Impact of Perioperative Fluid Administration on Postoperative Morbidity and Length of Hospital Stay Following Maxillomandibular Advancement for Obstructive Sleep Apnea

Accepted Manuscript Impact of perioperative fluid administration on postoperative morbidity and length of hospital stay following maxillomandibular advancement for obstructive sleep apnea Kyle S. Ettinger, DDS, MD, Cody C. Wyles, BS, Brett J. Bezak, DMD, Yavuz Yildirim, DDS, MD, Kevin Arce, DMD, MD, Christopher F. Viozzi, DDS, MD PII:

S0278-2391(15)00002-6

DOI:

10.1016/j.joms.2014.12.032

Reference:

YJOMS 56607

To appear in:

Journal of Oral and Maxillofacial Surgery

Received Date: 14 October 2014 Revised Date:

15 December 2014

Accepted Date: 23 December 2014

Please cite this article as: Ettinger KS, Wyles CC, Bezak BJ, Yildirim Y, Arce K, Viozzi CF, Impact of perioperative fluid administration on postoperative morbidity and length of hospital stay following maxillomandibular advancement for obstructive sleep apnea, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2014.12.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Title: Impact of perioperative fluid administration on postoperative morbidity and length of hospital stay following maxillomandibular advancement for obstructive sleep apnea.

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Authors: Kyle S. Ettinger, DDS, MD*, Cody C. Wyles, BS**, Brett J. Bezak, DMD*, Yavuz Yildirim, DDS, MD*, Kevin Arce, DMD, MD***, Christopher F. Viozzi, DDS, MD****

Clinic and Mayo College of Medicine, Rochester, MN

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*Resident, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo

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**Medical Student, Mayo Clinic and Mayo College of Medicine, Rochester, MN ***Assistant Professor of Surgery and Program Director, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo Clinic and Mayo College of Medicine, Rochester, MN

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****Assistant Professor of Surgery and Program Chair, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo Clinic and Mayo College of Medicine, Rochester,

Correspondence

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MN

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Kyle S. Ettinger, DDS, MD

Department of Surgery Mayo Clinic Rochester Division of Oral and Maxillofacial Surgery

Mail Code: ro_ma_12_12eres 200 First Street S.W Rochester, MN 55905 Email: [email protected]

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Abstract Purpose: The purpose of this study was to evaluate whether the volume of perioperative fluids administered to patients undergoing maxillomandibular advancement (MMA) for treatment of

complications and prolonged length of hospital stay.

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obstructive sleep apnea (OSA) is associated with increased incidence of postoperative

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Materials and Methods: A retrospective cohort study design was implemented and patients undergoing MMA for OSA at Mayo Clinic were identified from 2001-2013. The primary

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predictor variable was the total volume of intravenous fluids administered during MMA. The primary outcome variable was length of hospital stay in hours. Secondary outcome variables included the presence of complications incurred during postoperative hospitalization. Additional covariates abstracted included basic demographic data, preoperative body mass index,

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preoperative apnea-hypopnea index, preoperative Charlson comorbidity index, preoperative American Society of Anesthesiologists score, the type of intravenous fluid administered, surgical complexity score, duration of anesthesia, duration of surgery, and the use of planned ICU

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admission. Univariate and multivariable models were developed to assess associations between the primary predictor variable and covariates relative to both primary and secondary outcome

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variables.

Results: A total of 88 patients undergoing MMA for OSA were identified. Total fluid volume was significantly associated with increased length of stay (OR=1.34, 95% CI: 1.05-1.71, p=0.020) in univariate analysis. Total fluid volume did not remain significantly associated with increased length of hospital stay in stepwise multivariable modeling. Total fluid volume was

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significantly associated with the presence of postoperative complications (OR 1.69; 95% CI: 1.08-2.63; p=0.021) in univariate logistic regression.

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Conclusion: Fluid administration was not found to be significantly associated with increased length of hospital stay following MMA for OSA. Increased fluid administration is potentially associated with presence of postoperative complications following MMA; however, future large

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multicenter studies will be required to more comprehensively assess this association.

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Introduction

Since the initial characterization of obstructive sleep apnea (OSA) in 1976,1 healthcare providers across all medical and surgical specialties have become increasingly aware of the syndrome’s diagnostic clinical hallmarks and its pathophysiologic sequelae. Nevertheless, recent

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epidemiologic studies estimate that as many as 1 in 20 adults are currently affected by OSA and many of these individuals are likely unrecognized and undiagnosed.2 Extrapolating to the population of the United States, as many as 15.8 million adult Americans are potentially affected

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by OSA. Coupled with increasing recognition of sleep disordered breathing in children,3-5 the number of individuals affected by OSA is unlikely to diminish in the foreseeable future. Given

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this information, it is clear that untreated obstructive sleep apnea represents a significant public health burden; the annual cost associated with untreated OSA has been estimated to be $3.4 billion.6 Presently, positive airway pressure (PAP) therapy is the gold standard to which all other OSA treatments are measured. However, with as many as 50% of OSA patients ultimately intolerant of various forms of PAP therapy,7,8 alternative treatment modalities are of paramount clinical importance.

