Sex & Gender in Acute Care Medicine

1. Sex & Gender in Acute Care Medicine Chapter 6: Trauma

2. Chapter 6: Trauma Jason Cohen, Stefan Merrill, Federico Vaca

3. Case Study • A 23-year-old woman is driving home from work • As she rounds a curve, she sees several cars involved in a collision in front of her • She tries to brake but the road is icy and she skids, colliding with the cars in front of her

4. Case Study • At the hospital, she is diagnosed with a subarachnoid hemorrhage, an orbital wall fracture, multiple rib fractures, a pulmonary contusion, a splenic laceration, and a closed lower extremity fracture • She is admitted to the surgical ICU • She undergoes several surgeries and is eventually transferred to a rehabilitation facility

5. Case Study • How does gender impact her initial presentation and resuscitation? • How can her biochemical and proteomic makeup change her body’s response to stress and injury? • What will the long-term impact of her trauma be on her quality of life?

6. Introduction • Traumatic injury is a leading cause of death worldwide • It is currently the 3rd leading cause of death among men and women <45 years old in the industrialized world • Only in the past decade have researchers investigated the effects of gender on outcomes from traumatic injury

7. Introduction • Gender-based differences in exposure to high-risk activities appear to have a major effect on the nature and severity of injury • In the US, the vast majority (85%) of firearms-related deaths occur in men • ED data on traumatic brain injury in patients <19 demonstrates that young men are most likely to sustain head injuries while playing football • Young women, while engaging in playground activities

8. Introduction • In one study, sex itself was not associated with differences in the number of injuries sustained by school-age patients • Differences in incidences and mechanisms of injury affect ED care and treatment as well as public health interventions • Epidemiology of injury does not exclusively explain differing outcomes in injured men and women

9. Introduction • Animal and human studies have demonstrated sex-based differences in immune-mediated reactions to trauma and hemorrhagic shock • Following severe trauma, inflammatory pathways are activated leading to the recruitment of immune-modulating cells to the area of injury and system-wide • This can lead to reduced response to further infection as well as end organ damage

10. Introduction • This subsequent immunodepression following severe injury appears absent or greatly reduced in females and castrated males • These differences may be related to direct binding of sex hormones to immune system cells • Although the exact mechanisms are unknown, immunosuppression after injury may be a major contributor to adverse outcomes

11. Gender-Related Presentation • Anatomical differences explain some of the varying presentations between male and female trauma patients • Women’s shorter stature may result in an increase in lower body injuries following MVCs • Research has shown that traumatically injured women are more likely to have insurance and less likely to present with self-inflicted injury, suggesting that gender is also a factor

12. Age-Related Factors • Trauma in the elderly is complicated by impaired hemostasis, adverse drug reactions, drug-drug interactions, and decreasing immune function • In a systematic review (Jacoby et al.), multiple studies found a higher risk of mortality in injured men compared to women • Differences in immunologic function by sex may contribute but other reasons more specific to the elderly should be considered

13. Age-Related Factors • Elders often have comorbidities with prescribed medications that may alter physiologic responses to trauma • Vital signs can be altered by cardiac and antihypertensive meds, masking hypovolemia and early shock or exacerbating minor insults • Nevertheless, there is no evidence of a significant difference in the number of medications taken by elderly men and women

14. Age-Related Factors • Differing prevalence of certain medical conditions may also contribute to differences in injury presentation and outcome between elderly women and men • Osteoporosis is more common in women and is associated with increased risk of fractures • More than 75% of hip fractures occur in women, likely due to osteoporosis

15. Pregnancy • In the US, trauma is the leading cause of death in pregnant women • Women are at higher risk for intimate partner violence (IPV) during pregnancy • Emergency providers should have a high index of suspicion for IPV and should screen all pregnant patients presenting with injury or vague illness

16. Pregnancy • Procedures commonly performed in the ED require specific consideration in the traumatically injured pregnant patient • For example, when placing a chest tube in women in the 3rd trimester of pregnancy, the tube must be inserted one intercostal space above the usual site of insertion to avoid injuring the diaphragm, which is elevated due to the size and position of the gravid uterus

17. Immunology/Hormones • Several studies have reported that menstruating women who suffer a traumatic injury or sepsis have increased survival rates • The immune function of women who are immediately preovulatory remains fully active after trauma • Young men and post-menopausal women experience immune system impairment after significant trauma

18. Immunology/Hormones • One explanation is that estradiol enhances cell-mediated and humoral immunity, while androgens suppress the immune system • In animals, castration has been shown to improve survival after trauma • Premenopausal women are less likely to develop many of the life-threatening complications of trauma, including ARDS, pneumonia, and sepsis

19. Immunology/Hormones • However, women who do develop these complications have a greater case fatality rate than men • Women with any of these complications have an odds ratio of death of 1.2 compared to men • Sex hormones may be important therapeutic options in trauma, although clinical human studies have not demonstrated efficacy

20. Transgender Patients • ED providers must be aware of common hormone regimens used by transgender patients, which may effect injury outcomes • Hormone supplements are not always taken as prescribed and not always obtained from pharmacies • Providers should be aware of potential complications, such as increased rate of venous thromboembolic events

21. Traumatic Brain Injury • Rates of TBI-related ED visits increased in 2010 for both men and women • A recent study found that women who sustained a TBI during the luteal phase (when progesterone levels were high) had lower quality of life scores than women who sustained a TBI when estrogen levels were high • Suggests that estrogen may be neuroprotective

