Christoph Selig

Clonidine premedication in patients with sleep apnea syndrome: a randomized, double-blind, placebo-controlled study.

Patients with sleep apnea often present with cardiac diseases and breathing difficulties, with a high risk of postoperative respiratory depression. We conducted a randomized, double-blind, prospective study in 30 adult patients with obstructive sleep apnea, undergoing elective ear-nose-throat surgery. The patients were randomly assigned to receive placebo or clonidine (2 &mgr;g/kg oral) the night before and the next morning 2 h before surgery. Spo2, heart rate, mean arterial blood pressure, snoring, and oronasal airflow were monitored for 36 h. A standard anesthesia was used consisting of propofol and remifentanil. Anesthetic drug consumption, postoperative analgesics, and pain score were recorded. In the clonidine group, mean arterial blood pressures were significantly lower during induction, operation, and emergence from anesthesia. Both propofol dose required for induction (190 ± 32.2 mg) and anesthesia (6.3 ± 1.3 mg · kg−1 · h−1) during surgery were significantly reduced in the clonidine group compared with the placebo group (induction 218 ± 32.4, anesthesia 7.70 ± 1.5; P < 0.05). Piritramide consumption (7.4 ± 5.1 versus 14.2 ± 8.5 mg; P < 0.05) and analgesia scores were significantly reduced in the clonidine group. Apnea and desaturation index were not different between the groups, whereas the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo than in the clonidine group (76.7% ± 8.0% versus 82.4% ± 5.8%; P < 0.05). We conclude that oral clonidine premedication stabilizes hemodynamic variables during induction, maintenance, and emergence from anesthesia and reduces the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation.

Haematological Effects of RhGM-CSF in Dogs Exposed to Total-body Irradiation with a Dose of 2·4 Gy

It was the specific aim of this study to test the stimulatory effects of recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per day for 21 days caused strong but transient increases in the peripheral blood neutrophils. The monocyte counts also showed a transient rise during treatment in a dose-dependent fashion, whereas the lymphocyte counts increased only at the higher dose of rhGM-CSF and the platelet counts were transiently depressed during the course of the treatment. In the irradiated animals treatment with rhGM-CSF decreased the severity and shortened the duration of neutropenia but had no significant influence on monocyte or lymphocyte recovery. The granulocyte values showed a characteristic pattern of fluctuations with the first peak occurring at the same time (day 10 to day 13) when the abortive rise was observed in the untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed during the whole treatment course, similar to the untreated irradiated controls. These results indicate that treatment with GM-CSF can be an effective biological monotherapy for radiation-induced bone marrow failure, but that for higher radiation doses the number of GM-CSF responsive target cells will become a critical determinant of therapeutic efficacy.

Acceleration of hemopoietic recovery in dogs after extended-field partial-body irradiation by treatment with colony-stimulating factors: rhG-CSF and rhGM-CSF

PURPOSE The influence of treatment with the two colony-stimulating factors, rhG-CSF and rhGM-CSF, on the hemopoietic recovery in aplastic bone marrow sites after extended-field irradiation was studied in a canine model. METHODS AND MATERIALS The dogs received irradiation of the cranial part of their body with a single dose of 11.7 Gy, comprising approximately 72% of the total bone marrow mass. Anatomically this type of exposure corresponds to upper body irradiation (UBI) as employed under clinical conditions. Treatment with both the CSFs was employed for 7 days by daily injections of 30 microg/kg, starting 24 hr after irradiation. RESULTS Treatment with rhGM-CSF did not completely prevent the initial decrease of the granulocyte counts, but caused an accelerated, though incomplete, recovery in the period from day 5 to day 15. In contrast, treatment with rhG-CSF caused two phases of granulocytosis and an early recovery to normal levels at day 11 after irradiation. Treatment with rhG-CSF, but not with rhGM-CSF, was associated with a strong supra-normal increase of progenitor cells in the blood within the first 8 days and an accelerated hemopoietic recovery in the irradiated sites particularly within the first 7 days after the exposure. CONCLUSIONS These results indicate that under conditions of partial-body irradiation short term treatment with G-CSF is superior to GM-CSF in initiating the hemopoietic recovery on the basis of endogenous stem cell seeding.

