Improved survival in COVID-19 related sepsis and ARDS treated with a unique "triple therapy" including therapeutic plasma exchange: A single center retrospective analysis.

BACKGROUND: Throughout the COVID-19 pandemic, the mortality of critically ill patients remained high. Our group developed a treatment regimen targeting sepsis and ARDS which we labeled "triple therapy" consisting of (1) corticosteroids, (2) therapeutic plasma exchange (TPE), and (3) timely intubation with lung protective ventilation. Our propensity analysis assesses the impact of triple therapy on survival in COVID-19 patients with sepsis and ARDS. METHODS: Retrospective propensity analysis comparing triple therapy to no triple therapy in adult critically ill COVID-19 patients admitted to the Intensive Care Unit at Lexington Medical Center from 1 March 2020 through 31 October 2021. RESULTS: Eight hundred and fifty-one patients were admitted with COVID-19 and 53 clinical and laboratory variables were analyzed. Multivariable analysis revealed that triple therapy was associated with increased survival (OR: 1.91; P = .008). Two propensity score-adjusted models demonstrated an increased likelihood of survival in patients receiving triple therapy. Patients with thrombocytopenia were among those most likely to experience increased survival if they received early triple therapy. Decreased survival was observed with endotracheal intubation ≥7 days from hospital admission (P < .001) and there was a trend toward decreased survival if TPE was initiated ≥6 days from hospital admission (P = .091). CONCLUSION: Our analysis shows that early triple therapy, defined as high-dose methylprednisolone, TPE, and timely invasive mechanical ventilation within the first 96 hours of admission, may improve survival in critically ill septic patients with ARDS secondary to COVID-19 infection. Further studies are needed to define specific phenotypes and characteristics that will identify those patients most likely to benefit.

Influence of therapeutic plasma exchange treatment on short-term mortality of critically ill adult patients with sepsis-induced organ dysfunction: a systematic review and meta-analysis.

INTRODUCTION: The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the study is to assess the effect of adjunct TPE in this setting through a comprehensive literature review. METHODS: The National Library of Medicine's Medline, Ovid (Embase), the Cochrane Library database and clinicaltrial.gov from January 01, 1966, until October 01, 2022, were searched for terms: therapeutic plasma exchange, plasmapheresis, sepsis, and septic shock. We reviewed, selected and extracted data from relevant randomized clinical trials (RCTs) and matched cohort studies (MCSs) comparing short-term mortality in critically ill adult septic patients treated with standard therapy versus those receiving adjunct TPE. Risk of bias was assessed in the RCTs using Cochrane Collaboration tool and in MCSs using ROBINS-I tool. Summary statistics, risk ratios (RRs), and confidence intervals (CIs) were calculated using random effects model. RESULTS: This systematic review included 937 adult critically ill septic patients from five RCTs (n = 367) and fifteen MCSs (n = 570). Of these total, 543 received treatment with TPE in addition to standard care. The meta-analysis includes all five RCTs and only six MCSs (n = 627). The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47-0.74, I2 3%) compared to standard therapy alone (n = 327). The systematic review of all 20 trials revealed that adding TPE to the standard therapy of critically ill septic patients resulted in faster clinical and/or laboratory recovery. CONCLUSIONS: Our comprehensive and up-to-date review demonstrates that adjunct TPE may provide potential survival benefits when compared to standard care for critically ill adult patients with sepsis-induced organ dysfunction. While results of this meta-analysis are encouraging, large well-designed randomized trials are required to identify the optimal patient population and TPE procedure characteristics prior to widespread adoption into practice.

Penetrating thoracic injury requiring emergency pneumonectomy supported with two ECMO runs: A testament to multidisciplinary critical care medicine.

Post-traumatic pneumonectomies are uncommon and, if necessary, carry significant mortality. The use of extracorporeal membrane oxygenation (ECMO) for lung injury in trauma patient has demonstrated efficacy with minimal bleeding complications. We report a case of a young man with a penetrating thoracic injury that required a pneumonectomy supported with two separate ECMO runs for pulmonary failure postoperatively.

High-Frequency Oscillatory Ventilation for Refractory Hypoxemia in Severe COVID-19 Pneumonia: A Small Case Series.

BACKGROUND COVID-19 continues to place a tremendous burden on the healthcare system, with most deaths resulting from respiratory failure. Management strategies have varied, but the mortality rate for mechanically ventilated patients remains high. Conventional management with ARDSnet ventilation can improve outcomes but alternative and adjunct treatments continue to be explored. High-frequency oscillatory ventilation (HFOV), a modality now rarely used in adult critical care medicine, may offer an alternative treatment option by maximizing lung protection and limiting oxygen toxicity in critically ill patients failing conventional ventilator strategies. CASE REPORT We present 3 patients with severe acute respiratory distress syndrome (ARDS) and sepsis due to COVID-19 who all improved clinically after transitioning from conventional ventilation to HFOV. Two patients developed refractory hypoxemia with hemodynamic instability and multiple organ failure requiring vasopressor support and renal replacement therapy. After failing to improve with all available therapies, both patients stabilized and ultimately improved after being placed on HFOV. The third patient developed severe volutrauma/barotrauma despite extreme lung protection and ARDSnet ventilation. He showed improvement in oxygenation and signs of lung trauma slowly improved after initiating HFOV. All 3 patients were ultimately liberated from mechanical ventilation and discharged from the hospital to return to functional independence. CONCLUSIONS Our experience suggests that HFOV offers advantages in the management of certain critically ill patients with ARDS due to COVID-19 pneumonia and might be considered in cases refractory to standard management strategies.

Unprovoked serotonin syndrome-like presentation of SARS-CoV-2 infection: A small case series.

Clinicians and researchers have reported an array of neurological abnormalities in coronavirus disease 2019 (COVID-19), and while serotonin excess has been observed we are unaware of reports of central nervous system serotonin toxicity in COVID-19. We present two cases that resemble serotonin syndrome in COVID-19, but without identifiable inciting medications. A 54-year-old with multiple sclerosis and diabetes mellitus presented with altered mental status. His altered sensorium was attributed to diabetic ketoacidosis, but his condition quickly deteriorated with fever to 105 degrees Fahrenheit, rigidity in all extremities, inducible clonus, and hyperreflexia. He was intubated and was treated for possible meningitis and seizure. Neurologic workup was negative for acute pathology. Despite acetaminophen, his core temperature remained elevated to 105 degrees Fahrenheit. He was treated with external cooling and cyproheptadine and within 48 h, his fever, rigidity, hyperreflexia, and clonus resolved. He was extubated and discharged home on day 14. A 72-year-old with hyperlipidemia was admitted with tremors, 4 days after testing positive for COVID-19. His symptoms rapidly worsened, and he was transferred to the Intensive Care Unit on day 3 in extremis, febrile to 104.4 degrees Fahrenheit, heart rate of 180 beats per minute, and apparent whole body myoclonus. He was intubated and developed fever refractory to acetaminophen requiring external cooling. Extensive neurologic workup was negative. He received cyproheptadine and slowly improved. He was extubated and discharged to rehab on day 11. These cases represent a unique presentation in COVID-19 that must be considered and requires a high index of suspicion.

Physiologic Improvement in Respiratory Acidosis Using Extracorporeal Co2 Removal With Hemolung Respiratory Assist System in the Management of Severe Respiratory Failure From Coronavirus Disease 2019.

