M. Behne

DROPERIDOL CAUSES A DOSE-DEPENDENT PROLONGATION OF THE QT INTERVAL

To further investigate possible prolongation of the frequency-corrected QT interval (QTc interval) after administration of droperidol (DRO), we studied 40 surgical patients who were randomly assigned to one of three groups, receiving an intravenous (IV) injection of either 0.1 mg/kg (Group 1, n = 10), 0.175 mg/kg (Group 2, n = 10), or 0.25 mg/kg (Group 3, n = 20) of DRO at induction of anesthesia. The QTc interval, heart rate, and arterial pressure were registered before and 1, 2, 3, 4, 5, 7.5, and 10 min after the respective dose injection. Significant prolongations of the median QTc interval were found in patients from all groups, ranging from 37 ms (8.0%) in Group 1, to 44 ms (10.6%) in Group 2, to 59 ms (14.9%) in Group 3, when compared with control. The heart rate showed a significant increase in all groups. Mean arterial pressure (MAP) was slightly but significantly decreased in Groups 1 and 3. Prolongation of the QTc interval is a predictable and dose-dependent side effect after injection of high-dose DRO.

Prophylactically-administered rectal acetaminophen does not reduce postoperative opioid requirements in infants and small children undergoing elective cleft palate repair.

Rectal acetaminophen (Ac) is often administered prophylactically at anesthesia induction for postoperative pain management in small children and is thought to have an opioid-sparing effect. We assessed in this double-blinded, prospective, randomized study early opioid requirements after three doses of Ac (10, 20, and 40 mg/kg versus placebo) in 80 children (ASA physical status I, age 11.4 ± 9.9 mo) undergoing cleft palate repair. Single Ac plasma concentrations were measured. Pain scores assessed in the postanesthesia care unit of ≥4 of 10 resulted in the IV administration of 25 &mgr;g/kg piritramide, a popular European &mgr; receptor agonist (lockout time, 10 min; maximum 0.125 mg/kg). There were no significant differences between groups with regard to the early postoperative pain scores and the overall cumulative IV opioid requirements. Maximal plasma concentrations achieved were only subtherapeutic (Ac 10 mg/kg: 8 &mgr;g/mL; Ac 20 mg/kg: 13 &mgr;g/mL; Ac 40 mg/kg: 21 &mgr;g/mL after 122, 122, and 121 min, respectively). We conclude that rectal Ac up to 40 mg/kg has no opioid-sparing effect, does not result in analgesic Ac plasma concentrations, and lacks proof of its efficacy in infants and small children undergoing cleft palate repair, whereas titrated IV opioid boluses produced rapid and reliable pain relief.

Clinical Pharmacokinetics of Sevoflurane

Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the ‘older’ inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. The more rapid pharmacokinetics are a result of the low blood/gas partition coefficient of 0.69. With an oil/gas partition coefficient of 47.2, the minimum alveolar concentration (MAC) of sevoflurane is 2.05%. Two to 5% of the drug taken up is metabolised by the liver. The pharmacokinetics of sevoflurane do not change in children, obese patients or patients with renal insufficiency.The pharmacokinetics and pleasant odour of sevoflurane make mask induction feasible, which is an obvious advantage in paediatric anaesthesia. The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy.

Postoperative Schmerztherapie im Kindesalter : Ergebnisse einer repräsentativen Umfrage in Deutschland

