|Year : 2020 | Volume
| Issue : 1 | Page : 117-123
Microalbuminuria as an early postoperative detector of sepsis after major surgeries
Ali A Mahareak, Sameh H Seyam
Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||29-Nov-2019|
|Date of Acceptance||23-Dec-2019|
|Date of Web Publication||16-Apr-2020|
MD Ali A Mahareak
6308 King Khalid Street, 62461-4080 Khamis Mushait, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Background Recently, many prognostic markers have been developed for early prediction of sepsis.
Purpose To study if microalbuminuria has an early detection value in surgical sepsis and is correlated with other scoring systems.
Patients and methods This observational prospective correlation study was done in Al-Azhar University hospitals. A total of 26 patients aged between 21 and 65 years were included in the study. Patients were chosen after 48 h of admission to the ICU after major surgeries. The patients were evaluated upon admission and 24 h later for manifestations of sepsis. Spot urine samples were obtained at the preoperative time, on ICU admission [albumin/creatinine ratio 1 (ACR1)], 24 h postoperative (ACR2), and 48 h postoperative (ACR3). ICU scoring systems included Acute Physiological and Chronic Health Evaluation II (APACHE II) score evaluated every 24 h for 72 h, and the Sequential Organ Function Assessment (SOFA) score was evaluated daily until ICU discharge or up to a total of 28 days.
Results A total of 26 patients were involved in this correlational study after exclusions. There was no correlation between ACR1 and APACHE II score or SOFA score or the length of ICU stay. There was a positive correlation between ACR2 and ACR3 with APACHE score on day 1 and day 2 and SOFA score on day 1 and day 2. There was a positive correlation between ACR2 and ACR3 and the length of ICU stay. There was no statistically significant difference between ACR on admission, ACR on day 1, and ACR on day 2 in patients who needed vasopressors and those who needed dialysis therapy. Only ACR2 was a significant predictor for mortality in our patient population.
Conclusion Microalbuminuria a simple and ready tool that has a unique prognostic value in patients with sepsis following major surgeries.
Keywords: Acute Physiological and Chronic Health Evaluation, major surgeries, microalbuminuria, sepsis, Sequential Organ Function Assessment
|How to cite this article:|
Mahareak AA, Seyam SH. Microalbuminuria as an early postoperative detector of sepsis after major surgeries. Res Opin Anesth Intensive Care 2020;7:117-23
|How to cite this URL:|
Mahareak AA, Seyam SH. Microalbuminuria as an early postoperative detector of sepsis after major surgeries. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 May 31];7:117-23. Available from: http://www.roaic.eg.net/text.asp?2020/7/1/117/282588
| Introduction|| |
Sepsis continues to be a significant critical care entity with high mortality. Targeted therapies supposedly lose their effectiveness owing to delayed administration .
In critical care environments, anticipating the outcome of patients is of crucial importance to the intensivist. It allows deciding of early therapeutic maneuvers, optimum resource allotment, and appropriate advising of the family or patient .
By definition, microalbuminuria is a urinary albumin concentration of 30–200 mg/l. It is exhibited as the urinary albumin to creatinine ratio (ACR) to correct for alterations in urine output . Moreover, some studies demonstrate that microalbuminuria may be an early tool for anticipating mortality in numerous groups of critically ill patients .
Microalbuminuria has not only an anticipating value of organ impairment and vasopressor/inotropic requirements but also of mortality, being higher to the Sequential Organ Function Assessment (SOFA) score and Acute Physiological and Chronic Health Evaluation II (APACHE II) score .
| Aim|| |
The aim was to study the correlation value of microalbuminuria as an early postoperative detector in surgical sepsis with the primary outcome (severity of sepsis based on sepsis scores) and secondary outcomes (correlation with ICU stay, the need for cardio-respiratory support and mortality rate).
| Patients and methods|| |
This prospective observational single-blinded correlational study was approved by the Medical Ethics Committee at the Faculty of Medicine, Al-Azhar University. We prospectively enrolled 26 patients. Patients were chosen at the critical care unit following elective major surgeries. This correlational study was performed at the surgical critical care unit, Sayed Galal Hospital, Faculty of Medicine, Al-Azhar University, over the period from March 2016 to March 2017. Informed consent was given by the patient or first-degree relative. This study did not interfere with the current medical practice of the investigator. No invasive medical procedure is required by the study. The investigator can decide for any treatment that is in the best interest of his patients.
