Lance J. Oyen

Plasma Tranexamic Acid Concentrations During Cardiopulmonary Bypass

Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 &mgr;g/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg · kg−1 · h−1 via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (&mgr;g/mL; mean ± sd [95% confidence interval]) were 37.4 ± 16.9 (45.5, 29.3) after bolus, 27.6 ± 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 ± 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 ± 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 ± 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 ± 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time × creatinine concentration interaction (P < 0.001).

Rapid-Sequence Intubation A Review of the Process and Considerations When Choosing Medications

Objective: To summarize published data regarding the steps of rapid-sequence intubation (RSI); review premedications, induction agents, neuromuscular blockers (NMB), and studies supporting use or avoidance; and discuss the benefits and deficits of combinations of induction agents and NMBs used when drug shortages occur. Data Source: A search of Medline databases (1966–October 2013) was conducted. Study Selection and Data Extraction: Databases were searched using the terms rapid-sequence intubation, fentanyl, midazolam, atropine, lidocaine, phenylephrine, ketamine, propofol, etomidate thiopental, succinylcholine, vecuronium, atracurium, and rocuronium. Citations from publications were reviewed for additional references. Data Synthesis: Data were reviewed to support the use or avoidance of premedications, induction agents, and paralytics and combinations to consider when drug shortages occur. Conclusions: RSI is used to secure a definitive airway in often uncooperative, nonfasted, unstable, and/or critically ill patients. Choosing the appropriate premedication, induction drug, and paralytic will maximize the success of tracheal intubation and minimize complications.

Fixed-dose vasopressin compared with titrated dopamine and norepinephrine as initial vasopressor therapy for septic shock.

Study Objective. To investigate the early blood pressure effects of vasopressin compared with titrated catecholamines as initial drug therapy in patients with septic shock.

Plasma aprotinin concentrations during cardiac surgery: full- versus half-dose regimens.

Aprotinin is an effective but expensive drug used during cardiac surgery to reduce blood loss and transfusion requirements. Currently, aprotinin is administered to adults according to a fixed protocol regardless of the patient’s weight. The purpose of this study was to determine aprotinin levels in patients receiving full- and half-dose aprotinin regimens by a simple functional aprotinin assay and to design a more individualized aprotinin dosage regimen for cardiac surgical patients. The mean plasma aprotinin concentration peaked 5 min after the initiation of cardiopulmonary bypass (full 401 ± 92 KIU/mL, half 226 ± 56 KIU/mL). The mean plasma aprotinin concentration after 60 min on cardiopulmonary bypass was less (full 236 ± 81 KIU/mL, half 160 ± 63 KIU/mL). There was large variation in the aprotinin concentration among patients. A statistically significant correlation was found between aprotinin concentration and patient weight (r2 = 0.67, P < 0.05). Implications The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations among patients and a large variation within each patient over time. We combined the information provided by our study with that of a previous pharmacokinetic study to develop a potentially improved, weight-based, dosing regime for aprotinin.

Guidelines for therapeutic interchange-2004.

This publication is an update of the American College of Clinical Pharmacy (ACCP) Position Statement on “Guidelines for Therapeutic Interchange,” originally published in 1993. The ACCP supports the practice of therapeutic interchange, in which pharmacists collaborate with physicians and other health care professionals to develop policies and implement programs that improve drug use to provide the best possible patient care at the most affordable cost. The ACCP has established the following guidelines for implementing therapeutic interchange policies and procedures within health care organizations and other appropriate patient care settings:

Comparing intravenous amiodarone or lidocaine, or both, outcomes for inpatients with pulseless ventricular arrhythmias.

Objective:To compare survival rates of patients with in-hospital cardiac arrest due to pulseless ventricular tachycardia/ventricular fibrillation treated with lidocaine, amiodarone, or amiodarone plus lidocaine. Design:Multicenter retrospective medical record review. Setting:Three academic medical centers in the United States. Patients:Hospitalized adult patients who received amiodarone, lidocaine, or a combination for pulseless ventricular tachycardia/ventricular fibrillation between August 1, 2000, and July 31, 2002. Measurements and Main Results:Data were collected according to the Utstein style. In-hospital proportion of patients living at 24 hrs and discharge were analyzed using chi-square analysis. Of the 605 patient medical records reviewed, 194 met criteria for inclusion (n = 79 for lidocaine, n = 74 for amiodarone, n = 41 for combination). Available data showed no difference in proportion of patients alive 24 hrs post–cardiac arrest (p = .39). Cox regression analysis indicated a decreased likelihood of survival in patients with pulseless ventricular tachycardia/ventricular fibrillation as an initial rhythm as compared with those who presented with bradycardia followed by pulseless ventricular tachycardia/ventricular fibrillation and in those patients who received amiodarone as compared with lidocaine. However, only 14 patients (25%) in the amiodarone group received the recommended initial 300-mg intravenous bolus, and amiodarone was administered an average of 8 mins later in the code compared with lidocaine (p < .001). Conclusions:These results generate the hypothesis that inpatients with cardiac arrest may have different benefits from lidocaine and amiodarone than previously demonstrated. Inadequate dosing and later administration of amiodarone in the code were two confounding factors in this study. Prospective studies evaluating these agents are warranted. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Describe the recommended treatment of pulseless ventricular arrhythmias as outlined in the 2000 revision of the American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (“guidelines”). Compare the benefits of drugs used for the treatment of ventricular arrhythmias. Use this information in a clinical setting. Dr. Rea is on the speakers bureau of Sancfi Aventis. Dr. Seybert was/is the recipient of direct grant/research funds from Abbott and KOS and is/was on the speakers bureau of The Medicine Company, Millenium, Merck, and Wyeth. All of the remaining authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Effect of corticosteroids on arginine vasopressin–containing vasopressor therapy for septic shock: a case control study

