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Original Investigation |

Effect of Patient Sex on Intensive Care Unit Survival FREE

Hugo Romo, MD; André Carlos Kajdacsy-Balla Amaral, MD; Jean-Louis Vincent, MD, PHD
[+] Author Affiliations

From the Department of Intensive Care, Erasme Hospital, Free University of Brussels, Brussels, Belgium. The authors have no relevant financial interest in this article.


Arch Intern Med. 2004;164(1):61-65. doi:10.1001/archinte.164.1.61.
Text Size: A A A
Published online

Background  Human observations have shown different mortality rates between men and women with various pathological conditions, but this issue has not been widely studied in a heterogeneous population of critically ill patients.

Methods  Retrospective analysis of all patients admitted to a mixed medical-surgical, 31-bed intensive care unit (ICU) during 2 different years (1983 and 1995) to evaluate possible differences in mortality between male and female patients and between medical and surgical admissions and variations in these differences over time.

Results  From a total of 4420 admissions (1587 women, 2833 men), women showed a higher mortality, with an odds ratio (OR) of 1.18 (95% confidence interval [CI], 1.02-1.38). This pattern was the same for the 2 periods, and all patient data were therefore analyzed together. After age stratification, the differences were significant for female patients older than 50 years (OR, 1.33; 95% CI, 1.12-1.58) but not in the younger age group. The subgroup of medical admissions had a higher mortality (24.4% vs 7.4%, P<.001) and a higher female proportion (37.9% vs 34.2%, P = .01) than surgical admissions. In multivariate analysis, female sex remained an important predictor of mortality (OR, 1.54; 95% CI, 1.25-1.89). Women had a higher mortality than men in the subgroup of cardiovascular diseases. The highest mortality in female patients was present in the first days after admission and decreased over time, showing a covariance of time and sex.

Conclusions  In a mixed medical-surgical ICU, older women have a higher mortality rate than men. This difference is not apparent for patients staying longer in the ICU.

Figures in this Article

Recently, there has been increased interest in the possible influences of sex on disease development and intensive care unit (ICU) survival. Women have a lower incidence of coronary heart disease (CHD), an effect that is blunted with aging.1 After an acute myocardial infarction (AMI), women have a higher rate of early mortality,25 although long-term mortality after AMI is not different between the sexes.5 Higher mortality rates in men have been observed in some situations, including congestive heart failure6,7 and trauma,8,9 but in other areas, including sepsis,1016 mechanical ventilation,17,18 and burns,1921 the literature is conflicting.

The reasons behind possible sex differences have been explored in several experimental models, mainly focusing on the possible immunological effects of sex hormones. Numerous studies have shown that the immune response, including that associated with sepsis, may be modulated by sex hormones, with women and men treated with estrogens developing a more marked proinflammatory response2224 and having improved cardiac and hepatic function compared with men.25 These changes are influenced by the female reproductive cycle,26 and the cytokine response is reversed when older animals with decreased hormonal levels are compared.27 Indeed, higher male mortality rates have been observed,28,29 and treatment of septic male animals with dehydroepiandrosterone resulted in improved outcome.30 Whether these experimental findings can be translated to the clinical arena, however, remains unclear. The objective of this study was to observe if there were any differences in mortality rates and length of ICU stay between men and women in a mixed medical-surgical ICU population.

