Patterns of paediatric end-of-life care: a chart review across different care settings in Switzerland.

BACKGROUND: Paediatric end-of-life care is challenging and requires a high level of professional expertise. It is important that healthcare teams have a thorough understanding of paediatric subspecialties and related knowledge of disease-specific aspects of paediatric end-of-life care. The aim of this study was to comprehensively describe, explore and compare current practices in paediatric end-of-life care in four distinct diagnostic groups across healthcare settings including all relevant levels of healthcare providers in Switzerland. METHODS: In this nationwide retrospective chart review study, data from paediatric patients who died in the years 2011 or 2012 due to a cardiac, neurological or oncological condition, or during the neonatal period were collected in 13 hospitals, two long-term institutions and 10 community-based healthcare service providers throughout Switzerland. RESULTS: Ninety-three (62%) of the 149 reviewed patients died in intensive care units, 78 (84%) of them following withdrawal of life-sustaining treatment. Reliance on invasive medical interventions was prevalent, and the use of medication was high, with a median count of 12 different drugs during the last week of life. Patients experienced an average number of 6.42 symptoms. The prevalence of various types of symptoms differed significantly among the four diagnostic groups. Overall, our study patients stayed in the hospital for a median of six days during their last four weeks of life. Seventy-two patients (48%) stayed at home for at least one day and only half of those received community-based healthcare. CONCLUSIONS: The study provides a wide-ranging overview of current end-of-life care practices in a real-life setting of different healthcare providers. The inclusion of patients with all major diagnoses leading to disease- and prematurity-related childhood deaths, as well as comparisons across the diagnostic groups, provides additional insight and understanding for healthcare professionals. The provision of specialised palliative and end-of-life care services in Switzerland, including the capacity of community healthcare services, need to be expanded to meet the specific needs of seriously ill children and their families.

M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis.

INTRODUCTION: The pattern-recognition molecule M-ficolin is synthesized by monocytes and neutrophils. M-ficolin activates the complement system in a manner similar to mannan-binding lectin (MBL), but little is known about its role in host defense. Neonates are highly vulnerable to bacterial sepsis, in particular, due to their decreased phagocytic function. RESULTS: M-ficolin cord blood concentration was positively correlated with the absolute phagocyte count (ρ 0.51, P < 0.001) and with immature/total neutrophil ratio (ρ 0.34, P < 0.001). When comparing infants with sepsis and controls, a high M-ficolin cord blood concentration (>1,000 ng/ml) was associated with early-onset sepsis (EOS) (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003). Experimental exposure of phagocytes isolated from adult donors to Escherichia coli resulted in a significant time- and dose-dependent release of M-ficolin. DISCUSSION: In conclusion, M-ficolin concentrations were related to circulating phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M-ficolin release by phagocytes. Future studies should investigate whether M-ficolin may be used as a marker of neutrophil activation during invasive infections. METHODS: We investigated M-ficolin in 47 infants with culture-positive sepsis during the first 30 days of life (13 with EOS and in 94 matched controls. M-ficolin was measured in cord blood using time-resolved immunofluorometric assay (TRIFMA). Multivariate logistic regression was performed.

Rapid assessment of cerebral autoregulation by near-infrared spectroscopy and a single dose of phenylephrine.

Rapid bedside determination of cerebral blood pressure autoregulation (AR) may improve clinical utility. We tested the hypothesis that cerebral Hb oxygenation (HbDiff) and cerebral Hb volume (HbTotal) measured by near-infrared spectroscopy (NIRS) would correlate with cerebral blood flow (CBF) after single dose phenylephrine (PE). Critically ill patients requiring artificial ventilation and arterial lines were eligible. During rapid blood pressure rise induced by i.v. PE bolus, ΔHbDiff and ΔHbTotal were calculated by subtracting values at baseline (normotension) from values at peak blood pressure elevation (hypertension). With the aid of NIRS and bolus injection of indocyanine green, relative measures of CBF, called blood flow index (BFI), were determined during normotension and during hypertension. BFI during hypertension was expressed as percentage from BFI during normotension (BFI%). Autoregulation indices (ARIs) were calculated by dividing BFI%, ΔHbDiff, and ΔHbTotal by the concomitant change in blood pressure. In 24 patients (11 newborns and 13 children), significant correlations between BFI% and ΔHbDiff (or ΔHbTotal) were found. In addition, the associations between Hb-based ARI and BFI%-based ARI were significant with correlation coefficients of 0.73 (or 0.72). Rapid determination of dynamic AR with the aid of cerebral Hb signals and PE bolus seems to be reliable.

Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis.

BACKGROUND. The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis. METHODS. This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed. RESULTS. Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P = .005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P = .084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P = .017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P = .037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P = .036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P = .042). The concentrations of all the lectin pathway proteins increased with gestational age (P < .01). CONCLUSIONS. These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.

Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children.

BACKGROUND: Daily evaluation of multiple organ dysfunction syndrome has been performed in critically ill adults. We evaluated the clinical course of multiple organ dysfunction over time in critically ill children using the Pediatric Logistic Organ Dysfunction (PELOD) score and determined the optimal days for measuring scores. METHODS: We prospectively measured daily PELOD scores and calculated the change in scores over time for 1806 consecutive patients admitted to seven pediatric intensive care units (PICUs) between September 1998 and February 2000. To study the relationship between daily scores and mortality in the PICU, we evaluated changes in daily scores during the first four days; the mean rate of change in scores during the entire PICU stay between survivors and nonsurvivors; and Cox survival analyses using a change in PELOD score as a time-dependent covariate to determine the optimal days for measuring daily scores. RESULTS: The overall mortality among the 1806 patients was 6.4%. A high PELOD score (>or=20 points) on day 1 was associated with an odds ratio (OR) for death of 40.7 (95% confidence interval [CI] 20.3-81.4); a medium score (10-19 points) on day 1 was associated with an OR for death of 4.2 (95% CI 2.0-8.7). Mortality was 50% when a high score on day 1 increased on day 2. The course of daily PELOD scores differed between survivors and nonsurvivors. A set of seven days (days 1, 2, 5, 8, 12, 16 and 18) was identified as the optimal period for measurement of daily PELOD scores. INTERPRETATION: PELOD scores indicating a worsening condition or no improvement over time were indicators of a poor prognosis in the PICU. A set of seven days for measurement of the PELOD score during the PICU stay provided optimal information on the progression of multiple-organ dysfunction syndrome in critically ill children.

Patent arterial duct, bottle-meal, and fatal myocardial ischaemia.

A patent arterial duct in pre-term neonates is frequent. Systemic complications consecutive to left-to-right shunting are well known but fatal myocardial ischaemia has not been described till now. The presented premature baby died from catecholamine refractory cardiogenic shock. Autoptic examination revealed acute ischaemic changes predominantly in the inner third of myocardium, speaking of coronary hypoperfusion due to a steal phenomenon secondary to the patent arterial duct.

Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia.

Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.

Perinatal infratentorial haemorrhage: a rare but possibly life-threatening condition.

BACKGROUND: Perinatal infratentorial haemorrhage (PIH) is a rare birth complication associated with abnormal labour. CASE PRESENTATION: A baby boy was born by vacuum extraction at 41 weeks' gestational age. The pregnancy was uneventful and Apgar scores were 3/6/9. Following initial resuscitation, insufficient and irregular breathing, non-reactive pupils and absence of spontaneous movements were noted. A diagnosis of perinatal asphyxia with hypoxic-ischaemic encephalopathy (HIE) was considered. Therapeutic hypothermia (TH) for 72 hours was initiated. Cerebral ultrasound showed only a mildly hyperechogenic periventricular substance. A brain MRI on the fourth day of life revealed a subdural haemorrhage in the posterior fossa with compression of the fourth ventricle. CONCLUSION: PIH is an important differential diagnosis to HIE that can be missed with ultrasound. PIH is a treatable condition but may be aggravated by TH. Therefore, in neonates at risk for PIH, a more detailed ultrasound protocol or brain MRI should be considered early.

Decreased oxygen saturation levels in neonates with transposition of great arteries: Impact on appearance of cerebral veins in susceptibility-weighted imaging.

