Surgery alters parameters of vitamin D status and other laboratory results.

Fracture liaison services often perform laboratory testing, but these results may be altered by surgery. In 40 hip arthroplasty patients, many laboratory parameters of bone health relevance were reduced by 8-22% on the first post-operative day. Laboratory results obtained in the immediate post-surgery interval do not reliably ascertain baseline status. INTRODUCTION: As secondary causes of osteoporosis are common, fracture liaison services often perform laboratory testing in the immediate post-fracture interval. We hypothesized that laboratory results obtained shortly after surgery may not accurately ascertain baseline status. If true, such alterations might confound subsequent fracture prevention efforts. METHODS: Patients undergoing elective total hip arthroplasty were studied as a surrogate for hip fracture patients. Blood and urine were obtained 2 weeks before surgery, before anesthetic induction, on post-operative day one, and 6 weeks after surgery. Serum total and free 25-hydroxyvitamin D (25(OH)D), vitamin D-binding protein (DBP), calcium, creatinine, albumin (Alb), alkaline phosphatase (ALP), plasma hemoglobin (Hgb) and urinary DBP/creatinine ratio (UDBP/Cr) were measured. RESULTS: Forty volunteers (28 women; 12 men) with mean age of 65.7 [8.7] years were studied. Laboratory results were stable from 2 weeks before to the day of surgery. On the first day after surgery, total 25(OH)D, DBP, calcium, creatinine, ALP, and Alb declined 8-22% (p < 0.0001); free 25(OH)D and Hgb declined by 8 and 15% (p < 0.01), respectively; and UDBP/Cr increased 32% (p < 0.01). Using a 25(OH)D <30 ng/mL threshold, vitamin D inadequacy prevalence increased from 38% before surgery to 68% the day after (p < 0.001). All laboratory values returned to baseline at 6 weeks after surgery. CONCLUSIONS: Laboratory values are reduced immediately following elective total hip arthroplasty. Testing at that time does not accurately ascertain baseline status and may lead to elevated estimates of vitamin D inadequacy, incorrect interventions, and misallocation of healthcare resources.

Vitamin D deficiency in anesthesia department caregivers at the end of winter.

BACKGROUND: To test whether the vitamin D status of anesthesia department caregivers practicing at high Northern latitudes is compatible with current recommendations, the 25-hydroxyvitamin D (25(OH)D) levels of caregivers at hospitals in Iceland (64°08' N) and in Wisconsin (43°07' N) were compared at the end of winter. METHODS: Anesthesia department faculty and resident physicians, non-physician anesthetists, and critical care nurses completed a questionnaire, and provided blood samples for analysis of 25(OH)D by reverse-phase high performance liquid chromatography. RESULTS: One hundred and six participants in Iceland and 124 participants in Wisconsin were enrolled. No difference in mean serum 25(OH)D levels between Iceland [70.53 nmol/l, standard deviation (SD) 30.87 nmol/l] and Wisconsin (70.0 nmol/l, SD 30.0 nmol/l) was observed. In Iceland and Wisconsin, 25(OH)D levels below 25 nmol/l were observed in 4.7% and 4.0%, below 50 nmol/l in 34.9% and 25.0%, and below 75 nmol/l in 56.6% and 61.3% of caregivers, respectively. CONCLUSIONS: 25(OH)D levels below the 50 nmol/l (20 ng/ml) threshold recommended by the Institute of Medicine and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and below the 75 nmol/l (30 ng/ml) threshold recommended by The Endocrine Society, are highly prevalent among anesthesia caregivers working at two Northern hospitals at the end of winter who may otherwise not meet criteria to be tested. Anesthesia and critical care providers may wish to determine their 25(OH)D levels and use effective, safe, and low cost supplementation to target a 25(OH)D level compatible with optimal health.

Glycaemic control in the perioperative period.

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patient.

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.

Dexmedetomidine.