Records for all consecutive admissions to the ICU of Erasme University Hospital, Brussels, Belgium, during 2 different years, 1983 and 1995, were retrieved by searching the unit databases. These years were chosen because they were readily available from our databases and allowed a comparison of mortality rates over time. Erasme University Hospital is a 900-bed, academic, adult hospital with a multidisciplinary, mixed medical and surgical, 31-bed intensive care department. Patients with acute, uncomplicated coronary disease are admitted to a separate coronary care unit. Patients admitted several times during these years were included as new admissions. Demographic data, including sex, admission diagnosis, medical or surgical status, age, length of ICU stay, and ICU outcome, were collected. Univariate and multivariate analyses were performed to determine predictors of mortality in this population using statistical software (SPSS version 10.0.5; SPSS Inc, Chicago, Ill). Categorical variables were assessed with the χ2 test. The 2-tailed t test and Mann-Whitney U test were used as appropriate for continuous variables. Stratified analysis was performed using the Mantel-Haenszel test. General linear model and time-dependent Cox regression model were also applied. The actuarial method was used to assess cumulative differences in survival. P<.05 was considered statistically significant unless a Bonferroni correction was applied to evaluate multiple comparisons. Data are presented as mean ± SD, excepted where stated otherwise.

Demographic data for the 2 years are summarized in Table 1. There were 4420 admissions (1587 women, 2833 men), 1950 admitted in 1983 and 2470 in 1995. The proportion of female patients increased throughout the 12-year period. There were no significant differences in the mean ICU length of stay when both years were compared. Since mortality rates were similar in the 2 different periods, data from the 2 years were analyzed collectively.

Table Graphic Jump LocationTable 1. Demographic Data of 4420 Patients Admitted to the Intensive Care Unit During 2 Study Periods

From the total number of patients, 595 (13.5%) died during their ICU stay. Survivors were younger than nonsurvivors (55 ± 18 years vs 61 ± 18 years, P = .006), and they had a significantly shorter length of ICU stay (3.5 ± 5.7 days vs 5.4 ± 7.6 days, P<.001). Mortality increased with age from 9.9% in patients younger than 45 years, 11.8% in patients aged 45 to 65 years, and 18.1% in patients older than 65 years (χ2 trend = 40.5, P<.001). Women had a higher mortality rate than men (15% vs 13%; odds ratio [OR], 1.18; P<.05). When the sample was stratified according to age, women older than 50 years showed the highest risk of mortality (OR, 1.33; P<.001). The crude OR and the Mantel-Haenszel adjusted OR were not significantly different, showing no evidence of confounding. However, the homogeneity test across strata confirmed the presence of a significant interaction between sex and mortality when age was controlled (P<.001).

Medical patients represented 35.9% of the population; differences between the medical and surgical groups are depicted in Table 2. There were no differences in age between the medical and surgical groups as a whole or when stratified according to diagnosis or sex. There were more female than male medical patients (37.9% vs 34.2%, P = .01). Surgical patients had a shorter mean length of stay than medical patients (3.6 ± 6.1 days vs 4.1 ± 5.9 days, P = .04). The mortality rate was higher in medical vs surgical patients (24.4% vs 7.4%, P<.001). Cardiovascular problems were the most frequent source of admission to the ICU for the medical group, accounting for 29% of admissions. The mortality rate of female patients with cardiovascular disease was higher than that of their male counterparts (23% vs 12%; OR, 2.07; 95% CI, 1.50-2.87; P<.001) (Table 3).

Table Graphic Jump LocationTable 2. Differences Between Medical and Surgical Patients
Table Graphic Jump LocationTable 3. Admission Diagnoses With Corresponding Mortality Rates

Using the actuarial method, life tables were used to assess the median length of stay in the ICU until death. The median length of stay was 26 days for surgical patients and 14 days for medical patients (P<.001). Differences in mortality were observed from days 3 through 6, favoring men (Table 4), but after this initial period, the mortality rate was lower for women, although not significantly, suggesting that survival for men and women is not constant over time. The plot of survival curves (Figure 1) shows the cumulative proportion of patients staying in the ICU until death. The curves eventually cross each other due to interaction of sex with length of ICU stay; therefore, a time-dependent Cox regression model was used to assess the joint effects of prognostic factors, such as age, sex, and medical-surgical status, on length of stay in the ICU until death. The model showed mortality for women to be associated with an OR of 1.54 (95% CI, 1.25-1.89) overall and an OR of 0.95 (95% CI, 0.92-0.98) for each day of increase in length of stay, suggesting a reduction in the OR for longer stays (Table 5). This confirms the significant interaction of sex and time that was already found with the stratified analysis.

