Massive hemorrhage and transfusion in the operating room.

PURPOSE: In this Continuing Professional Development module, we review the pathophysiology and clinical manifestations associated with massive hemorrhage as well as laboratory investigations and appropriate therapeutic measures. In addition to reviewing the available blood/plasma products and adjunct therapy, we also explore the role of the anesthesiologist in a massive transfusion protocol scenario. PRINCIPAL FINDINGS: Massive hemorrhage can be either anticipated or unexpected. The coinciding presence of acidosis, hypothermia, and hypotension contribute greatly to a poor outcome. Red blood cells not only increase oxygen carrying capacity, but they also play a role in providing hemostasis. While timely laboratory results, including point-of-care testing, are important, transfusion remains a clinical decision. Adjunct therapies other than blood components have contributed to improved outcomes. The pathophysiology of massive obstetric hemorrhage is unique when compared with the non-obstetric population. The approach to massive hemorrhage and its treatment vary considerably from institution to institution. CONCLUSIONS: Massive hemorrhage is a multidisciplinary challenge that requires immediate response and communication between clinicians, nurses, other healthcare providers, laboratory testing, and blood banks. Basic knowledge and utilization of available products and therapies are inconsistent. A massive transfusion protocol can be used effectively to reduce chaos and ensure that correct treatments and proper dosing occur in a timely manner.

Cryoprotectant agent toxicity in porcine articular chondrocytes.

Large articular cartilage defects have proven difficult to treat and often result in osteoarthritis of the affected joint. Cryopreservation of articular cartilage can provide an increased supply of tissues for osteochondral allograft but cryoprotective agents are required; however, few studies have been performed on the toxicity of these agents. This study was designed to determine the order of toxicity of five commonly used cryoprotectant agents as well as interactions that occur between them. Isolated porcine articular chondrocytes were exposed to individual cryoprotectant agents and combinations of these agents at 1M and 3M concentrations for 5 min and 120 min. Cell viability was determined using membrane integrity dyes and a metabolic activity assay. Subsequently, a regression analysis based study was undertaken to extract the maximum amount of information from this data. Results of this study demonstrated that all 1M solutions were minimally toxic. The 3M solutions demonstrated varying toxicity after 120 min. Ethylene glycol and glycerol were less toxic than propylene glycol, dimethyl sulfoxide, and formamide. Combinations of cryoprotectant agents were less toxic than single cryoprotectant agents at the same concentration. This is the most comprehensive study investigating cryoprotectant agent toxicity in articular chondrocytes and has resulted in important information regarding the order of toxicity and interactions that occur between these agents.

Statistical prediction of the vitrifiability and glass stability of multi-component cryoprotective agent solutions.

Long-term biologic storage of articular cartilage has proven elusive due to cellular degradation over time or acute damage during attempts at cryopreservation. Vitrification is one option that may result in successful cryopreservation but difficulty with cryoprotective agent (CPA) toxicity at high concentrations of a single cryoprotectant has hindered development of successful protocols. This study was designed to determine the vitrifiability and glass stability of solutions containing combinations of commonly used CPAs and to document CPA interactions that occur. One hundred and sixty-four multi-CPA combination solutions of 6-9 M were evaluated for vitrifiability and glass stability using direct visualization after immersion in liquid nitrogen for 30 min and upon warming. Binary and ordinal logistic regression analysis was used to statistically analyze each CPA for its ability to vitrify and its effect on glass stability in multi-component CPA solutions. Propylene glycol had the greatest incremental contribution to vitrification while formamide had the least contribution. A threshold was established whereby the ability of a solution to vitrify could be determined by calculation. Glass stability was not as clearly defined due to variability in the results; however, contributions of interactions between CPAs to the glass stability of solutions were determined. This study provided values that predict if a solution will vitrify. Furthermore, the glass stability of solutions containing multiple CPAs do not behave as linear additions of binary solutions and interactions between CPAs have a significant effect on the glass stability of these solutions. These variables should be considered when designing vitrification solutions.