Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.

This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC0-24/MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.

Oxygenation During Venoarterial Extracorporeal Membrane Oxygenation: Physiology, Current Evidence, and a Pragmatic Approach to Oxygen Titration.

OBJECTIVES: This review aims to: 1) identify the key circuit and patient factors affecting systemic oxygenation, 2) summarize the literature reporting the association between hyperoxia and patient outcomes, and 3) provide a pragmatic approach to oxygen titration, in patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (ECMO). DATA SOURCES: Searches were performed using PubMed, SCOPUS, Medline, and Google Scholar. STUDY SELECTION: All observational and interventional studies investigating the association between hyperoxia, and clinical outcomes were included, as well as guidelines from the Extracorporeal Life Support Organization. DATA EXTRACTION: Data from relevant literature was extracted, summarized, and integrated into a concise narrative review. For ease of reference a summary of relevant studies was also produced. DATA SYNTHESIS: The extracorporeal circuit and the native cardiorespiratory circuit both contribute to systemic oxygenation during venoarterial ECMO. The ECMO circuit's contribution to systemic oxygenation is, in practice, largely determined by the ECMO blood flow, whereas the native component of systemic oxygenation derives from native cardiac output and residual respiratory function. Interactions between ECMO outflow and native cardiac output (as in differential hypoxia), the presence of respiratory support, and physiologic parameters affecting blood oxygen carriage also modulate overall oxygen exposure during venoarterial ECMO. Physiologically those requiring venoarterial ECMO are prone to hyperoxia. Hyperoxia has a variety of definitions, most commonly Pa o2 greater than 150 mm Hg. Severe hypoxia (Pa o2 > 300 mm Hg) is common, seen in 20%. Early severe hyperoxia, as well as cumulative hyperoxia exposure was associated with in-hospital mortality, even after adjustment for disease severity in both venoarterial ECMO and extracorporeal cardiopulmonary resuscitation. A pragmatic approach to oxygenation during peripheral venoarterial ECMO involves targeting a right radial oxygen saturation target of 94-98%, and in selected patients, titration of the fraction of oxygen in the mixture via the air-oxygen blender to target postoxygenator Pa o2 of 150-300 mm Hg. CONCLUSIONS: Hyperoxia results from a range of ECMO circuit and patient-related factors. It is common during peripheral venoarterial ECMO, and its presence is associated with poor outcome. A pragmatic approach that avoids hyperoxia, while also preventing hypoxia has been described for patients receiving peripheral venoarterial ECMO.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Anti-Factor-Xa and Activated Partial Thromboplastin Time Concordance and Outcomes in Adults Undergoing Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Pilot Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation Randomized Trial.

OBJECTIVES: To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. DESIGN: Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. SETTING: Two ICUs in two university hospitals. PATIENTS: Thirty-two critically ill patients who underwent ECMO and who had at least one paired aPTT and anti-Xa assay performed at the same time. INTERVENTIONS: We analyzed the concordance between aPTT and anti-Xa and identified factors associated with discordant paired aPTT/anti-Xa based on their respective therapeutic ranges. We also compared biological parameters between heparin resistance episode and no heparin resistance. MEASUREMENTS AND MAIN RESULTS: Of the 32 patients who were included in this study, 24 (75%) had at least one discordant paired aPTT/anti-Xa. Of the 581 paired aPTT/anti-Xa that were analyzed, 202 were discordant. The aPTT was relatively lower than anti-Xa in 66 cases (32.7%) or relatively higher than anti-Xa in 136 cases (67.3%). Thirty-three heparin resistance episodes were identified in six patients (19%). CONCLUSIONS: In these critically ill patients undergoing ECMO, one third of paired aPTT/anti-Xa measures was discordant. Coagulopathy and heparin resistance might be the reasons for discordance. Our results support the potential importance of routinely monitoring both tests in this setting.

