Baseline Illness Severity Research Articles

Cardiorespiratory stability in critically ill preterm infants following dexmedetomidine initiation.

To evaluate cardiorespiratory status in preterm infants receiving dexmedetomidine using high-resolution physiologic data. We analyzed preterm infants with continuous heart rate (HR) and oxygen saturation (SpO2) data for 24 hours preceding and 48 hours following dexmedetomidine initiation. Invasive arterial blood pressure (ABP), when available, was analyzed. In 100 infants with mean gestational age of 28 weeks and high baseline illness severity, mean HR decreased from 152 to 141 beats per minute while mean SpO2 increased from 91% to 93% in the 48 hours after dexmedetomidine initiation (p<0.01). In 57 infants with continuous ABP monitoring, mean ABP increased from 40 to 42 mmHg (p=0.01). Vasoactive-inotropic support increased before and after initiation. We observed cardiorespiratory changes in critically ill preterm infants following dexmedetomidine initiation; mean HR decreased and mean SpO2 increased in the 48 hours after initiation. In a subset, mean ABP increased along with vasoactive-inotropic support.

Child Opportunity Index and Pediatric Extracorporeal Membrane Oxygenation Outcomes; the Role of Diagnostic Category.

To study the impact of social determinants of health (SDoH) on pediatric extracorporeal membrane oxygenation (ECMO) outcomes. Retrospective study of children (< 18 yr) supported on ECMO (October 1, 2015 to March 1, 2021) using Pediatric Health Information System (44 U.S. children's hospitals). Patients were divided into five diagnostic categories: neonatal cardiac, pediatric cardiac, neonatal respiratory, pediatric respiratory, and sepsis. SDoH included the Child Opportunity Index (COI; higher indicates social advantage), race, ethnicity, payer, and U.S. region. Children without COI were excluded. Diagnostic category-specific clinical variables related to baseline health and illness severity were collected. None. Children supported on ECMO experienced a 33% in-hospital mortality (2863/8710). Overall, children with lower COI, "other" race, Hispanic ethnicity, public insurance and from South or West regions had greater mortality. Associations between SDoH and ECMO outcomes differed between diagnostic cohorts. Bivariate analyses found that only pediatric cardiac patients had an association between COI or race and mortality. Multivariable logistic regression analyses examined relationships between SDoH, clinical variables and mortality within diagnostic categories. Pediatric cardiac patients had 5% increased odds of death (95% CI, 1.01-1.09) for every 10-point decrement in COI, while Hispanic ethnicity was associated with higher survival (adjusted odds ratio [aOR] 0.72 [0.57-0.89]). Children with heart disease from the highest COI quintile had less cardiac-surgical complexity and earlier cannulation. Independent associations with mortality were observed in sepsis for Black race (aOR 1.62 [1.06-2.47]) and other payer in pediatric respiratory patients (aOR 1.94 [1.23-3.06]). SDoH are statistically associated with pediatric ECMO outcomes; however, associations differ between diagnostic categories. Influence of COI was observed only in cardiac patients while payer, race, and ethnicity results varied. Further research should investigate differences between diagnostic cohorts and age groups to understand drivers of inequitable outcomes.

Elevated venous lactate level as an early predictive marker of organ failure in acute pancreatitis: a retrospective study.

The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

Machine learning vs. traditional regression analysis for fluid overload prediction in the ICU

Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors. This was a retrospective, observational cohort study of adult patients admitted to an ICU ≥ 72 h between 10/1/2015 and 10/31/2020 with available fluid balance data. Models to predict fluid overload (a positive fluid balance ≥ 10% of the admission body weight) in the 48–72 h after ICU admission were created. Potential patient and medication fluid overload predictor variables (n = 28) were collected at either baseline or 24 h after ICU admission. The optimal traditional logistic regression model was created using backward selection. Supervised, classification-based ML models were trained and optimized, including a meta-modeling approach. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared between the traditional and ML fluid prediction models. A total of 49 of the 391 (12.5%) patients developed fluid overload. Among the ML models, the XGBoost model had the highest performance (AUROC 0.78, PPV 0.27, NPV 0.94) for fluid overload prediction. The XGBoost model performed similarly to the final traditional logistic regression model (AUROC 0.70; PPV 0.20, NPV 0.94). Feature importance analysis revealed severity of illness scores and medication-related data were the most important predictors of fluid overload. In the context of our study, ML and traditional models appear to perform similarly to predict fluid overload in the ICU. Baseline severity of illness and ICU medication regimen complexity are important predictors of fluid overload.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

BackgroundIt remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia.MethodsThis multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively.ResultsAt week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%).ConclusionsSymptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks.Trial registrationThis study was registered on Clinicaltrials.gov (NCT03451734).

Evaluation of medication regimen complexity as a predictor for mortality

While medication regimen complexity, as measured by a novel medication regimen complexity-intensive care unit (MRC-ICU) score, correlates with baseline severity of illness and mortality, whether the MRC-ICU improves hospital mortality prediction is not known. After characterizing the association between MRC-ICU, severity of illness and hospital mortality we sought to evaluate the incremental benefit of adding MRC-ICU to illness severity-based hospital mortality prediction models. This was a single-center, observational cohort study of adult intensive care units (ICUs). A random sample of 991 adults admitted ≥ 24 h to the ICU from 10/2015 to 10/2020 were included. The logistic regression models for the primary outcome of mortality were assessed via area under the receiver operating characteristic (AUROC). Medication regimen complexity was evaluated daily using the MRC-ICU. This previously validated index is a weighted summation of medications prescribed in the first 24 h of ICU stay [e.g., a patient prescribed insulin (1 point) and vancomycin (3 points) has a MRC-ICU = 4 points]. Baseline demographic features (e.g., age, sex, ICU type) were collected and severity of illness (based on worst values within the first 24 h of ICU admission) was characterized using both the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Sequential Organ Failure Assessment (SOFA) score. Univariate analysis of 991 patients revealed every one-point increase in the average 24-h MRC-ICU score was associated with a 5% increase in hospital mortality [Odds Ratio (OR) 1.05, 95% confidence interval 1.02–1.08, p = 0.002]. The model including MRC-ICU, APACHE II and SOFA had a AUROC for mortality of 0.81 whereas the model including only APACHE-II and SOFA had a AUROC for mortality of 0.76. Medication regimen complexity is associated with increased hospital mortality. A prediction model including medication regimen complexity only modestly improves hospital mortality prediction.

Driving Pressure: What Is the Harm?

Driving Pressure: What Is the Harm?

Propofol-Associated Hypertriglyceridemia in Adults With Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

The incidence and risk factors for propofol-associated hypertriglyceridemia (HTG) in patients receiving extracorporeal membrane oxygenation (ECMO) have not been evaluated. The purpose of this study was to determine the incidence and risk factors for propofol-associated HTG in patients with acute respiratory distress syndrome (ARDS) on ECMO. This retrospective, cohort study included 167 adults admitted to a medical intensive care unit (ICU) from July 1, 2013 to September 1, 2021, who received 24 hours of concurrent propofol and ECMO therapy. The primary outcome was the incidence of propofol-associated HTG. Secondary outcomes included HTG risk factors, time to development and resolution of HTG, and incidence of pancreatitis. HTG occurred in 58 (34.7%) patients. Patients with HTG had longer durations of ECMO (19 vs. 13 days, p < 0.001), longer ICU length of stay (26.5 vs. 23 days, p = 0.002), and higher in-hospital mortality (51.7 vs. 34.9%, p = 0.047). Baseline sequential organ failure assessment score was associated with an increased risk of developing HTG (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.09-1.30; p < 0.001). Propofol-associated HTG occurred in one-third of patients receiving ECMO for ARDS. Higher baseline illness severity and ECMO duration were associated with an increased risk of propofol-associated HTG.

