cardiac – Sleepy Time

Cardiac Clearance for Surgery

Are you healthy enough for surgery?

Calculators:

MDCalc: Revised Cardiac Risk Index for Pre-Operative Risk

2018 Prevention Guidelines Tool CV Risk Calculator

The Big Papers:

2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 9;130(24):2215-45.

UpToDate: Evaluation of cardiac risk prior to noncardiac surgery. March 2024.

StatPearls: Cardiac Risk Stratification. May 2023.

Preoperative Cardiac Risk Assessment. Am Fam Physician. 2002;66(10):1889-1897.

Infographics:

From 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 9;130(24):2215-45.

It seems that ever since that advent of dexmedetomidine, propofol has been pushed aside as the sedation drug of choice for sedation during and post-open heart surgery. But is the literature changing with the effects of dexmedetomidine on rates of atrial fibrillation?

From Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial. The Lancet, eClinicalMedicine: Volume 56, 101796, February 2023.

In patients older than 60 years with low baseline risk of postoperative delirium admitted to the ICU after cardiac surgery and extubated within 12 h of ICU admission, a post-extubation nighttime dose of dexmedetomidine may reduce the incidence of delirium on postoperative day one.
Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial. The Lancet, eClinicalMedicine: Volume 56, 101796, February 2023.

The study results showed no statistically significant difference between both groups with regard to age and body mass index. Group P patients were more associated with lower MAP and HR than Group D patients. There was no statistically significant difference between groups with regard to ABG findings, oxygenation, ventilation, and respiratory parameters. There was significant difference between both the groups in midazolam and fentanyl dose requirement and financial costs with a value of P < 0.05.
From Sedation Effects by Dexmedetomidine versus Propofol in Decreasing Duration of Mechanical Ventilation after Open Heart Surgery. Ann Card Anaesth. 2018 Jul-Sep; 21(3): 235–242.

Meta-analysis studies on the use of DEX during cardiac surgery also showed a reduction in the risk of atrial fibrillation, ventricular tachycardia and cardiac arrest [7, 12].

Our findings suggest that DEX may reduce short term postoperative pulmonary complications, time on mechanical lung ventilation, ICU and hospital stay following CABG surgery compared to propofol.
From Comparison between dexmedetomidine and propofol on outcomes after coronary artery bypass graft surgery: a retrospective study. BMC Anesthesiology volume 22, Article number: 51 (2022).

When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1.
From Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology February 2016, Vol. 124, 362–368.

Dexmedetomidine did not significantly impact ICU length of stay compared with propofol, but it significantly reduced the duration of mechanical ventilation and the risk of delirium in cardiac surgical patients. It also significantly increased the risk of bradycardia across ICU patient subsets.
From Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials. British Journal of Anaesthesia, 129 (4): 515e526 (2022).

The use of dexmedetomidine for sedation after cardiac surgery was associated with a lower incidence of atrial fibrillation and hence decreased the duration of intensive care stay.
Dexmedetomidine versus propofol in reducing atrial fibrillation after cardiac surgery. Egyptian Journal of Anaesthesia, 38:1, 72-77.

This trial demonstrated that dexmedetomidine sedation may be better able to improve microcirculation in cardiac surgery patients during the early postoperative period compared with propofol.
Dexmedetomidine Versus Propofol Sedation Improves Sublingual Microcirculation After Cardiac Surgery: A Randomized Controlled Trial. Journal of Cardiothoracic and Vascular Anesthesia, Vol 30, No 6 (December), 2016: pp 1509–1515.

Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study.
Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery. British Journal of Anaesthesia Volume 126, Issue 3, March 2021, Pages 665-673.

Dexmedetomidine infusion, started at anaesthetic induction and continued for 24 h, did not decrease postoperative atrial arrhythmias in patients recovering from cardiac surgery. Dexmedetomidine also worsened delirium, although not by a significant amount, possibly by provoking hypotension. Dexmedetomidine worsened kidney injury, but again not by a significant amount. The incidence of persistent surgical pain was similar in each group. Dexmedetomidine should be used cautiously in cardiac surgical patients with attention to preventing hypotension, and should not be given in expectation of reducing atrial fibrillation or delirium.
Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. The Lancet Volume 396, Issue 10245, 18–24 July 2020, Pages 177-185.

Dexmedetomidine-based sedation resulted in
achievement of early extubation more frequently than propofol-
based sedation. Mean postoperative time to extubation and
average hospital LOS were shorter with dexmedetomidine-
based sedation and met a statistical level of significance. There
was no difference in ICU-LOS or in-hospital mortality between
the two groups. Total hospital charges were similar, although
slightly higher in the propofol group.
Propofol-Based Versus Dexmedetomidine-Based Sedation in Cardiac
Surgery Patients. Journal of Cardiothoracic and Vascular Anesthesia, Vol 27, No 6 (December), 2013: pp 1289–1294.

