphragmatic dysfunction and pain, thoracotomy induces a severe postoperative restrictive syndrome. Compared with systemic opioids, thoracic epidural analgesia (TEA) allow patients to cough and breath deeply,4 both measures that increase lung volume. Therefore, we hypothesized that atelectasis may be prevented by better ‘dynamic’ analgesia with TEA.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The sample size for this study was based on atelectasis rates cited in previous studies.5 6 The data suggested that a power of 95% for detecting a 50% difference in atelectasis at an alpha level of 0.05 would be obtained with 23 patients in each group. The study procedure was approved by the ethics committee of Nice University (CCPPRB, Nice) and 54 patients gave their informed consent. Patients were scheduled for thoracic surgery (lung cancer) by postero-lateral thoracotomy. A smoking history of more than 20 pack yr was required. Criteria of non-inclusion were immune depression (corticosteroid therapy or HIV infection), history of fever or infection, poor nutrition or obesity (body mass index (BMI) less than 18 or over 30), atelectasis of all types on systematic preoperative computed tomography (CT) scan and contraindication for TEA, i.v. patient-controlled analgesia (i.v. PCA), or non-steroidal anti-inflammatory drugs (NSAIDs).

Respiratory characteristics were determined by clinical examination, chest x-ray, arterial blood gas analysis and respiratory function tests (forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC)). The day before surgery, patients were randomized in one of the two groups of analgesia using a table of random numbers to receive either postoperative i.v. opioid PCA or epidural ropivacaine–sufentanil (TEA).

All patients were premedicated with 100 mg oral hydroxyzine and were given 1.5 g cefuroxime 1 h before and for 24 h after surgery (750 mg every 8 h). In the TEA group, a 20-gauge catheter (Vygon, Les Ulis, France) was inserted 3–4 cm into the epidural space after midline puncture at T4–T5 with a Tuohy needle (Braun, Melsungen, Germany). Good position was defined by bilateral anaesthesia between T1 and T8 after injection of 3 ml of 2% lidocaine with 1/200 000 epinephrine via the epidural catheter. If the catheter could not be inserted or was accidentally withdrawn before day 3, the patient was given an i.v. PCA pump, but was kept in the TEA group for the intention to treat analysis.

General anaesthesia was standardized in groups. Induction was achieved with thiopental 5 mg kg–1, sufentanil 0.5 µg kg–1, and atracurium 0.5 mg kg–1. After tracheal intubation with a left side double lumen endobronchial tube (Carlens®, Rüsch, Germany) (39 French women, 41 French men) the lungs were ventilated by a volume-cycled ventilator (Cato®, Dräger, Germany) at zero end-expiratory pressure, with a tidal volume of 10 ml kg–1. The rate was adjusted to maintain an end-tidal carbon dioxide partial pressure near 35 mm Hg. After checking clinically that ventilation of the operative lung had ceased, anaesthesia was maintained with 0.5–1 MAC sevoflurane and 70–80% oxygen in air, with the same ventilatory parameters maintained during one lung ventilation. Continuous infusion of atracrium 0.6 mg kg–1 h–1 and sufentanil 0.3 µg kg–1 h–1 was also maintained. Central body temperature and urinary flow were monitored. Invasive arterial pressure was monitored with a radial catheter inserted under general anaesthesia and a central venous line measured central venous pressure. At the end of surgery, the upper lung was re-expanded by manual inflation under visual control with 50% nitrous oxide–oxygen. The final inflation was performed at Paw=40 cm H2O for 5 s. Patients were warmed until body temperature reached 36°C. When clinical signs of weaning were present, patients were extubated and oxygen administered via a nasal probe, adapted to pulse oximeter values (3–6 litre min–1). Patients were placed in the PACU for 4 days.

