Gabriela Rocha Lauretti

Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty.

This study was designed to examine postoperative analgesia with intrathecal neostigmine in a randomized, blinded trial with morphine as the active control in patients undergoing anterior and posterior vaginoplasty.A secondary aim was to provide preliminary data on the interaction between these two drugs. The incidence of adverse effects was also assessed. Forty-eight patients were divided into eight groups (50 micro gram, 100 micro gram, and 200 micro gram morphine [M]; saline; 50 micro gram, 100 micro gram, and 200 micro gram neostigmine [N]; and 50 micro gram morphine + 50 micro gram neostigmine). Anesthesia was provided with a balanced technique. All patients stayed 24 h in the recovery room where adequacy of postoperative analgesia and side effects were assessed. Increasing doses of intrathecal morphine (50 micro gram, 100 micro gram, and 200 micro gram) and intrathecal neostigmine (50 micro gram, 100 micro gram, and 200 micro gram) showed a dose-dependent pattern of analgesia (P < 0.001). The M50 + N50 combination resulted in a better analgesic effect with fewer side effects than M50, N50, and control groups. These preliminary data suggest that spinal neostigmine produces analgesia for vaginoplasty surgery similar in duration to spinal morphine and that the combination of morphine and neostigmine may allow a reduction in the dose of each component for postoperative analgesia. (Anesth Analg 1996;82:1182-7)

The effects of intrathecal neostigmine on somatic and visceral pain: improvement by association with a peripheral anticholinergic.

This study was designed to qualitatively evaluate the analgesic actions of intrathecal neostigmine alone and with intravenous (IV) N-butyl-scopolamine on somatic and visceral pain. Twenty-seven patients scheduled for both tubal ligation and vaginoplasty were divided into three groups. Patients received a standard anesthetic with thiopental, atracurium, and N2 O/O2/enflurane. N-butyl-scopolamine, 20 mg, or saline was administered as a 2-mL IV bolus 20 min before the end of the surgical procedure. The control group (CG) received spinal and IV saline; the neostigmine group (NG), spinal neostigmine and IV saline; and the neostigmine-N-butyl-scopolamine group (NSG), spinal neostigmine and IV N-butyl-scopolamine. Postoperatively, patients assessed their pain on a 10-cm visual analog scale (VAS). The CG had both visceral and somatic pain at the first 30-min assessment, and all patients requested morphine. Patients from the NG had only visceral pain from the first assessment; however, they had lower VAS scores (P = 0.026) and requested less morphine (P = 0.037). Patients from the NSG were pain free during all assessment times (P < 0.0001). Neostigmine was more effective for somatic pain than visceral pain. N-butyl scopolamine administration acted peripherally as an effective complement for treatment of visceral pain, reflecting an association between central cholinergic effects and peripheral anticholinergic effects in the treatment of visceral postoperative pain. (Anesth Analg 1996;82:617-20)

DOUBLE-BLIND EVALUATION OF TRANSDERMAL NITROGLYCERINE AS ADJUVANT TO ORAL MORPHINE FOR CANCER PAIN MANAGEMENT

STUDY OBJECTIVES To examine analgesia and adverse effects following transdermal application of nitroglycerine (a nitric oxide generator) combined with oral morphine, in cancer pain patients. DESIGN Randomized, double-blind study. SETTING Teaching hospital. PATIENTS 36 patients suffering from cancer pain. INTERVENTIONS Patients were divided into two groups (n = 18). All patients were regularly taking oral amitriptyline 50 mg at bedtime. Pain was evaluated using a 10-cm visual analog scale (VAS). The morphine regimen was individually adjusted to a maximal oral dose of 80 to 90 mg/day, to maintain the VAS score less than 4/10 cm. When patients complained of pain (VAS equal or greater than 4/10), despite taking 80 to 90 mg of oral morphine daily, the transdermal test drug was supplemented as follows: the control group received a placebo patch daily, and the nitroglycerine group received a 5-mg/24-hour nitroglycerine patch daily. Patients were free to manipulate their daily morphine consumption at the time the test drug was administered, to keep VAS less than 4/10 cm. After the introduction of the transdermal test drug, patients were evaluated by the staff on a weekly basis as outpatients, over four consecutive weeks. MEASUREMENTS AND MAIN RESULTS The groups were similar in respect to demographic data and VAS pain scores before the treatment. The daily consumption of oral morphine was smaller in the nitroglycerine group compared with the control group after the 14th day of evaluation (p < 0.002). Patients from the control group in general complained of somnolence, compared with the nitroglycerine group. CONCLUSION Transdermal nitroglycerine was an effective coadjuvant analgesic. In conjunction with its opioid tolerance sparing function, delivery of nitric oxide donors together with opioids may be of significant benefit in cancer pain management in delaying morphine tolerance and decreasing the incidence of adverse effects related to high doses of opioids.

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.

