Nonoperative Management Is as Effective as Immediate Splenectomy for Adult Patients with High-Grade Blunt Splenic Injury

Accepted Manuscript Non-Operative Management Is As Effective As Immediate Splenectomy For Adult Patients with High-Grade Blunt Splenic Injury John E. Scarborough, MD, FACS, Angela M. Ingraham, MD, MS, Amy E. Liepert, MD, FACS, Hee Soo Jung, MD, Ann P. O’Rourke, MD, MPH, FACS, Suresh K. Agarwal, MD, FACS PII:

S1072-7515(16)30082-5

DOI:

10.1016/j.jamcollsurg.2016.03.043

Reference:

ACS 8319

To appear in:

Journal of the American College of Surgeons

Received Date: 1 March 2016 Revised Date:

25 March 2016

Accepted Date: 28 March 2016

Please cite this article as: Scarborough JE, Ingraham AM, Liepert AE, Jung HS, O’Rourke AP, Agarwal SK, Non-Operative Management Is As Effective As Immediate Splenectomy For Adult Patients with High-Grade Blunt Splenic Injury, Journal of the American College of Surgeons (2016), doi: 10.1016/ j.jamcollsurg.2016.03.043. 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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Non-Operative Management Is As Effective As Immediate Splenectomy For Adult Patients with High-Grade Blunt Splenic Injury

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John E Scarborough, MD, FACS, Angela M Ingraham, MD, MS, Amy E Liepert, MD, FACS, Hee Soo Jung, MD, Ann P O’Rourke, MD, MPH, FACS, Suresh K Agarwal, MD, FACS

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Disclosure Information: Nothing to disclose.

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From the Wisconsin Surgical Outcomes Research Program, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI

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Corresponding Author: John E Scarborough, MD Associate Professor Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Department of Surgery University of Wisconsin School of Medicine and Public Health 600 Highland Avenue Madison, Wisconsin 53792-0001 Phone: (608)265-9574 E-mail: [email protected]

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Brief Title: Management of High-Grade Blunt Splenic Injury

Key Words: blunt splenic trauma, non-operative management, splenectomy, comparative effectiveness, splenic artery embolization

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Abstract Background: The comparative effectiveness of non-operative management (NOS) versus

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immediate splenectomy (IS) for hemodynamically stable adult patients with grade IV or V blunt splenic injury (BSI) has not been clearly established in the literature.

Study Design: Retrospective analysis of adult patients from the 2013-2014 American College of

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Surgeons Trauma Quality Improvement Program (TQIP) Participant Use Data Files who

sustained grade IV or V blunt splenic injury. Outcomes after IS versus attempted NOM were

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compared using propensity score analysis in order to adjust for patient- and injury-related variables.

Results: NOM was attempted in 1,489 (52.2%) of 2,746 patients who sustained grade IV or V blunt splenic injury. Propensity matching techniques resulted in a cohort of 758 IS and NOM

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patients who were well-matched for all known patient- and injury-related variables. In-hospital mortality was not different between the IS and NOM patients (11.5% vs. 10.0%, P = 0.33), although IS patients had a higher incidence of infectious complications (21.4% vs. 16.9%, P =

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0.02). The rate of NOM failure in our sample was 20.1%. Independent predictors of failed NOM included the presence of an bleeding disorder, early blood transfusion requirement, and grade V

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injury. Splenic artery embolization was associated with a decreased risk of NOM failure. Patients who failed NOM had a lower in-hospital mortality rate than IS patients (6.4% vs. 16.4%, P = 0.004), but required longer hospitalization. Conclusions: NOM is as effective as IS for hemodynamically stable adult patients with grade IV or V BSI. The delay in operative intervention that results from failed attempts at NOM does not adversely impact the outcomes of patients who ultimately require splenectomy.

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Introduction

While non-operative management (NOM) has become standard management for low-grade

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blunt splenic injury (BSI), its routine utilization in hemodynamically stable adults with grade IV or V BSI remains controversial.1-4 Historical attempts to manage patients with high-grade BSI were marked by high failure rates.5-7 Although the utilization of splenic artery embolization

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(SAE) has been shown by some groups to increase the success rate of NOM for grade IV or V injury, this finding has not been universal.6-14 Many of the studies which have reported improved

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outcomes with NOM compared to immediate splenectomy (IS) have included all splenic injury grades in their analysis, not just higher-grade injuries.5,15,16 The few comparative studies which have focused specifically on high-grade BSI have not adjusted for other patient- and injuryrelated factors which might confound the comparison.3,4 In addition, it remains uncertain

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whether the outcomes of patients with high-grade BSI who are initially managed non-operatively but who ultimately require splenectomy might be adversely affected by the delay in intervention.3-5,15-19 Therefore, despite the fact that current management guidelines do not

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specifically dissuade surgeons from pursuing NOM simply because of injury grade, the comparative effectiveness of this management approach versus immediate splenectomy (IS) for

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high-grade BSI has not been clearly established in the literature.20 The goal of the current study was to address three knowledge gaps about the role of NOM in the management of patients with high-grade (grade IV or V) BSI. The specific objectives of our analysis were: (1) to compare the risk-adjusted in-hospital outcomes of NOM versus IS in adult patients with high-grade BSI, (2) to determine whether the utilization of SAE alters the success rate of NOM in patients with high-grade BSI, and (3) to elucidate the consequences of NOM

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failure by comparing the risk-adjusted outcomes of high-grade BSI patients who fail NOM with those of otherwise similar patients who undergo immediate splenectomy.

