Benjamin A. Kohl

Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.

Objective:To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Methods:Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. Recommendations:The article is focused on a suggested glycemic control end point such that a blood glucose ≥150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ⩽70 mg/dL) and to minimize glycemic variability.Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and standardized approaches to infusion preparation, provision of consistent carbohydrate calories and nutritional support, and dextrose replacement for hypoglycemia prevention and treatment. Quality improvement of glycemic management programs should include analysis of hypoglycemia rates, run charts of glucose values <150 and 180 mg/dL. The literature is inadequate to support recommendations regarding glycemic control in pediatric patients. Conclusions:While the benefits of tight glycemic control have not been definitive, there are patients who will receive insulin infusion therapy, and the suggestions in this article provide the structure for safe and effective use of this therapy.

The inflammatory response to surgery and trauma.

Purpose of reviewThe inflammatory or stress response to injury has evolved to ensure survival. This review will examine this response in otherwise healthy patients. Additionally, the impact of several common comorbid conditions on the inflammatory response will be considered. What will become evident is that the stress response may be exaggerated in some conditions and suppressed in others. Rapid identification of both an abnormal response and its cause will allow clinicians to maximize a patients healing potential. Recent findingsRecent work has shown that an altered inflammatory response has marked effects on both immune competence and the endocrine system. Investigations are ongoing to delineate the mechanism of lymphocyte dysfunction. With regard to critical care endocrinopathies, the effects of insulin and hyperglycemia on inflammation and wound healing are being investigated. SummaryAn understanding of the stress response will aid the clinician in preparing for expected responses, recognizing and perhaps correcting deviations from the norm and accounting for potential complications that arise in the face of preexisting disease. Deviations from the normal time course may represent the effects of preexisting medical illness, treatment or postoperative/injury complications.

Plasma Levels of Receptor for Advanced Glycation End Products, Blood Transfusion, and Risk of Primary Graft Dysfunction

RATIONALE The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD. OBJECTIVES To test the association of soluble RAGE (sRAGE) levels with PGD in a prospective, multicenter cohort study. METHODS We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) within the first 72 hours after transplantation. MEASUREMENTS AND MAIN RESULTS Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearmans rho = 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02). CONCLUSIONS Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.

A Review of the Fundamental Principles and Evidence Base in the Use of Extracorporeal Membrane Oxygenation (ECMO) in Critically Ill Adult Patients

Extracorporeal membrane oxygenation (ECMO) comprises a commonly used method of extracorporeal life support. It has proven efficacy and is an accepted modality of care for isolated respiratory or cardiopulmonary failure in neonatal and pediatric populations. In adults, there are conflicting studies regarding its benefit, but it is possible that ECMO may be beneficial in certain adult populations beyond postcardiotomy heart failure. As such, all intensivists should be familiar with the evidence-base and principles of ECMO in adult population. The purpose of this article is to review the evidence and to describe the fundamental steps in initiating, adjusting, troubleshooting, and terminating ECMO so as to familiarize the intensivist with this modality.

Stroke After Aortic Valve Surgery Results From a Prospective Cohort

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P=0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P=0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality. # CLINICAL PERSPECTIVE {#article-title-47}

Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is often associated with elevations in pulmonary artery pressures. Although primary pulmonary arterial hypertension (PAH) has been associated with primary graft dysfunction (PGD), the role of secondary PAH in mediating PGD risk in patients with IPF is incompletely understood. The purpose of this study was to evaluate the relationship between mean pulmonary artery pressure (mPAP) and PGD among patients with IPF. METHODS We performed a multicenter prospective cohort study of 126 lung transplant procedures performed for IPF between March 2002 and August 2007. The primary outcome was grade 3 PGD at 72 h after lung transplant. The mPAP was measured as the initial reading following insertion of the right-sided heart catheter during lung transplant. Multivariable logistic regression was used to adjust for confounding variables. RESULTS The mPAP for patients with PGD was 38.5 ± 16.3 mm Hg vs 29.6 ± 11.5 mm Hg for patients without PGD (mean difference, 8.9 mm Hg [95% CI, 3.6-14.2]; P = .001). The increase in odds of PGD associated with each 10-mm Hg increase in mPAP was 1.64 (95% CI, 1.18-2.26; P = .003). In multivariable models, this relationship was independent of confounding by other clinical variables, although the use of cardiopulmonary bypass partially attenuated the relationship. CONCLUSIONS Higher mPAP in patients with IPF is associated with the development of PGD.

