Is non-operative management safe and effective for all splenic blunt trauma? A systematic review

Introduction The goal of non-operative management (NOM) for blunt splenic trauma (BST) is to preserve the spleen. The advantages of NOM for minor splenic trauma have been extensively reported, whereas its value for the more severe splenic injuries is still debated. The aim of this systematic review was to evaluate the available published evidence on NOM in patients with splenic trauma and to compare it with the operative management (OM) in terms of mortality, morbidity and duration of hospital stay. Methods For this systematic review we followed the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" statement. A systematic search was performed on PubMed for studies published from January 2000 to December 2011, without language restrictions, which compared NOM vs. OM for splenic trauma injuries and which at least 10 patients with BST. Results We identified 21 non randomized studies: 1 Clinical Controlled Trial and 20 retrospective cohort studies analyzing a total of 16,940 patients with BST. NOM represents the gold standard treatment for minor splenic trauma and is associated with decreased mortality in severe splenic trauma (4.78% vs. 13.5% in NOM and OM, respectively), according to the literature. Of note, in BST treated operatively, concurrent injuries accounted for the higher mortality. In addition, it was not possible to determine post-treatment morbidity in major splenic trauma. The definition of hemodynamic stability varied greatly in the literature depending on the surgeon and the trauma team, representing a further bias. Moreover, data on the remaining analyzed outcomes (hospital stay, number of blood transfusions, abdominal abscesses, overwhelming post-splenectomy infection) were not reported in all included studies or were not comparable, precluding the possibility to perform a meaningful cumulative analysis and comparison. Conclusions NOM of BST, preserving the spleen, is the treatment of choice for the American Association for the Surgery of Trauma grades I and II. Conclusions are more difficult to outline for higher grades of splenic injury, because of the substantial heterogeneity of expertise among different hospitals, and potentially inappropriate comparison groups.


Introduction
Trauma is the fourth cause of death in the overall population and the first one in individuals below the age of 40 in Western countries [1,2]. Abdominal trauma can be classified as blunt or penetrating according to the agent and its mechanism of action [1][2][3].
The spleen is the most frequently injured organ in abdominal blunt trauma, mainly because of its highly vascularized parenchyma and its anatomic location. Spleen is the only structure involved in almost 46% of blunt trauma (BT). On the other hand the liver (41.7%), kidneys (16.4%), mesentery (15.1%), small and large bowel (10.1% and 6.3%, respectively), pancreas (5%) and omentum may concur with splenic injuries in the remaning part of BT [1,2].
Splenectomy was the only treatment proposed for splenic trauma until the 1960s. In 1968, Upadhyaya and Simpson proposed Non-Operative Management (NOM) in a study on 52 pediatric patients with splenic trauma [4].
The ultimate goal of NOM is to preserve the spleen and it is based on specific principles and criteria. NOM procedures include conservative medical treatment and angioembolization (AE) without access to the peritoneal cavity. Advantages of NOM for minor splenic trauma (grades I and II according to the American Association for the Surgery of Trauma-AAST), have been extensively reported, whereas its value for severe splenic injuries (AAST grades IV and V) is still under debate [2][3][4]. The aim of this systematic review was to evaluate the available published evidence on NOM in patients with splenic trauma and to compare it with operative management (OM) in terms of mortality, morbidity and duration of hospital stay.

Methods
The criteria of the "Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement" were followed in this systematic review [5].

Inclusion criteria
We analyzed randomized controlled trials (RCTs) and non-randomized controlled studies (non-RCSs) comparing NOM vs. OM for blunt splenic trauma (BST). Only studies with at least 10 patients with BST were included. No language restrictions were imposed.

Exclusion criteria
Studies were excluded if they involved only penetrating splenic trauma or if respective numbers of penetrating and blunt trauma were not specified.

Participants
Participants were patients of all ages and either gender who had BST.

Type of intervention
The intervention types were NOM (clinical observation, medical treatment and proximal or distal splenic angioembolization) vs. OM (total or partial splenectomy, splenorrhaphy, application of hemostatic agents).