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Methods

The 2013-2014 American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) Participant Use Data Files (PUFs) were used for this study. TQIP was created

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in 2006 as an effort develop a national trauma-centered quality improvement program that

harnessed the infrastructure of the existing national trauma data registry (the National Trauma

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Data Bank, or NTDB).21 Participation in TQIP is confined to ACS- and/or state-designated Level I and II trauma centers. A total of 223 such centers participated in the program in 2013, and 300 centers participated in 2014.22 -23 Data abstractors and trauma registrars from participating centers undergo extensive training from the ACS, with special emphasis being

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placed on the need for complete data entry and importance of relying on uniform variable definitions provided by the National Trauma Data Standard when defining complications.21 Beginning in 2013, TQIP began to track early blood transfusion requirements and the utilization

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of SAE. Because the NTDB dataset and earlier releases of TQIP do not specifically include this specific information, which is of particular import to the study of management strategies of BSI,

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we chose to only utilize 2013-2014 TQIP data for our analysis. Our study population included adult (≥ 18 years old) blunt trauma patients who were

recorded as having high-grade (i.e., grade IV or grade V) BSI. In order to be considered as having splenic injury, a patient had to have both an International Classification of Diseases 9th Clinical Modification (ICD-9) diagnosis code (865, 865.00, 865.01, 865.02, 865.03, 865.04, 865.09, 865.10, 865,11, 865.12, 865.13, 865.14, or 865.19) and an Abbreviated Injury Scale

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(AIS) score that were consistent with injury to the spleen. Assignment of spleen grade was accomplished based on spleen AIS score and using the method described by Tinkoff and colleagues.24 Patients were excluded from our analysis if they were dead on arrival to the

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emergency department (ED), transferred to or from another hospital, were admitted to the ED more than 24 hours after their injury, or if they sustained an AIS score of 6 for any region of the body (since the unsurvivable nature of their injury would theoretically not be influenced by the

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choice of management strategy). Patients were also excluded if the time interval between

emergency department admission and splenectomy was unknown or if they were recorded as

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having undergone both splenic artery embolization (SAE) and splenectomy within the first 4 hours after admission. Missing data for other study variables was handled in one of two ways. For those variables in which the number of patients with missing data was very small (<1% of the study sample), patients with missing data were excluded from the study. For those variables

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in which the number of patients with missing data was >1% of the study sample, a missing indicator variable was created.

The outcome variables for our analysis were in-hospital mortality, length of

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hospitalization, length of intensive care unit (ICU) stay, number of days on mechanical ventilation, in-hospital infectious complication rate, in-hospital non-infectious complication rate,

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and non-routine discharge status. Infectious complications were defined as the development of high-grade sepsis, catheter-related blood stream infection, urinary tract infection, superficial or deep surgical site infection, organ/space surgical site infection, and/or pneumonia during index hospitalization. Non-infectious complications were defined as the development of deep venous thrombosis, pulmonary embolism, myocardial infarction, acute respiratory distress syndrome, and/or acute kidney injury during index hospitalization. It is important to note that TQIP utilizes

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strict variable definitions as outlined by the NTDS in order to define post-injury complications.25 Non-routine discharge was defined as any discharge to a site other than home (or to a skilled nursing facility if that was the patient’s place of residence prior to injury).

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The primary predictor variable for our analysis was the initial management strategy for high-grade BSI. Patients were classified as undergoing immediate splenectomy (IS group) if the underwent splenectomy within 4 hours of emergency department admission.15 All other patients

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were classified as undergoing initial non-operative management (“A-NOM” group). The

selection of 4 hours as the time threshold for assigning patients to the IS or A-NOM groups was

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made a priori, and was based on our opinion that patients in whom immediate splenectomy was deemed necessary should be able to have their operation started within 4 hours of their arrival to the ED. Recognizing the subjective nature of this definition, all study analyses were repeated using alternate time points (2, 3, and 6 hours post-admission) to define IS. The performance of

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a splenectomy was identified by an ICD-9 procedure code for “total splenectomy.” Patients with ICD-9 codes for “partial splenectomy” or “repair and plastic operations on spleen” were also classified as undergoing urgent splenectomy if their procedure occurred within 4 hours of

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emergency department admission. Secondary predictor variables included patient-, hospital-, and injury-related characteristics (Table 1). Early transfusion was defined as the number of units

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of packed red blood cells that the patient received in the first 4 hours after their emergency department admission.