The data were collected for each patient upon ICU admission, including age, sex, date and time of admission, type of surgery, and associated disorders such as diabetes, hypertension, and chronic renal disease. Laboratory data were collected and cultures sent.
An intensivist evaluated patients upon admission and 24 h later, for manifestations of systemic inflammatory response syndrome (SIRS) and/or infection. The diagnosis of infection depended on the clinical signs and laboratory markers of inflammation with the presence of polymorphonuclear cells in body fluids and/or culture or gram stain showing the presence of microorganisms.
According to the Society of Critical Care Medicine criteria of sepsis, postoperative onset was suspected by the treating physician by confirmed infection + criteria of SIRS. SIRS (Society of Critical Care Medicine criteria)  was diagnosed when there were two or more of the following: heart rate more than 90/min, respiratory rate more than 20/min or PaCO2 less than 32 mmHg, temperature more than 38°C or less than 36°C, white blood cell count more than 12 000/mm3 or less than 4000/mm3, or more than 10% immature neutrophils.
All patients (21–65 years) undergoing elective major surgery with ICU admission for more than 48 h were involved in the study. Patients with preoperative clinical manifestations or laboratory signs of infection were omitted from the study. Exclusion criteria included patients with diabetes or with concurrent treatment with any of the antiproteinuric drugs, angiotensin II, angiotensin I receptor blockers, lipid-lowering drugs such as statins or fibrates [angiotensin-converting enzyme inhibitors (ACE-I), and recently also oral glycosaminoglycans and sulodexide]; patients with chronic renal disease (serum creatinine level ≥2.0 mg/dl); patients on replacement therapy (dialysis); patients with no urine output on the first day of admission; patients with hematuria, and those with hospital stay less than 48 h were omitted from the study.
Patients included prospectively were selected in the study on the day of ICU admission and they were followed up for a terminal period of 28 days or until the day of discharge or demise.
Patient evaluation included full clinical evaluation including history and physical examination with special emphasis on vital signs (heart rate, blood pressure, respiratory rate, and temperature) and Glasgow Coma Scale which were evaluated at the preoperative time, on ICU admission, 24 h postoperative, and 48 h postoperative. Moreover, laboratory investigations involved complete blood count, including hemoglobin, hematocrit, white blood cells, and platelet count; arterial blood gases; liver function tests, including alanine aminotransferase, aspartate aminotransferase, bilirubin, and albumin; kidney function tests, including Na, K, creatinine, and urea; random blood sugar; and coagulation profile, including prothrombin time, prothrombin concentration, international normalization ratio, and partial thromboplastin time. These routine laboratory investigations were withdrawn on study day 1 and then daily for 3 days. The specific laboratory investigations for the study, exhibited as the urinary ACR to correct the alterations in urine output, were referred to as ACR .
Spot urine samples were taken at the preoperative time, on ICU admission (ACR1), 24 h postoperative (ACR2) and 48 h postoperative (ACR3). Urinary creatinine concentration was checked by a modified kinetic Jaffe reaction (Dimension RxL Max; Dade Behring Inc., 40 Liberty Boulevard Malvern, PA, United States of America), whereas urinary microalbumin concentration was checked by the immunoturbidimetric method .
Microalbuminuria was represented in our study by a ratio between albumin and creatinine and expressed as ACR if values occurred between 30 and 299 mg/g creatinine. Clinical proteinuria is considered if the ACR of more than 300 mg/g creatinine. A healthy human has ACR less than 30 mg/g creatinine . Values above 300 mg/g creatinine are suggestive of macroalbuminuria .
Microbiological studies included full sepsis workup (sputum, blood, urine, wound or biological fluid culture according to clinical suspicion) before antibiotic administration. Clinical data involved length of ICU stay, the primary outcome (severity of sepsis), or secondary outcome (correlation with ICU stay, the need for cardio-respiratory support and mortality rate) reported for all patients. Imaging studies were required to identify the source of sepsis, for example, chest radiography and ultrasound. ICU scoring systems included APACHE II score evaluated every 24 h for 72 h , and the SOFA score was evaluated daily until ICU discharge or up to a total of 28 days .
The documented clinical data were blinded by the investigator who examined the laboratory results.
Sample size calculation was based on a previous study, depending on a correlation coefficient (rho) of 0.55 between ACR2 and sepsis scores; we calculated that a total sample size of 24 patients would be sufficient to give α=0.05 with confidence interval 95% and actual power 80% and β=0.20. Assuming 10% potential for patients to drop out of the study, the total sample size was increased to 26 patients.