Patients in the TEA group received an epidural continuous infusion of ropivacaine 0.2% combined with sufentanil (1 or 0.5 µg ml–1 if age was over 70 yr). An infusion started 1 h before the end of surgery at a rate of 6 ml h–1, and was adjusted thereafter according to the visual analogue scale (VAS). In the recovery room, i.v. PCA patients received an initial i.v. bolus administration of morphine (3-mg doses every 5 min) titrated by a nurse until VAS was lower than 40 mm. At this time, a PCA pump (Abbott Pain Manager®, Abbott Laboratories, North Chicago, IL, USA) was connected using a 1.5 mg bolus and a 5 min lockout period. If pain control was considered insufficient (i.e. VAS greater than 40 mm) analgesia rescue doses were given and repeated until efficient analgesia was achieved. In the i.v. PCA group, patients received a supplemental morphine 3 mg bolus every 5 min and in the TEA group, patients were given a supplemental bolus of ropivacaine 6 ml and continuous infusion was increased by steps of 2 ml h–1 every 30 min if needed. Patient monitoring and treatment of hypotension, nausea, vomiting, and pruritus were standardized. In case of hypotension (defined as systolic arterial pressure lower than 90 or 100 mm Hg in patients with arterial hypertension history), patients were given boluses of ephedrine from 3 to 30 mg titrated to achieve values over 100 mm Hg. For nausea, droperidol 2.5 mg was given i.v. every 4 h as needed, followed by ondansetron 4 mg if control was insufficient or if vomiting occurred. For itching, propofol 10–20 mg was given i.v. every 6 h as needed. All patients received propacetamol 2 g, an injectable acetaminophen prodrug, every 6 h, and 300 mg per 24 h continuous infusion of ketoprofen for 3 days. Patients were encouraged to use the PCA as often as needed and before physiotherapy.

Physiotherapy was performed twice a day by the same physiotherapist, according to a standardized 20-min procedure: abdominal and diaphragmatic breathing, deep breathing exercises and effective coughing. All patients received terbutalin aerosol just before physiotherapy. Patients were maintained in a semirecumbent position, and sat in an armchair the day following surgery.

Characteristics of patients were noted as well as factors influencing respiratory function, for example, smoking habit (pack yr), current or past-smoker (i.e. patients who stopped smoking for more than 8 weeks).7 All patients received respiratory physiotherapy for almost 3 days preoperatively. Type of lung resection, duration of lung separation and anaesthesia, blood transfusion and volume of fluid infused during surgery were also noted. Blood gas analysis was performed daily at 07:00 in ambient air for 15 min, as well as a respiratory function test in a sitting position (Flow Meter®, Sherwood Medical, St Louis, MO, USA), measuring FVC and FEV1. The physician performing the respiratory function tests was blinded to the study group. The best of three measurements was retained for analysis.

Chest x-ray was performed immediately after extubation. Thoracic CT scan was performed on the third day after the surgery (ELITE®, Epscint, IL, USA). All patients were placed in the supine position with arms above the head. Images were obtained from lung apex to costodiaphragmatic angle without i.v. infusion of contrast. Scans were obtained after inspiration of an ordinary tidal volume (acquisition time=1.1 s per section, tube current=240 mA and 140 KVp, matrix 512x512). The slice thickness was 10 mm with a 20 mm interval. Some 1 mm thick slices were obtained in patients with atelectasis. The dorsal border of atelectasis was manually highlighted. The ventral border between atelectasis and normal lung tissue was evaluated. The exact amount of atelectasis was calculated as the sum of all pixels (picture elements) having a density between –100 and +100 Hounsfield units.8 Absolute lung area was calculated for each scan as atelectatic and aerated areas. The extent of atelectasis was expressed in square centimetres as a percentage of the total lung area. Atelectasis was also classified into four types depending on thickness: lamellar atelectasis <3 mm, plate atelectasis >3 mm and <10 mm, segmental atelectasis >10 mm and lobar atelectasis.9

Clinical complications were assessed daily. A chest x-ray was performed and analysed by a radiologist in case of tachypnea over 20 breaths min–1 associated with an arterial oxygen partial pressure below 60 mm Hg despite 6 litre min–1 oxygen and fever (above 38.5°C). Clinical respiratory complications were classified in two groups: (1) atelectasis with clinical intolerance requiring bronchial clearing by fibroscopy (CT scan was performed just before the fibroscopy) and (2) pneumonia (modified criteria of Andrews).10

