Abstract
Cerebral microcirculation is gradually compromised during sepsis, with significant reductions in the function of capillaries and blood perfusion in small vessels. Transcranial Doppler ultrasound (TCD) has been used to assess cerebral circulation in a typical clinical setting. This study was to systematically review TCD studies, assess their methodological quality, and identify trends that can be associated with the temporal evolution of sepsis and its clinical outcome. A meta-analysis of systematic reviews was conducted according to the PRISMA statement. Articles were searched from 1982 until the conclusion of this review in December 2015. Twelve prospective and observational studies were selected. Evaluations of cerebral blood flow, cerebral autoregulation, and carbon dioxide (CO2) vasoreactivity were summarized. A temporal pattern of the evolution of the illness was found. In early sepsis, the median blood flow velocity (Vm) and pulsatility index (PI) increased, and the cerebral autoregulation (CA) remained unchanged. In contrast, Vm normalization, PI reduction and CA impairment were found in later sepsis (patients with severe sepsis or septic shock). Cerebral haemodynamic is impaired in sepsis. Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators. A better understanding of cerebral hemodynamics may improve the clinical management of patients with sepsis and, consequently, improve clinical outcomes.
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Taccone FS, Su F, Pierrakos C, He X, James S, Dewitte O, Vincent JL, De Backer D. Cerebral microcirculation is impaired during sepsis: an experimental study. Crit Care. 2010;14(4):R140. doi:10.1186/cc9205.
Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED. Pathophysiology of septic encephalopathy: a review. Crit Care Med. 2000;28(8):3019–24.
Wilson JX, Young GB. Progress in clinical neurosciences: sepsis-associated encephalopathy: envolving concepts. Can J Neurol Sci. 2003;30(2):98–105.
Bleck TP, Smith MC, Pierre-Louis SJ, Jares JJ, Murray J, Hansen CA. Neurologic complications of critical medical illness. Crit Care Med. 1993;21:98–103.
Eidelman LA, Putterman D, Putterman C, Sprung CL. The spectrum of septic encephalopathy. Definitions, etiologies and mortalities. JAMA. 1996;275:470–3.
Sharshar T, Polito A, Checinski A, Stevens RD. Septic-associated encephalopathy-everything starts at a microlevel. Crit Care. 2010;14(5):199. doi:10.1186/cc9254.
Bowton DL, Bertels NH, Prough DS, Stump DA. Cerebral blood flow is reduced in patients with sepsis syndrome. Crit Care Med. 1989;17(5):399–403.
Semmler A, Hermann S, Mormann F, Weberpals M, Paxian SA, Okulla T, Schäfers M, Kummer MP, Klockgether T, Heneka MT. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J Neuroinflamm. 2008;5:38. doi:10.1186/1742-2094-5-38.
Pierrakos C, Antoine A, Velissaris D, Michaux I, Bulpa P, Evrard P, Ossemann M, Dive A. Transcranial Doppler assessment of cerebral perfusion in critically ill septic patients: a pilot study. Ann Intensive Care. 2013;3:28. doi:10.1186/2110-5820-3-28.
Pierrakos C, Attou R, Decorte L, Kolyviras A, Malinverni S, Gottignies P, Devriendt J, De Bels D. Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients. BMC Anestethesiol. 2014;14:45. doi:10.1186/1471-2253-14-45.
Sharshar T, Carlier R, Bernard F, Guidoux C, Brouland JP, Nardi O, de la Grandmaison GL, Aboab J, Gray F, Menon D, Annane D. Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med. 2007;33(5):798–806.
Taccone FS, Scolletta S, Franchi F, Donadello K, Oddo M. Brain perfusion in sepsis. Curr Vasc Pharmacol. 2013;11(2):170–86.
Nogueira RC, Bor-Seng-Shu E, Santos MR, Negrão CE, Teixeira MJ, Panerai RB. Dynamic cerebral autoregulation changes during sub-maximal handgrip maneuver. PLoS One. 2013;8(8):e70821. doi:10.1371/journal.pone.0070821.
Salinet AS, Robinson TG, Panerai RB. Effects of cerebral ischemia on human neurovascular coupling, CO2 reactivity, and dynamic cerebral autoregulation. J Appl Physiol. 2015;118(2):170–7. doi:10.1152/japplphysiol.00620.2014.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(6):e1000097. doi:10.1371/journal.pmed1000097.
Bowie RA, O’Connor PJ, Mahajan RP. Cerebrovascular reactivity to carbon dioxide in sepsis syndrome. Anaesthesia. 2003;58(3):261–5.
Matta BF, Stow PJ. Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies. Br J Anaesth. 1996;76(6):790–4.
Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Rüegg S, Strebel SP, Marsch SC, Pargger H, Steiner LA. Cerebral perfusion in sepsis-associated delirium. Crit Care. 2008;12(3):R63. doi:10.1186/cc6891.
Steiner LA, Pfister D, Strebel SP, Radolovich D, Smielewski P, Czosnyka M. Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults. Neurocrit Care. 2009;10(1):122–8. doi:10.1007/s12028-008-9140-5.
Szatmári S, Végh T, Csomós A, Hallay J, Takács I, Molnár C, Fülesdi B. Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit Care. 2010;14(2):R50. doi:10.1186/cc8939.
Terborg C, Schummer W, Albrecht M, Reinhart K, Weiller C, Röther J. Dysfunction of vasomotor reactivity in severe sepsis and septic shock. Intensive Care Med. 2001;27(7):1231–4.
Kadoi Y, Saito S, Kawauchi C, Hinohara H, Kunimoto F. Comparative effects of propofol vs dexmedetomidine on cerebrovascular carbon dioxide reactivity in patients with septic shock. Br J Anaesth. 2008;100(2):224–9. doi:10.1093/bja/aem343.
Thees C, Kaiser M, Scholz M, Semmler A, Heneka MT, Baumgarten G, Hoeft A, Putensen C. Cerebral haemodynamics and carbon dioxide reactivity during sepsis syndrome. Crit Care. 2007;11(6):R123.
Fülesdi B, Szatmári S, Antek C, Fülep Z, Sárkány P, Csiba L, Molnár C. Cerebral vasoreactivity to acetazolamide is not impaired in patients with severe sepsis. J Crit Care. 2012;27:337–43. doi:10.1016/j.jcrc.2011.11.002.
de Riva N, Budohoski KP, Smielewski P, Kasprowicz M, Zweifel C, Steiner LA, Reinhard M, Fábregas N, Pickard JD, Czosnyka M. Transcranial Doppler pulsatility index: what it is and what it isn’t. Neurocrit Care. 2012;17(1):58–66. doi:10.1007/s12028-012-9672-6.
Czosnyka M, Richards HK, Whitehouse HE, Pickard JD. Relationship between transcranial Doppler-determined pulsatility index and cerebrovascular resistance: an experimental study. J Neurosurg. 1996;84(1):79–84.
Brian JE Jr, Faraci FM. Tumor necrosis factor-alpha-induced dilatation of cerebral arterioles. Stroke. 1998;29(2):509–15.
Hernanz R, Alonso MJ, Briones AM, Vila E, Simonsen U, Salaices M. Mechanisms involved in the early increase of serotonin contraction evoked by endotoxin in rat middle cerebral arteries. Br J Pharmacol. 2003;140(4):671–80.
Skopál J, Turbucz P, Vastag M, Bori Z, Pék M, de Châtel R, Nagy Z, Tóth M, Karádi I. Regulation of endothelin release from human brain microvessel endothelial cells. J Cardiovasc Pharmacol. 1998;31(Suppl 1):S370–2.
Oliveira Md, de Azevedo DS, de Azevedo MK, Nogueira Rd, Teixeira MJ, Bor-Seng-Shu E. Encephalic hemodynamic phases in subarachnoid hemorrhage: how to improve the protective effect in patient prognoses. Neural Regen Res. 2015;10(5):748–52. doi:10.4103/1673-5374.156969.
Repessé X, Charron C, Vieillard-Baron A. Evaluation of left ventricular systolic function revisited in septic shock. Crit Care. 2013;17(4):164. doi:10.1186/cc12755.
Okamoto H, Ito O, Roman RJ, Hudetz AG. Role of inducible nitric oxide synthase and cyclooxygenase-2 in endotoxin-induced cerebral hyperemia. Stroke. 1998;29(6):1209–18.
Panerai RB. Transcranial Doppler for evaluation of cerebral autoregulation. Clin Auton Res. 2009;19(4):197–211. doi:10.1007/s10286-009-0011-8.
Bor-Seng-Shu E, Kita WS, Figueiredo EG, Paiva WS, Fonoff ET, Teixeira MJ, Panerai RB. Cerebral hemodynamics: concepts of clinical importance. Arq Neuropsiquiatr. 2012;70(5):352–6.
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de Azevedo, D.S., Salinet, A.S.M., de Lima Oliveira, M. et al. Cerebral hemodynamics in sepsis assessed by transcranial Doppler: a systematic review and meta-analysis. J Clin Monit Comput 31, 1123–1132 (2017). https://doi.org/10.1007/s10877-016-9945-2
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DOI: https://doi.org/10.1007/s10877-016-9945-2