Table Graphic Jump LocationTable 4. Cumulative Survival of Patients
Place holder to copy figure label and caption

Cumulative survival curves for female and male sex according to length of intensive care unit (ICU) stay (n = 595 patients).

Graphic Jump Location
Table Graphic Jump LocationTable 5. Time-Dependent Cox Regression Model

More male patients are admitted to the ICU than female patients, with men accounting for approximately two thirds of admissions.13,31 Our study confirms this proportion, although suggests a slight increase in the proportion of female admissions in more recent years.

In experimental studies,28,29,32 mortality rates have consistently been shown to be higher in male than female animals in various disease models, yet our study showed no significant differences in mortality rates between sexes, except in women older than 50 years, who had a higher mortality rate. So why do our results and those from other clinical studies14,19 differ from what we would expect from these experimental observations? First, experimental data are generally based on young women in their proestrus state. Clinical studies usually involve populations of mixed ages, with some women in the proestrus state and others in the postmenopausal state; thus, the hormonal milieu will be different from the controlled animal experiment.26 The difference in ages may not only be important because of decreased estrogen levels in older women, but, as shown by Kahlke et al27 in mice, the cytokine response is reversed so that older male mice show a better proinflammatory response than female mice. This factor could explain why, in our results as well as others,14 differences were noted only in older patients and why women fared worse. Second, it is possible that a female sex advantage may prevent women from developing a more severe state to the same insult. Wichmann et al13 studied the development of severe sepsis and septic shock in the postoperative state. These authors observed that the mortality from severe sepsis and septic shock was similar for men and women, but more men needed ICU care, and in this subgroup, more men developed severe sepsis and septic shock. Male sex has also been observed as a risk factor for sepsis and multiple organ dysfunction after burns33 and trauma,34 as well as for infections after surgery.35 This fact may limit the detection of any direct sex-related differences in mortality if patients are studied only in the ICU.

The greatest paradox is seen in CHD, because female sex protects against its development but still carries a greater mortality risk for acute events. Several factors can account for this finding. First, the most important difference is observed for the younger groups3; thus, younger women may have a more severe form of CHD, as manifested by a greater tendency to show eroded plaques,36 higher platelet reactivity,37 fewer collateral vessels,38 and a higher incidence of AMI with normal angiogram.39 Second, women have been shown to have more complications, such as arrhythmia, acute pulmonary edema, and cardiogenic shock,35,39 as well as more comorbid disease processes, such as congestive heart failure, arterial hypertension, and type 2 diabetes mellitus (DM). There may be a relationship among sex, CHD, and DM. Diabetic women seem to have a higher mortality from AMI than women without DM, whereas in men such a difference is not noted.40 Most interestingly, the risk of fatal AMI in women without DM may be lower than for men without DM.41 Third, a possible survival advantage of women may allow more of them to reach the hospital alive, giving a biased population of more severely ill female patients. These data are suggested by 2 studies42,43 that confirm a higher AMI prehospital mortality for men, higher hospital mortality for women, and, subsequently, the same overall mortality.

Our study is, to our knowledge, the first report of differences in mortality in a large population derived from a mixed medical-surgical ICU rather than in specific patient groups. We observed a significantly higher mortality in women older than 50 years and in the subgroup admitted for cardiovascular diseases. Although more women were admitted for medical reasons, and this subgroup had a higher mortality, in multivariate analysis female sex remained an important predictor of mortality. Importantly, patients with uncomplicated acute coronary syndromes were not included but have relatively low mortality rates; thus, for differences in mortality to be shown, large patient populations may be required. The ICU mortality rates are more valuable when controlled for severity of illness; unfortunately, one of the limitations of our study was the lack of a severity score, not widely used in 1983, to further explore our data and perhaps provide some explanations for the observed differences in mortality.

