Ishaq Lat

The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients.

Objective:Previously, delirium has been identified as an independent risk factor for mortality in critically ill medical patients. We undertook this study to examine the relationships among medication usage, delirium, and clinical outcomes in a critically ill surgical/trauma population. Design:Prospective, multicentered, observational study. Setting:Two surgical intensive care units in level 1 trauma centers. Patients:One hundred thirty-four consecutive surgical adult patients requiring mechanical ventilation (MV) for greater than 24 hours. Interventions:Daily delirium assessment with the Confusion Assessment Method-Intensive Care Unit tool, outcomes assessment, and prospective data collection. Measurement and Main Results:Of the 134 patients who met inclusion criteria, 84 patients (63%) developed delirium at some point during their intensive care unit (ICU) stay. Delirium was associated with more MV days (9.1 vs. 4.9 days, p < 0.01), longer ICU stay (12.2 vs. 7.4 days, p < 0.01), longer hospital stay (20.6 vs. 14.7 days, p < 0.01). Additionally, greater cumulative lorazepam dose (p = 0.012), and higher cumulative fentanyl dose (p = 0.035) were administered in the delirium group. Conclusions:Delirium in the surgical/trauma ICU cohort is independently associated with more days requiring MV, longer ICU length of stay, and longer hospital length of stay. Additionally, greater amounts of lorazepam and fentanyl were administered to patients with delirium.

Pharmacist Contributions as Members of the Multidisciplinary ICU Team

Critical care pharmacy services in the ICU have expanded from traditional dispensing responsibilities to being recognized as an essential component of multidisciplinary care for critically ill patients. Augmented by technology and resource utilization, this shift in roles has allowed pharmacists to provide valuable services in the form of assisting physicians and clinicians with pharmacotherapy decision-making, reducing medication errors, and improving medication safety systems to optimize patient outcomes. Documented improvements in the management of infections, anticoagulation therapy, sedation, and analgesia for patients receiving mechanical ventilation and in emergency response help to justify the need for clinical pharmacy services for critically ill patients. Contributions to quality improvement initiatives, scholarly and research activities, and the education and training of interdisciplinary personnel are also valued services offered by clinical pharmacists. Partnering with physician and nursing champions can garner support from hospital administrators for the addition of clinical pharmacy critical care services. The addition of a pharmacist to an interprofessional critical care team should be encouraged as health-care systems focus on improving the quality and efficiency of care delivered to improve patient outcomes.

A Review of Inhaled Nitric Oxide and Aerosolized Epoprostenol in Acute Lung Injury or Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are conditions associated with an estimated mortality of 40–50%. The use of inhaled vasodilators can help to improve oxygenation without hemodynamic effects. This article reviews relevant studies addressing the safety and efficacy of inhaled nitric oxide (iNO) and aerosolized epoprostenol (aEPO) in the treatment of life‐threatening hypoxemia associated with ARDS and ALI. In addition, the article also provides a practicable guide to the clinical application of these therapies. Nine prospective randomized controlled trials were included for iNO reporting on changes in oxygenation or clinical outcomes. Seven reports of aEPO were examined for changes in oxygenation. Based on currently available data, the use of either iNO or aEPO is safe to use in patients with ALI or ARDS to transiently improve oxygenation. No differences have been observed in survival, ventilator‐free days, or attenuation in disease severity. Further studies with consistent end points using standard delivery devices and standard modes of mechanical ventilation are needed to determine the overall benefit with iNO or aEPO.

Off-label medication use in adult critical care patients ☆

PURPOSE This study evaluated the use of off-label medications in the intensive care unit (ICU) setting and their varying levels of evidence. MATERIALS AND METHODS Thirty-seven ICUs from 24 US sites participated in this prospective, multicenter, observational study during a single 24-hour period. All medication orders were evaluated for Food and Drug Administration-labeled indications, strength of evidence, and strength of recommendation. Off-label medication orders were evaluated for indication, dose, route of administration, duration of therapy, and whether they were supported by institutional guidelines. RESULTS A total of 414 patients were enrolled, yielding 5237 medication orders for analysis. Of these, 1897 orders (36.2%) were off-label. The 3 drug classes that accounted for the most off-label orders were bronchorespiratory, gastrointestinal, and immunology. The majority of off-label medication orders (89.1%) were initiated after patient admission to the ICU. Nine hundred twenty-eight (48.3%) of the off-label medication orders had grade C or no evidence. CONCLUSIONS The use of off-label medication therapies in the US adult critical care units is common, a majority of which are initiated after admission to the ICU and a significant portion of which are supported with inferior levels of evidence.

