Cardiac arrest during endotracheal intubation of children with systolic dysfunction.

This multicenter study aimed to describe peri-intubation cardiac arrest in paediatric cardiac patients with significant (moderate or severe) systolic dysfunction of the systemic ventricle. Intubation data were collected from 4 paediatric cardiac ICUs in the United States (January 2015 - December 2017). Clinician practices during intubation of patients with significant dysfunction were compared to practices during intubation of patients without significant systolic dysfunction. There were 67 intubations in patients with significant systolic dysfunction. Peri-intubation cardiac arrest rate in this population was 14.9% (10/67); peri-intubation mortality was 3%. Majority (6/10; 60%) of the cardiac arrests were classified as pulseless electrical activity. Patients with cardiac arrest upon intubation had a higher serum lactate and lower serum pH than patients without peri-intubation cardiac arrest in the significant systolic dysfunction group.In comparing cardiac ICU patients with significant systolic dysfunction (n = 67) to patients from the same time period with normal ventricular function or mild dysfunction (n = 183), clinicians were less likely to use midazolam (11.9% versus 25.1%; p = 0.03) and more likely to use etomidate (16.4% versus 4.4%; p = 0.002) for intubation. Use of other sedative agents, video laryngoscopy, atropine, inotrope initiation, and consultation of an anaesthesiologist for intubation were not statistically different between the groups.This is the first study to describe the rate of and risk factors for peri-intubation cardiac arrest in paediatric cardiac ICU patients with systolic dysfunction. There was a higher peri-intubation cardiac arrest rate compared to published rates in critically ill children with heart disease and compared to children with significant systolic dysfunction undergoing elective general anaesthesia.

Deepening Responses after Upfront Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction Therapy.

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Achievement of complete response (CR) and minimal residual disease (MRD) negativity are associated with improved progression-free survival (PFS) and overall survival (OS). With superior triplet- and quadruplet-based induction regimens, a higher proportion of patients are achieving deep responses of at least a very good partial response (VGPR) or better. The probability of achieving different levels of deeper hematologic responses post-ASCT based on the pre-ASCT depth of response is less clear in the existing literature but would be of value to patients and providers in discussing the added benefit of ASCT. We assessed the rate of deepening the hematologic response with upfront ASCT in patients with NDMM, mainly to MRD-negative CR, based on the response achieved after induction therapy. We retrospectively reviewed 210 patients with NDMM who underwent upfront ASCT at Mayo Clinic Rochester between May 1, 2018, and July 31, 2019. In addition to the availability of next-generation flow cytometry (NGF) testing for MRD status, which yielded a sensitivity of 10-5, the more sensitive mass spectrometry-based assessment of peripheral blood (ie, MASS-FIX) for monoclonal proteins was used rather than conventional immunofixation. Pre-ASCT, 23 patients (11%) achieved MRD-negative CR, which increased to 66 patients (31%) post-ASCT. Of 187 patients not in MRD-negative CR pre-ASCT, 45 (24%) converted to MRD-negative CR. Patients with MRD-positive CR before ASCT had the highest rates of conversion to MRD-negative CR. HR cytogenetics did not impact rates of MRD-negative CR achievement post-ASCT irrespective of pre-ASCT IMWG response (P = 1.0). Overall, irrespective of IMWG response, 43 patients (20%) were MRD-negative pre-ASCT (19 in VGPR, 24 in CR or sCR), and 102 patients (49%) were MRD-negative post-ASCT (36 in VGPR, 66 in CR or sCR). Among 85 patients with VGPR post-ASCT, 36 achieved MRD negativity, of whom 8 (22%) progressed, whereas 49 had MRD-positive disease, of whom 24 (49%) progressed (P = .014). Upfront ASCT in patients with NDMM led to deeper responses, with 24% converting to MRD negative CR and more than doubling of the total rate of MRD negativity irrespective of IMWG response depth.

Treatment and outcomes of patients with light chain amyloidosis who received a second line of therapy post autologous stem cell transplantation.

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m2 compared to 41 months in the 140 mg/m2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m2 at diagnosis had better outcomes.

Stuttering priapism in a patient with sickle cell trait treated with automated red cell exchange transfusion.

