Xavier Mazoit

Efficacy of an Epidural Test Dose in Children Anesthetized with Halothane

The effect of an intravenous (iv) injection of lidocaine with epinephrine was studied to determine if such a test dose would cause a reliably detectable increase in heart rate and systemic blood pressure in children anesthetized with halothane and nitrous oxide. The effect of the injection of atropine before the test dose on these parameters was also determined. Sixty-five children 1 month to 11 yr of age and weighing 3.9-35 kg were studied. The children were assigned to one of four groups, each of which was anesthetized with 1% halothane and 50% nitrous oxide. Group 1 (n = 20) received 10 micrograms/kg atropine followed 5 min later by an iv dose of 0.1 ml/kg 1% lidocaine with 1/200,000 epinephrine (0.5 micrograms/kg) to simulate an intravascularly administered epidural test dose. Group 2 (n = 21) was identical to group 1 but did not receive atropine prior to the simulated intravascular test dose. Groups 3 (n = 12) and 4 (n = 11) were identical to groups 1 and 2, but the simulated intravascular test dose did not contain epinephrine: group 3 received atropine prior to the test dose and group 4 did not. The simulated intravascular test dose increased heart rate in group 1 (with atropine) at each time period from 15 to 120 s, but only at 45 and 60 s in group 2 (without atropine). Following the iv test dose, 6 of 21 children in group 2 had an increase in heart rate of less than 10 beats/min, while only one child in group 1 had an increase in heart rate of less than 10 beats/min. Intravenous test doses that did not contain epinephrine (groups 3 and 4) had no effect on heart rate or blood pressure. Atropine, 10 micrograms/kg, improves the reliability of an epidural test dose in children anesthetized with halothane and nitrous oxide but does not ensure total reliability in detecting an intravascular injection.

Relationship between clinical history, coagulation tests, and perioperative bleeding during tonsillectomies in pediatrics.

STUDY OBJECTIVE To determine the value of clinical history and preoperative coagulation tests. DESIGN Prospective, multicenter clinical investigation. SETTING Twenty-four centers over a one-year period. PATIENTS 1,706 children scheduled for tonsillectomy. In 1, 479 out of 1,706 children, studied age was ranged from 9 months to 15 years. Indications for surgery were tonsillar infection 54%, sleep apnea 33%, or both 13%. Surgical dissection was performed in 1, 284 cases (88%) and sluder technique in 172 cases (12%). MEASUREMENTS AND MAIN RESULTS Clinical history of bleeding, preoperative coagulation tests, and perioperative bleeding were recorded. Clinical history of bleeding was positive in 13 patients; clinical history cannot predict abnormal coagulation tests. Coagulation tests were abnormal in 57 children (4%). Only 8 patients had disease-induced bleeding; five children had a preoperative correction of the deficiency in factor of coagulation or received desmopressin acetate prior to surgery in the case of von Willebrands disease. Bleeding that occurred during the intraoperative period was assessed as abnormal by the surgeon in 101 children (7%) and during the postoperative period in 50 children (3%). Univariate analysis showed a relationship between intraoperative bleeding and age (p < 0.001), sluder technique (p < 0. 001), and abnormal preoperative coagulation tests (p < 0.05). Multivariate analysis showed the probability that bleeding was linked to the center where the surgery took place, the technique used, i.e., sluder technique, and the childs age, i.e., the older children. CONCLUSIONS Preoperative assessment based on the history of bleeding cannot predict abnormal laboratory tests. Neither the history of bleeding or laboratory tests can predict postoperative bleeding.

Effects of Age on Plasma Protein Binding of Sufentanil

The plasma protein binding of sufentanil has been studied in newborns, infants (0.5 +/- 0.3 yr), children (6.8 +/- 3.0 yr), and adults (39.5 +/- 9.0 yr). Binding of sufentanil was determined in vitro by equilibrium dialysis, and radioactive tritiated sufentanil was used for the determination of drug concentrations in plasma and buffer. The free fraction of sufentanil was significantly higher in the newborn (19.5 +/- 2.7%; P less than 0.01) than in the other age groups. The free fraction was also significantly higher in infants (11.5 +/- 3.2%; P less than 0.01) than in children (8.1 +/- 1.4%) or in adults (7.8 +/- 1.5%) but did not differ significantly between children and adults. The free fraction of sufentanil was strongly correlated with the alpha 1-acid glycoprotein plasma concentration (r = -0.73; P less than 0.001) whereas it was weakly correlated with albumin plasma concentration (r = -0.35; P less than 0.05). These data suggest that the lower concentration of alpha 1-acid glycoprotein in newborns and infants probably accounts for the decrease in protein binding of sufentanil in these age groups when compared with that in older children or adults. The increased free fraction in the neonate might contribute to the enhanced effects of lipophilic opioids in the neonate.

Preemptive Intravenous Morphine-6-glucuronide Is Ineffective for Postoperative Pain Relief

Background Morphine-6-glucuronide (M-6-G), a major metabolite of morphine, is reported to be more potent than morphine when administered intrathecally; however, its efficiency remains under debate when administered intravenously. This study was designed to assess the analgesic efficiency of intravenous M-6-G for the treatment of acute postoperative pain. Methods After informed consent was obtained, 37 adults (American Society of Anesthesiologists physical status I–II) who were scheduled for elective open knee surgery were enrolled in the study. General anesthesia was induced with thiopental, alfentanil, and vecuronium and was maintained with a mixture of nitrous oxide/isoflurane and bolus doses of alfentanil. At skin closure, patients were randomized into three groups: (1) morphine group (n = 13), which received morphine 0.15 mg/kg; (2) M-6-G group (n = 12), which received M-6-G 0.1 mg/kg; and (3) placebo group (n = 12), which received saline. At the time of extubation, plasma concentration of morphine and M-6-G was measured. Postoperative analgesic efficiency was assessed by the cumulative dose of morphine delivered by patient-controlled analgesia. Opioid-related side effects were also evaluated. Results No difference was noted in patient characteristics and opioid-related side effects. Morphine requirements (mean ± SD) during the first 24 h in the M-6-G group (41 ± 9 mg) and the placebo group (49 ± 8 mg) were significantly greater (P < 0.05) compared with the morphine group (29 ± 8 mg). Conclusion A single intravenous bolus dose of M-6-G was found to be ineffective in the treatment of acute postoperative pain. This might be related to the low permeability of the blood–brain barrier for M-6-G.

The Comparative Electrophysiologic and Hemodynamic Effects of a Large Dose of Ropivacaine and Bupivacaine in Anesthetized and Ventilated Piglets

Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 ± 22 to 49 ± 31 mm Hg and from 87 ± 17 to 58 ± 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 ± 95 to 689 ± 482 mm Hg/s and from 1963 ± 92 to 744 ± 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 ± 5 to 9 ± 5 mm Hg and from 6 ± 4 to 12 ± 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 ± 139 to 706 ± 228 ms and from 451 ± 87 to 666 ± 194 ms, respectively), atria His (from 71 ± 15 to 113 ± 53 ms and from 64 ± 6 to 86 ± 10 ms, respectively), and QTc (QTc = QT × R-R−0.5, Bazett formula; from 380 ± 71 to 502 ± 86 ms and from 361 ± 33 to 440 ± 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 ± 20 to 211 ± 60 ms versus from 91 ± 8 to 145 ± 38 ms, P < 0.05), QRS (from 58 ± 3 to 149 ± 34 ms versus from 60 ± 5 to 101 ± 17 ms, P < 0.05), and His ventricle interval (from 25 ± 4 to 105 ± 30 ms vs from 25 ± 4 to 60 ± 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.

Effect of interpleural administration of bupivacaine or lidocaine on pain and morphine requirement after esophagectomy with thoracotomy : a randomized, double-blind and controlled study

The purpose of the present study was to investigate the efficacy of interpleural (IP) analgesia with bupivacaine or lidocaine after esophageal surgery and to measure the plasma concentrations of bupivacaine and lidocaine after intermittent IP administrations.Two IP catheters were inserted percutaneously in the seventh intercostal space during operation. Patients in the bupivacaine group (Gr B) received 1 mg/kg of 0.5% bupivacaine with epinephrine 1:200000 in 20 mL of saline 0.9%, patients in the lidocaine group (Gr L) received 3 mg/kg of 2% lidocaine with epinephrine in 20 mL of saline 0.9%, and patients in the placebo group (Gr P) received 20 mL of saline 0.9% every 4 h during 2 days. Pain was assessed by visual analog scale (VAS) every 4 h at rest (VASR), after a deep breath or cough (VASC), at the thoracotomy (VAST), and at the laparotomy (VASL). Morphine consumption using a patient-controlled analgesia (PCA) device was recorded. There was no significant difference in the mean VASR, VASC, and VASL scores among the three groups. VAST scores were significantly lower in Gr B at 12, 16, 28, and 32 h when compared with Gr P and Gr L (P < 0.05). There was no statistical difference in mean VAST between Gr L and Gr P. Total consumption of morphine was lower in Gr B than in Gr P and Gr L (41.2 +/- 13 mg vs 66.1 +/- 21 mg in Gr P (P < 0.02) and 75.5 +/- 27 mg in Gr L (P < 0.01)), but were similar in Gr L when compared with Gr P. No patient had any symptoms suggestive of local anesthetic toxicity despite high peak plasma concentration (maximum 5.48 micro gram/mL and 3.91 micro gram/mL for lidocaine and bupivacaine respectively). We conclude that 1) IP analgesia with bupivacaine after esophagectomy reduced morphine requirements due to a decrease in the thoracic pain in comparison to a placebo; 2) IP analgesia with lidocaine was ineffective; and 3) if VAS values in the range 0-3 cm represent adequate analgesia, morphine administration by PCA was not sufficient even in association with bupivacaine IP analgesia. (Anesth Analg 1995;80:718-23)

