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.
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
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 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).
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
The case: Patient came in for laparoscopic colectomy. She had a history of severe COPD, newly diagnosed adenocarcinoma of colon, anemia (Hb 9), newly diagnosed ANCA vasculitis, h/o mitral stenosis s/p robotic mitral valve replacement, pulmonary HTN, severe TR, systemic HTN, normal EF. Patient had recent exacerbations of CHF with BNP in 1200s. Recent (within the last 3 months) history of coding on induction requiring chest compressions during robotic MVR (50mg propofol). On a steroid taper.
BPs 180-200s/90-110s; PAPs 40-60s/20-40s. 50kg.
Plan: aline, swan, R2, slow induction
Induction: fentanyl 50mcg, propofol 20mg, lidocaine 100mg, etomidate 10mg, roc 50mg. Gtt: epinephrine @ 0.02mcg/kg/min, norepinephrine @ 0.04mcg/kg/min. Milrinone arrived to OR after induction. Able to titrate off epinephrine to Milrinone 0.3mcg/kg/min even with insufflation of abdomen. Did not need to decrease insufflation pressures as hemodynamics were relatively stable.
Extubated safely at the end of the case. Received 100mcg fentanyl, 20mg ketamine, Exparel TAP block, pre-op PO Tylenol 1000mg for pain control. She’s doing well and pleased with her anesthetic management.
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.
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.
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.
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
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
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.