Anaesthesia in women and women in anaesthesia - Else Tønnesen - SSAI2017
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A talk by Else Tönnesen at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine. All available content from SSAI2017: https://scanfoam.org/ssai2017/ Content delivered in collaboration between scanFOAM, SSAI & SFAI.
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Anaesthesia in women and women in anaesthesia - Else Tønnesen - SSAI2017
- 1. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Anaesthesia in Women and Women in Anaesthesia Else Tønnesen Prof. emerita Institute for Clinical Medicine Aarhus University Hospital Denmark
- 4. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Anaesthesia in women Women in anaesthesia
- 5. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Anaesthesia in Women Known differences between women and men in their response to anaesthesia Main question: Are there differences between girls and boys?
- 6. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Is diphtheria –tetanus-pertussis (DTP) associated with increased mortality in girls?
- 7. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Anaesthesia in Women • Physiological differences between women and men • Pharmacological differences • Neurological differences • Gender differences in response to anaesthesia • Summary and conclusion
- 8. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Physiological differences between sex • Hormonal variability Female sex hormones, Cyclic released from menarche to menopause Steroid-based oestrogen, progesterone (LH, FSH)
- 9. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Effects of progesterone and its metabolites • Dose-dependent hypnosis • Anxiolytic • Anti-convulsive • Analgesia • Respiratory stimulating • Increases the potency of inhalational anaesthetics
- 10. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Body composition differences Females Body fat 5 to 10% higher Muscle mass 10% lower Total body water 15 to 20% less Electrolyte balance and extracellular fluid volume fluctuate during menstrual cycle
- 11. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Disparity between females and males The appearance
- 12. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Cardiovascular differences Females Cardiac mass Lower Diastolic function Better Stroke volume Larger Resting heart rate Higher Blood pressure Lower (premenopausal)
- 13. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Respiratiory differences Females Lung volume Lower Lung diffusion surface Lower Ventilatory response to hypercapnia Less Ventilatory response to exercise Less Ventilatory response to hypoxia Less Apnoeic threshold Less Transl Stroke Res 2013:4:462 Eur J Appl Physiol2003:89;595
- 14. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Physiological differences Renal function No major differences when accounted for body size Metabolism Metabolic rate lower in women due to smaller body size Metabolism and core body temp fluctuate with menstrual cycle
- 15. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Pharmacokinetic differences Females Volume of distribution(Vd) Lower for water soluble –drugs Higher sensitivity 20-30% for the non-depolarising muscle relaxants Require less doses Larger for lipid-soluble drugs Reduced sensitivity for benzodiazepines and propofol Require higher doses
- 16. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Pharmakinetic differences • Gender differences in hepatic enzyme activity are responsible for differences in hepatic metabolism and clearance • Differences in drug metabolism are believed to play a major role in gender differences Ann Rev Pharmacol Toxicol 2004;44:499
- 17. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Gender differences in relation to anaesthesia Acta Anaesthesiol Scand 2003;47:241; Anaesth Intensive Care 2009;37:207; Trans Stroke Res 2013;4:462 Anaesthetic variables Propofol and benzodiazepines Non-depolarising relaxants Time to eye-opening PONV Sore throat Postoperative pain Headache Backache Hospital stay Patient satisfaction Functional postoperative outcome Females Lower sensitivity Higher sensitivity Shorter Higher Higher Higher Higher Higher Longer Less Poorer
- 18. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Review Article H. Pleym, O. Spigset E.D. Kharasch, O. Dale. Gender differences in drug effects: implications for anesthesiologists Acta Anaesthesiol Scand 2003:47:241
- 19. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Summary Women recover faster from general anaesthesia They have higher postoperative sequelae such as PONV, sore throat, headache, and backache Worse recovery/outcome ( LOS, morbidity and mortality) following some types of major surgery
- 20. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Hormonal differences between men and women The leading hypothesis to explain gender differences in anaesthesia involves the hormonal differences between women and men Is the gender dependence just a question about hormone levels?
