Median Simplified Acute Physiology Score Research Articles

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan–Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55–74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22–47) and median BMI: 25.7 kg/m2 (IQR, 23.3–30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491–0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535–0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01–1.06, p = 0.005) and BMI (HR = 1.07, 95%CI: 1.00–1.14, p = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00–1.06, p = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20–12.5, p = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

Severe asthma exacerbation: Changes in patient characteristics, management, and outcomes from 1997 to 2016 in 40 ICUs in the greater Paris area

BackgroundDespite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area. MethodsIn this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality. ResultsA total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions (n=2841) between 1997 and 2001, 1.76% (n=1717) between 2002 and 2006, 1.05% (n=965) between 2007 and 2011, and 1.05% (n=1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32–59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13–28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV. ConclusionICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate.

Low attainment to PK/PD-targets for β-lactams in a multi-center study on the first 72 h of treatment in ICU patients

Severe infections are life-threatening conditions commonly seen in the intensive care units (ICUs). Antibiotic treatment with adequate concentrations is of great importance during the first days when the bacterial load is the highest. Therapeutic drug monitoring (TDM) of β-lactam antibiotics has been suggested to monitor target attainment and to improve the outcome. This prospective multi-center study in seven ICUs in Sweden investigated pharmacokinetic/pharmacodynamic-target (PK/PD-target) attainment for cefotaxime, piperacillin-tazobactam and meropenem, commonly used β-lactams in Sweden. A mid-dose and trough antibiotic concentration blood sample were taken from patients with severe infection daily during the first 72 h of treatment. Antibiotic plasma concentrations were analysed by liquid chromatography-mass spectrometry (LC–MS). Antibiotic concentrations 100% time above MIC (minimal inhibitory concentration), (100% T > MIC) and four times above MIC 50% of the time (50% T > 4xMIC) were used as PK/PD-targets. We included 138 patients with the median age of 67 years and the median Simplified Acute Physiology Score 3 (SAPS3) of 59. Forty-five percent of the study-population failed to reach 100% T > MIC during the first day of treatment. The results were similar the following two days. There was a three-fold risk of not meeting the PK/PD target if the patient was treated with cefotaxime. For the cefotaxime treated patients 8 out of 55 (15%) had at least one end-dose concentrations below the level of detection during the study. Low age, low illness severity, low plasma creatinine, lower respiratory tract infection and cefotaxime treatment were risk factors for not reaching 100% T > MIC. In Swedish ICU-patients treated with β-lactam antibiotics, a high proportion of patients did not reach the PK/PD target. TDM could identify patients that need individual higher dosing regimens already on the first day of treatment. Further studies on optimal empirical start dosing of β-lactams, especially for cefotaxime, in the ICU are needed.Trial registration: The protocol was retrospectively registered 100216 (ACTRN12616000167460).

Comparison of Acute Physiology and Chronic Health Evaluation (APACHE) IV and Simplified Acute Physiology Score (SAPS) II in a Tertiary Care Hospital ICU in India

Background: APACHE IV and SAPS II are ICU scoring systems used to predict mortality in critically ill patients in the ICU. Aim: To compare mortality prediction using APACHE IV and SAPS II in an Indian ICU. Methods: This prospective study included 225 patients. SAPS II and APACHE IV scoring and predicted mortality were obtained for each patient using online calculators and correlated with actual mortality and length of stay. Results: 183/225 of these admissions were due to medical causes. The mean±SD SAPS II score was 37.97 (±15.85) and APACHE IV score was 64.15 (±20.04). The median SAPS II predicted mortality rate was 19.6% and by APACHE IV was 17.4%. Actual mortality was 25.33%. Area under the curve (AUC) for SAPS II was 0.723 and APACHE IV was 0.701. AUC for SAPS II and APACHE IV for medical admissions were 0.712 and 0.681 respectively and for surgical admissions was 0.803 and 0.811 respectively. The best cut off value of SAPS II was 37 and APACHE IV was 70.5 for surgical patients. The mean predicted mortalities for patients with SAPS II score &lt;37 and .37 were 4.95±3.87% and 37.15±16.5% respectively and APACHE IV score &lt;70.5 and .70.5 were 16.82±11.48% and 40.6±15.72% respectively. There was no correlation between predicted and actual length of stay. Conclusions: Both APACHE IV and SAPS II ICU scoring systems are inaccurate in predicting overall mortality in our ICU. APACHE IV is not reliable in predicting length of stay of all patients in our ICU.

