Early predictive markers of peri-operative acute kindey injury

Acute kidney injury following major surgery represents a common, yet under-diagnosed entity which is known to be one of the most significant causes of perioperative morbidity and mortality, a fact which underscores the importance of this syndrome’s early diagnosis. While there is plenty of evidence regarding perioperative acute kidney injury in cardiac surgery patients, data for general surgery patients are limited. It is well known that serum creatinine concentration, which is still the most widespread method in assessing renal function and detecting renal damage, has rather limited value in the early detection of post-operative acute kidney injury and the assessment of acute changes in glomerular filtration rate, a fact which has resulted in the study of numerous alternative markers of acute kidney injury. The aim of the present study was a) to determine the incidence of acute kidney injury following major abdominal surgery and to recognize associated perioperative factors, b) to evaluate the role of serum cystatin C as well as other biochemical parameters of glomerular or tubular kidney damage as early markers of perioperative acute kidney ιinjury, before a diagnosis by traditional laboratory methods is established, in order to optimize perioperative patient management. Sixty-eight patients undergoing elective major abdominal surgery at the University Hospital of Heraklion were prospectively studied. Patients with chronic kidney disease stage IV or V, on hemodialysis or peritoneal dialysis as well as renal transplant patients were excluded. At pre-defined time points (preoperatively, recovery room and on postoperative days 1, 3, 5 and 7) the following parameters were measured: serum cystatine C, urea, creatinine, Na, K, prealbumin and retinol binding protein, as well as urine creatinine, urea, Na, K, Cl, a1- and b2-microglobulin, a2-macroglobulin, IgG, transferrin and albumin, while fractional excretions of sodium, potassium and urea, glomerular filtration rate, urine albumin to creatinine ratio and urine strong ion difference were calculated. Diagnosis of acute kidney injury was based on the Acute Kidney Injury Network criteria. This study showed that approximately one out of five elective major abdominal surgery patients developed perioperative acute kidney injury. Preoperative albuminuria, expressed as elevated urine albumin to creatinine ratio, was found to be independently associated with postoperative acute kidney injury development (OR = 5.47, 95% CI: 1.36-21.92, p = 0.019). The intraoperative factors found to be associated with perioperative acute kidney injury were blood loss (p = 0.002), RBC and FFP transfusion (p = 0.042 and 0.006 respectively), as well as the administered, by either crystalloid and/or colloid infusion, chloride load (p = 0.043). Compared to non-AKI patients, patients developing acute kidney injury had significantly lower urine sodium and chloride concentrations as well as a significantly higher fractional excretion of potassium. These differences were already evident in the recovery room, indicating an early decline in glomerular filtration rate, much earlier than AKI diagnosis by AKIN criteria can be established. Similarly, postoperative change in urine strong ion difference (ΔSIDU) was already in the recovery room significantly lower in AKI patients compared to non-AKI patients, indicating early impairment in chloride excretion due to tubular damage.Η οξεία νεφρική βλάβη μετά από μείζονα χειρουργική επέμβαση αποτελεί συχνή, πλην όμως υπο-διαγνωσμένη οντότητα, η οποία συνιστά μία από τις σημαντικότερες αιτίες περιεγχειρητικής νοσηρότητας και θνητότητας, γεγονός που καθιστά την έγκαιρη διάγνωσή της κεφαλαιώδους σημασίας. Πέραν τούτου, ενώ υπάρχει εκτεταμένη βιβλιογραφία ως προς την περιεγχειρητική οξεία νεφρική βλάβη σε καρδιοχειρουργικούς ασθενείς, τα αντίστοιχα δεδομένα για μείζονες χειρουργικές επεμβάσεις κοιλιάς είναι περιορισμένα. Είναι γνωστό ότι η συγκέντρωση της κρεατινίνης του ορού, που αποτελεί μέχρι και σήμερα την πιο διαδεδομένη μέθοδο εκτίμησης της νεφρικής λειτουργίας και ανίχνευσης τυχόν νεφρικής