Effects of sodium bicarbonate correction of metabolic acidosis on regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: To determine the effects of sodium bicarbonate (NaHCO3) correction of metabolic acidosis on cardiopulmonary, laboratory, and cerebral, renal and splanchnic regional oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) in extremely premature neonates during the first postnatal week. STUDY DESIGN: Observational cohort data were collected from 500 to 1250 g neonates who received NaHCO3 'half' corrections (0.3 * Weight (kg) * Base Deficit (mmol l(-1))) for presumed renal losses. RESULT: Twelve subjects with normal blood pressure and heart rate received 17 NaHCO3 corrections. Mean (±s.d.) gestational age was 27±2 week and birth weight was 912±157 g. NaHCO3 corrections provided a mean (±s.d.) 4.5±1.0 ml kg(-1) fluid bolus, shifted mean (±s.d.) base deficit from 7.6±1.8 to 3.4±2.1 mmol l(-1) (P<0.05), and increased median (±s.d.) pH from 7.23±0.06 to 7.31±0.05 (P<0.05). No significant changes in blood pressure, pulse oximetry, PCO2, lactate, sodium, blood urea nitrogen, creatinine or hematocrit were observed. Cerebral, renal and splanchnic rSO2 (74%, 66% and 44%, respectively, at baseline) and FTOE (0.21, 0.29 and 0.52, respectively, at baseline) were unchanged following NaHCO3 correction. CONCLUSION: NaHCO3 infusions decreased base deficits and increased pH though produced no discernible effects or benefits on cardiopulmonary parameters including rSO2 and FTOE. These findings warrant further prospective evaluation in larger populations with more significant metabolic acidosis to determine the utility of tissue oxygenation monitoring in differentiating metabolic acidosis due to oxygen delivery/consumption imbalance versus renal bicarbonate losses.

Quiescent variability of cerebral, renal, and splanchnic regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: In extremely premature neonates, data concerning the normal baseline variability of near-infrared spectroscopy (NIRS)-derived regional oxygen saturation (rSO2) are lacking. We sought to determine: 1) the quiescent variability of cerebral, renal, and splanchnic rSO2 in clinically stable, undisturbed very low birth weight neonates and 2) the effects of different data averaging epochs on site-specific variability. STUDY DESIGN: In this prospective, observational study, neonates between 500 and 1250 g underwent seven days of continuous, real-time cerebral, renal, and splanchnic NIRS monitoring starting within the first seventy-two postnatal hours. Demographic, cardiopulmonary, bedside care, and rSO2 data were collected. rSO2 variability was analyzed utilizing data from quiescent periods identified using pre-specified stability criteria. Between- and within-monitoring site comparisons of data averaging methods were made utilizing ANOVA. RESULT: Twenty-four subjects (GA 27 ± 0.3 wk, birth weight 988 ± 34 g; mean ± SEM) were monitored. Coefficients of variation (CoVar = SD/mean) were calculated for each monitoring site using varied data averaging epochs. CoVar was lowest for cerebral, intermediate for renal, and highest for splanchnic rSO2 (P < 0.01). For renal and splanchnic sites, shorter epochs (5- and 15-min) resulted in significantly smaller CoVars [P < 0.01 and P < 0.05, respectively]. Splanchnic variability was highly dependent on epoch length, ranging from 16% over 5 min to 23% over 60 min. CONCLUSION: 1) rSO2 variability differs significantly between monitoring sites and 2) shorter data sampling epochs decrease rSO2 variability. These observations may assist clinicians in operationally defining minimally significant departures to enable medical decision making utilizing this monitoring technique.

Monitoring regional tissue oxygen extraction in neonates <1250 g helps identify transfusion thresholds independent of hematocrit.