Clinical and microbiological features of drowning-associated pneumonia: a retrospective multicentre cohort study

ObjectivePneumonia is the most frequent infectious complication in patients who have experienced drowning that requires intensive care unit (ICU) admission. We aimed to describe clinical, microbiological, and therapeutic data as well as predictors and impacts of such pneumonia on patients' outcomes. MethodsWe conducted a retrospective, multicentre study (2013–2020) of 270 consecutive patients admitted for drowning to 14 ICUs in Western France. Their baseline characteristics and outcomes were compared according to the occurrence of drowning-associated pneumonia (DAP), defined as pneumonia diagnosed within 48 hours of ICU admission. A Cox regression model was used to compare survival on day 28, and logistic regression was used to identify risk factors for DAP. Microbiological characteristics and empirical antibacterial treatment were also analysed. ResultsAmong the 270 patients admitted to the ICU for drowning, 101 (37.4%) and 33 (12.2%) experienced pneumonia and microbiologically proven DAP, respectively. The occurrence of pneumonia was associated with higher severity scores at ICU admission (median Simplified Acute Physiology Score II, 34 [interquartile range {IQR}, 25–55] vs. 45 [IQR, 28–67]; p 0.006) and longer ICU length of stay (2 days [IQR, 1–3] vs. 4 days [IQR, 2–7]; p < 0.001). The 28-day mortality rate was higher among these patients (29/101 [28.7%] vs. 26/169 [15.4%]; p 0.013). Microbiologically proven DAP remained associated with higher 28-day mortality after adjustments for cardiac arrest and water salinity (adjusted hazard ratio, 1.86 [95% CI, 1.06–3.28]; p 0.03). A microbiological analysis of respiratory samples showed a high proportion of gram-negative bacilli (23/56; 41.1%), with a high prevalence of amoxicillin-clavulanate resistance (12/33; 36.4%). ConclusionsPneumonia is a common complication in patients admitted in the ICU for drowning and is associated with increased mortality.

ERCP in critically ill patients is safe and does not increase mortality.

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for minimally-invasive treatment of biliary or pancreatic tract disease. When treating patients on intensive care units (ICU) with ERCP, interventionalists are faced with considerably higher morbidity compared to patients in ambulatory settings. However, data on complications and outcome of critical ill patients undergoing emergency ERCP are limited.A retrospective analysis of 102 patients treated on ICUs undergoing 121 ERCP procedures at the University Hospital of Essen, Germany between 2002 and 2016 was performed. Indications, interventional success, outcome including survival and procedure-related complications were analyzed. Patients’ condition pre-ERCP was categorized by using the “Simplified Acute Physiology Score” (SAPS 3).66/102 patients (64.7%) were referred to ERCP from surgical ICU, 36/102 (35.3%) from nonsurgical ICU. The majority of patients were male (63.7%), the mean age was 54.1 ± 14.9 [21–88] years. Indications for ERCP were biliary complications after liver transplantation (n = 34, 33.3%), biliary leakage after hepatobiliary surgery (n = 32, 31.4%), and cholangitis/biliary sepsis (n = 36; 35.3%), respectively. 117/121 (96.7%) ERCPs were successful, 1 patient (1.0%) died during ERCP. Post-ERCP pancreatitis occurred in 11.8% of interventions. The median simplified acute physiology score 3 was 65 points, predicting a risk-adjusted estimated mortality of 48.8%, corresponding to an observed mortality of 52.2% (P = n.s.).ERCP is safe in critically ill patients on ICU, it does not increase overall mortality rate and has a relatively low rate of procedure-associated complications.

Effect of antibiotic therapy on the prognosis of ventilator-associated pneumonia caused by Stenotrophomonas maltophilia

