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Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: For the third International Consensus Definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):775-87. Available from: doi:10.1001/jama.2016.0289. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200-11. Available from: doi:10.1016/S0140-6736(19)32989-7. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock. Crit Care Med. 2016;43(3):304-77. Available from: doi:10.1007/s00134-017-4683-6. Smyth MA, Brace-McDonnell SJ, Perkins GD. Identification of adults with sepsis in the prehospital environment: A systematic review. BMJ Open. 2016;6(8). Available from: doi:10.1136/bmjopen-2016-011218. Bayer O, Schwarzkopf D, Stumme C, Stacke A, Hartog CS, Hohenstein C, et al. An early warning scoring system to identify septic patients in the prehospital setting: The PRESEP score. Acad Emerg Med. 2015;22(7):868–71. Available from: doi:10.1111/acem.12707. Koch C, Edinger F, Fischer T, Brenck F, Hecker A, Katzer C, et al. Comparison of qSOFA score, SOFA score, and SIRS criteria for the prediction of infection and mortality among surgical intermediate and intensive care patients. World J Emerg Surg. 2020;15(63). Available from: doi:10.1186/s13017-020-00343-y. Chakraborty RK, Burns B. Systemic Inflammatory Response Syndrome. StatPearls Publishing; 2020. Available from https://www.ncbi. nlm.nih.gov/books/NBK547669/ [cited 2021 Jan 21]. Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015;372(17):1629-38. Available from: doi:10.1056/NEJMoa1415236. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: For the third International Consensus Definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):762-74. Available from: doi:10.1001/jama.2016.0288. Kovach CP, Fletcher GS, Rudd KE, Grant RM, Carlbom DJ. Comparative prognostic accuracy of sepsis scores for hospital mortality in adults with suspected infection in non-ICU and ICU at an academic public hospital. PLoS One. 2019;14(9). Available from: doi:10.1371/ journal.pone.0222563. Peng Y, Zhang W, Xu Y, Li L, Yu W, Zeng J, et al. Performance of SOFA, qSOFA and SIRS to predict septic shock after percutaneous nephrolithotomy. World J Urol. 2020. Available from: doi:10.1007/s00345-020-03183-2. Costa RT, Nassar AP Jr, Caruso P. Accuracy of SOFA, qSOFA, and SIRS scores for mortality in cancer patients admitted to an intensive care unit with suspected infection. J Crit Care. 2018;45:52-7. Available from: doi:10.1016/j. jcrc.2017.12.024. Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score—development, utility and challenges of accurate assessment in clinical trials. Critical Care. 2019;23(1):74. Available from: doi:10.1186/s13054-019-2663-7. Freund Y, Lemachatti N, Krastinova E, Van Laer M, Claessens YE, Avondo A, et al. French Society of Emergency Medicine Collaborators Group. Prognostic accuracy of Sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA. 2017;317(3):301-8. Available from: doi:10.1001/jama.2016.20329. Jiang J, Yang J, Mei J, Jin Y, Lu Y. Head-tohead comparison of qSOFA and SIRS criteria in predicting the mortality of infected patients in the emergency department: A meta-analysis. Scand J Trauma Resusc Emerg Med. 2018;26(1). Available from: doi:10.1186/ s13049-018-0527-9. Critical Care Summit. New sepsis definitions and qSOFA - Craig Coopersmith MD, FACS, FCCM. [Video] 2016. Available from https:// www.youtube.com/watch?v=3kNbW_T-vrA [cited 2021 Jan 21]. Lee SM, An WS. New clinical criteria for septic shock: serum lactate level as new emerging vital sign. J Thorac Dis. 2016;8(7):1388-90. Available from: doi:10.21037/jtd.2016.05.55. Foucher CD, Tubben RE. Lactic Acidosis. Florida: StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK470202/ [cited 2021 Jan 21]. Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through 2 stimulation is a common mechanism involved in lactate formation during shock states. Shock. 2008;30(4):417-21. Available from: doi:10.1097/SHK.0b013e318167378f.
