Stephen J. Thomas

Thyroid hormone treatment after coronary-artery bypass surgery.

BACKGROUNDnThyroid hormone has many effects on the cardiovascular system. During and after cardiopulmonary bypass, serum triiodothyronine concentrations decline transiently, which may contribute to postoperative hemodynamic dysfunction. We investigated whether the perioperative administration of triiodothyronine (liothyronine sodium) enhances cardiovascular performance in high-risk patients undergoing coronary-artery bypass surgery.nnnMETHODSnWe administered triiodothyronine or placebo to 142 patients with coronary artery disease and depressed left ventricular function. The hormone was administered as an intravenous bolus of 0.8 microgram per kilogram of body weight when the aortic cross-clamp was removed after the completion of bypass surgery and then as an infusion of 0.113 microgram per kilogram per hour for six hours. Clinical and hemodynamic responses were serially recorded, as was any need for inotropic or vasodilator drugs.nnnRESULTSnThe patients preoperative serum triiodothyronine concentrations were normal (mean [+/- SD] value, 81 +/- 22 ng per deciliter [1.2 +/- 0.3 nmol per liter]), and they decreased by 40 percent (P < 0.001) 30 minutes after the onset of cardiopulmonary bypass. The concentrations in patients given intravenous triiodothyronine became supranormal and were significantly higher than those in patients given placebo (P < 0.001). However, the concentrations were once again similar in the two groups 24 hours after surgery. The mean postoperative cardiac index was higher in the triiodothyronine group (2.97 +/- 0.72 vs. 2.67 +/- 0.61 liters per minute per square meter of body-surface area, P = 0.007), and systemic vascular resistance was lower (1073 +/- 314 vs. 1235 +/- 387 dyn.sec.cm-5, P = 0.003). The two groups did not differ significantly in the incidence of arrhythmia or the need for therapy with inotropic and vasodilator drugs during the 24 hours after surgery, or in perioperative mortality and morbidity.nnnCONCLUSIONSnRaising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.

Improvement of outcomes after coronary artery bypass: A randomized trial comparing intraoperative high versus low mean arterial pressure

BACKGROUNDnThe objective of this randomized clinical trial of elective coronary artery bypass grafting was to investigate whether intraoperative mean arterial pressure below autoregulatory limits of the coronary and cerebral circulations was a principal determinant of postoperative complications. The trial compared the impact of two strategies of hemodynamic management during cardiopulmonary bypass on outcome. Patients were randomized to a low mean arterial pressure of 50 to 60 mm Hg or a high mean arterial pressure of 80 to 100 mm Hg during cardiopulmonary bypass.nnnMETHODSnA total of 248 patients undergoing primary, nonemergency coronary bypass were randomized to either low (n = 124) or high (n = 124) mean arterial pressure during cardiopulmonary bypass. The impact of the mean arterial pressure strategies on the following outcomes was assessed: mortality, cardiac morbidity, neurologic morbidity, cognitive deterioration, and changes in quality of life. All patients were observed prospectively to 6 months after the operation.nnnRESULTSnThe overall incidence of combined cardiac and neurologic complications was significantly lower in the high pressure group at 4.8% than in the low pressure group at 12.9% (p = 0.026). For each of the individual outcomes, the trend favored the high pressure group. At 6 months after coronary bypass for the high and low pressure groups, respectively, total mortality rate was 1.6% versus 4.0%, stroke rate 2.4% versus 7.2%, and cardiac complication rate 2.4% versus 4.8%. Cognitive and functional status outcomes did not differ between the groups.nnnCONCLUSIONnHigher mean arterial pressures during cardiopulmonary bypass can be achieved in a technically safe manner and effectively improve outcomes after coronary bypass.

Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study.

Advanced atheromatous disease of the thoracic aorta identified by transesophageal echocardiography (TEE) is a major risk factor for perioperative stroke.This study investigated whether varying degrees of atherosclerosis of the descending aorta, as assessed by TEE, are an independent predictor of cardiac and neurologic outcome in patients undergoing coronary artery bypass grafting (CABG). Intraoperative TEE of the descending aorta was performed on 189 of 248 patients participating in a randomized controlled trial of low (50-60 mm Hg) or high (80-100 mm Hg) mean arterial pressure during cardiopulmonary bypass for elective CABG. Aortic atheromatous disease was graded from I to V in order of increasing severity by observers blinded to outcome. Measured outcomes were death, stroke, and major cardiac events assessed at 1 wk and 6 mo. Nine of the 189 patients with TEE examinations had perioperative strokes by 1 wk. At 1 wk, no strokes had occurred in the 123 patients with atheroma Grades I or II, while the 1-wk stroke rate was 5.5% (2/36), 10.5% (2/19), and 45.5% (5/11) for Grades III, IV, and V, respectively (Fishers exact test, P = 0.00001). For 6-mo outcome, advancing aortic atheroma grade was a univariate predictor of stroke (P = 0.00001) and death (P = 0.03). By 6 mo there were one additional stroke, three additional deaths, and one additional major cardiac event. Atheromatous disease of the descending aorta was a strong predictor of stroke and death after CABG. TEE determination of atheroma grade is a critical element in the management of patients undergoing CABG surgery. (Anesth Analg 1996;83:701-8)

C5a and Thromboxane Generation Associated with Pulmonary Vaso- and Broncho-constriction during Protamine Reversal of Heparin

The authors conducted a study in humans to determine the mediators associated with acute pulmonary vaso- and broncho-constriction occurring episodically with protamine reversal of heparin anticoagulation. Of 48 adult patients investigated prospectively after termination of cardiopulmonary bypass, two presented a sudden increase of airway pressure, acute pulmonary hypertension, and systemic hypotension 1-3 min after right atrial protamine injection. In these two subjects, plasma levels of C5a increased from 0.7 and 2.2 to 9.8 and 9.9 ng/ml, respectively, and thromboxane B2 increased from 0.26 and 0.34 to 7.5 and 16.2 ng/ml 1 minute after drug injection. A third subject not identified prospectively had an identical reaction and mediator profile (C5a, 10.2 ng/ml; TxB2, 18.6 ng/ml at 1 min). The plasma levels of these mediators were unchanged in the remaining patients (C5a, 0.7 +/- 1.1 [x +/- S.D.] to 0.6 +/- 0.9 ng/ml; TxB2, 0.16 +/- 0.12 to 0.15 +/- 0.07 ng/ml). Plasma histamine was not involved in this type of reaction, but increased from 0.7-10.4 ng/ml in a fourth patient who became hypotensive without acute pulmonary hypertension, bronchoconstriction, or elevation of C5a or TxB2. The authors data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.

Comprehensive Multimodality Blood Conservation: 100 Consecutive CABG Operations Without Transfusion

BACKGROUNDnDespite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open heart surgical procedures. We hypothesized that a comprehensive multimodality blood conservation program applied algorithmically on the basis of bleeding and transfusion risk would provide a maximum, cost-effective, and safe reduction in postoperative bleeding and allogeneic blood transfusion.nnnMETHODSnOne hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor-based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group-matched patients.nnnRESULTSnOne hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 +/- 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 +/- 270 mL versus 370 +/- 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group-matched patients.nnnCONCLUSIONSnComprehensive risk factor-based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine - Preliminary Report.

Background The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication‐competent, recombinant vesicular stomatitis virus (rVSV)–based vaccine candidate designed to prevent EVD. Methods We conducted two phase 1, placebo‐controlled, double‐blind, dose‐escalation trials of an rVSV‐based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV‐ZEBOV vaccine (3 million plaque‐forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. Results The most common adverse events were injection‐site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme‐linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV‐Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. Conclusions This Ebola vaccine candidate elicited anti‐Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV&Dgr;G‐ZEBOV‐GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408.)

Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding

BACKGROUNDnPostoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. The benefit of the acute removal and reinfusion of fresh autologous blood around the time of cardiopulmonary bypass-a technique known as intraoperative autologous donation (IAD)-has not been universally accepted. We sought to more clearly evaluate the effects of IAD on allogeneic transfusion and postoperative bleeding by removing, preserving, and reinfusing a calculated maximum volume of fresh autologous whole blood.nnnMETHODSnNinety patients undergoing coronary artery bypass grafting or valvular operations were prospectively randomized to either have (IAD group) or not have (control group) calculated maximum volume IAD performed. Treatment was otherwise identical. Transfusion guidelines were uniformly applied to all patients.nnnRESULTSnAn average volume of 1,540 +/- 302 mL of fresh autologous blood was removed and reinfused in the IAD group. Postoperative hematocrits were significantly greater at 12 and 24 hours postoperatively in the IAD group versus the control group despite a significant decrease in both the percentage of patients in whom allogeneic red blood cells were transfused (17% versus 52%; p < 0.01) and the number of red blood cell units transfused per patient per group (0.28 +/- 0.66 and 1.14 +/- 1.19 units; p < 0.01). Conversely, chest tube output, incidence of excessive postoperative bleeding, postoperative prothrombin time, and platelet and coagulation factor transfusion requirement did not differ between groups.nnnCONCLUSIONSnThese results indicate that intraoperative autologous donation serves to preserve red blood cell mass. Its routine use in eligible patients is therefore justified. However, the removal and reinfusion of an individually calculated maximum volume of fresh autologous blood had no effect on postoperative bleeding or platelet and coagulation factor transfusion requirement. This lack of hemostatic effect belies the beliefs of many about the primary action of IAD, helps to delineate the optimal way in which to perform IAD, and carries implications regarding the use of allogeneic platelet and coagulation factors for the treatment of early postoperative bleeding.

The Effect of Hemodilution with Albumin or Ringer's Lactate on Water Balance and Blood Use in Open-Heart Surgery

To determine the effect of intraoperative albumin administration on blood use, water balance, and postoperative clinical course, we studied two groups of adult cardiac surgical patients. Group I (30 patients) received 25 gm of albumin during withdrawal of 2 units of blood prior to cardiopulmonary bypass (CPB) and 50 gm of albumin in the oxygenator prime. Group II (32 patients) received no albumin prior to the end of CPB. No difference in clinical course could be identified, nor was there a significant difference in blood use. Group I patients had lower hematocrit values intraoperatively from the time of blood withdrawal until the conclusion of operation. Coronary artery bypass operations were associated with greater positive water balance than were heat valve operations. Forty-three percent of the patients having coronary artery bypass grafting had a positive water balance greater than 5 liters, whereas 50% of those undergoing valve procedures had a balance less than 3 liters. We conclude that the principal effect of withholding albumin under these circumstances is to increase net positive water balance. The greater positive water balance does not appear to be detrimental.

Preventing Dengue — Is the Possibility Now a Reality?

Dengue is a mosquito-borne flaviviral illness that is endemic in the tropics and subtropics. An estimated 390 million infections occur annually, of which 96 million have clinical manifestations.1 Although mortality is relatively lower than that for other tropical infectious diseases, the scale of human suffering and economic resources that are expended to control dengue makes it a major global public health problem.2 The factors driving transmission and infection persist without evidence of decline. For these reasons, the world needs a safe and effective dengue vaccine. Infection with one of the four types of dengue virus (serotypes 1, 2, 3, and .xa0.xa0.

Computerized data collection in the operating room during coronary artery bypass surgery: A comparison to the hand-written anesthesia record

OBJECTIVEnTo investigate variability between hand-written and computerized anesthesia records and evaluate any associated bias.nnnDESIGN AND MEASUREMENTSnA computer system that was used to collect intraoperative data for a study of hemodynamic management during coronary artery bypass graft surgery is described. The system collected and recorded hemodynamic data automatically downloaded from the anesthesia monitor as well as surgical events and drug administration data entered through menu options. The system then combined, summarized, and graphed the data as well as formatted it for export to a commercially available database program. In a sample of 14 patients, blood pressure data collected by the computer system was compared with the blood pressure data charted in the hand-written anesthesia record.nnnMAIN RESULTSnAlthough general linear models controlling for within-patient variation and randomization assignment for mean arterial pressure range on cardiopulmonary bypass showed a significant relationship; low R2 values indicated that much of the variability could not be explained and that there was, therefore, poor agreement between the two records. Furthermore, a systematic bias in the hand-written anesthesia record was found when the computer system record was compared with the hand-written record and to the difference of the two records, so that extremes seen in the computer system record tended to be minimized in the hand-written anesthesia record.nnnCONCLUSIONSnBecause of the lack of explained variability between the computer system and hand-written anesthesia records and the bias in the hand-written anesthesia record, the hand-written anesthesia record should not be relied on as a source of accurate data for research purposes.