Clinical Summary | Critical Care, Emergency Medicine & Anaesthetics
Catecholamine concentration as a predictor of mortality in emergency surgical patients
Estimated Read Time: 7 minutes, 49 seconds
Originally Published: 18 July 2024
Source: International Journal of Emergency Medicine
Type of article: Clinical Research Summary
MedED Catalogue Reference: MCECS013
Category: Critical Care, Emergency Medicine & Anaesthetics
Cross-reference: Gerontology, Surgery
Keywords: serum epinephrine, nor-epinepherine gerontology, trauma, critical care, emergency surgery, morbidity
Originally Published in the International Journal of Emergency Medicine (18 July 2024) reproduced under Creative Commons Attribution 4.0 International License. This is a summary of the original clinical study and in no way represents the original research. Links to all original material can be found in the body of this summary.
Key Take Aways
1. The association between age and mortality in critical care settings is well-established
2. Undetectable serum epinephrine, which is more common in older patients, contributes to poor outcomes in these patients
3. The use of epinephrine might improve the clinical prognosis in older surgical patients with shock
Overview | Objectives | Study Design | Findings | Discussion| Limitations | Conclusion | Original Research | Funding | References
Overview
The correlation between age and mortality in trauma patients is well-documented, with age serving as a significant predictor of adverse outcomes. Previous studies, including those by Brattström et al.1, have established that in patients aged 55 years and older, age is an independent predictor of multiple organ failure, severe sepsis, and mortality.
In their 2012 study, Johansson et al.2, explored the relationship between sympathoadrenal activation—measured through circulating catecholamines—and biomarkers of coagulopathy in trauma patients. They identified that a trauma-induced catecholamine surge was closely associated with biomarkers that indicated tissue and endothelial damage, glycocalyx degradation, and coagulopathy, including hyperfibrinolysis, and is an independent predictor of mortality.
Their findings also revealed elevated plasma norepinephrine levels in these patients. Of interest, they found that the release of epinephrine was found to be attenuated in proportion to increases in the Injury Severity Score, particularly in older patients.
Building on these findings, in this study, Suh & da Roza et al. hypothesized that the use of vasopressin or norepinephrine in patients over 60 years of age would be associated with undetectable serum epinephrine levels. Furthermore, they posited that when serum epinephrine levels are undetectable, elevated serum norepinephrine levels would correlate with an increased risk of mortality.
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Study Purpose
This study aimed to determine whether the serum levels of epinephrine and norepinephrine at admission correlate with age and mortality in emergency surgical patients, including trauma and non-trauma patients.
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Study Design & Participant Selection
Participants
This prospective observational cohort study reviewed data from 90 patients who had been admitted to the ICU for post-operative care
• The majority of the patients were men [62 (68.9%)]; 28 (31.1%) were women
• Trauma patients (n =60) accounted for 66.7% of the admissions, and non-trauma patients (n=30) accounted for the remaining 33.3%
• All patients underwent emergency surgery
• 60 patients (66.7%) required mechanical ventilation
o Among the cohort, 44 patients (73%) were trauma cases, all of whom required mechanical ventilation within 24 hours prior to ICU admission
o The remaining 16 patients (27%) were non-trauma cases, with two of these patients requiring mechanical ventilation more than 48 hours before ICU admission
Data Collection
The following data was collected from ICU admission records and blood samples:
• Demographic data, including gender and age
• Pre-existing conditions, including diabetes mellitus, chronic obstructive pulmonary disease, hypertension, immunosuppression, congestive heart failure, coronary insufficiency, chronic kidney disease, or cancer
• Results from Sequential Organ Failure Assessment (SOFA) score, Glasgow Coma Scale score, and Simplified Acute Physiology Score III (SAPS III) at admission.
• Information related to the use of mechanical ventilation in ICU
• The use of vasoactive drugs such as norepinephrine (µg/kg per minute), epinephrine (µg/kg per minute), and vasopressin (units per hour)
• Surgical site (abdomen, brain, chest, or extremity).
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Findings
Levels of epinephrine and norepinephrine
The following were recorded:
• Serum levels of both epinephrine and norepinephrine exhibited significant variability, with standard deviations approximately 3 and 2 times greater than their respective means
• The mean levels of epinephrine and norepinephrine were considerably higher than the corresponding median values and third quartiles, contributing to the skewed distribution of these variables
• Notably, 60 (66.7%) of the 90 patients had undetectable serum levels of epinephrine, and as a result, these values were excluded from the calculation of descriptive statistics
• Undetectable serum epinephrine levels were predominantly observed in older patients receiving treatment with vasoactive drugs
Epinephrine Detection
On admission, the following was recorded:
• 34 patients were not receiving any vasoactive drugs
• 46 were receiving norepinephrine, vasopressin, or both, and eight were also receiving epinephrine
• Of the 60 patients who presented with undetectable serum levels of epinephrine – none were receiving exogenous epinephrine infusion
• Of the 46 patients who were receiving both vasopressin, norephedrine or both, serum ephedrine was detectable only in 36 (43,9%) individuals
• Seven of the patients who presented with the highest serum levels of epinephrine at admission were receiving exogenous epinephrine infusion
Age and serum levels of epinephrine
To assess whether age influenced the relationship between undetectable serum epinephrine levels and the administration of vasopressin or norepinephrine, the researchers compared outcomes between patients aged ≤ 60 years and those > 60 years.
• In patients over 60 years of age, the use of vasoactive drugs was significantly associated with undetectable epinephrine levels (OR [95% CI] = 6.36 [1.12, 36.08], p = 0.05).