OBJECTIVES: About 15% of hospitalized coronavirus disease 2019 patients require ICU admission, and most (80%) of these require invasive mechanical ventilation. Lung-protective ventilation in coronavirus disease 2019 acute respiratory failure may result in severe respiratory acidosis without significant hypoxemia. Low-flow extracorporeal Co2 removal can facilitate lung-protective ventilation and avoid the adverse effects of severe respiratory acidosis. The objective was to evaluate the efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System in correcting severe respiratory acidosis in mechanically ventilated coronavirus disease 2019 patients with severe acute respiratory failure. DESIGN: Retrospective cohort analysis of patients with coronavirus disease 2019 mechanically ventilated with severe hypercapnia and respiratory acidosis and treated with low-flow extracorporeal Co2 removal. SETTING: Eight tertiary ICUs in the United States. PATIENTS: Adult patients supported with the Hemolung Respiratory Assist System from March 1, to September 30, 2020. INTERVENTIONS: Extracorporeal Co2 removal with Hemolung Respiratory Assist System under a Food and Drug Administration emergency use authorization for coronavirus disease 2019. MEASUREMENTS AND MAIN RESULTS: The primary outcome was improvement in pH and Paco2 from baseline. Secondary outcomes included survival to decannulation, mortality, time on ventilator, and adverse events. Thirty-one patients were treated with Hemolung Respiratory Assist System with significant improvement in pH and Pco2 in this cohort. Two patients experienced complications that prevented treatment. Of the 29 treated patients, 58% survived to 48 hours post treatment and 38% to hospital discharge. No difference in age or comorbidities were noted between survivors and nonsurvivors. There was significant improvement in pH (7.24 ± 0.12 to 7.35 ± 0.07; p < 0.0001) and Paco2 (79 ± 23 to 58 ± 14; p < 0.0001) from baseline to 24 hours. CONCLUSIONS: In this retrospective case series of 29 patients, we have demonstrated efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System to improve respiratory acidosis in patients with severe hypercapnic respiratory failure due to coronavirus disease 2019.

The therapeutic efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure: a single-center experience.

BACKGROUND: Sepsis remains a common condition with high mortality when multiple organ failure develops. The evidence for therapeutic plasma exchange (TPE) in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct TPE for septic shock with multiple organ failure compared to standard therapy alone. METHODS: A retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine-resistant septic shock and multiple organ failure in intensive care units at a tertiary care hospital in Winston-Salem, NC, from August 2015 to March 2019. Adult patients with catecholamine-resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using age, gender, chronic co-morbidities (HTN, DM, CKD, COPD), APACHE II score, SOFA score, lactate level, and number of vasopressors was used to match patients, resulting in 40 patients in each arm. RESULTS: The mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients, respectively. The 28-day mortality rate was 40% in the TPE group versus 65% in the standard care group (p = 0.043). Improvements in baseline SOFA scores at 48 h were greater in the TPE group compared to standard care alone (p = 0.001), and patients receiving adjunct TPE had a more favorable fluid balance at 48 h (p = 0.01). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay (p = 0.003 and p = 0.006, respectively). CONCLUSIONS: Our retrospective, observational study in adult patients with septic shock and multiple organ failure demonstrated improved 28-day survival with adjunct TPE compared to standard care alone. Hemodynamics, organ dysfunction, and fluid balance all improved with adjunct TPE, while lengths of stay were increased in survivors. The study design does not allow for a generalized statement of support for TPE in all cases of sepsis with multiple organ failure but offers valuable information for a prospective, randomized clinical trial.

The successful use of therapeutic plasma exchange for severe COVID-19 acute respiratory distress syndrome with multiple organ failure.

