Intravenous regional block is similar to sympathetic ganglion block for pain management in patients with complex regional pain syndrome type I

Sympathetic ganglion block (SGB) or intravenous regional block (IVRB) has been recommended for pain management in patients with complex regional pain syndrome type I (CRPS-I). Forty-five patients were initially selected but only 43 were accepted for the study. The present study evaluated the efficacy of IVRB produced by combining 70 mg lidocaine with 30 µg clonidine (14 patients, 1 male/13 females, age range: 27-50 years) versus SGB produced by the injection of 70 mg lidocaine alone (14 patients, 1 male/13 females, age range: 27-54 years) or combined with 30 µg clonidine (15 patients, 1 male/14 females, age range: 25-50 years) into the stellate ganglion for pain management in patients with upper extremity CRPS-I. Each procedure was repeated five times at 7-day intervals, and pain intensity and duration were measured using a visual analog scale immediately before each procedure. A progressive and significant reduction in pain scores and a significant increase in the duration of analgesia were observed in all groups following the first three blocks, but no further improvement was obtained following the last two blocks. Drowsiness, the most frequent side effect, and dry mouth occurred only in patients submitted to SGB with lidocaine combined with clonidine. The three methods were similar regarding changes in pain intensity and duration of analgesia. However, IVRB seems to be preferable to SGB due to its easier execution and lower risk of undesirable effects.

Intravenous regional block is similar to sympathetic ganglion block for pain management in patients with complex regional pain syndrome type I.

Sympathetic ganglion block (SGB) or intravenous regional block (IVRB) has been recommended for pain management in patients with complex regional pain syndrome type I (CRPS-I). Forty-five patients were initially selected but only 43 were accepted for the study. The present study evaluated the efficacy of IVRB produced by combining 70 mg lidocaine with 30 µg clonidine (14 patients, 1 male/13 females, age range: 27-50 years) versus SGB produced by the injection of 70 mg lidocaine alone (14 patients, 1 male/13 females, age range: 27-54 years) or combined with 30 µg clonidine (15 patients, 1 male/14 females, age range: 25-50 years) into the stellate ganglion for pain management in patients with upper extremity CRPS-I. Each procedure was repeated five times at 7-day intervals, and pain intensity and duration were measured using a visual analog scale immediately before each procedure. A progressive and significant reduction in pain scores and a significant increase in the duration of analgesia were observed in all groups following the first three blocks, but no further improvement was obtained following the last two blocks. Drowsiness, the most frequent side effect, and dry mouth occurred only in patients submitted to SGB with lidocaine combined with clonidine. The three methods were similar regarding changes in pain intensity and duration of analgesia. However, IVRB seems to be preferable to SGB due to its easier execution and lower risk of undesirable effects.

Effects of intrathecal sufentanil on plasma oxytocin and cortisol concentrations in women during the first stage of labor.

BACKGROUND AND OBJECTIVES: Intrathecal sufentanil provides analgesia comparable to epidural bupivacaine for the first stage of labor. Both epidural local anesthetics and intrathecal opioid reduce some parameters of the neuroendocrine response to labor pain and the reflex release of oxytocin in animals. In humans, epidural local anesthetics only reduce the spurt release of oxytocin. This study compared the effect of intrathecal sufentanil and epidural bupivacaine administration on the plasma concentration of oxytocin and cortisol in women with labor pain during the first stage of labor. METHODS: Thirty healthy parturients requesting analgesia were enrolled in this randomized and open-label study. Each patient was in spontaneous labor at greater than 5 cm cervical dilatation. Using a combined spinal and epidural technique, patients received either intrathecal sufentanil 10 microg (SUF = intrathecal sufentanil group) or epidural plain bupivacaine 0.25%, 12 mL (BUPIV = epidural bupivacaine group). Analgesia was assessed using a visual analog scale, and blood samples for oxytocin and cortisol plasma concentration measurements were collected immediately before analgesia and 15, 30, 60, and 90 minutes after induction of the analgesia. Plasma cortisol and oxytocin concentrations were determined by specific radioimmunoassay. The values were expressed as mean +/- SEM. RESULTS: Intrathecal sufentanil provided faster and more complete analgesia within 15 and 30 minutes of its administration, compared with epidural bupivacaine. Plasma oxytocin concentrations were similar in the 2 groups before analgesia (7.24 +/- 2.1 and 6.6 +/- 3.1 pg/mL SUF and BUPIV, respectively). It decreased significantly in the SUF and increased in the BUPIV after analgesic administration. Cortisol concentrations were elevated in both groups before analgesia (51.6 +/- 5.3 and 54.2 +/- 4.8 microg/dL SUF and BUPIV, respectively). Both analgesic treatments significantly decreased the plasma cortisol levels. CONCLUSIONS: Intrathecal sufentanil analgesia decreases plasma concentrations of oxytocin and cortisol in women with labor pain during the first stage of labor, but epidural bupivacaine only reduced the cortisol concentration.