Mechanisms of analgesia of intravenous lidocaine

JUSTIFICATIVA Y OBJETIVOS: La lidocaina se utiliza por via venosa desde la decada de 60 para diversas finalidades. Su mecanismo de accion multimodal fue el objetivo principal de esta revision. CONTENIDO: Se revisaron mecanismos de accion divergentes del clasico bloqueo del canal de Na+, la accion diferencial de la lidocaina venosa en la sensibilizacion central, su accion analgesica y citoprotectora, como tambien las diferentes dosis de la lidocaina utilizadas por via venosa. CONCLUSIONES: La accion analgesica final de la lidocaina por via venosa refleja su aspecto multifactorial de accion. Con relacion a la sensibilizacion central, se sugiere una accion antihiperalgesica periferica de la lidocaina en el dolor somatico y central en el dolor neuropatico, con el resultante bloqueo de la hiperexcitabilidad central. La dosis de por via venosa no debe exceder la concentracion plasmatica toxica de 5 µg.mL-1, siendo consideradas seguras dosis inferiores 5 mg.kg-1, administradas lentamente (30 minutos), con monitorizacion.BACKGROUND AND OBJECTIVES Intravenous lidocaine has been used for several indications since the decade of 1960. Its multimodal mechanism of action was the objective of this review. CONTENTS Mechanisms of action that diverge from the classical Na+ channel blockade, the differential action of intravenous lidocaine in central sensitization, and the analgesic and cytoprotective actions, as well as the different doses of intravenous lidocaine were reviewed. CONCLUSIONS The final analgesic action of intravenous lidocaine is a reflection of its multifactorial action. It has been suggested that its central sensitization is secondary to a peripheral anti-hyperalgic action on somatic pain and central on neuropathic pain, which result on the blockade of central hyperexcitability. The intravenous dose should not exceed the toxic plasma concentration of 5 microg mL(-1); doses smaller than 5 mg kg(-1), administered slowly (30 minutes), under monitoring, are considered safe.

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.

Epidural morphine and neostigmine for postoperative analgesia after orthopedic surgery.

In this study, we examined the side effects and analgesia of the combination of epidural neostigmine and morphine in patients undergoing orthopedic surgery. Sixty patients undergoing knee surgery were divided into four groups. The intrathecal anesthetic was 15 mg of bupivacaine. The epidural test drug was diluted in saline to a final volume of 10 mL. The control group received saline as the epidural test drug. The morphine group received 0.6 mg of epidural morphine. The neostigmine group (NG) received 60 &mgr;g of epidural neostigmine. The morphine/neostigmine group received 0.6 mg of epidural morphine combined with 60 &mgr;g of epidural neostigmine. The groups were demographically the same and did not differ in intraop- erative characteristics. The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). One patient from the NG complained of intraoperative nausea, closely related to spinal hypotension. Postoperatively, two patients from the NG had vomited once. The time (min) to first rescue analgesic was longer in the morphine/neostigmine group (≈11 h) compared with the other groups (P < 0.05). The analgesic consumption (number of analgesic administrations in 24 h) was larger in the control group compared with the other groups (P < 0.05).

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.

Transdermal Ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade

We examined the postoperative analgesia of a controlled delivery ketamine transdermal patch after minor abdominal gynecological surgery using lidocaine epidural blockade. Fifty-two patients were randomized to one of two groups. Epidural anesthesia was performed with 25 mL 2% plain lidocaine. At the end of the surgical procedure, a controlled delivery transdermal patch containing either ketamine (25 mg/24 h) (Ketamine group) or placebo (Placebo group) was applied. Pain and adverse effects were assessed hourly postoperatively for 24 h. IM dipyrone was available at patient request. The two groups were demographically similar. The time to first rescue analgesic was longer in the Ketamine group (230 ± 112 min) compared with the Placebo group (94 ± 54 min); (P < 0.00001). There were more dipyrone dose injections in 24 h in the Placebo group compared with the Ketamine group (P < 0.0001). The incidence of adverse effects was similar between groups. We conclude that the transdermal-controlled delivery of ketamine prolonged the duration of analgesia after minor gynecological procedures. Implications Transdermal delivery of ketamine was an useful adjuvant to postoperative analgesia after epidural lidocaine blockade in the population studied.

Mecanismos envolvidos na analgesia da lidocaína por via venosa

JUSTIFICATIVA Y OBJETIVOS: La lidocaina se utiliza por via venosa desde la decada de 60 para diversas finalidades. Su mecanismo de accion multimodal fue el objetivo principal de esta revision. CONTENIDO: Se revisaron mecanismos de accion divergentes del clasico bloqueo del canal de Na+, la accion diferencial de la lidocaina venosa en la sensibilizacion central, su accion analgesica y citoprotectora, como tambien las diferentes dosis de la lidocaina utilizadas por via venosa. CONCLUSIONES: La accion analgesica final de la lidocaina por via venosa refleja su aspecto multifactorial de accion. Con relacion a la sensibilizacion central, se sugiere una accion antihiperalgesica periferica de la lidocaina en el dolor somatico y central en el dolor neuropatico, con el resultante bloqueo de la hiperexcitabilidad central. La dosis de por via venosa no debe exceder la concentracion plasmatica toxica de 5 µg.mL-1, siendo consideradas seguras dosis inferiores 5 mg.kg-1, administradas lentamente (30 minutos), con monitorizacion.BACKGROUND AND OBJECTIVES Intravenous lidocaine has been used for several indications since the decade of 1960. Its multimodal mechanism of action was the objective of this review. CONTENTS Mechanisms of action that diverge from the classical Na+ channel blockade, the differential action of intravenous lidocaine in central sensitization, and the analgesic and cytoprotective actions, as well as the different doses of intravenous lidocaine were reviewed. CONCLUSIONS The final analgesic action of intravenous lidocaine is a reflection of its multifactorial action. It has been suggested that its central sensitization is secondary to a peripheral anti-hyperalgic action on somatic pain and central on neuropathic pain, which result on the blockade of central hyperexcitability. The intravenous dose should not exceed the toxic plasma concentration of 5 microg mL(-1); doses smaller than 5 mg kg(-1), administered slowly (30 minutes), under monitoring, are considered safe.