Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Sepsis outcomes in solid organ transplant recipients.

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 < .05) due to early sepsis recognition and improved standard of care. Despite higher comorbidities in the SOT group, conditional logistic regression showed that in-hospital mortality for sepsis in SOT patients was similar compared with non-SOT patients (odds ratio [OR] =1.14 [95% confidence interval {CI}, 0.95-1.37], P = .161). However, heart and lung SOT subgroups had higher odds of dying compared with the non-SOT group (OR = 1.83 [95% CI, 1.30-2.57], P < .001 and OR = 1.77 [95% CI, 1.34-2.34], P < .001). On average, SOT patients had 2 days longer hospital length of stay compared with non-SOT admissions (17.00 ± 19.54 vs 15.23 ± 17.07, P < .05). Additionally, SOT patients had higher odds of hospital readmission within 30 days (OR = 1.25 [95% CI, 1.06-1.51], P = .020), and higher odds for DIC compared with non-SOT patients (OR = 1.76 [95% CI, 1.10-2.86], P = .021). CONCLUSION: Sepsis in solid organ transplants and non-solid organ transplant patients have similar mortality; however, the subset of heart and lung transplant recipients with sepsis has a higher rate of mortality compared with the non-solid organ transplant recipients. SOT with sepsis as a group has a higher hospital readmission rate compared with non-transplant sepsis patients.

Analysis of Rothman Index Data to Predict Postdischarge Adverse Events in a Medical Intensive Care Unit.

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.

Women in Intensive Care study: a preliminary assessment of international data on female representation in the ICU physician workforce, leadership and academic positions.

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.

A qualitative study exploring moral distress in the ICU team: the importance of unit functionality and intrateam dynamics.

OBJECTIVE: 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. DESIGN: Qualitative case study methodology using three recently resolved clinical cases. SETTING: A medical and surgical adult ICU in a 900-bed academic, tertiary Houston hospital. SUBJECTS: Twenty-nine ICU team members of diverse professional backgrounds interviewed between March 2013 and July 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Barriers and Facilitators to Initiating and Completing Time-Limited Trials in Critical Care.

OBJECTIVES: 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. DESIGN: Semistructured interviews: We analyzed interviews using qualitative description with constant comparative techniques. SETTING: Nine hundred-bed, academic, tertiary hospital in Houston, Texas. Interviewees were from open medical, surgical, neurosurgical, and cardiovascular ICUs. SUBJECTS: Thirty healthcare professionals were interviewed (nine surgeons, 16 intensivists, three nurse practitioners, and two "other" clinicians). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RATIONALE: We 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. OBJECTIVES: We 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. METHODS: We 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 RESULTS: Urinary 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]). CONCLUSIONS: Urinary [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).

Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome.

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.

Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

The goal of immediate post-cardiac arrest care is to optimize systemic perfusion, restore metabolic homeostasis, and support organ system function to increase the likelihood of intact neurological survival. The post-cardiac arrest period is often marked by hemodynamic instability as well as metabolic abnormalities. Support and treatment of acute myocardial dysfunction and acute myocardial ischemia can increase the probability of survival. Interventions to reduce secondary brain injury, such as therapeutic hypothermia, can improve survival and neurological recovery. Every organ system is at risk during this period, and patients are at risk of developing multiorgan dysfunction. The comprehensive treatment of diverse problems after cardiac arrest involves multidisciplinary aspects of critical care, cardiology, and neurology. For this reason, it is important to admit patients to appropriate critical-care units with a prospective plan of care to anticipate, monitor, and treat each of these diverse problems. It is also important to appreciate the relative strengths and weaknesses of different tools for estimating the prognosis of patients after cardiac arrest.

Familial aggregation of irritable bowel syndrome: a family case-control study.

OBJECTIVES: Irritable bowel syndrome (IBS) clusters in families, but previous studies documented family history only from patients. We have shown that patient-relative agreement on IBS status is poor. Thus, we conducted a family case-control study with direct survey of symptoms from family members to better quantitate the aggregation of IBS in families. The aims of this study were to (i) compare the prevalence of IBS in case-relatives with control-relatives, and (ii) determine whether gender, relationship, predominant symptom, and environmental risk factors affect familial aggregation. METHODS: Outpatients with IBS, matched controls, and their first-degree relatives completed a bowel symptom questionnaire. Percent of cases and controls with a family history were compared and odds ratios were computed using chi(2)-test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations. RESULTS: Data were collected from 477 cases, 297 controls, 1,492 case-relatives, and 936 control-relatives. Probands had a median age of 50 and 78% were women. 50% of case and 27% of control families had at least another relative with IBS yielding an odds ratio of 2.75 (95% CI: 2.01-3.76, P<0.0001). When aggregation estimates were reevaluated stratifying by relative relationship or proband gender, generational and gender effects were not observed. Familial clustering by bowel habit was weakest for diarrhea, and strongest for alternating bowel habits. CONCLUSIONS: IBS aggregates strongly in families. The strength of the association does vary somewhat by relationship to proband, but the lack of association in spouses supports either a possible genetic etiology or a shared household environmental exposure as an underlying cause of IBS.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Toxicology in the critical care unit.

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.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

The role of intrinsic efficacy in determining response to a beta2-agonist in acute severe asthma.

BACKGROUND: Current 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 beta(2)-agonist. METHODS: We conducted a randomized, double-blind, proof-of-concept study to investigate whether a full beta(2)-agonist, isoproterenol, offers a therapeutic advantage in adults presenting with acute severe asthma (FEV(1)<50%) who fail to respond to an initial treatment of the partial beta(2)-agonist, albuterol. Study subjects were randomized to receive a 2-h continuous nebulization of either albuterol (7.5mg/h) (n=10, mean FEV(1)=37% predicted) or isoproterenol (7.5mg/h) (n=9, mean FEV(1)=33% predicted). Respiratory symptoms, vital signs and pulmonary function measures were collected. RESULTS: Subjects from both treatment groups had similar baseline characteristics. The percent improvements from baseline FEV(1) at 60 and 120min were significantly higher in subjects receiving isoproterenol than those receiving albuterol (44 vs. 17% and 63 vs. 24%, respectively, P<0.05). The change in symptoms measured by the modified Borg score was also significantly greater in subjects receiving isoproterenol (P<0.01). Both treatments were well tolerated, though the mean increase in pulse rate at 60 and 120min (21 vs. 1 and 23 vs. 6beats/min, respectively, P<0.05) and the mean change in serum potassium at 120min (-0.52 vs. -0.07meq/L, P<0.05) from baseline were significantly greater in the isoproterenol group. CONCLUSIONS: Our data suggest that in subjects presenting with acute severe asthma who fail to show an initial response to albuterol, the use of a beta(2)-agonist of higher intrinsic efficacy can be more effective in improving lung function and symptoms.

What is an intensive care unit? A report of the task force of the World Federation of Societies of Intensive and Critical Care Medicine.

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.