Thomas Fuchs-Buder

Laryngeal Morbidity and Quality of Tracheal Intubation: A Randomized Controlled Trial

Background Vocal cord sequelae and postoperative hoarseness during general anesthesia are a significant source of morbidity for patients and a source of liability for anesthesiologists. Several risk factors leading to laryngeal injury have been identified in the past. However, whether the quality of tracheal intubation affects their incidence or severity is still unclear. Methods Eighty patients were randomized in two groups (n = 40 for each) to receive a propofol–fentanyl induction regimen with or without atracurium. Intubation conditions were evaluated with the Copenhagen Score; postoperative hoarseness was assessed at 24, 48, and 72 h by a standardized interview; and vocal cords were examined by stroboscopy before and 24 and 72 h after surgery. If postoperative hoarseness or vocal cord sequelae persisted, follow-up examination was performed until complete restitution. Results Without atracurium, postoperative hoarseness occurred more often (16 vs. 6 patients;P = 0.02). The number of days with postoperative hoarseness was higher when atracurium was omitted (25 vs. 6 patients;P < 0.001). Similar findings were observed for vocal cord sequelae (incidence of vocal cord sequelae: 15 vs. 3 patients, respectively, P = 0.002; days with vocal cord sequelae: 50 vs. 5 patients, respectively, P < 0.001). Excellent intubating conditions were less frequently associated with postoperative hoarseness compared to good or poor conditions (11, 29, and 57% of patients, respectively; excellent vs. poor:P = 0.008). Similar findings were observed for vocal cord sequelae (11, 22, and 50% of patients, respectively; excellent vs. poor:P = 0.02). Conclusions The quality of tracheal intubation contributes to laryngeal morbidity, and excellent conditions are less frequently associated with postoperative hoarseness and vocal cord sequelae. Adding atracurium to a propofol–fentanyl induction regimen significantly improved the quality of tracheal intubation and decreased postoperative hoarseness and vocal cord sequelae.

Can acceleromyography detect low levels of residual paralysis? A probability approach to detect a mechanomyographic train-of-four ratio of 0.9

Background: The incidence of residual paralysis, i.e., a mechanomyographic train-of-four (TOF) ratio (T4/T1) less than 0.9, remains frequent. Routine acceleromyography has been proposed to detect residual paralysis in clinical practice. Although acceleromyographic data are easy to obtain, they differ from mechanomyographic data, with which they are not interchangeable. The current study aimed to determine (1) the acceleromyographic TOF ratio that detects residual paralysis with a 95% probability, and (2) the impact of calibration and normalization on this predictive acceleromyographic value. Methods: In 60 patients, recovery from neuromuscular block was assessed simultaneously with mechanomyography and acceleromyography. To obtain calibrated acceleromyographic TOF ratios in group A, the implemented calibration modus 2 was activated in the TOF-Watch S®; to obtain uncalibrated acceleromyographic TOF ratios in group B, the current was manually set at 50 mA (n = 30 for each). In addition, data in group B were normalized (i.e., dividing the final TOF ratio by the baseline value). The agreement between mechanomyography and acceleromyography was assessed by calculating the intraclass correlation coefficient. Negative predictive values were calculated for detecting residual paralysis from acceleromyographic TOFs of 0.9, 0.95, and 1.0. Results: Group A: For a mechanomyographic TOF of 0.9 or greater, the corresponding acceleromyographic TOF was 0.95 (range, 0.86–1.0), and the negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 37% (95% CI, 20–56%), 70% (95% CI, 51–85%), and 97% (95% CI, 83–100%), respectively. Group B: Without normalization, an acceleromyographic TOF of 0.97 (range, 0.68–1.18) corresponded to a mechanomyographic TOF of 0.9 or greater, with negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 being 40% (95% CI, 23–59%), 60% (95% CI, 41–77%), and 77% (95% CI, 58–90%), respectively. After normalization, an acceleromyographic TOF of 0.89 (range, 0.63–1.06) corresponded to a mechanomyographic TOF of 0.9 or greater, and the negative predictive values of acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 89% (95% CI, 70–98%), 92% (95% CI, 75–99%), and 96% (95% CI, 80–100%), respectively. Conclusion: To exclude residual paralysis reliably when using acceleromyography, TOF recovery to 1.0 is mandatory.

