Changes in mean airway pressure during HFOV influences cardiac output in neonates and infants.

BACKGROUND: Changes in mean airway pressure affect cardiac output during conventional positive pressure ventilation. The effect of high-frequency oscillation ventilation (HFOV) on cardiac output is less studied. METHODS: A prospective study in a university hospital pediatric intensive care unit. Fourteen patients aged <1 year and weighing <10 kg who were on HFOV were included. All patients had been on HFOV for >12 h and were considered to be in a stable condition. In the study group (n = 9) the mean proximal airway pressure (Paw) was increased and decreased by +5 and -3 cmH2O, respectively, from baseline in each patient. Measurements were made at each level including baseline settings between each change. In a control group (n = 5) no changes in ventilatory parameters were made. Cardiac output was assessed with echocardiography and the Doppler technique at each level of Paw and at similar intervals in the control group. RESULTS: Cardiac output changed significantly when Paw was changed in the study group (P = 0.02), with the greatest change at the highest Paw at -11% (range: -19 to -9) compared with baseline. We found no significant changes over time in the control group. CONCLUSION: This study shows that CO is affected by changes in mean airway pressure during HFOV in concordance with the known effects of mean airway pressure during conventional positive pressure ventilation. The mean changes are smaller than expected compared with earlier studies of conventional mechanical ventilation. Further studies are needed to better understand these relationships.

Age-dependent variations in white adipose tissue glycerol and lactate production after surgery measured by microdialysis in neonates and children.

In previous studies, we observed that lactate concentrations in interstitial white adipose tissue are higher in small infants than in adults. Moreover, no lipolysis following catecholamine challenge has been reported in neonates and small infants. Our aim was to determine with microdialysis whether the above mentioned age-dependent changes could be detected in situ after surgery. A microdialysis catheter was introduced into the abdominal subcutaneous tissue in 13 neonates and 12 children undergoing surgery. Interstitial concentrations of glucose, lactate and glycerol were measured hourly during the first 20 postoperative hours. The concentrations of lactate in interstitial white adipose tissue were consistently higher in neonates compared to older children, with a significant difference during the 9-18 h postoperative period (P < 0.05). A significant difference in the lactate:glucose ratio was observed at 1-2, 8-10, 15 and 18 h postoperatively (P < 0.05). No significant differences were observed between the two groups with respect to glycerol and glucose concentrations. Interstitial lactate concentrations in white adipose tissue were higher in neonates compared with children in the early postoperative period. No age-dependent difference in postoperative lipolysis, measured as interstitial glycerol concentrations, was observed. Thus, an age-dependent difference in interstitial lactate production, but not lipolysis, was detected in the early postoperative period.

Successful EXIT (ex utero intrapartum treatment) procedure in a fetus diagnosed prenatally with congenital high-airway obstruction syndrome due to laryngeal atresia.

Congenital high-airway obstruction syndrome (CHAOS) is due to rare malformations and has been reported previously in only few cases. If the diagnosis can be made prenatally, the ex utero intrapartum treatment (EXIT) procedure may be life-saving. A healthy 28-year old nulli-para was referred because of isolated ascites found at gestational week 16 during routine ultrasound scan. Repeated scans showed overdistended hyperechogenic lungs with inverted diaphragm and a dilated trachea, which was interpreted as a CHAOS resulting from laryngeal atresia. The ascites eventually disappeared. An EXIT procedure was performed at 35 weeks of gestation. Anesthesia of the mother was induced with thiopental, succinylcholine and fentanyl followed by intubation, and maintained with isoflurane and nitrous oxide. A low abdominal midline incision was performed followed by a low transverse incision of the uterus. The fetal head, right arm and shoulder were delivered and intramuscular anesthesia was administered to the fetus. Immediate laryngoscopy confirmed the diagnosis and a tracheostomy was therefore performed. Surfactant was given after a few minutes of ventilation. Compliance improved and when the fetus was easy to ventilate, it was delivered. The baby is developing normally at 18 months of age. Surgical correction of the malformation will be performed after two years of age. It is concluded that some fetuses with a prenatal diagnosis of CHAOS can benefit from the EXIT procedure at delivery. This necessitates a multidisciplinary management team.