ECMO PAL: using deep neural networks for survival prediction in venoarterial extracorporeal membrane oxygenation.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a complex and high-risk life support modality used in severe cardiorespiratory failure. ECMO survival scores are used clinically for patient prognostication and outcomes risk adjustment. This study aims to create the first artificial intelligence (AI)-driven ECMO survival score to predict in-hospital mortality based on a large international patient cohort. METHODS: A deep neural network, ECMO Predictive Algorithm (ECMO PAL) was trained on a retrospective cohort of 18,167 patients from the international Extracorporeal Life Support Organisation (ELSO) registry (2017-2020), and performance was measured using fivefold cross-validation. External validation was performed on all adult registry patients from 2021 (N = 5015) and compared against existing prognostication scores: SAVE, Modified SAVE, and ECMO ACCEPTS for predicting in-hospital mortality. RESULTS: Mean age was 56.8 ± 15.1 years, with 66.7% of patients being male and 50.2% having a pre-ECMO cardiac arrest. Cross-validation demonstrated an inhospital mortality sensitivity and precision of 82.1 ± 0.2% and 77.6 ± 0.2%, respectively. Validation accuracy was only 2.8% lower than training accuracy, reducing from 75.5% to 72.7% [99% confidence interval (CI) 71.1-74.3%]. ECMO PAL accuracy outperformed the ECMO ACCEPTS (54.7%), SAVE (61.1%), and Modified SAVE (62%) scores. CONCLUSIONS: ECMO PAL is the first AI-powered ECMO survival score trained and validated on large international patient cohorts. ECMO PAL demonstrated high generalisability across ECMO regions and outperformed existing, widely used scores. Beyond ECMO, this study highlights how large international registry data can be leveraged for AI prognostication for complex critical care therapies.

The effect of drainage cannula tip position on risk of thrombosis during venoarterial extracorporeal membrane oxygenation.

BACKGROUND AND OBJECTIVES: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is able to support critically ill patients undergoing refractory cardiopulmonary failure. It relies on drainage cannulae to extract venous blood from the patient, but cannula features and tip position may impact flow dynamics and thrombosis risk. Therefore, this study aimed to investigate the effect of tip position of single-stage (SS) and multi-stage (MS) VA ECMO drainage cannulae on the risk of thrombosis. METHODS: Computational fluid dynamics was used to model flow dynamics within patient-specific geometry of the venous vasculature. The tip of the SS and MS cannula was placed in the superior vena cava (SVC), SVC-Right atrium (RA) junction, mid-RA, inferior vena cava (IVC)-RA junction, and IVC. The risk of thrombosis was assessed by measuring several factors. Blood residence time was measured via an Eulerian approach through the use of a scalar source term. Regions of stagnant volume were recognised by identifying regions of low fluid velocity and shear rate. Rate of blood washout was calculated by patching the domain with a scalar value and measuring the rate of fluid displacement. Lastly, wall shear stress values were determined to provide a qualitative understanding of potential blood trauma. RESULTS: Thrombosis risk varied substantially with position changes of the SS cannula, which was less evident with the MS cannula. The SS cannula showed reduced thrombosis risk arising from stagnant regions when placed in the SVC or SVC-RA junction, whereas an MS cannula was predicted to create stagnant regions during all tip positions. When positioned in the IVC-RA junction or IVC, the risk of thrombosis was higher in the SS cannula than in the MS cannula due to both high and low shear flow. CONCLUSION: Tip position of the drainage cannula impacts cannula flow dynamics and, subsequently, the risk of thrombosis. The use of MS cannulae can reduce high shear-related thrombosis, but SS cannulae can eliminate stagnant regions when advanced into the SVC. Therefore, the choice of cannula design and tip position should be carefully considered during cannulation.

Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation.

Rationale: Data suggest that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO). Objectives: The primary aim of this analysis was to describe the pharmacokinetics (PKs) of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve effective and safe exposure. Methods: This study was a prospective, open-labeled, PK study in six ICUs in Australia, New Zealand, South Korea, and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for 11 antimicrobials. PK parameters were estimated using noncompartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using predefined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks. Measurements and Main Results: We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years, and 61.2% were male. Thirty-eight patients (44.7%) were receiving renal replacement therapy during the first PK sampling. Large variations (coefficient of variation of ⩾30%) in antimicrobial concentrations were seen leading to more than fivefold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the predefined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and renal replacement therapy. Poor target attainment was observed across the most frequently used antimicrobials for ECMO recipients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%). Conclusions: Antimicrobial PKs were highly variable in critically ill patients receiving ECMO, leading to poor target attainment rates. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000559819).