Prevention of Succinylcholine-induced Fasciculation and Myalgia A Meta-analysis of Randomized Trials

Fifty-two randomized trials (5,318 patients) were included in this meta-analysis. In controls, the incidence of fasciculation was 95%, and the incidence of myalgia at 24 h was 50%. Nondepolarizing muscle relaxants, lidocaine, or magnesium prevented fasciculation (number needed to treat, 1.2–2.5). Best prevention of myalgia was with nonsteroidal antiinflammatory drugs (number needed to treat, 2.5) and with rocuronium or lidocaine (number needed to treat, 3). There was a dose-dependent risk of blurred vision, diplopia, voice disorders, and difficulty in breathing and swallowing (number needed to harm, < 3.5) with muscle relaxants. There was evidence of less myalgia with 1.5 mg/kg succinylcholine (compared with 1 mg/kg). Opioids had no impact. Succinylcholine-induced fasciculation may best be prevented with muscle relaxants, lidocaine, or magnesium. Myalgia may best be prevented with muscle relaxants, lidocaine, or nonsteroidal antiinflammatory drugs. The risk of potentially serious adverse events with muscle relaxants is not negligible. Data that allow for a risk–benefit assessment are lacking for other drugs.

Cerebrospinal fluid passage of intravenous magnesium sulfate in neurosurgical patients

Increasing evidence suggests a neuroprotective potential of magnesium sulfate (MgSO4). Only limited information about the passage of MgSO4 to the cerebrospinal fluid (CSF) is available in neurosurgical patients. However, with regard to the clinical relevance of magnesiums neuroprotective properties, quantitative data about its CSF passage are needed. The present study aims to assess the amount and the time course of magnesiums CSF passage in neurosurgical patients. To this end, 20 patients undergoing general anesthesia for neurosurgery and needing CSF drainage were included. Patients received an i.v. bolus of 60 mg/kg MgSO4. The increase in plasma and CSF magnesium concentration were measured 30, 90, and 240 min after the end of the MgSO4 infusion. These values were compared with the baseline levels taken before the start of the MgSO4 infusion. Thus, each patient served as his or her own control. Values are expressed as means +/- SD. The plasma magnesium levels were measured as follows: baseline, 0.74 +/- 0.12 mM; at 30 min, 1.24 +/- 0.1 mM (p < 0.01); at 90 min, 0.95 +/- 0.15 mM (p < 0.01), and at 240 min, 0.82 +/- 0.14 mM (p < 0.05). The CSF magnesium levels were measured as follows: baseline, 0.95 +/- 0.11 mM; at 30 min, 1.00 +/- 0.15 mM (NS); at 90 min, 1.10 +/- 0.17 mM (p < 0.01); and at 240 min, 1.13 +/- 0.19 mM (p < 0.001). We concluded that a bolus of 60 mg/kg of MgSO4 leads at least after 90 min to a significant increase in the CSF magnesium concentration. Moreover, the increase in plasma and CSF magnesium concentration is not parallel. Thus, plasma magnesium concentration cannot be used to predict the changes in CSF concentrations.

Single acceleromyographic train-of-four, 100-Hertz tetanus or double-burst stimulation: which test performs better to detect residual paralysis?

Background: Acceleromyography is regularly used as an isolated test to detect residual paralysis. The performance of acceleromyography, however, has not been investigated for the setting where calibration is impossible. This study first evaluated the reliability of a single acceleromyographic train-of-four (TOF) ratio (T4/T1) to detect residual paralysis and compared it with tactile estimation of fade after double-burst stimulation and 100-Hz, 5-s tetanus. The second part of the study investigated whether uncalibrated acceleromyographic TOF ratio can predict time to complete recovery. Methods: Anesthesia was induced and maintained with propofol and sufentanil. In the first part of the study (n = 40) neuromuscular blockade was assessed by mechanomyography. After signal stabilization 0.15 mg/kg cisatracurium was given. At the end of surgery a first physician evaluated manual fade after double-burst stimulation, then, in the same patient, a single acceleromyographic TOF ratio was recorded; thereafter a second physician, unaware of the results, assessed fade after a 100-Hz, 5-s tetanus. Sensitivity, specificity, and negative and positive predictive value of the three tests to detect a mechanomyographic TOF ≥0.9 were calculated. In the second part of the study (n = 25) neuromuscular recovery was assessed simultaneously with mechanomyography and uncalibrated acceleromyography (current set manually at 60 mA); the time intervals from acceleromyographic TOF ratios of 0.6, 0.7, 0.8, and 0.9 until complete recovery, i.e., adductor pollicis mechanomyography 0.9 TOF ratios, were determined. Results: The sensitivity of double burst stimulation was 29% (95% confidence interval [CI], 13–45%), its specificity was 100%, the negative predictive value was 29% (95% CI, 13–45%), and the positive predictive value was 100%. For a single acceleromyographic TOF ratio the respective values were 70% (95% CI, 54–86%), 88% (95% CI, 67–100%), 47% (95% CI, 23–71%) and 95% (95% CI, 86–100%). The respective values for 100-Hz, 5-s tetanus were 74% (95% CI, 59–89%), 55% (95% CI, 23–88%), 38% (95% CI, 12–64%), and 85% (95% CI, 72 -99%). At an uncalibrated acceleromyographic TOF ratio was 0.6, complete recovery occurred within 16 min (95% CI, 13.5–17.8 min). At acceleromyographic TOF ratios of 0.7, 0.8, and 0.9 this time interval was 12.5 min (95% CI, 10.2–14.8 min), 8 min (95% CI, 6.1–9.9 min), and 4 min (95% CI, 2.7–5.8 min), respectively. Conclusions: Acceleromyographic TOF performed better than double-burst stimulation or 100 Hz tetanus, but it did not reliably detect low degrees of residual paralysis when used as an isolated test at the end of surgery. The uncalibrated acceleromyographic TOF ratio, however, did predict the time to complete recovery.

Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine

BackgroundCuraremimetic nondepolarizing muscle relaxants are widely used in clinical practice to prevent muscle contraction either during surgery or during intensive care. Although primarily acting at the neuromuscular junction, these compounds can cause adverse effects, including modification of cardiac rhythm, arterial blood pressure, and in the worst cases, triggering of seizures. In this study, we assessed the interaction of atracurium and its metabolite, laudanosine, with neuronal nicotinic receptors. MethodsThe human neuronal nicotinic receptors &agr;4&bgr;2, &agr;3&bgr;4, &agr;3&agr;5&bgr;4, and &agr;7 are heterologously expressed in Xenopus laevis oocytes, and the effect of atracurium and its degradation product, laudanosine, were studied on these receptors. ResultsAtracurium and laudanosine inhibited in the micromolar range the major brain &agr;4&bgr;2 receptor and the ganglionic &agr;3&bgr;4 or &agr;3&bgr;4&agr;5 and the homomeric &agr;7 receptors. For all four receptors, inhibition was rapid and readily reversible within less than 1 min. Atracurium blockade was competitive at &agr;4&bgr;2 and &agr;7 receptors but displayed a noncompetitive blockade at the &agr;3&bgr;4 receptors. Inhibition at this receptor subtype was not modified by &agr;5. Laudanosine was found to have a dual mode of action; first, it competes with acetylcholine and, second, it blocks the ionic pore by steric hindrance. At low concentrations, these two drugs are able to activate both the &agr;4&bgr;2 and the &agr;3&bgr;4 receptors. ConclusionAdverse effects observed during atracurium administration may be attributed, at least partly, to an interaction with neuronal nicotinic receptors.

Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage.

Background: Neuromuscular blocking agents may exert central nervous system effects when they reach the brain. This study assessed the concentrations and the time course of passage of vecuronium, atracurium, and its metabolite laudanosine in the cerebrospinal fluid (CSF) of patients undergoing intracranial aneurysm clipping.