Labor analgesia in a patient with paroxysmal nocturnal hemoglobinuria with thrombocytopenia.

BACKGROUND AND OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is a form of acquired hemolytic anemia in which a defect of glycophosphatidylinositol anchor proteins in the cell membrane of bone marrow stem cells leads to activation of the complement system and consequent destruction of defective cells. The characteristics of this disease are an increased frequency of thrombotic events, anemia, and thrombocytopenia. METHODS: We report a case of a pregnant patient with PNH with thrombocytopenia who delivered vaginally after receiving epidural labor analgesia. Prophylaxis of thromboembolism was performed with heparin 1 hour after the removal of the epidural catheter, and repeated at 12-hour intervals. Sensory changes or motor changes and pain were monitored every 10 minutes for 8 hours after delivery. RESULTS: During analgesia, the patient reported complete pain relief. Delivery and the immediate postpartum period were without any untoward events. CONCLUSIONS: Four major factors influenced the anesthetic conduct used for the present patient: (1) the risk of an acute hemolytic crisis, (2) the need to perform prophylaxis for thromboembolism, (3) the need to reduce labor stress, and (4) minimizing the risk of missing an epidural hematoma. We also present a survey of the literature about PNH and discuss the anesthetic conduct in this patient.

Effects of lamotrigine on pain-induced chemo-somatosensory evoked potentials.

Lamotrigine, a sodium channel blocker that selectively inhibits the neuronal release of glutamate, has been shown to produce analgesia in acute and chronic pain models in rats without causing noticeable sedation. After oral administration it also reduces pain scores, as assessed by the cold pain test, in volunteers. The purpose of this study was to determine the analgesic effect of lamotrigine given by mouth to healthy volunteers as evidenced by alterations in chemo-somatosensory evoked potentials. The following factors were measured: latency to N1 and P100 peak (ms); amplitude between the N1 and P100 peak (microV); visual analogue pain intensity scores. A double-blind, randomised and crossover design was used in which 12 volunteers received either placebo or lamotrigine 300 mg on separate occasions as determined by the randomisation schedule. Volunteers were tested before and 2 h after the treatment. The plasma lamotrigine concentration was measured immediately after the end of the experimental sessions. Lamotrigine produced a significantly higher latency to P100 values at 2 h postdrug than placebo (p < 0.05) but had no significant effects on the other factors. Although plasma concentrations were similar to those observed in the cold pain test, we conclude that lamotrigine 300 mg by mouth had no analgesic effect in this acute pain model.

Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or combined with morphine in patients submitted to spinal anaesthesia: pilot studies.

