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Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

ICUs in the future will comprise a larger percentage of hospital beds as care of less seriously ill patients shifts to home and other environments. ICUs will need to adapt to increased demand for services and concomitant economic pressures with efficiency and innovation. The future ICU will see changes in form, function, personnel and patients. The type of patients in ICUs and their medical conditions will be different. Prevention, early detection, and timely treatment of conditions such as infection and respiratory failure should decrease the need for many ICU admissions. Patients needing ICU care will have multiple complex problems that shift the epidemiology of critical care. This shift in patient populations will not change the need for compassionate and empathetic care. Precision medicine for patient care is the goal of the future ICU—tailoring therapy for conditions based on individual characteristics, risk profile or genetic markers1. Protocols and guidelines will require the ability to adapt to defined patient groups. The physical ICU environment of the future must promote a healing environment for patients, families, visitors and ICU staff2. Optimal design should reduce noise, maximize work efficiency, minimize potential for errors, decrease infection risk, reduce stress and provide comfort for families and visitors. The environment will address sound, light, temperature, smell, art and entertainment needs. The ICU of the future must be a flexible environment with built-in adaptability for technological advances. Cohorting of critically ill patients in a defined ICU area will continue for efficiency but the flexibility to deliver critical care outside the physical ICU must also be provided. Patient-centered care will continue to drive services in the future. The ICU of the future continues to require a highly trained collaborative team of professionals but roles and responsibilities as well as composition of the team will change. Intensivists will still oversee these teams but advanced practice providers and non-intensivist physicians may play greater roles in direct patient care. Greater emphasis will be placed on preventing burn out in team members through use of smart technology, optimum work environment and professional support. Technology will be the most constantly changing variable in future ICUs that will affect the environment, patients, and staff. Sophisticated informatics will interface all hospital systems with the ICU and advance individualized care3. These systems must have characteristics of association, interoperability, integration, security, safety, and real-time synchronization4. Artificial intelligence and learning will address the challenges of information overload and integration of data to enable optimum decision making. Electronic “sniffers” will detect and interpret changes in patients’ clinical status and send alerts to clinicians or potentially initiate interventions. In addition, alarm systems will screen out irrelevant signals and decrease the danger of “alarm fatigue” but at the same time provide early alerts to safety issues and provide suggested actions. An outgrowth of advances in information technology will be the use of “big data” to optimize immediate patient care as well as advance research in the ICU5.

Critical care services provide care, monitoring, and therapeutic interventions to patients with life-threatening conditions or injuries and complex multi-organ dysfunction in and beyond the intensive care unit (ICU) settings. The ICU is a complex organizational system. Improvement in performance and outcomes depends on the structure and processes of such systems. High-intensity staffing and closed ICU organizational models are associated with improved outcomes. A dedicated ICU physician-led multidisciplinary team that provides collaborative high-quality critical care, the use of evidence-based care and protocols, and multidisciplinary patient and family-centered ICU rounds are key elements for the provision of critical care to seriously ill patients.

BACKGROUND We present data on a cohort of patients diagnosed with sepsis over a 10-year period comparing outcomes in solid organ transplant (SOT) and non-solid organ transplant (non-SOT) recipients. METHODS This is a retrospective single-center study of patients with diagnosis of sepsis from 1/1/06 to 6/30/16. Cases and controls were matched by year of sepsis diagnosis with propensity score matching. Conditional logistic regression and repeated measurement models were performed for binary outcomes. Trends over time for in-hospital mortality were determined using the Cochran-Armitage test. A gamma-distributed model was performed on the continuous variables. RESULTS Overall, there were 18 632 admission encounters with a discharge diagnosis of sepsis in 14 780 unique patients. Of those admissions, 1689 were SOT recipients. After 1:1 matching by year, there were three thousand three hundred and forty patients (1670 cases; 1670 controls) diagnosed with sepsis. There was a decreasing trend for in-hospital mortality for sepsis over time in SOT patients and non-SOT patients (P

