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1.
Crit Care ; 28(1): 24, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38229072

ABSTRACT

BACKGROUND: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein. METHODS: We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses. RESULTS: Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time. CONCLUSIONS: The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients. CLINICALTRIALS: gov Identifier: NCT03160547 (2017-05-17).


Subject(s)
Continuous Renal Replacement Therapy , Critical Illness , Adult , Humans , Critical Illness/therapy , Urea , Bayes Theorem , Renal Replacement Therapy
2.
Clin J Am Soc Nephrol ; 18(8): 997-1005, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37256861

ABSTRACT

BACKGROUND: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction. METHODS: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation. RESULTS: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72). CONCLUSIONS: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 .


Subject(s)
Cystatin C , Iohexol , Humans , Bayes Theorem , Creatinine , Critical Illness , Glomerular Filtration Rate/physiology , Kidney/diagnostic imaging , Kidney/physiology
3.
Crit Care Med ; 50(7): 1072-1082, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35220340

ABSTRACT

OBJECTIVES: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay. DESIGN: Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS]). SETTING: Multiple adult ICUs. PATIENTS: Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66-2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04-1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62-1.30; p = 0.566). CONCLUSIONS: The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.


Subject(s)
Critical Illness , Glutamine , Bayes Theorem , Creatinine , Critical Illness/therapy , Humans , Oxidative Stress , Urea
4.
JPEN J Parenter Enteral Nutr ; 46(4): 789-797, 2022 05.
Article in English | MEDLINE | ID: mdl-34462921

ABSTRACT

BACKGROUND: We sought to determine whether peaks in essential amino acid (EAA) concentration associated with intermittent feeding may provide anabolic advantages when compared with continuous feeding regimens in critical care. METHODS: We performed a secondary analysis of data from a multicenter trial of UK intensive care patients randomly assigned to intermittent or continuous feeding. A linear mixed-effects model was developed to assess differences in urea-creatinine ratio (raised values of which can be a marker of muscle wasting) between arms. To investigate metabolic phenotypes, we performed k-means urea-to-creatinine ratio trajectory clustering. Amino acid concentrations were also modeled against urea-to-creatinine ratio from day 1 to day 7. The main outcome measure was serum urea-to-creatinine ratio (millimole per millimole) from day 0 to the end of the 10-day study period. RESULTS: Urea-to-creatinine ratio trajectory differed between feeding regimens (coefficient -.245; P = .002). Patients receiving intermittent feeding demonstrated a flatter urea-to-creatinine ratio trajectory. With k-means analysis, the cluster with the largest proportion of continuously fed patients demonstrated the steepest rise in urea-to-creatinine ratio. Neither protein intake per se nor serum concentrations of EAA concentrations were correlated with urea-to-creatinine ratio (coefficient = .088 [P = .506] and coefficient <.001 [P = .122], respectively). CONCLUSION: Intermittent feeding can mitigate the rise in urea-to-creatinine ratio otherwise seen in those continuously fed, suggesting that catabolism may have been, to some degree, prevented.


Subject(s)
Amino Acids , Critical Illness , Amino Acids, Essential , Creatinine , Critical Care , Critical Illness/therapy , Humans , Urea
5.
Ann Intensive Care ; 11(1): 140, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34559325

ABSTRACT

BACKGROUND: Myoglobin and creatine kinase (CK) are both established markers of muscle injury but their hospital admission values have never been compared to predict post-traumatic acute kidney injury (AKI). METHODS: An observational registry study of consecutive trauma patients admitted to a major regional trauma centre. The primary outcome was stage 1 or more AKI in the first 7 days after trauma. We assessed the association of hospital admission myoglobin or CK with development of AKI both alone and when added to two existing risk prediction models for post traumatic AKI. RESULTS: Of the 857 trauma patients (median age 36 [25-52], 96% blunt trauma, median ISS of 20 [12-47]) included, 102 (12%) developed AKI. Admission myoglobin performed better than CK to predict AKI any stage with an AUC-ROC of 0.74 (95% CI 0.68-0.79) and 0.63 (95% CI 0.57-0.69), respectively (p < 0.001). Admission myoglobin also performed better than CK to predict AKI stage 2 or 3 [AUC-ROC of 0.79 (95% CI 0.74-0.84) and 0.74 (95% CI 0.69-0.79), respectively (p < 0.001)] with a best cutoff value of 1217 µg/L (sensitivity 74%, specificity 77%). Admission myoglobin added predictive value to two established models of AKI prediction and showed significant ability to reclassify subjects regarding AKI status, while admission CK did not. Decision curve analysis also revealed that myoglobin added net benefit to established predictive models. Admission myoglobin was better than CK at predicting development of significant rhabdomyolysis. CONCLUSIONS: Admission myoglobin better predicts the development of AKI and severe rhabdomyolysis after major trauma. Admission myoglobin should be added in established predictive models of post-traumatic AKI to early identify high-risk patients.

