Blade's Cases

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OKay,

Here are the pre-induction monitors for the case:

1. Standard ASA monitors
2. BIS
3. A-Line (this patient should have this pre-induction)
4. 16G I.V. (he was an easy stick and the 22 gauge was poor)


Ready to go if needed:

1. Phenyephrine
2. Ephedrine
3. Phenylephrine drip
4. Dobutamine (surgeon's choice-will discuss soon)
5. NTG drip

TEE planned post induction. Swan-Ganz Catheter not planned as of now but possible later after discussion with Surgeon. Double Stick the neck as per proman's post.

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Anybody want to rapid sequence this patient? I can tell you we see dozens of these Obese,GERD,Diabetics with heart disease on a daily basis.
I don't RSI them if their symptoms are well-controlled on a proton pump inhibitor or H2 blocker. That is just my opinion and you certainly wouldn't fail your Oral Boards if RSI is chosen for this patient.

Blade

The question still remains does the RSI work?
 
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Introduction


Aspiration occurs when some kind of material -particulate (food, foreign body) or fluid (gastric contents, blood, or saliva)-enters from the pharynx into the trachea, usually in the course of a general anesthesia, when the patient’s airway reflexes are depressed.
Fortunatelly, aspiration and its consequences are serious but not common complications in modern anesthetic practice. Aspiration pneumonitis is potencially preventable and its incidence is aproximately 1-7 cases of significant importance in 10.000 anesthetics.The severity of pulmonary outcomes after an aspiration event is associated with the presence of comorbid diseases (ASA physical status III and higher) and procedures performed emergently.

Risk factors


Several risk factors can be identified in most cases of aspiration. Usually these factors are related to a patient condition predisposing to delayed gastric emptying or regurgitation, emergency status, difficulty in airway management, type of surgery, and specific patients populations (extremes of age, obstetric patients, ambulatory surgery patients).See Table 1.
Table 1

Risk FactorsExtremes of age
Emergency status
Types of surgery (most common in cases of esophageal, upper abdominal, or
emergency laparotomy surgery )
Recent meal
Delayed gastric emptying and/or decreased lower esophageal sphincter tone
Trauma
Pregnancy
Pain and stress
Depressed level of conciousness
Morbid obesity
Difficult airway
Poor motor control
Esophageal disease

Physiopatology


The consequences of pulmonary aspiration depend on the type of material aspirated, its volume and pH. It is now accepted that even a small volume of acidic material can cause severe pneumonitis. Aspiration can produce pulmonary embarassmant by severe mechanisms, but the classic “Mendelson Syndrome” (sequence of events following the aspiration of gastric contents) is caused by chemical injury due to acid material. Critical values for gastric pH and volume, (only a guideline in humans), are considered to be pH < 2,5 and volume >0,4 ml/Kg.
 
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The rapid sequence induction revisited: obesity and sleep apnea syndrome.

FREID EB. Anesthesiol Clin North America 2005;23(3):551-64, viii.
Department of Anesthesiology, Nemours Children's Clinics, 807 Children's Way, Jacksonville, FL 32207, USA. [email protected]

Abstract:
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Pulmonary aspiration is a cause of anesthesia-related morbidity and mortality, with little change in incidence over the past 20 years. Rapid sequence induction is a common procedure in obese patients, who appear to be more at risk for both pulmonary gastric aspiration and difficult airways, and is required in obese and sleep apnea syndrome patients with symptomatic gastroesophageal reflux
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or other predisposing conditions. In the elective obese or sleep apnea patient with no other risk factors for pulmonary aspiration, the risks and benefits of rapid sequence induction and cricoid pressure should be weighed. If rapid sequence induction is required, succinylcholine remains the neuromuscular blocking agent of choice, if there are no contraindications.
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Anesthesiology:
July 2003 - Volume 99 - Issue 1 - pp 60-64
Clinical Investigations

Cricoid Pressure Displaces the Esophagus: An Observational Study Using Magnetic Resonance Imaging

Smith, Kevin J. M.D.; Dobranowski, Julian M.D., F.R.C.P.C.; Yip, Gordon M.D., F.R.C.P.C.; Dauphin, Alezandre M.D., F.R.C.P.C.; Choi, Peter T-L. M.D., F.R.C.P.C



Background: Cricoid pressure (CP) is often used during general anesthesia induction to prevent passive regurgitation of gastric contents. The authors used magnetic resonance imaging to determine the anatomic relationship between the esophagus and the cricoid cartilage (cricoid) with and without CP.
Cited Here...: Magnetic resonance images of the necks of 22 healthy volunteers were reviewed with and without CP. Esophageal and airway dimensions, distance between the midline of the vertebral body and the midline of the esophagus, and distance between the lateral border of the cricoid or vertebral body and the lateral border of the esophagus were measured.
Cited Here...: The esophagus was displaced laterally relative to the cricoid in 52.6% of necks without CP and 90.5% with CP. CP shifted the esophagus relative to its initial position to the left in 68.4% of subjects and to the right in 21.1% of subjects. Unopposed esophagus was seen in 47.4% of necks without CP and 71.4% with CP. Lateral laryngeal displacement and airway compression were demonstrated in 66.7% and 81.0% of necks, respectively, as a result of CP.
Conclusion: In the absence of CP, the esophagus was lateral to the cricoid in more than 50% of the sample. CP further displaced both the esophagus and the larynx laterally.
 
Anesthesiology:
August 1995 - Volume 83 - Issue 2 - p 431
Correspondence

Questionable Effectiveness of Cricoid Pressure in Preventing Aspiration

Kron, Steven S. MD

Free Access




Article Outline
Author Information



Anesthesiologist, New Britain General Hospital, P.O. Box 2870, New Britain, Connecticut 06050.


To the Editor:--Schwartz et al. [1] noted that 9 of 12 patients thought to be at risk for aspiration experienced infiltrates despite the use of cricoid pressure during intubation. The authors conclude that cricoid pressure "may have decreased the incidence of this complication." This seems like wishful thinking.
Cricoid pressure has been accepted as a standard of care since Sellick's paper. [2] Support for its use comes from cadaver and animal studies [3] and intuitive deduction based on the obliteration of the esophageal lumen. [4,5] Schwartz et al.'s paper is the first prospective, though uncontrolled, look at clinical outcome. A 75% failure rate just as easily could suggest that cricoid pressure causes aspiration. At the very least, further investigation is warranted.
In today's litigious atmosphere, mandating a clinically unproven technique as standard of care is not only bad science but bad business.
Steven S. Kron, M.D., Anesthesiologist, New Britain General Hospital, P.O. Box 2870, New Britain, Connecticut 06050.
(Accepted for publication May 1, 1995.)

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Anesth Analg 2006;102:943-949
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000194509.03916.02

GENERAL ARTICLES

Rocuronium Is Not Associated with More Vocal Cord Injuries than Succinylcholine After Rapid-Sequence Induction: A Randomized, Prospective, Controlled Trial

Thomas Mencke, MD*, Heike Knoll, MD
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, Jan-Uwe Schreiber, MD
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, Matthias Echternach, MD
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, Sarah Klein, MD
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, Gabriele Noeldge-Schomburg, MD*, and Malte Silomon, MD||


[SIZE=-1]*Department of Anaesthesia and Intensive Care Medicine, University of Rostock, Rostock,
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Department of Anaesthesia and Intensive Care Medicine,
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Department of Otorhinolaryngology, University of the Saarland, Homburg/Saar, ||Department of Anaesthesia and Intensive Care Medicine, Catholic Hospital, Koblenz, Germany [/SIZE]
[SIZE=-1]Address correspondence and reprint requests to Thomas Mencke, MD, Department of Anaesthesia and Intensive Care Medicine, University of Rostock, Schillingallee 35, 18057 Rostock Germany. Address e-mail to [email protected] .[/SIZE]
Postoperative hoarseness (PH), sore throat (ST), and vocal cord injuries (VCI) are common complications after general anesthesia. Excellent endotracheal intubating conditions are associated with less laryngeal morbidity than good or poor intubating conditions. Thus, we tested the hypothesis that a rapid-sequence induction (RSI) with succinylcholine would lead to less PH and VCI than with rocuronium. In this prospective trial, 160 patients were randomized in 2 groups to receive thiopental 5.0 mg/kg, fentanyl 3.0 µg/kg, succinylcholine 1.0 mg/kg, or rocuronium 0.6 mg/kg during RSI. PH and ST were assessed at 24, 48, and 72 h after surgery, VCI were examined by stroboscopy in those patients who had PH >3 days. Excellent and clinically acceptable intubating conditions were significantly increased in the succinylcholine group compared with the rocuronium group: 57% versus 21% and 89% versus 59%, respectively (P < 0.001). The incidence and severity of PH, and VCI between the succinylcholine and the rocuronium groups did not differ significantly: PH: 50% versus 51% (P = 0.99) and VCI: 3% versus 1% (P = 0.98), respectively. Similar findings were found for ST, 39% versus 28% (P = 0.22), and postoperative myalgia, 39% versus 29% (P = 0.25), respectively. Intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. The incidence and severity of ST and myalgia were not increased in the patients receiving succinylcholine. However, the rate of PH and VCI was similar to the rocuronium group.
 
