Gavin D. Divertie

Stimulation of Lipolysis in Humans by Physiological Hypercortisolemia

The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 μg · kg−1 · min−1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 μg · kg−1 · min−1 somatostatin, 0.05 mU · kg−1 · min−1 insulin, and 3 ng · kg−1 · min−1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to ∼970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by ∼60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area-under-the-curve analysis (152 ± 52 vs. −48 ± 23 μmol · kg−1 and 12.2 ± 4.1 vs. −4.9 ± 4.1 mmol · min−1 · L−1, respectively; P < 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 ± 0.3 vs. 6.1 ± 0.6 mM, NS) or saline (4.9 ± 0.2 vs. 4.9 ± 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress.

Perspectives of physicians and nurses regarding end-of-life care in the intensive care unit.

Context: The delivery of end-of-life care (EOLC) in the intensive care unit (ICU) varies widely among medical care providers. The differing opinions of nurses and physicians regarding EOLC may help identify areas of improvement. Objective: To explore the differences of physicians and nurses on EOLC in the ICU and how these differences vary according to self-reported proficiency level and primary work unit. Design: Cross-sectional survey of 69 ICU physicians and 629 ICU nurses. Setting: Single tertiary care academic medical institution. Results: A total of 50 physicians (72%) and 331 nurses (53%) participated in the survey. Significant differences between physicians and nurses were noted in the following areas: ability to safely raise concerns, do not resuscitate (DNR) decision making, discussion of health care directives, timely hospice referral, spiritual assessment documentation, utilization of social services, and the availability of EOLC education. In every domain of EOLC, physicians reported a more positive perception than nurses. Additional differences were noted among physicians based on experience, as well as among nurses based on their primary work unit and self-reported proficiency level. Conclusions: Even with an increased focus on improving EOLC, significant differences continue to exist between the perspectives of nurses and physicians, as well as physicians among themselves and nurses among themselves. These differences may represent significant barriers toward providing comprehensive, consistent, and coordinated EOLC in the ICU.

Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion

Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of several related proteins that bind and modulate the actions of IGFs. The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production. We report five sets of investigations that further define the characteristics of hepatic IGFBP-1 response to insulin. In normal subjects, a continuous high-dose insulin infusion caused a rapid decrease in plasma IGFBP-1 concentrations, with a rate of 0.24 +/- 0.04 microgram/L.min-1 and a t1/2 of 89 +/- 4 minutes. Conversely, a 3-hour somatostatin (SRIF) infusion caused a 4.5-fold increase in plasma IGFBP-1 levels. SRIF plus low-dose insulin infusion (to inhibit break-through insulin secretion) resulted in a plateau in IGFBP-1 concentrations at 5 to 8 hours, with a t1/2 to achieve steady state of 60 to 75 minutes. Under similar conditions, a stepped increase in plasma glucose level from 5 to 9 mmol/L had no effect on the rate of IGFBP-1 increase in plasma, indicating that an acute increase in glucose concentration within a physiologic range has no independent inhibitory effect on IGFBP-1 production in the presence of a nonsuppressive insulin level. Using SRIF plus sequential graded insulin infusions, the threshold peripheral (= portal) plasma insulin concentration for IGFBP-1 suppression was between 65 and 172 pmol/L. Subjects with insulin-dependent diabetes mellitus (IDDM) showed a similar dose-response pattern, suggesting that insulin regulation of IGFBP-1 may be normal in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Injury After Cardiopulmonary Arrest and Its Assessment With Diffusion-Weighted Magnetic Resonance Imaging

