[Technique and pathophysiology of isolated hypoxic perfusion of the abdomen]. / Technik und Pathophysiologie der isolierten hypoxischen Perfusion des Abdomens.

Isolated hypoxic perfusion (IHP) is a commonly used technique in the treatment of abdominal malignancies. During a phase II-study the pathophysiology of this technique was explored in patients with advanced pancreatic cancer. Twenty perfusions of the abdomen were performed in 17 patients. Under general anesthesia, femoral vessels were dissected and two balloon catheters were inserted into aorta and vena cava cranial the celiac trunk and the hepatic veins. After instillation of 40 mg of Mitomycin C (MMC) into the running perfusion system, the perfusion was maintained for further 20 minutes. Blood samples were taken in 5-minute intervals to determine pH value, blood gases as well as concentrations of electrolytes, lactate and MMC in the arterial blood. Simultaneously, blood samples were taken from the perfusion blood via a side-port of the extracorporeal perfusion system. Additionally, perfusion pressures, arterial and central venous pressure, heart rate, and the pressure in the aorta distal the balloon catheter were registered continuously. All 20 perfusions had been undertaken without perioperative mortality. After inflating the balloon catheters, blood pressure and heart rate increased rapidly. Within 5 minutes of perfusion an increase in pCO2 and the concentrations of K+ and lactate in the perfusate were registered, while pH and pO2 decreased. Fifteen minutes after instillation of MMC, concentrations of MMC in arterial and perfusion blood were equal. Twenty-four hours after the perfusion all parameters had returned to normal values. IHP was well feasible in 20 consecutive perfusions without major technical problems. A distinct but tolerable combined acidosis resulted from IHP. Despite the exact positioning and control of the balloon catheters a complete isolation was not possible.

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer.

AIMS: Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS: IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. RESULTS: Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusate's PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). CONCLUSIONS: The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

[Isolated hypoxic perfusion with mitomycin C confers no benefit for patients with advanced pancreatic carcinoma]. / Isolierte hypoxische Perfusion mit Mitomycin C bringt keinen Benefit für Patienten mit fortgeschrittenem Pankreaskarzinom.

Since therapy options in the treatment of advanced pancreatic cancer are rare, the present study has investigated whether patients with advanced pancreatic cancer may profit from isolated hypoxic perfusion (IHP) of the abdomen with mitomycin C. None of the 17 treated patients responded to IHP with mitomycin C, and the survival time corresponded to that of untreated patients. On the basis of these results, this procedure should no longer be used as treatment for patients with advanced pancreatic cancer.

[Mask induction and one-lung ventilation with sevoflurane]. / Maskeneinleitung und Ein-Lungenventilation mit Sevofluran.

The low blood/gas solubility, the rapid uptake and nonpungent odor permits mask induction with sevoflurane in adults. Depending on the induction techniques (tidal breathing, deep breaths or single-breath induction), the use of nitrous oxide and the concentration of inspired sevoflurane anesthesia can rapidly be induced within 41-178 s. Adverse effects like coughing, breath-holding or increased secretions occur with a low incidence of 2%-20%. Some 88 to 100% of the volunteers or patients would accept a mask induction again. Clinical experience shows that sevoflurane is well indicated for mask induction in adults. Acute severe bronchospasm is a feared complication of anesthesia with an incidence of 1.7%. Although halothane is often recommended as the agent of choice in patients with reactive airways, there is little evidence in humans that it is more effective than other volatile agents. The bronchodilating effects of sevoflurane are comparable to those of other volatile anesthetics, it produces minimal airway irritation and allows rapid adjustment of anesthetic depth. These properties and our clinical experience suggest that sevoflurane is a useful choice for patients with reactive airways. Hypoxemia during one-lung ventilation (OLV) occurs in 9-27% of patients and remains a clinical problem. Although hypoxic pulmonary vasoconstriction is directly inhibited by volatile anesthetics in in vitro studies, this effect is usually of minor clinical consequence. The use of volatile anesthetics may be advocated because of their salutory effects on bronchomotor tone, high potency (allowing high inspired concentration of oxygen while avoiding awareness) and rapid adjustment of anesthetic depth. Sevoflurane possesses these attributes and may be useful for OLV.

[Interactions of dry soda lime with enflurane and sevoflurane. Clinical report on two unusual anesthesias]. / Interaktion von trockenem Atemkalk mit Enfluran und Sevofluran. Klinischer Bericht über zwei ungewöhnliche Anästhesieverläufe.

