Absorbed dose estimates for 131I-labelled monoclonal antibody therapy in patients with intraperitoneal pseudomyxoma.

Seven patients with intraperitoneal pseudomyxoma originating from the appendix (4 cases) and from the ovary (3 cases) were treated with radioimmunotherapy. During the therapy, nine infusions of 3.0-4.2 GBq of 131I-labelled B72.3 monoclonal antibody were administered. We developed three-dimensional dose calculation software that can utilize activity maps based on SPET images to calculate the absorbed dose distribution using point source kernels. The dose calculation program was employed to calculate absorbed doses to various organs. The calculated dose distributions enable us to evaluate the variation in dose within the organs, which is normally not available using approaches based on geometric models. The patient-specific absorbed dose calculations were compared with doses based on a model that uses photon S-factors derived from a standard phantom. The compared doses agreed well on average, but in some organs showed large discrepancies.

The effect of three dimensional activity distribution on the dose planning of radioimmunotherapy for patients with advanced intraperitoneal pseudomyxoma.

BACKGROUND: Six patients with histologically proven peritoneal carcinomatous pseudomyxomas were treated with radioimmunotherapy. METHODS: All the patients received a tracer dose of iodine-131 (131I) labeled B72.3 anti-TAG-72 monoclonal antibody (MoAb) to test the in vivo affinity. After informed consent was obtained the therapeutic dose (>3.7 gigabecquerels [GBq], 100 mCi) of the 131I labeled B72.3 anti-TAG-72 MoAb was infused within 60 minutes intraperitoneally using 2 catheters on both sides of the abdomen. The patients were imaged with single photon emission computed tomography (SPECT) at 3, 10, and 24 days after the therapeutic infusion. Treatment-planning software has been developed in which functional information obtained from SPECT is integrated with anatomic information obtained from computed tomography (CT). The activity distribution from SPECT images is converted to absorbed dose distributions using a point source kernel convolution dose calculation. The absorbed dose calculation requires a radionuclide specific dose kernel. The activity map is divided into equally sized source voxels from which the distribution is calculated for the target voxels that cover the patient volume. The resulting three dimensional (3D) absorbed dose distribution is viewed as isodose contours superimposed on the CT images or as 3D isodose surfaces. RESULTS: The measured activity distribution shows that the cumulated activity and biologic half-life vary in the patient's body. The developed planning system provides a method for calculating patient specific absorbed dose distributions. CONCLUSIONS: The variation of biologic clearance indicates that a 3D dose calculation method incorporating measured activity distributions is needed to quantify absorbed dose distribution.

Intravenous ketoprofen for pain relief after total hip or knee replacement.

BACKGROUND: There are few studies in which ketoprofen, a propionic acid derivate NSAID, has been tested as an intravenous postoperative analgesic. The aim of this double-blind, randomized, placebo-controlled work was to study the tolerability and efficacy of intravenous ketoprofen in seventy-six patients undergoing hip or knee total endoprothesis surgery using three different doses. METHODS: The patients received either ketoprofen 50 mg, 100 mg or 150 mg, or placebo as an initial intravenous loading, followed by an infusion containing 50 mg, 100 mg or 150 mg or placebo, respectively, over the following eleven and a half hours. The consumption of fentanyl was recorded and the patients assessed their pain intensity on a 10-cm visual analogue scale (VAS) at 0, 2, 4 and 12 hours. Possible side-effects were recorded at the same intervals. RESULTS: Patients receiving ketoprofen showed significantly lower total fentanyl consumption and significantly better pain relief at 12 hours was achieved by a 300 mg dose of ketoprofen than by placebo. Side-effects were minimal, with no differences between the groups. CONCLUSION: A bolus of ketoprofen following continuous infusion of ketoprofen, coupled with a PCA-system, was an effective and safe approach for the relief of postoperative pain.

0.1% bupivacaine does not reduce the requirement for epidural fentanyl infusion after major abdominal surgery.

BACKGROUND AND OBJECTIVES: Although local anesthesia has been demonstrated to potentiate spinal morphine analgesia in animal studies, results comparing epidural local anesthesia/opioid mixtures with opioid alone are contradictory in clinical studies. The hypothesis was that, although the concentration of bupivacaine (0.1%) was low to minimize its adverse effects, if the infusion rate of a fentanyl/bupivacaine solution was closely adjusted according to need, the presence bupivacaine would reduce the requirement for epidural fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl (10 micrograms/mL) or a fentanyl/bupivacaine (0.1%) mixture epidurally corresponding to the dermatome of the surgical incision in a double-blind fashion for the first 18 hours after major abdominal surgery. The infusion was titrated for each patient to the rate required for pain relief during forced inspiration (pain score < or = 2, maximum 10). Pain scores, the fentanyl doses required, plasma concentrations of fentanyl at 18 hours, and the incidence and severity of adverse effects were recorded. RESULTS: Patients reported similar median pain scores and were equally satisfied with pain relief in both groups. The mean required post-operative fentanyl infusion rate (57.7 +/- 19.5 micrograms/h) and the plasma concentrations (0.84 +/- 0.36 ng/mL) in the fentanyl group were comparable to the infusion rate (54.4 +/- 19.2 micrograms/h) and the plasma concentrations (0.86 +/- 0.36 ng/mL) in the fentanyl/bupivacaine group. Respiratory and cardiovascular functions were preserved, and the incidence of nausea, pruritus, and periods of drowsiness or sleep were similar in both groups. CONCLUSIONS: In low concentrations (0.1%), bupivacaine did not reduce the titrated dose of epidural fentanyl required for adequate pain relief during forced inspiration after major abdominal surgery. The incidence and severity of adverse effects were also comparable whether or not low-dose bupivacaine infusion was used.