The characteristics and outcomes of IS and A-NOM patients were compared using

Pearson’s chi square tests for categorical variables and Wilcoxon rank sum tests for continuous variables. In order to account for the likelihood that the decision to pursue initial NOM is subject to non-random selection bias, we analyzed a subset of our entire patient sample that was

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matched for their propensity to undergo urgent splenectomy. In order to create the matched cohort, a non-parsimonious logistic regression model was created to estimate the likelihood of undergoing immediate splenectomy after high-grade BSI, with all of the variables that are listed

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in Table 1 being included as potential predictors of immediate splenectomy in this model. The logit coefficients obtained from this model were then used to calculate a propensity score for immediate splenectomy for each patient from the overall study sample that ranged from 0 to 1.

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The resulting propensity scores were then used to create an evenly matched cohort of IS and ANOM patients by a caliper matching algorithm with a caliper distance of 0.005 and controls

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being used only once in the matching procedure. Comparison of the characteristics and outcomes of the matched cohort of patients was then performed using McNemar’s chi-square tests for binary variables, univariate conditional logistic regression for multi-level categorical variables, and Wilcoxon signed rank tests for continuous variables.

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A-NOM patients from the overall study sample were then sub-classified as either having failed non-operative management if they underwent splenectomy at any point after the 4th hour of hospitalization (F-NOM group), or as having completed successful non-operative

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management of their splenic injury if they avoided splenic surgery throughout their entire hospitalization (S-NOM group). In order to identify predictors of F-NOM, we constructed a

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multivariate logistic regression model that included only patients from the A-NOM group. In this model, failure of non-operative management was the dependent variable. Potential predictor variables included the patient-, hospital-, and injury-related variables listed in Table 1 and whether or not the patient underwent SAE. In order to determine whether the initial delay in operative management affected the outcomes of patients who were initially managed non-operatively but who subsequently require

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splenectomy, F-NOM patients from the previously constructed propensity-matched cohort who ultimately underwent splenectomy were compared to their matched cohorts in the IS group.

<0.05 was considered statistically significant.

Results

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Stata Version 14 (College Station, TX) was used for all statistical analyses, and a P Value of

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A total of 2,746 patients with grade IV or V were included for analysis. Of these patients, 1,257 (45.8%) underwent immediate splenectomy within 4 hours of emergency

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department admission, while NOM was attempted in 1,489 (52.2%). Univariate comparison of the patient-, hospital-, and injury characteristics of patients in the IS and A-NOM groups is demonstrated in Table 1. Although there were few if any clinically significant differences in the patient- or hospital-level characteristics of these two groups, patients in the IS group were more

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likely to be hypotensive on ED admission, have a GCS ≤ 8, and have a Grade V (as opposed to Grade IV) splenic injury than patients in the A-NOM group. In addition, IS patients had a higher median ISS score than A-NOM patients and were more likely to have at least one body region

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AIS score of 4 or more. The transfusion requirement for IS patients in the first 4 hours after ED admission was also greater than for A-NOM patients.

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Table 2 demonstrates univariate comparison of the outcomes of patients in the A-NOM

and IS groups. As would be expected given their degree of splenic and other injury, patients in the IS group had a higher rate of in-hospital mortality, complications, length of ICU and total hospital stay, and rate of non-routine hospital discharge. A total of 1,516 patients from the overall study sample were matched on the basis of their probability of undergoing IS rather than A-NOM. The 731 A-NOM patients from the overall

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sample who were not included in the propensity-matched cohort tended to be less high-gradely injured than the 758 A-NOM patients who were successfully matched, while the 499 IS patients from the overall sample who were not included in the propensity-matched cohort tended to be

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more high-gradely injured than the 758 IS patients who were successfully matched (data not shown). As demonstrated by Table 3, the resulting cohort of A-NOM and IS patients were wellmatched for all known patient-, hospital-, and injury-related characteristics. When comparing

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the outcomes of this matched cohort (shown in Table 4), we found that patients who were

managed with A-NOM had a similar rate of mortality, length of ICU and overall hospital stay,

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and incidence of non-infectious complications as patients who were managed with IS. The only significant differences between the matched groups was in the median duration of mechanical ventilation (longer in the IS group) and the incidence of infectious complications (greater in the IS group). Of note, the incidence of organ/space SSI did not differ significantly between A-

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NOM and IS patients from the propensity-matched cohort (0.8% incidence in A-NOM patients versus 1.9% incidence in IS patients, P = 0.08).

Of the 1,489 patients from our overall study sample in whom NOM was attempted, 299

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(20.1%) ultimately required splenectomy. The NOM failure rate was 17.8% for patients with grade IV splenic injury, and 29.0% for patients with grade V splenic injury. SAE was performed

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in 191 (12.8%) A-NOM patients. Embolization was performed within 4 hours of arrival to the ED in 109 (57.1%) of these patients, and after 4 hours in 66 (34.6%). The timing of embolization was not known for 16 (8.4%) of the patients who underwent splenic artery embolization. The failure rate in A-NOM patients who underwent SAE was 11.0%, compared to 21.4% in those patients who did not undergo SAE. Time to embolization did not differ significantly between F-NOM and S-NOM patients who underwent SAE (median 3 versus 4

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hours, P = 0.14). Utilization of SAE was the only factor that appeared on multivariate analysis to protect against failure of NOM (see Table 5). Conversely, several factors appeared to increase the risk of NOM failure, including the need for any blood transfusion within 4 hours of ED

(versus grade IV) splenic injury (Table 5).

