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Background: Sugammadex rapidly reverses the nondepolarizing neuromuscular blocking agents (NMBAs) rocuronium and vecuronium. The role of sugammadex is not well-defined outside of the postoperative setting.Objective: This study aims to describe sugammadex use outside the postoperative setting for the reversal of nondepolarizing NMBAs.Methods: This was a single-center, retrospective cohort study conducted in patients who received sugammadex outside of the postoperative setting at an academic medical center between June 2016 and November 2022. The primary outcome was the effect of sugammadex use for rocuronium reversal, defined as any increase in train-of-four (TOF) after sugammadex administration and/or progress note documentation if TOF was unavailable. Secondary outcomes included adverse events and documentation of contraceptive counseling in patients taking hormonal contraceptives with child-bearing ability.Results: A total of 14 383 patients received sugammadex during the study period. Of those patients, 39 (0.3%) were outside of the postoperative setting for the reversal of rocuronium and included in the study. Twenty-nine (74%) patients had an increase in TOF after sugammadex administration and/or progress note documentation if TOF was unavailable. Ten (26%) patients lacked documentation regarding the effect of sugammadex. No adverse reactions were reported. Three (8%) patients included in the study were of child-bearing ability, and 1 of the 3 patients was counseled on using an alternative method of contraception following sugammadex administration.Conclusion and Relevance: There is a paucity of literature for the use of sugammadex outside of the postoperative setting. This study found that while the use of sugammadex was rare, overall, it was safe and well-tolerated.

Patients with critical illness often display variable hypo- and hypercoagulable sequalae requiring intense monitoring and anticoagulation pharmacotherapy to prevent or treat inappropriate clot formation. It is imperative to understand the various stages of the clotting cascade and where each pharmacotherapy agent exerts its therapeutic effect. Common coagulation tests are utilized to monitor the areas of the clotting cascade and the effects that anticoagulant pharmacotherapy exhibits. Many novel coagulation tests are also in development. The purpose of this narrative review is to evaluate commonly utilized coagulation tests that monitor anticoagulation while in the intensive care unit.

Background Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements.Objective The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS.Methods This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation.Results There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P= 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P= 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P= 0.04) and 7 of intubation (89 vs 4 mg; P= 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P= 0.02). There was no difference in 30-day mortality.Conclusion and Relevance Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et alin 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes.

Background:The optimal resuscitative fluid remains controversial. Objective:To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2= 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2= 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2= 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2= 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2= 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2= 42%). Conclusion and Relevance:Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Objective: To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT).Data Sources: A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed.Study Selection and Data Extraction: Studies were considered if they were available in English and conducted in humans.Data Synthesis: PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT.Relevance to Patient Care and Clinical Practice: This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations.Conclusions: With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

This study examines health outcomes in burn patients with sepsis. We hypothesized that burn patients with sepsis would have an increased odds risk for in-hospital death and longer intensive care unit (ICU) stays. This was a retrospective cohort of consecutive patients admitted to the burn ICU with total BSA (TBSA) ≥10% and/or inhalation injury between January 2008 and March 2015. Overall 407 burn patients were included; the case-rate for sepsis was 39.1% (n = 159); 20.1% (n = 82) patients were septic and 18.9% (n = 77) patients experienced septic shock. Patients with septic shock had the highest mortality rate (13.31% no sepsis vs 3.7% sepsis vs 49.4% septic shock, P < .01). Median 28-day ICU-free days was higher in patients without sepsis (23 days [Interquartile range (IQR) 14-27] no sepsis vs 0 days [IQR 0-10] sepsis vs 0 days [IQR 0-0] septic shock, P < .01). Sepsis (with or without shock) increased odds of in-hospital death (odds ratio 7.04, 95% confidence interval 1.93-25.7) in reference to the no sepsis group. With each incremental Sequential Organ Failure Assessment (SOFA) score or 10% TBSA increase, the odds risk for in-hospital death increased by 56 and 75%, respectively. Our study characterized outcomes in patients with sepsis after severe burn injury. The odds risk for in-hospital death was greater in patients with sepsis, increasing burn severity according to TBSA and SOFA score.

