Rationale for the administration of systemic 5-FU in combination with heated intraperitonal oxaliplatin.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (OX) is the standard of care for selected patients with peritoneal carcinomatosis of colorectal origin. Because 5-FU is mandatory to improve efficacy of OX when used by systemic route, several teams now empirically combine intravenous (IV) 5-FU with HIPEC OX, but this practice has yet to be supported by preclinical data. Using a murine model, we studied the impact of IV 5-FU on peritoneal absorption of HIPEC OX. METHODS: Under general anesthesia, 24 Sprague-Dawley rats were submitted to 4 different doses of IV 5-FU (0, 100, 400 and 800 mg/m2) and a fixed dose of HIPEC OX (460 mg/m2) perfused at 40 °C during 25 min. At 25 min, samples in different compartments were harvested (peritoneum, portal vein and systemic blood) and the concentrations of 5-FU and OX were measured by high performance liquid chromatography. RESULTS: Peritoneal absorption of OX was significantly higher (17.0, 20.1, 34.9 and 38.1 nmol/g, p < 0.0001) with increasing doses of 5-FU (0, 100, 400 and 800 mg/m2, respectively). Peritoneal absorption of OX reached a plateau between 400 and 800 mg/m2 of IV 5-FU. CONCLUSION: IV 5-FU enhances peritoneal absorption of HIPEC OX. The most efficient dose of IV 5-FU to be used in combination with HIPEC OX seems to be 400 mg/m2.

Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein.

In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.

Inhibition of the T-type Ca2+ current by the dopamine D1 receptor in rat adrenal glomerulosa cells: requirement of the combined action of the G betagamma protein subunit and cyclic adenosine 3',5'-monophosphate.

Modulation of ionic Ca2+ currents by dopamine (DA) could play a pivotal role in the control of steroid secretion by the rat adrenal glomerulosa cells. In the present study, we report that DA decreases the T-type Ca2+ current amplitude in these cells. The use of pharmacological agonists and antagonists reveals that this effect is mediated by activation of the D1-like receptors. Modulation by cAMP is complex inasmuch as preincubation of the cells with 8-Br-cAMP or the specific adenylyl cyclase inhibitor, 2',3'-dideoxyadenosine, have no effect per se, but prevent the DA-induced inhibition. The inhibitory effect of DA was abolished by addition of GDPbetaS to the pipette medium but not by pertussis toxin. If a cell is dialyzed with medium containing G alpha(s)-GDP, the inhibitory effect is reduced and cannot be recovered by the addition of GTPgammaS, indicating that the alpha(s) is not involved, but rather the betagamma-subunit. Indeed, DA-induced inhibition was mimicked by G betagamma in the pipette and 8-Br-cAMP in the bath. Similarly, G betagamma release from the activation of the AT1 receptor of angiotensin II did affect the current amplitude only in the presence of 8-Br-cAMP in the bath. The mitogen-activated protein kinase cascade, which can be activated by receptors coupled to Gs, was not involved as shown by the lack of activation of p42mapk by DA and the absence of effect of the mitogen-activated protein kinase inhibitor, PD 098059, on the DA-induced inhibition. Because the binding of G betagamma-subunits to various effectors involves the motif QXXER, we therefore tested the effect of the QEHA peptide on the inhibition of the T-type Ca2+ current induced by DA. The peptide, added to the medium pipette (200 microM), abolished the effect of DA. We conclude that the presence of the G betagamma and an increase in cAMP concentration are both required to inhibit the T-type Ca2+ current in rat adrenal glomerulosa cells.

Cellular mechanisms involved during oxytocin-induced prostaglandin F2alpha production in endometrial epithelial cells in vitro: role of cyclooxygenase-2.

