Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
CV | cardiovascular |
CVD | cardiovascular diseases |
DA | dopamine |
ED | emergency department |
HF | heart failure |
HFpEF | heart failure with preserved ejection fraction |
ICU | intensive care unit |
IHM | in-hospital mortality |
LOS | length of stay |
MAP | mean arterial pressure |
NIH | National Institute of Health |
NE | norepinephrine |
RCT | randomized controlled trial |
SAGER | Sex and Gender Equity in Research |
SGBA | sex- and gender-based analysis |
SOFA | sequential organ failure assessment |
SSC | Surviving Sepsis Campaign |
WHO | World Health Organization. |
References
- Singer, M.; Deutschman, C.S.; Seymour, C.; Seymour Manu Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.; et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016, 315, 801–810. [Google Scholar] [CrossRef] [PubMed]
- Evans, L.; Rhodes, A.; Alhazzani, W.; Antonelli, M.; Coopersmith, C.M.; French, C.; Machado, F.R.; Mcintyre, L.; Ostermann, M.; Pres-cott, H.C.; et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021, 47, 1181–1247. [Google Scholar] [CrossRef] [PubMed]
- Chiu, C.; Legrand, M. Epidemiology of sepsis and septic shock. Curr. Opin. Anaesthesiol. 2021, 34, 71–76. [Google Scholar] [CrossRef] [PubMed]
- Reinhart, K.; Daniels, R.; Kissoon, N.; Machado, F.R.; Schachter, R.D.; Finfer, S. Recognizing Sepsis as a Global Health Priority—A WHO Resolution. N. Engl. J. Med. 2017, 377, 414–417. [Google Scholar] [CrossRef] [PubMed]
- Rhodes, A.; Evans, L.E.; Alhazzani, W.; Levy, M.M.; Antonelli, M.; Ferrer, R.; Kumar, A.; Sevransky, J.E.; Sprung, C.L.; Nunnally, M.E.; et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit. Care Med. 2017, 45, 486–552. [Google Scholar] [CrossRef]
- Vincent, J.L.; De Backer, D. Circulatory shock. N. Engl. J. Med. 2013, 369, 1726–1734. [Google Scholar] [CrossRef] [PubMed]
- Guarino, M.; Perna, B.; Cesaro, A.E.; Maritati, M.; Spampinato, M.D.; Contini, C.; De Giorgio, R. 2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department. J. Clin. Med. 2023, 12, 3188. [Google Scholar] [CrossRef] [PubMed]
- Hernández, G.; Teboul, J.L.; Bakker, J. Norepinephrine in septic shock. Intensive Care Med. 2019, 45, 687–689. [Google Scholar] [CrossRef] [PubMed]
- Shi, R.; Hamzaoui, O.; De Vita, N.; Monnet, X.; Teboul, J.L. Vasopressors in septic shock: Which, when, and how much? Ann. Transl. Med. 2020, 8, 794. [Google Scholar] [CrossRef] [PubMed]
- Ammar, M.A.; Ammar, A.A.; Wieruszewski, P.M.; Bissell, B.D.; TLong, M.; Albert, L.; Khanna, A.K.; Sacha, G.L. Timing of vasoactive agents and corticosteroid initiation in septic shock. Ann. Intensive Care 2022, 12, 47. [Google Scholar] [CrossRef] [PubMed]
- Alshahrani, M.S.; Alatigue, R. Association Between Early Administration of Norepinephrine in Septic Shock and Survival. Open Access Emerg. Med. 2021, 13, 143–150. [Google Scholar] [CrossRef] [PubMed]
- Persichini, R.; Silva, S.; Teboul, J.L.; Jozwiak, M.; Chemla, D.; Richard, C.; Monnet, X. Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit. Care Med. 2012, 40, 3146–3153. [Google Scholar] [CrossRef] [PubMed]
- Varpula, M.; Tallgren, M.; Saukkonen, K.; Voipio-Pulkki, L.M.; Pettilä, V. Hemodynamic variables related to outcome in septic shock. Intensive Care Med. 2005, 31, 1066–1071. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Li, H.; Zhang, D. Timing of norepinephrine initiation in patients with septic shock: A systematic review and meta-analysis. Crit. Care 2020, 24, 488. [Google Scholar] [CrossRef] [PubMed]
- Jouffroy, R.; Hajjar, A.; Gilbert, B.; Tourtier, J.P.; Bloch-Laine, E.; Ecollan, P.; Boularan, J.; Bounes, V.; Vivien, B.; Gueye, P.N. Prehospital norepinephrine administration reduces 30-day mortality among septic shock patients. BMC Infect. Dis. 2022, 22, 345. [Google Scholar] [CrossRef] [PubMed]
- Xu, F.; Zhong, R.; Shi, S.; Zeng, Y.; Tang, Z. Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis. Am. J. Emerg. Med. 2022, 54, 287–296. [Google Scholar] [CrossRef] [PubMed]
- Hamzaoui, O.; Jozwiak, M.; Geffriaud, T.; Sztrymf, B.; Prat, D.; Jacobs, F.; Monnet, X.; Trouiller, P.; Richard, C.; Teboul, J.L. Norepinephrine exerts an inotropic effect during the early phase of human septic shock. Br. J. Anaesth. 2018, 120, 517–524. [Google Scholar] [CrossRef] [PubMed]
- Boyd, J.H.; Forbes, J.; Nakada, T.A.; Walley, K.R.; Russell, J.A. Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit. Care Med. 2011, 39, 259–265. [Google Scholar] [CrossRef] [PubMed]
- Bertorello, A.M.; Sznajder, J.I. The dopamine paradox in lung and kidney epithelia: Sharing the same target but operating different signaling networks. Am. J. Respir. Cell Mol. Biol. 2005, 33, 432–437. [Google Scholar] [CrossRef]
- Jia, L.; Wang, P.; Li, C.; Xie, J. The efficacy and safety of vasopressors for septic shock patients: A systemic review and network meta-analysis. Shock 2023, 60, 746–752. [Google Scholar] [CrossRef] [PubMed]
- Mauvais-Jarvis, F.; Merz, N.B.; Barnes, P.J.; Brinton, R.D.; Carrero, J.-J.; DeMeo, D.L.; De Vries, G.J.; Epperson, C.N.; Govindan, R.; Klein, S.L.; et al. Sex and gender: Modifiers of health, disease, and medicine. Lancet 2020, 396, 565–582. [Google Scholar] [CrossRef] [PubMed]
- Coen, S.; Banister, E. (Eds.) What a Difference Sex and Gender Make: A Gender, Sex and Health Research Casebook; Canadian Institutes of Health Research: Ottawa, ON, Canada, 2012. [Google Scholar]
- O’Neil, A.; Scovelle, A.J.; Milner, A.J.; Kavanagh, A. Gender/Sex as a Social Determinant of Cardiovascular Risk. Circulation 2018, 137, 854–864. [Google Scholar] [CrossRef] [PubMed]
- Connelly, P.J.; Azizi, Z.; Alipour, P.; Delles, C.; Pilote, L.; Raparelli, V. The Importance of Gender to Understand Sex Differences in Cardiovascular Disease. Can. J. Cardiol. 2021, 37, 699–710. [Google Scholar] [CrossRef]
- Pilote, L.; Raparelli, V. Participation of Women in Clinical Trials: Not Yet Time to Rest on Our Laurels. J. Am. Coll. Cardiol. 2018, 71, 1970–1972. [Google Scholar] [CrossRef] [PubMed]
- Zucker, I.; Beery, A.K. Males still dominate animal studies. Nature 2010, 465, 690. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Montroy, J.; Sharma, R.; Fergusson, D.A.; Mendelson, A.A.; Macala, K.F.; Bourque, S.L.; Schlechte, J.M.; Eng, M.K.; McDonald, B.; et al. The Effects of Biological Sex on Sepsis Treatments in Animal Models: A Systematic Review and a Narrative Elaboration on Sex- and Gender-Dependent Differences in Sepsis. Crit. Care Explor. 2021, 3, e0433. [Google Scholar] [CrossRef] [PubMed]
- Failla, K.R.; Connelly, C.D.; Ecoff, L.; Macauley, K.; Bush, R. Does Gender Matter in Septic Patient Outcomes? J. Nurs. Scholarsh. 2019, 51, 438–448. [Google Scholar] [CrossRef] [PubMed]
- Sunden-Cullberg, J.; Nilsson, A.; Inghammar, M. Sex-based differences in ED management of critically ill patients with sepsis: A nationwide cohort study. Intensive Care Med. 2020, 46, 727–736. [Google Scholar] [CrossRef] [PubMed]
