Epileptic attacks associated with wasp sting-induced anaphylaxis

Ovulation was obtained in a 29-year-old woman affected by premature ovarian failure who had previously failed to respond to two attempts performed administering human menopausal gonadotropin or follicle-stimulating hormone after the spontaneous gonadotropin production was suppressed using a gonadotropin-releasing hormone analog (buserelin). Induction of ovulation succeeded when 1000 mg/day growth hormone-releasing hormone was added to the induction scheme. Five mature follicles were obtained after 27 days therapy and the serum level of 17 beta-estradiol was 975 pg/ml (195 pg/ml per follicle) at the time of human chorionic gonadotropin administration.     

Decrease in isoflurane requirements and of postoperative pain with preanesthetic intrathecal morphine

OBJECTIVES: 1) To determine whether preanesthetic intrathecal administration of 0.5 mg morphine reduces isoflurane requirements for anesthetic maintenance. 2) To assess the duration of postoperative analgesia and the type and frequency of complications attributable to the procedure. PATIENTS AND METHODS: A series of 45 adults were distributed into 3 groups of 15 patients each based on site of surgery and site of preanesthetic (30 min) injection of 0.5 mg pure morphine. Control group (C0) patients underwent lumbar surgery and received subcutaneous morphine. Group C0.5 patients also underwent lumbar surgery but received intrathecal morphine. Group A0.5 patients underwent long-duration high abdominal surgery and received intrathecal morphine. Anesthesia was maintained with nitrous oxide (60%) in oxygen (40%) and a variable concentration of isoflurane. Isoflurane needs were assessed by averaging six consecutive measurements of end-tidal isoflurane pressure (M30FETiso) taken at intervals of 5 min. Postoperative analgesia was evaluated by means of a visual analog scale that was converted to numerical units (VASn). RESULTS: M30FETiso in group C0 (0.8%) was always higher (p < 0.01) than in the other two groups. M30FETiso in group A0.5 was higher (p < 0.01) than in group C0.5 during the first 150 min of surgery. After 180 min, there were no differences in M30FETiso (0.10-0.16%) between the two groups receiving intrathecal morphine. VASn results (mean +/- SD) in the first 4 hours were higher in group C0 (7.33 +/- 0.6) than in group C0.5 (1.13 +/- 0.35) and group A0.5 (1.07 +/- 0.26). The time of morphine-dependent analgesia was shorter (p < 0.01) in group C0 (0.62 +/- 0.38 hours) than in groups C0.5 (30.4 +/- 5.11 hours) and A0.5 (28 +/- 4.34 hours). There were no significant differences between the two groups receiving intrathecal morphine. CONCLUSIONS: Preanesthetic subarachnoid lumbar injection of 0.5 mg of pure morphine reduced early requirements for isoflurane in lumbar surgery (0.14% after 60 min). This reduction was initially less in patients undergoing abdominal surgery (0.44% at 60 min) but was the same after 150 min. Postoperative analgesia was long-term and independent of type or duration of surgery. There was no respiratory depression after surgery and the incidence of postoperative complications was similar in the two groups that received subarachnoid morphine.     

Dose-response relationship of intrathecal morphine for postcesarean analgesia

BACKGROUND: This series investigated the quality of analgesia and the incidence and severity of side effects of intrathecal morphine for post-cesarean analgesia administered over a dose range of 0.0-0.5 mg. METHODS: ONE hundred eight term parturients undergoing cesarean delivery at term and given spinal anesthesia were randomized to receive a single dose of intrathecal morphine (0.0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.4, or 0.5 mg). A patient-controlled analgesia (PCA) device provided free access to additional analgesics. PCA morphine use, incidence and severity of side effects, and need for treatment interventions were recorded for 24 h. Data were analyzed with analysis of variance and linear regression analysis for trends among groups. RESULTS: Patient-controlled analgesia use differed significantly between groups; PCA use was higher in the control group than in groups receiving 0.075, 0.1, 0.3, 0.4, or 0.5 mg. Twenty-four-hour PCA morphine use was 45.7 mg lower (95% CI, 4.8-86.6 mg lower) in the 0.075-mg group than the control group. There was no difference in PCA morphine use between the 0.075- and 0.5-mg groups (95% CI, 36.8 mg lower to 45.0 mg higher); despite a fivefold increase in intrathecal morphine dose, PCA morphine use remained constant. There was no difference between control and treatment groups or among treatment groups with respect to nausea and vomiting. Pruritus and the need for treatment interventions increased in direct proportion to the dose of intrathecal morphine (linear regression, P = 0.001 and P = 0.0002, respectively). CONCLUSIONS: These data indicate there is little justification for use of more than 0.1 mg for post-cesarean analgesia. For optimal analgesia, augmentation [corrected] of intrathecal morphine with systemic opioids may be necessary.     

Intestinal pseudo-obstruction associated with oral morphine

Infusion of the GPIIb/IIIa-inhibitor MK383 inhibits thrombin generation in platelet rich plasma by interfering with the production of platelet procoagulant phospholipid exposure. The effect is similar to that of 0.2 U/ml of heparin. Heparin infusion, well known to inhibit thrombin generation by fostering antithrombin activity, inhibits the formation of platelet-derived procoagulant microparticles, probably by decreasing the formation of free thrombin, which, under our circumstances, is the main platelet activator.     

Analgesic effect of morphine and its metabolites administered by an intracerebroventricular route

Intraventricular morphine administration is indicated, in some selected cases, to alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal fluid allowed us to formulate the theory of "Front de Recrutement". Then we were able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6-glucuronide concentrations. Morphine 6-glucuronide is the main analgesic metabolite of morphine and its presence in cerebro-spinal fluid could be due to a metabolism of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher than that of morphine. By demonstrating the 6-monoacetyl morphine potency (analgesic metabolite of heroin that is 20 times more potent than morphine), we showed the involvement of the 6 position in the analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin, morphine must be considered as a precursor whose metabolites have pharmacologic effects.     

Epileptic vertiginous seizure in a Japanese boy: a case report

Dizziness in childhood is not an infrequent symptom, but epileptic vertigo is a rare condition in children. Here we report an 8-year-old Japanese boy with epileptic vertiginous seizures. At age 8 years, he visited Nippon Medical School Hospital because of a ten day history of dizziness. The dizziness occurred more than twenty times a day and he was hospitalized. On physical examination, the patient appeared normal and there were no abnormal neurological findings, including eye movement and cerebellar signs. Ophthalmoscopy, otoscopy, vestibular function test and hearing test were normal. Computerized tomography scanning and MR imaging of the head revealed no significant abnormality. The dizziness observed on admission comprised sudden brief attacks of rotatory sensation without amnesia regarding the event. Sometimes the attacks were accompanied by tremor like movement and numbness of the right hand, followed by postictal unsteadiness. Interictal EEG revealed spike-and-wave complexes in the central region dominantly in the light sleep stage. On ictal EEG, seizure discharges were observed to begin in the left central region and they increased in amplitude and subsequently propagated to the frontal and occipital regions. These findings were most suggestive of partial seizures. The patient was treated with carbamazepine and the seizures became well under control.     

Effects of intrathecal NMDA and non-NMDA antagonists on acute thermal nociception and their interaction with morphine

BACKGROUND: N-methyl-D-aspartate (NDMA) antagonists have minimal effects on acute nociception but block facilitated states of processing. In contrast, the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists decrease acute noxious responses. Morphine (a mu-opioid agonist) can also decrease acute nociceptive processing. The authors hypothesized that the interaction between morphine and AMPA receptor antagonists would be synergistic, whereas morphine and NMDA antagonists show no such interaction in acute nociception. METHODS: Sprague-Dawley rats (weight, 250-300 g) were implanted with chronic lumbar intrathecal catheters and were assigned to receive one of several doses of morphine--ACEA 1021 (NMDA glycine site antagonist), ACEA 2085 (AMPA antagonist), AP-5 (NMDA antagonist), saline or vehicle--and were tested for their effect on the response latency using a 52.5 degrees C hot plate. The combinations of morphine and other agents also were tested. RESULTS: Intrathecal morphine (ED50:2 microg/95% confidence interval, 1-4 microg) and ACEA 2085 (6 ng/2-15 ng), but not AP-5 or ACEA 1021, yielded a dose-dependent increase in the thermal escape latency. A systematic isobolographic analysis was carried out between intrathecal morphine and ACEA 2085 using the ED50 dose ratio of 357:1. A potent synergy was observed with decreased side effects. Morphine dose-response curves were carried out for morphine and fixed doses of ACEA 1021 (12 microg) or AP-5 (10 microg). No synergistic interactions were noted. CONCLUSIONS: Spinal mu-receptor activation and AMPA receptor antagonism showed a synergistic antinociception in response to an acute thermal stimulus. NMDA or NMDA glycine site antagonism had no effect alone nor did they display synergy with morphine. These results suggest an important direction for development of acute pain strategies may focus on the AMPA receptor.     

