The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.
Aged
Aged, 80 and over
Deep Sedation
/ methods
Dexmedetomidine
/ adverse effects
Female
Humans
Hypnotics and Sedatives
/ adverse effects
Intensive Care Units
/ organization & administration
Male
Middle Aged
Respiration, Artificial
Retrospective Studies
Shock, Septic
/ drug therapy
Switzerland
Vasoconstrictor Agents
/ administration & dosage
Victoria
Dexmedetomidine
Hemodynamics
Noradrenaline
Sedation
Sepsis
Septic shock
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
16 07 2020
16 07 2020
Historique:
received:
24
04
2020
accepted:
29
06
2020
entrez:
18
7
2020
pubmed:
18
7
2020
medline:
15
4
2021
Statut:
epublish
Résumé
Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).
Sections du résumé
BACKGROUND
Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting.
METHODS
In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4).
RESULTS
Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio.
CONCLUSIONS
In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP.
TRIAL REGISTRATION
The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).
Identifiants
pubmed: 32678054
doi: 10.1186/s13054-020-03115-x
pii: 10.1186/s13054-020-03115-x
pmc: PMC7367420
doi:
Substances chimiques
Hypnotics and Sedatives
0
Vasoconstrictor Agents
0
Dexmedetomidine
67VB76HONO
Banques de données
ClinicalTrials.gov
['NCT01728558']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
441Investigateurs
Yahya Shehabi
(Y)
Yaseen Arabi
(Y)
Frances Bass
(F)
Rinaldo Bellomo
(R)
Simon Erickson
(S)
Belinda Howe
(B)
Suhaini Kadiman
(S)
Colin McArthur
(C)
Lynnette Murray
(L)
Michael Reade
(M)
Ian Seppelt
(I)
Jukka Takala
(J)
Steve A Webb
(SA)
Matthew P Wise
(MP)
Yahya Shehabi
(Y)
Belinda Howe
(B)
Rinaldo Bellomo
(R)
Yaseen M Arabi
(YM)
Michael J Bailey
(MJ)
Frances Bass
(F)
Suhaini Kadiman
(S)
Colin McArthur
(C)
Lynnette Murray
(L)
Michael Reade
(M)
Ian Seppelt
(I)
Jukka Takala
(J)
Steve A Webb
(SA)
Matthew P Wise
(MP)
Michael J Bailey
(MJ)
Belinda D Howe
(BD)
Lynette Murray
(L)
Vanessa Singh
(V)
Commentaires et corrections
Type : CommentIn
Références
Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8(10):776–87.
doi: 10.1038/nri2402
Ferreira J. The theory is out there: the use of ALPHA-2 agonists in treatment of septic shock. Shock. 2018;49(4):358–63.
doi: 10.1097/SHK.0000000000000979
Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med. 1993;328(20):1471–7.
doi: 10.1056/NEJM199305203282008
Pichot C, Geloen A, Ghignone M, Quintin L. Alpha-2 agonists to reduce vasopressor requirements in septic shock? Med Hypotheses. 2010;75(6):652–6.
doi: 10.1016/j.mehy.2010.08.010
Geloen A, Chapelier K, Cividjian A, Dantony E, Rabilloud M, May CN, Quintin L. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med. 2013;41(12):e431–8.
doi: 10.1097/CCM.0b013e3182986248
Parlow JL, Sagnard P, Begou G, Viale JP, Quintin L. The effects of clonidine on sensitivity to phenylephrine and nitroprusside in patients with essential hypertension recovering from surgery. Anesth Analg. 1999;88(6):1239–43.
doi: 10.1213/00000539-199906000-00010
Herr DL, Sum-Ping ST, England M. ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth. 2003;17(5):576–84.
doi: 10.1016/S1053-0770(03)00200-3
Inomata SNT, Kihara S, et al. Enhancement of pressor response to intravenous phenylephrine following oral clonidine medi- cation in awake and anaesthetized patients. Can J Anaesth. 1995;42:119–25.
doi: 10.1007/BF03028263
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.
doi: 10.1097/00000542-200008000-00016
Sanders RD, Maze M. Alpha2-adrenoceptor agonists. Curr Opin Investig Drugs. 2007;8(1):25–33.
pubmed: 17263182
Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, et al. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506–17.
doi: 10.1056/NEJMoa1904710
Shehabi Y, Forbes AB, Arabi Y, Bass F, Bellomo R, Kadiman S, Howe BD, McArthur C, Reade MC, Seppelt I, et al. The SPICE III study protocol and analysis plan: a randomised trial of early goaldirected sedation compared with standard care in mechanically ventilated patients. Crit Care Resusc. 2017;19(4):318–26.
