Sequential Extracorporeal Therapy of Pathogen Removal Followed by Cell-Directed Extracorporeal Therapy in Streptococcal Toxic Shock Syndrome Refractory to Venoarterial Extracorporeal Membrane Oxygenation: A Case Report.

BACKGROUND: Streptococcal toxic shock syndrome (STSS) is a fulminant complication of predominantly invasive group A streptococcal infections. STSS is often characterized by influenza-like symptoms, including fever, chills, and myalgia that can quickly progress to sepsis with hypotension, tachycardia, tachypnea, and multiple organ failure (kidney, liver, lung, or blood). Mortality can exceed 50% depending on the severity of symptoms. CASE SUMMARY: Here, we describe a novel, multi-extracorporeal intervention strategy in a case of severe septic shock secondary to STSS. A 28-year-old woman 5 days after cesarean section developed STSS with respiratory distress, hypotension, and multiple organ failure. Despite conventional therapy with intubation, antibiotics, vasopressors, and fluid resuscitation, her condition worsened. She was placed on venoarterial extracorporeal membrane oxygenation (VA-ECMO) with subsequent initiation of pathogen hemoperfusion using the Seraph 100 blood filter, followed by immunomodulation with the selective cytopheretic device (SCD). No device-related adverse events were observed. The patient's condition gradually stabilized with discontinuation of vasopressors after 4 days, ECMO decannulation after 6 days, evidence of renal recovery after 7 days, and extubation from mechanical ventilation after 14 days. She was transferred to conventional hemodialysis after 13 days and discontinued all kidney replacement therapy 11 days later. CONCLUSIONS: This is the first reported use of VA-ECMO, Seraph 100 hemoperfusion, and cell-directed immunomodulation with SCD. This multimodal approach to extracorporeal support represents a promising therapeutic strategy for the most refractory critical care cases. Further studies are needed to assess the safety and efficacy of this sequential approach.

Clinical Outcomes Associated With Overestimation of Oxygen Saturation by Pulse Oximetry in Patients Hospitalized With COVID-19.

Importance: Many pulse oximeters have been shown to overestimate oxygen saturation in persons of color, and this phenomenon has potential clinical implications. The relationship between overestimation of oxygen saturation with timing of COVID-19 medication delivery and clinical outcomes remains unknown. Objective: To investigate the association between overestimation of oxygen saturation by pulse oximetry and delay in administration of COVID-19 therapy, hospital length of stay, risk of hospital readmission, and in-hospital mortality. Design, Setting, and Participants: This cohort study included patients hospitalized for COVID-19 at 186 acute care facilities in the US with at least 1 functional arterial oxygen saturation (SaO2) measurement between March 2020 and October 2021. A subset of patients were admitted after July 1, 2020, without immediate need for COVID-19 therapy based on pulse oximeter saturation (SpO2 levels of 94% or higher without supplemental oxygen). Exposures: Self-reported race and ethnicity, difference between concurrent SaO2 and pulse oximeter saturation (SpO2) within 10 minutes, and initially unrecognized need for COVID-19 therapy (first SaO2 reading below 94% despite SpO2 levels of 94% or above). Main Outcome and Measures: The association of race and ethnicity with degree of pulse oximeter measurement error (SpO2 - SaO2) and odds of unrecognized need for COVID-19 therapy were determined using linear mixed-effects models. Associations of initially unrecognized need for treatment with time to receipt of therapy (remdesivir or dexamethasone), in-hospital mortality, 30-day hospital readmission, and length of stay were evaluated using mixed-effects models. All models accounted for demographics, clinical characteristics, and hospital site. Effect modification by race and ethnicity was evaluated using interaction terms. Results: Among 24 504 patients with concurrent SpO2 and SaO2 measurements (mean [SD] age, 63.9 [15.8] years; 10 263 female [41.9%]; 3922 Black [16.0%], 7895 Hispanic [32.2%], 2554 Asian, Native American or Alaskan Native, Hawaiian or Pacific Islander, or another race or ethnicity [10.4%], and 10 133 White [41.4%]), pulse oximetry overestimated SaO2 for Black (adjusted mean difference, 0.93 [95% CI, 0.74-1.12] percentage points), Hispanic (0.49 [95% CI, 0.34-0.63] percentage points), and other (0.53 [95% CI, 0.35-0.72] percentage points) patients compared with White patients. In a subset of 8635 patients with a concurrent SpO2 - SaO2 pair without immediate need for COVID-19 therapy, Black patients were significantly more likely to have pulse oximetry values that masked an indication for COVID-19 therapy compared with White patients (adjusted odds ratio [aOR], 1.65; 95% CI, 1.33-2.03). Patients with an unrecognized need for COVID-19 therapy were 10% less likely to receive COVID-19 therapy (adjusted hazard ratio, 0.90; 95% CI, 0.83-0.97) and higher odds of readmission (aOR, 2.41; 95% CI, 1.39-4.18) regardless of race (P for interaction = .45 and P = .14, respectively). There was no association of unrecognized need for COVID-19 therapy with in-hospital mortality (aOR, 0.84; 95% CI, 0.71-1.01) or length of stay (mean difference, -1.4 days; 95% CI, -3.1 to 0.2 days). Conclusions and Relevance: In this cohort study, overestimation of oxygen saturation by pulse oximetry led to delayed delivery of COVID-19 therapy and higher probability of readmission regardless of race. Black patients were more likely to have unrecognized need for therapy with potential implications for population-level health disparities.

