[Difficult Airway Management in Thoracic Anaesthesia]. / Atemwegsmanagement ­ der schwierige Atemweg beim thoraxchirurgischen Patienten.

Difficult airway management in thoracic anesthesia has rarely been addressed in current guidelines. However, difficult airway management may be a challenge in thoracic anaesthesia: Achieving lung separation and collapse in combination of potentially distorted upper airway anatomy (difficult upper airway), the presence of subglottic pathologies (difficult lower airway) and the need for one-lung ventilation (difficult lung separation). This review will focus on identification of patients at risk, recommendations and algorithms for the airway management in the anticipated and unexpected difficult in-/extubation, and choice of devices for lung separation in this context.

Anaesthetic management of patients with myopathies.

: The anaesthetic management of patients with myopathies is challenging. Considering the low incidence and heterogeneity of these disorders, most anaesthetists are unfamiliar with key symptoms, associated co-morbidities and implications for anaesthesia. The pre-anaesthetic assessment aims at the detection of potentially undiagnosed myopathic patients and, in case of known or suspected muscular disease, on the quantification of disease progression. Ancillary testing (e.g. echocardiography, ECG, lung function testing etc.) is frequently indicated, even at a young patient age. One must differentiate between myopathies associated with malignant hyperthermia (MH) and those that are not, as this has significant impact on preoperative preparation of the anaesthesia workstation and pharmacologic management. Only few myopathies are clearly associated with MH. If a regional anaesthetic technique is not possible, total intravenous anaesthesia is considered the safest approach for most patients with myopathies to avoid anaesthesia-associated rhabdomyolysis. However, the use of propofol in patients with mitochondrial myopathies may be problematic, considering the risk for propofol-infusion syndrome. Succinylcholine is contra-indicated in all patients with myopathies. Following an individual risk/benefit evaluation, the use of volatile anaesthetics in several non-MH-linked myopathies (e.g. myotonic syndromes, mitochondrial myopathies) is considered to be well tolerated. Perioperative monitoring should specifically focus on the cardiopulmonary system, the level of muscular paralysis and core temperature. Given the high risk of respiratory compromise and other postoperative complications, patients need to be closely monitored postoperatively.

Change of initial and ICU treatment over time in trauma patients. An analysis from the TraumaRegister DGU®.

BACKGROUND: Clinical guidelines have been standardized for pre- and in-hospital trauma management in the last decades. Therefore, it is known that prehospital management has changed significantly. Furthermore, in-hospital course may be altered to reduce complications and length of stay (LOS). However, the development of trauma patient in-hospital management as well as LOS in the intensive care unit (ICU) has not been investigated systematically over a long-term period in Germany. Aim of our study is to examine the changes in in-hospital management and LOS in the ICU in moderately and severely injured patients. METHODS: Patients documented in the TraumaRegister DGU® (TR-DGU) of the German Trauma Society from 2000 to 2011 and admitted to ICU were included in this study. Demographic data, the pattern of injury, injury severity, duration of mechanical ventilation, LOS in the ICU, hospital LOS, and discharge destination were evaluated. The mean values and the standard deviations are shown. The constant variables were calculated with changes over time analyzed by linear regression analysis, and categorical variables were calculated with the chi-square test. RESULTS: A total of 18,048 patients were analyzed. The rate of patients being intubated at the time of ICU admission decreased from 86.8 % in 2000 to 60.0 % in 2011 (p < 0.001). The time of mechanical ventilation decreased from 7.5 ± 10.5 to 4.7 ± 8.7 days. The intensive care unit LOS was reduced from 11.7 ± 12.8 to 9.0 ± 11.3 days and the length of hospital stay from 27.9 ± 28.7 to 21.1 ± 20.4 days (both p < 0.01). The ICU LOS remained stable in the subgroup of mechanically ventilated patients (12.7 ± 13.2 day in 2000, 12,6 ± 12.9 in 2011, p = 0.6), whereas it was reduced in non-mechanically ventilated patients (5.5 ± 6.8 days in 2000, 3.6 ± 4.5 days in 2011; p < 0.001). CONCLUSIONS: The reduction LOS in the analyzed dataset is mainly explained by the relevantly reduced rate of patients being intubated at the time of ICU admission. Our data demonstrate that trauma patients' in-hospital course is influenced by reduced intubation rate at the time of ICU admission.