Purpose of this study was to investigate a potential correlation between the pattern of cerebral veins (CV) on susceptibility-weighted imaging (SWI) and blood oxygen saturation, as well as preoperative brain injury, in neonates with transposition of the great arteries (TGA). Eleven neonates with TGA underwent MRI preoperatively, including SWI, T1- and T2-weighted scans. Images were retrospectively evaluated and appearance of CV was graded from 0 (normal appearance) to 3 (severe prominent appearance). White matter injuries (WMI) and strokes were analysed. Results were correlated with preductal arterial oxygen saturation. As findings one subject showed a normal CV appearance (grade 0) whereas 10 showed pathological prominent CV (grades 1-3); median 2. Mean oxygen saturation ranged between 67.5% and 89.0% (median 81.0%). CV grade and mean oxygen saturation correlated significantly (p = 0.011). WMI were absent in 5 cases, mild in 4, and moderate in 2 cases. We conclude, that SWI has the potential to be used to estimate the current hypoxic burden on brain tissue in TGA newborns by assessing the prominence of the CV.

The value of susceptibility-weighted imaging (SWI) in patients with non-neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: In susceptibility-weighted imaging (SWI) in the normal brain, cortical veins appear hypointense due to paramagnetic properties of deoxy-hemoglobin. Global cerebral anoxia decreases cerebral oxygen metabolism, thereby increasing oxy-hemoglobin levels in cerebral veins. We hypothesized that a lower cerebral oxygen extraction fraction in comatose patients with non-neonatal hypoxic-ischemic encephalopathy (IHE) produces a pattern of global rarefied or pseudo-diminished cortical veins due to higher oxy-hemoglobin. PURPOSE: (1) To investigate the topographic relationship between susceptibility effects in cortical veins and related diffusion restrictions on diffusion-weighted imaging (DWI) in patients with IHE. (2) To relate imaging findings to patterns of altered resting activity on surface EEG. METHODS: Twenty-three IHE patients underwent MRI. EEG patterns were used to classify the depth of coma. Regional vs. global susceptibility changes on SWI and patterns of DWI restrictions were compared with the depth of coma. RESULTS: All patients exhibited areas of restricted cortical diffusion and SWI abnormalities. The dominant DWI restrictions encompassed widespread areas along the precuneus, frontal and parietal association cortices and basal ganglia. For SWI, nineteen patients had generalized bi-hemispherical patterns, the EEG patterns correlated with coma grades III-V. Four patients had focal decreases of deoxy-hemoglobin following DWI restrictions; associated with normal EEGs. CONCLUSION: Focal patterns of diamagnetic effects on SWI according to relative decreases in deoxy-hemoglobin due to reduced metabolic demand are associated with normal EEG in IHE patients. Global patterns indicated increased depth of coma and widespread cortical damage. CLINICAL RELEVANCE: The results indicate a potential diagnostic value of SWI in patients with IHE.

Procedural factors associated with early postoperative arrhythmias after repair of congenital heart defects.

OBJECTIVES: Early postoperative arrhythmias frequently are a relevant problem in the early postoperative management after surgical intervention for congenital heart disease. Few data are available indicating risk factors for their occurrence. The hypothesis was tested that factors closely related to the surgical procedure itself were associated with a higher incidence of arrhythmias early in the postoperative course after repair of congenital heart disease. METHODS: All consecutive patients undergoing 1 of 3 well-defined surgical procedures were prospectively evaluated for the occurrence of arrhythmias during the entire postoperative hospital stay by means of continuous electrocardiographic monitoring in the intensive care unit and use of 24-hour Holter monitors. Patients examined were those undergoing transatrial closure of a ventricular septal defect, repair of complete atrioventricular canal, and tetralogy of Fallot. The relation between procedural variables and the occurrence of arrhythmias was independently evaluated for each of these 3 heart defects. RESULTS: Early postoperative arrhythmias occurred in 30% of patients with ventricular septal defect (n = 75), 35% of patients with tetralogy of Fallot (n = 52), and 47% of patients with atrioventricular canal (n = 45). Patients with arrhythmias tended to be younger (significant only in the ventricular septal defect group). In all 3 patient groups, there was a significant correlation between incidence of arrhythmias and longer extracorporeal bypass time (P <.05) and longer aortic crossclamp time (P <.01), as well as with higher maximum postoperative troponin serum levels (P <.01). In patients with atrioventricular canal, there was a significant relation between hemodynamically incomplete surgical results and the occurrence of arrhythmias (P <.01). CONCLUSIONS: The occurrence of early postoperative arrhythmias after repair of congenital heart disease was significantly associated with procedure-related risk factors in each of 3 independent patient groups undergoing well-defined surgical procedures.