OBJECTIVE: We sought to characterize the effects of "booster" packed red blood cell transfusions on multisite regional oxygen saturation in very low birth weight neonates during the first postnatal week and to examine the utility of fractional tissue oxygen extraction as an estimate of tissue oxygenation adequacy. STUDY DESIGN: Data were collected in an observational near-infrared spectroscopy (NIRS) pilot survey of 500-1250 g neonates during the first postnatal week. A before-after analysis of "booster" transfusions, defined as empiric 15 mL/kg transfusion following 10 mL/kg cumulative phlebotomy losses, was conducted upon cardiopulmonary, laboratory, and spectroscopy data. RESULT: Ten neonates (gestational age 26 ± 0 wk; birth weight 879 ± 49 g) received 14 transfusions at 3 ± 0 postnatal days. Mean hematocrit increased from 35.2 ± 1.2 to 38.5 ± 1.2 % (P < 0.05) following transfusion; pH, base deficit, lactate, creatinine, and cardiopulmonary parameters were unchanged. Cerebral, renal, and splanchnic tissue oxygenation increased 10, 18, and 16%, with concomitant decreases in calculated oxygen extraction of 27, 30, and 9% (all P < 0.05), consistent with enhanced tissue oxygenation. These findings were not observed in a non-transfused comparison group of nine patients. CONCLUSION: "Booster" transfusions improved indices of regional tissue oxygenation while no departures were observed in conventional cardiovascular assessments. We speculate that NIRS-derived oxygenation parameters can provide an objective, graded, and continuous estimate of oxygen delivery-consumption balance not evident using standard monitoring techniques.

Synthesis of a closed-loop combined plant and controller model.

In practice, a controlled system consists of two distinct entities: the plant and the controller. These two entities are coupled by a feedback mechanism to give the closed-loop behavior of the controlled system. Under this structure, the controlled behavior of the system can be analyzed by simulation which is costly and time consuming. In this study, we synthesize a combined plant and controller model. We consider the practical issues and propose a method which combines the advantages of Petri nets (PN) and the supervisory controller design based on Formal Language Theory. The resultant combined model is a PN and represents the controlled closed-loop behavior of the system. This model can be used for the functional and the performance analysis of the system, verification of the controller and the control code generation.

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes.

This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women.

Supervisory control of Petri nets using routing functions: starvation avoidance issues.

In this paper, we present a new point of view on supervisory control of Petri nets by using routing functions instead of the traditional control places. We first show the relation between the two notions. In the second part of the paper, we illustrate the use of routing functions by showing how to compute a routing function in order to avoid starvation in general Petri nets. This control uses a continuous version of the net and a description of the evolution of the net under the form of linear algebraic equations. As for the computational part, we use algebraic polynomial geometry in the continuous case and Diophantine equations for the discrete version of the Petri net under study.

Respiratory sinus arrhythmia during feeding: a measure of vagal regulation of metabolism, ingestion, and digestion in preterm infants.

Respiratory sinus arrhythmia (RSA), a non-invasive indicator of vagal regulation of the heart, and heart period (HP) were monitored before, during, and after oral or gastric-tube bolus feedings in 32 preterm infants. Group 1 infants (n=15) were < or =30 weeks gestational age (GA) at birth (mean 28.3 weeks) and group 2 infants (n=17) were > or =31 weeks GA at birth (mean=33.2 weeks). Mean postmenstrual ages at the time of study were 33.5 +/- 2.3 (SD) weeks in group 1 and 33.9 +/- 1.6 (SD) weeks in group 2. RSA and HP decreased in both groups during feeding. However, postfeeding RSA and HP increased toward prefeed levels only for group 2 infants. In addition, RSA and HP changes during feeding were correlated only for group 2 infants. The results suggest that the preterm infant may experience a maturational lag in vagal function and in the influence of vagal activity on metabolic mechanisms (i.e. heart rate) related to ingestive needs. This maturational lag may contribute to continued feeding difficulties and may be a measurable marker of subtle neurodevelopmental problems.

Effect of modulators of hypoxic pulmonary vasoconstriction on the response to inhaled nitric oxide in a neonatal model of severe pulmonary atelectasis.

