 |
|
A 12-Year Prospective Study of Postinjury Multiple Organ Failure
Has Anything Changed?
David J. Ciesla, MD;
Ernest E. Moore, MD;
Jeffrey L. Johnson, MD;
Jon M. Burch, MD;
Clay C. Cothren, MD;
Angela Sauaia, MD, PhD
Arch Surg. 2005;140:432-440.
ABSTRACT
| |
Hypothesis The incidence and severity of postinjury multiple organ failure (MOF) has decreased over the last decade.
Design A prospective 12-year inception cohort study ending December 31, 2003.
Setting Regional academic level I trauma center.
Patients One thousand three hundred forty-four trauma patients at risk for postinjury MOF. Inclusion criteria were aged older than 15 years, admission to the trauma intensive care unit, an Injury Severity Score higher than 15, and survival for more than 48 hours after injury. Isolated head injuries were excluded from this study. Previously identified risk factors for postinjury MOF were age, Injury Severity Score, and receiving a blood transfusion within 12 hours of injury.
Main Outcome Measures Multiple organ failure was defined by a Denver MOF score of 4 or more for longer than 48 hours after injury. Multiple organ failure severity was defined by the maximum daily MOF score and the number of MOF free days within the first 28 postinjury days.
Results Multiple organ failure was diagnosed in 339 (25%) of 1244 patients. The mean age and Injury Severity Scores increased and the use of blood transfusion during resuscitation decreased over the 12-year study period. After adjusting for age, injury severity, and amount of blood transfused during resuscitation, there was a decreased incidence of MOF over the study period. Of the patients who developed MOF, there was a decrease in disease severity and duration as measured by the maximum daily MOF score and the MOF free days. Although the overall mortality rate remained constant, the MOF-specific mortality decreased.
Conclusions The incidence, severity, and attendant mortality of postinjury MOF decreased over the last 12 years despite an increased MOF risk. Improvements in MOF outcomes can be attributed to improvements in trauma and critical care and are associated with decreased use of blood transfusion during resuscitation.
INTRODUCTION
Multiple organ failure (MOF) remains a major source of postinjury morbidity and the leading cause of in-hospital mortality despite more than 25 years of intense investigation.1-2 The current pathophysiologic model of MOF focuses on uncontrolled systemic hyperinflammation as a unifying concept following a variety of insults.3-5 Thus, therapeutic strategies aimed at decreasing postinjury morbidity have targeted systemic hyperinflammation as a means to control associated organ dysfunction and progression to organ failure. Examples include damage control surgery, recognition of abdominal compartment syndrome, lung protective ventilation strategies, and tight glucose level control.6-9
The incidence of postinjury MOF has been reported to be between 7% and 66% with an associated mortality rate between 31% and 80%.10-14 It has been suggested that MOF is disappearing owing to advances in trauma and critical care15; however, recent reports have not demonstrated a consistent change in either the incidence or the mortality rate associated with postinjury MOF. Some groups have reported no change in the incidence but a decreased mortality13 while others have reported both decreased incidence and mortality compared with historical control subjects.14, 16 The disparity reported in the literature is in part owing to different populations studied in relatively short study intervals. Consequently, an accurate estimation of the current risk of postinjury MOF and a description of clinical outcome remains to be established.
In 1987, we developed an MOF scale as a descriptive end point for clinical studies.17 Since 1992, we have prospectively collected clinical data on patients at risk for postinjury MOF for the first 28 postinjury days. We designed this study to characterize the changes in postinjury MOF presentation, risk factors, and clinical outcome in a homogeneous trauma population over time. We hypothesized that the incidence and severity of postinjury MOF has decreased over the last decade as a result of advances in trauma and critical care.