We report the analgesic and adverse effects of intrathecally administered hyperbaric neostigmine, alone or combined with morphine, in two patients suffering from severe lower limb ischaemic pain (group 1), five patients undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic surgery (group 3) under spinal anaesthesia. These patients were enrolled in three pilot studies undertaken before the initiation of the planned controlled studies. Hyperbaric neostigmine (50 micrograms in glucose 8%) produced analgesia lasting more than 6 h in patients of group 1, but the effect was accompanied by episodes of vomiting. A lower dose of hyperbaric neostigmine (25 micrograms), alone (two patients) or combined with morphine (50 micrograms) (one patient) produced no discernible analgesic effect but was followed by severe nausea and vomiting within 15 min of intrathecal injection in patients of group 2. Two patients who received hyperbaric morphine (100 micrograms) had analgesia for more than 24 h and exhibited mild pruritus. In patients of group 3, hyperbaric neostigmine alone (25 micrograms) produced analgesia of shorter duration than neostigmine (25 micrograms) plus morphine (50 micrograms) or morphine (100 micrograms). Neostigmine alone or combined with morphine was associated with adverse events, mainly nausea and vomiting that lasted up to 9-12 in some patients. Other adverse events observed included anxiety, somnolence and involuntary defaecation. Most patients who received the combination of neostigmine and morphine exhibited more severe nausea, vomiting and somnolence. The low clinical efficacy of intrathecally administered neostigmine alone or in combination with morphine impairs the design of a double-blind protocol and might restrict the clinical usefulness of the drug combination.

Effects of intrathecally administered lamotrigine, a glutamate release inhibitor, on short- and long-term models of hyperalgesia in rats.

BACKGROUND: Lamotrigine is a sodium channel blocker that inhibits the neuronal release of glutamate. Systemic administration of lamotrigine induces analgesia in short- and long-term models of hyperalgesia in rats. Considering the key role of N-methyl-D-aspartate receptors in the sensitization of dorsal horn neurons that leads to hyperalgesia, the author hypothesizes that intrathecally injected lamotrigine would be effective in reducing the hyperalgesia. METHODS: Short-term hyperalgesia was induced by unilateral intraplantar injection of prostaglandin E2. Long-term hyperalgesia was produced by treating rats with streptozotocin, which causes diabetic neuropathy and, in a different group of animals, by loose ligation of the sciatic nerve (chronic constriction injury). Hyperalgesia was assessed by measuring withdrawal reaction time after paw pressure, and analgesia was measured by the thermal tail-flick test. RESULTS: In the short-term model, intrathecally administered lamotrigine (12.5, 25.0, and 100.0 microg) produced a dose-dependent increase in the reaction time of the hyperalgesic paw. The highest dose that completely restored the reaction time to control levels (26-29 s) from the hyperalgesic levels (12-15 s) did not affect the reaction time of the normal contralateral paw. In the tail-flick test, a consistent effect could be observed only with doses of 200 microg, which caused transient motor impairment of the hind paws. In the long-term models of hyperalgesia, intrathecally administered lamotrigine produced a dose-dependent and long-lasting (24-48 h) antihyperalgesic effect. CONCLUSIONS: Intrathecally administered lamotrigine produced a spinal, dose-dependent, and long-lasting antihyperalgesic effect in short- and long-term neuropathic models of hyperalgesia.

Postoperative analgesic effect of intrathecal neostigmine and its influence on spinal anaesthesia.

A clinical trial was conducted to evaluate the postoperative analgesic efficacy and the safety of intrathecal neostigmine in patients undergoing anterior and posterior vaginoplasty under spinal anaesthesia. Thirty-six patients were randomly divided into three groups to receive: normal saline (1 ml), morphine (100 micrograms in 1 ml of saline) or neostigmine (100 micrograms in 1 ml of saline) intrathecally just before a spinal injection of hyperbaric bupivacaine (0.5%, 4 ml). The mean [SD] time to the first analgesic (nonsteroidal anti-inflammatory drug) administration was significantly prolonged by intrathecal neostigmine (10.7 [4.3] h) and morphine (15.3 [3.0] h) compared with saline (4.5 [1.0] h). The three groups also differed in the number of patients requiring subcutaneous morphine to complement the analgesia provided by the intramuscular nonsteroidal anti-inflammatory drugs and the mean [SD] times for their administration: eight patients in the saline group (8.0 [3.8] h), one patient in the morphine group (18 h) and two patients in the neostigmine group (8 and 12.9 h). The morphine and neostigmine groups showed similar analgesic effectiveness. The characteristics of spinal anaesthesia were not modified by intrathecal morphine or neostigmine. Severe nausea and vomiting, sweating and distress during surgery were the most obvious adverse effects of intrathecal neostigmine. On the other hand, less hypotension was observed in the neostigmine group. The usefulness of intrathecal neostigmine as the sole postoperative analgesic may be restricted by the severity of its adverse effects.