Clinical Global Impression of Cariprazine in Negative Symptom Schizophrenia Patients: Comparison of clinical trial data vs. real-world evidence

IntroductionThere is an increasing need to understand the effectiveness of novel medications in real-world context since despite being the gold standard, double-blind trials have their own limitations as well. Clinical Global Impression is a simple tool for clinicians to assess the severity of an illness (CGI-Severity) as well as to rate how much the patient’s disorder has improved or worsened relative to baseline (CGI-Improvement). In this poster, cariprazine, a third-generation antipsychotic medication that was found to be effective in the treatment of negative symptoms in schizophrenia will be evaluated.ObjectivesTo compare the effectiveness of cariprazine in clinical trial vs real-world setting via the CGI-S and CGI-I scales in negative symptom schizophrenia patients.MethodsWe compared the results of a clinical trial (Németh et al. Lancet 2017; 389:1103-13) and an observational study (Rancans et al. Int Clin Psychopharmacol. 2021;36(3):154-161). The latter was an open-label, flexible-dose, 16-week, observational study of cariprazine involving 116 outpatients in Latvia. Adult patients who have been diagnosed with schizophrenia, exhibited negative symptoms based on clinical judgement, were at least mildly ill according to the CGI-S scale and have not previously received cariprazine were eligible to take part in the study. Dosing of cariprazine was based on clinical judgement. The clinical trial was a randomized, double-blind, multi-centred, 26-week study with adults aged 18–65 years with long-term (&gt;2 year), stable schizophrenia and predominant negative symptoms (&gt;6 months). Patients were randomly assigned to monotherapy with cariprazine 4.5 mg/day or risperidone 4.0 mg/day.Results116 patients on flexible dose cariprazine (observational study) were compared with 227 patients on cariprazine 4.5 mg/day and 229 on risperidone 4.0 mg/day (clinical trial). Baseline severity of illness as measured by the CGI-S was between moderately and markedly ill in all three groups. By the end of the 26-week trial, cariprazine reduced the CGI-S score significantly (LS Mean Change: -0.9, p&lt;0.01). In contrast, the risperidone group achieved only -0.7-point change from baseline. In the observational study, cariprazine also achieved significant change (-0.9, p&lt;0.001) but by week 16. In terms of improvement, patients on cariprazine improved minimally to much in both the clinical trial and real-world setting.ConclusionsThe effectiveness of cariprazine in clinical trial and real-world setting do not seem to differ as measured by the scales in negative symptom patients.Disclosure of InterestE. Rancans Grant / Research support from: Gedeon Richter, Lundbeck, Consultant of: Abbvie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, Zentiva, Speakers bureau of: Abbvie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, Zentiva, Z. Dombi Employee of: Gedeon Richter Plc., R. Csehi Employee of: Gedeon Richter Plc., G. Németh Employee of: Gedeon Richter Plc.

Systemic thrombolytic and ultrasound-assisted catheter-directed thrombolysis for treatment of acute pulmonary embolism: a 7-year, multicenter experience.