UNLABELLED: We report two cases of unexpected courses of inhalation anaesthesia with sevoflurane and enflurane which were caused by the presence dry soda lime. Case 1: During mask induction of a healthy 46-year-old female patient for elective hysterectomy it was noted that the vaporizer setting of 5% sevoflurane (in 50% O2, 50% N2O) did not result in the expected increase of inspiratory sevoflurane concentration. At the same time, the anaesthesiologist observed that the patient did not lose consciousness while the temperature of the soda lime canister increased sharply and the colour of the soda lime turned to blue with condensing water visible in the tubing. It was later determined that this anaesthesia machine had not been used for more than 2 weeks. Analysis of the soda lime showed a water content of <1%. Case 2: Following intravenous induction of a non-smoking 64-year-old male patient for elective gastrectomy, it was noted that the concomitant inhalation of enflurane was associated with a sharp rise in the temperature of the soda lime canister, a colour change of the soda lime to blue and a decrease in the measured inspiratory enflurane concentration despite an unchanged or even increased vaporizer setting. Arterial blood gas analysis revealed a CO-Hb concentration of 8.8% with otherwise normal acidity and partial gas pressures. Immediate change of the absorbant resulted in a decline in the CO-Hb concentration to 6.9% within 3 h. It was later determined that the anaesthesia machine had not been used for 34 h. Analysis of the soda lime showed a water content of 5.4%. DISCUSSION: Both case reports were associated with a rise in temperature and a colour change to blue of the soda lime. Reactions of desflurane, enflurane or isoflurane with dry soda lime resulting in significant CO-Hb formation have been previously reported. Reactions of sevoflurane with dry soda lime have been observed but have so far not been published. Until further analysis of these phenomena is completed, it is mandatory for the patient's safety to guarantee that only soda lime with a sufficient water content be used for clinical anaesthesia.

[The plasma histamine level during anesthesia induction using midazolam]. / Plasmahistaminspiegel bei Anaesthesieeinleitung mit Midazolam.

Midazolam has not yet been investigated for its possible properties as a histamine releaser. The aim of the following study was to ascertain whether histamine release follows the i.v. injection of midazolam. METHODS. Twenty patients between 18 and 58 years of age were split into two groups at random. Either 0.15 mg/kg midazolam or 0.15 ml/kg NaCl 0.9% were injected i.v. Venous blood was drawn 2 min before and 2, 5, and 10 min after each injection. The content of histamine in plasma was determined by HPLC. RESULTS. In the midazolam group, histamine levels decreased from 0.37 ng/ml to 0.29 ng/ml after 5 min (P less than 0.05). The kinetics typical of histamine release could not be observed in any of the patients. We observed a slight decrease in the blood pressure or tachycardia in 3 patients, but even in these cases there was no increase in histamine level. In the NaCl group, the histamine level decreased from 0.34 ng/ml to 0.23 ng/ml after 2 min (P less than 0.05). The hemodynamics of these patients remained unchanged. One patient had an abnormally high histamine level prior to the injection (2.33 ng/ml). CONCLUSION. Our results show that midazolam is not a histamine releaser. The relevance of 1 patient having a high baseline level of histamine remains unclear.

[The pharmacokinetics of midazolam following intramuscular administration]. / Die Pharmakokinetik des Midazolam nach intramuskulärer Gabe.

There have been conflicting reports on the pharmacokinetics of midazolam, administered i.m. The aims of this study were to determine the pharmacokinetic data of midazolam following different doses and to test whether a correlation exists between its plasma level and sedative effect. METHODS. Fifteen patients between the ages of 18 and 50 were divided into three groups for i.m. administration of midazolam 0.05 mg/kg (group 1), 0.1 mg/kg (group 2), or 0.15 mg/kg (group 3) i.m. Venous blood was drawn 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 min, and 2, 3, 4, 6, 8 h after the injection. After the same times the sedative effect was estimated by the anesthetist (awake, sleeping but easy to wake, sleeping and difficult to wake, unconscious). The plasma midazolam levels were determined by gas chromatography. The following pharmacokinetic parameters were ascertained: Cmax (peak concentration), tmax (time to attain peak concentration), clearance, elimination half-life. RESULTS. The peak concentration is directly proportional to the dosage of midazolam and the relation between the two is linear. The median Cmax values were 35.3 ng/ml (group 1), 103 ng/ml (group 2) and 123.5 ng/ml (group 3). The duration of tmax was between 12 and 36 min (means = 27 min). There was no significant difference between the groups in clearance, tmax, or elimination half-life. A significant correlation was found between the plasma midazolam levels and the degree of sedation. However, we observed a considerable variability in the effect. CONCLUSION. A 95% confidence interval for the prediction of the peak concentration of midazolam after i.m. injection is stated. Midazolam should be administered at a dose of 0.05 mg/kg at the most, if unconsciousness after premedication is to be avoided.