Search

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. Conclusion: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. What is Known: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. What is New: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the clinical and echocardiography modulators of treatment response in hypoxemic preterm infants exposed to inhaled nitric oxide (iNO).Methods: In this multicentre retrospective study, clinical parameters, including oxygenation, ventilation and haemodynamics, were collected for preterm infants <36 weeks gestation before and 2 h after initiation of iNO for acute hypoxemia. Comprehensive echocardiography, performed near the time iNO initiation, was analysed by experts blind to the clinical course. Multiple logistic regression analysis was used to identify factors associated with iNO response as defined by a reduction in the fraction of inspired oxygen by >0.20.Results: A total of 213 infants met eligibility criteria, of which 73 had echocardiography data available and formed the study cohort. Response to iNO was demonstrated in 56% of patients. Younger post-natal age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.89, 0.99) and the presence of pulmonary hypertension (PH) (OR 4.47; 95% CI 1.23-11.9) were independently predictive of iNO response regardless of gestational age. Among neonates <72 h old with documented PH, iNO response was seen in 82%. The onset of a new diagnosis of severe (grade III/IV) intraventricular haemorrhage (IVH) after iNO treatment was seen in 6 of 40 patients <28 weeks' gestational age, with a greater frequency in responders (32 vs. 0%, P = 0.02).Conclusions: Positive response to iNO is greatest in the first 3 days of life and in patients with echo-confirmed PH, independent of gestational age. The association between critical illness, iNO administration and IVH in extremely premature infants may merit prospective delineation. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.Results: Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87-1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1-2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8-4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.Conclusions: Advanced gestational age was the predictor of non-response to SCI in preterm neonates. [ABSTRACT FROM AUTHOR]

Objective: To describe short-term and long-term outcomes of preterm neonates with severe acute pulmonary hypertension (aPHT) in relation to response to rescue inhaled nitric oxide (iNO) therapy.Design: Retrospective cohort studyover a 6 year period.Setting: Tertiary neonatal intensive care unit.Patients: 89 neonates <35 weeks gestational age (GA) who received rescue iNO for aPHT, including 62 treated at ≤3 days of age (early aPHT).Interventions: iNO ≥ 1 hour.Main Outcome Measures: Positive responders (reduction in fraction of inspired oxygen (FiO2) ≥0.20 within 1 hour of iNO) were compared with non-responders. Primary outcome was survival without moderate-to-severe disability at 18 months of age.Results: Mean (SD) GA and birth weight was 27.7 (3.0) weeks and 1077 (473) gm, respectively. Median (IQR) pre-iNO FiO2 was 1.0 (1.0, 1.0). Positive response rate to iNO was 46%. Responders showed improved survival without disability (51% vs 15%; p<0.01), lower mortality (34% vs 71%; p<0.01) and disability among survivors (17% vs 50%; p=0.06). Higher GA (adjusted OR: 1.44 (95% CI 1.10 to 1.89)), aPHT in context of preterm prolonged rupture of membranes (6.26 (95% CI 1.44 to 27.20)) and positive response to rescue iNO (5.81 (95% CI 1.29 to, 26.18)) were independently associated with the primary outcome. Compared with late cases (>3 days of age), early aPHT had a higher response rate to iNO (61% vs 11%; p<0.01) and lower mortality (43% vs 78%; p<0.01).Conclusion: A positive response to rescue iNO in preterm infants with aPHT is associated with survival benefit, which is not offset by long-term disability. [ABSTRACT FROM AUTHOR]