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

Rationale: Intravenous prostacyclin (PG) therapies are used for managing severe pulmonary arterial hypertension (PAH). Most PAH patients respond to PG therapies, but some experience complications associated with presence of indwelling catheters. We observed development of venous thromboses in patients and present our experience. Methods: A retrospective chart review of PAH patients on long-term intravenous PG therapy was conducted between 2008 and 2017.Demographic, hemodynamic, six-minute walk distance (6MWD), WHO/NYHA functional class (FC) and outcome data were collected. Results: Six of 63 patients on intravenous PG therapy were identified with venous thromboses. Mean age was 44±15 years (mean ±SD, range 31 to 70 years). All patients were female. Duration of PAH diagnosis 15±7 years; duration of IV PG therapy7.4±3.8 years. One patient had antiphospholipid antibody syndrome; hypercoagulable workup was negative for other five patients. Diagnostic right heart catheterization showed mean pulmonary artery pressure of 53.6±5.4 mmHg and thermodilution cardiac output was 4.94±1.4 l/min. Echocardiogram showed RAP of 8.3±6 mmHg. Development of thrombosis occurred 4±2 years after initiation of therapy. The most common site of thrombosis was subclavian vein followed by femoral vein. All patients were on anticoagulation therapy with warfarin or a novel oral anticoagulation agent prior to development of thrombosis. Because of repeated catheter infections and poor vascular access, two of three patients were successfully transitioned to oral therapies without significant change in FC. Conclusion: A small percentage of patients on intravenous PG therapy for PAH develop thrombosis in areas of venous access. There does not appear to be a difference in occurrence of thrombosis in patients who have idiopathic PAH or associated PAH. Anticoagulation did not prevent initial or subsequent thrombosis. Development of recurrent thrombosis limits vascular access available for infusion of intravenous PG, thereby necessitating transition to alternative therapy. Transitioning off intravenous PG could affect patient's symptoms and FC. Funding Statement: The authors state that no funding was received for this research. Declaration of Interests: The authors state: "The authors have no conflicts to disclose." Ethics Approval Statement: A waiver of consent was granted by the Institutional Review Board.

End-of-life care in the intensive care unit (ICU) was identified as an objective in a series of Task Forces developed by the World Federation of Societies of Intensive and Critical Care Medicine Council in 2014. The objective was to develop a generic statement about current knowledge and to identify challenges relevant to the global community that may inform regional and local initiatives. An updated summary of published statements on end-of-life care in the ICU from national Societies is presented, highlighting commonalities and differences within and between international regions. The complexity of end-of-life care in the ICU, particularly relating to withholding and withdrawing life-sustaining treatment while ensuring the alleviation of suffering, within different ethical and cultural environments is recognized. Although no single statement can therefore be regarded as a criterion standard applicable to all countries and societies, the World Federation of Societies of Intensive and Critical Care Medicine endorses and encourages the role of Member Societies to lead the debate regarding end-of-life care in the ICU within each country and to take a leading role in developing national guidelines and recommendations within each country.

Objective: Currently, there are no objective metrics included in the intensive care unit (ICU) discharge decision making process. In this study, we evaluate Rothman Index(RI) data for a possible metric as part of a quality improvement project. Our objectives were to determine whether RI could predict adverse events occurring within 72 hours of ICU discharge decision, the optimal clinical cutoff value for this metric, and to determine whether there is a relation between the RI warning alert 24 hours prior to discharge and adverse events postdischarge. Design: Retrospective observational study. Setting: Single center tertiary hospital. Patients: Adult medical ICU patients discharged from the ICU between January 20, 2015 and March 14, 2015. Interventions: None. Measurements and Main Results: A total of 194 patients were studied with mean age of 62.74 (18.37) years. Data collection included RI at the time of decision-making for ICU discharge and the presence of any warning signals in the previous 24 hours. A 72-hour follow-up chart review recorded any adverse events, including readmission to a higher level of care, discontinuation of discharge due to clinical status change, emergency department visit if discharged home, rapid response activation, or cardiopulmonary arrest postdischarge. Adverse events after ICU discharge were observed in 31 (16%) patients with 9 events being ICU readmission (4.6%). Based on an age-adjusted multivariate model, a higher RI was associated with lower odds of an adverse event (odds ratio [OR] = 0.969, P = .006, confidence interval [CI]: 0.9487-0.9911). An RI value ≥ 50 was associated with 72% lower odds of an adverse event (OR = 0.2887, 95% CI = 0.1278-0.6517 and P = .003) compared to RI < 50. This RI cutoff value was associated with the largest decrease in odds of events. As expected, patients with a very high-risk warning alert had a higher proportion of adverse events compared to patients who did not. (31.75% vs 12.65%, P = < .02). Conclusions: Patients who have an RI < 50 or a very high-risk warning alert have a higher risk of adverse events postdischarge from the ICU. Rothman Index may be a useful metric for ICU discharge decision-making.