22. Traumatic Brain Injury • Animal models have found beneficial effects on both anatomic and functional outcomes with progesterone therapy • A series of small human clinical trials have yet to demonstrate sufficient strength of evidence to recommend progesterone therapy for TBI • Several large, prospective trials are currently underway (ProTECT III and SyNAPSe)

23. Provider and Team Differences • It is important to consider the implications of gender differences among providers and in the resuscitation team • Significant research has been done on the qualities of effective trauma teams • No studies have examined the differences between male and female trauma team leaders

24. Provider and Team Differences • Historically, men have held more leadership roles • Masculine characteristics such as aggression and competitiveness have been associated with leadership • These characteristics may not be the most effective for trauma team leadership

25. Provider and Team Differences • Women’s leadership characteristics such as the ability to engender collaboration, manifest and encourage empathy, and provide emotional support to patient and team may be equally important or more useful • Leadership qualities are generally situation dependent and are based on personality factors as well as gender socialization

26. Provider and Team Differences • Beyond leadership, gender seems to affect other aspects of provider-patient interactions • A study revealed that nurses (the majority of whom are women) provide less analgesia to men than women • Conversely, male and female physicians are both more likely to undertreat female patients in pain

27. Provider and Team Differences • In a 2012 study, investigators found that pre-hospital providers were more likely to transport injured men to trauma centers than women • Even after controlling for age, comorbidities, injury severity score, and bodily region injured • Physicians showed the same bias in the decision to transfer patients to trauma centers from non- trauma designated emergency facilities

28. Long-term Sequelae • Advances in medical care have increased survival after traumatic injury • The complexities of sex and gender continue to influence the long-term effects of temporary and permanent disability • Women are less likely to hold jobs with adequate health or disability insurance • In many cultures, men are the sole providers of income for the household

29. Long-term Sequelae • No published articles examine gender differences in medical and socioeconomic outcomes after severe traumatic injury • The research that does exist focuses on outcomes after TBI and on psychological sequelae of trauma • A study on long-term sequelae of mild TBI found that women had increased incidence of persistent dizziness, headache, anxiety, and other symptoms

30. Long-term Sequelae • Long-term executive function and cognitive flexibility are more likely to be preserved in women than men 1 year after TBI • Although women have lower rates of traumatic injury, they develop PTSD at almost 2x the rate men do • Interestingly, the incidence rate of PTSD in women seems to reverse with age • Over age 50, men have higher incidence • May reflect a tendency in men to underreport PTSD symptoms and in women, to overreport

31. Conclusion • Our patient was hospitalized for 4 weeks and then discharged to inpatient rehab • She had persistent memory loss and pain in her injured leg • She could not bear weight for more than 15 minutes • She experienced frequent anxiety and difficulty sleeping and had to move in with family as she could not afford childcare

32. Conclusion • There is still much to be learned about sex and gender differences in the treatment of trauma • The biochemical mechanisms that appeared to explain sex differences in preclinical studies have not translated to the clinical realm • Additional attention and research on gender and sex is needed to help identify potential treatments and devise more effective public health and injury prevention strategies

33. Trauma Questions 1. An ambulance arrives at the emergency department with a ‘trauma alert,’ a 23 year-old female restrained driver in a motor vehicle collision. She informed paramedics that she is “almost 7 months pregnant” and she now complains of both chest and abdominal pain. When considering procedural intervention on a pregnant patient, which of the following is a correct? (A) In the event of a traumatic hemo- or pneumothorax, chest tube should be placed between the 5th and 6th ribs in the anterior axillary line. (B) Maintain patient position in the left lateral decubitus position to avoid decreased cardiac output and hypotension. (C) Screening for intimate partner violence is not indicated in this setting. (D) Pregnant trauma patients beyond 20-24 weeks estimated gestation who have sustained direct or indirect abdominal trauma, do not require dedicated fetal monitoring. (E) All the Above Answer: (B) In order to decrease the effect of the uterus obstructing the IVC, it is important to lie traumatically injured pregnant patients in the left lateral decubitus position. When inserting a chest tube, one must keep in mind that he gravid uterus alters female anatomy so the chest tube must be inserted one intercostal above (between ribs 4 & 5). Finally, women are more likely to suffer intimate partner violence (IPV) during pregnancy. EM provider and screening of ALL pregnant patients presenting for evaluation of an injury or vague illness has been demonstrated to decrease the effects of IPV and to improved pregnancy-related outcomes (Kiely et al. 2010). References: 1. Butcher. http://www.ncbi.nlm.nih.gov/pubmed/24810899 2. Morris. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC286253/ 3. Euser. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663594/

34. Trauma Questions 2. With regards to trauma and trauma patients, which of the following is most correct? (A) Trauma is the leading cause of death for men younger than 45 living in the industrialized world. (B) Within the US, firearms death rates occur in men and women equally. (C) Women are more likely than men to present with self-inflicted traumatic injury. (D) Gender-based differences in risk-taking behavior is a major effector of type and extent of injury. (E) None of the above. Answer: (D) Traumatic injury is the third leading cause of death for men and women younger than age 45 living in the industrialized world. Within the US, the vast majority of firearms-related deaths occur in men (85% in 2013). Women are less likely to present with self-inflicted injury as compared to men. Men present at a higher frequency than women in all areas of traumatic injury until age 72 (American College of Surgeons, 2014).