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Initially reported in the 1980’s,9-14 the use of maxillomandibular advancement (MMA) for the treatment of OSA has become an increasingly popular and successful strategy for managing patients intolerant of traditional PAP modalities. Maxillomandibular advancement has

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repeatedly been shown to have therapeutic efficacy equal to PAP therapy and it is now widely recognized to be the definitive surgical intervention for treatment of PAP intolerant patients when compared to alternative airway surgeries.15-17 However, despite a highly successful track

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record for improvement in polysomnographic indices such as apnea-hypopnea index (AHI), MMA is not without inherent risks and associated morbidity. Postoperative pharyngeal edema

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remains a real and omnipresent concern,18,19 which has led many to recommend the use of planned intensive care unit (ICU) admission as a means of more carefully monitoring and therefore possibly preventing potential airway embarrassment.20-25 Judicious administration of perioperative intravenous fluids has also been empirically recommended as a means of further

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reducing postoperative laryngeal edema,24 yet at present, studies specifically evaluating the impact of fluid administration on patients undergoing MMA for OSA are nonexistent within the literature.

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Over the past decade there has been an increasing level of attention afforded to perioperative fluid management and its impact on postoperative surgical outcomes within the

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field of anesthesiology.26-31 Liberal fluid administration has been correlated with impaired cardiac, pulmonary, and gastrointestinal function and also has been demonstrated to prolong postoperative surgical recovery.26,29,30 Conversely, restrictive fluid regimens can place patients at risk for postoperative hypovolemia, organ dysfunction, and in extreme cases multiple organ failure and death.32 However, in spite of numerous randomized clinical trials specifically evaluating the impact of perioperative fluid protocols on surgical outcomes, heterogeneity among

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studies and lack of standardization in fluid regimens has precluded definitive consensus regarding optimal fluid protocols to decrease postoperative morbidity and length of hospital stays.32 Nevertheless, optimization of perioperative fluid regimens is a readily modifiable aspect

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of surgical care that holds the potential for improving postoperative outcomes and shortening hospital stays—both of which are of critical importance for cost containment in healthcare

delivery. Given the already developing economic burden placed on the healthcare system by

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OSA and its associated sequelae, elucidation of the relationship between perioperative fluid

within the realm of OSA surgery.

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status and postoperative outcomes in MMA represents a potential area for quality improvement

The purpose of this study was to specifically evaluate impact of perioperative fluid administration on patients undergoing MMA for treatment of OSA. The investigators hypothesized that patients receiving higher perioperative fluid volumes would subsequently

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experience greater third spacing of fluids, increased facial/pharyngeal edema, and consequently require longer hospitalizations with increased incidence of postoperative complications. The specific aims of the study were to measure and compare various fluid volumes administered to

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OSA patients undergoing MMA and determine whether the volume of fluids received correlated with an increased incidence of postoperative complications and prolonged length of hospital

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stay. Further aims of the study also included the identification and description of additional factors associated with increased incidence of postoperative complications and prolonged hospital admission following MMA for OSA.

Materials and Methods Study Design/Sample

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To address the research purpose, the investigators designed and implemented a retrospective cohort study. A sample of subjects was derived from a population of patients being treated by the Division of Oral and Maxillofacial Surgery at Mayo Clinic in Rochester, MN

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between 2001 and 2014. Subjects were identified through an electronic database search of operative notes containing the keyword “sleep” within the preoperative or postoperative

diagnosis. Inclusion criteria for the study included maxillary and/or mandibular advancement

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(with or without advancement genioplasty) for the treatment of OSA within the specified time range, age greater than or equal to 12 years, adequate documentation of perioperative fluid

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administration, adequate documentation of postoperative hospital course and subsequent complications therein, and adequate documentation of dates of postoperative admission. Exclusion criteria for the study included independent or concomitant use of traditional Stage I surgical modalities33 for treatment of OSA (nasal septoplasty, turbinectomy,

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uvulopalatopharyngoplasty, genioglossal advancement surgeries, isolated advancement genioplasty, hyoid myotomy/suspension, tongue volume reduction surgery), age less than 12 years, inadequate documentation of intraoperative fluid administration, inadequate

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documentation of postoperative hospital stay and associated complications, lack of documentation of dates of postoperative admission, autogenous iliac crest bone grafting as a

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component of maxillomandibular advancement surgery, history of cleft lip and/or palate, any concomitant craniofacial syndrome, performance of simultaneous ancillary procedures in addition to standard maxillomandibular advancement surgery (i.e. cervicofacial liposuction, bilateral or unilateral prosthetic TMJ replacement, etc.), and surgery performed as a reoperation for previously failed maxillomandibular advancement. Approval from the Mayo Clinic Institutional Review Board was obtained for completion of this study.

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Variables The primary predictor variable for the study was the total volume of perioperative fluids

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administered on the day of surgery. The total volume of perioperative fluids administered

represents the combination of both colloid and crystalloid fluids volumes administered to the patient preoperatively in the preop holding area, intraoperatively during the procedure, and

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postoperatively until midnight on the day of the surgery. This method of calculating

perioperative fluid volume was selected in order to standardize the recording of fluid data among

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the subject population and to facilitate ease of abstraction from the electronic medical record. The primary outcome variable for the study was the length of hospital stay in hours following completion of the MMA for OSA. The length of hospital stay was recorded as the time elapsed in hours between the patient being admitted to the receiving ICU or general hospital

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floor following their procedure to the exact time of patient dismissal from the hospital as recorded in the electronic medical record. The method of calculating length of hospital stay was intentionally chosen to eliminate the time of the surgical procedure and is consequently why the

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start of admission occurs upon the patient reaching either the ICU or general hospital floor following the procedure.

