Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature.

Objective: Recent literature suggests that intravenous (IV) administration may cause hypotension in hospitalized patients; data further suggest that this effect is most pronounced in the critically ill. The purpose of this review is to identify and evaluate current literature that addresses the incidence and implications of IV acetaminophen-induced hypotension. Data Sources: A literature search of MEDLINE, Cochrane, and EMBASE databases was performed (2002-2019) using the following terms: acetaminophen, paracetamol, intravenous, and hypotension. Abstracts and peer-reviewed publications were reviewed. Study Selection and Data Extraction: Relevant English-language studies conducted in humans evaluating the hemodynamic effects of IV acetaminophen were considered. Data Synthesis: A majority of the 19 studies included in this review identified a statistically significant drop in hemodynamic variables after the administration of 500 to 1000 mg IV acetaminophen as measured by changes in systolic blood pressure, diastolic blood pressure, or mean arterial pressure. Of the trials reporting vasopressor use, the authors found a significant increase in vasopressor requirements following IV acetaminophen administration. Relevance to Patient Care and Clinical Practice: This review represents the first comprehensive review of IV acetaminophen-induced hypotension. The findings raise the question of whether IV acetaminophen is an appropriate choice for inpatient pain or temperature management in the critically ill. Conclusions: Available evidence indicates that the administration of IV acetaminophen may be harmful in the critically ill. Additional monitoring is likely required when using IV acetaminophen in this specific population, particularly if a patient is hemodynamically unstable prior to administration.

Evaluation of the protective effects of ß-blockers in the management of acute exacerbations of chronic obstructive pulmonary disease.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this study was to evaluate the association between early ß-blocker continuation and major inpatient events in patients hospitalized for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This single centre, retrospective, investigational review board approved cohort study evaluated patients admitted for a primary diagnosis of AECOPD. Patients were evaluated based on early continuation of a ß-blocker whether a ß-blocker was initiated within 24 hours of admission and continued for at least 72 hours. Patients with AECOPD who did not receive ß-blockers were assigned to the control group. Major inpatient events were a composite outcome composed of arrhythmias, myocardial infarction (MI) and death. Safety data were collected on the incidences of bradycardia, bronchospasms and hypotension. RESULTS AND DISCUSSION: Of the 96 patients admitted for AECOPD, fifty-five patients were included in the early ß-blocker group and forty-one patients in the control group. Early ß-blocker utilization was associated with a significantly lower rate of major inpatient events compared with the control group (40% vs 80.5%; P < 0.001). Arrhythmias were significantly less common in the early ß-blocker group (30.9% vs 65.9%; P = 0.001); however, there were no significant differences in the rates of MI (9.1% vs 14.6%; P = 0.54), death (0 vs 0) or safety outcomes between groups. WHAT IS NEW AND CONCLUSION: ß-blocker therapy could result in a paradigm shift in managing chronic obstructive pulmonary disease patients from a true cardiopulmonary approach. This retrospective cohort study demonstrated early ß-blocker continuation in patients admitted for an AECOPD was associated with less major inpatient events, primarily arrhythmias.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective ß-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Evaluation of Neuroleptic Utilization in the Intensive Care Unit During Transitions of Care.

PURPOSE: The purpose of this study was to identify risk factors associated with inappropriate continuation of neuroleptics postdischarge from the intensive care unit (ICU) and hospital. MATERIALS AND METHODS: A retrospective chart review was performed including all patients greater than 18 years of age who received neuroleptic medications in an ICU. RESULTS: One hundred sixty-one patients were included during the 12- month study period. There were 85 (53%) patients discharged from the ICU with inappropriate continuation of a neuroleptic medication. There were 54 (34%) patients discharged from the hospital with inappropriate continuation of a neuroleptic medication. Patients were more likely to be discharged from the ICU with an inappropriate neuroleptic if they were prescribed multiple neuroleptics ( P = .02), did not have a urine drug screen collected at admission ( P = .023), or if trazodone was utilized in their therapy ( P = .004). Patients were more likely to be discharged from the hospital with a neuroleptic if they had multiple neuroleptic orders ( P = .0001) or if trazodone was utilized in their therapy ( P = .0023). CONCLUSION: Risk factors associated with the continuation of inappropriate neuroleptic medications upon discharge from the ICU or the hospital include multiple neuroleptic medications prescribed, the lack of a urine drug screen upon admission, and the utilization of trazodone.