Collection of data
We developed a data collection sheet, including names of authors, type of study, number of patients, type of treatment (NOM vs. OM) and the number of patients per treatment arm, mean age, Injury Severity Score (ISS), blood pressure, gender, American Association for the Surgery of Trauma (AAST) grade of splenic injury. Two authors (RC, ST) extracted data from included studies according to the data collection sheet, while another author (CB) oversaw the process. Controversies were solved by involving a fourth author (GN).

Outcomes of interest
The primary endpoint of this systematic review was considered the overall mortality defined as any death that occurred after the start of NOM or OM and during the hospital stay.
Secondary endpoints were overall morbidity, overwhelming post-splenectomy infection (OPSI)/quality of life, blood transfusion, abdominal abscesses and length of hospital stay.

Statistical analysis
Two authors performed the statistical analysis according to the PRISMA and the "Cochrane Handbook for Systematic Reviews" guidelines. Odds ratios (OR), (that is, the possibility that an event occurs in the two groups of treatment) were calculated for dichotomous outcomes while a weighted mean difference (WMD) was calculated to summarize the continuous outcomes. The Mantel-Haenszel method was used to combine OR for outcomes of interest. We also verified homogeneity among the studies by calculating the Chi² and the inconsistency (I²). As I² detected absence of homogeneity (>50%), the fixed effect model could not be used, and we, therefore, used the random effect model for analysis. Statistical analysis was conducted using the statistical software Review Manager Version 5.0 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2008, Copenhagen, Denmark).

Study selection
Five hundred ninety-four studies were identified from our literature search. After review of titles and abstracts, 12 studies were excluded because of overlapping data and 495 because they were not relevant to the aims of our review. We analyzed the full texts of the 87 remaining studies, 21 of them met the inclusion criteria, while 66 were excluded ( Figure 1).

Quality of included studies
Quality of included studies was assessed by two authors (CR and ST) using the Newcastle-Ottawa Scale (NOS) [26] and is reported in Additional file 2: Table S2. All included studies had good methodological quality (>5 points) (mean 7.9 points, range 7 to 9).
Distribution of ages was not homogeneous, so it was not possible to compare studies according to this parameter.

Overall mortality
Only three studies [18,20,22] reported the mortality relative to the AAST grading of splenic injuries. In particular, the mortality rate in patients with grades I and II of splenic injuries treated with NOM was 0%, but it was not possible to confirm the grading in patients with minor splenic injuries treated with OM since they did never required surgery [18,20,22]. The mortality in patients with grade III injuries was reported only by Duchesne et al. [18] and was similar in the two treatment groups (16% vs. 23% in NOM and OM, respectively). In patients with grades IV and V of splenic injuries the mortality was analyzed and reported in three studies [18,20,22]; mortality was lower in OM than in the NOM groups (mean rate 5.4% (45/337) vs. 13.3% (29/534), respectively). Data on the injuries of grade V was available only in the studies by Duchense et al., this was not possible from the studies by Jim et al. [20] and Velmahos et al. [22]. In fact, Duchesne et al. [18] distinguished mortality in grades IV and V (mean rate 31.5% vs. 13.7% in NOM and OM for grade IV -12.5% vs. 66.6% in NOM and OM for grade V, respectively). Gaarder et al. [14] and Scappellato et al. [21], on the other hand, did not report the mortality with respect to the grade of lesion nor to treatment. (Additional file 5: Table S5).

Overall morbidity
Only three studies [10,18,22] compared morbidity in the NOM and OM groups; six studies [6,8,12,14,15,21] reported data on morbidity but did not distinguish between the two treatment groups. In those three studies [10,18,22], it was possible to analyze morbidity according to the classification of Dindo-Clavien (DC) (Additional files 6, 7

Overwhelming post-splenectomy infection (OPSI)/quality of life
None of the included studies reported post-operative follow-up. For this reason, it was not possible to calculate the incidence of OPSI or quality of life after the treatment.

Blood transfusion
Only seven studies [10,[13][14][15]18,19,24] reported the number of blood transfusions (Additional file 9: Table  S9). Only one study [24] reported the number of patients who received blood transfusions with respect to the type of treatment, specifying the number of patients who received more than one transfusion: 19/31 in the NOM group vs. 14/15 in the OM group.