Changes in stroke volume cause change in cardiac output in neonates and infants when mean airway pressure is altered.

BACKGROUND: Based on early studies in the lamb, and in spite of more recent studies in humans, it has been the received opinion that neonates and infants can not change their stroke volume significantly, but are mainly dependent on changes in heart rate, to change cardiac output. To further evaluate the relationship between cardiac output and stroke volume during mechanical ventilation of neonates and infants, we have studied the effects on cardiac output and stroke volume by two different ways of changing mean airway pressure. METHODS: In one group, mean airway pressure was decreased by using a patient triggered mode: pressure support ventilation; in the other, mean airway pressure was increased by increasing positive end-expiratory pressure (PEEP). Changes in cardiac output, heart rate and stroke volume were assessed with the Doppler technique, measuring blood flow velocity in the ascending aorta. RESULTS: Without a significant change in heart rate, we found a significant increase in cardiac output of +16+/-2% (P<0.01) with a decrease in mean airway pressure and a decrease in cardiac output of -13+/-4%, (P<0.02) with an increase in mean airway pressure, depicting a change in stroke volume of +17+/-2% (P<0.02) and -14+/-5%, (P<0.01) respectively. CONCLUSIONS: We conclude that neonates and infants are able to regulate cardiac output by changing the stroke volume to a greater extent than presumed, at least when cardiac output is influenced by changes in the mean airway pressure.

Microdialysis for metabolic monitoring in neonates after surgery.

Microdialysis is a new method for continuous metabolic monitoring. We studied the possibility of using microdialysis in neonates treated in a paediatric intensive care unit after surgery. A microdialysis catheter was inserted in the abdominal subcutaneous adipose tissue in 14 neonates for a median of 93 h (range 24-106 h). In four neonates, two microdialysis catheters were used simultaneously. Samples were taken hourly for analysis of glucose, lactate and glycerol. Dialysate and blood concentrations were compared. Serum/whole blood glucose values (n = 68) were in the range 2.1-15.4 mM. The serum glucose levels showed good agreement with the dialysate concentrations of glucose, although these infants were subjected to various forms of stress, drugs and glucose infusions. The whole blood glucose levels were significantly lower than the dialysate levels. The microdialysis concentrations of glucose varied considerably. As almost identical dialysate glucose levels were found when two microdialysis catheters were used simultaneously, the variability probably reflects true changes in blood glucose levels. Our results indicate that microdialysis can be used in neonates.

Pressure support ventilation increases cardiac output in neonates and infants.

Fifteen neonates and infants were investigated during pressure controlled ventilation (PCV) and pressure support ventilation (PSV) on a Servo 300 ventilator. Changes in cardiac output (aortic mean blood flow velocity) were assessed with the Doppler technique. During PSV cardiac output increased by 16% (P < 0.01) compared with PCV with equal ventilation. Mean airway pressure decreased significantly during PSV compared with PCV, which may explain the increased cardiac output. During PSV, when inspiratory/expiratory (I:E) relations are dependent on the patient, we found a lower I:E ratio compared with PCV. It can be assumed that at least part of the decreased mean airway pressure is caused by the lower I:E ratio. As the heart rate was unchanged, the variations in cardiac output were caused by alterations in stroke volume. It is concluded that a patient triggered mode should be preferred providing that the neonate/infant has the ability to elicit the ventilator's triggering system.

Adenosine for per-operative blood pressure control in an infant with neuroblastoma.

