Epidural methadone results in dose-dependent analgesia in cancer pain, further enhanced by epidural dexamethasone.

BACKGROUND: This study was designed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone. METHODS: In all, 72 cancer patients, 32- to 67-year-old were randomized to six groups (n=12) and prospectively studied to examine analgesia and adverse effects for 3 weeks. Patients received single-dose protocol epidural test drugs: Control group (CG) received epidural 40-mg lidocaine diluted to 10-ml volume with saline. Dexamethasone group (DG) 40-mg lidocaine plus 10-mg dexamethasone. The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine; the 5MetG, 5-mg epidural methadone plus 40-mg lidocaine, the 7.5MetG, 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG, 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone. RESULTS: Groups CG, DG and 2.5MetG were similar regarding analgesia and side effects. Patients from 5MetG and 7.5MetG took 3 ± 1 and 5 ± 1 days, respectively, to restart oral morphine. Patients from 7.5MetDG took 14 ± 2 to restart oral morphine (P<0.001). Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation (P<0.005). Fatigue improved for both DG and 7.5MetDG during 2-week evaluation (P<0.005). By the third week of evaluation, all patients were similar. CONCLUSIONS: Epidural methadone plus lidocaine resulted in dose-dependent analgesia, further improved by epidural dexamethasone, which also improved fatigue.

Early cleavage of human embryos: an effective method for predicting successful IVF/ICSI outcome.

BACKGROUND: The need for effective parameters for selecting the best embryos is paramount when a large number of them are available for transfer. Other studies have reported that transfer of pre-selected embryos, based on cleavage to the 2-cell stage at 25 h and 27 h post-insemination/intracytoplasmic sperm injection (ICSI), increases implantation and pregnancy rates. We investigated whether extending the time for selection of cleaved embryos to 29 h post-insemination/ICSI had a similar effect on pregnancy and implantation rates. METHODS: Cleavage to the 2-cell stage was assessed at 25, 27 and 29 h post-insemination/ICSI. Embryos that had cleaved at any of these time points were designated as 'early cleavage' (EC), while others were designated as 'non-early cleavage' (NEC). EC embryos were selected and preferentially transferred. RESULTS: EC occurred in 57% of the cycles (61% IVF; 51% ICSI). Significantly (P = 0.02) more clinical pregnancies occurred in the EC group (23/42, 55%) compared with the group that had no embryo undergoing first cleavage up to 29 h post-insemination/ICSI (8/32, 25%). The EC group of patients was significantly younger than the NEC. CONCLUSION: Transfer of selected embryos that reached the 2-cell stage between 25 and 29 h post-insemination/ICSI is a reliable prognostic tool for patients undergoing assisted reproduction techniques.

In situ variation of cervical mucus pH during exposure to atmospheric air

The objective of the present study was to determine if exposure of cervical mucus to air during specular examination could modify mucus pH. Detection of changes is justified because of their possible interference with sperm-mucus interaction, since an acidic pH is unfavorable to sperm penetration and is associated with infertility due to the cervical factor. Twenty women with good quality mucus were evaluated. pH measurements of ecto- and endocervical mucus were made in situ using a glass electrode after 0-, 5- and 10-min exposure to air. There was a progressive alkalinization of mucus pH. Mean values of ectocervical mucus pH were 6.91, 7.16 and 7.27, while mean values of endocervical mucus pH were 7.09, 7.34 and 7.46 at 0, 5 and 10 min, respectively. Significant differences were found between the mean values obtained at 0 and 5 min, and at 0 and 10 min (P<0.05), whereas the differences in mean values at 5 and 10 min were not significant at either site. We conclude that 5 to 10 min of exposure to atmospheric air affects cervical mucus pH in a significant way. Since tests used to evaluate sperm-mucus interaction generally have not considered this possibility, we suggest that they should be performed immediately after mucus collection in order to avoid misinterpretation of the results.

In situ variation of cervical mucus pH during exposure to atmospheric air.

The objective of the present study was to determine if exposure of cervical mucus to air during specular examination could modify mucus pH. Detection of changes is justified because of their possible interference with sperm-mucus interaction, since an acidic pH is unfavorable to sperm penetration and is associated with infertility due to the cervical factor. Twenty women with good quality mucus were evaluated. pH measurements of ecto- and endocervical mucus were made in situ using a glass electrode after 0-, 5- and 10-min exposure to air. There was a progressive alkalinization of mucus pH. Mean values of ectocervical mucus pH were 6.91, 7.16 and 7.27, while mean values of endocervical mucus pH were 7.09, 7.34 and 7.46 at 0, 5 and 10 min, respectively. Significant differences were found between the mean values obtained at 0 and 5 min, and at 0 and 10 min (P<0.05), whereas the differences in mean values at 5 and 10 min were not significant at either site. We conclude that 5 to 10 min of exposure to atmospheric air affects cervical mucus pH in a significant way. Since tests used to evaluate sperm-mucus interaction generally have not considered this possibility, we suggest that they should be performed immediately after mucus collection in order to avoid misinterpretation of the results.

Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery.

BACKGROUND: Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain. This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery. METHODS: Fifty-six patients were randomized to one of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline or 10 microg sufentanil). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control group received spinal saline and transdermal placebo. The sufentanil group received spinal sufentanil and transdermal placebo. The nitroglycerin group received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group (785+/-483 min) compared with the other groups (P<0.005). The time to first rescue analgesics was also longer for the sufentanil group compared with the control group (P<0.05). The sufentanil-nitroglycerin group group required less rescue analgesics in 24 h compared with the other groups (P<0.02) and had lesser 24-h pain visual analog scale scores compared with the control group (P<0.005), although these scores were similar to the sufentanil and nitroglycerin groups (P>0.05). The incidence of perioperative adverse effects was similar among groups (P>0.05). CONCLUSIONS: Transdermal nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in postoperative analgesia itself, but it prolonged the analgesic effect of spinal sufentanil (10 microg) and provided 13 h of effective postoperative analgesia after knee surgery.

Combined intrathecal fentanyl and neostigmine: therapy for postoperative abdominal hysterectomy pain relief.

STUDY OBJECTIVE: To evaluate the analgesic action of spinal neostigmine as part of a multimodal analgesic therapy approach including spinal neostigmine and spinal fentanyl for postoperative pain relief DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients undergoing abdominal hysterectomy. INTERVENTIONS: Patients were assigned to one of five groups (n = 10) to receive 15 mg bupivacaine plus 1 ml of the test drug intrathecally. The control group (CG) received saline as the test drug, the fentanyl group (FG) received 25 microg fentanyl; the neostigmine group (NG) received 25 microg neostigmine; the fentanyl-neostigmine 10 microg group (FNG10) was given 10 microg fentanyl plus 10 microg neostigmine; and the fentanyl-neostigmine 25 microg group (FNG25) received 25 microg fentanyl plus 25 microg neostigmine. Pain and nausea were evaluated using a 10-cm visual analog scale (VAS). MAIN RESULTS: The analgesic consumption, in 24 hours was greatest in CG, next highest in NG, FG, and FNG10 where consumption was the same in the three groups; and least in FNG25 (p < 0.05). The time to first rescue analgesic medication was greatest for FNG25 compared with the other groups (>5 hours compared with 2 to 3 hours; p < 0.05). VAS showed no statistically significant differences for pain impression, intraoperative and postoperative nausea, or occurrence of vomiting (p > 0.05). CONCLUSION: The combination of 25 microg neostigmine with 25 microg fentanyl given intrathecally with 15 mg of hyperbaric bupivacaine delayed postoperative pain and lowered the number of rescue analgesics. Because the better quality of analgesia was obtained with an increased (although not statistically significant difference) incidence of untoward side effects, larger samples should be studied before its routine use is recommended.

Intrathecal neostigmine for postoperative analgesia after orthopedic surgery.

STUDY OBJECTIVE: To establish a dose-response curve for the analgesic effect of intrathecal neostigmine in patients undergoing below knee surgery with spinal anesthesia. To assess adverse effects, principally nausea and vomiting. DESIGN: Randomized, double-blind, prospective study. SETTING: Teaching hospital. PATIENTS: 60 ASA physical status I and II premedicated patients undergoing orthopedic surgery (tibial or ankle reconstruction). INTERVENTION: Spinal anesthesia was performed at the sitting position, L3-L4 interspace, 4 ml final volume, injected at a rate of 1 ml/10 sec. The control group (CG) received 15 mg hyperbaric bupivacaine 0.5% plus saline. The 25 micrograms neostigmine group (25NG) received 15 mg hyperbaric bupivacaine plus 25 micrograms neostigmine; the 50 micrograms neostigmine group (50NG) received 15 mg hyperbaric bupivacaine plus 50 micrograms neostigmine; and the 100 micrograms neostigmine group (100NG) received 15 mg hyperbaric bupivacaine plus 100 micrograms neostigmine. Patients were placed supine after the spinal punction. MEASUREMENTS AND MAIN RESULTS: Time to first rescue analgesics, analgesia, and adverse effects at constant intervals were assessed using the 10 cm visual analog scale (VAS). Intrathecal neostigmine produced a dose-independent reduction in the postoperative rescue analgesic consumption (p < 0.0001). The time to first rescue analgesics was similar among groups (p > 0.05), and the overall 24-hour VAS pain scores were lowest for patients who had spinal neostigmine (p < 0.02). The 100NG group had the highest incidence of postoperative nausea and vomiting of all the groups (p < 0.05). CONCLUSION: Intrathecal neostigmine produced a dose-independent analgesia and a dose-dependent incidence of adverse effects with the doses studied.

Tramadol and beta-cyclodextrin piroxicam: effective multimodal balanced analgesia for the intra- and postoperative period.

BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the analgesic efficacy of tramadol, an analgesic with both opioid and nonopioid actions (norepinephrine and serotonin pathways), with beta-cyclodextrin piroxicam, a nonsteroidal antiinflammatory drug, in the perioperative setting. METHODS: The study population consisted of 48 patients scheduled for minor abdominal procedures, who were assigned to one of four groups of 12 patients each. The premedication was either a placebo tablet or a 192.1-mg beta-cyclodextrin piroxicam tablet, administered orally 30-40 minutes before anesthesia induction. After intravenous administration of tramadol 1.5 mg/kg, anesthesia was induced with an intravenous loading dose of propofol. Anesthesia was maintained an intravenous infusion of propofol at 6-12 mg/kg/h plus either saline or tramadol at 1.2 mg/kg/h, atracurium, and a 2:1 nitrous oxide-oxygen mixture. The control group received a placebo tablet and an infusion of saline with propofol for anesthesia maintenance; the tramadol group received a placebo tablet and a continuous tramadol-propofol infusion; the beta-cyclodextrin piroxicam (BCP) group received a BCP tablet and a continuous saline-propofol infusion; and the beta-cyclodextrin piroxicam-tramadol (BCPT) group received beta-cyclodextrin piroxicam and a continuous tramadol-propofol infusion. RESULTS: The relative propofol consumption by the four groups was control = BCP (P > .05) >tramadol (P < .001) > B-CPT (P < .0002). The time for analgesic rescue decreased in the order BCPT > BCP (P < .0002) = tramadol > control (P < .001). The degree of sedation and the visual analog scores 10-cm scale at the time patients requested rescue analgesics were similar among the groups (P > .05). CONCLUSIONS: The combination of tramadol and beta-cyclodextrin piroxicam provided better perioperative analgesia than tramadol alone.

Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

BACKGROUND AND OBJECTIVES: Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. METHODS: The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). RESULTS: Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P < .002). None of the antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. CONCLUSIONS: Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.

Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings.

According to the 15 autopsies performed at the Department of Pathological Anatomy, Escola Paulista de Medicina, São Paulo, Brazil, it was confirmed that acquired immunodeficiency syndrome (AIDS) occurs preferably in young homosexual males, who die in a short period of time of the disease, which leads to a consumptive state verified by cachexia of the cadavers. The most affected organs of this series were the lungs and encephalum, exactly the ones responsible for the immediate cause of death. In this series of autopsies there were 9 types of microorganisms represented by virus, bacteria, fungi, protozoans and two types of tumors, Kaposi's sarcoma and lymphoma of the central nervous system. From the microorganisms, the most frequent was the Cytomegalovirus and, from the tumors, Kaposi's sarcoma. The various types of microorganisms were frequently associated, principally in the central nervous and digestive systems. There was also association of microorganisms with tumors. Besides the lesions produced by microorganisms there were other associated alterations as brown atrophy of neuronia, which was related to the infiltration of cerebral lymphoma, and the lymphocytic depletion of lymphoid organs due to immunological exhaustion. Cellular reaction to microorganisms was practically none, principally with Pneumocystis carinii and Cryptococcus neoformans, the first one behaving as an inert mould in the pulmonary alveoli and the second proliferating freely in tissues. In two cases there was no granulomatous reaction to Mycobacterium tuberculosis. The primary lymphoma of the central nervous system should be interpreted as a microglioma, i.e., a reticulosarcoma of this system according to Hortega's school.

PIP: Clinical and autopsy findings obtained from 15 male patients treated for acquired immunodeficiency syndrome (AIDS) at 3 hospitals in Sao Paulo provided a clearer profile of AIDS cases in Brazil. Of the 12 patients whose sexual orientation was recorded, 9 were homosexual and 3 were bisexual. 75% were between the ages of 22-36 years; 14 were white. The duration of diseases ranged from 14 days-7 months in this series, confirming the rapid evolution of AIDS from 1st symptom to death. The most common clinical manifestations of disease were fever, cough, weight loss, diarrhea, and lymphadenopathy. Organs most frequently involved were the lungs (13 cases) and encephalum (9 cases). Microscopic findings revealed 9 types of microorganisms, fungi, and protozoa, the most common of which was Cytomegalovirus (7 cases). The cause of death was meningoencephalitis in 7 cases and panlobar pneumonia in 3 cases. The incidence of Kaposi's sarcoma (2 cases) was surprisingly low in this series. In addition to lesions produced by microorganisms, there were important associated lesions represented by lymphocytic depletion, acute myocarditis, brown atrophy of neuronia, acute pancreatitis, and liver cirrhosis. Several microorganisms and tumors in these AIDS patients were discovered only at autopsy, confirming the importance of necropsy to the study of the natural history of this disease. An unexpected pathological finding in this series was the absence of cellular reactions to microorganisms, particularly Pneumocystis carinii, Cryptococcus neoformans, and Mycobacterium tuberculosis.