Survival analysis showed that women's survival chances improve with longer length of stay, as shown by a decreasing hazard function for female patients, which crossed over the male hazard function. This finding is in parallel with studies that compare mortality in men and women after coronary events, which showed an increase in early mortality in women.2,44 This result could also be due to an enhanced initial proinflammatory reaction in women, as demonstrated in animal experiments,2225 followed by a more balanced reaction later, as indicated by a higher interleukin 10 level in women after 10 days.10 Hence, the timing of observations may be important when studying sex-related differences in mortality.

In conclusion, ICU survival depends on the effects of several predictors interacting with each other and with time. Clinical trials should consider that men and women respond differently to noxious stimuli, although the possible female advantages described in animals have not yet been confirmed in humans. Additional prospective studies observing not only sex but also hormonal status (including exogenous hormone use), associated with a better stratification according to age and disease state and severity of illness, are needed to further characterize these differences.

Corresponding author and reprints: Jean-Louis Vincent, MD, PhD, Department of Intensive Care, Erasme Hospital, Route de Lennik, 808, B-1070 Brussels, Belgium (e-mail: jlvincen@ulb.ac.be).

Accepted for publication January 31, 2003.

Jousilahti  PVartiainen  ETuomilehto  JPuska  P Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. Circulation. 1999;991165- 1172
PubMed Link to Article
Malacrida  RGenoni  MMaggioni  AP  et al.  A comparison of the early outcome of acute myocardial infarction in women and men: the Third International Study of Infarct Survival Collaborative Group. N Engl J Med. 1998;3388- 14
PubMed Link to Article
Vaccarino  VParsons  LEvery  NRBarron  HVKrumholz  HM Sex-based differences in early mortality after myocardial infarction: National Registry of Myocardial Infarction 2 Participants. N Engl J Med. 1999;341217- 225
PubMed Link to Article
Weaver  WDWhite  HDWilcox  RG  et al. GUSTO-I Investigators, Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. JAMA. 1996;275777- 782
PubMed Link to Article
Maynard  CEvery  NRMartin  JSKudenchuk  PJWeaver  WD Association of gender and survival in patients with acute myocardial infarction. Arch Intern Med. 1997;1571379- 1384
PubMed Link to Article
Adams  KF  JrSueta  CAGheorghiade  M  et al.  Gender differences in survival in advanced heart failure: insights from the FIRST study. Circulation. 1999;991816- 1821
PubMed Link to Article
Simon  TMary-Krause  MFunck-Brentano  CJaillon  P Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II). Circulation. 2001;103375- 380
PubMed Link to Article
Wohltmann  CDFranklin  GABoaz  PW  et al.  A multicenter evaluation of whether gender dimorphism affects survival after trauma. Am J Surg. 2001;181297- 300
PubMed Link to Article
Mostafa  GHuynh  TSing  RFMiles  WSNorton  HJThomason  MH Gender-related outcomes in trauma. J Trauma. 2002;53430- 435
PubMed Link to Article
Schroder  JKahlke  VStaubach  KHZabel  PStuber  F Gender differences in human sepsis. Arch Surg. 1998;1331200- 1205
