Brevibloc

By TOM CLARK BBI European Correspondent BARCELONA, Spain - The European Society of Anesthesiologists' annual meeting is unusual in that presentations - both oral and poster - are formally peer-reviewed to ensure high-quality research. As Sven Erik Gisvold, anesthesiologist at Trond-heim University Hospital in Norway, said, "Anesthe-sia is among the specialities with the greatest potential for risk. Considering what we do to our patients, this is not surprising. We induce unconsciousness, we par-alyze our patients and deprive them of their ability to breathe, and use a multi-tude of drugs that may kill if used wrongly. Despite this, severe morbidity and mortali-ty relating to anesthesia are extremely rare." A recent inquiry into perioperative deaths (CEPOD) gave a fig-ure of 1 to 185,000 for death solely attributable to anes-thesia. Improved anesthetics and anesthesia techniques have contributed greatly to the rapid spread of ambulatory surgery, and many new developments were presented at the recent European Anesthesiolo-gy Congress. Throughout Europe, there is a continu-ing move towards more surgical treatment in the community and less in the hospital. Much of this results from anesthesiology advances. Anesthesia in cardiovascular procedures More than 60% of cardiac surgery patients at the Hospital de Sant Pau (Barcelona, Spain) are dis-charged from hospital within five days or less under the Fast-Track recovery technique using fentanyl with isoflurance or propofol for anesthesia. The technique depends on early extubation and ambula-tion. Dr. Litvan and his group at the Hospital de Sant Pau commented that, contrary to earlier expe-riences with Fast-Track in the U.S., there were no resultant savings because more patients could be treated, thus increasing overall departmental costs. This results from a current annual central budgetary allocation system rather than individual patient cost allocation. Thoracic epidural analgesia (TEA) provides excellent analgesia for the cardiac surgical patient and allows early extubation with a decreased inci-dence of respiratory tract infection in the post-oper-ative period. Dennis Turfey and his team at Glasgow University (Glasgow, Scotland) and at HCI Medical Centre (Greenock, Scotland) concluded also that there was a trend towards decreases in other post-operative complications like arrythmias and the use of intropic agents. Although patients were randomized to receive either bupivicaine and cloni-dine or target-controlled infusion (TCI) of alfentanil with TCI controlled propofol, there were no signifi-cant differences between the two groups with respect to complications or the use of inatropes. Transcranial near-infrared spectroscopy (NIRS) can provide regional on-line measurement of satu-ration of hemoglobin in brain tissue, helping to monitor continuous regional cerebral oxygen satu-ration (rSO2). Dr. Durak and his group at the Turkiye Yuksek Ihtisas Hospital (Ankara, Turkey) measured rSO2 using an NIRS probe from Somanet-ics (Troy, Michigan) with simultaneous EEG record-ing. Their trials concluded that rSO2 values by the Somanetics cerebral oximeter and spectral edge fre-quency values (SEF) by EEG change in a positively correlated fashion, but that rSO2 levels always changed earlier than SEF during cardiopulmonary bypass procedures, but returned to pre-induction levels later. Using a Cardiomed flow measurement device from Medi-Stim (Oslo, Norway), intraoperative flow measurement can be measured accurately by the transit time technique. Thomas Carrel and his team at the University Hospital (Berne, Switzer-land) found that a normal coronary flow reserve could be measured in only 30% of patients undergo-ing myocardial revascularisation for coronary artery disease. The coronary flow reserve was measured during maximum vasodilation at increasing doses of adenosine. Brevibloc (esmolol HCl) is an ultra-short-acting beta-blocker from Gensia Pharmaceuticals (San Diego, California) which is designed to give anes-thetists precise hemodynamic control. Full therapeu-tic effect is developed in two minutes, and with a half-life of only nine minutes, the beta- blockade reverses rapidly. Brevibloc in its normal mode of action reduces both the heart rate and contractility, and trials are currently under way in Europe on its use in mini-mally invasive, beating-heart surgery. Nitric oxide in congenital heart disease Stefan