- Merdji, H.; Long, M.T.; Ostermann, M.; Herridge, M.; Myatra, S.N.; De Rosa, S.; Metaxa, V.; Kotfis, K.; Robba, C.; De Jong, A.; et al. Sex and gender differences in intensive care medicine. Intensive Care Med. 2023, 49, 1155–1167. [Google Scholar] [CrossRef]
- Failla, K.R.; Connelly, C.D. Systematic Review of Gender Differences in Sepsis Management and Outcomes. J. Nurs. Scholarsh. 2017, 49, 312–324. [Google Scholar] [CrossRef] [PubMed]
- Lakbar, I.; Einav, S.; Lalevée, N.; Martin-Loeches, I.; Pastene, B.; Leone, M. Interactions between Gender and Sepsis-Implications for the Future. Microorganisms 2023, 11, 746. [Google Scholar] [CrossRef] [PubMed]
- Riedel, K.; Deussen, A.J.; Tolkmitt, J.; Weber, S.; Schlinkert, P.; Zatschler, B.; Friebel, C.; Müller, B.; El-Armouche, A.; Morawietz, H.; et al. Estrogen determines sex differences in adrenergic vessel tone by regulation of endothelial β-adrenoceptor expression. Am. J. Physiol. Heart Circ. Physiol. 2019, 317, H243–H254. [Google Scholar] [CrossRef] [PubMed]
- Al-Gburi, S.; Deussen, A.; Zatschler, B.; Weber, S.; Künzel, S.; El-Armouche, A.; Lorenz, K.; Cybularz, M.; Morawietz, H.; Kopaliani, I. Sex-difference in expression and function of beta-adrenoceptors in macrovessels: Role of the endothelium. Basic. Res. Cardiol. 2017, 112, 29. [Google Scholar] [CrossRef] [PubMed]
- Dart, A.M.; Du, X.J.; Kingwell, B.A. Gender, sex hormones and autonomic nervous control of the cardiovascular system. Cardiovasc. Res. 2002, 53, 678–687. [Google Scholar] [CrossRef] [PubMed]
- Lee, R.M.; Gzik, D.J. Sympatholytic interventions and vascular remodelling. Basic. Res. Cardiol. 1991, 86 (Suppl. 1), 55–64. [Google Scholar] [PubMed]
- Loria, A.S.; Brinson, K.N.; Fox, B.M.; Sullivan, J.C. Sex-specific alterations in NOS regulation of vascular function in aorta and mesenteric arteries from spontaneously hypertensive rats compared to Wistar Kyoto rats. Physiol. Rep. 2014, 2, e12125. [Google Scholar] [CrossRef] [PubMed]
- Kneale, B.J.; Chowienczyk, P.J.; Brett, S.E.; Coltart, D.J.; Ritter, J.M. Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature. J. Am. Coll. Cardiol. 2000, 36, 1233–1238. [Google Scholar] [CrossRef] [PubMed]
- Freedman, R.R.; Sabharwal, S.C.; Desai, N. Sex differences in peripheral vascular adrenergic receptors. Circ. Res. 1987, 61, 581–585. [Google Scholar] [CrossRef] [PubMed]
- Hart, E.C.; Charkoudian, N.; Wallin, B.G.; Curry, T.B.; Eisenach, J.; Joyner, M.J. Sex and ageing differences in resting arterial pressure regulation: The role of the β-adrenergic receptors. J. Physiol. 2011, 589, 5285–5297. [Google Scholar] [CrossRef] [PubMed]
- Baker, S.E.; Limberg, J.K.; Ranadive, S.M.; Joyner, M.J. Neurovascular control of blood pressure is influenced by aging, sex, and sex hormones. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016, 311, R1271–R1275. [Google Scholar] [CrossRef]
- Heidari, S.; Babor, T.F.; De Castro, P.; Tort, S.; Curno, M. Sex and Gender Equity in Research: Rationale for the SAGER guidelines and recommended use. Res. Integr. Peer Rev. 2016, 1, 2. [Google Scholar] [CrossRef] [PubMed]
- Schreuder, W.O.; Schneider, A.J.; Groeneveld, A.B.; Thijs, L.G. Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Emphasis on right ventricular performance. Chest 1989, 95, 1282–1288. [Google Scholar] [CrossRef] [PubMed]
- Martin, C.; Papazian, L.; Perrin, G.; Saux, P.; Gouin, F. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993, 103, 1826–1831. [Google Scholar] [CrossRef] [PubMed]
