• 
• 

Three Part Question

In [very low birth weight infants] does [administering intravenous adrenaline][increase systemic blood pressure]?

Clinical Scenario

A 475g baby girl born at 24 weeks and 2 days gestation by emergency cesarean section following maternal pre-eclampsia, develops hypotension in the first 48 hours of life. She is given inotropic support with dopamine, dobutamine and adrenaline.

Search Strategy

'Dialog Data Star' was used to search Medline and Embase (1996 onwards).
Search terms used were [very low birth weight infant]AND [hypotension] AND [adrenaline] OR [epinephrine]
Search date 04/01/2006

Search Outcome

This produced 25 hits of which only one matched the criteria (see table 1).
By searching secondary sources (a reference in published review) one RCT was found.
Studies were excluded if they were not randomised controlled trials, the study group did not include very low birth weight infants and hypotension was not treated with adrenaline. One retrospective case study by Heckmann et al (1) was excluded because of poor quality.
Characteristics of included studies are listed in table 1.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Pellicer A 2005 Spain	60 infants <1501g birth weight, <32 weeks gestational age and <24 hours post natal age who experienced hypotension (mean blood pressure	Comparative prospective cohort. Randomized by number tables stratified for gestational age. CEBM level of evidence: 1b	Increase in systemic BP	Dopamine: 19/28 infants, Adrenaline: 20/32 infants, P¡Ü0.001	Power calculation included from pilot study in the trial.
			Increase in CBF	Mean increase in CBF of 0.70mL/100g
			Cerebral ultrasound outcome data	26 infants with normal ultrasound, no difference between groups
Campbell ME 2004 United Kingdom	91 infants <750g birth weight admitted to NICU between 1990-1994. 47 infants received continuous adrenaline infusion. 15 received cardiopulmonary resuscitation.	Retrospective study of patient case notes. CEBM level of evidence: 2c	Survival rate to discharge	Lower in group who received adrenaline: 10/47 compared to group who did not: 25/44 (P=0.0006)
			Neurological outcome (MDI <70).	4/10 in adrenaline group. 14/24 in non-adrenaline group.

Comment(s)

The study by Pellicer et al (2) is the only randomised study to address the effect of intravenous adrenaline infusion compared to dopamine on systemic blood pressure in hypotensive very low birth weight infants. Low dose intravenous infusion of adrenaline was as effective as low/medium dose dopamine at increasing systemic blood pressure and cerebral blood flow. Limitations of the study were that it did not measure the effect of the inotropes on systemic blood flow. The data from the pilot study used for power calculation was also included in the final results. Campbell and Byrne (3) conducted a retrospective case study on extremely low birth weight infants and found adrenaline to be associated with a 78% mortality rate.

Clinical Bottom Line

1. Adrenaline appears to be as effective at increasing systemic blood pressure when compared to dopamine in hypotensive VLBW infants. (Grade B, evidence category 1b) 2. More research is required on the efficacy, safety and long term outcome in VLBW infants treated with adrenaline to provide good evidence based care in this population.

References

1. 1. Heckmann M, Trotter A, Pohlandt F et al Epinephrine treatment of hypotension in very low birth weight infants. Acta Paediatr 2002;91:566-70
2. 2. Pellicer A, Valverde E, Elzora MD et al Cardiovascular support for low birth weight infants and cerebral hemodynamics: Pediatrics 2005; 115: 1501-12
3. 3. Campbell ME, Byrne PJ. Cardiopulmonary resuscitation and epinephrine infusion in extremely low birth weight infants in the neonatal intensive care unit. J Perinatol 2004;24:691-5.