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Biomedical subjects

Richard B Weiskopf

Publications and source records attributed to Richard B Weiskopf.

16 recordsLinked to original sources
PubMed2007

The role of data and safety monitoring in acute trauma resuscitation research.

BACKGROUND: The role of data and safety monitoring boards (DSMBs) in clinical research in acute trauma resuscitation is not well documented. Many of the difficulties conducting acute resuscitation research are exacerbated because multiinstitutional studies are needed to adequately power such research. STUDY DESIGN: The purpose of the study was to demonstrate how a well-organized DSMB, explicitly required for these types of clinical trials by many funding agencies, can be a valuable resource in their safe and successful conduct by maximizing data integrity and striving to standardize care by monitoring the consistent and accurate collection of data and adherence to protocol. As an example, the work of an external DSMB in an international multicenter trial of recombinant activated coagulation factor VIIa (rFVIIa) in blunt and penetrating trauma patients is presented. The DSMB in this study was responsible for reviewing all serious adverse event (SAE) data, performing an extended review of SAEs, and reviewing results of analyses of 48-hour and 30-day mortality according to prespecified study stopping rules. RESULTS: Application by the DSMB of uniform definitions of SAEs substantially improved the integrity of the study data and facilitated analysis of events, such as disseminated coagulopathy, pulmonary complications, and multiple organ failure. As a result of the DSMB's efforts, important insights were gained to guide site selection and conduct of future trials of rFVIIa in trauma-induced hemorrhage. CONCLUSIONS: Based on our experience as members of the study DSMB and on a review of the literature, we recommend a strong role for DSMBs in multicenter trials in acute resuscitative care.

Acute Disease↗
PubMed2006

Fresh blood and aged stored blood are equally efficacious in immediately reversing anemia-induced brain oxygenation deficits in humans.

BACKGROUND: Erythrocytes are transfused to treat or prevent imminent inadequate tissue oxygenation. 2,3-diphosphoglycerate concentration decreases and oxygen affinity of hemoglobin increases (P50 decreases) with blood storage, leading some to propose that erythrocytes stored for 14 or more days do not release sufficient oxygen to make their transfusion efficacious. The authors tested the hypothesis that erythrocytes stored for 3 weeks are as effective in supplying oxygen to human tissues as are erythrocytes stored for less than 5 h. METHODS: Nine healthy volunteers donated 2 units of blood more than 3 weeks before they were tested with a standard, computerized neuropsychological test (digit-symbol substitution test [DSST]) on 2 days, 1 week apart, before and after acute isovolemic reduction of their hemoglobin concentration to 7.4 and 5.5 g/dl. Volunteers randomly received autologous erythrocytes stored for either less than 5 h ("fresh") or 3 weeks ("stored") to return their hemoglobin concentration to 7.5 g/dl (double blinded). Erythrocytes of the alternate storage duration were transfused on the second experimental day. The DSST was repeated after transfusion. RESULTS: Acute anemia slowed DSST performance equivalently in both groups. Transfusion of stored erythrocytes with decreased P50 reversed the altered DSST (P < 0.001) to a time that did not differ from that at 7.4 g/dl hemoglobin during production of acute anemia (P = 0.88). The erythrocyte transfusion-induced DSST improvement did not differ between groups (P = 0.96). CONCLUSION: Erythrocytes stored for 3 weeks are as efficacious as are erythrocytes stored for 3.5 h in reversing the neurocognitive deficit of acute anemia. Requiring fresh rather than stored erythrocytes for augmentation of oxygen delivery does not seem warranted.

2,3-Diphosphoglycerate↗
PubMed2006

Anemia and perioperative red blood cell transfusion: a matter of tolerance.

In the past, anemia in the perioperative period has been treated by red blood cell (RBC) transfusions relatively uncritically. RBC transfusions were believed to increase oxygen delivery by increasing hemoglobin concentration. Arbitrary transfusion triggers such as the "10/30 rule" (i.e., RBC transfusion indicated below a hemoglobin concentration of 10 g/dL or a hematocrit of 30%) were applied. However, there is now increasing evidence that RBC transfusions are associated with adverse outcomes and should be avoided whenever possible. Restraining from RBC transfusions and maintaining normovolemia in patients suffering from surgical blood loss results in acute anemia. Therefore, knowing the compensatory mechanisms during acute anemia is crucial. This review focuses on acute anemia tolerance, its limits, and physiologic transfusion triggers in the perioperative period.

Acute Disease↗
PubMed2005

Acute isovolemic anemia impairs central processing as determined by P300 latency.

