Incidence and predictive risk factors of postoperative sepsis in orthopedic trauma patients

The development of postoperative sepsis is a common yet serious complication that has been associated with significant morbidity and death, resulting in mortality rates ranging from 28 to 50% [1‐4]. Its prevalence has been documented by numerous studies in the general medical as well as orthopedic literature, with postoperative rates of septicemia doubling between 1997 and 2006 [5‐9]. The severity and frequency of this condition have had a profound effect on inpatient care. Between 2000 and 2008, the rate of sepsis-induced hospitalizations more than doubled, and the development of septicemia has been associated with significant increases in inpatient length of stay and resource utilization [1, 4].

These challenges have created remarkable implications for healthcare expenditure in the United States. National costs associated with hospitalizations due to sepsis amounted to 16.7 billion dollars in 2001 [10], and had surpassed 20 billion dollars by 2011, thereby making sepsis the single most expensive condition treated that year [11]. In an effort to reduce the total cost of care in an increasingly challenging fiscal landscape, emerging reimbursement models are beginning to shift the costs associated with perioperative complications and readmissions onto providers [12‐14]. Although numerous basic science studies in orthopedics have suggested that orthopedic trauma injuries may be associated with immune responses that facilitate sepsis [15‐18], it is currently unclear whether orthopedic trauma patients are at increased risk for developing sepsis or septic shock. Existing studies have correlated trauma to large groups of adverse events, making it difficult to extrapolate associations to septic complications [19‐22]. However, the relationship between sepsis and high mortality, its enormous financial costs, and the increasing emphasis on quality metrics make it imperative that orthopedic surgeons are able to identify trauma patients who may be more likely to develop the condition. Early identification and supplemental monitoring of patients with an increased propensity for sepsis may aid traumatologists in maintaining lower overall complication rates, thereby improving clinical outcomes in high-risk groups.

Despite this, there is a dearth of literature assessing the preoperative risk factors that are associated with septicemia. Existing studies have examined broad diagnostic categories that are not specific to orthopedic surgery and do not achieve consensus regarding predictive characteristics [5, 6, 23]. Furthermore, the relationship between orthopedic trauma and sepsis following orthopedic intervention remains unexplored in the current literature. Thus, the purpose of this study was to utilize the American College of Surgeons National Surgical Quality Improvement (NSQIP) database in order to elucidate whether trauma patients are at increased risk for developing sepsis and septic shock compared to orthopedic patients without traumatic injuries. In addition, the demographic and preoperative characteristics that served as significant predictors of sepsis were identified using multivariable regression analysis. Early identification of patients who may be at increased risk for developing sepsis may facilitate the timely modification of controllable risk factors and potentially improve clinical outcomes.

The development of postoperative sepsis is a very serious complication that has been associated with high morbidity, mortality, and increased length of inpatient stay. In 2011, national healthcare payments for septicemia exceeded those of any other diagnosis, and numerous basic science studies have suggested that orthopedic trauma may be associated with immunosuppression that contributes to sepsis [16, 17]. Despite this, very little data describing the rates of postoperative sepsis in general orthopedics and orthopedic trauma exist in the current literature. While orthopedic trauma patients have been shown to develop greater rates of adverse events, no study has examined septic complications in isolation from other less serious conditions. As such, the purpose of this study was to assess differences in the rates of postoperative sepsis between trauma and nontrauma cohorts, evaluate orthopedic trauma as a potential predictor of postoperative sepsis in orthopedic surgery, and identify the preoperative comorbidities that significantly predicted the incidence of septic complications following orthopedic trauma surgery. Our data derived from a prospective, multicenter database demonstrated that rates of postoperative sepsis differed significantly between trauma and nontrauma subgroups. In addition, this study identified eight preoperative characteristics that were significant risk factors for septicemia in trauma patients. Hypertension and the use of corticosteroids were the modifiable comorbidities that were predictive of the development of sepsis following orthopedic trauma.

The overall rate of septic complications for the entire cohort of orthopedic patients was 0.70%, representing a very slight increase in incidence from the 0.68% determined using 2005–2011 NSQIP data [30]. Orthopedic trauma patients experienced postoperative septicemia at a rate of 1.6%. This is consistent with previous studies assessing the incidence of sepsis in other surgical populations, which reported rates of between 0.9 and 2.3% [6, 31, 32].

Bivariate analysis demonstrated that orthopedic trauma patients develop postoperative sepsis at significantly greater rates than those undergoing nontraumatic procedures. To the authors’ knowledge, this is the first study to assess the incidence of postoperative septicemia for a large cohort of orthopedic trauma patients. While Sathiyakumar et al. demonstrated that orthopedic trauma [21] and hip fracture patients [20] tend to experience adverse events at greater rates, sepsis was examined as part of a cohort that included many other complications, rather than in isolation. Similarly, other studies examining adverse events following orthopedic trauma do so using large clusters of complications, making it difficult to evaluate postoperative septicemia following these procedures. Our finding that orthopedic trauma patients are more likely to develop sepsis is consistent with a number of basic science studies purporting that traumatic injury induces an immunosuppressive effect on the rest of the body, thus facilitating septicemia [33‐35]. In evaluating differences in interleukin-10 release between patients undergoing reamed and unreamed femoral nailing, Smith et al. concluded that reamed intramedullary nailing was associated with decreased immune response [16]. Their findings were subsequently corroborated by Giannoudis et al., who documented a significant anti-inflammatory response following major orthopedic trauma [17]. This delayed hypersensitivity has since been demonstrated to increase patients’ risk of developing sepsis following trauma [36, 37]. As such, our clinical findings for a large cohort of orthopedic trauma and nontrauma patients are in line with the associations and suggestions described in the orthopedic basic science literature.

