Background Propofol (Disoprivan, AstraZeneca AG, Zug, Switzerland) has long been considered to be nonanalgesic. However, accumulating evidence shows that propofol possesses modulatory action on pain processing and perception. In this study, the authors investigated the modulatory effects of propofol and a formulation similar to the solvent of propofol (10% Intralipid; Fresenius Kabi, Stans, Switzerland) on pain perception and central sensitization in healthy volunteers. Methods Fourteen healthy volunteers were included in this randomized, double-blind, placebo-controlled, crossover study. Intracutaneous electrical stimulation (48.8 +/- 25.8 mA) induced spontaneous acute pain (Numeric Rating Scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia were assessed regularly before, during, and after a 45-min target-controlled infusion (2 microg/ml) of propofol, the solvent 10% Intralipid, and saline. Results During administration, propofol significantly decreased pain scores and areas of hyperalgesia and allodynia compared with both 10% Intralipid and saline (placebo-corrected mean Numerical Rating Scale score reduction by propofol: 38 +/- 28%). This difference disappeared shortly after cessation of the infusion. Thereafter, no significant group differences were observed in the Numerical Rating Scale score and the areas of hyperalgesia or allodynia. However, there was a trend to reduced hyperalgesia and allodynia after propofol treatment. Pharmacodynamic modeling regarding the analgesic effect of propofol showed an EC50 (half-maximum effect site concentration) of 3.19 +/- 0.37 microg/ml. Ten percent Intralipid was free of pain-modulatory effects in the authors' experiments. Conclusions Propofol showed short-lasting analgesic properties during its administration, whereas the solvent-like formulation 10% Intralipid had no effect on pain perception.

Background Potential risks of intrathecal catheters in cancer patients include infection, bleeding, and neurologic injury. Methods A systematic review and a pooled analysis of observational studies were performed. Articles reporting on adverse events (infections, bleeding, granuloma, and death) associated with intrathecal catheters and external pumps in cancer patients were identified. Electronic searches of PubMed, MEDLINE, and EMBASE were conducted. Observations from different studies were pooled using a generalized mixed-effect model. Model estimates and their standard errors (SEs) were used for calculating 95% confidence intervals (CIs) on the overall proportion. Results The analysis identified 10 articles, including a total of 821 patients. Twenty catheter-related infections were identified. Of these, 10 were superficial and 10 were deep infections, with rates of 2.3% (95% CI, 0.8-6.1) and 1.4% (95% CI, 0.5-3.8), respectively. Furthermore, the authors calculated that every 71st patient had a deep infection after an average catheter duration of 54 days. The risk of bleeding was found to be 0.9% (95% CI, 0-2.0), and for neurologic injury 0.4% (95% CI, 0-1.0). The infection rates are comparable to other intrathecal catheter techniques. Conclusions Serious complications are rare in both hospitalized and homebound patients with intrathecal catheters. This analysis supports the reasoning that the potential benefit of intrathecal catheters in the treatment of severe cancer pain is likely to outweigh the potential for serious complications associated with this technique. Therefore, an external intrathecal catheter can be considered an effective and low-cost solution for the control of pain in such patients.

Background Anesthetic choice for patients with chloride channel myotonia remains under debate. The authors have, therefore, investigated the in vitro effects of various anesthetic agents on pharmacologically induced chloride channel myotonia. Methods Functionally viable (> 10 mN force generation) rectus abdominis muscle preparations obtained from normal swine were investigated using in vitro muscle contracture test baths. During continuous 0.1-Hz supramaximal electrical stimulation, the chloride channel blocker 9-anthracenecarboxylic acid (64 microM) was added before the addition of propofol or one of three volatile anesthetics. The concentration of propofol in either Intralipid (n = 11) or dimethyl sulfoxide (n = 10) was doubled every 10 min (from 4-512 microM). The concentration of halothane (n = 8), isoflurane (n = 8), and sevoflurane (n = 8) was doubled from 0.25 vol% up to the maximum dose according to calibrated vaporizers. Control muscle bundles were either untreated (n = 30) or exposed to 9-anthracenecarboxylic acid (n = 19). Results The myotonic reactions induced by 9-anthracenecarboxylic acid were reversed by high-dose (> 64 microM) propofol (P < 0.01). Halothane, isoflurane, or sevoflurane each enhanced the myotonic reactions at 5.4 (P < 0.001), 0.21 (P < 0.01), and 0.5 minimum alveolar concentrations (P < 0.05), respectively. Conclusions The authors' in vitro data imply that propofol administration for general anesthesia may be better suited for patients with chloride channel myotonia versus volatile anesthetics. In isolated swine skeletal muscle bundles, propofol elicited a reversal of 9-anthracenecarboxylic acid-induced chloride channel myotonia, whereas volatile anesthetics further increased the associated myotonic reactions.

Background Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block. Methods Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition). Results Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes. Conclusions Variations in the genetic sequence of butyrylcholinesterase are frequent in patients with prolonged duration of action of succinylcholine. Direct sequencing of the whole butyrylcholinesterase gene is an appropriate method for genotyping and, accordingly, should be used in future clinical studies with drugs metabolized by this enzyme (e.g., succinylcholine, mivacurium).

Background For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients. Methods The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion. Results Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation. Conclusions In families with known MH mutations, there is a 50% chance of reliably confirming MH susceptibility by noninvasive testing. The authors found the negative predictive value of genetic testing to be 0.95 (95% confidence interval, 0.75-0.99), but for patient safety, they still recommend following the guidelines for genetic testing in MH and therefore performing an IVCT in case of negative genetic results.

Background Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics or succinylcholine. The disorder is heterogenetic and caused by abnormal calcium regulation within skeletal muscle cells. No clear metabolic differences have been found in MH-susceptible (MHS) persons in vivo while not having MH episodes, but some reported signs suggest that insulin action and energy turnover might be altered in muscle of MHS persons. Methods In fasting and insulin-stimulated conditions, using the glucose clamp technique and indirect calorimetry, we assessed in vivo resting energy expenditure (REE) and nutrient utilization rates in 10 MHS, 5 MH-equivocal (MHE) and 10 MH-negative (MHN) persons from 14 families. With a model using the persons' fat-free mass, fat mass, age, and gender, we calculated their predicted REE and compared it with measured REE in 10 MHS and 10 MHN persons (measured - predicted = residual REE). Results In vivo measured REE and glucose disposal rates were similar in 10 MHS and 10 MHN persons. Only during insulin stimulation was residual REE greater in MHS persons (6.4%; P = 0. 013). Conclusions In vivo insulin action is unimpaired in MHS persons. Although the absolute values of whole-body REE are the same in MHS and MHN persons, the part of REE independent of the determinants fat-free mass, fat mass, age, and gender is moderately greater in MHS than in MHN persons during insulin exposure. This suggests that MH susceptibility might influence insulin-stimulated energy turnover in muscle.