Nanometer-sized pipets pulled from glass or quartz capillaries have been extensively used as probes for scanning electrochemical microscopy (SECM) and scanning ion conductance microscopy (SICM). A small separation distance between such a probe and the sample, which is required for high-resolution SECM measurements, may be hard to attain because of considerable roughness of the pipet tip. In this Letter, we report the preparation and characterization of polished nanopipet SECM probes with a much smoother tip edge. Using polished pipets, quantitative SECM measurements were performed at extremely short tip/substrate distances (e.g., d ≈ 1 nm).

The authors describe a case of unfractionated heparin (UFH) unresponsiveness in the operating room secondary to reversal of rivaroxaban with coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). A 70-year-old man with a known 4.5-to 5.0-cm abdominal aortic aneurysm and atrial fibrillation managed with rivaroxaban presented with severe right-sided flank pain radiating to the left side of his abdomen. Computed tomography-angiography on arrival demonstrated a left retroperitoneal hematoma and a suspected ruptured abdominal aortic aneurysm. He received andexanet alfa to reverse rivaroxaban prior to an emergent endovascular aneurysm repair. During surgery, he received a total of 14,000 units (167 units/kg) of UFH with minimal changes in activated clotting time (132-144 sec; baseline 135 sec [reference range 74-137 sec]). This case highlights the potential complications of using UFH anticoagulation following reversal of factor Xa inhibitors with andexanet alfa and underscores the importance of peri-procedural anticoagulation planning. For patients who require intra-operative anticoagulation, providers should consider anticoagulation reversal with prothrombin complex concentrate instead of andexanet alfa or administration of a parenteral direct thrombin inhibitor, such as argatroban or bivalirudin during the surgical procedure. KEY WORDS andexanet alfa, factor Xa reversal, direct oral anticoagulants, unfractionated heparin unresponsiveness, rivaroxaban, abdominal aortic aneurysm, endovascular repair, endovascular aneurysm repair.

Colistin therapy is associated with the development of nephrotoxicity. We examined the incidence and risk factors of nephrotoxicity associated with colistin dosing. We included adult hospitalized patients who received intravenous (IV) colistin for >72 h between January 2014 and December 2015. The primary endpoint was the incidence of colistin-associated acute kidney injury (AKI). The secondary analyses were predictors of nephrotoxicity, proportions of patients inappropriately dosed with colistin according to the Food and Drug Administration (FDA), European Medicines Agency (EMA), and Garonzik formula and clinical cure rate. We enrolled 198 patients with a mean age of 55.67 ± 19.35 years, 62% were men, and 60% were infected with multidrug-resistant organisms. AKI occurred in 44.4% (95% CI: 37.4–51.7). Multivariable analysis demonstrated that daily colistin dose per body weight (kg) was associated with AKI (OR: 1.57, 95% CI: 1.08–2.30; p = 0.02). Other significant predictors included serum albumin level, body mass index (BMI), and severity of illness. None of the patients received loading doses, however FDA-recommended dosing was achieved in 70.2% and the clinical cure rate was 13%. The incidence of colistin-associated AKI is high. Daily colistin dose, BMI, serum albumin level, and severity of illness are independent predictors of nephrotoxicity.

A moderate agreement was found between both guidelines in terms of statin use when applied to an HIV patient population. Based on the 2013 guidelines and taking into account drug interactions with antiretrovirals, 44.2% of the patients were treated with an incorrect statin intensity.

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Objectives: To identify the prevalence of and evaluate factors associated with down-titration of sedation in patients receiving neuromuscular blockade. Design: Retrospective cohort study. Setting: Tertiary care teaching hospital in Boston, MA. Patients: All patients over 18 years old admitted to the medical, surgical, or cardiac ICUs from 2013 to 2016, and who received cisatracurium for at least 24 hours. Interventions: We examined patients for whom sedation was decreased despite accompanying ongoing neuromuscular blockade administration. Measurements and Main Results: Of the 300 patients who met inclusion criteria (39% female, mean age of 57 yr old), 168 (56%) had sedation down-titrated while receiving neuromuscular blockade with a mean decrease in sedation dose of 18.7%. Factors associated with down-titration of sedation were bispectral index usage (90/168 [53.6%] vs 50/168 [29.8%] patients; p < 0.01; odds ratio, 1.82; 1.12–2.94), and bolus dose of neuromuscular blockade prior to continuous infusion (138/168 [82.1%] vs 79/168 [47.0%] patients; p < 0.0001). Conclusions: Down-titration of sedation among mechanically ventilated patients receiving neuromuscular blockade was common and was correlated with bispectral index monitor usage. Clinicians should be aware of the limitations of quantitative electroencephalography monitoring devices and recognize their potential to cause inappropriate down-titration of sedation. Substantial opportunity exists to improve the quality of care of patients receiving neuromuscular blockade through development of guidelines and standardized care pathways.

Purpose A case of a nortriptyline overdose complicated by delayed ventricular arrhythmias necessitating prolonged sodium bicarbonate infusion is presented, along with a review of tricyclic antidepressant (TCA) toxicology and key concepts for massive overdose management. Summary A 61-year-old man presented after an intentional nortriptyline overdose with a possible consumption of up to 2500 mg of nortriptyline. Electrocardiogram on presentation demonstrated QRS widening to 240 milliseconds. Despite treatment with a sodium bicarbonate infusion and further narrowing of his QRS interval, his course was complicated by repeated episodes of wide complex tachycardia. Given these episodes, an elevated quantitative serum nortriptyline level of 468 μg/L on hospital day 6 and persistently positive TCA urine screens, the patient was continued on a sodium bicarbonate infusion until hospital day 14. Based on our patient’s quantitative serum nortriptyline levels, we calculated an elimination half-life of 184 hours, 6 days post ingestion as compared to the reported half-life of nortriptyline of 14 to 51 hours. Conclusion This case demonstrates that at toxic levels of ingestion, routine TCA pharmacokinetics may be unreliable due to delayed absorption, enterohepatic recirculation, large volume of distribution, and saturable kinetics. Therefore, in these cases, pharmacokinetic values derived from routine dosing should not be used to make clinical decisions (such as timing of discontinuation of sodium bicarbonate infusion). We found that urine TCA screens provided similar information to quantitative nortriptyline levels and can be used to guide therapy along the QRS duration.

OBJECTIVES: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2020. DATA SOURCES: The Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update group screened 36 journals monthly for impactful publications. STUDY SELECTION: The group reviewed a total of 119 articles during 2020 according to relevance for practice. DATA EXTRACTION: Articles were selected with consensus and importance to clinical practice from those included in the monthly Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. The group reviewed articles according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. Articles with a 1A grade were selected. DATA SYNTHESIS: Several trials were summarized, including two meta-analyses and five original research trials. Original research trials evaluating vitamin C, hydrocortisone, and thiamine versus hydrocortisone in sepsis, the use of nonsedation strategies, dexmedetomidine in cardiac surgery, remdesivir for severe acute respiratory syndrome coronavirus 2, and thrombectomy in acute ischemic stroke. Two meta-analyses determining the impact of norepinephrine initiation in patients with septic shock and the use of corticosteroids in severe acute respiratory syndrome coronavirus 2 was included. CONCLUSIONS: This clinical review provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2020.