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Secondary outcome variables for the study included the presence of various

complications incurred during the postoperative hospitalization. These complications were intentionally chosen (with minor additions and modifications) to mirror those set for by the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), which is the most widely recognized quality measurement system for non-cardiac surgery in the United States.34 The categories of postoperative complications and their definitions are as

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follows: 1) pulmonary (any unplanned intubation/mechanical ventilation following normal postoperative extubation, mechanical ventilation >48 hours, pneumonia, continued postoperative intubation beyond the PACU for any duration); 2) cardiovascular (ST elevation myocardial

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infarction, non-ST elevation myocardial infarction, heart failure, cardiac arrest, any new cardiac arrhythmia requiring medical treatment); 3) renal (acute kidney injury representing twofold increase in serum creatinine or urine output < 0.5 mL/kg/hr for 12 hours, acute renal failure

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representing threefold increase in serum creatinine or urine output < 0.3 mL/kg/hr for 24 hours or anuria for 12 hours); 4) genitourinary (urinary tract infection); 5) neurologic (ischemic or

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hemorrhagic cerebrovascular accident, coma); 6) hematologic (deep vein thrombosis, pulmonary embolism); 7) infectious (sepsis/septic shock); 8) postoperative blood transfusion; 9) unscheduled ICU admission. Postoperative complications occurring beyond the initial inpatient hospitalization were not recorded.

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Multiple covariates were also abstracted for the study and included: patient age (in years); preoperative body mass index (BMI); preoperative apnea-hypopnea index (AHI); duration of anesthesia (in hours); duration of surgery (in hours); sex (male/female); smoking

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status (never smoked, active smoker, former smoker); Charlson comorbidity index;35 preoperative American Society of Anesthesiologists score (ASA score); complexity of surgical

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procedure; specific type of colloid fluid administered (albumin, hydroxyethyl starches, packed red blood cells); and presence of a planned ICU admission (defined as the preoperative decision to admit the patient to an ICU setting following MMA irrespective of the postoperative outcome). Duration of anesthesia was recorded as the time elapsed in hours between the anesthesiology team assuming care of the patient upon entrance into the OR to the exact time of the post-anesthesia care unit (PACU) assuming care of the patient upon completion of the

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procedure. Duration of surgery was recorded as the time in hours from the documented time of incision to the documented time of closure within the electronic anesthesia record. The purpose of distinguishing between duration of anesthesia and duration of surgery was intentionally

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chosen in order to stratify differences among outcomes specifically resulting from anesthesia delays (i.e. delays in obtaining vascular access, delays in induction of general anesthesia, delays in postoperative extubation, etc) relative to intraoperative surgical delays resulting from

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challenges within the procedure itself. The Charlson comorbidity index35 represents a validated scoring system that predicts the ten-year mortality for a patient based on the presence of 22

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specific comorbid disease conditions. Each comorbid condition carries a specific score weighting based on the risk of mortality associated with the disease. The weighting system is as follows: 1 point (myocardial infarction, congestive heart failure, peripheral vascular disease, dementia, cerebrovascular disease, chronic lung disease, connective tissue disease, chronic liver

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disease, diabetes); 2 points (hemiplegia, moderate or severe kidney disease, diabetes with end organ damage, any tumor, leukemia, lymphoma); 3 points (moderate or severe liver disease); 6 points (malignant tumor, metastatic disease, AIDS). The summation of point values for each

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condition represents the overall comorbidity score. The complexity of the surgical procedure was quantified through the use of a previously described surgical complexity score.36 The type

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of maxillary procedure was recorded as a 1-piece LeFort, 2-piece LeFort, 3-piece LeFort, or not performed. The type of mandibular procedure was recorded as a bilateral sagittal split ramus osteotomy or not performed. The type of chin procedure was recorded as a 1 piece genioplasty or not performed. The complexity score for the procedure was set to an initial baseline value of 0 with 1 point added for a 1-piece LeFort, 1.5 points for a 2-piece LeFort, 1.75 points for a 3piece LeFort, 1 point for a bilateral sagittal split ramus osteotomy, and 1 point for advancement

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genioplasty. A summative value of the individual procedures performed during the operation was then calculated to represent the overall surgical complexity score. Perioperative steroid administration was not specifically abstracted as a covariate within

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the study. All subjects undergoing MMA within the specified time range were provided a single dose of intravenous steroids at the time of the procedure in the form of an 8- or 10-mg dose of intravenous dexamethasone depending on surgeon preference. Postoperatively all patients were

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placed on a scheduled steroid regimen consisting of intravenous dexamethasone every 12 hours for a total of 5 doses. Patients were not required to complete all 5 doses prior to dismissal. If

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less than 5 doses of steroids were administered, no additional outpatient steroids were provided. This steroid protocol remained constant throughout the years in which the subject pool was garnered (2001-2014).

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Data Collection

The electronic medical records of the subjects in the study pool were retrospectively reviewed for abstraction of all necessary study variables and demographic data. The collected

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data was securely stored in a Mayo Clinic sponsored Research Electronic Data Capture (REDCap) database designed specifically for the research project by the primary author (KE).

