Sorin J. Brull

Brief review: Nondepolarizing neuromuscular blocking drugs and critical illness myopathy

PurposeCriticallyill patients who receive nondepolarizing neuromuscular blocking drugs (NMBDs) may be at risk of developing profound muscle weakness that may last for months after the NMBD is discontinued, especially when large cumulative doses of NMBDs and corticosteroids are coadministered to septic, mechanically ventilated patients. This review focuses on the etiology and clinical features of critical illness myopathy (CIM), summarizes specific risk factors for its development, and discusses strategies that might be used to attenuate or even prevent the development of this potentially devastating syndrome.Clinical featuresThe etiology of CIM is unknown. Whether it can develop in atrisk patients who undergo lengthy operations during which they receive NMBDs is also unknown. In some patients following exposure to NMBDs their motor systems are impaired secondary to loss of thick (myosin) filaments that render the muscle unexcitable to direct electrical stimulation, while the sensory system is spared. Management of patients who develop NMBD myopathy is supportive, consisting of nutritional support, physical therapy, and daily trials of decreased ventilatory support.ConclusionRecent guidelines recommend that NMBDs be used in critically ill patients only when absolutely necessary, that the depth of muscle paralysis be monitored to avoid overdosing and metabolite accumulation, and that drug administration be curtailed periodically to allow interruption of sustained NMBD effect.RésuméObjectifLes patients des soins intensifs risquent de subir une faiblesse musculaire profonde pendant des mois après avoir eu des myorelaxants non dépolarisants (MRND), surtout si de fortes doses cumulatives de MRND et des corticostéroïdes ont été coadministrés en présence de septicémie et de ventilation mécanique. Notre revue se concentre sur les causes et les éléments cliniques de la myopathie de réanimation (MDR), résume les facteurs de risque spécifiques de son développement et discute des stratégies qui pourraient atténuer ou même prévenir l’évolution d’un syndrome possiblement dévastateur.Éléments cliniquesLes causes de la MDR sont inconnues. On ne sait pas non plus si elle peut se développer chez des patients à risque qui subissent de longues opérations pendant lesquelles ils reçoivent des MRND. Dans certains cas, une atteinte motrice survient à la suite d’une perte de filaments épais (myosine) et rend le muscle inexcitable à la stimulation électrique directe, alors que le système sensoriel n’est pas touché. Le traitement de la myopathie liée aux MRND consiste en un soutien nutritionnel, de la physio-thérapie et des tentatives quotidiennes de diminution de l’apport de la ventilation mécanique.ConclusionDe récentes recommandations veulent que les MRND ne soient utilisés qu’en cas de nécessité absolue chez les grands malades, que la profondeur de la paralysie musculaire soit surveillée pour éviter un surdosage et une accumulation de métabolite, et que l’administration de médicaments soit périodiquement restreinte pour stopper l’effet entretenu par les MRND.

Sugammadex: a novel selective relaxant binding agent

Sugammadex, a modified γ-cyclodextrin, is the first selective relaxant binding agent. Sugammadex forms very tight complexes in a 1:1 ratio with steroidal neuromuscular blocking agents (rocuronium > vecuronium >> pancuronium). This guest–host complex, which exists in equilibrium, is stable because of its very high association rate and very low dissociation rate. Sugammadex has no effect on acetylcholinesterases or on any receptor system in the body, eliminating the need for anticholinergic drugs, which have undesirable adverse effects. Phase I–III trials found that sugammadex can antagonize any level of neuromuscular blockade, including the profound blockade induced by rocuronium, adding flexibility to the use of nondepolarizing relaxants. Sugammadex rapidly clears from most organs. Sugammadex in doses ranging from 2 to 16 mg/kg is recommended, depending of the level of rocuronium- or vecuronium-induced blockade. Common (incidence of 1–10%) adverse effects are similar for sugammadex and placebo, and include anesthetic complications (movement, coughing, grimacing or suckling on the tracheal tube) and cough. The US FDA has had concerns regarding the safety of sugammadex (hypersensitivity and allergic reactions), but upcoming international studies and the drug’s widespread use in the EU will provide additional information.

