Changes in vitamin D metabolites at the time of critical illness and 6 months later-A prospective observational study.

BACKGROUND: Despite multiple studies suggesting that low 25(OH)D-vitamin levels are associated with worse outcomes in critically ill individuals, attempts to mitigate the outcomes by fixed dose enteral supplementation unguided by baseline or target blood levels have been unsuccessful. Since a single measurement of 25(OH)D may not optimally reflect an individual's vitamin D status, we studied the plasma concentration of different vitamin D metabolites and their recovery during and following resolution of acute critical illness. METHODS: A prospective observational study including patients 18 years and older admitted to a mixed medical-surgical ICU in Reykjavik, Iceland, located at a high-northern altitude (64° N). Vitamin D metabolites were measured at three timepoints; On admission (S1), 3-5 days following admission (S2) and after recovery from acute illness (median 178 days) (S3). Concentrations of total 25(OH)D-vitamin, cholecalciferol (D3 ), total 24,25(OH)D-vitamin, vitamin D binding protein (VDBP) were measured with LC-tandem mass spectrometry (LC-MS/MS) and free 25-(OH)D was measured with enzyme-linked immunosorbent assay. RESULTS: Most individuals were vitamin D deficient when assessed during critical illness, with 25(OH)D-vitamin levels under 30 ng/ml for 37/40 individuals at timepoint S1 and 34/38 at S2. After recovery, 18/30 patients were deficient at S3. Levels of all vitamin D metabolites measured were low during critical illness but rose substantially following resolution of acute illness. No strong correlation was found between markers of acute illness severity or duration and resolution of vitamin D metabolites in the interval between acute illness and recovery. CONCLUSIONS: In critically ill patients, levels of multiple vitamin D metabolites are low but substantial recovery occurs following resolution of acute illness. It is unclear whether a single metabolite is sufficient to assess vitamin D status of critically ill patients and guide potential supplementation.

Perioperative Considerations for Evolving Artificial Pancreas Devices.

Type 1 diabetes mellitus is a lifelong condition. It requires intensive patient involvement including frequent glucose measurements and subcutaneous insulin dosing to provide optimal glycemic control to decrease short- and long-term complications of diabetes mellitus without causing hypoglycemia. Variations in insulin pharmacokinetics and responsiveness over time in addition to illness, stress, and a myriad of other factors make ideal glucose control a challenge. Control-to-range and control-to-target artificial pancreas devices (closed-loop artificial pancreas devices [C-APDs]) consist of a continuous glucose monitor, response algorithm, and insulin delivery device that work together to automate much of the glycemic management for an individual while continually adjusting insulin dosing toward a glycemic target. In this way, a C-APD can improve glycemic control and decrease the rate of hypoglycemia. The MiniMed 670G (Medtronic, Fridley, MN) system is currently the only Food and Drug Administration-cleared C-APD in the United States. In this system, insulin delivery is continually adjusted to a glucose concentration, and the patient inputs meal-time information to modify insulin delivery as needed. Data thus far suggest improved glycemic control and decreased hypoglycemic events using the system, with decreased need for patient self-management. Thus, the anticipated use of these devices is likely to increase dramatically over time. There are limited case reports of safe intraoperative use of C-APDs, but the Food and Drug Administration has not cleared any device for such use. Nonetheless, C-APDs may offer an opportunity to improve patient safety and outcomes through enhanced intraoperative glycemic control. Anesthesiologists should become familiar with C-APD technology to help develop safe and effective protocols for their intraoperative use. We provide an overview of C-APDs and propose an introductory strategy for intraoperative study of these devices.

Glucose Meters: Here Today, Gone Tomorrow?

OBJECTIVE: This special article will review the history of blood glucose meter hospital use and current issues surrounding their use in this patient population. STUDY SELECTION: Secondary to accuracy concerns that have been known, but likely underappreciated for many years, the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services are moving toward eliminating current blood glucose meters for use with critically ill patients. DATA SOURCES: Recent guidance from the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services along with several recent publications will be used as the primary data sources. DATA EXTRACTION: U.S. Food and Drug Administration, Centers for Medicare and Medicaid Services communications combined with recent interpretation of this guidance were used to provide this overview. DATA SYNTHESIS: Centers for Medicare and Medicaid Services have issued a temporary moratorium on the prohibition of the use of blood glucose meters in the critically ill. They have not given a deadline for the moratorium or solicited comments. CONCLUSIONS: Physicians who care for critically ill patients need to be cognizant of the accuracy and interference limitations of blood glucose meters and aware of the current regulatory situation.

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.

OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management.

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed.

Critical illness-induced dysglycaemia: diabetes and beyond.

Type 2 diabetes has reached epidemic proportions in many parts of the world. The disease is projected to continue to increase and double within the foreseeable future. Dysglycaemia develops in the form of hyperglycaemia, hypoglycaemia and marked glucose variability in critically ill adults whether they are known to have premorbid diabetes or not. Patients with such glucose dysregulation have increased morbidity and mortality. Whether this is secondary to cause and effect from dysglycaemia or is just related to critical illness remains under intense investigation. Identification of intensive care unit (ICU) patients with unrecognised diabetes remains a challenge. Further, there are few data regarding the development of type 2 diabetes in survivors after hospital discharge. This commentary introduces the concept of critical illness-induced dysglycaemia as an umbrella term that includes the spectrum of abnormal glucose homeostasis in the ICU. We outline the need for further studies in the area of glucose regulation and for follow-up of the natural history of abnormal glucose control during ICU admission and beyond.

Review article: glucose measurement in the operating room: more complicated than it seems.

Abnormalities of blood glucose are common in patients undergoing surgery, and in recent years there has been considerable interest in tight control of glucose in the perioperative period. Implementation of any regime of close glycemic control requires more frequent measurement of blood glucose, a function for which small, inexpensive, and rapidly responding point-of-care devices might seem highly suitable. However, what is not well understood by many anesthesiologists and other staff caring for patients in the perioperative period is the lack of accuracy of home glucose meters that were designed for self-monitoring of blood glucose by patients. These devices have been remarketed to hospitals without appropriate additional testing and without an appropriate regulatory framework. Clinicians who are accustomed to the high level of accuracy of glucose measurement by a central laboratory device or by an automated blood gas analyzer may be unaware of the potential for harmful clinical errors that are caused by the inaccuracy exhibited by many self-monitoring of blood glucose devices, especially in the hypoglycemic range. Knowledge of the limitations of these meters is essential for the perioperative physician to minimize the possibility of a harmful measurement error. In this article, we will highlight these areas of interest and review the indications, technology, accuracy, and regulation of glucose measurement devices used in the perioperative setting.