Impact of CYP2D6 genotype on postoperative tramadol analgesia.

Stuber F.

Klinik und Poliklinik fur Anasthesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universitat Bonn, Sigmund-Freud-Strass 25, 53105 Bonn, Germany. ulrike.stamer ukb.uni-bonn.de

Genetic polymorphisms result in absent enzyme activity of CYP2D6 (poor metabolizers, PM) in about 10% of the Caucasian population. This study investigates whether the PM genotype has an impact on the response to tramadol analgesia in postoperative patients. A prospective study design was used and 300 patients recovering from abdominal surgery were enrolled. After titration of an individual loading dose, patients could self-administer 1 ml bolus doses of the drug combination tramadol 20 mg/ml, dipyrone 200 mg/ml and metoclopramide 0.4 mg/ml via patient-controlled analgesia (PCA). Patients' genotype was analyzed considering the most prevalent PM associated CYP2D6 mutations using a real-time PCR and hybridization based genotyping method. Demographic data, surgery related variables, pain scores, analgesic consumption and need for rescue medication were compared between extensive metabolizers (EM) and PM. The primary outcome criterion 'response' was defined as responder or non-responder status by the need for rescue medication and patients' satisfaction at the final interview. Demographic and surgery related data were comparable between EM (n=241) and PM (n=30). The percentage of non-responders was significantly higher in the PM group (46.7%) compared with the EM group (21.6%; p=0.005). Tramadol loading dose amounted to 108.2+/-56.9 and 144.7+/-22.6 mg (p<0.001) in EM and PM, respectively. More patients displaying the PM genotype needed rescue medication in the recovery room and during PCA period than patients with at least one wild type allele (21.6 versus 43.3%, p=0.02). PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM. Therefore, CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14499440&dopt=Abstract tramadol



Effects of tramadol on rat detrusor overactivity induced by experimental cerebral infarction.

Andersson KE.

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

OBJECTIVE: Cerebrovascular disease, such as stroke, frequently results in incontinence by reducing suprapontine micturition control. Intraluminal occlusion of the middle cerebral artery (MCA), which produces detrusor overactivity, has been introduced as a useful model of stroke-induced lower urinary tract dysfunction. Recently, the effective analgesic tramadol, was found to possess inhibitory actions on normal rat micturition. The current study aimed to examine the potential effect of tramadol on rat detrusor overactivity due to cerebral infarction. METHODS: In female Sprague-Dawley rats, cerebral ischemia was induced by occlusion of the MCA and the urinary bladder was catheterised. Three days later, continuous cystometry was performed in awake animals and the effects of tramadol given intravenously were studied. RESULTS: In cerebral infarcted rats, bladder capacity was lower (48+/-9%) and micturition pressure higher (76+/-21%) than in control rats. Tramadol 5 mg x kg(-1) given i.v., increased bladder capacity (59+/-29%) and threshold pressure (47+/-32%) to values similar to those in control rats. However, micturition pressure was not significantly altered. Tramadol induced diuresis in some, but not all, cerebral infarcted rats. CONCLUSION: Tramadol normalised detrusor overactivity in MCA-occluded rats. The drug might have a treatment potential in patients with detrusor overactivity after stroke.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14499688&dopt=Abstract tramadol



Influence of oral tramadol on the dynamic ventilatory response to carbon dioxide in healthy volunteers.

Dahan A.

Department of Anesthesiology, Leiden University Medical Center, The Netherlands.

We tested the effect of tramadol on ventilatory control by quantifying its effect on the steady-state ventilatory carbon dioxide response and by locating its site of respiratory action within the ventilatory control system. We imposed square-wave changes in end-tidal carbon dioxide (approximately 1 kPa; end-tidal oxygen concentration kept constant at resting levels) in 10 healthy volunteers (six men, four women) before and after oral ingestion of 100 mg tramadol, and measured the ventilatory responses. Each hypercapnic response was separated into a fast, peripheral and a slow, central component. Two control and two tramadol carbon dioxide studies were performed in each subject. Tramadol reduced the total ventilatory carbon dioxide sensitivity by approximately 30% from 12.8 (6.1) [lower (25%) and upper (75%) quartiles 7.4 and 16.6 litre min(-1) kPa(-1)] to 9.1 (5.3) (5.3-14.1) litre min(-1) kPa(-1) (P<0.001). The fast and slow response gains were reduced by 23 (46) (3-54)% (P<0.05) and 30 (22) (15-54)% (P<0.01) respectively. The ratio of these carbon dioxide sensitivities and the apnoeic threshold were not significantly changed by tramadol. We suggest that tramadol affects the ventilatory control system by acting at the mu-opioid receptors in the respiratory integrating centres within the brainstem.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11878687&dopt=Abstract tramadol



Pain management in a long-term care facility: compliance with JCAHO standards.

Wild TL.

Baptist Hospital of Cocke County, Newport, TN 37871, USA. rmullins planetc.com

An analysis of the treatment of nonmalignant pain in the elderly at a long-term facility was conducted to allow development of a pain management program that complies with both JCAHO guidelines for pain management and with the Tennessee Medicaid (TennCare) reimbursement schedule, and to determine if tramadol can meet the standards of pain management under these new guidelines. Inclusion criteria were residence in our long-term care facility; a pain intensity score > 4 on a modified Wong Baker Pain Scale; the patient having prescription orders for one or more of the following drugs: propoxyphene, meperidine, or high dosages of acetaminophen (approaching 4 g/day); suspected neuropathic or mixed nociceptive/neuropathic pain; and/or a diagnosis of diabetes, osteoarthritis, or degenerative joint disease. Exclusion criteria were history of seizures, history of opioid or alcohol abuse, and demonstrated hypersensitivity to tramadol or opioids. Tramadol administration began at a dose of 25 mg/day titrated up to a maximum of 300 mg/day over a 16-day period. Data were collected from computer records, dispensing reports, medication administration reports (MARs), current federal minimum data set (MDS) data, and weekly care plan meetings. Data were tabulated at baseline and 4-6 weeks after a stable dose of tramadol had been established. Fourteen residents (mean age 85 years, 1 male, 13 female) met the criteria and received tramadol up to 300 mg/day (qid). Tramadol reduced the residents' pain scores from an average of 6 to 2 using the Modified Wong Baker Pain Scale, reduced the percentage of residents taking propoxyphene from 50% to 14%, and reduced those taking high doses of APAP or APAP products from 43% to 14%. Tramadol reduced the percentage of residents falling, losing weight, showing no change or decline in activities in daily living (ADLs), displaying inappropriate behavioral symptoms, suffering depression, and/or taking psychotropic medications. In the state of Tennessee, new reimbursement schedules by TennCare have allowed our hospital to comply with the JCAHO standards of "optimal achievable care" for the treatment of pain by allowing the hospital staff to treat patients with newer, safer, more effective analgesics such as tramadol. Early results from this ongoing study have shown that tramadol can provide a safe and effective treatment on non-malignant pain in a long-term care facility and improve adherence to JCAHO and TennCare standards for proper pain management.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14649389&dopt=Abstract tramadol