The virtual pediatric intensive care unit. Practice in the new millennium.

Patients and their families meet with health care providers in a complex marketplace. The information revolution is providing access to vast amounts of information and new ways to understand it. More important, perhaps, is that it also is providing new ways of communicating information not only about health but also about the health care delivery process. This occurrence makes it possible for patients not only to diagnosis and treat themselves but also see how well the professionals do it. Like all marketplaces, asymmetries in information define the value of the interaction. Patients see physicians because they have no way of overcoming this knowledge barrier, and health care is a highly regulated market because of these asymmetries in information. New information technologies in general and telemedicine (which, in this broad sense, include distance learning for patients) can address and erode these information asymmetries. This technology threatens to have a profound effect on health care. Telemedicine offers to increase greatly the reach (connectivity) and richness (bandwidth, customization, and interactivity) of the health care information marketplace. This radically will change the way in which physicians practice critical care. Intensivists must ensure that patients continue to receive high-quality critical care. This practice will require embracing these new technologies. Resisting them will be catastrophic. What is the VPICU? It is a committed group of pediatric intensivits who are dedicated to supporting pediatric critical care medicine in the enhancement of knowledge about pediatric critical care. It includes application of information technologies to support the practice of pediatric critical care. It primarily is focused on understanding the health care delivery process and providing the tools for pediatric intensive care practitioners to better understand the care they deliver. It is the desire of the VPICU to create a virtual community in which pediatric critical care practitioners work together to understand the way they practice and to identify and implement better ways to deliver pediatric critical care. This virtual community will be responsible for clinical and economic performance in the practice of pediatric critical care. The VPICU realizes that this requires the tools to make high-quality decisions and that these decisions depend on data and communication. The author invites all pediatric intensivists to participate in the VPICU to achieve the goals of better practice through the application of information technologies in pediatric critical care.

Potential paracrine role of the pericardium in the regulation of cardiac function.

OBJECTIVE: Both coronary and endocardial endothelium regulate cardiac contractile function via paracrine pathways. We investigated whether pericardial fluid (PF) and pericardial mesothelial cells (PMC) could exert a similar paracrine action. METHODS: Both PF and PMC were extracted from sheep pericardial space. Endothelin-1, prostaglandins and atrial natriuretic factor were measured in PF in vivo. In the other hand, PMC were grown on T-75 flasks and microcarrier beads to investigate endothelin-1, nitric oxide and prostaglandin pathways in vitro. In addition, effects of PF and PMC effluent were tested on adult rat cardiac myocyte contraction in vitro. RESULTS: In vitro, cultured PMC expressed endothelin-1 mRNA but not the endothelial nitric oxide synthase III, and released endothelin-1 and prostaglandins. Both PF and cultured PMC superfusate induced a potent, rapidly reversible decrease in the shortening of isolated rat cardiac myocytes. This effect was not associated with changes in intracellular calcium. In vivo, prostaglandins, atrial natriuretic factor and endothelin were present in PF. A greater concentration of atrial natriuretic factor was present in PF than in serum, suggesting molecular diffusion from the myocardium to PF. Preliminary results show that the instillation of vasoactive agents into the pericardial space of dogs rapidly alter coronary and systemic vascular tone, consistent with a molecular diffusion of these substances from PF into the myocardium and circulation. CONCLUSIONS: In addition to its mechanical role, the pericardium may contribute to the integration and the regulation of cardiovascular function via a paracrine mechanism.

Pressure-support ventilation in children with severe asthma.

OBJECTIVE: To review the efficacy of pressure-support ventilation in the management of children with status asthmaticus requiring mechanical ventilation. DESIGN: A case series. SETTING: A university hospital. SUBJECTS: Children requiring mechanical ventilation due to respiratory failure despite medical therapy during an episode of acute asthma. INTERVENTIONS: Mechanical ventilation with pressure-support ventilation. MEASUREMENTS AND MAIN RESULTS: Respiratory parameters (ventilatory settings, minute ventilation, respiratory rate, airway pressures) and blood gases were determined before, on initiation, and for 6 hrs after pressure-support ventilation. Spontaneous ventilation with an initial respiratory rate of 45 breaths/min (range 31 to 46) and an inspiration/expiration ratio (I/E) of 1:1.2 (range 1:1.1 to 1:2) was readily established in each patient. Arterial pH normalized (7.41, range 7.39 to 7.43) within 6 hrs (4.25, range 2 to 6) of the time at which ventilation was begun and the Paco2 decreased (p < .02) to 44 torr (range 39 to 47) (5.9 kPa, range 5.2 to 6.3) during pressure support ventilation. CONCLUSION: Pressure-support ventilation permitted patient-cycled spontaneous ventilation in children with asthma. The ability of patients to determine their own respiratory pattern and to maintain forced exhalation during pressure-support ventilation may have important advantages in children with severe asthma who require mechanical ventilation.

