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Created June 3, 2015, last updated over 3 years ago.
Collection: 25, Score: 14492, Trend score: 0, Read count: 15540, Articles count: 23, Created: 2015-06-03 03:28:53 UTC. Updated: 2021-02-07 11:33:20 UTC.Notes
A collection of landmark papers relevant to anaesthesia and anesthesiology.
Generally, these papers are practice changing and hold current, ongoing significance beyond their historical importance.
This is a dynamic and changing document that will be updated, pruned and added to as appropriate. Many of these papers have free full-text provided by the publisher because of their significance.
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Collected Articles
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Randomized Controlled Trial Clinical Trial
Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group.
Intraoperative warming of patients avoids hypothermia, reduces wound infection and shortens hospital stay after colorectal surgery.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial.
Perioperative epidural analgesia in high-risk patients undergoing major abdominal surgery improves analgesia but does not have other morbidity or mortality benefits.
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Anesthesia and analgesia · Sep 2004
Multicenter StudyThe incidence of awareness during anesthesia: a multicenter United States study.
The incidence of awareness-with-recall under general anesthesia in the United States is 1-2 cases per 1,000 patients.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial.
BIS monitoring significantly reduces the risk of awareness under general anesthesia in high-risk adult surgical patients.
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Randomized Controlled Trial Comparative Study
Anesthesia awareness and the bispectral index.
BIS monitoring may not reduce the incidence of awareness under general anesthesia.
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Randomized Controlled Trial Multicenter Study Clinical Trial
A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.
Ondansetron, dexamethasone, droperidol and total intravenous anesthesia (TIVA) all have a roughly similar, productive effect to reduce postoperative nausea and vomiting (PONV) by about one third.
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Randomized Controlled Trial Comparative Study Clinical Trial
Randomized controlled trial comparing traditional with two "mobile" epidural techniques: anesthetic and analgesic efficacy.
This follow-up paper to the original COMET study describes in detail the high and low-dose epidural techniques and the subsequent anesthetic characteristics.
The low-dose techniques used infusions of 0.1% bupivacaine with 2 mcg/mL fentanyl, compared with 10mL boluses of 0.25% bupivacaine. Maternal analgesia experience was similar between the groups, all the CSE group experienced better analgesia in the first hour.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial.
Magnesium sulphate halves the risk of eclampsia in pre-eclamptic pregnant women without significant adverse effect.
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Randomized Controlled Trial Multicenter Study
Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
POISE showed that for every 1000 patients receiving metoprolol, 15 were prevented from suffering a myocardial infract, 3 from requiring cardiac revascularization along with 7 new cases of atrial fibrillation, but at a cost of causing an excess 8 deaths, 5 strokes, 53 hypotensive events and 42 episodes of bradycardia.
The harm associated with perioperative beta-blockade, at least in the form of non-titrated extended-release metoprolol, is greater than the demonstrated benefit. For every two cases of myocardial infract avoided there is one excess death.
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Randomized Controlled Trial Comparative Study Clinical Trial
The risk of cesarean delivery with neuraxial analgesia given early versus late in labor.
Neuraxial analgesia early in labor does not increase the risk of cesarean delivery or increase the duration of labor compared with analgesia later in labor.
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Randomized Controlled Trial Multicenter Study
Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial.
Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear. ⋯ Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.
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Randomized Controlled Trial Multicenter Study
The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.
Nitrous oxide use in non-cardiac surgery does not increase the risk of death, cardiovascular complications or wound infection.
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Randomized Controlled Trial Multicenter Study
Aspirin in patients undergoing noncardiac surgery.
Perioperative aspirin use does not reduce mortality or myocardial infraction, but does increase the risk of major bleeding.
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Randomized Controlled Trial Multicenter Study Comparative Study
Clonidine in patients undergoing noncardiac surgery.
Perioperative clonidine administration does not reduce mortality or myocardial infraction, but does increase the risk of hypotension and non-fatal cardiac arrest.
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Beware anesthesiologist number 7... the quality of intraoperative conduct of anesthesia effects patient outcomes.
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One of the earliest published case series linking post-operative hepatic necrosis to halothane anaesthesia.
We now know this occurs in about 1 in 10,000-30,000 adult halothane anaesthetics, and 1 in 60,000 in children, with a historical mortality of 30-70%. In 20% of cases the hepatitis is mild and self-limiting.
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Review Comparative Study
Intrathecal and epidural administration of opioids.
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Anesthesia and analgesia · Aug 2013
Multicenter StudyReversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
Sugammadex use does not avoid either the need or benefit of neuromuscular monitoring, although it does result in less residual neuromuscular block than neostigmine reversal.
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Randomized Controlled Trial Multicenter Study
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.
Why is this a landmark trial?
Three reasons:
- Clinical significance of the findings: reducing maternal mortality.
- Relevance to much of world's population, in particular to low resource settings where post-partum haemorrhage (PPH) is disproportionately burdensome.
- Quality – a massive, double-blinded randomised controlled trial.
So, what did they do?
They randomised 20,060 women with PPH to receive either 1g of tranexamic acid (100mg/min slow IV) or placebo, across 21 countries and 193 hospitals. Although only 569 (2.8%) patients were from a high resource country (UK).
What did they find?
Mortality due to haemorrhage was reduced by almost 20% (RR 0.81, NNT 267) after receiving tranexamic acid (TXA), and by 30% (RR 0.69) when given within 3 hours of birth.
Hysterectomies were not reduced by TXA use. There was no increased risk of thromboembolic events.