The COVID-19 pandemic has brought about an urgent need for effective treatment, while conserving vital resources such as intensive care unit beds and ventilators. Antivirals, convalescent plasma, and biologics have been used with mixed results. The profound "cytokine storm" induced endotheliopathy and microthrombotic disease in patients with COVID-19 may lead to acute respiratory distress syndrome, sepsis, and multi-organ failure. We present a case of SARS-COV2 pneumonia with septic shock and multi-organ failure that demonstrated significant clinical improvement after therapeutic plasma exchange. A 65-year-old female with multiple comorbidities presented with progressive dyspnea and dry cough. She was found to be COVID-19 positive with pneumonia, and developed progressive hypoxemia and shock requiring vasopressors, cardioversion, and non-invasive positive pressure ventilation. Given her worsening sepsis with multi-organ failure, she underwent therapeutic plasma exchange with rapid clinical improvement. Her case supports the theory that plasma exchange may help abate the "cytokine storm" induced endotheliopathy and microthrombosis associated with COVID-19. Further studies are needed to identify markers of this pathway and the potential role of plasma exchange in these critically ill patients.

Extracorporeal Carbon Dioxide Removal in the Management of Complex Bilateral Flail Chest Injury.

Flail chest is an uncommon consequence of traumatic injury. Medical management includes mechanical ventilation for internal pneumatic stabilization. Control of respiratory drive is necessary to avoid paradoxical movement and impairment of recovery. Traditional approaches include sedation and neuromuscular blockade, but these measures are at odds with current trends of keeping patients awake and implementing active rehabilitation. We hypothesized that extracorporeal carbon dioxide removal (ECCO2R) would suppress the respiratory drive sufficiently to permit synchronous mechanical ventilation, allowing rib fracture healing in an awake patient with extensive bilateral flail chest. A patient with 21 fractures underwent ECCO2R for 6 weeks to permit internal pneumatic stabilization with mechanical ventilation, targeting a partial pressure of carbon dioxide in arterial blood (PaCO2) of 25-30 mm Hg. The first 2 weeks were performed with extracorporeal membrane oxygenation (ECMO) for bilateral pulmonary contusions and acute respiratory distress syndrome. The last 4 weeks was with low-flow ECCO2R. Respiratory drive was suppressed during both ECMO and ECCO2R phases when the targeted hypocapnia range of 25-30 mm Hg was achieved, permitting synchronous positive pressure ventilation in an awake and cooperative patient undergoing active rehabilitation. Extracorporeal carbon dioxide removal targeting hypocapnia is a potential adjunct in extensive flail chest injury undergoing nonsurgical management.

Clinically Promising Biomarkers in Cystic Fibrosis Pulmonary Exacerbations.

Cystic fibrosis is a complex genetic disease hallmarked by repetitive infectious exacerbations that leads to destruction of airway architecture, acute on chronic inflammatory changes, and deterioration in lung function. Predicting an exacerbation may help preempt some of these changes by the initiation of swift antibiotic and anti-inflammatory therapy. A search for biomarkers that could predict exacerbations or help guide duration of antibiotic therapy is being aggressively sought. In this review, we discuss the most recent and promising biomarkers that hopefully will assist in the future management of the CF patient.

Variations in the cerebrospinal fluid proteome following traumatic brain injury and subarachnoid hemorrhage.

BACKGROUND: Proteomic analysis of cerebrospinal fluid (CSF) has shown great promise in identifying potential markers of injury in neurodegenerative diseases [1-13]. Here we compared CSF proteomes in healthy individuals, with patients diagnosed with traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) in order to characterize molecular biomarkers which might identify these different clinical states and describe different molecular mechanisms active in each disease state. METHODS: Patients presenting to the Neurosurgery service at the Louisiana State University Hospital-Shreveport with an admitting diagnosis of TBI or SAH were prospectively enrolled. Patients undergoing CSF sampling for diagnostic procedures were also enrolled as controls. CSF aliquots were subjected to 2-dimensional gel electrophoresis (2D GE) and spot percentage densities analyzed. Increased or decreased spot expression (compared to controls) was defined in terms of in spot percentages, with spots showing consistent expression change across TBI or SAH specimens being followed up by Matrix-Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). Polypeptide masses generated were matched to known standards using a search of the NCBI and/or GenPept databases for protein matches. Eight hundred fifteen separately identifiable polypeptide migration spots were identified on 2D GE gels. MALDI-MS successfully identified 13 of 22 selected 2D GE spots as recognizable polypeptides. RESULTS: Statistically significant changes were noted in the expression of fibrinogen, carbonic anhydrase-I (CA-I), peroxiredoxin-2 (Prx-2), both α and ß chains of hemoglobin, serotransferrin (Tf) and N-terminal haptoglobin (Hp) in TBI and SAH specimens, as compared to controls. The greatest mean fold change among all specimens was seen in CA-I and Hp at 30.7 and -25.7, respectively. TBI specimens trended toward greater mean increases in CA-I and Prx-2 and greater mean decreases in Hp and Tf. CONCLUSIONS: Consistent CSF elevation of CA-I and Prx-2 with concurrent depletion of Hp and Tf may represent a useful combination of biomarkers for the prediction of severity and prognosis following brain injury.