ZusammenfassungDie letzte anästhesiologische Repräsentativerhebung zur postoperativen Schmerztherapie in Deutschland stammt aus dem Jahre 1987, differenzierte Daten zur postoperativen Schmerztherapie im Kindesalter fehlen bisher. Ziel unserer Umfrage war es, den Status quo der postoperativen Schmerztherapie im Kindesalter in deutschen anästhesiologischen Kliniken im Jahre 2000 zu erfassen. An anästhesiologische Abteilungen und interdisziplinäre Intensivstationen (n=1.500) deutscher Krankenhäuser wurde ein detaillierter Fragebogen zur aktuellen Praxis der postoperativen Schmerztherapie im Kindesalter versendet. Die Rücklaufquote betrug 42,6%. Rektal appliziertes Paracetamol ist das Standardmedikament in der postoperativen Schmerztherapie im Kindesalter, Opioide werden im Vergleich zu früheren Untersuchungen vermehrt eingesetzt. Nichtsteroidale Antiphlogistika und Spasmolytika spielen ebenso wie Regionalanästhesietechniken in der postoperativen Schmerztherapie im Kindesalter eine untergeordnete Rolle. Im europäischen Vergleich werden neuere Methoden wie die patienten- oder elternkontrollierte Analgesie in Deutschland häufiger eingesetzt. Trotz moderner Organisationskonzepte und einer Vielzahl von angewandten Substanzen halten 71,7% der Anästhesisten die postoperative Schmerztherapie im Kindesalter für verbesserungswürdig.AbstractThe last survey addressing postoperative pain management in Germany was published in 1987, special data concerning postoperative pain management in pediatric patients had not been presented previously. The goal of this survey is to present the standard of postoperative pain management in pediatric patients in Germany. A detailed questionnaire was mailed to all German anaesthesia departments and interdisciplinary intensive care units (n=1,500) to determine the current management of postoperative pain management in pediatric patients. After eight weeks, 42.6% of the survey had been returned. Rectally administered acetaminophen is the standard drug regimen for postoperative analgesia in children. Compared to previous surveys, the use of opioids has increased in popularity. The routine use of non-steroid antiinflammatory drugs (NSAIDs) and spasmolytics as well as the application of regional anaesthesia techniques is uncommon in pediatric postoperative pain management. Compared to other European countries, patient- or parent-controlled analgesia is more popular in Germany. Despite modern concepts of organization and a great variety of drugs available today, 71.1% of the responding anesthesiologists in this survey still believe that pediatric postoperative pain management needs to be improved.

Prolongation of the QT–interval during induction of anesthesia in patients with coronary artery disease

During induction of anesthesia in 60 patients undergoing coronary artery bypass grafting (CABG), we measured the QT–interval (QTI) in the ECG, heart rate (HR) and mean arterial pressure (MAP). Based on the HR, we corrected the QT–interval (QTcI). Prior to induction, six patients(10%) already had abnormal prolongation of QTcI (≥440 ms). After injection of fentanyl and vecuronium, the QTcI increased significantly (P<0.01); to a far lesser extent after injection of hypnotics (i.e. etomidate, midazolam or propofol). Orotracheal intubation caused significant shortening of QTCI (P < 0.01). HR decreased markedly after injection of fentanyl. MAP decreased, however, only after injection of hypnotics. In the immediate post intubation period, HR and MAP increased significantly. The various hypnotics produced no significant difference in HR and QTcI at any measurement point. MAP changed only after injection of hypnotics. The decrease of HR and MAP during induction of anesthesia is thought to result from a corresponding reduction of adrenosympathetic stimulation. We believe that QTcI is similarly influenced.

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery.

Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials.We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) IV up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t1/2init), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after IV administration, t1/2init and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. Implications: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation. (Anesth Analg 1998;86:856-60)

Recovery and pharmacokinetic parameters of desflurane, sevoflurane, and isoflurane in patients undergoing urologic procedures

