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Biomedical subjects

Bruce D Spiess

Publications and source records attributed to Bruce D Spiess.

At least 19 recordsLinked to original sources

A new noninvasive method to determine central venous pressure.

UNLABELLED: Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. OBJECTIVES: We tested a noninvasive means of determining CVP (NICVP), by monitoring forearm volume changes in response to externally applied circumferential pressure to the upper arm veins. METHODS: Sixteen patients who were undergoing CVP monitoring as a part of their care had NICVP determined and compared with CVP. Volume changes were measured in the forearm with mercury-in-silastic strain gauge plethysmography. A pressure cuff is placed in the upper extremity. The cuff is inflated over 5s to a pressure above CVP but below diastolic arterial pressure (40 mmHg). This allows blood into the forearm but prevents venous return. After 45-60 s the cuff is rapidly deflated. NICVP was determined as the cuff pressure noted at the maximum derivative of the forearm volume decrease during deflation. NICVP was then compared to invasively measured CVP taken during the same period. RESULTS: A total of 48 trials (three per subject) were performed on 16 patients. The range of CVP recorded was 0-22 mmHg. The correlation between CVP and NICVP was 0.98 (95% CI: 0.95-0.98) (p<0.001). The bias between methods was 0.26 mmHg with the limits of agreement being 3.4 to -2.89 mmHg. When the average of three trials per patients was analysed the bias stayed at 0.26 mmHg but the limits of agreement improved to 2.54 and -2.03 mmHg. CONCLUSION: NICVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a valid tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.

Adult↗

Anticoagulation with bivalirudin for off-pump coronary artery bypass grafting: the results of the EVOLUTION-OFF study.

OBJECTIVES: Unfractionated heparin has many shortcomings, including indirect and partial inhibition of thrombin, antibody formation, and platelet activation. Bivalirudin, a short-acting direct thrombin inhibitor, avoids these limitations and has superior outcomes during percutaneous revascularization. This trial was performed to evaluate the safety and efficacy of bivalirudin in off-pump coronary artery bypass grafting. METHODS: An open-label, multicenter randomized trial compared heparin with protamine reversal to bivalirudin in patients undergoing off-pump coronary artery bypass. The primary objective was safety as demonstrated by similar rates of procedural success defined as freedom from a composite of death, myocardial infarction, stroke, and repeat revascularization. Twenty-one institutions randomized 105 patients to receive bivalirudin and 52 patients to receive heparin. RESULTS: The mean age was 65 years for both groups. The bivalirudin group had more grafts: 3.0 +/- 1 versus 2.5 +/- 1. Procedural success rates at 30 days were identical in bivalirudin- and heparin-treated patients (93%). Operative times, total blood loss, reoperations for bleeding, and major adverse events were not significantly different. Strokes were more frequent in the heparin group: 5.5% versus 0; P = .05. Mortality was 2% in each group. Repeat revascularization was required in 3% of bivalirudin- and 2% of the heparin-treated patients. CONCLUSIONS: For patients undergoing off-pump coronary artery bypass grafting, bivalirudin was an effective anticoagulant, without excessive bleeding and with a safety profile similar to that of heparin. Further trials are warranted to assess whether anticoagulation with bivalirudin improves clinical outcomes.

Aged↗

Bivalirudin anticoagulation for a patient with hypercoagulable immune syndromes undergoing mitral valve surgery.

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Adult↗

A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.

OBJECTIVES: Unfractionated heparin and its antidote, protamine sulfate, allow for rapid and reversible anticoagulation during cardiac surgery with cardiopulmonary bypass, yet limitations exist, including a variable dose-response, dependence on a cofactor for anticoagulant effect, and antigenic potential. This trial was performed to evaluate the safety and efficacy of bivalirudin as an alternative to heparin with protamine reversal in on-pump cardiac surgery. METHODS: We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass. The primary objective was to demonstrate comparable rates of in-hospital procedural success defined as freedom from death, Q-wave myocardial infarction, stroke, or repeat revascularization. Twenty-one institutions enrolled 101 patients randomized to bivalirudin and 49 patients to heparin treatment. RESULTS: The primary end point of procedural success was not significantly different between the bivalirudin arm and the heparin/protamine arms at 7 days, 30 days, or 12 weeks' follow-up. Adequate anticoagulation was achieved in all patients. Secondary end points including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar between the two arms. CONCLUSIONS: Bivalirudin is a safe and effective anticoagulant for patients undergoing a wide range of cardiac surgical procedures with cardiopulmonary bypass. Procedural success rates with bivalirudin were similar to rates in patients receiving heparin anticoagulation, with no difference in mortality. Avoidance of blood stasis and attention to the intraoperative medical management of patients is critical for successful use of bivalirudin during cardiopulmonary bypass.

Aged↗

Full-dose aprotinin use in coronary artery bypass graft surgery: an analysis of perioperative pharmacotherapy and patient outcomes.

BACKGROUND: Inappropriate activation of hemostasis and inflammation may contribute to postoperative morbidity and mortality. The serine protease inhibitor, aprotinin, has been shown to prevent tissue and organ injury in laboratory and animal studies. In this retrospective analysis, we evaluated the relationship of aprotinin therapy with organ dysfunction in humans undergoing coronary artery bypass graft surgery (CABG). METHODS: Data from prospective randomized, double-blind, placebo-controlled studies evaluating the safety and efficacy of full-dose aprotinin (2 million KIU load, 2 million KIU pump prime, and 0.5 million KIU/h continuous infusion) to reduce blood loss and transfusion requirements in patients undergoing CABG (placebo, n = 861; aprotinin, n = 862) were examined retrospectively. Primary end-points were death, adverse cerebrovascular outcome, myocardial infarction (MI), and pharmacological interventions (inotropic drugs, vasopressors, and antiarrhythmics). RESULTS: Univariate analysis showed that relative to placebo, full-dose aprotinin therapy was associated with significant effects on the incidence of adverse cerebrovascular outcome (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.19-0.93; P = 0.03) and use of inotropic drugs (OR 0.79, 95% CI 0.65-0.97; P = 0.02), vasopressors (OR 0.74, 95% CI 0.61-0.90; P < 0.01), and antiarrhythmics (OR 0.79, 95% CI 0.65-0.96; P = 0.02), but not death (OR = 1.00, 95% CI 0.54-1.85; P = 1.0) or MI (OR 0.92, 95% CI 0.64-1.31; P = 0.6). Multivariate analysis confirmed results of univariate analysis. CONCLUSIONS: This retrospective analysis of data collected from prospective, randomized, placebo-controlled studies in CABG shows that full-dose aprotinin use was associated with a lower risk of adverse cerebrovascular outcomes and a reduced need for use of vasoactive drugs; the risk of death and perioperative MI was not affected by aprotinin therapy.

Aged↗

Update on heparin-induced thrombocytopenia and cardiovascular interventions.

Although heparin/protamine has been the standard anticoagulation regimen in cardiac surgery for decades, it induces negative reactions within the vasculature. Heparin-induced thrombocytopenia (HIT) is a highly prothrombotic immune reaction to heparin that may result in death, limb ischemia leading to amputation, graft occlusion, and other severe thrombotic events. Patients undergoing cardiac surgery are at high risk for HIT antibody seroconversion and at risk for clinical HIT. For patients with acute or subacute HIT and needing urgent cardiac surgery, accepted protocols for alternative, non-heparin anticoagulation are needed. The direct thrombin inhibitor bivalirudin offers promise in this area and is currently being evaluated in multicenter trials as an alternative for heparin/protamine in patients with HIT undergoing cardiac surgery.

Anticoagulants↗

Systemic responses to hemodilution after transfusion with stored blood and with a hemoglobin-based oxygen carrier.

We assessed the systemic effects of exchanges with blood or hemoglobin (Hb) raffimer under conditions of critical oxygen delivery (Do(2)crit). We compared Do(2)crit in animals receiving Hb-based oxygen carrier (HBOC; Hemolink), fresh blood (collected <24 h), or stored blood (10 days) before hemodilution. Rats were randomized to control, blood, or HBOC isovolemic exchange. Oxygen consumption was measured by using expired gas (o(2)a) and blood (o(2)b) samples, whereas whole-body oxygen delivery (Do(2)) was calculated from cardiac output and arterial oxygen content. After exchange, rats were subjected to stepwise isovolemic hemodilution. Blood pressure, gases, acid-base status, glucose, Hb oxygen saturation, heart rate, and total peripheral resistance were also measured. We found that 1) HBOC-treated rats showed an increased mean arterial blood pressure and total peripheral resistance throughout the hemodilution, 2) Do(2)crit calculated with o(2)a or o(2)b gave identical results, 3) Do(2)crit was not different between animals receiving blood and those receiving HBOC, 4) the terminal Hb concentration (1.8 +/- 0.1 g/dL) and Do(2) (5 +/- 1 mL . min(-1) . kg(-1)) were similar for all animals, and 5) most oxygen transport and biochemical variables changed similarly during hemodilution. The data suggest that tolerance to Do(2)crit is not altered by 50% replacement of native Hb by stored blood or Hb raffimer.

Animals↗

Effect of perfluorocarbons on brain oxygenation and ischemic damage in an acute subdural hematoma model in rats.

OBJECT: This study was conducted to determine whether perfluorocarbons (PFCs) improve brain oxygenation and reduce ischemic brain damage in an acute subdural hematoma (SDH) model in rats. METHODS: Forty adult male Sprague-Dawley rats were allocated to four groups: (1) controls, acute SDH treated with saline and 30% O2; (2) 30-PFC group, acute SDH treated with PFC infusion in 30% O2; (3) 100-O2 group, acute SDH treated with 100% O2; and (4) 100-PFC group, acute SDH treated with PFC plus 100% O2. Ten minutes after the induction of acute SDH, a single dose of PFC was infused and 30% or 100% O2 was administered simultaneously. Four hours later, half of the rats were killed by perfusion for histological study to assess the extent of ischemic brain damage. The other half were used to measure brain tissue oxygen tension (PO2). The volume of ischemic brain damage was 162.4 +/- 7.6 mm3 in controls, 165.3 +/- 11.3 mm3 in the 30-PFC group, 153.4 +/- 17.3 mm3 in the 100-O2 group, and 95.9 +/- 12.8 mm3 in the 100-PFC group (41% reduction compared with controls, p = 0.002). Baseline brain tissue PO2 values were approximately 20 mm Hg, and after induction of acute SDH, PO2 rapidly decreased and remained at 1 to 2 mm Hg. Treatment with either PFC or 100% O2 improved brain tissue PO2, with final values of 5.14 and 7.02 mm Hg, respectively. Infusion of PFC with 100% O2 improved brain tissue PO2 the most, with a final value of 15.16 mm Hg. CONCLUSIONS: Data from the current study demonstrated that PFC infusion along with 100% O2 can significantly improve brain oxygenation and reduce ischemic brain damage in acute SDH.

Acute Disease↗

Experimental analysis of critical oxygen delivery.

Systemic variables were evaluated with respect to O(2) delivery to test the hypothesis that critical O(2) delivery and critical Hb can be estimated by multiple variables collected simultaneously. Rats were subjected to transfusion with either fresh or stored blood and then subjected to stepwise isovolemic hemodilution. Critical levels were measured by the dual-regression method from plots of systemic variables against O(2) delivery and Hb. Delivery was calculated from cardiac index and arterial O(2) content. We found that 1) after hemodilution, O(2) delivery changed in a nonlinear relationship with Hb; 2) critical delivery calculated using 30 different systemic variables was not statistically different from each other; 3) critical delivery and critical Hb were correlated but were not different between animals receiving fresh or stored blood; and 4) similar critical levels were found using a single variable from several animals and using several variables from the same subject. The best variables to estimate critical delivery were lactate, bicarbonate, base excess, O(2) extraction ratio, expired CO(2), pulse pressure, cardiac index, and systolic pressure. The data suggest that a multivariable analysis of critical delivery may help determine the physiological oxygenation boundary at the whole body level. This may assist in finding therapeutic triggers on an individual basis using systemic markers of the transition from aerobic to anaerobic metabolism.

Animals↗

Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes.

BACKGROUND: Platelet (PLT) transfusions are administered in cardiac surgery to prevent or treat bleeding, despite appreciation of the risks of blood component transfusion. The current analysis investigates the hypothesis that PLT transfusion is associated with adverse outcomes associated with coronary artery bypass graft surgery (CABG). STUDY DESIGN AND METHODS: Data originally collected during double-blind placebo-controlled phase III trials for licensure of Trasylol (aprotinin injection) were retrospectively analyzed. Adverse outcome data of patients (n = 1720) that received, and did not receive, perioperative PLT transfusion were compared. Logistic regression analysis was used to assess the association of perioperative adverse events with PLT transfusion. Propensity scoring analysis was used to verify results of the logistic regression. RESULTS: Patients receiving PLTs were more likely to have prolonged hospital stays, longer surgeries, more bleeding, re-operation for bleeding, and more RBC transfusions, and less likely to have full-dose aprotinin administration. Adverse events were statistically more frequent in patients that received one or more PLT transfusion. Logistic regression analysis showed that PLT transfusion was associated with infection, vasopressor use, respiratory medication use, stroke, and death. Propensity scoring analysis confirmed the risk of PLT transfusion. CONCLUSIONS: PLT transfusion in the perioperative period of CABG was associated with increased risk for serious adverse events. PLT transfusion may be a surrogate marker for sicker patients and have no causal role in the outcomes observed. However, a direct contribution to outcomes remains possible.

Aged↗

Transfusion of blood products affects outcome in cardiac surgery.

There remains controversy as to when patients undergoing cardiac surgery should receive a transfusion and whether a low hematocrit and its treatment with a transfusion of red cells influences outcome. The data related to this controversy are reviewed. Although the risk of known viral transmission is currently low, stored red cells do not function normally, and each unit contains activated inflammatory cells and mediators. These changes cause limited oxygen release, impaired microcirculatory flow, and immune suppression. A number of studies have observed decreased survival associated with transfusions in trauma, coronary artery bypass grafting, and intensive care unit patients. Studies that show an adverse outcome associated with low hematocrit are not definitive, because they fail to distinguish between the impact of low hematocrit per se and the possible adverse effects of transfusion, for what the low hematocrit may simply be a surrogate. The observation that a low hematocrit is associated with an adverse outcome does not necessarily prove that "treatment" of the anemia with a red cell transfusion will improve the outcome. Stored platelets contain a highly activated mixture of platelets with storage lesions and inflammatory mediators. Two retrospective post hoc multifactorial analyses suggest that platelet transfusions are associated with substantial increased morbidity and mortality. Clearly, large prospective studies are required to define the proper trigger for blood product transfusion to balance the adverse effects of anemia and platelet deficiency or dysfunction with the adverse effects of transfusion of blood products on morbidity and mortality associated with cardiac surgery and anesthesia.

Animals↗

Perfluorocarbon emulsion improves cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats.

OBJECTIVE: Cerebral ischemia is a common secondary sequela of traumatic brain injury (TBI). Experimental models of stroke have demonstrated reductions in ischemia after perfluorocarbon (PFC) administration; however, there are no published reports of PFC efficacy after TBI. The current study analyzed the effect of the PFC emulsion Oxygent (AF0144; Alliance Pharmaceutical Corp., San Diego, CA) on cerebral oxygenation, mitochondrial redox potential, and free radical formation after lateral fluid percussion injury. METHODS: After fluid percussion injury, five 2.25 ml/kg doses of PFC or saline were administered to rats breathing 100% O(2), and oxygen tension was recorded. In a second experiment, a single bolus (11.25 ml/kg) of PFC or saline was given after injury, and redox potential and free radical formation were measured at 1 or 4 hours with Alamar blue dye and dihydrorhodamine 123, respectively. RESULTS: Cerebral oxygen tension was significantly increased in both injured and sham animals treated with 11.25 ml/kg of PFC as compared with saline (P < 0.05). Likewise, PFC significantly increased mitochondrial redox potential as compared with saline at 4 hours after injury (P < 0.01). Mitochondrial peroxynitrite and peroxide production also increased with the administration of PFC (P < 0.05). CONCLUSION: The current study demonstrates that a PFC emulsion can significantly increase cerebral oxygenation after TBI and enhance mitochondrial function at 4 hours after injury as compared with saline. This study demonstrates a new therapeutic potential for PFC to enhance cerebral oxygenation and aerobic metabolism after TBI. However, the increased free radical formation with high-dose PFCs suggests the need for further studies combining PFCs with free radical scavengers.

Animals↗

Treatment of decompression sickness in swine with intravenous perfluorocarbon emulsion.

BACKGROUND: We examined an adjunctive treatment for severe decompression sickness (DCS) to be used when hyperbaric treatment is delayed or unavailable. HYPOTHESIS: It has been hypothesized that intravenous perfluorocarbon (PFC) emulsion combined with 100% inspired O2 would improve the outcome in severe DCS. METHODS: Swine (n = 45) were compressed to 4.9 ATA on air for 22 h and brought directly to 1 ATA at 0.9 ATA min(-1). The animals were then randomized to three groups. The first group breathed ambient air, the second group breathed 100% O2, and a third group received 6 ml x kg(-1) of perflubron emulsion (Oxygent) intravenously and breathed 100% O2. Outcomes of neurological and cardiopulmonary DCS and death were recorded. RESULTS: Animals that received PFC emulsion sustained less DCS (p < 0.01) than the other groups (53% vs. 93%). No animals in the PFC group sustained neurological DCS, which was present in 69% of the subjects in the other two groups. CONCLUSION: O2 breathing postdive did not significantly reduce morbidity or mortality in this model. Postdive treatment with PFC emulsion and 100% O2 decreased the incidence of DCS after nonstop decompression from saturation.

Animals↗