Oliver Bandschapp

The myotonias and susceptibility to malignant hyperthermia.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle in which volatile anesthetics trigger a sustained increase in intramyoplasmic Ca2+ via release from sarcoplasmic reticulum and, possibly, entry from the extracellular milieu that leads to hypermetabolism, muscle rigidity, rhabdomyolysis, and death. Myotonias are a class of myopathies that result from gene mutations in various channels involved in skeletal muscle excitation-contraction coupling and sarcolemmal excitability, and unusual DNA sequence repeats that result in the inability of many proteins, including skeletal muscle channels that affect excitability, to undergo proper splicing. The suggestion has often been made that myotonic patients have an increased risk of developing MH. In this article, we review the physiology of muscle excitability and excitation-contraction coupling, the pathophysiology of MH and the myotonias, and review the clinical literature upon which the claims of MH susceptibility are based. We conclude that patients with these myopathies have a risk of developing MH that is equivalent to that of the general population with one potential exception, hypokalemic periodic paralysis. Despite the fact that there are no clinical reports of MH developing in patients with hypokalemic periodic paralysis, for theoretical reasons we cannot be as certain in estimating their risk of developing MH, even though we believe it is low.

Serious complications associated with external intrathecal catheters used in cancer pain patients: a systematic review and meta-analysis.

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.

Tropisetron blocks analgesic action of acetaminophen: A human pain model study

&NA; Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double‐blind, placebo‐controlled crossover study. Intracutaneous electrical stimulation (46.1 ± 19.1 mA) induced acute pain (numeric rating scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia and allodynia were regularly assessed before, during, and after a 15‐min infusion of acetaminophen, tropisetron, the combination of both drugs, and saline. Acetaminophen concentrations were measured to rule out any pharmacokinetic interaction. Both acetaminophen and tropisetron led to decreased pain ratings as compared to saline. However, when acetaminophen and tropisetron were administered simultaneously, the pain ratings were not affected. There was no significant difference in the evolution of the hyperalgesic and allodynic areas during the study period between the study groups (P = .06 and P = .33, respectively). Acetaminophen serum levels were not significantly different when associated with tropisetron (P = .063), although we observed a trend toward lower acetaminophen concentrations when both drugs were concurrently administered. In summary, while the combination of acetaminophen and tropisetron showed no analgesic action, each drug administered alone led to decreased pain ratings as compared to saline. In an electrically evoked human pain model, the combination of acetaminophen with tropisetron was free of any analgesic potential. However, when administered on its own, both acetaminophen and tropisetron were mildly analgesic.

Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial.

Background:Although opioids in general and remifentanil in particular have been shown to induce hyperalgesia, data regarding fentanyl are scarce. Thus, the authors investigated the effect of fentanyl dosing on pain perception and central sensitization in healthy volunteers using established pain models. Methods:Twenty-one healthy, male volunteers were included in this randomized, double-blind, crossover study and received either intravenous low-dose (1 &mgr;g/kg) or high-dose (10 &mgr;g/kg) fentanyl. Pain intensities and hyperalgesia were assessed by intracutaneous electrical stimulation, and cold pressor pain was used as an additional measure of acute pain. The primary outcome was hyperalgesia from 4.5 to 6.5 h after fentanyl administration. Results:A higher dose of fentanyl led to significantly decreased pain scores as measured by the numeric rating scale (0.83 units lower [95% CI, 0.63 to 1.02]; P < 0.001) but increased areas of hyperalgesia (+30.5% [95% CI, 16.6 to 44.4%]; P < 0.001) from 4.5 to 6.5 h after fentanyl administration. Allodynia did not differ between groups (+4.0% [95% CI, −15.4 to 23.5%]; P = 0.682).The high dose also led to both increased cold pressor pain threshold (+43.0% [95% CI, 29.7 to 56.3%]; P < 0.001) and tolerance (+32.5% [95% CI, 21.7 to 43.4%]; P < 0.001) at 4.5 to 6.5h. In the high-dose group, 19 volunteers (90%) required reminders to breathe, 8 (38%) required supplemental oxygen, and 12 (57%) experienced nausea. Conclusions:A higher dose of fentanyl increased hyperalgesia from 4.5 to 6.5 h in healthy volunteers while simultaneously decreasing pain scores.

Intra- and postoperative intravenous ketamine does not prevent chronic pain: A systematic review and meta-analysis