Sickle cell trait (SCT) is typically an asymptomatic carrier state, but sickling complications can occur under extreme conditions. Priapism is known to be associated with sickle cell disease (SCD); The link with SCT is less well established. We report the case of a 19-year-old man with SCT presenting with prolonged priapism and a refractory, stuttering course requiring multiple invasive procedures over a 5-day period with no clear alternative triggers. In light of ongoing, stuttering priapism, he underwent red blood cell (RBC) exchange transfusion with decrease of hemoglobin S from 45.8% to 11.7%. This was followed by immediate and sustained cessation of stuttering priapism, with no further episodes at 5 months. Multiple cases of priapism associated with SCT have been reported in the literature. In most cases invasive interventions were required but RBC exchange was not attempted. RBC exchange has been reported in 2 people with exertional rhabdomyolysis in the context of SCT, with improvement in 1 case. In patients with SCT and priapism, conservative measures are used to treat brief episodes, but invasive management is required for persistent or prolonged episodes. RBC exchange transfusion may be considered for treatment of refractory, stuttering priapism in individuals with SCT.

Pulsatile ventricular assist device as a bridge to transplant for the early high-risk single-ventricle physiology.

BACKGROUND: The use of ventricular assist devices (VADs) as a bridge-to-transplant in patients with single-ventricle physiology post-stage one palliation has been associated with poor outcomes. We describe our center's successful experience in the use of paracorporeal pulsatile VADs in the palliation of high-risk single ventricle physiology before or after the first stage of palliation with an impetus on pre-palliation implant. METHODS: This is a single-center retrospective review of univentricular patients implanted with the Berlin Heart EXCOR VAD. Our center's approach includes early implantation of the Berlin Heart EXCOR with common atrial cannulation, a cardiac index between 3.5 and 5 L/min/m2, and a bivalirudin-based anticoagulation regimen. Patient-related data were collected postimplant at week 1 and months 1, 2, and 3. Post-transplant data, including neurological outcomes, were collected. RESULTS: Nine patients were supported. Survival to discharge post-transplant was 83% (5/6) in patients bridged-to-transplant and 33% (1/3) in patients bridged-to-decision. Six patients had no previous palliation. Median hospital stay before implantation was 111 days for nonsurvivors versus 20 days for survivors. The need for extracorporeal membrane oxygenation and cardiopulmonary resuscitation in nonsurvivors versus survivors was 1 in 3 versus 1 in 6 and 2 in 3 versus 1 in 6, respectively. There were no major central nervous system complications except for 1 significant hemorrhagic event. The pediatric overall performance category score on follow-up was normal to mild disability in 83% of survivors. Limitations include hemolysis and intermittent periods of infection and/or inflammation. CONCLUSIONS: The use of pulsatile paracorporeal VADs is a feasible option as a bridge-to-transplant in the peri-stage one high-risk single ventricle.

Bivalirudin and Alteplase for Pulmonary Embolism Requiring Veno-Arterial Extracorporeal Membrane Oxygenation in an Adolescent.

Saddle pulmonary embolism (PE) remains a challenge to diagnose and manage in pediatric patients. Current literature encourages early consideration of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in high-risk PE patients with impending right ventricular failure. We present a 17-year-old patient who was admitted to a pediatric cardiac intensive care unit with saddle PE requiring emergent VA-ECMO support because of cardiovascular collapse. Despite anticoagulation with bivalirudin and receiving systemic thrombolysis with alteplase, the clot burden was persistent with minimal improvement in right ventricular function. We proceeded to catheter thrombolysis while on VA-ECMO. This ultimately led to a successful resolution of the PE and allowed for weaning off VA-ECMO. PE is rare in children compared with adults, and pediatricians may be unaware of therapies becoming increasingly used in adults such as the use of VA-ECMO, with systemic and local thrombolysis. The concurrent use of a direct thrombin inhibitor for ECMO anticoagulation alongside the thrombolysis is a novel combination in this condition and age-group.

Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study.