DDAVP

DDAVP while re-warming on CPB = 0.3 mcg/kg

Managing the coagulopathy associated with cardiopulmonary bypass. J Thromb Haemost. 2021;19:617–632.

Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass? Circulation. 1988;77:1319–1323.

Achieving hemostasis after cardiac surgery with cardiopulmonary bypass. UpToDate.

Use of Desmopressin During Cardiac Surgery Debated: Side Effects Minimal. April 2018. Dr. Clemens Blog.

Effect of Desmopressin on Platelet Aggregation and Blood Loss in Patients Undergoing Valvular Heart Surgery. Chin Med J (Engl). 2015 Mar 5; 128(5): 644–647.

Prothrombin Complex Concentrate

PCC – StatPearls, Dec 2022.

PCC – Hosp Pharm. 2013 Dec; 48(11): 951–957.

PCC Dosing – Medscape

K Centra dosing calculator

Use of PCC – 2014? PCC Dosing – year?

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery A Randomized Pilot Trial. JAMA Netw Open. 2021;4(4):e213936.

A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients. Anaesthesia, 76: 381-392. https://doi.org/10.1111/anae.15181

In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg^-1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available.
In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg^-1) should be considered.
A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.

Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. The Lancet, Volume 385, Issue 9982, 2015, Pages 2077-2087,ISSN 0140-6736,https://doi.org/10.1016/S0140-6736(14)61685-8.

From Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. The Lancet, Volume 385, Issue 9982, 2015, Pages 2077-2087,ISSN 0140-6736,https://doi.org/10.1016/S0140-6736(14)61685-8.

In summary:
For the endpoint of rapid INR reduction, the results from our trial are consistent with previously published (mainly observational) data and demonstrate that 4F-PCC is non-inferior and superior to plasma for rapid INR reduction in patients on VKA therapy.
Furthermore, we noted that 4F-PCC could be given more rapidly than plasma, which is in agreement with previously published (retrospectively collected) data.²⁴
For the endpoint of clinical efficacy, we found no other adequately powered trial examining reversal of VKA therapy in patients needing urgent surgical procedures, and this trial therefore offers new insights into their treatment. We noted that 4F-PCC was superior to plasma for haemostatic efficacy.
Although our study was not powered to assess safety, we did not detect any between-treatment differences for the occurrence of thromboembolic events or deaths, a finding in agreement with the existing scientific literature.11, 17, 25, 26 Additionally, although these data guide clinicians on how best to achieve urgent VKA reversal, the scientific literature concerning which patients should be urgently reversed before surgical or invasive interventions continues to evolve; for example, findings from a recent trial showed the safety of pacemaker placement without interruption of anticoagulation.²⁹

Efficacy and safety of a four-factor prothrombin complex concentrate (4F-PCC) in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation, 128 (2013), pp. 1234-1243.

From Efficacy and safety of a four-factor prothrombin complex concentrate (4F-PCC) in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation, 128 (2013), pp. 1234-1243.

Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest, 133 (2008), pp. 160S-198S

Among the key recommendations in this article are the following:
For dosing of VKAs, we recommend the initiation of oral anticoagulation therapy, with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B); we suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C); and in elderly and other patient subgroups who are debilitated or malnourished, we recommend a starting dose of ≤ 5 mg (Grade 1C). The article also includes several specific recommendations for the management of patients with nontherapeutic INRs, with INRs above the therapeutic range, and with bleeding whether the INR is therapeutic or elevated.
For the use of vitamin K to reverse a mildly elevated INR, we recommend oral rather than subcutaneous administration (Grade 1A).
For patients with life-threatening bleeding or intracranial hemorrhage, we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR (Grade 1C).
For most patients who have a lupus inhibitor, we recommend a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A].
We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dose adjustments [Grade 1B].
In patients who are suitably selected and trained, patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management, with greater time in the therapeutic range and fewer adverse events. Patient self-monitoring or self-management, however, is a choice made by patients and physicians that depends on many factors. We suggest that such therapeutic management be implemented where suitable (Grade 2B).

Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study). Critical Care volume 18, Article number: R81 (2014).

In patients on VKA therapy presenting with severe hemorrhage, international guidelines recommend, as soon as the diagnosis is confirmed, the administration of PCC (≥20 UI/kg) and vitamin K (≥5 mg) to normalize coagulation (post-reversal INR ≤1.5).
A guideline-concordant administration dose of PCC and vitamin K administrated in the first eight hours was associated with a two-fold decrease in seven-day mortality overall and with a three-fold decrease in the ICH subgroup
The guideline-concordant reversal was performed in 38% of the patients within eight hours after admission
Whereas pre-reversal INR is not absolutely necessary, post-reversal INR is essential to evaluate treatment efficacy
The post-reversal INR target must be performed systematically and immediately after PCC administration

Heparin and Hypotension

Healthy appearing patient with afib s/p ablation and returning for repeat ablation for recurrent afib. Anesthesia induced normally and patient VSS. 3 minutes after a request of a heparin bolus, patient dropped their SBP into the upper 40s, lower 50s. Patient recovered well after small bolus of epinephrine. ICE used to rule out pericardial effusion as well as confirm normal LVEF and RVEF.

