Epidemiology and ethics in the neonatal intensive care unit.

There are many ethical dilemmas in the neonatal intensive care unit (NICU), and almost as many solutions as dilemmas. Religion, philosophy, natural law, civil law, criminal law, to name but a few, have each been invoked as a source of authority to resolve the inevitable conflicts arising at the confluence of uncertain outcome, physical pain, and financial expenditure. This article takes a different approach. Here we begin by envisioning what we would most like to know about NICU care that we do not currently know (or at least is not widely known), and then combine "thought experiments" with preliminary "real experiments" to acquire a hypothetical database from which ethics in the NICU can be informed.

Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets.

We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment. Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2 (PaCO2) approximately 40 torr). CBF was assessed by internal carotid artery blood flow (ICBF). Group 1 (n = 5) received a continuous infusion of STREP for 4 h (2.0-8.0 x 10(7) org/kg-min). Group 2 (n = 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion. Group 3 (n = 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter. Cerebral vascular reactivity to acute hypercarbia (PaCO2 approximately 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation. We found that 4 h of STREP infusion caused CO to fall significantly (634 +/- 121 to 324 +/- 172 mL/min, group 1; 600 +/- 68 to 291 +/- 80 mL/min, group 2) and BP to fall significantly (104 +/- 20 to 57 +/- 4 mm Hg, group 1; 91 +/- 11 to 53 +/- 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 +/- 181 to 375 +/- 159 mL/min) and BP (104 +/- 14 to 60 +/- 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2. At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 +/- 10.8 to 21.0 +/- 7.3 mL/min) and group 2 (22.9 +/- 9.9 to 13.1 +/- 4.3 mL/min), but not in nonseptic group 3 (23.1 +/- 7.4 to 19.6 +/- 6.3 mL/min). At baseline, hypercarbia induced an increase in ICBF (% delta ICBF = 68.7 +/- 13.0% in group 1, 62.2 +/- 15.6% in group 2, and 87.7 +/- 34.0% in group 3). After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 +/- 23.2% (group 1). Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as % delta ICBF fell during hypercarbia by -10.9 +/- 17.7% (group 2). In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8 +/- 23.2%, not significantly different from baseline, but significantly different from the decrease in % delta ICBF in groups 1 and 2. We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets. This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids.

Pediatric critical care physicians' attitudes about guidelines for the use of ribavirin in critically ill children with respiratory syncytial virus pneumonia.

OBJECTIVE: To determine the attitude of pediatric critical care physicians concerning the use of ribavirin in children with respiratory syncytial virus lung disease in light of the revised American Academy of Pediatrics practice guidelines. DESIGN: A questionnaire was sent to 145 pediatric critical care doctors in the United States. MEASUREMENTS AND MAIN RESULTS: Seventy-seven percent of questionnaires were returned. The vast majority (91%) of the respondents think that the available literature does not support the Academy's recommendations for the administration of ribavirin to critically ill children with respiratory syncytial virus pneumonia. The largest single group of respondents (42%) does not usually prescribe ribavirin for these patients, but may be persuaded to use it by colleagues or consultants in individual cases. Twenty-six percent of all respondents stated that they do not use ribavirin at any time, even in severely ill patients with documented infection. Twenty-two percent of the respondents say that they will prescribe ribavirin, not because they believe it is efficacious, but because they believe the Academy guidelines compel them to do so as a standard of care. The respondents reported adverse effects of the drug, most notably exacerbations of bronchospasm (92%), far more often than the Academy document asserts. When solicited for general comments, the respondents were frequently concerned that critical care physicians were not involved in the development of the guidelines, the guidelines were based on a paucity of reliable data, and that the guidelines could put them at risk of malpractice litigation should they choose to not use ribavirin. CONCLUSIONS: Practice guidelines are increasingly being incorporated into patient care and quality improvement regimens, and it is imperative both that appropriate experts be included in their development, and that they be based on valid scientific data. The pediatric critical care community currently treats most of the severely ill patients with respiratory syncytial virus pneumonia. As a group, they remain unconvinced about the efficacy and safety of this drug, and many pediatricians are concerned about the ramifications of individualizing ribavirin therapy in their patients in light of the revised Academy recommendations.

Ought 'standard care' be the 'standard of care'? A study of the time to administration of antibiotics in children with meningitis.

OBJECTIVE: To determine the time from triage in an emergency department until administration of parenteral antibiotics in children with bacterial meningitis. RESEARCH DESIGN: Retrospective review of medical records and survey of medical subspecialists in infectious diseases and emergency medicine. SETTING: Emergency departments of two university-affiliated pediatric hospitals. PARTICIPANTS: All children with bacterial meningitis identified in medical records from 1987 to 1989 (N = 93). MEASUREMENTS: For each child, the time from presentation to the emergency department until administration of antibiotics (AB time) was determined; when possible, time from triage to contact with a physician, from triage to lumbar puncture, and from lumbar puncture to administration of antibiotics was measured. We then surveyed specialists in both pediatric infectious diseases (n = 23) and pediatric emergency medicine (n = 54) as to their beliefs about AB time in children with meningitis. STATISTICAL ANALYSES: Mann-Whitney Rank Sum Test and Kruskal-Wallis Test. RESULTS: Median AB time was 2.0 hours (interquartile range, 1.25 to 3.33 hours). Only one (1%) of 93 children received antibiotics within 30 minutes of presentation. Median time from triage until contact with a physician was 0.45 hour. Median time from lumbar puncture until antibiotics administration was about 0.5 hour. The estimates of median AB time differed significantly between emergency medicine (0.93 hour) and infectious disease (1.45 hours) experts, and estimates from both differed significantly from the median AB time (2.0 hours) actually observed. CONCLUSIONS: These data reveal that the usual and customary practice (ie, standard medical care) by qualified physicians may differ from opinions of standard medical care promulgated by medical experts. Even among experts there is a wide range of (mistaken) opinions about standard medical care. Insofar as jurors in medical malpractice cases are instructed to consider what physicians "ordinarily do in similar circumstances," a data-based definition of "standard" medical care should supplant anecdotal testimony by individual expert witnesses.

Relationship between oxygen delivery and metabolic acidosis during sepsis in piglets.

OBJECTIVE: To determine if the preservation of oxygen delivery (DO2) ameliorates the development of metabolic acidosis during group B streptococcal infusion. METHODS: We examined 22 piglets (2 to 4 wks of age) that were anesthetized, intubated, and mechanically ventilated. Three groups of piglets were studied: group 1 (n = 6), in which DO2 was reduced progressively over 4 hrs by infusion of group B streptococci; group 2 piglets (n = 6) received a similar infusion of streptococci, but DO2 was preserved at presepsis levels by the infusion of dextran and exogenous porcine RBCs; group 3 piglets (n = 6) received no bacteria, but did receive a continuous infusion of 0.9% sodium chloride to maintain cardiac output, and thus, DO2, at baseline levels. To correlate arterial lactate concentrations with metabolic acidosis, four additional piglets received the continuous infusion of streptococci. RESULTS: DO2 decreased significantly in group 1 (14.2 to 5.7 mL oxygen/kg/min) but not in either group 2 or 3. The arterial pH decreased significantly in both septic groups, groups 1 and 2 (7.47 to 7.20; 7.45 to 7.36, respectively), but not in the uninfected group 3. The pH was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Base excess decreased significantly for group 1 and group 2 piglets (+1.5 to -13.9; -0.1 to -5.8 mM/L, respectively) but not in group 3. Base excess was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Oxygen extraction increased significantly for only the low DO2 group 1 piglets (32% to 73%), and did not differ comparing group 2 vs. group 3. In both groups of septic piglets, metabolic acidosis developed before any detectable reduction in oxygen consumption. The increase in circulating lactate concentration (1.0 to 4.6 mM/L) was correlated with the decrease in base excess (-1.0 to -9.7 mM/L) in the four additional piglets that received an infusion of streptococci. CONCLUSIONS: Maintaining DO2 at presepsis levels ameliorated the development of metabolic acidosis during streptococcal infusion. Nevertheless, a significant degree of metabolic acidosis developed despite the preservation of DO2.

Internal jugular venous oxygen saturation does not reflect sagittal sinus oxygen saturation in piglets.