Reproducibility of the blood flow index as noninvasive, bedside estimation of cerebral blood flow.

OBJECTIVE: To investigate the feasibility and reproducibility of the blood flow index (BFI) method for measuring cerebral blood flow. DESIGN AND SETTING: Prospective functional study in pediatric intensive care. PATIENTS AND PARTICIPANTS: 14 consecutive patients with median age of 2 months (range 1 days-11 years) requiring artificial ventilation, invasive arterial blood pressure monitoring, and central venous access. INTERVENTIONS: The first passage of an intravenous indocyanine green (ICG) bolus through the cerebral vasculature was monitored by noninvasive near-infrared spectroscopy. BFI was calculated by dividing maximal ICG absorption change by rise time. Reproducibility was evaluated by six ICG injections at 5-min intervals. RESULTS: Of all ICG injections 6% were canceled, and 4% were eliminated due to injection failures. Median BFI of 17 reproducibility determinations was 71 (range 12-213) and median coefficient of variation (CV) of BFI was 10% (4.9-18.5). The quantity of ICG bolus did not affect the CV (0.1 vs. 0.3 mg ICG/kg). Eight reproducibility tests in patients after cardiac surgery had smaller CV than the others, and the eight in newborns had higher CV than in older children. Patient parameters such as arterial blood pressure, endtidal CO(2), and percutaneous oxygen saturation were stable and showed CV below 2% during reproducibility determination. CONCLUSIONS: The BFI method allows rapid and repeated measurements of CBF with good feasibility and reproducibility. As a relative but not absolute measure of CBF, BFI seems to be suited for clinical evaluation of intraindividual CBF changes during determination of cerebrovascular reactivities or during therapeutic interventions.

Respiratory distress syndrome in near-term babies after caesarean section.

OBJECTIVE: Severe respiratory distress syndrome (RDS) caused by surfactant deficiency is described not only in preterm infants but also in (near-) term babies after caesarean section (CS), especially when carried out before the onset of labour. The aim of the present study was to document the severity of this theoretically avoidable entity in order to improve obstetric and perinatal care. PATIENTS: All neonates admitted to the paediatric intensive care unit of the University Hospital of Bern between 1988 and 2000 with RDS on the basis of hyaline membrane disease (HMD) needing mechanical ventilation (MV) after CS and with a birthweight > or = 2500 g were analysed. HMD was diagnosed when respiratory distress and the typical radiological signs were present. Patients were grouped into elective CS before onset of labour and before rupture of membranes (group 1, n = 34) and patients delivered by emergency CS or CS after onset of labour or rupture of membranes (group 2, n = 22). Analysed indices for severity of illness were duration of stay in intensive care unit and MV, ventilation mode, worst oxygenation index (OI), presence of pulmonary air leak, and systemic hypotension. RESULTS: Mean gestational age (GA) was 37 2/7 weeks in group 1 and 36 2/7 weeks in group 2; no patient had a GA of > or = 39 0/7 weeks. Duration of MV was 4.4 days in group 1 and 3.9 days in group 2. Thirteen patients (38%) of group 1 and 7 (32%) of group 2 had to be managed by rescue high-frequency ventilation. A total of 7 patients had an OI>40. Eight patients (24%) in group 1 and 4 (18%) in group 2 developed a pulmonary air leak. Fourteen neonates (41%) in group 1 had to be supported by catecholamines versus 5 (22%) in group 2. There was one death in group 1. CONCLUSION: Severe RDS on the basis of HMD can also occur in near-term babies after CS; even a fatal outcome can not be excluded. The severity of illness in elective CS without labour may be quite high and is comparable to newborns delivered by CS (after onset of labour and/or rupture of the membranes) who were 1 week younger. No case of HMD was found in our population when CS was carried out after completion of 39 post-menstrual weeks of gestation.

Early postoperative arrhythmias after open-heart procedures in children with congenital heart disease.

