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Metrics details. Preclinical data indicate that oestrogen appears to play a beneficial role in the pathophysiology of and recovery from critical illness. In few previous epidemiologic studies, however, have researchers analysed premenopausal women as a separate group when addressing potential gender differences in critical care outcome.

Our aim was to loshad if women of premenopausal age have a better outcome following critical care and to investigate the association between gender and use of intensive care unit ICU resources. For the cohort as a whole, and for those admitted with multiple trauma, male sex was associated with a higher nurse workload score and a longer ICU stay. Using information derived from a large multiple ICU register database, we found that premenopausal female sex was not associated with a survival advantage following intensive care in Sweden.

When the data were adjusted for age and severity of illness, we found that men used more ICU resources per admission than women did. There are substantial preclinical data on how male and female sex hormones play a role in the pathophysiology of and recovery from critical illness. Oestrogen is a potent antioxidant that appears to have a protective effect in trauma and haemorrhage [ 1 - 3 ], whereas high testosterone levels in critical conditions are associated with suppression of cardiac function and the immunologic response [ 4 - 7 ].

Despite the apparent advantage of females observed in the experimental setting, findings in epidemiologic critical care studies have been equivocal; risk-adjusted gender differences in mortality are reported to be disparate, potentially diagnosis-specific [ 8 - 11 ] or due to differences in treatment and resource allocation [ 12 - 14 ].

It was also recently shown that increasing blood oestrogen levels during ongoing intensive care are associated with mortality in both sexes, but it is unknown whether this association is causative or consequential [ 15 ]. If higher initial physiologic baseline oestrogen levels are beneficial in critical illness, one should expect premenopausal women to have a superior outcome. Indeed, some studies indicate that women of premenopausal age have higher intensive care unit ICU survival [ 16 ], a more beneficial physiologic response to severe trauma [ 17 ] and better outcome following cardiac arrest as compared loshad other demographic groups [ 18loshad ].

Other studies, however, have failed to demonstrate such an advantage [ 1220 ]. The compound SAPS III score can also be transformed into a probability called the estimated mortality risk EMRwhich is the predicted risk of death before being discharged from the hospital [ 23 ]. A strength of the NCR11 loshad is that it describes the nursing component of patient care and components related to medical procedures.

Nurse workload scores have previously been used to measure and compare resource allocation between sexes, with varying results [ 25 - 27 ]. In addition to looking at the entire unselected general intensive care cohort, we also wanted to apply this question in six more well-defined diagnostic subgroups.

We also set out to investigate the association of sex with use of intensive care resources. Admissions due to hospital bed shortage or for routine postoperative recovery were not considered ICU admissions for the purposes of the present study.

The primary diagnosis was used to define six major diagnostic subgroups sepsis, multiple trauma, cardiac loshad, chronic obstructive pulmonary disease COPD exacerbation, acute respiratory distress syndrome ARDS and pneumonia. Sepsis, multiple trauma and cardiac arrest were included because previous experimental data indicate that sex hormone levels may influence the sex of these conditions [ 2930 ].

Two reasons for not being able to obtain these mortality data are non-Swedish residency and patients with concealed identity. A value of 0 points is given if no procedure or measure within the category is performed during that nursing shift. At the end of each nursing shift, the scores are added and a total score out of 33 is given.

The length of ICU admission hours and the accumulated NCR11 score points for each admission were used in this study as a proxy for use of resources. The SIR is a prospectively collected nationwide database of individual intensive care patient records, and it operates within the legal framework of all Swedish national quality registers.

In accordance with this legal framework written informed consent was not sought and not required from each individual patient. All patients or their next of kin were however informed of the collection of data and had the opportunity to not contribute with data to the registry. The data from the SIR used in this study had all personal identifiers removed. Differences were analysed using the Mann—Whitney U test. For our primary analysis of the entire study cohort, multivariate logistic regression was used to assess sex between sex and the dependent variable day mortality, controlling for potential confounders.

The variables that were included in the main model of the primary analysis of the entire study cohort were then similarly used to assess the associations between sex and day mortality in the age subgroups and in the diagnostic subgroups.

There was no sex difference in day mortality for the entire study cohort female:male odds ratio OR1. Male sex was associated with a lower mortality rate in patients with cardiac arrest female:male OR, 1. In this multiple-ICU, nationwide Swedish register study, we investigated outcome and use of resources in critically ill loshad and women in age groups defined by the median onset of menopause.

Instead, a lower mortality was associated with male sex for cardiac arrest. Male sex was independently associated with greater use of intensive care resources for the entire cohort and for multiple trauma patients. Organizational, sociological and biological factors may contribute to sex differences when it comes to need for, use of and outcome after critical care.

Fifty-seven percent of our ICU admissions were men, and males were sicker on admission. These observations are in line with previously reported series [ 9101217 ] and it has been suggested that male patients are more likely to be admitted for intensive care and to receive aggressive life support [ 101636 ]. The rationale for the expectation that women of childbearing age will have superior outcomes following critical care is that studies in numerous rat models have shown how important oestrogens are in maintaining organ function during critical illness [ 2930 ].

In a small number of studies on human volunteers and critically ill patients, researchers have reported that women show more favourable physiologic and immunologic responses when challenged with sepsis and hypovolemia [ 13738 ], thus providing some clinical support for this notion.

We observed no improved outcome in women of premenopausal age following critical care. This does not exclude a protective effect of oestrogens, because such an advantage could be counteracted by opposing factors such as differences in management and resource use.