PubMed Link to Article
Schroder  JKahlke  VBook  MStuber  F Gender differences in sepsis: genetically determined? Shock. 2000;14307- 310
PubMed Link to Article
Bauerle  RRucker  ASchmandra  TCHolzer  KEncke  AHanisch  E Markov cohort simulation study reveals evidence for sex-based risk difference in intensive care unit patients. Am J Surg. 2000;179207- 211
PubMed Link to Article
Wichmann  MWInthorn  DAndress  HJSchildberg  FW Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2000;26167- 172
PubMed Link to Article
Eachempati  SRHydo  LBarie  PS Gender-based differences in outcome in patients with sepsis. Arch Surg. 1999;1341342- 1347
PubMed Link to Article
Crabtree  TDPelletier  SJGleason  TGPruett  TLSawyer  RG Gender-dependent differences in outcome after the treatment of infection in hospitalized patients. JAMA. 1999;2822143- 2148
PubMed Link to Article
McLauchlan  GJAnderson  IDGrant  ISFearon  KC Outcome of patients with abdominal sepsis treated in an intensive care unit. Br J Surg. 1995;82524- 529
PubMed Link to Article
Kollef  MHO'Brien  JDSilver  P The impact of gender on outcome from mechanical ventilation. Chest. 1997;111434- 441
PubMed Link to Article
Kollef  MH Ventilator-associated pneumonia: a multivariate analysis. JAMA. 1993;2701965- 1970
PubMed Link to Article
O'Keefe  GEHunt  JLPurdue  GF An evaluation of risk factors for mortality after burn trauma and the identification of gender-dependent differences in outcomes. J Am Coll Surg. 2001;192153- 160
PubMed Link to Article
Muller  MJPegg  SPRule  MR Determinants of death following burn injury. Br J Surg. 2001;88583- 587
PubMed Link to Article
Barrow  REHerndon  DN Incidence of mortality in boys and girls after severe thermal burns. Surg Gynecol Obstet. 1990;170295- 298
PubMed
Wichmann  MWZellweger  RDeMaso  CMAyala  AChaudry  IH Enhanced immune responses in females, as opposed to decreased responses in males following haemorrhagic shock and resuscitation. Cytokine. 1996;8853- 863
PubMed Link to Article
Angele  MKKnoferl  MWSchwacha  MG  et al.  Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage. Am J Physiol. 1999;277C35- C42
PubMed
Knoferl  MWDiodato  MDAngele  MK  et al.  Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage? Arch Surg. 2000;135425- 433
PubMed Link to Article
Mizushima  YWang  PJarrar  DCioffi  WGBland  KIChaudry  IH Estradiol administration after trauma-hemorrhage improves cardiovascular and hepatocellular functions in male animals. Ann Surg. 2000;232673- 679
PubMed Link to Article
Jarrar  DWang  PCioffi  WGBland  KIChaudry  IH The female reproductive cycle is an important variable in the response to trauma-hemorrhage. Am J Physiol Heart Circ Physiol. 2000;279H1015- H1021
PubMed
Kahlke  VAngele  MKAyala  A  et al.  Immune dysfunction following trauma-haemorrhage: influence of gender and age. Cytokine. 2000;1269- 77
PubMed Link to Article
Diodato  MDKnoferl  MWSchwacha  MGBland  KIChaudry  IH Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis. Cytokine. 2001;14162- 169
PubMed Link to Article
Zellweger  RWichmann  MWAyala  AStein  SDeMaso  CMChaudry  IH Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Crit Care Med. 1997;25106- 110
PubMed Link to Article