6.
Crit Care Med ; 49(11): e1157-e1162, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34048368

ABSTRACT

OBJECTIVES: Joblessness is common in survivors from critical care. Our aim was to describe rates of return to work versus unemployment following coronavirus disease 2019 acute respiratory distress syndrome requiring intensive care admission. DESIGN: Single-center, prospective case series. SETTING: Critical Care Follow-Up Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. PATIENTS: One hundred and one consecutive laboratory-confirmed coronavirus disease 2019 patients were discharged from our hospital following an ICU stay between March 1, 2020, and June 30, 2020. Twenty-five died in the ICU. Seventy-six were discharged alive from hospital. Two patients refused participation, while three were unreachable. The remaining 71 were alive at 6 months and interviewed. INTERVENTIONS: Baseline and outcome healthcare data were extracted from the electronic patient records. Employment data were collected using a previously published structured interview instrument that included current and previous employment status, hours worked per week, and timing of return to work. Health-related quality of life status was assessed using the Italian EQ-5D-5L questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 interviewed patients, 45 (63%) were employed prior to coronavirus disease 2019, of which 40 (89%) of them worked full-time. Thirty-three (73%) of the previously employed survivors had returned to work by 6 months, 10 (22%) were unemployed, and 2 (5%) were newly retired. Among those who returned to work, 20 (85%) of them reported reduced effectiveness at work. Those who did not return to work were either still on sick leave or lost their job as a consequence of coronavirus disease 2019. Reported quality of life of survivors not returning to work was worse than of those returning to work. CONCLUSIONS: The majority of coronavirus disease 2019 survivors following ICU in our cohort had returned to work by 6 months of follow-up. However, most of them reported reduced work effectiveness. Prolonged sick leave and unemployment were common findings in those not returning.


Subject(s)
COVID-19/epidemiology , Critical Care/statistics & numerical data , Respiratory Distress Syndrome/epidemiology , Return to Work/statistics & numerical data , Unemployment/statistics & numerical data , Age Factors , Aged , Comorbidity , Female , Frailty/epidemiology , Humans , Length of Stay , Male , Middle Aged , Patient Discharge/statistics & numerical data , Quality of Life , Retirement/statistics & numerical data , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Socioeconomic Factors
7.
Sci Rep ; 11(1): 9928, 2021 05 11.
Article in English | MEDLINE | ID: mdl-33976354

ABSTRACT

The long-term trajectory of kidney function recovery or decline for survivors of critical illness is incompletely understood. Characterising changes in kidney function after critical illness and associated episodes of acute kidney injury (AKI), could inform strategies to monitor and treat new or progressive chronic kidney disease. We assessed changes in estimated glomerular filtration rate (eGFR) and impact of AKI for 1301 critical care survivors with 5291 eGFR measurements (median 3 [IQR 2, 5] per patient) between hospital discharge (2004-2008) and end of 7 years of follow-up. Linear mixed effects models showed initial decline in eGFR over the first 6 months was greatest in patients without AKI (- 9.5%, 95% CI - 11.5% to - 7.4%) and with mild AKI (- 12.3%, CI - 15.1% to - 9.4%) and least in patients with moderate-severe AKI (- 4.3%, CI - 7.0% to - 1.4%). However, compared to patients without AKI, hospital discharge eGFR was lowest for the moderate-severe AKI group (median 61 [37, 96] vs 101 [78, 120] ml/min/1.73m2) and two thirds (66.5%, CI 59.8-72.6% vs 9.2%, CI 6.8-12.4%) had an eGFR of < 60 ml/min/1.73m2 through to 7 years after discharge. Kidney function trajectory after critical care discharge follows a distinctive pattern of initial drop then sustained decline. Regardless of AKI severity, this evidence suggests follow-up should incorporate monitoring of eGFR in the early months after hospital discharge.


