Shortening of the twitch stabilization period by tetanic stimulation in acceleromyography in infants, children and young adults (STSTS-Study): a prospective randomised, controlled trial.

Acceleromyography is characterised by an increase of the twitch response T1 (first twitch of the train-of-four [TOF]) during first 30 min of monitoring known as the staircase phenomenon. In adults the staircase phenomenon can be avoided by tetanic prestimulation. This study examined, if tetanic prestimulation eliminates the staircase phenomenon in children. After written informed consent, the neuromuscular function of 80 children, 10 in each age group (< 6 months, 6-12 months, 12-24 months, 2-3 years, 3-6 years, 6-12 years, 12-18 years, and ≥ 18 years) was measured on both arms simultaneously over 30 min under general anaesthesia. The ulnaris nerve was stimulated using the TOF technique every 15 s. The twitch response (T1, TOF ratio [TOFR]) was measured by acceleromyography. Before calibration, tetanic prestimmulation (50 Hz for 5 s) was administered to one randomly selected arm. The effect of tetanic prestimulation and age was analysed using general linear models based on the normalized T1 and TOFRs of both arms. Tetanic prestimulation significantly affected T1 values avoiding the staircase phenomenon (p < 0.0001). After 5.8 min [1.0-17.2 min] the normalized T1 values increased to 117% [102-147%] without prestimulation (p < 0.0001) independent of the age group (p = 0.539). The normalized TOFR was stable throughout the observation period of 30 min 100% [95-107%]. Infants (> 12 weeks), children, and young adults (< 18 years) develop similar characteristics of the staircase phenomenon than adults. Tetanic prestimulation prevents the staircase phenomenon in these age groups. The stability of the TOFR reading confirms its value to monitor neuromuscular function over time.Registration: The study was registered as NCT02552875 on Clinical Trials.gov on July 29, 2014.

Influence of early elective tracheostomy on the incidence of postoperative complications in patients undergoing head and neck surgery.

BACKGROUND: The incidence of postoperative complications after head and neck surgery is high. This study evaluated the influence of early elective tracheostomy on the incidence of postoperative pneumonia and delirium. METHODS: We reviewed the data of all patients who had undergone removal of an oropharyngeal tumor and microsurgical tissue transfer at our department in a two year period. Pearson's Chi-squared test and the Fischer's exact t-test were then used to measure the influence of patients' preexisting conditions and risk factors and of early elective tracheostomy on the incidence of postoperative complications. RESULTS: In total, 47 cases were analyzed. Patients with an endotracheal tube were ventilated for a longer time (3.4 days vs. 1.5 days) and were transferred to the regular ward later (after 6.9 days vs. 4.7 days) than patients with tracheostomy. Only 1 (2.1%) of the patients with a tracheostomy developed pneumonia in contrast to 5 intubated patients (10.6%) and only 2 patients with a tracheostomy developed postoperative delirium (9.5%) in contrast to 8 intubated patients (30.8%). CONCLUSION: Early primary tracheostomy in patients undergoing resection of oropharyngeal cancer seems to have numerous benefits, such as lower complication rates with regard to pneumonia and postoperative delirium and shorter duration of both mechanical ventilation and intensive care unit (ICU) stays. Further studies have to evaluate if these benefits also influence morbidity and mortality rates.

Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro.

BACKGROUND: Local anesthetics, especially bupivacaine, have myotoxic effects in clinically used concentrations and context. Detailed mechanisms of these effects are unknown, but an increase in intracellular calcium levels is suspected to be the most important trigger. Dantrolene and caffeine modify cellular calcium release from the sarcoplasmic reticulum. The aim of our study was to investigate the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in vitro. METHODS: A cell culture model of primary muscle cells of BALB/c AnNCrl mice was established. Cells were incubated simultaneously with increasing concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead cells was calculated after staining with propidium iodide and analysis by flow cytometry. The half-maximal inhibitory concentration of bupivacaine was calculated for each concentration. Group differences were determined by using 1-way analysis of variances with subsequent post hoc 1-way Dunnett t test. RESULTS: Both dantrolene and caffeine alone had no effect on muscle cell survival. Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose-dependently increased the fraction of dead cells. CONCLUSIONS: Dantrolene attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by modifying sarcoplasmic calcium release. This indicates that intracellular calcium release is an important factor for local anesthetic-induced cell death.