The Future of Anesthesiology: Should the Perioperative Surgical Home Redefine Us?

Anesthesiology is at a crossroads. The “Burning Platform” allegory highlights the dilemma facing clinical care and anesthesiology today. We are the workers trapped 150 feet above a stormy, cold ocean on a burning oil platform.a Balanced on that burning stage, our options are limited. None are attractive. For the oil rig worker, death is certain if he stays, and almost certain if he jumps. This metaphor emphasizes that in the face of uncertainty about the future, radical action is required of all of us. This analogy is particularly relevant to the practice of medicine in an unsustainable and rapidly evolving health care environment. Survival instincts (e.g., jumping 150 feet into icy water) trumps one’s instinct to hesitate and hope the current situation fades. For years, the flames of change have been nipping at the heels of the medical practice of anesthesiology. Some think we are “crying wolf.” But most health care experts and even the lay public acknowledge that we must change how we approach our patients and practice. We must adapt to new models of care. We must address some of the most vexing problems that compromise the patient-provider relationship and its impact on quality, safety, and health outcomes. As Dr. Karen Domino opined in her 2014 American Society of Anesthesiologists (ASA) Rovenstine Lecture, “This is no time for business as usual. The forces driving change are enormous, but they can be guided. The clock is ticking. The time to act is now.”

Real-time three-dimensional ultrasound for continuous interscalene brachial plexus blockade

Two-dimensional ultrasound guidance is used commonly for regional anesthetic techniques. This report describes the novel use of three-dimensional, ultrasound-guided, continuous interscalene regional analgesia, which was used in a 36-year-old woman undergoing left total elbow arthroplasty. Possible advantages of this novel technology over current two-dimensional methods include a larger area of available scan information that enables multiple planes of view without having to reposition the ultrasound probe, and three-dimensional visualization of local anesthetic deposition perineurally. Current technological limitations include an upper frequency of 7 MHz, which decreases the resolution of superficial scanning.

Reversal of neuromuscular blockade: "identification friend or foe".

T he article by McLean et al.2 builds on a burgeoning body of literature that for more than 50 yr has described potential complications associated with the use of neuromuscular-blocking agents (NMBAs). There seem to be two themes: The first irrefutable finding is affirmation that the use of NMBAs is associated with postoperative residual weakness that may lead to significant morbidity and, rarely, mortality. Although the second theme is also supported by good science, it is more controversial as it appears to “fly in the face” of the typical anesthesiologist who feels that administration of neostigmine to induce pharmacologic reversal is routinely and reliably sufficient to ensure adequate postoperative neuromuscular function (and thus avoid respiratory complications). however, both the anesthesia and the critical care medicine literature is replete with studies documenting that with or without neostigmine, a significant proportion of our patients exhibits significant residual neuromuscular block (defined as train-of-four [TOF] ratio <0.90) when tested objectively in the postanesthesia care unit (PACU).3 In a sense, NMBAs are similar to opioids—they are both “life-saving” and “complicationproducing” drugs. When used appropriately, NMBAs allow the performance of surgical procedures that would be much more difficult and sometimes impossible without the induced paralysis. Similarly, opioids allow the performance of surgical procedures that would otherwise induce a more significant physiologic trespass with increased risks and complications. But both NMBAs and opioids have significant, sometimes deadly, side effects unless monitored appropriately. Monitoring the depth of analgesia and respiratory depression produced by opioids can be difficult, inexact, and unreliable. Unlike opioids, however, the depth of neuromuscular block, and the adequacy of reversal, can and should be measured— easily, predictably, and routinely. We have the technology, and we have the proof—so far, we have just not had the resolve. It is inexplicable that monitoring of the depth of NMBA block and adequacy of pharmacologic reversal are still not used routinely, and several previous editorials have pointed out the lack of understanding of clinicians of, and perhaps interest in, neuromuscular monitoring.4,5 Why should this be? We believe that a host of factors6 provide some explanation and should include medical heuristics. These heuristics are mental shortcuts used to assist our everyday decisionmaking during patient care, but in essence these are educated Reversal of Neuromuscular Blockade

Conceptual and technical insights into the basis of neuromuscular monitoring

Unrecognised postoperative residual neuromuscular block remains a frequent occurrence in recovery rooms. Evidence indicates that current practice continues to perpetuate the status quo, in which 10–40% of patients experience postoperative residual weakness. A departure from the current practice requires small efforts on the clinicians’ part. This review addresses several selected core questions regarding neuromuscular blockade monitoring and provides a framework to rationally discuss and develop basic guidelines for the use of neuromuscular blocking agents in patient care.

Survey of the National Drug Shortage Effect on Anesthesia and Patient Safety: A Patient Perspective.

BACKGROUND:There are few data on patients’ desire to be informed of drug shortages before elective surgery. We surveyed patients who had previously undergone laparoscopic cholecystectomy for their opinions. METHODS:Nine hundred forty-nine Mayo Clinic patients were invited to participate in the survey. The postal survey posed a hypothetical surgical scenario and requested answers regarding the desire to be informed and to postpone scheduled surgery because of neostigmine shortage. Comparison was made with Canadian patients from a hospital in Ontario. RESULTS:Most of the 256 respondents wanted “to be told by the anesthesia doctor about the neostigmine shortage” if there were “slight differences” in side effects between the drug combinations (P < 0.0001). The percentage of patients wanting to know was 76.2% (95% confidence interval, 70.5%–81.3%). Secondary analyses tested the validity and reliability of the survey. With each increase in the differences in substituted drug’s side effects, there was a progressive increase in the patients’ desire for information (P < 0.0001; 73.2%, 76.2%, and 95.7% of 246, 256, and 253 respondents, respectively) and preference for delaying surgery (P< 0.0001; 33.6%, 39.4%, and 80.9% of 238, 246, and 241 respondents, respectively). There was no association with respondents’ sex (P = 0.19), age (P = 0.76), educational level (P = 0.39), or country (United States versus Canada [n = 58]; P = 0.87). CONCLUSIONS:The majority (>50%) of surveyed patients want to be informed of drug shortages that might affect their care.

Vascular air embolism: A silent hazard to patient safety

Purpose: To narratively review published information on prevention, detection, pathophysiology, and appropriate treatment of vascular air embolism (VAE). Materials and methods: MEDLINE, SCOPUS, Cochrane Central Register and Google Scholar databases were searched for data published through October 2016. The Manufacturer and User Facility Device Experience (MAUDE) database was queried for “air embolism” reports (years 2011–2016). Results: VAE may be introduced through disruption in the integrity of the venous circulation that occurs during insertion, maintenance, or removal of intravenous or central venous catheters. VAE impacts pulmonary circulation, respiratory and cardiac function, systemic inflammation and coagulation, often with serious or fatal consequences. When VAE enters arterial circulation, air emboli affect cerebral blood flow and the central nervous system. New medical devices remove air from intravenous infusions. Early recognition and treatment reduce the clinical sequelae of VAE. An organized team approach to treatment including clinical simulation can facilitate preparedness for VAE. The MAUDE database included 416 injuries and 95 fatalities from VAE. Data from the American Society of Anesthesiologists Closed Claims Project showed 100% of claims for VAE resulted in a median payment of

If one is good, are two always better?

325,000. Conclusions: VAE is an important and underappreciated complication of surgery, anesthesia and medical procedures. HighlightsReview prevention, detection, and treatment of vascular air embolism (VAE).VAE affects systemic circulation, respiratory, cardiac function with fatal sequelae.An organized team approach can facilitate preparedness and prevention of VAE.

Management Principles to Reduce the Risk of Residual Neuromuscular Blockade

Health care-associated infections are common and costly complications in hospitalized patients, especially the critically ill. The major nosocomial infections include surgical site infections (SSI), central line-associated bloodstream infections, ventilator-associated pneumonia, catheter-associated urinary tract infections, and Clostridium difficile-associated disease. Each infection accrues significant direct (e.g., additional medications and increased hospital length of stay), indirect (e.g., shortand long-term morbidity, lost income to the patient and family members), and intangible (e.g., pain and suffering, patient stress) costs. In addition to the increased risk of mortality, health care-associated infections increase attributable hospital costs by