Clopidogrel Hyperresponsiveness and Hemorrhagic Complications Using On-Label Clopidogrel Dosing after Pipeline Embolization.

Introduction: Clopidogrel hyperresponsiveness is a timely topic, with wide ranging reports of hemorrhagic complications, using various clopidogrel dosing strategies following neuroendovascular procedures. This study serves to investigate hemorrhagic complications using standard clopidogrel doses and timing of these complications in relation to the procedure. Materials and Methods: Retrospective cohort of consecutive adult patients undergoing flow diversion with Pipeline Embolization Device (PED) at an academic medical center, receiving on-label clopidogrel doses. Patients with clopidogrel hyperresponsiveness (VerifyNowTM P2Y12 reaction unit (PRU) ≤ 70) were compared to those who were normoresponsive. The primary outcome is the rate of hemorrhagic complications between groups. Results: Of 148 included patients, 54 (36.5%) were identified as clopidogrel hyperresponsive (PRU ≤ 70) and 94 (63.5%) as clopidogrel normoresponsive (PRU 71 - 194). There were no hemorrhagic complications observed in patients who were clopidogrel hyperresponsive, with 5 occurring in patients who were normoresponsive (P = 0.09). Three (60%) of the hemorrhages were intracranial with most occurring intra-procedure or within the first week of the procedure. Age > 60 years was the only candidate predictor for hemorrhagic complications (P = 0.004). Conclusion: Our findings are contradictory, with lower hemorrhagic complications in clopidogrel hyperresponders than prior literature, and most occurring intra-op or in the immediate acute post-op phase.

Vasopressin Initiation as a Second-Line VasoPressor in Early Septic Shock (VISPSS).

BACKGROUND: Vasopressin is recommended as a second-line vasoactive agent for the management of septic shock; however, a paucity of data to guide its optimal use remains. The aim was to evaluate the effect of time-to vasopressin initiation and norepinephrine (NE) dose at vasopressin initiation on clinical outcomes in patients presenting with septic shock. METHODS: This was a multi-centered, retrospective, observational study conducted in patients with septic shock. Patients were divided into 2 groups: patients initiated on vasopressin when NE-equivalent dose (NEE) < 0.25 mcg/kg/min or ≥ 0.25 mcg/kg/min. The primary outcome was time-to-vasopressor discontinuation (hours). Secondary outcomes included 28-day in-hospital mortality, intensive care unit (ICU) length of stay (LOS), fluid balance after 72 hours, and the change in NEE at 12 hours. RESULTS: A total of 302 patients were included in this study. After propensity-score matching, 73 patients in each group were identified for analysis. There was no significant difference in the time-to-vasopressor discontinuation (hours) between the groups (88.8 [55-187.5] vs 86.7 [47-172]); p = 0.7815). Fluid balance (mL) at 72 hours was significantly lower when vasopressin was initiated at NEE < 0.25 mcg/kg/min (1769 [71-7287] vs 5762 [1463-8813]; p = 0.0077). A multivariable linear regression showed shorter time to shock resolution with earlier vasopressin initiation, defined as within 4 hours (p < 0.05). CONCLUSION: In this propensity-score matched cohort, vasopressin initiation at NEE < 0.25 mcg/kg/min was not associated with shorter vasopressor duration. There was a lower fluid balance at 72 hours when vasopressin was initiated at lower NE doses.

Unanswered questions on the use of hydrocortisone, ascorbic acid, and thiamine therapy in sepsis and septic shock.

PURPOSE: To evaluate current evidence on the utility of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy for the management of septic shock. SUMMARY: The following keyword search terms were utilized in PubMed to identify relevant articles: ascorbic acid, thiamine, hydrocortisone, shock, and critical care. Articles relevant to HAT therapy in patients with septic shock were selected. Retrospective cohorts and randomized controlled trials were included in this review; case reports/series were excluded. Data from included studies illustrating the use of HAT therapy for the management of sepsis and septic shock, including data on time to HAT therapy initiation, severity of illness at baseline, duration of vasopressor therapy, progression of organ failure, and mortality, were evaluated. CONCLUSION: The utilization of HAT therapy for the management of sepsis and septic shock remains controversial. Hemodynamic benefits have been shown to be most pronounced when HAT therapy is initiated earlier. Future studies directed at earlier initiation may be necessary to confirm this theory.