Combined general and epidural anesthesia with ropivacaine for renal transplantation.

AIM: To evaluate the effectiveness and safety of epidural ropivacaine anesthesia in association with light general anesthesia during renal transplantation and compare epidural and endovenous analgesia techniques for postoperative pain control. METHODS: Experimental design: prospective randomized study. Setting: Organ Transplantation Center, Department of Surgery, "Tor Vergata" University of Rome, St. Eugenio Hospital, Rome. Patients: 25 patients affected by chronic renal failure were enrolled in this study. Thirteen constituted the combined epidural-general anesthesia group (EPI-GEN), mean age 40.15+/-9.81 years; while the others constituted the general anesthesia group (GEN), mean age 46.75+/-7.45 years. Operation: cadaveric renal transplantation. Group EPI-GEN: epidural anesthesia performed with 12-15 ml of a ropivacaine 0.75% and fentanyl 5 microg/ml solution followed by light intravenous or inhalatory general anesthesia and postoperative epidural analgesia with ropivacaine 0.2% and fentanyl 2 mg/ml. Group GEN: inhalatory or intravenous general anesthesia and intravenous Tramadol ( Generic Ultram ) postoperative analgesia. Measurements: hemo-dynamics, renal function, arterial blood gases analysis, acid-base balance and postoperative pain data was collected and examined. RESULTS: Postoperative epidural analgesia resulted significantly more effective than intravenous Tramadol ( Generic Ultram ). PaO(2)/FiO(2) ratio was significantly higher in group EPI-GEN patients both on awakening and throughout postoperative observation. Hemodynamics and renal function did not appear to differ significantly. CONCLUSION. Combined epidural-general anesthesia is as valid a technique as any for renal transplantation; however postoperative epidural ropivacaine analgesia resulted more effective than intravenous Tramadol ( Generic Ultram ). Respiratory function appeared less affected, facilitating a fast and uncomplicated postoperative recovery.

The inhibitory effects of ketamine and pentobarbital on substance p receptors expressed in Xenopus oocytes.

Substance P receptors (SPR) modulate nociceptive transmission within the spinal cord. The effects of IV anesthetics on SPR are not clear. In this study, we investigated the effects of IV anesthetics on SPR expressed in Xenopus oocytes. We examined the effects of ketamine, pentobarbital, propofol, and Tramadol ( Generic Ultram ) on SP-induced Ca(2+)-activated Cl(-) currents mediated by SPR expressed in Xenopus oocytes using a whole-cell voltage clamp. Ketamine and pentobarbital inhibited the SPR-induced currents at pharmacologically relevant concentrations, but propofol and Tramadol ( Generic Ultram ) had little effect on the currents. We also studied the effects of ketamine and pentobarbital on [(3)H]-SP to SPR. Ketamine and pentobarbital inhibited the specific binding of [(3)H]-SP to SPR expressed in Xenopus oocytes. Scatchard analysis of [(3)H]-SP binding revealed that ketamine and pentobarbital decreased the apparent dissociation constant for binding and maximal binding, indicating noncompetitive inhibition. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ketamine and pentobarbital on SP-induced Ca(2+)-activated Cl(-) currents. The results suggest that ketamine and pentobarbital inhibit SPR function. The mechanism of their inhibition on SPR function could not be through activation of the PKC pathway and may be due to noncompetitive displacing the SP binding. IMPLICATIONS: We investigated the effects of IV anesthetics on substance P receptors (SPR) expressed in Xenopus oocytes. Ketamine and pentobarbital inhibit SPR function via noncompetitive displacing SP binding. The findings imply that the inhibition of SPR function by these compounds may play a role in the analgesic effects of these IV anesthetics.

Introduction: Methods, Commentary, and Summary.

OBJECTIVES. Antipsychotics are widely used in geriatric psychiatric disorders. A growing number of atypical antipsychotics are available, expanding clinical options but complicating decision-making. Many questions about use of antipsychotics in older patients remain unanswered by available clinical literature. We therefore surveyed expert opinion on antipsychotic use in older patients (65 years of age or older) for recommendations concerning indications for antipsychotics, choice of antipsychotics for different conditions (e.g., delirium, dementia, schizophrenia, delusional disorder, psychotic mood disorders) and for patients with comorbid conditions or history of side effects, dosing strategies, duration of treatment, and medication combinations. METHOD. Based on a literature review, a 47-question survey with 1,411 options was developed. Approximately three quarters of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, experts were asked to write in answers. The survey was sent to 52 American experts on treatment of older adults (38 geriatric psychiatrists, 14 geriatric internists/family physicians), 48 (92%) of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Guidelines indicating preferred treatment strategies were then developed for key clinical situations. RESULTS. The expert panel reached consensus on 78% of options rated on the 9-point scale. The experts did not recommend using antipsychotics in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, neuropathic pain, severe nausea, motion sickness, or irritability, hostility, and sleep disturbance in the absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts'first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a moodd stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer plus an antipsychotic (57% first line) or a mood stabilizer alone (48% first line) and would discontinue any antidepressant the patient is receiving. For psychotic mania, treatment of choice is a mood stabilizer plus an antipsychotic (98% first line). Risperidone (1.25–3.0 mg/day) and olanzapine (5–15 mg/day) were first-line options in combination with a mood stabilizer for mania with psychosis, with quetiapine (50–250 mg/day) high second line. If a patient has responded well, the experts recommended the following duration of treatment before attempting to taper and discontinue the antipsychotic: delirium, 1 week; agitated dementia, taper within 3–6 months to determine the lowest effective maintenance dose; schizophrenia, indefinite treatment at the lowest effective dose; delusional disorder, 6 months–indefinitely at the lowest effective dose; psychotic major depression, 6 months; and mania with psychosis, 3 months. For patients with diabetes, dyslipidemia, or obesity, the experts would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency). Quetiapine is first line for a patient with Parkinson's disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. More than a quarter of the experts considered these combinations contraindicated: clozapine + carbamazepine, ziprasidone + tricyclic antidepressant (TCA), and a low-potency conventional antipsychotic + fluoxetine. In combining antidepressants and antipsychotics, the experts would be much more cautious with selective serotonin reuptake inhibitors that are more potent inhibitors of the CYP 450 enzymes (i.e., fluoxetine, fluvoxamine, paroxetine) and with nefazodone, TCAs, and monoamine oxidase inhibitors. The experts recommended extra monitoring when combining any antipsychotic with lithium, carbamazepine, lamotrigine, or valproate (except aripiprazole, risperidone, or a high-potency conventional plus valproate) or with codeine, phenytoin, or Tramadol ( Generic Ultram ). CONCLUSIONS. The experts reached a high level of consensus on many of the key treatment questions. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for common clinical dilemmas in the use of antipsychotics in elderly patients. Clinicians should keep in mind that no guidelines can address the complexities of an individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.