In vitro myotoxic effects of bupivacaine on rhabdomyosarcoma cells, immortalized and primary muscle cells.

BACKGROUND: Rhabdomyosarcoma is a rare malignant skeletal muscle tumor. It mainly occurs in children and young adults and has an unsatisfactory prognosis. Prior studies showed a direct myotoxic effect of bupivacaine on differentiated muscle cells in vitro and in vivo. Exact mechanisms of this myotoxicity are still not fully understood, but a myotoxic effect on malignant muscle tumor cells has not been examined so far. Thus, the aim of this study was to examine if bupivacaine has cytotoxic effects on rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells. METHODS: Cell lines of rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells were established. After microscopic identification, cells were exposed to various concentrations of bupivacaine (500, 1,000, 1,750, 2,500 and 5,000 ppm) for 1 and 2 h, respectively. 24 and 28 h after incubation the cultures were stained with propidium iodid and analyzed by flow cytometry. The fraction of dead cells was calculated for each experiment and the concentration with 50% cell survival (IC50) was computed. Cell groups as well as incubation and recovery time were compared (ANOVA/Bonferroni p < 0.01). RESULTS: The total number of cultured cells was similar for the different local anesthetics and examined concentrations. Increasing concentrations of bupivacaine led to a decrease in survival of muscle cells. IC50 was highest for immortalized cells, followed by rhabdomyosarcoma cells and differentiated cells. Exposure time, but not recovery time, had an influence on survival. CONCLUSION: Bupivacaine has clear but different cytotoxic effects on various muscle cell types in vitro. Differentiated primary cells seem to be more vulnerable than tumor cells possibly because of more differentiated intracellular structures.

Effect of caffeine on intrinsic mechanical properties of normal and malignant hyperthermia-susceptible muscle.

INTRODUCTION: Malignant hyperthermia (MH) is a potentially lethal anesthesic complication. Pathological symptoms develop after exposure to triggering substances. It remains uncertain whether cellular alterations pre-exist. Mechanical properties of isolated muscle bundles were examined before and after exposure to a triggering substance. METHODS: With prior written consent, muscle bundles of 12 MH-susceptible (MHS) and 56 MH-nonsusceptible (MHN) individuals were examined before and after exposure to incremental doses of caffeine. Mechanical properties (baseline tension, peak tension, time to peak tension, and relaxation time) were measured. Contraction and relaxation derivatives and contraction-relaxation coupling were calculated and analyzed. RESULTS: Mechanical properties were not different between the groups before caffeine application. Caffeine increased peak tension in both groups and baseline tension only in MHS muscle bundles; relaxation time/derivative and contraction-relaxation coupling were prolonged. CONCLUSIONS: Cellular changes seen in MH are not pre-existing. Exposure to triggering substance impairs relaxation in MHS muscle.

Subsyndromal delirium after cardiac surgery.

OBJECTIVES: To evaluate the incidence of subsyndromal delirium (SSD) after cardiac surgery and its impact on clinical outcome. DESIGN: In this prospective study, 506 patients were screened for SSD and clinical delirium (CD) using the Intensive Care Delirium Screening Checklist. RESULTS: 150 (34%) patients were classified as having SSD and 54 (12%) patients as having CD. 2% of SSD patients developed CD. Patients' age, EuroSCORE, postoperative the Acute Physiology and Chronic Health Evaluation II, the incidences of emergency operations, and the number of aortic surgery increased from non-delirious (ND) to SSD. Intensive care unit (ICU) and hospital stays were longer in CD compared with SSD patients. ND patients did not differ from SSD patients regarding duration of ventilation, ICU stay, or hospital stay. The rate of home discharge decreased from ND over SSD to CD patients. Mortality in SSD patients did not differ from ND or CD patients. CONCLUSION: SSD showed a prevalence of 34% in patients after cardiac surgery. SSD occurred independent of CD for the majority of patients. Except for a lower rate of home discharge, the clinical outcome did not differ from that of ND patients. According to our data, SSD does not represent a preliminary or resolving stage of delirium.