Subject(s)
Acute Kidney Injury/physiopathology , Kidney/physiopathology , Acute Kidney Injury/diagnosis , Adult , Aged , Critical Care , Critical Illness , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Patient Discharge , Time Factors
8.
Clin Med (Lond) ; 21(2): e179-e185, 2021 03.
Article in English | MEDLINE | ID: mdl-33762384

ABSTRACT

BACKGROUND: Non-communicable diseases (NCDs) are increasingly prevalent and were responsible for 40.5 million deaths (71%) globally in 2016. We examined the number of NCD-related emergency hospital admissions during the years 1998 to 2018 in the UK. METHODS: Demographic features for those admitted as an emergency with NCDs as their primary diagnosis were collated for all admissions in England, Wales and Scotland. NCDs recorded as secondary diagnoses for all admissions in England from 2012 to 2018 were additionally recorded. RESULTS: We identified 120,662,155 emergency episodes of care. From 1998 to 2018 there was an increase from 1,416,233 to 1,892,501 in annual emergency admissions due to NCDs. This, however, represented a fall in the proportion of NCD among all emergency admissions, from 33.4% to 26.9%. Mean age of all patients admitted increased from 46.3 to 53.8 years. CONCLUSION: Despite a fall in proportion of NCD admissions, the population acutely admitted to hospital was increasingly elderly and increasingly comorbid.


Subject(s)
Noncommunicable Diseases , Aged , England/epidemiology , Hospitals , Humans , Middle Aged , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/therapy , Scotland/epidemiology , Wales/epidemiology
9.
Biomarkers ; 26(1): 1-12, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33103483

ABSTRACT

PURPOSE: To examine reported prognostic associations of routine blood measurements in the intensive care unit. MATERIALS AND METHODS: We searched PubMed, EMBASE through 28th May 2020 to identify all studies in adult critical care investigating associations between parameters measured routinely in whole blood, plasma or serum, and length of stay or mortality. Registration: PROSPERO; CRD42019122058. RESULTS: A total of 128 studies, reporting 28 different putative prognostic biomarkers, met eligibility criteria. Those most frequently examined were red cell distribution width, neutrophil-to-lymphocyte ratio, C-reactive protein, and platelet count. A higher red cell distribution width, a lower platelet count, and a higher neutrophil-to-lymphocyte ratio were consistently associated with both increased mortality and length of stay. A lower level of albumin was consistently associated with greater mortality. C-reactive protein was inconsistent. Most studies (n = 110) used regression modelling with wide variation in variable selection and covariate-adjustment; none externally validated the proposed predictive models. CONCLUSIONS: Simple regression models have so far proved inadequate for the complexity of data available from routine blood sampling in critical care. Adoption of a direct causal framework may help better assess mechanistic processes, aid design of future studies, and guide clinical decision making using routine data.


Subject(s)
Biomarkers/blood , C-Reactive Protein/metabolism , Hematologic Tests/standards , Prognosis , Female , Humans , Intensive Care Units/standards , Length of Stay , Male
10.
Curr Opin Crit Care ; 26(6): 581-589, 2020 12.
Article in English | MEDLINE | ID: mdl-33027144

ABSTRACT

PURPOSE OF REVIEW: The aim of this study was to summarize the current evidence around the impact of individualizing patient care following an episode of acute kidney injury (AKI) in the ICU. RECENT FINDINGS: Over the last years, evidence has demonstrated that the follow-up care after episodes of AKI is lacking and standardization of this process is likely needed. Although this is informed largely by large retrospective cohort studies, a few prospective observational trials have been performed. Medication reconciliation and patient/caregiver education are important tenants of follow-up care, regardless of the severity of AKI. There is evidence the initiation and/or reinstitution of renin-angiotensin-aldosterone agents may improve patient's outcomes following AKI, although they may increase the risk for adverse events, especially when reinitiated early. In addition, 3 months after an episode of AKI, serum creatinine and proteinuria evaluation may help identify patients who are likely to develop progressive chronic kidney disease over the ensuing 5 years. Lastly, there are emerging differences between those who do and do not require renal replacement therapy (RRT) for their AKI, which may require more frequent and intense follow-up in those needing RRT. SUMMARY: Although large scale evidence-based guidelines are lacking, standardization of post-ICU-AKI is needed.


