Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and Intravenous Tissue Plasminogen Activator.

Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. For patients who present with an acute stroke despite dabigatran therapy, clinical data on the use of intravenous tissue plasminogen activator (IV-tPA) is limited. There is an anticipated increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in patients on dabigatran therapy. In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran. Dabigatran reversal with idarucizumab before administration of IV-tPA might reduce the risk of sICH. We report a case of a 69-year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who presented with an initial National Institutes of Health Stroke Scale (NIHSS) of 12. There was no early evidence of ischemic stroke or hemorrhage on head computed tomography, and coagulation studies implied therapeutic dabigatran levels. After controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA was administrated beginning 197 minutes after he was last seen at his baseline. Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated that he was at his prestroke baseline, except for a complaint of worsened short-term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and should be considered for acute stroke patients arriving in the IV-tPA time window.

Effect of paralytic type on time to post-intubation sedative use in the emergency department.

OBJECTIVE: To determine the difference between rocuronium and succinylcholine with regard to post-intubation sedative initiation in the emergency department. METHDS: This was a retrospective cohort study conducted in a tertiary care emergency department (ED) in the USA. Consecutive adult patients intubated in the ED using succinylcholine or rocuronium for paralysis were included. Data collected included patient demographics, vital signs, medications used post-intubation and times of drug administration. Patients were divided into two groups based on the type of paralytic used for rapid sequence intubation: (1) rocuronium or (2) succinylcholine. All patients received etomidate for induction of sedation. Time between intubation and post-intubation sedative use was compared between the two groups using an unpaired Student's t test. MAIN RESULTS: A total of 200 patients were included in the final analyses (100 patients in each group). There were no significant differences between the groups with regard to patient demographics, vital signs or other baseline characteristics. After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). The remaining patients received sedation as bolus doses only. Mean time between intubation and post-intubation sedative use was significantly greater in the rocuronium group compared with the succinylcholine group (27 min vs 15 min, respectively; p<0.001). CONCLUSIONS: Patients intubated with rocuronium had greater delays in post-intubation sedative initiation compared with succinylcholine.

Influence of genetic variation of the ß2-adrenergic receptor on lung diffusion in patients with cystic fibrosis.

RATIONALE: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the ß(2)-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled ß-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D(M)), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO(2)) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the ß(2)-adrenergic receptor (ADRB2). METHODS: To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 ± 7 vs. 24±4years; ht = 168 ± 8 vs. 174 ± 12 cm; wt = 64 ± 16 vs. 70 ± 13 kg; BMI = 23 ± 4 vs. 23±3 kg/m(2); FEV(1) = 72 ± 27 vs. 92 ± 12%pred; VO(2peak) = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV(1) and VO(2peak), mean ± SD, for CF and healthy, respectively). The study involved measurement of DLCO, D(M), V(C) and SaO(2) before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln(27)Gln vs. Glu(27)Glu/Gln(27)Glu. RESULTS: Within the healthy group, there were no differences in DLCO, D(M), V(C), D(M)/V(C) at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu(27)Glu/Gln(27)Glu group had higher D(M)/V(C) and SaO(2) when compared to the Gln(27)Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in V(C) and an improvement in D(M)/V(C) and SaO(2) in response to albuterol. Subjects with the Glu(27) genotype experienced a greater improvement in D(M)/V(C) with albuterol when compared to subjects homozygous for Gln at amino acid 27. CONCLUSION: These results suggest that there are differences in lung diffusion and peripheral SaO(2) according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype.

Under-dosing of etomidate for rapid sequence intubation in the emergency department.

OBJECTIVE: The objective of this study was to determine if patients who weigh ≥100 kg are more likely to receive under-dosing of etomidate compared to those who weigh <100 kg for rapid sequence intubation in the emergency department (ED). METHODS: This was a retrospective cohort study conducted in an academic ED in the United States. Adult patients who received etomidate for rapid sequence intubation were evaluated and categorized into two groups based on weight: 1) <100 kg or 2) ≥100 kg. The mean dose of etomidate (mg/kg) was compared between the groups using an unpaired Student's t-test. The percentage of patients who received under-dosing (less than 0.2 mg/kg) was compared between groups using the Chi-squared test. RESULTS: A total of 200 patients were included in the final analyses (100 patients in the <100 kg group and 100 patients in the ≥100 kg group). There were no baseline differences in age, sex, paralytic used, or trauma status between the treatment groups. The mean etomidate dose (mg/kg ± standard deviation) was significantly lower in the ≥100 kg group compared to the <100 kg group (0.18 ± 0.03 vs. 0.28 ± 0.07, respectively; p<0.001). There were significantly more patients in the ≥100 kg group who received under-dosing of etomidate compared to the <100 kg group (68% vs. 2%, respectively; p<0.001). CONCLUSIONS: Patients who weigh ≥100 kg are more likely to receive under-dosing of etomidate compared to those who weigh <100 kg for rapid sequence intubation in the ED.