Percutaneous cannulation for extracorporeal membrane oxygenation by intensivists: a retrospective single-institution case series.

OBJECTIVE: Extracorporeal membrane oxygenation provides support for patients with severe acute cardiopulmonary failure, allowing the application of lung or myocardial rest in anticipation of organ recovery, or as a bridge to long-term support. Advances in technology have improved the safety and ease of application of extracorporeal membrane oxygenation. Percutaneous cannulation is one of these advances and is now preferred over surgical cannulation in most cases. Percutaneous cannulation is increasingly performed by intensivists, cardiologists, interventional radiologists, and related specialties. The objective of this study is to review the experience of percutaneous cannulation by intensivists at a single institution. DESIGN: A retrospective review of 100 subjects undergoing percutaneous cannulation for extracorporeal membrane oxygenation. SETTING: Adult ICUs and PICUs at a tertiary academic medical institution. PATIENTS: Critically ill neonatal, pediatric, and adult subjects with severe respiratory and/or cardiac failure undergoing percutaneous cannulation for extracorporeal membrane oxygenation. Modes of support included venoarterial, venovenous, venovenoarterial, and arteriovenous. INTERVENTIONS: Percutaneous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Case reports submitted to the Extracorporeal Life Support Organization and hospital records of the subjects were retrospectively reviewed. Subject demographics, type of support, cannulation configuration, types of cannulas, use of imaging modalities, and complications were recorded and summarized. One hundred ninety cannulations with cannula sizes from size 12 to 31F were performed by four intensivists in 100 subjects. Twenty-three were arterial (12-16F) and 167 were venous (12-31F). Preinsertion ultrasound was performed in 93 subjects (93%), fluoroscopic guidance in 79 subjects (85% of nonarteriovenous subjects), and ultrasound-guided insertion was performed in 65 subjects (65%). Two major complications occurred, each associated with mortality. Cannulation was successful in all other subjects (98% of subjects and 99% of cannulations). There were no cases of cannula-related bloodstream infection. CONCLUSIONS: Percutaneous cannulation for extracorporeal membrane oxygenation by intensivists can be performed with a high rate of success and a low rate of complications when accompanied by imaging support.

Angiopoietins as promising biomarkers and potential therapeutic targets in brain injury.

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, and enormous economic costs to society. The full spectrum of neurological damage created by TBI or SAH is not usually manifested at the time of injury, but evolves gradually over the course of hours to days (or weeks) following these injuries. Angiopoietins, important regulators of vascular structure and function, are hallmark indicators of vascular injury and may therefore represent promising targets in the treatment of SAH and TBI. In animal models and human tissues, normal intracerebral and pial vessels show strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and appear to contribute to the remarkable loss of blood-brain barrier (BBB) in these injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may provide new therapeutic modalities which can modify 'secondary' forms of brain injury after TBI and SAH.

Clinical case of the month. Idiopathic pulmonary hemosiderosis presenting as a rare cause of iron deficiency anemia in a toddler--a diagnostic challenge.