A risk-benefit appraisal of injectable NSAIDs in the management of postoperative pain.

The inadequacy of pain treatment has been demonstrated in many patient groups suffering from acute pain. The injectable nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, diclofenac, ketoprofen and ketorolac, provide relief from the pain associated with several different conditions. When administered alone or in combination with low doses of opioids, NSAIDs provide good pain relief after musculoskeletal trauma or operation. The main advantage of these agents is that they may form the first-line therapy for pain relief and thus decrease the need of opioids. This avoids respiratory depression which can be associated with opioids. In contrast to opioids, NSAIDs do not cause respiratory depression or have marked adverse effects on the central nervous system. However, they may be associated with adverse effects of the gastrointestinal tract, liver and kidneys, and may increase pre- and postoperative bleeding and cause allergic reactions. These effects are related to the ability of NSAIDs to inhibit prostaglandin synthesis. Use of NSAIDs has to be considered carefully in patients with asthma, allergy to aspirin and NSAIDs, atopy, peptic ulcer or bleeding disorders (such as abnormalities in blood coagulation or coagulation deficits). These considerations are especially important in elderly patients. Having taken these contraindications into account, many clinical studies have demonstrated that NSAIDs are at least as safe as opioids when administered in the short term. However, few studies have specifically monitored adverse effects or included patients over 65 to 70 years of age. In addition, patients with risk factors have often been excluded from the trials. Therefore, the risk-benefit ratio of NSAIDs requires further assessment.

Epidural versus intravenous fentanyl for reducing hormonal, metabolic, and physiologic responses after thoracotomy.

BACKGROUND: Previous attempts to prevent all the unwanted postoperative responses to major surgery with an epidural hydrophilic opioid, morphine, have not succeeded. The authors' hypothesis was that the lipophilic opioid fentanyl, infused epidurally close to the spinal-cord opioid receptors corresponding to the dermatome of the surgical incision, gives equal pain relief but attenuates postoperative hormonal and metabolic responses more effectively than does systemic fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl epidurally and saline intravenously, or fentanyl intravenously and saline epidurally, in a double-blind fashion for the first 20 h after thoracotomy. For each patient, the fentanyl infusion was titrated to the rate required for pain relief (pain score < 3, maximum 10). Postoperative changes in blood pressure, heart rate, rectal temperature, and blood concentrations of adrenocorticotrophic hormone, beta-endorphin immunoreactivity, cortisol, growth hormone, prolactin, glucose, and leukocytes were assessed. RESULTS: Patients reported similar median pain scores, but the epidural group required about 40% less fentanyl than the intravenous group. Four hours postoperatively, the beta-endorphin immunoreactivity concentrations were less in the epidural than in the intravenous group. Plasma cortisol increased in a similar manner in both groups within 4 h of surgery, but the increase persisted to the next morning only in patients receiving intravenous fentanyl. Adrenocorticotropin, growth hormone, and prolactin responses were similar in both groups. The postoperative hyperglycemic response, leukocytosis, and blood pressure were greater, and mean rectal temperature was lower, in the intravenous than in the epidural fentanyl group. CONCLUSIONS: The authors' results indicate that some aspects of the hormonal response to surgery are blocked more completely with epidural than with intravenous fentanyl. Adequate pain relief with epidural fentanyl, with a smaller mean dose, led to a smaller increase of some hormonal, metabolic, and physiologic responses after thoracotomy than in association with the adequate pain relief provided by intravenous fentanyl.

Refundoplication for recurrent gastroesophageal reflux.

Reoperation after a failed antireflux procedure is a surgical challenge. Many operative techniques have been proposed, but reports on systematic follow-up with endoscopy and esophageal function tests are few. The purpose of the present study was to evaluate the results of repeated fundoplication in cases of recurrent reflux, including assessment of esophageal function. Of the 18 cases of repeat fundoplication performed for recurrent reflux during 1970-1991 at Tampere University Hospital, 15 were evaluated a median of 18 (range 5-152) months after reoperation. Follow-up studies included endoscopy in all and esophageal function tests (esophageal 24-hour pH recording, manometry, and radionuclide transit) in 14 cases. All the patients had defective fundic wrap before reoperation, whereas at follow-up 12 of the 15 wraps were intact. Reflux symptoms were diminished in all 15. Six patients (40%), however, had objective recurrence of reflux (esophagitis or pathologic pH recording). Three of the recurrences were due to slipped fundic wrap, but the others were probably caused by impaired esophageal function. By repeat fundoplication the wrap could be repaired as reliably as in primary operation. Symptomatic outcome and objective results were reasonable. The results were, however, not as good as after primary operation, which was due to more impaired esophageal motility caused by prolonged reflux or repeated surgery (or both).

A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy.

This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy, in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion. Forty patients were assigned randomly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion. For each patient the fentanyl infusion was titrated to a rate required for pain relief (pain score less than 3, maximum 10). Patients reported similar median pain scores, but in the epidural group the required mean fentanyl infusion rate was less (0.95 +/- 0.23 vs. 1.67 +/- 0.46 micrograms.kg-1.h-1, P = 0.0001) and plasma fentanyl concentrations were less at 4 and 18 h (4 h: 0.81 +/- 0.27 vs. 1.38 +/- 0.36 ng.ml-1, P = 0.0001; 18 h: 0.94 +/- 0.32 vs. 1.54 +/- 0.65 ng.ml-1, P = 0.0007) than those in the intravenous group. Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group. In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy.