The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid® ( n = 7) with Ringer's acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer's acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.

Incidence of severe local anaesthetic toxicity and adoption of lipid rescue in Finnish anaesthesia departments in 2011-2013.

BACKGROUND: Although the incidence of severe local anaesthetic systemic toxicity (LAST) has been declining, the risk of LAST still remains. There are no national treatment guidelines for LAST in Finland. We performed a national survey of the occurrence of LAST and its treatment in 2011-2013. METHODS: A structured electronic questionnaire was sent to the anaesthesia department chiefs of all Finnish public hospitals (n = 45) in spring 2014. We collected information about the occurrence and outcome of LASTs and existence of treatment protocols. RESULTS: The questionnaire response rate was 100% covering approximately 95% of all regional anaesthesias managed by anaesthesiologists in Finnish hospitals. The total number of regional anaesthesias, excluding spinal anaesthesia, performed by anaesthesiologists was approximately 211,700 during the survey period. Fifteen cases of LAST were reported (0.7 : 10,000); all patients recovered without negative sequelae. Fourteen patients, in five of whom ultrasound guidance had been applied, developed central nervous system toxicity symptoms and only one cardiac symptoms. Lipid emulsion was given to this latter patient, and to four of the other 14. The relative risk (95% confidence intervals) for occurrence of LAST in non-academic hospital vs. university hospitals was 3.3 (1.0-10.3; P = 0.04). Treatment protocols for LAST included lipid emulsion in 47% of the departments. CONCLUSIONS: The incidence of LAST in Finland is very low. Several departments have adopted lipid emulsion treatment for LAST despite lack of national recommendations and knowledge of the possible mechanism of action.

Snorc is a novel cartilage specific small membrane proteoglycan expressed in differentiating and articular chondrocytes.

OBJECTIVE: Maintenance of chondrocyte phenotype is a major issue in prevention of degeneration and repair of articular cartilage. Although the critical pathways in chondrocyte maturation and homeostasis have been revealed, the in-depth understanding is deficient and novel modifying components and interaction partners are still likely to be discovered. Our focus in this study was to characterize a novel cartilage specific gene that was identified in mouse limb cartilage during embryonic development. METHODS: Open access bioinformatics tools and databases were used to characterize the gene, predicted protein and orthologs in vertebrate species. Immunohistochemistry and mRNA expression methodology were used to study tissue specific expression. Fracture callus and limb bud micromass culture were utilized to study the effects of BMP-2 during experimental chondrogenesis. Fusion protein with C-terminal HA-tag was expressed in Cos7 cells, and the cell lysate was studied for putative glycosaminoglycan attachment by digestion with chondroitinase ABC and Western blotting. RESULTS: The predicted molecule is a small, 121 amino acids long type I single-pass transmembrane chondroitin sulfate proteoglycan, that contains ER signal peptide, lumenal/extracellular domain with several threonines/serines prone to O-N-acetylgalactosamine modification, and a cytoplasmic tail with a Yin-Yang site prone to phosphorylation or O-N-acetylglucosamine modification. It is highly conserved in mammals with orthologs in all vertebrate subgroups. Cartilage specific expression was highest in proliferating and prehypertrophic zones during development, and in adult articular cartilage, expression was restricted to the uncalcified zone, including chondrocyte clusters in human osteoarthritic cartilage. Studies with experimental chondrogenesis models demonstrated similar expression profiles with Sox9, Acan and Col2a1 and up-regulation by BMP-2. Based on its cartilage specific expression, the molecule was named Snorc, (Small NOvel Rich in Cartilage). CONCLUSION: A novel cartilage specific molecule was identified which marks the differentiating chondrocytes and adult articular chondrocytes with possible functions associated with development and maintenance of chondrocyte phenotype.

Contribution of muscle relaxant to the haemodynamic course of high-dose fentanyl anaesthesia: a comparison of pancuronium, vecuronium and atracurium.

To define the role of muscle relaxants in haemodynamic responses to high-dose (75 micrograms X kg-1) fentanyl anaesthesia and to noxius stimuli associated with intubation and sternal spread during coronary artery bypass surgery, we compared haemodynamics between three groups of patients given either pancuronium (0.1 mg X kg-1, n = 11), vecuronium (0.086 mg X kg-1, n = 11) or atracurium (0.43 mg X kg-1, n = 12). Additional doses of the relaxants were given to maintain a 90 per cent neuromuscular block. Patients given pancuronium showed no increases in mean values of heart rate, arterial pressure or cardiac output during the induction of anaesthesia or after intubation, whereas a decrease in these variables was observed in the vecuronium group. The haemodynamics in the atracurium group were intermediate compared with the other two study groups. In spite of a decrease in coronary perfusion pressure, no patient given vecuronium developed myocardial ischaemia. An advantage of vecuronium over pancuronium and atracurium was an attenuation of the blood pressure response to sternotomy. Patients given atracurium had a small increase in pulmonary vascular resistance during sternotomy. Our patients continued their beta-adrenergic antagonist medication until the morning of the day of operation and they were pretreated with a small intravenous dose of diazepam (0.1 mg X kg-1) before induction of anaesthesia. These drugs may have prevented the deleterious haemodynamic effects observed by some investigators after the administration of pancuronium during high-dose fentanyl anaesthesia.

Cardiovascular effects of pancuronium and vecuronium during high-dose fentanyl anesthesia.

To define the role of muscle relaxants in hemodynamic responses to high-dose (75 micrograms/kg) fentanyl anesthesia, we compared the circulatory effects of pancuronium (Pc) with those of vecuronium (Vc) in patients about to undergo coronary artery bypass surgery. The first measurements were made while the patients were awake. Thereafter the patients were anesthetized with fentanyl, intubated under succinylcholine relaxation and mechanically ventilated with a mixture of oxygen in air (FIO2 0.50). Ten minutes after completion of the fentanyl injection, the second set of measurements was made. Immediately thereafter, 0.1 mg/kg of either Pc (n = 10) or Vc (n = 10) was given, and no relaxant was administered to 10 control patients. Heart rate (HR) and cardiac index (CI), which had decreased significantly after fentanyl induction, decreased further after Vc, the latter decreases being significantly greater than the decreases in HR and CI observed in control patients. After Pc, HR and CI increased to control awake levels; rate-pressure product also increased and stroke index decreased. Five of ten patients receiving Vc had a HR below 45 beats/min; HRs this low were not seen in patients given Pc. Neither Pc nor Vc affected systemic vascular resistance, but filling pressures of the heart decreased abruptly after both relaxants. We conclude that if maintenance of preanesthetic hemodynamic status is the objective of anesthetic management of patients having coronary artery bypass surgery, Pc helps to achieve this objective during high-dose fentanyl anesthesia. On the other hand, many patients with limited coronary vascular reserve may well benefit from the negative chronotropic effect of Vc.

Attenuation of circulatory response to laryngoscopy and tracheal intubation: a comparison of two methods of topical anaesthesia.

Circulatory responses to laryngoscopy and endotracheal intubation were compared between three groups of patients, two of which were subjected to a procedure of topical anaesthesia before induction of general anaesthesia. Topical anaesthesia, achieved with either a lidocaine dose aerosol or by gargling with viscous lidocaine, attenuated the magnitude of the pressor response to laryngoscopy and intubation but had no effect on the heart rate response. Lidocaine aerosol had some advantages over viscous lidocaine; these were the significantly smaller haemodynamic response to the local anaesthetic procedure itself and probably shorter duration of the circulatory changes produced by intubation. It is concluded that both of these simple methods are relatively ineffective in preventing haemodynamic changes associated with laryngoscopy and intubation and should probably be combined with another preventive method.

Lidocaine concentration in blood after topical anaesthesia of the upper respiratory tract.

The venous blood concentration of lidocaine was determined after stepwise application of lidocaine spray (270 mg) to the upper respiratory tract in 10 patients scheduled for bronchography, and after oropharyngeal application (150 mg) to five intubated patients under general anaesthesia. The peak level of lidocaine (about 1 microgram)ml/occurred 20--30 min after spraying in the bronchography group, while there was a level plateau at about 0.5 microgram/ml after oropharyngeal application of the local anaesthetic. There was great variation in the lidocaine concentration in both groups, but the highest observed concentration, 2.7 micrograms/ml, was safely below the toxic level. The mean rise in systolic and diastolic blood pressures at the various stages of spraying and on passing the bronchography tube in the local anaesthesia patients was 14.5--17.5/6.5--11 mmHg (1.9--2.3/0.9--1.5 kPa) compared to preanaesthetic values. In a similar group of patients, also scheduled for diagnostic bronchography, thiopentone anaesthesia, succinylcholine relaxation and laryngotracheal lidocaine spray resulted in a peak blood pressure increase of 36.5/27 mmHg (4.9/3.6 kPa) on passing the tube. The mean increases in pulse rate (21--26/min) were similar in both bronchography patient groups. No serious cardiac arrhythmias were observed in any of the patients.

Bradycardia during antagonism of pancuronium-induced neuromuscular block.

Heart rate was compared in matched patients during antagonism of neuromuscular block induced by tubocurarine, pancuronium or alcuronium with neostigmine 0.03 mg kg-1 preceded by atropine 0.015 mg kg-1. The frequency of bradycardia was greater during antagonism of pancuronium compared with alcuronium. Although there was a difference between the group receiving pancuronium and that receiving tubocurarine, it was not statistically significant. The decrease in heart rate was more rapid and profound in the pancuronium group; seven of the 15 patients who received pancuronium required an additional dose of atropine as compared with only one patient who received tubocurarine. However, the difference in heart rate between those who received pancuronium and those receiving tubocurarine was short-lasting, whereas the heart rate of those who received alcuronium was higher than that in the other groups during the entire 60-min period of observation. The findings with pancuronium may be a result of its inhibitory effect on serum cholinesterase.