Extracorporeal Membrane Oxygenation as a Bridge to Surgical Repair of Postinfarct Ventricular Septal Defect.

Postinfarct ventricular septal defect (PIVSD) is associated with high mortality and the management of these patients has been a challenge with little improvement in outcomes. We commenced a protocol of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for those patients who present in cardiogenic shock with the aim to improve end-organ function before definitive surgical repair to reduce postoperative mortality. This study reviewed the results of this strategy. This was a single-center, retrospective review of all patients who were admitted to our institution with PIVSD in cardiogenic shock from September 2015 to November 2019. Clinical and investigative data were evaluated. Eight patients were referred with PIVSD during this period in cardiogenic shock. One patient had an anterior PIVSD and the other seven had inferior PIVSD. Six patients underwent surgical repair at a median (interquartile range, IQR) of 7 (5-8) days after initiation of VA ECMO. Two patients did not undergo surgical repair. Five patients survived after surgery and one patient died postoperatively due to multiorgan failure. Preoperative use of VA ECMO is a feasible strategy for PIVSD and may improve the results of repair.

Clinician Perspectives on Cannulation for Extracorporeal Cardiopulmonary Resuscitation: A Mixed Methods Analysis.

Out-of-hospital cardiac arrest is a leading cause of mortality with survival rates of less than 10%. In selected patients, survival may be improved via timely application of extracorporeal cardiopulmonary resuscitation (ECPR). However, ECPR is a complex and resource intensive intervention with a high risk of complications that impair widespread clinical adoption. This study employed a mixed approach of qualitative interview analysis embedded with quantitative data collection to uncover the major hurdles faced by clinicians during ECPR initiation. We conducted semi-structured interviews with eight ECPR intensive care specialists with 2-10 years of experience working at a large, tertiary ECPR center in Australia. Clinicians identified dilation as the most time-consuming step, followed by draping, and decision-making during extracorporeal membrane oxygenation patient selection. The most challenging step was the decision-making for patient selection, followed by dilation and imaging. These findings uncovered key barriers to ECPR, and identified priority areas for further research and clinical training. Major logistical hindrances will require well-defined protocols and improved clinical training. Engineering innovations in the identified areas may improve the delivery of ECPR, making it simpler and faster to deliver.

Incidence of death or disability at 6 months after extracorporeal membrane oxygenation in Australia: a prospective, multicentre, registry-embedded cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive procedure used to support critically ill patients with the most severe forms of cardiac or respiratory failure in the short term, but long-term effects on incidence of death and disability are unknown. We aimed to assess incidence of death or disability associated with ECMO up to 6 months (180 days) after treatment. METHODS: This prospective, multicentre, registry-embedded cohort study was done at 23 hospitals in Australia from Feb 15, 2019, to Dec 31, 2020. The EXCEL registry included all adults (≥18 years) in Australia who were admitted to an intensive care unit (ICU) in a participating centre at the time of the study and who underwent ECMO. All patients who received ECMO support for respiratory failure, cardiac failure, or cardiac arrest during their ICU stay were eligible for this study. The primary outcome was death or moderate-to-severe disability (defined using the WHO Disability Assessment Schedule 2.0, 12-item survey) at 6 months after ECMO initiation. We used Fisher's exact test to compare categorical variables. This study is registered with ClinicalTrials.gov, NCT03793257. FINDINGS: Outcome data were available for 391 (88%) of 442 enrolled patients. The primary outcome of death or moderate-to-severe disability at 6 months was reported in 260 (66%) of 391 patients: 136 (67%) of 202 who received veno-arterial (VA)-ECMO, 60 (54%) of 111 who received veno-venous (VV)-ECMO, and 64 (82%) of 78 who received extracorporeal cardiopulmonary resuscitation (eCPR). After adjustment for age, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) IV score, days between ICU admission and ECMO start, and use of vasopressors before ECMO, death or moderate-to-severe disability was higher in patients who received eCPR than in those who received VV-ECMO (VV-ECMO vs eCPR: risk difference [RD] -32% [95% CI -49 to -15]; p<0·001) but not VA-ECMO (VA-ECMO vs eCPR -8% [-22 to 6]; p=0·27). INTERPRETATION: In our study, only a third of patients were alive without moderate-to-severe disability at 6 months after initiation of ECMO. The finding that disability was common across all areas of functioning points to the need for long-term, multidisciplinary care and support for surviving patients who have had ECMO. Further studies are needed to understand the 180-day and longer-term prognosis of patients with different diagnoses receiving different modes of ECMO, which could have important implications for the selection of patients for ECMO and management strategies in the ICU. FUNDING: The National Health and Medical Research Council of Australia.

