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Orphanet Journal of Rare Diseases Aug 2015Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as... (Review)
Review
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.
Topics: Genetic Counseling; Humans; Malignant Hyperthermia
PubMed: 26238698
DOI: 10.1186/s13023-015-0310-1 -
Anesthesia and Analgesia Oct 2021With an estimated worldwide volume of 266 million surgeries in 2015, the call for general inhalation anesthesia is considerable. However, widely used volatile...
With an estimated worldwide volume of 266 million surgeries in 2015, the call for general inhalation anesthesia is considerable. However, widely used volatile anesthetics such as N2O and the highly fluorinated gases sevoflurane, desflurane, and isoflurane are greenhouse gases, ozone-depleting agents, or both. Because these agents undergo minimal metabolism in the body during clinical use and are primarily (≥95%) eliminated unchanged via exhalation, waste anesthetic gases (WAGs) in operating rooms and postanesthesia care units can pose a challenge for overall elimination and occupational exposure. The chemical properties and global warming impacts of these gases vary, with atmospheric lifetimes of 1-5 years for sevoflurane, 3-6 years for isoflurane, 9-21 years for desflurane, and 114 years for N2O. Additionally, the use of N2O as a carrier gas for the inhalation anesthetics and as a supplement to intravenous (IV) anesthetics further contributes to these impacts. At the same time, unscavenged WAGs can result in chronic occupational exposure of health care workers to potential associated adverse health effects. Few adverse effects associated with WAGs have been documented, however, when workplace exposure limits are implemented. Specific measures that can help reduce occupational exposure and the environmental impact of inhaled anesthetics include efficient ventilation and scavenging systems, regular monitoring of airborne concentrations of waste gases to remain below recommended limits, ensuring that anesthesia equipment is well maintained, avoiding desflurane and N2O if possible, and minimizing fresh gas flow rates (eg, use of low-flow anesthesia). One alternative to volatile anesthetics may be total intravenous anesthesia (TIVA). While TIVA is not associated with the risks of occupational exposure or atmospheric pollution that are inherent to volatile anesthetic gases, clinical considerations should be weighed in the choice of agent. Appropriate procedures for the disposal of IV anesthetics must be followed to minimize any potential for negative environmental effects. Overall, although their contributions are relatively low compared with those of other human-produced substances, inhaled anesthetics are intrinsically potent greenhouse gases and pose a risk to operating-room personnel if not properly managed and scavenged. Factors to reduce waste and minimize the future impact of these substances should be considered.
Topics: Air Pollutants, Occupational; Anesthesia, Inhalation; Anesthetics, Inhalation; Animals; Conservation of Natural Resources; Environmental Monitoring; Global Warming; Greenhouse Effect; Greenhouse Gases; Humans; Medical Waste; Medical Waste Disposal; Occupational Exposure; Occupational Health; Ozone Depletion; Risk Assessment; Risk Factors
PubMed: 33857027
DOI: 10.1213/ANE.0000000000005504 -
BMC Anesthesiology Dec 2019The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery... (Review)
Review
BACKGROUND
The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction.
MAIN BODY
This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer's disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment.
CONCLUSIONS
Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.
Topics: Anesthesia, General; Anesthesiology; Cognitive Dysfunction; Humans; Postoperative Cognitive Complications; Risk Factors
PubMed: 31881996
DOI: 10.1186/s12871-019-0903-7 -
The Cochrane Database of Systematic... Aug 2018The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced awareness of the environment and a disturbance in attention, typically occurs between 24 and 72 hours after surgery and can affect up to 60% of elderly surgical patients. Postoperative cognitive dysfunction (POCD) is a new-onset of cognitive impairment which may persist for weeks or months after surgery.Traditionally, surgical anaesthesia has been maintained with inhalational agents. End-tidal concentrations require adjustment to balance the risks of accidental awareness and excessive dosing in elderly people. As an alternative, propofol-based total intravenous anaesthesia (TIVA) offers a more rapid recovery and reduces postoperative nausea and vomiting. Using TIVA with a target controlled infusion (TCI) allows plasma and effect-site concentrations to be calculated using an algorithm based on age, gender, weight and height of the patient.TIVA is a viable alternative to inhalational maintenance agents for surgical anaesthesia in elderly people. However, in terms of postoperative cognitive outcomes, the optimal technique is unknown.