Don't stop taking aspirin before heart surgery - Mayo Clinic study

Main Category: Cardiovascular / Cardiology
Article Date: 31 Aug 2005 - 0:00 PDT

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Aspirin use associated with lower mortality, but doesn't raise bleeding risk -

"Aspirin reduces clotting of the blood, so it can help prevent a heart attack or stroke by making it less likely a clot will form and block an already narrowed artery," explains R. Scott Wright, M.D., the Mayo Clinic cardiologist who led the study. "However, many surgeons who are concerned about excessive bleeding due to inadequate clotting have advised their patients to stop taking aspirin in the days before their operation. We designed this study to provide guidance on whether continuing aspirin therapy in the days before surgery is beneficial or risky."

The researchers collected data from 1,636 patients who had first-time coronary artery bypass surgery at Mayo Clinic in 2000, 2001 and 2002. Patients were divided into two groups: those who had taken aspirin within the five days before surgery (1,316 patients), and those who had not (320). Characteristics of the two groups were similar, except patients in the aspirin group were more likely to have had a previous heart attack, while those not taking aspirin were more likely to be on dialysis. All members of both groups received aspirin therapy following surgery, starting six hours after their operation.

Results

The in-hospital mortality for the aspirin group (1.7 percent) was significantly less than that for those not receiving aspirin (4.4 percent), and there was no increased risk of reoperation for excessive internal bleeding.

The study results suggest a reduction in strokes and related events, but the trend was not strong enough to be statistically significant.

"This is a very strong association of survival with taking aspirin in the days leading up to surgery," says Dr. Wright. "The study further confirms aspirin's benefits for patients with known cardiovascular disease. It also shows there is no increased risk of bleeding, which eliminates the main reason why physicians and surgeons would ask patients to discontinue aspirin therapy. Patients with heart disease who are not taking aspirin should ask themselves -- and their doctors -- 'Why not?'"

The findings are published this week in Circulation: Journal of the American Heart Association. Other co-authors include Kevin Bybee, M.D., Brian Powell, M.D., Uma Valeti, M.D., A. Gabriela Rosales, M.S., Stephen Kopecky, M.D., and Charles Mullany, M.B. M.S.

The study was funded by Mayo Clinic's Division of Cardiovascular Diseases. Dr. Wright has previously received research grant support from Bayer Pharmaceuticals.

Lee Aase
[email protected]
507-284-5005
Mayo Clinic
http://www.mayoclinic.org/news
 

[FONT=Arial, Helvetica, sans-serif][SIZE=+2]Aspirin and Mortality from Coronary Bypass Surgery[/SIZE].

[SIZE=+1]Dennis T. Mangano, Ph.D., M.D., for the Multicenter Study of Perioperative Ischemia Research [/SIZE]
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[FONT=arial, helvetica, sans-serif][SIZE=-1]PubMed Citation[/SIZE].
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[FONT=arial, helvetica][SIZE=+1]ABSTRACT[/SIZE].
[FONT=arial, helvetica]Background There is no therapy known to reduce the risk of complications or death after coronary bypass surgery. Because platelet activation constitutes a pivotal mechanism for injury in patients with atherosclerosis, we assessed whether early treatment with aspirin could improve survival after coronary bypass surgery. .
[FONT=arial, helvetica]Methods At 70 centers in 17 countries, we prospectively studied 5065 patients undergoing coronary bypass surgery, of whom 5022 survived the first 48 hours after surgery. We gathered data on 7500 variables per patient and adjudicated outcomes centrally. The primary focus was to discern the relation between early aspirin use and fatal and nonfatal outcomes. .
[FONT=arial, helvetica]Results During hospitalization, 164 patients died (3.2 percent), and 812 others (16.0 percent) had nonfatal cardiac, cerebral, renal, or gastrointestinal ischemic complications. Among patients who received aspirin (up to 650 mg) within 48 hours after revascularization, subsequent mortality was 1.3 percent (40 of 2999 patients), as compared with 4.0 percent among those who did not receive aspirin during this period (81 of 2023, P<0.001). Aspirin therapy was associated with a 48 percent reduction in the incidence of myocardial infarction (2.8 percent vs. 5.4 percent, P<0.001), a 50 percent reduction in the incidence of stroke (1.3 percent vs. 2.6 percent, P=0.01), a 74 percent reduction in the incidence of renal failure (0.9 percent vs. 3.4 percent, P<0.001), and a 62 percent reduction in the incidence of bowel infarction (0.3 percent vs. 0.8 percent, P=0.01). Multivariate analysis showed that no other factor or medication was independently associated with reduced rates of these outcomes and that the risk of hemorrhage, gastritis, infection, or impaired wound healing was not increased with aspirin use (odds ratio for these adverse events, 0.63; 95 percent confidence interval, 0.54 to 0.74). .
[FONT=arial, helvetica]Conclusions Early use of aspirin after coronary bypass surgery is safe and is associated with a reduced risk of death and ischemic complications involving the heart, brain, kidneys, and gastrointestinal tract. .


http://content.nejm.org/cgi/content/abstract/347/17/1309
 
Low-dose aspirin beats high-dose after cardiac surgery

Second study attributes long-term heart attack survival rates to rising use of cardiac drugs