Approach to the Complicated Alcohol Withdrawal Patient.

Alcohol withdrawal syndromes are common causes for admission to the intensive care unit. As many as one-fifth of the admitted patients have an alcohol-associated disorder. Identifying the benefit of the γ-aminobutyric acid (GABA) agonists has shifted toward methods to improve benzodiazepine (BZD) utilization. Literature validating this treatment approach in severe withdrawal, especially in the critical care setting, is limited, and extrapolation to this population may be dangerous. Multiple therapies have been suggested or utilized in the literature including continuous infusion of GABA agonists, ethanol, dexmedetomidine, antiepileptics, and antipsychotics, introducing a significant amount of variability into clinical practice. This variability in treatment approaches highlights the lack of uniformity and recommendations available for the treatment of severe refractory patients. In patients progressing to severe withdrawal, it may be warranted to escalate care with adjunctive or more aggressive therapies. Although multiple practices are commonly used, the evidence supporting their use after failing symptom-triggered or aggressive therapy with BZDs is virtually nonexistent. These patients commonly receive a multimodal approach, which varies substantially between providers and institutions. Further literature should be directed at the approach most likely to provide benefit when standard of care has failed.

Idarucizumab for Reversal of Dabigatran-Associated Bleeding: Misnomer or Miracle?

BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding. DISCUSSION: Although existing clinical studies show a rapid reversal of coagulation assays, these studies did not describe a corresponding improvement in mortality or rapid cessation of hemorrhage. It is questionable how heavily clinicians can rely upon the use of the surrogate endpoints in clinical studies, such as ecarin clotting time and dilute thrombin time. Another issue is whether patients exhibiting re-elevation of coagulation assays would benefit from an additional dose of idarucizumab, because this has not been studied. It is currently unclear if blood products must be given in addition to idarucizumab can be used as monotherapy. CONCLUSIONS: The initial data suggest a definite role for idarucizumab in treatment of bleeding associated with dabigatran. As more clinical practice experience is gained with the agent and the remaining data on its use are released, clinicians can better guide the clinical use of idarucizumab. At present, there is currently not enough evidence for idarucizumab to be used as monotherapy.

The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting.

BACKGROUND: The utilization of bolus-dose phenylephrine (PHE) has transitioned to the emergency department (ED) for the treatment of acutely hypotensive patients, despite a paucity of literature in this setting. METHODS: This was a single center retrospective chart review of the utilization of bolus-dosed PHE for acute hypotension in the ED at an academic non-forprofit hospital. The primary objective of this study is to report the frequency of patients that were initiated on a continuous vasopressor infusion (CVI) within 30 minutes after the first administration of bolus-dose PHE. Secondary objectives included an observational description of the impact of early preload expansion (fluids) on the initiation of CVIs in the setting of bolus-dose PHE in the ED. RESULTS: Seventy-three patients met inclusion criteria for analysis. The primary outcome, 46.5% (n = 34) of patients were initiated on a CVI within 30 minutes following bolus-dose PHE. Initial preload expansion (30 mL/kg of IV fluids) was found to be significantly disproportionate with 34.2% appropriately fluid challenged vs 65.8% (P = .0048). In addition, a significant decrease in the number of PHE bolus doses were required [1.5 vs 2.3 (P = .01)] in the adequately IVF challenged group. For secondary endpoints, PHE was most commonly indicated for peri-intubation hypotension (n = 52, 71.2%). Significant adverse events were documented for 15 (20.5%) patients, with bradycardia (n = 7; 9.6%) as the most common adverse event. CONCLUSIONS: Initial preload IVF expansion was found to be significantly disproportionate, and appears to be associated with an increase number of phenylephrine bolus doses in our study population.

The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients.

INTRODUCTION: Thrombocytopenia in the intensive care unit (ICU) is a commonly experienced complication; the pathology is not always easily understood. Continuous renal replacement therapy (CRRT) provides a method to dialyze unstable critically ill patients. We hypothesized that CRRT may precipitate a form of thrombocytopenia. In trials thrombocytopenia occurred at rates as high as 70%. The etiology remains unknown and results in additional diagnostic workup, as well as possible drug therapy. The extent, duration and temporal relation of thrombocytopenia remain to be determined. OBJECTIVES: Identify a pattern in platelet fluctuations after the initiation of CRRT and its impact on health care. METHODS: A retrospective study was conducted in patients receiving CRRT for >24 h with no pre-existing thrombocytopenia. Patients initiated on CRRT had daily platelet counts monitored, and CRRT attributes and therapeutic interventions were collected. Platelets were assessed for time to nadir, degree of decline and time to return to baseline after discontinuation of CRRT. RESULTS: Forty-nine patients met inclusion criteria. Thirty-seven percent of patients receiving heparinoids were tested for heparin-induced thrombocytopenia (HIT), during CRRT, with 39% of these patients having therapy changed to non-heparinoid agents due to suspected HIT; no HIT antibodies were positive. Eleven patients (22%) receiving anticoagulants, prophylactically or therapeutically had them held for a drop in platelets. There was a mean decline in platelets of 48% with a mean of 4.6 days to the nadir. An average 2.48 days were observed until rebound to >150 × 10(3)/mm(3). Statistical analysis failed to identify any patient attributes that correlated with the probability of thrombocytopenia. CONCLUSION: CRRT appears to be associated with a drop in platelets within the first 5 days of therapy with an average decline of 48%. However, platelets appear to return to >150 × 10(3)/mm(3) after cessation of CRRT. This fluctuation should be considered in the setting of patients developing thrombocytopenia after initiation of CRRT.

Factors associated with bleeding after ultrasound-assisted catheter-directed thrombolysis for the treatment of pulmonary embolism.

Ultrasound-assisted catheter directed thrombolysis (US-CDT) is frequently used for the treatment of pulmonary embolism. Due to the variety of thrombolytic and anticoagulant dosing utilized in practice, patients with pulmonary embolism who undergo US-CDT may be at an increased risk of bleeding. The primary objective of this study was to determine factors associated with major bleeding occurring with US-CDT. Secondary outcomes included in-hospital mortality and ventilator-free days. This multicentre retrospective cohort study evaluated inpatients diagnosed with pulmonary embolism and treated with US-CDT and systemic anticoagulation. A total of 173 patients were included. Most patients receiving US-CDT had a submassive pulmonary embolism with a median Pulmonary Embolism Severity Index (PESI) score of 85. Major bleeding events occurred in 37 of the 173 patients (21%). In-hospital mortality occurred in four (11%) of the patients who experienced major bleeding and three (2%) patients who did not experience major bleeding (P = 0.04). Factors associated with a higher risk of major bleeding included female sex and anticoagulation strategy. The odds of major bleeding were 3.3 times higher for women than for men (odds ratio = 3.32, 95% confidence interval 1.29-8.54). In addition, for each second increase in goal aPTT the odds of major bleeding increased by 5% (odds ratio = 1.05, 95% confidence interval 1.02-1.09). In patients with pulmonary embolism treated with US-CDT, major bleeding may be underestimated. In this analysis, major bleeding was associated with female sex and higher goal aPTT levels. In addition, bleeding with US-CDT was associated with a higher risk of in-hospital mortality.

Impact of Clinical Sepsis Phenotypes on Mortality and Fluid Status in Critically Ill Patients.

BACKGROUND: Sepsis is associated with high rates of in-hospital mortality, despite being the focus of medical research and public health initiatives for several years. The primary objective of this study was to determine the influence of septic phenotypes on rates of in-hospital mortality throughout intensive care unit (ICU) admission. PATIENTS AND METHODS: Retrospective, single-center cohort study. Medical ICU of an academic medical center. Medical ICU patients admitted between January 2016 and August 2019 with a "sepsis alert" were screened for admitting diagnosis of "sepsis" or "septic shock." Patients were classified into one of four clinical sepsis phenotypes: multi-organ failure (MOF), respiratory dysfunction (RD), neurologic dysfunction (ND), or other patients (OP). RESULTS: An analysis of 320 patients was completed. In-hospital mortality was different between groups (P < 0.001). Patients with the MOF phenotype had the highest rate of mortality (48.4%), followed by the ND phenotype (39.7%), RD phenotype (20.8%), and OP phenotype (13.7%). There were differences in volume balances between phenotypes at 48 h (P = 0.001), 72 h (P < 0.001), and 96 h (P < 0.001) after hospital presentation, with the MOF and ND phenotypes having the largest volume balances at these time points. Ventilator-free days (P < 0.001) and ICU length of stay (LOS) (P = 0.030) were different between groups. There was no difference in hospital LOS (P = 0.479). CONCLUSIONS: This data supports the presence of marked intra-disease differences in septic patient presentation and correlation with clinical outcomes including mortality. Additionally, significantly more positive fluid balances were observed between survivors and non-survivors in some patient subsets. Using pragmatic clinical variables readily available to providers to classify patients into septic phenotypes has the propensity to guide treatment strategies in the future.

Evaluation of glycemic control in critically ill patients with bacteremia: a retrospective, single-center cohort study.

Dysglycemia is a common complication in hospitalized patients and has been suggested to play a significant role in the pathology and virulence of patients with bacteremia. The literature evaluating this relationship in critically ill patients, however, is limited. This retrospective, single-center cohort study aimed to investigate the relationship of glycemic control with 28-day intensive care unit (ICU)-free days in critically ill patients with bacteremia. Glycemic control was evaluated and determined based on time in targeted blood glucose range (TIR) of 70-140 mg/dL. Using a threshold of 80%, patients were then categorized into 2 groups: TIR-lo (<80%) and TIR-hi (≥80%). Unadjusted data identified a significant difference in ICU-free days (TIR-lo 21.29 days vs TIR-hi 24.08 days, p=0.007). However, due to an excess of zero ICU-free days, a zero-inflated Poisson model was used for analysis and demonstrated that patients in the TIR-lo group were 2.57 times more likely to have zero ICU-free days (p=0.033), which was attributed to mortality. Of the survivors, no difference was seen with TIR status and the number of ICU-free days (p=0.780). These findings demonstrate that glycemic control may increase the likelihood of being liberated from the ICU within a 28-day period, which the authors attributed to increased survival. However, of the patients who left the ICU, glycemic control was not associated with a significant difference in the number of ICU-free days.

Clinical factors associated with adverse outcomes in the acute period of management of submassive pulmonary embolism.

The majority of patients with intermediate-to-severe submassive pulmonary embolism are hemodynamically stable upon presentation. There is a lack of evidence for the clinical relevance and safety of initially employed therapies in this population. The objective of current analysis was to determine predictors associated with adverse outcomes in submassive pulmonary embolism patients. This was a single-center, retrospective chart review identifying patient characteristics and clinical factors associated with adverse outcomes within the management of patients presenting to the emergency department for submassive pulmonary embolism. A total of 122 admissions for submassive pulmonary embolism were included. Among these patients, 41% (n = 50) of admissions had an adverse outcomes. Fluid volume was associated with adverse events in an incremental manner (odds ratio 2.1, 95% confidence interval, 1.4-3.2). These findings demonstrate a significant incidence of adverse events in patients with submassive pulmonary embolism and an incremental increase in likelihood of adverse events with each liter of fluid.

