Corrected and republished from: Regional anesthesia and antithrombotic agents: instructions for use.

This corrects the article DOI: 10.23736/S0375-9393.16.11414-2.

The challenge of perioperative pain management in opioid-tolerant patients.

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone.

Regional anaesthesia and antithrombotic agents: instructions for use.

BACKGROUND: The use of anticoagulant agents represents a serious limitation of regional anesthesia, due to the risk of spinal hematoma. Examining all the principles currently available, it has been possible to notice that published guidelines are very often incomplete or also differ significantly on the rules to be followed relating to a specific drug. METHODS: We have carried out a comparison between the guidelines of major scientific societies in order to take a practical and simple user guide which operators can consult. We took into consideration the more and more frequent occurrence of patients who undergo dual antiplatelet and need to be subjected to surgery, considering the possibility of regional anesthesia as an alternative to general anesthesia in conditions of election and not deferrable urgency. RESULTS: We have described the main anticoagulant drugs used in therapy. Regarding the low molecular weight heparins (LMWH), we have reported the most important properties, highlighting the substantial differences of their use detectable by comparison between American and European Guidelines. A similar comparison has been made for the main antiplatelet drugs, including aspirin, and thrombin inhibitors. A particular chapter was dedicated to new oral anticoagulant drugs (NOACs), especially for the low possibility of allowing regional anesthesia. CONCLUSIONS: The comparison between the main guidelines often highlights substantial disparities and weak evidences, so operators must carry out a careful risk / benefit analysis prior to regional anesthesia.

A critical appraisal of the quality of analgosedation guidelines in critically ill patients.

BACKGROUND: The management of analgesia and sedation in critically ill patients is still a challenge due to the shortage of evidence-based treatments. The main objectives of the present study were to critically evaluate the quality of current clinical practice guidelines (CPGL) published on this matter and to identify the contrasting positions and unsolved questions. METHODS: Four members of the Italian Society of Anesthesia and Intensive Care (SIAARTI) council, with an extensive background in the management of critically ill patients and practice guidelines, evaluated CPGL on sedation and analgesia in critically ill patients published from January 2006 to December 2013. Evaluation was performed in accordance with the appraisal of guidelines for research and evaluation tool (AGREE II). RESULTS: Five documents proposed by European and American scientific societies of critical care medicine were identified and evaluated. The CPGL published in 2013 by the American Society of Critical Care Medicine showed the highest scores in all domains of the AGREE II tool, whereas scores for CPGL published in 2006 by SIAARTI showed the lowest scores. In all documents, most recommendations on the use of drugs or non-pharmacological strategies for analgesia, sedation and delirium treatment had low evidence. CONCLUSIONS: This quality evaluation indicated that CPGLs published by the German Association of Scientific Medical Societies, the American College of Critical Care Medicine and the PanAmerican and Iberica Federation of the Critical Care Medicine Societies should be recommended for use. Even in guidelines with a high quality rating, numerous recommendations have moderate or low levels of evidence.

Cystathionine ß-synthase-derived hydrogen sulfide is involved in human malignant hyperthermia.

Hydrogen sulfide is an endogenous gasotransmitter and its mechanism of action involves activation of ATP-sensitive K(+) channels and phosphodiesterase inhibition. As both mechanisms are potentially involved in malignant hyperthermia (MH), in the present study we addressed the involvement of the L-cysteine/hydrogen sulfide pathway in MH. Skeletal muscle biopsies obtained from 25 MH-susceptible (MHS) and 56 MH-negative (MHN) individuals have been used to perform the in vitro contracture test (IVCT). Quantitative real-time PCR (qPCR) and Western blotting studies have also been performed. Hydrogen sulfide levels are measured in both tissue samples and plasma. In MHS biopsies an increase in cystathionine ß-synthase (CBS) occurs, as both mRNA and protein expression compared with MHN biopsies. Hydrogen sulfide biosynthesis is increased in MHS biopsies (0.128±0.12 compared with 0.943±0.13 nmol/mg of protein per min for MHN and MHS biopsies, respectively; P<0.01). Addition of sodium hydrosulfide (NaHS) to MHS samples evokes a response similar, in the IVCT, to that elicited by either caffeine or halothane. Incubation of MHN biopsies with NaHS, before caffeine or halothane challenge, switches an MHN to an MHS response. In conclusion we demonstrate the involvement of the L-cysteine/hydrogen sulfide pathway in MH, giving new insight into MH molecular mechanisms. This finding has potential implications for clinical care and could help to define less invasive diagnostic procedures.