Subject(s)
Acute Kidney Injury , Aftercare , Acute Kidney Injury/therapy , Creatinine , Humans , Intensive Care Units , Renal Replacement Therapy , Retrospective Studies
12.
Clin Kidney J ; 13(2): 133-141, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32296515

ABSTRACT

Critically ill patients who develop acute kidney injury (AKI) are more than twice as likely to die in hospital. However, it is not clear to what extent AKI is the cause of excess mortality, or merely a correlate of illness severity. The Bradford Hill criteria for causality (plausibility, temporality, magnitude, specificity, analogy, experiment & coherence, biological gradient and consistency) were applied to assess the extent to which AKI may be causative in adverse short-term outcomes of critical illness. Plausible mechanisms exist to explain increased risk of death after AKI, both from direct pathophysiological effects of renal dysfunction and mechanisms of organ cross-talk in multiple-organ failure. The temporal relationship between increased mortality following AKI is consistent with its pathophysiology. AKI is associated with substantially increased mortality, an association that persists after accounting for known confounders. A biological gradient exists between increasing severity of AKI and increasing short-term mortality. This graded association shares similar features to the increased mortality observed in ARDS; an analogous condition with a multifactorial aetiology. Evidence for the outcomes of AKI from retrospective cohort studies and experimental animal models is coherent however both of these forms of evidence have intrinsic biases and shortcomings. The relationship between AKI and risk of death is maintained across a range of patient ages, comorbidities and underlying diagnoses. In conclusion many features of the relationship between AKI and short-term mortality suggest causality. Prevention and mitigation of AKI and its complications are valid targets for studies seeking to improve short-term survival in critical care.

13.
Intensive Care Med ; 45(12): 1718-1731, 2019 12.
Article in English | MEDLINE | ID: mdl-31531715

ABSTRACT

PURPOSE: Muscle wasting is common amongst patients with persistent critical illness and associated with increased urea production, but reduced creatinine production. We hypothesised that elevated urea:creatinine ratio would provide a biochemical signature of muscle catabolism and characterise prolonged intensive care (ICU) admissions after major trauma. METHODS: Using pre-specified hypotheses, we analysed two existing data sets of adults surviving ≥ 10 days following admission to ICU after major trauma. We analysed trauma-ICU admissions to the major trauma centre serving the North East London and Essex Trauma Network, with a verification cohort of trauma-ICU cases from the MIMIC-III database. We compared serum urea, creatinine, and urea:creatinine ratio (ratio of concentrations in mmol/L) between patients with persistent critical illness (defined as ICU stay of ≥ 10 days) and those discharged from ICU before day 10. In a sub-group undergoing sequential abdominal computerised tomography (CT), we measured change in cross-sectional muscle area (psoas muscle at L4 vertebral level and total muscle at L3 level) and assessed for relationships with urea:creatinine ratio and ICU stay. Results are provided as median [interquartile range]. RESULTS: We included 1173 patients between February 1st, 2012 and May 1st, 2016. In patients with ICU stay ≥ 10 days, day 10 urea:creatinine ratio had increased by 133% [72-215], from 62 [46-78] to 141 [114-178], p < 0.001; this rise was larger (p < 0.001) than in patients discharged from ICU before day 10, 59% [11-122%], 61 [45-75] to 97 [67-128], p < 0.001. A similar separation in trajectory of urea:creatinine ratio was observed in 2876 trauma-ICU admissions from MIMIC-III. In 107 patients undergoing serial CTs, decrease in L4 psoas and L3 muscle cross-sectional areas between CTs significantly correlated with time elapsed (R2 = 0.64 and R2 = 0.59, respectively). Rate of muscle decrease was significantly greater (p < 0.001 for interaction terms) in 53/107 patients with the second CT during evolving, current or recent persistent critical illness. In this group, at the second CT urea:creatinine ratio negatively correlated with L4 psoas and L3 muscle cross-sectional areas (R2 0.39, p < 0.001 and 0.44, p < 0.001). CONCLUSION: Elevated urea:creatinine ratio accompanies skeletal muscle wasting representing a biochemical signature of persistent critical illness after major trauma. If prospectively confirmed, urea:creatinine ratio is a potential surrogate of catabolism to examine in epidemiological and interventional studies.