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admission, increasing patient age, the presence of an underlying bleeding disorder, and grade V

In order to determine whether the delay in operative management in patients who failed

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NOM impacted their outcomes, we then compared the 171 F-NOM patients from our propensitymatched cohort with their IS counterparts (see Table 6). The mortality of F-NOM was

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significantly lower than their matched IS counterparts (6.4% vs. 16.4%, P = 0.004), but they had a significantly longer overall length of hospital stay (median 13 days vs. 10 days, P = 0.005). There were no other statistically significant differences in the outcomes of the propensitymatched F-NOM and IS patients.

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Table 7 shows the results of our sensitivity analysis in which we used alternate time points after ED admission in order to define a patient with high-grade BSI as having received IS as opposed to A-NOM. Not surprisingly, earlier time points resulted in a lower percentage of

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patients being classified in the IS group, and a greater percentage of patients from the A-NOM group being classified as NOM failures. When assessing the impact of our definition of IS on

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the major outcomes of our study, however, we found that our general findings did not change significantly. Using earlier thresholds to define IS resulted in length of mechanical ventilation as being the only outcome that differed significantly between propensity-matched IS and A-NOM patients. Using 6 hours as the threshold resulted in a greater number of outcome differences between the groups, all of which favored A-NOM as the preferred management strategy. Using different time thresholds to define IS did not significantly impact our comparison of the

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outcomes of patients who failed NOM with those of the propensity-matched group that underwent IS.

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Discussion

The first objective of our study was to determine the comparative effectiveness of ANOM with IS for patients with grade 4 or 5 BSI. Using 4 hours after ED admission as an a

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priori definition to distinguish IS from A-NOM, we found that 45.8% of patients underwent IS for high-grade BSI while NOM was attempted in 52.2%. We used propensity-matching

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techniques in order to generate a subgroup of IS and A-NOM patients who were well-matched for all study variables. Comparison of the outcomes of this well-matched cohort revealed no significant differences between the two groups in in-hospital mortality rate or median lengths of ICU and hospital stay. The only significant differences between the two groups were in the

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length of mechanical ventilation requirement (higher in the IS group) and in the incidence of infectious complications (greater in the IS group). Given the subjective nature of our definition of IS, we repeated our propensity matching algorithm and subsequent outcome comparisons

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using alternate time points to define IS. When earlier time points were used to define IS, the only difference between groups was a longer median duration of mechanical ventilation in IS

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patients. When operation within six hours of admission was used to define IS, the outcomes between the two groups were more disparate, and uniformly favored A-NOM. We conclude from these results that, A-NOM is as safe and effective as IS for the initial management of hemodynamically stable patients with high-grade BSI. To our knowledge, this is one of the first published analyses that have used multivariate risk adjustment in order to compare the

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effectiveness of A-NOM relative to IS for high-grade BSI, rather than just reporting the success and failure rates of A-NOM. An important feature of our study is our attempt to reduce the potential impact that

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selection bias has on our comparison of IS and A-NOM patients. An unknown proportion of the patients in the pre-matched IS group underwent immediate operation for a universally

acknowledged indication such as hemodynamic instability or peritonitis. Unfortunately, multi-

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center registry-based data sources such as TQIP and NTDB do not contain information about abdominal exam findings or about a patient’s hemodynamic profile beyond their admission

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systolic blood pressure. In an effort to minimize the selection bias that would result from inclusion of unstable patients in the IS group, we utilized propensity-matching techniques in order to create a cohort of IS and A-NOM patients from the overall study sample that were matched for data elements that are included in TQIP, such as abdominal AIS score, early

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transfusion requirements, and SBP on ED admission. Reviewing the characteristics of those IS patients who were excluded from the matched cohort with those of the IS patients who were included, we found the excluded group to have a higher ISS, be more likely to have an

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abdominal AIS score of 4 or 5, and be more likely to be hypotensive on ED admission. While it is impossible to completely eliminate the possibility of selection bias from our analysis, these

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findings give us reassurance that we were able to reduce as much as possible the impact of such bias as on our subsequent comparison of outcomes. Similar methodology has been used previously by Zarzaur and colleagues, although that analysis of NTDB data from 2007 included all splenic injury grades.16

The second objective of our study was to identify patient- and/or injury-related factors which are independently associated with success or failure of NOM in patients with grade IV or

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V BSI. The only variable in our analysis that was significantly associated with successful NOM was the utilization of SAE. This procedure was utilized in 12.8% of the patients in our A-NOM group (12.1% of patients with grade IV injury and 15.5% of patients with grade V injury). The

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NOM failure rate in patients who underwent SAE was 11.0%, compared to a failure rate of

21.4% in patients who did not undergo SAE. Our analysis therefore supports the findings of

in patients who sustain high-grade BSI.8-11,14

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previous studies which have suggested that SAE may improve the likelihood of successful NOM

Several factors were independently associated with failure of NOM in patients with high-

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grade BSI. These included grade V (versus grade IV) splenic injury, hypotension on ED admission, increasing age, the presence of an underlying bleeding disorder, alcoholism, and any requirement for blood transfusion within the first four hours after ED admission. Although we do not believe that these factors should be considered contraindications to NOM, their presence

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should reinforce the importance of careful monitoring and continual reassessment of high-grade BSI patients in whom NOM is attempted.

A final objective of our analysis was to determine whether delay in splenectomy

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negatively impacts the outcomes of high-grade BSI patients who ultimately fail NOM. Several groups have previously compared the outcomes of patients who fail NOM with those of patients

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who are successfully managed without operation.4,7,15-18 In many respects, however, this is an artificial comparison. We believe that the more relevant question is whether patients who ultimately require operation after a period of attempted NOM would have been better served by undergoing IS. However, few if any of the studies which have compared the outcomes of FNOM patients with IS patients have included any type of risk adjustment.2,5,19 In the current analysis, we compared the outcomes of those patients from our propensity-matched group who

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failed NOM with their IS counterparts. Again, the patients in this subgroup comparison were well matched for all known patient- and injury-related factors. We found that patients in the IS group had a greater incidence of mortality than patients who failed NOM. While it is possible

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that some degree of selection bias might have influenced this comparison, at the very least we have concluded that efforts to spare hemodynamically stable patients with grade IV or V BSI will not jeopardize their outcomes should they ultimately require splenectomy.

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Our study has several important limitations. First, as mentioned previously, the time threshold that we have used to define IS versus A-NOM is subjective. Although we performed a

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sensitivity analysis using alternate time points to define IS, our data source does not permit us to know the true intention of the attending surgeons who formulated the plans for IS versus ANOM in the patients of our study. Second, our study population consists of patients from ACSand/or state-designated Level I or II trauma centers that participate in TQIP. As a result, our

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findings with respect to the safety and efficacy of NOM for high-grade BSI may not be generalizable to all trauma centers. Third, we have utilized AIS codes in order to define splenic injury grade. Although this technique has been previously validated, we did not have access to

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the reports of initial computed tomography scans or intra-operative findings.24 Fourth, we do not know the actual indications for SAE and/or splenectomy in our study patient, or whether the

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centers that participate in TQIP employ specific protocols for the utilization of SAE, or the extent of splenic artery embolization (proximal versus distal artery). As a result, we cannot make definitive recommendations regarding the appropriate use of angioembolization, or the relative efficacy of proximal versus distal artery embolization in facilitating successful NOM. Despite these limitations, our study provides additional evidence to support current practice management guidelines which recommend high-grade BSI patients who are

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hemodynamically stable and without signs of peritonitis on examination.20 We have also identified several variables that portend an increased risk of failure of NOM, and have redemonstrated the utility of SAE as a means of splenic salvage in patients with grade IV or V

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injuries. Finally, we have demonstrated that the delay in operative intervention that results from failed attempts at NOM will not significantly impact the outcomes of patients with high-grade BSI who ultimately require splenectomy. As such, the findings of our study suggest that

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attempted NOM can be pursued in all high-grade BSI patients who are hemodynamically stable

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and without some other indication for immediate laparotomy.

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References 1. Hildebrand DR, Ben-sassi A, Ross NP, et al. Modern management of splenic trauma. BMJ 2014; 348: g1864.

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2. Cirocchi R, Boselli C, Corsi A, et al. Is non-operative management safe and effective for all splenic blunt trauma? A systematic review. Critical Care 2013; 17: 8185.

3. Watson GA, Rosengart MR, Zenati MS, et al. Nonoperative management of high-grade

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blunt splenic injury: are we getting better? J Trauma 2006; 61: 1113-1119.

4. Velhamos GC, Zacharias N, Emhoff TA, et al. Management of the most high-gradely

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injured spleen. Arch Surg 2010; 145: 456-460.

5. Peitzman AB, Heil B, Rivera L, et al. Blunt splenic injury in adults: Multi-institutional study of the Eastern Association for the Surgery of Trauma. J Trauma 2000; 49: 177189.

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6. Requarth JA, D’Agostino RB, Miller PR. Non-operative management of blunt splenic injury with and without splenic artery embolization: a meta-analysis. J Trauma 2011; 71: 898-903.

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7. Smith J, Armen S, Cook CH, Martin LC. Blunt splenic injuries: have we watched long enough? J Trauma 2008; 64: 656-663.

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8. Skattum J, Naess PA, Eken T, Gaarder C. Defining the role of splenic angiographic embolization in high-grade splenic injuries. J Trauma Acute Care Surg 2013; 74: 100-

103.

9. Zarzaur BL, Savage SA, Croce MA, Fabian TC. Trauma center angiography use in highgrade blunt splenic injuries: timing is everything. J Trauma Acute Care Surg 2014; 77: 666-673.

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10. Miller PR, Chang MC, Hoth JJ, et al. Prospective trial of angiography and embolization for all grade III to V blunt splenic injuries: nonoperative management success rate is significantly improved. J Am Coll Surg 2014; 218: 644-651.

review. J Trauma 2004; 56: 542-547.

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11. Haan JM, Biffl W, Knudson MM, et al. Splenic embolization revisited: a multicentre

12. Harbrecht BG, Ko SH, Watson GA, et al. Angiography for blunt splenic trauma does not

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improve success rate of nonoperative management. J Trauma 2007; 63: 44-49.