Treatment of acute pulmonary embolism (PE) varies based upon risk stratification and ranges from outpatient oral anticoagulation to emergency surgical embolectomy. Patients with high-risk PE can be considered for systemic thrombolytic (ST) based upon guideline recommendations, but intermediate-risk PE does not currently have strong evidence to guide primary reperfusion strategies via thrombolytic administration. Ultrasound-assisted catheter-directed thrombolysis (USAT) is an alternative reperfusion option to ST but is not currently recommended as first line in any key guidelines due to limited available evidence. This retrospective, multicenter, observational study compares 210 patients treated with USAT (n = 105) or ST (n = 105) for acute high- or intermediate-risk PE in three hospitals. Baseline characteristics were significant in that severity of illness was higher in those that received ST, which limited comparisons of outcomes. The primary outcome of major bleeding in patients receiving USAT was 15.2% and 22.9% in those that received ST. Efficacy of reperfusion strategy was observed to be 86.7% of patients in USAT group and 65.7% in ST group. Reperfusion strategies had no difference in in-hospital death, intensive care length of stay, or hospital length of stay. Predefined subgroup analysis found that high-risk PE had higher mortality (14.7%) than intermediate-risk PE (0%) regardless of reperfusion strategy. Upon multivariate analysis, high-risk PE was the only independent risk factor for major bleeding while USAT therapy and intermediate-risk PE were independent predictors of efficacy. Due to the difference in baseline severity of illness, direct comparisons in primary outcomes to each group was not performed. We have described real world usage of both USAT and ST and which patients were likely to receive each therapy at these institutions.

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients

BackgroundSedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults.MethodsThis was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis.ResultsOne hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20–0.93] vs 0.14 [0.08–0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26–0.4] vs 0.38 [0.31–0.48]), noradrenaline (4.27 [3.12–5.85] vs 6.2 [4.6–8.5]), adrenocorticotropic hormone (17.1 [15.1–19.5] vs 18.1 [15.9–20.5]) and cortisol (515 [409–648] vs 618 [491–776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis.ConclusionsEarly sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation.

Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital.

Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ± 12.5 years), were studied. 65.9% (n = 27) had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.

Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection.

Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) – that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness. Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors. The sample included 484 subjects (51% female, median age 32, IQR 19–44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34–0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30–0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery. Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71–2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.

Prone positioning for mechanically ventilated patients with coronavirus disease 2019: the experience of an Irish regional hospital intensive care unit.

BackgroundThe benefits of prone positioning in acute respiratory distress syndrome (ARDS) have been known for many years. While some controversy exists regarding whether coronavirus disease 2019 (COVID-19) pneumonia should be treated with the same therapeutic strategies as for non-COVID ARDS, the Surviving Sepsis Campaign still provide a weak recommendation to utilise prone positioning in this setting.AimsThe aims of this study are to ascertain if prone positioning improves oxygenation significantly in mechanically ventilated patients with severe COVID-19 ARDS and to describe the feasibility of frequent prone positioning in an Irish regional hospital intensive care unit (ICU) with limited prior experience.MethodsIn this retrospective, observational cohort study, we investigate if the PaO2/FiO2 ratio and ventilatory ratio improve during and following prone positioning, and whether this improvement correlates with patient baseline characteristics or survival.ResultsBetween March 2020 and 2021, 12 patients underwent prone positioning while mechanically ventilated for severe COVID ARDS. Sixty-six percent were male, mean age 60.9 (± 10.5), mean BMI 33.5 (± 6.74) and median APACHE II score on admission to ICU was 10.5 (7.25–16.3). Further, 83% were proned within 24 h of being intubated due to refractory hypoxaemia. PaO2/FiO2 ratio improved from 11.6 kPa (9.80–13.8) to 15.80 kPa (13.1–19.6) while prone, p < 0.0001.ConclusionsWe found prone positioning to be a safe method of significantly improving oxygenation in mechanically ventilated patients with severe COVID-19 ARDS. We did not find a relationship between patient baseline characteristics nor illness severity and degree of PaO2/FiO2 ratio improvement, nor did we find a relationship between degree of PaO2/FiO2 ratio improvement and survival.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11845-022-03085-9.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

PurposeAlthough there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19.MethodsMulticentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated.ResultsBetween February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65–0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58–0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14–1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61–0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia.ConclusionCorticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06726-w.

