12 ISICEM News Wednesday 21 March 2018 Issue 2

Ultra-short-acting beta blockers could play important role in minimizing decatecholaminization

uring yesterday’s Amomed- evidence that perhaps we need a logical phenotype that can identify “Catecholaminergic vasopressors sponsored symposium little bit of sympathetic stimula- those patients who will benefit from may induce adverse cardiac events. D‘Decatecholaminization tion in our lives, but too much the drug. When it comes to using We need to think about the nega- What’s new?’, Matthias Heringlake, of a good thing becomes bad, beta-blockers for these patients, the tive side effects when using catecho- Professor of Anesthesiology at the and unfortunately once a patient single-center trial from Morelli et lamines and consider alternatives University of Lübeck, Germany becomes ill we then ply them with al. in patients with resistant septic – one possibility being vasopressin.” and Johann Knotzer, Head of the even more stimulation in the form shock showed that esmolol was Vasopressin works in the Department of Anesthesiology at of catecholamines.” effective in reducing heart rate to endothelium mainly through VI: Hospital Wels-Grieskirchen, Aus- “Alternatives include vasopres- target levels without an increase “Relative vasopressin deficiency tria, spoke about the role of ultra- sin, but the clinical trials conducted in adverse outcomes compared to backs up the rationale for early- short-acting beta blockers in sepsis, so far have not shown any differ- standard treatment, and that out- phase combinations of vasopres- and after cardiac surgery. ence in outcomes, although a recent comes, including time on vasopres- sin and norepinephrine in cardiac Managing septic shock remains post-hoc analysis of the VASST sors and mortality, were improved.2 surgery patients,” said Dr Knotzer. a significant therapeutic challenge. trial1 in Canada did suggest benefits “As a consequence, the UK “In the presence of constant mean Ultra-short-acting beta blockers in hypotensive patients not meeting Department of Health has funded a arterial pressure, norepinephrine can effectively control the heart the Sepsis-3 shock criteria,” said multicenter study called STRESS-L, doses may be minimized.” rate and may have other significant Professor Singer. using landiolol to treat patients in The VANCS trial3, published in non-cardiac benefits, the ISICEM “The challenge is to find a bio- septic shock, which is now starting 2017, investigated early applica- audience heard. to recruit,” said Profes- tion of vasopressin in hypotensive Introducing the sym- sor Singer. “Alternatives cardiac surgery patients. This was a posium was session chair, “Despite [the fact that] we include vasopressin, but randomized double-blind controlled Mervyn Singer, Professor of the clinical trials conducted trial with 330 patients present- Intensive Care Medicine at don’t have the data yet so far have not shown any ing hypotension following heart University College London, for landiolol’s effectiveness difference in outcomes, surgery. Severe hypotension was UK. Professor Singer noted although the recent VANCS defined as mean arterial pressure that although norepinephrine in sepsis patients, it is not trial3 in Canada did find <65 mmHg and a cardiac index of is the standard treatment for some benefits in a subgroup >2.2 l/min/m2. Half of the patients low blood pressure in septic unlikely that it will be even of patients.” This trial were randomly assigned to receive shock, it is associated with more effective than esmolol was discussed in greater either first-line vasopressin (0.01 multiple negative effects detail by Dr Knotzer during to 0.06 IU/min), and the other half too. These include tachyar- since it has less negative the session. first-line norepinephrine (10 to 60 rhythmias, digital ischemia, effect on blood pressure.” Dr Knotzer addressed μg/min). The primary endpoint was immunosuppression, stimula- the audience about a combination of mortality and tion of bacterial growth and Matthias Heringlake catecholamine toxicity, ex- severe complications. virulence, and increases in plaining that, to avoid this, “The study showed that acute myocardial stress, oxygen norepinephrine shouldn’t kidney failure and atrial fibrillation consumption and damage. Mortal- be given at high doses, nor for long occur significantly more often in ity rises with norepinephrine dose periods of time. norepinephrine patients than vaso- and this may not be simply related Speaking to ISICEM News pressin patients (49% vs 32% to illness severity. ahead of the session, Dr Knotzer [p = 0.0014]),” Dr Knotzer Professor Singer said: “I’m a said the severity and duration of explained. VANCS also found a believer – and there is quite a lot hypotension in cardiac anesthesia is significantly lower rate of atrial of pre-clinical and some clinical associated with a negative outcome: fibrillation in the vasopressin group

