Niranjan “Tex” Kissoon, MD, FRCP(C), FAAP, FCCM, FACPE Vice President, Medical Affairs, BC Children’s Hospital and Sunny Hill Health Centre Professor, BCCH and UBC Global Child Health Department of Paediatrics and Emergency Medicine University of British Columbia Senior Scientist, Child and Family Research Institute
Vasoactive Drugs in Shock
Uses and Limitations
Vasoactive Drugs in Shock
• Rationale and Pathophysiology • When should they be used • What are the choices?
– Vasopressors? – Inotropes? – Vasodilators?
• Conclusion
Macrocirculation Increased vascular permeability Myocardial dysfunction Vasodilatation Hypovolemia
PATHOPHYSIOLOGY
Landry DW N. Engl J Med 2001; 45:588-595 Annane A. Lancet. 2005;365:63-78
Microcirculation
The Hemodynamic Goal
Vasoactive Drugs in Shock
• Rationale and Pathophysiology • When should they be used? • What are the choices?
– Vasopressors? – Inotropes? – Vasodilators?
• Conclusion
MANAGEMENT FAILURES
VARIABLE CASES (%) Controls (%) Odds ratio (95% CI)
P value
Too little fluid vs adequate fluid therapy*
32/131† (24) 27/246† (11) 2.5(1.4 to4.7) 0.004
Inadequate inotropes ‡ 54/122 § (44) 13/91§ (14) 5.8 (2.3 to14) <0.001
*Biviarate analysis controlled for needing fluid † Denominator is number needing fluid
‡ Bivariate analysis controlled for needing inotropes § Denominator is number needing inotropes
Nims, et al. BMJ. 2005
When ?
• When an appropriate fluid challenge fails
to restore adequate circulation, therapy
with inotropes and vasopressor agents
should be started.
Vasoactive Drugs in Shock
• Rationale and Pathophysiology • When should they be used? • What are the choices?
– Vasopressors? – Inotropes? – Vasodilators?
• Conclusion
Children have Progressive Myocardial not Vascular dysfunction
05
1015202530354045
Day 1 Day 3
InotropeVasodilatorVasopressor
(Ceneviva G et al Pediatrics 1998)
VIS and Mortality in Septic Shock
Haque A et al Indian Pediatrics 2015;52:311 (Pakistan)
Mortality 42 (59.2%); 23 (38.9%) and 19 (100%) children expired from Group-L and Group-H
Vasopressors for Hypotensive Shock
Gamper G, et al Cochrane Database of Systematic Reviews 2016;2. Art. No.: CD003709. DOI: 10.1002/14651858.CD003709.pub4.
• No difference in total mortality between several vasopressors.
• Dopamine increases the risk of arrhythmia vs. norepinephrine
• No other differences between any of the six vasopressors • Treatment goals most often employed are of limited
clinical value.
• Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.
Dopamine Versus Epinephrine in Septic Shock
Ventura AMC et al Crit Care Med 2015;43:2292–2302
Dopamine Versus Epinephrine in Septic Shock
Ventura AMC et al Crit Care Med 2015;43:2292–2302
Baseline characteristics and therapeutic were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p = 0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1–37.8; p = 0.037) and healthcare–associated infection (odds ratio, 67.7; 95% CI, 5.0–910.8; p = 0.001). The use of epinephrine was associated with a survival odds ratio of 6.49.
Dopamine Versus Epinephrine in Septic Shock
Ventura AMC et al Crit Care Med 2015;43:2292–2302
Ramaswamy K et al PCCM 2016; 17:e502–e512
Dopamine vs. Epinephrine in Refractory SS
Dopamine vs. Epinephrine in Refractory SS
Ramaswamy K et al PCCM 2016; 17:e502–e512
November 2016
Treatment protocol for Limited Fluid and Early Norepinephrine cohort using Multimodal Monitoring
PICC Toronto 2016 20
Variables Early NE group
(n= 27)
ACCM cohort (n=41)
P Value
Weight (kg) 24.3 + 19.04 21.1 + 12.7 0.856 PRISM 19.9 + 7.8 16.02 + 8.4 0.06
Number with hypotensive shock
19 (70.4%) 20 (48%) 0.09
Shock resolution 26 39 1.00 Mortality 3(11.1%) 4 (9.8%) 1.00
21
Results: Early NE group vs ACCM Group
0-6 hour fluid requirement (mL/kg)
37.4 + 15.1 88.9 + 31.3 0.0001*
Days on invasive ventilation (median)
1(1-1.7) 4(2.5-5.25) 0.0001*
PICU days (median)
4(3-6) 6 (4-8) 0.002*
Conclusion
• Rationale for use is based on pathophysiology
• Should be used as soon as necessary
• What should be used depends on experience and understanding of choices