Endotoxin induces organ-specific endothelial cell injury.

Endothelial cell (EC) injury is observed in clinically important pathological processes, including bacterial endotoxemia. We hypothesized that such pathological processes may exhibit target organ heterogeneity due to organ-specific heterogeneity of endothelial cells. To test this hypothesis, endothelial cells of aorta (AO), pulmonary artery (PA), left ventricle (LV), and right ventricle (RV) were cultured from individual sheep and exposed to bacterial endotoxin. Marked heterogeneity in endotoxin-induced cytotoxicity was observed. AOEC were the most sensitive, followed by PAEC, LVEC, and RVEC. This cytotoxicity was manifested as programmed cell death (apoptosis). All cells were able to express both interleukin-6 and endothelin-1 (ET-1) transcripts. Following exposure to bacterial endotoxin, interleukin-6 transcripts accumulated in all cells, whereas ET-1 expression was constant or slightly decreased. These data suggest that organ-specific heterogeneity of EC responsiveness to endotoxin is a potential determinant of organ-specific resistance to endotoxin and other mediators of injury.

17 beta-Estradiol inhibits flow- and acute hypoxia-induced prostacyclin release from perfused endocardial endothelial cells.

BACKGROUND: Because of the marked difference in the incidence and severity of cardiovascular diseases between men and premenopausal women, several groups have studied the effect of sex steroids, particularly estrogen, on vascular endothelial prostacyclin (PGI2) release. No previous studies have addressed the effect of estrogen on endocardial endothelial cells (EECs), which are involved in the modulation of the myocardium and potentially in downstream pulmonary and systemic vascular tone. Furthermore, all previous studies of estrogen effects on cultured endothelial cell function have used cells grown under standard static cell culture conditions, thereby ignoring the contribution of flow, the ubiquitous environmental endothelial stimulus. METHODS AND RESULTS: The effect of 17 beta-estradiol pretreatment (100 ng/mL, 72 hours) on cultured sheep EEC PGI2 release in response to multiple physiologically relevant stimuli was studied. EECs were grown in six-well plates (static conditions) or on microcarrier beads and perfused at a constant flow with normoxic (PO2 = 150 mm Hg, PCO2 = 35 mm Hg) or hypoxic (PO2 = 35 mm Hg, PCO2 = 35 mm Hg) Krebs solution. The stable metabolite of PGI2, 6-keto-PGF1 alpha, was determined in samples from both static and perfusion experiments by direct radioimmunoassay. 17 beta-Estradiol pretreatment did not alter basal or stimulated (arachidonic acid, 1 mumol/L, 10 mumol/L; A23187, 10 mumol/L; and bradykinin, 1 mumol/L) PGI2 release in static conditions. Untreated and acutely treated (100 ng/mL added to perfusate) EECs responded to flow with a time-dependent increase in PGI2 release that plateaued between 60 and 100 minutes. In contrast, 17 beta-estradiol-pretreated, perfused EECs did not increase PGI2 release over time. During perfusion, acute hypoxia increased PGI2 release: 140 +/- 65 (normoxia) to 296 +/- 113 pg (hypoxia) 6-keto-PGF1 alpha/mg per minute. 17 beta-Estradiol inhibited hypoxia-induced PGI2 release: 296 +/- 113 pg (untreated EECs, hypoxia) versus 159 +/- 60 pg (17 beta-estradiol pretreated, hypoxia) 6-keto-PGF1 alpha/mg per minute. CONCLUSIONS: This study demonstrates for the first time an inhibitory effect of 17 beta-estradiol on flow- and acute hypoxia-induced increase in PGI2 release from perfused EECs in the absence of any effect on pharmacologically stimulated PGI2 release from static cultures. These effects of 17 beta-estradiol may explain in part the well-recognized gender and estrogen effects in cardiovascular diseases and highlight the importance of flow in studies of endothelial cell function.

Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells.

BACKGROUND: Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined. METHODS AND RESULTS: We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (<< 1 kD) superfusate fractions. CONCLUSIONS: These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability.

Optimal release time during airway pressure release ventilation in neonatal sheep.