Patients assessed pain using VAS ranging from 0 (no pain) to 100 mm (worst pain imaginable) at rest and while coughing every 4 h. All patients were instructed how to use the VAS preoperatively. Side effects arising from the analgesic procedure were also recorded. General effects including hypotension (systolic arterial pressure <90 mm Hg or 100 if hypertension history), heart rate, sedation (0=awake, 1=sleepy but awakened by oral order, 2=sleepy but awakened by nociceptive stimulation, 3=not responsive), respiratory depression (respiratory rate less than 8 breaths min–1), confusion, nausea, vomiting, and pruritus, were recorded at 4-h intervals for 4 days. Lower limb motor block was assessed twice a day with the Bromage score (0=no paralysis; 1=unable to raise the leg, 2=enable to bend the knee, 3=paralysis). Local complications were also sought, including neurological complications, catheter occlusion, kinks, and displacement.

On the fourth day, the epidural catheter was withdrawn, and bacteriological analysis performed. At the end of the study, global satisfaction concerning pain was evaluated on a VAS (0 mm=not satisfied; 100 mm=entirely satisfied).

The perioperative characteristics were compared using chi-squared analysis for category and the Kruskall–Wallis test for continuous variables. The overall incidence of atelectasis in the two groups was compared with chi-squared analysis, whereas the percentage of atelectasis was evaluated with a Wilcoxon test. Postoperative assessment for all variables measured over time was evaluated using repeated measures analysis of variance. Results are presented as mean (SD). A significance threshold of P<0.05 was retained.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Fifty-four patients were randomly assigned to one of the two groups of the study. Four patients were excluded: two in the i.v. PCA group (one atelectasis because of twist of the middle lobe diagnosed early at day 1, one myocardial infarction at day 2), two patients in the TEA group (one lung exclusion over 2.5 h because of difficult surgical procedure with postoperative lobar atelectasis diagnosed on chest x-ray just after extubation, one cardiac failure because of atrial arrhythmia). Statistical analysis, therefore, concerned 50 patients (i.v. PCA n=25, TEA n=25). Characteristics and preoperative respiratory evaluation tests were comparable in the two groups (Table 1). Accidental withdrawal of the epidural catheter before day 3 occurred in two patients and these were given an i.v. PCA pump.


View this table:
[in this window]
[in a new window]
 
Table 1 Perioperative data and preoperative respiratory characteristics of patients. Values are mean (SD). Differences between the two groups were not statistically significant
 
The number of patients with lobar or infralobar atelectasis was comparable in the two groups (Table 2). The amount of atelectasis (expressed as a percentage of total lung volume) observed on the CT scans (mean (SD) [range]) did not differ significantly in the patients with TEA 7.1 (2.8) (0–28) i.v. PCA 6.71 (3.2) (0–31 i.v.)%. These data provided a 99% chance of detecting a 2% difference in atelectasis surface at an alpha level of 0.05. Two patients in each group developed poor respiratory function before day 3, and had a CT scan before any treatment (bronchial fibroscopy for atelectasis, or mechanical ventilation). Two patients in the TEA group, and one in the i.v. PCA group developed documented pneumonia requiring re-intubation and mechanical ventilation. The overall incidence of clinical respiratory complications was 14% (i.v. PCA: n=4; TEA: n=3). Three patients (all right pneumonectomy) died following these complications (6%), two in the TEA group, and one in the i.v. PCA group.


View this table:
[in this window]
[in a new window]
 
Table 2 Number of patients with at least one atelectasis of each type, assessed by CT scan. Values are expressed in numbers and percentage of patients. Differences between the two groups were not statistically significant
 
Compared with the preoperative value, FEV1 decreased by 56% in the i.v. PCA group (P<0.05) and 44% in the epidural group (P<0.05) after surgery. FVC values also fell by 63 and 55%, respectively (P<0.05) (Fig. 1). No differences were seen between groups. Arterial blood gas analysis also disclosed an approximately 15% decrease in PaO2, similar and significant (P<0.05) for the two groups (Fig. 2).