Abdominal abscesses
Only two studies [6,14] reported the incidence of abdominal abscesses, without specifying the method used for their detection. Furthermore, the authors did not specify in which group (NOM vs. OM) abscesses occurred and in how many cases they were associated with sepsis (Additional file 10: Table S10).
The analysis of subgroups according to the DC classification and AAST grading for splenic trauma was possible only in the study by Duchesne et al. [18] (see Additional files 6 and 12, Tables S6 and S12). Among 76 patients that underwent NOM, 1 patient presented a AAST grade I lesion and was classed DC grade IV; in 2 patients, AAST grade II lesions were associated with DC grade IV complications. Twelve patients had AAST grade III lesions, seven of whom had DC grade IV while five had DC grade V complications. Among 15 patients with AAST grade IV lesions, 11 had DC grade IV and 4 had DC grade V complications. Among six patients with AAST grade V injury, four had DC grade IV and two had DC grade V complications. Among 78 patients that were treated with OM, 7 had AAST grade III injuries. Three of these patients had DC grade IV and four had DC grade V complications. Among eight patients with AAST grade IV lesions, two had DC grade IV and six had DC grade V complications. Among seven patients with AAST grade V, three had DC grade IV and four DC grade V complications. Overall, hospital stay in the NOM group was shorter than in OM, even if some studies reported a longer hospital stay in NOM because of more lasting monitoring and later return to daily activities [12,15].

Discussion
In our systematic review, NOM represented the gold standard treatment for AAST grades I and II in 21 nonrandomized studies (Additional file 1: Table S1) and was associated with decreased mortality in severe splenic trauma (AAST grades III to V) (4.78% vs. 13.5% in NOM and OM, respectively) (Additional file 5: Table  S5) [20,22]. Mortality in OM group was higher, even if splenic bleeding was not always indicated as the single cause of death. In severe splenic trauma, it was not possible to determine post-treatment morbidity [10,18,22]. Furthermore, we could not establish which one of the treatments was more beneficial in terms of other analyzed outcomes (hospital stay and number of blood transfusions), since results either were not comparable among the studies or they were not reported [19,[27][28][29][30][31][32][33][34][35].
At present, it appears that NOM can also be the first line treatment in some cases of severe splenic trauma (AAST grades III to V) when the decision between NOM and OM depends on careful risk-benefit analysis for each patient [10,[31][32][33]56,57] as well as on the expertise of the surgeon and of the multidisciplinary team of the hospital.
Clinical observation of the patient at the moment of hospitalization and monitoring of clinical conditions represent Ariadne's thread that brings caretakers through the labyrinth of laboratory and investigational tests and finally to success (or failure) of NOM [64][65][66][67][68][69].

Conclusions
In conclusion, NOM has been accepted as standard treatment for AAST grades I and II BST, whereas this was not found to be safe in higher grades of splenic trauma. Currently, there is no consensus in the management of severe splenic trauma. Velmahos, a distinguished trauma surgeon [22], stated that "generalization about the overall success rates of NOM, should not represent severe blunt splenic injury".
Unfortunately, this review does not clarify the controversies regarding the safest therapeutic approach to severe splenic trauma (AAST grades IV and V) because of the selection bias in the recruitment of the NOM and OM groups, as well as missing data and heterogeneity of the studies included. Furthermore, all studies included in our review were retrospective and none were randomized due to the obvious difficulties in designing a randomized study on NOM of trauma patients.
Given the substantial heterogeneity between levels of expertise in the different hospitals, inclusion of patients with concurrent injuries of other organs and potentially inappropriate comparison groups the conclusions of the review may not be reliable for severe splenic trauma (AAST grades IV and V).

Key messages
-NOM has been accepted as standard treatment for splenic trauma grades I and II.
-Advantages of NOM for the more severe splenic injuries are still debated. -This review does not clarify the controversies regarding the safest treatment approach for severe splenic trauma because of the selection bias in the recruitment of the NOM and OM groups, as well as missing data and heterogeneity of the studies included.
-NOM can also be the initial treatment in some cases of severe splenic trauma when the decision between NOM and OM depends on careful riskbenefit analysis for each patient as well as on the expertise of the surgeon and of the multidisciplinary team of the hospital.
-The definition of hemodynamic stability varied greatly in the literature.