Sedation and analgesia needs in methamphetamine intoxicated patients: much ado about nothing.

BACKGROUND: Methamphetamine (M) is a widely used, powerful sympathomimetic drug that produces significant CNS stimulation. Its use is associated with psychiatric disorders, abnormal brain chemistry, and cardiovascular disease. Pre-hospital M use is associated with increased intubation, intensive care unit admission, and hospital length of stay. The purpose of this study was to determine the influence of acute M use on analgesia and sedation requirements in mechanically ventilated trauma patients. METHODS: This single center retrospective cohort study included injured adult patients (≥16 years) admitted to the trauma intensive care unit (TICU) between 2016 and 2018 who were mechanically ventilated and had a urine drug screen (UDS) completed. The primary outcome was the median sedation and total analgesia administered during the first 48 hours of TICU admission, expressed as propofol, dexmedetomidine, lorazepam, and morphine equivalents. Secondary endpoints included the median Richmond Agitation Sedation Scale (RASS) score, median Critical Pain Observation Tool (CPOT) score, ventilator days, length of stay, in-hospital mortality, and discharge disposition. RESULTS: A total of 245 patients were included in the final analysis (53 M+ and 192 M-). The patients were mostly men (78%) and sustained blunt trauma (89%) with a median age of 35 (IQR 26-52) years and median ISS of 11 (IQR 4-24). A M+ UDS was associated with increased morphine requirements, defined as greater than the cohort median of 1.91 mg/kg, during the first 12 hours of admission on the univariable analysis (OR 2.03; 95% CI, 1.07-3.82). There was no difference in median propofol (M+ 30 mcg/kg/min vs. M- 30 mcg/kg/min, p=0.58) or total morphine equivalents (M+ 5.42 mg/kg s. M- 3.89 mg/kg, p=0.30) over 48 hours between M+ and M- groups to achieve similar RASS and CPOT scores. CONCLUSION: To achieve the same level of pain control and depth of sedation, intubated TICU patients with a M+ UDS do not require more analgesia and sedation than patients with a M- UDS during the first 48 hours of admission.

Protocolized warfarin reversal with 4-factor prothrombin complex concentrate versus 3-factor prothrombin complex concentrate with recombinant factor VIIa.

INTRODUCTION: Life-threatening bleeding can complicate warfarin therapy. Rapid anticoagulant reversal via replacement of vitamin-K dependent clotting factors is essential for hemostasis. We compare two methods of rapid factor replacement for warfarin reversal. METHODS: A retrospective cohort study of warfarin-treated patients experiencing life-threatening bleeding who received a reversal protocol comprised of 4F PCC or 3F PCC and rFVIIa was performed. Demographic, clinical and anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. RESULTS: 195 patients were included in final analysis. While baseline demographics were similar between groups, the 3F-PCC group had a longer ICU LOS and higher in-hospital mortality (p < .01, .01). Pre-reversal INR was similar between both groups, but post-reversal INR was significantly lower in the 3F-PCC group, 0.8 versus 1.3 (p < .01). Significantly more patients experienced thromboembolic complications in the 3F-PCC group than the 4F-PCC group (p < .01). Receipt of rFVIIa was significantly associated with thromboembolic complications. DISCUSSION: A 4F PCC reversal strategy is efficacious in INR reversal and provides lower thromboembolic risk as compared to 3F PCC with rFVIIa.

Risk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa.

Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3-factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications.