CONTINUOUS FINGER-CUFF BLOOD PRESSURE MONITORING

28 Aug 2023THE ANESTHESIA CONSULTANT Leave a comment

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Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group

Richard Novak, MD is a Stanford physician board certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
emailrjnov@yahoo.com

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EDWARDS CLEARSIGHT FINGER-CUFF BLOOD PRESSURE MONITOR

Picture this: prior to surgery you place a blood pressure cuff around the middle phalanx of your patient’s right middle finger, instead of a standard cuff on the upper arm, to measure blood pressure. Is this the future? After decades of watching intermittent readings from oscillometric (standard) blood pressure cuffs, will we be monitoring data from a continuous finger-cuff instead?

Perhaps.

A study in the September 2023 issue of Anesthesiology showed that continuous finger-cuff arterial pressure monitoring helped anesthesia professionals a) reduce hypotension during the 15 minutes following induction of general anesthesia, and b) reduce hypotension during the duration of noncardiac surgery, compared to traditional intermittent oscillometric arterial pressure monitoring.

The study was done in a single medical center, the University Medical Center Hamburg–Eppendorf in Hamburg, Germany. A total of 242 patients aged 45 and older who were scheduled for noncardiac surgery were randomized to continuous finger-cuff arterial pressure monitoring or to intermittent traditional oscillometric arterial pressure monitoring. The continuous finger-cuff arterial pressure monitor used was the ClearSight system manufactured by Edwards Lifesciences, USA.

Edwards ClearSight Monitoring System

An appropriately sized finger-cuff (small, medium, or large) was positioned on the middle phalanx of the third or fourth finger of every patient, along with a standard intermittent oscillometric arterial pressure monitor on the opposite arm. Traditional oscillometric arterial pressures were measured at 2.5 minute intervals. The clinical monitoring for each patient was randomized to be either 1) unblinded continuous finger-cuff arterial pressure monitoring, or 2) intermittent standard oscillometric arterial pressure monitoring with the finger-cuff data blinded. The Hamburg medical center’s institutional routine was to maintain MAP (mean arterial pressure) above 65 mmHg, and intraoperative hypotension was treated with intravenous norepinephrine, which was given at the discretion of each attending anesthesiologist.

The Anesthesiology study had two primary endpoints. The first was the amount of hypotension during the 15 minutes following the induction of anesthesia, and the second was the time-weighted average MAP less than 65 mmHg during the entire surgery. Results showed that continuous finger-cuff arterial pressure monitoring helped anesthesia providers a) reduce hypotension within the first 15 minutes after starting induction of anesthesia, and b) reduce hypotension during the entire noncardiac surgery. Patients assigned to continuous finger-cuff monitoring received more than twice as much norepinephrine both within 15 minutes after starting induction of anesthesia and during the entire surgery, when compared with patients assigned to intermittent oscillometric monitoring. This presumably explains why there was significantly less hypotension in the continuous finger-cuff monitoring group.

Intraoperative hypotension carries risks of major postoperative complications, including acute kidney injury, myocardial injury, and death. Previous studies have validated that both the severity and the duration of intraoperative hypotension are associated with postoperative complications and mortality. Two previous trials validated the efficacy of continuous finger-cuff arterial pressure monitoring during surgery. In a study of 160 patients undergoing orthopedic surgery, continuous finger-cuff monitoring resulted in less than half the number of hypotensive events, defined as a MAP less than 60 mmHg (19 vs. 51 events). A second study of 316 patients undergoing noncardiac surgery showed that continuous finger-cuff arterial pressure monitoring nearly halved the amount of intraoperative hypotension, defined as the time-weighted average MAP less than 65 mmHg.

The Edwards Lifesciences website describes the ClearSight continuous finger-cuff monitoring system. In addition to continuous blood pressure monitoring, the ClearSight system records advanced hemodynamic parameters from the noninvasive finger cuff, including graphic trend displays on the Edwards Lifesciences HemoSphere monitor of:
• Cardiac output (CO)
• Stroke volume (SV)
• Stroke volume variation (SVV), and
• Systemic vascular resistance (SVR).

These parameters provide additional information which, if validated, can expand the information an anesthesia provider can monitor routinely. The parameters of continuous blood pressure (ART), continuous Mean Arterial Pressure (MAP), Cardiac output (CO) and Stroke volume (SV) are shown on the HemoSphere monitor below.

The technology behind the ClearSight continuous finger-cuff monitor involves a principle called the volume clamp method. Per the Edwards Lifesciences website, this “involves clamping the artery in the finger to a constant volume, by dynamically providing equal pressure on either side of the arterial wall. The volume is measured by a photo-plethysmograph built into the cuff. The counter pressure is applied by an inflatable bladder inside the cuff and is adjusted 1000 times per second to keep the arterial volume constant. Continuous recording of the cuff pressure results in real-time finger pressure waveform.^”

Volume clamp cross section

Interior of the Edwards finger-cuff

Dr. Daniel Sessler, one of the world’s most respected and prolific anesthesia researchers, is a co-author of the recent Anesthesiology study. To me this validates the notion that continuous finger-cuff technology may eventually gain widespread adoption in operating room monitoring. (Note also that Dr. Sessler is a consultant for Edwards Lifesciences, and has received research funding from the company, as have some of the other authors of the Anesthesiology study.)

Unanswered questions regarding continuous finger-cuff blood pressure monitoring include:

Would data show that more frequent utilization of oscillometric (standard) blood pressure readings, recordedwith our existing equipment every one minute instead of every 2.5 minutes, give as much information as a continuous finger-cuff?
If a patient’s hand or fingers are jiggled or moved during monitoring, would the continuous finger-cuff give significant artifacts?
Would clinicians use both traditional blood pressure cuff monitoring and continuous finger-cuff monitoring on the same patient, and make physiologic conclusions from both sources of input?
Will other models of finger-cuff monitoring, different from the Edwards Lifesciences ClearSight model, vary in accuracy? Will clinicians trust new finger-cuff monitoring devices and their data?
What will be the price of this technology?

The benefit/risk ratio of continuous finger-cuff monitoring appears to be high. The technology is noninvasive and unlikely to harm our patients in any way, as long as the data is accurate. The dollar cost of this new technology will influence its rate of adoption. Existing intermittent oscillometric (traditional) blood pressure monitoring devices are already present in every operating room as standard equipment on today’s budgets. If continuous finger-cuff blood pressure monitoring is both accurate and inexpensive, the new technology may be universally adopted. But because a majority of anesthetics are administered to reasonably healthy ASA 1 or ASA 2 patients, many of them in outpatient surgery centers, one could argue that measuring intermittent blood pressures every 2.5 to 3 minutes with oscillometric (traditional) blood pressure monitoring devices is an adequate monitoring interval for these patients. If the added cost of continuous finger-cuff monitoring is excessive, this technology may be limited to hospitals, where sicker patients are anesthetized for bigger and more invasive surgical procedures, and which present increased risk for patients with hypotension.

The Food and Drug Administration recently approved an additional monitoring system based on finger-cuff technology from Edwards Lifesciences, the Acumen Hypotension Prediction Index (HPI) software system. This system uses machine learning to alert clinicians of the likelihood a patient is trending toward hypotension, or low blood pressure.

Keep your eyes open for further studies on the ClearSight system, the Acumen system, and other continuous finger-cuff monitoring equipment. This technology may become part of our operating room life in the near future.

READ ABOUT RICK NOVAK’S FICTION WRITING AT RICK NOVAK.COM

THE TOP 10 LIVING ANESTHESIOLOGISTS 2022

12 Jan 202219 Sep 2023THE ANESTHESIA CONSULTANT 2 Comments

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THE ANESTHESIA CONSULTANT

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group

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TheAnesthesiaConsultant.com presents its 2022 ranking of The Top 10 Living Anesthesiologists. These individuals made significant original contributions to the practice and/or education of anesthesiologists throughout the world. As a physician anesthesiologist who has attended to patients in the 1980s, 1990s, 2000s, 2010s, and now the 2020s, in both university and community settings, I’m uniquely qualified to identify and honor the leaders in our field over this time.

Here’s the list:

#10. David Gaba MD, Stanford University School of Medicine. Dr. Gaba developed the anesthesia crisis simulator, and his group developed the Stanford Anesthesia Emergency Manual. Both are landmark contributions toward reducing medical errors by anesthesia providers and improving patient outcomes. Dr. Gaba has authored 242 publications in major medical journals. He is a Professor at the Stanford University Department of Anesthesiology, Perioperative and Pain Medicine, and the Associate Dean for Immersive and Simulation-Based Learning at the Stanford University School of Medicine.

#9. James Eisenach MD, Wake Forest University. Dr. Eisenach served as Editor-in-Chief of Anesthesiology for 10 years from 2007-2016, and in 2016 became the President and CEO of the Foundation for Anesthesia Education and Research (FAER), a key organization supporting research in our field. Dr. Eisenach has authored 562 publications in major medical journals and is nationally renowned for his research on the mechanisms of pain. Dr. Eisenach is a Professor of Anesthesia at Wake Forest University.

#8. Robert Stoelting MD, University of Indiana. https://patientsafetymovement.org/speaker/robert-k-stoelting-md/ Dr. Stoelting is the author of the textbook Pharmacology and Physiology in Anesthetic Practice, co-author of the textbooks Basics of Anesthesia and Anesthesia and Co-Existing Disease, and co-editor of the textbook Clinical Anesthesia. During his 19 years as President of the Anesthesia Patient Safety Foundation, Dr. Stoelting was instrumental in developing and expanding the APSF as a leading publication in the anesthesia literature. Dr. Stoelting is a Professor Emeritus and Past Chair, Department of Anesthesia, Indiana University School of Medicine (1977-2003).

#7. Brian Bateman MD, Stanford University. Dr. Bateman is the current Chairman of the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford. An expert in obstetric anesthesia, Dr. Bateman was the Chief of Obstetric Anesthesia at the Brigham and Women’s Hospital in the Harvard system until 2021 when he moved to Stanford. He is an Editor for Anesthesiology, the world’s leading journal in our specialty. Dr. Bateman has over 200 peer-reviewed publications.

#6. Jonathan Benumof MD, University of California San Diego. Dr. Benumof was the main originator of the American Society of Anesthesiologists Difficulty Airway Algorithm, first published in 1996. The Difficult Airway Algorithm described pathways to safe airway management, and its application has saved countless lives that might have been lost to mismanaged airway disasters. He also single-authored the textbook Anesthesia for Thoracic Surgery as well as 311 publications in major medical journals. Dr. Benumof is an Emeritus Professor of Anesthesiology at the University of California San Diego School of Medicine.

Dr. Steven Shafer testifying at the Michael Jackson manslaughter trial

#5. Steven Shafer MD PhD, Stanford University. Dr. Shafer’s area of expertise is the pharmacology of intravenous anesthetic drugs. He was the Editor-in-Chief of Anesthesia and Analgesia for 10 years and authored 293 publications in major medical journals, many of them the initial studies on the pharmacokinetics of propofol. He is currently the Editor-in-Chief of The ASA Monitor. Dr. Shafer appeared as an expert witness in the Michael Jackson manslaughter trial, in which Dr. Conrad Murray was convicted of the inappropriate administration of propofol in Jackson’s bedroom. Dr. Shafer is a Professor Emeritus at the Stanford University Department of Anesthesiology, Perioperative and Pain Medicine.

#4. Lee Fleisher MD, University of Pennsylvania. Dr. Fleisher authored the textbooks Anesthesia and Uncommon Diseases, and Complications in Anesthesia, as well as 421 publications in major medical journals, with a concentration in the preoperative evaluation of the surgical patient. His most noteworthy contribution was the classic paper Preoperative Cardiac Evaluation for Noncardiac Surgery, published in 1992 in Anesthesia and Analgesia. This paper set the standards for how anesthesiologists should approach the preoperative cardiac evaluation of their patients. Dr. Fleisher was the long-term Chair of the Department of Anesthesiology and Critical Care (2004-2020), and the Robert Dunning Dripps Professor of Anesthesia at the University of Pennsylvania Health System. He is currently the Chief Medical Officer and Director of The Center for Clinical Standards and Quality at the Centers for Medicare & Medicaid Services (CMS), a part of the Department of Health and Human Services (HHS).

#3. Daniel Sessler MD, Cleveland Clinic. Dr. Sessler has authored an astounding total of 1089 publications in major medical journals, and has raised total extra-mural research funding of $65 million so date. Dr. Sessler is an editor for Anesthesiology and serves as a reviewer for more than 50 journals. He has given invited lectures at more than 350 institutions. His papers have been cited more than 37,000 times, making him the world’s most published and cited anesthesiologist. Dr. Sessler is currently Professor and Chairman, Department of Outcomes Research, Anesthesiology Institute at the Cleveland, and Clinical Professor of Anesthesiology at Case Western Reserve University.

Dr. Archie Brain and his invention, the LMA

#2. Archie Brain MB, London Hospital, Whitechapel, England. Dr. Brain is the British anesthesiologist who invented the laryngeal mask airway (LMA), which he patented in 1982. Dr. Brain’s objectives for the LMA were to provide a better method of maintaining a patient’s airway than by face mask, with the benefit that the LMA was less hemodynamically stressful than the insertion of an endotracheal tube. The LMA has been used over 300 million times worldwide in elective anesthesia and emergency airway management, and is one of the most significant anesthesia inventions in the last 50 years. The LMA Classic was sold by LMA International NV, a company which sold to Teleflex Inc in 2012 for $276 million.

#1. Ronald Miller MD. University of California San Francisco. Dr. Miller is best known as the initial lead author of Miller’s Anesthesia, the most widely used textbook of anesthesiology in the world, first published in 1981 and now in its Ninth Edition. https://anesthesia.ucsf.edu/news/ronald-d-miller-distinguished-professorship Dr. Miller was the Chairman of Anesthesia at UCSF from 1983-2009, and built what was arguably the finest anesthesiology department in the world, with a particular focus on research, as well as expanding the role of anesthesiologists in the pain clinic and in the intensive care unit.

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NOTE: This list does not include the inventor of the GlideScope, the first commercial video laryngoscope (developed in 2001 and an outstanding contribution to the field of anesthesiology), because Dr. John Allen Pacey, the inventor of the GlideScope, was not an anesthesiologist but a vascular and general surgeon at the University of British Columbia.

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NOTE: This list of The Top 10 Living Anesthesiologists does not contain any females or diversity. All ten nominees are white males. Such was the state regarding the advances in our specialty over the past five decades. Future lists may honor females or diversity, depending on the state of career achievements over the coming years.

MYOCARDIAL INJURY AFTER NONCARDIAC SURGERY . . . COMMON, SILENT, AND DEADLY. WHAT CAN WE DO?

20 Feb 20188 Oct 2018THE ANESTHESIA CONSULTANT 2 Comments

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THE ANESTHESIA CONSULTANT

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group

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You’re a 55-year-old man with hypertension, scheduled for surgery for a right colon removal for colon cancer. How likely is your death within 30 days after surgery?

Higher than you would think.

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Your 30-day morality following this inpatient surgery is 1.2%. What can we do to improve myocardial injury after noncardiac surgery? Read on…

Dr. Daniel Sessler, Chairman of the Department of Outcomes Research at the Anesthesia Institute of the Cleveland Clinic, spoke at the Stanford Anesthesia Grand Rounds last week. His lecture, titled “Perioperative Myocardial Injury,” answered the questions above. Let me share what Dr. Sessler had to say:

