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T J Luger

Publications and source records attributed to T J Luger.

33 records · Page 2Linked to original sources
PubMed1995

The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats.

The authors investigated the effects of spinal and supraspinal administration of the benzodiazepine receptor agonist midazolam alone and with opioids on tests of nociception (tail-flick and hot-plate tests) and motor function (catalepsy) in rats. At the spinal level, the dose-response curves for peak effect and area under the curve for morphine were shifted to the left (indicating potentiation) by a submaximal dose of intrathecal (i.t.) midazolam (20 micrograms) in both nociceptive tests. Additionally, 2.5 micrograms of i.t. midazolam, a dose having no effect when given alone, increased antinociception in both tests when given with i.t. morphine. Isobolographic analysis confirmed that i.t. injection of midazolam potentiated antinociception induced by i.t. morphine. At the supraspinal level, intracerebroventricular (i.c.v.) injection of 4 micrograms of midazolam inhibited morphine antinociception, i.e., the dose-response curve for morphine in the hot-plate test shifted to the right. Midazolam did not affect morphine antinociception in the tail-flick test. Catalepsy occurred only when the highest doses of i.t. or i.c.v. morphine or midazolam were injected alone. The differing effect of midazolam on morphine-induced antinociception suggests that different mechanisms are involved in the spinal cord and brain.

Analgesia↗
PubMed1995

Effect of the NMDA-antagonist, MK 801, on benzodiazepine-opioid interactions at the spinal and supraspinal level in rats.

1. Benzodiazepines potentiate morphine antinociception at the spinal level via GABAergic mechanisms. At the supraspinal level, the inhibitory effect of midazolam on morphine antinociception cannot be easily explained by GABAA receptor activation. Since excitatory amino acids play a role in central transmission, we investigated the effect of dizocilpine (MK 801) on this interaction in spinal cord and brain. 2. In rats with an intrathecal or intracerebroventricular catheter, the mechanisms of the antinociceptive effect of benzodiazepine-morphine combinations were tested during thermal nociceptive tests. 3. The principal findings of this study were that at the spinal level, midazolam potentiation of morphine antinociception can be antagonized by the NMDA antagonist, MK 801 (10 micrograms), as assessed by hot-plate and tail-flick tests. When drugs were administered supraspinally, midazolam inhibited morphine antinociception only in the hot-plate test, an effect also inhibited by MK 801. In the tail-flick assay, midazolam failed to influence the morphine response. 4. The NMDA antagonist significantly affected midazolam antinociception at the spinal level, but was not effective following i.c.v. administration of the drugs. MK 801 had no effect on morphine antinociception after i.t. and i.c.v. administration of the drugs. 5. The paradoxical effect of midazolam on morphine antinociception and its reversal by MK 801 might be due to modulation at various levels of the neuraxis and/or modulation of different pathways mediated via both GABAA and NMDA receptor mechanisms.

Animals↗
PubMed1994

Mechanisms of the influence of midazolam on morphine antinociception at spinal and supraspinal levels in rats.

The mechanisms for the combined antinociceptive effect of midazolam and morphine administered at spinal (intrathecal, i.t.) and supraspinal (intracerebroventricular, i.c.v.) levels were investigated in rats. Nociceptive test results showed that co-administration of midazolam and morphine at the spinal level potentiated morphine-induced antinociception, and that this interaction was blocked by intraperitoneal (i.p.) naloxone and reversed by i.t. bicuculline and i.p. flumazenil. Also, bicuculline and flumazenil blocked midazolam-induced antinociception at the spinal level, and naloxone completely reversed morphine antinociception. In contrast, when drugs were injected intracerebroventricularly, midazolam inhibited the antinociceptive effect of morphine (as determined by the hot-plate test). The inhibitory effects of i.c.v. midazolam upon i.c.v. morphine antinociception were partly blocked by flumazenil and bicuculline. Midazolam-induced antinociception was increased by bicuculline and decreased by flumazenil; naloxone i.p. blocked both i.c.v. morphine antinociception and i.c.v. morphine-midazolam antinociception. Results after i.t. injection may be due to an interaction between morphine and midazolam/GABAA receptor-activated systems. At the supraspinal level, this interaction may also activate other systems that are distinct from those governing the individual action of each agonist.