The hemodynamic effects of heparin and their relation to ionized calcium levels. J THoRAc CARDIOVASC SURG 91:303-306, 1986.

Histamine blockade and cardiovascular changes following heparin administration during cardiac surgery. J Cardiothorac Anesth . 1990 Dec;4(6):711-4.

Heparin-Mediated Hypotension Associated with Cardiac Surgery. Anesthesia & Analgesia: September 2000 – Volume 91 – Issue 3 – p 766-767.

Preoperative Heparin Therapy Causes Immune-Mediated Hypotension Upon Heparin Administration for Cardiac Surgery. Journal of Cardiothoracic and Vascular Anesthesia. Volume 24, Issue 1, February 2010, Pages 69-72.

Prediction of heparin induced hypotension during cardiothoracic surgery: A retrospective observational study. Anaesth pain & intensiv care 2019;23(2):145-150.

Angiotensin Receptor Blocker (ARB) Reversal

From Angiotensin Axis Blocking Drugs In the Perioperative Period. Anesthesiology News, Feb 2016

What does an angiotensin receptor blocker (ARB) do?

Angiotensin II receptor blockers (ARBs) represent a newer class of effective and well tolerated antihypertensive agents ¹. Several clinical studies have indicated the beneficial effects of ARBs in hypertensive patients such as reduction of left ventricular hypertrophy, decrease in ventricular arrhythmias, and improved diastolic function ¹. Inhibitors of the renin-angiotensin system (RAS), either angiotensin converting enzyme (ACE) inhibitors or ARBs, mediate vasodilation and consequently decrease blood-pressure by different mechanisms ¹. ARBs specifically inhibit angiotensin II from binding to its receptor, the Angiotensin-1 (AT ₁) receptor on vascular smooth muscle cells. This blockade results in increased angiotensin II and normal bradykinin plasma levels. ARBs were developed to overcome several deficiencies of ACE inhibitors, which, by comparison, lead to decreased angiotensin II, but increased bradykinin levels. Hence, the key advantage of ARBs over ACE inhibitors is their lack of adverse effects related to bradykinin potentiation. ARBs have been shown to reduce morbidity and mortality associated with hypertension, and therefore, it is not surprising that an increasing number of patients scheduled for surgery are chronically treated with ARBs ². However, RAS blockade increases the risk of severe hypotension during and after anesthetic induction. ACE-inhibitors are well known for inducing severe circulatory side effects during anesthesia, which led to the general recommendation to withhold the drug on the day of surgery ³.
Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Comparison of Angiotensin‐Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Management Strategies Before Cardiac Surgery: A Pilot Randomized Controlled Registry Trial. Journal of the American Heart Association. 2018;7:e009917.

Consequences of continuing renin angiotensin aldosterone system antagonists in the preoperative period: a systematic review and meta-analysis. BMC Anesthesiol. 2018 Feb 26;18(1):26.

How do I reverse an ARB in an emergency?

Chronic AT ₁ blockade also reduces the vasoconstrictor response to α ₁ receptors activated by norepinephrine, which explains why ARB-induced hypotension can be so resistant to phenylephrine, ephedrine and norepinephrine ^{2, 8} Clinical studies have shown significant vasoconstrictor effects of vasopressin and increased cardiac filling during echocardiographic measurements ².
Vasopressin or its synthetic analogues can restore the sympathetic response and may be useful pressors in cases of refractory hypotension during anaphylaxis ⁹ and septic shock ¹⁰ as well as in patients on RAS inhibitors, although norepinephrine has been reported to have a more favorable effect on splanchnic perfusion and oxygen delivery ¹¹.
Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Angiotensin Axis Blocking Drugs In the Perioperative Period. Anesthesiology News, Feb 2016.

