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Land of confusion: anaesthetic management during thrombectomy for acute ischaemic stroke

2019; Elsevier BV; Volume: 122; Issue: 3 Linguagem: Inglês

10.1016/j.bja.2018.12.004

1471-6771

A. Venema, Maarten Uyttenboogaart, Anthony Absalom,

Cerebrovascular and Carotid Artery Diseases

Stroke is a major global health issue, contributing to an age-standardised global death rate for cerebrovascular diseases of 86.5 per 100 000.1Feigin V.L. Roth G.A. Naghavi M. et al.Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet Neurol. 2016; 15: 913-924Abstract Full Text Full Text PDF PubMed Scopus (898) Google Scholar, 2Benjamin E.J. Virani S.S. Callaway C.W. et al.Heart disease and stroke statistics—2018 update: a report from the American Heart Association.Circulation. 2018; 137: e492Google Scholar, 3Béjot Y. Bailly H. Durier J. Giroud M. Epidemiology of stroke in Europe and trends for the 21st century.Presse Méd. 2016; 45: e398Google Scholar, 4Naghavi M. Abajobir A.A. Abbafati C. et al.Global, regional, and national age–sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2017; 390: 1151-1210Abstract Full Text Full Text PDF PubMed Scopus (2986) Google Scholar In the USA and Europe, the majority of strokes are ischaemic.2Benjamin E.J. Virani S.S. Callaway C.W. et al.Heart disease and stroke statistics—2018 update: a report from the American Heart Association.Circulation. 2018; 137: e492Google Scholar, 3Béjot Y. Bailly H. Durier J. Giroud M. Epidemiology of stroke in Europe and trends for the 21st century.Presse Méd. 2016; 45: e398Google Scholar Since the introduction of intravenous thrombolytic agents, systemic reperfusion therapy has become the gold standard in the management strategy for acute ischaemic strokes.5Powers W.J. Rabinstein A.A. Ackerson T. et al.2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2018; 49: e46-e99Crossref PubMed Scopus (3336) Google Scholar However, a more recent series of studies on intra-arterial thrombectomy published in 2015 has significantly changed "the way we walk" the acute stroke management landscape.6Berkhemer O.A. Fransen P.S.S. Beumer D. et al.A randomized trial of intraarterial treatment for acute ischemic stroke.N Engl J Med. 2015; 372: 11-20Crossref PubMed Scopus (4597) Google Scholar, 7Goyal M. Demchuk A.M. Menon B.K. et al.Randomized assessment of rapid endovascular treatment of ischemic stroke.N Engl J Med. 2015; 372: 1019-1030Crossref PubMed Scopus (4184) Google Scholar, 8Campbell B.C.V. Mitchell P.J. Kleinig T.J. et al.Endovascular therapy for ischemic stroke with perfusion-imaging selection.N Engl J Med. 2015; 372: 1009-1018Crossref PubMed Scopus (3931) Google Scholar, 9Saver J.L. Goyal M. Bonafe A. et al.Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.N Engl J Med. 2015; 372: 2285-2295Crossref PubMed Scopus (3541) Google Scholar, 10Jovin T.G. Chamorro A. Cobo E. et al.Thrombectomy within 8 hours after symptom onset in ischemic stroke.N Engl J Med. 2015; 372: 2296-2306Crossref PubMed Scopus (3373) Google Scholar, 11White P.M. Bhalla A. Dinsmore J. et al.Standards for providing safe acute ischaemic stroke thrombectomy services (September 2015).Clin Radiol. 2017; 72: 175.e9Google Scholar These abovementioned studies investigated the influence of intra-arterial thrombectomy together with standard care on outcome after acute ischaemic strokes. The first study to be published was the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) trial.6Berkhemer O.A. Fransen P.S.S. Beumer D. et al.A randomized trial of intraarterial treatment for acute ischemic stroke.N Engl J Med. 2015; 372: 11-20Crossref PubMed Scopus (4597) Google Scholar The evidence of benefit was so compelling that investigators involved in other trials felt obliged to perform interim analyses, which confirmed the efficacy of intra-arterial thrombectomy—which resulted in these trials being terminated early.7Goyal M. Demchuk A.M. Menon B.K. et al.Randomized assessment of rapid endovascular treatment of ischemic stroke.N Engl J Med. 2015; 372: 1019-1030Crossref PubMed Scopus (4184) Google Scholar, 8Campbell B.C.V. Mitchell P.J. Kleinig T.J. et al.Endovascular therapy for ischemic stroke with perfusion-imaging selection.N Engl J Med. 2015; 372: 1009-1018Crossref PubMed Scopus (3931) Google Scholar, 9Saver J.L. Goyal M. Bonafe A. et al.Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.N Engl J Med. 2015; 372: 2285-2295Crossref PubMed Scopus (3541) Google Scholar, 10Jovin T.G. Chamorro A. Cobo E. et al.Thrombectomy within 8 hours after symptom onset in ischemic stroke.N Engl J Med. 2015; 372: 2296-2306Crossref PubMed Scopus (3373) Google Scholar, 11White P.M. Bhalla A. Dinsmore J. et al.Standards for providing safe acute ischaemic stroke thrombectomy services (September 2015).Clin Radiol. 