13. Duchesne JC, Simmons JD, Schmieg RE Jr., et al. Proximal splenic angioembolization

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does not improve outcomes in treating blunt splenic injuries compared with splenectomy: a cohort analysis. J Trauma 2008; 65: 1346-1351.

14. Bhullar IS, Frykberg ER, Siragusa D, et al. Selective angiographic embolization of blunt splenic traumatic injuries in adults decreases failure rate of nonoperative management. J

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Trauma Acute Care Surg 2013; 74: 105-111.

15. McIntyre LK, Schiff M, Jurkovich GJ. Failure of nonoperative management of splenic injuries. Arch Surg 2005; 140: 563-569.

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16. Zarzaur BL, Croce MA, Fabian TC. Variation in the use of urgent splenectomy after blunt splenic injury in adults. J Trauma 2011; 71: 1333-1339.

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17. Demetriades D, Scalea TM, Degiannis E, et al. Blunt splenic trauma: splenectomy increases early infectious complications: a prospective multicenter study. J Trauma

2012; 72: 229-234.

18. Crandall M, Shapiro MB, West MA. Does splenectomy protect against immunemediated complications in blunt trauma patients? Mol Med 2009; 15: 263-267.

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19. Sirriatsivawong K, Zenati M, Watson GA, Harbrecht BG. Nonoperative management of blunt splenic trauma in the elderly: does age play a role? Am Surg 2007; 73: 585-589. 20. Stassen NA, Bhullar I, Cheng JD, et al. Selective nonoperative management of blunt

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splenic injury: An Eastern Association for the Surgery of Trauma practice managment guideline. J Trauma Acute Care Surg 2012; 73: S294-S300.

21. Hemmila MR, Nathens AB, Shafi S, et al. The Trauma Quality Improvement Program:

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pilot study and initial demonstration of feasibility. J Trauma 2010; 68: 253-262.

22. User Manual, Trauma Quality Improvement Program (TQIP) Participant User File

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Admission Year 2013. American College of Surgeons, Chicago, IL. Available from URL (Au: provide URL and access date)

23. User Manual, Trauma Quality Improvement Program (TQIP) Participant User File Admission Year 2014. American College of Surgeons, Chicago, IL. Available from

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URL (Au: provide URL and access date)

24. Tinkoff G, Esposito TJ, Reed J, et al. American Association for the Surgery of Trauma Organ Injury Scale I: spleen, liver, and kidney, validation based on the National Trauma

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Data Bank. J Am Coll Surg 2008; 207: 646-655. 25. National Trauma Data Standard of the NTDB. Available from URL

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http://www.ntdsdictionary.org/dataElements/datasetDictionary.html. Accessed February

11, 2016.

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Table 1. Patient and Injury Characteristics of All Patients with High-Grade Blunt Splenic Injury, Stratified by Management Strategy

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931 (74.1) 96 (7.6) 143 (11.4) 56 (4.5) 31 (2.5) 704 (56.0)

SC

1,096 (73.6) 136 (9.1) 145 (9.7) 74 (5.0) 38 (2.6) 883 (59.3)

Immediate splenectomy (n = 1,257) 36 (24-51) 372 (29.6)

p Value

RI PT

36 (24-52) 477 (32.0)

TE D

Age, y, median (IQR) Female Race/ethnicity White Black Latino Other Unknown University hospital setting Trauma center level Level I Level II Missing/unknown Number of hospital beds ≤ 350 351-500 >500 Number of trauma surgeons 0-6 7-8 >8 Respiratory disease Obesity Diabetes Smoker CHF Bleeding disorder Alcoholism Hypotension (SBP <90 mmHg) at ED admission No Yes Missing Low GCS (≤ 8) at ED admission No Yes Missing Grade V spleen injury Early transfusion need

Attempted NOM (n = 1,489)

M AN U

Characteristic

1,077 (72.3) 391 (26.3) 21 (1.4)

905 (72.0) 338 (26.9) 14 (1.1)

386 (25.9) 467 (31.4) 636 (42.7)

359 (28.6) 317 (25.2) 581 (46.2)

806 (54.1) 363 (24.4) 320 (21.5) 81 (5.4) 163 (11.0) 111 (7.5) 350 (23.5) 14 (0.9) 52 (3.5) 136 (9.1)

630 (50.1) 336 (26.7) 291 (23.2) 70 (5.6) 131 (10.4) 68 (5.4) 256 (20.4) 12 (1.0) 36 (2.9) 101 (8.0)

1,324 (88.9) 145 (9.7) 20 (1.3)

922 (73.4) 312 (24.8) 23 (1.8)

1,260 (84.6) 187 (12.6) 42 (2.8) 303 (20.4)

877 (69.8) 361 (28.7) 19 (1.5) 553 (44.0)

