Study of Dopamine Versus Vasopressin for Treatment of Low Blood Pressure in Low Birth Weight Infants

Not Applicable

Completed

Conditions: Hypotension

Interventions: Drug: Arginine Vasopressin
Drug: Dopamine

Registration Number: NCT01318278

Lead Sponsor: Baylor College of Medicine

Brief Summary: Low blood pressure or hypotension is a very important problem that is often seen in premature babies, especially those with low birth weight. Severe hypotension leads to significant problems including brain bleeds, developmental delays, kidney and liver problems, and other issues that can affect babies for the rest of their lives. An important aspect in the management of infants with hypotension is the decision of when to treat and with what agent. Research is being conducted to try to find the best medication to use in these situations. Dopamine is often used first, but it does not always prove to be effective, and it has several concerning side effects. This study will look at vasopressin, which has fewer side effects, as a first-line medication for low blood pressure in extremely low birth weight infants.

Hypotheses and Specific Aims: This study will show superiority of vasopressin to dopamine in preterm, extremely low birth weight infants who have hypotension within the first 24 hours of life. We will specifically look at its ability to raise blood pressure values, improve clinical symptoms seen, any adverse effects, and clinical outcomes of babies being treated.

Detailed Description: Hypotension in the low birth weight (LBW) and extremely low birth weight (ELBW) infant is often encountered in the postnatal adaptation phase. Severe, prolonged hypotension contributes to cellular dysfunction and cell death. Systemic hypotension affects close to half of all ELBW infants and a significant portion of LBW infants. The true definition of hypotension remains to be a question. There is a linear association between birth weight, gestational age, and mean blood pressure but blood pressure can vary significantly in the first day of life. The critical period tends to be the first 24-36 hours of life as blood pressure tends to rise significantly in the first 72 hours of life regardless of gestational age. Preterm infants suffering from hypotension have a higher incidence and increased severity of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and long-term neurodevelopmental sequelae compared to normotensive preterm infants. Effects on other organ systems can result in renal injury, hepatic injury, and the development of necrotizing enterocolitis among other complications. An important aspect in the management of infants with hypotension is the decision of when to treat and with what agent. Dopamine is commonly used as first-line therapy, but issues with efficacy and its side effect profile have lessened its favorability over the years. Few studies compare dopamine to other agents as a first -line treatment. This study hopes to contribute to the literature information on vasopressin as a potential first-line agent for treatment of neonatal hypotension in low birth weight infants.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

Inclusion Criteria

Infants less than 24 hours of age
Infants with birth weight of <1001 grams and/or gestational age of <29 weeks
Not initiated on any continuous pressor therapy prior to enrollment
Intravenous line in place
Outborn infants meeting eligibility criteria

Exclusion Criteria

Infants not meeting eligibility criteria
Infants with life-threatening congenital defects
Infants with congenital hydrops
Infants with frank hypovolemia (perinatal history consistent with decreased circulating blood volume plus clinical signs of hypovolemia)
Infants with other unresolved causes of hypotension (air leaks, lung overdistention, or metabolic abnormalities).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vasopressin treatment	Arginine Vasopressin	Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr
Dopamine treatment	Dopamine	Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min

Primary Outcome Measures

Name	Time	Method
Number of Subjects in Each Group Who Have Achieved an Optimal Mean Blood Pressure Value at 24 Hours of Life	24 hours of life	Optimal mean blood pressure (OMBP) will be defined as either a 10% increase in mean blood pressure value or a 2-3 mmHg rise in mean blood pressure value AND an improvement in tissue perfusion as demonstrated by a resolution in the specified clinical symptom (designated upon enrollment) within 4-6 hours of having reached OMBP

Secondary Outcome Measures

Name	Time	Method
Acid-base Status	96 hours or until hypotension resolved and medication completely stopped
Hyponatremia	96 hours or until medication completely stopped
Urine Output	96 hours or until hypotension resolved and medication completely stopped
Evidence of Ischemic Changes	96 hours or until medication completely stopped	Physical examinations were done on at least a twice daily basis to evaluate for any ischemic lesions (especially on the limbs) of all subjects. The presence of any lesion considered to be due to ischemia would have been reported in this data.
Necrotizing Enterocolitis	until hospital discharge, up to 12 weeks
Ventilator Days	Until hospital discharge, up to 15 months
Presence of Patent Ductus Arteriosus (PDA)	until hospital discharge, up to 12 weeks
Grade 3 Intraventricular Hemorrhage or Worse on Head Ultrasound	Until hospital discharge, up to 15 months
Retinopathy of Prematurity Stage 3 or Higher	Until hospital discharge, up to 15 months	All subjects were followed by an ophthalmologist with initial exam at 4-6 weeks of age. The Stages describe the ophthalmoscopic findings at the junction between the vascularized and avascular retina. Each subject is followed until cleared by ophthalmology. For this outcome measure, the most severe stage of disease was used in analysis. Stage 1 is a faint demarcation line. Stage 2 is an elevated ridge. Stage 3 is extraretinal fibrovascular proliferation (neovascularization). Stage 4 is sub-total retinal detachment. Stage 5 is total retinal detachment. Stages 1 and 2 do not lead to blindness. However, they can progress to the more severe stages.
Presence of Bronchopulmonary Dysplasia (BPD)	36 weeks postmenstrual age	Infants were evaluated for oxygen need at 36 weeks postmenstrual age. If they required supplemental oxygen, they were diagnosed with BPD
Heart Rate Change From Baseline	96 hours or until hypotension completely resolved and medications stopped	Heart rate change from baseline during study drug administration
All Cause Mortality	admission to hospital discharge, up to 15 months