Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice.

BACKGROUND: Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity. RESULTS: Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups. CONCLUSIONS: In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.

Rescue oxygenation success by cannula or scalpel-bougie emergency front-of-neck access in an anaesthetised porcine model.

In the obese, the evidence for the choice of the optimal emergency front-of-neck access technique is very limited and conflicting. We compared cannula and scalpel-bougie emergency front-of-neck access techniques in an anaesthetised porcine model with thick pretracheal tissue. Cannula and scalpel-bougie cricothyroidotomy techniques were performed in 11 and 12 anaesthetised pigs, respectively. Following successful tracheal access, oxygenation was commenced and continued for 5 min using Rapid-O2 device for cannula and circle breathing system for scalpel-bougie study groups. The primary outcome was a successful rescue oxygenation determined by maintenance of arterial oxygen saturation >90% 5 min after the beginning of oxygenation. Secondary outcomes included success rate of airway device placement, time to successful airway device placement, and trauma to the neck and airway. The success rate of rescue oxygenation was 18% after cannula, and 83% after scalpel-bougie technique (P = 0.003). The success rate of airway device placement was 73% with cannula and 92% with scalpel-bougie technique (P = 0.317). Median (inter-quartile-range) times to successful airway device placement were 108 (30-256) and 90 (63-188) seconds (P = 0.762) for cannula and scalpel-bougie emergency front-of-neck access, respectively. Proportion of animals with iatrogenic trauma additional to the procedure itself was 27% for cannula and 75% for scalpel-bougie technique (P = 0.039). Thus, in the porcine model of obesity, the scalpel-bougie technique was more successful in establishing and maintaining rescue oxygenation than cannula-based technique; however, it was associated with a higher risk of severe trauma.

Neurotoxicity of intraneural injection of bupivacaine liposome injectable suspension versus bupivacaine hydrochloride in a porcine model.

OBJECTIVE: To test whether neurotoxic effects of a bupivacaine liposome injectable suspension differ from those of a standard formulation of bupivacaine hydrochloride (HCl) after intraneural injection into the sciatic nerves in pigs. STUDY DESIGN: Prospective, randomized study. ANIMALS: Fifteen pigs, hybrids of Landrace and Large White. METHODS: After the National Ethics Committee approval, 15 pigs were randomly allocated to three groups (n = 5/group) to receive intraneural injections of 4 mL of 1.33% bupivacaine liposome injectable suspension, 0.5% bupivacaine HCl or normal saline. Serial neurologic examinations were conducted to detect sensory and motor response to noxious stimuli using a modified Thalhammer's scale at 2 hour intervals for the first 12 hours after injection and daily thereafter for 2 weeks. Fiber characteristics (density) of the harvested sciatic nerves were measured during histomorphometric analysis. Inflammatory response was studied using immunohistochemical analysis. Data were tested using analyses of variance; p values for paired comparisons were Bonferroni adjusted. RESULTS: Compared with bupivacaine HCl, bupivacaine liposome injectable suspension provided longer sensory (11.2 ± 1.8 hours versus 3.2 ± 1.1 hours, respectively, p < 0.0001) and motor (10.0 ± 2.0 hours versus 4.0 ± 1.4 hours respectively, p < 0.0001) blockade. Histomorphometric parameters were similar among the groups. No changes in axonal density or myelin structure indicative of injury to the sciatic nerves were observed in any of the groups. Number of immunopositive cells did not differ between the bupivacaine liposome injectable suspension (23 ± 6 cells per mm2) and the bupivacaine HCl groups (21 ± 4 cells per mm2), p > 0.90. CONCLUSIONS AND CLINICAL RELEVANCE: Intraneural injections of bupivacaine liposome injectable suspension or bupivacaine HCl in our porcine model did not result in evidence of neurotoxicity.

UPPER AIRWAY BLOCKS FOR AWAKE DIFFICULT AIRWAY MANAGEMENT.

Airway anesthesia is pivotal for successful awake intubation provided either topically or by blocks. Airway blocks are considered technically more difficult to perform and carry a higher risk of complications. However, in experienced hands, they can be useful as they provide excellent intubating conditions. For complete upper airway anesthesia, bilateral glossopharyngeal and superior laryngeal nerve blocks with translaryngeal injection are required. Superior laryngeal nerve block and translaryngeal injection can be performed easily, safely and with a high success rate in patients with normal anatomy. In those with difficult landmarks, ultrasound can be of assistance. For the superior laryngeal nerve block, other targets than the nerve itself must be established to make the technique consistently successful, easy to teach, learn and perform. The same applies to the translaryngeal injection, where the use of ultrasound is necessary for correct midline identification. Intraoral glossopharyngeal nerve block is also safe and easy to perform, but associated with long lasting discomfort. Bilateral extraoral peristyloid approach should be discouraged since inadvertent blocks of the closely adjacent vagus nerve cannot be prevented in this location. A safe and easy method of blocking the distal portions of the glossopharyngeal nerve for awake intubation is therefore required.

