Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean section.

UNLABELLED: Seventy-eight pregnant women at term, scheduled for elective cesarean section, were enrolled in this multicenter trial to compare the analgesic efficacy and side effect profile of a spinal block with hyperbaric bupivacaine alone (Group B) or combined with 75 microg of clonidine (Group BC) or with clonidine 75 microg and fentanyl 12.5 microg (Group BCF). Intraoperatively, clonidine increased the spread of the sensory block and decreased pain (pain scores 23+/-7 mm vs 17+/-6 and 2+/-1 mm for Group B versus Groups BC and BCF; P < 0.05) and analgesic supplementation. This improved analgesia was best with the clonidine-fentanyl combination (Group BC versus Group BCF; P < 0.05). Postoperative analgesia was prolonged only in Group BCF (215+/-79 min vs 137+/-35 and 183+/-80 min for Group BCF versus Groups B and BC; P < 0.05). Blood pressure and heart rate changes were not significantly different among groups, whereas sedation and pruritus were significantly more frequent in Group BCF. Nausea and vomiting were decreased in Groups BC and BCF. Apgar scores and umbilical artery blood pH were not different among groups. We conclude that adding a small dose of intrathecal clonidine to bupivacaine increases the quality of intraoperative analgesia and decreases pain during cesarean section. Combining clonidine with fentanyl further improved analgesia. IMPLICATIONS: In this study, we demonstrate improved intraoperative spinal analgesia by adding 75 microg of clonidine to bupivacaine; side effects were not increased. The combination of clonidine and fentanyl further improved analgesia but moderately increased sedation and pruritus.

Continuous extradural infusion of ropivacaine 2 mg ml-1 for pain relief during labour.

We have assessed the dose-response relationship of a solution of ropivacaine 2 mg ml-1, given as a continuous extradural infusion to women in labour. A total of 133 parturients were allocated randomly to one of four groups to receive a fixed rate ropivacaine infusion of 4, 6, 8 or 10 ml h-1 with additional bolus doses as necessary. Contraction pain, quality of analgesia, sensory block, motor block and neonatal Apgar scores were assessed. There were no significant differences between groups in terms of analgesia or motor block, although significantly more bolus doses were required by the group receiving 4 ml h-1 (P < 0.05 compared with the other groups), and a significantly higher total dose of ropivacaine was administered to the 10-ml h-1 group compared with the 6-ml h-1 group (P = 0.044). There were no significant differences between groups in terms of obstetric or neonatal outcome. We conclude that ropivacaine 2 mg ml-1 was effective and well tolerated when given as a continuous extradural infusion at 6-8 ml h-1 and may be used as the sole analgesic during labour.

[Morphine in cesarean section and postoperative analgesia]. / Les morphiniques dans les césariennes et en analgésie postopératoire.

Epidural opioids for caesarean section are routinely used by many anaesthesists. Combined epidural injection of a local anaesthetic and an opioid provides a more rapid onset of profound analgesia. No side effects are observed in either the mother or the neonate with epidural "microdoses" of sufentanil or fentanyl, but the postoperative analgesia is of short duration. Combined intrathecal injection on 0.1-0.2 mg morphine and 0.5% hyperbaric bupivacaine provides a better intra- and postoperative analgesia. Opiates used during anaesthesia in toxemic women before delivery imply strict subsequent paediatric care. Good postoperative analgesia can be obtained with intrathecal morphine or patient-controlled analgesia. Using other techniques depends on care and surveillance facilities. Opiates by spinal or intravenous route are not dangerous for breast-fed newborns.

Inhibitor effects of diltiazem, nicardipine, nifedipine and verapamil on the norepinephrine-induced contractions of the canine saphenous vein in calcium-free medium.

