Michel Pinaud

KETAMINE AND MIDAZOLAM NEUROTOXICITY IN THE RABBIT

Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.

Continuous peripheral nerve blocks with stimulating catheters.

Background and Objectives This study evaluated the efficacy of stimulating catheters used for continuous peripheral nerve blocks as a means of immediate verification and confirmation of correct catheter position. Methods This observational study presents our experience with 130 stimulating catheters used in 40 intersternocleidomastoid, 24 axillary, 47 femoral, and 19 lateral midfemoral sciatic nerve blocks. Placement characteristics (amperage, depth of introducer needle or catheter insertion, elicited motor responses), subsequent postoperative analgesia, and catheter position evaluated with the radiopaque dye analysis were all studied. Results Except in femoral blocks, characteristics of motor responses elicited (1 Hz, 0,1 ms) by the introducer assembly and catheter differed. The amperage required to elicit motor responses typically was higher with the catheter than with the introducer needle (1.6 [0.2 to 4 mA] v 0.5 [0.4 to 1 mA] P < .0001). The ability to elicit a motor response with the stimulating catheter correlated with successful clinical anesthesia in 124 cases. Opacified radiography showed no aberrant position in these cases. Three catheters for upper limb block failed to stimulate, provided poor anesthesia, and had radiologic evidence of aberrant position. Even though they failed to stimulate, 3 catheters for sciatic block functioned well, and the opacified radiography showed correct position. Conclusion The ability to electrostimulate nerves using an in situ catheter increases success rate in catheter placement for continuous peripheral nerve blocks. Further controlled investigations are necessary to compare this technique with more conventional methods in terms of cost and utility for various peripheral nerve blocks. Reg Anesth Pain Med 2003;28:83-88.

Intrathecal Anesthesia: Ropivacaine Versus Bupivacaine

We compared intrathecal ropivacaine to bupivacaine in patients scheduled for transurethral resection of bladder or prostate. Doses of ropivacaine and bupivacaine were chosen according to a 3:2 ratio found to be equipotent in orthopedic surgery. One hundred patients were randomly assigned to blindly receive either 10 mg of isobaric bupivacaine (0.2%, n = 50) or 15 mg of isobaric ropivacaine (0.3%, n = 50) over 30 s through a 27-gauge Quincke needle at the L2-3 level in the sitting position. Onset and offset times for sensory and motor blockades and mean arterial blood pressure were recorded. Pain at surgical site requiring supplemental analgesics was recorded. Cephalad spread of sensory blocks was higher with bupivacaine (median level, cold T4 and pinprick T7) than with ropivacaine (cold T6 and pinprick T9) (P <0.001). Eight patients in Group Ropivacaine received IV alfentanil (P <0.01). Onset time (mean ± sd) to T10 anesthesia and offset time at L2 were not different (bupivacaine = 13 ± 8 min, 127 ± 41 min; ropivacaine = 11 ± 7 min, 105 ± 29 min). Complete motor blockade occurred in 43 patients with bupivacaine and in 41 patients with ropivacaine (not significant). Total duration of motor blockade was not different. No difference in hemodynamic effects was detected between groups. No patient reported back pain. We conclude that 15 mg of intrathecal ropivacaine provided similar motor and hemodynamic effects but less potent anesthesia than 10 mg of bupivacaine for endoscopic urological surgery. Implications Inadequate intrathecal anesthesia was observed in 16% of patients with 15 mg of ropivacaine, whereas intensity and duration of motor blockade was not different in comparison to 10 mg of bupivacaine. Ropivacaine appears to be less potent than bupivacaine at doses used in spinal anesthesia.

A novel supraclavicular approach to brachial plexus block

We describe a novel supraclavicular approach to the brachial plexus.Designated as the intersternocleidomastoid technique, this new approach was tested in unembalmed cadavers. It was then applied for evaluation to 150 ASA grade I or II patients scheduled for elective surgery or physiotherapy of the upper limb or for treatment of reflex sympathetic dystrophy associated with painful shoulder. The new approach was easy to master because of a very simple surface landmark, i.e., the triangle formed by the sternocleidomastoid heads, which were visible and palpable in most patients studied (90%). The procedure was effective intraoperatively, providing satisfactory anesthesia in 140 patients (93%), partially satisfactory blocks in 6 (4%), and unsatisfactory blocks in only 4 (3%). The catheter entry point is cephalad enough not to obscure the surgical field on the shoulder. Catheter insertion was successful in 63 of 70 patients. Postoperative analgesia was provided for 48 h or more in 45 patients and for 24 h in 18 patients. Only minor complications were observed: asymptomatic phrenic nerve block in 89 patients (60%), transient Horners syndrome in 15 (10%), transient recurrent laryngeal nerve blockade in 2, and misplacement of the catheter into the subclavian vein in 1 patient. No pneumothorax was observed. (Anesth Analg 1997;85:111-6)

Left ventricular function during propofol and fentanyl anesthesia in patients with coronary artery disease: assessment with a radionuclide approach

Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol alone and in combination with fentanyl on left ventricular (LV) volumes and function were investigated in 10 ASA III, unpremedicated patients (51–75 years) with coronary artery disease (NYHA II-III). Anesthesia was induced with propofol (2 mg/kg) followed by an infusion (100 μg-kg1min−1). Vecuronium (0.05 mg/kg) was administered and ventilation (FiO2, 1.0) was manually controlled via a face mask (FECO2, 4–5%). Data acquisitions were serially obtained over 15 minutes after the bolus IV injection of propofol and 5 minutes after the injection of fentanyl (5 μg/kg). Propofol induced a rapid decrease (15%) in mean arterial pressure (MAP) exclusively related to a decrease in cardiac index (CI), without reduction in indexed systemic, vascular resistances (SVRI). Despite the decrease in MAP, heart rate did not change. The decrease in CI was associated with a lower preload. After the addition of fentanyl, MAP decreased significantly (35%) below the last set of propofol measurements. The decrease in MAP was associated with a reduction in CI and SVRI. Fentanyl was also associated with a significant decrease in heart rate (16%) resulting in a decrease in CI, whereas stroke index and end diastolic volume did not change. Neither global ejection fraction (EF) nor end systolic volume changed significantly at any time, nor were there changes in the ECG or in regional ejection fractions (REF). The absence of changes in REF was consistent with lack of wall motion abnormalities of the left ventricle. Propofol alone and in combination with fentanyl does not alter LV performance in patients with good LV function. However, the magnitude of MAP reduction might jeopardize coronary perfusion in severe ischemic heart disease.

Intrathecal bupivacaine in humans: influence of volume and baricity of solutions.

BACKGROUND The effects of volume and baricity of spinal bupivacaine on block onset, height, duration, and hemodynamics were studied. METHODS Ninety patients undergoing endoscopic urologic procedures were randomized to receive 10 mg of intrathecal bupivacaine at L2-L3 level in sitting position. In the operating room, commercial products were diluted as needed with NaCl 0.9% to obtain isobaric solutions (density, 1.005-1.008) or with NaC 10.9% and glucose 30% to obtain hyperbaric solutions (density, 1.031-1.037) of 2, 5, or 10 ml (six groups of 15 patients each). Three minutes after spinal injection the patients were placed in lithotomy position. Sensory blockade was assessed using pinprick and cold sensation tests, and motor blockade was assessed using a four-point scale. RESULTS Onset times to maximal cephalad spread of spinal blockade were similar with isobaric and hyperbaric solutions. A greater maximal cephalad spread of anesthesia was obtained with diluted isobaric bupivacaine but was not associated with more hypotension. Volume had no effect on cephalad extent of anesthesia with hyperbaric bupivacaine. Times for regression of anesthesia to L2 and offset of motor block were longer with isobaric than with hyperbaric solutions of bupivacaine. The intensity of motor blockade was decreased with diluted hyperbaric bupivacaine. No patient reported back pain. CONCLUSION In this study, volume had no significant influence on either cephalad spread or duration of sensory blockade for either isobaric or hyperbaric bupivacaine. Time for offset of anesthesia was shorter with hyperbaric bupivacaine compared with isobaric solutions.