OBJECTIVES
To compare maintenance of general anaesthesia for elderly people undergoing non-cardiac surgery using propofol-based TIVA or inhalational anaesthesia on postoperative cognitive function, mortality, risk of hypotension, length of stay in the postanaesthesia care unit (PACU), and hospital stay.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE (1946 to November 2017), Embase (1974 to November 2017), PsycINFO (1887 to November 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) with participants over 60 years of age scheduled for non-cardiac surgery under general anaesthesia. We planned to also include quasi-randomized trials. We compared maintenance of anaesthesia with propofol-based TIVA versus inhalational maintenance of anaesthesia.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings.
MAIN RESULTS
We included 28 RCTs with 4507 randomized participants undergoing different types of surgery (predominantly cardiovascular, laparoscopic, abdominal, orthopaedic and ophthalmic procedures). We found no quasi-randomized trials. Four studies are awaiting classification because we had insufficient information to assess eligibility.All studies compared maintenance with propofol-based TIVA versus inhalational maintenance of anaesthesia. Six studies were multi-arm and included additional TIVA groups, additional inhalational maintenance or both. Inhalational maintenance agents included sevoflurane (19 studies), isoflurane (eight studies), and desflurane (three studies), and was not specified in one study (reported as an abstract). Some studies also reported use of epidural analgesia/anaesthesia, fentanyl and remifentanil.We found insufficient reporting of randomization methods in many studies and all studies were at high risk of performance bias because it was not feasible to blind anaesthetists to study groups. Thirteen studies described blinding of outcome assessors. Three studies had a high of risk of attrition bias, and we noted differences in the use of analgesics between groups in six studies, and differences in baseline characteristics in five studies. Few studies reported clinical trials registration, which prevented assessment of risk of selective reporting bias.We found no evidence of a difference in incidences of postoperative delirium according to type of anaesthetic maintenance agents (odds ratio (OR) 0.59, 95% confidence interval (CI) 0.15 to 2.26; 321 participants; five studies; very low-certainty evidence); we noted during sensitivity analysis that using different time points in one study may influence direction of this result. Thirteen studies (3215 participants) reported POCD, and of these, six studies reported data that could not be pooled; we noted no difference in scores of POCD in four of these and in one study, data were at a time point incomparable to other studies. We excluded one large study from meta-analysis because study investigators had used non-standard anaesthetic management and this study was not methodologically comparable to other studies. We combined data for seven studies and found low-certainty evidence that TIVA may reduce POCD (OR 0.52, 95% CI 0.31 to 0.87; 869 participants).We found no evidence of a difference in mortality at 30 days (OR 1.21, 95% CI 0.33 to 4.45; 271 participants; three studies; very low-certainty evidence). Twelve studies reported intraoperative hypotension. We did not perform meta-analysis for 11 studies for this outcome. We noted visual inconsistencies in these data, which may be explained by possible variation in clinical management and medication used to manage hypotension in each study (downgraded to low-certainty evidence); one study reported data in a format that could not be combined and we noted little or no difference between groups in intraoperative hypotension for this study. Eight studies reported length of stay in the PACU, and we did not perform meta-analysis for seven studies. We noted visual inconsistencies in these data, which may be explained by possible differences in definition of time points for this outcome (downgraded to very low-certainty evidence); data were unclearly reported in one study. We found no evidence of a difference in length of hospital stay according to type of anaesthetic maintenance agent (mean difference (MD) 0 days, 95% CI -1.32 to 1.32; 175 participants; four studies; very low-certainty evidence).We used the GRADE approach to downgrade the certainty of the evidence for each outcome. Reasons for downgrading included: study limitations, because some included studies insufficiently reported randomization methods, had high attrition bias, or high risk of selective reporting bias; imprecision, because we found few studies; inconsistency, because we noted heterogeneity across studies.
AUTHORS' CONCLUSIONS
We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes.
Topics: Aged; Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthetics, Inhalation; Anesthetics, Intravenous; Cognition; Cognition Disorders; Delirium; Desflurane; Humans; Hypotension; Isoflurane; Methyl Ethers; Middle Aged; Postoperative Complications; Propofol; Randomized Controlled Trials as Topic; Sevoflurane; Surgical Procedures, Operative
PubMed: 30129968
DOI: 10.1002/14651858.CD012317.pub2