OBJECTIVE: To systematically investigate the effect of altering release time during airway pressure release ventilation in a neonatal animal model before and after oleic acid-induced acute lung injury. DESIGN: Prospective, nonrandomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Eight neonatal sheep (aged < 7 days, weight 5.1 +/- 0.3 kg). INTERVENTIONS: Throughout this study, airway pressure release ventilation was performed with an FIO2 of 0.21 at a frequency of 0.5 Hz (30 breaths/min) and an airway plateau pressure set to deliver tidal volumes between 10 and 15 mL/kg with a release time of 1 sec. Release time was changed in decrements of 0.2 sec starting at 1 sec and ending at 0.2 sec at 10-min intervals. Cardio-respiratory profiles were recorded at the end of each interval. The total exhaled respiratory system time constant (tau) was measured by plotting exhaled volume (integration of exhaled air flow) vs. time. Acute lung injury was induced by oleic acid infusion. The protocol was repeated with increased plateau airway pressure to maintain tidal volumes between 10 and 15 mL/kg at a release time of 1 sec. MEASUREMENTS AND MAIN RESULTS: During airway pressure release ventilation at a release time of 1 sec, oleic acid-induced acute lung injury decreased dynamic lung compliance (9.9 +/- 2.2 vs. 7.5 +/- 2.0 mL/cm H2O, p < .01), the expiratory time constant (0.15 +/- 0.04 vs. 0.12 +/- 0.02 sec, p < .05), and mean arterial pressure (80 +/- 5 vs. 62 +/- 12 mm Hg, p < .01). Alveolar ventilation was maintained as long as release times were > 0.4 sec (approximately 3 tau or greater). PaO2 decreased with release times of < 0.3 sec, but the alveolar-arterial oxygen tension difference was unchanged. In this protocol, with higher plateau and mean airway pressures, oleic acid-induced acute lung injury had no effect on the relationship between release time and oxygenation or ventilation. CONCLUSIONS: In this neonatal laboratory model, release times that were much shorter than previously reported maintained clinically acceptable oxygenation and ventilation. The optimal duration of the release time is a function of the time constant of the respiratory system. During airway pressure release ventilation, alveolar ventilation was maintained without apparent lung volume loss with release times of between 4 tau and 10 tau.

Preoperative evaluation of children.

Preoperative evaluation and preparation are directed toward minimizing the intrinsic risks of anesthesia and surgery by having the child in the healthiest possible condition prior to surgery. The pediatrician can contribute to this goal by understanding the effects of general anesthesia on the physiology of children. This knowledge allows an appreciation of the anesthesiologists' concerns regarding underlying diseases, which may seem "stable" (and, therefore, of little present concern to the pediatrician) but which may have grave consequences during anesthesia. The preoperative evaluation is designed to ensure that the child's preoperative needs may be met by providing the anesthesiologist both qualitative and quantitative information regarding the child's state of health and disease. The relationship between the child, parents, and pediatrician places the pediatrician in an ideal position to prepare families for their children's surgical experience.

Postoperative analgesia following thoracotomy in children: interpleural catheters.

The authors retrospectively review their experience in children with the latest addition to the postoperative analgesic armamentarium: interpleural analgesia (IPA). IPA was used in 14 children following thoracotomy. There were 9 boys and 5 girls. Patients varied in age from 2 months to 17 years 4 months (mean +/- SEM = 7.6 +/- 1.6 yr). Catheters were left in place from 10 to 72 hours (mean +/- SEM = 45.1 +/- 4.6 h). Four patients received intermittent bolus doses and 10 patients received a continuous infusion through the interpleural catheters. Adequate analgesia, as judged by both subjective responses (decreased irritability or complaints of pain) and by objective physiologic responses (decreased heart rate, respiratory rate, and systolic blood pressure), was achieved in 13 of 14 patients. Eight of the 14 children required no additional analgesic agents. One child received 2 doses of oral codeine and 4 patients received 2 to 3 doses of intravenous narcotic during IPA. IPA was not effective in one patient who required 6 doses of intravenous meperidine. Patients more than 10 years of age required significantly more (P < 0.05) intravenous narcotic supplementation than patients less than 10 years of age (1.60 +/- 0.50 v 0.14 +/- 0.11 mg meperidine/kg/d). No complications related to placement or subsequent use of IPA were identified in any of the patients. IPA provides effective postoperative analgesia following thoracotomy in children.

Cardiorespiratory responses to epidural analgesia in the awake child: a retrospective review of postoperative patients.