Effects of Neuromuscular Blocking Agents on Excitatory Transmission and γ-Aminobutyric Acid-A-mediated Inhibition in the Rat Hippocampal Slice

Background Although neuromuscular blocking agents do not cross the blood‐brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences. Methods The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques. Results Application of atracurium in the perfusion medium resulted in a dose‐dependent enhancement of excitatory synaptic responses averaging 48.7 +/‐ 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma‐aminobutyric acidA receptor‐mediated potentials. These effects were observed only at concentrations > 1 micro Meter and were not reproduced by pancuronium bromide and vecuronium bromide. Conclusions Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma‐aminobutyric acid sub A ‐mediated synaptic responses.

Postoperative Myalgia After Succinylcholine: No Evidence for an Inflammatory Origin

A common side effect associated with succinylcholine is postoperative myalgia. The pathogenesis of this myalgia is still unclear; inflammation has been suggested but without convincing evidence. We designed the present study to investigate whether an inflammatory reaction contributes to this myalgia. The incidence and severity of succinylcholine-associated myalgia was determined in 64 patients pretreated with saline or dexamethasone before succinylcholine (n = 32 for each). Incidence and severity of myalgia did not differ significantly between the two groups: 15 patients in the dexamethasone group complained of myalgia compared with 18 patients in the saline group, and severe myalgia was reported by five patients and three patients, respectively (not significant). At 48 h after surgery, 12 patients in both groups still suffered from myalgia (not significant). In addition, interleukin-6 (IL-6) as an early marker of inflammation was assessed in a subgroup of 10 patients pretreated with saline. We found an increase of IL-6 for only three patients, but only one patient reported myalgia; no relationship between myalgia and the increase of IL-6 was found. In conclusion, there is no evidence for an inflammatory origin of succinylcholine-associated myalgia. IMPLICATIONS: Administration of dexamethasone before succinylcholine was not effective in decreasing the incidence or the severity of succinylcholine-induced postoperative myalgia. Furthermore, there was no significant relationship between postoperative myalgia and time course of interleukin-6 concentrations, a marker of inflammation. Pretreatment with dexamethasone is not justified to prevent postoperative myalgia after succinylcholine.

Succinylcholine: The Dilemma with the Evidence

To the editor: n nWe have read with interest the case report by Terijian and colleagues and the comment from Brodsky et al. [1, 2]. n nWe fully agree with the authors that succinylcholine-associated myalgia might be a serious issue for many patients, especially for morbidly obese patients. But we were a little bit surprised about the authors’ opinion that there are no proven strategies to reduce succinylcholine-associated myalgia significantly. The authors have cited a meta-analysis by Schreiber et al. that was published in 2005 in Anesthesiology [3]. In this article it has been shown that the relative risk of postoperative myalgia can be reduced significantly by using a pretreatment with low-dose non-depolarizing neuromuscular blockers or sodium channel blockers such as lidocaine. Currently, the paper represents the best available evidence on the prevention of succinylcholine-associated myalgia. n nFurthermore, we agree that sugammadex, a new binding agent for the reversal of rocuronium and vecuronium, will improve the safety profile of these agents but we are not convinced that this will be the solution of all of our problems. In case of a rapid sequence induction, the anesthesiologist wants optimal intubation conditions within seconds and in this specific situation succinylcholine still seems to be superior compared to high-dose rocuronium—according to a recent systematic review that was very well done by Perry et al. [4]. n nThe dilemma of systematic reviews and meta-analyses might be that they cannot focus onto specific patient populations. This could be seen as a limitation of evidence-based approaches. On the other hand, it represents the best way—unless the contrary has been proven. n nAnother aspect emerges from this case report. After dramatic improvements in clinical anesthesia during the last 50xa0years, a dirty drug that may cause potentially fatal complications such as malignant hyperthermia or hyperkalemia still represents the gold standard for rapid sequence induction. Surely, a non-depolarizing agent with a comparable pharmacological profile but no side effects would be the best replacement. Unfortunately, it has not been found yet.