Analgesic effect of subarachnoid neostigmine in two patients with cancer pain.

Two patients suffering with severe pain due to metastatic abdominal neoplasm were selected to examine whether subarachnoid neostigmine provided effective pain relief. Neostigmine was injected through a catheter introduced into the subarachnoid space at L4-L5. Patients were monitored for changes in arterial blood pressure, cardiac and respiratory rates, body temperature, level of consciousness and neurologic change. Pain was classified by the patients on a verbal four-grade scale, and analgesia was classified on a verbal three-grade scale. Complete pain relief was obtained 2 h after neostigmine (0.2 mg) in one patient and 4 h after neostigmine (0.1 mg) in the second patient. Pain of mild intensity returned 20 and 22 h after drug administration, respectively. Gastrointestinal discomfort was observed in both cases, but nausea and vomiting occurred only in the patient treated with the highest dose of neostigmine. No significant change in the monitored parameters was observed, except for a 6-h period of decreased blood pressure in the patient treated with the lower dose of neostigmine which required no specific treatment. The results obtained in these anecdotal cases indicate that subarachnoid neostigmine may provide analgesia in patients with pain arising from neoplasia, but further studies using controlled trials are needed before the drug is brought into clinical use.

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 micrograms, 100 micrograms, and 200 micrograms morphine [M]; saline; 50 micrograms, 100 micrograms, and 200 micrograms neostigmine [N]; and 50 micrograms morphine + 50 micrograms 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 micrograms, 100 micrograms, and 200 micrograms) and intrathecal neostigmine (50 micrograms, 100 micrograms, and 200 micrograms) 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.

Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain.

The sites of the rat brain in which intracerebral administration of carbachol (0.4 microgram/0.5 microliter) elevates the nociceptive threshold to thermic (tail-flick test) and mechanical (calibrated-pinch test) noxious stimuli were examined. An extensive mapping (510 sites) ranging from AP + 10.5 to AP-0.1 mm revealed that antinociception was obtained from 119 sites (23%) widely scattered in the brain, and reached structures distant from, or within the immediate vicinity of the ventricular system. The effects from most placement were demonstrated using the tail-flick test, whereas a smaller proportion (approximately 13%) of sites was effective in reducing the response to mechanical stimuli only. Structures containing sensitive sites include the dorsal raphe nucleus, lateral border of the superior cerebellar peduncle, caudal portion of the superior colliculus, medial geniculate body, habenular complex, amygdala, temporal pole of the ventral hippocampus, rostral aspect of the dorsal hippocampus, lateral septal area, and triangular nucleus of the septum. Analysis of the distribution of responsive sites indicated that they are poorly superposed to the known distribution of opiate-sensitive areas. Most of the structures found to be responsive to carbachol are also known to possess cholinergic receptors and to evoke antinociception following focal electrical stimulation. In various placements, particularly in limbic structures, microinjection of carbachol evoked jumping to mechanical noxious stimulation, hyperexcitability to non-noxious stimuli, convulsive reactions, and other less frequent reactions. On few occasions, however, these changes were accompanied by antinociception.

An improved pinch test for assessing pain and antinociception in rats.

The present paper describes a simple and inexpensive device for assessing responses of rats to calibrated noxious pinching of the dorsal skin. The method has advantages over the classic pinch test because it permits assessment of slight variations in the nociceptive threshold with little risk of skin damage, and a more precise evaluation of changes in the time course of antinociceptive procedures. The magnitude and time course of analgesia induced by morphine are evaluated using this method and the tail-flick test.

An improved pinch test for assessing pain and antinociception in rats

The present paper describes a simple and inexpensive device for assessing responses of rats to calibrated noxious pinching of the dorsal skin. The method has advantages over the classic pinch test because it permits assesment of slight variations in the nociceptive threshold with little risk of skin damage, and a more precise evaluation of changes in the time course of antinociceptive procedures. The magnitude and time course of analgesia induced by morphine are evaluated using this method and the tail-flick test