Iron deficiency anemia is the most common cause of anemia in all age groups. Idiopathic pulmonary hemosiderosis is an extremely rare etiology of iron deficiency anemia seen predominantly in the pediatric population. Idiopathic pulmonary hemosiderosis is characterized by the triad of symptoms consisting of iron deficiency anemia, diffuse pulmonary infiltrates, and hemoptysis. The clinical presentation is extremely variable, and all three symptoms may not always be seen. Due to the rarity of the disease and the variability in clinical presentation, diagnosis is usually delayed. Early diagnosis and treatment with corticosteroids prevents further episodes of recurrent alveolar hemorrhage and improves the clinical outcome. Hence, a high index of suspicion is required for the diagnosis of this condition in young patients presenting with severe iron deficiency anemia and diffuse pulmonary infiltrates. We report a toddler with idiopathic pulmonary hemosiderosis whose initial clinical presentation was severe iron deficiency anemia.

Diabetic ketoacidosis preceding thrombocytopenia associated multiple organ failure in a child.

CONTEXT: Thrombocytopenia associated multiple organ failure is a rare but increasingly recognized condition in children. Diabetic ketoacidosis preceding thrombocytopenia associated multiple organ failure is previously unreported in pediatric patients. CASE REPORT: A 12-year-old female presented with diabetic ketoacidosis along with acute pancreatitis. She further developed thrombocytopenia and renal failure over the next two days. Although hemolytic uremic syndrome/thrombotic thrombocytopenic purpura spectrum was considered, the clinical picture seemed most consistent with thrombocytopenia associated multiple organ failure. The patient was treated with serial therapeutic plasma exchanges and made a complete recovery. CONCLUSION: A high index of suspicion of thrombocytopenia associated multiple organ failure is required in patients with diabetic ketoacidosis or pancreatitis who present with thrombocytopenia and renal failure. Plasma exchange is a life-saving intervention in such cases.

Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A--an associated respiratory failure and hemodynamic shock.

OBJECTIVE: Acute pneumonitis with acute lung injury is a cause of significant mortality related to the 2009 pH1N1 influenza A virus. Widespread lung inflammation and increased pulmonary vascular permeability has been noted on autopsy. Also, many of these patients present with significant hemodynamic compromise suggesting systemic cytokine release. Therefore, attenuating circulating cytokines, and other mediators, by blood purification techniques is a theoretically attractive strategy. We report the use therapeutic plasma exchange in three children with 2009 H1N1 related acute lung injury with severe hemodynamic compromise that had failed conventional therapeutic interventions. DESIGN: Case series. SETTING: Pediatric intensive care unit in a university children's hospital. PATIENTS: Three children, aged 8, 11, and 17 yrs, with acute respiratory distress syndrome and hemodynamic compromise related to the 2009 pH1N1 influenza A virus documented by polymerase chair reaction. All patients were on mechanical ventilation and inhaled nitric oxide, and one patient was on extracorporeal membrane oxygenation. Therapeutic plasma exchange was used as a rescue strategy. INTERVENTIONS: Each patient received three exchanges of 35-40 mL/kg on consecutive days. MEASUREMENTS: All three patients had dramatic reduction in pediatric logistic organ dysfunction scores, oxygen requirements, and vasopressor requirements after two exchanges. All survived with good functional recovery. MAIN RESULTS: In this small series of patients with H1N1/acute respiratory distress syndrome and hemodynamic compromise, therapeutic plasma exchange appeared to benefit as a method of mitigating the associated cytokine storm. The procedure was well tolerated with no reported side effects. All three patients survived, defying the predicted mortality. Because these procedures used the filtration exchange method, it was performed in a timely fashion by intensive care unit personnel and on equipment already available in the intensive care unit for renal support. CONCLUSIONS: This very limited case series suggest there may be a role for therapeutic plasma exchange as a rescue therapy in severe shock and acute lung injury related to pH1N1 that has not responded to traditional therapy.