pubmed: 29202258
Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, et al. Angiotensin II for the treatment of Vasodilatory shock. N Engl J Med. 2017;377(5):419–30.
doi: 10.1056/NEJMoa1704154
Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489–99.
doi: 10.1001/jama.2009.56
Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151–60.
doi: 10.1001/jama.2012.304
Lankadeva YR, Booth LC, Kosaka J, Evans RG, Quintin L, Bellomo R, May CN. Clonidine restores pressor responsiveness to phenylephrine and angiotensin II in ovine sepsis. Crit Care Med. 2015;43(7):e221–9.
doi: 10.1097/CCM.0000000000000963
Lankadeva YR, Ma S, Iguchi N, Evans RG, Hood SG, Farmer DGS, Bailey SR, Bellomo R, May CN. Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury. Kidney Int. 2019;96(5):1150–61.
doi: 10.1016/j.kint.2019.06.013
Morelli A, Sanfilippo F, Arnemann P, Hessler M, Kampmeier TG, D'Egidio A, Orecchioni A, Santonocito C, Frati G, Greco E, et al. The effect of propofol and dexmedetomidine sedation on norepinephrine requirements in septic shock patients: a crossover trial. Crit Care Med. 2019;47(2):e89–95.
doi: 10.1097/CCM.0000000000003520
Quintin L. Alpha-2 adrenoceptor agonists and sepsis: improved survival? Crit Care. 2010;14(4):429 author reply 429.
doi: 10.1186/cc9096
Geloen A, Pichot C, Leroy S, Julien C, Ghignone M, May CN, Quintin L. Pressor response to noradrenaline in the setting of septic shock: anything new under the sun-dexmedetomidine, clonidine? A minireview. BioMed Res Int. 2015;2015:863715.
doi: 10.1155/2015/863715
Hernandez G, Tapia P, Alegria L, Soto D, Luengo C, Gomez J, Jarufe N, Achurra P, Rebolledo R, Bruhn A, et al. Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock. Crit Care. 2016;20(1):234.
doi: 10.1186/s13054-016-1419-x
Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW, investigators M. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38.
doi: 10.1186/cc8916
Nelson KM, Patel GP, Hammond DA. Effects from continuous infusions of dexmedetomidine and propofol on hemodynamic stability in critically ill adult patients with septic shock. J Intensive Care Med. 2018. https://doi.org/10.1177/0885066618802269 .
Mermet C, Quintin L. Effect of clonidine on catechol metabolism in the rostral ventrolateral medulla: an in vivo electrochemical study. Eur J Pharmacol. 1991;204(1):105–7.
doi: 10.1016/0014-2999(91)90842-E
Gu J, Chen J, Xia P, Tao G, Zhao H, Ma D. Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice. Acta Anaesthesiol Scand. 2011;55(10):1272–8.
doi: 10.1111/j.1399-6576.2011.02526.x
Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, Xia P, Maze M, Ma D. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. 2011;15(3):R153.
doi: 10.1186/cc10283
Hofer S, Steppan J, Wagner T, Funke B, Lichtenstern C, Martin E, Graf BM, Bierhaus A, Weigand MA. Central sympatholytics prolong survival in experimental sepsis. Crit Care. 2009;13(1):R11.
doi: 10.1186/cc7709
Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004;32(6):1322–6.
doi: 10.1097/01.CCM.0000128579.84228.2A
Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22(3):221–8.
doi: 10.1007/s00540-008-0611-9
Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, Zhou C, Huang L, Li X, Zhou C. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-kappaB pathway. Mediat Inflamm. 2013;2013:562154.
Xiang H, Hu B, Li Z, Li J. Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Inflammation. 2014;37(5):1763–70.
doi: 10.1007/s10753-014-9906-1
Shimamura K, Toba M, Kimura S, Ohashi A, Kitamura K. Clonidine induced endothelium-dependent tonic contraction in circular muscle of the rat hepatic portal vein. J Smooth Muscle Res. 2006;42(2–3):63–74.
doi: 10.1540/jsmr.42.63
Abril MK, Khanna AK, Kroll S, McNamara C, Handisides D, Busse LW. Regional differences in the treatment of refractory vasodilatory shock using Angiotensin II in High Output Shock (ATHOS-3) data. J Crit Care. 2019;50:188–94.
doi: 10.1016/j.jcrc.2018.12.007