William D. Spotnitz

Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation

BACKGROUND Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia. METHODS We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%). RESULTS In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012). CONCLUSIONS Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.

Hemostats, sealants, and adhesives: components of the surgical toolbox

The surgical toolbox is expanding, and newer products are being developed to improve results. Reducing blood loss so that bloodless surgery can be performed may help minimize morbidity and length of stay. As patients, hospital administrators, and government regulators desire less invasive procedures, the surgical technical challenge is increasing. More operations are being performed through minimally invasive incisions with laparoscopic, endoscopic, and robotic approaches. In this setting, tools that can reduce bleeding by causing blood to clot, sealing vessels, or gluing tissues are gaining an increasing importance. Thus, hemostats, sealants, and adhesives are becoming a more important element of surgical practice. This review is designed to facilitate the readers basic knowledge of these tools so that informed choices are made for controlling bleeding in specific clinical situations. Such information is useful for all members of the operative team. The team includes surgeons, anesthesiologists, residents, and nurses as well as hematologists and other medical specialists who may be involved in the perioperative care of surgical patients. An understanding of these therapeutic options may also be helpful to the transfusion service. In some cases, these materials may be stored in the blood bank, and their appropriate use may reduce demand for other transfusion components. The product classification used in this review includes hemostats as represented by product categories that include mechanical agents, active agents, flowables, and fibrin sealants; sealants as represented by fibrin sealants and polyethylene glycol hydrogels; and adhesives as represented by cyanoacrylates and albumin cross‐linked with glutaraldehyde. Only those agents approved by the Food and Drug Administration (FDA) and presently available (February 2008) for sale in the United States are discussed in this review.

Neurosurgical applications of fibrin glue: augmentation of dural closure in 134 patients

In a wide variety of neurosurgical procedures performed on 134 patients over a 3-year period, fibrin glue has been applied as an adjunct to dural closure. Overall success at preventing cerebrospinal fluid (CSF) leakage was 90% (121 of 134, 90% effective). In patients considered to be at high risk for CSF leakage intraoperatively but without pre-established fistulae (Group 1), the success rate was higher (111 of 119, 93% effective). In patients with pre-established CSF fistulae (Group 2), the success rate was lower (10 of 15, 67% effective). As single donor sources of concentrated fibrinogen are now available with reduced risks of blood-borne disease transmission, fibrin glue may be a valuable clinical tool for the neurosurgeon.

Fibrin Sealant: Past, Present, and Future: A Brief Review

BackgroundFibrin sealant is a two-component topical hemostat, sealant, and tissue adhesive consisting of fibrinogen and thrombin that has been used in the United States as a blood bank- or laboratory-derived product since the 1980s and has been commercially available since 1998.Methods/resultsInitially, surgeons employed hospital-based materials because of the lack of availability of a commercially produced agent. At present, there are five U.S. Food and Drug Administration (FDA)-approved forms including products derived from pooled or autologous human plasma as well as bovine plasma. On-label indications include hemostasis, colonic sealing, and skin graft attachment. Recent clinical and experimental uses include tissue or mesh attachment, fistula closure, lymphatic sealing, adhesion prevention, drug delivery, and tissue engineering.ConclusionsThe modern literature on fibrin sealant now exceeds 3000 articles and continues to expand. This brief review presents the history of this material, its present clinical use, and its future applications.

Commercial fibrin sealants in surgical care.

Fibrin sealants can be a valuable adjunct to surgical procedures. A variety of commercial products have been developed. Specific uses include hemostasis, tissue sealing, and even drug delivery. This review summarizes the components, mechanism of action, and clinical uses of fibrin sealants in modern surgical care.

Fibrin sealant reduces the duration and amount of fluid drainage after axillary dissection: a randomized prospective clinical trial.

BACKGROUND Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect. STUDY DESIGN Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant. RESULTS The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect. CONCLUSIONS Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.

THE ROLE OF SUTURES AND FIBRIN SEALANT IN WOUND HEALING

Sutures and fibrin sealant are important surgical aids for facilitating wound closure and creating an optimal setting for wound healing. Most commonly, sutures are used to close wounds because suture material provides the mechanical support necessary to sustain closure. A wide variety of suturing material is available, and the surgeon can choose among sutures with a range of attributes to find the one best suited to his or her needs. Considerations when choosing an appropriate suture for wound closure and healing include strength of suture, holding power of tissue, absorbability, risk of infection, and inflammatory reaction associated with the suture material. Other factors to be considered include type of incision, suturing technique, and appearance of wound site. Fibrin sealant, in contrast, is a biologic tissue adhesive that can function as a useful adjunct to sutures. Fibrin sealant can be used in conjunction with sutures or tape to promote optimal wound integrity, or it can be used independently to seal wound sites where sutures cannot control bleeding or would aggravate bleeding. This adhesive can effectively seal tissue planes and eliminate potential spaces. Fibrin sealant has been used clinically in many surgical applications, although an FDA-approved commercially available product does not yet exist in the United States. Clinically, fibrin sealant has resulted in a low rate of infection and has promoted healing. Further study is needed to determine the best fibrin sealant mixtures both to achieve hemostasis and to encourage healing. It may even be desirable to use different sealant formulations for particular clinical situations.

Four years' experience with fibrin sealant in thoracic and cardiovascular surgery

A single-donor fibrin sealant system was used in 689 thoracic and cardiovascular surgical procedures over the 4-year period between April 1, 1985, and March 31, 1989. An excellent overall success rate (646/689, 94% effective) was achieved with specific applications, including reduction of leakage of air (29/33, 88% effective), blood (595/634, 94% effective), and fluid (14/14, 100% effective), as well as positioning of anatomical structures such as coronary bypass grafts (8/8, 100% effective). Application methods included use of spray bottles (477/497, 96% effective), syringes (165/186, 89% effective), and a Silastic cannula through the flexible fiber-optic bronchoscope (4/6, 67% effective). The system was used in a wide variety of cardiac, pulmonary, esophageal, and vascular procedures to seal staple lines, suture lines, anastomoses, conduits, fistulas, and raw surfaces. No complications with this single-donor system secondary to blood-borne disease have been documented. Overall infection occurred at a nominal rate (16/689, 2%). Thus, fibrin sealant has been a useful tool to control the leakage of air, blood, and fluid during a wide variety of thoracic and cardiovascular procedures and may be of benefit to other surgeons.

Albumin Microbubble Persistence During Myocardial Contrast Echocardiography Is Associated With Microvascular Endothelial Glycocalyx Damage

BACKGROUND We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury. METHODS AND RESULTS The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K+ content, pH, PO2, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP. CONCLUSIONS Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.

Method for the Quantitation of Myocardial Perfusion During Myocardial Contrast Two-Dimensional Echocardiography

This article describes the hardware and software components of two systems designed for quantitative analysis of data obtained during myocardial contrast two-dimensional echocardiography. One system is meant for off-line analysis of data, whereas the other is designed for on-line analysis, especially in the operating room. The algorithms used for data transfer, selection of appropriate frames, data alignment, derivation of time-intensity plots, and curve-fitting and parameter generation are described in some detail. It is hoped that this information will be of use to others who work in the field of myocardial perfusion imaging.