The use of medicines to fight cardiovascular disease has been a primary focus of research in this area for the past several decades, as combinations of interventions and medicinal therapy have gradually begun to increase long-term survival rates. Two studies presented today at the American College of Cardiology's 56th Annual Scientific Session look at the measurable impact of the use of aspirin and other maintenance therapies, and one demonstrates that lower doses of therapies may prove to be just as beneficial while also lowering side effects. ACC.07 is the premier cardiovascular medical meeting, bringing together cardiologists and cardiovascular specialists to further breakthroughs in cardiovascular medicine.
"Cardiovascular disease is the leading cause of death today, and the major focus of research is to find better ways to help these patients through prevention, immediate intervention and long-term treatment regimens," said Douglas P. Zipes, M.D., Distinguished Professor of the Indiana University School of Medicine. "As we continue to discover the benefits of these therapies, we expect to see continued and measurable improvements in overall survival and quality of life."
Effects of Aspirin dose on Ischemic Events and Bleeding after Percutaneous Coronary Intervention (PCI): Insights from the PCI-CURE Study (Presentation Number: 2805-9)
After patients with acute coronary syndromes (ACS, a group of symptoms related to acute ischemia, or chest pain related to arterial damage) undergo percutaneous coronary interventions (PCI, including stenting), a significant concern among cardiologists is the risk of major internal bleeding. Aspirin (ASA) acts as a blood thinner to prevent clotting complications, but high levels can cause potentially serious bleeding. While PCI trials have traditionally used high-dose ASA (more than 200 mg) in combination with other medicines to prevent thrombosis and ischemic events, a sub-analysis from a clinical trial presented by researchers at McMaster University in Hamilton, Ontario suggests that low-dose aspirin may be just as effective as high doses to prevent thrombosis while reducing the risk of major bleeding in patients who have undergone PCI.
As a sub-analysis of the PCI-CURE study, researchers compared the safety and efficacy of varying doses of aspirin: low (less than 100 mg), intermediate (101-199 mg) and high (more than 200 mg). A total of 2,658 patients with ACS undergoing PCI were divided according to the most commonly used dose, and each dose group was evaluated for event rates relating to cardiovascular (CV) death, MI (heart attack) or stroke as well as major bleeding.
The researchers found similar rates of CV death, MI or stroke in all of the aspirin dose groups at 30 days and 8 months. While the incidence of major bleeding was not significantly different between the groups at 30 days, the rate of major bleeding was noticeably reduced with low-dose aspirin after 8 months, an important factor in the practice of aspirin dosing for patients in this population.
"In this large observational analysis, low-dose ASA appeared to be just as effective as high-dose ASA in preventing recurrent cardiac events in ACS patients after PCI, while reducing the long-term risk of major bleeding," said Sanjit Jolly, of Hamilton Health Sciences and lead author of the trial. "These data are intriguing, since low-dose aspirin is most commonly prescribed in Europe, but in the United States, higher doses are most commonly used. Our data suggest that lower doses may be safer, but this finding needs confirmation in a dedicated randomized trial," said Shamir R. Mehta, M.D., Associate Professor of Medicine at McMaster University and study principal investigator.
Dr. Mehta and an international team of investigators have started a large randomized trial called CURRENT-OASIS 7 involving 16,000 patients in over 40 countries to definitively answer the question of optimal aspirin dose.
Dr. Sanjit Jolly, a co-author on the study, will present the subanalysis from the PCI-CURE study on Monday, March 26, at 2:15 p.m. in room 242.
Increased Use of Cardiovascular Drugs Explains Recent Trends in Prognosis after Myocardial Infarction (Presentation Number: 1018-148)
As we continue to make progress in the area of cardiovascular medicine, including new technologies, better therapies and ultimately improved patient survival, researchers are taking a look back to determine the major factors that have contributed to growing survival rates in cardiovascular patients. This large observational study conducted by researchers from Brigham and Womens Hospital in Boston suggests the value of the use of maintenance therapies, and in particular, the increasing use of statins, beta-blockers (BB), and angiotensin-converting enzyme-inhibitors (ACEI) or angiotensin-II-receptor blockers (ARB) after a heart attack.
To determine the actual impact of the increasing use of cardiovascular medicines, the research team used Medicare and pharmacy assistance programs records from 1995 through 2004 to identify nearly 22,000 patients who had been hospitalized due to a heart attack and survived more than 30 days after discharge. These patients were followed from the index date (30 days after discharge) until they died or until the end of the study period.
Of the 21,848 patients in the study, about half (12,142) eventually died during the 74,982 person-years of follow-up. After adjusting for demographics and comorbidities, the post-heart attack mortality rates showed significant decline from 1995 to 2004 (adjusted HR=.97), corresponding to a three percent reduction in mortality each year. After introducing the therapy variables, the team found strong indications that the improvement in mortality after heart attack may be explained primarily by the increasing use of these drugs.
"Long-term prognosis in elderly patients with MI has improved considerably over time, and this study supports evidence that this can be attributed to the increasing use of cardiovascular medicines after discharge from MI," said Soko Setoguchi, of Brigham and Women's Hospital and lead author of the study. "As the rate of heart risks continues to increase among the general population, treatment regimens that include the use of cardiovascular medicines will have considerable benefits in overall long-term survival rates," said Dr. Setoguchi.
Dr. Setoguchi will present this study on Monday, March 26, at 9:00 a.m. in Hall H.
###​
 
Okay,

The patient gets the monitors and lines placed (including a-line) pre-induction. BIS Monitor reads 73 after Midazolam 5 mg I.V. and Fentanyl 250 micrograms I.V. Ketamine 50 mg I.V. added to decrease the BIS to 45. Then, muscle relaxant of choice given to facilitate intubation. Once the tube is in place the two IJ central lines are placed (Introducer plus triple lumen).

Now, here is where things start getting interesting. The CRNA in the room has been giving Phenylephrine in large doses the entire time you were putting in the lines. Despite an End tidal gas reading of 0.5% Isoflurane and a BIS of 58 the Blood Pressure is low. So, you start the Phenylephrine drip and the CRNA keeps pushing a few stick of Phenyephrine.

At this point the Tranxemic acid is going along with the Phenylephrine.
You are running an Air/O2/Isoflurane mixture. BP=94/48 HR=51 Sat=99%

Does anyone know why the pressure is so low? What should you be concerned about during the case? What is your plan?
 
Angiotensin-converting enzyme inhibitors increase vasoconstrictor requirements after cardiopulmonary bypass


KJ Tuman, RJ McCarthy, CJ O'Connor, WE Holm and AD Ivankovich
[SIZE=-1]Department of Anesthesiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.[/SIZE] Preoperative use of angiotensin-converting enzyme (ACE) inhibitors is common and has been associated with hypotension at separation from cardiopulmonary bypass (CPB). This study prospectively examined the influence of chronic preoperative ACE inhibitor use and other perioperative factors on the incidence of vasoconstrictor therapy required to maintain systolic blood pressure at more than 85 mm Hg despite a normal cardiac output after CPB in 4301 adults undergoing elective coronary artery and/or valve surgery. Hypothermic, nonpulsatile CPB and either opioid or ketamine-benzodiazepine anesthesia were common features of the operations. At least two vasoconstrictor infusions (phenylephrine, norepinephrine, or dopamine) were required for low perfusion pressure despite adequate cardiac output after CPB in 7.7% of 519 ACE-inhibited patients and 4.0% of 3782 patients not receiving ACE inhibitors (P = 0.0001). In the first 4 h after arrival in the intensive care unit, the need for vasoconstrictor infusions to treat hypotension with adequate cardiac output did not differ, although more ACE-inhibited patients (6.4%) exhibited low values of systemic vascular resistance (< 600 dyne.s.cm-5) than patients not receiving ACE inhibitors (2.8%; P = 0.0002). Logistic regression analysis identified preoperative ACE inhibitor use, congestive heart failure, poor left ventricular function, duration of CPB, reoperative surgery, age, and opioid anesthesia as independent risk factors for requiring > or = 2 vasoconstrictor infusions after CPB. No other preoperative drug therapy significantly altered this outcome.
 
Reviews
Selecting a Vasopressor Drug for Vasoplegic Shock After Adult Cardiac Surgery: A Systematic Literature Review

Moritoki Egi, MDa, Rinaldo Bellomo, MDa,*, Christoph Langenberg, MDa, Michael Haase, MDa, Anja Haase, B Pharma, Laurie Doolan, MDb, George Matalanis, MDc, Siven Seevenayagam, MDc, Brian Buxton, MDc

[SIZE=-1]a Department of Intensive Care and Medicine, University of Melbourne, Austin Hospital, Heidelberg Victoria, Australia
b Department of Anesthesia, Austin Hospital, Heidelberg Victoria, Australia
c Department of Cardiac Surgery, Austin Hospital, Heidelberg Victoria, Australia [/SIZE]
[SIZE=-1]* Address correspondence to Dr Bellomo, Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg Victoria, 3084 Australia. (Email: [email protected] ).[/SIZE]

The choice of vasopressors to treat vasodilatory shock after cardiac surgery is a matter of controversy. We have systematically reviewed the literature and found that the data are insufficient to guide choice of agent. However, we found sufficient evidence that when a target blood pressure can not be achieved with a single agent, addition of another is more likely to help achieve the blood pressure target. We also found that there is no evidence that vasopressors induce organ ischemia. Finally, the lack of high quality data indicate that large multicenter trials are needed in this field.
 
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Should angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists be omitted before cardiac surgery to avoid postoperative vasodilation?

Shahzad G. Raja* and Naveed Fida

[SIZE=-1]Department of Cardiothoracic Surgery, Harefield Hospital, Hill End Road, Harefield, UB9 6JH, Middlesex, UK [/SIZE]
[SIZE=-1]*Corresponding author. Tel.: +44 1895 828665; fax: +44 1895 828666.

E-mail address: [email protected] (S.G. Raja).[/SIZE] A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the omission of angiotensin converting inhibitors (ACEI)/angiotensin II receptor antagonists (AIIA) before cardiac surgery leads to avoidance of postoperative vasodilation. Using the reported search 421 papers were identified. Eleven papers including three randomised controlled trials (RCTs) represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated for these. Whereas the three small RCTs on this topic provided conflicting evidence, the remaining seven large cohort and case-control studies confirmed that preoperative ACEI therapy resulted in postoperative low systemic vascular resistance (SVR)/vasoplegia. Only two small RCTs with conflicting conclusions specifically addressed the issue of omitting ACEI/AIIA before cardiac surgery. We conclude that preoperative administration of ACEI/AIIA in patients undergoing cardiac surgery contributes to lowering of SVR/vasoplegia postoperatively thereby making omission of ACEI/AIIA before cardiac surgery a rational strategy to avoid postoperative vasodilation. However, the current available evidence to support this strategy is weak.
 