Objective This study aimed to compare the outcomes for symmetrical (sSGA) versus asymmetrical (aSGA) small for gestational age (SGA) < 32 weeks preterm infants. Study Design A total of 12,179 eligible infants admitted to the Canadian tertiary neonatal intensive care units (NICUs) over a 7-year-period in the Canadian Neonatal Network database were subcategorized as aSGA (n = 536), sSGA (n = 732), or appropriate for GA (AGA, n = 10,911). Baseline demographics, mortality, and major morbidities were compared using multivariable analysis to calculate adjusted odds ratios (AOR) and 95% confidence interval (CI). Results sSGA had higher GA (p < 0.01) and more antenatal tobacco exposure (p ¼ 0.03). Although both the SGA groups had worse outcomes than AGA controls, aSGA versus sSGA comparison revealed lower odds (AOR [CI]) for mortality and chronic lung disease (CLD) for aSGA in the entire cohort (0.45 [0.27, 0.75] and 0.61 [0.44, 0.84], respectively) as well as for infants < 28 weeks GA (0.50 [0.27, 0.92] and 0.47 [0.29, 0.77], respectively). aSGA infants < 28 weeks GA had comparable outcomes to AGA except higher odds for CLD (1.61 [1.13, 2.27]). sSGA infants needed longer hospital stay and had higher use of oxygen and continuous positive airway pressure than aSGA. Conclusion Among SGA infants < 32 weeks GA, significant intragroup differences exist in the neonatal outcomes and hospital resource utilization depending upon the presence or absence of relative “head sparing.” [ABSTRACT FROM AUTHOR]

Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤ 72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41 ± 7 vs. 47 ± 9 mmHg, p = 0.02) and higher shock index (4.02 ± 0.80 vs. 3.44 ± 0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32–0.77). The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants. • Right ventricular dysfunction (RVd) is difficult to detect clinically in preterms. • Study supports use of timely echocardiography in preterm pulmonary hypertension. • Qualitative RVd diagnosis may be valid but is only moderately reliable in preterms. • Qualitative method may over-diagnose RVd in preterm pulmonary hypertension. • Normative dataset of quantitative echocardiography measures in preterms is needed. [ABSTRACT FROM AUTHOR]

To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH). A systematic review and meta-analysis of observational studies was conducted to examine the association between immediate response (improved oxygenation ≤6 h) compared to non-response, and all-cause mortality among preterm infants <34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 h after birth. The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95 % confidence interval (95 % CI) (0.10–0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 h demonstrated consistent findings of reduced mortality [OR 0.21 95 % CI (0.13–0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate. There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH. • There is paucity of trials of inhaled nitric oxide in preterm infants with pulmonary hypertension. • Experts support iNO for hypoxemic respiratory failure when pulmonary hypertension is confirmed. • Immediate oxygenation improvement following iNO is associated reduced pre-discharge mortality. [ABSTRACT FROM AUTHOR]

Background: Vasoactive-Inotropic Score (VIS) is a weighted sum of various vasopressors and inotropes; its utility among preterm neonates is understudied.Objective: To investigate the association between maximum VIS (VISmax) during the first 12, 24 and 48 h of treatment among preterm neonates who received vasopressors/inotropes, and the composite outcome of death/severe neuroinjury (sNI).Methods: Retrospective cohort study, over 6-years, including neonates <35 weeks gestational age (GA). Infants who met the primary composite outcome of death or sNI (defined as new intraventricular hemorrhage ≥grade 3 or periventricular leukomalacia) were compared to those who survived without sNI. Maximum VIS was categorized as <10, 10-19 or ≥ 20 for comparison.Results: 192 infants (mean GA and birth weight 26.8 ± 3.3 weeks and 952 ± 528 g, respectively) were included. The most common primary diagnosis was sepsis/necrotizing enterocolitis (69 %). Median VIS for the entire cohort was 10. Death/sNI was associated with lower GA at birth and treatment, as well as higher frequency of VISmax of 10-19 or ≥20, compared to <10, during each time period (all p < 0.01). Multivariable regression revealed GA at treatment and VISmax ≥ 20 [not 10-19, referenced to <10] were associated death/sNI; adjusted odds ratio (95 % CI) for VISmax ≥ 20 within 12, 24, and 48 h were 4.2 (1.6-11.0), 4.9 (1.9-12.3), and 6.7 (2.7-16.7), respectively.Conclusions: Vasoactive-Inotropic Score may be a valid measure to quantify cardiovascular support in preterm infants needing hemodynamic support. Maximum VIS ≥20 within 48 h of treatment initiation may identify patients at high risk of adverse outcomes. [ABSTRACT FROM AUTHOR]