PGs are important regulators of reproductive processes. At the time ofluteolysis in vivo, PGF2alpha is produced by endometrial cells, in response to oxytocin (OT). The mechanism by which OT induces the release of PGF2alpha remains to be defined. We have used 13 different cultures of bovine epithelial endometrial cells to study the effect of OT on the regulation of PGF2alpha and to identify the possible involvement of cyclooxygenases (COXs). OT induced a dose-dependent increase of both inositol phosphates (IPs) and [Ca2+]i concentration in epithelial cells labeled with [3H]-myoinositol or loaded with fura-2 (using a fluorescent microscope imaging system), respectively. OT induced a dose-dependent increase of both PGF2alpha production and COX-2 gene expression (as demonstrated by RT-PCR and Northern blots). PGF2alpha production was increased from 13.3 +/- 2.0 to 166.8 +/- 22.5 ng/ml (P < 0.0001). On the other hand, COX-2/beta-actin mRNA gene expression (as determined by densitometric analysis) was increased 5.1 +/- 0.7-fold (P < 0.001) with OT (10[-7] M) treatment, compared with control. Addition of indomethacin (1 microM) and a specific COX-2 inhibitor (NS-398, 1 microM) blocked the OT-induced PGF2alpha production. COX-1 and phospholipase A2 mRNA were expressed at steady-state levels, but no effect of OT was detected on their regulation. Combined to OT, 10 microq/ml of recombinant ovine interferon-tau (roIFN-tau) was able to decrease significantly (P < 0.0001) the dose-dependent increase of PGF2alpha production. Furthermore, partial bovine COX-1 (777 pb) and COX-2 (449 bp) cDNAs were cloned and sequenced. An homology of 83% and 97% was found in relation with rat and sheep, for COX-1, respectively. COX-2 was found to bear 84%, 86%, and 87% of homology in relation to rat, guinea pig, and human, respectively. Collectively, these results demonstrate, for the first time, that COX-2 is involved in the mechanism by which OT regulates PGF2alpha production in the endometrium.

Ontogeny of oxytocin receptors and oxytocin-induced stimulation of prostaglandin synthesis in prepubertal heifers.

Developmental aspects of oxytocin (OT) receptors (OTR) in uterine tissues before puberty are not known. Bovine ovaries secrete some estradiol, but no progesterone, before puberty; the circulating levels of estradiol are between 1 and 3 pg/ml until puberty. Cross-bred Angus-Brahman heifers, in which puberty occurs around 12 months of age, were used to determine the concentrations of OTR from the late fetal stage to adulthood. PGF2alpha release in response to OT was determined in 3-, 6-, and 9-month-old heifers (n = 4 each). Myometrium, endometrium, and cervical mucosa were obtained from 3-week-old, 3-month-old, 6-month-old, and 9-month-old heifers and from adult cows at estrus. Whole uterus and cervix were taken from third trimester fetuses and at birth. [3H]OT binding and specificity, localization of immunoreactive (ir) OTR, OTR messenger RNA, and OT-induced release of PGF2alpha were determined. The uterus from fetuses and the neonate expressed OTR messenger RNA and bound [3H]OT. At 3 weeks of age, OTR concentrations per mg protein were very low, but at 3 months of age they had increased markedly in all three tissues. At 6 and 9 months of age, levels of OTR had risen further and were similar to those in adult cows at estrus. Prepubertal uterus also possessed separate vasopressin VP1 subtype receptors. The ir-OTR was localized in luminal epithelial cells of endometrium and cervical mucosa, most of which were ir positive, whereas in myometrium, clusters of ir-OTR-positive cells were found among large numbers of ir-OTR-negative cells. The PGF2alpha response to OT was insignificant in heifers of all age groups, in contrast to that in cows at estrus. Endometrial cells from 4- to 5-month-old heifers did not respond to OT with PG release in the absence or presence of added arachidonic acid. Tumor promoters, lipopolysaccharide, and interleukin-2 also failed to elicit PG release in vitro, although they induced PG release in similar cell cultures from cyclic cows. In summary, uterine tissues of prepubertal heifers have high levels of OTR, which appear to be developmentally regulated. These receptors are not coupled to PG synthase, or alternatively, the PG synthase gene is not expressed before puberty, possibly because the tissues have had no previous exposure to progesterone.

Patient-controlled epidural analgesia with fentanyl-bupivacaine: influence of prior dural puncture.