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All authors participating in data abstraction were calibrated on the appropriate use and population of the REDCap database prior to initiating chart review. Access to the REDCap database was limited to the primary author, the authors involved with data abstraction, and the project biostatistician. Any missing data following initial abstraction attempts was subsequently identified and incorporated into the database by the primary author. Data Analysis

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Total fluid was calculated as the sum of crystalloid and colloid volumes administered perioperatively. Length of stay was grouped as <52 hours, ≥52 but <76 hours, and ≥76 hours based on clear clustering patterns of discharge times within the subject pool. These length of

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stay groupings corresponded to approximately 1-2 days, 3 days, and 4+ days of postoperative admission (counting the day of surgery as postoperative day 0). Continuous features were

summarized with medians, interquartile ranges (IQRs), and ranges; categorical features were

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summarized with frequency counts and percentages. Univariate associations among the primary predictor variable (total fluid volume) and the multiple covariates relative to the primary

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outcome variable (length of stay group: 1-2 days, 3 days, 4+ days) were evaluated using proportional odds models to account for the ordinal nature of the endpoint and were summarized with odds ratios and 95% confidence intervals (CIs). The proportional odds assumption was tested for each model to verify that the assumption was appropriate. A multivariable model

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using stepwise selection was then applied to all variables reaching statistical significance in the initial univariate analysis relative to length of stay. The significance level for a variable to enter or leave the stepwise multivariable model was set to 0.05. Univariate associations among the

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primary predictor variable (total fluid volume) and the multiple covariates relative to the secondary outcome variables (presence of postoperative complications) was then evaluated using

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a logistic regression model and were summarized with odds ratios and 95% confidence intervals. Statistical analyses were performed using the SAS software package (SAS Institute, Cary, NC). All tests were two-sided and p-values <0.05 were considered statistically significant.

Results

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The study population was composed of 185 subjects who were identified on the initial electronic database search of operative notes containing the keyword “sleep” in either the preoperative or postoperative diagnosis text between 2001 and 2014. Ten subjects were

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immediately excluded from the study population due to lack of appropriate research

authorization on file. Twenty-six subjects were excluded due to the isolated performance of traditional Stage I surgeries. Three subjects were excluded due to concomitant performance of

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traditional Stage I surgeries in addition to MMA. Twenty-six patients were excluded due to the concomitant performance of ancillary procedures in addition to the MMA (cervicofacial

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liposuction, unilateral or bilateral prosthetic TMJ replacement, etc.). Eighteen patients were excluded due to concomitant use of autogenous iliac crest bone grafting in conjunction with MMA. Three patients were excluded due to the presence of cleft lip and/or palate. Five patients were excluded due to presence of a craniofacial syndrome. Six patients were excluded on the

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basis of a reoperation for a previously failed MMA. The final study sample was composed of a total of 88 subjects. All 88 subjects met the appropriate inclusion criteria and their electronic medical records were retrospectively reviewed for abstraction of primary/secondary variables

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and covariates.

Features for the 88 subjects studied are summarized in Table 1. Sample sizes for features

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with missing data are indicated in italics in parentheses. There was a clear male predominance in the study population with 62 male subjects (70%) and 26 female subjects (30%) represented. A total of 40 subjects (45%) received crystalloid fluid alone, whereas 48 subjects (55%) received combinations of crystalloid and colloid fluids. Hydroxyethyl starches were the most commonly administered colloid fluid with 35 subjects (40%) receiving this fluid type. Albumin was administered to 14 subjects (16%), and only 2 subjects (2%) received blood product (both

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receiving packed red blood cells). Planned ICU admission was utilized for 64 subjects (73%), whereas the remaining 24 subjects (27%) were allowed to transfer directly to a general care floor after meeting criteria for PACU dismissal. Subject distribution among length of stay groupings

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was fairly evenly allocated across the study pool. There were a total of 36 subjects (41%)

whose length of stay corresponded to discharge on postoperative day 1 or 2, 31 subjects (35%) whose length of stay corresponded to discharge on postoperative day 3, and 21 subjects (24%)

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whose length of stay corresponded to discharge occurring on postoperative day 4 or later.

A total of 9 subjects (10%) experienced postoperative complications. The type and

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distribution of postoperative complications by subject are presented in Table 2. Four of the 9 subjects were deemed to require continued postoperative intubation beyond the length of the procedure, which consequently necessitated ICU admission for mechanical ventilation. This complication occurred in 3 patients who were already planned for ICU admission at the outset of

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the procedure and were thus categorized as also requiring unplanned mechanical ventilation. For the 1 patient who required continued postoperative intubation that was not initially planned for postoperative ICU admission, the complication also coincided with an unscheduled ICU

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admission and unplanned mechanical ventilation by definition. The decision to continue intubation postoperatively was made at the discretion of the attending anesthesiologist in each of

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the 4 cases where this complication was recorded. Only 1 of the 4 patients requiring continued postoperative intubation remained ventilator dependent for greater than 48 hours before being extubated. The 1 patient requiring unscheduled ICU admission alone was extubated at the completion of the procedure, however was subsequently admitted to the ICU as a precautionary measure due to copious secretions requiring frequent suctioning while still in the PACU. Only 1

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patient experienced a postoperative pneumonia. A total of 4 patients required postoperative transfusions of packed red blood cells for hemoglobin levels ranging from 6.6 to 8.4 g/dL. Descriptive features by length of stay group are summarized in Table 3. Packed red

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blood cells were not included in this table since only 2 patients received this product

intraoperatively. Univariate associations between the primary predictor variable (total fluid volume) and all abstractive covariates relative to the primary outcome (length of stay) are

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summarized in Table 4. Univariately, total fluid volume was significantly associated with increased length of stay (OR=1.34, 95% CI: 1.05-1.71, p=0.020). More specifically, the

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univariate odds ratio of 1.34 for total fluid indicates that each 1000-unit increase in total fluid volume was associated with a 34% increased odds of a length of stay ≥76 hours compared with <76 hours, as well as a 34% increased odds of a length of stay ≥52 but <76 hours compared with <52 hours. Additionally, covariates of higher ASA score, higher surgical complexity score, and

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planned ICU admissions were also found to be significantly associated with longer lengths of stay in univariate analysis (OR=2.66; 95% CI: 1.16-6.12; p=0.021), (OR=2.63; 95% CI: 1.096.37; p=0.032), and (OR=2.50; 95% CI: 1.00-6.20; p=0.049) respectively.