0.42 0.17

0.41

0.08 0.75

0.002

0.11 0.88 0.66 0.03 0.05 0.97 0.35 0.31

< 0.001

<0.001 < 0.001 < 0.001

ACCEPTED MANUSCRIPT 20

SC

RI PT

None 1,165 (78.2) 526 (41.9) 1-2 units 158 (10.6) 212 (16.9) 3-4 units 75 (5.0) 148 (11.8) >4 units 91 (6.1) 371 (29.5) Injury severity score median (IQR) 29 (25-38) 38 (29-45) <0.001 Extremity AIS ≥ 4 32 (2.2) 49 (3.9) 0.007 Spine AIS ≥ 4 9 (0.6) 23 (1.8) 0.003 Chest AIS ≥ 4 285 (19.1) 327 (26.0) <0.001 Abdominal AIS ≥ 4 111 (7.5) 167 (13.3) <0.001 Head AIS ≥ 4 176 (11.8) 258 (20.5) <0.001 AIS, Abbreviated Injury Scale; CHF, congestive heart failure; ED, emergency department; GCS, Glasgow Coma Scale; IQR, interquartile range; NOM, non-operative management; SBP, systolic blood pressure

AC C

EP

TE D

M AN U

All data expressed as number (percentage) unless otherwise indicated.

ACCEPTED MANUSCRIPT 21

Table 2. Outcomes of All Patients with High-Grade Blunt Splenic Injury, Stratified by Management Strategy Immediate splenectomy (n = 1,257)

Outcome

93 (6.3)

Hospital length of stay, d, median (IQR)

7 (5-13)

ICU length of stay, d, median (IQR)

3 (2-6)

207 (16.5) 10 (6-20) 5 (2-12)

SC

In-hospital death, n (%)

EP

TE D

M AN U

Duration mechanical ventilation, d, 0 (0-2) 2 (0-8) median (IQR) Infectious complications, n (%) 191 (12.8) 294 (23.4) Non-infectious complications, n (%) 126 (8.5) 182 (14.5) Non-routine discharge status, n (%) 391 (28.0) 426 (40.6) ICU, intensive care unit; IQR, interquartile range; NOM, non-operative management

AC C

p Value

RI PT

Attempted NOM (n = 1,489)

< 0.001 < 0.001 < 0.001

<0.001 <0.001 <0.001 <0.001

ACCEPTED MANUSCRIPT 22

Table 3. Patient and Injury Characteristics of Propensity-Matched Cohort of Patients with HighGrade Blunt Splenic Injury, Stratified by Management Strategy

EP

AC C

556 (73.4) 68 (9.0) 82 (10.8) 33 (4.4) 19 (2.5) 428 (56.5)

SC

566 (74.7) 62 (8.2) 82 (10.8) 33 (4.4) 15 (2.0) 434 (57.3)

Immediate splenectomy (n = 758) 37 (25-51) 233 (30.7)

p Value

RI PT

37 (24-53) 239 (31.5)

TE D

Age, y, median (IQR) Female Race/ethnicity White Black Latino Other Unknown University hospital setting Trauma center level Level I Level II Missing/unknown Number of hospital beds ≤ 350 351-500 >500 Number of trauma surgeons 0-6 7-8 >8 Respiratory disease Obesity Diabetes Smoker CHF Bleeding disorder Alcoholism Hypotension (SBP <90 mmHg) at ED admission No Yes Missing Low GCS (≤ 8) at ED admission

M AN U

Characteristic

Attempted NOM (n = 758)

538 (71.0) 210 (27.7) 10 (1.3)

541 (71.4) 205 (27.0) 12 (1.6)

205 (27.0) 223 (29.4) 330 (43.5)

209 (27.6) 215 (28.4) 334 (44.1)

384 (50.7) 204 (26.9) 170 (22.4) 46 (6.1) 84 (11.1) 46 (6.1) 160 (21.1) 6 (0.8) 24 (3.2) 67 (8.8)

391 (51.6) 200 (26.4) 167 (22.0) 43 (5.7) 73 (9.6) 47 (6.2) 163 (21.5) 4 (0.5) 22 (2.9) 61 (8.1)

624 (82.3) 122 (16.1) 12 (1.6)

620 (81.8) 125 (16.5) 13 (1.7)

0.76 0.74

0.94

0.75

0.88

0.89

0.94 0.74 0.34 0.91 0.85 0.53 0.77 0.58

0.95

0.80

ACCEPTED MANUSCRIPT 23

M AN U

SC

RI PT

No 590 (77.8) 580 (76.5) Yes 157 (20.7) 166 (21.9) Missing 11 (1.5) 12 (1.6) Grade V spleen injury 261 (34.4) 246 (32.5) 0.35 Early transfusion need None 446 (58.8) 452 (59.6) 1-2 units 149 (20.0) 126 (16.6) 0.27 3-4 units 74 (9.8) 77 (10.2) >4 units 89 (11.7) 103 (13.6) Injury severity score, median (IQR) 34 (26-42) 34 (26-42) 0.46 Extremity AIS ≥ 4 23 (3.0) 26 (3.4) 0.66 Spine AIS ≥ 4 8 (1.1) 4 (0.5) 0.24 Chest AIS ≥ 4 171 (22.6) 178 (23.5) 0.66 Abdominal AIS ≥ 4 75 (9.9) 84 (11.1) 0.45 Head AIS ≥ 4 132 (17.4) 128 (16.9) 0.78 AIS, Abbreviated Injury Scale; CHF, congestive heart failure; ED, emergency department; GCS, Glasgow Coma Scale; IQR, interquartile range; NOM, non-operative management; SBP, systolic blood pressure

AC C

EP

TE D

All data expressed as number (percentage) unless otherwise indicated.