Angele  MKCatania  RAAyala  ACioffi  WGBland  KIChaudry  IH Dehydroepiandrosterone: an inexpensive steroid hormone that decreases the mortality due to sepsis following trauma-induced hemorrhage. Arch Surg. 1998;1331281- 1288
PubMed Link to Article
Vincent  JLBihari  DSuter  PM  et al.  The prevalence of nosocomial infection in intensive care units in Europe: the results of the EPIC study. JAMA. 1995;274639- 644
PubMed Link to Article
Schneider  CPNickel  EASamy  TS  et al.  The aromatase inhibitor, 4-hydroxyandrostenedione, restores immune responses following trauma-hemorrhage in males and decreases mortality from subsequent sepsis. Shock. 2000;14347- 353
PubMed Link to Article
Cumming  JPurdue  GFHunt  JLO'Keefe  GE Objective estimates of the incidence and consequences of multiple organ dysfunction and sepsis after burn trauma. J Trauma. 2001;50510- 515
PubMed Link to Article
Oberholzer  AKeel  MZellweger  RSteckholzer  UTrentz  OErtel  W Incidence of septic complications and multiple organ failure in severely injured patients is sex specific. J Trauma. 2000;48932- 937
PubMed Link to Article
Offner  PJMoore  EEBiffl  WL Male gender is a risk factor for major infections after surgery. Arch Surg. 1999;134935- 938
PubMed Link to Article
Burke  APFarb  AMalcom  GTLiang  YSmialek  JVirmani  R Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation. 1998;972110- 2116
PubMed Link to Article
Berglund  UWallentin  Lvon Schenck  H Platelet function and plasma fibrinogen and their relations to gender, smoking habits, obesity and beta-blocker treatment in young survivors of myocardial infarction. Thromb Haemost. 1988;6021- 24
PubMed
Johansson  SBergstrand  RSchlossman  DSelin  KVedin  AWilhelmsson  C Sex differences in cardioangiographic findings after myocardial infarction. Eur Heart J. 1984;5374- 381
PubMed
Ciraulo  DABresnahan  GFFrankel  PSIsely  PEZimmerman  WRChesne  RB Transmural myocardial infarction with normal coronary angiograms and with single vessel coronary obstruction: clinical-angiographic features and five-year follow-up. Chest. 1983;83196- 202
PubMed Link to Article
Donahue  RPGoldberg  RJChen  ZGore  JMAlpert  JS The influence of sex and diabetes mellitus on survival following acute myocardial infarction: a community-wide perspective. J Clin Epidemiol. 1993;46245- 252
PubMed Link to Article
Abbott  RDDonahue  RPKannel  WBWilson  PW The impact of diabetes on survival following myocardial infarction in men vs women: the Framingham Study. JAMA. 1988;2603456- 3460
PubMed Link to Article
Sonke  GSBeaglehole  RStewart  AWJackson  RStewart  FM Sex differences in case fatality before and after admission to hospital after acute cardiac events: analysis of community based coronary heart disease register. BMJ. 1996;313853- 855
PubMed Link to Article
Tunstall-Pedoe  HMorrison  CWoodward  MFitzpatrick  BWatt  G Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991: presentation, diagnosis, treatment, and 28-day case fatality of 3991 events in men and 1551 events in women. Circulation. 1996;931981- 1992
PubMed Link to Article
Demirovic  JBlackburn  HMcGovern  PGLuepker  RSprafka  JMGilbertson  D Sex differences in early mortality after acute myocardial infarction (the Minnesota Heart Survey). Am J Cardiol. 1995;751096- 1101
PubMed Link to Article