Do we foresee new emerging drugs to treat malignant hyperthermia?

Malignant hyperthermia (MH) is a life-threatening genetic sensitivity of skeletal muscles to volatile anesthetics and depolarizing neuromuscular blocking drugs occurring during or after anesthesia. Mortality of MH has been significantly reduced by using the skeletal muscle relaxant dantrolene. However, pharmacological disadvantages are known. By approval of a nanocrystalline dantrolene sodium suspension (DSS), a new product enters the market. DSS is a promising substance, but clinical data are lacking up to now. Especially with regard to newer knowledge on MH and its associated clinical presentations, there might be an increasing interest on DSS.

Factors influencing lengths of stay in the intensive care unit for surviving trauma patients: a retrospective analysis of 30,157 cases.

INTRODUCTION: There are many potential influencing factors that affect the duration of intensive care treatment for patients who have survived multiple trauma. Yet the respective factors' relevance to ICU length of stay (LOS) has been rarely studied. Thus, the aim of the present study was to investigate to what extent specific factors influence ICU LOS in surviving trauma patients. METHODS: We retrospectively analyzed a dataset of 30,157 surviving trauma patients from the TraumaRegister DGU® who were older than six years of age and received subsequent intensive care treatment for more than one day, from 2002 to 2011. Univariate analysis and multiple linear regression analysis were used to examine 25 categorical pre- and post-trauma parameters. RESULTS: Univariate analysis confirmed the impact of all analyzed factors. In subsequent multiple linear regression analyses, coefficients ranged from -1.3 to +8.2 days. The factors that influenced the prolongation of ICU LOS most were renal failure (+8.1 days), sepsis (+7.8 days) and respiratory failure (+4.9 days). Patients spent one additional day in the ICU for every 5 additional points on the Injury Severity Score (regression coefficient +0.2 per point). Furthermore, massive transfusion (+3.3 days), invasive ventilation (+3.1 days), and an initial Glasgow Coma Scale score ≤8 (+3.0 days) had a significant impact on ICU LOS. The coefficient of determination for the model was 44% (R2). CONCLUSIONS: Treatment regimens, as well as secondary effects and complications of trauma and intensive care treatment, prolong ICU LOS more than the mechanism of trauma or pre-trauma patient conditions. Successful prevention of complicated courses of illness, such as sepsis and renal and respiratory failure, could significantly abbreviate the ICU stay in trauma patients. Therefore, the staff's attention should be focused on preventive strategies.

3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic crisis in pigs with and without a genetic disposition for malignant hyperthermia.

BACKGROUND: Clinical symptoms of acute 3,4-methylenedioxymethamphetamine (MDMA) intoxication and malignant hyperthermia have many similarities. At present, however, there is contradictory evidence concerning the malignant hyperthermia trigger potency of MDMA. OBJECTIVE: This study was designed to investigate whether MDMA has malignant hyperthermia trigger potential and leads to malignant hyperthermia in pigs with or without a genetic predisposition to the condition. In addition, the therapeutic effectiveness of a new dantrolene sodium suspension was examined. DESIGN: Experimental study, using an animal model of Piétrain pigs. SETTINGS: Institute for Research in Operative Medicine, University of Witten/Herdecke, Hospital Cologne Merheim, Cologne, Germany, October 2006 to February 2007. Trigger-free anaesthesia was performed on seven malignant hyperthermia-susceptible and six malignant hyperthermia-normal Piétrain pigs, and cumulative doses of MDMA were administered to each animal. INTERVENTIONS: After achieving predefined malignant hyperthermia criteria, standardised therapy was initiated; dantrolene sodium suspension (5 mg kg(-1)) was administered and the injection was repeated after 24 min. MAIN OUTCOME MEASURES: The malignant hyperthermia trigger potency of MDMA was analysed by monitoring pH, PaCO2 and temperature. In addition, concentrations of thyroid hormone, mitochondrial uncoupling protein 3, noradrenaline and free fatty acids during administration of MDMA and dantrolene sodium suspension were analysed. RESULTS: MDMA administration led to fulminant hypermetabolic and hyperthermic responses in malignant hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant decreases in pH (susceptible: pH 7.21 ± 0.11, normal: pH 7.21 ± 0.07), severe hypercapnia (susceptible: paCO2 10.3 ± 3.5 kPa, normal: paCO2 9.8 ± 1.7 kPa), and hyperthermia (susceptible: 40.6 ± 2.0°C, normal: 40.1 ± 0.4°C). There were no significant differences in changes in clinical and laboratory variables between groups. The dantrolene therapy regimen was effective in treating the MDMA-induced metabolic crises. CONCLUSION: MDMA is not a classic trigger for the development of malignant hyperthermia reactions in pigs. MDMA intoxication leads to severe, long-lasting hyperthermia and hypermetabolism in both malignant hyperthermia-susceptible and hyperthermia-normal pigs, with life-threatening malignant hyperthermia-like symptoms which are responsive to supportive treatment and dantrolene sodium suspension.