: J Hosp Med. 2008 Jul;3(4):319-25. Links

Clinical consequences of withholding versus administering renin-angiotensin-aldosterone system antagonists in the preoperative period.

Rosenman DJ, McDonald FS, Ebbert JO, Erwin PJ, LaBella M, Montori VM.
Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. [email protected]
BACKGROUND: Hospitalists involved in perioperative care either stop or continue until the day of surgery renin-angiotensin-aldosterone system antagonists (either angiotensin-converting enzyme inhibitors [ACEI] or angiotensin II receptor subtype 1 antagonists [ARA]) in patients who use these agents chronically. This practice variation reflects uncertainty regarding the risks and benefits of either approach. PURPOSE: The purpose of this study was to assess the clinical consequences of preoperatively continuing versus withholding ACEI/ARAs in patients treated chronically with these agents. DATA SOURCES AND STUDY SELECTION: We comprehensively searched 7 major electronic databases, considered references from selected reviews, hand-searched journals, and communicated with experts. We included randomized trials and observational studies. DATA EXTRACTION: We evaluated the relative risk (RR) of hypotension requiring vasopressors and of myocardial infarction in patients who did or did not receive an immediate preoperative dose of ACEI or ARA. DATA SYNTHESIS: Random-effects meta-analysis from 5 studies totaling 434 patients suggested that patients receiving an immediate preoperative ACEI/ARA dose were more likely (RR 1.50, 95% CI 1.15-1.96) to develop hypotension requiring vasopressors at or shortly after induction of anesthesia. Sufficient data were not available to assess other outcomes. CONCLUSION: Preoperative administration of ACEI/ARAs increases intraoperative hypotension. The long-term clinical consequences of continuing versus withholding preoperative ACEI/ARAs are unknown. This uncertainty stems in part from the absence to date of randomized trials designed specifically to examine patient-important consequences of this decision. Copyright 2008 Society of Hospital Medicine.
PMID: 18698608 [PubMed - indexed for MEDLINE]
 
The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists.

Brabant SM, Bertrand M, Eyraud D, Darmon PL, Coriat P.
Department of Anesthesiology, University Hospital Pitié-Salpêtrière, Paris, France.
The use of angiotensin II receptor subtype-1 antagonists (ARA), recently introduced as antihypertensive drugs, is becoming more prevalent. We studied the prevalence and severity of hypotension after the induction of general anesthesia in 12 patients treated with ARA until the morning of surgery. The hemodynamic response to induction was compared with that of patients treated with beta-adrenergic blockers (BB) and/or calcium channel blockers (CB) (BB/CB group, n = 45) and angiotensin-converting enzyme inhibitors (ACEI) (ACEI group, n = 27). A standardized anesthesia induction protocol was followed for all patients. Hypotension occurred significantly (p < or = 0.05) more often in ARA-treated patients (12 of 12) compared with BB/CB-treated patients (27 of 45) or with ACEI-treated patients (18 of 27). There was a significantly (P < or = 0.001) increased ephedrine requirement in the ARA group (21+/-3 mg) compared with the BB/CB group (10+/-6 mg) or the ACEI group (7+/-4 mg). Hypotension refractory to repeated ephedrine or phenylephrine administration occurred significantly (P < or = 0.05) more in the ARA group (4 of 12) compared with the BB/CB group (0 of 45) or the ACEI group (1 of 27), but it was treated successfully by using a vasopressin system agonist. Treatment with angiotensin II antagonism until the day of surgery is associated with severe hypotension after the induction of anesthesia, which, in some cases, can only be treated with an agonist of the vasopressin system. IMPLICATIONS: Hypotensive episodes occur more frequently after anesthetic induction in patients receiving Angiotensin II receptor subtype-1 antagonists under anesthesia than with other hypotensive drugs. They are less responsive to the vasopressors ephedrine and phenylephrine. The use of a vasopressin system agonist was effective in restoring blood pressure when hypotension was refractory to conventional therapy.
 
1: Middle East J Anesthesiol. 2008 Jun;19(5):1111-28. Links

Hemodynamic effects of anesthetic induction in patients treated with beta and calcium channel blockers.

Samad K, Khan F, Azam I.
Dept. of Anaesthesia, Agha Khan Univ., Karachi, Pakistan. [email protected]
BACKGROUND: The response to anesthetic induction and airway manipulation in the presence of cardiovascular disease and antihypertensive therapy has not been adequately investigated. METHODS: The blood pressure, pulse pressure and heart rate changes at induction and following tracheal intubation were compared in patients who were on either preoperative beta-adrenergic blocker therapy (BB group, n = 20) or a combination of beta-adrenergic blocker and calcium channel blocker therapy (BB + CCB group, n = 20). A standardized anesthesia induction protocol was followed, in the two gourps. RESULTS: No statistical difference was observed in the hemodynamic parameters between the two groups. The total number of hypotensive patients (SAP 90 <mmHg) and bradycardic episodes following induction of anesthesia were one in the BB group and eighteen in BB + CCB group and were treated with ephedrine (p = 0.000002). Two episodes of hypotension without bradycardia occurred in BB group and six in BB + CCB group and were treated with phenylephrine (p = 0.25). CONCLUSION: Hypotension requiring treatment in patients receiving a combination of BB + CCB is more frequent after induction of anesthesia.
PMID: 18637611 [PubMed - indexed for MEDLINE]

Related Articles

 
1: Anesth Analg. 1993 Aug;77(2):318-23. Links

Diltiazem reduces the dose requirement for nitroprusside-induced hypotension.

Bernard JM, Moren J, Demeure D, Hommeril JL, Passuti N, Pinaud M.
Département d'Anesthésie-Réanimation Chirurgicale, Hôtel-Dieu, Nantes, France.
The efficacy of diltiazem, a calcium channel blocker, for reducing the dose requirement for nitroprusside-induced hypotension was studied in 20 healthy patients during spine fusion for scoliosis. Anesthesia included methohexital (3 mg/kg followed by 3 mg.kg-1.h-1 intravenously), nitrous oxide, and alfentanil (40 micrograms/kg, followed by 0.7 microgram.kg-1.min-1 intravenously). Patients were assigned randomly to two groups, receiving either nitroprusside alone or nitroprusside and diltiazem (bolus of 80 micrograms/kg with two consecutive infusions of 4.5 micrograms.kg-1.min-1 during the first 30 min and then 1.3 micrograms.kg-1.min-1). Nitroprusside was used to maintain mean arterial pressure at 55-60 mm Hg in both groups. Hypotension was obtained in similar times, 4 min in the group receiving nitroprusside alone (range, 1-8 min) and 2 min in the group receiving nitroprusside and diltiazem (range, 1-8 min). Nitroprusside administration lasted 186 +/- 17 min (mean +/- SEM) in the group receiving nitroprusside alone and 214 +/- 26 min (mean +/- SEM) in the other group (NS). After hypotension, arterial blood pressure returned to its initial value in a time of 7 min in the group receiving nitroprusside alone (range, 5-9 min) and 9 min in the group receiving nitroprusside and diltiazem (range, 7-13 min) (NS). Cumulative doses of nitroprusside were larger in the group receiving nitroprusside alone (0.47 +/- 0.07 mg/kg; mean +/- SEM) than in the other group (0.24 +/- 0.05 mg/kg; mean +/- SEM) (P < 0.01). Significant increase in plasma thiocyanate concentration, cardiac index, and heart rate was observed only in the group receiving nitroprusside alone, but no intergroup differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)
 
Now,

What is your plan? What should you expect during this case after going on Cardiopulmonary bypass? What are your options?

Remember he took all THREE of his anti-HTN medications just a few hours ago:

1. Vasotec
2. Cardizem
3. Clonidine

That is quite a combo for HYPOTENSION under General Anesthesia with a Pump run.
 
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Okay,

The patient gets the monitors and lines placed (including a-line) pre-induction. BIS Monitor reads 73 after Midazolam 5 mg I.V. and Fentanyl 250 micrograms I.V. Ketamine 50 mg I.V. added to decrease the BIS to 45.