When conventional therapies such as: decreasing the anesthetic agent, volume expansion, phenylephrine, ephedrine, norepinephrine, and epinephrine are not effective, exogenous vasopressin may improve hypotension. To date, at least 5 clinical trials have demonstrated that patients on chronic ACEI/ARB undergoing general anesthesia, respond to exogenous vasopressin derivatives with an increase in blood pressure and fewer hypotensive episodes.^6,7 Typically, a 0.5-1 unit bolus of AVP is administered to achieve a rise in mean arterial pressure.⁴ The subsequent recommended infusion dose is 0.03U/min for AVP and 1-2 mcg/kg/h for terlipressin. Caution should be used as V1 agonists have been associated with the following deleterious effects: reduction in cardiac output and systemic oxygen delivery, decreased platelet count, increased serum aminotransferases and bilirubin, hyponatremia, increased pulmonary vascular resistance, decrease in renal blood flow, increase in renal oxygen consumption, and splanchnic vasoconstriction.
Studies involving cardiac surgical patients suggest that MB treatment for patients with VS may reduce morbidity and mortality.⁵ It has also been suggested that the early use (preoperative use in patients at risk for VS) of MB in patients undergoing coronary artery bypass grafting may reduce the incidence of VS.5,9A bolus dose of 1-2mg/kg over 10-20 minutes followed by an infusion of 0.25mg/kg/hr for 48-72 hours is typically utilized in clinical practice and trials (with a maximum dose of 7 mg/kg).¹⁰ Side effects include cardiac arrhythmias (transient), coronary vasoconstriction, increased pulmonary vascular resistance, decreased cardiac output, and decreased renal and mesenteric blood flow.¹ Both pulse and cerebral oximeter readings may not be reliable during MB administration due to wavelength interference.^11,12 The use of MB is absolutely contraindicated in patients with severe renal impairment because it is primarily eliminated by the kidney.¹³ It may also cause methemoglobinemia and hemolysis.¹³ At high doses, neurotoxicity may occur secondary to the generation of oxygen free radicals. Neurologic dysfunction may be more severe in patients receiving serotoninergic agents such as: tramadol, ethanol, antidepressants, dopamine agonists and linezolid. Recommended doses for VS ranging from 1-3 mg/kg do not typically cause neurologic dysfunction.¹⁴ However, recent reports suggest that MB in doses even ≤ 1mg/kg in patients taking serotonin reuptake inhibitors (SSRIs) may lead to serotonin toxicity due to its monoamine oxidase (MAO) inhibitor property.¹⁵

Vasoplegic Syndrome and Renin-Angiotensin System Antagonists. APSF Newsletter, Circulation 94,429 • Volume 27, No. 1 • Summer-Spring 2012 .

Vasopressin for persistent hypotension due to amlodipine and olmesartan overdose: A case report. Ann Med Surg (Lond). 2021 May; 65: 102292.

Vasoplegic syndrome following cardiothoracic surgery—review of pathophysiology and update of treatment options. Crit Care. 2020; 24: 36.

Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker. F1000Research 2013, 2:12.

Terlipressin for refractory hypotension following angiotensin-II receptor antagonist overdose. Anaesthesia, 2006,61, pages 402–414.

Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430.

Vasopressin: physiology and clinical use in patients with vasodilatory shock: a review. Neth J Med. 2005 Jan;63(1):4-13.

Treatment of intraoperative refractory hypotension with terlipressin in patients chronically treated with an antagonist of the renin-angiotensin system. Anesth Analg. 1999 May;88(5):980-4.

Role of vasopressinergic V1 receptor agonists in the treatment of perioperative catecholamine-refractory arterial hypotension. Best Pract Res Clin Anaesthesiol. 2008 Jun;22(2):369-81.

Predicting response to methylene blue for refractory vasoplegia following cardiac surgery. Pharmacotherapy Conference: 2013 American College of Clinical Pharmacy Annual Meeting. October 2013.

Tranexamic Acid vs. Amicar

** Updated July 2023** Scroll down for update

Over the years, our hospital has been using Amicar… until there was a drug shortage. With that drug shortage came a different drug called tranexamic acid. We’ve been using it for awhile and I can’t seem to tell a difference in coagulation between the two drugs. Let’s break down each one and also discuss cost-effectiveness.

Amicar

What is it?

Tranexamic Acid

What is it?

Tranexamic acid acts by reversibly blocking the lysine binding sites of plasminogen, thus preventing plasmin activation and, as a result, the lysis of polymerised fibrin.¹² Tranexamic acid is frequently utilised to enhance haemostasis, particularly when fibrinolysis contributes to bleeding. In clinical practice, tranexamic acid has been used to treat menorrhagia, trauma-associated bleeding and to prevent perioperative bleeding associated with orthopaedic and cardiac surgery.^13–16 Importantly, the use of tranexamic acid is not without adverse effects. Tranexamic acid has been associated with seizures,^{17 18} as well as concerns of possible increased thromboembolic events, including stroke which to date have not been demonstrated in randomised controlled trials.

Fibrinolysis is the mechanism of clot breakdown and involves a cascade of interactions between zymogens and enzymes that act in concert with clot formation to maintain blood flow.²⁵ During extracorporeal circulation, such as cardiopulmonary bypass used in cardiac surgery, multiplex changes in haemostasis arise that include accelerated thrombin generation, platelet dysfunction and enhanced fibrinolysis.²⁶ Tranexamic acid inhibits fibrinolysis, a putative mechanism of bleeding after cardiopulmonary bypass, by forming a reversible complex with plasminogen.