Background Despite increasing female enrolment into medical schools, persistent gender gaps exist in the physician workforce. There are limited published data on female representation in the critical care medicine workforce. Methods To obtain a global perspective, societies (n = 84; 79,834 members (40,363 physicians, 39,471 non-physicians)) registered with the World Federation of Societies of Intensive and Critical Care Medicine were surveyed. Longitudinal data on female trainee and specialist positions between 2006-2017 were obtained from Australia and New Zealand. Data regarding leadership and academic faculty representation were also collected from national training bodies and other organisations of critical care medicine. Results Of the 84 societies, 23 had a registered membership of greater than 500 members. Responses were received from 27 societies (n = 55,996), mainly high-income countries, covering 70.1% of the membership. Amongst the physician workforce, the gender distribution was available from six (22%) participating societies—mean proportion of females 37 ± 11% (range 26–50%). Longitudinal data from Australia and New Zealand between 2006 and 2017 demonstrate rising proportions of female trainees and specialists. Female trainee and specialist numbers increased from 26 to 37% and from 13 to 22% respectively. Globally, female representation in leadership positions was presidencies of critical care organisations (0–41%), representation on critical care medicine boards and councils (8–50%) and faculty representation at symposia (7–34%). Significant gaps in knowledge exist: data from low and middle-income countries, the age distribution and the time taken to enter and complete training. Conclusions Despite limited information globally, available data suggest that females are under-represented in training programmes, specialist positions, academic faculty and leadership roles in intensive care. There are significant gaps in data on female participation in the critical care workforce. Further data from intensive care organisations worldwide are required to understand the demographics, challenges and barriers to their professional progress. Electronic supplementary material The online version of this article (10.1186/s13054-018-2139-1) contains supplementary material, which is available to authorized users.

Our study objectives were to determine the key sources of moral distress in diverse critical care professionals and how they manage it in the context of team-based models.Qualitative case study methodology using three recently resolved clinical cases.A medical and surgical adult ICU in a 900-bed academic, tertiary Houston hospital.Twenty-nine ICU team members of diverse professional backgrounds interviewed between March 2013 and July 2013.None.All members of the ICU team reported experiencing moral distress. Intrateam discordance served as a key source of distress for all healthcare disciplines. Interviewees identified two situations where intrateam discordance creates moral distress: 1) situations involving initiation or maintenance of nonbeneficial life-sustaining treatments and 2) situations involving a lack of full disclosure about interventions. Healthcare professionals engaged in a variety of management techniques, which can be grouped according to maladaptive behaviors (pas-de-deux, "fighting," and withdrawing) and constructive behaviors (venting, mentoring networks, and building team cohesion). Maladaptive behaviors were more common in the surgical ICU. Constructive behaviors were more prevalent in the medical ICU and typically used by nurses and ancillary staff members. Physicians report becoming detached as morally distressing cases unfold, whereas nurses report becoming more emotionally invested.This study identified the ways in which moral distress manifests across critical care disciplines in different ICU environments. Our results have potential implications for patient care. First, when clinicians alter the content of their goals-of-care conversations with patients or families to accommodate intrateam discordance (as part of the "pas-de-deux"), subsequent decisions regarding medical care may be compromised. Second, when different team members respond differently to the same case-with nurses becoming more emotionally invested and physicians becoming more withdrawn-communication gaps are likely to occur at critical moral distress junctures. Finally, our findings suggest that physicians and any healthcare professionals in surgical units might be susceptible to unmitigated moral distress because they report less engagement in constructive behaviors to recalibrate their distress.

Drug-induced interstitial lung disease is associated with significant morbidity and mortality. Everolimus is an inhibitor of mTOR, a mammalian target of rapamycin, used as an immunosuppressant agent in solid organ transplant. Everolimus has been associated with interstitial lung disease in solid organ transplant patients but has been rarely reported in the liver transplant patient population. We report a case of interstitial pneumonitis in a liver transplant patient associated with everolimus which completely resolved after discontinuation of the medication.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The panel consisted of five sections: hemodynamics infection adjunctive therapies metabolic and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians.

