Multicenter study evaluating target attainment of anti-Factor Xa levels using various enoxaparin prophylactic dosing practices in adult trauma patients.

STUDY OBJECTIVE: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients. DESIGN: Multicenter, retrospective review. DATA SOURCE: Electronic health records from participating institutions. PATIENTS: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement. INTERVENTION: Dosing strategy used to determine initial prophylactic dose of enoxaparin. MEASUREMENTS: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL). MAIN RESULTS: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant. CONCLUSIONS: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients.

Overlapping Physiologic Signs of Sepsis and Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: Exploring A Clinical Conundrum.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria. METHODS: We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2 weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis. RESULTS: During the first 2 weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH. CONCLUSIONS: In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses.

New-Onset Atrial Arrhythmias Are Independently Associated With In-Hospital Mortality in Veno-Venous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore if atrial arrhythmias are associated with in-hospital mortality in veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients. DESIGN: Retrospective observational cohort study. SETTING: Quaternary care academic medical center. PARTICIPANTS: Patients with respiratory failure requiring VV-ECMO for >24 hours between January 1, 2016, and January 1, 2019. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen VV-ECMO patients were included. Patients were stratified by absence or presence of clinically significant atrial arrhythmias during the VV-ECMO run. Atrial arrhythmias were defined as either atrial fibrillation or atrial flutter that occurred during VV-ECMO and required pharmacologic or electrical intervention. The primary outcome was in-hospital mortality. Secondary outcomes included a composite of thrombotic events, which included ischemic stroke and on-pump arterial thrombosis. Other objectives of this analysis included characterization of atrial arrhythmia incidence, risk factors, and management. A total of 67 patients (30.5%) experienced new-onset atrial arrhythmias post-ECMO cannulation. Age, male sex, and norepinephrine use were independently associated with atrial arrhythmia development. In-hospital mortality was significantly higher in the atrial arrhythmia group (38.8% v 19.1%; p = 0.003). In the multivariate logistic regression analysis, atrial arrhythmias during VV-ECMO were independently associated with increased odds of in-hospital mortality (odds ratio, 2.21; 95% confidence interval, 1.08-4.55; p = 0.03), after controlling for Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score, acute renal failure, total norepinephrine dose, and total cannulation time. CONCLUSIONS: New-onset atrial arrhythmias are a frequent complication during VV-ECMO and are independently associated with excessive in-hospital mortality. Thus, their presence may serve as an important prognostic tool in this patient population.

Impact of Enteral Albuterol on Bradycardic Events After Acute Cervical Spinal Cord Injury.

BACKGROUND: Acute cervical spinal cord injury (ACSCI) is commonly complicated by spinal shock, resulting in hemodynamic instability characterized by bradycardia and hypotension that can have fatal consequences. Current guidelines recommend the use of intravenous beta and dopamine agonists, such as norepinephrine and dopamine, respectively. We sought to determine whether enteral albuterol would be a safe and feasible treatment for bradycardia without an increase in the occurrence of known side effects of albuterol in patients with ACSCI. METHODS: A retrospective review of patients with ACSCI admitted to an intensive care unit at a level I trauma center and treated with enteral albuterol was conducted. Patients were excluded for the following reasons: pure beta blocker use prior to injury, concurrent use of pacemaker, age of less than 18 years, or age more than 75 years. As part of the standard of care, all patients underwent mean arterial pressure (MAP) augmentation to reach a goal of greater than 85 mm Hg during the first 7 days post injury. All eligible patient charts were reviewed for demographic characteristics, daily minimum and maximum heart rate and MAP, and concomitant vasoactive medication use. Bradycardia and tachycardia were defined as heart rate less than 60 beats per minute (bpm) and greater than 100 bpm, respectively. Factors found to be associated with bradycardia on univariate analysis were entered into a multivariable generalized estimating equation analysis to determine factors independently associated with bradycardia during the study period. RESULTS: There were 58 patients with cervical ASCI (age 45 ± 18 years, 76% men) admitted between January 1, 2016, and December 31, 2017, that met the study criteria. The mean time to initiation of albuterol was 1.5 ± 1.7 days post injury, with a duration of 9.3 ± 4.5 days and a mean daily dosage of 7.8 ± 4.5 mg. Bradycardia was observed in 136 of 766 patient days (17%). There were a few episodes of hyperglycemia (1%) and tachycardia (3%), but no episodes of hypokalemia. In a multivariable analysis, female sex (P = 0.006) and American Spinal Cord Injury Association grade A, B, or C (P < 0.001) were associated with a higher risk of developing bradycardia, whereas dosage of albuterol (P = 0.009) and norepinephrine use (P = 0.008) were associated with a lower risk of developing bradycardia. CONCLUSIONS: Albuterol administration in ASCI is a safe and feasible treatment for bradycardia, given that no significant side effects, such as hyperglycemia, hypokalemia, or tachycardia, were observed. The administration of enteral albuterol was well tolerated and, in a dose-dependent manner, associated with a lower occurrence of bradycardia. Further prospective trials for the use of enteral albuterol after SCI are warranted.