Premedication with promethazine and transdermal scopolamine reduces the incidence of nausea and vomiting after intrathecal morphine

Intrathecal morphine provides effective postoperative pain relief in major orthopaedic surgery. In use, however, is associated with unpleasant side effects like nausea and vomiting. The effect of different premedications on postoperative emetic sequelae induced by intrathecal morphine was studied in a prospective, double blind study. Sixty patients scheduled for arthroplasty surgery of the lower extremity were anaesthetized with spinal anaesthesia with a combination of isobaric bupivacaine 20 mg and morphine 0.3 mg. For premedication the patients were randomised to three groups of equal size. They received either oral diazepam (5-15 mg), oral promethazine (10 mg) or a combination of promethazine and transdermal scopolamine (1.5 mg). Sixty percent of the patients with both promethazine and transdermal scopolamine were totally free from postoperative nausea and vomiting (PONV) symptoms compared to those premedicated with diazepam (40%) or promethazine alone (30%). Promethazine together with transdermal scopolamine reduced significantly the number of patients with vomiting (to 25%) and also vomiting episodes. This combination was also more efficient in reducing the incidence of nausea (to 25%) and nausea episodes than promethazine along (P < 0.05). Combination also reduced the requests for additional pain relief (P < 0.05). PONV occurred in a majority of patients during the first 12 hours of the 24 hour study period and the need for additional analgesics thereafter. The incidence of itching (50-65%) and urinary catheterisation (55-70%) was similar in all groups. In conclusion, the combination of oral promethazine and transdermal scopolamine was most effective in reducing PONV symptoms and also reduced the need for postoperative pain treatment.     

Comparison of pre- versus post-incision administration of intrathecal bupivacaine and intrathecal morphine in a rat model of postoperative pain

BACKGROUND: Preclinical studies in experimental animals suggest that preemptive analgesia may improve postoperative pain management. The beneficial effects of preemptive analgesia appear less remarkable clinically. The purpose of this study is to examine the effect of pre- and post-incision administration of intrathecal bupivacaine and intrathecal morphine in a rat model for postoperative pain. METHODS: Rats with intrathecal catheters were anesthetized with halothane, and the surgical field was prepared. A saline vehicle or the test drug was administered 15 min before an incision was made in the plantar aspect of the hindpaw or after the incision was completed. After recovery, mechanical hyperalgesia to punctate and nonpunctate stimuli was measured. Rats were tested on the day of surgery for the first 5 h and each day for 6 days. RESULTS: In saline vehicle-treated rats, the median withdrawal threshold decreased from 522 mN to 54 mN or less, and the response frequency to pressure from application of the plastic disc increased from 0 +/- 0% to 96 +/- 12% or greater after incision. Hyperalgesia was persistent through 2 days after surgery and then gradually returned toward preincision values over the next 4 days. Pre- or postincision administration of either intrathecal morphine or intrathecal bupivacaine reduced hyperalgesia on the day of surgery; at all subsequent times, there were no differences between the saline vehicle groups and the drug treatment groups. There were never any significant differences between pre- and postincision treatments. CONCLUSIONS: Early reduction in pain behaviors either by pre- or postincision management had no impact on subsequent measures of hyperalgesia in this model. These results agree with a number of clinical studies and suggest that incisional pain may be initiated and maintained differently than pain in other models.     

Properties of human glial cells associated with epileptic seizure foci

We studied physiological properties of glial cells from acute slices of biopsies from patients operated for intractable mesio-temporal lobe epilepsy using whole-cell patch-clamp recordings. Cells were filled with Lucifer Yellow (LY) during recordings to allow morphological reconstruction and immunohistochemical cell identification. Seizure-associated astrocytes had complex, arborized, highly branched processes giving them a stellate appearance, and cells stained intensely for the intermediate filament GFAP as previously reported for 'reactive' astrocytes. GFAP-positive astrocytes from epilepsy biopsies consistently expressed voltage-activated, TTX-sensitive Na+ channels that showed fast activation and inactivation kinetics. Unlike comparison astrocytes, derived from tissues that were not associated with seizure foci, these astrocytes expressed Na+ channels at densities sufficient to generate slow action potentials (spikes) in current clamp studies. In these cells, the ratio of Na+ to K+ conductance was consistently 3-4-fold higher than in comparison human or control rat astrocytes. Four of 17 astrocytes from epilepsy patients versus 14/14 from control rat hippocampus and four of five in comparison human tissue showed a lack of inwardly rectifying K+ currents, which in normal astrocytes are implicated in the control of extracellular K+ levels. These results suggest that astrocytes surrounding seizure foci differ in morphological and physiological properties, and that glial K+ buffering could be impaired at the seizure focus, thus contributing to the pathophysiology of seizures.     

Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence

The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. naloxone. In butorphanol-dependent rats, the spinal kappa-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal delta- and mu-opioid receptors did. In contrast, the spinal mu-opioid receptor became more sensitive than the delta-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.     

Lignocaine plus morphine in bolus patient-controlled intravenous analgesia lacks post-operative morphine-sparing effect

PURPOSE: Eyelid myoclonic jerks have been described in fixation-off-sensitive (FOS) epilepsy, but their relationship to nonconvulsive status epilepticus (NCSE) or to catamenial exacerbations is little reported. METHODS: We describe a woman of normal intelligence with catamenial periods of prolonged NCSE who exhibited various intra- and interseizure thresholds of polyspike suppression when her eyes were open, with particular visual inputs and with antiepileptic drug (AED) treatment. RESULTS: In one episode, on the first day of the woman's menstrual period, bursts of bilateral synchronous polyspike activity were briefly suppressed with visual fixation but were more lastingly suppressed after administration of lorazepam (LZP). During another period of NCSE, the SE was completely suppressed by visual fixation on objects and patterned checkerboard screens and by ocular convergence, was incompletely suppressed when her eyes were open in a dark room and when her eyes were open without visual fixation, but was not suppressed by mental activation alone. CONCLUSIONS: FOS polyspike bursts with eyelid myoclonic jerks may exhibit catamenial exacerbations, varying from completely suppressible with visual fixation to nonsuppressible during NCSE. These findings suggest an interplay between humoral factors, AEDs, and seizure threshold in this condition.     

An intravenous fluid bolus is not necessary before administration of intrathecal fentanyl for labor analgesia

The acute phase response to inflammation is mediated in part by the endogenous production of pro-inflammatory cytokines. Interleukin 6 (IL-6) and members of its superfamily, including ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) have been implicated as primary mediators of the hepatic acute phase response. In the present report, mice suffering a turpentine-induced myositis were passively immunized with antibodies against either IL-6, CNTF or LIF. Passive immunization against IL-6 attenuated the anorexia and completely prevented the hypoalbuminaemia, and increases in the serum concentration of the acute phase reactants, amyloid P, amyloid A and seromucoid. In contrast, passive immunization against either CNTF or LIF failed to modulate the anorexia, weight loss or hepatic acute phase protein responses. The findings suggest that IL-6, but not other members of its superfamily, is primarily responsible for the hepatic acute phase response, and contributes to the anorexia, associated with turpentine-induced myositis.     

Prenatal morphine exposure induces age-related changes in seizure susceptibility in male rats

The purpose of this study was to investigate the effects of prenatal exposure to morphine (5-10 mg/kg on days 11-18 of gestation) on flurothyl seizure susceptibility in adult and developing male rats. In adult rats, prenatal morphine exposure increased the threshold to clonic seizures but not to tonic-clonic seizures. The effects of prenatal morphine exposure on clonic seizures were age dependent. At postnatal day (PND) 15, prenatal drug exposure did not alter the seizure threshold. At PND 25, there was a reduction in the threshold but by PND 38, the clonic seizure threshold was increased and this increase persisted into adulthood. Prenatal exposure to morphine did not alter the tonic-clonic seizure threshold in any age group of intact male rats. A group of male rats prenatally exposed to morphine was gonadectomized in adulthood. In gonadectomized rats both clonic and tonic-clonic thresholds were increased. These results suggest that exposure to morphine during mid to late gestation induces age-dependent alterations in the susceptibility to clonic but not tonic-clonic seizures. In adult male rats the threshold to tonic-clonic seizures is influenced by prior gonadectomy in adulthood.     

Epidural opioid analgesia after caesarean section: a comparison of patient-controlled analgesia with meperidine and single bolus injection of morphine

The quality of analgesia, patient satisfaction and incidence of side effects following a single bolus of epidural morphine were compared with patient-controlled epidural analgesia (PCEA) with meperidine during the first 24 hr after elective Caesarean section. Seventy-five women were randomly assigned to three equal groups. Group I received 30 mg epidural meperidine after delivery and PCEA with meperidine; Group 2 received 3 mg epidural morphine after delivery and PCEA with saline in a double-blind fashion. Group 3 received 3 mg epidural morphine after delivery without saline PCEA. Visual analogue pain scores (VAS) were higher with PCEA meperidine from 8-16 hr post-operatively (P < 0.05) than in both epidural morphine groups. Two patients in Group 1 and one in Group 3 required supplemental parental analgesia. The incidence of nausea was 16% in Group 1, compared with 52% in Group 2 and 56% in Group 3 (P < 0.01). Pruritus occurred in 24% of Group 1 patients, 84% of patients in Group 2 and 68% of patients in Group 3 (P < 0.001). Forty-six percent of patients in Group 1 were very satisfied with pain management, compared with 77% in Group 2 and 79% in Group 3. Nurse workload was higher in the PCEA study groups than in Group 3 (P < 0.05). A single bolus of epidural morphine provides superior analgesia and satisfaction at low cost, but with a higher incidence of nausea and pruritus than PCEA with meperidine.     