Data were collected and analyzed using SPSS computer software version 22 (SPSS Inc., Chicago, Illinois, USA). Data were expressed as a mean (±SD), median (interquartile range), frequencies (number of cases), and relative frequencies (percentages) when appropriate. A nonparametric test (Mann–Whitney U test) was used for comparison between survival and nonsurvival patients regarding quantitative variable to test a positive or negative relationship between the two variables. Receiver operator characteristic analysis was done to define a cutoff value of a variable. Sensitivity was estimated as true positive/(true positive plus false negative), and specificity was estimated as true negative/(true negative plus false positive). Statistical significance was considered if P value less than 0.05, otherwise it was insignificant.
| Results|| |
Patients who developed sepsis throughout the study period were 39 patients; from this number, only 26 patients were included for the study after exclusions. A total of 13 patients were excluded from the study. Patient’s demographic data (age, sex, BMI, and ASA physical status), types of surgeries, and etiology of sepsis are summarized in [Table 1].
[Table 2] shows ACR, APACHE II score, and SOFA score on admission, at 24 and 48 h. [Table 3] shows the clinical course of patients during ICU stay, including ICU stay, the need for mechanical ventilation, vasopressors, and dialysis. Three (11.5%) of the 26 patients died in the ICU.
There was no correlation between ACR1 (admission ACR) and APACHE II score or SOFA score or the length of ICU stay. There was a positive correlation between both ACR2 and ACR3 and APACHE score on day 1 and day 2 and SOFA score on day 1 and day 2. Moreover, there was a positive correlation between both ACR2 and ACR3 and the length of ICU stay ([Table 4]).
|Table 4 Correlation between albumin/creatinine ratio 1, albumin/creatinine ratio 2, and albumin/creatinine ratio 3 and Sequential Organ Function Assessment, Acute Physiological and Chronic Health Evaluation scores, and ICU stay|
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There was no significant difference between ACR upon admission and ACR on day 1 in patients who needed and those who did not require mechanical ventilation, whereas ACR on day 2 was significantly higher in patients who required mechanical ventilation compared with those who did not need ([Table 5]).
|Table 5 Microalbuminuria and in need of vasopressor support, mechanical ventilation, and dialysis|
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There was no statistically significant difference between ACR on admission, ACR on day 1, and ACR on day 2 in patients who need vasopressors and those who need dialysis therapy ([Table 5]).
A comparison between the survivors and nonsurvivors showed that median ACR3, APACHE II scores, SOFA scores, and duration of ICU stay were significantly higher in patients who died ([Table 6]).
|Table 6 Comparing microalbuminuria, Acute Physiological and Chronic Health Evaluation II scores, Sequential Organ Function Assessment scores, and ICU stay between survival and nonsurvival patients|
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Regarding prognostic value of microalbuminuria, the ROC curve was calculated for the use of microalbuminuria as a predictor of the severity of sepsis. Owing to the small area under the curve, it is not feasible to calculate a cutoff value for ACR1 to predict the severity of sepsis, but the area under the curve is larger for ACR2 and ACR3 so the cutoff value can easily be calculated. Only ACR2 was a significant predictor for the severity of sepsis in our patient population, with an increase in sensitivity and a decrease in specificity with the increase of cutoff values ([Table 7], [Figure 1]).
|Table 7 Microalbuminuria sensitivity and specificity for severity of sepsis prediction|
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|Figure 1 Receiver operator characteristic curve (ROC curve) of ACR1, ACR2, and ACR3 for mortality prediction. ACR1, albumin/creatinine ratio on admission; ACR2, albumin/creatinine ratio after 24 h postoperative; ACR3, albumin/creatinine ratio after 48 h postoperative.|
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| Discussion|| |
Sepsis is common in critical patients following major surgeries . Early detection of sepsis effect in those patients is of great value in the clinical management, so rapid induction of microalbuminuria that occurs within a few hours of an inflammatory process is strongly important than the relatively delayed procalcitonin and C-reactive protein .
We tried in this study to investigate the value of microalbuminuria as a detection tool for early detection, clinical progression, severity, and mortality in critically ill patients after major surgeries. Microalbuminuria was previously used in several studies as an important prognostic marker of illness severity and mortality in critically ill nonsurgical patients with a high risk of morbidity and mortality .