Dosing:

Cardiac Surgery
- Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med 2017; 376:136-148.
  - In summary, we found no evidence that tranexamic acid increases the risk of death and thrombotic complications after coronary-artery surgery. Tranexamic acid was associated with a lower risk of bleeding complications than placebo but also with a higher risk of postoperative seizures.
- Tranexamic acid in cardiac surgery: a systematic review and meta-analysis (protocol). BMJ Open. 2019; 9(9): e028585.
- Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials. BMC Anesthesiology volume 19, Article number: 129 (2019).
  - The study used a high-dose regimen, in which either 50 mg/kg or 100 mg/kg of TXA was delivered for each patient. There is a possibility that lower dose of TXA can be equally effective while causing less adverse effects. In fact, TXA plasma concentrations required to suppress fibrinolysis and plasmin-induced platelet activation are merely 10 and 16 μg/ml, respectively [7, 8]. This relatively low plasma concentration can be reached in cardiac surgery when 10 mg/kg of TXA is administered as a bolus then followed by continuous infusion of 1 mg kg/h and 1 mg/kg in CPB [9]. But another potential mechanism of TXA action might be the increase in thrombin formation, which requires concentrations more than 126 μg/ml to be effective [10, 11]. 30 mg/kg of TXA administered as a bolus followed by 16 mg/kg/h and 2 mg/kg in CPB prime solution was able to maintain the plasma concentration above 114 μg/ml [9].
- Optimal Tranexamic Acid Dosing Regimen in Cardiac Surgery: What Are the Missing Pieces? Anesthesiology February 2021, Vol. 134, 143–146.
  - Using their model-based meta-analysis, the authors conclude that low-dose tranexamic acid (total dose of 20 mg/kg of actual body weight) provides the best balance between reduction in postoperative blood loss and red blood cell transfusion and the risk of clinical seizure. The use of higher doses would only marginally improve the clinical effect at the cost of an increased risk of seizure.
- Tranexamic Acid Dosing for Cardiac Surgical Patients With Chronic Renal Dysfunction: A New Dosing Regimen. Anesthesia & Analgesia: December 2018 – Volume 127 – Issue 6 – p 1323-1332.
  - Low-risk group received a single 50 mg/kg TXA bolus after induction of anesthesia. The high-risk group received Blood Conservation Using Anti-fibrinolytics Trial (BART) TXA regimen, consisting of 30 mg/kg bolus infused over 15 minutes after induction, followed by 16 mg/kg/h infusion until chest closure with a 2 mg/kg load within the pump prime.
- What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery? Interactive CardioVascular and Thoracic Surgery, Volume 21, Issue 3, September 2015, Pages 384–388.
  - Risk of seizure is dose-dependent, with the greatest risk at higher doses of tranexamic acid. We conclude that, in general, patients with a high risk of bleeding should receive high-dose tranexamic acid, while those at low risk of bleeding should receive low-dose tranexamic acid with consideration given to potential dose-related seizure risk. We recommend the regimens of high-dose (30 mg kg⁻¹ bolus + 16 mg kg⁻¹ h⁻¹ + 2 mg kg⁻¹ priming) and low-dose (10 mg kg⁻¹ bolus + 1 mg kg⁻¹ h⁻¹ + 1 mg kg⁻¹ priming) tranexamic acid, as these are well established in terms of safety profile and have the strongest evidence for efficacy.
- Exposure–Response Relationship of Tranexamic Acid in Cardiac Surgery: A Model-based Meta-analysis. Anesthesiology 2021; 134:165–78.
  - The exposure value with the low-dose tranexamic acid regimen proposed by Horrow et al. (10 mg/kg followed by 1 mg/kg/h over 12 h) was close to the 80% effective concentration for postoperative blood loss and above the 80% effective concentration for erythrocyte transfusion. Compared to this regimen, a fivefold increase in total dose (100 mg/kg) achieved only a 58 ml (95% credible interval,54 to 65 ml) increment in the reduction of postoperative blood loss, up to 48 h postsurgery, with a decrease in erythrocyte transfusion rate from 46% to 44%.
  - Concentrations close to 80% effective concentration can be achieved at the end of surgery with a low-dose regimen administered either as a preoperative bolus plus infusion (10mg/kg followed by 1mg/kg/h) or as a single preoperative loading dose of 20mg/kg (fig. 6). Postoperative administration of tranexamic acid appears unnecessary because tranexamic acid concentrations will decrease but nevertheless remain sufficient (greater than or equal to EC50) up to the end of the drug’s contribution to blood loss reduction (8 h after the start of surgery).
  - The type of surgery and the duration of CPB both affected the risk of seizure. Open-chamber surgery resulted in a 5.5-fold increase in the risk of seizure compared to closed-chamber procedures (95% credible interval, 3.2 to 10). Each additional hour of CPB doubled the risk of seizure (2.0;95% credible interval, 1.2 to 3.2).