HOSPITAL CHARACTERISTICS ARE ASSOCIATED WITH CLINICAL OUTCOMES IN PATIENTS WITH CARDIOGENIC SHOCK.

ABSTRACT: Background: Regionalized systems of care for the management of cardiogenic shock (CS) are increasingly being utilized. This study aims to assess whether receiving hospital characteristics such as the availability of 24-hour coronary angiography, on-site cardiac surgery, and annual treated CS volume influence outcomes in patients transferred by emergency medical services (EMS) to hospital with CS. Methods: This population-based cohort study included consecutive adult patients with CS who were transferred to hospital by EMS between January 1, 2015 and June 30, 2019 in Victoria, Australia. Data were obtained from individually linked ambulance, hospital, and state death index data sets. The primary outcome assessed was 30-day mortality stratified by the availability of 24-hour coronary angiography (cardiac center) at the receiving hospital. Results: A total of 3,217 patients were transferred to hospital with CS. The population had an average age of 67.9 +/- 16.1 years, and 1,289 (40.1%) were female. EMS transfer to a cardiac center was associated with significantly reduced rates of 30-day mortality (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.64-0.95), compared with noncardiac centers. Compared with the lowest annual CS volume quartile (<18 cases per year), hospitals in the highest volume quartile (>55 cases per year) had reduced risk of 30-day mortality (aOR, 0.71; 95% CI, 0.56-0.91). A stepwise reduction in the adjusted probability of 30-day mortality was observed in patients transferred by EMS to trauma level 1 centers (34.6%), compared with cardiothoracic surgical centers (39.0%), noncardiac surgical metropolitan (44.9%), and rural (51.3%) cardiac centers, all P < 0.05. Conclusion: Receiving hospital characteristics are associated with survival outcomes in patients with CS. These finding have important implications for establishing regionalized systems of care for patients with CS who are transferred to hospital by EMS.

Association of intentional cooling, achieved temperature and hypothermia duration with in-hospital mortality in patients treated with extracorporeal cardiopulmonary resuscitation: An analysis of the ELSO registry.

AIM: To investigate whether intentional cooling, achieved temperature and hypothermia duration were associated with in-hospital death in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest. METHODS: This is a retrospective analysis of the Extracorporeal Life Support Organization Registry. Patients 18-79 years of age who received ECPR between 2010 and 2019 were included. We compared outcomes for intentional cooling versus no intentional cooling. Then, among those who completed intentional cooling, we compared the outcomes between i) achieved temperature ≤ 34 °C, 34-36 °C, and > 36 °C, and ii) duration ≤ 36 °C for < 12 h, 12-48 h, and ≥ 48 h. The primary outcome was in-hospital mortality within 90 days. Cox proportional hazard models were generated with adjustment for covariates. RESULTS: Among 4,214 ECPR patients, 1,511 patients were included in the final analysis. After multivariable adjustment, there was no significant difference in in-hospital mortality between patients with intentional cooling and no intentional cooling (hazard ratio [HR], 1.06 [95% CI 0.93-1.21]; p = 0.394). In the 609 patients who completed intentional cooling, temperature at 34-36 °C had a significantly lower adjusted HR for in-hospital mortality compared with > 36 °C (HR, 0.73 [0.55-0.96]; p = 0.025). Moreover, temperature ≤ 36 °C for 12-48 h had a significantly lower adjusted HR for in-hospital mortality compared with ≤ 36 °C for < 12 h (HR, 0.69 [0.53-0.90]; p = 0.005). CONCLUSION: Intentional cooling was not associated with lower in-hospital mortality in ECPR patients. However, among patients with intentional cooling, achieving temperature of 34-36 °C for 12-48 h was associated with lower in-hospital mortality.