STUDY OBJECTIVE To compare the pharmacokinetics and the speed of recovery after inhalation anesthesia with desflurane, sevoflurane, and isoflurane in elective surgery. DESIGN Prospective, randomized study. SETTING University medical center. PATIENTS 30 ASA physical status I and II adults presenting for elective surgery. INTERVENTIONS Anesthesia was induced with etomidate and maintained with desflurane (n = 10), sevoflurane (n = 10), or isoflurane (n = 10) and nitrous oxide. The inhalation drugs were titrated until an adequate clinical depth of anesthesia was reached. At the end of anesthesia, the patients breathed oxygen via the endotracheal tube and after extubation via a face mask. MEASUREMENTS AND MAIN RESULTS The groups were similar with respect to age, weight, duration of anesthesia, and mean arterial pressure. Mean end-tidal concentration (FA = FA0) at the end of anesthesia was 6.34 +/- 1.15% after desflurane, 1.85 +/- 0.42% after sevoflurane, and 1.10 +/- 0.24% after isoflurane. FA/FA0 decreased significantly faster with desflurane than with isoflurane, while there was little difference between desflurane and sevoflurane. As for the terminal half-life (t1/2), there were no differences among the groups (8.16 +/- 3.15 min after desflurane, 9.47 +/- 4.46 min after sevoflurane, and 10.0 +/- 5.57 min after isoflurane). The time until a command was followed for the first time was the same in all three groups (13.0 +/- 4.7 min after desflurane, 13.4 +/- 4.4 min after sevoflurane, and 13.6 +/- 3.4 min after isoflurane). There was no significant correlation between duration of anesthesia and the time until recovery. CONCLUSIONS There are only minor differences with regard to the recovery phase in premedicated patients who receive clinically titrated inhalation anesthesia with desflurane, sevoflurane, or isoflurane.

Thoracoscopic microsurgical technique for vertebral surgery--anesthetic considerations.

Background: The thoracoscopic microsurgical technique (TMT) for vertebral and spinal cord surgery is associated with the benefits of reduced postoperative pain, accelerated return to physical activity and reduced complication rates. However, because of the surgeons requirement of a non‐ventilated lung, it confronts the anesthesiologist with the need for extremely long duration of single‐lung ventilation (SLV).

Die Anwendung von Lithiumhydroxid als Kohlendioxidabsorbens verhindert das Entstehen von Compound A während Sevoflurananästhesie

ZusammenfassungFragestellung: In einer klinischen Studie wurde die Degradation von Sevofluran bei Verwendung von wasserfreiem Lithiumhydroxid zur Kohlendioxidabsorption im Vergleich zu feuchtem Drägersorb® 800 untersucht. Methodik: Bei jeweils 8 Patienten wurde die Konzentration von Compound A im Inspirationsgas und die Fluoridkonzentration im Serum der Patienten gemessen. Ergebnisse: Bei Einsatz von wasserfreiem Lithiumhydroxid zur Kohlendioxidabsorption blieb die Compound A Konzentration im Inspirationsgas im Bereich der Nachweisgrenze (um 1 ppm). Demgegenüber wurden bei Verwendung von feuchtem Drägersorb® 800 in Übereinstimmung mit der Literatur Werte um 20 ppm gemessen. Die Fluoridkonzentration im Serum stieg zu Beginn der Narkose auch bei Einsatz von Lithiumhydroxid an (15,0±4,8 μmol/l gegenüber 21,9±4,0 μmol/l nach 60 min). Schlußfolgerungen: In den Untersuchungen wurde nachgewiesen, daß bei Verwendung von Lithiumhydroxid Compound A nur in Spuren aus Sevofluran gebildet wird. Aus dem Anstieg der Fluoridkonzentration im Serum bei beiden Patientengruppen kann gefolgert werden, daß dieses vorwiegend aus dem Metabolismus des Sevofluran stammt. Die Kapazität des Lithiumhydroxid zur Kohlendioxidabsorption ist der des Drägersorb® 800 vergleichbar. Damit kann durch Verwendung von Lithiumhydroxid die Narkosesicherheit erhöht werden.SummaryAim of the study was the clinical investigation of sevoflurane degradation when using water-free lithiumhydroxide versus moist Drägersorb® 800 for carbon dioxide absorption. Methods: Concentrations of Compound A in the inspiratory gas mix and serum fluoride levels were measured in two groups of 8 patients each. Results: When water-free lithiumhydroxide was used for carbon dioxide absorption, concentration of Compound A in the inspiratory gas mix was ca. 1 ppm (near minimal level of detection) as compared to ca. 20 ppm for moist Drägersorb® 800. The concentration of fluoride increased during sevoflurane anesthesia (15,0±4,8 μmol/l with lithiumhydroxide versus 21,9±4,0 μmol/l with Drägersorb® 800 after 60 mins). Conclusions: When lithiumhydroxide is used, there is only minimal formation of compound A from sevoflurane degradation. Since serum fluoride levels increased in both patient groups, we conclude that this is caused mainly by metabolism of sevoflurane. Capacity of lithiumhydroxide for carbon dioxide absorption is similar to that of Drägersorb® 800. Therefore, the use of lithiumhydroxide increases patient safety.