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The multivariable model developed using stepwise selection is shown in Table 5. In this multivariable model, after adjusting for ASA score, surgical complexity score, and planned ICU

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admission, the association between total fluid volume and length of stay was no longer found to be statistically significant (OR 1.15; 95% CI: 0.87-1.50; p=0.33). The covariates of ASA score, surgical complexity score, and planned ICU admission all remained significantly associated with increased length of hospital stay within the stepwise multivariable model. Surgical complexity score and planned ICU admission remained the two strongest predictors of prolonged length of

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hospital stay within this model (OR 7.86; 95% CI: 2.51-24.64; p<0.001) and (OR 5.86; 95% CI: 1.85-18.49; p=0.003) respectively. Descriptive features for subjects who did and did not experience postoperative

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complications are summarized in Table 6. Univariate associations between the primary outcome variable (total fluid volume) and abstracted covariates relative to the secondary outcome

(presence of postoperative complications) are shown in Table 7. Univariately, total fluid was

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significantly associated with the presence of postoperative complications (OR 1.69; 95% CI: 1.08-2.63; p=0.021). Additional covariates also found to be significantly associated with

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presence of postoperative complications in univiariate analysis included duration of anesthesia and administration of hydroxyethyl starches (OR 1.54; 95% CI: 1.02-2.34; p=0.042) and (OR 6.38; 95% CI: 1.24-32.79; p=0.027) respectively. Lack of planned ICU admission was not significantly associated with the presence of postoperative complications (OR 0.74; 95% CI:

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0.14-3.85, p=0.74) in univariate analysis. No multivariable modeling was explored since only 9 patients experienced complications and the requisite numbers required for a multivariable

Discussion

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analysis were not observed.

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The primary objective of this study was to clarify the relationship between perioperative

fluid administration and outcomes in MMA surgery for the treatment of OSA. The a priori hypothesis was that liberal perioperative fluid administration would lead to greater third spacing of fluids, increased facial/pharyngeal edema, and consequently longer hospitalizations with greater incidence of postoperative complications. The study also aimed to identify and describe

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additional factors associated with an increased incidence of postoperative complications and prolonged hospital admission following MMA for OSA. Higher perioperative fluid administration was ultimately found to be significantly

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associated with both increased length of hospitalization and presence of postoperative

complications in univariate analyses. However, in multivariable modeling fluid volume was no longer found to be significantly associated with increased length of hospital stay after controlling

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for confounders of ASA score, surgical complexity, and planned ICU admission. Additionally, despite a statistically significant univariate association between fluid administration and

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postoperative complications, no multivariable modeling could be explored secondary to an under-powering of the study relative to the observed rates of medical complications following MMA.

Multiple covariates were ultimately found to be significantly associated with prolonged

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length of hospital stay following MMA. These covariates included higher ASA score, surgical complexity, and the use of planned ICU admission. These covariates remained significantly associated with prolonged length of hospital stay both in the initial univariate model, as well as

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the subsequent stepwise multivariable model. In addition to total fluid volume a number of covariates were also identified as being associated with the presence of postoperative

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complications. These included the duration of anesthesia (but not the duration of surgery) and the use of hydroxyethyl starches. It is interesting to note that neither planned ICU admission or lack of planned ICU admission were associated with increased rates of postoperative complications. Specifically evaluating medical complications as an outcome for MMA surgery

represents a particularly difficult proposition, particularly when attempting to do so on the basis of a non-multicenter study with a limited subject pool. The subject population garnered for the

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present study represents more than a decade’s worth of operative experience from a number of surgeons incorporating MMA into their scope of practice, yet it still remained inadequately powered to utilize medical complications as an outcome for multivariable modeling. The limited

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sample size in the present study is in part owing to the relatively strict selection criteria

implemented in order to reduce heterogeneity within the subject pool. Given that the primary outcome was to assess for perioperative fluids’ impact on length of hospital stay, a number of

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selection criteria needed to be implemented in order to reduce for potential confounders that would have erroneously lengthened the duration of admission. For instance, a number of

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subjects needed to be excluded from the study pool on the basis of concomitant autogenous iliac crest bone grafting used during MMA. If these subjects were to be incorporated into the study pool, any prolonged length of hospital stay may have been a reflection of postoperative ambulatory difficulties rather than a direct effect of perioperative fluid administration itself.