Our findings could sex be interpreted such that differences in basal oestrogen levels are of less importance in a modern real-life clinical setting where aggressive intensive care resuscitation protocols may diminish any relative advantage of a premenopausal female hormone profile [ 15 ]. Furthermore, we do not know to what extent rodent experiments can be applied to humans, because primates, in contrast to rodents, can increase their peripheral, non-gonadal oestrogen production in response to stress [ 3940 ].

Nursing workload scores have previously been used to describe critical care resource use in men and women with severe sepsis [ 25 ] and trauma [ 26 ]. The NCR11 score includes medical procedures as well as nursing components of patient care, which makes it a feasible proxy for measuring overall ICU resource use. Its limitations and generalizability must be considered however, since a range of different factors all can increase the score; e.

Positive effects of female sex hormones have particularly been suggested in trauma sex 2930 ], and the results of an ongoing study where male haemorrhaging trauma patients were randomized to oestrogen or placebo in the acute sex phase may soon be available [ 42 ].

The composition of our multiple trauma subgroup was similar to previously reported series with respect to age, sex and injury severity [ 4344 ], and we detected no sex difference with regard to risk-adjusted mortality in any of the age groups, which is in line with previous observations [ 1645 ].

Male trauma patients had higher NCR11 scores and longer ICU stays than female patients in our study, and similar observations were recently made in a Brazilian trauma cohort [ 26 ]. An increased incidence of complications, such as sex organ failure and sepsis, in male trauma patients could possibly explain the difference in resource use [ loshad45 ], but other studies suggest that patient sex does not influence complication rates following multiple trauma [ 46 ].

Nearly three of four trauma patients in our cohort were men, and the fact that severe trauma patients are usually men may provide an alternative, albeit speculative, reason for the observed sex difference in resource use.

Clinical skills and therapeutic intuition are partly empirical, and clinicians promptly recognize conditions, events and clinical presentations that they have experienced before [ 47 ]. This may lead to a difference in diagnostic and therapeutic interventions in the comparatively rare female trauma group. Furthermore, Swedish cardiac arrest patients are primarily admitted to the ICU for controlled hypothermia treatment when they fail to regain consciousness following resuscitation and return of spontaneous circulation ROSC.

Our ICU cardiac arrest cohort is thus very different from an ER-treated prehospital cardiac arrest population that includes those who regain consciousness as well as those who never have ROSC. Sex steroids do influence the sepsis-induced complex immunological responses that involve cytokines, immune and endothelial cell interactions [ 50 ]. Women may have an increased propensity to develop ARDS [ 53 loshad, but previous audits have not identified sex as an independent predictor of outcome [ 3233 ].

A strength of this study is that we analysed a large, nationwide multicentre cohort for sex differences with respect sex day mortality. Hospital and ICU admissions are relatively short in Scandinavia [ 55 ], presumably reflecting a low number of hospital and ICU beds per capita [ 56 ], a high standard of care and the provision of palliative care outside the ICU setting. Half of the admissions in our cohort lasted less than 24 hours in duration, and this may have distorted any sex differences present loshad those receiving critical care for a longer period of time.

It should also be noted that the definition of the diagnostic subgroups in this study is strict. Each admission could therefore never belong to more than one diagnostic subgroup, even if clinical criteria were met for more than one of the six selected diagnoses.

For conditions such as cardiac arrest, sepsis and multiple trauma, the choice of a primary diagnosis is generally evident, but there are invariably cases where the selection of the primary ICD diagnosis can be difficult, such as when a patient with COPD is admitted to the ICU in respiratory failure and diagnosed with pneumonia.

In this study, we found no evidence that women of premenopausal age have lower risk-adjusted mortality than men and postmenopausal women in a general non-selected nationwide ICU cohort, nor did we find such evidence in six major diagnostic subgroups. In patients older sex the median age of menopause onset, we identified sex-associated, risk-adjusted mortality differences in patients admitted due to cardiac arrest, where a male survival advantage was identified.

Male sex was further independently associated with receiving more ICU care per admission. A more detailed analysis of admission characteristics, therapeutic interventions and incidence of complications in the diagnostic subgroups is needed to identify factors underlying the differences observed. There was no evidence of lower risk-adjusted day mortality in females of premenopausal age in a 4-year, nationwide Swedish ICU cohort.

Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers. Crit Care Med. Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Am J Physiol Cell Physiol. Testosterone: the culprit for producing splenocyte immune depression after trauma hemorrhage.

Testosterone: the crucial hormone responsible for depressing myocardial function in males after trauma-hemorrhage. Ann Sex. Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock.

Testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph. J Trauma. Influence of patient gender on admission to intensive care.

J Epidemiol Community Health. Impact of gender on treatment and outcome of ICU patients. Sex Anaesthesiol Scand. Gender-related differences in intensive care: a multiple-center cohort study of therapeutic interventions and outcome in critically ill patients.

Impact of gender on outcomes after blunt injury: a definitive analysis loshad more than 36, trauma patients. J Am Coll Surg. Sex- and age-based differences in the delivery and outcomes of critical care. Gender specific differences in the frequency of admission to intensive care units, duration of stay and the application of intensive medical care measures in men and women aged 75 years and above in an Austrian region.

Gender differences in mortality in patients with severe sepsis or septic shock. Gend Med. Trends in estradiol during critical illness are associated with mortality independent of admission estradiol.

Association of gender with outcomes in critically ill patients. Crit Care. Hormonally active women tolerate shock-trauma better than do men: a prospective study of over trauma patients. Females of childbearing age have a survival benefit after out-of-hospital cardiac arrest. Mortality after thermal injury: no sex-related difference.

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