Costs and outcomes after cardiac surgery in patients refusing transfusion compared with those who do not: a case-matched study.

BACKGROUND: Although numerous studies have demonstrated the feasibility of cardiac surgery for blood refusal patients, few studies match to controls, and fewer examine cost. This historical cohort study aims to compare costs and outcomes after cardiac surgery in Jehovah's Witness patients who refuse blood transfusion with a group of matched patients accepting transfusion. STUDY DESIGN AND METHODS: A retrospective database review was performed to find all patients having cardiac surgery who refused blood products from January 2005 to July 2012 at Duke University Medical Center. These 45 patients were closely matched 1:2 with controls who accepted transfusion based on characteristics likely to influence transfusion. Cost from day of surgery to hospital discharge and other outcome data (length of stay [LOS], discharge hemoglobin [Hb], acute kidney injury) were analyzed retrospectively. RESULTS: Forty-five Witnesses having cardiac surgery were temporally matched to two controls having the same surgery. Median euroSCORE was the same in both groups (6.0, p = 0.9981). In the matched-pairs comparison of cost, there was no significant difference in total cost for Witnesses and controls. There was no difference in intensive care unit LOS (median, 1 day, both groups) or total LOS (median, 9 days for Witnesses vs. 7 days for controls). Mean Hb at discharge was higher in Witnesses than in controls (11.7 g/dL vs. 9.8 g/dL, p < 0.001). Thirty-day mortality was zero in both groups. CONCLUSION: Utilizing applicable blood conservation measures, cardiac surgery may be performed with similar outcomes and cost from day of surgery to discharge compared to controls in select patients without blood transfusion.

Respiratory variation and cardiopulmonary interactions.

It is often unclear whether or not a patient's stroke volume will increase following a fluid bolus. Volume responsiveness is defined by an increase in stroke volume following a fluid bolus. For patients being mechanically ventilated, the cardiopulmonary interactions associated with positive pressure ventilation create pulse pressure and stroke volume variation in the arterial pressure waveform that can be used to assess fluid responsiveness, so-called dynamic preload assessment. However, lung-protective ventilation is increasingly being used to avoid the adverse outcomes of higher tidal volume ventilation, and pulse pressure and stroke volume variation do not effectively predict volume responsiveness in the setting of lung-protective ventilation without using special techniques. Dynamic preload assessment is more effective at determining whether a patient will be fluid responsive than static measures of preload, but further studies are needed to more conclusively show that outcomes are improved with this approach to fluid management.

Hypoventilation after inhaled anesthesia results in reanesthetization.

BACKGROUND: During emergence from volatile anesthesia, hypoventilation may result from many causes. In this study, we examined the effect of hypoventilation after initial emergence from volatile anesthesia and the potential for reanesthetization. METHODS: The uptake and excretion of desflurane (Des), sevoflurane, and isoflurane were studied using the Gas Man® computer simulation program for a 70-kg simulated patient. The vaporizer setting was adjusted so that a VRG (vessel-rich tissue group, including brain) level of 0.75 minimum alveolar concentration (MAC), 1.0 MAC, and 1.5 MAC was rapidly achieved and maintained within tight limits for a 1-, 2-, 4-, and 6-hour period of anesthesia.At the end of the simulated period of anesthesia, the vaporizer was set to 0 and fresh gas flow was set to 8 L/min. Ventilation (VA) was continued at 4 L/min until the anesthetic level in the VRG reached MAC awake, equal to 0.33 MAC for each drug. Then, the VA was adjusted to 0.1 L/min to simulate near-apnea and 0.0 L/min to simulate true apnea. Severe reanesthetization was said to occur if the VRG level increased to or above 0.5 MAC. Mild reanesthetization was said to occur if VRG increased from its value of 0.33 MAC but did not reach 0.5 MAC. The minimum VA required to avoid severe reanesthetization was studied by trials of decreased VA beginning at the time the VRG reached 0.33 MAC. RESULTS: After emergence from 1 hour of anesthesia, all simulated patients were protected against mild and severe reanesthetization if anesthesia was at 0.75 or 1.0 MAC. After 4 or 6 hours of anesthesia, severe reanesthetization occurred with all drugs with near or true apnea if anesthesia was at 1.0 or 1.5 MAC. The minimum alveolar VA to protect against severe reanesthetization after 6 hours of anesthesia was no more than 0.5 L/min for all drugs at 0.75 MAC, no more than 0.5 L/min at 1.0 MAC, and no more than 1.2 L/min at 1.5 MAC. In all simulated cases, the source of anesthetic drug that allowed reanesthetization was muscle (MUS), which reached a value of 0.8 MAC within 4 hours with all drugs and reached a value of 0.75 MAC with desflurane after 2 hours. Fat levels of anesthetic remained less than 0.15 MAC for all drugs up to the 6 hours tested. CONCLUSIONS: Reanesthetization from hypoventilation after inhaled anesthesia is possible. After initial emergence, muscle is a source of anesthetic and predisposes to reanesthetization while fat is a sink for anesthetic and fosters continued emergence. Severe hypoventilation will cause some degree of reanesthetization from anesthetic released from muscle after 4 hours of 1 MAC inhaled anesthesia with desflurane, sevoflurane, or isoflurane.