OBJECTIVES: Endotracheal intubation is associated with hemodynamic adverse events, including cardiac arrest, especially in patients with cardiac disease. There are only a few studies that have evaluated the rate of and risk factors for endotracheal intubation hemodynamic complications in critically ill pediatric patients. Although some of these studies have assessed hemodynamic complications during intubation in pediatric cardiac patients, the frequency of and risk factors for peri-intubation cardiac arrest have not been adequately described in high acuity cardiac patients. This study aims to describe the frequency of and risk factors for peri-intubation cardiac arrest in critically ill pediatric cardiac patients admitted to specialized cardiac ICUs. DESIGN: Multicenter retrospective cohort study. SETTING: Three pediatric cardiac ICUs in the United States. PATIENTS: Critically ill pediatric patients with congenital or acquired heart disease requiring endotracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endotracheal intubations performed in three cardiac ICUs between January 2015 and December 2017 were reviewed. Clinical variables-including data on patients, clinical providers, and procedure-were evaluated for their association with peri-intubation cardiac arrest. There was a total of 186 intubation events studied, occurring in 151 individual (index) patients. The rates of peri-intubation cardiac arrest and peri-intubation mortality in this cohort were 7% and 1.6%, respectively. Among those patients with moderate or severe systolic dysfunction of the systemic ventricle, peri-intubation cardiac arrest rate was 20.7%. Statistically significant risk factors for peri-intubation cardiac arrest included: significant systolic dysfunction of the systemic ventricle, pre-intubation hypotension, pre-intubation lactate elevation, lower pre-intubation pH, and documented oxygen desaturations (> 10%) during intubation procedure. CONCLUSIONS: Our most significant finding was a peri-intubation cardiac arrest rate which was much higher than previously published rates for both cardiac and noncardiac children who underwent endotracheal intubation in ICUs. Peri-intubation mortality was also high in our cohort. Regarding risk factors for peri-intubation arrest, significant systolic dysfunction of the systemic ventricle was strongly associated with cardiac arrest in this cohort.

Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta-analysis.

BACKGROUND: Guidelines recommend at least 3 months of anticoagulation for venous thromboembolism (VTE). Evidence supporting indefinite anticoagulation exists in certain conditions; however, for many patients, uncertainty regarding when to discontinue anticoagulation persists. OBJECTIVE: We aimed to investigate the efficacy and safety of extended direct oral anticoagulants (DOAC) therapy in patients with VTE and clinical uncertainty regarding extended anticoagulation. METHODS: We searched EMBASE, MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases for randomized control trials examining extended anticoagulation with DOACs as compared to non-extended therapy for the treatment of VTE. RESULTS: Of 560 citations identified by the search, three studies were eligible. Extended anticoagulation reduced VTE recurrence (relative risk [RR] 0.18, 95% confidence interval [CI] 0.12 to 0.25), and mortality (RR 0.39, 95% CI 0.19 to 0.80) with a low total number of deaths in the DOAC group (n = 12) versus placebo (n = 18). Extended anticoagulation increased clinically relevant non-major bleedings (RR 2.51, 95% CI 1.37 to 4.59). There was no difference in rates of major bleeding (RR 1.87, 95% CI 0.19 to 17.85); however, there was a low number of major bleeding events in both DOAC (n = 9) and placebo groups (n = 4). The results were mostly driven by one study (AMPLIFY-EXT), with significant heterogeneity between studies noticed when assessing bleeding outcomes. CONCLUSION: Extended DOAC therapy for 1 year in patients with clinical uncertainty for ongoing anticoagulation can reduce VTE recurrence and mortality; however, it could increase clinically relevant non-major bleeding events.

The Platelet Count and its Implications in Sickle Cell Disease Patients Admitted for Intensive Care.

BACKGROUND AND AIMS: In sickle cell disease (SCD) patients admitted for intensive care, evaluation of platelet counts in different types of sickle cell complications and its prognostic relevance are not well-studied. Illuminating these aspects were the objectives of this study. MATERIALS AND METHODS: A chart review of 136 adult SCD patients consecutively admitted to our Intensive Care Unit (ICU) was done. The prognosis on day 1 was assessed by Acute Physiology and Chronic Health Evaluation (APACHE II) and multiple organ dysfunction scores (MODS). Receiver operating characteristic (ROC) curves evaluated the ability of platelet counts, MODS, and APACHE II scores to predict survival. RESULTS: The most common types of crises were severe pain (n = 53), acute chest syndrome (n = 40), and infection (n = 18); 17 patients were nonsurvivors. Platelet counts varied widely (range, 19-838 × 109/L) with thrombocytopenia (n = 30) and thrombocytosis (n = 11). Counts correlated directly with leukocytes and reticulocytes; inversely with lactate dehydrogenase, APACHE, and MODS scores. Areas under ROC curve for platelets, MODS, and APACHE scores to predict survival were 0.73, 0.85, and 0.93, respectively. CONCLUSIONS: In severe sickle cell crisis thrombocytopenia is more common than thrombocytosis. In the ICU, day 1 platelet counts correlate inversely with prognostic scores and are significantly reduced in multi-organ failure and nonsurvivors. A platelet count above 175 × 109/L predicts patient survival with high specificity and positive predictive value but lacks sensitivity.