ACCEPTED MANUSCRIPT 24

Table 4. Outcomes of Propensity-Matched Cohort of Patients with High-Grade Blunt Splenic Injury, Stratified by Management Strategy Attempted NOM (n = 758)

p Value

RI PT

Outcome

Immediate splenectomy (n = 758) 87 (11.5) 10 (6-18) 4 (2-10)

AC C

EP

TE D

M AN U

SC

In-hospital death, n (%) 76 (10.0) Hospital length of stay, d, median (IQR) 9 (5-17) ICU length of stay, d, median (IQR) 4 (2-9) Duration mechanical ventilation, d, 0 (0-4) 1 (0-6) median (IQR) Infectious complications, n (%) 128 (16.9) 162 (21.4) Non-infectious complications, n (%) 87 (11.5) 96 (12.7) Non-routine discharge status, n (%) 261 (38.3) 234 (34.9) ICU, intensive care unit; IQR, interquartile range; NOM, non-operative management

0.33 0.15 0.71 < 0.001 0.02 0.46 0.21

ACCEPTED MANUSCRIPT 25

Table 5. Independent Predictors of Success or Failure of Non-operative Management for Patients with High-Grade Blunt Splenic Injury

AC C

EP

TE D

M AN U

SC

RI PT

Adjusted odds Characteristic ratio for failure 95% CI p Value of NOM Bleeding disorder 3.45 1.85-6.43 <0.001 Early transfusion of 1-2 units (Ref: No Tfx) 2.37 1.47-3.81 <0.001 Early transfusion of >4 units (Ref: No Tfx) 2.28 1.26-4.14 0.007 Grade V spleen injury 2.15 1.47-3.15 <0.001 Early transfusion of 3-4 units (Ref: No Tfx) 2.05 1.07-3.93 0.03 Alcoholism 1.84 1.19-6.43 0.007 Increased patient age (per year increase) 1.02 1.01-1.03 <0.001 Splenic artery embolization 0.27 0.15-0.47 <0.001 CI, confidence interval; NOM, non-operative management; Ref, reference; Tfx, transfusion

ACCEPTED MANUSCRIPT 26

Table 6. Comparison of Outcomes of Patients Who Failed Non-operative Management for HighGrade Blunt Splenic Injury with Those of Propensity Score-Matched Patients Who Underwent Urgent Splenectomy

Outcome

Immediate splenectomy (n = 171) 28 (16.4) 10 (5-18) 5 (2-10)

EP

TE D

M AN U

SC

In-hospital death, n (%) 11 (6.4) Hospital length of stay, d, median (IQR) 13 (7-24) ICU length of stay, d, median (IQR) 6 (2-14) Duration mechanical ventilation, d, 2 (0-10) 2 (0-7) median (IQR) Infectious complications, n (%) 49 (28.7) 41 (24.0) Non-infectious complications, n (%) 32 (18.7) 21 (12.3) Non-routine discharge status, n (%) 75 (46.9) 58 (40.6) ICU, intensive care unit; IQR, interquartile range; NOM, non-operative management

AC C

p Value

RI PT

Failed NOM (n = 171)

0.004 0.005 0.09 0.43 0.32 0.10 0.22

ACCEPTED MANUSCRIPT 27

Table 7. Variation in Major Study Results Using Different Time Thresholds to Define “Immediate Splenectomy” “Immediate Splenectomy” defined as operating within: 2 hours 3 hours 4 hours 6 hours

Failure rate of NOM, %

IS: Longer ventilator requirement

35.3

IS: Greater incidence mortality

AC C

EP

Significant outcome differences between F-NOM and IS patients in propensity-matched cohort

IS: Longer ventilator requirement

TE D

Significant outcome differences between A-NOM and IS patients in propensity-matched cohort

1,598 (58.2)

1,489 (52.2)

1,410 (51.4)

IS: Longer ventilator requirement

IS: Longer ventilator requirement

RI PT

1,839 (67.0)

SC

Patients with ANOM, n (%)

M AN U

Outcome

25.5

IS: Greater incidence mortality

IS: Greater incidence Infectious complications

20.1

IS: Longer ICU stay IS: Longer hospital stay

IS: Greater incidence infectious complications 15.6

IS: Greater incidence mortality No differences F-NOM: Longer hospital stay

A-NOM, attempted non-operative management; F-NOM, failed non-operative management; ICU, intensive care unit; IS, immediate splenectomy; NOM, non-operative management

ACCEPTED MANUSCRIPT 28

Precis Non-operative management is as effective as immediate splenectomy for hemodynamically

RI PT

stable adult patients with high-grade blunt splenic injury. The delay in undergoing splenectomy

AC C

EP

TE D

M AN U

SC

does not adversely impact patients in whom non-operative management fails.