Subject(s)
Biomarkers/blood , Creatinine/blood , Critical Illness , Metabolism/physiology , Muscles/injuries , Muscles/physiopathology , Urea/blood , Adult , Aged , Cohort Studies , England , Female , Humans , Male , Middle Aged
14.
Semin Nephrol ; 39(5): 473-483, 2019 09.
Article in English | MEDLINE | ID: mdl-31514911

ABSTRACT

Intravenous crystalloid therapy is one of the most ubiquitous aspects of hospital and critical care medicine. In recent years, there has been increasing focus on the electrolyte composition, and particularly chloride content, of crystalloid solutions. This has led to increasing clinical adoption of balanced solutions, containing substrates for bicarbonate generation and consequently a lower chloride content, in place of 0.9% saline. In this article we review the physiochemical rationale for avoidance of 0.9% saline and the effects of hyperchloremic acidosis on renal physiology. Finally, we review the current evidence and rationale for use of balanced solutions greater than 0.9% saline in acutely ill patients in a variety of clinical settings, as well as considering the role for sodium bicarbonate in preventing or correcting metabolic acidosis. In conclusion, there is a strong physiological rationale for avoidance of iatrogenic hyperchloremic acidosis from 0.9% saline administration in acutely unwell patients and an association with adverse renal outcomes in several studies. However, evidence from large definitive multicenter randomized trials is not yet available to establish the dose-relationship between 0.9% saline administration and potential harm and inform us if some 0.9% saline use is acceptable or if any exposure confers harm.


Subject(s)
Acidosis/prevention & control , Acute Kidney Injury/drug therapy , Acute Kidney Injury/prevention & control , Bicarbonates/administration & dosage , Chlorides/administration & dosage , Crystalloid Solutions/administration & dosage , Acidosis/chemically induced , Bicarbonates/adverse effects , Bicarbonates/blood , Chlorides/adverse effects , Chlorides/blood , Humans
15.
Curr Opin Crit Care ; 25(6): 565-572, 2019 12.
Article in English | MEDLINE | ID: mdl-31503027

ABSTRACT

PURPOSE OF REVIEW: A summary of recent research into the epidemiology, cause, management and outcomes of trauma-associated acute kidney injury (AKI). There is an increasing focus on subtypes of AKI to better target clinical management and future research. RECENT FINDINGS: AKI associated with trauma occurs in 20-24% of patients admitted to ICU. On the basis of creatinine and/or urine output, AKI occurs in the first few days of traumatic illness. Although various associations have been identified, shock and high-volume blood transfusion are the most consistent risks for development of trauma-associated AKI. Short-term outcomes appear worse for patients with AKI, but extent of longer term kidney function recovery remains unknown. Recent research in the general critical care population is beginning to better inform AKI management; however, currently, preventive and supportive strategies remain the mainstay of AKI management after trauma. SUMMARY: Well-designed, prospective research is required to better understand the phenotype, pathophysiology and recovery trajectory of trauma-associated AKI. Only then can potentially unique therapeutic targets be developed for this common subtype of AKI.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Wounds and Injuries/complications , Acute Kidney Injury/epidemiology , Critical Care , Humans , Treatment Outcome
17.
J Trauma Acute Care Surg ; 86(1): 141-147, 2019 01.
Article in English | MEDLINE | ID: mdl-30358765

ABSTRACT

BACKGROUND: As more patients are surviving the initial effects of traumatic injury clinicians are faced with managing the systemic complications of severe tissue injury. Of these, acute kidney injury (AKI) may be a sentinel complication contributing to adverse outcomes. OBJECTIVE: To establish the incidence of AKI in patients admitted to critical care after major trauma, to explore any risk factors and to evaluate the association of AKI with outcomes. DATA SOURCES: Systematic search of MEDLINE, Excerpta Medica database and Cochrane library from January 2004 to April 2018. STUDY SELECTION: Studies of adult major trauma patients admitted to critical care that applied consensus AKI criteria (risk injury failure loss end stage [RIFLE], AKI network, or kidney disease improving global outcomes) and reported clinical outcomes were assessed (PROSPERO Registration: CRD42017056781). Of the 35 full-text articles selected from the screening, 17 (48.6%) studies were included. DATA EXTRACTION AND SYNTHESIS: We followed the PRISMA guidelines and study quality was assessed using the Newcastle-Ottawa score. The pooled incidence of AKI and relative risk of death were estimated using random-effects models. MAIN OUTCOMES AND MEASURES: Incidence of AKI was the primary outcome. The secondary outcome was study-defined mortality. RESULTS: We included 17 articles describing AKI outcomes in 24,267 trauma patients. The pooled incidence of AKI was 20.4% (95% confidence interval [CI], 16.5-24.9). Twelve studies reported the breakdown of stages of AKI with 55.7% of patients classified as RIFLE-R or stage 1, 30.3% as RIFLE-I or stage 2, and 14.0% as RIFLE-F or stage 3. The pooled relative risk of death with AKI compared was 3.6 (95% CI, 2.4-5.3). In addition, there was a concordant increase in odds of death among six studies that adjusted for multiple variables (adjusted odds ratio, 2.7; 95% CI, 1.9-3.8; p = <0.01). CONCLUSION: Acute kidney injury is common after major trauma and associated with increased mortality. Future research is warranted to reduce the potential for harm associated with this subtype of AKI. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Critical Care/methods , Wounds and Injuries/complications , Acute Kidney Injury/epidemiology , Adult , Case-Control Studies , Critical Care Outcomes , Guidelines as Topic , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Humans , Incidence , Intensive Care Units/statistics & numerical data , Middle Aged , Quality Assurance, Health Care , Retrospective Studies , Risk Factors , Wounds and Injuries/epidemiology
18.
Curr Opin Crit Care ; 24(6): 443-449, 2018 12.
Article in English | MEDLINE | ID: mdl-30239409