BACKGROUND AND OBJECTIVES: Combined spinal epidural anesthesia (CSEA) involves the epidural administration of local anesthetic and opioid solutions adjacent to the prior dural puncture, potentially increasing their diffusion into the subarachnoid space. This study was designed to evaluate the influence of dural puncture on the adequacy and extent of analgesia, and drugs requirements of patient-controlled epidural analgesia (PCEA) in the postoperative period. METHODS: In this prospective double-blind study, 40 patients undergoing major abdominal surgery under general anesthesia followed with PCEA were randomly assigned to either group I (preoperative insertion of an epidural catheter) or group II (preoperative dural puncture with a 25-g Quincke needle + insertion of an epidural catheter). Postoperatively, a PCEA pump delivered an infusion of 0.1% bupivacaine + fentanyl (3 microg/mL) at 5 mL/h. Participants were allowed to self-administer 5-mL boluses of the same solution with a 15-minute lock-out interval. Hourly epidural solution requirements were recorded for 40 hours. Sensory and motor block, and pain scores were also analyzed. RESULTS: There was no difference between groups with regard to epidural solution requirements, pain scores, spread of sensory blockade, or intensity of motor block. CONCLUSION: Dural puncture with a 25-gauge Quincke needle, performed as part of CSEA, does not influence the drug requirements when a combination of 0.1% bupivacaine and fentanyl (3 microg/mL) is used for PCEA after major abdominal surgery.

[Evaluation of the activity of a postoperative analgesia department in a Canadian hospital]. / Bilan d'activité d'un service d'analgésie postopératoire dans un hôpital canadien.

OBJECTIVE: To describe the setting up and the activity of an acute pain service (APS). STUDY DESIGN: Retrospective descriptive study including two surveys among the nursing staff, the first one eight months after the setting up of the APS and the second one ten months later. RESULTS: In the first 19 months, 3,404 patients were treated in the APS: 1,456 with patient-controlled analgesia (PCA), 1,299 with epidural analgesia, 589 with spinal opioids and 60 with continuous nerve blocks. The resulting overall incidence of respiratory depression was 0.7%. It ranged from 0% with continuous nerve block to 1.2% with PCA. It was at 0.3% with epidural analgesia and 0.5% with spinal opioids. Both surveys confirmed that nurses had a positive attitude toward the APS, mainly because they believed it offered patients significant advantages. Many of them thought that epidural analgesia and PCA were likely to impede patient's ambulation and most of them agreed that these techniques increased their work load. CONCLUSION: Although the incidence of respiratory depression was low among the APS patients, it can probably still be decreased by a more refined patient selection. Setting up an APS is viewed positively by the nursing staff in spite of some perceived disadvantages.

Efficacy of preoxygenation with non-invasive low positive pressure ventilation in obese patients: crossover physiological study.

OBJECTIVE: The impact of non-invasive positive pressure ventilation (NIPPV), which is a combination of inspiratory positive airway pressure (IPAP) and positive end expiratory pressure (PEEP), on the effectiveness of preoxygenation in obese patients was evaluated. DESIGN: Randomized, controlled, double blinded, crossover study comparing NIPPV vs. tidal volume breathing (TVB) with regard to the expiratory O(2) fraction (FeO(2)). PATIENTS AND METHODS: Thirty participants with body mass index (BMI) greater or equal to 30 kg/m(2) scheduled for elective surgery were included. Patients with facial hair, and airway anomalies were excluded. Each patient underwent 3 minutes 100% O(2) preoxygenation with the two following methods in a random order: 1: TVB; 2: NIPPV (4 cmH(2)O IPAP+4 cmH(2)O PEEP). Primary outcome was FeO(2) after 3 minutes. Secondary outcomes were the number of patients reaching FeO(2) greater or equal to 90%, tidal volume, respiratory rate, and patient comfort on a 4-point scale. RESULTS: No differences between methods were found regarding the FeO(2) change with time or after 3 minutes (89 ± 6% with TBV vs. 91 ± 4% with NIPPV). FeO(2) greater or equal to 90% was reached more frequently with NIPPV (80%) than with TVB (60%) (P=0.008). Tidal volume (m ± SD) was larger throughout preoxygenation with TBV (837 ± 440 mL) than with NIPPV (744 ± 368 mL), (P=0.0005). Respiratory rate did not differ between regimens. Patient comfort was good and similar. CONCLUSION: This study suggests that providing a positive pressure of 4 cmH(2)O throughout inspiration and expiration during preoxygenation in obese patients provided benefits with regard to the FeO(2).