Lundin, consultant anesthetist at the Sahlgrenska University Hospital (Goteborg, Swe-den), has been studying the use of inhaled nitric oxide (iNO) for the past six years, with a special interest in the treatment of persistent pulmonary hypertension of the newborn. AGA Healthcare (Lidingo, Sweden) has been leading European efforts to register iNO as a drug so health care pro-fessionals can benefit from detailed guidelines and documentation, clinical trial results, training and quality controls. The European Neonatal and Pedi-atric Nitric Oxide Study Group published a report last year which concluded that iNO is capable of improving oxygenation in both newborn and pedi-atric patients with pulmonary hypertension and impaired gas exchange. Lundin commented, "The most convincing case I have treated was three years ago: that of an 11-year-old girl who was suffering from acute heart failure due to congenital heart disease. The blood vessels in the lungs were extremely con-stricted, and a heart and lung transplant was need-ed to save the child. We were, however, experienc-ing difficulties in obtaining suitable organs." He added, "There is no doubt in my mind that iNO pulled her through the operation: it dilated the pulmonary vessels, making it possible for us to transplant the heart only, and obviating the need for a lung transplant." AGA Healthcare's marketing director, Robert Strom, said, "Many intensive-care physicians believe there is a clinical benefit from iNO. However, today iNO is available to European doctors for compassion-ate use only or clinical trials." AGA's aim is to regis-ter iNO as a drug so that health care professionals can benefit. AGA has an exclusive European patent, granted in 1997, which covers the indications devel-oped to date for inhaled nitric oxide. Ohmeda holds the U.S. license for the iNO patent. Strom noted that a multicenter trial on ARDS, sponsored by AGA and Ohmeda (Helsinki, Finland), is going ahead according to schedule and should be finalized in 1999. Results from a new French ARDS trial will be published later this year. The French drug agency, Agence du Medicament, has been asked by the European Union Medical Board to present a sum-mary of currently available iNO documentation in order to make a statement on the present status from the regulatory perspective. Dr. Lonnqvist of Karolinska Hospital (Stock-holm, Sweden) summed up the situation: "The speed at which iNO is registered as a drug is complicated by the fact that the process is completely unregulated. Traditionally, gases such as nitric oxide have always been available from neighborhood gas dealers, but now that the body of medical evidence is growing, NO deserves the proper recognition and back up of a regularized drug." This problem is exemplified by a joint study between the National Institute of Child Health and Human Development, in collaboration with a group of Canadian researchers, which was stopped two months ahead of schedule in May 1996 because the results with iNO were so promising that the physi-cians involved could no longer ethically deny the therapy to the control group.

Hemodynamic monitoring of cardiac output Two Spanish groups at the Hospital Puerta di Hierro (Madrid) and Hospital Juan Canalejo (La Coruna) have compared cardiac output measurement by thermodilution using a Swan Ganz REF-1 from Bax-ter (Deerfield, Illinois) with esophageal Doppler mea-surement using an ODMII transducer from Abbott Laboratories (Abbott Park, Illinois). The two groups found good correlation in cardiac output measure-ments and corrected flow time (FTc). Anumber of presentations reviewed the perfor-mance of the PiCCO monitoring system from Pul-sion (Munich, Germany). The pulse contour (PCCO) method measures hemodynamic parame-ters by a beat-to-beat analysis of the arterial pres-sure wave calibrated by a simple arterial thermodi-lution measurement. PiCCO uses a central venous catheter and an arterial access, less invasive than the traditional pulmonary artery technique. Del Rocca and his group from the Istituto di Anestesia e Rianimazione at the University of Rome evaluat-ed the PiCCO system in various major surgical pro-cedures including lung transplantation, liver trans-plantation and thoracic surgery, and found results correlated well with pulmonary artery catheter measurements but with a lower level of invasive-ness. Doppler flowmetry monitoring Interscalene brachial plexus