- Ruokonen, E.; Takala, J.; Kari, A.; Saxén, H.; Mertsola, J.; Hansen, E.J. Regional blood flow and oxygen transport in septic shock. Crit. Care Med. 1993, 21, 1296–1303. [Google Scholar] [CrossRef] [PubMed]
- Marik, P.E.; Mohedin, M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994, 272, 1354–1357. [Google Scholar] [CrossRef] [PubMed]
- Guérin, J.P.; Levraut, J.; Samat-Long, C.; Leverve, X.; Grimaud, D.; Ichai, C. Effects of dopamine and norepinephrine on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy balance in vasoplegic septic patients. Shock 2005, 23, 18–24. [Google Scholar] [CrossRef]
- Mathur, S.K.; Chakraborty, A.; Rajiv, D. Comparison of norepinephrine and dopamine in the management of septic shock using impedance cardiography. Indian J. Crit. Care Med. 2011, 11, 186–191. [Google Scholar]
- De Backer, D.; Biston, P.; Devriendt, J.; Madl, C.; Chochrad, D.; Aldecoa, C.; Brasseur, A.; Defrance, P.; Gottignies, P.; Vincent, J.L.; et al. Comparison of dopamine and norepinephrine in the treatment of shock. N. Engl. J. Med. 2010, 362, 779–789. [Google Scholar] [CrossRef] [PubMed]
- Patel, G.P.; Grahe, J.S.; Sperry, M.; Singla, S.; Elpern, E.; Lateef, O.; Balk, R.A. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 2010, 33, 375–380. [Google Scholar] [CrossRef] [PubMed]
- Agrawal, A.; Gupta, A.; Consul, S.; Shastri, P. Comparative study of dopamine and norepinephrine in the management of septic shock. Saudi J. Anaesth. 2011, 5, 162–166. [Google Scholar] [CrossRef] [PubMed]
- Rudd, K.E.; Johnson, S.C.; Agesa, K.M.; Shackelford, K.A.; Tsoi, D.; Kievlan, D.R.; Colombara, D.V.; Ikuta, K.S.; Kissoon, N.; Finfer, S.; et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study. Lancet 2020, 395, 200–211. [Google Scholar] [CrossRef] [PubMed]
- Thompson, K.J.; Finfer, S.R.; Woodward, M.; Leong, R.N.F.; Liu, B. Sex differences in sepsis hospitalizations and outcomes in older women and men: A prospective cohort study. J. Infect. 2022, 84, 770–776. [Google Scholar] [CrossRef] [PubMed]
- Sakr, Y.; Elia, C.; Mascia, L.; Barberis, B.; Cardellino, S.; Livigni, S.; Fiore, G.; Filippini, C.; Ranieri, V.M. The influence of gender on the epidemiology of and outcome from severe sepsis. Crit. Care 2013, 18, R50. [Google Scholar] [CrossRef] [PubMed]
- Hubacek, J.A.; Stüber, F.; Fröhlich, D.; Book, M.; Wetegrove, S.; Ritter, M.; Rothe, G.; Schmitz, G. Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: Gender-specific genetic predisposition to sepsis. Crit. Care Med. 2001, 29, 557–561. [Google Scholar] [CrossRef] [PubMed]
- Laupland, K.B.; Gregson, D.B.; Church, D.L.; Ross, T.; Pitout, J.D. Incidence, risk factors and outcomes of Escherichia coli bloodstream infections in a large Canadian region. Clin. Microbiol. Infect. 2008, 14, 1041–1047. [Google Scholar] [CrossRef] [PubMed]
- Sato, R.; Kuriyama, A.; Takada, T.; Nasu, M.; Luthe, S.K. Prevalence and risk factors of sepsis-induced cardiomyopathy: A retrospective cohort study. Medicine 2016, 95, e5031. [Google Scholar] [CrossRef] [PubMed]
- Guidet, B.; Maury, E. Sex and severe sepsis. Crit. Care 2013, 15, 144. [Google Scholar] [CrossRef] [PubMed]
- Antequera, A.; Madrid-Pascual, O.; Solà, I.; Roy-Vallejo, E.; Petricola, S.; Plana, M.N.; Bonfill, X. Female under-representation in sepsis studies: A bibliometric analysis of systematic reviews and guidelines. J. Clin. Epidemiol. 2020, 126, 26–36. [Google Scholar] [CrossRef] [PubMed]
- Scott, P.E.; Unger, E.F.; Jenkins, M.R.; Southworth, M.R.; McDowell, T.Y.; Geller, R.J.; Elahi, M.; Temple, R.J.; Woodcock, J. Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs. J. Am. Coll. Cardiol. 2018, 71, 1960–1969. [Google Scholar] [CrossRef] [PubMed]
- Kragholm, K.; Halim, S.A.; Yang, Q.; Schulte, P.J.; Hochman, J.S.; Melloni, C.; Mahaffey, K.W.; Moliterno, D.J.; Harrington, R.A.; White, H.D.; et al. Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non-ST-Segment Elevation Acute Coronary Syndrome Patients: Insights from Clinical Trials over 17 Years. Circ. Cardiovasc. Qual. Outcomes 2015, 8, 357–367. [Google Scholar] [CrossRef] [PubMed]
- Hopper, I.; Kotecha, D.; Chin, K.L.; Mentz, R.J.; von Lueder, T.G. Comorbidities in Heart Failure: Are There Gender Differences? Curr. Heart Fail. Rep. 2016, 13, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Steinberg, J.R.; Turner, B.E.; Weeks, B.T.; Magnani, C.J.; Wong, B.O.; Rodriguez, F.; Yee, L.M.; Cullen, M.R. Analysis of Female Enrollment and Participant Sex by Burden of Disease in US Clinical Trials Between 2000 and 2020. JAMA Netw. Open 2021, 4, e2113749. [Google Scholar] [CrossRef] [PubMed]
- Bierer, B.E.; Meloney, L.G.; Ahmed, H.R.; White, S.A. Advancing the inclusion of underrepresented women in clinical research. Cell Rep. Med. 2022, 3, 100553. [Google Scholar] [CrossRef] [PubMed]
- NIH Guidelines on the inclusion of women and minorities as subjects in clinical research. Fed. Reg. 1994, 59, 14508–14513.
- Clayton, J.A.; Collins, F.S. Policy: NIH to balance sex in cell and animal studies. Nature 2014, 509, 282–283. [Google Scholar] [CrossRef] [PubMed]
- Liccardo, D.; Arosio, B.; Corbi, G.; Cannavo, A. Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases. J. Clin. Med. 2022, 11, 4280. [Google Scholar] [CrossRef] [PubMed]
- Subramaniapillai, S.; Galea, L.A.M.; Einstein, G.; de Lange, A.M.G. Sex and gender in health research: Intersectionality matters. Front. Neuroendocrinol. 2023, 72, 101104. [Google Scholar] [CrossRef]
- Parthasarathy, S.; Chi, F.W.; Metz, V.; Kline-Simon, A.; Asyyed, A.; Campbell, C.I.; Sterling, S. Disparities in the receipt of alcohol brief intervention: The intersectionality of sex, age, and race/ethnicity. Addiction 2023, 118, 1258–1269. [Google Scholar] [CrossRef] [PubMed]
- Misiura, M.B.; Butts, B.; Hammerschlag, B.; Munkombwe, C.; Bird, A.; Fyffe, M.; Hemphill, A.; Dotson, V.M.; Wharton, W. Intersectionality in Alzheimer’s Disease: The Role of Female Sex and Black American Race in the Development and Prevalence of Alzheimer’s Disease. Neurotherapeutics 2023, 20, 1019–1036. [Google Scholar] [CrossRef] [PubMed]
- Rushovich, T.; Boulicault, M.; Chen, J.T.; Danielsen, A.C.; Tarrant, A.; Richardson, S.S.; Shattuck-Heidorn, H. Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups. J. Gen. Intern. Med. 2021, 36, 1696–1701. [Google Scholar] [CrossRef] [PubMed]
- Fitzgerald, J.C.; Reddy, A.R.; Woods-Hill, C.Z. Let’s get loud: Amplifying female voices in sepsis research. EBioMedicine 2022, 86, 104370. [Google Scholar] [CrossRef]
First Author | Year | Study Design | Multi-Centric | Patients (n) | Mean Age (y) | Primary Outcome | Conclusions |
---|---|---|---|---|---|---|---|
Schreuder et al. [43] | 1989 | Prospective study | No | 10 | 57 | Compare NE vs. DA on hemodynamics, oxygen metabolism, and right ventricular performance. | NE was superior to DA in all the outcomes. |
Martin et al. [44] | 1993 | RCT | No | 32 | 52 | Compare NE vs. DA in reversing hemodynamic and metabolic abnormalities in septic shock. | NE is more effective and reliable than DA. |