Abstract Background and aims The development of postoperative chronic pain (POCP) after surgery is a major problem with a considerable socioeconomic impact. It is defined as pain lasting more than the usual healing, often more than 2–6 months. Recent systematic reviews and meta-analyses demonstrate that the N-methyl-D-aspartate-receptor antagonist ketamine given peri- and intraoperatively can reduce immediate postoperative pain, especially if severe postoperative pain is expected and regional anaesthesia techniques are impossible. However, the results concerning the role of ketamine in preventing chronic postoperative pain are conflicting. The aim of this study was to perform a systematic review and a pooled analysis to determine if peri- and intraoperative ketamine can reduce the incidence of chronic postoperative pain. Methods Electronic searches of PubMed, EMBASE and Cochrane including data until September 2013 were conducted. Subsequently, the titles and abstracts were read, and reference lists of reviews and retrieved studies were reviewed for additional studies. Where necessary, authors were contacted to obtain raw data for statistical analysis. Papers reporting on ketamine used in the intra- and postoperative setting with pain measured at least 4 weeks after surgery were identified. For meta-analysis of pain after 1, 3, 6 and 12 months, the results were summarised in a forest plot, indicating the number of patients with and without pain in the ketamine and the control groups. The cut-off value used for the VAS/NRS scales was 3 (range 0–10), which is a generally well-accepted value with clinical impact in view of quality of life. Results Our analysis identified ten papers for the comprehensive meta-analysis, including a total of 784 patients. Three papers, which included a total of 303 patients, reported a positive outcome concerning persistent postsurgical pain. In the analysis, only one of nine pooled estimates of postoperative pain at rest or in motion after 1, 3, 6 or 12 months, defined as a value ≥3 on a visual analogue scale of 0–10, indicated a marginally significant pain reduction. Conclusions Based on the currently available data, there is currently not sufficient evidence to support a reduction in chronic pain due to perioperative administration of ketamine. Only the analysis of postoperative pain at rest after 1 month resulted in a marginally significant reduction of chronic postoperative pain using ketamine in the perioperative setting. Implications It can be hypothesised, that regional anaesthesia in addition to the administration of perioperative ketamine might have a preventive effect on the development of persistent postsurgical pain. An additional high-quality pain relief intra- and postoperatively as well after discharge could be more effective than any particular analgesic method per se. It is an assumption that a low dose infusion ketamine has to be administered for more than 72 h to reduce the risk of chronic postoperative pain.

Pathophysiologic and anesthetic considerations for patients with myotonia congenita or periodic paralyses

Myotonia congenita and periodic paralyses are hereditary skeletal muscle channelopathies. In these disorders, various channel defects in the sarcolemma lead to a severely disturbed membrane excitability of the affected skeletal muscles. The clinical picture can range from severe myotonic reactions (e.g., masseter spasm, opisthotonus) to attacks of weakness and paralysis. Provided here is a short overview of the pathomechanisms behind such wide‐ranging phenotypic presentations in these patients, followed by recommendations concerning the management of anesthesia in such populations.

Induction of Therapeutic Hypothermia Requires Modulation of Thermoregulatory Defenses

Hypothermia has been linked to beneficial neurologic outcomes in different clinical situations and its therapeutic value is considered important. For example, in asphyctic neonates and in patients with out-of-hospital cardiac arrest (with ventricular fibrillation as the initial cardiac rhythm), rapid installation of hypothermia has been reported to add substantial therapeutic benefits over nonthermal standard treatments. Yet, in other groups of patients in which the application of therapeutic hypothermia may be applied with clinical benefits, the optimization of therapy remains less straightforward, as the body possesses vigorous defense mechanisms to protect it from inducing hypothermia, that is, especially in conscious patients and/or in those in which the hypothalamus remains intact, such as stroke patients or patients who suffer a myocardial infarction or spinal cord injury. This overview summarizes the bodys primary reactions to hypothermia and the defense mechanisms available or evoked. Then, clinically applicable ways to overcome these forceful cold defenses of the body are described to ensure both an optimal induction process for therapeutic hypothermia and maximal subjective comfort for these conscious patients.

Lactic acid restores skeletal muscle force in an in vitro fatigue model: are voltage-gated chloride channels involved?

High interstitial K(+) concentration ([K(+)]) has been reported to impede normal propagation of electrical impulses along the muscle cell membrane (sarcolemma) and then also into the transverse tubule system; this is one considered underlying mechanism associated with the development of muscle fatigue. Interestingly, the extracellular buildup of lactic acid, once considered an additional cause for muscle fatigue, was recently shown to have force-restoring effects in such conditions. Specifically, it was proposed that elevated lactic acid (and intracellular acidosis) may lead to inhibition of voltage-gated chloride channels, thereby reestablishing better excitability of the muscle cell sarcolemma. In the present study, using an in vitro muscle contractile experimental setup to study functionally viable rectus abdominis muscle preparations obtained from normal swine, we examined the effects of 20 mM lactic acid and 512 μM 9-anthracenecarboxylic acid (9-AC; a voltage-gated chloride channel blocker) on the force recovery of K(+)-depressed (10 mM K(+)) twitch forces. We observed a similar muscle contractile restoration after both treatments. Interestingly, at elevated [K(+)], myotonia (i.e., hyperexcitability or afterdepolarizations), usually present in skeletal muscle with inherent or induced chloride channel dysfunctions, was not observed in the presence of either lactic acid or 9-AC. In part, these data confirm previous studies showing a force-restoring effect of lactic acid in high-[K(+)] conditions. In addition, we observed similar restorative effects of lactic acid and 9-AC, implicating a beneficial mechanism via voltage-gated chloride channel modulation.

Tissue oedema is not associated with skeletal muscle weakness in septic patients

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Different protocols used today to achieve total opioid-free general anesthesia without locoregional blocks

With increasing awareness of both short- and long-term problems associated with liberal perioperative opioid administration, the need for routinely and clinically feasible alternatives is greater than ever. Opioid-free anesthesia-previously reserved for bariatric surgery-is receiving increasing attention in mainstream anesthesia. In this review, we present the truly multimodal concept of opioid-free anesthesia, which circumvents a number of opioid-related problems. For a concrete clinical perspective, we present in depth our opioid-free protocol for bariatric surgery. However, clinicians must be aware of potential problems related to opioid-free anesthesia.