The effect of succinylcholine on malignant hyperthermia events in susceptible swine.

BACKGROUND: While the impact of volatile anaesthetics to induce malignant hyperthermia (MH) is abundantly clear, the role of succinylcholine still remains controversial. To evaluate the influence of succinylcholine on porcine MH events, the authors investigated the hemodynamic and metabolic responses in MH susceptible (MHS) and non-susceptible (MHN) swine following either succinylcholine or halothane application alone or a combination of both substances. METHODS: With approval of the local animal care committee 27 MHS and 30 MHN pigs were anaesthetized and mechanically ventilated. Fiberoptic probes for continuous PCO2 measurement were inserted into the femoral vein and the triceps muscle. Group A received succinylcholine 4 mg/kg, group B incremental doses of halothane (0.5, 1.0 vol%) and group C succinylcholine and halothane simultaneously. Vital signs were recorded continuously. RESULTS: Prior to drug application measured values did not differ between MHS and MHN. While MHN pigs did not show relevant alterations, succinylcholine, halothane and the combination of both lead to significant hemodynamic and metabolic changes in MHS swine. CONCLUSIONS: Hemodynamic and metabolic alterations following succinylcholine were similar to halothane in MHS pigs. The combination of both pharmacological agents potentiated the observed effects. According to these results succinylcholine acted as an independent and supportive factor during onset of an MH episode.

Screening test for malignant hyperthermia in patients with persistent hyperCKemia: a pilot study.

INTRODUCTION: Persistently elevated serum creatine kinase (CK) is frequently associated with predisposition to malignant hyperthermia (MH). We investigated whether a minimally invasive metabolic test is suitable to diagnose MH susceptibility among patients with hyperCKemia. METHODS: Thirty-nine participants were included: 10 were MH susceptible (MHS); 21 MH were non-susceptible (MHN); and 8 had MHN with persistent hyperCKemia >500 U/L. Microdialysis probes were inserted into the vastus lateralis muscle, and halothane or caffeine was injected via an attached microtubing catheter. Lactate concentrations in dialysis samples were measured spectrophotometrically. RESULTS: Baseline lactate did not differ between the groups. After local application of halothane or caffeine, a significant lactate increase was detected only in the MHS group. CONCLUSIONS: Test results were not influenced by hyperCKemia. To avoid risks and complications of a surgical muscle biopsy this microdialysis test might be a useful screening tool for MH susceptibility among patients with persistent CK elevation.

The myotoxic effect of bupivacaine and ropivacaine on myotubes in primary mouse cell culture and an immortalized cell line.