Be smart
While on the surface this suggests we should move to routine use of TXA in managing all PPH, the risk of PPH-death in most high resource countries is relatively low. 99% of all PPH deaths are in low resource countries.
In the WOMAN trial the risk of death in the placebo group was 1.9%. In contrast the latest maternal mortality data from MBRACE-UK (2014-16) reports 0.78 haemorrhage-deaths per 100,000 maternities, which using a conservative 5% PPH incidence (depending on definition), yields a PPH-mortality risk of 0.016% – 100x less than the study population.
Thus in a high resource setting the TXA NNT to avoiding one maternal death is generously at least 20,000 PPH cases.
In high resource settings, TXA use should be considered second-line therapy in managing severe PPH when other measures are inadequate. In low resource settings where maternal PPH mortality Is high, TXA reduces maternal mortality and should be routinely used.
Context is everything.
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The incidences of mortality and morbidity associated with anaesthesia were reviewed. Most of the published incidences for common complications of anaesthesia vary considerably. Where possible, a realistic estimate of the incidence of each morbidity has been made, based on the best available data. ⋯ The incidences of anaesthetic complications are compared with the relative risks of everyday events, using a community cluster logarithmic scale, in order to place the risks in perspective when compared with other complications and with the inherent risks of surgery. Documentation of these risks and discussion with patients should allow them to be better informed of the relative risks of anaesthetic complications. Depending on specific comorbidities and the severity of operation, these risks associated with anaesthesia may increase for any one individual.
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Randomized Controlled Trial Multicenter Study
Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.
What’s all the fuss?
Significant observational evidence suggested an association between mortality and deep anaesthesia, in particular a 2017 meta-analysis. However it has been suspected that anaesthetic depth may merely be a surrogate marker for intraoperative hypotension, a well-established risk factor for post-operative mortality and morbidity.
With this large RCT, the Balanced Anaesthesia Study Group has shown that deep general anaesthesia is not associated with an increase 1-year mortality.
What did they do?
The researchers conducted an ambitious, large (6,644 patients), multi-center, randomised controlled trial. Patients aged ≥60 years undergoing major surgery (expected ≥2h surgery and ≥2d hospital stay) were randomised to receive volatile general anaesthesia targeting BIS 50 or BIS 35.
To minimise intra-operative blood pressure as a confounder, anaesthetists were required to specify a target MAP before BIS-group allocation.
They found...
Not only was there no mortality difference between the BIS 50 and BIS 35 groups, there were also no major or moderate morbidity differences, or difference in recovery or length of stay. BIS targets were adequately achieved, though not perfect, and MAP was clinically similar for both groups.
Context is everything
This is about as high-quality as a large, modern study looking at longer-term outcomes can get. It is widely applicable to most populations and common general anaesthetic scenarios, except for a few important caveats:
- Very few ASA 4 (5%) patients were enrolled.
- Only volatile-maintenance anaesthesia was studied not propofol/TIVA.
- We can draw no conclusion regarding the consequences of extreme-depth (ie. BIS << 35).
- The actual depth difference between the BIS-35 and BIS-50 groups was not as much as perhaps ideal: mean BIS 39 vs 47 respectively...
Final thought
...there was (only) one case of awareness in the light-depth BIS 50 group, despite 39% of patients receiving volatile < 0.7 MAC.
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Randomized Controlled Trial Multicenter Study
Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial.
In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. ⋯ US National Institutes of Health, US Food and Drug Administration, Thrasher Research Fund, Australian National Health and Medical Research Council, Health Technologies Assessment-National Institute for Health Research (UK), Australian and New Zealand College of Anaesthetists, Murdoch Children's Research Institute, Canadian Institutes of Health Research, Canadian Anesthesiologists Society, Pfizer Canada, Italian Ministry of Health, Fonds NutsOhra, UK Clinical Research Network, Perth Children's Hospital Foundation, the Stan Perron Charitable Trust, and the Callahan Estate.
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Randomized Controlled Trial Multicenter Study
Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial.
What makes this a landmark study?
Since Exadaktylos’ (2006) extraordinary retrospective study showing a 30% reduction in breast cancer recurrence with a regional analgesia technique, we have been anxious to learn whether anaesthetic choice my impact cancer outcome.
Various in vitro studies suggested plausible explanations for how opioids and volatiles could promote cancer recurrence, although quality evidence remainded missing.
The Breast Cancer Recurrence Collaboration has filled this gap, setting out to answer this question with an international, multicenter, randomised controlled trial.
What did they do?
Over 12 years 2,132 women were enrolled and ranomised to either paravertebral block & propofol, or sevoflurane. Some in the paravertebral group were exposed to sevoflurane when required (17%), and did receive intraoperative fentanyl, although roughly half as much on average as the volatile group.
And they found?
There was no difference in cancer recurrence rate or persistent wound pain between groups. Even when analysing only patients who received no sevoflurane (83% of regional group) no difference was identified.
This does not mean that a paravertebral technique offers no benefit: it almost eliminated the need for volatile anaesthesia, reduced opioid demand and reduced post-operative nausea & vomiting – all positive outcomes. But it did not reduce cancer recurrence.
Be smart
This result cannot be generalised beyond breast cancer to more invasive, stress-inducing cancer surgery (eg. prostatectomy, pneumonectomy). Our knowledge of perioperative factors that depress host defences (surgical stress, volatiles and opioids) are still relevant when we consider how anaesthetic choices may contribute to improving patient outcomes.
Explore further...
Dig deeper with other articles collected in Anesthesia technique and cancer recurrence.
summary
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