The goal of this statement is to develop consensus recommendations aimed at measuring and optimizing outcomes after in-hospital cardiac arrest (IHCA). For the purposes of this statement, IHCA is defined as a cardiac arrest that occurs in a hospital (whether the patient is admitted or not) and for which resuscitation is attempted with chest compressions, defibrillation, or both. Members of the writing group were selected for their expertise in cardiac resuscitation and post–cardiac arrest care. Monthly telephone conferences and “webinars” over a 10-month period were used to define the scope of the statement and to assign writing teams for each section. The first draft of each section was discussed and sent to the chair to be compiled into a single document. Revised versions were then sent to all writing group members until consensus was achieved. The final draft underwent 3 sets of independent peer review before publication. The American Heart Association (AHA) is committed to the highest ethical standards. The AHA believes that having experts who have a relationship with industry or other relevant relationships on writing groups can strengthen the writing group effort when these relationships are transparent and managed. The AHA conflict of interest policy requires each member to declare relevant and current conflicts of interest. The chair may not have any relationship with industry relevant to the topic. The majority of writing group members (defined as>50% +1) must be free of relevant relationships with industry. Every writing group member agrees to maintain his or her current status with respect to relationships with industry throughout the development of the manuscript to publication. In addition, each member formally declares his or her conflict of interest or relationship with industry at the time of publication. All members of this writing group were compliant with this policy (“Writing Group Disclosures”). IHCA …

Since their widespread introduction more than half a century ago, intensive care units (ICUs) have become an integral part of the health care system. Although most ICUs are found in high-income countries, they are increasingly a feature of health care systems in low- and middle-income countries. The World Federation of Societies of Intensive and Critical Care Medicine convened a task force whose objective was to answer the question “What is an ICU?” in an internationally meaningful manner and to develop a system for stratifying ICUs on the basis of the intensity of the care they provide. We undertook a scoping review of the peer-reviewed and gray literature to assemble existing models for ICU stratification. Based on these and on discussions among task force members by teleconference and 2 face-to-face meetings, we present a proposed definition and classification of ICUs. An ICU is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. Although an ICU is based in a defined geographic area of a hospital, its activities often extend beyond the walls of the physical space to include the emergency department, hospital ward, and follow-up clinic. A level 1 ICU is capable of providing oxygen, noninvasive monitoring, and more intensive nursing care than on a ward, whereas a level 2 ICU can provide invasive monitoring and basic life support for a short period. A level 3 ICU provides a full spectrum of monitoring and life support technologies, serves as a regional resource for the care of critically ill patients, and may play an active role in developing the specialty of intensive care through research and education. A formal definition and descriptive framework for ICUs can inform health care decision-makers in planning and measuring capacity and provide clinicians and patients with a benchmark to evaluate the level of resources available for clinical care.

Demand for intensive care unit (ICU) resources often exceeds supply, and shortages of ICU beds and staff are likely to persist. Triage requires careful weighing of the benefits and risks involved in ICU admission while striving to guarantee fair distribution of available resources. We must ensure that the patients who occupy ICU beds are those most likely to benefit from the ICU's specialized technology and professionals. Although prognosticating is not an exact science, preference should be given to patients who are more likely to survive if admitted to the ICU but unlikely to survive or likely to have more significant morbidity if not admitted. To provide general guidance for intensivists in ICU triage decisions, a task force of the World Federation of Societies of Intensive and Critical Care Medicine addressed 4 basic questions regarding this process. The team made recommendations and concluded that triage should be led by intensivists considering input from nurses, emergency medicine professionals, hospitalists, surgeons, and allied professionals. Triage algorithms and protocols can be useful but can never supplant the role of skilled intensivists basing their decisions on input from multidisciplinary teams. Infrastructures need to be organized efficiently both within individual hospitals and at the regional level. When resources are critically limited, patients may be refused ICU admission if others may benefit more on the basis of the principle of distributive justice.

The role of the critical care specialist has been unequivocally established in the management of severely ill patients throughout the world. Data show that the presence of a critical care specialist in the intensive care unit (ICU) environment has reduced morbidity and mortality, improved patient safety, and reduced length of stay and costs. However, many ICUs across the world function as "open ICUs," in which patients may be admitted under a primary physician who has not been trained in critical care medicine. Although the concept of the ICU has gained widespread acceptance amongst medical professionals, hospital administrators and the general public; recognition and the need for doctors specializing in intensive care medicine has lagged behind. The curriculum to ensure appropriate training around the world is diverse but should ideally meet some minimum standards. The World Federation of Societies of Intensive and Critical Care Medicine has set up a task force to address issues concerning the training, functions, roles, and responsibilities of an ICU specialist.