Pharmacodynamic Dose-response and Safety Study of Cisatracurium (51w89) in Adult Surgical Patients During N2 O-o2-opioid Anesthesia

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2 O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 times ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release. (Anesth Analg 1996;83:823-9)

Left ventricular performance during propofol or methohexital anesthesia : isotopic and invasive cardiac monitoring

Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect.

Long-term hypotensive technique with nicardipine and nitroprusside during isoflurane anesthesia for spinal surgery.

Short-term infusion of nicardipine can be used to induce deliberate hypotension but may result in plasma drug accumulation. To assess long-term nicardipine administration for deliberate hypotension in 10 patients in a moderately hemodiluted state who were undergoing spinal surgery, hemodynamics and plasma nicardipine concentrations were concomitantly measured before and 20, 80, and 140 min after starting nicardipine, at drug discontinuation, and 20 and 80 min later. A dose of 6.2 ± 0.9 mg (mean ± SEM) of nicardipine was initially required to obtain mean arterial blood pressures at 55--60 mm Hg. Maintenance doses of nicardipine were 3--5 mg/h. The duration of nicardipine administration was 270 ± 20 mins (mean ± SEM). Hypotension was associated with decreased systemic and pulmonary vascular resistances, increased cardiac index, and decreased arteriovenous difference in O2 contents. Only two patients required homologous blood transfusion. Plasma nicardipine concentrations peaked at 110 ± 21 ng/mL (mean ± SEM) and then decreased to 38 ± 11 ng/mL (mean ± SEM) without changes in arterial blood pressure. After vasodilator discontinuation, hypotension was observed during a mean time of 43 min (range 27--88 min) despite plasma concentrations <20 ng/mL. No relationship was found between plasma nicardipine concentrations and hemodynamics. These findings suggest that an increasing effect of nicardipine over time may occur during prolonged administration. Because the reasons for this hysteresis remain unclear, use of nicardipine infusion during major surgery and anesthesia requires particular caution.

Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study.

Background Ropivacaine is available for spinal or intrathecal use in humans, although data on neurotoxicity after spinal injection are not yet available. The authors experimentally determined the relationship between doses of intrathecal ropivacaine and spinal effects and local neurotoxic effects. Methods Eighty rabbits equipped with an intrathecal lumbar catheter were studied. Sixty were randomly assigned to receive 0.2 ml of intrathecal solutions as a sole injection of: 0.2%, 0.75%, 1.0%, and 2.0% ropivacaine (doses from 0.4–4.0 mg; groups R0.2 to R2.0), 5.0% lidocaine (10 mg; group L), or 0.9% NaCl as control (group C). Twenty other rabbits received either repeated injections of 0.2 ml of 0.2% ropivacaine every 2 days during 2 weeks (total dose of 2.8 mg; group RINT); or a continuous intrathecal infusion of 0.2% ropivacaine at the rate of 1.8 ml/h over 45 min (2.7 mg; group RCONT). Injection rate was 30 s in all groups except Rcont. Time to onset, duration and extent of motor block, and variations of mean arterial blood pressure were recorded in all groups. Somatosensory evoked potentials were also recorded in group RCONT and RINT. Seven days after the last intrathecal injection spinal cord and nerves were sampled for histopathologic study. Results In groups R0.2 and RINT, the lowest dose of ropivacaine induced a clinically visible spinal block in only 50% of rabbits, but SEPs recorded in group RINT were decreased by 70% in the lumbar dermatome. Complete motor block was observed with doses greater than 1.5 mg of ropivacaine (group RCONT and R0.75 to R2.0). Onset time was shorter and duration of block increased as doses of ropivacaine increased. Significant hypotension was observed only with 4.0 mg of ropivacaine (concentration of 2.0%). Complete paralysis and hypotension were observed with 5.0% lidocaine. No neurologic clinical lesion was observed in rabbits receiving saline or ropivacaine within the 7 days after the last intrathecal injection, and histopathologic study revealed no sign of neurotoxicity in these groups. In contrast, intrathecal lidocaine induced clinical and histopathologic changes. Conclusion Ropivacaine induced dose-dependent spinal anesthesia, and did not induce any neurotoxicologic lesion in this experimental animal model.