[Inspiratory support versus spontaneous breathing during preoxygenation in healthy subjects. A randomized, double blind, cross-over trial]. / Intérêt de la ventilation non invasive en pression positive au masque facial pour la préoxygénation chez le sujet sain : étude randomisée, en double insu, croisée.

OBJECTIVE: Applying an inspiratory support (AI) and a positive end expiratory pressure (PEP) could increase the effectiveness of the preoxygenation. STUDY DESIGN: This randomized double blinded controlled study compares the impact on the expiratory oxygen fraction (FEO(2)) of two levels of AI with PEP to a traditional preoxygenation. PATIENTS AND METHODS: Twenty healthy volunteers were studied. The criteria of exclusion were a body mass index >30, the presence of beard or moustache and the claustrophobia. Each subject went through three modes of preoxygenation during 3 minutes each in a random order: 1-spontaneous ventilation (VS), 2-preoxygenation with AI with 4 cmH(2)O/PEP 4 cmH(2)O (AI-4/PEP-4), 3-preoxygenation with AI with 6 cmH(2)O/PEP 4 cmH(2)O (AI-6/PEP-4). Subject's tolerance and leaks were also noted. RESULTS: The FEO(2) at the end of the 3 minutes of preoxygenation was higher (p<0,001) with AI-4/PEP-4 (94+/-3%) and AI-6/PEP-4 (94+/-4%) than with technique VS (89+/-6%). One hundred percent and 90% of the participants reached one FEO(2)=90% with AI-4/PEP-4 and AI-6/PEP-4 respectively vs 65% with VS (p=0.0013). The participants tolerated better the VS and the AI-4/PEP-4 than the AI-6/PEP-4. More leaks were noted with the AI-6/PEP-4 than with the VS and the AI-4/PEP-4. CONCLUSION: This study shows applying AI plus PEP during preoxygenation improves its effectiveness in the healthy subjects. It also suggests that, in a population of healthy volunteers, combination AI-4/PEP-4 is preferable to AI-6/PEP-4 because so effective, but better tolerated.

Thoracic versus lumbar administration of fentanyl using patient-controlled epidural after thoracotomy.

BACKGROUND AND OBJECTIVES: Epidural fentanyl injection can provide analgesia following thoracotomy, but where to insert the catheter is a matter of debate. The study compares the effects of thoracic and lumbar patient-controlled epidural fentanyl on analgesia, fentanyl requirements, and plasma levels after thoracotomy. METHODS: Thirty patients were randomized into two groups to receive either thoracic or lumbar patient-controlled epidural fentanyl for postoperative analgesia. Postoperative pain (10 cm, visual analog scale [VAS]) and fentanyl requirements were assessed every 4 hours for 24 hours and at 12-hour intervals for the next day. Fentanyl plasma levels were measured at 8 and 16 hours after surgery. Results were expressed as mean +/- 1 SD and analyzed using Student's t-test, ANOVA, and chi-square analysis at P < .05. RESULTS: Twenty-nine patients completed the study (14 in the lumbar and 15 in the thoracic group). The VAS scores and fentanyl requirements were not significantly different at any time interval in the thoracic group as compared to the lumbar group. VAS scores at 0 hours (4.6) and 4 hours (4.6) in the lumbar group were higher than VAS scores at 12 hours (2.8; P = .04), 16 hours (2.5; P = .02), and 20 hours (2.2; P = .01) in the same group. No significant difference was found between the fentanyl plasma levels of the two groups after 8 hours (lumbar, 0.26 +/- 0.37 ng/mL; thoracic, 0.22 +/- 0.20 ng/mL) or 16 hours (lumbar, 0.36 +/- 0.17 ng/mL; thoracic, 0.44 +/- 0.32 ng/mL). CONCLUSIONS: The authors concluded that there is little if any advantage of thoracic over lumbar patient-controlled epidural fentanyl administration in patients after thoracotomy with respect to analgesia, fentanyl requirements, and plasma levels.