Contractile responses to norepinephrine (noradrenaline, NE 10(-5) M) in the canine saphenous vein (SV) are significantly, although slightly, reduced (14%) when induced in a physiological medium depleted of calcium for 1 hour (+ EGTA). In contrast, they are inhibited by about 75% after 24 hr in calcium free physiological saline solution (P.S.S.). ED50 of norepinephrine in 1-hr calcium-free medium and in normal Ca++ P.S.S. are 6 x 10(-7)M and 4.2 x 10(-7)M, respectively. Two blockers of extracellular calcium entry have also been cited as inhibitors of intracellular calcium pool refilling. At concentrations of 10(-6)M, 10(-5)M and 10(-4)M, diltiazem and nicardipine inhibit the norepinephrine-induced contractions (NIC) in a concentration-dependent manner. At 10(-4)M, the two calcium blockers inhibit the NIC by 70% and by 72% respectively in Ca++ free (+ EGTA) P.S.S. Nifedipine and verapamil only begin to significantly inhibit NIC in Ca++ free (+ EGTA) P.S.S. at concentrations equal to or greater than 10(-5)M. At 10(-4)M concentration, control inhibition in Ca++ free P.S.S. was observed as 60% and 49%, respectively. Contrary to the other 3 calcium antagonists tested, diltiazem antagonises NIC significantly less in calcium-containing medium (45%) than in calcium-free medium (72%). Procaine at a concentration of 10(-3)M, described as sufficient to totally inhibit calcium release from its intracellular storage sites, only inhibits NIC by 52% in calcium free (+ EGTA) P.S.S. These results are consistent with the following conclusion: i) in the canine saphenous vein (SV), NIC is mainly mediated by calcium mobilization from its intracellular storage sites; ii) the calcium antagonists tested here and procaine are unable to totally inhibit, even at high concentrations, the contractions induced via intracellular calcium release; this characteristic is nonsignificant for nifedipine and verapamil at low concentrations (10(-6)M). iii) verapamil and nifedipine, like diltiazem and nicardipine at high concentrations, may not only possess the characteristics of extracellular calcium entry blockers, but also that of partial antagonist of NIC via non specific mechanisms; iv) diltiazem may relax the vascular smooth muscle of SV, not only by the above two properties, but also through another mechanism yet unknown; v) partial persistence of NIC on the SV under conditions of short or long extracellular calcium depletion may be due to a mechanism of intracellular Ca++ recycling, the smooth muscle cell partially retaining its intracellular Ca++.

[Acquired experience in anesthesia and perioperative intensive care in percutaneous nephrolithotomy. Current approach in the endoscopic treatment of lithiasis and pyelo-ureteral junction anomalies]. / Expérience acquise en anesthésie et réanimation péri-opératoire dans la néphrolithotomie percutanée. Attitude actuelle dans le traitement endoscopique de la lithiase et de l'anomalie de la jonction pyélo-urétérale.

Percutaneous endoscopic treatment of the kidney retains a place in the treatment of renal stones (percutaneous nephrolithotomy--PCNL) and ureteropelvic junction abnormalities (endopyeloplasty). It requires anaesthesia ensuring surgical comfort and safety for the patients despite changes in position and the prolonged ventral supine position. The operation carries certain iatrogenic risks related to caliceal irrigation in patients with more or less documented episodes of infection and carries risks of haemorrhage and effraction of adjacent organs. 282 patients treated by PCNL between 1984 and 1991 were reviewed in order to define the respective indications for general anaesthesia and peridural anaesthesia and to determine the modalities, to evaluate the risk and severity of absorption of irrigation fluid and to assess the risk of infection by defining the indications for prophylactic antibiotics. General anaesthesia, using etomidate and propofol via an infusion pump, ensures surgical comfort, anaesthetic safety and better control of intraoperative complications. The renewed interest in this technique must be counterbalanced by the growing incidence of anaphylactic reactions related to anaesthetic drugs. Operations lasting more than 2 hours, raised intracaliceal pressure, the initially exclusive use of glycine for irrigation induce haemodilution complications, possibly aggravated by glycine intoxication. Repeated surgery is preferable with the use of an Amplatz tube as often as possible and physiological saline, except when required by the operation. Patients with a history of urinary tract infection or infected stones should receive prolonged and effective antibiotics before, during and after the operation. Prophylactic antibiotics are reserved for those patients with no history of infection. These principles equally apply to percutaneous nephrolithotomy and endopyeloplasty.