Zur Prophylaxe myokardialer Ischämien: Untersuchung während aortokoronarer Bypassoperation mit dem Kalziumantagonisten Diltiazem

ZusammenfassungDa die Häufigkeit postoperativer Myokardinfarkte (MI) der Inzidenz perioperativer myokardialer Ischämien proportional ist, hat deren Prophylaxe erhebliche Bedeutung. Bei 90 Patienten zur aortokoronaren Bypassoperation (ACB) wurde eine perioperative Prophylaxe mit Nitroglycerin (NTG), Diltiazem (DIL) bzw. der Kombination DIL/NTG durchgeführt. Ischämische Episoden (IE) wurden mit einer automatisierten EKG-ST-Strecken-Analyse registriert. In der DIL-Gruppe (6,7%) traten signifikant weniger IE im Untersuchungszeitraum auf als in der NTG-Gruppe (13,2%) bzw. DIL/NTG-Gruppe (13,5%). In der DIL-Gruppe (58,1%) wurden signifikant weniger begleitende hämodynamische Veränderungen registriert als in der NTG- (89,1%) bzw. DIL/NTG-Gruppe (80,0%). Die Herzfrequenz war in der DIL-Gruppe deutlich geringer. Bei ACB war die Gesamtzahl IE während DIL-Prophylaxe gegenüber anderen Prophylaxeformen signifikant geringer. Ursächlich hierfür kann die geringere Inzidenz von Hypo- oder Hypertensionen bzw. Brady- oder Tachykardien speziell nach extrakorporaler Zirkulation durch DIL angeführt werden. Die perioperative Prophylaxe myokardialer Ischämien mit dem Kalziumantagonisten Diltiazem bei Patienten mit KHK während ACB könnte gegenüber anderen Prophylaxeformen Vorteile bieten.AbstractThe incidence of postoperative myocardial infarction (MI) is proportional to the incidence of myocardial ischaemic episodes. Therefore, the prevention of such episodes is of great clinical importance. Methods. In 90 patients undergoing coronary artery bypass grafting (CABG), perioperative i.v. treatment with either nitroglycerin (NTG), diltiazem (DIL), or the combination of DIL/NTG was used until arrival in the intensive care unit. Myocardial ischaemic episodes were monitored with an automatic ECG-ST-trend analyser (Marquette 7010). Results. Significantly less ischaemic episodes were seen in the DIL group (6.7%) compared to the NTG group (13.2%) or DIL/NTG group (13.5%). Furthermore, significantly less ischaemic episodes were associated with relevant haemodynamic alterations in the DIL group (58.1%) compared to the NTG (89.1%) or DIL/NTG group (80.0%). Increases in heart rate were markedly reduced in the DIL group. Discussion. DIL results in marked haemodynamic stabilisation during CABG, especially in the period immediately after extra-corporeal circulation. This might serve as an explanation for the significant reduction in ischaemic episodes in the DIL group compared to the other two groups. Therefore, perioperative prevention of myocardial ischaemia with the calcium antagonist DIL seems to be favourable in patients during CABG.