block used in sur-gical procedures of the arm and shoulder pro-duces effective motor and sensory block, but may also produce microcirculatory side effects attrib-utable to changes in vasoconstrictor tone. A research group at Umea University Hospital (Umea, Sweden) used the Periflex PF4001 noninvasive laser Doppler from Perimed (Solna, Sweden) on the index fingers of both arms to compare and measure sympathetic blockade following regional anesthesia. Perflubron maintains normovolemia Perflubron fluorocarbon emulsion from Alliance Pharmaceutical (San Diego, California) has been compared in a multicenter (Zurich, Switzerland; Leu-ven, Belgium; Munster, Giessen and Munich, Ger-many) study with autologous blood and hydrox-yethyl starch colloid infusions in reversing physio-logic transfusion triggers, and in delaying the neces-sity for additional blood transfusions after opera-tions. The trials were carried out on 147 patients undergoing elective orthopedic surgery with 450ml of autologous blood or colloid infusion being trans-fused after surgery. The Perflubron study group's report comments that Perflubron emulsion was well tolerated at the two treatment levels of 0.9 and 1.8g/kg body weight. Perflubron emulsion at 1.8g/kg was significantly more effective than either autologous blood or colloid infusion in reversing physiologic transfusion triggers such as tachycardia, hypotension or reduced cardiac output arising after intraoperative blood losses. Low molecular weight colloid launched Although artificial colloids have a reputation for impairing hemostasis, this effect appears to be more problematical with high molecular weight (450 kD) hydroxyethyl starch (HES) than with medium levels of around 200kD used by Fresenius (Bad Homberg, Germany) in its major HAES-sterile colloid plasma substitute solution. The Blood Interaction Research and Cardiotho-racic Anesthesiology Group (Groningen, the Netherlands) has been studying the effects of molec-ular weight of hydroxyethyl starch colloids on hemostasis, using the availability of Factor VIII/von Willebrand Factor (vWF). They found that a new HES colloid solution, with a lower molecular weight averaging 130 kD which has been developed by Fre-senius, produced significantly higher vWF concen-trations as well as better prothrombin time (PTT) and platelet numbers. These improved figures arose from trials on the use of 200 kD and 130 kD HES priming solutions in cardiopulmonary bypass proce-dures. Donat Spahn and his team at University Hospital (Zurich, Switzerland) compared hydroxyethyl starch colloids derived from corn starch (Fresenius) and a new colloid, Infukoll, derived from potato starch by Serum-Werk Bemburg (Bemburg, Germany). Their main findings were that blood coagulation is more seriously affected by potato starch HES than corn starch HES. Joachim Wixforth and a team at the University of Koln (Koln, Germany) also compared safety and tolerance of the new Fresenius HES 130/0.4 colloid with their existing HES 200/0.5 in prevention of hypotension (more than 20% decrease in systolic blood pressure) during and after blood donation. They found performances were comparable. More importantly, Fresenius says that although HES 130/0.4 has a comparable vascular half-life to HES 200/0.5, it is more rapidly and more completely excreted by the kidneys once the solution has left the intravascular space. Low molecular weight HES fractions are rapidly eliminated since many of their molecules are in the range of the renal thresh-old (around 70,000 Daltons), while larger mole-cules must be broken down by circulating alpha-amylase prior to excretion. Clearly, therefore, lower molecular weight HES will tend to be cleared more rapidly, although the rate of enzy-matic cleavage depends also on the molecular structure. Day-care anesthesia developments Inhalational anesthetics like halothane, enflurane and isoflurane are still widely used in Europe in out-patient and ambulatory surgery procedures. Pediatric anesthetists are increasingly using Sevoflurane from Abbott Laboratories since induction with Sevoflu-rane is both swift and pleasant. Desflurane (Suprane) from Pharmacia and Upjohn (London) also reaches target concentrations rapidly and permits faster con-trol of hemodynamic response and of depth of anes-thesia. Tom Ogg, of the International Association for Ambulatory Surgery (Cambridge, United Kingdom), commented, "Desflurane has a low