Admission Features Associated With Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: A Case-Control Study.

OBJECTIVES: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients. DESIGN: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients. SETTING: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018. PATIENTS: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission. CONCLUSIONS: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.

Control of Shivering During Targeted Temperature Management.

Targeted temperature management (TTM) is used frequently in patients with a variety of diseases, especially those who have experienced brain injury and/or cardiac arrest. Shivering is one of the main adverse effects of TTM that can often limit its implementation and efficacy. Shivering is the body's natural response to hypothermia and its deleterious effects can negate the benefits of TTM. The purpose of this article is to provide an overview of TTM strategies and shivering management.

Oxandrolone in Patients on Venovenous Extracorporeal Membrane Oxygenation: A Case Series.

Venovenous extracorporeal membrane oxygenation (VV ECMO) induces a systemic inflammatory response, which may progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The anabolic steroid oxandrolone may improve the metabolic aberrations of PICS. We report our experience with 3 patients on VV ECMO who received oxandrolone after demonstrating refractory catabolism on serial nitrogen balance (NB) studies or persistent weakness. Patients in cases 1 and 3 were started on oxandrolone on VV ECMO days 45 and 29, respectively, for negative NB despite nutrition optimization. The case 2 patient started oxandrolone for persistent weakness 68 days after cannulation. All patients demonstrated improvements in NB results. One patient developed mild transaminitis while on oxandrolone, which did not alter his medication course and resolved after the medication was discontinued. The impact of oxandrolone on functional capacity varied between patients. Oxandrolone may be beneficial in persistently catabolic VV ECMO patients to improve NB results. In some patients, this may support functional recovery. Additional research is needed to identify optimal patients for therapy and to investigate the impact of oxandrolone in this population.

Collaborative Management Strategies for Drug Shortages in Neurocritical Care.

Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients.

Impact of Ketamine Use on Adjunctive Analgesic and Sedative Medications in Critically Ill Trauma Patients.

BACKGROUND: Ketamine may be used to manage pain and agitation that is refractory to what are usually considered traditional agents such as fentanyl, propofol, benzodiazepines, and dexmedetomidine; however, literature describing the use of ketamine continuous infusions for this purpose in critically ill trauma patients is limited. OBJECTIVES: The primary objective of this study was to determine the impact of the initiation of a ketamine continuous infusion on sedative and analgesic use in critically ill trauma patients. Secondary objectives were to identify the patient population in which ketamine was initiated, assess the proportion of time patients were at their goal level of sedation, and determine the dosing patterns of adjunctive sedative agents. METHODS: This single-center retrospective chart review over a 19-month period included critically ill mechanically ventilated adult trauma patients in whom a ketamine continuous infusion was initiated for management of sedation and agitation. Patients who received ketamine for other indications or by the acute pain management service were not included in this evaluation. RESULTS: Thirty-six patients were included in the study. Patients in whom ketamine was initiated tended to be white men with blunt trauma. Overall, the initiation of ketamine was associated with a decrease in the amount of opioids and propofol used and an increase in the amount of ziprasidone and dexmedetomidine needed to achieve the goal Richmond Agitation Sedation Score. When compared with the time period before ketamine initiation, the proportion of time that patients achieved goal sedation was not significantly different after the addition of ketamine. CONCLUSIONS: Although the use of ketamine in critically ill mechanically ventilated adult trauma patients was associated with decreased opioid use, it was also associated with increased use of dexmedetomidine and ziprasidone to achieve and maintain sedation. Further examination of clinical outcomes associated with these differences in drug use in a larger population of trauma patients is warranted before routine use of ketamine for analgesia and sedation can be recommended.

Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

BACKGROUND: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. METHODS: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. RESULTS: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. CONCLUSIONS: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

Dexmedetomidine as an adjunct for sedation in patients with traumatic brain injury.

BACKGROUND: In patients with traumatic brain injury (TBI), optimizing sedation is challenging because maintaining a clinical examination is important in being able to detect neurological deterioration. Propofol (PROP) is frequently used as a sedative in TBI since it has been shown to reduce the cerebral metabolic rate, but it may lead to PROP-related infusion syndrome and hemodynamic compromise. Dexmedetomidine (DEX) is a sedative that produces minimal respiratory depression with opioid-sparing effects. The purpose of this study was to determine whether sedation with DEX would be safe in patients with severe TBI. METHODS: This prospective observational single-center study was conducted from 2011 to 2013. Patients with severe TBI were treated according to standard of care per the Brain Trauma Foundation guidelines. Sedative agents were titrated using the Richmond Agitation Sedation Scale (RASS) while maintaining intracranial pressure of less than 20 mm Hg and cerebral perfusion pressure of greater than 60 mm Hg. The primary outcome measure was the mean time in target RASS (0 = alert and calm to -2 = light sedation). RESULTS: A total of 198 patients were enrolled in the study. Patient-days (1,028 in total) were stratified into four groups: DEX only (n = 222), DEX + PROP (n = 148), PROP only (n = 599), and NEITHER (n = 59). Regression analyses indicated a significant difference in target RASS between sedative agents (p = 0.001). The DEX-only group had the highest adjusted mean daily estimate of 16.0 hours in target RASS. Hypotension was significantly higher in both the DEX only (p = 0.01) and DEX + PROP (p = 0.01) groups than in the PROP-only group. CONCLUSIONS: Dexmedetomidine was found to be associated with significantly more hypotension. Therefore, larger studies are needed to identify the role of DEX in TBI. LEVEL OF EVIDENCE: Therapeutic study, level III.