Ruokonen et al. [45] | 1993 | RCT | No | 21 | 43 | Compare NE vs. DA in measuring the blood flow distribution and regional oxygen transport in septic shock. | Both NE and DE improved blood flow distribution and oxygen transport in septic shock. |
Marik et al. [46] | 1994 | RCT | No | 20 | 46 | Compare NE vs. DA on systemic and splanchnic hemodynamics in septic patients. | DA may cause an uncompensated increase in splanchnic oxygen requirement in septic patients. NE may have a more favorable hemodynamic profile. |
Guerin et al. [47] | 2005 | Prospective study | No | 12 | 40 | Compare NE vs. DA on systemic and splanchnic hemodynamics in septic patients. | NE was as effective as DA in maintaining splanchnic perfusion. The metabolic response might favor NE. |
Mathur et al. [48] | 2007 | RCT | No | 50 | 53 | Compare NE vs. DA in reversing hemodynamic and metabolic abnormalities in sepsis. | NE is more effective and reliable than DA on primary outcome. |
De Backer et al. [49] | 2010 | RCT | Yes | 1679 | 67 | Compare NE vs. DA on 28-day mortality in patients with shock. | No differences between NE and DA were detected. DA was associated with more adverse events. |
Patel et al. [50] | 2010 | RCT | No | 252 | N/A | Compare NE vs. DA on 28-day mortality in septic shock. | No differences between NE and DA were detected. DA was associated with more adverse events. |
Agrawal et al. [51] | 2011 | RCT | No | 50 | 53 | Compare NE vs. DA in reversing hemodynamic and metabolic abnormalities in septic shock. | NE was more useful than DA in reversing hemodynamic and metabolic abnormalities in septic shock. |
Authors | Reported Identity (Sex/Gender) | Other Categories (Yes/No) | Females n (%) | Males n (%) | Sensitivity Analysis by Sex (Yes/No) | Subgroup Analysis by Sex (Yes/No) | Post-Hoc Analysis by Sex (Yes/No) | Disaggregated Report of Results by Sex (Yes/No) |
---|---|---|---|---|---|---|---|---|
Schreuder et al. [43] | Sex | No | 6 (60.0%) | 4 (40.0%) | No | No | No | No |
Martin et al. [44] | Sex | No | 8 (25.0%) | 24 (75.0%) | No | No | No | No |
Ruokonen et al. [45] | N/A | No | N/A | N/A | No | No | No | No |
Marik et al. [46] | Sex | No | 9 (45.0%) | 11 (55.0%) | No | No | No | No |
Guerin et al. [47] | Sex | No | 1 (8.3%) | 11 (91.7%) | No | No | No | No |
Mathur et al. [48] | Sex | No | 18 (36.0%) | 32 (64.0%) | No | No | No | No |
De Backer et al. [49] | Sex | No | 723 (43.1%) | 956 (56.9%) | No | No | No | No |
Patel et al. [50] | Sex | No | 136 (54.0%) | 116 (46.0) | No | No | No | No |
Agrawal et al. [51] | Sex | No | 18 (36.0%) | 32 (64.0%) | No | No | No | No |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Perna, B.; Raparelli, V.; Tordo Caprioli, F.; Blanaru, O.T.; Malacarne, C.; Crosetti, C.; Portoraro, A.; Zanotto, A.; Strocchi, F.M.; Rapino, A.; et al. Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World? Microorganisms 2024, 12, 821. https://doi.org/10.3390/microorganisms12040821
Perna B, Raparelli V, Tordo Caprioli F, Blanaru OT, Malacarne C, Crosetti C, Portoraro A, Zanotto A, Strocchi FM, Rapino A, et al. Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World? Microorganisms. 2024; 12(4):821. https://doi.org/10.3390/microorganisms12040821
Chicago/Turabian StylePerna, Benedetta, Valeria Raparelli, Federica Tordo Caprioli, Oana Teodora Blanaru, Cecilia Malacarne, Cecilia Crosetti, Andrea Portoraro, Alex Zanotto, Francesco Maria Strocchi, Alessandro Rapino, and et al. 2024. "Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?" Microorganisms 12, no. 4: 821. https://doi.org/10.3390/microorganisms12040821