ORIGINAL ARTICLES
Predictors of Prolonged Postoperative Endotracheal Intubation in Patients
Undergoing Thoracotomy for Lung Resection
Jacek B. Cywinski, MD,* Meng Xu, MS,† Daniel I. Sessler, MD,‡ David Mason, MD,§ and
Colleen Gorman Koch, MD, MS¶
Objective: The aim of this study was to identify predictors
of delayed endotracheal extubation defined as the need for
postoperative ventilatory support after open thoracotomy
for lung resection.
Design: An observational cohort investigation.
Setting: A tertiary referral center.
Participants: The study population consisted of 2,068 patients who had open thoracotomy for pneumonectomy, lobectomy, or segmental lung resection between January
1996 and December 2005.
Interventions: Not applicable.
Measurements and Main Results: Preoperative and intraoperative variables were collected concurrently with the patient’s care. Risk factors were identified using logistic regression with stepwise variable selection procedure on 1,000
bootstrap resamples, and a bagging algorithm was used to
summarize the results. Intraoperative red blood cell transfu-
sion, higher preoperative serum creatinine level, absence of a
thoracic epidural catheter, more extensive surgical resection,
and lower preoperative FEV1 were associated with an increased risk of delayed extubation after lung resection.
Conclusion: Most predictors of delayed postoperative extubation (ie, red blood cell transfusion, higher preoperative serum creatinine, lower preoperative FEV1, and more extensive
lung resection) are difficult to modify in the perioperative period and probably represent greater severity of underlying lung
disease and more advanced comorbid conditions. However,
thoracic epidural anesthesia and analgesia is a modifiable factor that was associated with reduced odds for postoperative
ventilatory support. Thus, the use of epidural analgesia may
reduce the need for post-thoracotomy mechanical ventilation.
© 2009 Elsevier Inc. All rights reserved.
D
demographic variables, comorbid conditions, laboratory values, and
operative and outcome variables were collected concurrently with
patient care by individuals trained in database management in the
Department of Cardiothoracic Anesthesiology. Institutional review
board approval was obtained to perform analyses from the department
registry. Perioperative anesthetic care was not dictated by any specific
protocol. Decisions about patient management were left to the discretion of the attending anesthesiologist with the goal to provide optimal
surgical conditions and the ability to extubate at the end of the surgical
procedure. However, it has been the authors’ practice to initiate epidural catheters during the surgical procedure to achieve adequate
analgesia at the time of emergence from general anesthesia.
Descriptive statistics were calculated for all key predictors and demographic variables. Continuous variables were described with median and
25th and 75th percentiles, with p values for tests of differences between the
2 groups (extubated in the OR v not extubated in the OR). Categoric
variables were described with frequencies and percents, with p values for
tests of differences between groups. Univariate analysis was performed
with a chi-square test or Fisher exact test and Wilcoxon rank sum test
where appropriate. Categoric outcomes in the two groups were compared
with a chi-square test or Fisher exact test as appropriate.
Multivariable logistic regression was used to determine variables that
were associated with postoperative ventilatory support. Risk factors were
selected by using logistic regression with a stepwise variable selection
procedure on 1,000 bootstrap resamples. A bagging algorithm was used to
summarize the results. Entry criterion and stay criterion for the stepwise
selection processes were 0.07 and 0.05, respectively. The final logistic
regression models for the outcomes were built by using risk factors that
appeared in 50% of all models from the bootstrap resamples.
ELAYED POSTOPERATIVE EXTUBATION prolongs
the duration of recovery, increases cost, and may augment
postoperative morbidity.1 Early extubation (defined as extubation
in the operating room [OR]) decreases resource utilization, improves patients’ comfort, reduces morbidity related to mechanical
ventilation, and possibly allows for early ambulation and rehabilitation.2,3 After thoracic procedures and especially after lung resection, an additional benefit of limiting positive-pressure mechanical ventilation may include reducing pressure stress on the lung
tissue suture line, potentially decreasing postoperative air leak.4-6
Identifying patients at risk for delayed extubation may allow
clinicians to institute appropriate interventions perioperatively,
which might in turn decrease the duration of postoperative
ventilatory support and allow for more efficient resource allocation. The authors’ objective was to identify preoperative
variables associated with delayed postoperative extubation after thoracotomy for lung resection.