Spinal cord compression by catheter granulomas in high-dose intrathecal morphine therapy: case report

OBJECTIVE AND IMPORTANCE: The use of chronic intrathecal morphine for the treatment of intractable, nonmalignant pain is becoming more prevalent. A rare but devastating complication of this therapy is the development of spinal cord compression secondary to the formation of intrathecal granulomas. CLINICAL PRESENTATION: We report three cases of intrathecal granuloma formation in the thoracic subarachnoid space, associated with intrathecal morphine pumps. These three patients were receiving high doses of morphine to control their pain (25 mg/d, 28 mg/d, and 45 mg/d, respectively) when they presented with signs and symptoms of thoracic spinal cord compression. Myelography and postmyelographic computed tomography of the spine revealed masses causing spinal cord compression. INTERVENTION: Two patients underwent thoracic laminectomies for resection of these masses, and the other patient had the intrathecal catheter removed. A pathological examination revealed sterile granulomas in the resected masses. CONCLUSION: Intrathecal granulomas are likely to occur with increasing frequency as the use of chronic intrathecal morphine delivery increases in patients with nonmalignant pain. The cause of intrathecal granulomas is unknown, although it is likely that morphine plays a major role in their formation. We think that those patients receiving high doses of morphine are at greater risk for developing this complication.     

A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain

OBJECTIVE: To examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less invasive modalities. METHODS: Forty patients with severe, chronic nonmalignant pain poorly managed by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty participants reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed before treatment was begun and at defined intervals during the subsequent 24 months. Intrathecal opioid use and pharmacological and device-related complications were also monitored. RESULTS: The participants had a mean age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three percent of the study participants were women. Pain type was characterized as mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with failed back surgery syndrome. Significant improvement over baseline levels of visual analog scale pain was measured at each follow-up examination after implant. Overall, 50% (11 of 22 patients) of the population reported at least a 25% reduction in visual analog scale pain after 24 months of treatment. In addition, the McGill Pain Questionnaire, visual analog scale measures of functional improvement and pain coping, and several subscales of the Chronic Illness Problem Inventory showed improvement throughout the follow-up period. Pharmacological side effects were managed medically by morphine dose reduction, addition of bupivacaine, or replacement of morphine with hydromorphone. Device-related complications requiring repeat operations were experienced by 20% of the patients. CONCLUSION: Continuous intrathecal morphine can be a safe, effective therapy for the management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function.     

Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery

Very small doses of intrathecal (i.t.) morphine (25-200 microg) have been used in an effort to provide effective postoperative pain relief while minimizing side effects after cesarean delivery. We performed a double-blinded study in 40 patients presenting for elective cesarean delivery in which i.t. morphine was administered along with oral hydrocodone/acetaminophen and other medications commonly administered after cesarean delivery. We administered i.t. morphine by up-down sequential allocation of doses. For the purposes of this study, adequate postoperative analgesia was defined as comfort not requiring i.v. morphine for 12 h after spinal anesthesia with bupivacaine, fentanyl, and morphine. In addition, a time and cost comparison was performed for study patients receiving intrathecal morphine compared with a historical group of patients receiving patient-controlled analgesia with i.v. morphine. We were unable to determine with meaningful precision a dose of i.t. morphine to provide analgesia in this context. However, very small doses of i.t. morphine combined with oral hydrocodone/acetaminophen and other medications commonly prescribed after cesarean delivery provided postoperative pain relief with no more time commitment than patient-controlled analgesia (148 +/- 61 vs 150 +/- 57 min) and with significantly less acquisition cost ($15.13 +/- $4.40 vs $34.64 +/- $15.55). Implications: When used along with oral analgesics, very small doses of spinal morphine provide adequate pain relief after cesarean delivery. Spinal anesthetics, oral analgesics, and other medications commonly prescribed to treat side effects after cesarean delivery contribute significantly to this analgesia. When small doses of spinal morphine are used in this setting, they provide adequate analgesia and patient satisfaction that is time- and cost-effective.