Can blood samples from the internal jugular vein (IJ) be used reliably in place of sagittal sinus (SS) samples in the calculation of cerebral oxygen extraction? To test this question we compared the O2 saturation (Sat) of blood samples drawn from SS, IJ vein, and pulmonary artery (MV) during hypercarbia, eucarbia and hypocarbia in 7 paralyzed, ventilated piglets. Cerebral blood flow was assessed by measuring unilateral internal carotic artery blood flow (ICABF), determined by an electromagnetic flow probe placed around the common carotid artery after ligation of the external carotid artery. During hypocarbia, eucarbia and hypercarbia SatSS (37.3 +/- 9.3, 48.9 +/- 10.2, 70.8 +/- 11.8%, respectively) was significantly different from SatIJ (54.8 +/- 8.9, 54.5 +/- 9.0, 62.0 +/- 15.1%) and SatMV (55.9 +/- 5.5, 58.7 +/- 5.3, 53.5 +/- 11.2%). The mean slope of the SatSS vs. PaCO2 regression lines was +0.583 +/- 0.303%/mm Hg, significantly greater than the mean slope of the regression lines for SatIJ vs. PaCO2 (+0.087 +/- 0.310%/mm Hg) or SatMV vs. PaCO2 (-0.112 +/- 0.230%/mm Hg). The relationship of ICABF vs. PaCO2 (mean slope = 0.444 +/- 0.294 ml/min/mm Hg) was statistically significant, while the relationship of cardiac output (determined by an electromagnetic flow probe placed around the pulmonary artery) vs. PaCO2 (mean slope = 0.470 +/- 1.617 ml/min/mm Hg) was not. We conclude that blood samples from the IJ do not reliably reflect cerebral venous blood and cannot be substituted for SS samples in piglets. It is most probable that the substitution of IJ for SS blood is not valid in piglets because the IJ receives venous effluent from noncerebral tissue.

Effects of dextran infusion on cardiac output, oxygen delivery, and oxygen utilization in piglets during the first month of life.

We determined the effects of volume infusion on cardiac output, oxygen delivery (Do2), oxygen consumption (Vo2), and oxygen extraction (O2 extr) in piglets at ages 5 to 14 days and 3 to 5 wk. Eighteen piglets were anesthetized, intubated, and mechanically ventilated. Six piglets (5 to 14 days old) and six piglets (3 to 5 wk old) received iv dextran (MW 70,000 daltons; 30 to 40 ml/kg) sufficient to raise mean left atrial pressure (LAP) from approximately 4 to 15 mm Hg over 30 min. Six piglets received 0.9% NaCl at 4 ml/kg.h to maintain LAP constant at 4 mm Hg over a 30-min period. All piglets receiving dextran had increased cardiac output (mean elevation 39 +/- 16 [SD]%; range +19% to +73%; p less than .005). This response was mediated entirely by an elevation in stroke volume, as heart rate did not change significantly. However, all piglets receiving dextran reduced Hgb concentration (10.1 +/- 1.5 to 7.5 +/- 1.4 g/dl, p less than .001), a decrease which completely offset the increase in cardiac output. Consequently, Do2 did not increase after dextran infusion (17.4 +/- 1.8 to 18.4 +/- 2.8 ml/min.kg). Neither Vo2 nor O2 extr changed significantly after dextran. No differences were noted in the response to dextran infusion comparing 5 to 14-day-old piglets with 3 to 5-wk-old piglets. Unlike fetal lambs, newborn piglets are able to elevate cardiac output significantly in response to volume loading. However, if these data can be extrapolated to human infants, volume infusion without concurrent blood transfusion is likely to increase systemic cardiac output but not improve Do2.

Metoclopramide promotes enteral feeding in preterm infants with feeding intolerance.

We hypothesized that the feeding difficulties experienced by premature infants are related to immature peristaltic activity and that a bowel accelerant might promote feeding in prematures. We administered metoclopramide (Meto) to 14 infants admitted to the Intensive Care Nursery at The University of Chicago between January 1, 1984, and January 1, 1987. Each infant had failed enteral feeding on at least two separate occasions. At the time of initiation of Meto, the group of infants tolerated only 11.7 +/- (SEM) 3.6 cm3/kg/day enterally. Feeding tolerance improved steadily after Meto was initiated, and by 29 days the infants tolerated 134 +/- 12.6 cm3/kg/day enterally. The average slope of the post-Meto feeding regression lines was +4.21 +/- 0.94 cm3/kg/day/day, significantly greater than -0.67 +/- 0.59 cm3/kg/day/day pre-Meto. The percentage of feedings followed by significant gastric residual volumes was 33.1 +/- 4.6% pre-Meto, compared to 6.9 +/- 2.5% post-Meto. No child receiving Meto developed any extrapyramidal neurologic symptoms, worsening of hepatic function, or necrotizing enterocolitis. Meto may have a role in the treatment of premature infants with enteral feeding intolerance.

