Extracorporeal Membrane Oxygenation for Acute Lung Injury in Idiopathic Inflammatory Myopathies-A Potential Lifesaving Intervention.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO. METHODS: Patients with IIM from tertiary care centers in Belgium, Canada, Denmark, United States, and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized. RESULTS: The study included 22 patients (50% female, mean±SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (p= 0.03) and had higher median Charlson comorbidity index scores (p= 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, p= 0.94). CONCLUSION: In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.

Anticholinergic Toxidrome as a Possible Explanation for Methylene Blue Toxicity.

BACKGROUND Methylene blue has multiple uses in medicine. It is generally used to treat refractory vasoplegia and methemoglobin toxicity, and can be used as a dye to localize the parathyroid glands intra-operatively. In refractory vasoplegia, methylene blue inhibits endothelial nitric oxide and guanylate cyclase, causing vasoconstriction and potentially stabilizing blood pressure. Multiple complications have been associated with the use of methylene blue. These are related to either the sole effect of methylene blue or the combined effect of methylene blue and certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). To the best of our knowledge, in the setting of post-cardiac surgery vasoplegia, there have been no reports of the neurological toxicity of methylene blue in the absence of SSRI use. In this case report, we describe the anticholinergic manifestations associated with the use of methylene blue in post-cardiac surgery vasoplegia. CASE REPORT A male patient in his mid-sixties with severe mitral regurgitation underwent elective mitral valve replacement. Postoperatively, he was hypotensive and required a high dose of vasopressors. Methylene blue was administered to treat refractory vasoplegia. The patient became anuric and febrile, with bilateral mydriasis. Internal cooling and continuous renal replacement therapy were initiated, and symptoms rapidly resolved. The patient was discharged after prolonged hospitalization with a permanent catheter for hemodialysis. CONCLUSIONS Anticholinergic toxidrome may explain the neurological adverse effects associated with high doses of methylene blue. Physicians should be cautious when using methylene blue in combination with other anticholinergic drugs and in conditions of renal failure. The development of methylene blue toxicity warrants the urgent discontinuation of the agent and early drug elimination.

Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review.

PURPOSE: Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exist for antimicrobial dosing adjustments in patients requiring extracorporeal membrane oxygenation (ECMO) therapy, particularly in the pediatric population. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill neonates and children requiring ECMO therapy. METHODS: Medline, EMBASE, Global Health and All EBM Reviews databases were queried. Grey literature was examined. All clinical studies reporting PK/PD parameters of antimicrobials in critically ill pediatric patients treated with ECMO were included, except for case reports and congress abstracts. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently extract data and evaluate the methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK reporting guidelines. Patient and study characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Broad dosing recommendations were formulated based on the available data for specific antimicrobials. RESULTS: Twenty-nine clinical studies were included; most were observational and uncontrolled. Patient characteristics and co-treatments were often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the drugs and population studied. It was only possible to formulate dosing recommendations for a few antimicrobials given the paucity of data, its overall low quality and heterogeneity in reporting. CONCLUSION: Limited data exists on the PK/PD of antimicrobials during ECMO therapy in the pediatric population. Rigorously designed population PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring this therapeutic modality. The use of therapeutic drug monitoring for antimicrobials in pediatric patients on ECMO should be encouraged to optimize dosing. TRIAL REGISTRY: PROSPERO registration number: CRD42018099992 (Registered: July 24th 2018).

Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy.

BACKGROUND: Nausea and vomiting in pregnancy often require pharmacotherapy for symptom management. Serotonin syndrome is a rare clinical entity that can be precipitated by the medications used to treat nausea and vomiting in pregnancy. CASE: A 35-year-old pregnant individual with a history of hyperemesis gravidarum in an earlier pregnancy requiring prolonged hospitalization presented with nausea and vomiting at 7 weeks of gestation. She was incidentally found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when she was universally screened at the time of admission. She required pharmacotherapy, including prochlorperazine and ondansetron for treatment of nausea as well as sumatriptan for migraine. She developed acute spasticity, autonomic dysfunction, and temperature rise, precipitated by antiemetic therapy, consistent with serotonin syndrome. The syndrome resolved with supportive care and benzodiazepines. CONCLUSION: Serotonin syndrome is a serious clinical entity that can be provoked by the pharmacotherapy given to treat nausea and vomiting in pregnancy. This medical emergency requires early recognition and prompt management.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

Clinical and Histopathologic Features of Myocarditis in Multisystem Inflammatory Syndrome (Adult)-Associated COVID-19.

