Tramadol has no effect on cortical renal blood flow--despite increased serum catecholamine levels--in anesthetized rats: implications for analgesia in renal insufficiency.

Shigematsu A.

Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.

Tramadol is an analgesic that inhibits norepinephrine (NE) reuptake. Although NE released from renal sympathetic nerves causes renal hypoperfusion, the effects of tramadol on renal hemodynamics have not been well characterized. We investigated the effects of tramadol on renal blood flow (RBF), mean arterial blood pressure (MAP), and heart rate (HR) by using a laser Doppler flowmeter, both in normal anesthetized rats and in rats with experimentally-induced nephritis secondary to anti-Thy 1.1 antibody administration. We also studied the effects of tramadol on serum NE levels. Tramadol increased MAP and decreased HR without changing RBF in normal rats at clinical doses. Serum NE levels increased up to 176% of control after a 2 mg/kg bolus injection of tramadol. Continuously infused, increasing doses of tramadol (0.5-4 mg.kg(-1).h(-1)) did not affect MAP, HR, or RBF. Tramadol also increased MAP and decreased HR without changing RBF in rats with experimentally induced renal insufficiency. These findings suggest that a bolus injection of tramadol does not alter RBF, although it causes a decrease in HR and an increase in MAP and serum NE in both normal rats and in rats with renal insufficiency. These results suggest that tramadol may have little effect on RBF during the postoperative period. IMPLICATIONS: A bolus and continuous injection of tramadol does not alter renal blood flow (RBF) in normal rats. A bolus injection of tramadol has little effect on RBF in rats with experimentally induced renal insufficiency. These results suggest that tramadol would be a safe analgesic for maintaining RBF during the postoperative period.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11867386&dopt=Abstract tramadol



[Post-surgical paediatric pain: Nursing- PCA vs continuous I.V. infusion of tramadol ]

[Article in Spanish]

Ruiz Jimenez JI.

Servicio de Anestesiologia, Hospital Universitario Virgen de la Arrixaca, Ctra. del Palmar s/n, Murcia.

AIM: To evaluate the efficiency in the control of the post-surgical paediatric pain of the combination of a weak opioid [tramadol (T)] and an NSAID (paracetamol), comparing its administration through "Nursing-PCA" (NCA) techniques or through continuous i.v. infusion. METHODS: The investigation has been carried out in 30 patients (mean 9.5 months) selected according to their foreseeable degree of moderate-hard pain. All of them consumed in the postoperative period: rectal paracetamol (20 mg/Kg) every 8 hours and tramadol in two groups. Group I: PCA pump with tramadol that was handled by the nurse. Initial dose: 0.5 mg/Kg NCA, bolus injection 0.3 mg/Kg with an interval of 10 minutes for security and a highest dose of 1.2 mg/Kg/4 h every 4 hours. Group II: continuous infusion i.v. of tramadol (6 mg/Kg/24 h). The pain was evaluated, as well as the sedative action, saturation oxygen, respiratory and hemodynamics parameters, adverse effects, and efficiency during the first 24 hours, as well as the number of total dose of drugs asked in the Nursing PCA group. RESULTS: Pain decreased in both groups. There were more sedative effects in group II and the total dose of tramadol was higher. There were no cases of respiratory depression. CONCLUSIONS: The combination of tramadol and paracetamol through "Nursing PCA" has turned out to be an efficient method in the treatment of the post-surgical pain in little children and those whose are in their lacteal period. It is a possible alternative of the continuous infusion of Morphine in these patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12793291&dopt=Abstract tramadol



Tramadol inhibits rat detrusor overactivity caused by dopamine receptor stimulation.

Andersson KE.

Department of Clinical Pharmacology, Institute for Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden.

PURPOSE: In patients with Parkinson's disease an imbalance between stimulatory D2-like receptors and inhibitory D1-like receptors may contribute to detrusor overactivity. Apomorphine, which stimulates D1-like and D2-like dopamine receptors, induces detrusor overactivity in rats. Tramadol is an analgesic drug that stimulates opioid receptors and inhibits reuptake of serotonin and noradrenaline. To evaluate a potentially inhibitory effect of tramadol the drug was given to rats with apomorphine induced detrusor overactivity. MATERIAL AND METHODS: Female Sprague-Dawley rats were used. During anesthesia catheters were introduced into the bladder dome, femoral vein and subcutaneously (SC). Three days later the rats were placed in a metabolism cage and voiding was stimulated by infusing saline into the bladder. Micturition parameters were recorded and compared after the administration of apomorphine and tramadol or vehicle. Desmopressin was given as pretreatment to suppress the diuresis produced by tramadol. RESULTS: While 30 microg kg-1 apomorphine SC was devoid of effect, 60 and 100 microg kg-1 apomorphine SC induced a transient detrusor overactivity. Tramadol (1 mg kg-1) was without effect but 5 and 10 mg kg-1 tramadol intravenously attenuated the effects of apomorphine, while inducing prominent diuresis. Pretreatment with desmopressin, which did not alter cystometry or the effects of apomorphine, abolished diuresis. In these rats 5 and 10 mg kg-1 tramadol intravenously abolished the overactivity caused by apomorphine SC. CONCLUSIONS: Tramadol effectively suppresses apomorphine induced detrusor overactivity in doses shown to have analgesic activity. Hence, tramadol may provide an approach to treat lower urinary tract disorders in which dopamine receptor activation is involved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12796703&dopt=Abstract tramadol



[Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers]

[Article in German]

Neruda B.

Abteilung fur Gefasschirurgie und Nierentransplantation, Medizinische Einrichtungen der Heinrich-Heine-Universitat, Moorenstrasse 5, D-40225 Dusseldorf.

Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic, has been supposed to have little effect on propulsive gastrointestinal motility. However, this has not been specifically studied in man. Following institutional approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone, and codeine, respectively, in a double-blind randomised cross-over design. Additionally, 12 further volunteers were given 100 mg of each opioid in a double-blind, randomised fashion, followed by measurement of gastrocoecal transit time. Gastrointestinal transit time was measured using the lactulose H(2)-breath test. A threefold increase in end-expiratory hydrogen when compared to the control value was considered the end point of gastrocoecal transit. At the low dose (50 mg) the three opioids did not differ significantly with regard to their effect on gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7 SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/- 12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The increase in gastrocoecal transit time was significant (P < 0.01) for high doses of tilidine/naloxone and codeine in contrast to the effect of the low doses. This lesser constipation effect may be due to the reduced affinity of tramadol to the mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of tilidine/naloxone and codeine than after tramadol. Perspiration was significantly higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and codeine. Sedation is considered a typical symptom of analgesics interacting with centrally located opioid receptor sites. The higher incidence of perspiration after tramadol suggests that monominergic pathways may be involved in thermoregulation. In conclusion, the opioids tilidine/naloxone and codeine at the doses used significantly prolong gastrointestinal transit time in the high-dose range. Since tramadol does not induce a dose-related increase in gastrocoecal transit time, it may be a useful analgesic in patients who are prone to developing constipation during high-dose opioid therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12799847&dopt=Abstract tramadol