J Pain Symptom Manage. 2003 Jun;25(6):499-511.
Palliative care in a national cancer center: results in 1987 vs. 1993 vs. 2000.

De Conno F, Panzeri C, Brunelli C, Saita L, Ripamonti C.

Rehabilitation and Palliative Care Operative Unit, National Cancer Institute of Milan, Milan, Italy.

In the last few years, palliative care for advanced and terminal cancer patients has undergone considerable evolution. We determined the characteristics of patients admitted to the 4-bed Palliative Care Unit (PCU) of the National Cancer Institute (NCI) of Milan in 1987, 1993 and 2000 to evaluate how our diagnostic and therapeutic approaches have changed over the years. We reviewed the charts of every patient admitted to the PCU in 1987, 1993, and the first ten months of 2000. We recorded demographic data; the primary tumor sites; the main reason for admission; the types of therapies administered (oncologic, analgesic, surgical, neurosurgical analgesic procedures, and supportive therapy); the type and number of cardiological, radiological and endoscopic examinations, as well as specialist consultations; the duration of stay and eventual death on the Unit. There were no significant differences regarding gender, age, primary tumor site and death in hospital of the patients admitted during these years. The time spent in hospital increased over time (P = 0.006). A significant increase was observed in the percentage of patients admitted for supportive therapy (P < 0.001) and investigation concerning the stage of the disease (P < 0.001). There was a significant decrease in admission for invasive analgesic procedures (P < 0.001), as well as for pain diagnosis and/or uncontrolled pain. Uncontrolled pain remained the most frequent reason for admission. Over the years, during hospitalization, 7% to 12% of the patients underwent radiotherapy,1% to 9% had computerized tomography, and 4% to 8% had palliative surgery. More than 50% of the patients received intravenous hydration; a few patients received hypodermoclysis in 1987. Over time, there was a significant increase in "as needed" administration of nonsteroidal anti-inflammatory drugs and a significant reduction in their regular administration (from 24% in 1987 and 1993 to 3% in 2000) (P < 0.001). The use of codeine, tramadol and methadone increased (P < 0.001), whereas the use of oral morphine, buprenorphine and oxycodone decreased in 2000 (P < 0.001). There was a reduction in the use of antidepressants (no significant constant trend) and a significant increase in the use of anticonvulsants, laxatives and pamidronate (P < 0.001). Regularly administered hypnotics decreased in 1993 and increased in 2000 (P < 0.001). Over these years, no significant differences were found in the routes of opioid administration, in route switching and in the mean maximum oral opioid dose (ranging from 108 to 126 mg/day). The percentage of patients undergoing percutaneous cordotomy significantly decreased in 1993 and 2000 (P < 0.001). Over time, there was an increase in requests for specialist consultations, which was significant for neurological, cardiological and oncological consults (P < 0.001). Although the characteristics of the patients admitted to the PCU did not change over these years, there have been significant modifications in our therapeutic approaches, above all in the use of supportive therapy, adjuvant drugs, opioids and neurosurgical invasive procedures. Moreover, a major collaborative interaction with other specialists of the NCI took place with the aim to tailor treatment for each single patient.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12782430&dopt=Abstract tramadol Ultram

hotmail.com

BACKGROUND AND OBJECTIVE: We investigated the following aspects of pharmacokinetic-guided total intravenous anaesthesia with remifentanil and propofol in patients undergoing surgical myocardial revascularization: anaesthetic efficacy, haemodynamic effects, impact on extubation of the trachea and analgesia after operation. METHODS: Thirty-two patients undergoing on-pump coronary bypass surgery received intravenous anaesthesia with remifentanil and propofol. Both drugs were dosed and titrated based on computer-assisted pharmacokinetic models to maintain constant plasma concentrations. The propofol target plasma concentration was 1.2 microg mL(-1) throughout the procedure. A remifentanil target plasma concentration of 8 ng mL(-1) was achieved over 2 min for induction. After tracheal intubation, the opioid plasma concentration was reduced to 4 ng mL(-1), and then titrated up to 8 ng mL(-1) during surgery. Postoperative analgesia was managed with remifentanil infusion until 4 h after tracheal extubation, and a continuous infusion of tramadol was started 1 h before the remifentanil was stopped. RESULTS: After induction of anaesthesia, heart rate (-20%) and cardiac index (-6%) decreased significantly. No hypotensive episodes (mean arterial pressure < 60 mmHg) occurred. Intraoperative haemodynamics were stable. Three cases of myocardial ischaemia were detected: two by transoesophageal echocardiography and one with ST-segment monitoring. The duration of postoperative mechanical ventilation of the lungs was 95 +/- 13 min and the time to extubation was 150 +/- 18 min. Postoperative analgesia was satisfactory in all patients. CONCLUSIONS: Pharmacokinetic-based total intravenous anaesthesia with remifentanil and propofol provides adequate anaesthesia during coronary surgery with cardiopulmonary bypass and allows safe early extubation after operation.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12790210&dopt=Abstract tramadol Ultram [PubMed - in process]

