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Biomedical subjects

Donald S Prough

Publications and source records attributed to Donald S Prough.

54 records · Page 3Linked to original sources

Peroxynitrite generated in the rat spinal cord induces oxidation and nitration of proteins: reduction by Mn (III) tetrakis (4-benzoic acid) porphyrin.

To determine whether peroxynitrite at the concentration and duration present after spinal cord injury induces protein oxidation and nitration in vivo, the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) was administered into the gray matter of the rat spinal cord for 5 hr. The cords were removed at 6, 12, 24, and 48 hr after SIN-1 exposure, immunohistochemically stained with antibodies to dinitrophenyl (DNP) and nitrotyrosine (Ntyr), markers of protein oxidation and nitration, respectively, and the immunostained neurons were counted. The percentages of DNP-positive (P = 0.023-0.002) and Ntyr-positive (P < 0.001 for all) neurons were significantly higher in the SIN-1-exposed groups than in the ACSF controls at each time, suggesting that peroxynitrite induced intracellular oxidation and nitration of proteins. The percentages of DNP- and Ntyr-positive neurons were not significantly different over time in either SIN-1- or ACSF-exposed groups (P = 0.20-1.00). The percentage of DNP-positive neurons was 7.6 +/- 3% to 12 +/- 4.2% at 6-24 hr, and it was 14 +/- 2% to 19 +/- 2% at 6-24 hr for Ntyr-positive neurons after SIN-1-exposure, whereas both ranged over 2-3% in ACSF controls. Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP, a broad-spectrum scavenger of reactive species) significantly reduced the percentages of DNP- and Ntyr-positive neurons (P = 0.04 and 0.002, respectively) compared to a SIN-1-exposed, untreated group at 24 hr after SIN-1 exposure. There were no significant differences between MnTBAP-treated and ACSF controls (P = 0.7 for DNP and 0.2 for Ntyr). These results further demonstrate peroxynitrite-induced protein oxidation and nitration and the efficiency of MnTBAP in scavenging peroxynitrite.

2,4-Dinitrophenol↗

Traumatic cerebral vascular injury: the effects of concussive brain injury on the cerebral vasculature.

In terms of human suffering, medical expenses, and lost productivity, head injury is one of the major health care problems in the United States, and inadequate cerebral blood flow is an important contributor to mortality and morbidity after traumatic brain injury. Despite the importance of cerebral vascular dysfunction in the pathophysiology of traumatic brain injury, the effects of trauma on the cerebral circulation have been less well studied than the effects of trauma on the brain. Recent research has led to a better understanding of the physiologic, cellular, and molecular components and causes of traumatic cerebral vascular injury. A more thorough understanding of the direct and indirect effects of trauma on the cerebral vasculature will lead to improvements in current treatments of brain trauma as well as to the development of novel and, hopefully, more effective therapeutic strategies.

Animals↗

Isoflurane but not mechanical ventilation promotes extravascular fluid accumulation during crystalloid volume loading.

BACKGROUND: The combination of isoflurane anesthesia and mechanical ventilation reduces urinary output and promotes redistribution of a crystalloid bolus into the extravascular space. The authors hypothesized that mechanical ventilation rather than isoflurane causes this alteration. METHODS: The fate of a 25-ml/kg, 20-min, 0.9% saline fluid bolus was studied in four different experiments per sheep: while conscious and spontaneously ventilating (CSV), while conscious and mechanically ventilated (CMV), while anesthetized with isoflurane and mechanical ventilated (ISOMV), and while anesthetized with isoflurane and spontaneously ventilating (ISOSV). RESULTS: By calculations based on the indicator dilution and mass balance principles, plasma expansion was similar between protocols. Isoflurane but not mechanical ventilation reduced urinary output and increased interstitial fluid volume (P < 0.001): At 180 min, mean total urinary outputs were 15.6 +/- 2.1 and 15.9 +/- 2.9 ml/kg in the CSV and CMV protocols and 2.7 +/- 0.6 and 3.1 +/- 1.1 ml/kg in the ISOSV and ISOMV protocols, respectively. The net changes in extravascular volume, assumed to be interstitial fluid volume, were 8.6 +/- 3.3 and 8.1 +/- 3.1 ml/kg, and 22.5 +/- 1.5 and 22.1 +/- 1.6 ml/kg in the corresponding protocols. Volume kinetic analysis demonstrated extravascular fluid accumulation associated with isoflurane anesthesia similar to the calculated interstitial accumulation of 20.2 +/- 0.5 and 26.5 +/- 0.3 ml/kg in the ISOSV and ISOMV protocols, respectively. CONCLUSION: Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.

Anesthetics, Inhalation↗

Near-infrared spectroscopy-guided closed-loop resuscitation of hemorrhage.

BACKGROUND: Endpoint resuscitation has been suggested as a better means to resuscitate penetrating injury. We performed computer-controlled closed-loop resuscitation using invasive cardiac output (CO) or noninvasive skeletal muscle oxygen saturation (SkMusSO(2)) via near infrared spectroscopy (NIRS). METHODS: Conscious sheep received a 4.0-mm aortotomy and uncontrolled hemorrhage at t = 0 min (T0) while resuscitation started at T20 using lactated Ringer's solution. RESULTS: The aortotomy rapidly decreased the mean arterial pressure (MAP) to approximately 30 mm Hg and CO to 20% to 30% of baseline. The SkMusSO(2) endpoint group required only half as much fluid through 4 hours of resuscitation as the CO endpoint group (34.9 +/- 8.4 mL/kg vs. 63.1 +/- 9.4 mL/kg). CO and MAP were lower in the SkMusSO(2) group after T60. Mean infusion volumes were 180% and 100% of the bled volume collected at autopsy in the CO and SkMusSO(2) groups. Brain and muscle oxygenation and base excess were as high or higher in the CO endpoint group. CONCLUSION: Closed-loop resuscitation with either CO or SkMusSO(2) endpoints effectively performs fluid resuscitation of severe uncontrolled hemorrhagic shock. Limited resuscitation may achieve favorable clinical results with volumes less than recommended by Advanced Trauma Life Support guidelines.

Animals↗

Organizational factors affect comparisons of the clinical productivity of academic anesthesiology departments.

UNLABELLED: Productivity measurements based on "per operating room (OR) site" and "per case" are not influenced by staffing ratios and have permitted meaningful comparisons among small samples of both academic and private-practice anesthesiology groups. These comparisons have suggested that a larger sample would allow for clinical groups to be compared using a number of different variables (including type of hospital, number of OR sites, type of surgical staff, or other organizational characteristics), which may permit more focused benchmarking. In this study, we used such grouping variables to compare clinical productivity in a broad survey of academic anesthesiology programs. Descriptive, billing, and staffing data were collected for 1 fiscal or calendar year from 37 academic anesthesiology departments representing 58 hospitals. Descriptive data included types of surgical staff (e.g., academic versus private practice) and hospital centers (e.g., academic medical centers and ambulatory surgical centers [ASCs]). Billing and staffing data included total number of cases performed, total American Society of Anesthesiologists units (tASA) billed, total time units billed (15-min units), and daily number of anesthetizing sites staffed (OR sites). Measurements of total productivity (tASA/OR site), billed hours per OR site per day (h/OR/d), surgical duration (h/case), hourly billing productivity (tASA/h), and base units/case were compared. These comparisons were made according to type of hospital, number of OR sites, and type of surgical staff. The ASCs had significantly less tASA/OR site, fewer h/OR/d, and less h/case than non-ASC hospitals. Community hospitals had significantly less h/OR/d and h/case than academic medical centers and indigent hospitals and a larger percentage of private-practice or mixed surgical staff. Academic staffs had significantly less tASA/h and significantly more h/case. tASA/h correlated highly with h/case (r = -0.68). This study showed that the hospitals at which academic anesthesiology groups provide care are not all the same from a clinical productivity perspective. By grouping based on type of hospital, number of OR sites, and type of surgical staff, academic anesthesiology departments (and hospitals) can be better compared by using clinical productivity measurements based on "per OR site" and "per case" measurements (tASA/OR, billed h/OR/d, h/case, tASA/h, and base/case). IMPLICATIONS: Organizational factors, including type of hospital, number of operating rooms, and type of surgical staff, influence the clinical productivity of academic anesthesiology departments. Reporting quartile data by focused grouping variables allows anesthesiology groups to compare their clinical productivity with groups practicing in similar clinical settings.

Academic Medical Centers↗

Inclusion of turnover time does not influence identification of surgical services that over- and underutilize allocated block time.

UNLABELLED: Allocation of operating room (OR) block time is an ongoing challenge for OR managers. In this study, we sought to determine whether inclusion or exclusion of turnover time in comparisons of block utilization would identify different surgical services as under- or overused. For a 13-mo period, we evaluated data extracted from the OR information system of a large academic medical center. During that time period, 15 surgical services performed 12,245 surgical procedures. Allocated block hours, number of first cases performed, total number of cases, and average case durations were determined. The average turnover time for each service was determined by a manual, case-by-case review of data from 1 mo. Raw utilization (RU; case durations only) and adjusted utilization (AU; case duration plus turnover time) were calculated for each service. Turnover time was credited to the service performing surgery after room turnover. Case du-ration was limited to surgeries performed during resource hours. Two indices of utilization (i.e., the usage rate of the service divided by the overall use of all ORs in the suite) were used to compare services: the RU or AU Index (RUI or AUI). Outliers were services with indices that were >1.15 or <0.85. The RUI identified three services as underutilizers and one service as an overutilizer. Using the AUI, the same outliers were identified, and no new services were identified. Examining the changes in index (between AUI and RUI), the percentage of to-follow cases highly correlated with changes in index (r(2) = 0.60); the average turnover time did not (r(2) = 0.002). Inclusion of turnover time did not change the services that were identified as under- and overutilizer. IMPLICATIONS: Turnover time is difficult to determine from existing operating room information systems. This study determined the use of block time with and without turnover time for each surgical service in a large academic hospital. Turnover time did not change identification of surgical services that over- (one service) or underused (three services) allocated block time.

Operating Rooms↗

Labor costs incurred by anesthesiology groups because of operating rooms not being allocated and cases not being scheduled to maximize operating room efficiency.

UNLABELLED: Determination of operating room (OR) block allocation and case scheduling is often not based on maximizing OR efficiency, but rather on tradition and surgeon convenience. As a result, anesthesiology groups often incur additional labor costs. When negotiating financial support, heads of anesthesiology departments are often challenged to justify the subsidy necessary to offset these additional labor costs. In this study, we describe a method for calculating a statistically sound estimate of the excess labor costs incurred by an anesthesiology group because of inefficient OR allocation and case scheduling. OR information system and anesthesia staffing data for 1 yr were obtained from two university hospitals. Optimal OR allocation for each surgical service was determined by maximizing the efficiency of use of the OR staff. Hourly costs were converted to dollar amounts by using the nationwide median compensation for academic and private-practice anesthesia providers. Differences between actual costs and the optimal OR allocation were determined. For Hospital A, estimated annual excess labor costs were $1.6 million (95% confidence interval, $1.5-$1.7 million) and $2.0 million ($1.89-$2.05 million) when academic and private-practice compensation, respectively, was calculated. For Hospital B, excess labor costs were $1.0 million ($1.08-$1.17 million) and $1.4 million ($1.32-1.43 million) for academic and private-practice compensation, respectively. This study demonstrates a methodology for an anesthesiology group to estimate its excess labor costs. The group can then use these estimates when negotiating for subsidies with its hospital, medical school, or multispecialty medical group. IMPLICATIONS: We describe a new application for a previously reported statistical method to calculate operating room (OR) allocations to maximize OR efficiency. When optimal OR allocations and case scheduling are not implemented, the resulting increase in labor costs can be used in negotiations as a statistically sound estimate for the increased labor cost to the anesthesiology department.

Anesthesiology↗

The effects of surgical case duration and type of surgery on hourly clinical productivity of anesthesiologists.

Surgical duration (hours per case; h/case) and type of surgery (ASA base units per case; base/case) determine the hourly clinical productivity (total ASA units per hour of anesthesia care; tASA/h) for anesthesiology groups. In previous studies, h/case negatively influenced tASA/h, but base/case did not differ significantly. However, when cases are grouped by surgical service, the mean base/case varies. In this study we evaluated the effect of h/case and base/case on tASA/h when these are grouped by surgical services. Data from one calendar year were collected from an academic anesthesiology department's billing database. All surgical cases for which the anesthesiology department provided care were included. Cases performed outside the main operating room, e.g., remote sites or obstetrics, were excluded. Any care not billed with ASA units was also excluded. Mean base/case and h/case were determined. For each service, tASA/h was calculated by dividing the sum of base/case and (4 x h/case) by h/case. A total of 12,769 cases were performed by 19 different surgical services. Mean base/case was 6.1 U, with a range of 4.0 U (orthopedics) to 16.0 U (cardiothoracic). Mean h/case was 2.9 h, with a range of 0.9 h (otolaryngology pediatric) to 5.4 h (orthopedic spine). Mean tASA/h was 6.35 U/h, with a range of 5.01 U/h (plastic surgery) to 9.71 U/h (otolaryngology pediatric). The services with high base/case did not necessarily have high tASA/h because of the longer h/case. The services with the shortest h/case had the highest tASA/h. The accurate prediction of both clinical and billing productivity requires inclusion of both base/case and surgical duration data. Anesthesiology groups should consider surgical duration when making strategic decisions.

Algorithms↗

Optoacoustic technique for noninvasive monitoring of blood oxygenation: a feasibility study.

Replacement of invasive monitoring of cerebral venous oxygenation with noninvasive techniques offers great promise in the management of life-threatening neurologic illnesses including traumatic brain injury. We developed and built an optoacoustic system to noninvasively monitor cerebral venous oxygenation; the system includes a nanosecond Nd:YAG laser and a specially designed optoacoustic probe. We tested the system in vitro in sheep blood with experimentally varied oxygenation. Our results demonstrated that (1) the amplitude and temporal profile of the optoacoustic waves increase with blood oxygenation in the range from 24% to 92%, (2) optoacoustic signals can be detected despite optical and acoustic attenuation by thick bone, and (3) the system is capable of real-time and continuous measurements. These results suggest that the optoacoustic technique is technically feasible for continuous, noninvasive monitoring of cerebral venous oxygenation.

Feasibility Studies↗

Anesthetic management of traumatic brain injury.

The management of TBI remains an important and frustrating component of the practice of anesthesiology and critical care medicine. The difficulties in management of TBI as well as the poor response rates to medical therapy after TBI are not new. The following passage appeared in the introductory chapter of a text on TBI from 1897: "The manner of treatment is of importance in only a minority of cases, since many subjects of intracranial injury are fated to die whatever measures may be adopted for their relief, and a still greater number are destined to recover though left entirely to the resources of nature. It is probable that in by far the larger proportion of cases in which the issue is determined by treatment it is met in the initial stage, and by insuring restoration from primary shock" [111]. Although secondary insults from factors such as hypotension, hypoxemia, and hyperventilation increase morbidity and mortality, data are not yet available to indicate whether scrupulous prevention and prompt treatment of secondary injuries will reduce morbidity and mortality. In addition, no specific intervention to date has improved overall long-term outcome. With ongoing research, perhaps active interventions will become available. Until that time, thoughtful and careful attention to physiologic management provides the greatest opportunity for a good outcome.

Anesthesia↗

Influence of rate and volume of infusion on the kinetics of 0.9% saline and 7.5% saline/6.0% dextran 70 in sheep.

UNLABELLED: We examined whether volume kinetic variables obtained during infusion of a short bolus of 0.9% saline (NS) or 7.5% saline/6.0% dextran 70 (HSD) predict the dilution-time curve resulting from a 20-min infusion of the same fluid. Each of six conscious, splenectomized sheep (mean body weight, 36 +/- 3 kg), on 4 different days, in a random order, received each of 4 IV boluses: NS at a rate of 1.2 mL. kg(-1). min(-1) over 5 min or 20 min or 4.0 mL/kg of HSD over 2 min or 20 min. One, 2, and 3-volume kinetic models were fitted to the dilution of the arterial hemoglobin concentration and the urinary excretion as sampled during 180 min. The maximum dilution of arterial plasma at the end of the 5-min and 20-min infusions of NS was approximately 10% and 22%, respectively, and after the 2-min and 20-min infusions of HSD, maximum dilution was 24% and 21%, respectively. The median absolute performance error was virtually identical when the mean variable estimates from the 5-min infusion of NS were used to predict the individual dilution-time curves of the 5-min (mean, 0.027 dilution units) and 20-min (mean, 0.027) infusions and when the 2-min infusion of HSD was used to predict the dilution during the individual 2-min (mean, 0.050) and 20-min infusions (mean, 0.047). Computer simulations indicated that the difference at the end of infusion between the volume effects of NS and HSD is larger after longer infusions. We concluded that the volume kinetic variables obtained during a short infusion can be used to predict the outcome of a longer one, even if the longer infusion also delivers a larger volume. IMPLICATIONS: Kinetic analysis of a short infusion of 7.5% saline/6% dextran or 0.9% saline accurately predicts the effects of a longer infusion of the same volume (7.5% saline/6% dextran) or of a larger volume (0.9% saline).

Animals↗

Volume kinetic analysis of the distribution of 0.9% saline in conscious versus isoflurane-anesthetized sheep.

BACKGROUND: The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. METHODS: Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes. RESULTS: The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma. CONCLUSIONS: In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.

Algorithms↗

Comparing clinical productivity of anesthesiology groups.

BACKGROUND: Intergroup comparisons of clinical productivity are important for strategic planning and evaluation of clinical and business operations. However, in a preliminary study, comparisons of two anesthesiology groups using "per full-time equivalent" measurements were confounded by different concurrencies or staffing ratios, whereas measurements based on "per operating room (OR) site," "per case," and "billed American Society of Anesthesiologists (ASA) units per hour of care" permitted meaningful comparisons despite differing concurrencies. The purpose of this study was to determine whether these measurements would allow for meaningful comparisons when applied to multiple groups. METHODS: Annual totals of total ASA units (tASA), 15-min time units, and the number of cases billed, as well as the average number of daily anesthetizing sites (OR sites) staffed and the average number of anesthesiologists required to the staff sites, were collected from each group that participated. All anesthesia care billed with ASA units was included, except for obstetric care. Any clinical service not billed using ASA units was excluded. Productivity measurements (concurrency, tASA/OR site, hours billed per OR site per day, hours billed per case, tASA billed per hour of anesthesia care, and base units per case) were calculated. Median and range for all groups and for private-practice and academic groups were determined. RESULTS: Eleven private-practice and nine academic groups from 12 states participated in the study. Productivity measurements that are influenced by duration of surgery (hours billed per case, tASA billed per hour of anesthesia care) differed significantly between groups, with private-practice groups having shorter duration than academic groups (median hours billed per case, 1.5 2.6, respectively). Although tASA/OR site measurements were similar in private-practice and academic groups, academic groups worked significantly longer hours billed per OR site per day (median, 6.0 h 7.8, respectively) to achieve the same level of tASA/OR site. Hourly billing productivity (tASA billed per hour of anesthesia care) correlated highly with surgical duration (hours billed per case). CONCLUSION: This study demonstrates a method of comparing departmental clinical productivity between anesthesiology groups. Private-practice groups provided care for cases of shorter duration than academic groups. This difference was evident in several productivity measurements.

Anesthesiology↗