Back pain following epidural anesthesia with 2-chloroprocaine (EDTA-free) or lidocaine.

BACKGROUND AND OBJECTIVES: Severe lumbar pain following epidural injection of 2-chloroprocaine is usually associated with the Nesacaine-MPF solution available in the United States. The purpose of this study was to determine if the solution distributed in Canada (Nesacaine-CE), which contains calcium disodium edetate (0.1 mg/mL) and sodium bisulfite (0.7 mg/mL) but no disodium ethylenediaminetetraacetic acid, is associated with back pain or spasm when compared with epidural lidocaine. METHODS: With use of a prospective, double-blind, randomized design, 30 patients scheduled to undergo outpatient knee arthroscopy under epidural anesthesia were divided into two groups to received 30 mL of either Nesacaine-CE 3% (group A) or lidocaine 1.33% (group B). Postoperative pain in the lumbar area was assessed twice by a 10-cm visual analog scale (VAS) before patients left the hospital and 24 hours later by phone. The lumbar area was palpated to search for muscle spasm before discharge from hospital. RESULTS: More patients receiving Nesacaine-CE than receiving lidocaine suffered from back pain in the recovery room (four vs none P = .03) and before leaving the hospital (nine vs one P = .001). Higher VAS scores (mean +/- SE) were obtained after Nesacaine CE then after lidocaine in the recovery room (0.5 +/- 0.24 vs 0.0 +/- 0.0, p = .049) and before leaving the hospital (1.8 +/- 0.5 vs 0.1 +/- 0.1, P = .001). No difference existed 24 hours later between the two groups with regard to the prevalence of back pain or VAS scores. No muscle spasm was detected. CONCLUSION: No cases of severe backache were observed. However, epidural Nesacaine-CE 3% was associated with mild back pain, generally confined to the area of needle insertion, when compared with lidocaine 1.33%.

[Locoregional neuraxial anesthesia and vascular surgery: the benefits]. / L'anesthésie loco-régionale neuraxiale et la chirurgie vasculaire: les bénéfices.

PURPOSE: To assess the advantages of neuraxial blockade (NB) during and after vascular surgery and to confront them with the risk of epidural or spinal hematoma. MAIN FINDINGS: NB may reduce the risk of thrombotic occlusion following lower extremity vascular reconstruction. This effect of NB may be attributed to reduced hypercoagulability, decreased peripheral resistance and increased graft flow. In patients under general anesthesia, only those authors using an aggressive perioperative management (pulmonary artery catheter monitoring, intensive care unit admission) were able to report grafts patency rates similar to those obtained with NB. NB facilitates the modulation of the hemodynamic and hormonal stress responses during the perioperative period. It also produces superior postoperative analgesia. Still, the impact of NB on cardiac morbidity following aortic reconstructive surgery remains open to debate. Only very few cases of epidural hematomas associated to NB following vascular surgery have been reported. They implicated patients who received either fibrinolytic medication, continuous heparin infusion, or both. Low molecular weight heparins may increase the risk or epidural hematoma and, should their administration become more frequent during vascular surgery, the safety of NB would then have to be reassessed. CONCLUSION: NB during vascular surgery is a safe and well-established practice. It offers many theoretical and demonstrated advantages. NB is particularly beneficial and economical for lower extremity vascular reconstruction. Still, NB may not be the best approach if the administration of fibrinolityc medication or prolonged heparin infusion is contemplated.

[The use of magnesium sulfate during surgery of pheochromocytoma: apropos of 2 cases]. / L'utilisation du sulfate de magnésium pendant la chirurgie du phéochromocytome: à propos de deux cas.

