Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Background: Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca2+ release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.

Methods: Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.

Results: Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 [mu]g/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.     

Induction of anaesthesia with target-controlled inhalation of sevoflurane in adults with the ZEUS anaesthesia machine

Objectives. – To evaluate if the new anaesthesia platform ZEUS^® (Dräger Medical) allows the induction of anaesthesia with target-controlled inhalation of sevoflurane.Study design. – Prospective clinical study.Patients. – Adult ASA I or II patients scheduled for elective surgery under general anaesthesia.Methods. – After preoxygenation during 3 min at 100% oxygen, patients were asked to breathe normally; the target end-tidal concentration of sevoflurane was fixed at 4% without priming of the circuit. Sufentanil (target concentration 0.5 ng/ml) was administered 40 s after.Results. – Ten patients (48 ± 22 yrs) were included. Sevoflurane was detected in the circuit after 36 ± 5 s; the target end-tidal concentration of sevoflurane was obtained at 130 ± 19 s. Loss of consciousness was observed after 119 ± 7 s. The induction was achieved in all patients without any incident.Conclusion. – This new anaesthesia system make available the induction of anaesthesia with sevoflurane without priming of the circuit.     

Previous safe administrations of neuromuscular blocking agents do not exonerate from the risk of anaphylactic shock

We describe a grade IV anaphylactic shock to atracurium. A 34-year-old woman was scheduled for her ninth abdominal surgery. Within the last 10 months, for previous abdominal procedures she had received atracurium, cisatracurium or suxamethonium. No adverse event was reported. In the present case, a cardiac arrest occurred within 1 min after atracurium injection. Anaphylaxis was immediately evoked and treatment started. The diagnosis of anaphylaxis to atracurium was confirmed by the allergological assessment. This case report highlights the fact that patients without any previous adverse events to neuromuscular blocking agents are never exempt from risk of anaphylactic shock, even with a designated low-risk agent of sensitization.     

Mitochondria in anaesthesia and intensive care

Objective

Mitochondria play a key role in energy metabolism within the cell through the oxidative phosphorylation. They are also involved in many cellular processes like apoptosis, calcium signaling or reactive oxygen species production. The objectives of this review are to understand the interactions between mitochondrial metabolism and anaesthetics or different stress situations observed in ICU and to know the clinical implications.

Data sources

References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: mitochondria, anaesthesia, anaesthetics, sepsis, preconditioning, ischaemia, hypoxia.

Data synthesis

Mitochondria act as a pharmacological target for the anaesthetic agents. The effects can be toxic like in the case of the local anaesthetics-induced myotoxicity. On the other hand, beneficial effects are observed in the anaesthetic-induced myocardial preconditioning. Mitochondrial metabolism could be disturbed in many critical situations (sepsis, chronic hypoxia, ischaemia-reperfusion injury). The study of the underlying mechanisms should allow to propose in the future new specific therapeutics.     

Brutal decrease in pulse oxymetry in paediatric anaesthesia: a story of artefact

Pulse oxymetry is frequently used in anaesthesia, notably in paediatric anaesthesia. This device can however present artefacts. We report the case of a sudden decrease in pulse oxymetry during surgical exploration of wound of the face in a child. This was preceded by the injection of patent blue, used for vascular cartography, and interfering with pulse oxymetry. After excluding real oxygen desaturation, this error of measurement has to be confirmed by arterial gazometry. In our case, pulse oxymetry normalized few hours later, without complication.     

XXVIIIe congrès du CREGG, 25–26 septembre 2009, Marne-la-Vallée

Journées du Cregg

XXVIII^e congrès du CREGG, 25–26 septembre 2009, Marne-la-Vallée     

Effects of bupivacaine on mitochondrial energy metabolism in heart of rats following exposure to chronic hypoxia

BACKGROUND: Adaptation to chronic exposure to hypoxia alters energy metabolism in the heart, particularly in the left ventricle, which undergoes a loss in oxidative capacity. Highly lipophilic local anesthetics interfere with mitochondrial energy metabolism. The purpose of this study was to compare the effects of bupivacaine on mitochondrial energy metabolism in heart of rats subjected to normoxic or hypoxic environments. METHODS: Male Wistar rats (n = 10) were subjected to hypobaric hypoxia (simulated altitude = 5,000 m, 380 mmHg) for 2 weeks. Control rats (n = 10) were maintained in an ambient normoxic environment. Mitochondrial metabolism (oxygen consumption and adenosine triphosphate synthesis) was assessed using saponin-skinned ventricular fibers. Bupivacaine (0-5 mM) was tested on both left and right ventricles of normoxic or hypoxic heart. RESULTS: In animals exposed to hypobaric hypoxia for 14 days, cardiac mass significantly increased, and the right-to-left ventricular ratio was approximately twofold (0.48 +/- 0.11 vs. 0.22 +/- 0.04, P < 0.05). Oxygen consumption and adenosine triphosphate synthesis were significantly lower in the hypoxic left ventricles but not in the right ones. The uncoupling effect of bupivacaine was more pronounced in the left ventricle from hypoxic heart than in the right ventricle; the bupivacaine-induced decrease in the adenosine triphosphate synthesis rate and in the adenosine triphosphate-to-oxygen ratio was significantly greater in the hypoxic left ventricle than in the normoxic one. CONCLUSIONS: Chronic hypoxia impairs cardiac energy metabolism in left ventricles and enhances the depressant effects of bupivacaine on mitochondrial functions.