Hypoxic pulmonary vasoconstriction (HPV) is an intrinsic mechanism that facilitates ventilation to perfusion matching and preservation of oxygenation. We investigated the neonatal HPV response from extensive atelectasis and tested the hypothesis that (I) the resulting hypoxemia is corrected by inhaled nitric oxide (NO); (2) the "pulmonary steal" of blood away from hypoxic area is further improved by modulators of the HPV. Intratracheal injection of steel beads in 32 piglets (7 to 20 days) resulted in atelectasis of 50% to 75% of the lungs. The piglets were then randomized to receive saline (control), indomethacin (IND) 2 mg/kg, doxapram (DOX) 0.5 mg/kg/h or almitrine (ALM) 4 micrograms/kg/min. After 30 minutes, all animals were subjected to NO at 40 ppm. Atelectasis resulted in severe impairment in oxygenation (PaO2 - 105 +/- 6 mm Hg, AaDO2 = 536 +/- 9 mm Hg; shunt fraction = 31% +/- 2%) and moderate pulmonary hypertension. Mean pulmonary artery pressure (PAP) increased to 35 +/- 0.8 mm Hg. NO reduced pulmonary vascular resistance (PVR) from 128 +/- 14 mm Hg/kg/mL/min to 74 +/- 9 mm Hg/kg/mL/min and improved gas exchange (PaO2 = 180 +/- 50 and AaDO2 = 438 +/- 50 mm Hg). Following the development of atelectasis, the peripheral chemoreceptor agonists (ALM and DOX) did not modify gas exchange and had no significant cardiovascular effect. ALM and DOX failed to enhance the response to NO. IND did not alter HPV, but prevented the improvement in gas exchange associated with NO-induced pulmonary vasodilation.

Patent ductus arteriosus increases lung fluid filtration in preterm lambs.

Previous studies showed that increased pulmonary blood flow from a patent ductus arteriosus had little or no effect on the amount of fluid in the lungs of mechanically ventilated preterm lambs. The purpose of this study was to examine the effect of a patent ductus arteriosus on lung vascular permeability and to see whether increased pulmonary lymph flow might compensate for the increased rate of fluid filtration. Using a model that allows mechanical control of ductus patency, we studied the effects of increased pulmonary blood flow on lung vascular pressures in six mechanically ventilated premature lambs at 136 +/- 2 d gestation (mean +/- SD) (term = 145 d). We measured lung lymph flow and protein concentrations in lymph and plasma to assess pulmonary vascular fluid filtration and protein permeability. We studied each lamb during sequential steady state periods, first with the ductus open and then with it closed. When the ductus was open, pulmonary blood flow was twice what it was when the ductus was closed. Mean pulmonary artery pressure and left ventricular end-diastolic pressure were greater with the ductus open [40 +/- 5 torr (5.3 +/- 0.7 kPa) and 8 +/- 3 torr (1.1 +/- 0.4 kPa), respectively] than when it was closed [24 +/- 3 torr (3.2 +/- 0.4 kPa) and 4 +/- 2 torr (0.5 +/- 0.3 kPa), respectively]. When the ductus was open, lymph flow was 68% greater and lymph protein concentration was 17% lower than when the ductus was closed. Lymph protein clearance (lymph flow x lymph protein concentration/plasma protein concentration) was 39% greater when the ductus was open.(ABSTRACT TRUNCATED AT 250 WORDS)

Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.

To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared by in situ cannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1-2, 7, and 18 mm Hg (0.13-0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined: 1) with ductus closed, 2) with ductus open, and 3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 mumol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism.

The effects of the patent ductus arteriosus on diaphragmatic blood flow and function.