Maintenance of haemodynamic stability during anaesthesia for phaeochromocytoma resection is still a challenge. If magnesium sulfate is widely used for the control of arterial pressure during preeclampsia, its use during phaeochromocytoma resection has only been published by one author. We describe two cases where magnesium sulfate is the main agent used to control arterial pressure during resection of a phaeochromocytoma. Magnesium sulfate's hypotensive, antiarrhythmic and antiadrenergic properties are reviewed. The total doses administered were 11 g and 12 g, given as an infusion and boluses. Magnesium sulfate could be part of the anaesthetist's pharmacopoeia during phaeochromocytoma resection.

Ulnar nerve palsy at the elbow after general anaesthesia.

Ulnar nerve palsy is a recognized complication of general anaesthesia. Many authors have reported several series of patients and found different incidences. In this literature review, the patho-physiology of the lesion and the anatomical characteristics of the cubital tunnel at the elbow are described together with its related conditions "cubital tunnel compression syndrome" and "recurrent ulnar nerve dislocation at the elbow." A precise and early diagnosis should be made using electromyography to determine the exact location of the lesion and the precise time-relationship of the pathology. The importance of careful positioning of the patient under anaesthesia in the prevention of ulnar nerve palsy is stressed. Unfortunately, treatment of the established lesion gives, at best, mixed results.

Anatomy of the posterior approach to the lumbar plexus block.

The purpose of this study was to describe the relation of the lumbar plexus with the psoas major and with the superficial and deep landmarks close to it. Four cadavers were dissected and 22 computed tomography files of the lumbosacral region studied. Cadaver dissections demonstrated that the lumbar plexus, at the level of L5, is within the substance of the psoas major muscle rather than between this muscle and the quadratus lumborum. The femoral nerve lies between the lateral femoral cutaneous and obturator nerves. However, while the lateral femoral cutaneous nerve is in the same fascial plane as the femoral nerve, the obturator nerve can be found in the same plane as the two other nerves or in its own muscular fold. Radiological data provided the following measurements: the femoral nerve is at a depth of 9.01 +/- 2.43 cm; the psoas major medial border is at 2.73 +/- 0.64 cm from the median sagittal plane; and its lateral border is at 6.41 +/- 1.61 cm from the same plane. It is concluded that the lumbar plexus is within the psoas major, that the obturator nerve localization within the psoas major varies and that computed tomography data define precisely the relationship of the lumbar plexus with superficial and deep landmarks.

Posterior approach to the lumbar plexus combined with a sciatic nerve block using lidocaine.

A combination of lumbar plexus block, by a posterior technique, and sciatic nerve block can be a useful technique for outpatient anaesthesia. The purpose of this study was to examine the clinical characteristics of these blocks using lidocaine and to measure the serum lidocaine concentrations. Forty-five patients, undergoing lower extremity surgery, were studied. Sciatic nerve and lumbar plexus blocks were made with lidocaine, 680 mg with adrenaline 0.3 mg. For each patient the following data were collected: weight, age, sex, site of surgery, time to perform each block, needle depth, speed of onset of the sensory and motor blocks in the territories of the sciatic, femoral, obturator and lateral cutaneous (sensory) nerves and postoperative analgesic requirements. Lidocaine serum concentrations were measured in ten of these patients at 0, 2, 5, 10, 30, 60, 90 and 120 min after the second block. Analgesia was complete in 88% (40/45) of the patients. The remaining five patients needed analgesics (fentanyl 150 micrograms or less). Despite the high dose of lidocaine, the serum concentrations were within safe limits (mean +/- SD) (CMAX = 3.66 +/- 2.21 micrograms.ml-1). Only one patient had a serum concentration > 5 micrograms.ml-1 (CMAX = 9.54 micrograms.ml-1). This was associated with a contra-lateral extension of the block. We conclude that this combination of blocks is a valuable alternative for unilateral lower extremity anaesthesia. However, clinicians must be aware of the implications of a contra-lateral extension of the block.

Direction of injection does not affect the spread of spinal bupivacaine in parturients.