There is increased predominance of microalbuminuria in critically ill patients, frequently caused by endothelial dysfunction arising from the effects of inflammatory mediators, released during the severe inflammatory aggressions that are appended with critical illnesses leading to a systemic increase in capillary permeability .
Microalbuminuria would be a unique marker for the early perception of sepsis-induced inflammation in patients with a high risk of morbidity and mortality. This would allow the ICU physician to decide early therapeutic interventions in patients most likely to get benefit from its use, especially in situations of financial limitations . Measurement of the amount of microalbumin excreted in urine, expressed as ACR , is a simple, sincere, and low-cost test that adjusts for different urine concentrations among critically ill patients and avoids the need for a timed urine collection; moreover, it can be done while the patient in bed, and results can be obtained as early as 15 min .
On the contrary, the ICU prognostic scores such as APACHE and SOFA scores require variable data collection within 24 h and involve meticulous statistical analyses to anticipate mortality as an outcome.
In our study, there was no correlation between ACR1 (admission ACR) and SOFA score or APACHE II score or the length of ICU stay. There was a positive correlation between both ACR 2 and ACR3 and APACHE score on day 1 and day 2 and SOFA score on day 1 and day 2. There was a positive correlation between both ACR2 and ACR3 and the duration of ICU stay.
Our findings are compatible with the study by Saeed et al. , they included 40 adult patients with sepsis, but the type of sepsis was not specified. They found no significant correlation between ACR1 upon admission and either SOFA or APACHE IV scores, though ACR2 measured after 24 h was significantly correlated with SOFA score but was not statistically significantly correlated with APACHE IV score. Moreover, the SOFA but not APACHE IV score is higher in patients with a rising reading of ACR. Usually, APACHE IV involves more data which may be not significant during the first few days postoperatively like PaO2, creatinine, and other data. So, this may be the explanation of why no correlation between ACR2 and APACHE IV score 24 h later after admission.
In the present study, we found that ACR upon admission and ACR on day 1 were not statistically different in patients who needed and those who did not need mechanical ventilation, whereas ACR on day 2 was significantly higher in patients who needed mechanical ventilation compared with those who did not need. Moreover, there was no statistically significant difference between ACR upon admission, ACR on day 1, and ACR on day 2 in patients who need vasopressors and those who need dialysis therapy. The paucity of an alliance between the ACR and the need for dialysis therapy can appertain to the small sample size and a small number of patients who needed dialysis (only six patients). Compared with other researches, also we did not follow up and assess the evolution of acute kidney injury (AKI) that did not reach the level of renal replacement therapy, so we may miss an association between ACR and kidney injury.
According to Gosling et al. , ACR is inversely related to the PaO2/FiO2 ratio in post-trauma patients and was associated with significantly more need for mechanical ventilation in patients with initially normal lung functions. What we have observed in the current study is the strong correlation between ACR2 and the need for mechanical ventilation.
Our results were also coinciding with Zhang et al.  in patients with sepsis and normal kidney results. They found that ACR on second day postadmission was greater in critically ill patients who developed AKI, and also they found that ACR on the second day of admission (43 mg/g) was 91.7% sensitive and 79.2% specific for anticipating AKI in patients complaining of sepsis.
In our study, a comparison between the survivors and nonsurvivors showed that median ACR3, SOFA scores, APACHE II scores, and the duration of ICU stay were significantly higher in patients who died.
In agreement with our study, Gosling et al.  observed that median ACR1 amid survivors was 37.2 and ACR1 amid nonsurvivors was 161.8, with P value less than 0.0002, which was significant statistically.Gopal et al.  concluded that ACR may carry promise as an anticipating tool of mortality. ROC curve and area under the curve obtained by Bhadade et al.  for anticipating of mortality were highest for ACR2 (0.943) and changes in ACR overtime (0.943), followed by APACHE II (0.835), SOFA (0.788), and ACR1 (0.725). Bhadade and colleagues did there study on 125 critically ill patients with nonsurgical sepsis, and for these types of patients, the inflammatory process is more earlier, so this may be the explanation why ACR1 reading was approximately high in comparison with ACR2. ACR2 is as good as APACHE II for anticipating of mortality, and this was also achieved by Basu et al. .
| Conclusion|| |
Microalbuminuria a simple, ready tool that has a unique prognostic benefit in patients with sepsis following major surgeries, owing to its role in predicting disease severity, clinical progression, the primary outcome (severity of sepsis), and secondary outcome (correlation with ICU stay, the need for cardio-respiratory support, and mortality rate).
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]