βλάβης, έχει περιορισμένη αξία στην έγκαιρη ανίχνευση της νεφρικής βλάβης και στην εκτίμηση των οξέων μεταβολών του ρυθμού σπειραματικής διήθησης, με αποτέλεσμα να έχει μελετηθεί ένας σημαντικός αριθμός εναλλακτικών της κρεατινίνης δεικτών οξείας νεφρικής βλάβης. Σκοπός της παρούσας μελέτης ήταν α) ο προσδιορισμός της επίπτωσης της οξείας νεφρικής βλάβης μετά από μείζονες χειρουργικές επεμβάσεις κοιλιάς καθώς και των περιεγχειρητικών παραγόντων κινδύνου που σχετίζονται με την εμφάνισή της και β) η αξιολόγηση του ρόλου της κυστατίνης C του ορού, καθώς και άλλων βιοχημικών παραμέτρων (πειραματικών και ρουτίνας) του ορού και των ούρων ως πρώιμοι δείκτες περιεγχειρητικής οξείας νεφρικής βλάβης (σπειραματικής ή/και σωληναριακής), πριν αυτή διαγνωσθεί με τις παραδοσιακές εργαστηριακές μεθόδους, με σκοπό τη βελτιστοποίηση της περιεγχειρητικής διαχείρισης των ασθενών αυτών.Μελετήθηκαν προοπτικά 68 ασθενείς, οι οποίοι υποβλήθηκαν σε προγραμματισμένη μείζονα χειρουργική επέμβαση κοιλιάς στο Πανεπιστημιακό Γενικό Νοσοκομείο Ηρακλείου. Αποκλείσθηκαν ασθενείς με χρόνια νεφρική νόσο σταδίου IV και V, ασθενείς σε περιτοναϊκή κάθαρση ή αιμοκάθαρση, καθώς και ασθενείς μετά από μεταμόσχευση νεφρού. Μελετήθηκαν οι εξής βιοχημικές παράμετροι: κυστατίνη C, ουρία, κρεατινίνη, Na, K, προλευκωματίνη, πρωτεΐνη δέσμευσης της ρετινόλης ορού καθώς και κρεατινίνη, ουρία, α1- και β2-μικροσφαιρίνη, α2-μακροσφαιρίνη, IgG, τρανσφερρίνη, λευκωματίνη, Να, Κ, Cl ούρων στις ακόλουθες προκαθορισμένες χρονικές στιγμές: προεγχειρητικά, στην Αίθουσα Ανάνηψης, καθώς και την 1η, 3η, 5η και 7η μετεγχειρητική ημέρα. Επίσης υπολογίσθηκαν οι κλασματικές απεκκρίσεις νατρίου, ουρίας και καλίου, ο ρυθμός σπειραματικής διήθησης, το SID ούρων καθώς και ο λόγος λευκωματίνης προς κρεατινίνη ούρων. Η διάγνωση της οξείας νεφρικής βλάβης βασίσθηκε στα κριτήρια του Acute Kidney Injury Network. Τα κύρια αποτελέσματα της παρούσας μελέτης συνοψίζονται στα εξής: 1. Περίπου 1 στους 5 ασθενείς στον μελετηθέντα πληθυσμό εμφάνισε μετεγχειρητική οξεία νεφρική βλάβη μετά από προγραμματισμένη μείζονα χειρουργική επέμβαση κοιλιάς. 2. Η προεγχειρητική λευκωματινουρία (αυξημένος λόγος λευκωματίνης/κρεατινίνης ούρων) αναγνωρίσθηκε ως ανεξάρτητος παράγοντας εμφάνισης μετεγχειρητικής οξείας νεφρικής βλάβης (OR = 5.47, 95% CI: 1.36-21.92, p = 0.019). 3. Οι διεγχειρητικές παρεμβάσεις, που σχετίσθηκαν με την εμφάνιση μετεγχειρητικής οξείας νεφρικής βλάβης ήταν η απώλεια αίματος (p = 0.02), η μετάγγιση με παράγωγα αίματος (p = 0.042 για RBCs’ και p = 0.006 για FFP αντίστοιχα) και το χορηγηθέν μέσω κρυσταλλοειδών ή κολλοειδών φορτίο χλωρίου (p = 0.043). 4. Οι ασθενείς που εκδήλωσαν μετεγχειρητική οξεία νεφρική βλάβη εμφάνισαν ήδη από την αίθουσα ανάνηψης στατιστικά σημαντικά χαμηλότερες τιμές νατρίου και χλωρίου ούρων καθώς και αυξημένη κλασματική απέκκριση καλίου, ευρήματα δηλωτικά μιας πρώιμης ελάττωσης του ρυθμού σπειραματικής διήθησης, πολύ νωρίτερα από τη διάγνωση της οξείας νεφρικής βλάβης με βάση τα κριτήρια ΑΚΙΝ. Επίσης, η μετεγχειρητική ποσοστιαία μεταβολή του SID ούρων (ΔSIDU) ήταν στατιστικά σημαντικά χαμηλότερη στην αίθουσα ανάνηψης στους ασθενείς με οξεία νεφρική βλάβη, υποδηλώνοντας την ύπαρξη πρώιμης διαταραχής της ικανότητας αποβολής χλωρίου συνεπεία σωληναριακής βλάβης. 5. Ούτε η κυστατίνη C ορού, ούτε κανείς εκ των λοιπών μετρηθέντων ή υπολογισθέντων βιοχημικών δεικτών δεν εμφάνισαν στατιστικά σημαντικές διαφορές μεταξύ των ασθενών με και χωρίς οξεία νεφρική βλάβη, αποτυγχάνοντας ως διαγνωστικοί οδείκτες περιεγχειρητικής οξείας νεφρικής βλάβης

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study

Purpose: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). Methods: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). Results: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. Conclusions: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections

Purpose: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). Methods: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. Results: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. Conclusion: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study

Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes