Performance Evaluation of a New Point of Care Viscoelastic Coagulation Monitoring System in Major Abdominal, Orthopaedic and Vascular Surgery.

Viscoelastic Coagulation Testing (VCT), or Thromboelastography has the potential to improve the cost and clinical effectiveness of surgical and medical care by preventing unnecessary treatment and by improving treatment for bleeding, via targeted transfusion strategies. Recently a new viscoelastic coagulation monitoring system, the VCM System, has been developed, which has several advantages over existing systems. The VCM system is a small, portable device, that is designed to be simple to operate and can be used to reliably perform viscoelastic testing at the patient's bedside. The aim of this study was to evaluate the performance of the VCM system by comparing it to that of the ROTEM® delta. The CT, CFT, alpha angle, A10, A20, MCF and lysis results obtained from blood samples run in parallel on the VCM System and the ROTEM® NATEM test were compared for 86 patients undergoing planned abdominal, major orthopedic or vascular surgery. There was good correlation between the VCM and ROTEM® NATEM tests results for CT, A10, A20 and MCF, with Spearman Rank values of 0.70, 0.80, 0.80 and 0.73 respectively. The correlation between the two systems for CFT and alpha was moderate (Spearman Rank values of 0.68 and 0.51). There was also good agreement between the lysis parameters for the two systems. No problems with the usability of the VCM system, or difficulties with training on the system were reported by any of the clinical staff involved in the study. The VCM system is capable of making viscoelastic measurements of the hemostasis of blood samples within a rapid timeframe and addresses the accessibility, robustness and training issues associated with the larger traditional systems.

De-mystifying the "Mixifusor".

Total intravenous anesthesia (TIVA) using a mixture of propofol and remifentanil in the same syringe has become an accepted technique in Pediatric Anesthesia. A survey by a group of respected UK anesthetists demonstrated a low incidence of serious complications, related to the pharmacology and dose of the drugs. However, a current guideline for the safe use of TIVA recommends against this practice. Pharmaceutical concerns include the physical stability of the emulsion when remifentanil is mixed with propofol; changes in drug concentration over time; nonuniform mixing of propofol and remifentanil; the risk of bacterial contamination; and the potential for drug administration errors. Propofol and remifentanil have markedly different pharmacokinetic profiles. When remifentanil is mixed with propofol and delivered as a target-controlled infusion (TCI) of propofol, remifentanil delivery is not target-controlled but passively follows the variable infusion rates calculated by the syringe driver to deliver predicted plasma or effect-site concentrations of propofol. The pharmacokinetic consequences can be illustrated using pharmacokinetic modeling similar to that used in TCI pumps. The clinical consequences reflect the dose-dependent pharmacodynamics of remifentanil. Increasing the target propofol concentration produces a rapid increase and peak in remifentanil concentration that risks apnea, bradycardia, and hypotension, especially with higher concentrations of remifentanil. The faster decline in remifentanil concentration with falling propofol concentrations risks inadequate narcosis and unwanted responses to surgical stimuli. Remifentanil delivery is inflexible and dosing cannot be adjusted to the clinical need and responses of individual patients. The medicolegal considerations are stark. In UK and EU Law, mixing propofol and remifentanil creates a new, unlicensed drug and the person mixing takes on the responsibilities of manufacturer. If a patient receiving anesthesia in the form of a mixed propofol-remifentanil infusion suffered a critical incident or actual harm, the clinician's practice may come under scrutiny and criticism, potentially involving a legal challenge and the Medical Regulator.

Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice.

The proposition that white adipose tissue is involved in the inflammatory response and metabolic dysregulation of endotoxaemia has been examined. Mice were injected with lipopolysaccharide (LPS; 25 mg/kg) and epididymal, perirenal and subcutaneous adipose tissue removed 4 or 24 h later. The expression of genes encoding key inflammation-related adipokines was measured by real-time polymerase chain reaction. At 24 h after the administration of LPS, there was no change in leptin mRNA level, and adiponectin mRNA fell. However, major increases in TNFalpha, MCP-1 (up to 40-fold) and IL-6 (up to 250-fold) mRNA levels were evident; a substantial elevation in these mRNAs occurred by 4 h, and adipose tissue IL-6 protein also increased (three- to eightfold). At 24 h, the responses in the subcutaneous depot were much lower than in epididymal and perirenal adipose tissue, but at 4 h, the subcutaneous tissue showed major increases in IL-6, MCP-1 and TNFalpha gene expression. In contrast to the inflammatory adipokines, the mRNA level of two macrophage markers, F4/80 and MAC-1, was unaltered in adipose tissue during endotoxaemia. Expression of the hypoxia-sensitive transcription factor, HIF-1alpha, gene was increased at both 4 and 24 h, and HIF-1alpha protein was elevated at 4 h, suggesting that the tissue was hypoxic. It is concluded that white adipose tissue may play an important role in the production of inflammatory mediators in endotoxaemia.