ixir.com

BACKGROUND AND OBJECTIVE: In recent human and animal studies, intrathecal administration of various doses of neostigmine produces analgesia without neurotoxicity. The aim was to examine the effects of intrathecal neostigmine and bupivacaine in patients undergoing perianal surgery under spinal anaesthesia. METHODS: The patients were randomly allocated into three groups of 15: Group 1 (controls) received hyperbaric bupivacaine 10 mg + dextrose 5%, 1 mL, to a total volume of 3 mL; Group 2 received hyperbaric bupivacaine 10 mg + neostigmine 25 microg in dextrose 5%, 1 mL, to a total volume of 3 mL; and Group 3 received hyperbaric bupivacaine 10 mg + neostigmine 50 microg in dextrose 5%, 1 mL, to a total volume of 3 mL. RESULTS: The onset of sensory block was significantly earlier for Group 2 and 3 patients compared with Group 1 patients (P < 0.05). The full time to recovery of motor block and sensory block was significantly longer in Group 3 compared with Group 1 (P < 0.05). In Group 3, the average time until the first dose of tramadol was longer than Group 1 (P < 0.05). The incidence rate of nausea and vomiting was significantly higher in Groups 2 and 3 than in Group 1 (P < 0.05). CONCLUSIONS: The use of intrathecal neostigmine as an analgesic drug in perianal surgery is unsatisfactory because of prolonged motor blockade and nausea.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12790214&dopt=Abstract tramadol Ultram [PubMed - in process]




Schmerz. 1999 Aug 19;13(4):273-8.
[Switching opioids to transdermal fentanyl in a clinical setting]

[Article in German]

Elsner F, Radbruch L, Sabatowski R, Brunsch-Radbruch A, Loick G, Grond S.

Klinik und Poliklinik fur Anasthesiologie und Operative Intensivmedizin, Universitat Koln, Cologne

INTRODUCTION: The use of transdermal fentanyl is gaining in importance in the management of cancer pain. We describe the reasons for switching opioid medication to transdermal fentanyl in a pain management unit. METHODS: Case records of patients treated with transdermal fentanyl in our pain clinic were evaluated retrospectively. Conversion ratios were calculated from the opioid dosage before and after conversion. Pain intensities were assessed on a numeric rating scale (NRS 0: no pain, 10: worst pain imaginable). RESULTS: From October 1995 to December 1997 101 patients received transdermal fentanyl. Thirty-six patients had been treated with transdermal fentanyl before admission to our pain clinic, and relevant information was missing for one patient, so 64 patients were evaluated. Opioid therapy was switched to transdermal fentanyl during in-patient treatment for 53 patients and during out-patient treatment for 11 patients. Before conversion patients were treated with slow-release morphine (48%), immediate-release morphine (17%), buprenorphine (11%), tramadol (11%), levomethadone (5%), tilidine/naloxone (5%) and piritramid (3%). Reasons for opioid rotation were inadequate pain relief ( 33%), the patients' wish to reduce oral medication (20%), gastrointestinal side effects such as nausea (31%), vomiting (13%) and constipation (19%), dysphagia (27%) or others. Reduction of side effects was reported by 10 of 19 patients. In 12 of 21 patients, in whom the medication was switched because of inadequate pain relief, a reduction in pain intensity was reported. DISCUSSION: Conversion to transdermal therapy may readjust the balance between opioid analgesia and side effects. The opioid switch resulted in more pain relief or fewer side effects in half of the patients. A proposed equianalgesic conversion ratio between 70:1 and 100:1 from oral slow-release morphine to transdermal fentanyl can be confirmed by our data. Conversion rates from other opioids to transdermal fentanyl are suggested.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12799928&dopt=Abstract tramadol Ultram




Schmerz. 1999 Jun 11;13(3):183-95.
[Therapy with opioids in liver or renal failure]

[Article in German]

Tegeder I, Geisslinger G, Lotsch J.

Zentrum der Pharmakologie, Klinikum, Johann-Wolfgang-Goethe-Universitat Frankfurt/Main.

In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the dose. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and buprenorphine, which undergo primarily glucuronidation, and remifentanil which is cleared by esther hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys and may accumulate in patients with renal insufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With high concentrations they may cause narcotic effects or respiratory depression. In addition, special risks are known for normepridine that has been shown to exert neurotoxic effects with the risk of seizures. Few cases of respiratory depression following the administration of codeine, dihydrocodeine and tramdol have been reported. The elimination half-life of these drugs was prolonged. Lastly, the disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appears to be unaffected in renal failure.In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decreased drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil) and increased oral bioavailability due to reduced first-pass metabolism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and its oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administrations. As for patients with renal failure, special risks are known for meperidine with potential accumulation of normeperidine, which can cause seizures, and for propoxyphene for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine. In the case of reduced metabolism in chronic liver disease, the analgesic action of these drugs may be compromised. Lastly, the disposition of a few opioids, such as fentanyl, sufentanil, and remifentanil, appears to be unaffected in liver disease.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12799931&dopt=Abstract tramadol Ultram