Effective use of sedative-hypnotic and analgesic agents is an integral part of providing patient comfort and safety. Of the numerous drugs administered, benzodiazepines, propofol, and narcotics are the most popular. Even these proven, time-tested sedative-hypnotics and analgesics are not perfect, however, and modern intensive care demands a more ideal product. The development of dexmedetomidine, an alpha2-agonist, is an attempt to improve sedative/analgesic use and provide a drug that possesses the characteristics outlined in Table 1. It stimulates alpha2-adrenergic receptors in the locus ceruleus to provide sedation and in the spinal cord to enhance analgesia. It also causes sympatholysis via central and peripheral mechanisms. Dexmedetomidine binds alpha2-receptors eight times more avidly than clonidine and is shorter acting. It was initially evaluated as an anesthetic, but was associated with excessive bradycardia and hypertension, followed by hypotension. In late 1999, dexmedetomidine was approved for adult ICU use for less than 24 hours as a sedative infusion. It currently lacks approval in Europe. Most of the clinical experience with dexmedetomidine has been with surgical patients undergoing cardiac and vascular procedures. Careful patient selection and proper drug infusion are needed to avoid excessive deleterious hemodynamic results. Slower bolus loading over 20 minutes results in minimally decreased heart rate and blood pressure. Continuous infusion maintains unique sedation (patients appear to be asleep, but are readily roused), analgesic sparing effect, and minimal depression of respiratory drive. More experience with dexmedetomidine infusion in medical ICU patients and patients with complex end-organ dysfunction such as respiratory failure or systemic inflammatory response syndrome is needed before conclusions can be drawn about the drug's potential for wider application and its long-term (> 24 h) safety and effectiveness.

Commentary. Balancing sedation and analgesia in the critically ill.

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.

Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit.

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.

Perioperative management of selected endocrine disorders.

Anesthesiologists routinely encounter patients with endocrine disorders. Good perioperative outcome depends on preoperative identification, risk stratification and optimization of the patients' endocrinopathies and their sequelae; intraoperative control of metabolic and physiological parameters; and appropriate postoperative pain management, stress modulation, and evaluation of neurological, cardiovascular, and renal function.

Critical care and perioperative medicine. How goes the flow?

The specialty of anesthesiology is at a crossroad. Do anesthesiologists stay in the illusionary safe harbor of the operating room and allow critical care anesthesiologists to float alone? How can in-fighting with other medical and nonmedical providers be avoided, while maintaining or expanding the historic and hopefully future roles of anesthesiologists as hospital-based physicians? A different tact is required to redefine the scope of the practice with broadened training to provide increased expertise in the evolving medical marketplace. This approach would include solid training in business, informatics, data management, and critical thinking on outcomes. This paradigm shift may be challenging, and requires redirection, reallocation of assets, re-education, and a new mindset. If successfully applied, however, it presents a means to strengthen the respected position of the specialty and to promote the medical care and practice of perioperative specialists in the rapidly changing landscape of modern medicine. Regarding the question of turf and ownership of the ICU, the authors suggest pursuing the higher ground of an excellent scope of practice, which facilitates the care and activities of surgical and primary care colleagues. These colleagues, administrators, and governmental agencies will have to be re-educated to support training and provide equitable remuneration. Appropriately trained anesthesiologist-intensivists can complement many other care providers, while providing a wide range of services with an economy of care, whether in a semiclosed or closed ICU setting.

Massive rhabdomyolysis and multiple organ dysfunction syndrome caused by leptospirosis.

We report a case of leptospiral infection in a 63-year-old man who acquired the infection while swimming in canals and streams in Hawaii. The patient's course was atypical in that he was anicteric and had no evidence of meningitis when he presented with fever, rapidly progressive and severe rhabdomyolysis, thrombocytopenia, acute renal failure, and respiratory distress syndrome. Although he recovered after a protracted illness, he required major life support, including mechanical ventilation and hemodialysis. Initial antimicrobial therapy was designed to cover major bacterial and atypical pathogens, including leptospires. An in-depth work-up for causes of this catastrophic illness confirmed acute leptospirosis. Although rare, leptospirosis is a potentially lethal infection classically associated with hepatitis, azotemia, and meningitis. Most patients experience self-limited illness, with fever, myalgias, and malaise followed by an immune-mediated aseptic meningitis. A small proportion develop shock and multiple organ dysfunction. Whereas myalgias are ubiquitous in leptospiral infection, and most patients show mildly elevated muscle enzymes, life-threatening rhabdomyolysis is rare. This atypical case is reported to urge clinicians to consider leptospirosis in the evaluation of a patient with cryptogenic sepsis who develops multiple organ dysfunction associated with rhabdomyolysis. Appropriate antimicrobial therapy, with penicillin or doxycycline, can be life-saving.