Decreased diaphragmatic blood flow (Qdi) is associated with decreased contractility in adult animals. To see whether the decrease in Qdi associated with a patent ductus arteriosus was associated with a decrease in diaphragmatic contractility (Pdi), we prepared 11 near-term fetal lambs by infiltrating the ductus with formalin and placing a snare around it to regulate its patency. The lambs (with open chest) were delivered and mechanically ventilated, and the phrenic nerves and diaphragm were paced (using transvenous wires) at rates of 20/min, 60/min, and 100/min (Inspiratory time/total respiratory cycle time = 0.5) for 7-min contraction periods after 30-min recovery periods. Qdi was measured with radiolabeled microspheres at the end of each contraction period. Diaphragmatic performance was determined by comparing Pdi at the start (Pdi-start) and end (Pdi-end) of the contraction period. When the ductus was closed, Qdi increased 6.9-fold at 20/min and 9.8-fold at 100/min (compared with Qdi at rest). Pdi-end was less than Pdi-start at all contraction rates, but the reduction was significantly greater at 100/min (Pdi-end/Pdi-start: 0.80 +/- 0.10 at 20/min; 0.67 +/- 0.17 at 100/min). Pdi-start also decreased with increasing rates of contraction. When the ductus was open, the left-to-right shunt was 64 +/- 11% of left ventricular output. Qdi in the unpaced diaphragm was significantly reduced (open 4.0 +/- 3.8 versus closed, 7.4 +/- 2.4 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of methylprednisolone on hypoxic pulmonary vasoconstriction in the newborn late-gestation lamb.

Methylprednisolone (30 mg/kg), which inhibits a number of mediators of hypoxic pulmonary vasoconstriction derived from arachidonic acid, has been found to alleviate hypoxic pulmonary vasoconstriction in adult humans and in the isolated rat lung preparation. We studied the effect of 30 mg/kg of methylprednisolone on the pulmonary vascular response to hypoxia in six late-gestation newborn lambs. During hypoxia, pulmonary vascular resistance nearly doubled compared with the baseline hyperoxic state. This was true both before and after administration of methylprednisolone. We conclude that methylprednisolone, when administered at the dosage used in previous studies of adult humans and animals, does not affect the response of the pulmonary vascular bed to hypoxia in newborn lambs.

Effect of patent ductus arteriosus on water accumulation and protein permeability in the lungs of mechanically ventilated premature lambs.

To examine the effect of a patent ductus arteriosus on water accumulation and protein permeability in the premature, ventilated lung, we studied 16 lambs at 121-127 d gestation (term = 145 d). Water accumulation was assessed by the wet:dry wt ratio of the blood-free left lung. Protein permeability was assessed by the albumin content and by the recovery of 125I-albumin in the right lung lavage fluid 1 h after intravenous injection. Using a model that allows mechanical control of ductus patency, we compared nine lambs with patent ductus (left-to-right shunts 42 +/- 18% to left ventricular output) with seven lambs with closed ductus. The animals were studied over 3 h. In the open ductus lambs, 0.85 +/- 0.36 and 1.76 +/- 1.87%/h of the injected 125I-albumin was recovered in the lavage fluid and lung tissue, respectively. In the closed ductus lambs, the corresponding amounts were 0.71 +/- 0.21 and 0.71 +/- 0.22%/h; these differences were not statistically significant. Similarly, blood-free wet:dry ratios did not differ significantly between the two groups (7.01 +/- 1.28 open ductus versus 6.55 +/- 0.82 closed ductus). We concluded that patency of the ductus arteriosus does not significantly affect water accumulation and net protein transudation into the airways of preterm lambs in the first hours of life. Therefore, some other feature of immaturity must be responsible for the large protein leaks previously observed by others.

Congenital abnormalities of the aortic arch: MR imaging.

Thirty-four patients, 1 month to 63 years old, with known or suspected congenital abnormalities of the aortic arch underwent magnetic resonance (MR) imaging. Sixteen patients were studied retrospectively, 18 prospectively. In all retrospective studies, the aortic arch abnormality was seen with MR imaging. In the prospective studies, MR imaging enabled diagnosis in 15 of 18 (83%) patients. Twenty-nine of 34 patients underwent two-dimensional echocardiography; nine were studied retrospectively, 20 prospectively. In the prospective studies, echocardiography enabled diagnosis in 13 of 20 (65%) patients. Although two-dimensional echocardiography has a high sensitivity in the detection of aortic arch abnormalities in the neonate, arch abnormalities in the neonate, its sensitivity is lower in older children, adults, and postoperative patients. The authors' experience shows that MR imaging is an important, noninvasive modality in the evaluation of older children, adults, and postoperative patients with congenital aortic arch abnormalities.