Undiagnosed myopathy before surgery and safe anaesthesia table.

Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy. With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a "Safe Anaesthesia Table", listing both the anaesthetic drugs to be avoided and those considered harmless for myopathic patients, irrespective of age and type of pathology. In addition, a brief outline about the clinical aspects suggestive of a possible muscle pathology is also provided. Using "safe drugs" during routine surgical procedures in subjects with suspected undiagnosed myopathy will enable the anaesthesiologist to avoid delaying surgery, while protecting them from anaesthesia complications. By following this approach the presumed myopathy can be properly investigated after surgery.

Analgesia in PACU: indications, monitoring, complications.

The correct treatment of postoperative pain, in the early period immediately following surgery, is founded on the following four principles: 1-correct diagnosis of the source and magnitude of nociception; 2-understanding of the relationship of ongoing nociception and other components of pain including anxiety, ethnocultural components, meaning, prior experience; 3-treatment by establishment and maintenance of drug level at active sites to achieve and maintain analgesia and anxiolysis as appropriate; 4-continued re-evaluation of the therapy and refinement of the approach. The PACU standard of cure requires a strict accordance between intra and postoperative analgesia. It requires "proactive preoperative plan" that includes: preoperative patient evaluation; discussion with a single patient on different treatment options; patient and family education; pre-emptive measures as indicated; intra-operative multimodal analgesia; a correct triage of analgesia, just after initial evaluation of vital parameters in PACU; re-evaluation of analgesia plan, if analgesia is inadequate; a new titration, intravenous or epidural way, in order to achieve a stable VAS < 3; plan a new analgesia scheme or confirm a preoperative plan; control of adverse events, related to analgesia plan (gastric bleeding and/or bleeding of the surgical wound site, NSAIDs-induced renal damage, respiratory depression, delayed canalisation, nausea, vomiting, excessive sedation, difficulty in bladder emptying, itchiness); a transmission of analgesia plan to ward nurses; a control quality for verify at prefixed times patients satisfaction level, analgesia performed, adverse effects percent, analgesia related, plan variations percent.

Scanning for mutations of the ryanodine receptor (RYR1) gene by denaturing HPLC: detection of three novel malignant hyperthermia alleles.

BACKGROUND: Malignant hyperthermia (MH) is a fatal autosomal dominant pharmacogenetic disorder characterized by skeletal muscle hypertonicity that causes a sudden increase in body temperature after exposure to common anesthetic agents. The disease is genetically heterogeneous, with mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) at 19q13.1 accounting for up to 80% of the cases. To date, at least 42 RYR1 mutations have been described that cause MH and/or central core disease. Because the RYR1 gene is huge, containing 106 exons, molecular tests have focused on the regions that are more frequently mutated. Thus the causative defect has been identified in only a fraction of families as linked to chromosome 19q, whereas in others it remains undetected. METHODS: We used denaturing HPLC (DHPLC) to analyze the RYR1 gene. We set up conditions to scan the 27 exons to identify both known and unknown mutations in critical regions of the protein. For each exon, we analyzed members from 52 families with positive in vitro contracture test results, but without preliminary selection by linkage analysis. RESULTS: We identified seven different mutations in 11 MH families. Among them, three were novel MH alleles: Arg44Cys, Arg533Cys, and Val2117Leu. CONCLUSION: Because of its sensitivity and speed, DHPLC could be the method of choice for the detection of unknown mutations in the RYR1 gene.