PURPOSE Studies showing corticosteroids decrease time to shock reversal in septic shock did not include arginine vasopressin, which also may reduce the duration of catecholamine therapy. Thus, the effect of corticosteroids on vasopressin-containing vasopressor regimens is unknown. We designed this study to evaluate the effect of corticosteroids on time to vasopressin-containing vasopressor withdrawal and the proportion of patients alive without vasopressors at day 7. METHODS This retrospective, case-control study included patients admitted to the intensive care units of an academic medical center who received vasopressin-containing vasopressor regimens for septic shock with or without concomitant corticosteroids. Twenty-one corticosteroid-treated patients were matched to those without corticosteroids. RESULTS Both groups had similar Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores. There was no significant difference in median time to vasopressor withdrawal (65 hours vs 20 hours, P = .09) whether corticosteroids were given or withheld. Patients who received corticosteroids, however, were significantly more likely alive without vasopressors at day 7 than patients who received a vasopressin-containing vasopressor regimen alone (80.9% vs 47.6%, P = .02). CONCLUSIONS Although corticosteroids did not improve the time to withdrawal of vasopressin-containing vasopressor therapy they significantly increased the proportion of patients alive without vasopressors at day 7.

ANALGESIC AGENTS: Pharmacology and Application in Critical Care

Evaluation of analgesic agents is multifactorial. The authors know of no direct comparisons among the choices in analgesic agents that suggest one therapy over another in global outcomes such as mortality or morbidity. Therefore, until further outcome differentiation between agents is proved, understanding the primary difference of delivery routes, mechanisms of action, pharmacokinetics, and adverse effects serves as the best guide for selecting the appropriate agent for each patient.

Oxygen therapeutics: oxygen delivery without blood.

Nearly 14 million units of packed red blood cells are transfused in the United States each year. According to the U.S. Department of Health and Human Services, in 1999, 6% of hospitals reported a shortage of blood, resulting in the cancellation or postponement of surgical procedures. The many limitations and risks of transfusions of packed red blood cells in critically ill patients have facilitated interest in developing alternative agents for oxygen delivery. Over the past few decades, safe and effective substitutes have been in development. However, no currently approved agent provides both oxygen transport and volume in place of packed red blood cells. Oxygen therapeutic products have several advantages compared with packed red blood cells, including a prolonged shelf‐life, lack of a cross‐matching requirement, and minimal infectious risks or concerns about immunogenicity Hemoglobin‐based oxygen carriers and perfluorocarbons are being developed. Two products are undergoing clinical trials. Polyheme is undergoing a phase III study in trauma patients, and Hemopure is being evaluated in a phase II study in patients undergoing cardiopulmonary bypass surgery. A third product (Hemolink) was being evaluated in a phase III study in patients undergoing coronary artery bypass grafting surgery; however, the trial was suspended. In addition, several other hemoglobin‐based oxygen carriers are in the preclinical stages. Oxygen therapeutics have several potential clinical applications in the management of perioperative blood loss, trauma, acute normovolemic hemodilution, traumatic brain injury, and blood requirements in patients who refuse or have contraindications to transfusions of red blood cells.

A study of a weight-adjusted aprotinin dosing schedule during cardiac surgery.

UNLABELLED Aprotinin is effective during cardiac surgery for reducing blood loss and transfusion requirements, but it is expensive. Aprotinin is usually administered to adults according to a fixed protocol regardless of the patients weight. We previously developed a weight-based dosing protocol for aprotinin. The purpose of this prospective observational study was to determine aprotinin levels in four patient groups (n = 10 each) using the new weight-based aprotinin dosing schedule that should achieve concentrations over 100, 150, 200, and 250 kallikrein inhibitory units/mL compared with full-dose aprotinin regimen (n = 10) by a simple functional aprotinin assay. There was no difference in patient demographic or surgical variables among groups. There was less within patient variation in plasma aprotinin concentrations over time in the new weight-based aprotinin dosing schedule groups compared with the full-dose aprotinin regimen group (P < 0.02 for all comparisons). The mean plasma aprotinin concentration achieved with the new weight-based aprotinin dosing schedule was similar to the desired concentrations, but we were unable to reduce between-patient variability in aprotinin concentrations. IMPLICATIONS The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations between patients and a large variation within each patient over time. A new weight-based dosing schedule reduced variation of aprotinin concentration over time, but was unable to reduce between-patient variability in aprotinin concentration.