BackgroundVentilator-associated pneumonia (VAP) caused by Stenotrophomonas maltophilia is poorly described in the literature. However, it has been shown to be associated with increased morbidity and mortality. Probabilistic antibiotic therapy against S. maltophilia is often ineffective as this pathogen is resistant to many antibiotics. There is no consensus at present on the best therapeutic strategy to adopt (class of antibiotics, antibiotic combination, dosage, treatment duration). The aim of this study was to evaluate the effect of antibiotic therapy strategy on the prognosis of patients with VAP caused by S. maltophilia.ResultsThis retrospective study evaluated all consecutive patients who developed VAP caused by S. maltophilia between 2010 and 2018 while hospitalized in the intensive care unit (ICU) of a French university hospital in Reunion Island, in the Indian Ocean region. A total of 130 patients with a median Simplified Acute Physiology Score II of 58 [43–73] had VAP caused by S. maltophilia after a median duration of mechanical ventilation of 12 [5–18] days. Ventilator-associated pneumonia was polymicrobial in 44.6% of cases, and ICU mortality was 50.0%. After multivariate Cox regression analysis, the factors associated with increased ICU mortality were older age (hazard ratio (HR): 1.03; 95% CI 1.01–1.04, p = 0.001) and high Sequential Organ Failure Assessment score on the day of VAP onset (HR: 1.08; 95% CI 1.03–1.14, p = 0.002).Appropriate antibiotic therapy, and in particular trimethoprim–sulfamethoxazole, was associated with decreased ICU mortality (HR: 0.42; 95% CI 0.24–0.74, p = 0.003) and decreased hospital mortality (HR: 0.47; 95% CI 0.28–0.79, p = 0.04).Time to start of appropriate antibiotic therapy, combination therapy, and duration of appropriate antibiotic therapy had no effect on ICU mortality (p > 0.5).ConclusionIn our study, appropriate antibiotic therapy, and in particular trimethoprim–sulfamethoxazole, was associated with decreased ICU and hospital mortality in patients with VAP caused by S. maltophilia.

Association of Oliguria With Acute Kidney Injury Diagnosis, Severity Assessment, and Mortality Among Patients With Critical Illness

The current definition and staging of acute kidney injury (AKI) considers alterations in serum creatinine (sCr) level and urinary output (UO). However, the relevance of oliguria-based criteria is disputed. To determine the contribution of oliguria, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, to AKI diagnosis, severity assessment, and short- and long-term outcomes. This cohort study included adult patients admitted to a multidisciplinary intensive care unit from January 1, 2010, to June 15, 2020. Patients receiving long-term dialysis and those who declined consent were excluded. Daily sCr level and hourly UO measurements along with sociodemographic characteristics and severity scores were extracted from electronic medical records. Long-term mortality was assessed by cross-referencing the database with the Swiss national death registry. The onset and severity of AKI according to the KDIGO classification was determined using UO and sCr criteria separately, and their agreement was assessed. Using a multivariable model accounting for baseline characteristics, severity scores, and sCr stages, the association of UO criteria with 90-day mortality was evaluated. Sensitivity analyses were conducted to assess how missing sCr, body weight, and UO values, as well as different sCr baseline definitions and imputations methods, would affect the main results. Among the 15 620 patients included in the study (10 330 men [66.1%] with a median age of 65 [IQR, 53-75] years, a median Simplified Acute Physiology Score II score of 40.0 [IQR, 30.0-53.0], and a median follow-up of 67.0 [IQR, 34.0-100.0] months), 12 143 (77.7%) fulfilled AKI criteria. Serum creatinine and UO criteria had poor agreement on AKI diagnosis and staging (Cohen weighted κ, 0.36; 95% CI, 0.35-0.37; P < .001). Compared with the isolated use of sCr criteria, consideration of UO criteria enabled identification of AKI in 5630 patients (36.0%). Those patients had a higher 90-day mortality than patients without AKI (724 of 5608 [12.9%] vs 288 of 3462 [8.3%]; P < .001). On multivariable analysis accounting for sCr stage, comorbidities, and illness severity, UO stages 2 and 3 were associated with a higher 90-day mortality (odds ratios, 2.4 [95% CI, 1.6-3.8; P < .001] and 6.2 [95% CI, 3.7-10.5; P < .001], respectively). These results remained significant in all sensitivity analyses. The findings of this cohort study suggest that oliguria lasting more than 12 hours (KDIGO stage 2 or 3) has major AKI diagnostic implications and is associated with outcomes irrespective of sCr elevations.

Exudative glutamine losses contribute to high needs after burn injury.