Neither nitroglycerin nor nitroprusside selectively reduces sepsis-induced pulmonary hypertension in piglets.

No therapeutic agent consistently decreases pulmonary arterial pressure (PAP) more than aortic pressure in neonates with persistent pulmonary hypertension of the newborn. We have investigated whether nitroglycerin (NG) or nitroprusside (NP) selectively decreases PAP in an animal model of sepsis-induced pulmonary hypertension. Piglets were anesthetized, intubated, and ventilated. Pulmonary hypertension was induced by an iv infusion of group B Streptococci. Piglets were then divided into three groups with group B Streptococci infusion ongoing. Neither PAP nor the pulmonary vascular resistance index was decreased significantly by either NP or NG. NP decreased significantly both mean aortic pressure and the systemic vascular resistance index. Cardiac index decreased significantly during both NG and placebo infusion. These data suggest that neither NP nor NG is likely to be beneficial in sepsis-induced pulmonary hypertension in newborns.

Oxygen delivery, oxygen consumption, and metabolic acidosis during group B streptococcal sepsis in piglets.

The development of metabolic acidosis during neonatal sepsis with group B streptococci (GBS) has been attributed to progressive tissue ischemia resulting from reduced oxygen delivery (QO2). Using an animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic QO2, one septic and one not. Eighteen anaesthetized piglets were instrumented to observe aortic pressure, cardiac output, arterial and mixed venous blood gases, oxygen content, and hemoglobin concentration. QO2, oxygen consumption, and oxygen extraction ratio were calculated. Six piglets (group 1) received continuous infusion of live GBS organisms; six piglets (group 2) received continuous infusion of phenylephrine (PE), beginning with 10-micrograms/kg/min and increasing as required to match the PE-induced reduction in QO2 to the fall observed in the group 1 (GBS) piglets at each 30-min interval. Group 3 piglets (n = 6) received 0.9% saline and served as controls. No differences in either cardiac output or QO2 were noted comparing GBS and PE piglets at any time interval from 0-180 minutes. At 120, 150, and 180 minutes, both QO2 and cardiac output were lower in GBS and PE piglets compared to controls. Despite equivalent reductions in cardiac output and QO2, only GBS piglets developed significant metabolic acidosis, while pH and base deficit for PE piglets did not differ from controls. Oxygen consumption did not differ significantly among the three experimental groups at any observation time. Oxygen extraction ratio did not differ comparing PE and GBS piglets at any observation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective elevation of systemic blood pressure by epinephrine during sepsis-induced pulmonary hypertension in piglets.

In a piglet model of group B beta Streptococci (GBS)-induced pulmonary hypertension, we have determined hemodynamic responses to epinephrine (EPI) infusion in both the systemic and pulmonary circulations. Three groups of piglets (GBS + EPI, n = 6; GBS + placebo, n = 6; placebo, n = 6) were studied. GBS, infused intravenously at approximately 5 X 10(7) organisms/kg/min, reduced cardiac index and stroke volume index while elevating pulmonary artery pressure and pulmonary vascular resistance index. Systemic vascular resistance index, heart rate and aortic pressure did not change during GBS infusion. Six piglets received intravenous EPI after cardiac index had fallen by 30% during GBS infusion. At 3.5, 7.0, and 15 micrograms/kg/min, respectively, EPI raised aortic pressure by 18.5, 31.0, and 45.0 mm Hg while EPI reduced pulmonary artery pressure by 5.2, 6.3, and 8.2 mm Hg. At each dose, EPI elevated systemic vascular resistance index and lowered pulmonary vascular resistance index. At 3.5 micrograms/kg/min, the elevation of aortic pressure was associated with an increase in both cardiac index and systemic vascular resistance index. At higher EPI doses, the rise in aortic pressure was accounted for entirely by an increase in systemic vascular resistance index. Systemic acid/base status and PaO2 did not differ among piglets who received GBS + EPI, GBS alone, or placebo. Extrapolation of these data to human infants must be approached with extreme caution. However, selective elevation of systemic blood pressure may be a feasible strategy for some infants to impede right-to-left shunting of blood often associated with sepsis-induced pulmonary hypertension.