• An additional significant relationship was observed between serum epinephrine levels, the administration of vasoactive drugs, and the type of surgery performed
Among the 90 patients analysed, 29 (32.2%) underwent brain surgery, 19 (21.1%) thoracic surgery, 26 (28.9%) abdominal surgery, and 17 (18.9%) extremity surgery.
o In patients undergoing brain surgery, 89% of those who received some form of norepinephrine and vasopressin had undetectable serum epinephrine levels, compared to 60% of those who did not receive these drugs.
o In thoracic surgery patients, serum epinephrine levels were similarly undetectable in 77% of individuals, compared to the 47% of individuals who did not receive these drugs
In hospital mortality and serum levels of epinephrine
Of the patients who had undetectable levels of epinephrine, the in-hospital mortality was higher among patients with a norepinephrine level ≥ 2006.5 pg/mL (OR [95% CI] = 4.00 [1.27, 12.58]), p = 0.03)
There was, however, was, no evidence to suggest an association between serum norepinephrine levels and in-hospital mortality when epinephrine was detectable
In the > 60-year age group, the mortality rate was 47.6%, compared with 20.8% in the ≤ 60-year age group (OR [95% CI] = 3.45 [1.37, 8.70], p = 0.01)
• Mortality was higher among patients with norepinephrine levels above 2006.5 pg/mL (OR [95% CI] = 2.94 [1.13, 7.64], p = 0.02)
Discussion
The study found that in patients over 60 years old, the use of vasopressin or norepinephrine was linked to undetectable serum epinephrine levels.
It also demonstrated that patients with undetectable serum epinephrine and serum norepinephrine levels ≥2006.5 pg/mL had a higher risk of death. The findings suggest that patients with a lower intrinsic sympathetic response might face worse outcomes and require more vasopressors in critical care settings.
Catecholamine secretion relies on the adaptation of chromaffin cells in the adrenal medulla through mechanisms such as neurotransmission at the cholinergic splanchnic–adrenal synapse, intercellular communication, and activation of voltage-gated calcium channels.
Disruptions in these mechanisms are common in critically ill patients, with up to 20% of critically ill patients and 60% of those with sepsis experiencing hypothalamic–pituitary–adrenal axis dysfunction, abolishing or reducing the intensity of cortisol activity. The study aligned with previous findings that this dysfunction is more pronounced in patients over 60 years of age. 3,4,5
Moreover, the increased likelihood of undetectable epinephrine levels in patients over 60 years old aligns with the established understanding that hypothalamic–pituitary–adrenal axis dysfunction is more common in critically ill individuals within this age group, as reported by Rushworth et al.5 and the study by Johansson et al.1, which found lower epinephrine levels in older trauma patients.
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Limitations
Suh & da Roza et al. noted the following limitations of their study:
- The study was observational and lacked a control group.
- Data prior to ICU admission and before vasoactive drug administration were not accessible, limiting the analysis of the autonomic mechanisms involved.
- The sample group was heterogeneous, encompassing varying trauma severities and including non-trauma patients.
- Relying on single measurements rather than serial ones made it challenging to assess the intensity and duration of hypothalamic–pituitary–adrenal axis dysfunction and its correlation with the evaluated variables.
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Conclusion
Despite the study's limitations, the researchers highlight that the findings raise a crucial question: whether administering higher doses of epinephrine in older critically ill patients and surgical patients with shock, who already exhibit elevated serum norepinephrine levels, could potentially improve outcomes.
They conclude that their study demonstrates a clear association between age and mortality in surgical critical care patients. The findings suggest that undetectable levels of epinephrine, which are more frequently observed in older patients, may contribute to the poor outcomes seen in this group.
Further studies with larger patient samples are needed in order to corroborate the study findings.
Access the original research
Suh, J.I., da Roza, D.L., Cadamuro, F.M. et al. Catecholamine concentration as a predictor of mortality in emergency surgical patients. Int J Emerg Med 17, 95 (2024). https://doi.org/10.1186/s12245-024-00676-4
Reproduced under Creative Commons Attribution 4.0 International License
Conflict of Interest, Funding and Support
Role of the Funder/Sponsor:
The study was approved by the Research Ethics Committee of the Hospital das Clinicas of the University of Sao Paulo School of Medicine (Reference no. 3.449.754) and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patients or their legal guardian.
Conflict of Interest Disclosures:
No conflicts of interest disclosed
Funding/Support:
L. Andrade is the recipient of a grant from the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development; Grant no. 309683/2021-1).
This study was reproduced under Creative Commons Attribution 4.0 International License. The Creative Commons Public Domain Dedication waiver applies to the data made available in the study.
References
1. Brattström O, Granath F, Rossi P, Oldner A. Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit.Acta Anaesthesiol Scand. 2010;54(8):1007-1017. doi:10.1111/j.1399-6576.2010.02266.x
2. Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. High circulating adrenaline levels at admission predict increased mortality after trauma. J Trauma Acute Care Surg. 2012;72(2):428-436. doi:10.1097/ta.0b013e31821e0f93
3. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises in older patients. Lancet Diabetes Endocrinol. 2020;8(7):628-639. doi:10.1016/S2213-8587(20)30122-4
4. Rushworth, R. L., Goubar, T., Ostman, C., McGrath, S., & Torpy, D. J. (2020). Interaction between hypotension and age on adrenal crisis diagnosis. Endocrinology, diabetes & metabolism, 4(2), e00205. https://doi.org/10.1002/edm2.205
5. Cooper, M. S., & Stewart, P. M. (2003). Corticosteroid insufficiency in acutely ill patients. The New England journal of medicine, 348(8), 727–734. https://doi.org/10.1056/NEJMra020529
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