METHODS
Trauma patients admitted to the Rocky Mountain Regional Trauma Center’s surgical intensive care unit (ICU), Denver Health Medical Center, Denver, Colo, were studied prospectively from May 10, 1992, until December 31, 2003. The Denver Health Medical Center is a state-designated level I trauma center verified by the American College of Surgeons’ Committee on Trauma. Inclusion criteria were an Injury Severity Score exceeding 15, survival for longer than 48 hours after injury, admission to the surgical ICU within 24 hours of injury, and aged 15 years or older. Patients with isolated head injuries and head injuries with an external or extremity Abbreviated Injury Score less than 2 were excluded from this study.
Daily physiologic and laboratory data were collected through surgical ICU day 28 and clinical events were recorded thereafter until death or hospital discharge. Data collection and storage processes are in compliance with Health Insurance Portability and Accountability Act regulations and have been approved by our institutional review board. The database is maintained on an IBM-compatible personal computer using Microsoft Access 97 (Microsoft Corp, Redmond, Wash).
Organ dysfunction is defined using the Denver MOF scoring system.17-19 In brief, 4 organ systems (pulmonary, hepatic, renal, and cardiac) are evaluated daily throughout the patient’s ICU stay and organ dysfunction is graded on a scale from 0 (best) to 3 (worse) (Table 1). The pulmonary score has been simplified to assign a dysfunction grade based on the PaO2–fraction of inspired oxygen ratio.20 The values that determine the division points have been adjusted for altitude by multiplication of the value by the ratio of atmospheric pressure in Denver to that at sea level (630 mm Hg/760 mm Hg, respectively). The MOF score is calculated as the sum of the simultaneously obtained individual organ scores on each hospital day. Single organ failure is defined as an organ failure grade greater than 0 and MOF is defined as a total score of 4 or more occurring 48 hours after injury.18 Postinjury day 0 was defined as the first 24 hours following injury.
|
|
|
|
Table 1. Denver Postinjury Multiple Organ Failure (MOF) Score*
|
|
|
The annual incidence of MOF was defined as the number of patients who developed MOF relative to the number of patients at risk for MOF in a calendar year. The maximum MOF score was defined as the maximum score calculated using the Denver MOF scale during the first 28 postinjury days.21 The number of MOF free days was defined as the total number of days in which the calculated MOF score was less than 4 subtracted from 28. The MOF score on the day of death was carried out to day 28 for those patients who died within 28 days after injury. The ICU length of stay was defined as the difference between the date of injury and the date of ICU discharge or transfer to a non-ICU acute care facility. Multiple organ failure–related mortality was defined as the number of patients with MOF who died while MOF-specific mortality was defined as those whose cause of death was attributable to MOF. Cause of death was determined from the patient’s medical record and death certificate.
Statistical analyses were performed using SAS for Windows (SAS Institute, Cary, NC). Categorical variables were analyzed using a  2 test with the Yates correction for continuity or the Fisher exact test when expected cell values were less than 5. For continuous variables with normal distribution, analysis of variance, or t tests (with the appropriate Welch modification when the assumption of equal variances did not hold) were used. Multivariate analyses were performed using logistic regression for categorical outcome variables and standard linear regression for continuous numeric variables. Study year was used as an independent variable to examine the changes in outcome variables over time with 1992 defined as year 1. Continuous data are reported as mean ± SD unless otherwise noted. P<.05 was considered statistically significant.
RESULTS
Data were collected on 1344 severely injured patients over a 12-year period ending December 31, 2003. The distribution of patients with and without MOF according to study year is shown in Figure 1. Most (975 [73%]) were male, and the mean age was 37.5 ± 16.5 years (Figure 2). Blunt, penetrating, and mixed mechanisms accounted for 1013 (75%), 235 (17%), and 96 (7%) injuries, respectively, with an overall mean Injury Severity Score (ISS) of 29.3 ± 11.2 (Figure 3). Multiple organ failure developed in 339 patients (25%); 112 (8%) died. Ninety (26%)of 342 patients in whom MOF developed died. The unadjusted incidence of MOF and mortality did not change over the study period (P = .32 and P = .45, respectively) (Figure 4).
