Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit.

OBJECTIVE: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction models to dynamic probabilistic models in early critical illness. DESIGN: We developed models to simulate disease trajectories of critically ill COVID-19 patients across different disease states. Eighty per cent of cases were randomly assigned to a training and 20% of the cases were used as a validation cohort. Conventional risk prediction models were developed to analyse different disease states for critically ill patients for the first 7 days of intensive care unit (ICU) stay. Daily disease state transitions were modelled using a series of multivariable, multinomial logistic regression models. A probabilistic dynamic systems modelling approach was used to predict disease trajectory over the first 7 days of an ICU admission. Forecast accuracy was assessed and simulated patient clinical trajectories were developed through our algorithm. SETTING AND PARTICIPANTS: We retrospectively studied patients admitted to a Cleveland Clinic Healthcare System in Ohio, for the treatment of COVID-19 from March 2020 to December 2022. RESULTS: 5241 patients were included in the analysis. For ICU days 2-7, the static (conventional) modelling approach, the accuracy of the models steadily decreased as a function of time, with area under the curve (AUC) for each health state below 0.8. But the dynamic forecasting approach improved its ability to predict as a function of time. AUC for the dynamic forecasting approach were all above 0.90 for ICU days 4-7 for all states. CONCLUSION: We demonstrated that modelling critical care outcomes as a dynamic system improved the forecasting accuracy of the disease state. Our model accurately identified different disease conditions and trajectories, with a <10% misclassification rate over the first week of critical illness.

Radiation Exposure in Extracorporeal Life Support.

Extracorporeal membrane oxygenation (ECMO) exposes patients to multiple radiologic studies. We hypothesized ECMO patients endure radiation exposure in excess of the International Commission of Radiological Protection (ICRP) recommendations of cumulative effective dose (CED, >20 mSv and 5-year cumulative limit of CED >100 mSv). We conducted a retrospective observational study in an academic medical center between January 2016 and December 2018 involving adult admissions (N = 306) on ECMO. Ionizing radiation was calculated from reference values to determine CED. Approximately 9.4% (N = 29) patients accrued CED >50 mSv and 4.5% (N = 14) accrued CED >100 mSv during ECMO. Over the entire hospitalization, 28% (N = 85) accrued >50 mSv and 14.7% (N = 45) accrued CED >100 mSv. Median CED during ECMO was 2.3 mSv (IQR, -0.82 to 8.1 mSv), and the entire hospitalization was 17.4 mSv (IQR, -4.5 to 56.6 mSv). Thirteen percent of the median CED accrued during hospitalization could be attributed to ECMO. Longer hospitalization was associated with a higher CED (50 days [IQR, -25 to 76 days] in CED >50 vs. 19 days [IQR, -10 to 32 days] in CED <50). Computer tomography (CT) scans and interventional radiology (IR) procedures contributed to 43.8% and 44.86%, respectively, of CED accrued on ECMO and 52.2% and 37.1% of CED accumulated during the whole hospitalization. Guidelines aimed at mitigating radiation exposure are urgently needed.

Using a Low-Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) System in the Management of Refractory Status Asthmaticus: A Case Series.

Rescue treatments for status asthmaticus remain limited. Current literature has mainly focused on using extracorporeal membrane oxygenation (ECMO) as a primary modality of care for these patients. Low-flow extracorporeal CO2 removal (ECCO2R) systems are an attractive option to improve refractory hypercapnic respiratory acidosis because of status asthmaticus. This is a retrospective case series that describes the feasibility and efficacy of the use of a low-flow ECCO2R device, the Hemolung Respiratory Assist System, in patients with refractory hypercapnic respiratory failure because of status asthmaticus. Eight patients were treated with the Hemolung Respiratory Assist System in eight separate locations globally. Seven (88%) of the patients survived to discharge in this case series. Both CO2 and pH resolution were seen in 6 hours. None of the ECCO2R runs were stopped because of mechanical- or device-related complications. One patient necessitated transition to ECMO. Low-flow ECCO2R systems is an effective option for resolution of refractory hypercapnia in status asthmaticus. Use of these systems are also associated with a survival rate of close to 90% in patients with status asthmaticus.

