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OBJECTIVE: This purpose of this study was to identify clinicians' perceptions of the benefits of aquatic therapy for young children with autism. METHODS: Eighteen aquatic occupational therapists treating young children with autism responded to a survey soliciting their opinions on changes in skill performance resulting from aquatic therapy. RESULTS: A majority of clinicians reported a substantial increase in swim skills, attention,muscle strength, balance, tolerating touch, initiating/maintaining eye contact, and water safety. CONCLUSION: The impairments, activity limitations, and participation restrictions seen in children with autism can be wide-ranging and outcomes can be difficult to operationally define and measure. In this preliminary study, clinicians identified the areas they perceived as improving as a result of aquatic therapy. This information could help narrow the field of likely outcomes as a first step toward studies of the effectiveness of aquatic therapy for children with autism. [ABSTRACT FROM AUTHOR]

The study investigated the safety and efficacy of two antithrombin III (ATIII) products in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) by performing a retrospective analysis of patients who received either recombinant ATIII (rATIII) or human-derived ATIII (hATIII). Twenty-two patients were included in the study from January 2014 to September 2015 and all received unfractionated heparin (UFH) as anticoagulation during ECMO. In total, 86 doses of ATIII were included in the analysis in which 37 doses (43%) were rATIII and 49 doses (57%) were hATIII. Unfractionated heparin rates were also evaluated for all cases (n = 86) at 24 hours post-ATIII supplementation. The UFH rate decreased after the administration of both types of ATIII. However, neither the reduction in UFH rate between the two ATIII products (p = 0.52) nor the UFH rates pre- and post-ATIII supplementation at 24 hours (p = 0.08) reached statistical significance. There was a significant difference in cost favoring the rATIII product (p < 0.0001). An ad-hoc estimation of waste associated with ATIII supplementation showed >$100,000 in financial loss of unused drug. Future studies are warranted to evaluate the efficacy of ATIII supplementation in pediatric ECMO.

There is growing recognition that variation in animal personality traits can influence survival and reproduction rates, and consequently may be important for wildlife population dynamics. Despite this, the integration of personality research into conservation has remained uncommon. Alongside the establishment of personality as an important source of individual variation has come an increasing interest in factors affecting the development of personality. Recent work indicates the early environment, including natal nutrition, may play a stronger role in the development of personality than previously thought. In this study, we investigated the importance of three personality metrics (activity, boldness and acclimation time) for estimating survival of a threatened species, the hihi (Notiomystis cincta), and evaluated the influence of early natal nutrition on those metrics. Our results showed that boldness (as measured from a one-off cage test) had a positive effect on the probability of juvenile hihi surviving to adulthood. There was also a tendency for juveniles that received carotenoid supplementation in the nest to be bolder than those that did not, suggesting that the early environment had some influence on the expression of boldness in juvenile hihi. Linking the development of personality traits with ultimate effects on vital rates may benefit conservation management, as it could enable developmentally targeted management interventions. To our knowledge, this study is the first to identify potential linkages between early natal nutrition, personality and fitness in a wild-living population. This article is part of the theme issue 'Linking behaviour to dynamics of populations and communities: application of novel approaches in behavioural ecology to conservation'.

Purpose: Anti- N -methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series., Methods: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies. The literature search was conducted using the terms NMDA, anti-NMDA, Anti- N -methyl-d-aspartate, pediatric encephalitis, and anti-NMDAR and included articles published between 2005 and May 1, 2016., Results: Forty-eight references met inclusion criteria accounting for 373 cases. For first-line treatments, 335 (89.8%) received high-dose corticosteroids, 296 received intravenous immunoglobulin (79.3%), and 116 (31%) received therapeutic plasma exchange. In these, 187 children (50.1%) had a full recovery with only minor deficits, 174 patients (46.7%) had partial recovery with major deficits, and 12 children died. In addition, 14 patients were reported to require mechanical ventilation., Conclusion: Anti-NMDA encephalitis is a formidable disease with great variation in clinical presentation and response to treatment. With early recognition of this second most common cause of pediatric encephalitis, a multidisciplinary approach by physicians may provide earlier access to first- and second-line therapies. Future studies are needed to examine the efficacy of these current therapeutic strategies on long-term morbidity.