Ortho/Spine

Trauma

Currently at our hospital (June 2022):

TXA DOSING AND ADMINISTRATION OVERVIEW

How supplied from Pharmacy	TXA 1000mg/10mL vials Will not provide premade bags like with Amicar; Amicar is a more complex mixture than TXA Will take feedback on this after go-live and reassess
Where it will be supplied from Pharmacy	POR-SUR1 Omnicell (in HeartCore Room) Perfusion Tray (will replace aminocaproic acid vials 6/7)
Recommended Dosing (see below for evidence)	~20 mg/kg total dose Can give as: 20 mg/kg x 1, OR 10 mg/kg x 1, followed by 1-2 mg/kg/h* Perfusion may also prime bypass solution with 2 mg/kg x 1*
Preparation & Administration	IV push straight drug (1000mg/10mL) from vial AND/OR Mix vial of 1000mg/10mL TXA with 250mL NS for continuous infusion*

TXA & Amicar ADRs

SEIZURE RISK with TXA
- TXA has shown dose-dependent increased risk of seizure compared to placebo. (Myles, et al. N Engl J Med 2017)
- TXA may also have an increased risk of post-operative seizures compared to Amicar (Martin, et al. J Cardiothorac Vasc Anesth. 2011)

Seizure risk may be increased also by duration of prolonged open-chamber surgery based on findings from Zuffery, et al. Anesthesiology 2021.
Per OR pharmacist at Scripps Mercy, they have not seen an increased incidence of seizures in their patient-population (anecdotally)

RENAL DYSFUNCTION WITH AMICAR (LOWER RISK WITH TXA)
- In the Martin study, TXA showed a lower risk of post-op renal dysfunction compared to Amicar (Martin, et al. J Cardiothorac Vasc Anesth. 2011)

DOSING EVIDENCE

There are a number of dosing strategies in the literature. What I recommend for maximal safety and efficacy is taken from Zuffery, et al. Anesthesiology 2021 meta-analysis and is practiced at Scripps Mercy.

~ 20 mg/kg total dose recommended in this meta-analysis.
Two dosing strategies they report that were as effective as high-dose but with lower seizure risk than high dose:
- 20 mg/kg preoperative bolus x 1 (taken from Lambert, et al. Can J Anaesth. 1998)
- OR 10 mg/kg preoperative bolus x1, followed by 1 mg/kg/h for up to 12 hours (from Horrow, et al. Anesthesiology. 1995)

UPDATE JULY 2023

Carrie our pharmacist provided some really helpful research and updates:

So really we have two questions here I am seeking to answer with your group: (1) Is TXA best given as a bolus or as an infusion during cardiac surgery, and my other question (2) What is the optimal TXA dosage?

The JAMA 2022 study focuses on the question of dosing, though I believe it also helps answer the question about continuing drips post-op.

In this study, they did a bolus/infusion but only during the surgery.

They performed a randomized double-blind trial of 2 different TXA dosing strategies for adults undergoing cardiac surgery with CPB. They two dosing strategies:

“High dose”: TXA 30mg/kg bolus followed by 16mg/kg/h during surgery only and 2mg/kg pump prime
“Low dose”: TXA 10mg/kg bolus followed by 10mg/kg/h during surgery only and 1mg/kg pump prime

Results:

Efficacy: 21.8% of patients in the high-dose group received at least 1 allogeneic RBC transfusion compared to 26.0% in the low-dose group (p=0.004).

Safety: The composite safety endpoint (seizure, kidney dysfunction, thrombotic events, and all-cause mortality) was 17.6% in high-dose vs 16.8% in low-dose (p=0.004 for noninferiority)

I like this infographic on their study and results:

My takeaway on the JAMA study: I’m not sold on the “high dosing” regimen because I’m not overly impressed by their efficacy endpoint. Transfusion of at least 1 PRBC by itself doesn’t say much (in my opinion – let me know what you think!). Transfusion of FFP, platelets, cryo were no different between dosing groups. Chest tube output was not statistically different post-op. Duration of mechanical ventilation, ICU length of stay, and hospital length of stay were not statistically different.

Furthermore, if you comb through their secondary safety endpoints, you can see where TXA “low dose” patients had lower rates of seizures compared to high dose. This was especially true for open chamber surgery.

This doesn’t answer the question you asked about dosing strategy – bolus versus drip. However, they did only run TXA intraoperatively and did NOT give it post-op, which at least supports the idea we don’t need it upon ICU transfer.

I’m in favor of us moving toward the above JAMA “low dose” strategy among our anesthesiologists who are running drips. I think we can actually increase the rate of the infusion and STOP it before patient transfers, because at that point TXA will have already done all the leg work it is going to do.

Okay, so back to the question on bolus versus infusion:

The 2021 Zuffery article from Anesthesiologydoes not really take a stance on how to administer, though they do include a couple articles where the researchers only used bolus dosing (e.g. Lambert et al, who studied 20 mg/kg bolus compared to higher dosing regimens).

