Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2005
ReviewNitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies.
Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. ⋯ Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures.
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Anesthesia and analgesia · Aug 2005
ReviewIntraoperative fluid restriction improves outcome after major elective gastrointestinal surgery.
Fluid therapy is one of the most controversial topics in perioperative management. There is continuing debate with regard to the quantity and the type of fluid resuscitation during elective major surgery. However, there are increasing reports of perioperative excessive intravascular volume leading to increased postoperative morbidity and mortality. ⋯ Furthermore, predetermined algorithms that suggest replacement of third space losses and losses through diuresis are unnecessary. Significant reduction in crystalloid volume can be achieved without encountering intraoperative hemodynamic instability or reduced (i.e., < 0.5 mL x kg(-1) x h(-1)) urinary output just by avoiding replacement of third space losses and preloading. Finally, there is a need for well-controlled studies in a well-defined patient population using clear criteria or end-points for perioperative fluid therapy.
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Anesthesia and analgesia · Aug 2005
Changes in concentrations of free propofol by modification of the solution.
Because free propofol is thought to be responsible for pain on injection, we investigated the changes in concentrations of free propofol by modifying two kinds of propofol products in a medium- and long-chain triglyceride (MCT/LCT) emulsion and in an LCT emulsion. The techniques used in this study were 1) mixing 2% lidocaine (10:1), 2) mixing 5% dextrose in acetated Ringer's solution to reduce pH (10:1), and 3) changing the temperature to 4 degrees , 20 degrees , and 36 degrees C. The propofol preparations were dialyzed for 24 h, and the receptor medium was analyzed using high-performance liquid chromatography. The concentration of free propofol in propofol MCT/LCT was significantly smaller by 30% than that in propofol LCT. Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products, but the concentrations were reduced by a decrease in pH and by an increase in temperature. Because mixing lidocaine can induce instability in an emulsion of propofol and warming can rapidly induce microbial growth, injection of lidocaine before propofol administration is recommended to reduce the pain on injection. The concentrations of free propofol in propofol MCT/LCT were significantly smaller (by approximately 30%-45%) than those in propofol LCT during any situation in this study. ⋯ Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products but the concentrations were reduced by a decrease in pH and by an increase in temperature. Propofol medium- and long-chain triglycerides had significantly smaller concentrations by approximately 30%-45% than those in propofol long-chain triglycerides during any situation in this study.
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Anesthesia and analgesia · Aug 2005
Clinical TrialMonitoring activated clotting time for combined heparin and aprotinin application: an in vitro evaluation of a new aprotinin-insensitive test using SONOCLOT.
The kaolin-based activated clotting time (ACT) is commonly used for monitoring heparin-induced anticoagulation alone and combined with aprotinin during cardiopulmonary bypass. However, aprotinin prolongs ACT measurements. Recently, a new so-called 'aprotinin-insensitive' ACT test (SaiACT) has been developed for the SONOCLOT analyzer. In this study we evaluated and compared this new test for the SONOCLOT analyzer in vitro with an established kaolin-based ACT from HEMOCHRON (HkACT). Twenty-five patients undergoing elective valve surgery donated 80 mL of blood after induction of anesthesia. The blood was withdrawn in citrated tubes and processed to analyze effects of heparin (0, 1, 2, and 3 U x mL(-1)), aprotinin (0, 200 kIU x mL(-1)), and 25% hemodilution with calcium-free lactated Ringer's solution on ACT measurements. A total of 400 blood samples were analyzed and ACT was measured in a wide, clinically relevant range in duplicate with SaiACT and HkACT. Addition of aprotinin to heparinized blood samples induced no significant changes of SaiACT measurements. By contrast, HkACT readings increased significantly: aprotinin prolonged HkACT in heparinized blood samples by 20% +/- 37% (2 U x mL(-1)) and 24% +/- 18% (3 U x mL(-1)), respectively, and in vitro hemodilution increased this effect. ⋯ Current standard techniques to measure heparin-induced anticoagulation during cardiopulmonary bypass are affected by aprotinin, a drug widely used in this setting. The aim of this study was to investigate in vitro a new, so-called 'aprotinin-insensitive' test from SONOCLOT to measure heparin-induced anticoagulation more reliably in combination with aprotinin.
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Anesthesia and analgesia · Aug 2005
Preoperative "fentanyl challenge" as a tool to estimate postoperative opioid dosing in chronic opioid-consuming patients.
When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression. We studied 20 chronically opioid-consuming patients having elective multilevel spine fusion. Preoperatively, each patient received a fentanyl infusion of 2 microg x kg(-1) x min(-1) until the respiratory rate was <5 breaths/min. Pharmacokinetic simulations were used to estimate the effect site concentration at the time of respiratory depression and to predict the patient-controlled analgesia settings that would provide an effect-site fentanyl concentration that was 30% of the concentration associated with respiratory depression. Postoperatively, patient-controlled analgesia settings were adjusted to achieve 2-3 demand doses per hour. At steady-state patient-controlled analgesia settings, arterial blood gases and plasma fentanyl levels were measured. Sixteen patients required no adjustment or one patient-controlled analgesia adjustment. The median arterial Pco(2) level was 41 mm Hg and the interquartile range was 39-46 mm Hg. Plasma fentanyl levels demonstrated a significant correlation to the estimated effect-site concentration associated with respiratory depression determined during the preoperative fentanyl challenge. A preoperative fentanyl challenge used with pharmacokinetic simulations may be a useful tool to individualize the administration of analgesics to chronically opioid-consuming patients. ⋯ In chronically opioid-consuming patients, doses causing respiratory depression and analgesia may differ from those in opioid-naive individuals. A preoperative infusion of fentanyl, used in conjunction with pharmacokinetic simulation, may be a valuable tool for identifying clinical end-points, such as respiratory depression and analgesia, and individualizing postoperative treatment of pain in patients who chronically consume opioids.