Time course of radiometric detection of positive blood cultures in childhood.

We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children.

Early and late hemodynamic consequences of group B beta streptococcal sepsis in piglets: effects on systemic, pulmonary, and mesenteric circulations.

We have modified our previously described experimental model of neonatal sepsis using group B beta hemolytic streptococci (GBS) in piglets and report here early and late hemodynamic responses to GBS infusion in the systemic, pulmonary, and mesenteric circulations. Piglets were anesthetized, intubated, and ventilated. Aortic blood pressure (AOP), pulmonary artery pressure (PAP), central venous pressure (CVP), left atrial pressure (LAP), cardiac index (CI), mesenteric blood flow index (MBFI), and heart rate (HR) were measured directly. Systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), mesenteric vascular resistance index (MVRI), and stroke volume index (SVI) were calculated. Sepsis was induced by continuous IV infusion of live GBS beginning at 0.5 X 10(7) organisms/kg/min. LAP was held constant throughout the sepsis protocol. PAP and PVRI were the most sensitive hemodynamic indices of early GBS sepsis, rising to greater than two times baseline levels within 11 min of the onset of bacteremia (approximately 1.0 X 10(8) cumulative organisms/kg). In contrast, AOP was unaffected during the first 83 min of GBS sepsis (approximately 25 X 10(8) organisms/kg) but fell from 84 to 47 mmHg in the final 31 min of the experiment. Both CI and MBFI fell monotonically as a function of cumulative GBS dose, reaching 72% and 64% of baseline at 55 min (approximately 12.5 X 10(8) organisms/kg) and 40% and 34% of baseline by 3 hr of sepsis (approximately 125 X 10(8) organisms/kg), respectively. At every GBS dose, the fall in CI was entirely accounted for by a reduction in SVI. SVRI, MVRI, and PVRI were elevated at all times during GBS sepsis. Despite a 34% reduction in systemic oxygen delivery during the first 83 min of GBS infusion (approximately 25 X 10(8) organisms/kg), arterial pH and base excess did not change significantly. Thereafter, pH fell monotonically reflecting the progressive development of metabolic acidosis.

Effects of phenylephrine on systemic and pulmonary artery pressure during sepsis-induced pulmonary hypertension in piglets.

The effects of intravenous phenylephrine (PE) on aortic blood pressure (AOP), pulmonary artery pressure (PAP), and cardiac output (CO) were evaluated in piglets with normal PAP and piglets with sepsis-induced pulmonary hypertension. Anesthetized, ventilated piglets (1-4 weeks; n = 22) were divided into four groups - group 1 (n = 5) received group B beta streptococci (GBS) followed by PE (300 micrograms/kg); group 2 (n = 6) received GBS alone; group 3 (n = 6) received placebo infusion; group 4 (n = 5) received PE alone (300 micrograms/kg). Infusion of GBS in piglets (groups 1 and 2) elevated PAP by 149 and 176%, reduced CO by 34 and 28%, and did not affect AOP. Administration of PE (groups 1 and 4) raised AOP by 30 and 27% without significantly affecting PAP. However, CO fell after PE by 31 and 39%, respectively. If selective elevation of systemic blood pressure is to become an effective strategy for human newborns with right-to-left shunts caused by sepsis-induced pulmonary hypertension, agents other than PE, with less associated reduction of CO, need to be identified.

Salmonella enteritidis bacteremia in childhood.

We have reviewed the clinical course of 32 children with Salmonella enteritidis bacteremia and compared them with 135 children with acute gastroenteritis caused by S. enteritidis at Wyler Children's Hospital over 4.5 years. Analysis of symptoms of infection, the initial laboratory evaluation, the initial impression of the severity of illness, the clinical course, and the eventual outcome showed no differences between children with bacteremia and those with acute gastroenteritis, nor did a comparison between older children (one year of age or older) and younger children, with either bacteremia or acute gastroenteritis, show appreciable differences. We conclude that bacteremia occurring with acute gastroenteritis was clinically elusive and more common than previously recognized. Furthermore, in the absence of documented risk factors, bacteremia occurring with acute gastroenteritis was not associated with any greater morbidity than was acute gastroenteritis occurring alone.

Successful therapy of unilateral pulmonary emphysema: mechanical ventilation with extremely short inspiratory time.