Extracorporeal Membrane Oxygenation for Acute Respiratory Failure Due to COVID-19: A Multicenter Matched Cohort Study.

Mechanical ventilation for respiratory failure due to COVID-19 is associated with significant morbidity and mortality. Veno-venous extracorporeal membrane oxygenation (ECMO) is an attractive management option. This study sought to determine the effect of ECMO on hospital mortality and discharge condition in this population. We conducted a retrospective multicenter study to emulate a pragmatic targeted trial comparing ECMO to mechanical ventilation without ECMO for severe COVID-19. Data were gathered from a large hospital network database in the US. Adults admitted with COVID-19 were included if they were managed with ECMO or mechanical ventilation for severe hypoxemia and excluded if they had significant comorbidities or lacked functional independence on admission. The groups underwent coarsened exact matching on multiple clinical variables. The primary outcome was adjusted in-hospital mortality; secondary outcomes included ventilator days, intensive care days, and discharge destination. A total of 278 ECMO patients were matched to 2,054 comparison patients. Adjusted in-hospital mortality was significantly less in the ECMO group (38.8% vs. 60.1%, p < 0.001). Extracorporeal membrane oxygenation was associated with higher rates of liberation from mechanical ventilation, intensive care discharge, and favorable discharge destination. These findings support the use of ECMO for well-selected patients with severe acute respiratory failure due to COVID-19.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Clinical outcomes of severe COVID-19 patients receiving early VV-ECMO and the impact of pre-ECMO ventilator use.

Acute respiratory distress syndrome (ARDS) in COVID-19 patients is associated with poor clinical outcomes and high mortality rates, despite the use of mechanical ventilation. Veno-Venous Extracorporeal membrane Oxygenation (VV-ECMO) in these patients is a viable salvage therapy. We describe clinical outcomes and survival rates in 52 COVID-19 patients with ARDS treated with early VV-ECMO at a large, high-volume center ECMO program. Outcomes included arterial blood gases, respiratory parameters, inflammatory markers, adverse events, and survival rates. Patients' mean age was 47.8 ± 12.1 years, 33% were female, and 75% were Hispanic. At the end of study period, 56% (n = 29) of the patients survived and were discharged and 44% (n = 23) of the patients expired. Survival rate was 75.0% (9 out of 12) in patients placed on ECMO prior to mechanical ventilation. Longer duration on mechanical ventilation prior to ECMO intervention was associated with a 31% (aOR = 1.31, 95% CI, 1.00-1.70) increased odds of mortality after adjusting for age, gender, BMI, number of comorbid conditions, and post-ECMO ventilator days. Early and effective ECMO intervention in critical ill COVID-19 patients might be a valuable strategy in critical care settings to increase their odds of survival.

An Extracorporeal Membrane Oxygenation First Strategy in COVID-19 Acute Respiratory Distress Syndrome.