- 22. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN The brain and the CNS it the main target of anaesthesia/anaesthetics The sexually dimorphic brain Sexual differentiation begins in the womb and continues until early adulthood Triggered by intrauterine testosterone, progesterone and oestrogen - and sex chromosome genes Many gender differences in brain structure, volume and function from birth and throughout life Transl Stroke Res 2013;4:462-475; Biobehav Res 2014; 39:34
- 23. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Disparity between females and males The behaviour Mission: Visit the shopping centre and buy 1 bottle of milk and 2 sodas Female Male Women’s wear COOP Elec- tronics Result – Female: Total price: 159 € or 189 US$ Result – Male: Total price: 2,20 € or 2,64 US$
- 24. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Anaesthesia in children Evidence from animal studies of damaging effects of anaesthesia on the developing brain Frederiksson et al. Anesthesiology 2007;107:427. Viberg et al. Toxicology 2008;249: 152 Epidemiological studies – no evidence of negative effects Hansen TG et al. Editorial. Acta Anaesthesiol Scand 2016;60:280 Gender specific differences were not studied
- 25. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Conclusion There is a (surprisingly) huge knowledge gap about gender differences in children´s response to anaesthesia
- 26. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Summary Males and females are physiologically different in their response to anaesthetic agents The brain is the main target of anaesthesia The brain is sexually dimorphic from birth and throughout life Gender has major impact on the influence of anaesthetics in the brain
- 27. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Summary In adults, sex differences are apparent in the induction, maintenance, and recovery phases of general anaesthesia. Sex differences most pronounced in adulthood Puberty exacerbates the differences supporting the role of hormones
- 28. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Concerns Females are often excluded from basic and clinical research (breeding, pregnancy and hormonal changes) Males are often preferred in animal studies The exclusion of females in anaesthesia related research leaves a knowledge gap in the literature J Neurol Sci 2002;199:79; Neurosci Biobehav Res 2014; 39:34; Open Anatomy J 2010;2:37;
- 29. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Women in Anaesthesia Some reflections after 30 years in anaesthesia
- 30. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN The reverse henhouse 1995 A multitude of roosters and two lonely hens
- 31. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Professors in anaesthesiology, intensive care, emergency medicine, teaching/education Ratio women/men (DK)
- 32. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Share of female full professors by main field of science, 2010 Mathias Wullum Nielsen. Scand J Educational Research 1017;61:295.
- 33. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Proportion of male and female first authors of original papers published in BJA 2011 BJA 2013 11;139-42
- 34. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Gender Parity in Critical Care Medicine AJRCCM 2017 Review of 413 clinical practice guidelines published between January 2012 and July 2016 •Female physicians comprised 25% of authors overall •Only 13% of female authors of critical care guidelines •Absent from the Sepsis-3 definitions JAMA 2016;315:801 • and the Berlin ARDS definitions JAMA 2012;307:2526
- 36. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN ” I am considering recommending to her Majesty the Queen’s Cabinet Secretary that you are awarded the Knight’s Cross of the Order of Dannebrog” “This requires you are not subject to any pending or spent criminal convictions, which would make such an award untenable” Letterfromthe Permanent Secretary to the Ministry of Science, Technology and Higher Education 17th November2006
- 40. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN THE woman in anaesthesia
- 41. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Virginia Apgar (1909-1974) The first female full professor at Columbia University College of Physicians and Surgeons, NY 1949 Designed and introduced the Apgar Score, the first standardized method for evaluating a assessing the health of newborn babies
- 42. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Virginia Apgar • Graduated from Columbia University in 1933 • Completed a surgical residency in 1937 • Six months training with Dr Ralph Waters Dept. of Anaesthesia - the first in the US - at the University of Wisconsin – Madison • Six months with Dr Ernest Rovenstine at Bellevue Hospital in NY • Back to Columbia University in 1938 as director of the division of anaesthesia and as attending anaesthetist
- 43. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Virginia Apgar Anaesthetist at Columbia University 1938 • Troubles with recruiting physicians • Surgeons did not accept anaesthetists as equals • Low pay for the less respected specialty • The only staff member until mid-1940s • Anaesthesia medical specialty in 1946 • In 1949 it became an academic department with Virginia Apgar as full professor until 1959
- 44. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Virginia Apgar • 1953: introduced the Apgar score • 1959: Left Columbia University and anaesthesia – Master of Public Health degree • Advocated for universal vaccination to prevent mother –to - child transmission of rubella • Promoted Rh-testing of women – identifying women at risk for transmission of maternal AB across placenta
- 45. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Virginia Apgar – other activities • Violin player • Violin, viola and cello maker • Enthusiastic gardener • Enjoyed fly-fishing, golfing and stamp collecting • Took flying lessons
- 46. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Honours and Awards • Honorary doctorate, Women’s Med College Pennsylvania 1964 • Honorary doctorate, Mount Holyke College 1965 • Distinguished Service Award, ASA 1966 • Elizabeth Blackwell Award, the Am Women’s Med Ass 1966 • Honorary doctorate, New Jersey Coll Med Dentistry 1967 • Alumni Gold Medal for Distinguished Achievement, Columbia University Coll Phys Surg 1973 • Ralph Waters Award, ASA 1973 • Woman of the Year in Science, Ladies Home Journal 1973 • Fellow of the NY Academy of Medicine, the American Public Health Association, and the NY Academy of Sciences
- 47. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Post humous recognition In 1995 honoured by the US Postal Service with a 20¢ Great Americans series postage stamp
- 49. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN The woman in anaesthesia Avoided organized women´s movements (liberation, feminism) ”Women are liberated the time the leave the womb” ”- being female has not imposed significant limitations on my medical career”
- 51. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Thank you for your attention
- 52. Institut forKliniskMedicin Aarhus Universitet ELSE TØNNESEN Disparity between females and males The appearance
Editor's Notes
- Thanks to the organizing committee – Congress president Mikael Bodelsen Excellent collaboration between the Scandinavian Countries with a free labour market for doctors
- I have two topics in my lecture.
- My clinical work as an anaesthetist was intensive care in the ICU - . The background for choosing this topic is a little bit strange
- An ongoing discussion between Peter Aaby´s research group from the Bandim Health Project, Guinea-Bissau and WHO The effect of some specific vaccinations differed between girls and boys with respect to mortality.
- This is basic knowledge: Males and females are physiologically distinct Several well known physiological and pharmacological differences between men and women modulate the effects of anaesthetics. And differences in physiology can impact how anaesthetics interact with the body.
- When you read studies reporting gender differences in anaesthesia many or most conclusions refere to the hormonal differences between men and women. Many of the physiological differences between men and women could be the result of the direct or indirects actions of female sex hormones. FSH and luteinising hormens are released from the pituitary during the cycle, they play a minor role compared with oestrogen and progesterone Oestrogen mediates vasodilation via NO-release, progesterone has respiratiory stimulating effects
- Progesterone increases the potency of inhalationl anaesthetics Decreases the anaesthetic requirement
- BASIC KNOWLEDGE Females have lower relative body-weight, higher average body fat, lower average plasma volume than males that can influence
- Men and women are born with the same number of myocytes, but cardiac mass increases more in men. Despite this younger women have better diastolic function and large ventricular EF compared with men. Resting heart rate varies during menstrual cycle. When compared with men women have a lower mean BT in the order of 6-10 mmHG. This changes after menopause and by the age of 70 years blood pressure exceeds that of men. Oestrogen causes vasodilation via increased secretion of NO. Progesterone has also a lowering effect in BT
- Women have smaller lung volumes, smaller diffusion surfaces Lower vetilatory response to exercise
- Metabolic rate is lower in women due to their smaller body size. Metabolic fluctuation with stage of menstrual cycle. (Preogesterone stimulates metabolism). Body temperature fluctuates during menstrual cycle
- Body size and body composition differ between males and femalse. Body fat increases in both sexes with age but the volume of distribution for water soluble drugs is lower in women. Lower doses are needed to produce equivalent effect to that in men. Veco, pancu recuro, attracurium – not cisatra Benzodiazepins: diazepam and midazolam. Reduced sensitivity in women means they require higher doses propofol/midazolam to lose consciousness. Vd defines as the ratio of the total amount of drug in the body and drug plasma cincentration
- Sex differences in hepatic enzyme activity is responsible for hepatic metabolism and therefor clearance of a drugs without difference between sexses.
- Reduced propofol sensitivity is supported by requirements for more propofol to lose conscisness - recover more rapidly from g.a. PONV: A common problem and a major contributing factor impairing a patient´s quality of recovery. It also prolongs recovery time and delays discharge. Women have a two to three fold increased risk, but this disappears decreases after the age of 50 years. This suggest that hormonal influences may be contributing to PONV sensitivity.
- Male and female brains are different from the beginning! Sexual differentiation of the brain begins in the womb triggered by intrauterine exposure to testosterone, estogen and progestorone and the sex chromosome genes
- Very few issues with in pediatric anaesthesia have caused so much concern as a number animal studies have shown that exposure to anaesthesia during a vulnerable period of brain develpoment have harmful effects later in life
- Reproductive cyclus, pregnancy. Females are excluded for the variations that occur in the reproductice cycle To avoid the complication of pregnancy, breeding and hormonal changes
- Women have been involved indeveloping many critical care consensus statements and clinical practise guidelines. However, they have been absent from others. Review of
- ..to work for her The pay for the less respected spcialty was low She was the only staff
- Introduced the Apgar score to assess the health of newborns from John Hopkins School of Hygiene and Public Public Health
- Privately she might expressher frustrations with gender inequalities – especially in the matters of salaries)