|
|
|
|
Figure 1. Number of patients at risk for postinjury multiple organ failure (MOF) and patients in whom MOF developed during the 12-year study period.
|
|
|
|
|
|
|
Figure 2. Age distribution of patients at risk for postinjury multiple organ failure.
|
|
|
|
|
|
|
Figure 3. Injury Severity Score (ISS) distribution of patients at risk for postinjury multiple organ failure.
|
|
|
|
|
|
|
Figure 4. Unadjusted multiple organ failure (MOF) and mortality rates of patients at risk for postinjury MOF.
|
|
|
Changes in previously identified MOF risk factors (age >55 years, ISS >24, and >6 U of red blood cells transfused within 12 hours of injury) were examined over the study period.19, 22-23 There was a significant increase in both the annual mean age ( = .33, P = .01) and the proportion of at-risk patients older than 55 years (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = .01) during the study period (Figure 5). Similarly, there was a significant increase in the annual mean ISS ( = .58, P<.001) and the proportion of patients with an ISS higher than 24 (OR, 1.11; 95% CI, 1.07-1.14; P<.001; Figure 6). In contrast, the annual mean number of 12-hour bloodtransfusions decreased ( = –.14; P = .049) as did the proportion of patients who received more than 6 U of blood within 12 hours of injury (OR, 0.96; 95% CI, 0.92-0.99; P = .04; Figure 7). The decrease in blood use over time remained statistically significant after adjusting for age and ISS (mean number of units 12-hour red blood cells; = –.20, P = .006, >6 U of red blood cells in 12 hours: OR, 0.94; 95% CI, 0.90-0.98; P = .003). Indeed, after adjusting for age and ISS, the patients admitted in 1992 were 1.5 times more likely to receive more than 6 U of red blood cells within the first 12 hours after injury than the patients admitted in 2002.
|
|
|
|
Figure 5. Age and proportion of patients with multiple organ failure. A, Age (mean ± SEM) of patients at risk for postinjury multiple organ failure. B, Proportion of patients older than 55 years. Solid line indicates 12-year multiple organ failure trend; dashed line, 12-year mortality trend.
|
|
|
|
|
|
|
Figure 6. Injury Severity Score (ISS) and proportion of patients with an ISS exceeding 24. A, The mean ISS (mean ± SEM) of patients at risk for postinjury multiple organ failure. B, Proportion of patients with an ISS exceeding 24.
|
|
|
|
|
|
|
Figure 7. Mean age and proportion of patients older than 55 years increased over the study period. A, Total number (mean ± SEM) of red blood cells transfused within 12 hours (RBC12) of injury in patients at risk for postinjury multiple organ failure. B, Proportion of patients who received more than 6 U of RBC12.
|
|
|
After adjusting for these risk factors, we found there was a significant decrease in the incidence of MOF. The results of the multiple logistic regression adjusting MOF incidence for age, ISS, and 12-hour blood transfusion after injury (as continuous or categorical values) is given in Table 2. Regardless of the confounding variable formats, MOF incidence in 1992 was almost twice (OR per 10 years = 1.8) the rate observed after 2002. The goodness-of-fit of the models using continuous and categorical formats was similar with a slight advantage for the continuous variables model. Although the interaction between ISS and time was not significant (P = .12), the time reduction seemed to be more pronounced among patients with an ISS higher than 40 after adjusting for patient age and blood transfusion received during resuscitation (Figure 8).
|
|
|
|
Table 2. Multiple Logistic Regression of Multiple Organ Failure Incidence for Age, Injury Severity Score, and 12-Hour Red Blood Cell Transfusion
|
|
|
|
|
|
|
Figure 8. Incidence of postinjury multiple organ failure (MOF) stratified by Injury Severity Score (ISS). Solid line indicates 12-year trend of MOF incidence in patients with an ISS of 40 to 75; dashed and dotted line, 12-year trend of MOF incidence in patients with an ISS of 25 to 39; and dashed line, 12-year trend of MOF incidence in patients with an ISS of 16 to 24.
