80 something year old male came for reverse total shoulder replacement. He had severe COPD as well as an EF 20% with CHF. He had been appropriately optimized. Preoperatively, we performed an anterior approach suprascapular block (10ml, 0.25% bupi) combined with an infraclavicular block (20ml, 0.25% bupi). In retrospect, we could have used 5ml for suprascapular block and 15ml for infraclavicular block.
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
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.
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.
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.
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 . 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 .
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.
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.
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.
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).
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
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:
I was asked to consult on a 30-something year old patient who had a recent subdural hemorrhage. It was a spontaneous event without trauma. After a week of stabilization of the SDH, the patient started developing positional headaches. CT scan showed a CSF leak from C4-T5 ventrally and another one from T6-T10 dorsally.
CT head: Small evolving right greater than left bilateral subdural hematomas, not significantly changed compared to prior. No evidence of new hemorrhage. Trace right to left midline shift is unchanged.
Cspine/T-spine/L-spine with contrast: Extensive CSF leak. The dominant component of this process is a ventral epidural contrast collection extending from C6-T4 levels, but there is also abnormal dorsal epidural contrast extending from T5-T10. The contrast is densest in the cervicothoracic ventral epidural space, also suggesting that this is the primary leakage site.
MRA neck without acute abnormalities. MRI cervical/thoracic/lumbar spine which incidentally revealed multifocal demyelinating lesions in the cervical cord with a focal lesion at T7 and MRI brain showed multiple foci of T2 flair hyperintensity in the supratentorial white matter of the brain, suspicious for undiagnosed demyelinating disease.
Typically, anesthesia gets consulted for lumbar epidural blood patches after lumbar CSF leaks. However, in this case, the CSF leak occurs quite high in the cervicothoracic spine. Oftentimes, it’s very difficult to inject a greater volume of blood in the lumbar epidural space due to back pain to reach the higher cervical and thoracic areas.
Why not do a lumbar epidural blood patch to reach the cervical or thoracic space?
One question that is often asked is whether CEBPs are necessary, or would lumbar EBPs suffice, even for dural leaks at the cervical levels. There are several reports indicating that lumbar EBP can permanently alleviate the headache regardless of whether or not the site of leakage is identified . However, other reports demonstrate that lumbar EBP does not always result in permanent relief [36–38]. A study by Diaz suggests that the site of leakage should be identified by radioisotope cisternography and treated with EBP targeted to CSF leak site levels . Cousins et al suggested that placement of the EBP close to the site of CSF leakage is important . Studies have shown that blood injected at the lumbar level does reach the cervical levels. Ferrante et al., for instance, performed epidural blood patch at L3-4 and placed in the patient in trendelenburg for 22 hours . He was able to show presence of blood in the epidural space at the cervical levels on postprocedure MRIs. The mean spread of the blood patch in the epidural space has been found to be 4.6 ± 0.9 vertebral levels . Most of the blood spread in the cephalad direction . However, the amount of blood that reaches the higher cervical levels in comparison to the amount of blood needed to form a stable clot is unclear. Despite spread of blood to cervical levels, Beards did note that after an epidural blood patch, the majority of the clot and mass effect appears to be concentrated in the area around the injection site .
Utilizing this information, I thought this patient would be better suited for a CT-guided targeted (cervicothoracic) ventral epidural blood patch performed by the IR team. Additionally, I recommended conservative therapy: hydration, caffeine, Fioricet, lying flat, and an abdominal binder.
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
20-something year old primip came today with preeclampsia and was deemed a c/s candidate for her 26 week baby. She was 5’8″, 165lb and had no prior issue with previous surgeries. She was started on magnesium preop. The mag was held intraoperatively and would resume postoperatively. Pt was in sitting position for her spinal, which was placed at L4-5. Good clear CSF return. 0.75% bupi dosed at 13.5 mg with intrathecal fentanyl 15mcg and intrathecal morphine 0.2mg. BP decreased from 150s to 130s, which was appropriate. Patient stated she had increased tingling and decreased mobility in her legs. All symptoms and signs appropriate with her spinal. Patient passed the Allis clamp test prior to incision. She was quite anxious: propofol was given IV for anxiolysis. Patient was adamant about breastfeeding/pumping for her baby. No complications with delivery. Uterus was externalized and patient was sensitive to pressure and tugging/manipulation. IV fenatnyl and IV morphine were given along with IV propofol. When uterus was internalized, patient felt more pressure that seemed unbearable. More IV pain meds were given. Suggestion was made for intraperitoneal chloroprocaine. Patient able to tolerate fascial closure as well as staple skin closure.