CARC13: Early Low Pulsatility in VA-ECMO is Associated with Acute Brain Injury

Background: Pulse pressure (or pulsatility) is a dynamic marker of cardiovascular function and is often decreased in patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), which provides non-pulsatile flow. We explored the impact of pulse pressure on development of acute brain injury (ABI) in VA-ECMO patients. Methods: We retrospectively analyzed all adult (≥18 years old) patients receiving VA-ECMO at a single tertiary care center between 7/2016 and 1/2021. All patients received routine neurocritical care consultations with standardized neuromonitoring. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressure (BP) was recorded every 15 minutes during the first 24 hours after ECMO initiation. Pulse pressure (systolic minus diastolic pressure) was categorized as: very low (<10mmHg), low (1029mmHg), moderate (30-44mmHg), and high (≥45mmHg). Multivariable logistic regression, controlling for baseline illness severity, operative characteristics, and left ventricle (LV) venting strategy, was performed for the association of pulse pressure with ABI. LV venting strategies included intra-aortic balloon pump (IABP), percutaneous ventricular assist device, right superior pulmonary vein, and left ventricle apex vents. Results: We collected 9,179 pressure measurements from 123 VA-ECMO patients (median age=63, 63% male), of which 41 (33%) experienced ABI. Demographics, baseline clinical characteristics, and pre-ECMO arterial blood gases were not significantly different between those with and without ABI. Those with ABI had a lower median pulse pressure than those without (20 mmHg vs. 32, p=0.038). In a multivariable model controlling for cannulation site, preECMO lactate, and left ventricle venting strategy, low (adjusted odds ratio/aOR=7.04, 95%CI: 1.72-28.82, p=0.007) and very low pulse pressure (aOR=5.14, 95%CI: 1.18-22.34, p=0.029) were associated with ABI (Figure 1). In a model with the same covariates, every 10-mmHg decrease in pulse pressure was associated with a 1.29 increased adjusted odds of ABI (95%CI: 1.00-1.65, p=0.047) (Figure 2). In a sensitivity analysis, adjusting for systolic BP yielded similar associations between pulse pressure and ABI, suggesting pulse pressure acts independently of BP in mediating ABI. Conclusions: Decreased pulsatility in the first 24 hours of VA-ECMO was associated with ABI. Special attention should be given to management practices which sustain sufficient pulse pressure early during ECMO. Figure 1. Forest plot for multivariable model of pulse pressure and acute brain injury (ABI), with the covariates of central cannulation, lactate on ECMO day 1, and left ventricle venting strategy. Covariates are not shown in the figure. Dots represent adjusted odds ratios and brackets represent 95% confidence intervals. Low and very low pulse pressure were associated with increased odds of ABI. This model had a C-index of 0.76. Figure 2. Multivariable logistic regression model with pulse pressure treated as a continuous variable, with the covariates of central cannulation, lactate on ECMO day 1, and left ventricle venting strategy. The adjusted relative odds of acute brain injury decrease as pulse pressure increases.

Comparison of the predictive ability of clinical frailty scale and hospital frailty risk score to determine long-term survival in critically ill patients: a multicentre retrospective cohort study