Analgesia↗
PubMed1992

Liposome encapsulation prolongs alfentanil spinal analgesia and alters systemic redistribution in the rat.

The effect of liposome encapsulation on the analgesia produced by intrathecally administered alfentanil was examined in the rat. In rats prepared with chronic intrathecal catheters, alfentanil in doses of 1-50 micrograms was administered intrathecally in either saline or in multilamellar liposomes (dipalmitoylphosphatidylcholine and cholesterol). Animals were then tested for analgesia by hot-plate and paw-pressure tests. A second group of animals received intrathecal injections of 30 micrograms alfentanil in saline or liposomes, and blood samples were obtained at 5, 15, 45, and 135 min thereafter for measurement of alfentanil plasma concentrations. The liposome preparation markedly prolonged spinal analgesia in the paw-pressure test and to a lesser extent in the hot-plate test. Neither the time to peak analgesia nor the intensity of analgesia differed between the saline and liposome groups. Liposome encapsulation significantly reduced the peak alfentanil plasma concentration at 5 min and prolonged the period in which low but measurable levels of alfentanil could be measured in plasma. These pharmacokinetic data demonstrate that liposome encapsulation resulted in a slow but prolonged appearance of free alfentanil into a diffusible pool available for uptake into the spinal cord. Consistent with the lower peak plasma concentration of alfentanil, the liposome group demonstrated a significantly lower incidence of catalepsy, indicating less systemic redistribution of alfentanil to supraspinal sites. Liposome encapsulation thus appears to produce a significant reduction in peak plasma concentration with a concomitant reduction in systemic side effects and an increase in the duration of action for a given intrathecal dose of the otherwise rapidly cleared alfentanil.

Alfentanil↗
PubMed1992

Can midazolam diminish sufentanil analgesia in patients with major trauma? A retrospective study with 43 patients.

Benzodiazepine agonists in combination with opioid analgesics are commonly used for combined analgesia and sedation in intensive care patients as well as for anesthesia. In animals, studies indicate either agonistic or antagonistic interactions of benzodiazepine agonists and opioids. This retrospective study of 43 patients evaluated the possible clinical relevance of benzodiazepine-opioid interactions related to pain management. We observed an increase of greater than 50% of the maximal sufentanil infusion rate in significantly more patients in group 2 (13 patients vs 6 patients; chi 2: p = 0.04) and a decrease of the sufentanil infusion rate in eight group 1 patients, but only in one patient in group 2 (chi 2: p = 0.03). We believe that an interaction between midazolam and sufentanil on nociceptive transmission and/or a rapid development of tolerance to sufentanil may be responsible for the observed difference. Contrary to the common clinical impression that midazolam potentiates opioid analgesia, these results indicate that systemic co-administration of midazolam over a period of more than three days can diminish sufentanil efficacy.

Adult↗
PubMed1991

Improvement of septic syndrome after administration of recombinant human growth hormone (rhGH)?

Twenty patients with generalized sepsis were studied prospectively to evaluate the effects of recombinant human growth hormone (rhGH) administration. Five patients had developed sepsis after major abdominal surgery, 15 patients after multiple trauma with head injury (HTI-ISS 38 +/- 2 and Glasgow Coma Scale 4 +/- 1). The urea production rate (UPR) could be significantly reduced by the intramuscular administration of 1.5 IU of rhGH/kg bodyweight (BW) per day (UPR day: 5, 62 +/- 6.7 gm/d vs. UPR day: 10, 42.6 +/- 5.9 gm/d). The catabolic index of Bistrian (BI) was significantly lower after rhGH therapy on day 10 compared to day 5. IGF-1 increased significantly after the administration of rhGH. The nitrogen balance, however, did not become positive, despite the administration of rhGH. The changes in sepsis were estimated by the scoring system according to Elebute and Stoner on days 3, 5, 7, 10, and 13. In those patients who were available for post-treatment evaluation the parameters had returned to baseline values after the withdrawal of rhGH. Results indicate that this therapy might ameliorate the nitrogen intake, but has no influence on the course of sepsis. Compared to previously published results in nonseptic patients, the somatomedin inhibitors as well as the split-products of the complement system and the metabolites of arachidonic acid may have been responsible for this weak effect of rhGH and IGF-1 in septicemia.

Adult↗
PubMed1991

[Impairment of the cognitive faculties and the reaction capability caused by midazolam despite reversal using flumazenil].

Imidazobenzodiazepine (flumazenil) is a specific competitive benzodiazepine antagonist. It antagonizes the sedative-hypnotic, anticonvulsive, anxiolytic and the muscle-relaxant effects of benzodiazepines. Its efficacy is prompt and complete. In several studies rebound phenomena have been observed. It was the aim of this randomized double blind study to investigate the efficacy of flumazenil by psychometric tests. The psychometric parameters we used were cognition and choice reaction time of 12 young and healthy volunteers. Three medication groups (A, B and C) were formed for this investigation. In a cross over design all volunteers had to be treated in each of these three medication groups. Between the groups we set a test-free interval of 7 days for every volunteer. In medication group A (midazolam/flumazenil) we applied 15 mg midazolam. Reversion was performed after 60 min with 0.5 mg flumazenil. In medication group B (placebo/flumazenil) midazolam was replaced by a physiological solution of sodium chloride. In medication group C (placebo/placebo) midazolam and flumazenil were substituted by a physiological solution of sodium chloride. For the investigation of the psychometric parameters (cognition and choice reaction time) we used the so called syndrome kurz test (SKT) and the decision reaction time measuring instrument ("Entscheidungs-Reaktionszeit-Messgerät"; ERM). Psychometric investigations were performed in all groups at intervals of 5, 30, 60, 90, 120, 180 and 240 min. Our results show that cognitive abilities remain impaired up to 60 min after the administration of flumazenil. Decision time and choice reaction time improved 120 min after administration of the antagonist. In our investigation neither rebound phenomena nor agonistic reactions of flumazenil were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Additional subcutaneous administration of flumazenil does not shorten recovery time after midazolam.

We assessed the efficacy of subcutaneous administration of flumazenil (Anexate, Roche), a specific benzodiazepine antagonist, in preventing resedation after initial reversal of midazolam sedation in 30 patients (ASA I-II) undergoing gynaecological surgery. In the post-operative period, the patients received flumazenil i.v. and placebo s.c. (group A), flumazenil i.v. and flumazenil s.c. (group B), or placebo i.v. and placebo s.c. (control group) in a randomized, double-blind procedure. Flumazenil (group A: 0.47 (SD 0.12) mg i.v., group B: 0.48 (0.06) mg i.v.) was significantly more effective than placebo in antagonizing the sedative effects of midazolam, but was accompanied by rebound sedation after 90 min. Additional s.c. administration of flumazenil 0.1 mg (group B) did not eliminate resedation. Undesirable side effects include nausea and vomiting. Local tolerance of the subcutaneous administration of flumazenil was good.

Adult↗
PubMed1990

[Weaning an asthmatic using biphasic positive airway pressure together with continuous sufentanil administration].

A patient presenting with acute severe asthma associated with protracted hypoventilation (paCO2 = 90 mmHg) and impaired consciousness underwent sedation and controlled mechanical ventilation. The peak airway pressure could be reduced by constant-volume mechanical ventilation and analgosedation with midazolam and ketamine. When the gas exchange had stabilized, the first attempt at weaning was made by synchronized intermittent mechanical ventilation (SIMV). After this and two other attempts had failed, the patient was given continuous sufentanil (0.8-1.0 micrograms/kg), as well as additional bolus injections of 2 micrograms/kg and 0.35 micrograms/kg for analgosedation. Controlled mechanical ventilation was replaced by the system of biphasic positive airway pressure (BIPAP). The mechanical ventilatory support was gradually reduced, as was the dose of continuous sufentanil. Extubation was possible at a dose of 0.2 micrograms/kg per h sufentanil and CPAP. From this case, it is not possible to determine whether the BIPAP system or the analgosedation with Sufentanil was the decisive factor in the therapeutic success. It may well have been the combination of both therapeutic measures that--in our opinion--supplemented each other in an ideal way.

Fentanyl↗
PubMed1990

[Infusion or repetitive bolus injection? A clinical study of midazolam/fentanyl and diazepam/fentanyl combination anesthesia in neurosurgical operations].

The objectives of this study were to compare two narcotic/benzodiazepine combinations given either as continuous infusion or intermittent bolus injections in neurosurgical patients. 24 patients scheduled for elective craniotomy were investigated. They were assigned randomly to four different groups for treatment. Groups 1 and 2 received a combination of midazolam and fentanyl, groups 3 and 4 a combination of diazepam and fentanyl. Anaesthesia was maintained either by continuous infusion (groups 1 and 3) or intermittent bolus injections (groups 2 and 4). At six key intervals cardiovascular variables were compared. Furthermore, total drug dosage requirements were measured and compared. Except for measurement 3 (skin incision), cardiovascular dynamics were not markedly different between bolus and infusion groups. Haemodynamic response to skin incision was less in both bolus groups. Furthermore, the bolus technique revealed a non-significant reduction in total drug dosage requirements in the bolus groups. Our data indicate that for neurosurgical anaesthesia conventional bolus injection of intravenous anaesthetics is superior to continuous infusion with respect to intraoperative haemodynamics. The typically reduced level of pain with short peaks only, characteristic for neurosurgical operations, is one of the factors contributing to these surprising results. Furthermore, the simple method of infusion chosen influences the results decisively. Certain advantages might be achieved by the use of sophisticated pharmacokinetic infusion models. Total drug dosage requirements were reduced in the bolus groups mainly because of the typical anaesthetic requirements of craniotomy, disposing it for bolus technique.

Adult↗
PubMed1990

[Nalbuphine as compared with pethidine for postoperative pain therapy].

Nalbuphine is a new partly agonistic antagonistic opioid, that may offer some advantages especially in postoperative pain relief. We compared meperidine (1 mg kg-1) in 100 patients and nalbuphine (0.3 mg kg-1) in 70 patients, administering both agents intravenously after gynaecological operations. Standardised halothane anaesthesia without any opioid was used. After arrival in the recovery room, vigilance (sedation), quality and duration of pain relief were measured by different methods at four different times (0, 15, 30, and 60 minutes). Sedation was significantly more pronounced in the nalbuphine group, but no difference could be found in pain relief and duration between both groups. 6 patients of the n-group showed a short lasting wake-up reaction due to receptor antagonism. 36 patients had to be reinjected at the end of the first hour. We consider nalbuphine to be a safe opioid, however, the marked sedation should be taken into account.

Adult↗
PubMed1990

[Determination of hemoglobin concentration using the hemoglobin azide method in traumatic emergencies].