Objective  Congenital anomalies of the kidney and urinary tract constitute up to 30% of anomalies identified in the neonatal period. In utero oligohydramnios is often associated with pulmonary hypoplasia and respiratory failure in the neonate who may not be responsive to mechanical ventilation. Placement of these neonates on extracorporeal membrane oxygenation (ECMO) remains controversial and is considered in most centers to be a relative contraindication. The objective of this study is to use the Extracorporeal Life Support Organization (ELSO) database to describe the outcomes and complications of patients with congenital renal and urogenital anomalies with pulmonary hypoplasia who underwent ECMO in the neonatal period. Data Sources  Data from the ELSO registry were retrospectively reviewed for all patients with congenital renal and urogenital anomalies with pulmonary hypoplasia treated with ECMO support between 1990 and November 2014 using ICD-9 diagnosis codes. Data Synthesis  We identified 45 patients. The average age of the patient at the time of ECMO was 1.7 days (range: 0-14 days) and weight was 3.1 kg (interquartile range [IQR]: 2.5-3.3). Patients spent an average of 162 hours on ECMO (IQR: 81-207). The majority of patients were managed with venoarterial ECMO (60%), and the overall survival of this cohort was 42%. Survivors had higher weights (3.4 vs. 2.8 kg; p  < 0.019) and were more likely to be male (90 vs. 44%; p  < 0.002). Patients with obstructive urogenital lesions had an overall survival of 71 versus 16.6% in patients with a primary intrinsic renal diagnosis ( p  = 0.004). Renal replacement therapy was required in 51% of the patients during their ECMO support. Conclusion  Neonates with renal or urogenital disease and pulmonary hypoplasia have an overall survival rate of 42%. Patients with a diagnosis of urogenital obstruction have much more favorable outcomes when compared with those with intrinsic renal disease such as polycystic kidney disease.

Background: High-flow nasal cannula (HFNC) is increasingly utilized in pediatrics, delivering humidified air and oxygen for respiratory conditions causing hypoxia and distress. In the neonatal ICU, it has been associated with better tolerance, lower complications, and lower cost. Few data exist regarding indications for use and the epidemiology of disease/pathology that warrants HFNC in the pediatric ICU., Methods: This study is a retrospective cohort study of patients admitted to a tertiary children's hospital pediatric ICU and placed on HFNC from October 1, 2011 to October 31, 2013. Descriptive statistics were used to describe demographics and utilization data. t test comparisons were used for comparison data., Results: Over the enrollment study period, 620 subjects with HFNC were managed, which represented 27% of total ICU admissions. The average age was 3.74 y (range 0-18.1 y), and subjects were 44% female and 65% African American. Reported primary indications for the utilization of HFNC were status asthmaticus (24%), status asthmaticus with pneumonia (17%), and bronchiolitis (16%). Of the subjects admitted with a primary diagnosis of status asthmaticus, 41% required management with terbutaline. Respiratory viral infections were detected by polymerase chain reaction in 334 subjects managed with HFNC (53.8%) and included 260 subjects testing positive for rhinovirus/enterovirus. When compared with all other respiratory viral illness, subjects with rhinovirus/enterovirus required a higher peak flow (14.9 L vs 13.1 L, P = .01); however, this was an older population, and peak oxygen concentration did not differ between the 2 groups (49.8% vs 47.1%, P = .25). HFNC was used as postextubation support in 16% of the subjects. Of the 63 subjects with congenital heart disease, 92% of the utilization was postextubation., Conclusions: HFNC was utilized in 27% of all pediatric ICU admissions for a wide range of indications. Development of protocols for the initiation, escalation, and weaning of HFNC would optimize the utilization., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

Objectives: To examine the impact of an ICU bundle on delirium screening and prevalence and describe characteristics of delirium cases., Design: Quality improvement project with prospective observational analysis., Setting: Nineteen-bed PICU in an urban academic medical center., Patients: All consecutive patients admitted from December 1, 2013, to September 30, 2015., Interventions: A multidisciplinary team implemented an ICU bundle consisting of three clinical protocols: delirium, sedation, and early mobilization using the Plan-Do-Study-Act cycles as part of a quality improvement project. The delirium protocol implemented in December 2013 consisted of universal screening with the Cornell Assessment of Pediatric Delirium revised instrument, prevention and treatment strategies, and case conferences. The sedation protocol and early mobilization protocol were implemented in October 2014 and June 2015, respectively., Measurements and Main Results: One thousand eight hundred seventy-five patients were screened using the Cornell Assessment of Pediatric Delirium revised tool. One hundred forty patients (17%) had delirium (having Cornell Assessment of Pediatric Delirium revised scores ≥ 9 for 48 hr or longer). Seventy-four percent of delirium positive patients were mechanically ventilated of which 46% were younger than 12 months and 59% had baseline developmental delays. Forty-one patients had emerging delirium (having one Cornell Assessment of Pediatric Delirium revised score ≥ 9). Statistical process control was used to evaluate the impact of three ICU bundle process changes on monthly delirium rates over a 22-month period. The delirium rate decreased with the implementation of each phase of the ICU bundle. Ten months after the delirium protocol was implemented, the mean delirium rate was 19.3%; after the sedation protocol and early mobilization protocols were implemented, the mean delirium rate was 11.84%., Conclusions: Implementation of an ICU bundle along with staff education and case conferences is effective for improving delirium screening, detection, and treatment and is associated with decreased delirium prevalence.