Bispectral index (BIS) and suppression ratio (SR) as an early predictor of unfavourable neurological outcome after cardiac arrest

INTRODUCTION Predicting the neurological outcome after cardiopulmonary resuscitation (CPR) is extremely difficult. We tested the hypothesis whether monitoring of bispectral index (BIS) and suppression ratio (SR) could serve as an early prognostic indicator of neurological outcomes after CPR. METHODS Cerebral monitoring (BIS, SR) was started as soon as possible after initiation of CPR and was continued for up to 72h. The functional neurological outcome was measured on day 3, day 7 and again one month after CPR via a clinical examination and assessment according to the cerebral performance category score (CPC). RESULTS In total 79 patients were included. Of these, 26 patients (32.9%) survived the observation period of one month; 7 of them (8.9%) showed an unfavourable neurological outcome. These 7 patients had significantly lower median BIS values (25 [21;37] vs. 61 [51;70]) and higher SR (56 [44;64] vs. 7 [1;22]) during the first 4h after the initiation of CPR. Using BIS<40 as threshold criteria, unfavourable neurological outcome was predicted with a specificity of 89.5% and a sensitivity of 85.7%. The odds ratio for predicting an unfavourable neurological outcome was 0.921 (95% CI 0.853-0.985). The likelihood to remain in a poor neurological condition decreased by 7.9% for each additional point of BIS, on average. CONCLUSION Our results suggest that BIS and SR are helpful tools in the evaluation of the neurological outcomes of resuscitated patients. Nevertheless, therapeutic decisions have to be confirmed through further examinations due to the far-ranging consequences of false positive results.

Radioprotective effect of N-acetylcysteine on granulocyte/macrophage colony-forming cells of human bone marrow

N-Acetylcysteine, known as a radical scavenger, was examined for its influence on the radiotolerance of progenitor cells of granulocytopoiesis. Added before and after irradiation in a dose of 2 mg/ml to suspension cultures of non-adherent low-density human bone marrow cellsN-acetylcysteine (AcCys) clearly improved the survival. TheD0 value of the survival curve for granulocyte/macrophage colony-forming cells increased by a factor of 1.56 as compared to non-treated control suspensions. The improvement of radiation tolerance is probably not only based on the radical scavenger properties (radioprotective component) of AcCys, but also on the support of repair processes.

The effects of fenoterol inhalation after acid aspiration-induced lung injury.

BACKGROUND: Acid aspiration is a serious complication that can occur during general anesthesia. Studies show that &bgr;-agonists have beneficial effects on lung injury. Therefore, we tested the effect of the nebulized &bgr;-agonist fenoterol on lung variables in a rodent model of acid-induced lung injury. METHODS: In a prospective, randomized, and controlled study, we evaluated the effects of fenoterol inhalation on lung oxygenation, inflammation, and pulmonary histology in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anesthesia with tracheotomy and carotid catheter insertion. Lung injury was induced by instillation of 0.4 mL/kg 0.1 M hydrochloric acid. The lungs were ventilated for 6 h and randomized to receive either fenoterol inhalation 10 &mgr;g or saline inhalation, both at 15 and 180 min after acid aspiration. Mean arterial blood pressures and peak airway pressures were documented, arterial blood gases were determined at 30, 90, 180, 270, and 360 min, and postmortem histology was subsequently examined. Additionally, fenoterol concentrations in bronchoalveolar lavage fluid (BALF) and plasma were determined by liquid chromatography/tandem mass spectroscopy. After 360 min tumor necrosis factor (TNF)-&agr; and interleukin (IL)-6 were determined in the BALF, and lungs were dried for determination of the wet/dry ratio. RESULTS: Inhalation treatment with 10 &mgr;g fenoterol significantly increased oxygenation after 270 and 360 min when compared with placebo. Fenoterol-treated rats showed a significant decrease in IL-6 and TNF-&agr; levels and in the wet/dry weight ratio of the lungs. The histologic appearance showed significantly less interstitial edema and leukocyte infiltration in the fenoterol group. The concentration of fenoterol was 10.3 &mgr;g/L (median) in the BALF and <1 &mgr;g/L in the plasma. CONCLUSIONS: Fenoterol inhalation improved oxygenation after 270 and 360 min, attenuated the release of TNF-&agr; and IL-6, and diminished the lung edema and infiltration of polymorphonuclear leukocytes.

Radiation-induced DNA damage in canine hemopoietic cells and stromal cells as measured by the comet assay

Stromal cell progenitors (fibroblastoid colony‐forming unit; CFU‐Fs) are representative of the progenitor cell population of the hemopoietic microenvironment in bone marrow (BM). Previous studies of the radiation dose—effect relationships for colony formation have shown that canine CFU‐Fs are relatively radioresistant as characterized by a D0 value of about 2.4 Gy. In contrast, hemopoietic progenitors are particularly radiosensitive (D0 values = 0.12‐0.60 Gy). In the present study, the alkaline single‐cell gel electrophoresis technique for the in situ quantitation of DNA strand breaks and alkalilabile sites was employed. Canine buffy coat cells from BM aspirates and cells harvested from CFU‐F colonies or from mixed populations of adherent BM stromal cell (SC) layers were exposed to increasing doses of X‐rays, embedded in agarose gel on slides, lysed with detergents, and placed in an electric field. DNA migrating from single cells in the gel was made visible as “comets” by ethidium bromide staining. Immediate DNA damage was much less in cultured stromal cells than in hemopoietic cells in BM aspirates. These results suggest that the observed differences in clonogenic survival could be partly due to differences in the type of the initial DNA damage between stromal cells and hemopoietic cells.

