Patients With Cystic Fibrosis Undergoing Posterior Lumbar Fusion Are at an Increased Odds of Perioperative Complications

Abstract

Introduction:

Perioperative outcomes for patients with cystic fibrosis (CF) have not been previously described following spine surgery. This study used PearlDiver to examine the 90-day postoperative outcomes and 4-year revision rates after posterior lumbar fusion (PLF) for patients with CF compared with matched controls.

Methods:

This study examined a cohort of PLF patients with versus without CF. Patients were matched 1:10 for age, sex, Elixhauser Comorbidity Index, and the number of levels. Ninety-day postoperative outcomes and 4-year revision rates were compared.

Results:

One hundred twenty-seven patients with CF were matched with 1263 controls without CF. On multivariable logistic regression, those with CF had statistically significantly increased 90-day odds of the following: venous thromboembolism (odds ratio [OR], 4.2), pleural effusion (OR, 3.4), dyspnea (OR, 3.2), respiratory failure (OR, 2.8), pneumonia (OR, 2.6), acute kidney injury (OR, 2.4), hospital readmissions, (OR, 2.2), and emergency department visits (OR, 2.1). Notably, patients with CF were not at increased odds of 4-year subsequent lumbar surgery.

Discussion:

Patients with CF were at significantly increased odds of pulmonary and other defined adverse events. These findings are pertinent in the perioperative risk assessment, patient/family recommendations, and surgical preparations for patients with CF being considered for PLF.

Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the CF transmembrane conductance regulator with autosomal recessive inheritance.¹ Perioperative surgical outcomes and subsequent revision surgery have not been previously described for any spine surgery for patients with CF.

First described by Andersen and Hodges² in 1938 as a fatal condition, patients with CF died before the age of 1 year. But, more than 80 years later, the median survival was found to be 65.6 years old in 2021.³ In 2022, there were almost 50,000 people with CF living in the United States alone.⁴ Common orthopaedic concerns with patients with CF include muscle weakness,⁵ osteoporosis,⁶ reduced bone mineral density⁷ likely associated with vitamin D deficiency,⁸ kyphotic posture,^6,9 and fractures.⁶ With patients with CF living longer and their increased orthopaedic manifestations, patients with CF are being increasingly considered for spine surgery.

CF affects multiple bodily systems, for example, respiratory,^10,11 hepatobiliary complications,¹² diabetes,¹³ pancreatic insufficiency,¹⁴ metabolic abnormalities,¹² renal disease,^15,16 meconium ileus,¹⁷ mental health conditions (depression and anxiety),¹⁸ and infections,¹⁹ among other conditions.²⁰ The correlation of these comorbidities and conditions on surgical outcomes has been examined in total joint arthroplasty where Halperin et al²¹ found increased postoperative risk of sepsis, pleural effusions, pneumonia, respiratory failure, atelectasis, and urinary tract infections but not 2-year revision rates. However, postoperative outcomes of patients with CF have not been examined in spine surgery.

To address the noted gap in the literature, this study aimed to use a large, national, administrative data set to examine the 90-day postoperative outcomes and 4-year revision rates after posterior lumbar fusion (PLF) surgery for patients with CF compared with matched controls.

Methods

Data Source/Study Population

This study abstracted data from 2010 to Q3 2022 PearlDiver M165 Mariner Patient Claims Database (PearlDiver Technologies, Colorado Springs). This database is well established in the spine literature.²² As the outputs from PearlDiver are deidentified and aggregated, our institutional review board found studies using this database exempt from review.

Patients who underwent PLF were identified with the Current Procedural Terminology codes CPT-22612, CPT-22630, and CPT-22633. Inclusion criteria were 18 years or older, active in the database for at least 90 days after surgery, and the first occurrence of PLF. Exclusion criteria were having any other spinal procedure on the same day as well as a spinal trauma, neoplasm, or infection diagnosis. The number of levels was then identified using CPT-22614 (single-level PLF, two-level PLF, and three-level PLF).