Toxicologic conditions are encountered in critically ill patients due to intentional or unintentional misuse of or exposure to therapeutic or illicit drugs. Additionally, toxicities related to medical interventions may develop in hospitalized patients. This review focuses on recent developments in the field of critical care toxicology. Early interventions to decrease absorption or enhance elimination of toxins have limited value. Specific interventions to manage toxicities due to analgesics, sedative-hypnotics, antidepressants, antipsychotics, cardiovascular agents, alcohols, carbon monoxide, and cholinergic agents are reviewed. Hospital-acquired toxicities due to methemoglobinemia, propylene glycol, and propofol should be recognized and treated. The clinician is continually required to incorporate clinical judgment along with available scientific data and clinical evidence to determine the best therapy for toxicologic conditions.

The recommendations in this 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1,2 and was completed in February 2015.3,4 In this in-depth evidence review process, ILCOR examined topics and then generated a prioritized list of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,5 and then search strategies and inclusion and exclusion criteria were defined and a search for relevant articles was performed. The evidence was evaluated by the ILCOR task forces by using the standardized methodological approach proposed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.6 The quality of the evidence was categorized based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias). Then, where possible, consensus-based treatment recommendations were created. To create this 2015 Guidelines Update, the AHA formed 15 writing groups, with careful attention to manage conflicts of interest, to assess the ILCOR treatment recommendations and to write AHA treatment recommendations by using the AHA Class of Recommendation (COR) and Level of Evidence (LOE) system. The recommendations made in the Guidelines are informed by the ILCOR recommendations and GRADE classification, in the context of the delivery of medical care in North America. The AHA writing group made new recommendations only on topics specifically reviewed by ILCOR in 2015. This chapter delineates instances where the AHA writing group developed recommendations that are significantly stronger or weaker than the ILCOR statements. In the online …

A time-limited trial is an agreement between clinicians and patients or surrogate decision makers to use medical therapies over a defined period of time to see if the patient improves or deteriorates according to agreed-upon clinical milestones. Although time-limited trials are broadly advocated, there is little empirical evidence of the benefits and risks of time-limited trials, when they are initiated, when and why they succeed or fail, and what facilitates completion of them. Our study objectives were to 1) identify the purposes for which clinicians use time-limited trials and 2) identify barriers and facilitators to initiating and completing time-limited trials.Semistructured interviews: We analyzed interviews using qualitative description with constant comparative techniques.Nine hundred-bed, academic, tertiary hospital in Houston, Texas. Interviewees were from open medical, surgical, neurosurgical, and cardiovascular ICUs.Thirty healthcare professionals were interviewed (nine surgeons, 16 intensivists, three nurse practitioners, and two "other" clinicians).None.Interviewees reported initiating time-limited trials for three different purposes: to prepare surrogates and clinicians for discussion and possible shifts toward comfort-care only therapies, build consensus, and refine prognostic information. The main barriers to initiating time-limited trials involve clinicians' or surrogate decision makers' disagreement on setting a time limit. Barriers to completing time-limited trials include 1) requesting more time; 2) communication breakdowns because of rotating call schedules; and 3) changes in clinical course. Finally, facilitators to completing time-limited trials include 1) having defined goals about what could be achieved during an ICU stay, either framed in narrow, numeric terms or broad goals focusing on achievable activities of daily living; 2) applying time-limited trials in certain types of cases; and 3) taking ownership to ensure completion of the trial.An understanding of barriers and facilitators to initiating and completing time-limited trials is an essential first step toward appropriate utilization of time-limited trials in the ICUs, as well as developing educational or communication interventions with clinicians to facilitate time-limited trial use. We provide practical suggestions on patient populations in whom time-limited trials may be successful, the setting, and clinicians likely to benefit from educational interventions, allowing clinicians to have a fuller sense of when and how to use time-limited trials.