We describe a novel approach to the mechanical ventilation of two neonates with life-threatening unilateral pulmonary emphysema (UPE). Using a standard time-cycled, pressure-limited ventilator, we achieved resolution of UPE with shorter inspiratory times than previously reported effective in human newborns (0.10-0.15 sec). We elected this ventilatory strategy in order to direct tidal volume preferentially toward units of lung with relatively normal time constants, while avoiding inflation of longer time-constant emphysematous areas.

Unsuspected mesenteric hypoperfusion despite apparent hemodynamic recovery in the early phase of septic shock in piglets.

We have developed an animal model of group B beta Streptococcal sepsis especially conducive to observation of hemodynamic sequelae of the early phases of septic shock. In piglets (N = 7), direct continuous measurements were made of aortic pressure (AOP), left atrial pressure (LAP), central venous pressure (CVP), mesenteric artery blood flow (QMES), and pulmonary artery blood flow, equivalent to cardiac output (CO). Systemic vascular resistance (SVR) and regional mesenteric vascular resistance (MVR) were calculated. Sepsis was induced by bolus intravenous administration of live, washed, type 1b group B beta Streptococcus (GBS) at approximately 1 X 10(10) organisms/kg. Early in septic shock, AOP, LAP, CO, and QMES fell to 66%, 20%, 62%, and 34% of pre-GBS levels, respectively, while SVR and MVR rose to 139% and 224% of control. The decrease in QMES and increase in MVR were significantly more extensive than the fall in CO or the rise in SVR, respectively. Subsequently, systemic hemodynamic function improved over time while regional mesenteric circulation did not. AOP and CO recovered to 86% and 88% of pre-GBS levels, respectively, and SVR returned to 105% of baseline. However, QMES remained only 48% of control, and MVR continued at 173% of pre-GBS levels. Mesenteric blood flow could not accurately be inferred from measurements of either AOP or CO during sepsis in these piglets. Relative mesenteric hypoperfusion persisted despite systemic hemodynamic recovery during this GBS sepsis protocol.

Nonhomogeneous redistribution of mesenteric blood flow after tolazoline during group B streptococcal sepsis in piglets.

The effect of tolazoline (Tz) on mesenteric blood flow was evaluated in a piglet model of group B streptococcal (GBS) sepsis. GBS infusion decreased cardiac output and mesenteric blood flow equivalently, while increasing systemic and mesenteric vascular resistance. At three doses between 2 and 25 mg/kg, Tz increased cardiac output and decreased systemic vascular resistance. However, at no dose did Tz improve the diminished mesenteric artery blood flow which accompanied GBS sepsis. The potential use of Tz in neonatal sepsis may be limited by its nonhomogeneous redistribution of blood flow.

Hemodynamic consequences of tolazoline in neonatal group B streptococcal bacteremia: an animal model.

Using a piglet model of neonatal sepsis, we have determined that Group B streptococcal (GBS) bacteremia is associated with a state of vascular hyper-resistance in both the pulmonary and systemic circulations. This elevated vascular resistance is accompanied by a significant fall in cardiac output despite the assurance of constant intravascular fluid volume. Pulmonary artery pressure rises extensively while systemic blood pressure remains essentially unchanged during this GBS infusion protocol. We report here our attempts to relieve the vascular hyperresistance of GBS infusion by administration of an alpha-sympathetic antagonist, tolazoline (Tz). We found that Tz, in a dose-related fashion, decreased both systemic and pulmonary vascular resistance over the entire range from 2 to 25 mg/kg. Further, at all doses tested, the resistance-reducing effect of Tz was equal in the systemic and pulmonary vascular beds. No selective pulmonary or systemic vasodilatory effect was demonstrated by Tz in this model of neonatal pulmonary hypertension. The reduction of systemic vascular resistance was accompanied by a significant elevation in total body cardiac output at all Tz doses. Compared to pre-Tz values, cardiac output rose by 24, 55, and 55% after Tz at 2, 8.3, and 25 mg/kg respectively. In addition, administration of Tz to septic normovolemic piglets reliably produced a transient decrease of systemic blood pressure. For Tz doses of 2 and 8.3 mg/kg, steady state systemic blood pressure returned to pre-Tz levels within 10 min. However, after Tz at 25 mg/kg, steady state systemic blood pressure remained significantly below pre-Tz levels.