The mean platelet volume (MPV) in the neonatal period.

Previous studies in adults have demonstrated that the mean platelet volume (MPV), which is now routinely measured during blood counting performed by the Coulter Counter S Plus, is an important parameter and may serve as a predictor of the hemostatic potential of patients with severe thrombocytopenia. MPVs and platelet counts were determined in 155 neonates in order to establish the normal values of the mean platelet volume during the neonatal period. Analysis of variance performed in 119 neonates of birthweight greater than 2 kg revealed a significant rise with age of both platelet count (P less than 0.0001 and MPV (P less than 0.02) during the neonatal period. The platelet counts of these 119 neonates (323336 +/- 106918; mean +/- SD) were significantly higher (P less than 0.05) than the platelet counts (283805 +/- 114130) of 36 neonates where birthweight was less than 2 kg. There was no significant difference between the MPV values of the two groups (8.67 +/- 1.03 micron3 and 8.89 +/- 1.10 micron3, respectively). Since increased MPV is observed during periods of platelet production, the above results suggest that the rise of platelet count associated with increased MPV in newborn infants is due to increased production of platelets in the early postnatal weeks.

Ruptured mitral chordae tendineae may be a frequent and insignificant complication in the mitral valve prolapse syndrome.

In this study, we performed 512 echocardiographic studies on 264 consecutive unselected patients with the idiopathic mitral valve prolapse syndrome. Twenty-eight patients (10.6%) had evidence of ruptured chordae tendineae of the mitral valve on M-mode examination and in 24 the diagnosis was confirmed by two-dimensional echocardiography. Mild to severe mitral insufficiency was proven in all of them by left ventriculography during cardiac catheterization. Eight patients underwent surgery to relieve symptomatic severe mitral regurgitation. At operation all had myxomatous degeneration of the mitral valve, two patients were found to have rupture of anterior mitral chordae, and six had rupture of posterior mitral chordae. Twenty (71%) patients with chordal rupture had either mild symptoms or were completely asymptomatic. It is concluded that chordal rupture in patients with the mitral valve prolapse syndrome may be present in asymptomatic patients and go undetected clinically in a substantial number of patients unless a high index of suspicion is maintained. Serial M-mode and two-dimensional echocardiographic studies are of importance in identifying the progression of prolapse findings and may reveal the natural history of this pathologic condition in asymptomatic patients.

False diagnosis of persistent fetal circulation caused by misplacement of umbilical artery catheter.

We have described two cases in which persistent fetal circulation was mistakenly diagnosed because umbilical artery catheters were placed in too high a position. In one case, repeated doses of tolazoline were given unnecessarily. While high placement of umbilical artery catheters is commonly accepted, misplacement may not always be apparent on routine AP chest films taken to confirm catheter positioning.

Percutaneous subclavian venous catheters in premature infants weighing less than 1500 gm.

Thirty-two percutaneous subclavian venous catheters were inserted in critically ill, low birthweight (less than 1500 gm) neonates. No complication occurred secondary to insertion. The total number of catheter-patient days was 754 days, with the average duration of a single catheter being 23.5 days. The incidence of primary catheter-related clinical sepsis was 3.1%. The safety and bedside feasibility of the procedure, as well as long catheter duration make it the best option for long-term venous access in this unique group of patients.

Meconium plugs and intussusception in a premature infant.

Neonatal intussusception in premature infants is uncommon and may mimic other abdominal disorders. We present a case of intussusception in a very low birthweight neonate. Presenting signs initially suggested necrotizing enterocolitis and meconium disease, and the diagnosis was confirmed at laparotomy.