I really like their Figure 6, where they show pharmacokinetics and outcomes based on four different TXA regimen simulations. You can see where TXA 20mg/kg bolus (represented with yellow) is pretty similar outcomes and PK-wise to the green 10mg/kg bolus followed by 1mg/kg/h for 12 hours. AKA what you’re doing vs. what most of your colleagues are doing – same outcomes represented in this simulation.

“The following tranexamic acid regimens were simulated: 100 mg/kg preoperative loading dose (*blue dashed line* and *blue triangle*); 30 mg/kg preoperative loading dose followed by 16 mg · kg^–1 · h^–1 during surgery with a further 2 mg/kg added to the cardiopulmonary bypass (CPB) pump prime (*red solid line* and *red triangle* for 3 h of surgery, *red circle* for 4 h of surgery); 10 mg/kg preoperative loading dose followed by 1 mg · kg^–1 · h^–1 for 12 h (*green solid line* and *green circle*); 20 mg/kg preoperative loading dose (*yellow dashed line* and *yellow triangle*). *Top left*, Predicted concentrations of tranexamic acid for various regimens indicated as described above, the *dark gray column* representing the mean duration of CPB in the meta-analysis. *Top right*, Predicted postoperative mediastinal blood loss without tranexamic acid (*gray solid line*) and for the different tranexamic acid regimens indicated as described above. *Bottom*, As a function of the mean tranexamic acid concentration from start of surgery up to 12 h, the probability of erythrocyte transfusion (*left*) and of seizure (*right*). *Bottom right*, The *black solid line* represents model-based study-level predictions of a hypothetical trial of patients undergoing coronary artery bypass grafting with a mean duration of surgery and CPB of 3 h and 1.5 h, respectively; the *black dot-dash line* represents model-based predictions at the study level of a hypothetical trial in patients undergoing open-chamber surgery with a mean duration of surgery and CPB of 4 h and 2.5 h, respectively; the average weight was 74 kg.”

This NEJM RCT from 2017 from Myles, et al studied 50mg/kg and dosed as follows : “30-min loading dose of 12.5 mg/kg with a maintenance infusion of 6.5 mg/kg/hr, and 1 mg/kg added to the CPB prime, will be used” > Infusions again, but intraop only. This study also started with giving 100 mg/kg!! Patients were seizing, so they pulled back 50mg/kg.

My plan:

TXA 20mg/kg over 20 minutes prior to incision + 2mg/kg in pump prime. No infusion.

Exparel

Liposomal bupivacaine (Exparel) is a longer acting form of traditional bupivacaine that delivers the drug by means of a multivesicular liposomal system.

Exparel FDA drug sheet

Max Dose: 266 mg or 4mg/kg (6yo-17yo). Interscalene NB max dose (adults) =133mg

Exparel dosing company info: Pocket Dosing Guide , Billing Guide

Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012; 5: 257–264.

Emerging roles of liposomal bupivacaine in anesthesia practice. J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun; 33(2): 151–156.

Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. Cochrane Database Syst Rev. 2016 Aug 25;2016(8):CD011476.

Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev. 2017 Feb; 2017(2): CD011419.

Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future. Anesth Pain Med. 2022 Feb; 12(1): e123112.

Cardiac/Thoracic

The role of liposomal bupivacaine in thoracic surgery. J Thorac Dis. 2019 May; 11(Suppl 9): S1163–S1168.

Intercostal nerve blockade for thoracic surgery with liposomal bupivacaine: the devil is in the details. J Thorac Dis. 2019 May; 11(Suppl 9): S1202–S1205.

VATs: Dilute liposomal bupivacaine (266 mg, 20 cc) mixed with 20 cc injectable saline. We use two syringes to save time (refill syringe between injections).
For planned thoracotomy, we add 60 cc injectable saline for wider injection.
The efficacy of this strategy requires attention to specific details, such as timing and technique of injection, dilution with saline, and injection of multiple interspaces (typically interspaces 3–10 when technically possible).
Inject EXPAREL slowly and deeply (generally 1-2 mL per injection) into soft tissues using a moving needle technique (ie, inject while withdrawing the needle)
Infiltrate above and below the fascia and into the subcutaneous tissue
Aspirate frequently to minimize the risk of intravascular injection
Use a 25-gauge or larger-bore needle to maintain the structural integrity of the liposomal particles
Inject frequently in small areas (1-1.5 cm apart) to ensure overlapping analgesic coverage

Liposomal Bupivacaine Versus Bupivacaine for Intercostal Nerve Blocks in Thoracic Surgery: A Retrospective Analysis. Pain Physician. 2020 Jun;23(3):E251-E258.

Intercostal Blocks with Liposomal Bupivacaine in Thoracic Surgery: A Retrospective Cohort Study. J Cardiothorac Vasc Anesth. 2021 May;35(5):1404-1409.

