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.

Fentanyl-Induced Rigid Chest Syndrome in Critically Ill Patients.

BACKGROUND: Opioid induced chest wall rigidity was first described in the early 1950s during surgical anesthesia and has often been referred to as fentanyl induced rigid chest syndrome (FIRCS). It has most commonly been described in the setting of procedural sedation and bronchoscopy, characterized by pronounced abdominal and thoracic rigidity, asynchronous ventilation, and respiratory failure. FIRCS has been infrequently described in the setting of continuous analgesia in critically ill adult patients. We postulate that FIRCS can occur in this setting and is likely under recognized, leading to increased morbidity and mortality. METHODS: Patients admitted to the intensive care unit with suspected FIRCS were included in this retrospective analysis. The objective of this analysis is to describe the clinical presentation and treatment strategies for FIRCS. RESULTS: Forty-two patients exhibiting symptoms of FIRCS were included in this analysis. Twenty-two of the forty-two patients with descriptive documentation had evidence of thoracic or abdominal rigidity on examination (52.4%). Twelve of sixteen (75%) patients treated solely with naloxone had documented ventilator compliance following intervention, compared to six of eleven (55%) managed with cisatracurium alone. Nine of twelve patients who ultimately received naloxone after initial treatment with cisatracurium had documented ventilator compliance following naloxone administration (75%). Standard interventions, including sedation optimization and ventilator adjustments were attempted to rule out and treat other potential causes of dyssynchrony. In most cases, the administration of naloxone resulted in appropriate compliance with both ventilator and patient-initiated breaths, suggesting the ventilator dyssynchrony was due to fentanyl. CONCLUSIONS: This is the largest case series to date describing FIRCS in the intensive care setting. Recognition and prompt management is necessary for improved patient outcomes. Research is needed to increase awareness and recognition, identify patient risk factors, and analyze the efficacy and safety of interventions.

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.

Role of therapeutic plasma exchange in the management of COVID-19-induced cytokine storm syndrome.

The risk of mortality in patients with coronavirus disease 2019 (COVID-19) is largely related to an excessive immune response, resulting in a hyperinflammatory and hypercoagulable condition collectively referred to as cytokine storm syndrome (CSS). Management of critically ill patients with COVID-19 has included attempts to abate this process, prevent disease progression, and reduce mortality. In this context, therapeutic plasma exchange (TPE) offers an approach to eliminate inflammatory factors and cytokines, offset the pathologic coagulopathy, and reduce the CSS effects. The aim of this review is to analyze available data on the use of TPE for the treatment of CSS in patients with COVID-19. Systematic searches of PubMed, Scopus and COVID-19 Research were conducted to identify articles published between March 1, 2020 and May 26, 2021 reporting the use of TPE for the treatment of COVID-19-induced CSS. A total of 34 peer-reviewed articles (1 randomized controlled trial, 4 matched case-control series, 15 single-group case series, and 14 case reports), including 267 patients, were selected. Despite the low evidence level of the available data, TPE appeared to be a safe intervention for critically ill patients with COVID-19-induced CSS. Although inconsistencies exist between studies, they showed a general trend for decreased interleukin-6, C-reactive protein, ferritin, D-dimer, and fibrinogen levels and increased lymphocyte counts following TPE, supporting the immunomodulatory effect of this treatment. Moreover, TPE was associated with improvements in clinical outcomes in critically ill patients with COVID-19. While TPE may offer a valuable option to treat patients with COVID-19-induced CSS, high-quality randomized controlled clinical trials are needed to confirm its potential clinical benefits, feasibility, and safety. Moreover, clear criteria should be established to identify patients with CSS who might benefit from TPE.

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.

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.