BackgroundBurnpatients characteristically have increased energy, glucose, and protein requirements. Glutamine supplementation is strongly recommended during early‐phase treatment and is associated with improved immunity, wound healing, and reduced mortality. This study evaluated if early burn exudative losses might contribute to higher supplementation needs.MethodsPatients admitted to the burn intensive care unit (ICU) had exudate collection from tight bandages applied to arms or legs during the first week (exudate aliquot twice daily). Seven amino acids (alanine, arginine, cystEine, glutamine, leucine, lysine, and methionine) were quantified by liquid chromatography–mass spectrometry. Descriptive analysis of all results is provided as median and interquartile range or in value ranges.ResultsEleven patients aged 19–77 years, presenting with burns on 18%–70% of the body surface, with a median simplified acute physiology score II of 33 (range, 16–56) were included during the study period. The highest amino acid losses were observed during the first 3 days with an important interpatient and intrapatient variability. Glutamine and alanine losses were highest, followed by leucine and lysine in all patients; amino acid exudate concentrations were in the range of normal plasma concentrations and were stable over time. Total glutamine losses were correlated to the burned surface (r2 = 0.552, P = .012), but not to enteral glutamine supplements.ConclusionsThe study shows significant exudative losses during early‐stage burn recovery and particularly for glutamine and alanine. Glutamine loss generally decreased with wound closure, the subsequent decline of exudation, and the evolving size of burn surfaces.

Covid-19 severe hypoxemic pneumonia: A clinical experience using high-flow nasal oxygen therapy as first-line management

PurposeTo report a French experience in patients admitted to Intensive Care Unit (ICU) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring high fractional concentration of inspired oxygen supported by high flow nasal cannula (HFNC) as first-line therapy. MethodsRetrospective cohort study conducted in two ICUs of a French university hospital. All consecutive patients admitted during 28-days after the first admission for SARS-CoV-2 pneumonia were screened. Demographic, clinical, respiratory support, specific therapeutics, ICU length-of-stay and survival data were collected. ResultsData of 43 patients were analyzed: mainly men (72%), median age 61 (51–69) years, median body mass index of 28 (25–31) kg/m2, median simplified acute physiology score (SAPS II) of 29 (22–37) and median PaO2/fraction of inspired oxygen (FiO2) (P/F) ratio of 146 (100–189) mmHg. HFNC was initiated at ICU admission in 76% of patients. Median flow was 50 (45–50) L/min and median FiO2 was 0.6 (0.5–0.8). 79% of patients presented at least one comorbidity, mainly hypertension (58%). At day (D) 28, 32% of patients required invasive mechanical ventilation, 3 patients died in ICU. Risk factors for intubation were diabetes (10% vs. 43%, P=0.04) and extensive lesions on chest computed tomography (CT) (P=0.023). Patients with more than 25% of lesions on chest CT were more frequently intubated during ICU stay (P=0.012). At ICU admission (D1), patients with higher SAPS II and Sequential Organ Failure Assessment (SOFA) scores (respectively 39 (28–50) vs. 27 (22–31), P=0.0031 and 5 (2–8) vs. 2 (2–2.2), P=0.0019), and a lower P/F ratio (98 (63–109) vs. 178 (126–206), P=0.0005) were more frequently intubated. Among non-intubated patients, the median lowest P/F was 131 (85–180) mmHg. Four caregivers had to stop working following coronavirus 2 contamination, but did not require hospitalization. ConclusionOur clinical experience supports the use of HFNC as first line-therapy in patients with SARS-COV-2 pneumonia for whom face mask oxygen does not provide adequate respiratory support.

Comparison of Approaches for Prediction of Renal Replacement Therapy-Free Survival in Patients with Acute Kidney Injury

Background/Aims: Acute kidney injury (AKI) in critically ill patients is common, and continuous renal replacement therapy (CRRT) is a preferred mode of renal replacement therapy (RRT) in hemodynamically unstable patients. Prediction of clinical outcomes in patients on CRRT is challenging. We utilized several approaches to predict RRT-free survival (RRTFS) in critically ill patients with AKI requiring CRRT. Methods: We used the Medical Information Mart for Intensive Care (MIMIC-III) database to identify patients ≥18 years old with AKI on CRRT, after excluding patients who had ESRD on chronic dialysis, and kidney transplantation. We defined RRTFS as patients who were discharged alive and did not require RRT ≥7 days prior to hospital discharge. We utilized all available biomedical data up to CRRT initiation. We evaluated 7 approaches, including logistic regression (LR), random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), multilayer perceptron (MLP), and MLP with long short-term memory (MLP + LSTM). We evaluated model performance by using area under the receiver operating characteristic (AUROC) curves. Results: Out of 684 patients with AKI on CRRT, 205 (30%) patients had RRTFS. The median age of patients was 63 years and their median Simplified Acute Physiology Score (SAPS) II was 67 (interquartile range 52–84). The MLP + LSTM showed the highest AUROC (95% CI) of 0.70 (0.67–0.73), followed by MLP 0.59 (0.54–0.64), LR 0.57 (0.52–0.62), SVM 0.51 (0.46–0.56), AdaBoost 0.51 (0.46–0.55), RF 0.44 (0.39–0.48), and XGBoost 0.43 (CI 0.38–0.47). Conclusions: A MLP + LSTM model outperformed other approaches for predicting RRTFS. Performance could be further improved by incorporating other data types.