cells and into the blood as waste products.25 Decreased blood flow from sepsis results in elevated levels of metabolic waste in the bloodstream.26 As such, etCO2 levels are inversely proportional to lactate levels.26 Hunter et al. developed a general guideline for EMS personnel to follow, showing that etCO2 levels below 25 mmHg are strongly correlated with serum lactate levels above 4 mmol/L.27 Wiryana et al. further validate these findings, demonstrating a strong correlation between etCO2 and lactate levels.28 DISCUSSION As the severity of sepsis is exacerbated by delayed treatment, its early recognition in the pre-hospital setting is paramount to increasing patient survival rates. Current EMS sepsis protocols lack standardization and result in poor recognition of sepsis among EMS teams. Thus, the implementation of a pre-hospital screening tool that is simple, accurate, and timeefficient is crucial to patient survival. Through evaluating the existing systems in place for sepsis identification, it should be underscored that the speed of qSOFA tests can be complemented by the accuracy provided by lactate measurements, thus making it an ideal candidate for pre-hospital sepsis screening. The qSOFA tool is heavily criticized for its poor sensitivity; yet, when measured in combination with lactate as a biomarker, its performance is improved. Research consistently demonstrates that LqSOFA scores can predict in-hospital mortality more accurately than qSOFA, SOFA, and SIRS.29-31 As discussed previously, capnography may serve as a novel lactate measuring technology for EMS personnel: they produce results instantaneously, are already part of ambulance equipment, and require minimal additional training to be applied in a sepsis context. Integrating lactate testing via capnography into the qSOFA criteria may thus be ideal for prehospital paramedic use. Some EMS centres have already adopted sepsis protocols measuring lactate via etCO2 readings. Sepsis Alert —an EMS protocol that has been introduced in Denver, Colorado— is nearly identical to qSOFA apart from the additional criterion of etCO2 levels less than or equal to 25 mmHg. When Sepsis Alert was initiated in Denver, the overall mortality for severe sepsis patients transported by EMS was nearly halved, from 26.7% to 13.6%.32
While LqSOFA tests may serve as a promising tool, it is essential that EMS centres reinforce training to improve sepsis detection rates.22 As EMS personnel treat patients in emergency situations, the identification of immediate injuries may be prioritized over the diagnosis of later-onset sepsis.33 Studies by Green et al. show that three-hour training sessions for EMS clinicians on identifying sepsis in patients increase early-diagnosis of sepsis in 40%–50% of emergency cases.32 However, the introduction of qSOFA and lactate technologies are more efficient to use and provide ambulatory clinicians with greater time and opportunity to identify sepsis. Hence, strengthening training on sepsis diagnosis, particularly the use of qSOFA and etCO2 technologies, may assist EMS personnel in improving the identification of sepsis. Though current studies suggest that LqSOFA criteria may significantly improve rates of patient diagnosis, there are limitations to this proposal. Few studies have clinically tested the effectiveness of qSOFA paired with etCO2 levels. Research by Guerra et al. demonstrated that the Sepsis Alert protocol could reduce mortality for sepsis patients arriving via EMS. These benefits are challenged by Daniel J. Lane, who suggested that this hybrid criteria yields no significant improvements in sensitivity or specificity compared to qSOFA alone.30,34 Green et al. explains that different clinical settings may benefit from different technologies to varying extents. In summary, additional research needs to be conducted to assess the validity of using etCO2 measurements to enhance qSOFA screening.34 CONCLUSION Of existing in-hospital sepsis screening tools, qSOFA demonstrates the greatest potential for practical usage in an EMS setting. While qSOFA’s simplicity impacts its accuracy, the addition of a novel lactate biomarker may significantly improve test sensitivity. Research presents capnography devices as a promising alternative for existing lactate laboratory tests that, when used in combination with qSOFA and effective training, may improve early diagnosis of sepsis by EMS providers. Further research is needed to assess the accuracy of an LqSOFA score in a pre-hospital setting.