Diagnostic Yield, Radiation Exposure, and the Role of Clinical Decision Rules to Limit Computed Tomographic Pulmonary Angiography-Associated Complications.

OBJECTIVES: Computed tomographic pulmonary angiography (CT-PA) is associated with significant cost, contrast, and radiation exposure. Clinical decision rules (CDRs) reduce the need for diagnostic imaging; however, their utility in the medical intensive care unit (MICU) remains unknown. We explored the diagnostic yield and complications associated with CT-PA (radiation exposure and contrast-induced acute kidney injury [AKI]) while investigating the efficacy of CDRs to reduce unnecessary testing. METHODS: All CT-PAs performed in an academic MICU for 4 years were retrospectively reviewed. The Wells and revised Geneva scores (CDRs) and radiation dose per CT-PA were calculated, and the incidence of post-CT-PA AKI was recorded. RESULTS: A total of 439 studies were analyzed; the diagnostic yield was 11% (48 PEs). Positive CT-PAs were associated with a higher Wells score (5.8 versus 3.2, P < 0.001), but similar revised Geneva scores (6.4 versus 6.0, P = 0.32). A Wells score of ≥4 had a positive likelihood ratio of 2.1 with a negative predictive value of 98.2. More than half (88.9%) of patients with a Wells score of ≤4 developed an AKI, with 55.6% of those having recovery of renal function. CONCLUSIONS: There is overutilization of CT-PA in the MICU. The Wells score retains its negative predictive value in critically ill adult patients and may aid to limit radiation exposure and contrast-induced AKI in MICU.

Physiologic Markers of Disease Severity in ARDS.

Despite its significant limitations, the PaO2 /FIO2 remains the standard tool to classify disease severity in ARDS. Treatment decisions and research enrollment have depended on this parameter for over 50 years. In addition, several variables have been studied over the past few decades, incorporating other physiologic considerations such as ventilation efficiency, lung mechanics, and right-ventricular performance. This review describes the strengths and limitations of all relevant parameters, with the goal of helping us better understand disease severity and possible future treatment targets.

Outcomes after cardiac arrest in Medical Intensive Care Unit: A propensity score matching analysis of COVID-19 MICU vs non COVID-19 MICU cardiac arrest.

AIM: To assess whether there were differences in resuscitation efforts and outcomes for medical intensive care unit (MICU) in-hospital cardiac arrest (IHCA) during the COVID-19 pandemic when compared to pre-pandemic. METHODS: Comparing COVID-19 MICU-IHCA patients (03/2020 to 10/2020) to non-COVID-19 MICU IHCA (01/2014 to 12/2018) at Clevleand Clinic Health System (CCHS) of NE Ohio. Propensity score matching analysis (PSMA) was used to create comparable groups. RESULTS: There were a total of 516 patients, 51 in COVID-19 MICU IHCA cohort and 465 in the non-COVID-19 MICU IHCA cohort. The mean (SD) age of the study population was 60.9 (16) years and 56% were males. In 92.1% (n = 475) patients, initial arrest rhythm was non-shockable. At the time of ICU admission, compared to the non-COVID-19 MICU-IHCA cohort, the COVID-19 MICU IHCA cohort had a lower mean APACHE III score (70 [32.9] vs 101.3 [39.6], P = <0.01). The COVID-19 cohort had a higher rate of survival to hospital discharge (12 [23.5%] vs 59 [12.7%], P = 0.03). Upon PSMA, the algorithm selected 40 COVID-19 patients and 200 non-COVID-19 patients. Imbalances in baseline characteristics, comorbidities, and APACHE III were well-balanced after matching. Survival rate after matching became non-significant; (10 [25%] vs 42 [21%], P = 0.67). Further, there were no significant differences in ICU or hospital length-of-stay or neurological outcomes at discharge for survivors in the two matched cohorts. CONCLUSION: It is imperative that COVID-19 patients receive unbiased and unrestricted resuscitation measures, without any discouragement.

Successful treatment of pulmonary mucormycosis (Lichtheimia spp.) in a post-partum patient with COVID-19 ARDS requiring extra-corporeal membrane oxygenation using salvage therapy.