We describe a child with a localised pelvic neuroblastoma and a hypertensive crisis during the first weeks of life due to elevated systemic norepinephrine of tumoural origin. In spite of treatment with high doses of alpha-blockers, blood pressure did not respond fully and the boy had a very unstable circulation. Surgery was performed at one month of age. Adenosine, a potent short-acting vasodilator, was used for peroperative blood pressure control to protect the patient from an uncontrolled hypertensive crisis. During tumour manipulation the child became hypertensive with systolic pressure exceeding 130 mm Hg and adenosine infusion (100 micrograms.kg-1.min-1) was started with a prompt normalisation of the blood pressure. Adenosine infusion could be discontinued after tumour removal. Norepinephrine, dopamine, homovanillic acid and vanillylmandelic acid in urine were elevated preoperatively and normalised at follow up. Plasma concentrations of norepinephrine and dopamine were elevated preoperatively. Norepinephrine increased during hypertension due to tumour manipulation. Plasma neuropeptide Y increased during tumour manipulation but still within the normal range for infants. It is concluded that adenosine can be used peroperatively in children with severe hypertension and in this case no adverse effects of adenosine were noted. Furthermore, tumour synthesis and systemic release of norepinephrine, but not neuropeptide Y, contributed to hypertension in this child with neuroblastoma.

Inhaled nitric oxide in neonates and children with pulmonary hypertension.

Fourteen critically ill neonatal and paediatric intensive care patients with various primary diagnoses and signs of associated pulmonary hypertension received inhaled nitric oxide (NO), 20-80 ppm, after failure of conventional therapy to improve oxygenation. NO administration was found to be associated with a significant improvement in postductal arterial oxygen tension (pre-NO: 3.75 (SD 1.39) kPa; post-NO: 6.05 (SD 1.70) kPa; p = 0.004). In 10 patients, NO was found to increase arterial oxygen tension with more than 1 kPa. In 2 of these patients, ECMO treatment could be avoided due to the pronounced improvement in gas exchange seen after the initiation of NO administration. The remaining 4 patients failed to respond to NO administration. One patient developed methaemoglobinaemia (13.9%) which required treatment with methylthionine. Since we were unable to produce any beneficial effect of NO in the late phase of the pulmonary disease process, we believe that, in order to be successful, inhaled NO should be instituted when conventional treatment has failed and the administration of an iv vasodilator is usually considered.

Expression of beta 1- and beta 2-receptor genes and correlation to lipolysis in human adipose tissue during childhood.

beta 1- and beta 2-adrenoceptor (bar1 and bar2) mRNA levels were measured in adipose tissue obtained from children (between 1 month and 10 yr of age) and adults during inguinal hernia operations. Bar1 mRNA levels were constant in all age groups studied. In infants and children less than 7 yr old, bar2 levels were twice as high (P < 0.01) as those in adults, and in infants 1-4 months old, bar2 mRNA levels were higher than bar1 levels (P < 0.01). The bar2/bar1 ratio gradually decreased, and in adults, there was 2.3-fold higher bar1 mRNA expression (P < 0.01). In infants 1-5 months old, the lipolytic sensitivity to noradrenaline was 5 times lower (P < 0.05) than that in adults, whereas the sensitivity to adrenaline and isoprenaline was unchanged. The maximal lipolytic response to adrenaline was higher than that to noradrenaline in infants (P < 0.01), whereas the opposite was found in adults (P < 0.01). The lipolytic sensitivity to the bar1-selective agonist dobutamine was not influenced by age, whereas the sensitivity to the bar2-selective agonist terbutaline was 10,000 times higher in infants than in adults. In conclusion, these data indicate subtype-specific developmental changes in bar expression, with higher bar2 mRNA levels accompanied by increased bar2-induced lipolysis during infancy.

Lack of lipolytic response in infants after endotracheal intubation.

The sympathoadrenal response to endotracheal intubation was investigated in nine infants 2-4 months old and in eight adults 23-45 years old at the start of inguinal hernia operations. In both infants and adults, heart rate and diastolic blood pressure increased significantly immediately after intubation. In both groups, moreover, there was a mean (SD) reduction in microvascular blood flow in the abdominal skin (infants -21 (14)%, adults -14 (7)%) and in the adipose tissue (infants -7 (4)%, adults -5 (4)%). However, the plasma glycerol concentration did not increase in the infants whereas it increased in the adults by 50 (12)%. In conclusion, infants and adults showed similar circulatory reactions during endotracheal intubation but the markedly increased lipolysis rate observed in adults was not seen in the infants. This may indicate that catecholamine induced lipolysis in vivo as well as in vitro is poor during infancy.

Early development in healthy children of serum opsonins against nonpathogenic Neisseria meningitidis.

In an earlier study, with the use of chemiluminescence (CL) and phagocytic killing, we could show that in the presence of serum from healthy adults polymorphonuclear leukocytes (PMNL) efficiently handle nonpathogenic Neisseria meningitidis strains, in sharp contrast to those associated with clinical disease. The major part of this difference was dependent on serum factors. In the present study 84 serum samples from children 1-3, 4-6, 7-9, and 10-14 years old were studied by the CL technique according to their ability to opsonize meningococci. There was a highly significant difference (p less than 0.001) in all four age groups when the CL indexes obtained with the pathogenic meningococci of the serogroups A, B and C were compared with those of the nonpathogenic menigococci: serogroup 29E and nongroupable meningococci. These findings imply that the ability to opsonize so-called nonpathogenic meningococci is developed early in life and may explain why they are only occasionally able to cause disease.

Long-term use of central venous catheters in paediatric oncology treatment.

During a 26-month period, 158 central venous catheters were inserted in 114 children (median age: 4.5 years) with malignant diseases. Polyurethane catheters were used, inserted either using a cut-down procedure or percutaneously in the external or internal jugular vein. All catheters were tunnelled from the point of insertion to the midpoint of the manubrium or upper sternum. The catheter tip reached the superior caval vein or the right atrium in 94% of the cases. The catheters were used for all infusions, including total parenteral nutrition, and for blood sampling. The median catheter duration was 104 days (range 5-835 days). Sixty-eight (43%) of the catheters were removed as they were no longer needed, and 31 (20%) were removed due to local infection or septicaemia. During a total of 23,486 catheter days (64.4 years), 110 episodes of septicaemia occurred. This represents one episode per 214 catheter days. In 43 of the 110 episodes of septicaemia, blood cultures showed growth of bacteria of the kind usually found in the gastrointestinal and respiratory tracts. All septicaemias were treated with intravenous broad-spectrum antibiotics and in 21 cases the catheters were removed due to septicaemia. Thirty-four (22%) catheters were removed accidentally. There were two cases of subclavian vein thrombosis.

Low field magnetic resonance imaging of the central nervous system in 15 children with autistic disorder.

Fifteen children, 10 boys and 5 girls, with autistic disorder, were studied with low field magnetic resonance imaging (MRI). The age ranged from 2.7-13.1 years, with a mean of 8.3 years. All patients but one (who refused) had a normal CT scan of the C.N.S. The MRI investigation was performed during anaesthesia with a low field magnetic resonance imager. The cerebrum, cerebellum, and brain stem were examined. No pathological changes were found in any of the patients studied.

Circulatory monitoring of children during anaesthesia in low-field magnetic resonance imaging.

Anaesthesia for patients in a Magnetic Resonance Imaging (MRI) scanner provides some problems for the design of both the anaesthetic and the monitoring equipment. This report presents a technique for continuously displaying the heart rate during anaesthesia for children in an MRI scanner. The monitoring system used light to detect differences in skin capillary circulation, and the light was transferred to and from the patient via fiberoptic cables. After amplification, the signal was displayed "on line" on a cardioscope, thus continuously presenting heart rate and, in part, a qualitative view of the skin vascular resistance.

Changes in muscle sympathetic nerve activity, venous plasma catecholamines, and calf vascular resistance during mechanical ventilation with PEEP in humans.

The sympathetic reflex response to mechanical ventilation with PEEP was studied in conscious human volunteers (n = 8). Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve, calf blood flow, forearm venous plasma catecholamines, blood pressure, heart rate, airway pressure, and end-tidal CO2 (%) during spontaneous breathing and during mechanical ventilation with 0-20 cmH2O PEEP. MSNA increased (P less than 0.01) during PEEP ventilation, from 22 bursts.min-1 at spontaneous breathing to 39 bursts.min-1 at 20 PEEP. This increase in MSNA was accompanied by an increase (P less than 0.01) in calf vascular resistance (CVR) from 35 PRU100 at spontaneous breathing to 48 PRU100 at 15 PEEP with no further increase at 20 PEEP. Venous plasma norepinephrine concentrations increased (P less than 0.01) during PEEP ventilation from 0.19 ng.ml-1 at spontaneous breathing to 0.31 ng.ml-1 at 20 PEEP, whereas plasma epinephrine and dopamine were less than 0.03 ng.ml-1 during the experiment. Blood pressure and heart rate were not affected by PEEP ventilation except at 20 PEEP, where blood pressure and heart rate increased (P less than 0.01). The results show that PEEP ventilation induces a considerable reflex increase of MSNA, reflected also by an increase in CVR and venous plasma norepinephrine. It is proposed that the main mechanism responsible for these reflex adjustments is caused by a decreased activity of the cardiopulmonary low-pressure baroreceptors, in turn resulting from a decrease in cardiac transmural pressures due to PEEP ventilation.

Effects of hypovolaemia or isoprenaline infusion on the sympathetic reflex response to PEEP ventilation in rats.

The aim of this investigation was to study vagally mediated sympathetic reflex responses to mechanical ventilation with positive end-expiratory pressure (PEEP), during hypovolaemia or during high inotropic stimulation of the heart by isoprenaline infusion. Renal sympathetic nerve activity (RSNA), heart rate and mean arterial pressure were studied during mechanical ventilation with zero end-expiratory pressure (ZEEP) and 5 and 10 cmH2O PEEP in chloralose anaesthetized Wistar rats. Experiments were performed on two groups of rats: eight animals were subjected to 10% blood volume depletion, and seven animals to infusion of isoprenaline. PEEP ventilation was applied during control conditions and during hypovolaemia or isoprenaline infusion before and after vagotomy. In the intact (control) situation, there was a significant increase in RSNA from ZEEP to 10 PEEP in both groups (+75%, +51%). During hypovolaemia or isoprenaline infusion, PEEP ventilation did not induce any significant increase in RSNA in both groups after vagotomy, 10 PEEP induced a significant increase in both groups (+56%, +54%). These results indicated that under conditions of hypovolaemia or increased cardiac inotropism, PEEP ventilation may elicit a vagally mediated reflex with an inhibitory action on sympathetic activity, in turn probably caused by an activation of left ventricular receptors.

Radial arterial catheters in children and neonates: a prospective study.

Over a 3-yr period (1982 to 1984), 533 arterial catheters were inserted in 476 patients admitted to the pediatric ICU or the operating room. Radial arterial catheterization with small-bore, 0.8-mm, 22-ga Teflon cannulas was the most common method (376 of 533 cannulations), and 296 of these catheters were inserted in patients less than 1 yr of age. All catheters were flushed intermittently with heparin (12.5 U/ml) in isotonic saline. The mean catheter duration was 2.6 days, and only minor complications were noted. The main reason for catheter removal was malfunction of the arterial line. There was no difference in duration or complication rate between catheters inserted percutaneously or by cutdown. Over a 6-month period (1985 to 1986), 42 0.8-mm, 22-ga radial arterial catheters were inserted in 39 patients less than 1 yr of age; all catheters were maintained by a continuous flushing system using heparin (5 U/ml) in isotonic saline. The mean duration was 6.3 days. No complications were noted, and the proportion of catheter malfunction decreased. This study confirms the safety of radial arterial catheterization in children and neonates. The continuous flushing system considerably improved catheter patency compared to a method using intermittent flushing.