Critical care telemedicine: evolution and state of the art.

Objectives: To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda. Data Sources: Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee. Data Synthesis: Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65–0.96) and hospital mortality (0.83; 95% CI, 0.73–0.94) and shorter ICU (–0.62 d; 95% CI, –1.21 to –0.04 d) and hospital (–1.26 d; 95% CI, –2.49 to –0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed. Conclusions: The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.

Who should care for intensive care unit patients

The question of who should direct the care of critically ill patients is both multifaceted and timely. Currently, only about 30% of critical care units in the United States are staffed by dedicated intensivists. This number is likely to increase as groups such as Leapfrog financially reward hospitals that have dedicated intensivists around the clock. The problem, however, is that the supply of intensivists by training is not projected to increase, whereas the demand for health care, by all accounts, will significantly increase in the near future. There is an increasing body of literature suggesting not only morbidity and mortality benefits but decreased length of stay and profound cost savings when a team directed by critical care physicians cares for patients in the intensive care unit. Despite this, many have argued that a consultant-based unit (so called open unit) is less alienating to a patients primary care physician or surgeon and promotes continuity of care. In addition, although much of the literature has suggested purported benefit derived from a dedicated intensivist staffing model, little has been published regarding optimal intensivist/patient ratios. If dedicated critical care teams decrease complications in the intensive care unit, one may logically reason that as the intensivist/patient ratio decreases, morbidity or mortality, or both, might increase. This, however, has not yet been shown. This article will address many of these issues, discuss the history of critical care medicine in the United States, and review the pertinent literature. With the projected shortage of critical care-trained physicians and an increasingly aging population, it is imperative that health professionals evaluate this issue sooner rather than later.

Elevated Plasma Clara Cell Secretory Protein Concentration Is Associated with High-Grade Primary Graft Dysfunction

Primary graft dysfunction (PGD) is the leading cause of early posttransplant morbidity and mortality after lung transplantation. Clara cell secretory protein (CC16) is produced by the nonciliated lung epithelium and may serve as a plasma marker of epithelial cell injury. We hypothesized that elevated levels of CC16 would be associated with increased odds of PGD. We performed a prospective cohort study of 104 lung transplant recipients. Median plasma CC16 levels were determined at three time points: pretransplant and 6 and 24 h posttransplant. The primary outcome was the development of grade 3 PGD within the first 72 h after transplantation. Multivariable logistic regression was performed to evaluate for confounding by donor and recipient demographics and surgical characteristics. Twenty‐nine patients (28%) developed grade 3 PGD within the first 72 h. The median CC16 level 6 h after transplant was significantly higher in patients with PGD [13.8 ng/mL (IQR 7.9, 30.4 ng/mL)] than in patients without PGD [8.2 ng/mL (IQR 4.5, 19.1 ng/mL)], p = 0.02. Elevated CC16 levels were associated with increased odds of PGD after lung transplantation. Damage to airway epithelium or altered alveolar permeability as a result of lung ischemia and reperfusion may explain this association.

Critical Care Basic Ultrasound Learning Goals for American Anesthesiology Critical Care Trainees: Recommendations from an Expert Group.

OBJECTIVE:In this review, we define learning goals and recommend competencies concerning focused basic critical care ultrasound (CCUS) for critical care specialists in training. DESIGN:The narrative review is, and the recommendations contained herein are, sponsored by the Society of Critical Care Anesthesiologists. Our recommendations are based on a structured literature review by an expert panel of anesthesiology intensivists and cardiologists with formal training in ultrasound. Published descriptions of learning and training routines from anesthesia–critical care and other specialties were identified and considered. Sections were written by groups with special expertise, with dissent included in the text. RESULTS:Learning goals and objectives were identified for achieving competence in the use of CCUS at a specialist level (critical care fellowship training) for diagnosis and monitoring of vital organ dysfunction in the critical care environment. The ultrasound examination was divided into vascular, abdominal, thoracic, and cardiac components. For each component, learning goals and specific skills were presented. Suggestions for teaching and training methods were described. DISCUSSION:Immediate bedside availability of ultrasound resources can dramatically improve the ability of critical care physicians to care for critically ill patients. Anesthesia--critical care medicine training should have definitive expectations and performance standards for basic CCUS interpretation by anesthesiology--critical care specialists. The learning goals in this review reflect current trends in the multispecialty critical care environment where ultrasound-based diagnostic strategies are already frequently applied. These competencies should be formally taught as part of an established anesthesiology-critical care medicine graduate medical education programs.