BACKGROUND: Multisystem inflammatory syndrome (MIS) associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a life-threatening condition first described in children (MIS-C). It is characterized by a hyperinflammatory state that involves the cardiovascular, gastrointestinal, dermatologic, and neurologic systems without severe respiratory system involvement. Myocarditis is one of the cardiovascular presentations of MIS that might be complicated with cardiogenic shock. There are few case reports describing SARS-CoV-2-related MIS in adults (MIS-A). CASE SUMMARY: Three cases of healthy young adults diagnosed with severe acute respiratory syndrome-CoV-2 related (MIS-A). The main presentation was cardiogenic shock secondary to histologically proven myocarditis, which resolved rapidly after initiation of medical therapy including anti-inflammatory and immunosuppressive drugs. All the cases, however, required mechanical circulatory support (MCS) as a bridge to recovery. CONCLUSIONS: It appears reasonable to treat the patient with fulminant myocarditis in SARS-CoV-2-associated MIS-A with high-dose corticosteroid "pulse" therapy in order to suppress the inflammatory response and MCS to correct initial metabolic derangement and reestablish/maintain vital organ perfusion. Addition of IV immunoglobulin and other immunomodulators should be assessed in a case-by-case basis especially considering the associated cost resource allocation.

Allogeneic Hematopoietic Stem Cell Transplant Infusion During Venovenous Extracorporeal Membrane Oxygenation Support.

Management of hematopoietic stem cell transplant complicated by respiratory failure has been facilitated by the use of extracorporeal membrane oxygenation as a bridge to curative chemotherapeutic options. This is the first report of hematopoietic stem cell transplantation on extracorporeal membrane oxygenation in the adult population. CASE SUMMARY: A 28-year-old woman diagnosed with idiopathic aplastic anemia complicated by acute respiratory distress syndrome secondary to pneumonia required venovenous extracorporeal membrane oxygenation to supplement oxygenation and ventilation. She received hematopoietic stem cell transplantation while she was on extracorporeal membrane oxygenation support. MAIN RESULTS AND CONCLUSION: Delivery of the stem cell through extracorporeal membrane oxygenation circuit was successful in the described patient. There was no sequestered stem cell in extracorporeal membrane oxygenation circuit, and she was found to have 90% donor chimerism suggesting successful engraftment. This report showed that infusion of stem cell through extracorporeal membrane oxygenation circuit is safe and feasible, and our results suggest that successful engraftment is possible.

Haemophagocytic lymphohistiocytosis in an adult with postacute COVID-19 syndrome.

Haemophagocytic lymphohistiocytosis (HLH) causing multiorgan failure has been reported as an acute clinical presentation of COVID-19. However, the literature surrounding HLH in the context of a postacute COVID-19 syndrome is limited. This report presents a case of a life-threatening HLH occurring 6 weeks after a pauci-symptomatic COVID-19 infection in a previously healthy adult. A bone marrow aspirate confirmed the HLH and the patient was successfully treated with dexamethasone and etoposide. To our knowledge, this is the first case of HLH occurring as a postacute COVID-19 syndrome following a pauci-symptomatic initial infection.

Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review.

PURPOSE: Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill adult patients requiring ECMO. METHODS: Medline, EMBASE, Global Health, and All EBM Reviews databases were searched. Grey literature was examined. All studies reporting PK/PD parameters of antimicrobials in critically ill adults treated with ECMO were included, except for case reports and congress abstracts. Ex vivo studies were included. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently abstract data and evaluate methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK guidelines. Patients' and studies' characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Dosing recommendations were formulated based on data from controlled studies. RESULTS: Thirty-two clinical studies were included; most were observational and uncontrolled. Fourteen ex vivo studies were analysed. Information on patient characteristics and co-treatments was often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the studied drugs. Few dosing recommendations could be formulated given the lack of good quality data. CONCLUSION: Limited data exist on the PK/PD of antimicrobials during ECMO therapy. Rigorously designed and well powered populational PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring ECMO support. PROSPERO REGISTRATION NUMBER: CRD42018099992 (Registered: July 24th 2018).