Effects of Tramadol ( Generic Ultram ) on alpha2-adrenergic receptors in the rat brain.Faron-Gorecka A, Kusmider M, Inan SY, Siwanowicz J, Dziedzicka-Wasylewska M.Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Cracow PL-31-343, Poland.In recent years, it has been postulated that Tramadol ( Generic Ultram ), used mainly for the treatment of moderate to severe pain, might display a potential as an antidepressant drug. The present study investigated the effects of acute and repeated Tramadol ( Generic Ultram ) administration on the binding of [3H]RX 821002, a selective alpha2-adrenergic receptor ligand, in the rat brain. Male Wistar rats were used. Tramadol ( Generic Ultram ) (20 mg/kg, i.p.) administered acutely (single dose), at 24 h after dosing, induced a significant decrease in the alpha2-adrenergic receptors in all brain regions studied. The most pronounced effects were observed in all subregions of the olfactory system, nucleus accumbens and septum, thalamus, hypothalamus, amygdala, and cerebral cortex. Repeated treatment with Tramadol ( Generic Ultram ) (20 mg/kg, i.p., once daily for 21 days) also induced statistically significant downregulation of [3H]RX 821002 binding sites in the rat brain. However, the effect--although statistically significant--was less pronounced than in the group treated acutely with the drug. Since drugs such as mianserin and mirtazapine are potent antagonists of central alpha2-adrenergic receptors and are effective antidepressants, it is tempting to suggest that, in addition to other alterations induced by Tramadol ( Generic Ultram ), downregulation of these receptors may represent a potential antidepressant efficacy. On the other hand, one should be careful to avoid the treatment of chronic pain with Tramadol ( Generic Ultram ) in patients already receiving antidepressant drugs. Tramadol ( Generic Ultram )-induced downregulation of alpha2-adrenergic receptors--when combined with ongoing antidepressant therapy with drugs, which themselves inhibit serotonin reuptake or are antagonists of alpha2-adrenergic receptors--might cause threatening complications.

Complementary and synergistic antinociceptive interaction between the enantiomers of Tramadol ( Generic Ultram ).

The explanation for the co-existence of opioid and nonopioid components of Tramadol ( Generic Ultram )-induced antinociception appears to be related to the different, but complementary and interactive, pharmacologies of its enantiomers. The (+) enantiomer had Ki values of only 1.33, 62.4 and 54.0 microM at mu, delta and kappa receptors, respectively. The (-) enantiomer had even lower affinity at the mu and delta sites (Ki = 24.8, 213 and 53.5 microM, respectively. The (+) enantiomer was the most potent inhibitor of serotonin uptake (Ki = 0.53 microM) and the (-) enantiomer was the most potent inhibitor of norepinephrine uptake (Ki = 0.43 microM). Basal serotonin release was preferentially enhanced by the (+) enantiomer and stimulation-evoked norepinephrine release was preferentially enhanced by the (-) enantiomer. The (+) and (-) enantiomers each independently produced centrally mediated antinociception in the acetylcholine-induced abdominal constriction test (ED50 = 14.1 and 35.0 micrograms i.t., respectively). Racemic Tramadol ( Generic Ultram ) was significantly more potent (P < .05) than the theoretical additive effect of the enantiomers (antinociceptive synergy). Synergy was also demonstrated (P < .1) in the mouse 55 degrees C hot-plate test (i.p. route) and (P < .05) the rat Randall-Selitto yeast-induced inflammatory nociception model (i.v. and i.p. routes). Critically, the enantiomers interacted less than synergistically in two side-effects of inhibition of colonic propulsive motility and impairment of rotarod performance. The racemate and the (+) enantiomer were active in a chronic (arthritic) inflammatory pain model. Taken together, these findings provide a rational explanation for the coexistence of dual components to Tramadol ( Generic Ultram )-induced antinociception and might form the basis for understanding its clinical profile.

Anaphylactoid reactions and histamine release do not occur after application of the opioid Tramadol ( Generic Ultram ).

After an i.v. application of 100 mg Tramadol ( Generic Ultram ) in 13 healthy volunteers no change in plasma histamine concentration could be detected,( systemic anaphylactoid reactions did not occur, cutaneous reactions were not rated as anaphylactoid since itching and erythema were seen only once after Tramadol ( Generic Ultram ) whereas erythema was also observed twice after saline, blood pressure and heart rate were only very slightly and transiently elevated without any abnormalities in ECG-readings and only side effects typical for opioid therapy were observed.