Myocardial injury after noncardiac surgery, abbreviated as MINS, is a common, silent, and deadly problem. Dr. Sessler described mortality related to surgery as the third leading cause of death in America, behind cardiovascular disease and cancer, and he cited myocardial injury as the leading cause of death after surgery.
Devereaux, Sessler, and colleagues measured postoperative hsTnT (high sensitive troponin T) in 21,842 patients over the age of 45 who had inpatient noncardiac surgery at 23 medical centers in 13 countries.¹ (For my nonmedical readers: hsTnT or cardiac troponin is a biomarker for acute myocardial infarction, i.e. heart attack.) Two hundred sixty-six patients died within 30 days after surgery, for an overall mortality rate of 1.2%. A total of 3904 patients had elevated hsTnT, diagnostic for MINS, for an overall incidence of tropinin elevation = 18% of the patients. Ninety-three percent of these patients had no ischemia-related symptoms, and would not have been detected without the hsTnT measurements.
Puelacher published similar data in an older population (all patients over the age of 65).² He studied postoperative hsTnT levels in 2018 consecutive inpatients and found perioperative myocardial injury (PMI) occurred in 397 (16% of the patients). Only 24 (6% of the patients) had typical chest pain, and only 72 (18% of the patients) had ischemic symptoms. The 30-day mortality was 8.9% for patients with PMI, compared to 1.5% for patients without PMI.
hsTnT isn’t commonly measured in current practice, which means the majority of MINS patients go undiagnosed. Sessler recommended that all patients diagnosed with MINS be seen by a cardiologist, to consider further diagnostic or therapeutic intervention. He specifically mentioned the possibilities of statin and/or aspirin therapy, as well as smoking cessation and weight loss.
Sessler suggested that a future approach to MINS detection would be to measure postoperative hsTNT for three days in every inpatient noncardiac surgery patient over 65 years old, and in those over 45 with one or more cardiovascular risk factor.
What about preoperative clearance for noncardiac surgery? Sessler described exercise tolerance and the echocardiogram cardiac stress test as two inaccurate screening tools. He rated the two most effective screening tools as the Revised Cardiac Risk Index (see below), and the preoperative measurement of BNP (Brain Natriuretic Peptide).
The Revised Cardiac Risk Index (RCRI) evaluates these 6 patient factors:

■ High-Risk Surgery – the following surgeries are deemed high risk for perioperative cardiac complications:

- Intraperitoneal

– Intrathoracic

– Suprainguinal vascular

■ History of ischemic heart disease – characterized by either a history of a positive test, a diagnosed MI, current chest pain suspicion of myocardial ischemia, nitrate therapy, or evidence of pathological Q waves on electrocardiogram.

■ History of congestive heart failure – described as the presence of either:

– Pulmonary edema, bilateral rales or S3 gallop;

– Paroxysmal nocturnal dyspnea;

– A CXR showing pulmonary vascular redistribution.

■ History of cerebrovascular disease – e.g. a prior TIA or stroke.

■ Pre-operative insulin treatment.

■ Pre-operative creatinine more than 2 mg/dL.

Positive findings of these factors define 4 classes of postoperative cardiac complication percentage rates:

■ 0 factors – Class I – risk 0.4%;

■ 1 factor – Class II – risk 0.9%;

■ 2 factors – Class III – risk 6.6%;

■ 3 to 6 factors – Class IV – risk 11%.

Preoperative BNP concentration is a powerful independent predictor of perioperative cardiovascular complications.³ At best, clinicians can utilize both a low score in the preoperativeRevised Cardiac Risk Index plus a low value of the BNP or the N-terminal proB-type natriuretic peptide (NT-proBNP) plasma level.⁴ Sessler stated that a BNP test costs 1/20^th as much as an echo stress test, and is more accurate in predicting postoperative cardiac mortality. He stated that a NT-proBNP level of < 300 ng/mL correlated well with a safe perioperative cardiovascular course.
Elevated preoperative troponin or hsTnT concentrations were also significantly associated with postoperative MI and long-term mortality after noncardiac surgery.⁵
Metoprolol, aspirin, and clonidine all failed as preoperative interventions to decrease cardiac risk. Metoprolol decreased postoperative myocardial infarction, but there were more deaths and an increased rate of stroke in the metoprolol group than in the placebo group.⁶ Aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of death or nonfatal myocardial infarction, and increased the risk of major bleeding.⁷ Low-dose clonidine did not reduce the rate death or nonfatal myocardial infarction, and increased the risk of clinically important hypotension and nonfatal cardiac arrest.⁸
Eliminating nitrous oxide from the anesthetic regimen had no effect in decreasing myocardial injury.⁹
Intraoperative hypotension correlated with postoperative myocardial injury. Mascha studied the time-weighted average intraoperative mean arterial pressure (TWA-MAP), and found that lower mean arterial pressure strongly correlated with mortality.¹⁰ Sessler stated that a mean blood pressure of 50 torr for even one minute was a risk factor for postoperative myocardial injury. Targeting a specific systolic blood pressure reduced the risk of postoperative organ dysfunction.¹¹
Sessler stated that 1/3 of intraoperative hypotension occurred during the time between induction of anesthesia and time of the surgical incision. By analyzing large databases from electronic anesthesia recording systems, hypotension was documented during this time period when general anesthesia lacked any surgical stimulus to keep blood pressure elevated. Sessler’s recommendation was to maintain the MAP > 65 torr throughout noncardiac surgery.
The use of vasopressors to treat hypotension was safe.
Tachycardia was not a risk factor. “It hardly matters,” Sessler said.
Preoperative angiotensin-converting-enzyme inhibitors (ACE inhibitors), e.g. lisinopril, Lotensin, or Altace, and Angiotensin II receptor blockers (ARBs), e.g. Diovan or Cozaar, were risk factors for intraoperative hypotension and cardiovascular morbidity. Roshanov studied data from 14,687 patients aged 45 years or older for inpatient noncardiac surgery.¹² Four thousand eight hundred and two of these patients were taking ACE inhibitors or ARBs preoperatively. The patients who withheld their ACE inhibitors/ARB drugs in the 24 hours before surgery were less likely to suffer the outcomes of death, stroke, or myocardial injury. The authors recommended that patients withhold these drugs for 24 hours before surgery.