Case Summary: A 31-year-old female presented to a regional hospital at 27 weeks pregnant and was found to have COVID-19 ARDS. She underwent intubation and caesarian section for worsening hypoxia and non-reassuring fetal heart tones. Hypoxemia was refractory to proning requiring ECMO and transfer to a tertiary care center. Admission chest radiography showed a new right lower lobe cavitating lesion with computed tomography scan revealing a large multi-loculated cavity in the right lung and extensive bilateral ground-glass opacities. The patient was started on amphotericin and posaconazole, with final respiratory cultures growing Lichtheimia spp. Source control was discussed via possible open thoracostomy, but medical management alone was continued. Total ECMO support was 3 weeks. At the time of discharge to acute rehab, 1 month of amphotericin and posaconazole had been completed, with continuation of posaconazole. At last update, she had been discharged from rehab and was back home with her infant. Conclusion: Pulmonary mucormycosis, even in the non-ECLS population, carries a high mortality. Treatment in pulmonary disease with surgery improves mortality but is not always feasible. Salvage therapy with extended course antifungal medications may be an option for those not amendable.

On the horizon: Extracorporeal carbon dioxide removal.

Extracorporeal carbon dioxide removal (ECCO2R) uses mechanical systems to treat hypercapnic respiratory failure. Its utility has been investigated in acute respiratory distress syndrome (ARDS), acute exacerbations of chronic obstructive pulmonary disease (COPD), and status asthmaticus, and as a bridge to lung transplant. In this review, we discuss how it works, why it should help, and current evidence supporting its use.

Evaluation of anticoagulation with bivalirudin for heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.

INTRODUCTION: Unfractionated heparin is the most commonly utilized anticoagulant in extracorporeal membrane oxygenation (ECMO) due to clinician familiarity, ease of reversal, and low cost compared to alternative agents. However, heparin's anticoagulant effect can be unpredictable and its use accompanies a risk of heparin induced thrombocytopenia (HIT). Successful use of bivalirudin as an alternative to heparin in non-HIT ECMO patients has previously been described. However, there is a paucity of data regarding its utilization in patients with confirmed HIT on ECMO. METHODS: This single-center retrospective chart review at Cleveland Clinic Main Campus included 12 ECMO patients who were managed with bivalirudin for a new diagnosis of HIT. Descriptive statistical analyses were performed utilizing median with interquartile range and number with percent as appropriate. RESULTS: Of the 12 patients included, median ECMO duration was 328.5 (218.8-502.1) h and venoarterial ECMO was the most common configuration. No patients experienced the primary outcome of in-circuit thrombosis while on bivalirudin. One patient developed a deep vein thrombosis 22.5 h after switching from heparin to bivalirudin. Major bleeding occurred during bivalirudin therapy in 8 (66.7%) patients. CONCLUSIONS: Overall, our study results suggest that bivalirudin is effective for the management of HIT and did not show evidence of in-circuit thrombosis. A high incidence of major bleeding was observed with bivalirudin use within this study. Clinicians should view bivalirudin as an acceptable agent for the treatment of HIT in the ECMO population, but must consider bleeding risk given the lack of effective reversal agents.

Characteristics of Cumulative Annual Radiation Exposure in Young Intensive Care Unit Survivors.

OBJECTIVES: Patients admitted to the intensive care unit (ICU) are at high risk for hazardous medical radiation exposure. However, the cumulative annual radiation exposure in ICU survivors remains unknown. METHODS: This was a single-center retrospective study of all critically ill adult patients admitted to the 64-bed adult medical ICU at a quaternary medical center. The study included patients aged 18 to 39 years admitted through the year 2013 (January 1, 2013-December 31, 2013) who survived their respective ICU admission. RESULTS: A total of 353 patients were included in the study. The median cumulative effective dose (CED) for the calendar year was 9.14 mSv (interquartile range, 1.74-27 mSv). In 11.6% of the patients (n = 41), CED was more than 50 mSv, while 5.1% of the patients (n = 18) exceeded annual CED of 100 mSv. Overall, radiation exposure from ICU-related imaging studies was lower than those from other medical settings (mean difference, -9.2 ± 83.6; P < 0.05). However, there was no statistically significant difference in exposure (ICU versus non-ICU) when restricting the analysis to patients with a CED of greater than 50 and greater than 100 mSv. Eighty-seven percent of the original cohort was alive at the end of the year. CONCLUSIONS: Young ICU survivors are at risk for high annual radiation exposure from both ICU and non-ICU sources. A subset is exposed to hazardous annual radiation exposure in excess of 100 mSv.