Major publications in the critical care pharmacotherapy literature: January-December 2014.

PURPOSE: Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

PURPOSE: Ten recently published articles with important implications for critical care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of ß-lactam antibiotics in severe sepsis. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

Evaluation of dexmedetomidine: safety and clinical outcomes in critically ill trauma patients.

BACKGROUND: To compare safety and clinical outcomes of prolonged infusions with standard-dose (≤0.7 µg/kg/h) dexmedetomidine (SDD) or high-dose (>0.7 µg/kg/h) dexmedetomidine (HDD) to propofol in critically ill trauma patients. METHODS: This was a retrospective review of 127 adult mechanically ventilated trauma patients between 2008 and 2009, who received propofol, SDD, or HDD for >24 hours. Primary outcomes were significant changes in blood pressure or heart rate. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS), ventilator time, and any concomitant analgesic, sedative, and antipsychotic use. Pairwise comparisons were based on Wilcoxon rank-sum test for continuous data and Pearson's chi-square test for categorical data. Statistical significance was defined as p value <0.05. RESULTS: Patients in HDD group had higher rate of hypotension (98% vs. 78%; p = 0.02) but no significant differences in heart rate compared with propofol group. These patients had median longer hospital LOS (25 days vs. 12 days; p < 0.001), ICU LOS (20 days vs. 12 days; p = 0.004), and longer ventilator time (14 days vs. 7 days; p = 0.008). They also had increased requirements for oxycodone (74% vs. 40%; p = 0.003), midazolam (36% vs. 8%; p = 0.004), and haloperidol (50% vs. 24%; p = 0.02). Patients in SDD group had longer hospital LOS compared with propofol group (21 days vs. 13 days; p < 0.001). CONCLUSION: Higher doses of dexmedetomidine may result in higher incidence of hypotension, longer LOS, and increased concomitant analgesic, sedative, and antipsychotic use, requiring further evaluation in trauma patients.

Celecoxib-induced nephrotoxicity in a renal transplant recipient.

A 47-year-old renal transplant recipient came to the transplant clinic with a serum creatinine level that was elevated above her baseline value. She had been taking celecoxib for arthritic pain. She was told to discontinue the drug, and shortly after, her serum creatinine level returned to baseline. Several case reports describe nephrotoxicity with cyclooxygenase (COX)-2 inhibitors. However, only two of these reports involved renal transplant recipients, and in both, rofecoxib was the COX-2 inhibitor of concern. To our knowledge, this is the first case report of a renal transplant recipient who developed nephrotoxicity while taking celecoxib. The potential renal effects of COX-2 inhibitors have received little attention, even though nonsteroidal anti-inflammatory drugs are considered to carry the risk of nephrotoxicity in patients with comorbidities such as diabetes mellitus and hypertension. Further studies are necessary to determine the safety of COX-2 inhibitors in transplant recipients and other patient groups that may be at heightened risk of nephrotoxicity.

Recombinant factor VIIa for refractory bleeding following orthotopic heart transplantation.

OBJECTIVE: To report a case of successful use of recombinant factor VIIa (rFVIIa) for the treatment of refractory bleeding in a patient undergoing orthotopic heart transplantation. CASE SUMMARY: A 57-year-old white male with idiopathic cardiomyopathy was taken to the operating room for explantation of his left-ventricular assist device and orthotopic heart transplantation. He experienced excessive generalized oozing that required transfusions of multiple units of blood products and significant amounts of Cellsaver (washed red blood cells via autotransfusion) without achieving adequate hemostasis. After ruling out any obvious surgical sources of bleeding and attempting to correct all coagulation deficiencies, the clinicians administered rFVIIa 90 microg/kg. The oozing rapidly declined to a negligible level, chest tubes and sternal wires were placed, and the chest was closed. The patient was on minimal inotropic support and was transferred to the intensive care unit in stable condition. DISCUSSION: Cardiac surgery is often associated with significant disruption of the coagulation system, particularly in high-risk patients, such as those undergoing removal of a ventricular assist device and subsequent orthotopic heart transplantation. This can lead to life-threatening bleeding that can require multiple hemostatic agents and significant transfusions to restore hemostasis. Recently, rFVIIa has been utilized as an alternative to massive transfusion for treatment of refractory bleeding in several patient populations, including some cardiac surgery patients. CONCLUSIONS: rFVIIa appears to be a viable option as rescue therapy for treatment of refractory bleeding following orthotopic heart transplantation. Despite the anecdotal success of rFVIIa in this setting, further clinical research is needed.

Use of epoetin alfa in critically ill patients.

OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.