BACKGROUND: The 2 local anesthetics (LAs) bupivacaine and ropivacaine have acute cytotoxic effects on different tissues. In this respect, LA-induced myotoxicity has been subject to various studies; however, the exact mechanisms are still not fully understood. Most in vitro studies use immortalized cell lines because of feasibility. Thus, establishing a primary cell line might result in more accurate results. In this study, we examined the effects of immortalization on bupivacaine- and ropivacaine-induced myotoxicity in vitro. METHODS: An immortalized (N = 6) and a primary cell line (N = 8) of the same tissue and species were established, and differentiation in myotubes was induced. Cells were exposed to increasing concentrations of bupivacaine and ropivacaine for 1 or 2 hours, respectively. Twenty-four and 48 hours after treatment, the fractions of dead and vital cells were measured using flow cytometry. Significance was tested through 1-way analysis of variance with post hoc Dunnett T3 test. Medians of dataset pairs were compared by T test. RESULTS: In both cell lines, increasing concentrations of both LAs resulted in decreased cell survival (e.g., P < 0.001 for 5000 ppm bupivacaine, 1 or 2 hours of incubation, and 24 hours recovery in both cell lines). For the same LA concentrations, survival was significantly higher in the immortalized cell culture (e.g., P < 0.001 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). In addition, equal concentrations of bupivacaine resulted in significantly fewer vital cells compared with ropivacaine (e.g., P = 0.032 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). Two hours of incubation resulted in a significantly higher rate of dead cells compared with 1 hour of incubation (e.g., P = 0.004 for C2C12 cells, 2500 ppm bupivacaine, and 24 hours recovery). CONCLUSIONS: Primary skeletal muscle cells are more vulnerable to LAs than immortalized cells. The higher myotoxic potential of bupivacaine compared with ropivacaine in vivo can be reproduced in vitro. Incubation time has an influence on cell survival.

Succinylcholine in malignant hyperthermia: evaluation of a novel in vivo model.

INTRODUCTION: Malignant hyperthermia (MH) is a potentially lethal anesthetic complication characterized by muscle hypermetabolism and generalized rigor. The exact mechanism of succinylcholine as an MH trigger cannot be examined in existing in vitro models. Therefore, a novel in vivo model was used to examine the metabolic response to succinylcholine. METHODS: With institutional review board approval, 6 MH susceptible (MHS) and 6 MH non-susceptible (MHN) pigs were anesthetized with hemodynamic and systemic metabolic monitoring. Microdialysis catheters were placed intramuscularly. After equilibration, succinylcholine, halothane, and Ringer solution were injected. Lactate was measured in the dialysate and statistically analyzed by Mann-Whitney U-test (significance level P < 0.05). RESULTS: Hemodynamic and systemic metabolic parameters were not different between the groups throughout the experiment. In the MHS pigs, halothane induced a significant increase of lactate. In MHN pigs, no substance induced a reaction. CONCLUSIONS: Halothane, but not succinylcholine, induced a hypermetabolic reaction in this model. Therefore, the role of succinylcholine as an MH trigger remains questionable.

Fluoroquinolones influence the intracellular calcium handling in individuals susceptible to malignant hyperthermia.

INTRODUCTION: The mechanisms of fluoroquinolone-induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. An in vitro contracture test used to investigate cellular processes in malignant hyperthermia (MH) can be applied to study the effects of fluoroquinolones. METHODS: With approval of the local ethics committee, muscle biopsies of 18 MH susceptible (MHS) and 12 MHS non-susceptible (MHN) pigs were performed. Individual bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After equilibration they were exposed to ciprofloxacin or levofloxacin. The measured baseline tension was analyzed (Wilcoxon test: P < 0.05). RESULTS: There were no differences in weight, length, or predrug tension between the groups. Both levofloxacin an ciprofloxacin induced significant contractures in MHS muscle bundles but not in MHN. CONCLUSIONS: Fluoroquinolones appear to have a pathological influence on intracellular calcium handling. A pre-existing impairment of the calcium homeostasis, however, seems to be necessary for this behavior.

Magnesium does not influence the clinical course of succinylcholine-induced malignant hyperthermia.