Hemodynamic and Cardiac Electrophysiologic Effects of Lidocaine–Bupivacaine Mixture in Anesthetized and Ventilated Piglets

Background The sensory blockade induced by a lidocaine–bupivacaine mixture combines the faster onset of lidocaine and the longer duration of bupivacaine. The current study compared the effects of large doses lidocaine (16 mg/kg), bupivacaine (4 mg/kg), and a mixture of 16 mg/kg lidocaine–4 mg/kg bupivacaine on hemodynamic and cardiac electrophysiologic parameters in anesthetized and ventilated piglets. Methods After carotid artery cannulation, a double micromanometer measured mean aortic pressure, left ventricular end diastolic pressure, and the first derivative of left ventricular pressure. Electrocardiogram recording and a bipolar electrode catheter measured RR, PQ, QRS, QTc, JTc, AH, and HV intervals. Lidocaine, bupivacaine, or the mixture was administered intravenously over 30 s, and studied parameters were measured throughout 30 min. Results Mean aortic pressure decreased in all groups (P < 0.05). The first derivative of left ventricular pressure was decreased in all groups (P < 0.001) but to a greater extent with the mixture compared with lidocaine (P < 0.04). RR, QTc, and JTc intervals were similarly increased in all groups (P < 0.05). In all groups, PQ, AH, HV, and QRS intervals were widened (P < 0.001). The lengthening of PQ was greater with bupivacaine (P < 0.02). The lengthening of AH was greater and delayed with bupivacaine compared with lidocaine (P < 0.03). The lengthening of HV and the widening of QRS were greater and delayed with bupivacaine (P < 0.01). The widening of QRS was greater with the mixture than with lidocaine (P < 0.01). Conclusions The alterations of ventricular conduction parameters are greater with 4 mg/kg bupivacaine than with a mixture of 16 mg/kg lidocaine–4 mg/kg bupivacaine, whereas the hemodynamic parameters are similarly altered.

A comparison of ropivacaine and bupivacaine for cervical plexus block.

We compared bupivacaine 0.5% and ropivacaine 0.75% for cervical plexus block (CB). Forty patients scheduled for carotid artery surgery were allocated randomly to undergo superficial and deep CB with 30 mL of one of the two anesthetic solutions. We evaluated the onset of anesthetic block; the requirement for supplementation during the surgery; the patients’ satisfaction; postoperative pain on a visual analog scale at 1, 2, and 3 h; and the use of paracetamol as a rescue analgesic medication. Arterial blood was sampled immediately and 1, 3, 5, 10, 15, 30, 45, and 60 min after CB for measurements of bupivacaine or ropivacaine concentrations. Patients in both groups had equivalent onset of CB, local infiltration with lidocaine during surgery, and satisfaction scores. In the Bupivacaine group, visual analog scale scores were lower at 2 and 3 h, and the delay before paracetamol administration was prolonged. Observed peak concentrations were larger in the Ropivacaine group (4.25 [2.07–6.59 mg/L] vs 3.02 [0.98–5.82 mg/L]), but time to reach peak concentrations was comparable (5 [1–15 min] vs 5 [0–45 min] in the Ropivacaine and Bupivacaine groups, respectively). We conclude that ropivacaine has no advantage over bupivacaine for CB.

PHARMACOKINETICS OF INTRAPLEURAL LIDOCAINE ADMINISTRATION IN TRAUMA PATIENTS

Local anesthetics have been administered interpleurally for postoperative pain relief (l), and the pharmacokinetics involved have been studied in spontaneously breathing postoperative patients (2,3). Local anesthetics also have been used interpleurally for pain relief in patients with multiple rib fractures (4). These patients may have abnormal pharmacokinetics because they have sustained chest trauma, but there are no data to support or refute this hypothesis. Similarly, patients with multiple rib fractures are usually mechanically ventilated, but the effect of mechanical ventilation on the lidocaine pharmacokinetics after interpleural injection is not known. The aim of this study was to provide information on the effect of chest trauma and mechanical ventilation on the pharmacokinetics of interpleural lidocaine.