3,4-Methylenedioxymethamphetamine (Ecstasy) increases the sensitivity of the contractile apparatus to calcium ions in both malignant hyperthermia-susceptible and normal skeletal muscle fibres.

CONTEXT AND OBJECTIVES: The present study was designed to investigate whether 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') increases the sensitivity of the contractile apparatus to calcium in muscle fibres from malignant hyperthermia-susceptible and malignant hyperthermia-negative pigs, whether it causes calcium ion release from the sarcoplasmic reticulum and whether it inhibits calcium reuptake into the sarcoplasmic reticulum. DESIGN: Experimental study, using a model of porcine saponin-skinned fibres. RESULTS: Administration of MDMA in concentrations of 1, 2 and 4 mmol l(-1)l did not result in relevant force transients in skinned muscle fibres of malignant hyperthermia-susceptible or malignant hyperthermia-negative pigs. Furthermore, MDMA in these concentrations did not alter calcium ion loading of the sarcoplasmic reticulum in either group. With regard to changes in the calcium ion sensitivity of the contractile proteins, however, MDMA dose-dependently increased (pCa50) values (negative decadic logarithm of [Ca2+] at which isometric force is half-maximal) in both groups. CONCLUSION: In the present study, we were able to demonstrate that MDMA dose-dependently increases the sensitivity of the contractile apparatus to calcium in both malignant hyperthermia-susceptible and malignant hyperthermia-negative fibres. Consequently, the malignant hyperthermia status should not affect the calcium sensitivity of the contractile apparatus. However, the increased calcium sensitivity is an important finding that must be appreciated, particularly in relation to the agonistic effect of MDMA at the nicotinic acetylcholine receptor, which increases intracellular calcium ion concentrations.

Effects of theophylline on anesthetized malignant hyperthermia-susceptible pigs.

BACKGROUND: Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine. METHODS: MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5 mg·kg⁻¹. The clinical occurrence of MH was defined by changes of central-venous pCO2, central-venous pH, and body core temperature. RESULTS: Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation. CONCLUSIONS: The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.

Comparison of the therapeutic effectiveness of a dantrolene sodium solution and a novel nanocrystalline suspension of dantrolene sodium in malignant hyperthermia normal and susceptible pigs.