Dr. Sessler closed his lecture with the following recommendations:

In the future, clinicians should measure high-sensitivity troponin (hsTnT) for three days postoperatively on inpatient surgery patients of age > 65, or patients age >45 with one cardiovascular risk factor. Elevated shTnT will identify patients who with MINS, and these MINS patients should be referred for cardiology/internal medicine follow up.
In the future, clinicians should screen for preoperative cardiovascular risk by a combination of the BNP and hsTnT assays prior to surgery.
There is no known preoperative medical prophylaxis against MINS.
Maintain intraoperative mean arterial pressure > 65.
Hold ACE inhibitors/ARBs for 24 hours prior to surgery.

One of our professors asked Dr. Sessler if the current practice at the Cleveland Clinic included measuring preoperative BNP and three-day postoperative hsTnT. Sessler’s answer was, “not yet, but we’re working on it.”

What about your practice and mine?

This is a new topic and a cutting edge issue to most anesthesiologists, with the key studies only published in the last year. I’m impressed by the MINS data, and I don’t want any patient of mine joining the MINS mortality list. I already withhold ACE inhibitors/ARBs for 24 hours preoperatively. I will continue to be vigilant to maintain MAP > 65, using vasopressors as necessary. I currently use the Revised Cardiac Risk Index as well as cardiology consultations as indicated to screen patients preoperatively. At the present time both the cardiologists and I depend on exercise tolerance history and echo treadmill tests for preoperative cardiac clearance. I expect in the near future our healthcare systems will adopt the standards of checking BNP preoperatively and hsTnT for three days postoperatively for inpatient surgery patients of age > 65, or patients age >45 who have one cardiovascular risk factor. Stay tuned for future recommendations.

References:

Devereaux PJ et al. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. 2017Apr 25;317(16):1642-1651.
Puelacher C et al. Perioperative Myocardial Injury After Noncardiac Surgery. Circulation. 2018;137, 1-12.
Rodseth RN et al. The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis. J Am Coll Cardiol.2014 Jan 21;63(2):170-80.
Vetrugno L et al. The Possible Use of PreoperativeNatriuretic Peptides for Discriminating Low Versus Moderate-High Surgical Risk Patient. Semin Cardiothorac Vasc Anesth. 2018 Jan 1.
Nagele P et al. High-sensitivity cardiac troponin T in prediction and diagnosis of myocardial infarction and long-term mortality after noncardiac surgery. Am Heart J.2013 Aug;166(2):325-332.
Devereaux PJ et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. 2008 May 31;371(9627):1839-47.
Devereaux PJ et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med.2014 Apr 17;370(16):1494-503.
Devereaux PJ et al. Clonidine in patients undergoing noncardiac surgery. N Engl J Med.2014 Apr 17;370(16):1504-13.
Myles PS et al. 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. Lancet. Volume 384, No. 9952, October 2014, 1446-1454.
Mascha EJ. Intraoperative Mean Arterial Pressure Variability and 30-day Mortality in Patients Having Noncardiac Surgery. 2015 Jul;123(1):79-91.
Futlier E et al. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. 2017Oct 10;318(14):1346-1357.
Roshanov PS et al. Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort. 2017Jan;126(1):16-27.