Pharmacotherapy for Acute Respiratory Distress Syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of a clinical syndrome of respiratory failure due to refractory hypoxia. Acute respiratory distress syndrome is differentiated from ALI by a greater degree of hypoxemia and is associated with higher morbidity and mortality. The mortality for ARDS ranges from 22–41%, with survivors usually requiring long‐term rehabilitation to regain normal physiologic function. Numerous pharmacologic therapies have been studied for prevention and treatment of ARDS; however, studies demonstrating clear clinical benefit for ARDS‐related mortality and morbidity are limited. In this focused review, controversial pharmacologic therapies that have demonstrated, at minimum, a modest clinical benefit are discussed. Three pharmacologic treatment strategies are reviewed in detail: corticosteroids, fluid management, and neuromuscular blocking agents. Use of corticosteroids to attenuate inflammation remains controversial. Available evidence does not support early administration of corticosteroids. Additionally, administration after 14 days of disease onset is strongly discouraged. A liberal fluid strategy during the early phase of comorbid septic shock, balanced with a conservative fluid strategy in patients with ALI or ARDS during the postresuscitation phase, is the optimum approach for fluid management. Available evidence supports an early, short course of continuous‐infusion cisatracurium in patients presenting with severe ARDS. Evidence of safe and effective pharmacologic therapies for ARDS is limited, and clinicians must be knowledgeable about the areas of controversies to determine application to patient care.

Pharmacoepidemiology of stress ulcer prophylaxis in the United States and Canada.

PURPOSE This study sought to identify the medication class most commonly prescribed for stress ulcer prophylaxis (SUP), assess trends in SUP utilization, and report the use of acid suppressive therapy stratified by bleeding risk. MATERIALS AND METHODS This multicenter, prospective, point prevalence study reviewed adult patients over a 24-hour period for demographics, medications used for SUP, and risk factors for clinically important bleeding. Stress ulcer prophylaxis was deemed appropriate if acid suppressive therapy was administered to patients at high risk for bleeding or no therapy in patients considered at low bleeding risk. High risk was defined as the presence of mechanical ventilation, coagulopathy, or shock. For patients receiving acid suppression before hospital admission, SUP was considered appropriate if the same drug class was continued regardless of risk factors. A planned subgroup analysis was conducted whereby patients on acid suppressive medications before admission were excluded. RESULTS There were 584 patients from 58 intensive care units in 27 hospitals. The most common drug class was proton pump inhibitors (70%). Despite receiving other enteral/oral medications, 36% received intravenous acid suppressive therapy. Overall, SUP was considered appropriate in 78% of patients and 68% when patients on acid suppression before admission were excluded. When stratified by risk, acid suppressive medications were used in 92% of high-risk patients and 71% of low-risk patients. CONCLUSION Stress ulcer prophylaxis is frequently administered to patients who are not at high risk for clinically important bleeding. Proton pump inhibitors are the overwhelming first choice among practitioners. Several opportunities exist for improvement regarding the provision of SUP.

A Comparison of Initial Monotherapy with Norepinephrine Versus Vasopressin for Resuscitation in Septic Shock

BACKGROUND Early goal-directed therapy is a time-sensitive therapeutic algorithm with a tiered approach to target hypoperfusion and cardiovascular collapse within the first 6 hours of septic shock. The Surviving Sepsis Campaign guidelines recommend norepinephrine or dopamine as the initial vasoactive agent for resuscitation in septic shock, reserving the administration of vasopressin as adjunctive therapy. OBJECTIVE To determine whether vasopressin was noninferior to norepinephrine as the initial vasopressor to achieve a mean arterial pressure (MAP) goal in the first 6 hours of shock onset. METHODS This retrospective cohort study evaluated adults who received monotherapy with either norepinephrine or vasopressin as initial vasoactive therapy for the management of septic shock. Patients were excluded if the treatment arm was not monotherapy, if they were admitted to a cardiology or cardiothoracic surgery service, or if they lacked a comparator-based 1:1 frequency matching. RESULTS A total of 130 patients were included, 65 in each treatment arm. The proportion of patients who achieved a goal MAP in the vasopressin group was 63% (95% CI 51%–75%) and was 67.7% (95% CI 56%–79%) in the norepinephrine group. This observed difference between goal MAP attainment did not exceed the predefined noninferiority margin of −25% (CI for 4.7% difference −21.2% to 12%), suggesting noninferiority of vasopressin. No significant difference was identified between vasopressin and norepinephrine for final mean (SD) MAP achieved (75 [9.6] and 76.0 [8.2] mm Hg, respectively; p = 0.06) or the mean total change from baseline MAP to goal (14.1 [8.4] and 15.1 [9.1] mm Hg, respectively; p = 0.6). CONCLUSIONS Vasopressin was noninferior to norepinephrine for the achievement of a MAP goal in the first 6 hours from onset of septic shock. Further prospective analysis is warranted; however, the results are useful for consideration of alternative vasopressors in the setting of drug shortages.