Bispectral index monitoring during cardiopulmonary resuscitation repeated twice within 8 days in the same patient: a case report

Research on cardiac resuscitation has led to various changes in the techniques and drug administration involved in modern advanced life support. Besides improving primary cardiac survival, interest is increasingly focused on a favourable neurological outcome. However, until now there has been no on-site equipment to support the clinical observations of the cardiopulmonary resuscitation (CPR) team. Bispectral index (BIS) monitoring has been used for avoiding awareness during anaesthesia for many years. We report a case of a 68-year-old patient suffering twice from cardiac arrest due to thromboembolism within a few days. While the first cardiac resuscitation was survived without neurological consequences, the patient died after the second event. Both resuscitation events were monitored using the BIS. We discuss the course of BIS values and their possible contribution to the prediction of outcome.

Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro

Summary. Ficoll‐separated mononuclear cells (MNC) of cryopreserved human bone marrow were incubated with isotoxic doses of diltiazem, N‐acetylcysteine (NAC), glycopolysaccharide extract of spirulina platensis (SPE), tempol, thiopental, WR2721 and WR1065. After irradiation with a single dose of 0·73 Gy, survival of granulocyte/macrophage colony‐forming cells (GM‐CFC) was determined at d 10–14, using an agar culture system. Diltiazem, NAC, tempol and WR1065 significantly improved radiotolerance with protection factors (PF) between 1·21 and 1·36 (n = 5, P < 0·05) at 0·73 Gy (PF‐0·73 Gy). The survival curves of diltiazem (D0 = 0·88 Gy, n = 1·00), NAC (D0 = 0·92 Gy, n = 1·10), tempol (D0 = 0·99 Gy, n = 1·10), WR1065 (D0 = 0·89 Gy, n = 1·16) and control (D0 = 0·78 Gy, n = 1·00) over 0·36–2·91 Gy showed a significant radioprotective effect for D0 only for tempol (P = 0·018) and for the extrapolation number ‘n’ only in the case of NAC (P = 0·023). Cell cycle analysis of the CD34+ cell subpopulation (control‐0 h: G1 = 82·7%, S = 13·7%, G2/M = 3·6%) revealed that all compounds with a significant PF‐0·73 Gy also caused a significant increase in CD34+ cells in S phase up to 48 h. Within the first 24 h, only NAC (26·7 ± 4·1%), tempol (14·3 ± 1·0%) and possibly WR1065 (15·5 ± 1·6%) had higher fractions of CD34+ S‐phase cells compared with controls. This observation and the improvement of GM‐CFC cloning efficiency indicated that only NAC was able to recruit progenitor cells in the cell cycle, whereas tempol and WR1065 possibly inhibited cell cycle progression by S and G2/M arrest. Of the radioprotectors tested, NAC, tempol and WR1065 may be suitable to support, alone or combined with cytokine therapy, accelerated haematopoietic recovery after irradiation.

Differences in radiation response between cells in S-phase and non-S-phase cells of the granulocyte/macrophage progenitor (GM-CFC) compartment

Studies were performed to investigate the radiation response of granulocyte/macrophage progenitor cells from canine bone marrow in different proliferative states, and in which way it will change if the S-phase cells are eliminated from the irradiated populations. To obtain progenitor cells of different proliferative states, bone marrow cell suspensions were kept in liquid cultures for 1 or 3 days in the presence of colony stimulating activity. Radiation dose response curves were determined (a) for the total population of progenitor cells under normal conditions (fraction of cells in S-phase 35%), (b) in a state of rapid cycling (fraction of S-phase cells 53% to 57%), and (c) after sterilization of S-phase cells by pretreatment with 3H-thymidine. The rapidly proliferating progenitor cells showed a strong decrease in their radiosensitivity (D0 = 0.84 Gy) within the first day in suspension culture when compared to the normal population (D0 = 0.50 Gy). The cell populations from which the S-phase cells had been eliminated were found more sensitive than the respective total populations (D0 values in the range from 0.44 Gy to 0.50 Gy). The D0 values for the S-phase cells were between 0.57 Gy and 1.13 Gy depending on the proliferative state of the cell populations. These data indicate that granulocyte/macrophage progenitor cells during progression through the S-phase become less radiosensitive than they are in other phases of the cell cycle.