Objective: To compare withdrawal symptoms among pediatric intensive care patients receiving clonidine to those not receiving clonidine while being weaned from long-term dexmedetomidine., Methods: This retrospective analysis evaluated Withdrawal Assessment Tool-1 (WAT-1) scores and hemodynamic parameters in pediatric patients on dexmedetomidine for 5 days or longer between January 1, 2009, and December 31, 2012. The primary objective was to compare withdrawal symptoms based on the number of elevated WAT-1 scores among patients on clonidine to those not on clonidine, while being weaned from long-term dexmedetomidine. The secondary objective was to describe withdrawal symptoms associated with long-term dexmedetomidine use., Results: Nineteen patients (median age, 1.5 years; interquartile range [IQR], 0.67-3.3) received 20 treatment courses of dexmedetomidine for at least 5 days. Clonidine was received by patients during 12 of the treatment courses. The patients in the clonidine group had an average of 0.8 (range, 0-6) elevated WAT-1 scores 24 hours post wean compared to an average of 3.2 (0-8) elevated WAT-1 scores in the no clonidine group (p = 0.49). There were no significant difierences between prewean and postwean systolic or diastolic blood pressures among the 2 groups. The average heart rate during the postwean period was 112 beats per minute (bpm) (range, 88.5-151.5) in the clonidine group compared to 138.4 bpm (range, 117.8-168.3) in the no clonidine group (p = 0.003). In the clonidine group, the mean change in heart rate postwean compared to prewean was an increase of 3.6 bpm (range, -39.6 to 47.5), compared to a mean increase of 29.9 bpm (range, 5.5-74.7) in the no clonidine group (p = 0.042)., Conclusions: There was no difierence in WAT-1 scores between groups, with the clonidine group displaying a trend towards fewer elevated WAT-1 scores during the 24 hours post dexmedetomidine wean. Patients who received clonidine had significantly lower heart rates than the no clonidine group.

Dietary access to carotenoids is expected to determine the strength of carotenoid-based signal expression and potentially to maintain signal honesty. Species that display carotenoid-based yellow, orange, or red plumage are therefore expected to forage selectively for carotenoid-rich foods when they are depositing these pigments during molt, but whether they actually do so is unknown. We set out to address this in the hihi ( Notiomystis cincta ), a New Zealand passerine where males, but not females, display yellow carotenoid-based plumage. We measured circulating carotenoid concentrations in male and female hihi during breeding and molt, determined the nutritional content of common foods in the hihi diet, and conducted feeding observations of male and female hihi during molt. We found that although male and female hihi do not differ significantly in plasma carotenoid concentration, male hihi have a greater proportion of carotenoid-rich foods in their diet than do females. This is a consequence of a greater fruit and lower invertebrate intake than females and an avoidance of low-carotenoid content fruit. By combining behavioral observations with quantification of circulating carotenoids, we present evidence that colorful birds forage to maximize carotenoid intake, a conclusion we would not have drawn had we examined plasma carotenoids alone.

Why do some bird species show dramatic sexual dichromatism in their plumage? Sexual selection is the most common answer to this question. However, other competing explanations mean it is unwise to assume that all sexual dichromatism has evolved by this mechanism. Even if sexual selection is involved, further work is necessary to determine whether dichromatism results from competition amongst rival males, or by female choice for attractive traits, or both. Here, we test whether sexually dichromatic hihi (Notiomystis cincta) plumage is currently under sexual selection, with detailed behavioural and genetic analyses of a free-living island population. Bateman gradients measured for males and females reveal the potential for sexual selection, whilst selection gradients, relating reproductive success to specific colourful traits, show that there is stabilizing selection on white ear tuft length in males. By correlating colourful male plumage with different components of reproductive success, we show that properties of yellow plumage are most likely a product of male-male competition, whilst properties of the black and white plumage are an outcome of both male-male competition and female choice. Male plumage therefore potentially signals to multiple receivers (rival males and potential mates), and this may explain the multicoloured appearance of one of the most strikingly dichromatic species in New Zealand., (© 2014 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

