199 - The comparative effectiveness of norepinephrine and dopamine as first-line agents for the treatment of hypotension associated with sepsis in preterm infants

Poster Number: 199
Publication Number: 199.219

Sagee Nissimov, Mount Sinai Hospital, Toronto, Toronto, ON, Canada; Ashraf Kharrat, Mount Sinai Hospital, Toronto, ON, Canada; Gabriella Ripstein, Queen's University, Toronto, ON, Canada; Faith Zhu, Mount Sinai Hospital, Toronto, Toronto, ON, Canada; Sébastien Joye, CHUV, Mont sur rolle, Vaud, Switzerland; Julie Choudhury, Sunnybrook Health Sciences Centre, Scarborough, ON, Canada; Michelle Baczynski, Sinai Health System, Toronto, ON, Canada; Bonny Jasani, The Hospital for Sick Children, Toronto, ON, Canada; Poorva Deshpande, Mount Sinai Hospital, Mississauga, ON, Canada; Dany E. Weisz, University of Toronto, Toronto, ON, Canada; Amish Jain, University of Toronto/ Mount Sinai Hospital, Toronto, ON, Canada

Background: While in adults and children with fluid-unresponsive septic shock, guidelines recommend the use of norepinephrine (NE) over dopamine (DA), due to lack of comparative data, DA remains the commonest vasopressor agent used in hypotensive preterm infants in neonatal intensive care units (NICUs).

Objective: To compare clinical outcomes in association with the use of DA vs. NE as first-line agents for treatment of hypotension during acute illness in preterm infants.

Design/Methods: This retrospective cohort study, conducted at 2 tertiary perinatal NICUs in Toronto, from 2010 to 2019, included neonates < 35 weeks gestational age (GA), who received cardiotropic drugs for hypotension in relation to the following acute illnesses: culture positive sepsis, culture negative sepsis (antibiotics >5 days) or necrotizing enterocolitis (NEC) >stage 2a. Neonates who received DA or NE as first-line therapies were included for comparison, while those who received other agents first or had congenital/genetic anomalies were excluded. Data extracted included demographics, illness severity markers during 12 hours pre-treatment initiation and relevant outcomes, including episode-related ( < 7 days from treatment: mortality, use of additional agents, duration of inotrope use in survivors) and post-episode (new subsequent diagnosis of sepsis/NEC, pre-discharge mortality, prematurity-related morbidities in survivors). Regression analyses were conducted to evaluate outcomes with DA vs. NE, incorporating covariates associated with pre-discharge mortality on univariate analysis [p < 0.1; GA at birth and illness, maternal age, highest pre-treatment FiO2 and mean airway pressure (MAP), primary diagnosis sepsis vs. NEC]. 

Results: A total of 158 neonates were included for analysis; 113 received DA and 45 NE. Baseline characteristics were similar (Table 1). Pre-treatment, NE group had higher MAP, heart rate and FiO2 and DA group had a worse base deficit (Table 2). After adjustment for confounders, NE use was associated with lower episode-related mortality and lower odds of subsequent new diagnosis of NEC/sepsis in those who survived the acute episode (Table 3). Overall mortality was lower in NE group but difference was not statistically significant.   Conclusion(s): NE may be a more effective first-line agent for treatment of acute illness related hypotension in preterm neonates than DA.   
Table 1: Baseline demographic characteristics of preterm infants who received treatments with dopamine vs. norepinephrine as first-line agent for hypotension associated with sepsis or NEC.Data is presented as number (frequency), mean ± standard deviation or median (interquartile range), as appropriate. Data was available for all patients unless specified as denominator. NEC, necrotizing enterocolitis; PPROM, preterm prolonged rupture of membranes; SNAP-II, score for neonatal acute physiology; SIP, spontaneous intestinal perforation; IVH, intraventricular hemorrhage; PMA, post menstrual age. Intergroup comparisons performed using Chi-square or Fishers exact test for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables, as appropriate. NS = p ≥0.10.
Table 2: Comparison of baseline illness severity markers extracted from health records during the 12 hours prior to treatment initiation between preterm neonates receiving dopamine vs. norepinephrine as first-line agent for hypotension associated with sepsis or NEC.Data is presented as number (frequency) or mean ± standard deviation, as appropriate. Data was available for all patients unless specified as denominator. NEC, necrotizing enterocolitis; cmH2O, centimeters of water; bpm, beats per minute; mmHg, millimeters of mercury; FiO2, fractional inspired oxygen; PCO2, partial pressure of carbon dioxide on blood gas results; mmol/L, millimoles per litre. NS = p ≥0.10.