COVID-19 can be associated with acute respiratory distress syndrome, which increases the likelihood of morbidity and mortality. Ventilator-induced lung injury is a known complication of mechanical ventilation (MV) and can further compound lung injury and recovery. Escalation to extracorporeal membrane oxygenation can be required in patients who deteriorate on MV. We report our experience with complete avoidance of MV using an ECMO First strategy deployed in an awake nonintubated COVID-19 patient with severe pneumonia.

Joint Society of Critical Care Medicine-Extracorporeal Life Support Organization Task Force Position Paper on the Role of the Intensivist in the Initiation and Management of Extracorporeal Membrane Oxygenation.

OBJECTIVES: To define the role of the intensivist in the initiation and management of patients on extracorporeal membrane oxygenation. DESIGN: Retrospective review of the literature and expert consensus. SETTING: Series of in-person meetings, conference calls, and emails from January 2018 to March 2019. SUBJECTS: A multidisciplinary, expert Task Force was appointed and assembled by the Society of Critical Care Medicine and the Extracorporeal Life Support Organization. Experts were identified by their respective societies based on reputation, experience, and contribution to the field. INTERVENTIONS: A MEDLINE search was performed and all members of the Task Force reviewed relevant references, summarizing high-quality evidence when available. Consensus was obtained using a modified Delphi process, with agreement determined by voting using the RAND/UCLA scale, with score ranging from 1 to 9. MEASUREMENTS AND MAIN RESULTS: The Task Force developed 18 strong and five weak recommendations in five topic areas of extracorporeal membrane oxygenation initiation and management. These recommendations were organized into five areas related to the care of patients on extracorporeal membrane oxygenation: patient selection, management, mitigation of complications, coordination of multidisciplinary care, and communication with surrogate decision-makers. A common theme of the recommendations is extracorporeal membrane oxygenation is best performed by a multidisciplinary team, which intensivists are positioned to engage and lead. CONCLUSIONS: The role of the intensivist in the care of patients on extracorporeal membrane oxygenation continues to evolve and grow, especially when knowledge and familiarity of the issues surrounding extracorporeal membrane oxygenation selection, cannulation, and management are applied.

Acute Kidney Injury Before and After Liver Transplant.

The development of acute kidney injury in the setting of liver disease is a significant event both before and after liver transplant. Whether acute kidney injury is the cause of or merely associated with worse outcomes, the development of renal failure is significant from a prognostic as well as from a diagnostic and therapeutic standpoint. Although not every etiology is reversible, there are number of etiologies that are correctable, to include hypovolemia, nephrotoxic medications, and acute tubular necrosis. In the post-liver transplant period, renal failure is associated with graft failure as well as worse outcomes overall. Prompt recognition, workup, and intervention can significantly impact outcomes and survival both before and after liver transplant.

Salvage extracorporeal membrane oxygenation in induction-associated acute respiratory distress syndrome in acute leukemia patients: A case series.

BACKGROUND:: The prognosis of hematologic malignancies has improved over the past three decades. However, the prognosis in hematologic malignancies with severe acute respiratory distress syndrome has remained poor. Initial reports regarding the utility of extracorporeal membrane oxygenation in hematologic malignancies have been controversial, with limited evaluations of acute leukemia patients supported by extracorporeal membrane oxygenation. METHODS:: We conducted a retrospective review of patients with acute leukemia who developed acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation support at our facility from July 2015 through August 2017. RESULTS:: Four cases of acute myelogenous leukemia with respiratory failure and acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation while undergoing induction chemotherapy were identified. All patients completed induction therapy with addition of extracorporeal membrane oxygenation support, with two patients dying secondary to their acute leukemia and the other two surviving to allogeneic hematopoietic stem cell transplant. Overall, 75% (three of four) survived to decannulation with a 1-year survival rate following extracorporeal membrane oxygenation of 50% (two of four). CONCLUSION:: Currently, the use of extracorporeal membrane oxygenation in patients with hematologic malignancies who develop severe acute respiratory distress syndrome remains controversial. Although extracorporeal membrane oxygenation in post-allogeneic hematopoietic stem cell transplant is associated with poorer outcomes, our data suggest that salvage extracorporeal membrane oxygenation support is a viable option to manage moderate to severe acute respiratory distress syndrome while completing therapeutic chemotherapy and following in the peri-induction phase of acute leukemia.

Revisiting extracorporeal membrane oxygenation for ARDS in burns: A case series and review of the literature.