Now, here is where things start getting interesting. The CRNA in the room has been giving Phenylephrine in large doses the entire time you were putting in the lines. Despite an End tidal gas reading of 0.5% Isoflurane and a BIS of 58 the Blood Pressure is low. So, you start the Phenylephrine drip and the CRNA keeps pushing a few stick of Phenyephrine.

At this point the Tranxemic acid is going along with the Phenylephrine.
You are running an Air/O2/Isoflurane mixture. BP=94/48 HR=51 Sat=99%

Does anyone know why the pressure is so low? What should you be concerned about during the case? What is your plan?

First thing i though ketamine didn't affect BIS reading but since i don't like BIS i've never experienced the combination.

With everything you've given you have more than a mac on board so i wouldn't hesitate to turn the dial lower (let's remember that there is 5mg of midaz around so awareness doesn't concern me too much).
On a side note 94/48 is a bit low but nothing exceptional as long as the ST's are stable. Shove the TEE probe down his throat and his pressure will look great.

On bypass you might experience some hypotension but nothing major. What can you do about it: make sure you're not behind volume wise before bypass, don't be too aggressive with the mannitol (if used by perfusionist) keep running your phenyl or levo drip.
 
First thing i though ketamine didn't affect BIS reading but since i don't like BIS i've never experienced the combination.

With everything you've given you have more than a mac on board so i wouldn't hesitate to turn the dial lower (let's remember that there is 5mg of midaz around so awareness doesn't concern me too much).
On a side note 94/48 is a bit low but nothing exceptional as long as the ST's are stable. Shove the TEE probe down his throat and his pressure will look great.

On bypass you might experience some hypotension but nothing major. What can you do about it: make sure you're not behind volume wise before bypass, don't be too aggressive with the mannitol (if used by perfusionist) keep running your phenyl or levo drip.


Okay. But, clearly you have not done enough cases or you would realize that "things happen" unexpectedly; or, in this case, the potential for MASSIVE HYPOTENSION is in the making. It is naive at best to assume the combination of all three anti-HTN drugs won't cause you a problem particulary on bypass.

Yes, after stimulation the BP rises and you are able to turn up the Isoflurane a bit. After the Surgeon starts his work (saw to sternum) the Phenyephrine is turned off completely. The CRNA starts feeling better and the ECHO exam doesn't reveal any new data (EF is 30-35%).

The real problem starts after going on CPB (bypass). That is when the perfusionist needs a ton of phenyephrine and has minimal Isoflurane going.
The perfusionist ask you to do something about this- then, the Cardiac Surgeon asks the same thing. The mean pressure is 35 despite BIG doses of Phenylephrine. What now?
 
On this patient I actually used Pentothal 100 mg I.V. as my induction agent and not Ketamine. However, Ketamine would have been a fine choice.

You are correct in stating the BIS is NOT Accurate when Ketamine is used as agent. I believe the Ketamine effect is more pronounced at the start of the case.

© The Board of Management and Trustees of the British Journal of Anaesthesia 2004. All rights reserved. For Permissions, please e-mail: journal.permissions{at}oupjournals.org

Comparative effects of ketamine on Bispectral Index and spectral entropy of the electroencephalogram under sevoflurane anaesthesia

P. Hans*, P.-Y. Dewandre, J. F. Brichant and V. Bonhomme

CHR Citadelle, University Department of Anaesthesia and Intensive Care Medicine, Liège, Belgium
* Corresponding author. E-mail: [email protected]
Background. The Bispectral Index (BIS) and spectral entropy of the electroencephalogram can be used to assess the depth of hypnosis. Ketamine is known to increase BIS in anaesthetized patients and may confound that index as a guide to steer administration of hypnotics. We compared the effects of ketamine on BIS, response entropy (RE) and state entropy (SE) during surgery under sevoflurane anaesthesia.
Methods. Twenty-two women undergoing gynaecological surgery were enrolled in this double-blind, randomized study. Anaesthesia was induced i.v. and maintained with sevoflurane. Under stable surgical and anaesthetic conditions, patients were assigned to receive either a bolus of ketamine 0.5 mg kg–1 or the same volume of saline. Blood pressure, heart rate, BIS, RE and SE were measured every 2.5 min from 10 min before (baseline) until 15 min after ketamine or saline administration. The maximum relative increase in BIS, RE and SE compared with baseline was calculated for each patient. Values are mean ([SIZE=-2]SD[/SIZE]).
Results. Baseline values were BIS 33 (4), RE 31 (5), SE 30 (5) for the ketamine patients and BIS 35 (3), RE 33 (5) and SE 32 (6) for the patients receiving saline. BIS, RE and SE increased significantly from 5 min (BIS) and 2.5 min (RE and SE) after ketamine administration, peaking at 46 (8) (BIS), 52 (12) (RE) and 50 (12) (SE) respectively. The maximum relative increase in RE [42.2 (10.4%)] and SE [41.6 (10.9)%] was higher than that of BIS [29.4 (10.4%)]. Blood pressure, heart rate and RE–SE gradient did not change in either group.
Conclusions. Ketamine administered under sevoflurane anaesthesia causes a significant increase in BIS, RE and SE without modification of the RE–SE gradient. This increase is paradoxical in that it is associated with a deepening level of hypnosis.
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2000
Effect of Pretreatment Vs Posttreatment Administration of Midazolam on Ketamine-Induced BIS ChangesChi-Chen Wu, M.D.; Martin S. Mok, M.D.; Sin-Ru Han, M.D.; Chao-Shun Lin, M.D.
Anesthesiology, Taipei Medical College Hospital, Taipei, TaiwanIntroduction: Benzodiazepines are frequently used in conjunction with ketamine to reduce the incidence of psychomimetic effect of ketamine anesthesia. Ketamine has been shown to cause a paradoxical increase of EEG-Bispectral Index (BIS) when patient was induced into the dissociative state of ketamine anesthesia(1). The present study evaluated the effect of midazolam given before vs after ketamine on the BIS changes.

Methods: Forty adult patients of ASA class I and II without history of cardiovascular disease who were scheduled for elective gynecologic surgeries were enrolled into this single blind, randomized, prospective study. No premedication was given to the patient. EEG-BIS was recorded continuously from the frontal electrodes using Aspect A-1000 monitor on arrival to the operating room. Blood pressure and heart rate were also recoreded every minute throughout the study. After steady baseline readings patients were randomly divided into two equal groups: Group 1 (n=20) received midazolam 0.05 mg/kg I.V. followed by ketamine 1.5 mg/kg I.V. at 3 min later and Group 2 (n=20) received ketamine 1.5 mg/kg I.V. followed by midazolam 0.05 mg/kg I.V. at 3 min later. At 5 min after the above induction medications rocuronium 0.6 mg/kg I.V. was given to facilitate intubation after which inhalation of sevoflurane at 1.5 MAC in 60% N20 and 40% O2 was used for anesthesia maintenance. BIS values were recorded throughout the entire anesthetic course until the patient was fully awake.

Results: The demographic data were comparable between the two groups. The average value of BIS during the awake basal state was 93 for Group 1 and 94 for Group 2 respectively. After midazolam BIS gradually declined to 83 at 3 min and after ketamine all the patients in Group 1 drifted into an anesthetized state in 2 min after which the BIS values increased progressively to an average of 96 at 5 min. In Group 2 after the administration of ketamine BIS increased to 97, 97 and 98 at the 1st, 2nd, and the 3rd min post drug and remained unchanged at 97-98 after midazolam administration. However, upon the administration of inhalation anesthetic the BIS index in both groups decreased gradually to below 60 in about 6 min and remained below that value throughout surgery in both groups. After termination of aneshtesia all patients became awake within 15 min with BIS above 80. No patient in either group had recall, delirium, or hallucination when questioned in the recovery room.

Conclusion: Our study confirmed that ketamine at aneshtetic dose of 1.5 mg/kg caused elevated BIS values and showed that midazolam at the clinically recommended dose for the prevention of psychomimetic effect of ketamine did not alter the BIS changes induced by ketamine when given either before or after ketamine administration. The hypnotic effect of midazolam appears to be superceded by ketamine and the interacting effect of the two drugs on the central nervous system cannot be monitored by the BIS monitor at the present time.
 
A1039
October 16, 2006
2:00 PM - 4:00 PM
Room Hall E, Area IIntravenous Ketamine Can Not Increase the Sympathetic Response during Propofol Anesthesia in HumanSatoko Saikawa, M.D., Syunsuke Izumi, M.D., Junichi Okubo, M.D., Manabu Kakinohana, M.D., Ph.D., Kazuhiro Sugahara, M.D., Ph.D.
Anesthesiology, University of the Ryukyus, Nishihara, Okinawa, JapanIntroduction: Although the effect of ketamine on the EEG variables duirng propofol infusion had already been studied, the effect of ketamine during propofol anesthesia on heart rate variability has not been studied. In this study, we investigated the effect of intravenous ketamine on sympathetic activity, processed EEG variables, e.g, bispectral index (BIS), 95 % spectral edge frequency (95% SEF) during propofol anesthesia.

Methods: After obtaining written informed consents, 18 patients (20 &#8211; 45 y.o, ASA PS I) were randomized to two groups, ketamine administration group (K) or saline administration group (S). Induction of anesthesia was performed with propofol using by target-controlled infusion system (TCI). Tracheal intubation was facilitated with 0.1 mg / kg of vecuronium. All patients received 2.5 mcg/ml of predicted propofol concentraion. 5 min after intubation, 1 mg/kg of ketamine (10 mg/mL) in Group K, or 0.1 ml/kg of saline in Group S was injected intravenously. Blood pressure (BP), heart rate (HR), Heart rate variability (HRV) and EEG (Makin 2 &#8482;; Suwa Trust, Tokyo, Japan), and BIS were monitored until 10 minutes after ketamine or saline administration. Two-way repeated measures analysis of variance followed by post-hoc test were used to analyze BP, HR, HRV, BIS and 95% SEF. A p-value < 0.05 was considered statistically significant.

Results: There were no significant difference bwtween Group K and Group S in BP, HR, HRV, BIS and 95% SEF before ketamine injection. In both groups, neither BP nor HR changed significantly after administration of ketamine or saline (Figure). After injection of ketamine in Group K, BIS and 95% SEF were increased significantly (BIS; 43.1 ± 7.4 to 72.9 ± 12.0, 95 % SEF; 11.3 ± 3.2 to 19.8 ± 2.9), but those changes were not observed after injection of saline in Group S. In both Groups, however, the ratio of low-frequency component to high-frequency component (cardiac sympathetic activity) did not change after injection of ketamine or saline (Figure).

Conclusion: Our results demonstrated that ketmaine can induce the increase of processed EEG variables, but not HR, BP or the sympathetic activity during propofol anesthesia. It was suggested that propofol can suppress the effect of ketamine on autonomic nervous system, and that processed EEG variables may be inadequate index for depth of anesthesia under the additional ketamine administration during propofol anesthesia.[figure1]

Anesthesiology 2006; 105: A1039
 
Our Local BIS guy (Friedberg?) based in Southern Cal uses the BIS plus Ketamine and Propofol routinely. I assume that is 99% of his cases.

If I understand him, a BIS number 70 can be used on non-paralyzed patients as an indication of sufficient anesthetic depth on the ketafol patients. His work shows Propofol followed by Ketamine (small doses) may raise the BIS value some. For example, a BIS of 60 went to 70 using this technique. Of Course, despite a small rise in BIS or no change the patients were all quite "anesthetized" with the ketafol. THe key here is to remember a high BIS value when adding Ketamine to your technique is fine.

However, the effect of the Ketamine (if no more is given) will begin to wane over time; Thus, BIS may be used as a monitor during the case. The question remains at what time point (15 minutes, 40 minutes, 60 minutes, etc.) after the ketamine administration the BIS becomes a reliable monitor again.

Anyway, sorry for the side-track as this case is not about Ketamine/BIS
 
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You are on bypass now. The Cardiac Surgeon and Perfusionist want you to DO something NOW. Both of these guys are SEASONED VETERANS of the Heart room and tell you "this is the worst hypotension I have ever seen." Damn.

You ask "turn up the flow" and anything else you can do? The answer is NO and even the CRNA says, "Dr. BLade, you read all those journals can't you come up with something better than ten bags of Neosynephrine?"

Now, I don't have time to open my books, go to pubmed, or even ask SDN members for help. The way I figure it this patient has severe "vasoplegic syndrome" and action is required.

The patient has normal renal function so I weigh my options:

1. Vasopressin

2. Methylene Blue

I remembered reading an article about Methylene Blue for Vasoplegic syndrome a year or so earlier. I figure if HIGH DOSE phenyephrine doesn't work then option one may or may not work as well. I go with option number 2.

I tell the Surgeon, Perfusionist and CRNA about option 2. The surgeon reluctantly agrees.

Amazingly, the Methylene Blue (3 mg/kg via the central line) worked like magic. The mean pressure began to stabilize and the patient required "normal" doses of phenylephrine. Even the CRNA was impressed.

The rest of the case was uneventful. We floated a PA catheter at the end of the case per the Surgeon's request.

So, is that the end of the story? I thought so but there is more.
 
[SIZE=+1]Vasopressin therapy for vasoplegic syndrome following cardiopulmonary bypass.[/SIZE]

Masetti P, Murphy SF, Kouchoukos NT.

Division of Cardiovascular and Thoracic Surgery and the Heart Center, Missouri Baptist Medical Center, St. Louis, Missouri, USA.

BACKGROUND: Hypotension refractory to maximal doses of alpha-adrenergic drugs after cardiac operations employing cardiopulmonary bypass (CPB) has been referred as "vasoplegic syndrome." Vasopressin has been used for its therapy with encouraging results. MATERIAL AND METHODS: 16 patients (mean age 71, range 47 to 84 years) were treated with intravenous vasopressin (0.1-1 IU/min) for hypotension refractory to maximal doses (>30 microg/kg/min) of norepinephrine after undergoing complex cardiac operations employing CPB. Preoperative ejection fraction was 40.5% (mean, range 20% to 60%), preoperative NYHA class was 3.5 (mean). Hemodynamic measurements were obtained one hour before and one hour after beginning vasopressin infusion; urine output was measured for the 4 hours before and the 4 hours after beginning the infusion. Duration of vasopressin treatment was 58.8 +/- 37.3 hours (mean +/- SD). RESULTS: Systolic blood pressure increased from 89.6 +/- 7.9 to 119.6 +/- 10.5 mmHg (mean +/- SD) (p < 0.001); systemic vascular resistance increased from 688.0 +/- 261.7 to 1043.3 +/- 337.1 dyne/s/cm2 (mean +/- SD) (p < 0.001); cardiac index decreased from 2.69 +/- 0.8 to 2.2 +/- 0.5 L/min/m2 (mean +/- SD) (p < 0.008); urine output increased from 36.8 +/- 30.4 to 72.8 +/- 38.2 mL/h (mean +/- SD) (p < 0.001). Seven patients (44%) survived the hospital stay. CONCLUSIONS: High-dose vasopressin is effective in the treatment of the vasoplegic syndrome after cardiac operations employing cardiopulmonary bypass.

PMID: 12643457 [PubMed - indexed for MEDLINE]
 
Preoperative methylene blue administration in patients at high risk for vasoplegic syndrome during cardiac surgery.

Ozal E, Kuralay E, Yildirim V, Kilic S, Bolcal C, Kucukarslan N, Gunay C, Demirkilic U, Tatar H. Ann Thorac Surg 79:1615-1619, 2005.
Reviewer: Mark A. Chaney, MD
University of Chicago

Abstract: Specific preoperative medications (angiotensin-converting enzyme inhibitors, calcium channel blockers, heparin) have been shown to increase risk of vasoplegic syndrome in patients following cardiac surgery. These investigators prospectively studied whether preoperative methylene blue administration would prevent the vasoplegic syndrome in these high-risk patients. One hundred patients scheduled for coronary artery bypass graft surgery with assist of cardiopulmonary bypass and deemed at high risk for postoperative vasoplegia (preoperative angiotensin-converting enzyme inhibitors, calcium channel blockers, heparin) were randomly assigned to either receive preoperative methylene blue (n = 50) or not receive it (n = 50). When given, methylene blue (1% solution) was administered intravenously at a dose of 2 mg/kg over thirty minutes approximately one hour prior to surgery. Although similar in terms of all demographic and operative variables, patients receiving methylene blue experienced significantly less postoperative vasoplegia than patients not receiving methylene blue (0 of 50 versus 13 of 50, respectively, p < 0.001). In six patients, vasoplegic syndrome was refractory to norepinephrine (four survived, two remained refractory to aggressive vasopressor therapy and ultimately died of multiorgan failure). Patients receiving methylene blue also had shorter intensive care unit stays (1.2 ± 0.5 days versus 2.1 ± 1.2 days, respectively, p < 0.001) and left the hospital sooner ( 6.1 ± 1.7 days versus 8.4 ± 2.0 days, respectively, p< 0.001) when compared to patients not receiving methylene blue. These investigators conclude that their results suggest that preoperative methylene blue administration reduces the incidence and severity of vasoplegic syndrome in high risk patients, ensuring adequate systemic vascular resistance during the intraoperative and postoperative periods and also shortens both intensive care unit stays and hospitals stays. Comments: Cardiopulmonary bypass may induce a vasoplegic syndrome that occurs in the immediate postoperative period (incidence may be as high at 10%) that is characterized by severe hypotension, decreased systemic vascular resistance, decreased arteriolar reactivity, and increased requirements for filling volume and vasopressive therapy, despite adequate cardiac output. Recent clinical work has established that preoperative angiotensin-converting enzyme inhibitors, calcium channel blockers, and heparin increase risk for postoperative vasoplegic syndrome and its presentation worsens overall prognosis.
Nitric oxide appears to play an important role via guanylate cyclase enzyme activation, cyclic guanosine monophosphate production, and smooth muscle vascular relaxation. Thus, inhibiting nitric oxide may limit or prevent the vasoplegic syndrome. Recent clinical work has revealed that methylene blue (via nitric oxide inhibition) administration in response to the vasoplegic syndrome can restore systemic vascular resistance. These investigators found that preoperative methylene blue administration, in patients at high risk for vasoplegic syndrome, decreased incidence and severity of the syndrome, a potentially important finding.
The rennin-angiotensin system plays an important role in vascular tone changes that occur postoperatively. Angiotensin-converting enzyme inhibitors decrease angiotensin II levels and increase plasma levels of bradykinin, a vasodilator. The increase in plasma bradykinin is due to the fact that cardiopulmonary bypass excludes the lungs, the major site of bradykinin catabolism. Angiotensin-converting enzyme inhibitors certainly play a major role in initiating vasoplegic syndrome. As more and more patients scheduled for cardiac surgery are taking these drugs, this represents a real clinical problem. Conventional treatment of vasoplegic syndrome usually involves phenylephrine, norepinephrine, or vasopressin. While these drugs increase blood pressure, they also have potential adverse effects (unwanted vasoconstriction to major organs). Thus, it would be advantageous to avoid these drugs, if possible.
Over the last decade, methylene blue has emerged as a useful drug to treat vasoplegic syndrome that is unresponsive to conventional treatment. This is the first clinical study to use preoperative methylene blue to ward off development of the syndrome. It appears to work. It should be noted, however, that methylene blue, like all vasoconstrictors, also has potential adverse effects. The drug may cause cardiac arrhythmias, coronary vasoconstriction, decreased cardiac output, decreased renal blood flow, decreased mesenteric blood flow, increased pulmonary vascular pressure, increased pulmonary vascular resistance, and gas exchange deterioration. Methylene blue is also well known to turn the urine greenish-blue and may initiate mild skin discoloration (observed in this study's patients). While one cannot at this time recommend routine preoperative use, all cardiac anesthesiologists should be aware of the emerging beneficial effects of methylene blue in the treatment of vasoplegic syndrome.
 
Methylene Blue for CPB

Andrew D. Maslow, MD, Carl S. Schwartz, MD, Gary Stearns, CCP, Parag Batula, BMS, Jeffrey Gough, CCP, and Arun K. Singh, MD

[SIZE=-1]Department of Anesthesiology, [email protected] (Maslow, Schwartz) Department of Perfusion Therapy (Stearns) Brown Medical School, Rhode Island Hospital, Providence Rhode Island (Batula) [/SIZE]
[SIZE=+1]In Response:[/SIZE] We thank Drs. Valchanov and Falter (1) for their interest the timing of methylene blue administration as discussed in our manuscript (2). Three studies have evaluated the benefits of methylene blue in cardiac surgical patients. Two studies examined methylene blue administration after the diagnosis of vasoplegia was made (3, 4). One study administered methylene prophylactically (5). This latter study documented less inotropic support, less fluid administration, fewer blood transfusions, and shorter intensive care unit and hospital stays as well as a 0% incidence of vasoplegia in patients receiving methylene blue compared with 26% incidence in the control group (5). In our investigation we sought any benefits immediately after cardiopulmonary bypass to determine if a beneficial effect could still be seen (2). Consistent with these other studies we demonstrated hemodynamic and metabolic benefits. Together these studies demonstrate the benefit of methylene blue administration prior to, during, and after cardiopulmonary bypass.
 
CARDIOVASCULAR ANESTHESIA
The Hemodynamic Effects of Methylene Blue When Administered at the Onset of Cardiopulmonary Bypass

Andrew D. Maslow, MD*, Gary Stearns, CCP
dagger.gif
, Parag Batula, BMS
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, Carl S. Schwartz, MD*, Jeffrey Gough, CCP, and Arun K. Singh, MD
Dagger.gif


[SIZE=-1]From the Departments of *Anesthesiology,
dagger.gif
Perfusion Therapy, and
Dagger.gif
Cardiac Surgery,
sect.gif
Brown Medical School, Rhode Island Hospital, Providence Rhode Island. [/SIZE]
[SIZE=-1]Address correspondence and reprint requests to Andrew Maslow MD, 63 Prince St, Needham Ma, 02492. Address e-mail to [email protected] .[/SIZE]
Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.
 
Okay. But, clearly you have not done enough cases or you would realize that "things happen" unexpectedly; or, in this case, the potential for MASSIVE HYPOTENSION is in the making. It is naive at best to assume the combination of all three anti-HTN drugs won't cause you a problem particulary on bypass.

Well i'm clearly not a seasoned veteran but how many cardiac patients are on multiple HTN therapy? a lot and how often do you see this kind of vasoplegia? hopefully not so often.

I've seen methylene blue used in the icu for refractory vasoplegic shock. :thumbup:
 
Well i'm clearly not a seasoned veteran but how many cardiac patients are on multiple HTN therapy? a lot and how often do you see this kind of vasoplegia? hopefully not so often.

I've seen methylene blue used in the icu for refractory vasoplegic shock. :thumbup:

Yes. I agree with you. But, now you know the LITERATURE. Clearly, for refractory hypotension in the heart room keep those drugs in mind.

Heart Surgeon:

You are on bypass now. The Cardiac Surgeon and Perfusionist want you to DO something NOW. Both of these guys are SEASONED VETERANS of the Heart room and tell you "this is the worst hypotension I have ever seen." Damn.
 
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The following day the CRNA that did the case with me gave me a compliment: "Blade that was a nice job yesterday."

I was feeling pretty good until about an hour later when the Cardiac Surgeon called me: " Hey, Blade what did you give that guy yesterday?"
I responded "what do you mean? he is fine today, right?" The heart surgeon says "he is acting real funny today and his wife wants to talk with you. Did you give him any Ketamine?" I answered "no, just soduim pentothal and the usual stuff except for the one dose of Methylene Blue. But, I will go visit the guy and his wife."

Now, I am feeling pretty down. I go and talk with the wife. I ask her how her husband is doing. I suspect that maybe the midazolam is the culprit or the ICU Nurses gave him some BEnzo's or morphine. However, after talking with the wife I find out the following:

1. The patient is acting almost drunk

2. He took TWICE his normal Clonidine dose before the Surgery because he thought it would help lower his pressure. He was anxious.

3. The wife said her husbad started an anti-depressant two weeks ago.

That got me thinking. So, I did a literature search and guess what I found?
 