BackgroundThe Clinical Frailty Scale (CFS) is the most commonly used frailty measure in intensive care unit (ICU) patients. The hospital frailty risk score (HFRS) was recently proposed for the quantification of frailty. We aimed to compare the HFRS with the CFS in critically ill patients in predicting long-term survival up to one year following ICU admission.MethodsIn this retrospective multicentre cohort study from 16 public ICUs in the state of Victoria, Australia between 1st January 2017 and 30th June 2018, ICU admission episodes listed in the Australian and New Zealand Intensive Care Society Adult Patient Database registry with a documented CFS, which had been linked with the Victorian Admitted Episode Dataset and the Victorian Death Index were examined. The HFRS was calculated for each patient using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes that represented pre-existing conditions at the time of index hospital admission. Descriptive methods, Cox proportional hazards and area under the receiver operating characteristic (AUROC) were used to investigate the association between each frailty score and long-term survival up to 1 year, after adjusting for confounders including sex and baseline severity of illness on admission to ICU (Australia New Zealand risk-of-death, ANZROD).Results7001 ICU patients with both frailty measures were analysed. The overall median (IQR) age was 63.7 (49.1–74.0) years; 59.5% (n = 4166) were male; the median (IQR) APACHE II score 14 (10–20). Almost half (46.7%, n = 3266) were mechanically ventilated. The hospital mortality was 9.5% (n = 642) and 1-year mortality was 14.4% (n = 1005). HFRS correlated weakly with CFS (Spearman’s rho 0.13 (95% CI 0.10–0.15) and had a poor agreement (kappa = 0.12, 95% CI 0.10–0.15). Both frailty measures predicted 1-year survival after adjusting for confounders, CFS (HR 1.26, 95% CI 1.21–1.31) and HFRS (HR 1.08, 95% CI 1.02–1.15). The CFS had better discrimination of 1-year mortality than HFRS (AUROC 0.66 vs 0.63 p < 0.0001).ConclusionBoth HFRS and CFS independently predicted up to 1-year survival following an ICU admission with moderate discrimination. The CFS was a better predictor of 1-year survival than the HFRS.

Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis.

What is known and objectiveTimely and appropriate dosing of antibiotics is essential for the treatment of bacterial sepsis. Critically ill patients treated with continuous kidney replacement therapy (CKRT) often have physiologic derangements that affect pharmacokinetics (PK) of antibiotics and dosing may be challenging. We sought to aggregate previously published piperacillin and tazobactam (pip‐tazo) pharmacokinetic data in critically ill patients undergoing CKRT to better understand pharmacokinetics of pip‐tazo in this population and better inform dosing.MethodsThe National Library of Medicine Database was searched for original research containing piperacillin or tazobactam clearance (CL) or volume of distribution (V) estimates in patients treated with CKRT. The search yielded 77 articles, of which 26 reported suitable estimates of CL or V. Of the 26 articles, 10 for piperacillin and 8 for tazobactam had complete information suitable for population pharmacokinetic modelling. Also included in the analysis was piperacillin and tazobactam PK data from 4 critically ill patients treated with CKRT in the Military Health System, 2 with burn and 2 without burn.Results and DiscussionMedian and range of literature reported PK parameters for piperacillin (CL 2.76 L/hr, 1.4–7.92 L/hr, V 31.2 L, 16.77–42.27 L) and tazobactam (CL 2.34 L/hr, 0.72–5.2 L/hr, V 36.6 L, 26.2–58.87 L) were highly consistent with population estimates (piperacillin CL 2.7 L/hr, 95%CI 1.99–3.41 L/hr, V 25.83 22.07–29.59 L, tazobactam CL 2.49 L/hr, 95%CI 1.55–3.44, V 30.62 95%CI 23.7–37.54). The proportion of patients meeting pre‐defined pharmacodynamic (PD) targets (median 88.7, range 71%–100%) was high despite significant mortality (median 44%, range 35%–60%). High mortality was predicted by baseline severity of illness (median APACHE II score 23, range 21–33.25). Choice of lenient or strict PD targets (ie 100%fT >MIC or 100%fT >4XMIC) had the largest impact on probability of target attainment (PTA), whereas presence or intensity of CKRT had minimal impact on PTA.What is new and conclusionPip‐tazo overexposure may be associated with increased mortality, although this is confounded by baseline severity of illness. Achieving adequate pip‐tazo exposure is essential; however, risk of harm from overexposure should be considered when choosing a PD target and dose. If lenient PD targets are desired, doses of 2250–3375 mg every 6 h are reasonable for most patients receiving CKRT. However, if a strict PD target is desired, continuous infusion (at least 9000–13500 mg per day) may be required. However, some critically ill CKRT populations may need higher or lower doses and dosing strategies should be tailored to individuals based on all available clinical data including the specific critical care setting.

Acute kidney injury-attributable mortality in critically ill patients with sepsis.