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients.

BACKGROUND: Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. METHODS: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. RESULTS: Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. CONCLUSION: The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

Factors Associated With Mortality Among Patients Managed for Large Volume Hemorrhage in a Medical Intensive Care Unit.

PURPOSE: Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes. PATIENTS AND METHODS: This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality. RESULTS: Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013-1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1-6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175-1.437). CONCLUSION: In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.

Mortality associated with acute respiratory distress syndrome, 2009-2019: a systematic review and meta-analysis.

Background: Acute respiratory distress syndrome (ARDS) occurs commonly in intensive care units. The reported mortality rates in studies evaluating ARDS are highly variable. Objective: To investigate mortality rates due to ARDS from before the 2009 H1N1 influenza pandemic began until the start of coronavirus disease 2019 (COVID-19) pandemic. Design: We performed a systematic search and then ran a proportional meta-analysis for mortality. We ran our analysis in three ways: for randomised controlled trials only, for observational studies only, and for randomised controlled trials and observational studies combined. Data sources: MEDLINE and Embase, using a highly sensitive criterion and limiting the search to studies published from January 2009 to December 2019. Review methods: Two of us independently screened titles and abstracts to first identify studies and then complete full text reviews of selected studies. We assessed risk of bias using the Cochrane RoB-2 (a risk-of-bias tool for randomised trials) and the Cochrane ROBINS-1 (a risk-of-bias tool for non-randomised studies of interventions). Results: We screened 5844 citations, of which 102 fully met our inclusion criteria. These included 34 randomised controlled trials and 68 observational studies, with a total of 24 158 patients. The weighted pooled mortality rate for all 102 studies published from 2009 to 2019 was 39.4% (95% CI, 37.0-41.8%). Mortality was higher in observational studies compared with randomised controlled trials (41.8% [95% CI, 38.9-44.8%] v 34.5% [95% CI, 30.6-38.5%]; P = 0.005). Conclusions: Over the past decade, mortality rates due to ARDS were high. There is a clear distinction between mortality in observational studies and in randomised controlled trials. Future studies need to report mortality for different ARDS phenotypes and closely adhere to evidence-based medicine. PROSPERO registration: CRD42020149712 (April 2020).

Surge capacity and capability of intensive care units across a large healthcare system: An operational blueprint for regional integration.

OBJECTIVE: Many hospitals were unprepared for the surge of patients associated with the spread of coronavirus disease 2019 (COVID-19) pandemic. We describe the processes to develop and implement a surge plan framework for resource allocation, staffing, and standardized management in response to the COVID-19 pandemic across a large integrated regional healthcare system. SETTING: A large academic medical center in the Cleveland metropolitan area, with a network of 10 regional hospitals throughout Northeastern Ohio with a daily capacity of more than 500 intensive care unit (ICU) beds. RESULTS: At the beginning of the pandemic, an equitable delivery of healthcare services across the healthcare system was developed. This distribution of resources was implemented with the potential needs and resources of the individual ICUs in mind, and epidemiologic predictions of virus transmissibility. We describe the processes to develop and implement a surge plan framework for resource allocation, staffing, and standardized management in response to the COVID-19 pandemic across a large integrated regional healthcare system. We also describe an additional level of surge capacity, which is available to well-integrated institutions called "extension of capacity." This refers to the ability to immediately have access to the beds and resources within a hospital system with minimal administrative burden. CONCLUSIONS: Large integrated hospital systems may have an advantage over individual hospitals because they can shift supplies among regional partners, which may lead to faster mobilization of resources, rather than depending on local and national governments. The pandemic response of our healthcare system highlights these benefits.