It is well established that the expression of many ornamental traits is dependent on the current condition of the bearer. However, conditions experienced in early life are also known to be important for an individual's subsequent fitness and therefore, directly or indirectly, for the fitness of their mate. Specifically, a recent hypothesis suggests that sexually selected traits might be sensitive to conditions experienced during early-life development and thereby function as honest indicators of developmental history. Whether this applies to colourful male plumage, however, is largely unknown. We tested this idea with a field experiment by manipulating neonatal nutrition in a sexually dichromatic passerine, the hihi (Notymystis cincta). We found that carotenoid supplementation increased nestling plasma carotenoid concentration, which was in turn correlated with increased yellow saturation in male breeding plumage after moulting. We also found that the post-moult luminance (lightness) of the white ear-tufts tended to be reduced in males that had received an all-round nutritional supplement as nestlings. Black breeding plumage was not affected by neonatal nutritional treatment. Although the mechanisms that generate colourful plumage are evidently diverse, our results show that at least some parts of this display are accurate indicators of environmental conditions during development.

It has been my great fortune to have spent this past summer traveling across North America with my husband. We left our home state of New Hampshire in June and, in late July, arrived in the 49th state, Alaska, where we have settled in for the winter. From Manitoulin Island and the shores of Lake Huron to the Black Hills of South Dakota and on through the Canadian Rockies, we traveled through a number of North American Native communities. It is this experience and my recent introduction to Alaskan Native culture and peoples that are the impetus for this feature, where I will explore the historical and re-emerging use of art to promote health and healing in Native communities.

Objective: This purpose of this study was to identify clinicians' perceptions of the benefits of aquatic therapy for young children with autism., Methods: Eighteen aquatic occupational therapists treating young children with autism responded to a survey soliciting their opinions on changes in skill performance resulting from aquatic therapy., Results: A majority of clinicians reported a substantial increase in swim skills, attention,muscle strength, balance, tolerating touch, initiating/maintaining eye contact, and water safety., Conclusion: The impairments, activity limitations, and participation restrictions seen in children with autism can be wide-ranging and outcomes can be difficult to operationally define and measure. In this preliminary study, clinicians identified the areas they perceived as improving as a result of aquatic therapy. This information could help narrow the field of likely outcomes as a first step toward studies of the effectiveness of aquatic therapy for children with autism.

Purpose: We describe a pediatric patient with sickle cell disease and life-threatening acute chest syndrome who was successfully treated with venovenous extracorporeal membrane oxygenation (ECMO)., Patient and Methods: An 8-year-old boy with sickle cell disease presented with vaso-occlusive crisis, which progressed to fulminant acute chest syndrome requiring a partial exchange transfusion and mechanical ventilation. Despite very high ventilator settings and significant barotrauma, hypoxia persisted and circulatory failure occurred. He was then successfully treated with venovenous ECMO for 11 days. One month after decannulation he had a seizure associated with abnormalities on magnetic resonance images (MRIs). His disease has been managed with a chronic transfusion program since then. Follow-up after 5 years reveals normal pulmonary function tests, a normal magnetic resonance angiogram (MRA), and above-average cognitive skills., Conclusion: This is the first report of a pediatric patient with acute chest syndrome successfully managed with venovenous ECMO. His course was complicated by a seizure associated with MRI abnormalities, although the outcome has been excellent. This case suggests that treatment with venovenous ECMO should be strongly considered for sickle cell patients with life-threatening acute chest syndrome, despite maximal conventional support.