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal hypermetabolic syndrome. Volatile anesthetics and/or succinylcholine lead to an increase of the intracellular calcium concentration resulting in activation of various intracellular processes. A production of carbon dioxide, and later lactate, are early signs of increased cellular energy consumption. On a cellular level, magnesium acts as a physiological calcium inhibitor resulting in less-intense calcium liberation from the sarcoplasmic reticulum. In this study, we examined the effects of IV magnesium administration on the clinical course of an MH crisis. METHODS: Sixteen Pietrain pigs (10 MH-susceptible [MHS] and 6 MH-nonsusceptible [MHN]) were anesthetized without an MH trigger substance. Invasive hemodynamic monitoring was established before 4 mg/kg succinylcholine was administered. Four of the MHS pigs received 10 mg/kg magnesium sulfate 10 minutes later. Hemodynamic changes (heart rate, mean arterial blood pressure, and oxygen saturation as measured by pulse oximetry) were continuously monitored. Venous and arterial blood gases (pH, Pco(2), Po(2), base excess, and lactate) were taken at 15-minute intervals. The H test and U test were used with P < 0.05 for significant differences among the groups. RESULTS: No differences among the groups were seen for weight, hemodynamic, and metabolic variables before administration of succinylcholine. In all MHS animals, succinylcholine led to a marked decrease of mean arterial blood pressure and increase of heart rate. Animals in both MHS groups developed combined metabolic and respiratory acidosis. Succinylcholine had no effect on animals in the MHN group. Hemodynamic and metabolic values were not different between the 2 MHS groups but were between groups MHS and MHN. CONCLUSION: Succinylcholine led to a hemodynamic and metabolic reaction in only MHS pigs. Treatment with magnesium did not influence the clinical course. The intervention had no beneficial effect in the acute phase of an MH crisis.

In-vitro contracture testing for susceptibility to malignant hyperthermia: can halothane be replaced?

BACKGROUND: Malignant hyperthermia is a potentially lethal inherited hypermetabolic syndrome that develops in susceptible individuals following administration of depolarising neuromuscular relaxants or volatile anaesthetics. Genetic analysis can only confirm a diagnosis of malignant hyperthermia in about 70%, and in the remainder an in-vitro contracture test, with halothane and caffeine, on muscle obtained from open muscle biopsy is required to establish the diagnosis. As the licence for clinical use of halothane expired in 2005, its continuing availability is in doubt. More modern volatile anaesthetics such as enflurane, isoflurane, desflurane and sevoflurane are less potent triggers of malignant hyperthermia in humans and pigs. The aim of this study was to investigate whether these agents can be considered possible substitutes for halothane in a modified in-vitro contracture test. METHOD: With institutional review board approval and prior written consent, muscle bundles of 30 patients with a personal or family history of malignant hyperthermia were investigated. Of these, 13 were diagnosed malignant hyperthermia susceptible and 17 nonsusceptible. Surplus muscle was tested with increasing concentrations of enflurane, isoflurane, desflurane and sevoflurane. RESULTS: There were no differences in weight, length or predrug tension of the muscle bundles. At increasing concentration, all volatile anaesthetics except sevoflurane induced significantly greater contractures in malignant hyperthermia susceptible compared to malignant hyperthermia nonsusceptible muscle. In malignant hyperthermia susceptible muscle bundles, halothane led to significantly higher contractures compared to the other investigated substances. CONCLUSION: Halothane was the strongest discriminator for malignant hyperthermia in the in-vitro contracture tests. It remains the ideal substance for diagnostic testing and cannot simply be replaced by other agents in this test.

A randomized trial comparing two cuffed emergency cricothyrotomy devices using a wire-guided and a catheter-over-needle technique.

BACKGROUND: According to different algorithms of airway management, emergency cricothyrotomy is the final step in managing the otherwise inaccessible airway. As an alternative to an open surgical procedure, minimally invasive approaches exist. Various sets for different methods are commercially available. QuickTrach™ (VBM Medizintechnik GmbH, Sulz am Neckar, Germany) contains a plastic cannula over a metal needle for direct placement in the trachea, whereas a guide-wire is used for the actual placement of the cannula in the Melker Set™ (Cook Group Incorporated, Bloomington, IN). OBJECTIVE: We hypothesize that the direct puncture involving less discrete steps is faster to perform. However, it will lead to more complications due to the higher force needed to place the relatively thick needle. METHOD: After approval of the local ethics committee, the study was performed on cadavers of 16 adult sheep. A wire-guided cricothyrotomy was compared with a catheter-over-needle technique. Successful placement and performance time were compared. Complication rate and maximal achieved airway pressure were evaluated. Data is given as mean and interquartile range, and Mann-Whitney U-test (p < 0.05) for significant differences. RESULTS: With the wire-guided technique, successful placement was possible in all attempts. The catheter-over-needle method was successful in 63% and had a higher complication rate (75% vs. 13%). The cannula-over-needle method allowed a faster cricothyrotomy (32 [2-34] vs. 53 [52-56] s). Both methods allowed the delivery of similar maximal airway pressures (50 [44-51] vs. 48 [43-53] mbar). CONCLUSION: The wire-guided method proved to be the more reliable technique, leading to fewer complications. However, the direct puncture was faster to perform. Placed accurately, both devices allowed sufficient ventilation.