METHODS
The patient population consisted of 2,068 patients who had open
lung resection surgery (pneumonectomy, lobectomy, or segmental lung
resection) between January 1996 and December 2005. Preoperative
From the Departments of *General Anesthesiology, †Quantitative
Health Sciences, ‡Outcomes Research, §Thoracic and Cardiovascular Surgery, and ¶Cardiothoracic Anesthesia, Cleveland Clinic, Cleveland, OH.
Address reprint requests to Jacek B. Cywinski, MD, Department of
General Anesthesia/E31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: [email protected]
© 2009 Elsevier Inc. All rights reserved.
1053-0770/09/2306-0002$36.00/0
doi:10.1053/j.jvca.2009.03.022
766
KEY WORDS: anesthesia, thoracotomy, postoperative mechanical ventilation, lung resection, extubation
RESULTS
Table 1 presents a comparison of patients who were extubated
in the OR versus those who arrived to a recovery area intubated,
based on categoric preoperative and intraoperative variables. Pa-
Journal of Cardiothoracic and Vascular Anesthesia, Vol 23, No 6 (December), 2009: pp 766-769
PROLONGED POSTOPERATIVE ENDOTRACHEAL INTUBATION
767
Table 1. Comparison of Patients Who Were Extubated in the OR Versus Those Who Arrived to a Recovery Area Intubated Based on
Categoric Preoperative and Intraoperative Variables
Arrived Extubated
Factor
(%)
Arrived Intubated
Level
Total
N
N
(%)
No
Yes
912
1,156
788
989
44.3
55.7
124
167
42.6
57.4
No
Yes
1,566
502
1,355
422
76.3
23.8
211
80
72.5
27.5
No
Yes
1,820
248
1,572
205
88.5
11.5
248
43
85.2
14.8
No
Yes
1,978
90
1,707
70
96.1
3.9
271
20
93.1
6.9
No
Yes
2,061
7
1,771
6
99.7
0.34
290
1
99.7
0.34
No
Yes
493
1,575
427
1,350
24.0
76.0
66
225
22.7
77.3
No
Yes
1,857
211
1,643
134
92.5
7.5
214
77
73.5
26.5
No
Yes
2,064
4
1,774
3
99.8
0.17
290
1
99.7
0.34
No
Yes
345
1,723
256
1,521
14.4
85.6
89
202
30.6
69.4
No
Yes
1,892
176
1,637
140
92.1
7.9
255
36
87.6
12.4
SLR
LOL
CP
241
1,501
326
225
1,298
254
12.7
73.0
14.3
16
203
72
5.5
69.8
24.7
No
Yes
1,882
186
1,649
128
92.8
7.2
233
58
80.1
19.9
Male sex
p Value*
0.58
History of COPD or asthma
0.17
History of diabetes
0.11
History of stroke
0.023
History of end-stage renal disease requiring dialysis
0.99†
History of smoking
0.62
⬍0.001
Intraoperative RBC transfusion
Intraoperative placement of intercostal nerve block
0.46†
⬍0.001
Use of thoracic epidural analgesia
⬍0.001
Use of lumbar epidural analgesia
⬍0.001
Procedure
⬍0.001
Reintubated
Abbreviations: LOL, lobectomy of lung; SLR, segmental lung resection; CP, complete pneumonectomy; COPD, chronic obstructive pulmonary
disease; RBC, red blood cell.
*Chi-square test unless noted.
†Fisher exact test.
tients who were not extubated in the OR had more intraoperative
red blood cell (RBC) transfusions, a history of preoperative stroke,
lower use of thoracic epidural analgesia (TEA), and a higher rate
of intraoperative use of lumbar epidural analgesia. A comparison
of continuous variables is summarized in Table 2. Patients who
were not extubated in the OR had a lower preoperative forced
expiratory volume in 1 second (FEV1), lower forced vital capacity
(FVC), lower preoperative hematocrit and albumin, and higher
preoperative creatinine.
The median intubation time in the OR was 3.9 hours (with
25th and 75th percentile of 3.0 and 5.0 hours). The median
postoperative intubation time (total intubation time minus the
OR intubation time) was 7.93 hours, with the 25th percentile
being 2.75 hours and the 75th percentile 20.67 hours for patients who were not extubated in the OR.