The authors retrospectively evaluated the cardiorespiratory effects of epidural administration of bupivacaine in 17 awake children during the immediate postoperative period. Responses to dosing were assessed by comparing heart rate, blood pressure, and respiratory rate before and after administration. Additionally, hourly heart rates were compared between those patients receiving intermittent bolus doses and those receiving a continuous infusion. The patients included 11 boys and 6 girls, ranging in age from 4 months to 12 1/2 years and in weight from 7.4 to 48 kg. All catheters were placed after the induction of general anesthesia. Surgical procedures included exploratory laparotomy (9 patients), bladder reconstruction (4 patients), wound debridement and skin grafting (2 patients), amputation (1 patient), and Nissen fundoplication (1 patient). A total of 37 bolus doses of 0.25% bupivacaine were administered to 7 patients. A significant (P < .001) decrease in heart rate (187 +/- 2 to 137 +/- 1 beats/min), respiratory rate (42 +/- 2 to 25 +/- 1 breaths/min), and systolic blood pressure (125 +/- 3 to 86 +/- 1 mm Hg) was noted after administration. When postdosing cardiorespiratory parameters were compared with preoperative values obtained the day before surgery during the preoperative anesthesia evaluation, there was no significant difference in heart rate (131 +/- 14 versus 137 +/- 13 beats/min), respiratory rate (21 +/- 7 versus 25 +/- 1.0 breaths/min), and systolic blood pressure (93 +/- 9 versus 86 +/- 2 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Intravascular volume loading reversibly decreases airway cross-sectional area.

High-resolution computed tomography was used to directly determine the short-term effects of intravascular volume expansion on airway caliber. The change in airway cross-sectional area caused by intravascular volume expansion (30 ml/kg, Ringer's lactate) was studied in six anesthetized mini-pigs within 5 min. Twenty-five of 27 large airways (diameter, 2.01 to 5.0 mm) demonstrated decreased internal cross-sectional area (10.56 +/- 1.26 vs 8.66 +/- 1.03 mm2, p < 0.001). Twenty of 24 small airways (diameter, 0.75 to 2.0 mm) showed decreased internal cross-sectional area (1.82 +/- 0.16 vs 1.44 +/- 0.16 mm2, p < 0.001). These changes were rapidly (< 6 min) reversed by intravascular volume reduction. The external airway cross-sectional area did not change. These data suggest rapid, reversible bronchial mucosal vascular engorgement as a cause of increased airway resistance in heart failure.

[Functional HR-CT of the lung. Experimental studies of the pulmonary vascular and airway reactions]. / Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefäss- und Atemwegsreaktionen.

We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 microns and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 microns through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced bronchoconstriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualizes adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method.

Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2.

The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone.

High-resolution computed tomography--physiologic correlation.

High-resolution computed tomography (HRCT) as a tool for investigation of bronchovascular and pulmonary responses to various physiologic and pharmacologic stimuli is a new field of application. The potential of this method has only recently been investigated in animal experiments. To date, research has focused on the determination of airway responses in the context of agonist challenge such as aerosolized or i.v. histamine, isotonic saline, halothane anesthesia, and hypoxia. Likewise, physiologic HRCT has been used in the elucidation of the pulmonary circulatory response to acute hypervolemia and hypoxia. Early results indicate that significant observations can be derived from HRCT as it is the only existing method that not only detects physiologic responses but, unlike existing methods, can characterize their site and locoregional differences. In this article, the rationale for and present status of physiologic HRCT is presented.

Halothane enhances pulmonary artery endothelial eicosanoid release.

To determine whether anesthetics alter endothelial eicosanoid release, cultured bovine pulmonary artery endothelial cells were studied during constant flow and pressure perfusion at two oxygen tensions (hypoxia, 50 +/- 2 mm Hg; normoxia, 144 +/- 5 mm Hg; mean +/- SEM) with and without 1% halothane. Endothelialized microcarriers containing approximately 5 x 10(6) cells were loaded into cartridges and perfused (3 mL/min) with Krebs' solution (pH 7.4, at 37 degrees C) equilibrated with each gas mixture. Eicosanoids (6-keto prostaglandin F1 alpha, thromboxane B2, and total peptidoleukotrienes [C4, D4, E4, F4]) were measured by radioimmunoassay and quantified per gram of cellular protein per minute. Eicosanoid release did not vary over time. The 6-keto prostaglandin F1 alpha release increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng.min-1 x g protein-1; P < 0.01). Halothane (H) increased release of each eicosanoid during both normoxia and hypoxia: 6-keto prostaglandin F1 alpha-normoxia 291 +/- 27 versus normoxia + H 356 +/- 32 ng.min-1 x g protein-1, hypoxia 395 +/- 35 versus hypoxia + H 464 +/- 40 ng.min-1 x g protein-1, P < 0.05; thromboxane B2-normoxia 19 +/- 2 versus normoxia + H26 +/- 2 ng.min-1 x g protein-1, hypoxia 20 +/- 2 versus hypoxia + H 38 +/- 5 ng.min-1 x g protein-1, P < 0.001; leukotriene-normoxia 363 +/- 35 versus normoxia + H 489 +/- 52 ng.min-1 x g protein-1, hypoxia 329 +/- 29 versus hypoxia + H 455 +/- 39 ng.min-1 x g protein-1, P = 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)