New-Onset Atrial Fibrillation Is an Independent Predictor of Mortality in Medical Intensive Care Unit Patients:

Background: Atrial fibrillation (AF) has been extensively studied in postoperative critically ill surgical patients, but little literature exists to describe the outcomes of patients in the medical intensive care unit (ICU). Objectives: To determine the incidence of new-onset AF in patients admitted to a medical ICU and if new-onset AF was associated with adverse clinical outcomes. Methods: This was a single-center, retrospective study of all adult patients admitted to the medical ICU at an academic medical center for >24 hours between December 2008 and April 2010. Collected data included past medical history, incidence of new-onset AF, Acute Physiology and Chronic Health Evaluation II scores, organ failure, length of stay in the ICU and hospital, and in-hospital and 60-day survival. Results: A total of 741 patients were included. New-onset AF occurred in 53 patients (7.2%). In-hospital mortality was significantly greater for patients with new-onset AF (45% vs 16%; adjusted odds ratio [OR] = 2.21, 95% CI 1.07-4.54, P = 0.032), as was 60-day mortality (51% vs 23%; adjusted OR = 1.99, 95% CI = 1.01-3.91, P = 0.047). Patients with new-onset AF experienced greater ICU (6 ± 10.2 days vs 3 ± 3.6 days, P < 0.01) and hospital (15 ± 19 days vs 7 ± 9 days, P < 0.01) lengths of stay. Conclusions: Medical ICU patients who developed new-onset AF experienced a 2-fold increase in the odds of in-hospital mortality and death at 60 days. Further research investigating contributing factors to new-onset AF and potential treatments is warranted.

Drug-induced acute liver failure and gastrointestinal complications.

The objective of this article is to describe adverse drug events related to the liver and gastrointestinal tract in critically ill patients. PubMed and other resources were used to identify information related to drug-induced acute liver failure, gastrointestinal hypomotility, constipation, diarrhea, gastrointestinal bleeding, and pancreatitis in critically ill patients. This information was reviewed, and data regarding pathophysiology, common drug causes, and guidelines for prevention and management were collected and summarized. In cases in which data in critically ill patients were unavailable, data were extrapolated from other patient populations. Drug-induced acute liver failure can be caused by many drugs routinely used in the intensive care unit and may be associated with significant morbidity and mortality. Drug-related hypomotility and constipation and drug-related diarrhea are reported with many drugs, and these are common adverse drug events in critically ill patients that can substantially complicate the care of these patients. Drug-induced gastrointestinal bleeding and drug-induced pancreatitis occur less frequently, can range in disease severity, and can be associated with morbidity and mortality. Many drugs used in critically ill patients are associated with adverse drug events related to the liver and gastrointestinal tract. Critical care clinicians should be aware of common drug causes of drug-induced acute liver failure, gastrointestinal hypomotility, constipation, diarrhea, gastrointestinal bleeding, and pancreatitis, and should be familiar with the prevention and management of these diverse conditions.

Clinical controversies in thrombolytic therapy for the management of acute pulmonary embolism.

Acute pulmonary embolism is a common complication in hospitalized patients, spanning multiple patient populations and crossing various therapeutic disciplines. Due to the heterogeneous clinical manifestations, the selection of management strategies for patients with acute pulmonary embolism is a challenge for clinicians, and a nuanced understanding of the relevant literature is required. Previous studies that evaluated thrombolytic therapy in patients with acute pulmonary embolism are limited and controversial. Thus, we sought to identify the clinical controversies related to thrombolytic therapy in acute pulmonary embolism and reviewed the recent literature that impacts clinical practice. To apply these controversies into daily clinical practice and decision making, we provide an overview of risk stratification and assessment of pulmonary embolism. Specific areas of controversies that are discussed relate to the impact of thrombolytic therapy on outcomes, specifically in submassive pulmonary embolism, including mortality, composite primary end points, and intensive care unit length of stay. Other controversies relate to the impact of the patients sex on outcomes, the most safe and effective thrombolytic dose, optimal administration techniques including infusion duration or concurrent anticoagulation, and therapeutic strategies when thrombolytic therapy is unsuccessful. Despite published guidelines and review articles, select aspects of thrombolytic therapy for the management of pulmonary embolism remain controversial; therefore, clinical practice varies from institution to institution and from practitioner to practitioner. When making decisions about the role of thrombolytic therapy in patients with pulmonary embolism, clinicians must be knowledgeable about areas with limited evidence and the therapys associated risks. In every situation, practitioners must consider the trajectory of the patients status and the ability to intervene in an appropriate time frame.