PURPOSE: One of the factors that can affect the distribution of local anaesthetic solutions in the subarachnoid space is the direction of the spinal needle through which injections are made. This study investigated the effect of the direction of the aperture of the Whitacre needle on the spread of hyperbaric bupivacaine in parturients undergoing elective caesarean section. METHODS: Forty healthy term parturients scheduled for caesarean delivery under spinal anaesthesia with 12 mg hyperbaric bupivacaine + 0.2 mg morphine were randomly assigned to one of two groups: needle orifice cephalad (I) or caudad (II). Spinal blocks were administered in the sitting position with patients being positioned supine immediately after. A blinded observer assessed the dermatome level of analgesia to ice every minute for the first 10 minutes, every three minutes for the following 35 min, then every 15 min until the sensory level regressed to T10. RESULTS: There was no difference between the groups regarding the maximal number of segments blocked cephalad to T11 (11.4 +/- 3.4: group I and 12.0 +/- 3.4: group II), time to highest cephalad spread of sensory block (22 +/- 10: group I and 19 +/- 10 min: group II), or time to regression to T10 (164 +/- 26: group I and 153 +/- 24 min: group II). The maximum decrease in blood pressure (33.9 +/- 9.6: group I and 36.8 +/- 11.8 mmHg: group II) and dosage of ephedrine administered (14.7 +/- 10.7: group I and 16.2 +/- 11.0 mg: group II) did not differ. CONCLUSION: The direction of the aperture of the Whitacre needle does not influence the spread of hyperbaric bupivacaine in the term parturient.

Comparison of rocuronium and d-tubocurarine for prevention of succinylcholine-induced fasciculations and myalgia.

PURPOSE: We compared d-tubocurarine and rocuronium for the prevention of succinylcholine-induced fasciculations and postoperative myalgia (POM) and evaluated the influence of both drugs on the speed of onset and recovery of succinylcholine. METHODS: Seventy-five women undergoing surgery of short duration were studied. They were randomized to one of three groups: group SAL received normal saline followed three minutes later by 1.0 mg.kg-1 succinylcholine; group ROC received 0.05 mg.kg-1 rocuronium + 1.5 mg.kg-1 succinylcholine; group DTC received 0.05 mg.kg-1 d-tubocurarine + 1.5 mg.kg-1 succinylcholine. Single-twitch stimulation was applied to the ulnar nerve every 10 sec and the EMG response of the adductor pollicis was recorded. Fasciculations were assessed by a blinded observer on a scale of 0-3. Patients were asked 24 and 48 hr later to rate POM using a scale of 0-10. RESULTS: The interval needed for twitch height to decrease to 10% of initial value after succinylcholine was longer in group ROC (58 +/- 20 sec) (mean +/- SD) compared with group SAL (44 +/- 13 sec) (P < 0.05). Recovery to 20% occurred faster in group ROC (324 +/- 83 sec) than in groups SAL (456 +/- 103 sec) and DTC (450 +/-132 sec) (P < 0.05). Fasciculations were more intense in groups SAL than in groups ROC and DTC (P < 0.001). Patients rated POM as less intense 24hr postoperatively only in group ROC (1.2 +/- 2.4) compared with group SAL (3.3 +/- 3.5) (P < 0.05). CONCLUSION: Rocuronium prevents succinylcholine-induced fasciculations and POM. Rocuronium also delays the onset of succinylcholine and shortens its duration compared with d-tubocurarine.

In vitro response to oxytocin and interferon-Tau in bovine endometrial cells from caruncular and inter-caruncular areas.