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for the use of blood products in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis.The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591.In the absence of extenuating circumstances and following resolution of tissue hypoperfusion, red blood cell transfusion should be targeted to maintain hemoglobin at 7.0 g/dL or greater. Erythropoietin is not recommended as a specific treatment for sepsis-associated anemia. Fresh-frozen plasma should be given for documented deficiency of coagulation factors and in the presence of active bleeding or before surgical or invasive procedures. Antithrombin administration is not recommended. Specific platelet transfusion thresholds are based on the presence or absence of bleeding, significant risk for bleeding, plans for surgery or invasive procedures, and platelet count/=5,000/mm.

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management.Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pHor =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control.Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).

To determine the safety, pharmacokinetics, biological effects, and immunogenicity of recombinant soluble complement receptor 1 (TP10) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Open label, ascending dosage, phase I trial.Two academic teaching hospitals.A total of 24 patients diagnosed with ALI/ARDS.A single, 30-min intravenous infusion of 0.1, 0.3, 1, 3, or 10 mg/kg TP10.Serum levels of TP10 increased in proportion to the dose. Mean variable estimates (+/-SD) were half-life of disposition 69.7 +/- 39.7 hrs, plasma clearance 2.39 +/- 1.32 mL/hr/kg, and volume of distribution 190.6 +/- 135.0 mL/kg. Inhibition of complement activity, measured by CH50, was significant for the interaction of dose and time (p = .024). The C3a levels demonstrated a trend for dose which did not reach statistical significance (p = .090) and soluble C5b-9 levels were significant only for dose (p = .023). As expected by the proposed physiologic mechanism, C4a levels were not affected by TP10, dose, or time. The overall mortality rate was 33%. Neither the type nor the frequency rate of specific adverse events were substantially different between dose groups. Seven adverse events in four patients were thought to be possibly related to TP10.TP10 has a half-life of approximately 70 hrs and at dosesor =1 mg/kg, significantly inhibits complement activity at the levels of C3 and C5 in patients with ALI/ARDS. Complement inhibition was more prolonged over time with TP10 doses of 3 and 10 mg/kg. TP10 appears to be safe at the doses tested. Further studies will be required to completely assess the impact of TP10 on pathophysiology and clinical outcome in patients with ALI/ARDS.

Various adjunctive interventions have been undertaken with mechanical ventilation to improve lung or cardiovascular function and reverse lung injury. This article reviews the use of systemic and inhaled vasodilators in conjunction with mechanical ventilation. Vasodilators affect the pulmonary vasculature and result in a decrease in pulmonary artery pressure (PAP). Since many pulmonary and cardiovascular conditions requiring mechanical ventilation are associated with pulmonary artery hypertension, a reduction of pulmonary vascular pressures could potentially decrease extravasation of fluid into the interstitial space, improve right ventricle (RV) function and reduce hemodynamic instability. A recognized disadvantage of some vasodilators is deterioration in oxygenation owing to worsening intrapulmonary shunt from an increase in blood flow to poorly ventilated lung units. If the effects of a vasodilator are not limited to the pulmonary vasculature, systemic hypotension and hemodynamic instability may result. Because of these adverse effects, modified systemic vasodilators and inhaled vasodilators have been developed. The agents that will be reviewed include inhaled nitric oxide (NO), parenteral prostaglandin E 1 (PGE 1 ), and parenteral and aerosolized prostacyclin (PGI 2 ).

Objectives To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed. Design Prospective, multicenter, randomized, double-blind, placebo-controlled study. Setting Intensive care units of 30 academic, teaching, and community hospitals in the United States. Patients Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization. Interventions Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm. Measurements and main results Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm. Conclusions From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.

OBJECTIVES We sought to determine whether there might be acute changes in hemodynamics attributable to HA-1A, a monoclonal antibody to endotoxin, in patients with presumed Gram-negative sepsis. DESIGN Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled study. PATIENTS A total of 543 patients with severe sepsis presumed to be caused by Gram-negative bacteria who were enrolled in a clinical trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody. INTERVENTIONS Patients were randomly assigned to receive either 100 mg of HA-1A or placebo. MEASUREMENT AND MAIN RESULTS Patients were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were monitored from before, until 72 hrs after infusion of the study drug. For the entire study population (n = 543), no changes over time attributable to study drug were noted in the mean arterial pressure (p > .19), heart rate (p > .53) or the need for vasopressor administration (p > .62). One hundred ninety-seven patients underwent pulmonary artery catheterization and had hemodynamic data available from before the infusion of HA-1A or placebo until at least 12 hrs after infusion. Evaluating all 197 patients on an intent to treat basis demonstrated no significant differences over time in cardiac index (p > .15), oxygen delivery index (p > .43), or left ventricular stroke work index (p > .48) between patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and study drug received also failed to demonstrate any significant difference attributable to HA-1A in mean arterial pressure (p > .54), heart rate (p > .84), cardiac index (p > .13), oxygen delivery index (p > .05), or left ventricular stroke work index (p > .48) between populations. CONCLUSION There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic profiles over the 72-hr study period.