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Analogously, patients undergoing concomitant procedures such as cervicofacial liposuction were also excluded from the pool on the basis that the additional surgical time incurred from the ancillary procedure would have inadvertently lengthened the time of the operation and thus

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increased the volumes of fluids that were administered. Perhaps the greatest impediment relative to the use of medical complication rates as an

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outcome within the current study stems from the exceedingly low rates of postoperative complications seen with MMA overall. There presently only a limited number of studies available within the OSA literature specifically detailing the incidence of medical complications following MMA.16 The majority of the available studies focus on surgical complications such as facial paresthesias, surgical site bleeding, loss of hardware fixation, local infections, postoperative malocclusion, speech changes, dysphagia, and velopharyngeal insufficiency.17,21,37-

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42

In what is perhaps the largest systematic review on outcomes for MMA in the treatment of

OSA, Holty et al15 identified only three major medical complications occurring in 455 consecutive patients undergoing MMA (two nonfatal cardiac arrests and one new onset

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arrhythmia).43 Adding to this the results of Riley et al21 who identified an additional five patients with medical complications in a series 182 patients (four new onset atrial fibrillation and one new onset unstable angina), a total of 8 medical complications in 637 patients have been reported

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within the literature (~1%). While this complication rate is lower than the rate of complications reported in the current study (10%) it should be noted that the present study used a much more

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robust subset of variables from which complications could be defined. Thus, the 1% medical complication rate reported within the literature should be interpreted cautiously as this value is generated from a small number of heterogeneous studies lacking cross-study standardization on how complications were characterized. Ultimately large multi-center investigations capable of

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generating sizable subject pools will be required in order to adequately assess the impact of perioperative fluid administration on incidence of postoperative medical complications, as this likely represents the only way to generate sufficient sample sizes with which adequately power

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such a study. The present study represents an initial undertaking upon which future investigations may potentially be developed, as the precedence for an association between fluid

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status and postoperative complications has now been described—despite the lack of power prohibiting subsequent multivariable modeling. It is interesting to note that within the present study the preoperative ASA score as well

as the preoperative Charlson comorbidity index were not found to be significantly associated with the presence of postoperative complications in univariate analysis. Given the well documented cardiovascular and metabolic sequelae associated with OSA,2 it is surprising that

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both measures of comorbid disease burden were not predictive of postoperative complications. There is undoubtedly a ubiquitous perception within the community of airway surgeons that OSA patients undergoing MMA are inherently “high risk” individuals given their pre-existing

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cardiometabolic derangements. This perception also likely augments the rationale for planned ICU admission for MMA patients when additionally considering the concerns for postoperative pharyngeal edema. In the first OSA surgical risk management protocol developed by Powell et

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al20 in 1988 it was recommended that all MMA patients be routinely admitted to an ICU setting for a minimum of the first postoperative night following surgery. This endorsement of planned

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ICU admission was reinforced by subsequent studies by Li et al18,19 wherein 98 and 70 patients undergoing MMA for treatment of OSA were found by nasopharyngolaryngoscopy to exhibit varying degrees of lateral pharyngeal wall edema. Within this same study population a total of 18 patients were also found to have ecchymosis and edema of the pyriform sinuses and

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aryepiglottic folds, with 4 patients also exhibiting hypopharyngeal hematomas.18,19 However, despite these findings, none of the patients in either of these two studies were ultimately found to have any evidence of postoperative airway obstruction or evidence of postoperative hypoxemia

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based on continuous pulse oximetry.18,19 These studies nevertheless often serve as the foundation for concerns regarding postoperative airway embarrassment following MMA despite

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the authors’ own acquiescence that the presence of hypopharyngeal hematoma is of unknown clinical significance and may in fact represent an incidental finding.19 These same authors also acknowledge that less deference is often afforded the thousands of individuals undergoing similar procedures in the form of routine orthognathic surgery where pharyngeal edema is also highly likely and yet postoperative airway complications are exceedingly rare.19,44-48 Ultimately, given the low rates of medical complications seen within the present study as well as within the

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existing OSA literature, planned ICU admission for all MMA patients on the basis of a “highrisk” status stemming from either their comorbid disease burden or their risk of postoperative pharyngeal edema may potentially need to be revisited.

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The finding within the present study that the use of planned ICU admission was significantly associated with increased length of hospitalization in both univariate and

multivariable modeling adds yet another consideration for airway surgeons when deliberating the

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utility of this practice. Minimizing the time of postoperative hospitalizations for all types of surgical procedures has become the trend rather than the exception when it comes to controlling

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costs associated with healthcare delivery. Efforts to reduce the duration of hospitalization have been further fuelled by the elucidation of risk factors associated with prolonged hospital stays.4952

While the present study represents the first reporting of planned ICU admission as a risk

factor for prolonged hospitalization following MMA within the OSA literature, similar findings

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have also been reported within the realm of orthognathic surgery. Jarab et al53 also identified postoperative ICU admission as being significantly associated with increased length of hospitalization in a series of 92 patients undergoing routine orthognathic surgery in a single

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institution. However, while operatively comparable in terms of procedural similarity, orthognathic surgery and MMA patients do represent distinct patient populations both in terms of

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baseline demographics and incidence of postoperative complications.25 These inherent differences make direct comparisons between these two patient populations problematic despite their foundational similarities in surgical technique. Without any additional studies specifically evaluating planned ICU admission as a risk factor for prolonged hospitalization in the MMA population, the study by Jarab et al53 remains the closest available for comparison.

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In order to find comparative study populations relative to perioperative fluid administration as a risk factor for length of hospitalization in MMA surgery, one must again look to the field of orthognathic surgery given a paucity of data specifically evaluating this parameter

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within the OSA literature. Two recent studies by Huamán et al54 and Ettinger et al36 both

retrospectively identified associations between intraoperative fluid administration and length of postoperative hospitalizations in series of 627 and 136 patients, respectively, undergoing routine

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orthognathic surgery at two independent institutions. However, analogous to the findings of the present study, fluid volume failed to remain significantly associated with increased length of

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hospitalization following multivariate modeling.36,54 Yet, the findings of Huamán et al,54 Ettinger et al,36 and the present study, are all subject to the inherent shortcomings associated with retrospective designs and it remains possible that an association between fluid administration and length of hospital stay is not fully borne out within the confines of these limitations.