or intensive

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(63.8% vs 82.1%; p = 0.0004) and advantages of using landiolol is that References shorter mean length of hospital stay it has only minimal effects on blood 1. Russell JA, Lee T, Singer J, et al. Vasopressin and Septic Shock Trial (VASST) Group. The (10 vs 13 days; p=0.0016). pressure, even in patients who are Septic Shock 3.0 Definition and Trials: A “The VANCS trial is a promis- hemodynamically compromised, and Vasopressin and Septic Shock Trial Experience. ing and very interesting trial, with can be used to titrate the heart rate Crit Care Med. 2017;45:940–8. 2. Morelli A, Ertmer C and Westphal M. Effect good results,” said Dr Knotzer. and optimize stroke volume – an of heart rate control with esmolol in hemo- “We know that vasopressin has a important physiological regulator. dynamic and clinical outcome in patients positive effect in cardiac surgery “Despite [the fact that] we don’t with septic shock. A randomised Controlled trial. JAMA.2013;310(16):1683-1691. patients according to a decrease have the data yet for landiolol’s 3. Hajjar L, Vincent J, Galas F, et al. Vasopres- in atrial fibrillation and in renal effectiveness in sepsis patients, it sion versus Norepinephrine in Patients with replacement therapy. Furthermore, is not unlikely that it will be even Vasoplegic Shock After Cardiac Surgery; The VANCS Randomized Controlled Trial. in the VANCS trial, vasopres- more effective than esmolol since Anesthesiology 1 2017, Vol.126, 85-93. sin was tested as a verum against it has less negative effect on blood norepinephrine, and not on top of pressure,” he said. “Additionally, Additional information norepinephrine. However, no ben- based on the experience in patients • Tamura T, Yokoyama M. ‘Prevention of atrial fibrillation after cardiac surgery using low efit in outcome was detected. The undergoing cardiac surgery, and dose landiolol. A systematic review and meta- door is open for a large randomized in patients with heart failure, analysis. J. Clinical Anesth 2017 Nov: 42:1-6. • Nagai R, Kinugawa K, Inoue H, Atarashi H, controlled trial to show a mortal- landiolol may be used to prevent Seino Y, Yamashita T. Urgent management of ity benefit.” atrial fibrillation also in patients rapid heart rate in patients with atrial fibrilla- tion/ flutter and left ventricular dysfunction: To sum up, he said presenting with sepsis. This, comparison of the ultra-short-acting landiolol severity and duration of however, also needs to be shown in with digoxin (J-Land Study). Circ J. 2013; “We need to 77 (4):908-16. hypotension is associated future trials.” with a negative outcome, think about the Professor Heringlake summed and catecholaminergic drugs up his talk by relaying that septic may induce cardiac events. negative side shock leads to vascular hyper Vasopressin is an alternative effects when using responsiveness and myocardial vasopressor, but there are still dysfunction and said that increased open questions on mortality, catecholamines and sympathetic tone and high doses of benefit, dosage, time point catecholamines may perpetuate sys- and the right patients. consider alternatives temic inflammation and increases In his talk, Professor – one possibility mortality. He said vasopressin used Heringlake focused on lan- in septic shock restores vascular diolol, which acts as a highly being vasopressin.” tone, avoids catecholamine toxicity, cardio-selective ultra-short- ameliorates AKI and may be associ- Johann Knotzer acting beta blocker. Used as ated with reduced mortality. an anti-arrhythmic agent, it “Beta-blocking agents (and has shown it can achieve rapid and artery bypass grafting, valvular avoidance of classical catechola- reversible heart rate reduction with surgery or other interventions and mines) may be useful in septic cir- minor effects on blood pressure. is associated with a significant culatory failure – beyond prevention Landiolol has been available increase in post-operative morbidity of atrial fibrillation,“ said Profes- in Europe since July 2017 but has and mortality. sor Heringlake. been used in Japan for 15 years “Landiolol is particularly effec- “Stroke volume optimization in the prevention and treatment tive for this treatment, as pointed improves visceral perfusion, and of 3.5-million atrial fibrillation out by several recent meta-analyses; other benefits include re- patients following cardiac surgery or a feature possibly related to its high duced inflammation, and intensive care. Postoperative atrial β-1 cardioselectivity,” said Profes- improved hemodynam- “The challenge overall fibrillation develops in 30 to 50% of sor Heringlake. ics and outcomes during cardiac patients following coronary He added that one of the main septic shock.” is finding a biological phenotype to identify those patients who may benefit from the drug.”

Mervyn Singer

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