BackgroundTo assess whether acute kidney injury (AKI) is independently associated with hospital mortality in ICU patients with sepsis, and estimate the excess AKI-related mortality attributable to AKI.MethodsWe analyzed adult patients from two distinct retrospective critically ill cohorts: (1) Medical Information Mart for Intensive Care IV (MIMIC IV; n = 15,610) cohort and (2) Wenzhou (n = 1,341) cohort. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We applied multivariate logistic and linear regression models to assess the hospital and ICU mortality, hospital length-of-stay (LOS), and ICU LOS. The excess attributable mortality for AKI in ICU patients with sepsis was further evaluated.ResultsAKI occurred in 5,225 subjects in the MIMIC IV cohort (33.5%) and 494 in the Wenzhou cohort (36.8%). Each stage of AKI was an independent risk factor for hospital mortality in multivariate logistic regression after adjusting for baseline illness severity. The excess attributable mortality for AKI was 58.6% (95% CI [46.8%–70.3%]) in MIMIC IV and 44.6% (95% CI [12.7%–76.4%]) in Wenzhou. Additionally, AKI was independently associated with increased ICU mortality, hospital LOS, and ICU LOS.ConclusionAcute kidney injury is an independent risk factor for hospital and ICU mortality, as well as hospital and ICU LOS in critically ill patients with sepsis. Thus, AKI is associated with excess attributable mortality.

1228. Outcomes Associated with Empiric Cefepime or Meropenem for Bloodstream Infections Caused by Ceftriaxone-Resistant, Cefepime-Susceptible Escherichia coli and Klebsiella pneumoniae

BackgroundCefepime is a 4th generation cephalosporin frequently used for empiric sepsis therapy. Dose- and MIC-dependent efficacy of cefepime is supported by the Clinical & Laboratory Standards Institute, however its use in infections due to extended-spectrum beta-lactamase-producing Enterobacterales is controversial. This study aims to compare outcomes in patients given empiric meropenem or cefepime for bloodstream infections (BSI) caused by ceftriaxone-resistant E. coli and K. pneumoniae.MethodsThis single-center retrospective cohort included adults hospitalized from 2010 - 2020 and received empiric cefepime or meropenem for BSI caused by ceftriaxone-resistant E. coli or K. pneumoniae. In the cefepime group, only organisms with MIC ≤ 2 mg/L were included. Patients who received the empiric agent for < 48 hours, or received an additional active agent within 48 hours were excluded. The primary outcome was 30-day mortality; secondary outcomes were recurrent infection, readmission, and time to clinical stability. Chi-squared or Fisher’s exact was used for categorical variables and Mann-Whitney-U for continuous variables. Inverse probability treatment weighing was used to determine the impact of empirical therapy on clinical stability at 48 hours. ResultsFifty-four patients were included: 36 received empiric meropenem, 18 received cefepime. There were no significant differences in baseline severity of illness or comorbid conditions. Urinary source was less common in the meropenem group compared to cefepime (52.8 vs 83.8%, p=0.028) (Table 1). There was no difference in 30-day mortality between meropenem and cefepime (2.8 vs 11.1%, p = 0.255). More patients achieved clinical stability at 48 hours on empiric meropenem compared to cefepime (75 vs 44.4%, p = 0.027), and time to clinical stability was significantly shorter (median 21.3 vs 38.5 hours, p = 0.016). Most patients in the meropenem and cefepime groups completed definitive treatment with a carbapenem (88.9 vs 72.2%, p=0.142). Table 1: Results Summary of primary and secondary outcomesConclusionThere was no difference in mortality between patients receiving empiric cefepime for BSI due to ceftriaxone-resistant Enterobacterales, with cefepime MIC ≤ 2 mg/L, compared to meropenem; however, time to clinical stability was significantly delayed. Disclosures James Kirby, MD, D(ABMM), First Light Biosciences (Board Member)TECAN, Inc. (Research Grant or Support)