Is liposomal bupivacaine superior to standard bupivacaine for pain control following minimally invasive thoracic surgery? Interactive CardioVascular and Thoracic Surgery, Volume 31, Issue 2, August 2020, Pages 199–203, https://doi.org/10.1093/icvts/ivaa083

Paravertebral Nerve Block With Liposomal Bupivacaine for Pain Control Following Video-Assisted Thoracoscopic Surgery and Thoracotomy. J Surg Res. 2020 Feb;246:19-25.

Rib fractures case report: ESP block

Evaluation of an Enhanced Recovery After Surgery Protocol Including Parasternal Intercostal Nerve Block in Cardiac Surgery Requiring Sternotomy. Am Surg. 2021 Dec;87(10):1561-1564.

Ultrasound-guided Modified Parasternal Intercostal Nerve Block: Role of Preemptive Analgesic Adjunct for Mitigating Poststernotomy Pain. Anesth Essays Res. 2020 Apr-Jun; 14(2): 300–304.

Comparison of preincisional and postincisional parasternal intercostal block on postoperative pain in cardiac surgery. J Card Surg. 2020 Jul;35(7):1525-1530.

Ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in mediastinal mass resection by median sternotomy: a randomized, double-blind, placebo-controlled trial. BMC Anesthesiol. 2021; 21: 98.

Pain Relief Following Sternotomy in Conventional Cardiac Surgery: A Review of Non Neuraxial Regional Nerve Blocks. Ann Card Anaesth. 2020 Apr-Jun; 23(2): 200–208.

A Novel Use of Liposomal Bupivacaine in Erector Spinae Plane Block for Pediatric Congenital Cardiac Surgery. Case Rep Anesthesiol. 2021; 2021: 5521136.

Breast/Gen Surg

Evaluating the Efficacy of Two Regional Pain Management Modalities in Autologous Breast Reconstruction. Plast Reconstr Surg Glob Open. 2022 Jan 19;10(1):e4010.

Perioperative Blocks for Decreasing Postoperative Narcotics in Breast Reconstruction. Anesth Pain Med. 2020 Oct; 10(5): e105686.

Opioid-sparing Strategies in Alloplastic Breast Reconstruction: A Systematic Review. Plast Reconstr Surg Glob Open. 2021 Nov 16;9(11):e3932.

Comparison of the efficacy of erector spinae plane block performed with different concentrations of bupivacaine on postoperative analgesia after mastectomy surgery: ramdomized, prospective, double blinded trial. BMC Anesthesiol. 2019; 19: 31.

Efficacy of liposomal bupivacaine versus bupivacaine in port site injections on postoperative pain within enhanced recovery after bariatric surgery program: a randomized clinical trial. Surg Obes Relat Dis. 2019 Sep;15(9):1554-1562.

The use of extended release bupivacaine with transversus abdominis plane and subcostal anterior quadratus lumborum catheters: A retrospective analysis of a novel technique. J Anaesthesiol Clin Pharmacol. 2020 Jan-Mar; 36(1): 110–114.

Ortho

Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block. Clin Orthop Relat Res. 2017 Jan;475(1):110-117.

OB

Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial. Anesth Analg. 2020 Dec; 131(6): 1830–1839.

Fascia Iliaca blocks for TAVR under conscious sedation

Editorial: The use of Fascia iliaca Block with Minimal Conscious Sedation in Transcatheter Aortic Valve Replacement: Advances in TAVR Anesthesia. Cardiovasc Revasc Med. 2020 May;21(5):602-603. doi: 10.1016/j.carrev.2020.03.017.

Local Anesthesia-Conscious Sedation: The Contemporary Gold Standard for Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2018 Mar 26;11(6):579-580. doi: 10.1016/j.jcin.2018.01.238.

Transfemoral Transcatheter Aortic Valve Replacement Using Fascia Iliaca Block as an Alternative Approach to Conscious Sedation as Compared to General Anesthesia. Cardiovasc Revasc Med. 2020 May;21(5):594-601. doi: 10.1016/j.carrev.2019.08.080. Epub 2019 Sep 7.

**NYSORA U/S guided Fascia Iliaca nerve block**

TCT-808 Transfemoral Transcatheter Aortic Valve Replacement Using Fascia Iliaca Block as an Alternative Approach to Conscious Sedation as Compare to General Anesthesia: Findings From a Single Center. J Am Coll Cardiol. 2019 Oct, 74 (13_Supplement) B792

Handoffs in Medicine

Patient safety is crucial for the delivery of effective, high-quality healthcare¹ and is defined by the World Alliance for Patient Safety of WHO as ‘the reduction of risk of unnecessary harm associated with healthcare to an acceptable minimum’. The practice and delivery of healthcare is argued to be fundamentally and critically dependent on effective and efficient communication. Depending on physicians’ needs and responsibilities, handoff content will vary, requiring customization by individual physician groups; there is no “one size fits all” content.