Phlegmasia cerulea dolens with compartment syndrome: a complication of femoral vein catheterization.

OBJECTIVE: Central venous catheterization is commonly performed in the critically ill. The femoral vein is widely accepted as an insertion site with complications thought to be comparable to other central access sites. We used serial ultrasound examinations with Doppler to examine the evolution of a heretofore undescribed complication of femoral vein catheterization, phlegmasia cerulea dolens with compartment syndrome. DESIGN: Serial ultrasounds were performed in patients before the insertion of femoral venous catheters and sequentially every 48 hrs while the catheters were in place. The noncatheterized leg served as a control. SETTING: A trauma and life support center of a tertiary multidisciplinary critical care unit. PATIENT: A 32-yr-old man with respiratory failure as a consequence of a severe community-acquired pneumonia that required central venous access for antibiotics because no peripheral sites could be obtained. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The initial ultrasound examination of both legs before femoral catheter insertion revealed no sign of venous thrombosis. Ultrasound of the catheterized leg at 48 hrs revealed a small nonocclusive thrombosis, whereas the opposite leg remained normal. At 72 hrs, the catheterized leg had clinical and ultrasonographic evidence of a massive thrombosis. A compartment syndrome defined by pressure measurements soon ensued and required emergent surgical release. CONCLUSIONS: This case report and a review of the available literature suggest that thrombosis associated with femoral vein catheterization should be considered when clinicians decide where to obtain central venous access when multiple sites are available. This report also suggests the utility of serial ultrasound examinations to define clinically nonapparent thrombosis as an early indicator of a potentially catastrophic complication.

An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung.

Samples of normal human lung and six major types of human lung carcinomas were immunostained for antioxidant enzymes (manganese and copper, zinc superoxide dismutases, catalase, and glutathione peroxidase) and six isoenzymes of glutathione S-transferase staining was generally low in tumor cells compared with the high level of staining noted in respiratory epithelium. A notable exception was heterogeneity in immunostaining for manganese superoxide dismutase in lung adenocarcinoma, which showed both positive and negative cells in the same tumor. Tumor stromal cells (fibroblast-appearing cells) often showed strong immunostaining for manganese superoxide dismutase, while stromal cells were negative for other antioxidant and glutathione S-transferase enzymes. None of the carcinomas studied had significant levels of catalase or glutathione peroxidase; this finding has potential clinical relevance since it indicates that these tumors cannot detoxify hydrogen peroxide. The low levels of antioxidant and glutathione S-transferase enzymes in tumor cells is consistent with the hypothesis that these enzymes are markers of cell differentiation.

Pharmacodynamics and pharmacokinetics of milrinone administration to increase oxygen delivery in critically ill patients.

