Effects of ropivacaine, bupivacaine and sufentanil in colon and pancreatic cancer cells in vitro.

The perioperative period is supposed to be a vulnerable period for cancer progression. Results of clinical studies indicate that the use of regional anesthesia can influence and improve oncological outcome of cancer patients. Uncontrolled cell proliferation and resistance to apoptotic cell death are important characteristics of solid tumors. The aim of this study was to investigate the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon (HT 29 and SW 480) and pancreatic (PaTu 8988t and PANC 1) cancer cell lines in vitro. Cell proliferation was measured by Cell Proliferation ELISA BrdU Assay. Apoptosis was analyzed by annexin V staining and cell cycle distribution was detected by flow cytometry. Ropivacaine, bupivacaine and sufentanil did not change apoptosis rate and cell cycle distribution in clinically concentration. Only high concentrations of ropivacaine or bupivacaine revealed antiproliferative potency. Protective effects of epidural anesthesia observed in clinical studies seem not to be based on direct effects of these drugs on cancer cells.

Magnesium-induced recurarisation after reversal of rocuronium-induced neuromuscular block with sugammadex.

A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 µg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a sugammadex-reversed, rocuronium-induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex--particularly in combination with magnesium injection--to prevent post-operative residual curarisation.

[Malignant hyperthermia]. / Maligne Hyperthermie.

Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.

Ultrasound guidance for neuraxial analgesia and anesthesia in obstetrics: a quantitative systematic review.

PURPOSE: The aim of this quantitative systematic review was to assess the efficacy and safety of ultrasound-guided neuraxial blocks in obstetric analgesia and anesthesia. MATERIALS AND METHODS: A systematic search for clinical trials investigating the efficacy and safety of ultrasound-assisted neuraxial blocks in comparison to any other technique was performed in MEDLINE, EMBASE, CINAHL and CENTRAL. Relative risks (RR) were calculated for dichotomous data (e. g. number of patients with vascular punctures), and mean differences (MD) were calculated for continuous outcomes (e. g. number puncture attempts), along with the respective 95 % confidence intervals (95 % CI). RESULTS: Six clinical trials (published between 2001 and 2009) including the data of 659 patients satisfied the inclusion criteria. Ultrasound-facilitated neuraxial blocks required a lower number of puncture attempts (MD: -0.92; 95 % CI: -1.11 to -0.74; p < 0.00001) and fewer puncture levels (MD: -0.2; 95 % CI: -0.31 to -0.1; p = 0.0002) in comparison with the more conventional loss of resistance. The success rate with the first attempt under ultrasound guidance in supposedly difficult patients was 71 % in comparison to 20 % using a conventional technique. Patients receiving ultrasound-assisted neuraxial blocks had a lower rate of procedure-related complications (post-dural puncture headache, spinal or vascular puncture). CONCLUSION: There is some evidence that ultrasound guidance may improve the efficacy and safety of neuraxial blocks in obstetrics. If technical difficulties are anticipated, ultrasound may lower the rate of procedure-related adverse events.

Sevoflurane as a potential replacement for halothane in diagnostic testing for malignant hyperthermia susceptibility: results of a preliminary study.

BACKGROUND: To diagnose malignant hyperthermia (MH) susceptibility, muscle bundles are exposed to halothane and caffeine. We investigated whether sevoflurane, which is more clinically relevant but less potent of an anesthetic, could replace halothane in diagnostic MH testing. METHODS: With prior written consent, muscle bundles from 6 malignant hyperthermia susceptible (MHS) and 5 non-susceptible (MHN) individuals were exposed to increasing concentrations of sevoflurane (1.3; 2.6; 5.2 vol%). In addition, muscles from 9 MHS and 8 MHN were tested with a rapid exposure to 8 vol% of sevoflurane. Maximal contractures were measured and statistically analyzed (Mann-Whitney-U-test; P<0.05). RESULTS: There were no differences in weight, length or pre-drug tension of the muscle bundles. Incremental sevoflurane concentrations induced no differences in contracture between susceptible and non-susceptible muscles. The rapid application of sevoflurane induced significant contractures in all malignant hyperthermia susceptible compared with non-susceptible individuals. CONCLUSION: The rapid application of a high sevoflurane concentration but not an increasing stepwise application allowed for the diagnostic discrimination of susceptible individuals.

Emergency cricothyrotomy in infants--evaluation of a novel device in an animal model.