A case-report of successful use of thromboelastography to manage anticoagulation therapy in a patient with concomitant catastrophic antiphospholipid syndrome and heparin-induced thrombocytopenia.

: Catastrophic antiphospholipid syndrome (CAPS) is a severe but rare form of antiphospholipid syndrome (APS) that results in multiple thrombosis of multiple organs within a week . Similarly, heparin-induced thrombocytopenia (HIT) has been associated with severe and life-threatening thrombosis, both conditions mediated by an autoimmune disorder resulting in a highly thrombotic state . Both conditions requiring aggressive therapeutic anticoagulation when coinciding CAPS complicated by HIT presents a therapeutic challenge. Current recommendations advocate for the use of anti-Xa activity monitoring in the setting of APS because of the common laboratory interaction with commercially available tests, such as prothrombin and activated partial thromboplastin times . With the recommendations to utilize direct thrombin inhibitors (DTI) in the presence of HIT this precludes the possibility of anti-Xa monitoring making for a monitoring predicament. The current case presents a patient where thromboelastography (TEG) was utilized to direct anticoagulation in the setting of concurrent CAPS and HIT without complication.

Failure of chemical thromboprophylaxis in critically ill medical and surgical patients with sepsis.

PURPOSE: Critically ill patients who develop sepsis may be at a higher risk of venous thromboembolism (VTE) prophylaxis failure; however, studies in this population are limited. The objective of this study was to identify the incidence of VTE prophylaxis failure in this population. METHODS: This retrospective review of patients admitted to the intensive care unit between February 2013 and September 2015 included patients who were diagnosed with sepsis and received heparin or enoxaparin VTE prophylaxis. RESULTS: Of the 355 patients included, 42 (12.5%) developed a VTE. Acute respiratory distress syndrome (ARDS) (31% vs 16.7%, P = .0272) and higher positive end expiratory pressure (10 vs 8, P = .0066) were associated with increased risk of VTE prophylaxis failure. Logistic regression identified ARDS an event risk factor (odds ratio, 2.58; 95% confidence interval, 1.22-5.42). The VTE was associated with an increased intensive care unit (14 vs 9 days, P = .01) and hospital length of stay (26 vs 15 days, P < .0001). The median time from sepsis diagnosis to VTE event was 9 days (interquartile range, 5-13). CONCLUSION: Critically ill patients with sepsis had a high rate of VTE prophylaxis failure with ARDS being identified as a risk factor for VTE prophylaxis failure.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia.

PURPOSE: This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. MATERIALS AND METHODS: This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals. The primary outcome included the diagnostic performance characteristics of the assay. Secondary outcomes included the change in negative predictive value (NPV) over time, rate of acute kidney injury, and cost avoidance associated with vancomycin and monitoring. RESULTS: In 400 patients meeting inclusion criteria, the prevalence of culture confirmed MRSA pneumonia was 9.3%. When compared to initial cultures, the PCR assay demonstrated 91.89% sensitivity and 84.3% specificity with a positive predictive value and NPV of 37.36% and 99.03%. The NPV decreased to 87.5% at 21.9 days. No difference was found in rates of acute kidney injury. A cost avoidance of $108 per patient was estimated in patients de-escalated based on negative results. CONCLUSION: In critically ill patients, an MRSA nasal PCR assay has a high NPV for nosocomial pneumonia and can be used to guide vancomycin de-escalation.

Impact of an antimicrobial stewardship initiative to evaluate ß-lactam allergy in patients ordered aztreonam.