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Given that the volume of perioperative fluids administered to patients represents an easily modifiable aspect of surgical care, it will be important for future prospective studies to be designed specifically to evaluate this parameter within the field of OSA surgery. Understanding

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the relationship between fluid administration and its potential impact on perioperative outcomes will also become critically important as trends in healthcare and continue to push for shortened

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hospital stays. As the many providers who ascribe to the original risk management protocol by Powell et al20 begin to consider ways to reduce or eliminate the need for postoperative intensive care monitoring in the field of MMA surgery, perioperative fluid administration will likely remain at the forefront of this discussion. With the precedent for improved outcomes using restrictive fluid regimens already prospectively demonstrated within other surgical

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disciplines,26,29,30 it will be of paramount importance for airway surgeons to further investigate the implications of these findings within their own patient populations.

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Acknowledgements

The authors would like to acknowledge the time and efforts of the project’s biostatistician Christine M. Lohse, MS for her aid in preparing and executing statistical analysis for the

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in the programing of the project’s REDCap database.

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manuscript. The authors would also like to acknowledge Peggy L. Harmsen for her critical role

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Table 1: Summary of features; N=88 Median (IQR; Range) 43.5 (36-53; 14-71) 30.5 (26.8-34.7; 19.8-50.9) 46 (25-62; 3-113) 7.6 (6.8-8.8; 3.1-12.5) 6.1 (5.1-7.4; 2.1-10.1) 4849 (4054-6121; 1403-9114) 67.6 (45.8-75.6; 24.5-287.2)

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Feature Age in years Preoperative BMI Preoperative AHI (N=86) Duration of anesthesia in hours Duration of surgery in hours Total fluid in mL Length of stay in hours Sex Female Male Smoking status (N=78) Never Active Former Charlson score 0 1 2 3 ASA score 1 2 3 Maxillary procedure None 1 piece LeFort 2 piece LeFort 3 piece LeFort Bilateral sagittal split ramus osteotomy Chin procedure None 1 piece genioplasty Complexity of procedure 1 2 2.75 3 Complexity of procedure Low (1, 2) High (2.75, 3) Colloid Albumin

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N (%) 26 (30) 62 (70)

51 (65) 5 (6) 22 (28)

68 (77) 12 (14) 7 (8) 1 (1) 8 (9) 66 (75) 14 (16)

2 (2) 85 (97) 0 1 (1) 88 (100)

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65 (74) 23 (26) 2 (2) 62 (70) 1 (1) 23 (26) 64 (73) 24 (27) 48 (55) 14 (16)

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Hydroxyethyl starches Packed red blood cells Planned ICU admission Length of stay in hours <52 ≥52 but <76 ≥76 Postoperative complication

35 (40) 2 (2) 64 (73)

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36 (41) 31 (35) 21 (24) 9 (10)

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Table 2: Distribution of complications by subject; N=9 Complication

Patient 1

Unscheduled ICU admission

Patient 2

Postoperative transfusion

Patient 3

Continued postoperative intubation Unscheduled ICU admission Unplanned mechanical ventilation

Patient 4

Postoperative transfusion

Patient 5

Continued postoperative intubation Unplanned mechanical ventilation

Patient 6

Pneumonia

Patient 7

Continued postoperative intubation Unplanned mechanical ventilation Mechanical ventilation > 48 hours

Patient 8

Continued postoperative intubation Unplanned mechanical ventilation Postoperative transfusion

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Postoperative transfusion

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Patient 9

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Median (IQR; Range) 47 (37-56; 17-67) 32.8 (28.7-36.7; 20.3-45.2) 51.5 (22-68; 3-113) 7.4 (7.0-8.5; 3.8-11.8) 6.1 (5.5-7.0; 3.0-10.1) 5087 (4390-6151; 1403-8223)

39 (33-53; 19-65) 29.6 (25.9-34.3; 19.8-50.9) 37 (23.5-64.5; 5-104) 7.6 (7.3-9.4; 5.8-12.5) 6.3 (5.8-8.1; 4.4-9.4) 5426 (4564-7322; 2401-8727)

10 (28) 26 (72)

N (%) 8 (26) 23 (74)

8 (38) 13 (62)

18 (64) 10 (36)

11 (61) 7 (39)

30 (83) 6 (17)

24 (77) 7 (23)

14 (67) 7 (33)

5 (14) 29 (81) 2 (6)

1 (3) 24 (77) 6 (19)

2 (10) 13 (62) 6 (29)

29 (81) 7 (19) 17 (47) 6 (17) 11 (31) 23 (64)

24 (77) 7 (23) 18 (58) 4 (13) 14 (45) 22 (71)

11 (52) 10 (48) 13 (62) 4 (19) 10 (48) 19 (90)

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22 (69) 10 (31)

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42 (36.5-49.5; 14-71) 30.0 (26.8-33.3; 20.9-38.2) 47 (27-60; 3-101) 7.6 (6.2-8.8; 3.1-10.7) 6.1 (4.8-7.4; 2.1-9.3) 4468 (3291.5-5755; 1803-9114)

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Sex Female Male Smoking status (N=78) Never Active, former Charlson score 0 >0 ASA score 1 2 3 Complexity of procedure Low (1, 2) High (2.75, 3) Colloid Albumin Hydroxyethyl starches Planned ICU admission