View larger version (17K):
[in this window]
[in a new window]
 
Fig 1 Spirometry values in both analgesic groups before and after surgery. VC=vital capacity; FEV1=forced expiratory volume in 1 s; TEA group=group of patients with epidural analgesia. D-1=preoperative day 1; D0=recovery room; D1=first postoperative day. Values are mean (SD).

 


View larger version (20K):
[in this window]
[in a new window]
 
Fig 2 Arterial blood gases before and after surgery in both groups. PaO2=arterial oxygen tension; PaCO2=arterial carbon dioxide tension. D-1=preoperative day 1; D0=recovery room; D1=first postoperative day. Values are mean (SD).

 
The VAS was scored every 4 h at rest and while coughing. Figures 3 and 4 show the highest score recorded over the preceding 12 h for 4 days. At rest, the VAS score was lower the first day in TEA group and similar to i.v. PCA on the next day. Likewise, TEA provided better analgesia while coughing for the 4 days compared with PCA. In the i.v. PCA group, total amount of morphine given was 55 (SD 15) mg during the first 24 h and 147 (26) mg for 4 days. Mean rate of ropivacaine–sufentanil mixture given was 7.5 (1.4) ml h–1. No side effect attributed to NSAIDs was noted.



View larger version (16K):
[in this window]
[in a new window]
 
Fig 3 Evaluation of analgesia by VAS at rest. In the recovery room, two patients in the TEA group and seven patients in the PCA group were unable to score their pain on the VAS. Values are mean (SD). *P<0.05 between the two groups.

 


View larger version (19K):
[in this window]
[in a new window]
 
Fig 4 Evaluation of analgesia by VAS score during a cough. Values are mean (SD). *P<0.05 between the two groups.

 
On the first day, sedation scores were higher with i.v. PCA and episodes of arterial hypotension requiring boluses were more frequent with TEA (Table 3). Lowest recorded systolic arterial pressure was 77 (15) in the TEA group vs 115 (12) in the i.v. PCA group. There was no difference between the two groups with respect to other side effects during the 4 days of the study (Table 3). Three patients in each group developed mild temporal and spatial disorientation lasting 24 h. No cause was found including local anaesthetic toxiciy. During this period, the VAS score was not recorded and compliance with physiotherapy was unsatisfactory. In addition, the patients lost the ability to use the i.v. PCA pump. In the TEA group, no motor block (Bromage 2 or 3) was noted. One patient experienced paraesthesia of the upper limb, which resolved after withdrawal of the epidural catheter. No patient developed an infection at the puncture site but two patients (8%) had catheters colonized by coagulase negative staphylococci (greater than 200 c.f.u.). The length of hospitalization was 13.8 (3.9) (i.v. PCA group) vs 13.5 (4) days (TEA group) (P=0.12). Score of satisfaction for the two techniques of analgesia were: TEA 86 (12) and i.v. PCA 83 (15) cm (P=0.12).


View this table:
[in this window]
[in a new window]
 
Table 3 Principal side effects with the two analgesic techniques. Values are expressed in percentage of patients. Arterial hypotension defined by value below 90 or 100 mm Hg if arterial hypertension history. *P<0.05
 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
After thoracotomy, most postoperative deaths are the consequence of respiratory complications.11 12 The incidence of these complications varies widely from one study to another (5–70%) because no clear definitions are presently available and clinical assessment may be subjective. CT scans provide an objective measure of the state of the lung resulting from the influence of analgesia on ventilatory mechanical dysfunction. Functional residual capacity decreases sharply in the postoperative period, leading to the formation of collapsed lung tissue, beginning in the dependent regions. Active physiotherapy and pain control increase lung volume and may prevent consolidation.13 Atelectasis is also thought to be an important cause of morbidity, leading to hypoxaemia, pneumonia and/or respiratory failure.14 15 Diagnoses is generally based on daily chest x-rays. The incidence is 20–30%.16 A comparison with data from CT scans shows that chest x-rays are rather insensitive, particularly for low position consolidation in the lower lung.17 More than half of our patients presented with lung collapse (plate, segmental, and/or lobar atelectasis).