OBJECTIVE: Acute anemia slows the responses to clinical tests of cognitive function. We tested the hypothesis that these slowed responses during acute severe isovolemic anemia in healthy unmedicated humans result from impaired central processing. METHODS: A blinded operator measured the latency of the P300 peak in nine healthy volunteers at each volunteer's baseline hemoglobin concentration (Hb), and again after isovolemic hemodilution to Hb 5 g/dL. At both Hb concentrations, the P300 latency was measured twice: with the blinded subject breathing air or 100% oxygen, administered in random order. RESULTS: Anemia increased P300 latency significantly from baseline values (P < 0.05). Breathing oxygen during induced anemia resulted in a P300 latency not different from that at baseline when breathing air (P = 0.5) or oxygen (P = 0.8). CONCLUSIONS: Impaired central processing is, at least in part, responsible for the slowed responses and deficits of cognitive function that occur during acute isovolemic anemia at Hb 5-6 g/dL. SIGNIFICANCE: The P300 latency appears to be a potential measure of inadequate central oxygenation. In healthy young adults with acute anemia, erythrocytes should be transfused to produce Hb>5-6 g/dL. As a temporizing measure, administration of oxygen can reverse the cognitive deficits and impaired central processing associated with acute anemia.

Adult↗
PubMed2005

Extracellular potassium concentrations in red blood cell suspensions after irradiation and washing.

BACKGROUND: Extracellular potassium concentration [K(+)e] increases with duration of red blood cell storage. Sometimes red blood cells (RBC) are washed before transfusion to infants to reduce [K(+)e] of these components. AABB standards permit storage of washed RBCs at 4 degrees C for 24 hours. The [K(+)e] of washed RBCs during storage is not known. Experiments were performed to provide those data. STUDY DESIGN AND METHODS: One day after outdating, 26 RBC units were washed without irradiation or before or after irradiation (25 Gy), and [K(+)e] was measured for 24 hours. [K(+)e] was measured also immediately before transfusion of 29 nonoutdated irradiated and washed RBC units. RESULTS: After washing, [K(+)e] increased in a time-dependent fashion. [K(+)e] increased more rapidly in preparations of irradiated than nonirradiated RBCs. [K(+)e] was less after washing after irradiation (1.6 +/- 0.3, 2.4 +/- 0.3, 3.0 +/- 0.3, 3.6 +/- 0.3. 4.2 +/- 0.4, 5.3 +/- 0.5, 8.6 +/- 1.0, and 14.3 +/- 1.3 mEq/L at 0, 1, 2, 3, 4, 6, 12, and 24 hr; mean +/- SD) than washing before irradiation (p < 0.001). The increase in [K(+)e] during the first 6 hours after washing after irradiation was linear (0.61 +/- 0.08 mEq K(+)/L/hr). The probability of a unit of RBCs having a [K(+)e] greater than 5 mEq per L is 0.0 to 0.2 percent 3 hours after washing irradiated RBCs and 0.0 to 1.1 percent 6 hours after washing nonirradiated RBCs. CONCLUSIONS: [K(+)e] increases after washing irradiated and nonirradiated packed RBCs. After irradiation and washing, the [K(+)e] for the initial 6 hours can be predicted from the [K(+)e] immediately after washing. There is a low probability that a unit of RBCs would have a [K(+)e] greater than 5 mEq per L during 6 hours of storage at 4 degrees C after washing if the cells are not irradiated and for 3 hours if the cells are irradiated.

Blood Preservation↗
PubMed2005

Solubility of volatile anesthetics in bovine white matter, cortical gray matter, thalamus, hippocampus, and hypothalamic area.

Although known for whole brain, values are lacking for solubilities of modern volatile anesthetics in specific brain regions. Some regions should differ from others (e.g., gray matter versus white matter) because they differ in lipid content and because potent inhaled anesthetics are lipophilic. In the present report, we examined this issue in bovine brain, finding that white matter/gas partition coefficients are 1.6 (desflurane) to 2.4 (halothane) times larger than gray matter/gas partition coefficients, with values for isoflurane and sevoflurane lying between these at 1.9. Values for thalamus/gas, hypothalamic area/gas, and hippocampal/gas partition coefficients lie between those for gray and white matter. These data may be useful in defining the parts of the brain involved with return to consciousness during recovery from anesthesia.

Algorithms↗
PubMed2005

A procedure for rapid issue of red cells for emergency use.

