A dose-response study of epidural liposomal bupivacaine in rabbits.

Liposomes are drug delivery systems used to prolong local effects of bupivacaine. We studied the relationships between motor and hemodynamic changes and epidural doses of plain bupivacaine (P) and liposomal bupivacaine (L) in rabbits equipped with chronical lumbar epidural and femoral arterial catheters. Liposomal (phosphatidylcholine-cholesterol) suspensions contained 20 mg ml-1 of lipid, and different doses of bupivacaine (Lipo 7.5=7.5-; Lipo 3.7=3. 75-; Lipo 2.5=2.5-; Lipo 1.2=1.25-; and Lipo 0.7=0.65-mg of bupivacaine per ml). Forty rabbits were randomly assigned to five groups to receive epidural anesthesia (1 ml) as follows: Groups I to V received 0.65 to 7.5 mg of bupivacaine as P then as L. Release rate of bupivacaine from liposome was significantly slower using Lipo 3.7 than after Lipo 2.5 (Td was 3.9 h and 1.7 h respectively). Increasing the doses of L and P resulted in faster onset time for complete motor blockade and in a prolonged duration of motor effects. Liposomal formulation appears to be a powerful delivery system to prolong the motor effects of bupivacaine since E50 was lower and Emax higher than after the use of plain solution (E50 4.49+/-1.81 mg and Emax 152+/-40 min for P; and E50 2.61+/-0.23 mg and Emax 202+/-9 min for L). Hemodynamic changes were linearly related to doses of bupivacaine injected. The best bupivacaine-to-lipid ratio to prolong motor effects using our model was 3.75 mg and 20.0 mg respectively (Lipo 3.7).

[General or locoregional anesthesia: which to choose for a patient at risk?]. / Anesthésie générale ou anesthésie locorégionale: que choisir chez le sujet à risque?

HIGH RISK SITUATIONS: The risk of surgery is higher in certain situations (subjects over 70 years of age, underlying disease states). Procedures lasting more than 3 hours or performed in emergency situations also increase the risk. The question is often raised as to which type of anesthesia, general or locoregional, is the most appropriate to lower the risk of complications in such situations. ANESTHESIA-DEPENDENT EFFECTS: Respiratory complications during or after surgery are more frequent if general anesthesia is used. Cardiovascular complications are not influenced by the type of anesthesia. Local-regional anesthesia can lower the risk of post-operative venous thrombosis and the development of thrombus formation secondary to vascular surgery. It also eliminates the neuroendocrine response to surgical stress. MODEST EFFECT: Only a few precise parameters can differentiate risk between general and locoregional anesthesia. However, the type of anesthesia has little effect on overall morbidity or mortality, which depend more on the general status of the patient and the surgical procedure performed.

[Diagnosis of a persistent left superior vena cava in the operating room during a central venous catheterization]. / Diagnostic d'une veine cave supérieure gauche persistante au bloc opératoire lors d'un cathétérisme veineux central.

A 2-year-old boy was admitted for surgical excision of a hepatoblastome. A central venous catheter was inserted by a subclavian approach, without difficulty. The chest radiograph showed the catheter positioned along the left heart border. The diagnosis of persistent left superior vena cava was suspected after analysis of the central venous pressure curve. An postoperative chest X-ray confirmed the diagnosis. The catheter was maintained for five days without any complication.

[Cardiac surgery: predictive mortality index, severity and care of illness. 243 cases]. / Chirurgie cardiaque: indice de mortalité prédictif et scores de gravité et de soins 243 observations.

OBJECTIVES: Medical teams are keenly aware of the need to evaluate health care quality and the cost/benefit ratio. We prospectively applied three proposed indexes, designed for predicting mortality, for evaluating disease gravity, and for evaluating health care in intensive care patients, in two populations of patients undergoing heart surgery. METHODS: From January to June 1991, 243 patients (mean age 58.1; 55 females, 188 males) underwent coronary bypass surgery (n = 116; mean number of bypasses = 2.94 per patient) or valve replacement (n = 127). The patients were divided into 3 groups of increasing gravity on the basis of the preoperative presentation (Groups 1, 2 and 3 for Parsonnet's index, a specific index for predicting mortality in patients with acquired cardiopathies undergoing heart surgery = 0-9, 10-19 and > 20 respectively). A comparison was then performed for each population (bypass surgery and valve replacement) between the predicted mortality and the APACHE II index of disease gravity and the OMEGA index of intensive care. RESULTS: Overall mortality was 3.7% (2.85% in the bypass population and 4.72% in the valve population). The specific Parsonnet index (PI) for cardiac surgery gave a good indication of mortality risk (observed deaths 0.7% for PI = Group 1; 2.6% for PI = Group 2; 13.1% for PI = Group 3) and of postoperative morbidity since inotropic support was required in 18, 45 and 59% for PI Groups 1, 2 and 3 respectively. For patients in the PI Group 3, postoperative care in the intensive care unit lasted > 3 days and required ventilatory support for > 24 hours. APACHE II and OMEGA did not contribute to evaluating the Parsonnet index. CONCLUSION: A high risk population undergoing cardiac surgery can be defined among patients with a Parsonnet index above 20. Under this threshold, the risk of mortality falls to 1.4%.

Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia.

BACKGROUND: Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, alpha-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days. METHODS: Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters. RESULTS: No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 microg/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at 2 and 20 microg/ml, respectively. CONCLUSIONS: Because of a low AAG concentration and a low intrinsic clearance, unbound bupivacaine increased to concentrations greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed after surgery did not fully buffer this unbound fraction. Similarly, the buffer capacity of erythrocytes did not sufficiently increase at high concentration to compensate the saturation of the AAG system. Thus, we propose the use of a maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.

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 Horner's 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.

A new axillary approach for continuous brachial plexus block. A clinical and anatomic study.

Catheter insertion in the neurovascular space by axillary approach allows a continuous brachial plexus block and/or postoperative analgesia. We developed a perivenous technique whereby the approach to the neurovascular sheath is guided under fluoroscopy by a preopacified axillary vein. A randomized study compared this technique to the technique of Selander in ASA grade I-II patients scheduled for surgery or painful physiotherapy of the hand. The study was performed in 36 patients randomly divided into two groups. In Group 1 (n = 18), the catheter was placed according to the technique described by Selander. In Group 2 (n = 18), the catheter was placed using our perivenous technique. A complete block was obtained in all the patients of Group 2 vs only 50% of the patients in Group 1 (P < 0.05). In Group 1 a partial block was observed in 17%, with failure in 33% of the patients. There was no difference in the two groups regarding the time required to perform either technique, the duration of the complete block, the pain score, or the amount of continuously administrated bupivacaine during the first 48 h postoperatively. The plasma concentrations of total bupivacaine (high-performance liquid chromatography) were low in successful blocks, with no differences in the two groups; the median value was 0.68 microgram/mL (95% confidence interval: 0.62-0.89). The concentrations were higher (P < 0.01) in failed blocks; the median value was 1.69 micrograms/mL (95% confidence interval: 0.58-2.8). A complementary anatomic study of three arms from fresh cadavers allowed verification of the correct localization of the Teflon cannula and flexible catheter, as well as homogeneous diffusion of the methylene blue inside the brachial plexus. The perivenous technique for continuous axillary brachial plexus block may improve the success rate due to its radiologic and accurate location of the neurovascular sheath.