Although orthopaedic trauma status was significantly associated with postoperative sepsis for all orthopedic surgery patients using bivariate chi-squared analysis, it interestingly fell out of significance when employing a binary multivariable regression model. Because of the low standard error and high tolerance associated with this variable, it is unlikely that significant multicollinearity between patient factors impacted the results. Further studies are thus needed in order to elucidate the predictive effect of trauma on the incidence of sepsis in the context of other preoperative variables.

In order to better understand the parameters that were associated with the greater incidence of septicemia among orthopedic trauma patients, preoperative risk factors that significantly predicted septic complications were identified. Several of these predictors are consistent with the existing literature examining the risk factors for sepsis, although no prior studies have done so for orthopedic trauma. In particular, associations between male gender [23, 38, 39], age greater than 65 [40], and sepsis-related complications have been reported in a number of studies. In their analysis of the risk factors of sepsis after multiple trauma, Wafaisade et al. utilized a multivariate regression to identify male gender, increased age, and pre-existing conditions as significant predictors [23]. However, their cohort comprised an array of trauma patients, only a fraction of whom experienced orthopedic injuries. Additionally, individual preoperative comorbidities were not evaluated, making it difficult to identify potential avenues for clinical change. Preoperative mechanical ventilation, which was reported as a risk factor for sepsis in this study, has also been associated with increased risk of postoperative sepsis in pediatric cardiothoracic surgery [41]. To our knowledge, this is one of the very few studies to report hypertension, prior pain at rest, history of sepsis, and corticosteroid use as predictive risk factors for septicemia, and the first to do so for orthopedic surgery.

Although several of our identified risk factors are demographic in nature and cannot be modified prior to surgery, they nevertheless form the groundwork on which risk calculations and further analyses can be made. Awareness of factors such as age, functional dependence, history of pain at rest, and prior sepsis could facilitate additional monitoring of these patients in conjunction with internists, and is important for truly informed consent. Clinicians may consider counseling patients who present with prior history of sepsis along with other predictive risk factors.

Preoperative hypertension and use of corticosteroids, however, are modifiable factors that warrant further research exploring their relationship with septic complications. Hypertension, for instance, has previously been associated with increased mortality from sepsis [42, 43]. Hypertensive patients may also be sicker overall and have previously been documented to experience a higher number of complications compared to their nonhypertensive counterparts in orthopedic cases [44‐47]. It is therefore possible that achieving preoperative control over high blood pressure may yield clinical benefits for surgery-bound patients. The use of corticosteroids prior to surgery may also be clinically relevant for orthopedic trauma patients. Exposure to corticosteroids has been associated with not only a greater risk of developing postoperative infection [48‐50], but the potential to induce immunosuppression and adrenocortical suppression during sepsis [51]. The known immunosuppressive effect of corticosteroid use coupled with the demonstrated role of immunosuppression in the development of sepsis following orthopedic trauma necessitates further studies examining this topic [17, 37, 52]. While it is plausible that eliminating corticosteroids could mitigate this factor, further evidence is necessary to draw meaningful conclusions and make sound clinical recommendations.

Preoperative mechanical ventilation has previously been associated with increased incidence of sepsis in children, and prolonged ventilator use was reported to correlate with incidence of postoperative infections [41, 53]. Although preoperative modification of this risk factor may not be possible in a sizeable number of cases, clinicians could consider weaning patients off ventilators prior to surgery. Further research examining the association between mechanical ventilation and postoperative infections in orthopedics is needed.

The use of NSQIP-derived risk factors as part of a screening algorithm has already been demonstrated to reduce sepsis-associated morbidity and mortality. In a study by Moore et al., the authors utilized the NSQIP database to identify age, presence of comorbidities, and emergency surgery as risk factors that were predictive of sepsis in the general surgery population [31]. Their subsequent implementation of mandatory screening for these high-risk groups resulted in reduced mortality due to septicemia at their affiliated medical center. The strength of our study lies in the identification of specific comorbidities as well as demographics that could be incorporated into such a screening model. Further investigations assessing how increased monitoring of patients with the risk factors identified in the present study may affect incidence of sepsis in orthopedic trauma are thus warranted.

The results of our study should be evaluated in the context of limitations that were inherent to utilizing a national database. First, the development of sepsis or septic shock was recorded within the first 30 days following the procedure. It is possible that additional episodes of sepsis-related complications occurred after that time frame, resulting in our reported rates of sepsis underestimating actual occurrence. Second, the NSQIP dataset incorporates only 20% of clinical volume from reporting medical centers. However, a stringent auditing and sampling technique is employed in order to mitigate selection bias, and the validity of the NSQIP dataset for these kinds of prognostic investigations has been shown [24, 28]. Third, the study was confined to using the variables collected and stored in the prospective database. Miscellaneous preoperative characteristics including patients’ socioeconomic status as well as orthopedic-specific postoperative complications such as hardware failure could not be evaluated. Nevertheless, the large, prospective, and multicenter origins of the data coupled with the stringent clinical evidence required for sepsis classification mitigates potential bias and is a strength compared to prior studies. In addition, the wide variety of preoperative comorbidities that were collected and controlled for in the multivariable regression mitigated potential confounding factors while yielding several predictors that were corroborated in previous studies.

This investigation utilized more than 50,000 orthopedic trauma patients from over 250 medical centers throughout the country. The data demonstrated an increased incidence of postoperative septicemia among patients undergoing orthopedic trauma procedures compared to those with nontraumatic orthopedic intervention. In addition, several unique predictive factors, including hypertension, corticosteroid use, ventilator use, and history of pain at rest, were identified. Clinicians may be interested in counseling at-risk groups and consider addressing modifiable comorbidities before surgery.