ECPR2: Expert Consensus on PeRcutaneous Cannulation for Extracorporeal CardioPulmonary Resuscitation.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising resuscitation strategy for select patients suffering from refractory out-of-hospital cardiac arrest (OHCA), though limited data exist regarding the best practices for ECPR initiation after OHCA. METHODS: We utilized a modified Delphi process consisting of two survey rounds and a virtual consensus meeting to systematically identify detailed best practices for ECPR initiation following adult non-traumatic OHCA. A modified Delphi process builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Consensus was achieved when items reached a high level of agreement, defined as greater than 80% responses for a particular item rated a 4 or 5 on a 5-point Likert scale. RESULTS: Snowball sampling generated a panel of 14 content experts, composed of physicians from four continents and five primary specialties. Seven existing institutional protocols for ECPR cannulation following OHCA were identified and merged into a single comprehensive list of 207 items. The panel reached consensus on 101 items meeting final criteria for inclusion: Prior to Patient Arrival (13 items), Inclusion Criteria (8), Exclusion Criteria (7), Patient Arrival (8), ECPR Cannulation (21), Go On Pump (18), and Post-Cannulation (26). CONCLUSION: We present a list of items for ECPR initiation following adult nontraumatic OHCA, generated using a modified Delphi process from an international panel of content experts. These findings may benefit centers currently performing ECPR in quality assurance and serve as a template for new ECPR programs.

Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

INTRODUCTION: This study aimed to describe the pharmacokinetics (PK) of ciprofloxacin in critically ill patients receiving ECMO and recommend a dosing regimen that provides adequate drug exposure. METHODS: Serial blood samples were taken from ECMO patients receiving ciprofloxacin. Total ciprofloxacin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. Dosing simulations were performed to ascertain the probability of target attainment (PTA) represented by the area under the curve to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 125. RESULTS: Eight patients were enrolled, of which three received concurrent continuous venovenous haemodiafiltration (CVVHDF). Ciprofloxacin was best described in a two-compartment model with total body weight and creatinine clearance (CrCL) included as significant predictors of PK. Patients not requiring renal replacement therapy generated a mean clearance of 11.08 L/h while patients receiving CVVHDF had a mean clearance of 1.51 L/h. Central and peripheral volume of distribution was 77.31 L and 90.71 L, respectively. ECMO variables were not found to be significant predictors of ciprofloxacin PK. Dosing simulations reported that a 400 mg 8 -hly regimen achieved > 72% PTA in all simulated patients with CrCL of 30 mL/min, 50 mL/min and 100 mL/min and total body weights of 60 kg and 100 kg at a MIC of 0.5 mg/L. CONCLUSION: Our study reports that established dosing recommendations for critically ill patients not on ECMO provides sufficient drug exposure for maximal ciprofloxacin activity for ECMO patients. In line with non-ECMO critically ill adult PK studies, higher doses and therapeutic drug monitoring may be required for critically ill adult patients on ECMO.

Determinants of Undertaking Coronary Angiography and Adverse Prognostic Predictors Among Patients Presenting With Out-of-Hospital Cardiac Arrest and a Shockable Rhythm.

Characteristics of patients presenting with out-of-hospital cardiac arrest (OHCA) selected for coronary angiography (CA) and factors predicting in-hospital mortality remain unclear. We assessed clinical characteristics associated with undertaking CA in patients presenting with OHCA and shockable rhythm (CA group). Predictors of in-hospital mortality were evaluated with multivariable analysis. Of 1,552 patients presenting with cardiac arrest between 2014 and 2018 to 2 health services in Victoria, Australia, 213 patients with OHCA and shockable rhythm were stratified according to CA status. The CA group had shorter cardiopulmonary resuscitation duration (17 vs 25 minutes) and time to return of spontaneous circulation (17 vs 26 minutes) but higher proportion of ST-elevation on electrocardiogram (48% vs 24%) (all p <0.01). In-hospital mortality was 38% (n = 81) for the overall cohort, 32% (n = 54) in the CA group, and 61% (n = 27) in the no-CA group. Predictors of in-hospital mortality included non-selection for CA (odds ratio 4.5, 95% confidence interval 1.5 to 14), adrenaline support (3.9, 1.3 to 12), arrest at home (2.7, 1.1 to 6.6), longer time to defibrillation (2.5, 1.5 to 4.2 per 5-minute increase), lower blood pH (2.1, 1.4 to 3.2 per 0.1 decrease), lower albumin (2.0, 1.2 to 3.3 per 5 g/L decrease), higher Acute Physiology and Chronic Health Evaluation II score (1.7, 1.0 to 3.0 per 5-point increase), and advanced age (1.4, 1.0 to 2.0 per 10-year increase) (all p ≤0.05). In conclusion, non-selection for CA, concomitant cardiogenic shock requiring inotropic support, poor initial resuscitation (arrest at home, longer time to defibrillation and lower pH), greater burden of co-morbidities (higher Acute Physiology and Chronic Health Evaluation II score and lower albumin), and advanced age were key adverse prognostic indicators among patients with OHCA and shockable rhythm.