Awake Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 Acute Respiratory Failure.

Implantation of venovenous extracorporeal membrane oxygenation as an alternative to invasive mechanical ventilation, an "awake approach," may facilitate a lung- and diaphragm-protective ventilatory strategies without the associated harms of endotracheal intubation, positive pressure ventilation, and continuous sedation. This report presents the characteristics and outcomes of the patients treated with the awake venovenous extracorporeal membrane oxygenation approach. DESIGN: Retrospective case series. SETTING: Monocenter study. PATIENTS: Severe acute respiratory syndrome coronavirus 2 patients with acute respiratory failure treated with venovenous extracorporeal membrane oxygenation instead of invasive mechanical ventilation from March 2020 to March 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic and laboratory data were collected at admission to the ICU, prior to and after venovenous extracorporeal membrane oxygenation implantation, and at decannulation. Seven patients were treated with venovenous extracorporeal membrane oxygenation instead of invasive mechanical ventilation due to hypoxemia with a median Pao2/Fio2 ratio at implantation of 76 (interquartile range, 59-92). Four patients in the awake group subsequently required invasive mechanical ventilation, and only one patient (14.3%) died. There were no significant complications attributed venovenous extracorporeal membrane oxygenation. CONCLUSIONS: This report demonstrates that in a selected group of patients, an "awake" venovenous extracorporeal membrane oxygenation approach is feasible and may result in favorable outcomes.

Intracellular pH regulation and the acid delusion.

The hydrogen ion concentration ([H+]) in intracellular cytoplasmic fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation, failure to consider the roles played by differences in the concentration of strong ions (strong ion difference, SID), the conservation of mass, the principle of electrical neutrality, and that [H+] and bicarbonate ions [HCO3-] are dependent variables. This argument is based on the late Peter Stewart's physical-chemical analysis of [H+] regulation reported in this journal nearly forty years ago (Stewart. 1983. Can. J. Physiol. Pharmacol. 61: 1444-1461. Doi:10.1139/y83-207). We start by outlining the principles of Stewart's analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominate regulation of [H+]. The primary strong ions are Na+, K+, and Cl-, and a few organic strong anions. The second independent variable, partial pressure of carbon dioxide (PCO2), can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles will potentially provide new insights into ICF pH regulation.

A Giant Internal Iliac Artery Aneurysm with Arteriovenous Fistulization.

BACKGROUND: Isolated iliac artery aneurysms are rare and occur predominantly in men at an older age. Such aneurysms can rupture into an adjacent organ (such as the bowel, bladder or ureter) or into the adjacent common iliac vein, resulting in an arteriovenous fistula. INTRODUCTION: Formation of an internal iliac arteriovenous fistula caused by spontaneous rupture of an atherosclerotic iliac artery aneurysm wall is an exceedingly rare yet serious complication. CASE PRESENTATION: This article presents a case of an internal iliac arteriovenous fistula caused by rupture of an atherosclerotic giant iliac artery aneurysm. CONCLUSION: Rapid diagnosis and meticulous surgical technique improve outcomes in patients with this rare vascular complication.

Diagnosis and Management of Acquired von Willebrand Disease in Heart Disease: A Review of the Literature.

The incidence of acquired von Willebrand syndrome (AvWS) in patients with heart disease is commonly perceived as rare. However, its occurrence is underestimated and underdiagnosed, potentially leading to inadequate treatment resulting in increased morbidity and mortality.In patients with cardiac disease, AvWS frequently occurs in patients with structural heart disease and in those undergoing mechanical circulatory support (MCS).The clinical manifestation of an AvWS is usually characterized by apparent or occult gastrointestinal (GI) or mucocutaneous hemorrhage frequently accompanied by signs of anemia and/or increased bleeding during surgical procedures. The primary change is loss of high-molecular weight von Willebrand factor multimers (HMWM). Whereas the loss of HMWM in patients with structural heart disease is caused by increased HMWM cleavage by von Willebrand factor (vWF)-cleaving protease, ADAMTS13, AvWS in MCS patients is predominantly a result of a high shear stress coupled with mechanical destruction of vWF itself.This manuscript provides a comprehensive review of the evidence regarding both diagnosis and contemporary management of AVWS in patients with heart disease.