OBJECTIVE: Evaluation of occurrence, clinical course, necessity of treatment, and outcome of early postoperative cardiac arrhythmias after open-heart surgery. DESIGN: Prospective study. SETTING: Tertiary pediatric intensive care and pediatric cardiology unit. PATIENTS: All consecutive pediatric patients undergoing cardiac surgery on cardiopulmonary bypass were studied for the occurrence of cardiac arrhythmias during the whole perioperative hospital stay. Measurements: All patients had continuous electrocardiographic monitoring (with memory function) during the whole intensive care stay. A 24-hr Holter recording was done thereafter in patients with arrhythmias. RESULTS: Of 310 patients studied, 83 (27%) had postoperative arrhythmias. The occurrence rate was not different whether surgical access was by atriotomy or ventriculotomy (26% vs. 28%, respectively). Infants (39%) and cyanotic patients (36%) had a higher occurrence rate of arrhythmias (p <.05). Arrhythmias were more common after prolonged cardiopulmonary bypass time and with higher postoperative maximum troponin serum levels. In addition, patients with hemodynamically significant residual findings after correction had an increased occurrence rate of arrhythmias (18 of 43; 42%; p <.01). Of the 83 children with arrhythmias, 53 (64%) required specific antiarrhythmic treatment. The use of antiarrhythmic drugs was required in only 7 of these patients. Only one patient (1.2% of patients with arrhythmias) died from arrhythmia. No major complications resulting from arrhythmias occurred during the postoperative clinical course in the other patients. CONCLUSIONS: Although they occur frequently, postoperative arrhythmias after open-heart procedures in children are associated with low morbidity and mortality.

Feasibility and safety of passive cooling in a cohort of asphyxiated newborn infants.

OBJECTIVE: Therapeutic hypothermia has become a standard neuroprotective treatment in term newborn infants following perinatal asphyxia. Active cooling with whole body surface or head cooling is complex, expensive and often associated with initial hypothermic overshoot. We speculated that passive cooling might suffice to induce and maintain hypothermia. METHODS: We analysed 18 asphyxiated term newborns treated with hypothermia in three tertiary neonatal and paediatric intensive care units. Target temperatures of 33.5 °C or 33.0 °C were induced and maintained by turning off the heating system of the open neonatal care unit and by using analgesics and sedatives. We compared our results with matching published data from the hypothermia trial of the National Institute of Child Health and Human Development (NICHD) neonatal research network. RESULTS: Four infants required no active cooling at all during the whole cooling period. The other 14 infants had passive cooling during 85% of the total cooling time, and active cooling with ice packs in 15% of the total cooling time. Overshoot was smaller in the present study than in the NICHD study. CONCLUSION: Passive cooling for asphyxiated newborns appears to be feasible for induction and maintenance of hypothermia with a lower risk of overshoot.

Analgesia and sedation for painful interventions in children and adolescents.

BACKGROUND: Painful procedures on children and adolescents often have to be performed with the aid of analgesia and sedation in order to prevent pain and emotional distress. Moreover, many procedures can be performed more rapidly and more effectively in a relaxed patient. Because the combination of analgesia and sedation can cause serious or even life-threatening complications, it must be accompanied by the same safety precautions as a general anesthetic. METHODS: Selective review of the literature. RESULTS: A high level of safety can be achieved by adherence to the published guidelines of the societies for anesthesiology and pediatrics. The depth of sedation during procedures performed under combined analgesia and sedation is often equivalent to that resulting from general anesthesia. Therefore, in order to avoid serious complications, combined analgesia and sedation should only be administered by physicians trained in pediatric anesthesia or pediatric critical care. This is particularly so when propofol is used, because it has a narrow therapeutic range and can cause cardiorespiratory respiratory problems without warning. As long as the appropriate safety precautions are followed, non-anesthesiologists can also administer propofol in combination with an analgesic, such as ketamine, to children and adolescents. CONCLUSION: In children and adolescents, the combination of analgesia and sedation can prevent the emotional trauma that would result from a painful procedure, while often enhancing the quality of the procedure itself. This method should be considered a variant of general anesthesia. Accordingly, any non-anesthesiologist employing this method must be as well versed as an anesthesiologist in the management of its specific side effects and complications.

Hemostasis management in pediatric mechanical circulatory support.

In a 9-year-old boy, bridging to transplantation was successful with an external biventricular device, the Berlin Heart Excor (Berlin Heart, Berlin, Germany), during a 7-month period. Main long-term complications consisted of infection and hypercoagulability with clotting inside the chambers necessitating six pump exchanges, but without thromboembolic events. This report reviews hemostasis monitoring and management of long-term mechanical circulatory support.