PURPOSE: An evaluation of the clinical and economic impact of an antimicrobial stewardship quality initiative (ASQI) focusing on allergy assessment in patients with a documented ß-lactam allergy prescribed aztreonam was conducted. METHODS: This retrospective study was executed at a hospital with an interdisciplinary antimicrobial stewardship program (ASP). A total of 186 patients with self-reported ß-lactam allergies who were prescribed aztreonam while admitted during a 36-month time period surrounding the ASQI implementation were included. The primary study outcome was median time in hours to aztreonam discontinuation among nonanaphylactic patients. RESULTS: After implementation of the ASQI, the percentage of patients continued on aztreonam for the duration of therapy was nearly cut in half, and a greater percentage of patients were switched to ß-lactam antibiotics. No adverse effects associated with ß-lactam therapy were observed in any study patient. Antimicrobial cost savings was not associated with any difference in clinical outcomes. Overall, hospitalwide aztreonam prescribing and aztreonam use declined. Institutional aztreonam orders per 1000 patient-days decreased from 1.5 to 1 after implementation of the ASQI. Additionally, hospitalwide aztreonam days of therapy per 1000 patient-days was reduced from 3.6 in the pre-ASQI period to 1.8 in the post-ASQI period. CONCLUSION: An ASQI that included critical evaluation of patient-reported ß-lactam allergies led to decreased aztreonam use, reduced antimicrobial expenditure, and similar clinical outcomes to those observed before implementation.

The impact of endocrine supplementation on adverse events in septic shock.

PURPOSE: The objective of this study was to compare the incidence of severe adverse events of vasopressin vs hydrocortisone for endocrine support therapy in patients with septic shock. MATERIALS AND METHODS: This was a retrospective, propensity-matched cohort of patients admitted to the medical intensive care unit with septic shock between February 2012 and February 2015. Patients were included if vasopressin or hydrocortisone was administered for hemodynamic support secondary to norepinephrine. RESULTS: In the unmatched cohort of 124 patients, vasopressin was associated with a significant decrease in the number of severe adverse events (P=.03). In the matched cohort, severe adverse events occurred 3 times as often in patients receiving hydrocortisone; however, this difference was not statistically significant. (odds ratio, 3.33; 95% confidence interval, 0.92-12.11; P=.06). In the matched cohort, vasopressin was associated with a faster time to hemodynamic stability (P<.05) and discontinuation of hemodynamic support (P<.01) with an increased requirement for third-line therapy (P<.01). No statistical differences were seen in length of stay (intensive care unit and hospital), length of mechanical ventilation, and in-hospital mortality. CONCLUSION: Given the lower incidence of adverse events and faster time to hemodynamic stability, vasopressin appears to be the most advantageous endocrine agent for hemodynamic support in septic shock.

The role of inhaled prostacyclin in treating acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute lung injury that is characterized by noncardiogenic pulmonary edema and severe hypoxemia second to a pathogenic impairment of gas exchange. Despite significant advances in the area, mortality remains high among ARDS patients. High mortality and a limited spectrum of therapeutic options have left clinicians searching for alternatives, spiking interest in selective pulmonary vasodilators (SPVs). Despite the lack of robust evidence, SPVs are commonly employed for their therapeutic role in improving oxygenation in patients who have developed refractory hypoxemia in ARDS. While inhaled epoprostenol (iEPO) also impacts arterial oxygenation by decreasing ventilation-perfusion (V/Q) mismatching and pulmonary shunt flow, this effect is not different from inhaled nitric oxide (iNO). The most effective and safest dose for yielding a clinically significant increase in PaO2 and reduction in pulmonary artery pressure (PAP) appears to be 20-30 ng/kg/min in adults and 30 ng/kg/min in pediatric patients. iEPO appears to have a ceiling effect above these doses in which no additional benefit may be derived. iNO and iEPO have shown similar efficacy profiles; however, they differ with respect to cost and ease of therapeutic administration. The most beneficial effects of iEPO have been seen in adult patients with secondary ARDS as compared with primary ARDS, most likely due to the difference in etiology of the two disease states, and in patients suffering from baseline right ventricular heart failure. Although iEPO has demonstrated improvements in hemodynamic parameters and oxygenation in ARDS patients, due to the limited number of randomized clinical trials and the lack of studies investigating mortality, the use of iEPO cannot be recommended as standard of care in ARDS. iEPO should be reserved for those refractory to traditional therapies.