Anita Leocádia de Mattos

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.

Antinociceptive effect of low-dose intrathecal neostigmine combined with intrathecal morphine following gynecologic surgery.

Background The purpose of this study was to determine whether combination of 1–5 &mgr;g intrathecal neostigmine would enhance analgesia from a fixed intrathecal dose of morphine. Methods A total of 60 patients undergoing gynecologic surgery were randomized to one of five groups. Patients received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline, 100 &mgr;g morphine, or 1–5 &mgr;g neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 &mgr;g neostigmine group received spinal morphine and 1 &mgr;g neostigmine. The morphine + 2.5 &mgr;g neostigmine group received spinal morphine and 2.5 &mgr;g neostigmine. Finally, the morphine + 5 &mgr;g neostigmine group received spinal morphine and 5 &mgr;g neostigmine. Results The groups were demographically similar. The time to first rescue analgesic (minutes) was longer for all patients who received intrathecal morphine combined with 1–5 &mgr;g neostigmine (median, 6 h) compared with the control group (median, 3 h) (P < 0.02). The morphine group (P < 0.05) and the groups that received the combination of 100 &mgr;g intrathecal morphine combined with neostigmine (P < 0.005) required less rescue analgesics in 24 h compared with the control group. The incidence of perioperative adverse effects was similar among groups (P > 0.05). Conclusions The addition of 1–5 &mgr;g spinal neostigmine to 100 &mgr;g morphine doubled the duration to first rescue analgesic in the population studied and decreased the analgesic consumption in 24 h, without increasing the incidence of adverse effects. The data suggest that low-dose spinal neostigmine may improve morphine analgesia.

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.

Epidural nonsteroidal antiinflammatory drugs for cancer pain

A lthough pain relief with multimodal therapy is excellent in 45%-90% of cancer patients (l), dose escalation eventually occurs. The concurrent use of nonsteroidal antiinflammatory drugs (NSAIDS) to enhance opioid effects while decreasing the dose is recommended. Should NSAIDS and opioids fail, the spinal administration of opioids often results in improved analgesia with reduced opioid side effects w. Several reports have suggested a spinal site of action for NSAIDS (3-7) and synergy with spinal morphine (5). However, appropriate preclinical toxicity testing has not been performed for any commercially available NSAID, and intraspinal application is premature (8). We describe two cases in which epidural NSAIDS were administered by our ambulatory cancer patients without our initial knowledge or approval.

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.

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 betacyclodextrin 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.

Comparative study between 0.5% bupivacaine and 0.5% enantiomeric mixture of bupivacaine (S75-R25) in epidural anesthesia

JUSTIFICATIVA Y OBJETIVOS: La mezcla enantiomerica de bupivacaina (S75-R25) viene siendo empleada por su propiedad anestesica con menor toxicidad de que la bupivacaina racemica. El objetivo de este estudio es comparar la bupivacaina a 0,5% con la mezcla enantiomerica de bupivacaina a 0,5% (S75-R25) en anestesia peridural. METODO: Fueron incluidos en el estudio 44 pacientes divididos en dos grupos (n=22) denominados de Bupivacaina y S75-R25. Los pacientes fueron medicados con midazolam por via venosa. La anestesia peridural fue realizada en el espacio L3-L4 o L2-L3, y administrado 16 a 24 ml de la solucion del anestesico local. El grupo Bupivacaina recibio bupivacaina a 0,5% con vasoconstrictor. El grupo S75-R25 recibio la mezcla enantiomerica de bupivacaina a 0,5% con vasoconstrictor. Fueron evaluados la temperatura del miembro inferior antes y despues del bloqueo peridural, el tiempo de latencia del bloqueo, el tipo de alteracion referida por el paciente, posibles fallas sensoriales, nivel sensorial metamerico y el grado de bloqueo motor. En la sala de recuperacion pos-anestesica, fue anotado el tiempo de requisicion del primero analgesico. RESULTADOS: Hicieron parte de la evaluacion final 41 pacientes. Los grupos fueron demograficamente semejantes. La dosis per-operatoria de midazolam, el volumen de anestesico local por via peridural, el tiempo de latencia para la instalacion del bloqueo, fallas sensoriales la picada de la aguja, temperatura del miembro inferior en los diferentes tiempos, el tipo de sensacion parestesica, y el nivel anestesico en dermatomos fueron semejantes entre los grupos. El grado de bloqueo motor fue mas intenso para el grupo Bupivacaina, comparado al grupo S75-R25 (p = 0,0117). El tiempo para requisicion del primero analgesico en el periodo pos-operatorio fue superior para el grupo S75-R25, comparado al grupo Bupivacaina (596 ± 436 minutos versus 463 ± 270 minutos, respectivamente; p = 0,04572). La incidencia de efectos adversos fue semejante entre los grupos. CONCLUSIONES: La mezcla enantiomerica de bupivacaina (S75-R25) presento mayor tiempo analgesico y menor grado de bloqueo motor, comparada con la solucion de bupivacaina racemica

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.

Efficacy of the Greater Occipital Nerve Block for Cervicogenic Headache: Comparing Classical and Subcompartmental Techniques

The aim of the study was to compare the efficacy of the greater occipital nerve (GON) block using the classical technique and different volumes of injectate with the subcompartmental technique for the treatment of cervicogenic headache (CH).

Transdermal Ketamine and S(+)-Ketamine as Adjuvants Following Orthopaedic Surgery under Bupivacaine Spinal Anaesthesia

The aim of the study was to examine the perioperative analgesic effect of topical deliver of either ketamine or S(+)- ketamine in orthopaedic postoperative pain through clinical and laboratorial evaluation. 45 patients following minor orthopaedic surgery were randomized to one of three groups (n=15). Spinal anaesthesia was performed with 15 mg hyperbaric bupivacaine. Twenty min after the spinal puncture, a controlled delivery topical cream containing either 25 mg ketamine (KG), 25 mg S(+)-ketamine (+KG) or placebo (PG) was applied. Pain and adverse effects were assessed postoperatively for 24 h. Intravenous ketoprofen was available at patient request. The plasmatic concentration of ketamine and S(+)-ketamine was measured prior the spinal puncture, 30 min, 4-hour, 8-hour, 16-hour and 24-hour after topical application by High Performance Liquid Chromatography (HPLC). Time to first rescue analgesic was longer to both KG and +KG (10 hours) compared to the PG (5 hours); (p<0.05). Ketoprofen consumption (mg) in 24 hour was higher in the PG compared to the others (p<0.0005). Thirty-min after the transdermal application, ketamine and S(+)-ketamine were detectable in plasma in both KG and +KG by HPLC, and showed a dose-ranging curve during the 24-hour evaluation (p<0.02). Adverse effects were similar among groups. As conclusions, transdermal 25 mg ketamine or 25 mg S(+)- ketamine similarly prolonged the duration of analgesia following orthopaedic procedures under bupivacaine spinal blockade, demonstrated by clinical and laboratorial data.