|
|
|
Next we compared the ORs associated with the risk factors we previously identified for postinjury MOF in the first 12 hours after injury in the first 5 years with the association observed in the second half of the study period (Table 3). All factors remained highly predictive of MOF, but the association between an ISS greater than 24 and MOF became less strong in the second half, further suggesting that the effect of injury severity on the development of MOF decreased over time.
|
|
|
|
Table 3. Risk Factors for Postinjury Multiple Organ Failure (MOF) in the First 12 Hours After Injury in Each 5 Years of the Study
|
|
|
The degree of postinjury MOF was assessed by examining the maximum daily MOF score and the number of MOF free days in the first 28 days after injury. Among the patients with MOF, there was a significant decrease in the annual maximum daily MOF score ( = –.15, P<.001) after adjusting for patient age, ISS, and amount of red blood transfused during resuscitation (Figure 9). There was also a significant increase in the annual MOF free days ( = .44, P = .006) after adjusting for age, ISS, and 12-hour RBC transfusion (Figure 10). The surgical ICU length of stay among patients with MOF did not change over time after adjusting for age, ISS, death, and the presence of a head injury ( = .49, P = .08).
|
|
|
|
Figure 9. Maximum daily multiple organ failure (MOF) score among patients in whom MOF developed.
|
|
|
|
|
|
|
Figure 10. Multiple organ failure (MOF) free days among patients in whom MOF developed.
|
|
|
Finally, MOF as a cause of death was examined over the study period. Overall, 112 of 1244 patients died (mortality rate 8%) and 90 of 339 MOF patients died (MOF-related mortality rate, 27%). Of the 112 patients who died, 57 patients (51%) died of MOF, 26 (23%) died of severe head injury, 25 (22%) had care withdrawn, and 4 (4%) died of other causes (2 of pulmonary embolus, 1 of acute myocardial hemorrhage, and 1 of a bleeding gastric ulcer). The overall and MOF-related mortality rates did notchange over the study period even after adjusting for patient age, ISS, 12-hour red blood cell transfusion after injury, mechanism, and the presence of head injury. However, the annual proportion of patients who died of MOF decreased significantly (Figure 11) after adjusting for age, ISS, 12-hour red blood cell transfusion after injury, mechanism of injury, and the presence of head injury (OR, 0.90; 95% CI, 0.83-0.97; P = .001).
|
|
|
|
Figure 11. Proportion of patients dying of multiple organ failure (MOF). Solid line indicates the mean Injury Severity Score (ISS) and proportion of patients with an ISS less than 24 increased over the study period. Solid line indicates 12-year trend of proportion of patients dying of MOF.
|
|
|
COMMENT
Disparities in study design have made interpretation of the postinjury MOF literature difficult with respect to changes in MOF presentation and outcome over time. In 1987, we developed an MOF scale to characterize organ dysfunction following injury.17 This scale was used consistently throughout this study period and has been used to identify risk factors and develop predictive models of postinjury MOF.18-19,24 We enrolled patients at risk for postinjury MOF into this prospective study since 1992. In concert with other studies, we found that most patients in this population were male (73%) victims of blunt trauma (83%). Our study population limited to those patients with an ISS exceeding 15 demonstrated an overall MOF incidence (25%), mortality rate (8%), and MOF-related mortality rate (26%).
The present study has confirmed that age, injury severity, and the use of blood transfusion during resuscitation are significant risk factors for postinjury MOF. Over the 12-year study period, we found an increase in both patient age and injury severity. The increase in age is expected considering the aging of the US population and projected change in the general surgery patient population.25-26 The increase in injury severity may be explained by our ongoing efforts to serve as the Rocky Mountain Regional Trauma Center. As a result, our hospital has experienced an increased number of trauma admissions over the past several years.27 Increases in both age and injury severity would be expected to be associated with an increase in the incidence of MOF. In contrast, the use of blood transfusion during resuscitation decreased during the study period. Blood transfusion was recognized as a consistent early risk factor for postinjury MOF independent of other indices of shock in 1997 and has since been reported to be a major contributing factor to worse outcomes in trauma and critical illness.24, 28-31 These findings have prompted more judicious use of blood transfusion during resuscitation and in the postresuscitation surgical ICU setting.32-33 In this study we found a decrease in both the number of units of blood transfused and the proportion of patients receiving more than 6 U of packed red blood cells during resuscitation. The changes in the risk factor distribution among the at-risk patient population also had an effect on our previously developed predictive model of postinjury MOF.23 Both age and injury severity had less influence on the conditional probability of developing MOF in the patients admitted in the first half of the study period compared with those admitted during the second. In contrast, the influence of blood transfusion during resuscitation was greater during the second half of the study. These findings further support a change in the presentation of MOF over the last decade and warrant a reevaluation of MOF risk factors in the context of current trauma and surgical ICU care.
The purpose of this study was to characterize the changes in MOF incidence and its risk factors over 12 years using an accepted MOF definition uniformly applied to a homogeneous trauma population. The primary end points of this study were MOF incidence and measures of MOF severity. Although the incidence of MOF in the population as a whole did not change, there was a decreased incidence among the more severely injured after adjusting for age and for receiving a blood transfusion. These findings are encouraging because there appears to be progress in preventing progression of MOF in the population at highest risk. Moreover, indices of MOF severity improved over the study period with a decrease in the maximum daily MOF score and an increase in the number of MOF free days. The overall surgical ICU length of stay and mortality rate did not change which may be reflective of the underlying severity of injury. However, death due to MOF decreased with a commensurate increase in death due to severe head injury or following withdrawal of care. We believe that this represents an improved ability to support patients who would have otherwise succumbed to MOF only to realize the full potential of the underlying injury. Alternatively, this may represent earlier recognition of futile care by both the patient’s representative and the critical care team.
CONCLUSIONS
We have found a decrease in the incidence of postinjury MOF among the most severely injured and an overall improvement in the indices of MOF severity over the last 12 years. Of the risk factors studied, only reduction in blood transfusion during the resuscitation period correlated with improvement in outcome. Several other major advances in trauma and critical care also occurred over the last decade that may have influenced our results. The concept of damage control surgery, which appeared in the late 1980s and matured during the 1990s, is widely accepted and applied in a variety of situations includingthoracic, abdominal, and vascular injuries, as well as for orthopedic and neurologic trauma.34-39 Recognition of abdominal compartment syndrome and decompressive laparotomy also emerged during the 1990s.6, 40 Improvements in respiratory support such as lung protective ventilation decreased ventilator-induced lung injury and improved outcome following adult respiratory distress syndrome.7, 41 The use of intensive insulin therapy, described in 2001, was shown to reduce morbidity and mortality in the critically ill including patients with postinjury MOF.9 More recently, cortisol replacement therapy for acute adrenal insufficiency has been shown to improve the outcome in the critically ill.42-43 Each of these advances has influenced our approach to trauma and critical care although the relative effect of any one advance on postinjury MOF outcome awaits further study. Nevertheless, our prospectively collected patient data indicate a substantial reduction in the incidence and severity of MOF following severe injury over the last decade.
AUTHOR INFORMATION
Correspondence: David J. Ciesla, MD, Department Surgery, Denver Health Medical Center, 777 Bannock St, Denver, CO 80204 (David.ciesla{at}dhha.org).
Accepted for Publication: December 28, 2004.
Funding/Support: This study was supported in part by grants P50GM49222, T32GM08315, and U546M62119 from the National Institutes of Health, Bethesda, Md; and the Jourdan Block Trauma Research and Development Foundation, Denver.
Previous Presentation: This paper was presented at the 112th Scientific Session of the Western Surgical Society; November 8, 2004; Las Vegas, Nev; and is published after peer review and revision. The discussions that follow this article are based on the originally submitted manuscript and not the revised manuscript.
Author Affiliations: Denver Health Medical Center and the University of Colorado Health Sciences Center, Denver.
REFERENCES
| |
1. Eiseman B, Beart R, Norton L. Multiple organ failure. Surg Gynecol Obstet. 1977;144:323-326.
ISI
| PUBMED
2. Baue AE, Durham R, Faist E. Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle? Shock. 1998;10:79-89.
ISI
| PUBMED
3. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995;75:257-277.
ISI
| PUBMED
4. Goris RJ, te Boekhorst TP, Nuytinck JK, Gimbrere JS. Multiple-organ failure: generalized autodestructive inflammation? Arch Surg. 1985;120:1109-1115.
ABSTRACT
5. Nuytinck HK, Offermans XJ, Kubat K, Goris JA. Whole-body inflammation in trauma patients: an autopsy study. Arch Surg. 1988;123:1519-1524.
ABSTRACT
6. Ivatury RR, Porter JM, Simon RJ, Islam S, John R, Stahl WM. Intra-abdominal hypertension after life-threatening penetrating abdominal trauma: prophylaxis, incidence, and clinical relevance to gastric mucosal pH and abdominal compartment syndrome. J Trauma. 1998;44:1016-1023.
ISI
| PUBMED
7. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308.
FREE FULL TEXT
8. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347-354.
FREE FULL TEXT
9. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-1367.
FREE FULL TEXT
10. Fry DE, Pearlstein L, Fulton RL, Polk HC Jr. Multiple system organ failure: the role of uncontrolled infection. Arch Surg. 1980;115:136-140.
ABSTRACT
11. Regel G, Lobenhoffer P, Grotz M, Pape HC, Lehmann U, Tscherne H. Treatment results of patients with multiple trauma: an analysis of 3406 cases treated between 1972 and 1991 at a German level I trauma center. J Trauma. 1995;38:70-78.
ISI
| PUBMED
12. Sauaia A, Moore FA, Moore EE, Norris JM, Lezotte DC, Hamman RF. Multiple organ failure can be predicted as early as 12 hours after injury. J Trauma. 1998;45:291-303.
ISI
| PUBMED
13. Nast-Kolb D, Aufmkolk M, Rucholtz S, Obertacke U, Waydhas C. Multiple organ failure still a major cause of morbidity but not mortality in blunt multiple trauma. J Trauma. 2001;51:835-842.
ISI
| PUBMED
14. Durham RM, Moran JJ, Mazuski JE, Shapiro MJ, Baue AE, Flint LM. Multiple organ failure in trauma patients. J Trauma. 2003;55:608-616.
ISI
| PUBMED
15. Levine JH, Durham RM, Moran J, Baue A. Multiple organ failure: is it disappearing? World J Surg. 1996;20:471-473.
FULL TEXT
|
ISI
| PUBMED
16. Regel G, Grotz M, Weltner T, Sturm JA, Tscherne H. Pattern of organ failure following severe trauma. World J Surg. 1996;20:422-429.
FULL TEXT
|
ISI
| PUBMED
17. Moore FA, Moore EE, Poggetti R, et al. Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma. J Trauma. 1991;31:629-638.
ISI
| PUBMED
18. Ciesla DJ, Moore EE, Johnson JL, et al. Multiple organ dysfunction during resuscitation is not postinjury multiple organ failure. Arch Surg. 2004;139:590-595.
FREE FULL TEXT
19. Sauaia A, Moore FA, Moore EE, Lezotte DC. Early risk factors for postinjury multiple organ failure. World J Surg. 1996;20:392-400.
FULL TEXT
|
ISI
| PUBMED
|
