Norepinephrine Salt Formulations and Risk of Therapeutic Error: Results of a National Survey.

OBJECTIVES: Norepinephrine is available commercially in solution containing its salt (eg, tartrate), but only the base form (ie, norepinephrine base) is active pharmacologically. Unfortunately, the outer label of drug packages frequently reports the dosage of norepinephrine as a salt, which can lead potentially to therapeutic errors when prescribing norepinephrine. We performed a survey to assess the level of awareness of this issue. DESIGN: National survey. SETTING: Acute care units of Italian hospitals. PARTICIPANTS: Acute care physicians and nurses. INTERVENTIONS: A 15-item online survey was emailed to 305 critical care practitioners in Italy. Questions included information on the participants' background, methods of diluting norepinephrine, interpretation of recommended doses from guidelines, and a sample case related to the preparation and administration of the drug. MEASUREMENTS AND MAIN RESULTS: We collected 106 responses from 54 hospitals. All hospitals used norepinephrine bitartrate salt. Of the participants, 53% responded that the guidelines express norepinephrine dosages as a salt, 23% as the base form, and 24% were unsure or unaware about it. The simulated patient-dose calculation was resolved in 81% of cases with an incorrect calculation referring to the norepinephrine salt and only in 19% referring to the norepinephrine base. CONCLUSIONS: There is significant variability in dosage management of norepinephrine across different hospital units, as well as a lack of knowledge regarding the salt-to-base ratio. Scientific publications (eg, guidelines) should specify whether they are referring to the base or salt form of norepinephrine. The adoption of different labeling and national standards for dilution may decrease the risk of therapeutic errors.

Acute normovolemic hemodilution in cardiac surgery: rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Organ donation after extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest in a metropolitan cardiac arrest centre in Milan, Italy.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival in refractory out-of-hospital cardiac arrest (OHCA) but also expand the donor pool as these patients often become eligible for organ donation. Our aim is to describe the impact of organ donation in OHCA patients treated with ECPR in a high-volume cardiac arrest centre. METHODS: Rate of organ donation (primary outcome), organs harvested, a composite of patient survival with favourable neurological outcome or donation of ≥1 solid organ (ECPR benefit), and the potential total number of individuals benefiting from ECPR (survivors with favourable neurological outcome and potential recipients of one solid organ) were analysed among all-rhythms refractory OHCA patients treated with ECPR between January 2013-November 2022 at San Raffaele Hospital in Milan, Italy. RESULTS: Among 307 adults with refractory OHCA treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 256 (83%) died during hospital stay, 33% from brain death. Donation of at least one solid organ occurred in 58 (19%) patients, 53 (17%) after determination of brain death and 5 (1.6%) after determination of circulatory death, contributing a total of 167 solid organs (3.0 [IQR 2.5-4.0] organs/donor). Overall, 196 individuals (29 survivors with favourable neurological outcome and 167 potential recipients of 1 solid organ) possibly benefited from ECPR. ECPR benefit composite outcome was achieved in 87 (28%) patients. Solid organ donation decreased from 19% to 16% in patients with low-flow <60 min and to 11% with low-flow <60 min and initial shockable rhythm. CONCLUSIONS: When ECPR fails in patients with refractory OHCA, organ donation after brain or circulatory death can help a significant number of patients awaiting transplantation, enhancing the overall benefit of ECPR. ECPR selection criteria may affect the number of potential organ donors.

Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review.

INTRODUCTION: Recent studies suggested that Macklin sign is a predictor of barotrauma in patients with acute respiratory distress syndrome (ARDS). We performed a systematic review to further characterize the clinical role of Macklin. METHODS: PubMed, Scopus, Cochrane Central Register and Embase were searched for studies reporting data on Macklin. Studies without data on chest CT, pediatric studies, non-human and cadaver studies, case reports and series including <5 patients were excluded. The primary objective was to assess the number of patients with Macklin sign and barotrauma. Secondary objectives were: occurrence of Macklin in different populations, clinical use of Macklin, prognostic impact of Macklin. RESULTS: Seven studies enrolling 979 patients were included. Macklin was present in 4-22% of COVID-19 patients. It was associated with barotrauma in 124/138 (89.8%) of cases. Macklin sign preceded barotrauma in 65/69 cases (94.2%) 3-8 days in advance. Four studies used Macklin as pathophysiological explanation for barotrauma, two studies as a predictor of barotrauma and one as a decision-making tool. Two studies suggested that Macklin is a strong predictor of barotrauma in ARDS patients and one study used Macklin sign to candidate high-risk ARDS patients to awake extracorporeal membrane oxygenation (ECMO). A possible correlation between Macklin and worse prognosis was suggested in two studies on COVID-19 and blunt chest trauma. CONCLUSIONS: Increasing evidence suggests that Macklin sign anticipate barotrauma in patients with ARDS and there are initial reports on use of Macklin as a decision-making tool. Further studies investigating the role of Macklin sign in ARDS are justified.

Anticoagulation Strategies in Critically Ill Patients With SARS-CoV-2 Infection: The Role of Direct Thrombin Inhibitors.

OBJECTIVES: To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: An observational study. SETTING: At the intensive care unit of a university hospital. PARTICIPANTS AND INTERVENTIONS: Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p = 0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p = 0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p = 0.08). CONCLUSIONS: Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.