The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included.

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions.

Introduction: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.

Methods: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved.

The concept of hemoglobin equivalency of perfluorochemical emulsions.

Perfluorochemical (PFC) emulsions have been in development as intravenous oxygen carriers for a number of years and many publications have dealt with their oxygen transport characteristics in both experimental models and in clinical trials. Though it has been stressed on numerous occasions that PFCs deliver oxygen to the tissues in very different ways to those by which Hemoglobin (Hb) releases oxygen (O2), no serious attempts have been made to correlate the oxygen delivery capacity of PFCs to those of Hb. This paper presents theoretical ways in which this can be done and demonstrates that a 2.

Perflubron emulsion (AF0144) augments harvesting of autologous blood: a phase II study in cardiac surgery.

Objective: To assess tolerance and preliminary efficacy of a perfluorocarbon emulsion (AF0144) used with acute normovolemic hemodilution to reduce allogeneic blood transfusion for patients undergoing coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB).

Design: Controlled, single-blind, parallel-group phase II dose escalation trial.

Setting: Single-institution university medical center.

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs.

Hypervolaemic haemodilution makes myocardial perfusion more homogenous as reflected by reduced fractal dimension of regional myocardial perfusion. The clinically more commonly performed acute normovolaemic haemodilution, however, has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen is used in conjunction with haemodilution to compensate for low oxygen content by increasing physically dissolved oxygen in plasma.

Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs.

Background: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system.

Effects of hyperoxic ventilation on hemodilution-induced changes in anesthetized dogs.

Background: In subjects who have undergone acute preoperative normovolemic hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate return of autologous blood collected during ANH. Simply increasing blood oxygen content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might compensate for the acute anemia, allow further ANH, and delay onset of autologous blood return.

Hemodilution and hyperoxia locally change distribution of regional pulmonary perfusion in dogs.

In seven anesthetized dogs, the effects of acute normovolemic hemodilution (ANH) to a hematocrit of 20 and 8% and the effects of hyperoxic ventilation (100% oxygen) on distribution of regional pulmonary blood flow (rPBF; radioactive microspheres) were investigated. Normovolemia was monitored with blood volume measurements (indocyanine green dilution kinetics). Before ANH, fractal dimension (D) of rPBF in the whole lung was 1.

A pilot study of the effects of a perflubron emulsion, AF 0104, on mixed venous oxygen tension in anesthetized surgical patients.

A pilot study of a perfluorochemical (PFC) emulsion was undertaken to determine whether administration of a perflubron emulsion could result in measurable changes in mixed venous oxygen tension. Seven adult surgical patients received a 0.9-g PFC/kg intravenous dose of perflubron emulsion after acute normovolemic hemodilution (ANH).

Effects of a perfluorocarbon emulsion for enhanced O2 solubility on hemodynamics and O2 transport in dogs.

Perfluorocarbon emulsions raise blood O2 solubility and thus augment O2 transport, but their cardiopulmonary effects at higher doses may limit their use. We therefore examined effects of increasing doses of perfluorooctylbromide emulsion (Oxy) on 1) pulmonary gas exchange, 2) pulmonary and systemic hemodynamics, and 3) mixed venous PO2 (PVO2). After hematocrit reduction to 24-26% by exchange with 5% albumin, anesthetized ventilated dogs breathing 100% O2 were given Oxy (n = 6) or 5% albumin (n = 5) intravenously in four successive 3 ml/kg doses.

Effect of supplemental perfluorocarbon administration on hypotensive resuscitation of severe uncontrolled hemorrhage.

Recent animal studies of acute hemorrhage in the presence of a vascular injury have demonstrated improved survival and decreased hemorrhage volume with hypotensive resuscitation, but this has occurred at the expense of tissue perfusion. It was hypothesized that addition of an oxygen-carrying perfusate would improve tissue oxygen delivery during hypotensive resuscitation. Hypotensive resuscitation of severe uncontrolled hemorrhage was compared with and without supplementation with Oxygent HT, an emulsion of perflubron (perfluorooctylbromide; PFOB; Alliance Pharmaceutical Corporation, San Diego, CA), an oxygen-carrying perfusate.

Mechanisms and efficacy of fluorochemical oxygen transport and delivery.

Fluorochemicals for medical use are metabolically inert liquids with a high solubility for gases, and can dissolve 50 percent or more of their own volume of oxygen (O2) at ambient pressures. The solubility is directly proportional to the oxygen tension (PO2) and transport is thus not saturable, unlike the O2 saturation of hemoglobin (Hb) which follows the well known "S" shaped relationship with PO2. Intravenously-injected emulsions of fluorocarbons transport only about one seventh as much O2 as Hb on a gram for gram basis, even when high concentrations of O2 are respired.

Improvement in circulatory and oxygenation status by perflubron emulsion (Oxygent HT) in a canine model of surgical hemodilution.

To examine the effect of a low dose of Oxygent HT on hemodynamics and oxygen transport variables in a canine model of profound surgical hemodilution, two groups of adult anesthetized splenectomized beagles were hemodiluted with Ringer's solution to Hb 7 g/dL. The treated group received 1 mL/kg Oxygent HT (90% w/v perflubron emulsion [perfluorooctyl bromide], Alliance Pharmaceutical Corp.) and both groups (7 controls and 10 treated) were further hemodiluted using 6% hydroxyethyl starch until cardiorespiratory decompensation occurred.

Enhanced oxygen delivery by perflubron emulsion during acute hemodilution.

A high-concentration 90% w/v perflubron (perfluorooctyl bromide [PFOB]) emulsion (Oxygent HT) is being evaluated as an oxygen carrier for use during surgery. This study was done to assess oxygen delivery by Oxygent HT during acute normovolemic hemodilution. Anesthetized mongrel dogs, instrumented with femoral and pulmonary artery catheters, were hemodiluted to a hematocrit of 25% with 3:1 (v/v) of Ringers-lactate (R-L).

Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure.

We investigated the efficacy of intratracheal perfluorocarbon (PFC) administration combined with mechanical ventilation to support gas exchange in adult animals with acute respiratory failure. These were compared with a similar group of animals treated with continuous positive-pressure ventilation (CPPV) with respect to respiratory parameters and postmortem lung histology. After lung lavage with saline, 18 adult rabbits were divided into three groups (n = 6 per group).

Intratracheal perfluorocarbon administration combined with mechanical ventilation in experimental respiratory distress syndrome: dose-dependent improvement of gas exchange.

Objectives: To test the efficacy of intratracheal instillation of a perfluorocarbon, combined with conventional mechanical ventilation, as well as to establish the dose response of this application on pulmonary parameters in adult animals with acute respiratory failure.

Design: Prospective, randomized, placebo-controlled study.

Setting: Anesthesiology laboratory of a university.

Increased plasma O2 solubility improves O2 uptake of in situ dog muscle working maximally.

A perfluorocarbon emulsion [formulation containing 90% wt/vol perflubron (perfluorooctylbromide); Alliance Pharmaceutical] was used to increase O2 solubility in the plasma compartment during hyperoxic low hemoglobin concentration ([Hb]) perfusion of a maximally working dog muscle in situ. Our hypothesis was that the increased plasma O2 solubility would increase the muscle O2 diffusing capacity (DO2) by augmenting the capillary surface area in contact with high [O2]. Oxygen uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 4) while working for 6 min at a maximal stimulation rate of 1 Hz (isometric tetanic contractions) on three to four separate occasions for each muscle.