CONTEXT: A College of American Pathologists Q-Probe revealed that the median turnaround times for emergency requests for red blood cells from the operating room were 30 minutes to release of cells from the blood bank and 34 minutes to delivery to the operating room. These times may not be adequate to permit the red cells to provide sufficiently rapid delivery of oxygen in massively bleeding patients. OBJECTIVE: To improve the time from emergency request for red cells to delivery to the operating room. DESIGN: A new emergency issue program was implemented for only the operating rooms; emergency issue to all other hospital locations remained unchanged. Six units of group O Rh-negative red blood cells (RBCs) are maintained in the blood bank in a separate basket with transfusion forms containing the unit numbers and expiration dates and a bag with one blood tubing segment from each unit. The times to issue and to delivery to the operating room suite were compared with time to issue of 2 group O Rh-negative RBCs for other hospital locations using the older system during the same time period and with the time to issue of 2 units to all other hospital locations during the preceding 2 years. SETTING: A university hospital. MAIN OUTCOME MEASURES: Time between emergency request for red cells and delivery to the operating room. RESULTS: The time between blood bank notification and arrival in the operating room of the 6 units of RBCs was significantly shorter than the time required to just issue (not including delivery time) 2 units of RBCs to other hospital locations. With the new procedure, 82% of units issued reached the operating room within 2 minutes of request, 91% arrived within 3 minutes, and 100% arrived within 4 minutes. These percentages are significantly higher than those for only issue of blood (without delivery) using the older issuing procedure for all hospital locations during the previous 2 years (37%, 49%, and 66%, respectively; P = .007, .009, and .02, respectively) and for other locations during the same 7-month period (29%, 46%, and 73%, respectively; P = .004, .01, and .09, respectively). Time (mean [95% confidence interval]) from blood bank notification to delivery of RBCs to the operating room suite (2.1 [1.6-2.6] minutes, of which approximately 50-60 seconds is attributable to delivery time) was less than issue times (not including delivery times) using the older issuing procedure for other hospital locations during the same period (4.1 [3.1-5.0] minutes; P = .007). CONCLUSIONS: An emergency issue procedure can be used to issue several units of RBCs within 1 minute and have them delivered to the operating room within 2 minutes while maintaining sufficient controls and providing required information to satisfy patient and blood bank requirements.

Blood Banks↗
PubMed2004

The use of recombinant activated coagulation factor VII for spine surgery.

This article focuses on our current understanding of the role of activated coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the European Union and the USA) for patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX. High circulating concentrations of FVIIa, achieved by exogenous administration, initiate hemostasis by combining with tissue factor at the site of injury, producing thrombin, activating platelets and coagulation factors II, IX and X, thus providing for the full thrombin burst that is essential for hemostasis. This "bypass" therapy has led some clinicians to use rFVIIa "off-label" for disorders of hemostasis other than hemophilia. Based on clinical experience, case reports and limited information from clinical trials, rFVIIa may be efficacious in states of decreased concentration of coagulation factors, thrombocytopenia, and at least some states of altered platelet function. The former two can occur intra-operatively during spinal surgery as a consequence of substantial blood loss and normal consumption. Preliminary reports have indicated that rFVIIa does not increase the perioperative incidence of thromboembolic events. However, full reports from large clinical trials regarding the efficacy and safety of rFVIIa in settings other than hemophilia have yet to appear in peer-reviewed publications. Until adequate data demonstrating safety and efficacy are fully reported, it would seem appropriate to reserve the use of rFVIIa in spinal surgery to those instances where conventional therapy cannot provide adequate hemostasis, and "rescue" therapy is required.

Blood Coagulation↗
PubMed2003

Heart rate increases linearly in response to acute isovolemic anemia.

BACKGROUND: The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested. STUDY DESIGN AND METHODS: Acute isovolemic anemia to a Hb concentration of approximately 5 g per dL in 95 unmedicated healthy humans was produced by simultaneous withdrawal of blood and IV replacement with 5-percent HSA and autologous platelet-rich plasma. The relationship between heart rate and Hb concentration was examined using a mixed-effects linear regression model that allowed each person to have a fitted line with its own slope and intercept. Cubic and quadratic terms were added to determine if these improved the goodness of fit. The effect of gender was tested by including it and its interactions with Hb in the mixed model. RESULTS: The relationship between heart rate and Hb concentration was linear (p < 0.001) and consistent among the population studied: heart rate = 116.0-4.0 [Hb] (slope 95% CI: -4.2 to -3.8 beats/min/g Hb). Adding a cubic or quadratic term did not significantly improve the goodness of fit of the mathematical expression to the data, confirming the linear nature of the relationship between heart rate and Hb concentration. For women, the slope of the heart rate response was significantly greater than it was for males (difference +/- SE: 0.70 +/- 0.23, p < 0.005). CONCLUSION: In 95 unmedicated, healthy humans, heart rate was a linear function of Hb during acute isovolemic anemia. Females had a significantly greater slope of increase in heart rate with decreasing Hb concentration than did males. The relationship is consistent among individuals, is similar to that reported for conscious dogs, and differs from that found previously in anesthetized humans.