The final multivariate logistic regression identified the following predictors of postoperative prolonged intubation: intraoperative RBC transfusion (odds ratio ⫽ 2.68 [1.92, 3.74], p ⬍ 0.001),
absence of TEA catheter (odds ratio ⫽ 2.27 [1.72, 3.03], p ⬍ 0.001),
elevated preoperative serum creatinine level (odds ratio ⫽ 1.42 [1.20,
1.69], p ⬍ 0.001), and preoperative FEV1 (per 1 unit decrease [odds
ratio ⫽ 1.47 (1.23, 1.72), p ⬍ 0.001]) as well as the extent of the
lung resection for segmental lung resection, lobectomy, and complete pneumonectomy (more extensive lung resection was predictive of postoperative ventilation, Table 3 and Fig 1).
DISCUSSION
Early postoperative extubation after lung resection is desirable because it saves medical resources and may help to avoid
ventilator-related complications.6 An ability to identify periop-
768
CYWINSKI ET AL
Table 2. Comparison of Patients Who Were Extubated in the OR Versus Those Who Arrived to a Recovery Area Intubated Based on
Continuous Variables
Arrived Extubated
Arrived Intubated
Factor
N
Median (25th, 75th)
N
Median (25th, 75th)
p Value*
Age (y)
BSA (m2)
BMI
Preoperative Measured FEV1
Preoperative Measured FVC
Preoperative HCT
Preoperative serum creatinine (mg/dL)
Preoperative albumin (g/dL)
Core temperature at the end of the case (°C)
1,777
1,777
1,777
1,639
1,639
1,776
1,774
1,738
1,720
65.0 (56.5, 72.3)
1.9 (1.7, 2.0)
26.3 (23.3, 30.1)
2.2 (1.7, 2.8)
3.2 (2.5, 4.0)
40.5 (37.6, 43.2)
0.9 (0.7, 1.0)
4.2 (3.9, 4.4)
36.0 (35.5, 36.5)
291
291
291
267
266
291
291
282
279
66.6 (57.1, 72.5)
1.8 (1.7, 2.0)
26.3 (22.2, 30.5)
2.0 (1.6, 2.5)
2.9 (2.3, 3.6)
39.7 (36.3, 42.8)
1.0 (0.8, 1.1)
4.1 (3.8, 4.3)
36.0 (35.5, 36.5)
0.24
0.21
0.61
⬍0.001
⬍0.001
0.003
⬍0.001
⬍0.001
0.81
Abbreviations: BSA, body surface area; BMI, body mass index; HCT, hematocrit.
*Wilcoxon sum rank test used.
erative modifiable predictors of delayed extubation may help
clinicians design interventions to reduce postoperative ventilation time. However, identifying nonmodifiable predictors is
also helpful because it allows patients to be risk stratified and
facilitates appropriate allocation of clinical resources.
Patients with poor preoperative lung function had a higher
incidence of postoperative morbidity including prolonged mechanical ventilation.7 Lower preoperative FEV1 is frequently considered a strong predictor of postoperative complications (including prolonged mechanical ventilation) after lung resection,8
although it is not uniformly accepted as a predictor of postoperative cardiopulmonary complications.6,9-11 In the authors’ patients,
low preoperative FEV1 was associated with greater odds of postoperative ventilation. However, it seems likely that lower FEV1 is
simply a marker for advanced lung disease, which would be
difficult to correct with perioperative interventions. Recognizing
the association between low FEV1 and delayed postoperative
extubation may nonetheless help allocate resources (ie, postoperative disposition recovery room v intensive care unit) to patients
who are likely to require postoperative mechanical ventilation.
The present investigation showed that intraoperative RBC
transfusion was strongly predictive of delayed extubation. The
association of intraoperative RBC transfusion with postoperative intubation may well be related to the fact that RBC trans-
fusion provokes a harmful inflammatory response that may
contribute to lung injury.12 However, it is more likely that
higher requirements for intraoperative RBC are surrogates for
more complex and technically difficult procedures, which
themselves may adversely affect postoperative respiratory outcomes.6 Furthermore, the need for RBC transfusion may indicate that patients suffer advanced comorbid conditions, which
then prompts clinicians to use more liberal thresholds for the
transfusion as compared with “healthier” patients.
Adequate pain control after thoracic surgery may improve
ventilatory function (better expansion of the chest, deeper respiration, and stronger coughing), which contributes to a patient’s readiness to be extubated.13 For example, Bauer et al14
showed that postoperative pain relief was better in patients
randomized to TEA after lobectomy at rest and on coughing (as
compared with intravenous morphine) and that there was less
impairment of FVC and FEV1 postoperatively. It is unknown if
the same beneficial effect of TEA on FVC and FEV1 can be
achieved immediately at the end of the surgical procedure, but
it is plausible to assume that reduction in pain and pain-related
impairment of chest mechanics can facilitate earlier extubation.