Newly evidenced pyrimidinoceptors and the P2x purinoceptors are present on the vascular smooth muscle and respectively mediate the UTP- and ATP-induced contractions of the dog maxillary internal vein.

P2 purinergic receptors and pyrimidinoceptors were studied by comparing the contractile responses to UTP with those to ATP, in the dog internal maxillary vein (IMV) after endothelium removal. The contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. alpha beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 (RB2) was incapable of antagonizing contractions to ATP and UTP in this vessel. We showed that Nicardipine, a calcium antagonist, was more potent on the UTP-induced than on the ATP-induced contractions. The fact that RB2 did not potentialize the UTP-induced contractions, unlike what has been observed in the dog saphenous vein, suggests that a new category of pyrimidinoceptors have been evidenced on the IMV. Our results also indicate that ATP induces contraction via P2x rather than P2y purinoceptors. The receptors described here are localized on the vascular smooth muscle.

[Radical prostatectomy and biologic glue]. / Prostatectomie radicale et colle biologique.

Fibrin glue (reconstituted fibrin glue-Tissu-col-Immuno-France) was used in 24 patients following radical prostatectomy with ilio-obturator lymphadenectomy (Group II) to improve haemostasis of the operative field, to decrease or eliminate lymphatic oozing and to promote healing of the urethrovesical anastomosis. The results in terms of duration of drainage, quantity of fluid evacuated by these drains, operative complications and length of hospital stay were compared to those obtained in 24 clinically identical patients operated previously without the use of fibrin glue (Group I). Although fibrin glue is easy to use, ensures a particularly dry operative field at the end of the operation and does not induce any infectious complications (abscess, hepatitis), it increases the cost of the operation (5 ml vial = 2,500 FF) and the use of this product does not reduce the drainage time (Group I: 7 +/- 4.6 days; Group II: 8.5 +/- 5.4 days) the volume of blood or lymphatic discharge (Group I: 500 +/- 570 ml; Group II: 660 +/- 825 ml) or the length of hospital stay (Group I: 16.5 +/- 4.8 days; Group II: 17.4 +/- 5.5 days). These results argue against the routine use of fibrin glue in radical prostatectomy.

Cardiac beta-adrenoceptor sensitivity and Parkinson's disease.

Certain clinical manifestations of Parkinson's disease (PD) (speech or/and balance disturbances) are not linked to brain dopamine deficiency. The purpose of the present study was to search for a possible relationship between those so-called "non-dopamine-dependent" extrapyramidal manifestations and the sensitivity of cardiac beta-adrenoceptors. Fourteen patients aged 51 to 69 were included in the study after having given their informed consent. Any factor or pathology susceptible to modify receptor sensitivity entailed exclusion. In the absence of a reference model for measuring the reactivity of central beta-adrenoceptors, a computation of the isoprenalin dose necessary to increase the resting heart rate by 20 bpm was used as an index for beta-adrenergic system reactivity. In addition to that test, other parameters were recorded: disease duration, motor status scale (Columbia), some cognitive functions (MMS and image differed recall). The cardiac beta-receptor decrease in reactivity to isoproterenol is correlated to PD duration (r = 0.8, P less than 0.001). Conversely, the sensitivity of these receptors appeared to be unrelated to the extrapyramidal severity of the disease, hence to the degree of the so-called "non dopamine-dependent" disturbances. Furthermore, such results raise the meaning of the impairment of peripheral aminergic receptors in the cognitive disturbances linked to ageing and/or PD.

Constriction of the smooth muscle of rat tail and femoral arteries and dog saphenous vein is induced by uridine triphosphate via 'pyrimidinoceptors', and by adenosine triphosphate via P2x purinoceptors.

Adenosine triphosphate (ATP) and uridine triphosphate (UTP) receptors were studied by comparing the contractile responses to UTP with those to ATP in the rat tail and femoral arteries and dog saphenous vein, after endothelium removal confirmed by histology, and near abolition of relaxation to acetylcholine. Contractions induced by ATP and UTP were dose dependent, as assessed from preparations at resting tension. Contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. In the rat tail artery and the dog saphenous vein, quinidine, nordihydroguaiaretic acid (NDGA) and phentolamine inhibited the contractions induced by ATP, whereas those induced by UTP were only slightly reduced in the presence of NDGA and were not antagonized by quinidine and phentolamine. In all three vessels, alpha-beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 was incapable of antagonizing contractions to ATP and UTP in these preparations. In addition, UTP-induced contractions were hardly inhibited in a calcium-free Krebs solution, whereas ATP was totally inhibited. We showed that a calcium antagonist, nicardipine, was more potent on the UTP-induced than on the ATP-induced contractions. These results showed the UTP-induced contraction to be mediated by a new class of receptors, qualified here as 'pyrimidinoceptors', for which no antagonist is known. These results were obtained in the tail and femoral arteries of the rat and from the dog saphenous vein. ATP induced contraction in these three vessels via P2x purinoceptors. P2x purinoceptors and 'pyrimidinoceptors' are localized on the vascular smooth muscle.

Randomized double-blind trial of injectable heptaminol for controlling spontaneous or bromocriptine-induced orthostatic hypotension in parkinsonians.

Heptaminol is a molecule with experimental cardiovascular analeptic properties. In this double-blind vs placebo trial, the potency, so far unproven, of the injectable form of a 626 mg dose of heptaminol chlorhydrate on spontaneous or induced orthostatic hypotension (OH), was assessed. Nineteen patients were included in the study: 7 displayed spontaneous OH, and in the other 12 OH was induced by bromocriptine, as monitored 103 min/after an oral intake of 6.6 mg on average. Neither spontaneous nor induced OH were recorded in 32% of the Parkinsonian population registered, with no obvious distinctive characteristics. Potency tilt-trials, performed 15, 30 and 45 min after parenteral administration of heptaminol, revealed a significant and expressive potency of the molecule on the systolic blood pressure after 15 min (P less than 0.05). Clinical and biological tolerance was excellent. Low plasma renin activity and the absence of response to orthostatism indicated, in this population of Parkinsonian extrapyramidal syndromes, a loss in positive tonus likely to be of sympathetic origin. The anti-hypotensive action of heptaminol does not seem to be related to any renal or even sympathetic interaction.

[Pharmacokinetics and antibiotic therapy of the child]. / Pharmacocinétique et antibiothérapie chez l'enfant.

Pharmacokinetics is too often unknown while ordering antibiotics, particularly to children. The aim of that paper is to recall the pharmacokinetic characteristics of the most ordered families in pediatric dentistry: penicillin A and macrolides, as well as the modifications peculiar to children, due to pathology, or subsequent to drug interactions.

Randomized, double-blind trial of exifone versus cognitive problems in Parkinson's disease.

Exifone is a novel substance of the benzophenone group that possesses potent scavenging properties. Initial findings demonstrate beneficial effects on age-related cognitive disorders. In this double-blind clinical trial versus placebo, the efficacy of 2 dosages (600 and 1200 mg/d) was evaluated with regard to Parkinson's disease (PD)-related cognitive disorders, for which there is increasing suspicion of a free-radicals origin. Despite disparities between the treatment groups as assessed by validated scales and subtests, and a considerable placebo effect on main parameters, both dose levels of exifone produced statistically significant improvement of the cognitive items most commonly impaired by PD: immediate recall, naming of objects presented, spatiotemporal orientation, and calculation. These properties suggest a new slot for exifone in the range of therapeutics available.

Erythromycin lactobionate: pharmacokinetics and uterine tissue levels.

Erythromycin is well-known for its properties of tissular diffusion. An estimation of its concentration in uterine tissue seemed worthwhile, in order to justify the use of erythromycin lactobionate in uterine infections by sensitive micro-organisms. The authors studied the uterine levels of this macrolid, after perfusion of 1g of erythromycin lactobionate, over a period of one hour. The protocol involved a group of 15 women, who were to undergo a hysterectomy for benign non-inflammatory pathology. The uterine specimens and plasmatic pharmacokinetics of the antibiotic constitute the data. The concentrations of antibiotic were determined by microbiological methods. 2 sets of results emerge: during perfusion, the uterine erythromycin levels are equal or inferior to simultaneous serum levels. after perfusion, the uterine levels are superior to serum levels. A bicompartmental linear model was used, which simulated the tissular levels in standard treatment with erythromycin lactobionate. If the erythromycin 4 micrograms/ml critical concentration is compared with uterine tissue concentration, the antibiotic may be expected to be active against a uterine affected by sensitive micro-organisms during a period of approximately 5 hours. This result must be confirmed by a clinical study.