Acute Disease↗
PubMed2003

Acute isovolemic anemia does not impair peripheral or central nerve conduction.

BACKGROUND: Previous studies have found subtle slowing of responses in tests of addition and digit-symbol substitution during acute severe isovolemic anemia to a hemoglobin concentration of 5 g/dl in healthy unmedicated humans. In this study, the authors tested the hypothesis that such changes relate to the slowing of afferent neural traffic. METHODS: The median nerve was stimulated at the wrist in seven healthy unmedicated volunteers before and after induction of acute isovolemic anemia to a nadir hemoglobin concentration of 5.1 +/- 0.3 g/dl (mean +/- SD). Times for neural impulses to travel from the stimulus site to the brachial plexus, cervical spinal cord, and cerebral cortex were measured using somatosensory evoked potentials. Tests were repeated during acute anemia with the subject breathing oxygen. As a control for time and intrasubject variation, the testing was repeated on a separate day when anemia was not produced at times equivalent to those on the experimental day. RESULTS: Induced acute severe isovolemic anemia decreased nerve conduction latencies from the wrist to the contralateral cerebral cortex (i.e., to the N20 peak) by 2.3 +/- 1.6% compared with values at a mean hemoglobin concentration of 12.7 g/dl (P < 0.01). These decreased latencies were due solely to an increased peripheral conduction velocity, from the wrist to the brachial plexus (P < 0.05), and were not altered when subjects breathed oxygen (P > 0.05). Conduction velocity from the brachial plexus or cervical spinal cord to the cerebral cortex did not change with acute anemia (P > 0.05). Latencies did not differ on the control day among the times of testing (all P > 0.05), nor did they differ at baseline between the control and experimental days (all P > 0.05). CONCLUSION: Somatosensory evoked potential latencies were not increased by acute severe isovolemic anemia, making it unlikely that the afferent portion of the neural system is responsible for slowing of cognitive responses previously observed during acute anemia. Because severe isovolemic anemia did not increase somatosensory evoked potential latencies, etiologies other than anemia should be sought if latencies are increased during intraoperative monitoring.

Acute Disease↗
PubMed2003

A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery.

UNLABELLED: Major surgery evokes a stress response that can produce deleterious consequences, especially in a population at high risk for those complications. We tested the hypothesis that decreasing or eliminating one of the sources of stress by providing intense analgesia in the immediate postoperative period via application of neuraxial opioids would decrease major nonsurgical complications. Two-hundred-seventeen patients scheduled to undergo abdominal aortic surgery were randomly allocated to receive either general anesthesia alone (control) or general anesthesia combined with intrathecal opioid (1 micro g/kg sufentanil with 8 micro g/kg preservative-free morphine injected at the L4-5 interspace). Postoperative care was identical in the two groups, including patient-controlled analgesia. Each patient provided an assessment of postoperative pain using a visual analog scale. Postopera-tive complications were recorded according to criteria established a priori. The administration of intrathecal opioid provided more intense analgesia than patient-controlled analgesia during the first 24 h postoperatively (P < 0.05). There was no difference between groups for the incidence of combined major cardiovascular, respiratory, and renal complications (P > 0.05) or mortality (P > 0.05). The incidence of myocardial damage or infarction, as defined by abnormal plasma concentration of troponin I, did not differ between the two groups (P > 0.05). In patients undergoing major abdominal vascular surgery, decrease of one contributor to postoperative stress, by provision of intense analgesia for the intraoperative and initial postoperative period, via application of neuraxial opioid, does not alter the combined major cardiovascular, respiratory, and renal complication rate. IMPLICATIONS: Provision of intense analgesia for the initial postoperative period after major abdominal vascular surgery, via the administration of neuraxial opioid, does not alter the combined incidence of major cardiovascular, respiratory, and renal complications.

Aged↗
PubMed2002

Oxygen reverses deficits of cognitive function and memory and increased heart rate induced by acute severe isovolemic anemia.

BACKGROUND: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia. METHODS: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test. RESULTS: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia. CONCLUSION: The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.

Acute Disease↗