Effect of Phenobarbitone on Amplitude-Integrated Electroencephalography in Neonates with Hypoxic-Ischemic Encephalopathy during Hypothermia

<b><i>Background:</i></b> Phenobarbitone induces suppression of cerebral electrical activity on amplitude-integrated electroencephalography (aEEG) in neonates with hypoxic-ischemic encephalopathy (HIE); however, its effect during therapeutic hypothermia (TH) has not been well characterized. <b><i>Objective:</i></b> To evaluate the effect of phenobarbitone on aEEG in neonates with HIE undergoing TH. <b><i>Methods:</i></b> Thirty-five neonates born at ≥35⁰ weeks gestational age (GA), who received phenobarbitone as first-line antiepileptic drug during TH for ≥ Sarnat stage II HIE with aEEG recordings were retrospectively studied. Background pattern, upper and lower margin voltages were characterized for a 30-min period before and 30–60 min after phenobarbitone administration. Primary outcome was presence of severely abnormal aEEG pattern after phenobarbitone administration. <b><i>Results:</i></b> Mean (±SD) GA and median birth weight were 38.2 ± 1.9 weeks and 3.1 (2.5–3.9) kg, respectively. Phenobarbitone (10–20 mg/kg), administered at median age 16.8 h, was associated with background pattern worsening in 19/29 (65.5%) cases. Severe background patterns were more prevalent in post- versus pre-phenobarbitone tracings (21/29 [72%] vs. 11/29 [38%]; <i>p</i> = 0.01). Presence of severe pattern versus either continuous normal voltage or discontinuous normal voltage pattern post-phenobarbitone, (20/25 [80%] vs. 3/8 [38%]; <i>p</i> = 0.036) was associated with death or moderate-to-severe injury on MRI brain. Median time to trace recovery, when measurable, was 4 h (45 min–72 h). <b><i>Conclusions:</i></b> Phenobarbitone induces significant suppression on aEEG in infants with HIE undergoing TH. Development of severe aEEG background patterns after phenobarbitone may unmask a population at greater risk of abnormal outcome.

The Association of Orthostatic Hypotension with Ambulatory Blood Pressure Phenotypes in SPRINT

Background Clinic blood pressure (BP) when measured in the seated position, can miss meaningful BP phenotypes, including low ambulatory BP (white coat effects [WCE]) or high supine BP (nocturnal non-dipping). Orthostatic hypotension (OH) measured via both seated (or supine) and standing BP, could identify phenotypes poorly captured by seated clinic BP alone. Methods We examined the association of OH with WCE and night-to-daytime systolic BP (SBP) in a subpopulation of SPRINT, a randomized trial testing the effects of intensive or standard (&lt;120 versus &lt;140mmHg) SBP treatment strategies in adults at increased risk of cardiovascular disease. OH was assessed during follow-up (6, 12, 24 months) and defined as a decrease in mean seated SBP ≥20 or diastolic BP ≥10 mmHg after 1 min of standing. WCE, based on 24-hour ambulatory BP monitoring performed at 27 months, was defined as the difference between 27-month seated clinic and daytime ambulatory BP ≥20/≥10 mmHg. Reverse dipping was defined as a ratio of night-to-daytime SBP &gt;1. Results Of 897 adults (mean age 71.5±9.5 years, 29% female, 28% black), 128 had OH at least once. Among those with OH, 15% had WCE (versus 7% without OH). Moreover, 25% of those with OH demonstrated a non-dipping pattern (versus 14% without OH). OH was positively associated with both WCE (OR=2.24; 95% CI: 1.28,4.27) and reverse dipping (OR=2.29; 95% CI: 1.31, 3.99). Conclusions The identification of OH in clinic was associated with two BP phenotypes often missed with traditional seated BP assessments. Further studies on mechanisms of these relationships are needed.