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

BackgroundTo date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae.MethodsThis multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression.FindingsBetween Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU.InterpretationAcute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.FundingNone.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.

Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study.

Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission. Prospective multicenter cohort study. Three mixed ICU from April 2014 to December 2017. Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included. None. "State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg). Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.

The 28-day survive for critically ill cancer patients undergoing continuous renal replacement with postoperative acute kidney injure: a retrospective study of 86 cases.

BackgroundAdvances in oncology led to a substantial increase in the number of patients requiring admission to the intensive care unit (ICU). It remains controversial to start continuous renal replacement therapy (CRRT) for acute kidney injure (AKI) in critically ill patients with cancer because of the poor outcome and high costs.MethodsIn this retrospective study, we collected data from patients with cancer with postoperative AKI-stage 3 [Kidney Disease: Improving Global Outcomes (KDIGO), 2012] undergoing CRRT in the ICU of Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to January 2019. Patients were followed up until the time of death or the point of 28-day after ICU admission. Univariate and multivariate analysis was performed to identify risk factors for 28-day survive.ResultsOf 8,030 cancer patients after surgical operation admitted by ICU, a total of 86 (1.1%) patients developed postoperative AKI: male/female: 62/24, median age 61 [27–82] years. The number of digestive tract/lung/other types of cancer was 59, 10 and 17, respectively. The median Simplified Acute Physiology Score III (SAPS III) was 65 [49–109] and the median Sequential Organ Failure Assessment (SOFA) score was 6 [1–19]. There were 35 deaths eventually and all the deaths occur within 28 days after ICU admission. Twenty-eight-day survive rate was 57.1%±5.8%. In multivariate cox regression analysis, two risk factors independently affected 28-day survive: SAPS III score ≥65 [hazard ratio (HR): 3.451 (1.272–9.365), P=0.015], the presence of shock at the start of CRRT [HR: 10.262 (2.210–47.660), P=0.003]. The cancer status (P=0.076), cancer types (P>0.05 for both) and neoadjuvant therapy associated with cancer (P=0.949) showed no effects on 28-day survive.ConclusionsFor cancer patients, postoperative AKI-stage 3 is a serious complication with a low 28-day survive rate. Patients with the presence shock at the start of CRRT or SAPS III ≥65 will have a poor 28-day survive. It should be emphasized that the cancer characteristics (status, types or treatment) don’t affect 28-day survive.

Bioactive Adrenomedullin, Organ Support Therapies, and Survival in the Critically Ill: Results from the French and European Outcome Registry in ICU Study.

Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin. Prospective multicenter observational cohort study. Data from the French and euRopean Outcome reGistry in ICUs study. Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included. Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality. Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92). Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients.

PK/PD targets of amikacin and gentamicin in ICU patients

ObjectivesWe aimed to evaluate the probability to achieve PK-PD targets in patients with sepsis hospitalized in the intensive care unit (ICU) after a single dose of 30mg/kg of amikacin or 8mg/kg of gentamicin. Patients and methodsThis single-center prospective study included 138 ICU patients with severe sepsis or septic shock with an indication for intravenous amikacin (N=89) or gentamicin (N=49). Maximum concentration (Cmax) was measured 30 minutes after infusion completion. PK/PD objectives were respectively Cmax≥60mg/L and ≥30mg/L for amikacin and gentamicin for empirical therapy, and a Cmax/MIC ratio≥8, as per French guidelines. ResultsThe median Simplified Acute Physiology Score II was 43 and ICU case fatality rate was 34.8%. A causative bacterial agent was identified in 94 patients (68.1%). Three pathogens had acquired aminoglycoside resistance and 15 were naturally resistant. The targeted Cmax for the first dose was achieved in 53 patients (59.6%) receiving amikacin, and one (2.2%) patient receiving gentamicin. Cmax/MIC ratio≥8 was obtained in all patients infected with susceptible pathogens (N=72). Factors associated with Cmax≥60mg/L of amikacin in multivariate analysis were dose per kg of adapted body weight (OR=1.39, P<0.001) and renal clearance estimated with CKD-EPI formula (OR=0.98, P=0.003). ConclusionsDespite high doses, amikacin and gentamicin first Cmax remain dramatically low in ICU patients. However, an adequate Cmax/MIC ratio was reached in all patients.