Intraneural and perineural inflammatory changes in piglets after injection of ultrasound gel, endotoxin, 0.9% NaCl, or needle insertion without injection.

BACKGROUND: Ultrasound gel nerve inflammation has been reported. We evaluated the extent and nature of inflammation after gel injection with endotoxin (positive), saline, or dry needle puncture (negative) controls after peripheral blocks in piglets. METHODS: Selected nerves of 12 piglets were localized by landmarks and nerve stimulator. Forty-eight hours after injection, specimens were examined for immunohistochemical cell differentiation/quantification and cytokine expression by using quantitative polymerase chain reaction. RESULTS: Both gel and endotoxin injections resulted in a significantly higher density of inflammatory cells (lymphocytes/granulocytes) as compared with needle insertions and/or saline injections (both P < 0.001). Cytokines were not detected in any of the specimens. CONCLUSIONS: Perineural gel injections cause significant inflammation. The lack of cytokines suggests injectate-related changes rather than mechanical trauma.

Inflammatory response after injection of aqueous gel into subarachnoid space in piglets.

BACKGROUND: Ultrasound-guided neuraxial anesthesia requires the application of ultrasound gel between the transducer and the skin to avoid signal drop-off. As the needle is inserted, the gel may be introduced intrathecally. The purpose of this study was to examine the evidence of an inflammatory response in the subarachnoid space after intrathecal gel introduction. METHODS: Twelve piglets were sedated with azaperone 0.5 mg/kg intramuscularly and anesthetized via face mask (2%-4% isoflurane in 50% air-oxygen mixture). After collection of cerebrospinal fluid by lumbar puncture with a 22-gauge needle (baseline), 0.2 mL of ultrasound gel mixed with 1 mL of saline was injected intrathecally into 9 piglets (gel group). In 3 piglets (control group), 1 mL of saline was administered. Behavioral and neurologic assessments were recorded on a 4-grade scale. Following the preinjection and postinjection cerebrospinal fluid collection, the piglets were killed, and samples of spinal cord with meninges were excised. Five cross sections (1 mm apart) were processed using immunohistochemistry. RESULTS: After anesthesia, all piglets displayed short-lived mild (grade 1) motor and behavioral deficits. Mean ± SD protein concentrations in the gel and baseline samples were 14.1 ± 3.0 and 1.3 ± 0.5 g/L, respectively (P = 0.001). No differences were found in protein concentration between baseline (1.8 ± 0.7 g/L) and control samples (2.8 ± 0.8 g/L) (P = 0.4). In the gel group, numerous immunopositive cells were found in the pia, arachnoid, and inner layer of dura. CONCLUSION: Subarachnoid injection of ultrasound gel in piglets results in an inflammatory response within neuraxial space.

Comparison of continuous thoracic epidural with paravertebral block on perioperative analgesia and hemodynamic stability in patients having open lung surgery.

BACKGROUND: Epidural analgesia can result in perioperative hypotension in patients having thoracotomy. This randomized prospective study assessed the effects of epidural and paravertebral analgesia on hemodynamics during thoracotomy. METHODS: Thirty-two patients were randomized to receive either epidural analgesia (n = 16, 0.25% levobupivacaine and 30 µg/kg morphine) or paravertebral block (n = 16; 0.5% levobupivacaine and 30 µg/kg morphine). Oxygen delivery, stroke volume and systemic vascular resistance indices, heart rate, and mean arterial pressure measurements were performed before administration of local anesthetic, after induction of general anesthesia, institution of 1-lung ventilation, first skin incision, retractor placement, lung-inflation maneuver, and at last skin suture. The primary end point was the volume of the colloid infusion necessary to maintain oxygen delivery index of 500 mL/min per squared meter or higher. Postoperative analgesia was provided immediately after surgery by an infusion of 0.125% levobupivacaine and 20 µg/mL morphine in epidural/paravertebral infusion. Pain, rescue-analgesia consumption, arterial pressure, and heart rate were recorded at 6, 24, and 48 hrs after surgery. Administration of anesthesia and data collection were done by research staff blinded to the regional analgesia technique. RESULTS: The groups did not differ significantly in heart rate, mean arterial blood pressure, or systemic vascular resistance indices. However, to maintain the targeted oxygen delivery index, a greater volume of colloid infusion and phenylephrine were required, respectively, in the epidural than in the paravertebral group (554 ± 50 vs 196 ± 75 mL, P = 0.04; and 40 ± 10 vs 17 ± 4 µg, P = 0.04). Pain intensity before and after respiratory physiotherapy as well as 24 hr rescue piritramide consumption was similar in the epidural (4.1 ± 3.1 mg) and the paravertebral (2.5 ± 1.5 mg) groups (P = 0.14). Systolic blood pressure after 24 and 48 hrs was lower in the epidural group. CONCLUSIONS: Under the conditions of our study, continuous paravertebral block resulted in similar analgesia but greater hemodynamic stability than epidural analgesia in patients having thoracotomy. Paravertebral block also required smaller volume of colloids and vasopressors to maintain the target oxygen delivery index (DO2I).

Pharmacokinetics of levobupivacaine 0.5% after superficial or combined (deep and superficial) cervical plexus block in patients undergoing minimally invasive parathyroidectomy.

STUDY OBJECTIVE: To evaluate the pharmacokinetic profile of 0.35 mL/kg of 0.5% levobupivacaine during superficial and combined (deep and superficial) cervical plexus block (CPB) in patients undergoing minimally invasive parathyroidectomy. DESIGN: Prospective randomized study. SETTING: Operating theater of a university hospital. PATIENTS: 12 ASA physical status II and III patients (11 women and 1 man), scheduled for minimally invasive parathyroidectomy. INTERVENTIONS: Seven and 5 patients were randomly assigned to receive either superficial or combined CPB, respectively. The superficial CPB was performed with an injection of 0.35 mL/kg of 0.5% levobupivacaine subcutaneously along the posterior border of the sternocleidomastoid muscle and deeper on its medial surface. The combined CPB was initiated by the deep block at the C3 level vertebra by injecting 0.2 mL/kg of 0.5% levobupivacaine, followed by the superficial block with an injection of the remaining 0.15 mL/kg. After completion of the block, venous blood was sampled at the intervals of 5, 10, 15, 20, 30, 45, and 60 minutes. MEASUREMENTS AND MAIN RESULTS: Venous plasma concentrations were measured using gas chromatography-mass spectroscopy. Mean +/- SD of maximal concentrations of levobupivacaine was 0.58 +/- 0.41 mg/L in group superficial and 0.52 +/- 0.28 mg/L in group combined (P = 0.71). The median (range) time required to reach the maximal concentrations was 30 minutes (20-30 min) in group superficial and 20 minutes (15-30 min) in group combined (P = 0.45). The areas under the drug concentration/time curve (AUC(10-60)) were also similar in both groups. No signs of central nervous system or cardiovascular toxicity or other untoward events were observed in any patient. CONCLUSION: With the given dose regimen, levobupivacaine plasma concentrations were within safe ranges.

A prospective, randomized comparison between combined (deep and superficial) and superficial cervical plexus block with levobupivacaine for minimally invasive parathyroidectomy.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) can be performed under cervical plexus block (CPB). Superficial CPB has been reported to be easier to perform with similar efficacy and less anesthesia-related complications than combined deep and superficial CPB. In this study, we compared the efficacy of superficial and combined (deep and superficial) CPB in patients undergoing MIP. METHODS: Forty-two patients with primary hyperparathyroidism due to a solitary adenoma were randomized to receive either a superficial (group superficial, n = 20) or a combined deep and superficial CPB (group combined, n = 22) using 0.35 mL/kg of 0.5% levobupivacaine. The primary end-point was the amount of supplemental fentanyl required to complete surgery. RESULTS: There were no differences in onset of block, pain scores during surgery, or time to first analgesic request between groups. Fentanyl consumption was similar in both groups, i.e., 50 (0-200) microg in group superficial and 50 (0-100) microg in group combined (P = 0.60). Six patients [1 in group superficial (5%) and 5 in group combined (22.7%)] were converted to general anesthesia for surgically required bilateral neck dissection (P = 0.18). General anesthesia for block failure was reported in three superficial (15%) and two combined group patients (9%) (P = 0.99). In group combined, only one patient (4.5%) showed diaphragmatic paresis after the block (P = 0.99). CONCLUSION: Superficial CPB is an alternative to combined block for MIP.