Figures

Place holder to copy figure label and caption

Cumulative survival curves for female and male sex according to length of intensive care unit (ICU) stay (n = 595 patients).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic Data of 4420 Patients Admitted to the Intensive Care Unit During 2 Study Periods
Table Graphic Jump LocationTable 2. Differences Between Medical and Surgical Patients
Table Graphic Jump LocationTable 3. Admission Diagnoses With Corresponding Mortality Rates
Table Graphic Jump LocationTable 4. Cumulative Survival of Patients
Table Graphic Jump LocationTable 5. Time-Dependent Cox Regression Model

References

Jousilahti  PVartiainen  ETuomilehto  JPuska  P Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. Circulation. 1999;991165- 1172
PubMed Link to Article
Malacrida  RGenoni  MMaggioni  AP  et al.  A comparison of the early outcome of acute myocardial infarction in women and men: the Third International Study of Infarct Survival Collaborative Group. N Engl J Med. 1998;3388- 14
PubMed Link to Article
Vaccarino  VParsons  LEvery  NRBarron  HVKrumholz  HM Sex-based differences in early mortality after myocardial infarction: National Registry of Myocardial Infarction 2 Participants. N Engl J Med. 1999;341217- 225
PubMed Link to Article
Weaver  WDWhite  HDWilcox  RG  et al. GUSTO-I Investigators, Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. JAMA. 1996;275777- 782
PubMed Link to Article
Maynard  CEvery  NRMartin  JSKudenchuk  PJWeaver  WD Association of gender and survival in patients with acute myocardial infarction. Arch Intern Med. 1997;1571379- 1384
PubMed Link to Article
Adams  KF  JrSueta  CAGheorghiade  M  et al.  Gender differences in survival in advanced heart failure: insights from the FIRST study. Circulation. 1999;991816- 1821
PubMed Link to Article
Simon  TMary-Krause  MFunck-Brentano  CJaillon  P Sex differences in the prognosis of congestive heart failure: results from the Cardiac Insufficiency Bisoprolol Study (CIBIS II). Circulation. 2001;103375- 380
PubMed Link to Article
Wohltmann  CDFranklin  GABoaz  PW  et al.  A multicenter evaluation of whether gender dimorphism affects survival after trauma. Am J Surg. 2001;181297- 300
PubMed Link to Article
Mostafa  GHuynh  TSing  RFMiles  WSNorton  HJThomason  MH Gender-related outcomes in trauma. J Trauma. 2002;53430- 435
PubMed Link to Article
Schroder  JKahlke  VStaubach  KHZabel  PStuber  F Gender differences in human sepsis. Arch Surg. 1998;1331200- 1205
PubMed Link to Article
Schroder  JKahlke  VBook  MStuber  F Gender differences in sepsis: genetically determined? Shock. 2000;14307- 310
PubMed Link to Article
Bauerle  RRucker  ASchmandra  TCHolzer  KEncke  AHanisch  E Markov cohort simulation study reveals evidence for sex-based risk difference in intensive care unit patients. Am J Surg. 2000;179207- 211
PubMed Link to Article
Wichmann  MWInthorn  DAndress  HJSchildberg  FW Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2000;26167- 172
PubMed Link to Article
Eachempati  SRHydo  LBarie  PS Gender-based differences in outcome in patients with sepsis. Arch Surg. 1999;1341342- 1347
PubMed Link to Article
Crabtree  TDPelletier  SJGleason  TGPruett  TLSawyer  RG Gender-dependent differences in outcome after the treatment of infection in hospitalized patients. JAMA. 1999;2822143- 2148
PubMed Link to Article
McLauchlan  GJAnderson  IDGrant  ISFearon  KC Outcome of patients with abdominal sepsis treated in an intensive care unit. Br J Surg. 1995;82524- 529
PubMed Link to Article
Kollef  MHO'Brien  JDSilver  P The impact of gender on outcome from mechanical ventilation. Chest. 1997;111434- 441
PubMed Link to Article
Kollef  MH Ventilator-associated pneumonia: a multivariate analysis. JAMA. 1993;2701965- 1970
PubMed Link to Article
O'Keefe  GEHunt  JLPurdue  GF An evaluation of risk factors for mortality after burn trauma and the identification of gender-dependent differences in outcomes. J Am Coll Surg. 2001;192153- 160
PubMed Link to Article
Muller  MJPegg  SPRule  MR Determinants of death following burn injury. Br J Surg. 2001;88583- 587
PubMed Link to Article
Barrow  REHerndon  DN Incidence of mortality in boys and girls after severe thermal burns. Surg Gynecol Obstet. 1990;170295- 298
PubMed
Wichmann  MWZellweger  RDeMaso  CMAyala  AChaudry  IH Enhanced immune responses in females, as opposed to decreased responses in males following haemorrhagic shock and resuscitation. Cytokine. 1996;8853- 863
PubMed Link to Article
Angele  MKKnoferl  MWSchwacha  MG  et al.  Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage. Am J Physiol. 1999;277C35- C42
PubMed
Knoferl  MWDiodato  MDAngele  MK  et al.  Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage? Arch Surg. 2000;135425- 433
PubMed Link to Article
Mizushima  YWang  PJarrar  DCioffi  WGBland  KIChaudry  IH Estradiol administration after trauma-hemorrhage improves cardiovascular and hepatocellular functions in male animals. Ann Surg. 2000;232673- 679
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