Defining optimal dosing of ciprofloxacin in patients with septic shock.

Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics. To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients. Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa. We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios. In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.

Fluid therapy and outcome: a prospective observational study in 65 German intensive care units between 2010 and 2011

BackgroundOutcome data on fluid therapy in critically ill patients from randomised controlled trials may be different from data obtained by observational studies under “real-life” conditions. We conducted this prospective, observational study to investigate current practice of fluid therapy (crystalloids and colloids) and associated outcomes in 65 German intensive care units (ICUs). In total, 4545 adult patients who underwent intravenous fluid therapy were included. The main outcome measures were 90-day mortality, ICU mortality and acute kidney injury (AKI). Data were analysed using logistic and Cox regression models, as appropriate.ResultsIn the predominantly post-operative overall cohort, unadjusted 90-day mortality was 20.1%. Patients who also received colloids (54.6%) had a higher median Simplified Acute Physiology Score II [25 (interquartile range 11; 41) vs. 17 (7; 31)] and incidence of severe sepsis (10.2 vs. 7.4%) on admission compared to patients who received exclusively crystalloids (45.4%). 6% hydroxyethyl starch (HES 130/0.4) was the most common colloid (57.0%). Crude rates of 90-day mortality were higher for patients who received colloids (OR 1.845 [1.560; 2.181]). After adjustment for baseline variables, the HR was 1.666 [1.405; 1.976] and further decreased to indicate no associated risk (HR 1.003 [0.980; 1.027]) when it was adjusted for vasopressor use, severity of disease and transfusions. Similarly, the crude risk of AKI was higher in the colloid group (crude OR 3.056 [2.528; 3.694]), after adjustment for baseline variables OR 1.941 [1.573; 2.397], and after full adjustment OR 0.696 [0.629; 0.770]), the risk of AKI turned out to be reduced. The same was true for the subgroup of patients treated with 6% HES 130/0.4 (crude OR 1.931 [1.541; 2.419], adjusted for baseline variables OR 2.260 [1.730; 2.953] and fully adjusted OR 0.800 [0.704; 0.910]) as compared to crystalloids only.ConclusionsThe present analysis of mostly post-operative patients in routine clinical care did not reveal an independent negative effect of colloids (mostly 6% HES 130/0.4) on renal function or survival after multivariable adjustment. Signals towards a reduced risk in subgroup analyses deserve further study.Trial registration ClinicalTrials.gov Identifier: NCT01122277, registered May 11th, 2010

Early biliary drainage is associated with favourable outcomes in critically-ill patients with acute cholangitis.

IntroductionAcute cholangitis (AC) is a clinical condition that requires prompt medical management with IV fluids, antibiotics, and biliary drainage (BD). The optimal timing for BD remains unclear.AimTo investigate the effect of biliary drainage timing on clinical outcomes in AC.Material and methodsWe conducted a retrospective study of patients with AC admitted to the ICU using the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Emergency department to BD time, hospital death, length of stay (LOS), and severity scores were extracted from the database. We investigated the effect of BD timing on mortality rates, persistent organ failure, and LOS.ResultsA total of 177 patients were included; 50% were males; median age was 75 years, in-hospital mortality was 9.6%, mean time-to-ERCP was 32 h (range: 0.42–229.6) with 76% meeting the Tokyo Guidelines (TG13) criteria for severe cholangitis, and median Simplified Acute Physiology Score II (SAPS II) was 42 (IQR: 33–51). Using 24 h as a cut-off, patients who underwent BD ≤ 24 h had less persistent organ failure (OR = 0.49; 95% CI: 0.26–0.96, p = 0.040), shorter ICU LOS (3.25 vs. 4.95 days, p = 0.040), shorter hospital LOS (7.71 vs. 13.57 days, p = 0.001), but no difference in either in-hospital mortality (OR = 0.47, 95% CI: 0.17–1.29, p = 0.146) or 28-day mortality (OR = 0.61, 95% CI: 0.24–1.53, p = 0.297).ConclusionsIn critically-ill patients with acute cholangitis, early biliary drainage ≤ 24 h is associated with less persistent organ failure and shorter length of stay but had no effect on patient survival.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation

To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. A 16-year multicenter retrospective study. Fifteen university and nonuniversity ICUs in France. Patients admitted in ICU for pheochromocytoma crisis. None. We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.