Intraoperative activation of an epidural catheter also spares
opioids, which presumably improves postoperative respiratory
function. Consistent with this theory, the authors found that the use
Table 3. Risk Factors for Delayed Extubation From the
Multivariable Regression Model
Factor
Odds Ratio (CI)
p Value
Intraoperative RBC transfusion
(yes/no)
Preoperative serum creatinine
Presence of thoracic epidural
Lower preoperative
measured FEV1
Type of procedure
2.68 (1.92, 3.74)
⬍.001
1.42 (1.20, 1.69)
0.44 (0.33, 0.58)
1.47 (1.23, 1.72)
⬍0.001
⬍0.001
⬍0.001
⬍0.001
SLR v CP: 0.33 (0.20, 0.56) ⬍0.001
LOL v CP: 0.70 (0.52, 0.95)
0.022
SLR v LOL: 0.47 (0.30, 0.75) 0.001
Abbreviations: LOL, lobectomy of lung; SLR, segmental lung resection; CP, complete pneumonectomy; RBC, red blood cell; CI, confidence interval.
Fig 1. A forest plot showing odds ratio and 95% confidence interval of all variables associated with prolonged intubation after open
thoracotomy for lung resection. LOL, lobectomy of lung; SLR, segmental lung resection; CP, complete pneumonectomy; RBC, red
blood cell.
PROLONGED POSTOPERATIVE ENDOTRACHEAL INTUBATION
769
of TEA improved the odds of OR extubation in the present
patients. Other methods of postoperative pain control after thoracotomy have been reported in the literature including paravertebral
and intercostal blocks and interpleural and subarachnoid administration of drugs. Among these alternatives, paravertebral blocks
appear to be the most effective alternative when epidural blocks
cannot be performed.15,16 Thus, it seems likely that a paravertebral
block would provide benefits similar to TEA.
Preoperative renal dysfunction is a well-recognized risk for increased morbidity after cardiac and thoracic surgery.7 Renal impairment is considered by many as a marker of cardiovascular dysfunction and by itself can make perioperative fluid management more
difficult, potentially affecting lung function after resection.7 As
might be expected, elevated preoperative creatinine was associated
with delayed endotracheal extubation in the present patients.
The authors found that the volume of the surgical lung resection
was a good predictor of delayed postoperative extubation (the
more extensive the resection, the greater the chance for postoperative mechanical ventilation). However, it would be an oversimplification to assume that a larger volume of resected lung tissue
alone predisposes to extended mechanical ventilation because in
many cases the resected, diseased portion of the lung does not
participate in respiratory function. That fact can explain why in the
present analysis preoperative FEV1 was strongly associated with
the chance for postoperative ventilation without adjustment for the
loss of lung function after resection.
Of course, extensive lung resection is also likely to be a surrogate
for a more advanced and/or extensive disease process, which
presumably contributes independently to postoperative respiratory
morbidity. Clinicians must also consider that factors besides the
extent of lung tissue removed account for the loss in respiratory
function observed early after lung resection including impairment
in chest wall compliance, accumulated bronchial secretions, bronchial hyperreactivity, microatelectasis, increased lung water content,
diaphragmatic dysfunction, and reduced surfactant activity.17,18
The main limitation of the present analysis is its retrospective nature, which could not account for all variables, potentially affecting decisions of when to extubate the patient. Furthermore, patients in the present study represent a population
treated over a period of 9 years; hence, changes in the practice
could play a role in the decision regarding timing of extubation.
And, finally, the authors were unable to analyze the association
between predicted postoperative FEV1 and delayed extubation,
which might have been, as some suggest, a stronger predictor
of postresection lung function than preoperative FEV1 alone.
In summary, the authors found most predictors of delayed
endotracheal extubation to be difficult to correct in the perioperative period. Lower FEV1, elevated preoperative creatinine, and
intraoperative requirements for RBC transfusion may simply represent a more advanced underlying lung disease, advanced comorbid conditions, or technically more difficult surgical procedures.
Recognizing the predictive importance of these factors may nonetheless help identify patients at risk for extended postoperative
mechanical ventilation and help to allocate postoperative resources. In contrast, the use of TEA is a straightforward intervention that may reduce the odds of prolonged postoperative ventilation.
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