INTRODUCTION: Recent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit. METHODS: This is a case series of consecutive patients placed on ECMO at our burn center from the initiation of our program in September 2012 to September 2017. We included only adult patients who had been placed on ECMO with burn injury, TEN, or inhalation injury and severe ARDS. RESULTS: Fourteen patients with burn injury, inhalation injury or TEN were placed on ECMO from the initiation of the ECMO program to September 1st 2017. The average total body surface area burned in the 11 patients with burn injury was 27% (range 0.25-76%). The cause of ARDS in these patients included inhalation injury, airway trauma and bacterial pneumonia. Four patients had an inhalation injury and 1 patient had a grade 3 inhalation injury but no burn injury. In the majority of cases, prone positioning and use of neuromuscular blockade was also used in an attempt to improve oxygenation and patient synchrony with mechanical ventilation. The average time on ECMO was 276h (range 63-539h). Ten of the 14 patients survived to decanulation from ECMO (71%) and eight of 14 patients (57%) survived to hospital discharge. CONCLUSIONS: To our knowledge, this is the lowest mortality rate reported to date in burn patients with ARDS place on ECMO. ECMO is a viable therapy that can be utilized successfully as a rescue modality when conventional interventions are unsuccessful.

Telemedicine to Reduce Medical Risk in Austere Medical Environments: The Virtual Critical Care Consultation (VC3) Service.

One of the core capabilities of prolonged field care is telemedicine. We developed the Virtual Critical Care Consult (VC3) Service to provide Special Operations Forces (SOF) medics with on-demand, virtual consultation with experienced critical care physicians to optimize management and improve outcomes of complicated, critically injured or ill patients. Intensive-care doctors staff VC3 continuously. SOF medics access this service via phone or e-mail. A single phone call reaches an intensivist immediately. An e-mail distribution list is used to share information such as casualty images, vital signs flowsheet data, and short video clips, and helps maintain situational awareness among the VC3 critical care providers and other key SOF medical leaders. This real-time support enables direct communication between the remote provider and the clinical subject matter expert, thus facilitating expert management from near the point of injury until definitive care can be administered. The VC3 pilot program has been extensively tested in field training exercises and validated in several real-world encounters. It is an immediately available capability that can reduce medical risk and is scalable to all Special Operations Command forces.

Case of a 5-Year-Old Foreign National Who Sustained Penetrating Abdominal Trauma.

OBJECTIVE: Review application of telemedicine support for penetrating trauma. Clinical context: Special Operations Resuscitation Team (SORT) deployed in Africa Area of Responsibility (AOR) Organic expertise: Internal Medicine physician, two Special Operations Combat medics (SOCMs), and one radiology technician Closest surgical support: Non-US surgical support 20km away; a nonsurgeon who will perform surgeries; neighboring country partner-force surgeon 2 hours by fixedwing flight. Earliest evacuation: Evacuated 4 days after presentation to a neighboring country with surgical capability.

Management of Complications of End-Stage Liver Disease in the Intensive Care Unit.

The management of critically ill patients with end-stage liver disease can be challenging due to the vulnerability of this population and the wide-ranging complications of the disease. This review proposes an approach based on the major organ systems affected, to provide a framework for managing the most common complications. Although considerable practice variation exists, a focus on the evidence behind the most common practices will ensure the development of the optimal skillset to appropriately manage this disease.

Arterial blood pressure and heart rate regulation in shock state.

PURPOSE OF REVIEW: Circulatory shock is a complicated problem that carries a high risk of complications and mortality for critically ill patients. The heart rate and blood pressure targets to which a patient in shock should be resuscitated remain a challenge to intensivists. RECENT FINDINGS: While the ideal blood pressure and heart rate in circulatory shock are still not definitive, recent studies have begun to refine these targets. A recent trial comparing a mean arterial pressure target of 80-85 mmHg with a target of 65-70 mmHg showed no difference in mortality, with a decreased need for renal replacement therapy in patients with pre-existing hypertension based on subgroup analysis. Regulation of heart rate was defined by a trial demonstrating that heart rate control in patients with severe sepsis on high-dose norepinephrine with esmolol titration did not result in additional adverse events. SUMMARY: The ideal target blood pressure in the resuscitation of circulatory shock is variable and likely depends on prior blood pressure. Heart rate regulation with ß-blockade appears to be safe in selected patients when accompanied by adequate resuscitation and monitoring.