Peroperative atelectasis was virtually eliminated by performing re-expansion manoeuvres.18 CT scans were obtained on the third day when the impact of analgesia was greatest. The scans were obtained after the inspiration of a normal tidal volume because the patients could not sustain a prolonged expiration. Radiological abnormalities seen earlier could have been influenced by the intraoperative period and pain was less intense up to day 3. We observed no atelectasis resulting from extrinsic compression, such as pleural effusion or gastric distention. This supports the idea that the reported incidence of these abnormalities reflects the quality of analgesia and postoperative physiotherapy.

Our main objective for analgesia was to obtain a VAS score at rest of less than 40 mm at rest at all times. Some authors have reported delays of 6–12 h before obtaining effective analgesia with i.v. PCA.19 We attempted to avoid these delays by concentrating on early pain scores and giving rescue analgesia doses to either group to obtain efficient, prolonged pain control at rest. However, pain relief during coughing or deep breathing exercises could only be obtained with TEA and local anaesthetics, in agreement with previous studies.4 A meta-analysis has also demonstrated that postoperative atelectasis is reduced by epidural analgesia.20 However, the control patients were given nurse-controlled intermittent parenteral injections of opioids, which may have resulted in an inappropriate plasma opioid concentration. The absence of difference between our groups could be a result of two factors: first, better pain control provided by i.v. PCA, as plasma opioid concentrations remained within the therapeutic index;21 second, the effect of multimodal analgesia, which reduces morphine consumption and improves the quality of analgesia.22

Respiratory physiotherapy designed to increase pulmonary volume prevents atelectasis and pulmonary complications.23 24 Because all patients were informed preoperatively about the importance of physiotherapy to prevent respiratory complications, all of them, in the i.v. PCA group sustained 20-min physiotherapy sessions twice a day, despite their pain. In addition, deep breathing exercises were done with the same efficiency whatever the analgesic techniques used, as all the groups had comparable forced vital capacity values. Respiratory comfort during physiotherapy was better with TEA than with multimodal analgesia, but it had no beneficial effect on postoperative lung consolidation.

Our patients could be classified as low respiratory risk on the basis of preoperative pulmonary function tests. However, there is no data suggesting that spirometry can identify high risk patients because of its variable predictive value.13 All the patients had been heavy smokers and almost half of them were smokers at the time of surgery; both of these factors are clinical respiratory risks.25 26 Most of the patients in other studies had no clinical risk factors, which explains the lack of difference between systemic opioids and TEA in pulmonary complications.5 Our population is representative of the large majority of patients undergoing thoracotomy, but it would be valuable to study the influence of TEA in a high risk groups selected with high risk factors.

We found no difference in clinical respiratory complications or in the length of hospital stays for the two groups of thoracotomized patients. The lack of statistical power to detect significant differences in true clinical outcomes could explain these results, as 150 patients would be required. Yeager and colleagues found an improvement in postoperative morbidity after thoracic surgery in high risk patients given epidural analgesia.27 However, in the absence of preoperative respiratory characteristics, clear definitions and sensitive diagnosis assessment of atelectasis and clinical respiratory complications, it is difficult to affirm a clear benefit of central block on postoperative pulmonary morbidity compared with parenteral opioids in that study.

In summary, despite optimization of i.v. PCA, the administration of local anaesthetics and opioids delivered via a thoracic epidural catheter provides better analgesia while coughing. However, compared with multimodal analgesia and active physiotherapy, TEA does not improve spirometric or oxygenation parameters, nor the amount and size of atelectasis on a standard population of smokers undergoing resection of lung cancer.


    Acknowledgements
 
The authors thank the nurses of the PACU of Thoracic Surgery, Dr Caroline Touati for the bacteriological analysis, Dr Françoise Guillot and Jean-François Ciais for help and for reviewing the manuscript.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
1 Liu SS, Carpenter RL, Mackey DC, et al. Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology 1995; 83: 757–65[ISI][Medline]

2 Wasylak TJ, Abbott FV, English MJ, Jeans MEF. Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 1990; 37: 726–31[Abstract]

3 Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91: 8–15[ISI][Medline]

4 George KA, Wright PM, Chisakuta AM, Rao NVF. Thoracic epidural analgesia compared with patient controlled intravenous morphine after upper abdominal surgery. Acta Anaesthesiol Scand 1994; 38: 808–12[ISI][Medline]