blood/gas parti-tion coefficient and is stable when exposed to soda lime. However, this inhalational agent requires a spe-cially designed expensive vaporizer." This is a refer-ence to the Ohmeda Tec 6 evaporator, which is simi-lar to the Ohmeda Tec 4 and Tec 5 models and fits standard anesthesia systems. There is also a desflu-rane adaptor which fits evaporators from Drager (Lubeck, Germany). According to Jan van Hemelrijck of the Uni-versitair Ziekenhuis (Leuven, Belgium), anesthe-sia conditions in neurosurgical operations can depend on many factors, with the choice of anes-thetic agent playing only a modest role. He said, "The cerebral effects of new volatile anesthetic agents desflurane and sevoflurane appear to be very similar to the effects of isoflurane. It may therefore be expected that both agents can be used for neurosurgical procedures within the same lim-its that exist for isoflurane." He added, "While remifentanil (Ultiva from Glaxo Wellcome, Uxbridge, England) seems an attractive alternative for other opioids from a theoretical point of view, clinical advantages in neuroanesthesia appear to be less distinct." Cost vs. quality Over the past decade, new anaesthetic, analgesic and muscle-relaxant drugs have been introduced which give a faster onset, better control and a more rapid recovery. These drugs and anesthetic tech-niques have clearly helped the growth of ambulatory surgery. In his presentation on the selection of drugs and techniques, Paul White, MD, of the South-western Medical School (Dallas, Texas) cautioned that most of these new drugs and techniques are more expensive than older ones. It therefore is important to examine "total costs rather than sim-ply the acquisition cost of the drug when choosing between anesthetic agents." Although the major perioperative cost is personnel, earlier discharge readiness may not necessarily save money if nurs-ing practices mandate a minimum recovery room stay, if non-medical factors delay actual dis-charge or if the time between consecutive proce-dures in the same operating room is prolonged. Use of Ultiva (remifentamil) from Glaxo Well-come, together with isoflurane, enflurane or propo-fol from Zeneca (Macclesfield), may make it possi-ble for more short surgical procedures presently being done on an inpatient basis to be performed as day cases. That was the conclusion of a European multicenter 845-patient study on patients undergo-ing gynecological laparoscopy, varicose vein or arthroscopic surgery. Post-operative nausea and vomiting was much lower in the group of patients receiving remifentanil and propofol. Patient-maintained sedation Two British studies, one on sedation during colonoscopy and the other on pre-surgery anxiety states have shown very favorable effective results for patient-controlled sedation using propofol and pre-programmed, target-controlled infusion pumps. In both cases patient satisfaction was recorded as high. A recent study by Gordon Hall and his group at the Department of Clinical Psychology, University of Liverpool (Liverpool, United Kingdom) reviewed patient experiences and opinions after patient con-trolled analgesia. "Positive" patients reported sig-nificantly better pain relief and better control over pain. Concerns from less-positive responders cen-tered around safety concerns and worries about overdosing. Levobupivicaine approved Chiroscience's (Oxford, United Kingdom) Lev-obupivicaine takes advantage of chiral separation in order to separate unwanted side effects of the dextro-enantiomer from desirable therapeutic anesthetic potency of the other levo-enantiomer. Levobupivicaine has been widely investigated for use in obstetric anesthesia since it should have equivalent potency to bupivicaine, widely used in Europe, but with an enhanced safety profile. Lev-obupivicaine, has now been authorized for European sale with marketing and distribution to be handled by Zeneca. Target-controlled infusion Diprifusor is the target-controlled infusion (TCI) software system developed for Zeneca for use with Diprivan propofol anesthetic and anesthesia syringe pumps from Graseby Medical (Watford, United King-dom), Fresenius Vial (Brezius, France) and Alaris Medical (San Diego, California). The use of TCI with propofol facilitates the use of the total intravenous anesthesia (TIVA) technique, avoiding the use of inhalational gases.

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