Effects of implementing a protocol for arterial blood gas use on ordering practices and diagnostic yield.

BACKGROUND: The arterial blood gas (ABG) is a valuable and commonly used laboratory test. This prospective cohort study examined the variability of ABG ordering through the implementation of an evidence-based protocol. METHODS: The study consisted of two 6-week periods. The protocol consisted of evidence-based and consensus opinion based indications for ABGs. In the first phase (initial 6 weeks), respiratory therapists recorded the indications for ABGs ordered by clinicians. In the second phase, all medical and surgical physicians were trained on the clinical rationale behind the protocol and were instructed to write the indication for each ABG with the order. Rates of ABGs/patient/day were measured in aggregate and per indication. Multivariate regression was used for adjusted comparisons between indications within the protocol. RESULTS: After protocol implementation, there was a significant decrease in ABGs from 2158 to 1674 (p=0.001), and after adjusting for daily census, there was a significant decrease from 35.3 ABGs/100 patients/day to 26.5 ABGs/100 patients/day (p<0.001), with no change in mortality or demographic characteristics between the populations. The percent of ABGs with normal range values for pH, PaCO2, and PaO2 decreased from 13.3% to 9.6% after implementation (p<0.001). Multivariate analysis revealed a 14% decrease in daily ABGs (p=0.001), a 15% decrease in weaning trial ABGs (p=0.039), and a 15% increase in ABGs ordered following a change in minute ventilation (p=0.004). Cost minimization analysis estimated annual institutional savings to be $87,565. CONCLUSIONS: Implementation of an evidence based protocol for ABG use resulted in fewer ABGs/patient/day largely from reduction of routine, daily ABGs. Ordering patterns for ABGs appeared to shift towards more clinically appropriate/relevant indications. LEVEL OF EVIDENCE: 2b.

Hemostatic resuscitation during surgery improves survival in patients with traumatic-induced coagulopathy.

BACKGROUND: Although hemostatic resuscitation with a 1:1 ratio of fresh-frozen plasma (FFP) to packed red blood cells (PRBC) after severe hemorrhage has been shown to improve survival, its benefit in patients with traumatic-induced coagulopathy (TIC) after >10 units of PRBC during operation has not been elucidated. We hypothesized that a survival benefit would occur when early hemostatic resuscitation was used intraoperatively after injury in patients with TIC. METHODS: A 7-year retrospective study of patients with emergency department diagnosis of TIC after transfusion of >10 units of PRBC in the operating room. TIC was defined as initial emergency department international normalized ratio > 1.2, prothrombin time > 16 seconds, and partial thromboplastin time > 50 seconds. Patients were divided into FFP:PRBC ratios of 1:1, 1:2, 1:3, and 1:4. Patients with diagnosis of TIC who received transfusion of both FFP and PRBC during surgery were included. Other variables evaluated included age, gender, mechanism of injury, initial base deficit, mean operative time, trauma intensive care unit length of stay (TICU LOS) and Injury Severity Score. The primary outcome measure evaluated was the impact of the early FFP:PRBC ratio on mortality. RESULTS: Four hundred thirty-five patients underwent emergency operations postinjury and received FFP with >10 units of PRBC in the operating room; 135 (31.0%) of these patients had TIC and 53 died (39.5% mortality). Mean operative time was 137 minutes (SD +/- 49). There were no differences with regard to age, gender, mechanism of injury, initial base deficit, or Injury Severity Score among all groups. A significant difference in mortality was found in patients who received >10 units of PRBC when FFP:PRBC ratio was 1:1 versus 1:4 (28.2% vs. 51.1%, p = 0.03). Intermediate mortality rates were noted in patients with 1:2 and 1:3 ratios (38% and 40%, respectively). From a linear regression model, 13 days of increased TICU LOS was observed among 1:4 group compared with 1:1 group (p < 0.01). CONCLUSION: TIC is common after severe injury and is associated with a high mortality in patients transfused with >10 units of PRBC during surgery. Early hemostatic resuscitation during first hours after injury improves survival with shorter TICU LOS in patients with TIC.