5 Jayr C, Thomas H, Rey A, Farhat F, Lasser P, Bourgain JLF. Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral opioids. Anesthesiology 1993; 78: 666–76[ISI][Medline]

6 Mann C, Pouzeratte Y, Boccara G, et al. Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000; 92: 433–41[ISI][Medline]

7 Warner MA, Divertie MB, Tinker JHF. Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients. Anesthesiology 1984; 60: 380–3[ISI][Medline]

8 Drummond GB. Computed tomography and pulmonary measurements. Br J Anaesth 1998; 80: 665–671[ISI][Medline]

9 Westcott JL, Cole S. Plate atelectasis. Radiology 1985; 155: 1–9[Abstract]

10 Andrews CP, Coalson JJ, Smith JD, Johanson WG Jr. Diagnosis of nosocomial bacterial pneumonia in acute, diffuse lung injury. Chest 1981; 80: 254–8[Abstract]

11 Nagasaki F, Flehinger BJ, Martini NF. Complications of surgery in the treatment of carcinoma of the lung. Chest 1982; 82: 25–9[Abstract]

12 Patel RL, Townsend ER, Fountain SWF. Elective pneumonectomy: factors associated with morbidity and operative mortality. Ann Thorac Surg 1992; 54: 84–8[Abstract]

13 Smetana GWF. Preoperative pulmonary evaluation. N Engl J Med 1999; 340: 937–44[Free Full Text]

14 Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna G. Airway closure, atelectasis and gas exchange during general anesthesia. Br J Anaesth 1998; 81: 681–6[Abstract/Free Full Text]

15 Schwieger I, Gamulin Z, Suter PM. Lung function during anesthesia and respiratory insufficiency in the postoperative period: Physiology and clinical implications. Acta Anaesthesiol Scand 1989; 33: 527–34[ISI][Medline]

16 Goodman LRF. Postoperative chest radiograph: II. Alterations after major intrathoracic surgery. Am J Roentgenol 1980; 134: 803–13[ISI][Medline]

17 Beydon L, Saada M, Liu N, et al. Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery? A comparison with computed tomography scan. Chest 1992; 102: 1697–703[Abstract]

18 Rothen HU, Sporre B, Engberg G, Wegenius G, Hedenstierna GF. Re-expansion of atelectasis during general anaesthesia: a computed tomography study. Br J Anaesth 1993; 71: 788–95[Abstract]

19 Raffin L, Fletcher D, Sperandio M, et al. Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for postthoracotomy analgesia. Anesth Analg 1994; 79: 328–34[Abstract]

20 Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: 598–612[Abstract]

21 Mather L, Owen H. The pharmacology of patient-administered opioids. In: Ferrante FM, Covino BG eds. Patient-Controlled Analgesia. Boston: Blackwell Scientific, 1990; 27–50

22 Kehlet H, Dahl JBF. The value of ‘multimodal’ or ‘balanced analgesia’ in postoperative pain treatment. Anesth Analg 1993; 77: 1048–56[ISI][Medline]

23 Gracey DR, Divertie MB, Didier EP. Preoperative pulmonary preparation of patients with chronic obstructive pulmonary disease: a prospective study. Chest 1979; 76: 123–9[Abstract]

24 Thomas JA, McIntosh JM. Are incentive spirometry, intermittent positive pressure breathing, and deep breathing exercises effective in the prevention of postoperative pulmonary complications after upper abdominal surgery? A systematic overview and meta-analysis. Phys Ther 1994; 74: 3–10[ISI][Medline]

25 Celli BRF. Perioperative respiratory care of the patient undergoing upper abdominal surgery. Clin Chest Med 1993; 14: 253–61[ISI][Medline]

26 Bluman LG, Mosca L, Newman N, Simon DGF. Preoperative smoking habits and postoperative pulmonary complications. Chest 1998; 113: 883–9[Abstract/Free Full Text]

27 Yeager MP, Glass DD, Neff RK, Brinck-Johnsen TF. Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 1987; 66: 729–36[ISI][Medline]