BACKGROUND AND OBJECTIVE: Stopping trigger agents and prompt administration of dantrolene are the cornerstones of treatment of malignant hyperthermia. However, significant time is lost in treatment of the condition because of the cumbersome preparation and administration of the commercially available dantrolene sodium for injection. A potential improvement has become available in the form of a novel nanocrystalline dantrolene sodium suspension (DSS), which is 150 times more concentrated (50 mg ml(-1)) than the standard dantrolene sodium solution (0.33 mg ml(-1)). The aims of this study were to measure the effects of DSS on clinical and laboratory variables in malignant hyperthermia normal pigs and to compare the therapeutic management and clinical effectiveness of DSS with standard dantrolene sodium in a fulminant malignant hyperthermia crisis in susceptible pigs. The pig model is a well accepted method of studying the malignant hyperthermia crisis and is an ideal way to evaluate the variables of interest in this study. METHODS: Seven malignant hyperthermia normal and 10 malignant hyperthermia susceptible pigs were studied. Malignant hyperthermia susceptible pigs (body weight approximately 24 kg) were allocated to a dantrolene sodium group or a DSS group. After induction of anaesthesia, a 22-gauge catheter was placed in an ear vein and trigger-free anaesthesia was performed. After achieving stable conditions, administration of halothane was started with 0.1% and then 0.15%. Halothane was discontinued after the administration of 0.2% (malignant hyperthermia normal pigs) or when a fulminant malignant hyperthermia crisis was achieved (malignant hyperthermia susceptible pigs). After halothane was discontinued, FIO2 was set to 1.0, respiratory minute volume was doubled and sodium bicarbonate 2 mmol kg(-1) was administered. The time required to prepare and administer each formulation was measured. To simulate the administration of the substances under typical clinical conditions for a child weighing approximately 24 kg, dantrolene sodium (5 mg kg(-1)) or DSS (5 mg kg(-1)) was prepared and injected via the intravenous 22-gauge cannula. Bolus administrations of dantrolene sodium or DSS were repeated after 24 min. RESULTS: Arterial pH, arterial pCO2, mean arterial pressure and arterial lactate concentration remained stable during the experiment with DSS in malignant hyperthermia normal pigs. A significant decrease in cardiac index and increases in systemic vascular resistance and serum potassium concentration occurred after administration of DSS. In all malignant hyperthermia susceptible animals, the inhaled administration of halothane 0.15% led to a fulminant malignant hyperthermia crisis. The therapeutic regimens with administration of dantrolene sodium or DSS were successful in treating the malignant hyperthermia crisis in all animals. The course of the malignant hyperthermia crisis and the therapeutic effects of dantrolene sodium or DSS were comparable in the two groups. The time needed to prepare DSS for administration was significantly shorter (51 ± 9 s) compared to dantrolene sodium (860 ± 202 s). The time taken to inject DSS (4 ± 2 s) was significantly shorter than for dantrolene sodium (472 ± 51 s). CONCLUSION: The therapeutic action of DSS in a malignant hyperthermia crisis in pigs was effective and comparable to that of standard dantrolene sodium. However, preparation and administration of DSS were significantly faster, which may offer a clinically significant advantage in the treatment of a fulminant malignant hyperthermia crisis and may result in a reduction in stress for the anaesthesia team.

Parecoxib versus dipyrone (metamizole) for postoperative pain relief after hysterectomy : a prospective, single-centre, randomized, double-blind trial.

BACKGROUND AND OBJECTIVE: Selective cyclo-oxygenase-2 (COX-2) inhibitors provide postoperative pain relief similar to conventional NSAIDs. However, many of these non-opioid analgesics are available only for oral administration, and are therefore ineffective in patients experiencing postoperative nausea or vomiting. The aim of this study was to compare the analgesic efficacy of the COX-2 inhibitor parecoxib with that of dipyrone (metamizole) administered intravenously for 48 hours after vaginal hysterectomy. METHODS: Fifty women undergoing vaginal hysterectomy under general anaesthesia were randomly assigned to two groups: the parecoxib group, who received intravenous parecoxib 40 mg intraoperatively and every 12 hours after surgery over a period of 48 hours, and the dipyrone group, who received intravenous dipyrone 2.5 g injected intraoperatively, followed by dipyrone 1 g every 6 hours after surgery over a period of 48 hours. Because of the double-blinded study protocol, patients in the parecoxib groups were required to receive placebo infusions 6, 18, 30 and 42 hours after the operation. Visual analogue scale (VAS [scale 0-10]) scores were recorded 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 24, 36 and 48 hours after surgery. To assess the cumulative opioid administration, all patients were fitted with an intravenous patient-controlled analgesia (PCA) device containing the opioid piritramide. An alpha value of 0.05 was considered statistically significant. RESULTS: VAS scores did not differ between groups with one exception: VAS scores were lower in the parecoxib group 12 hours after surgery than in the dipyrone group (1 and 2, respectively; p < 0.05). No significant differences in cumulative piritramide administration were measured between groups 1 hour or 24 hours after surgery (parecoxib 14.7 [+/- SD 4.4] and 30.6 [+/- 12.8] mg, respectively; dipyrone 11.8 [+/- 4.9] and 36.5 [+/- 10.7] mg, respectively). CONCLUSIONS: Parecoxib 40 mg twice daily provides postoperative pain relief equivalent to that of dipyrone 4 g daily during the first 48 hours in patients after hysterectomy.

The effectiveness of an intensive care quick reference checklist manual--a randomized simulation-based trial.

PURPOSE: We aimed to test the effectiveness of checklists for emergency procedures on medical staff performance in intensive care crises. MATERIALS AND METHODS: This is a prospective single-center randomized trial in a high-fidelity simulation center modeling an intensive care unit (ICU) in a tertiary care hospital in Germany. Teams consisted of 1 ICU resident and 2 ICU nurses (in total, n = 48). All completed 4 crisis scenarios, in which they were randomized to use checklists or to perform without any aid. In 2 of the scenarios, checklists could be used immediately (type 1 scenarios); and for the remaining, some further steps, for example, confirming diagnosis, were required first (type 2 scenarios). Outcome measurements were number of predefined items and time to completion of more than 50% and more than 75% of steps, respectively. RESULTS: When using checklists, participants initiated items faster and more completely according to appropriate treatment guidelines (9 vs 7 items with and without checklists, P < .05). Benefit of checklists was better in type 2 scenarios than in type 1 scenarios (2 vs 1 additional item, P < .05). In type 2 scenarios, time to complete 50% and 75% of items was faster with the use of checklists (P < .005). CONCLUSIONS: Use of checklists in ICU crises has a benefit on the completion of critical treatment steps. Within the type 2 scenarios, items were fulfilled faster with checklists. The implementation of checklists for intensive care crises is a promising approach that may improve patients' care.

Ryanodine contracture threshold times for diagnosis of malignant hyperthermia susceptibility: an experimental approach from a single laboratory.

STUDY OBJECTIVES: To define threshold times for ryanodine contracture testing (RCT) using skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and control individuals. DESIGN: Prospective study. SETTING: Malignant hyperthermia (MH) laboratory at a university hospital. PATIENTS: 8 patients with previous fulminant MH and 53 control patients undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. INTERVENTIONS: Biopsies of the quadriceps femoris muscle were performed with a 3-in-1 nerve block, with spinal anesthesia, or with trigger-free general anesthesia. MEASUREMENTS AND MAIN RESULTS: Patients were classified as MHS, MH normal (MHN), or MH equivocal (MHE) by the IVCT according to the protocol of the European MH Group (EMHG). Ryanodine 1 microM was added as a bolus to the organ bath to extra vital muscle specimens. Contracture levels were defined as: 1 = start of contracture (OT; min); 2 = time (min) to reach a contracture of 2 mN, and 3 = time (min) to reach a contracture of 10 mN. The effects of ryanodine on contracture responses were measured. Ryanodine induced contractures in all specimens. MHS specimens reached all defined contracture levels significantly sooner than did the controls. Ryanodine contracture test enables a clear discrimination of MHS specimens from controls at contracture levels of OT and 2 mN, whereas at 10 mN a small overlap was observed. CONCLUSIONS: Using this test, which is an experimental approach from a single laboratory, an assignment to MHS or MHN is possible. To define contracture levels for RCT more precisely and to agree on commonly used thresholds, multicenter studies with larger numbers of patients are required.

In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.

BACKGROUND: In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated. METHODS: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS: Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS: The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.

Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy").

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine. METHODS: MH-nontriggering general anesthesia was performed in six MH-susceptible (MHS) and six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5, 1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central venous pH /= 2.0 degrees C. Once MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and hyperventilation with 100% oxygen was initialized. RESULTS: Administration of 8 mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed clinical signs of hypermetabolism, but even after administration of 12 mg/kg MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs of MH immediately. CONCLUSIONS: MDMA induces MH in genetically susceptible swine in relevant doses. Therefore, MHS patients should avoid use of MDMA or related drugs. Patients with a personal or family history of MDMA-induced hyperthermia should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in therapy of MDMA-induced porcine MH.