UNLABELLED: The present study examined the clinical practicability of a new hemoglobin measurement device based on a modified azide-methemoglobin reaction (HiN3 method) in trauma patients. The accuracy of the HiN3 method was compared to the internationally well accepted hemiglobincyanide method (HiCN method) in arterial, capillary, and venous blood samples. PATIENTS AND METHODS: 1. Comparison of the methods. In 62 trauma patients, hemoglobin measurements using the HiN3 method were compared to results obtained by the HiCN method. Blood samples were taken simultaneously from the same patient to evaluate each measurement procedure in arterial (group 1), capillary (group 2), and venous blood samples (group 3). 2. Accuracy. To evaluate the accuracy of both methods we compared two venous blood samples taken simultaneously from the same patient. 3. Reproducibility. For measurement of the reproducibility of the HiN3 method, the first two results of each three-time-measurement were compared. Statistical analysis of the results was performed using regression analysis. RESULTS: 1. Comparison of the methods. Comparing the results of hemoglobin measurements resulting from the HiN3 and HiCN methods, a strong correlation was found in arterial (Fig. 2), capillary (Fig. 3), and venous blood (Fig. 4). 2. Accuracy. The HiN3 method had an accuracy of +/- 1.47% and the HiCN method +/- 2.55%. 3. The reproducibility of the HiN3 method was +/- 1.25% (Fig. 5); however, one pair of samples did show a significantly different initial value (Hb 8.4 g/dl in I, but 10.4 g/dl in I and III). DISCUSSION: From our examinations in trauma patients, we can recommend this easy to handle device, particularly for acute diagnostic purposes in emergency patients and for trend evaluations both in the hospital and in the prehospital period for rapid and precise hemoglobin determinations.

Adult↗
PubMed1989

[The behavior of hGH (human growth hormone) and somatomedin C following anesthesia induction with propofol in comparison with diazepam and thiopental].

It was the aim of present study to examine possible interactions between human growth hormone (hGH) and Somatomedin C (SmC), when inducting anaesthesia with propofol in healthy patients. Moreover these effects of propofol should be compared with that of diazepam and thiopentone. 30 patients scheduled for elective plastic-surgery were divided randomly into 3 groups. Induction of anaesthesia was performed in group 1 with diazepam, in group 2 with thiopentone and in group 3 with propofol. Measurements of hGH, SmC as well as blood glucose were performed at 4 different given times: (1.) preoperatively, (2.) 15 minutes, (3.) 30 minutes, (4.) 60 minutes after inducting anaesthesia. Diazepam and thiopentone lead to increases in hGH secretion already in a very early phase after induction of anesthesia (15 minutes) and remained on elevated level. Concentrations of Somatomedin C, as well as of blood glucose, however, remained unchanged during the whole observation period. In comparison to that findings propofol did not show any influence on hGH and consecutively on Somatomedin C activity at any time. Based on our results we can conclude that propofol should be the induction-agent of choice predominantly when anaesthetizing patients with unknown hormonal state (outpatients scheduled for operation).

Adult↗
PubMed1988

[Response of human growth hormone to anesthesia induction with propofol].

Although there are distinct differences in both pharmacokinetics and chemical structure, propofol has sedative effects similar to those of benzodiazepines. Both diazepam and thiopental, commonly used agents for inducing anaesthesia, show some typical neuroendocrine effects such as liberation of human growth hormone (hGH) in addition to their well-known influences on the cardiovascular system. It was our aim to examine the endocrine response of hGH after induction of anaesthesia with propofol and to compare any possible effects with those of diazepam and thiopental. The study was performed on 30 non-premedicated patients, who underwent plastic-surgery (mean age: x = 35 +/- 8.3 years, mean body weight: x = 68.9 +/- 23.2 kg). No signs of endocrine disturbances were found in the patients prior to the study. Patients were divided in a random fashion into 3 groups of 10 persons each: In group 1 propofol was given in a bolus injection (2 mg/kg) and then by infusion for a period of 10 min (0.2 mg/kg/min). In group 2 diazepam (0.3 mg/kg) and in group 3 thiopental (5 mg/kg) were administered as a bolus to induce anesthesia. All patients were intubated immediately after induction of anesthesia and then relaxed using vecuronium (1 mg/kg). Ventilation was performed mechanically during the entire operative period (N2O/O2 - FiO2:0.33, tidal volume 10 ml/kg, respiratory rate: 14/min). To maintain anesthesia halothane (0.5-1.0 vol.-%) and meperidine (0.75 mg/kg) were added 15 min after induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