Canadian Journal of Anesthesia 55:36-41 (2008)
© Canadian Anesthesiologists' Society, 2008
Case Reports/Case Series
Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review

[Syndrome sérotoninergique suite à une perfusion de bleu de méthylène pendant une parathyroïdectomie : présentation de cas et analyse bibliographique]

Bradley K.W. Ng, MBChB, Andrew J.D. Cameron, FANZCA, Rhea Liang, MBChB and Habib Rahman, FRACS

[SIZE=-1]From the Department of Surgery, Middlemore Hospital, Auckland, New Zealand. [/SIZE]
[SIZE=-1]Address correspondence to: Dr. Bradley Ng, P.O. BOX 25–109, St Heliers, Auckland, New Zealand. Phone: +64–9–521–8071; E-mail: [email protected] [/SIZE]

Purpose: To report a case of autonomic, neurological and neuromuscular instability following methylene blue infusion for parathyroidectomy; to advance the argument for a diagnosis of serotonin syndrome; and to consider this diagnosis in previous, unexplained reports of adverse reactions amongst patients undergoing parathyroidectomy using methylene blue.
Clinical features: Methylene blue was administered to a 58-yr-old woman undergoing a parathyroidectomy under general anesthesia. The patient had a background of obsessive compulsive disorder treated with paroxetine. Postoperatively, she demonstrated symptoms and signs of serotonin syndrome; specifically tachycardia, agitation, dystonia and abnormal eye movements. These clinical findings spontaneously resolved themselves over the subsequent 48 hr. Conclusion: An interaction between methylene blue and serotonergic agents may give rise to the serotonin syndrome. Consideration should be given to avoiding methylene blue in patients taking serotonergic agents. The diagnosis should be considered in patients with autonomic, neuromuscular or neurological changes and should be managed accordingly
 
Anesth Analg 2004;99:1573-1574
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000134860.73875.CF

GENERAL ARTICLES

Prolonged Postoperative Disorientation After Methylene Blue Infusion During Parathyroidectomy

Kevin K. Bach, MD*, Fred W. Lindsay, MD*, Lamont S. Berg, MD
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, and Red S. Howard, MD PhD
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[SIZE=-1]Department of *Otolaryngology and
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Anesthesiology, Naval Medical Center San Diego, California [/SIZE]
[SIZE=-1]Address correspondence and reprint requests to Red Howard, Department of Anesthesiology, Naval Medical Center, 34800 Bob Wilson Dr., San Diego, CA 92134. Address e-mail to [email protected]. [/SIZE]
Methylene blue 7.5 mg/kg is frequently given at our institution during parathyroidectomy. The dye preferentially stains the parathyroids so as to provide better surgical visualization. Other than causing a pseudocyanosis, the technique is generally considered to be rather innocuous. We report a case of a patient who, after this procedure, had a postoperative course that was unusual because of slowly resolving altered mental status. IMPLICATIONS: We report the case of a patient who, after a large dose of methylene blue, had a postoperative course that was unusual because of slowly resolving altered mental status.
 
The moral of the story is that "stuff happens" and you live and you learn. The more cases you do the more weird stuff you see.

I hope you guys learned something because I sure did.

Blade
 
Assuming the patient had renal insufficiency and refractory hypotension on CPB which drug would you choose? Vasopressin or Methylene Blue?



My Answer:

Since Methylene Blue is newer and I have limited experience with it I probably would go with Vasopressin in that scenario.
 
Well i'm clearly not a seasoned veteran but how many cardiac patients are on multiple HTN therapy? a lot and how often do you see this kind of vasoplegia? hopefully not so often.

I've seen methylene blue used in the icu for refractory vasoplegic shock. :thumbup:

One of the things you need to learn is the more options available the better off you are.

For example, were you taught the scientific data behind RSI and Cricoid Pressure? Does it really work? Are you still going to use it?

Now, you can add Methylene Blue to the list of things for hypotension while on CPB.
 
Ever had to give EPI for a high spinal to avoid cardiac arrest?

Ever had to give EPI to maintain BP on a patient taking Calcium Channel Blockers and an ACE Inhibitor under GA?

Ever used Dantrolene to treat an actual MH?

Ever had to do an emergency tracheostomy?

Now, I don't see those things very often but I have seen them all at least once. So, you need to be ready and prepared for that kind of "shi# happens" scenario.
 
Ever had to give EPI for a high spinal to avoid cardiac arrest?

No.

Ever had to give EPI to maintain BP on a patient taking Calcium Channel Blockers and an ACE Inhibitor under GA?

No

Ever used Dantrolene to treat an actual MH?

No

Ever had to do an emergency tracheostomy?

No

Now, I don't see those things very often but I have seen them all at least once. So, you need to be ready and prepared for that kind of "shi# happens" scenario.

Absolutely
 
Okay,

The patient gets the monitors and lines placed (including a-line) pre-induction. BIS Monitor reads 73 after Midazolam 5 mg I.V. and Fentanyl 250 micrograms I.V. Ketamine 50 mg I.V. added to decrease the BIS to 45. Then, muscle relaxant of choice given to facilitate intubation. Once the tube is in place the two IJ central lines are placed (Introducer plus triple lumen).

Now, here is where things start getting interesting. The CRNA in the room has been giving Phenylephrine in large doses the entire time you were putting in the lines. Despite an End tidal gas reading of 0.5% Isoflurane and a BIS of 58 the Blood Pressure is low. So, you start the Phenylephrine drip and the CRNA keeps pushing a few stick of Phenyephrine.

At this point the Tranxemic acid is going along with the Phenylephrine.
You are running an Air/O2/Isoflurane mixture. BP=94/48 HR=51 Sat=99%

Does anyone know why the pressure is so low? What should you be concerned about during the case? What is your plan?

pressure seems to be low albeit stable. Drop the TEE and take a look.
 
Okay. But, clearly you have not done enough cases or you would realize that "things happen" unexpectedly; or, in this case, the potential for MASSIVE HYPOTENSION is in the making. It is naive at best to assume the combination of all three anti-HTN drugs won't cause you a problem particulary on bypass.

Yes, after stimulation the BP rises and you are able to turn up the Isoflurane a bit. After the Surgeon starts his work (saw to sternum) the Phenyephrine is turned off completely. The CRNA starts feeling better and the ECHO exam doesn't reveal any new data (EF is 30-35%).

The real problem starts after going on CPB (bypass). That is when the perfusionist needs a ton of phenyephrine and has minimal Isoflurane going.
The perfusionist ask you to do something about this- then, the Cardiac Surgeon asks the same thing. The mean pressure is 35 despite BIG doses of Phenylephrine. What now?

assuming the volume and pump flow is adequate, vasopressin is a consideration.
 
You are on bypass now. The Cardiac Surgeon and Perfusionist want you to DO something NOW. Both of these guys are SEASONED VETERANS of the Heart room and tell you "this is the worst hypotension I have ever seen." Damn.

You ask "turn up the flow" and anything else you can do? The answer is NO and even the CRNA says, "Dr. BLade, you read all those journals can't you come up with something better than ten bags of Neosynephrine?"

Now, I don't have time to open my books, go to pubmed, or even ask SDN members for help. The way I figure it this patient has severe "vasoplegic syndrome" and action is required.

The patient has normal renal function so I weigh my options:

1. Vasopressin

2. Methylene Blue

I remembered reading an article about Methylene Blue for Vasoplegic syndrome a year or so earlier. I figure if HIGH DOSE phenyephrine doesn't work then option one may or may not work as well. I go with option number 2.

I tell the Surgeon, Perfusionist and CRNA about option 2. The surgeon reluctantly agrees.

Amazingly, the Methylene Blue (3 mg/kg via the central line) worked like magic. The mean pressure began to stabilize and the patient required "normal" doses of phenylephrine. Even the CRNA was impressed.

The rest of the case was uneventful. We floated a PA catheter at the end of the case per the Surgeon's request.

So, is that the end of the story? I thought so but there is more.

thats interesting, I've only read about methylene blue being used in vasoplegia assocaited with protamine adminisitration. gotta read up on that.
 
What is the proposed mechanism of the serotonin syndrome from the combo of methylene blue and SSRIs? I gotta take a look at that report, but it would be interesting to see if anything else was given during that surgery that could explain the serotonin syndrome.
 
Anybody want another case in a few days? If so, let me know and I will prepare it (that means literature/references).

All cases are welcome but you might want to slow the pace of questions + references down to give more time to people to analyse and post. :thumbup:
 
Ok,

I will slow the pace down. My references do explain the Serotonin Syndrome with Methylene Blue.

I will start a new thread for each case from now on.
 
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