OBJECTIVES: The positive inotropic and vasodilator actions of phosphodiesterase (PDE) inhibitor drugs may offer therapeutic alternatives to beta-agonists in critically ill patients. We hypothesized that milrinone administration would increase cardiac index (CI) and oxygen delivery (Do2) in ICU patients, and that a pharmacokinetic model previously developed in cardiac surgery patients may be used to predict milrinone plasma concentrations in a medical-surgical ICU population. SETTING: ICU in two tertiary-care, university medical centers. DESIGN AND INTERVENTIONS: A prospective, open-label, multicenter, dose-escalating study in three successive groups of eight ICU patients who received a 10-min loading dose of milrinone (25 micrograms/kg [LOW], 50 micrograms/kg [MED], and 75 micrograms/kg [HIGH]). In addition, all patients then received a milrinone infusion of 0.5 microgram/kg/min for 1 h. MEASUREMENTS: Hemodynamic measurements included heart rate (HR); mean arterial, pulmonary artery, central venous, and pulmonary artery occlusion pressures; and thermodilution cardiac output. Oxygen transport indexes included arterial and venous blood oxygen tensions to determine Do2 and oxygen consumption (Vo2). Data were analyzed by univariate repeated measures analysis of covariance, with baseline values utilized as covariate regressors. RESULTS: Twenty-four adult ICU patients 20 to 84 years of age completed the study. The three groups did not differ, except that the patients in the MED group were significantly older (67 +/- 4 years, mean +/- SEM) compared with either the patients in the LOW (48 +/- 7 years) or HIGH (47 +/- 6 years) group. While HR did not change in the LOW group (90 +/- 4 to 93 +/- 3 beats/min), HR increased significantly in the HIGH group (94 +/- 5 to 112 +/- 8 beats/min) (baseline to 60 min infusion time points). All milrinone doses increased both CI and Do2. At the end of the 10-min loading dose, CI increased 0.3 L/min/m2 in the LOW group, 1.1 L/min/m2 in the MED group, and 0.9 L/min/m2 in the HIGH group. Do2 increased 8% in the LOW group, 33% in the MED group, and 23% in the HIGH group, similar to the changes in CI. Mixed venous oxygen saturation increased 3 to 5% during the 10-min loading dose of milrinone. During this same time period, mean arterial pressure decreased 6 to 16% and pulmonary artery pressures decreased 9 to 15%. Peak plasma milrinone concentrations increased as a function of the loading dose (159 +/- 9 ng/mL in the LOW group, 302 +/- 33 ng/ml in the MED group, and 411 +/- 45 ng/mL in the HIGH group). However, milrinone concentrations were similar in all three groups after the 1-h infusion; 113 +/- 14 ng/ml (LOW), 147 +/- 22 ng/mL (MED), and 119 +/- 14 ng/ml (HIGH). In all patients with final plasma milrinone concentrations greater than 100 ng/mL (15/23), the CI increased by at least 0.4 L/min/m2 (range, 0.4 to 1.8 L/min/m2). CONCLUSIONS: Our study confirms that a milrinone loading dose of 50 micrograms/kg/min followed by an infusion of 0.5 microgram/kg/min achieves adequate plasma concentrations of 100 ng/mL or greater, which significantly increases both CI and Do2. In addition, a previously established pharmacokinetic model of milrinone disposition is confirmed in this mixed ICU population.

Pulmonary effects of short term selenium deficiency.

BACKGROUND: Selenium dependent glutathione peroxidase (GPx) reduces hydrogen peroxide (H2O2) and organic hydrogen peroxides in both normal and pathological states. Chronic dietary deficiency of selenium results in a gradual decrease in GPx and altered response to environmental stress. However, glutathione-S-transferase (GST) isozymes may increase and compensate for chronic GPx deficiency. The pattern of antioxidant enzyme activity and immunolocalisation of various enzymes in rat lung has not been described in short term (< 3 weeks) acute selenium deficiency. METHODS: The time course of GPx depletion from rat lung (measured every five days in subgroups of rats) during acute dietary selenium deficiency was evaluated. After 20 days of depletion, enzyme activity of lung GPx, catalase, superoxide dismutase (SOD), glutathione reductase (GR), glucose-6-phosphodiesterase (G-6-PD), and GST were determined. Immunohistochemical localisation of GPx and SOD was also performed. The response to lethal hyperoxia (> 95%) in control and selenium deficient rats was then established. RESULTS: At 20 days, lung GPx activity in the rats fed a selenium deficient diet was one third less than in control animals who received a normal diet, while changes in blood enzymes between control and deficient animals were similar. Other lung enzyme activities remained normal with the exception of cyanide inhibited SOD activity measured in selenium deficient rat lungs which declined to approximately 50% of normal. Immunohistochemical localisation of GPx showed a generalised loss of the enzyme throughout the lung parenchyma with some possible sparing of activity in epithelial cells of the bronchioles. When exposed to lethal hyperoxia, selenium deficient animals were more susceptible than control rats. CONCLUSIONS: This is the earliest time at which dietary selenium deficiency has been shown to produce moderate loss of GPx activity. This change in activity was associated with increased susceptibility to pulmonary oxidant stress. However, the role of decreased SOD activity (presumed to represent copper, zinc SOD), although unexpected, may have been a major contributor to increased damage from hyperoxia. These results emphasise the complex potential interaction of elemental deficiency with the natural antioxidant response to lethal hyperoxia.