2017; 72: 175.e9Google Scholar A meta-analysis of five randomised trials confirmed the impressive efficacy of intra-arterial thrombectomy: the number-needed-to-treat for a favourable outcome (reduced disability of at least 1 point on the modified Rankin scale) was 2.6.12Goyal M. Menon B.K. van Zwam W.H. et al.Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.Lancet. 2016; 387: 1723-1731Abstract Full Text Full Text PDF PubMed Scopus (3955) Google Scholar These results have led to a substantial increase in the use of intra-arterial thrombectomy.13Smith E.E. Saver J.L. Cox M. et al.Increase in endovascular therapy in get with the guidelines—stroke after the publication of pivotal trials.Circulation. 2017; 136: 2303-2310PubMed Google Scholar This increase in caseload has significant consequences for anaesthetists, as anaesthetic support for patients undergoing intra-arterial thrombectomy poses particular challenges.14Dinsmore J. Elwishi M. Kailainathan P. Anaesthesia for endovascular thrombectomy.BJA Educ. 2018; 18: 291-299Abstract Full Text Full Text PDF Scopus (5) Google Scholar For the treatment of acute ischaemic strokes, speed is essential, leading to the frequently stated aphorism 'time is brain'.15Froehler M.T. Saver J.L. Zaidat O.O. et al.Interhospital transfer before thrombectomy is associated with delayed treatment and worse outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).Circulation. 2017; 136: 2311Crossref PubMed Scopus (245) Google Scholar, 16Campbell B.C.V. Donnan G.A. Davis S.M. Optimizing systems of care for endovascular thrombectomy in ischemic stroke.Circulation. 2017; 136: 2322Google Scholar, 17Mulder M.J.H.L. Jansen I.G.H. Goldhoorn R.B. et al.Time to endovascular treatment and outcome in acute ischemic stroke: MR CLEAN Registry results.Circulation. 2018; 138: 232-240Crossref PubMed Scopus (95) Google Scholar When intra-arterial thrombectomy is indicated and general anaesthesia is required, the personnel and equipment must be available at short notice in a radiology suite that is usually remote from the operating theatre, with potential adverse consequences for the elective or emergency procedure schedule. The increasing use of intra-arterial thrombectomy where general anaesthesia is required might necessitate changes in the logistics and staffing of operating theatres, in particular of on-call teams. Besides the logistical challenges, another emerging challenge for anaesthetists is to determine how they can best assist interventionists to optimise treatment and clinical outcome for patients undergoing intra-arterial thrombectomy. This is a hotly debated topic, and much more research is needed before there is a sufficiently solid evidence base upon which to base management guidelines.5Powers W.J. Rabinstein A.A. Ackerson T. et al.2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2018; 49: e46-e99Crossref PubMed Scopus (3336) Google Scholar, 11White P.M. Bhalla A. Dinsmore J. et al.Standards for providing safe acute ischaemic stroke thrombectomy services (September 2015).Clin Radiol. 2017; 72: 175.e9Google Scholar One debated issue is whether general anaesthesia, sedation, or local anaesthesia alone is best for patient outcome. Most of the evidence so far comes from studies not primarily designed to answer this question as the studies were designed to investigate the influence of intra-arterial thrombectomy on outcome. Campbell and colleagues18Campbell B.C.V. van Zwam W.H. Goyal M. et al.Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.Lancet Neurol. 2018; 17: 47-53Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar performed a meta-analysis of the data from seven such studies. They found that of those patients who underwent intra-arterial thrombectomy, those who did so under general anaesthesia had worse outcomes than those who received sedation or only local anaesthesia. This led the authors to conclude that general anaesthesia is harmful and, when possible, should be avoided during intra-arterial thrombectomy. Soon afterwards several groups began to avoid general anaesthesia, thereby attenuating the additional burden on their anaesthetic departments. Do the abovementioned data18Campbell B.C.V. van Zwam W.H. Goyal M. et al.Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.Lancet Neurol. 