Dynamic cerebral autoregulatory response to blood pressure rise measured by near-infrared spectroscopy and intracranial pressure.

OBJECTIVES: Noninvasive near-infrared spectroscopy (NIRS) continuously monitors changes in cerebral hemoglobin saturation (Hb(Diff) ) and content (Hb(Total)). It may allow visualization of the dynamic cerebral autoregulatory response to rapid blood pressure increases without relevant contamination of the NIRS signal from extracerebral hemoglobin. DESIGN: Prospective cohort study. SETTINGS: Multidisciplinary pediatric intensive care unit. PATIENTS: Six consecutive children in coma due to severe encephalopathy (head trauma, five patients; mumps encephalitis, one patient) requiring artificial ventilation, invasive arterial blood, and intracranial pressure monitoring. INTERVENTIONS: Frontotemporal recording of Hb(Diff) and Hb(Total) while rapidly elevating blood pressure by bolus injection of phenylephrine. MEASUREMENTS AND RESULTS: During an increase of blood pressure of 13 +/- 1 mm Hg with a "rise time" of 16 +/- 1 secs (mean of a total of 31 injections +/- sem), a significant linear correlation was found between Hb(Diff) and intracranial pressure signals (mean coefficient, 0.46 +/- 0.04) but not between Hb(Total) and intracranial pressure. Three response patterns were observed. First, Hb(Diff) and intracranial pressure reduction, corresponding with vasoconstriction and normal dynamic autoregulation (n = 3); second, Hb(Diff) and intracranial pressure increase, corresponding with persistent vasodilation and abolished autoregulation (n = 11); and third, transient Hb(Diff) and intracranial pressure increase followed by a decrease at peak blood pressure elevation, called impaired autoregulation (n = 15). In one patient with fatal brain swelling, phenylephrine testing showed no effect on NIRS signals (n = 2). Furthermore, there were significant correlations between 31 pooled interindividual pairs of Hb(Diff) changes with intracranial pressure changes (values at baseline averaged over 60 secs subtracted from values at peak blood pressure elevation averaged over 5 secs), with a correlation coefficient of .82 (p <.001). CONCLUSIONS: NIRS represents a new and promising technique for bedside determination of dynamic cerebral autoregulation during acutely induced blood pressure rise. The significant correlations found between NIRS signals and intracranial pressure excluded relevant extracerebral contamination of the NIRS signals. In our patients with severe encephalopathy, dynamic autoregulation was in most instances not fully preserved.

Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats.

Hypothermia may be an ideal neuroprotective intervention in hypoxic-ischemic encephalopathy after perinatal asphyxia. The present study describes the long-term effects of prolonged resuscitative whole-body hypothermia initiated 2 h after hypoxic-ischemic injury on brain morphology and neuropsychological behavior in 7-d-old rats. After right common carotid artery ligation and exposure to hypoxia of 8% O(2) for 105 min, 10 animals were kept normothermic at 37 degrees C and 10 animals were cooled to 30 degrees C rectal temperature for 26 h, starting 2 h after the hypoxic-ischemic insult. All hypoxic-ischemic animals were gavage fed to guarantee long-term survival. Neuroprotection was evaluated by magnetic resonance imaging and behavioral testing. Hypothermia significantly reduced the final size of cerebral infarction by 23% at 6 wk after the insult. The most extended tissue rescue was found in the hippocampus (21%, p = 0.031), followed by the striatum (13%, p = 0.143) and the cortex (11%, p = 0.160). Cooling salvaged spatial memory deficits verified at 5 wk of recovery with Morris Water Maze test; whereas circling abnormalities after apomorphine injection and sensory motor dysfunctions on rotating treadmill improved, yet did not reach statistical significance. When compared with controls, hypoxic-ischemic animals performed worse in all behavioral tests. Hypothermia did not influence functional outcome in controls. Significant correlations between behavioral performance and corresponding regional brain volumes were found. We conclude that 26 h of mild to moderate resuscitative hypothermia leads not only to brain tissue rescue, but most important to long-lasting behavioral improvement throughout brain maturation despite severity of injury and delayed onset of cooling.