OBJECTIVE To characterize the frequency and pattern of diffusion-weighted imaging (DWI) abnormalities detected as part of brain magnetic resonance imaging (MRI) and their association with short-term neurologic outcomes in patients successfully resuscitated after cardiopulmonary arrest (CPA). PATIENTS AND METHODS We retrospectively analyzed a case series of patients who experienced CPA between May 1, 2000, and April 29, 2004, at St Lukes Hospital in Jacksonville, Fla. Eligible patients required treatment by the Code Blue team and had 1 DWI study before discharge or death. Two neuroradiologists jointly classified DWI abnormalities by anatomic location. Outcome was measured by Cerebral Performance Category score. RESULTS Resuscitation was performed 628 times during the 48-month study period. Of 514 CPA survivors, 18 (3.5%) had MRI studies. The median age was 62 years (interquartile range [IQR], 49-73), and 10 were men. Median code duration was 16 minutes (IQR, 11-19 minutes), and median code-to-scan time was 72 hours (IQR, 28-229 hours). A DWI abnormality was noted in 9 (50%) of 18 patients. Cortical areas (global and regional) were the most common sites of restricted diffusion. Diffusion-weighted imaging abnormalities were present in 7 (70%) of 10 patients with a poor neurologic outcome at discharge. CONCLUSION Magnetic resonance imaging is performed rarely after survival of CPA. In this study with limited sample size, a greater proportion of patients with normal DWI findings had a good neurologic outcome at the time of hospital discharge vs those with abnormal findings. Prospective studies of early and serial MRI (with DWI) are needed to confirm this association and to clarify the prognostic usefulness of such studies.

Tracer disequilibrium in CO2 compartments during NaH14CO3 infusion.

The failure of labeled CO2 to equilibrate between extracellular and intracellular CO2 compartments may influence the accuracy of substrate oxidation measurements during infusion of carbon-labeled tracers because it may generate errors in estimate of fixation of labeled CO2 derived from control experiments in which labeled bicarbonate is infused. In this study, normal volunteers received a 14-hour overnight primed continuous infusion of NaH14CO3. Over the last 4 hours of the study, steady-state conditions were achieved in the specific activities (SAs) of expired 14CO2 and plasma urea, which was used as a probe for hepatic intracellular CO2 SA. Plasma urea SA was approximately 17% lower than expired CO2 SA (46.4 +/- 5.6 v 56.8 +/- 3.9 disintegrations per minute.mumol-1, P < .02). Fractional 14CO2 recovery was 94.8% +/- 0.8%; when corrected for failure to equilibrate with intracellular CO2, fractional recovery was 89.5% +/- 1.9%. These data indicate that compartmentalization of CO2 may occur in humans. The duration of our experiments, required because of the long half-life of plasma urea, may have minimized the apparent magnitude of compartmentalization. Furthermore, it is possible that compartmentalization in extrahepatic tissues could be of either lesser or greater magnitude than that which we observed in liver. Whether this phenomenon contributes to incomplete recovery of 14CO2 during NaH14CO3 infusion cannot be determined from our results. Additional studies using different experimental approaches will be required to better measure CO2 compartmentalization.

A comparison of intensive care unit physician staffing costs at the 3 Mayo Clinic sites

OBJECTIVES To determine the provider cost of administering intensive care unit (ICU) services, comparing 3 different staffing models for ICU coverage, and to compare the costs of using house staff vs nonphysician providers (NPPs). METHODS Data were collected on total staff composition and number of beds In ICUs from January 1, 2004, through December 31, 2004, at the 3 Mayo Clinic sites: Rochester, Minn; Jacksonville, Fla; and Scottsdale, Ariz. Institutional or national average staff salaries were used to determine total staffing costs per ICU bed per year at each site. Medicare medical education reimbursements were also taken into account. RESULTS Costs per ICU bed for physician staffing were

Multidisciplinary Perioperative Management of Pulmonary Arterial Hypertension in Patients Undergoing Noncardiac Surgery

18,630 in Rochester,

Cortisol increases plasma insulin-like growth factor binding protein-1 in humans

37,515 in Jacksonville, and

Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation

38,010 in Scottsdale. When NPPs were substituted for house staff, the costs per bed were

Safety and Efficacy of Levetiracetam for Critically Ill Patients with Seizures

72,466 in Rochester,