Impact of transfusion of autologous 7- versus 42-day-old AS-3 red blood cells on tissue oxygenation and the microcirculation in healthy volunteers.

BACKGROUND: Stored red blood cells (RBCs) accumulate biochemical and biophysical changes. Maximum storage duration is based on acceptable in vitro characteristics and 24-hour survival, but not RBC function. Relatively little is known about the impact of RBC storage duration on oxygenation and the microcirculation. STUDY DESIGN AND METHODS: Eight healthy subjects donated a double RBC apheresis, which were prestorage leukoreduced and processed in AS-3. Subjects were transfused 1 unit of RBCs at 7 and 42 days after blood collection. Measurements of percentage of tissue oxygenation in the thenar eminence muscle (StO2) and brain (SctO2) were recorded with Food and Drug Administration-cleared noninvasive devices. Sublingual microvascular blood flow (microcirculatory flow index [MFI]) was quantified before and after RBC transfusion using a video microscope. Raw electronic data for all measurements were analyzed by a blinded observer at a core laboratory. RESULTS: The only pre- versus posttransfusion change observed in measurements of SctO2, StO2, or MFI was a very small increase in SctO2, from 70.4 to 71.8 (means, p=0.032) at 7 days. There was no significant difference in the amount of pre-post change at 7 days versus 42 days for any of the measures. CONCLUSION: Transfusion of 1 unit of 42-day-stored RBCs to healthy subjects has no overt detrimental effect on tissue oxygenation or the microcirculation assessed by clinically available monitors.

Impact of red blood cell transfusion on global and regional measures of oxygenation.

Anemia is common in critically ill patients. Although the goal of transfusion of red blood cells is to increase oxygen-carrying capacity, there are contradictory results about whether red blood cell transfusion to treat moderate anemia (e.g., hemoglobin 7-10 g/dL) improves tissue oxygenation or changes outcomes. Whereas increasing levels of anemia eventually lead to a level of critical oxygen delivery, increased cardiac output and oxygen extraction are homeostatic mechanisms the body uses to prevent a state of dysoxia in the setting of diminished oxygen delivery due to anemia. In order for cardiac output to increase in the face of anemia, normovolemia must be maintained. Transfusion of red blood cells increases blood viscosity, which may actually decrease cardiac output (barring a state of hypovolemia prior to transfusion). Studies have generally shown that transfusion of red blood cells fails to increase oxygen uptake unless oxygen uptake/oxygen delivery dependency exists (e.g., severe anemia or strenuous exercise). Recently, near-infrared spectroscopy, which approximates the hemoglobin saturation of venous blood, has been used to investigate whether transfusion of red blood cells increases tissue oxygenation in regional tissue beds (e.g., brain, peripheral skeletal muscle). These studies have generally shown increases in near-infrared spectroscopy derived measurements of tissue oxygenation following transfusion. Studies evaluating the effect of transfusion on the microcirculation have shown that transfusion increases the functional capillary density. This article will review fundamental aspects of oxygen delivery and extraction, and the effects of red blood cell transfusion on tissue oxygenation as well as the microcirculation.

Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes.

beta cell dysfunction is a central component of the pathogenesis of type 2 diabetes. Using oligonucleotide microarrays and real-time PCR of pancreatic islets isolated from humans with type 2 diabetes versus normal glucose-tolerant controls, we identified multiple changes in expression of genes known to be important in beta cell function, including major decreases in expression of HNF4alpha, insulin receptor, IRS2, Akt2, and several glucose-metabolic-pathway genes. There was also a 90% decrease in expression of the transcription factor ARNT. Reducing ARNT levels in Min6 cells with small interfering RNA (siRNA) resulted in markedly impaired glucose-stimulated insulin release and changes in gene expression similar to those in human type 2 islets. Likewise, beta cell-specific ARNT knockout mice exhibited abnormal glucose tolerance, impaired insulin secretion, and changes in islet gene expression that mimicked those in human diabetic islets. Together, these data suggest an important role for decreased ARNT and altered gene expression in the impaired islet function of human type 2 diabetes.

African elephant sesquiterpenes. II. Identification and synthesis of new derivatives of 2,3-dihydrofarnesol.

A search for potential semiochemicals revealed nerolidol (6), albicanol (7), and the new 2,3-dihydrofarnesol derivatives 8-10 in the temporal gland secretions of African elephants. A novel synthesis from (E,E)-farnesol (1) provided compounds 8-10 for GC-MS comparison to the natural products. This study confirms the farnesol family as frequently occurring secondary metabolites in African elephant temporal gland secretions.