Outcomes of patients with refractory out-of-hospital cardiac arrest transported to an ECMO centre compared with transport to non-ECMO centres.

Objective: To compare the outcomes of patients with refractory out-of-hospital cardiac arrest (OHCA) transported to a hospital that provides extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) with patients transported to hospitals without ECPR capability. Design, setting: Retrospective review of patient care records in a pre-hospital and hospital setting. Participants: Adult patients with OHCA who left the scene and arrived with cardiopulmonary resuscitation in progress at 16 hospitals in Melbourne, Australia, between January 2016 and December 2019. Intervention: For selected patients transported to the ECPR centre, initiation of ECMO. Main outcome measures: Survival to hospital discharge and 12-month quality of life. Results: There were 223 eligible patients during the study period. Of 49 patients transported to the ECPR centre, 23 were commenced on ECMO. Of these, survival to hospital with good neurological recovery (Cerebral Performance Category [CPC] score 1/2) occurred in 4/23 patients. Four other patients developed return of spontaneous circulation in the ECPR centre before cannulation of whom one survived, giving overall good functional outcome at 12 months survival of 5/49 (10.2%). There were 174 patients transported to the 15 non-ECPR centres and 3/174 (2%) had good functional outcome at 12 months. After adjustment for baseline differences, the odds ratio for good neurological outcome after transport to an ECPR centre compared with a non-ECPR centre was 4.63 (95% CI, 0.97-22.11; P = 0.055). Conclusion: The survival rate of patients with refractory OHCA transported to an ECPR centre remains low. Outcomes in larger cities might be improved with shorter scene times and additional ECPR centres that would provide for earlier initiation of ECMO.

Six-month outcomes following venovenous ECMO for severe COVID-19 and viral pneumonitis: 2019-2020 Australian experience.

Objective: To compare the characteristics, treatments and 6-month functional outcomes of patients with coronavirus disease 2019 (COVID-19) versus non-COVID-19 viral pneumonitis supported by venovenous extracorporeal membrane oxygenation (VV-ECMO). Design: Prospective, observational cohort study in seven intensive care units (ICUs) across Australia. Participants: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 or viral pneumonitis requiring VV-ECMO. Results: From 30 March 2019 to 31 December 2020, 13 patients were initiated on VV-ECMO for COVID-19 and 23 were initiated for non-COVID-19 viral pneumonitis. Patients with COVID-19 were older and had a longer duration from intubation to ECMO initiation, but had similar illness severity and APACHE IV scores at the time of initiation. Overall disability, health-related quality of life, and mortality were similar, but ICU and hospital length of stay were significantly longer in patients with COVID-19. Conclusions: Six-month functional outcomes and mortality were similar between COVID-19 and viral pneumonitis patients treated with VV-ECMO. However, length of stay was longer in COVID-19 patients, which may have resource implications.

Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study).

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analyzed using a population PK approach on Pmetrics. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC0-24) of 400-700 mg · h/liter at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 ml/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT, and total body weight found as significant predictors of clearance and central volume of distribution (Vc). The mean vancomycin renal clearance and Vc were 3.20 liters/h and 29.7 liters respectively, while the clearance for patients on RRT was 0.15 liters/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5-20 mg/kg every 12 h are associated with a 97-98% probability of efficacy and 11-12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT. (This study is registered with the Australian New Zealand Clinical Trials Registry [ANZCTR] under number ACTRN12612000559819.).