2018; 17: 47-53Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar mean that anaesthetists can relax and retreat to the familiar territory of the operating theatre, and leave the radiologist to perform these procedures with no or only minimal operator-administered sedation? Our view is certainly not. As Dinsmore19Dinsmore J. HERMES: a helpful messenger in the anaesthesia for thrombectomy debate?.Lancet Neurol. 2018; 17: 21-23Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar pointed out in the excellent accompanying editorial, the strength of this conclusion was somewhat overstated given that the study suffered from most of the potential weaknesses of a retrospective secondary analysis of data from studies with a different goal. Among these were that the patients enrolled in these studies were randomised to treatment groups (intra-arterial thrombectomy vs standard care) and the choice of anaesthetic technique was at the discretion of the responsible clinicians, thereby introducing the risk of selection bias as it is plausible that patients in worse condition would be selected to receive general anaesthesia.19Dinsmore J. HERMES: a helpful messenger in the anaesthesia for thrombectomy debate?.Lancet Neurol. 2018; 17: 21-23Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 20Brinjikji W. Pasternak J. Murad M.H. et al.Anesthesia-related outcomes for endovascular stroke revascularization.Stroke. 2017; 48: 2784-2791Crossref PubMed Scopus (108) Google Scholar Moreover, important information such as whether or not there were pre-specified protocols for choice and dose of anaesthetic or sedative agents, depth of anaesthesia or sedation, and blood pressure (BP) management was often lacking. More recently, three RCTs have specifically addressed this issue. Patients were randomly assigned to general anaesthesia or non-general anaesthesia groups.21Schönenberger S. Uhlmann L. Hacke W. et al.Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial.JAMA. 2016; 316: 1986-1996Crossref PubMed Scopus (313) Google Scholar, 22Löwhagen Hendén P. Rentzos A. Karlsson J. et al.General anesthesia versus conscious sedation for endovascular treatment of acute ischemic stroke.Stroke. 2017; 48: 1601-1607Crossref PubMed Scopus (249) Google Scholar, 23Simonsen C.Z. Yoo A.J. Sørensen L.H. et al.Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke: a randomized clinical trial.JAMA Neurol. 2018; 75: 470-477Crossref PubMed Scopus (235) Google Scholar Even though the care provided in both groups differed between studies, without exception these studies either found no difference in outcome or a tendency to better outcomes in the general anaesthesia group. These data, combined with the benefit to the interventionalist if the patient is immobile, suggest that general anaesthesia may well be the optimal option. To be able to better guide the management of patients undergoing intra-arterial thrombectomy under general anaesthesia, important questions remain to be answered (Table 1). For example, which hypnotic agent is most beneficial for maintenance of anaesthesia? By definition each successful intra-arterial thrombectomy procedure generates an iatrogenic ischaemia–reperfusion injury. Vlisides and colleagues24Vlisides P.E. Avidan M.S. Mashour G.A. Reconceptualising stroke research to inform the question of anaesthetic neurotoxicity.Br J Anaesth. 2018; 120: 430-435Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar have suggested that these procedures provide an ideal 'model' for studying the potential neurotoxic or neuroprotective effects of currently used anaesthetic agents on neurological recovery and survival. Should such studies show beneficial effects on clinical outcomes, it would provide a strong argument for using general anaesthesia during all intra-arterial thrombectomy procedures and provide guidance for the choice of anaesthetic technique to be used: total intravenous anaesthesia or inhalational.Table 1Research suggestionsTopicSuggested research strategyOptimal ventilation strategy and Paco2Randomisation to mild hypocarbia, normocarbia, and mild hypercarbia to determine optimal Paco2Investigate influence of Paco2 on cerebral autoregulation after recanalisationOptimal FiO2 and Pao2Randomisation to different Pao2Investigate influence of Pao2 on arteriolar tone after recanalisationOptimal blood pressure management (targets, medications, reperfusion injury/haemorrhagic complications)Randomisation to different arterial pressure thresholdsSeparate consideration of optimal haemodynamic targets before and after reperfusionEffects of arterial pressure variability during intra-arterial thrombectomy on outcomeInfluence of the combination of volume status and different vasoactive/inotropic agents on cerebral tissue oxygenationInfluence of anaesthetic maintenance