Patients with CF were identified using the International Classification of Diseases codes ICD-9-D-27700, ICD-9-D-27701, ICD-9-D-27702, ICD-9-D-27703, ICD-9-D-27709, ICD-10-D-E840, ICD-10-D-E8411, ICD-10-D-E8419, ICD-10-D-E848, and ICD-10-D-E849. PLF patients with and without CF were matched in a 1:10 ratio based on age, sex, Elixhauser Comorbidity Index (ECI, a comorbidity index/score of overall comorbidity burden²³), and the number of levels (one-, two-, or three-level PLF).

Ninety-Day Postoperative Outcomes and 4-Year Revision Rates

After patient matching, the 90-day postoperative outcomes and revision rates were examined. The outcomes used are previously described²⁴ and identified based on International Classification of Diseases codes.

These 90-day postoperative events included: pulmonary events (atelectasis, dyspnea, pleural effusion, pneumonia, and respiratory failure), nonpulmonary events (acute kidney injury [AKI], cardiac event, sepsis, surgical site infection, transfusion, urinary tract infection, venous thromboembolism [VTE], includes deep vein thrombosis as well as pulmonary embolism], and wound complication), readmissions, and emergency department (ED) visits.

Subsequent lumbar surgery within 4 years were identified based on any subsequent lumbar surgery including débridement, and incision and drainage. In examining the subsequent surgery rate, patients who were not active in the database for 4 years after the index surgery were excluded.

Data Analysis

Patient characteristics of patients with and without CF were compared, including age, sex, ECI, and number of levels. This was done before and after matching using univariable analyses (chi squared and Student t-test).

Ninety-day postoperative events and revision rates were compared between the matched cohorts. Univariable (Student t test and chi squared) and multivariable logistic regression (controlling for age, sex, ECI, and number of levels) was done to compare the outcomes between the cohorts. Multivariable logistic regression allowed for the analysis of each variable independent of controlled for variables and calculation of odds ratios (ORs) and 95% confidence intervals.

Data collection and statistical analysis were performed using PearlDiver Bellwether. Significance was set at P = 0.05 for both univariable and multivariable analyses.

Results

Patient Cohorts

Before matching, the cohort of PLF patients without CF (+PLF-CF) was 267,323 and the cohort of PLF patients with CF (+PLF+CF) was 134. These two populations were statistically different with regard to sex and ECI (Table 1, left columns).

Table 1.

Characteristics of Unmatched and Matched (10:1) Cohort of Patients Undergoing Posterior Lumbar Fusion With and Without Cystic Fibrosis

Factor or Variable	Unmatched			Matched
	+PLF-CF	+PLF+CF	P Value	+PLF-CF	+PLF+CF	P Value
Total	267,323	134		1263	127
Age (average ± SD), yr	61.7 ± 12.1	60.4 ± 12.8	0.2371	61.6 ± 10.7	62.0 ± 10.9	0.7811
Sex			0.0129			1.0000
Female	154,151 (57.7%)	92 (68.7%)		893 (70.7%)	90 (70.9%)
Male	113,172 (42.3%)	42 (31.3%)		370 (29.3%)	37 (29.1%)
ECI (average ± SD)	4.0 ± 3.4	7.8 ± 4.4	<0.0001	7.5 ± 4.2	7.6 ± 4.3	0.8938
No. of levels
Single level	158,349 (59.2%)	77 (57.5%)	0.7418	745 (59.0%)	75 (59.1%)	1.0000
Two level	51,040 (19.1%)	22 (16.4%)	0.4979	200 (15.8%)	20 (15.7%)	1.0000
Three level	57,934 (21.7%)	35 (26.1%)	0.2525	318 (25.2%)	32 (25.2%)	1.0000

Bold values indicate the statistical significance set at P < 0.05.