Introduction Assessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study. Methods ARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted. Results At 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion. Conclusions ARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population. Trial Registration A Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296

OBJECTIVE To evaluate the in vivo performance of a continuous intra-arterial blood gas monitor as compared with in vitro arterial blood gases for measurements of PaO2, PaCO2, and arterial pH. DESIGN Consecutive patient enrollment. SETTING Medical intensive care unit of a county teaching hospital. PATIENTS Five critically ill patients. INTERVENTIONS All patients had a fiberoptic sensor placed through a 20-gauge cannula inserted into the radial artery. Sensor and arterial blood gas measurements were monitored up to 68 hrs. Arterial blood gases were analyzed on two blood gas analyzers. MEASUREMENTS AND MAIN RESULTS A total of 104 arterial blood gases were obtained for comparison of sensor measurements with blood gas analyzer values. Comparison of the sensor values with the blood gas analyzer values showed bias and precision values of -0.021 and 0.037 for arterial pH, 1.74 and 6.06 torr (0.23 and 0.81 kPa) for PaCO2, and -5.89 and 13.19 torr (-0.79 and 1.76 kPa) for PaO2, respectively. Comparison of the two blood gas analyzer measurements showed bias and precision values of -0.030 and 0.010 for arterial pH, 1.96 and 2.55 torr (0.26 and 0.34 kPa) for PaCO2, and -5.77 and 17.15 torr (-0.77 and 2.29 kPa) for PaO2, respectively. No complications attributable to the sensor were detected. CONCLUSIONS The performance of this fiberoptic continuous intra-arterial blood gas monitor is comparable to that of blood gas analyzers and compares favorably with previously reported studies utilizing other sensors in reliably and reproducibly approximating PaO2, PaCO2, and arterial pH values. This monitoring capability was accomplished with no patient morbidity. Further study is indicated to confirm these initial results and to establish the role of a continuous intra-arterial blood gas monitor in critically ill patients.

OBJECTIVES To determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis. DESIGN Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTING Twelve academic medical center intensive care units in the United States and Europe. PATIENTS Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONS Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTS The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment. Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator. TNF levels were higher (206.7 +/- 60.7 vs. 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs. 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock. CONCLUSIONS The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations. Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis.

There is increasing recognition that systematic post–cardiac arrest care after return of spontaneous circulation (ROSC) can improve the likelihood of patient survival with good quality of life. This is based in part on the publication of results of randomized controlled clinical trials as well as a description of the post–cardiac arrest syndrome. 1–3 Post–cardiac arrest care has significant potential to reduce early mortality caused by hemodynamic instability and later morbidity and mortality from multiorgan failure and brain injury. 3,4 This section summarizes our evolving understanding of the hemodynamic, neurological, and metabolic abnormalities encountered in patients who are initially resuscitated from cardiac arrest. The initial objectives of post–cardiac arrest care are to ● Optimize cardiopulmonary function and vital organ perfusion. ● After out-of-hospital cardiac arrest, transport patient to an appropriate hospital with a comprehensive post–cardiac arrest treatment system of care that includes acute coronary interventions, neurological care, goal-directed critical care, and hypothermia. ● Transport the in-hospital post–cardiac arrest patient to an appropriate critical-care unit capable of providing comprehensive post–cardiac arrest care. ● Try to identify and treat the precipitating causes of the arrest and prevent recurrent arrest.

Acid–base disorders present some of the most challenging problems in the care of critically ill patients. They alter physiologic function and contribute to morbidity and mortality. Proper management of these disorders is not possible without the understanding of blood gas interpretation and basic acid–base balance physiology.