BACKGROUND: According to different algorithms of airway management, emergency cricothyrotomy is the final step in managing an otherwise not accessible airway. As an alternative to an open surgical procedure, minimally invasive approaches exist. Quicktrach baby™ is a commercially available set for a minimal invasive cricothyrotomy in infants. The set consists of a plastic cannula over a metal needle for direct placement in the trachea. So far, this device has not been evaluated for its intended use. OBJECTIVES: We hypothesize that Quicktrach baby™ allows the establishment of an emergency airway. The aim was to prove that the device is easy to handle and the cricothyrotomy fast to perform. METHODS: After approval of the local ethics committee, the study was performed on the cadavers of 10 adult rabbits. Cricothyrotomy was performed with Quicktrach baby™. Successful placement, performance time, and complication rate were documented. Possible ventilation with a breathing bag was evaluated. Data are reported as mean and interquartile range. RESULTS: Successful placement of Quicktrach baby™ was possible in all attempts. The placement took 31 [23-43] s. In two cases, a fracture of the cricoid's cartilage was seen. In one animal, damage to the posterior wall mucosa was observed. In all cases, sufficient ventilation was possible. CONCLUSIONS: Quicktrach™ baby proved to be a reliable technique. In the animal model, it is easy and fast to perform. Only a few minor complications occurred. Sufficient ventilation was possible in all attempts.

Statins alter intracellular calcium homeostasis in malignant hyperthermia susceptible individuals.

AIMS: Statines, HMG-CoA reductase inhibitors, are widely used to treat hypercholesterinemia. These substances are well tolerated, but myotoxic effects have been reported. The exact mechanisms of the induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. Individuals susceptible to malignant hyperthermia (MH) have an impaired calcium homeostasis. An in vitro test measuring contracture responses of isolated muscle bundles is used to investigate cellular processes of MH. Aim of this study was to investigate if statins modify the contracture response of isolated muscle bundles from MH susceptible (MHS) and nonsusceptible (MHN) pigs. METHODOLOGY: With approval of the local ethics committee muscle biopsies of 18 MH susceptible and 12 nonsusceptible pigs were performed. Muscle bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After establishment of a stable baseline, muscle bundles were exposed to simvastatin, atorvastatin, gemfibrocil, and the pure solvent. Baseline tension was measured and analyzed for changes with P < 0.05 considered to be significant. RESULTS: There were no differences in weight, length, and predrug baseline tension between the groups. Both simvastatin and atorvastatin induced significant contractures in muscle bundles from MHS pigs. Gemfibrocil and the solvent methanol showed no effect. In MHN muscle bundles, none of the tested substances induced a contracture. Statines induce contractures only in MHS muscle bundles. CONCLUSION: We therefore conclude that the underlying mechanism may be a pathologic influence on intracellular calcium handling that is absent in MHN. A preexisting impairment of the calcium homeostasis seems to be necessary for this behavior because muscle bundles of MHN pigs showed no pathologic reaction. A higher muscle cell vulnerability toward statins is assumed in MHS patients. Statins ought to be used with caution in these individuals. Analogous a diagnostic workup for MH should be considered for patients with statin-induced rhabdomyolyis.

Coma after spinal anaesthesia in a patient with an unknown intracerebral tumour.

Spinal anaesthesia is contraindicated in patients with elevated intracranial pressure or space-occupying intracranial lesions. Drainage of the lumbar cerebrospinal fluid (CSF) can increase the pressure gradient between the spinal, supratentorial and infratentorial compartments. This can result in rapid herniation of the brain stem or occluding hydrocephalus. We present a case of a female patient with an occult brain tumour who received a spinal anaesthesia for an orthopaedic procedure. The primary course of anaesthesia was uneventful. Several hours after surgery, the patient became increasingly disoriented and agitated. The next day, she was found comatose. A computed tomogram of the head revealed herniation of the brain stem, resulting in an occluding hydrocephalus due to a prior not known infratentorial mass. By acute relieving of the intracranial pressure by external CSF drainage, the mass was removed 2 days later. The further post-operative course was uneventful and the patient was discharged from the hospital without neurological deficit 3 weeks after the primary surgery.

[In-vivo diagnosis of malignant hyperthermia susceptibility: a microdialysis study]. / In-vivo-Diagnostik einer malignen-Hyperthermie-Disposition: Eine Mikrodialysestudie.

BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.

A minimally invasive metabolic test with intramuscular injection of halothane 5 and 6 vol% to detect probands at risk for malignant hyperthermia.

We hypothesised that intramuscular halothane injection increases local Pco(2) concentrations in malignant hyperthermia susceptible (MHS) but not in non-susceptible (MHN) individuals. Pco(2) probes with attached microtubing catheters for halothane injection were placed into the lateral vastus muscle of eight MHS and eight MHN probands. Following equilibration, a single bolus of 200 microl halothane 5 and 6 vol% was injected. Pco(2) was measured spectrophotometrically. Baseline Pco(2) concentrations were similar between groups. Maximum Pco(2) and maximum rate of Pco(2) increase was significantly enhanced by halothane 5 and 6 vol% in MHS compared to MHN probands. Systemic haemodynamic and metabolic parameters did not differ between both groups. Local halothane application induces a hypermetabolic reaction with a significant Pco(2) increase in MHS compared to MHN probands, indicating a susceptibility to malignant hyperthermia. Intramuscular halothane injection with Pco(2) measurement seems to be a suitable method for the development of a minimally invasive metabolic test to diagnose malignant hyperthermia susceptibility.