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.

Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study.

A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea.

Heparinization of alimentation solutions administered through peripheral veins in premature infants: a controlled study.

A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.

Polymorphous ventricular tachycardia in acute myocardial infarction.

Polymorphous ventricular tachycardia (VT) is thought to be uncommon in acute coronary heart disease, but its prevalence has not been determined. Seven hundred seventy-one consecutive patients admitted with acute myocardial infarction (MI) were reviewed for the occurrence of this arrhythmia. Nine patients (1.2%) had polymorphous VT. No patient had any of the predisposing factors previously associated with polymorphous VT. The arrhythmia was resistant to multiple drugs, and repeated cardioversion was effective in only 3 patients. Overdrive pacing was ineffective in the 3 patients in whom it was attempted. Verapamil was effective in 3 of 4 patients in whom it was tried. Six patients with polymorphous VT died during hospitalization; the remaining 3 died within 6 months of discharge. It is concluded that, when compared with regular VT, polymorphous VT in MI carries a poor prognosis. When the arrhythmia occurs in the context of acute ischemia, it appears to be more difficult to treat compared with its occurrence due to other predisposing factors. Verapamil, not usually indicated for ventricular arrhythmias, should be tested in a therapeutic trial.

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.

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.

Regional distribution of the MB isoenzyme of creatine kinase in the human heart.

Human myocardial tissue obtained at autopsy from ten patients was examined for content of the MB isoenzyme of creatine kinase (CK-MB). We wished to determine whether this isoenzyme is distributed homogeneously throughout the heart. In eight cases, there was no history or pathological evidence of heart disease. Two had a history of previous myocardial infarction; in these, tissue was obtained from sites distant from the scar. Difference was found between the CK-MB content of the right atrium and the left atrium, and between the right ventricle and left ventricle. In all cases, the CK-MB content of the right side of the heart significantly exceeded that of the left side of the heart. Statistically significant differences were also found between the CK-MB content of the anterior interventricular septum and that of the posterior septum. These topographical variations in CK-MB content may be related to differences in the density of contractile elements in various parts of the heart and, moreover, are not taken into account in the enzymatic estimation of infarct size.

M-mode and two-dimensional contrast echocardiography in adult patients with atrial septal defects.

M-mode and two-dimensional echocardiographic studies, with and without contrast injection, were performed in 14 adult patients with clinical and radiological signs of atrial septal defects. Two-dimensional contrast echocardiography was found to be the most sensitive technique, allowing a definitive diagnosis to be made noninvasively in 12 patients (86%) of those patients studied. M-mode contrast echocardiography demonstrated an atrial shunt in 6 patients (43%). Regular two-dimensional echocardiography produced a high proportion of false-positive and false-negative results, while the findings on M-mode echocardiography are sensitive but nonspecific. All 14 patients described had the diagnosis confirmed on cardiac catheterization. Performance of the Valsalva maneuver during contrast echocardiography was found to be diagnostically unhelpful. The findings suggest that contrast echocardiography, particularly two-dimensional, is an effective, noninvasive diagnostic technique to be applied on clinical suspicion of atrial septal defects.

Complete atrioventricular block, shock, and hyperkalemia induced by toxic adenoma of the thyroid gland.

The case of a 74-year-old woman with toxic thyroid adenoma, presenting as complete heart block, is described. Upon admission the patient was in a state of circulatory collapse with metabolic acidosis and hyperkalemia. After initiation of right ventricular pacing the circulatory and metabolic disorders rapidly normalized without any other specific therapy. Since treatment and attainment of the euthyroid state the patient has had no conduction delays or arrhythmias. Complete heart block in thyrotoxicosis is uncommon and previous reports relate to its occurrence in Graves' disease, usually complicated by infectious disorders. This is the only case known to us of complete heart block in toxic thyroid adenoma.

Discrete membraneous sub-aortic stenosis in adult patient obtained by echocardiography and not proved by catheterization.

A case of a 60-year-old patient with discrete membranous sub-aortic stenosis is described. The diagnosis was established bases on echocardiographic evaluation by demonstration of a premature aortic valve closure and a sub-aortic membrane. No evidence of the sub-aortic membrane was noticed on cardiac catheterization. At operation, a discrete sub-aortic membrane was found 9 mm below the aortic valve, leaving an aperture of 1 cm diameter and a mildly deformed stenotic aortic valve. We stress the importance of careful pre-operative echocardiographic evaluation of every patient suspected of having any kind of left ventricular outflow tract obstruction, even if catheterization data are not contributory.

The efficacy of Ajmaline in ventricular arrhythmias after failure of lidocaine therapy in the acute phase of myocardial infarction.

Forty-three patients in the acute phase of myocardial infarction who were resistant to conventional doses of lidocaine received Ajmaline intravenously (50 mg bolus followed by constant infusion rate of 1-1.5 mg/min). Dangerous ventricular arrhythmias were abolished in 72% of this group of patients (group A). In the remaining patients (28%), Ajmaline was found to be ineffective (group B). There was no reduction of systolic or diastolic blood pressure and there was an insignificant increase in heart rate. Atrio-ventricular or intraventricular conduction defects appeared in 46% of the patients described. There was a statistically significant increase in occurrence of heart blocks in group B patients and among these complete left bundle branch block (CLBBB) was the most prevalent. Atrio-ventricular or intraventricular conduction defects were transient, appearing between 8-36 h (mean 23 h), and were not accompanied by reduction of ventricular rate. Conduction defects disappeared within several hours (up to 24 hours) after Ajmaline was discontinued. It is concluded that Ajmaline administered by this regimen is an effective alternative agent for patients with ventricular arrhythmia not controlled by lidocaine in the acute phase of myocardial infarction.

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.

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.

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.

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.

Endocardial fibrosis and hydrops fetalis in a premature infant.

We describe a premature neonate with endocardial fibrosis associated with hydrops fetalis. The infant did not have any other cardiac disorder and expired with congestive heart failure when five days old. Endocardial fibroelastosis has been previously described in neonates but is rare and is usually associated with other cardiac malformations. In only two previous reports was endocardial fibroelastosis associated with hydrops and in both of these cases there were also valvular deformities. We also discuss the possible significance of this association.