Rosemarie C. Tan

Neonatal Drug Withdrawal

Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

Levels of Neonatal Care

Provision of risk-appropriate care for newborn infants and mothers was first proposed in 1976. This updated policy statement provides a review of data supporting evidence for a tiered provision of care and reaffirms the need for uniform, nationally applicable definitions and consistent standards of service for public health to improve neonatal outcomes. Facilities that provide hospital care for newborn infants should be classified on the basis of functional capabilities, and these facilities should be organized within a regionalized system of perinatal care.

Strategies for Prevention of Health Care-Associated Infections in the NICU

Health care–associated infections in the NICU result in increased morbidity and mortality, prolonged lengths of stay, and increased medical costs. Neonates are at high risk of acquiring health care–associated infections because of impaired host-defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of their skin, use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotic agents. This clinical report reviews management and prevention of health care–associated infections in newborn infants.

Respiratory support in preterm infants at birth.

Current practice guidelines recommend administration of surfactant at or soon after birth in preterm infants with respiratory distress syndrome. However, recent multicenter randomized controlled trials indicate that early use of continuous positive airway pressure with subsequent selective surfactant administration in extremely preterm infants results in lower rates of bronchopulmonary dysplasia/death when compared with treatment with prophylactic or early surfactant therapy. Continuous positive airway pressure started at or soon after birth with subsequent selective surfactant administration may be considered as an alternative to routine intubation with prophylactic or early surfactant administration in preterm infants.

Use of Inhaled Nitric Oxide in Preterm Infants

Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤34 weeks’ gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population.

Cellular mechanism of the functional refractory period in ventricular muscle

A premature action potential elicited in ventricular muscle during the functional refractory period of a preceding action potential requires an increased stimulus intensity for successful propagation. We measured the cellular basis for these relative decreases in tissue excitability during the recovery phase by performing parallel experiments on rabbit left papillary muscle and isolated rabbit ventricular cells in addition to conducting theoretical studies with numerical simulations of action potential initiation. For each experimental preparation, the pacing protocol consisted of a train of 10 stimuli (S1) at an S1-S1 interval of 500 msec with a premature stimulus (S2) of variable S1-S2 intervals following the tenth S1 action potential. The stimulus threshold for initiation of an S2 action potential (I2) was then measured as a function of the time of occurrence of the S2 stimulus relative to the time of 95% repolarization of the tenth S1 action potential (stimulus delay [SD] time). In the tissue preparation, the I2 increased sharply for SD times less than 0 msec to a value that was 100% above the S1 stimulus threshold for SD time = -5 +/- 2.4 msec (n = 8). Similar experiments on the isolated ventricular cell showed no increases in I2 as a function of SD time but rather significant decreases in both the action potential amplitude (APA) and the maximum rate of rise of the action potential upstroke (Vmax) of the S2 action potential. The APA and Vmax for the S2 action potential were decreased to 50% of the S1 action potential values for SD time = -5.2 +/- 2.1 msec and SD time = 0.3 +/- 1.6 msec, respectively (n = 8). Both parameters reached 100% recovery by SD time = 10 msec. These results and our numerical simulations are consistent with the hypothesis that the decreases in tissue excitability that occur with premature stimulation have a cellular mechanism as a result of a decrease in cellular responsiveness (APA, Vmax) rather than an intrinsic decrease in cellular excitability.

Developmental Changes in the Electrophysiologic Properties of Rabbit Papillary Muscles

ABSTRACT: We studied the electrophysiological properties of adult (AD) and newborn (NB) rabbit papillary muscles in vitro with superfusion of normal Tyrodes solution, solutions with elevated [K+]o, and in solutions with various concentrations of tetrodotoxin. In control solutions, the NB papillary muscles had a more negative resting membrane potential (−83.6 ± 1.2 versus−80.0 ± 1.5 mV), a higher rate of rise of phase 0 (134± 5 versus 120± 5 V/S) and a higher, longer-lasting action potential plateau than the AD papillary muscles. Exposure to elevated [K+]o led to a significant post-repolarization refractoriness in AD papillary muscles that was more than that for NB papillary muscles even when NB papillary muscles were depolarized to the same resting membrane potential as the AD papillary muscles. The NB papillary muscles were comparatively resistant to tetrodotoxin in terms of percent reduction of conduction velocity and percent rise in the current threshold for excitation. The conduction velocity for AD papillary muscles in control solution (66± 6 cm/s) was more than for NB papillary muscles (44 ±4 cm/s), which would not be expected from the data on the rate of rise of the action potential, suggesting that the cable properties of NB papillary muscles (specifically a greater surface to volume ratio of the ventricular cells) are also significantly different from the AD papillary muscles.

Modulation of the Purkinje-ventricular muscle junctional conduction by elevated potassium and hypoxia.

Action potential transmission in the canine ventricle normally occurs from the Purkinje (P) system into the ventricular muscle (VM) at specific P-VM junction sites. Transitional (T) cells are located between the Purkinje and the ventricular (V) cells at these P-VM junction sites. It has been shown that exposure to elevated [K+]0 in combination with hypoxia produces an increase in the P-VM conduction time. To examine this increase in P-VM conduction time, simultaneous measurements of the action potential upstrokes of T cells and the activation times of the local P and V cells at P-VM junctional sites were obtained from in vitro canine papillary muscles. The effects of elevated [K+]0 and hypoxia on conduction from P cells to T cells was then compared with the conduction from T cells to V cells to assess the relative contribution of each to the increase in the P-VM conduction time. We found that this intervention has approximately equal effects on the two sequential steps involved in P-VM conduction. We then analyzed the increased delay from T cells and V cells on the basis of three hypothetical mechanisms: 1) increased coupling resistance, 2) decreased V cell excitability, and 3) decreased cellular responsiveness of the T cells. Our results show that the effects of elevated [K+]0 and hypoxia on T-VM delay can be accounted for by a decreased responsiveness of the T cells without any significant electrical uncoupling between T and V cells or decrease in VM excitability.

EFFECTS OF INTERCELLULAR RESISTIVE COUPLING ON ACTION POTENTIAL INITIATION

The response of an isolated cell to an increased frequency of stimulation is strongly altered by the presence of a coupling resistance (R) to another cell. As the coupling R is gradually decreased, the stimulated cell becomes able to respond successfully to more rapid stimulation and then, at levels of coupling R which allow conduction between the two cells, the coupled pair of cells exhibit arrhythmic interactions not predicted by the intrinsic properties of either cell.