agent on outcomeRandomised controlled trial to investigate biomarker and clinical outcome variables after different anaesthetic agents and techniquesNeurological monitoringFeasibility and clinical and prognostic utility of cerebral oximetry/near-infrared spectroscopy/transcranial Doppler ultrasound during intra-arterial thrombectomyUniform reporting template and definitionsMulti-disciplinary Delphi procedure and consensus statement on uniform definitions and research parameters Open table in a new tab An argument often used against providing general anaesthesia during intra-arterial thrombectomy is that general anaesthesia can lead to absolute or relative decreases in arterial BP compared with the pre-induction pressure. Radiologists, neurologists, and anaesthetists seem convinced that hypotension is harmful during intra-arterial thrombectomy procedures. However, the optimal BP management during intra-arterial thrombectomy has not yet been determined. Although general anaesthesia is associated with more hypotension and higher vasopressor requirements than conscious sedation,21Schönenberger S. Uhlmann L. Hacke W. et al.Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial.JAMA. 2016; 316: 1986-1996Crossref PubMed Scopus (313) Google Scholar, 22Löwhagen Hendén P. Rentzos A. Karlsson J. et al.General anesthesia versus conscious sedation for endovascular treatment of acute ischemic stroke.Stroke. 2017; 48: 1601-1607Crossref PubMed Scopus (249) Google Scholar, 23Simonsen C.Z. Yoo A.J. Sørensen L.H. et al.Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke: a randomized clinical trial.JAMA Neurol. 2018; 75: 470-477Crossref PubMed Scopus (235) Google Scholar no correlations between BP changes and early and late neurological outcomes have been found.25Schonenberger S. Uhlmann L. Ungerer M. et al.Association of blood pressure with short- and long-term functional outcome after stroke thrombectomy: post hoc analysis of the SIESTA trial.Stroke. 2018; 49: 1451-1456Google Scholar, 26Rasmussen M. Espelund U.S. Juul N. et al.The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.Br J Anaesth. 2018; 120: 1287-1294Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar It has been argued that this lack of association is because of good compliance with strict BP management protocols in these studies.25Schonenberger S. Uhlmann L. Ungerer M. et al.Association of blood pressure with short- and long-term functional outcome after stroke thrombectomy: post hoc analysis of the SIESTA trial.Stroke. 2018; 49: 1451-1456Google Scholar Despite the weak or absent evidence, it seems logical and prudent for anaesthetists to maintain a sufficiently high BP.25Schonenberger S. Uhlmann L. Ungerer M. et al.Association of blood pressure with short- and long-term functional outcome after stroke thrombectomy: post hoc analysis of the SIESTA trial.Stroke. 2018; 49: 1451-1456Google Scholar, 26Rasmussen M. Espelund U.S. Juul N. et al.The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.Br J Anaesth. 2018; 120: 1287-1294Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The challenge remains to define an adequate individualised BP, as it is unlikely that 'one size fits all'. It is also conceivable that there are other parameters, such as duration of hypotension and variability of peri-procedural BP, that are important as well.27Wesselink E.M. Kappen T.H. Torn H.M. Slooter A.J.C. van Klei W.A. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review.Br J Anaesth. 2018; 121: 706-721Abstract Full Text Full Text PDF PubMed Scopus (298) Google Scholar Once we know the optimal BP, we also need to determine the optimal method of keeping the BP on target. Research in volunteers shows that phenylephrine and norepinephrine might actually decrease cerebral tissue oxygenation.28Poterman M. Vos J.J. Vereecke H.E. et al.Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia: a randomised controlled trial.Eur J Anaesthesiol. 2015; 32: 571-580Crossref PubMed Scopus (33) Google Scholar We also need to understand better the influence of recanalisation on cerebral autoregulation, as well as the influence of Pao2 and Paco2 on vascular tone in the affected vascular beds. Although little is known about this, it is likely that after recanalisation autoregulation is not present in the territory of the affected vessel, and that blood flow in the recanalised vessel is pressure passive (so called vasoplegia). If this is the case, then we might need different BP management strategies before and after recanalisation, or tailor-made strategies based on individual and real-time assessments of autoregulatory capacity in order to prevent haemorrhagic complications of reperfusion injury. High Pao2 can cause vasospasm in some vascular beds.29Kety S.S. Schmidt C.F. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men.J Clin Invest. 1948; 27: 484-492Crossref PubMed Scopus (1107) Google Scholar Does this apply to the affected vascular bed after recanalisation such that high FiO2 should be avoided after recanalisation? Does CO2 reactivity remain in the affected vascular bed after re-canalisation? It seems unlikely to be present if autoregulation is absent. However, we need to know for certain because if CO2 reactivity is absent then hyperventilation should be actively avoided, as it may cause a steal phenomenon with hyperaemia in the affected bed. If CO2 reactivity remains, then hypoventilation (and hypercarbia) should also be avoided. If there is vasoplegia in the reperfused vascular territory, then it is also likely that the resulting regional hyperaemia influences the availability of blood for other territories. There are many research opportunities in this area. Many of the published studies seem to have been performed without help from anaesthesia colleagues. Anaesthetists should become more involved as their deep understanding of the complex interplay between BP, Paco2, Pao2, and cerebral blood flow can provide useful input during the planning and conduct of studies. We can use intra-arterial thrombectomy as a model to explain important questions of general relevance to anaesthesia (e.g. anaesthetic conditioning). Anaesthetists can also play an important role in clinical practise, even when general anaesthesia is not used. Where sedation is desirable, anaesthetists are experts at providing safe sedation to vulnerable patients and at rescuing patients from the adverse consequences of sedation. Even if future studies show compelling evidence for avoiding general anaesthesia, there will always be situations where general anaesthesia is still needed (restless patient, failed sedation, excessive sedation, threatened airway in deeply comatose patient). In such cases, and especially when we do eventually know what BP is optimal, anaesthetists will be uniquely qualified to manage the haemodynamic status of these patients. Achievement of optimal outcomes after acute ischaemic strokes depends on factors such as speed and optimal haemodynamic management, and for these multi-disciplinary teamwork and communication are essential. Further intra-arterial thrombectomy research might identify additional ideas to implement in future studies. In resuscitation research the 'Utstein template' has been in use for more than two decades to create more uniformity in definitions and reporting of results.30Chamberlain D. Cummins R.O. Abramson N. et al.Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the 'Utstein style': prepared by a task force of representatives from the European Resuscitation Council, American Heart Association, Heart and Stroke Foundation of Canada, Australian Resuscitation Council.Resuscitation. 1991; 22: 1-26Abstract Full Text PDF PubMed Scopus (217) Google Scholar This template has been updated, and for several specific areas of resuscitation research (e.g. drowning) additional templates have been introduced.31Idris A.H. Bierens J.J.L.M. Perkins G.D. et al.2015 revised Utstein-style recommended guidelines for uniform reporting of data from drowning-related resuscitation.Resuscitation. 2017; 118: 147-158Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar They now form a solid base for conducting resuscitation research and are used in the disciplines (anaesthesiology, cardiology, etc.) involved in this area of research. Such a consensus-based template might be of value in studying the care of patients undergoing intra-arterial thrombectomy as well. In conclusion, currently available data are not yet strong enough to clearly guide anaesthetic management during intra-arterial thrombectomy; results are conflicting and there is a lack of standardised reporting of relevant parameters. We encourage anaesthetists working in centres performing intra-arterial thrombectomy to get actively involved in their neuro-interventional team. They can make an important contribution in researching and formulating the optimal strategy for treating and monitoring stroke patients during the perioperative phase of intra-arterial thrombectomy. Conception of the material presented: AMV, ARA, MU. Writing of the manuscript: AMV, ARA. Critical revision of the material presented: AMV, ARA, MU. AMV and MU report no conflicts of interest. ARA is an editor of the British Journal of Anaesthesia. The University Medical Center Groningen.