Safety and Flight Considerations for Mechanical Circulatory Support Devices During Air Medical Transport and Evacuation: A Systematic Narrative Review of the Literature.

OBJECTIVE: The air medical transportation industry has seen a steady rise in the use of mechanical circulatory support devices (eg, intra-aortic balloon pumps, ventricular assist devices, and extracorporeal membrane oxygenation) during transport missions, either for definitive management or repatriation. As these complex devices become more common, the industry will have to adapt to support their use in their clientele. The goal of this narrative review was to assess our current experiences regarding mechanical circulatory support devices in air medical transportation and to identify important factors to ensure successful transport. METHODS: We conducted a systematic search on MEDLINE and Embase using the following search terms: aeromedical transportation, air transportation, intra-aortic balloon pump, ventricular assist device, and extracorporeal membrane oxygenation. Results were cross-referenced to identify articles addressing both air medical transport and mechanical circulatory support devices. RESULTS: After a systematic review of the available literature, 49 articles addressing mechanical support devices transported by rotary wing and fixed wing aircraft were reviewed. In summary, our review encompassed 811 total aerial transports (152 by balloon pumps, 12 by ventricular assist devices, and 647 by extracorporeal membrane oxygenation). We found air medical transportation with these devices carried out in the public, private, or military sectors, to be safe, with low rates of serious adverse events. Dedicated training sessions focused on device troubleshooting and problem-solving during transport, optimal medical crew composition, predeparture logistical preparations, and on-demand specialist consultation can improve mission success. CONCLUSION: We report that air medical transportation of patients supported by mechanical circulatory support devices is safe. Complications can be mitigated by training and addressed either during the predeparture or in-transportation phase.

Falsely elevated valve gradients by echocardiography in the 3f aortic bioprosthesis.

The 3f Aortic Bioprosthesis (Medtronic, Inc, Minneapolis, MN) is a stentless aortic valve with a novel design that resembles a "tube within a tube." Although it has the potential for improved durability and hemodynamic performance, long-term data on this valve remain elusive. We present here 3 patients in whom postoperative echocardiography revealed significantly elevated transvalvular gradients of the 3f valve while transcatheter gradients proved to be negligible. By virtue of the unique design of the 3f bioprosthesis, great caution should be taken when interpreting echocardiographically derived gradients.

Preoperative hospital length of stay as a modifiable risk factor for mediastinitis after cardiac surgery.

BACKGROUND: As high-risk cardiac patients frequently remain within hospital while waiting for surgery, the aim of the present study was to determine the role of preoperative length of hospital stay on mediastinitis, and also, to assess contemporary risk factors for this complication. METHODS: The source population consisted of 6653 consecutive patients undergoing coronary bypass surgery, valve surgery, or both between September 2000 and September 2009 at a single tertiary care hospital. A retrospective cohort analysis was used to assess the effect of 18 preoperative variables, including length of stay, on mediastinitis. RESULTS: Mediastinitis developed in 108 patients (1.6%) resulting in an in-hospital mortality rate of 13.9%. Independent predictors of mediastinitis included obesity (2.59, CI 1.58-4.23), COPD (2.44, CI 1.55-3.84), diabetes (2.16, CI 1.44-3.24), and impaired estimated glomerular filtration rate. Preoperative hospital stay was also found to be an independent risk factor leading to a 15% increased risk of mediastinitis per week of stay. The primary wound pathogen was coagulase negative staphylococcus (82%) followed by multi-flora isolates (49%), but was unrelated to hospital stay. CONCLUSIONS: In addition to the traditional risk factors, prolonged preoperative hospital stay is also a significant and potentially modifiable predictor for the development of mediastinitis following cardiac surgery. All efforts should be made to minimize the delay in operating on hospitalized patients awaiting heart surgery.