Caruncules are differentiated sites of the endometrium in which placentation occurs in ruminants. We investigated whether the response to agents involved at the time of recognition of pregnancy differed in the caruncular (CAR) and inter-caruncular (ICAR) areas of the endometrium in vitro. The specialization in prostaglandin (PG) production previously described in cells from whole endometrium was reproduced in the CAR and ICAR areas: PGF2alpha and PGE2 were produced in greater proportions, respectively, in epithelial and stromal cells. The relative production of PGE2 was equivalent in epithelial cells from CAR and ICAR regions, but the production of PGF2alpha was higher (p < 0.05) in the ICAR region (2.2 +/- 0.5 vs. 4.0 +/- 0.2 ng/ microg DNA, respectively). In stromal cells, the ICAR area produced more PGE2 than did the CAR area (3.4 +/- 0.4 vs. 2.1 +/- 0.4 ng/ microg DNA, p < 0.05), and the respective PGE2:PGF2alpha ratio was significantly higher in the ICAR area (p < 0.05). The production of PGs was measured first in response to oxytocin (OT, 10(-9) to 10(-5) M) and then to recombinant ovine interferon-tau (roIFN-tau, 0.02 to 20 microg/ml) in a separate set of experiments. In epithelial cells, OT stimulated the production of PGF2alpha 6.3-fold in the CAR area and more than 33.0-fold in the ICAR area (7.1 +/- 3.2 vs. 36.3 +/- 9.8 ng/ microg DNA, respectively, p < 0.05). Production of PGE2 was also increased in both regions and reached a plateau at 4.1 +/- 0.4 ng/ microg DNA. In epithelial cells from the ICAR but not the CAR region, the PGE2:PGF2alpha ratio was decreased in the presence of OT (p < 0.05). In separate experiments, addition of roIFN-tau stimulated PGE2 production significantly (p < 0.05), and no difference (p > 0.8) was observed between CAR and ICAR regions. An increase in PGE2:PGF2alpha ratio was observed in epithelial cells from both CAR and ICAR regions, but it was significant only in the CAR region (p < 0.05). In stromal cells, roIFN-tau stimulated PGE2 production significantly in cells from the CAR and ICAR regions (35.6 +/- 2.9 vs. 24.1 +/- 3.8 ng/ microg DNA, respectively, p < 0.05). In summary, the ICAR region seems to be the privileged site for regulation of PGF2alpha production by OT, but the caruncules may be a preferred site for recognition of the embryonic IFN-tau signal. Endometrial cells from the CAR and ICAR areas appear to exhibit specialized responses, with cells from the ICAR region more responsive to OT and those from the CAR region more sensitive to roIFN-tau.

Dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block during N2O-enflurane-alfentanil anaesthesia.

The purpose of this study was to determine the dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block. Seventy-five ASA I or II adults were given mivarcurium 0.15 mg x kg(-1) followed by an infusion (7 micrograms x kg(-1) x min(-1) during alfentanil-propofol-N2O-enflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 20 sec and the response of the adductor policis was recorded (Relaxograph NMT-100, Datex, Helsinki, Finland). Mivacurium infusion was modified at five-minute intervals in order to keep the height of the first twitch in TOF(T1) at 5% of its control value. At the end of surgery, edrophonium (0.0, 0.125, 0.25, 0.5, or 1.0 mg x kg(-1) combined glycopyrrolate (0.0, 0.0012, 0.0025, 0.005, or 0.01 mg x kg(-1) were administered by random allocation. Edrophonium doses of 0.25, 0.5 and 1.0 mg x kg(-1) were different from placebo with regard to time to attain a TOF ratio (fourth twitch in TOF/T1) = 0.7 (13.8 +/- 4.5, 11.1 +/- 3.5, 11.4 +/- 3.0 vs 19.7 +/- 4.7 min P< 0.05). Doses of 0.5 and 1.0 mg x kg(-1) permitted faster recovery time of T1 from 10 to 95% (T10-95) than did placebo (7.5 +/- 3.8, 8.9 +/- 3.5 vs 14.5 +/- 5.0 min P<0.05). Edrophonium 0.5 mg x kg(-1) was different from placebo with regard to recovery time of T1 from 25 to 75% (T25-75) (3.3 +/- 2.0 vs 6.7 +/- 2.0 min P<0.05). Only edrophonium 0.5 mg x kg(-1) provided faster recovery than placebo with regard to all three indices. It is concluded that edrophonium 0.5 + glycopyrrolate 0.005 mg x kg(-1) allow the fastest recovery from a mivacurium-induced block during enflurane-N2O anaesthesia.