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