[Cerebral edema: intra-cellular or extra-cellular mechanisms?]. / L'oedème cérébral: mécanisme intra-cellulaire ou extra-cellulaire?

Many cerebral pathological processes are attended by edema defined as an increase in brain volume associated with an increase in brain water and sodium contents. The aggravation of lesions induced by this edema warrants a pharmacological and therapeutic approach based on a detailed knowledge of its physiopathological mechanisms. Experimental models and in vitro studies have shown that the fundamental mechanisms leading to edema are: cold, acute hypoxia, ischaemia, arachidonic acid, toxic substances and plasma hypo-osmolarity. To the various types of edema described (vasogenic, cytotoxic, hydrocephalic) correspond different mechanisms. Vasogenic edema essentially depends on osmotic and hydrodynamic factors; cytotoxic edema results from perturbations in energy-dependent cellular osmoregulation. The underlying biochemical disorders have now been demonstrated, mostly in ischaemic edema; they include, during the revascularization phase, disruption of the blood-brain barrier (vasogenic component) and changes in ion concentrations, neurotransmitters and energetic mechanisms. Key factors in the development of edema are cyclic AMP, serotonin and Na-K-ATPase.

[Heterogeneity of purinergic P2 receptors at the level of the caudal artery of the rat and the saphenous vein of the dog]. / Hétérogénéité des récepteurs purinergiques P2 au niveau de l'artère caudale du rat et de la veine saphène du chien.

Phentolamine (10(-5) M) and an inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (N. D. G. A.; 8 10(-6) M) antagonized the ATP induced contraction but not antagonized the UTP induced contraction on both rat tail artery and dog saphenous vein. We conclude that the receptors to ATP are distinct from receptors to UTP and that the P2 purinoceptors are an heterogeneous group.

[Pharmacology of the venous system]. / Pharmacologie du système veineux.

The presence of alpha 1-receptors has been demonstrated in numerous venous fragments for various animal models. On the other hand, the presence of alpha 2-receptors in the saphenous of the dog is a matter of debate. Beta 2-receptors are activated by isoproterenol, noradrenaline and adrenaline in precontracted veins (part of the facial vein of the rabbit may be an exception). Preferential blocking by atenolol of beta 1-receptors in the jugular veins of the rat suggests that these receptors may mediate vasodilation. The saphenous veins of the dog provide the only example where specific dopaminergic receptors have been noted following partial antagonism with haloperidol. The vasoconstrictive action of acetylcholine has been seen in venous segments of numerous species and indicates the presence of muscarinic receptors. The existence of angiotensin receptors can be postulated despite the weak and inconstant in vitro and in vivo (the dorsal cerebral sinus in the dog excepted) reactions observed and the use of a non-specific antagonist. The same is true for bradykinin and vasopressin. The marked vasoconstrictive action of serotonin on all veins studied is evidence for the presence of receptors. The nature of the antagonists is subject to some divergence of opinion. Nevertheless, D tryptamine muscular receptors (or 5 HT2) can be identified due to the lack of morphine-mediated response and the efficacy of methysergide. The presence of a third type of serotoninergic receptor has only been reported once, following observations of vasodilation in the sheep. H1 receptors are involved in histamine-mediated vasoconstriction. The presence of H2 receptors which mediate vasodilation in precontracted veins remains hypothetical. Prostaglandins exhibit different efficacies in producing contraction in isolated veins; PGF2 alpha is more efficacious than PGE1 and PGE2. Prostacyclin induces contraction of human saphenous veins in a dose-dependent manner. PGE2 and particularly PGE1 can induce relaxation in precontracted veins, as is also true for prostacyclin. Receptors for these prostaglandins must exist at the post-junctional level. P2-receptors mediate transmission of the vasoconstrictive action of various purine derivatives.