BackgroundNonsense and frameshift mutations in the maternally imprinted, paternally expressed gene MAGEL2,located in the Prader-Willi critical region 15q11-15q13, have been reported to cause Schaaf-Yang syndrome (SYS), a genetic disorder that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties and autism spectrum disorder. Prader-Willi syndrome (PWS) is a genetic disorder characterised by severe infantile hypotonia, hypogonadotrophic hypogonadism, early childhood onset obesity/hyperphagia, developmental delay/intellectual disability and short stature. Scoliosis and growth hormone insufficiency are also prevalent in PWS.There is extensive documentation of the endocrine and metabolic phenotypes for PWS, but not for SYS. This study served to investigate the hormonal, metabolic and body composition phenotype of SYS and its potential overlap with PWS.MethodsIn nine individuals with SYS (5 female/4 male; aged 5–17 years), we measured serum ghrelin, glucose, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3, follicle-stimulating hormone, luteinising hormone, thyroid-stimulating hormone, free T4, uric acid and testosterone, and performed a comprehensive lipid panel. Patients also underwent X-ray and dual-energy X-ray absorptiometry analyses to assess for scoliosis and bone mineral density.ResultsLow IGF-1 levels despite normal weight/adequate nutrition were observed in six patients, suggesting growth hormone deficiency similar to PWS. Fasting ghrelin levels were elevated, as seen in individuals with PWS. X-rays revealed scoliosis >10° in three patients, and abnormal bone mineral density in six patients, indicated by Z-scores of below −2 SDs.ConclusionThis is the first analysis of the hormonal, metabolic and body composition phenotype of SYS. Our findings suggest that there is marked, but not complete overlap between PWS and SYS.

Background:Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA. Objective:To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times. Methods:This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital. Results:Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group (P< 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% (P< 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (βcoefficient −23.5 minutes, 95% confidence interval [95% CI] −38.6 to −8.50 minutes). Conclusion:A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.

Objective:The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. Methods:This was a retrospective cohort review conducted over a 2-year period measuring total and mean dosage of various vasopressors used between two racial groups during the treatment of patients admitted with septic shock. The study included patients admitted to the intensive care unit with septic shock at an 805-bed tertiary, academic center. All septic shock patients were managed with vasopressors. Vasopressor selection, dosage, and duration were at the discretion of the treating physician. Total, mean, and duration of vasopressor dosing requirements were obtained for study participants. Comorbidities, prehospitalization antihypertensive medication requirements, intravenous fluids given during the septic shock phase, and source of infection were analyzed. Results:One hundred fifty-nine patients with septic shock were analyzed, of which 96 (60.4) were AAs (P< 0.059). African Americans had higher rates of end-stage renal disease and hypertension compared with whites, 85.7 vs. 14.3 (P< 0.011; odds ratio OR, 15.684) and 68.3 vs. 31.7 (P< 0.007; OR, 3.357), respectively. Norepinephrine (NE) was administered to 150 patients, 57.2 of which were AAs (P< 0.509). Thirteen patients received dopamine (5 AAs, P< 0.588), 40 patients received phenylephrine (15.7 AAs, P< 0.451), and five patients received epinephrine (1.9 AAs, P< 0.660). Comparing vasopressors between races, only NE showed statistical significance via logistic regression modeling for the AA race in terms of total dosage (AAs 736.8 SD, 897.3 g vs. whites 370 SD, 554.2 g, P< 0.003), duration of vasopressor used (AAs 38.38 SD, 34.75 h vs. whites 29.09 SD, 27.11 h, P< 0.037), and mean dosage (AAs 21.08 SD, 22.23 gh vs. whites 12.37 SD, 13.86 gh, P< 0.01). Mortality between groups was not significant. Logistic regression identified discrepancy of the mean dose NE in AAs compared with whites, with OR of 1.043 (P= 0.01). Conclusions:African American patients with septic shock were treated with higher doses of NE and required longer duration of NE administration compared with white patients.

This study examined the phenomenology and predictors of early response and remission among youth with obsessive-compulsive disorder (OCD) receiving cognitive-behavioral therapy (CBT).

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Objective.To identify the perceptions and benefits of participation in a web-based journal club by the critical care pharmacy residents who presented and their mentors.