CF = cystic fibrosis, ECL = Elixhauser Comorbidity Index, PLF = posterior lumbar fusion

After 10:1 matching based on age, sex, ECI, and number of levels, there were 1,263 patients without CF and 127 with CF. These cohorts were no longer statistically significantly different (Table 1, right columns).

Ninety-Day Postoperative Outcomes and 4-Year Revision Rates

On univariable analysis, matched PLF patients with CF had statistically significant increased 90-day postoperative outcomes of any adverse event, pulmonary adverse event, dyspnea, pleural effusion, respiratory failure, pneumonia, VTE, AKI, hospital readmissions, and ED visits (Table 2, left columns).

Table 2.

Univariable and Multivariable Analysis of 90-Day Outcomes and Overall Revisions Among Matched Cohort of +Posterior Lumbar Fusion +Cystic Fibrosis and +Posterior Lumbar Fusion -Cystic Fibrosis

Factor or Variable	Univariable			Multivariable (+PLF+CF compared with +PLF-CF)
	+PLF -CF (1,263)	+PLF +CF (127)	P Value	OR (95% CI)	P Value
90-day outcomes
Any adverse event	325 (25.7%)	53 (41.7%)	0.0002	2.1 (1.5-3.2)	0.0001
Pulmonary	159 (12.6%)	38 (29.9%)	<0.0001	3.1 (2.0-4.8)	<0.0001
Pleural effusion	18 (1.4%)	<11	0.0181	3.4 (1.2-8.5)	0.0111
Dyspnea	92 (7.3%)	25 (19.7%)	<0.0001	3.2 (1.9-5.2)	<0.0001
Respiratory failure	38 (3.0%)	<11	0.0091	2.8 (1.3-5.8)	0.0061
Pneumonia	32 (2.5%)	<11	0.0323	2.6 (1.1-5.7)	0.0200
Atelectasis	50 (4.0%)	<11	0.1511	1.9 (0.8-3.7)	0.1010
Nonpulmonary	238 (18.8%)	31 (24.4%)	0.1629	1.4 (0.9-2.2)	0.1320
VTE	31 (2.5%)	12 (9.4%)	<0.0001	4.2 (2.0-8.1)	<0.0001
AKI	51 (4.0%)	11 (8.7%)	0.0292	2.4 (1.1-4.7)	0.0181
Sepsis	27 (2.1%)	<11	0.1287	2.3 (0.8-5.4)	0.0780
UTI	90 (7.1%)	15 (11.8%)	0.0839	1.8 (0.9-3.1)	0.0608
Transfusion	30 (2.4%)	<11	0.4391	1.7 (0.6-4.1)	0.2994
Cardiac event	15 (1.2%)	<11	1.0000	1.3 (0.2-4.8)	0.7235
Wound complication	49 (3.9%)	<11	0.5394	0.6 (0.1-1.7)	0.3882
Surgical site infection	45 (3.6%)	<11	0.3554	0.4 (0.1-1.4)	0.2501
Readmission	134 (10.6%)	26 (20.5%)	0.0015	2.2 (1.4-3.5)	0.0011
ED visit	235 (18.6%)	40 (31.5%)	0.0008	2.1 (1.4-3.2)	0.0004
Subsequent lumbar surgery (4-yr)	68 (9.5%)	15 (13.3%)	0.2849	1.4 (0.8-2.6)	0.2417

AKI = acute kidney injury, CF = cystic fibrosis, CI = confidence interval, ECL = Elixhauser comorbidity index, ED = emergency department, PLF = posterior lumbar fusion, OR = odds ratio, UTI = urinary tract infection, VTE = venous thromboembolism

Odds ratios represent the odds of 90-day outcomes and any revision surgery among patients who are +PLF+CF compared with +PLF-CF patients.

Bold values indicate the statistical significance set at P < 0.05.

For the multivariable outcomes (Table 2, right columns and Figure 1), matched PLF patients with CF had statistically significantly increased 90-day postoperative odds of any adverse event (OR, 2.1, P = 0.0001).

Figure 1.