ABSTRACT

PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is now the mainstay of renal organ support in the critically ill. As our understanding of CRRT delivery and its impact on patient outcomes improves there is a focus on researching the potential benefits of tailored, patient-specific treatments to meet dynamic needs. RECENT FINDINGS: The most up-to-date studies investigating aspects of CRRT prescription that can be individualized: CRRT dose, timing, fluid management, membrane selection, anticoagulation and vascular access are reviewed. The use of different doses of CRRT lack conventional high-quality evidence and importantly studies reveal variation in assessment of dose delivery. Research reveals conflicting evidence for clinicians in distinguishing which patients will benefit from 'watchful waiting' vs. early initiation of CRRT. Both dynamic CRRT dosing and precision fluid management using CRRT are difficult to investigate and currently only observational data supports individualization of prescriptions. Similarly, individualization of membrane choice is largely experimental. SUMMARY: Clinicians have limited evidence to individualize the prescription of CRRT. To develop this, we need to understand the requirements for renal support for individual patients, such as electrolyte imbalance, fluid overload or clearance of systemic inflammatory mediators to allow us to target these abnormalities in appropriately designed randomized trials.


Subject(s)
Acute Kidney Injury/therapy , Critical Illness/therapy , Precision Medicine/methods , Renal Replacement Therapy , Humans , Patient Selection , Practice Guidelines as Topic , Renal Replacement Therapy/methods
19.
Sci Rep ; 8(1): 3665, 2018 02 26.
Article in English | MEDLINE | ID: mdl-29483607

ABSTRACT

Acute Kidney Injury (AKI) complicating major trauma is associated with increased mortality and morbidity. Traumatic AKI has specific risk factors and predictable time-course facilitating diagnostic modelling. In a single centre, retrospective observational study we developed risk prediction models for AKI after trauma based on data around intensive care admission. Models predicting AKI were developed using data from 830 patients, using data reduction followed by logistic regression, and were independently validated in a further 564 patients. AKI occurred in 163/830 (19.6%) with 42 (5.1%) receiving renal replacement therapy (RRT). First serum creatinine and phosphate, units of blood transfused in first 24 h, age and Charlson score discriminated need for RRT and AKI early after trauma. For RRT c-statistics were good to excellent: development: 0.92 (0.88-0.96), validation: 0.91 (0.86-0.97). Modelling AKI stage 2-3, c-statistics were also good, development: 0.81 (0.75-0.88) and validation: 0.83 (0.74-0.92). The model predicting AKI stage 1-3 performed moderately, development: c-statistic 0.77 (0.72-0.81), validation: 0.70 (0.64-0.77). Despite good discrimination of need for RRT, positive predictive values (PPV) at the optimal cut-off were only 23.0% (13.7-42.7) in development. However, PPV for the alternative endpoint of RRT and/or death improved to 41.2% (34.8-48.1) highlighting death as a clinically relevant endpoint to RRT.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Wounds and Injuries/complications , Acute Kidney Injury/surgery , Adult , Cohort Studies , Critical Care , Female , Humans , Incidence , Intensive Care Units/statistics & numerical data , Logistic Models , Male , Middle Aged , Renal Replacement Therapy , Retrospective Studies , Risk Factors
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