Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study.
BACKGROUND
Terlipressin bolus infusion may reduce cardiac output and global oxygen supply. The present study was designed to determine whether dobutamine may counterbalance the terlipressin-induced depression in mixed-venous oxygen saturation (Svo) in patients with catecholamine-dependent septic shock.


METHODS
Prospective, randomized, controlled study performed in a university hospital intensive care unit. Septic shock patients requiring a continuous infusion of norepinephrine (0.9 microg kg(-1) min(-1)) to maintain mean arterial pressure (MAP) at 70 (sd 5) mm Hg were randomly allocated to be treated either with (i) sole norepinephrine infusion (control, n=20), (ii) a single dose of terlipressin 1 mg (n=19), or (iii) a single dose of terlipressin 1 mg followed by dobutamine infusion titrated to reverse the anticipated reduction in Svo2 (n=20). Systemic, pulmonary, and regional haemodynamic variables were obtained at baseline and after 2 and 4 h. Laboratory surrogate markers of organ (dys)function were tested at baseline and after 12 and 24 h.


RESULTS
Terlipressin (with and without dobutamine) infusion preserved MAP at 70 (5) mm Hg, while allowing to reduce norepinephrine requirements to 0.17 (0.2) and 0.2 (0.2) microg kg(-1) min(-1), respectively [vs1.4 (0.3) microg kg(-1) min(-1) in controls at 4 h; each P<0.001]. The terlipressin-linked decrease in Svo2 was reversed by dobutamine at a mean dose of 20 (8) microg kg(-1) min(-1) [Svo2 at 4 h: 59 (11)% vs 69 (12)%, P=0.028].


CONCLUSIONS
In human catecholamine-dependent septic shock, terlipressin (with and without concomitant dobutamine infusion) increases MAP and markedly reduces norepinephrine requirements. Although no adverse events were noticed in the present study, potential benefits of increasing Svo2 after terlipressin bolus infusion need to be weighted against the risk of cardiovascular complications resulting from high-dose dobutamine.
Morelli
A
A
Department of Anesthesiology and Intensive Care, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy.
Ertmer
C
C
Lange
M
M
Dünser
M
M
Rehberg
S
S
Van Aken
H
H
Pietropaoli
P
P
Westphal
M
M
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003422:Critical Care / Q000379:methods; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D010865:Pilot Projects; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D004280:Dobutamine; D008236:Lypressin; D000077585:Terlipressin; D010100:Oxygen; D009638:Norepinephrine