Influencing factors of early cognitive deficits after ambulatory anesthesia.

BACKGROUND: Anesthesia has an influence on early postoperative cognitive function. This is specifically relevant in ambulatory surgery. At discharge, patients must return to their normal life and manage simple tasks. Goal was to detect influencing factors of early postoperative cognitive dysfunction after ambulatory anesthesia. METHODS: With approval of the local ethics committee, 102 individuals scheduled for ambulatory anesthesia were examined with a specific test battery. Cued and uncued reaction time, divided and selective attention were tested prior to anesthesia and at the time of discharge. Differences between the two examinations and potential influencing factors including age, premedication, type and duration of anesthesia were evaluated with the Student t-test and linear regression. P < 0.05 considered significant. RESULTS: In all, 86 individuals completed the study. Both reaction times were reduced after anesthesia compared to before. No differences were seen for divided and selective attention. Age influenced on the post-anesthesia reaction time while all other factors did not. CONCLUSION: Reaction time but not attention as more complex cognitive function is influenced by anesthesia. Age seems to be an important factor in early postoperative cognitive dysfunction.

Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome.

INTRODUCTION: Local anesthetics (LAs) are frequently used during anesthesia; however, they may influence granulocyte function which in turn could modify immune responses in the perioperative period. Therefore, the aim of this study was to investigate the impact of clinically used doses of bupivacaine and lidocaine on granulocyte function with regard to migration, reactive oxygen species (ROS) production, neutrophil extracellular traps (NETosis) formation, and viability. METHODS: A total of 38 granulocyte-enriched samples from healthy subjects were obtained by whole blood lysis. Polymorphonuclear neutrophil (PMN) samples were incubated simultaneously with different concentrations of either bupivacaine (0.03-3.16 mmol/L) or lidocaine (0.007-14.21 mmol/L), or without drug (control). Live cell imaging was conducted in order to observe granulocyte chemotaxis, migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression. RESULTS: The track length (TL) of PMNs exposed to bupivacaine concentrations of 0.16 mmol/L and above significantly decreased compared to the control. Low concentrations of lidocaine were associated with slight but significant increases in TL, whereas this changed with concentrations above 1.4 mmol/L, showing a significant decrease in TL. PMN incubated with bupivacaine concentrations of 1.58 mmol/L and above or lidocaine concentrations of at least 3.6 mmol/L showed no migration or chemotaxis at all. Time to onset of maximal ROS production and time for half-maximal NETosis decreased in a dose-dependent manner for both substances. Equipotency in NETosis induction was reached by bupivacaine (1.1 mmol/L) at significantly lower concentrations than lidocaine (7.96 mmol/L). Cell viability and oxidative burst were unaffected by LAs. CONCLUSION: Local anesthetics in clinically used doses ameliorate granulocyte defense mechanisms, thus indicating their potentially decisive effect during the perioperative period.

Effectiveness of pre-anesthetic video information on patient anxiety and economical aspects.