The pathogenesis of acute myocardial ischemia or infarction following cocaine abuse is not known. Cocaine causes an increase in circulating catecholamines. Therefore alpha-adrenergic mediated focal or generalized coronary artery spasm has been presumed to be the likely mechanism to induce ischemia. However, coronary vasospasm in chronic cocaine abusers has not been demonstrated angiographically. Moreover, it has been observed that patients commonly manifest ischemic changes hours up to a week after abusing cocaine. In order to evaluate direct effects of cocaine on coronary vasculature, 6 chronic cocaine abusers admitted with prolonged chest pain and electrocardiographic ST- and T-wave changes were studied. Cocaine administered intravenously (maximum 32 mg) produced subjective sensation of central nervous stimulation (the "high") in all patients. However there was no significant change in coronary artery diameter (assessed by computer-assisted quantitative technique), myocardial perfusion (assessed by contrast echocardiography) or left ventricular wall motion (assessed by two-dimensional echocardiography) as compared with the baseline values. Coronary sinus flow (thermodilution) showed an upward trend, a probable reflection of a significant increase in cardiac output (average 62%, p less than 0.007). Despite a significant elevation in heart rate (average 56%, p less than 0.007), mean systemic arterial pressure (average 12%, p less than 0.05) and rate-pressure product (average 69%, p less than 0.005), no symptomatic or acute electrocardiographic changes were observed. It is concluded that recreational doses of cocaine do not cause focal or generalized coronary vasospasm or reduced myocardial perfusion in patients who present with chest pain temporally related to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose To provide recommendations and standard operating procedures for intensive care units and hospital preparedness for an influenza pandemic. Methods Based on a literature review and expert opinion, a Delphi process was used to define the essential topics. Results Key recommendations include: Hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas. Hospitals should have appropriate beds and monitors for these expansion areas. Establish a management system with control groups at facility, local, regional and/or national levels to exercise authority over resources. Establish a system of communication, coordination and collaboration between the ICU and key interface departments. A plan to access, coordinate and increase labor resources is required with a central inventory of all clinical and non-clinical staff. Delegate duties not within the usual scope of workers’ practice. Ensure that adequate essential medical equipment, pharmaceuticals and supplies are available. Protect patients and staff with infection control practices and supporting occupational health policies. Maintain staff confidence with reassurance plans for legal protection and assistance. Have objective, ethical, transparent triage criteria that are applied equitably and publically disclosed. ICU triage of patients should be based on the likelihood for patients to benefit most or a ‘first come, first served’ basis. Develop protocols for safe performance of high-risk procedures. Train and educate staff. Conclusions Mortality, although inevitable during a severe influenza outbreak or disaster, can be reduced by adequate preparation. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-1759-y) contains supplementary material, which is available to authorized users.

SummaryBackgroundCurrent guidelines recommend repeated doses of albuterol for the emergency treatment of acute asthma. However, approximately one-third of patients show little or no initial response to this partial β2-agonist.MethodsWe conducted a randomized, double-blind, proof-of-concept study to investigate whether a full β2-agonist, isoproterenol, offers a therapeutic advantage in adults presenting with acute severe asthma (FEV1

The lack of evidence-based information in toxicology results in debate and differing recommendations on management issues. Gastric lavage is often utilized to remove toxins from the stomach but a clinical benefit of the procedure has not been definitively demonstrated. A selective approach is warranted in each patient, and gastric lavage can be considered in patients with life-threatening ingestions if it can be performed within 60 minutes of ingestion. Whole bowel irrigation is a method of GI decontamination utilizing isotonic electrolyte solution. Although safe, there is currently insufficient data to establish definite indications for use. This technique can be considered for potentially toxic ingestions of lithium, iron, and sustained-release or enteric-coated drugs. Multiple-dose activated charcoal has been used to enhance elimination of drugs already absorbed into the body but the optimum dose and frequency of administration is not established. Based on volunteer studies and limited clinical reports, multiple-dose activated charcoal may be considered in patients with life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. A variety of interventions in addition to hemodialysis have been proposed to enhance lithium elimination. Forced saline diuresis and diuretics are not indicated. Although studies suggest that sodium polystyrene sulfonate may enhance elimination of lithium, no beneficial effects on clinical outcomes have been demonstrated and potential complications include hypokalemia and hypernatremia. Blood alkalinization for cyclic antidepressant toxicity has become standard therapy. Alkalinization is most effective in treating significant cardiac toxicity. Sodium bicarbonate, rather than hyperventilation, should be used initially to alkalinize blood. The benefit of blood alkalinization in the treatment of hypotension and seizures is not established.