Forest plot showing the odds ratios and 95% confidence intervals for the 90-day postoperative outcomes and 4-year subsequent lumbar surgery rates.

For pulmonary outcomes, patients with CF had statistically significantly increased 90-day postoperative odds of (in descending OR order) pleural effusion (OR, 3.4, P = 0.0111), dyspnea (OR, 3.2, P < 0.0001), pulmonary event (OR, 3.1, P < 0.0001), respiratory failure (OR, 2.8, P = 0.0061), and pneumonia (OR, 2.6, P = 0.0200).

For nonpulmonary outcomes, patients with CF had statistically significantly increased 90-day postoperative odds of VTE (OR, 4.2, P < 0.0001) and AKI (OR, 2.4, P = 0.0181). PLF patients with CF also had increased 90-day odds of hospital readmissions (OR, 2.2, P = 0.0011) and ED visits (OR, 2.1, P = 0.0004).

Finally, on univariable and multivariable logistic regression, PLF patients with CF did not have increased odds of 4-year subsequent lumbar surgery rates.

Discussion

Patients with CF are living longer, and the population of adult patients with CF is growing in the United States.^3,4 With increased age, patients with CF are being increasingly considered for PLF. That being said, there is a dearth of literature examining postoperative outcomes after spine surgery in patients with CF. This study leveraged a large, national database to examine the postoperative outcomes of a cohort of 127 PLF patients with CF relative to matched controls.

After PLF, consistent with expectations, patients with CF were associated with significantly increased odds of multiple pulmonary adverse events for which odds were defined (pleural effusion OR, 3.4; dyspnea OR, 3.2; respiratory failure OR, 2.8; pneumonia OR, 2.6). As CF affects multiple systems in patients, including respiratory,^10,11 diabetes,¹³ metabolic abnormalities,¹² and infection susceptibility,¹⁹ many of the increased odds of adverse events (particularly the mentioned pulmonary events) are to be expected and related to comorbidities in patients with CF.^10,11,25

Furthermore, CF patients were at increased odds of VTE (OR, 4.2) and AKI (OR, 2.4). Several studies have found an association between CF and VTE in pediatric and adult populations.^26-30 This is likely due to higher rates of protein S deficiency, protein C deficiency, increased coagulation factors, antiphospholipid antibodies, and platelet activation.^31-35 The increased odds of AKI is also consistent with prior studies, which have found that patients with CF have higher rates of renal disease.^36-38 Pertinent negatives of this study include no increased odds of having surgical site infections or wound complications in CF patients after PLF, which was reassuring given those with CF have been shown to be at an increased risk of infection in general.¹²

In terms of hospital utilization, CF patients were also at increased odds of readmission (OR, 2.2) and ED visits (OR, 2.1). Given the increased risk for adverse events, this would be expected that patients with CF would have increased odds of readmissions and ED visits. Preventive measures and care pathways for patients with CF might decrease these odds.

Finally, PLF patients with CF did not have increased odds of 4-year subsequent lumbar surgery rates. Although patients with CF have a wide variety orthopaedic manifestations, including muscle weakness,⁵ osteoporosis,⁶ decreased bone mineral density⁷ likely due to vitamin D deficiency,⁸ kyphotic posture,^6,9 and fractures,⁶ patients with CF did not experience an increased rate of subsequent lumbar surgery.

This study is the first to examine PLF outcomes in patients with CF, but it does have limitations. First, this study relies on the accuracy of the administrative coding of the data set used. Next, the spectrum of severity of CF was not able to be assessed or controlled for with the data available. Also, using PearlDiver, this study was unable to distinguish or stratify the type of PLF procedure performed. Finally, spine-specific pathology and outcomes were not able to be assessed.

Conclusion

Overall, after PLF, patients with CF had increased odds of multiple adverse events (particularly pulmonary events) but not subsequent 4-year lumbar surgery rates. These findings are pertinent in the perioperative risk assessment, patient/family recommendations, and surgical preparations for patients with CF considering PLF.