BACKGROUND: Adequate preoperative information can lessen patient anxiety. Delivering sufficient information during a personal interview, however, is time consuming, and therefore a relevant economical aspect. We investigated whether video information given to the patient before the pre-anesthetic interview has an influence on the patient's anxiety and the duration of the interview. METHOD: We randomized 302 patients undergoing different types of anesthesia. In all, 151 patients watched a short video with general information about the anticipated anesthesia procedure. Afterward, all patients had a standard pre-anesthetic interview. Patients' anxiety and satisfaction with pre-anesthesia care were assessed after the interview using a visual analogue scale. The duration of the interview was documented. Student t-test and P < 0.05 for differences between the groups. RESULTS: There was no difference in gender, age, ASA physical status, previous anesthesia experience, and the planned anesthesia procedure between the two groups. No difference in anxiety and satisfaction with pre-anesthesia care was observed. The duration of the pre-anesthetic interview was also not different between the groups. DISCUSSION: Preoperative multimedia information did not reduce anxiety or increase the patient satisfaction undergoing anesthesia. The video containing general information did not save time in the pre-anesthetic interview.

Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model.

BACKGROUND: Sepsis is a leading cause of morbidity and mortality worldwide. Many patients suffering from sepsis are treated on intensive care units and many of them require mechanical ventilation under sedation or general anesthesia. Propofol, a drug used for these purposes, is known to interact with polymorphonuclear granulocytes (PMNs). Therefore, the aim of this study was to investigate the influence of propofol on PMN functions after experimental Gram-negative induced sepsis using lipopolysaccharide (LPS) stimulation. METHODS: A total of 34 granulocyte-enriched samples were collected from healthy subjects. PMNs were isolated by density gradient centrifugation and incubated simultaneously with either 6 µg/mL or 60 µg/mL propofol, or none (control). Additionally, the experimental sepsis samples were incubated with either 40 pg/mL or 400 pg/mL LPS. Live cell imaging was conducted in order to observe granulocyte chemotactic migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression. RESULTS: Propofol led to significantly reduced PMN track length (p < 0.001) and track speed (p < 0.014) after LPS-induced sepsis in a dose-dependent manner. NETosis (p = 0.018) and ROS production (p = 0.039) were accelerated by propofol without LPS incubation, indicating improved immune function. Propofol also ameliorated LPS-induced increased NETosis and ROS-production. Antigen expression for CD11b, CD62l and CD66b was unaffected by propofol. CONCLUSION: Propofol improves LPS-induced exaggerated PMN activation in an ex vivo model. Beneficial effects due to restored immune function in septic patients might be possible, but needs further investigation.

Intramuscular injection of malignant hyperthermia trigger agents induces hypermetabolism in susceptible and nonsusceptible individuals.

BACKGROUND AND OBJECTIVE: A new minimally invasive metabolic test for the diagnosis of susceptibility for malignant hyperthermia measuring intramuscular p(CO(2)) and lactate following local application of caffeine and halothane in humans was recently proposed. The present study tested the hypothesis that a more simplified test protocol allows a differentiation between malignant hyperthermia susceptible (MHS) and malignant hyperthermia nonsusceptible (MHN) and control individuals. METHODS: With approval of the local ethics committee and informed consent, microdialysis and p(CO(2)) probes with attached microtubing were placed into the lateral vastus muscle of six MHS, seven MHN and seven control individuals. Following equilibration, boluses of 500 microl caffeine 80 mmol l(-1) and halothane 10 vol% dissolved in soybean oil were injected locally. p(CO(2)) and lactate were measured spectrophotometrically. RESULTS: The maximal rate of p(CO(2)) increase was significantly higher in MHS than in MHN and control individuals following application of halothane and caffeine, respectively. Intramuscular caffeine injection leads to a significantly higher increase of local lactate levels in MHS than in MHN and control individuals, whereas halothane increased local lactate levels in all investigated groups. Haemodynamic and systemic metabolic parameters did not differ between the investigated groups. CONCLUSION: Local caffeine and halothane injection increased intramuscular metabolism in MHS individuals significantly more than in the two other groups. In contrast to previous investigations, direct injection of the concentrations of halothane described here increased lactate and p(CO(2)) even in MHN skeletal muscle.