≥52 but <76 hours N=31

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Feature Age in years Preoperative BMI Preoperative AHI (N=86) Duration of anesthesia in hours Duration of surgery in hours Total fluid in mL

<52 hours N=36

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Table 3: Summary of features by length of stay group, N=88 ≥76 hours N=21

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Table 4: Univariate associations of features with length of stay group, N=88 Feature

Odds Ratio (95% CI)

P-value

1.07 (0.78-1.47)1

0.69

1.0 (reference) 0.74 (0.32-1.74)

0.49

1.0 (reference) 1.28 (0.54-3.05) 1.03 (0.96-1.09)2 1.01 (0.87-1.16)1

0.57 0.45 0.92

1.0 (reference) 1.95 (0.77-4.93) 2.66 (1.16-6.12)2 1.23 (0.97-1.55)2 1.22 (0.96-1.56)2

0.16 0.021 0.087 0.11

1.0 (reference) 2.63 (1.09-6.37) 1.34 (1.05-1.71)3 1.59 (0.73-3.48) 1.06 (0.37-3.04) 1.77 (0.80-3.92) 2.50 (1.00-6.20)

0.032 0.020 0.25 0.92 0.16 0.049

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Age in years Sex Female Male Smoking status (N=78) Never Active, former Preoperative BMI Preoperative AHI (N=86) Charlson score 0 >0 ASA score Duration of anesthesia in hours Duration of surgery in hours Complexity of procedure Low (1, 2) High (2.75, 3) Total fluid Colloid Albumin Hydroxyethyl starches Planned ICU admission

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1. Odds ratio represents a 10-unit increase. 2. Odds ratio represents a 1-unit increase. 3. Odds ratio represents a 1000-unit increase.

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Table 5: Multivariable model to predict length of stay group, N=88 Feature

Odds Ratio (95% CI)

P-value

2.75 (1.12-6.72)2

0.027

1.0 (reference) 7.86 (2.51-24.64) 5.86 (1.85-18.49)

<0.001 0.003

Total Fluid†

1.15 (0.87-1.50)1

0.33

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ASA score Complexity of procedure Low (1, 2) High (2.75, 3) Planned ICU admission

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1. Odds ratio represents 1000-unit increase. 2. Odds ratio represents a 1-unit increase. † Illustrative purposes only. Did not reach significance level to remain in the model.

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Table 6: Summary of features between patients with and without a postoperative complication, N=88 No Complication N=79

Median (IQR; Range) 43 (35-52; 14-71) 48 (39-57; 19-62) 30.7 (26.9-34.8; 20.7-45.2) 29.6 (22.3-34.3; 19.8-50.9) 46 (27-62; 3-113) 33 (23-59; 6-80) 7.5 (6.8-8.6; 3.1-11.8) 7.8 (7.6-10.2; 7.3-12.5) 6.1 (5.1-7.2; 2.1-10.1) 6.9 (6.3-8.4; 6.0-9.0) 4809 (3707-6032; 1403-9114) 6086 (4600-7703; 4151-8727)

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Feature Age in years Preoperative BMI Preoperative AHI (N=86) Duration of anesthesia in hours Duration of surgery in hours Total fluid in mL

N (%)

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21 (27) 58 (73)

5 (71) 2 (29)

63 (80) 16 (20)

5 (56) 4 (44)

7 (9) 62 (78) 10 (13)

1 (11) 4 (44) 4 (44)

60 (76) 19 (24) 41 (52) 13 (16) 28 (35) 57 (72)

4 (44) 5 (56) 7 (78) 1 (11) 7 (78) 7 (78)

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5 (56) 4 (44)

46 (65) 25 (35)

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Sex Female Male Smoking status (N=78) Never Active, former Charlson score 0 >0 ASA score 1 2 3 Complexity of procedure Low (1, 2) High (2.75, 3) Colloid Albumin Hydroxyethyl starches Planned ICU admission

Complication N=9

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Table 7: Univariate associations of features with postoperative complication, N=88 Feature

Odds Ratio (95% CI)

P-value

1.26 (0.70-2.28)1

0.45

1.0 (reference) 0.29 (0.07-1.18)

0.084

1.0 (reference) 0.74 (0.13-4.07) 0.99 (0.89-1.12)2 0.93 (0.71-1.21)1

0.73 0.92 0.58

1.0 (reference) 3.15 (0.76-13.09) 3.25 (0.82-12.83)2 1.54 (1.02-2.34)2 1.54 (0.99-2.39)2

0.11 0.093 0.042 0.058

1.0 (reference) 3.95 (0.96-16.21) 1.69 (1.08-2.63)3 3.24 (0.63-16.59) 0.64 (0.07-5.52) 6.38 (1.24-32.79) 1.35 (0.26-7.01) 0.74 (0.14-3.85)

0.057 0.021 0.16 0.68 0.027 0.72 0.72

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Age in years Sex Female Male Smoking status (N=78) Never Active, former Preoperative BMI Preoperative AHI (N=86) Charlson score 0 >0 ASA score Duration of anesthesia in hours Duration of surgery in hours Complexity of procedure Low (1, 2) High (2.75, 3) Total fluid Colloid Albumin Hydroxyethyl starches Planned ICU admission No planned ICU admission

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1. Odds ratio represents a 10-unit increase. 2. Odds ratio represents a 1-unit increase. 3. Odds ratio represents a 1000-unit increase.

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