Evaluation of High-Frequency Oscillatory Ventilation as a Rescue Strategy in Respiratory Failure.

BACKGROUND: The use of high-frequency oscillatory ventilation (HFOV) is backed by sound physiologic rationale, but clinical data on the elective use of HFOV have been largely disappointing. Nonetheless, HFOV is still occasionally used as a rescue mode in patients with severe hypoxemia. The evidence that supports this practice is sparse. METHODS: This was a retrospective single-center analysis that involved subjects admitted to the medical ICU at Cleveland Clinic, Cleveland, Ohio. We included all adult patients (ages > 18 y) who received rescue HFOV between January 1, 2010, and December 31, 2018, and analyzed their clinical outcomes. RESULTS: A total of 48 subjects were included in the analysis. The most common primary diagnosis was pneumonia (n = 33 [68.8%]), followed by aspiration (n = 6 [12.5%]) and diffuse alveolar hemorrhage (n = 2 [4.2%]). Switching to HFOV improved oxygenation but also increased vasopressor requirements at 3 h. The mortality rate of the study population was 92% (44/48). CONCLUSIONS: Our study did not support utilization of HFOV as a "last-ditch" rescue measure in subjects with respiratory failure. The delayed timing of HFOV initiation and its detrimental hemodynamic effects are among the potential reasons for the high mortality rate.

Adherence to blood product transfusion guidelines-An observational study of the current transfusion practice in a medical intensive care unit.

BACKGROUND: Blood transfusions though life-saving are not entirely benign. They are the most overused procedure in the hospital and have been under scrutiny by the 'Choosing Wisely campaign'. The strict adoption of restrictive transfusion guidelines could improve patient outcomes while reducing cost. OBJECTIVES: In this study, we evaluate adherence to restrictive transfusion guidelines, along with hospital mortality and length of stay (LOS) in transfusion events with a pre-transfusion haemoglobin (Hb) ≥7 g/dl. Additionally, we evaluated associated costs accrued due to unnecessary transfusions. METHODS: We conducted a retrospective observational study in a 64-bed medical intensive care unit (MICU) of an academic medical centre involving all adult patients (N = 957) requiring packed red blood cell transfusion between January 2015 and December 2015. RESULTS: In total, 3140 units were transfused with a mean pre-transfusion Hb of 6.75 ± 0.86 g/dl. Nine hundred forty-four (30%) transfusion events occurred with a pre-transfusion Hb ≥7 g/dl, and 385 (12.3%) of these occurred in patients without hypotension, tachycardia, use of vasopressors, or coronary artery disease. Forgoing them could have led to a savings of approximately 0.3 million dollars. Transfusion events with pre-transfusion Hb ≥7 g/dl were associated with an increased mortality in patients with acute blood loss (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.88; p = 0.02) and LOS in patients with chronic blood loss (ß1 .8.26, 95% CI 4.09-12.43; p < 0.01). CONCLUSION: A subset of anaemic patients in the MICU still receive red blood cell transfusions against restrictive guidelines offering hospitals the potential for effective intervention that has both economic and clinical implications.

A case of hypereosinophilic syndrome with STAT5b N642H mutation.

Hypereosinophilia is defined as persistent eosinophilia (>1.5 × 109/L). Hypereosinophilic syndrome (HES) is a term used to describe a group of disorders characterized by sustained hypereosinophilia associated with end-organ damage. Based on underlying molecular mechanism of eosinophilia, there are different subtypes of HES. Diagnosis of HES subtype can be challenging, especially in the absence of overt lymphoid/myeloid neoplasms or discernable secondary causes. Long-term outpatient follow-up with periodic complete blood count and repeated bone marrow biopsy may be needed to monitor disease activity. Somatic signal transducer and activation transcription 5b (STAT5b) N642H mutation was recently found to be associated with myeloid neoplasms with eosinophilia. We report a case of HES who presented with pulmonary embolism and acute eosinophilic pneumonia, found to have recurrent STAT5b N642H mutation by next-generation sequencing, suggesting possible underlying myeloid neoplasm.