Objective: To study the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cerebral autoregulation in the newborn lamb., Design: Animal studies, using newborn lambs, with comparison of two randomized treatment groups., Subjects: Newborn lambs of mixed breed, 1 to 7 days of age, were randomized into two study groups: control animals, with jugular vein ligation but no ECMO (n = 6), and ECMO animals placed on venovenous ECMO (n = 6)., Setting: Laboratory animal facilities of the Department of Anesthesiology and Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD., Interventions: Animals were anesthetized with pentobarbital, intubated, and ventilated, and monitoring catheters were inserted. Control animals had their right jugular vein ligated, and a cerebral autoregulation curve was performed after 1 hr of stabilization. ECMO animals were placed on venovenous ECMO and after 1 hr of stabilization, they had a cerebral autoregulation curve performed. Cerebral autoregulation was examined by increasing intracranial pressure, thereby decreasing cerebral perfusion pressure. Intracranial pressure was increased by infusion of artificial cerebrospinal fluid into the lateral ventricle of the brain., Measurements and Main Results: Four ranges of cerebral perfusion pressure were evaluated: a) baseline (1 hr after initiation of bypass in venovenous ECMO or completion of surgery in controls); b) cerebral perfusion pressure of 55 to 40 mm Hg; c) cerebral perfusion pressure of 39 to 25 mm Hg; and d) cerebral perfusion pressure of < 25 mm Hg. Cerebral blood flow (radiolabeled microspheres), cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. In ECMO animals, cerebral blood flow (cerebral hemispheres) decreased from a baseline measurement of 46 +/- 9 (SD) mL/100 g/ min to 29 +/- 12 mL/100 g/min at a cerebral perfusion pressure of < 25 mm Hg. In the control group, cerebral blood flow was unchanged from baseline at any range of cerebral perfusion pressure. Cerebral oxygen consumption was unchanged from baseline as cerebral perfusion pressure decreased in either group. When cerebral oxygen consumption was compared between the two groups, it was lower in the ECMO group at baseline and at a cerebral perfusion pressure of < 25 mm Hg. At a cerebral perfusion pressure of < 25 mm Hg, cerebral blood flow, cerebral oxygen delivery, and metabolic rate were lower in the ECMO group than in the control group, and fractional oxygen extraction and cerebral vascular resistance were higher, indicating that autoregulation was impaired. There was no difference between blood flow in the right and left cerebral hemispheres when autoregulation was impaired in the ECMO animals., Conclusions: These findings indicate that cerebral autoregulation was altered in animals on venovenous ECMO, with cerebral blood flow decreasing at a cerebral perfusion pressure of < 25 mm Hg, compared with control animals which showed no changes at the same cerebral perfusion pressure. This disruption of cerebral autoregulation decreased cerebral oxygen metabolism despite an increased oxygen extraction in ECMO animals.

Objective: To determine factors associated with acute respiratory failure after bone marrow transplantation which can be identified before the onset of lung disease., Design: Population-based, retrospective study., Setting: A referral-based pediatric intensive care unit and bone marrow transplant center., Patients: Thirty-nine patients with lung disease (abnormal chest radiograph or a need for supplemental oxygen) were identified from a group of 318 pediatric bone marrow transplant patients from 1978 to 1988. Thirty-four of 39 patients with complete data were further classified into patients with mild lung disease (recovery without needing endotracheal intubation, n = 16) and patients with acute respiratory failure (requirement for endotracheal intubation, n = 18)., Interventions: Regression analyses were performed to define risk factors for development of respiratory failure (multivariate logistic regression) and for a shortened interval between the identification of lung disease and respiratory failure (Cox proportional hazards analysis)., Measurements and Main Results: Ninety-three percent (15/16) of patients with mild lung disease survived. Conversely, only 9% (2/23) of patients with respiratory failure survived. Predictors of respiratory failure included graft vs. host disease (odds ratio 28.3, 95% confidence interval 1.9-421, p = .015), a prelung disease (baseline) circulating creatinine concentration of > 1.5 mg/dL (> 132.6 mumol/L) (odds ratio 28.4, 95% confidence interval 1.4-577, p = .029), and male gender (odds ratio 14.6, 95% confidence interval 1-210, p = .049). Predictors of a shortened time to onset of respiratory failure included baseline serum creatinine value of > 1.5 mg/dL (> 132.6 mumol/L) (hazard ratio 6.2, 95% confidence interval 1.5-26.5, p = .013) and baseline total bilirubin concentration > 1.4 mg/dL (> 23.9 mumol/L) (hazard ratio 4.5, 95% confidence interval 0.98-20.7, p = .053). The median time to onset of respiratory failure was 4 days in patients with baseline creatinine values > or = 1.5 mg/dL (> 132.6 mumol/L) and 5 days in patients with baseline bilirubin concentrations > or = 1.4 mg/dL (> 23.9 mumol/L) vs. > 26 days in patients with creatinine < 1.5 mg/dL (< 132.6 mumol/L) and > 29 days in patients with bilirubin < 1.4 mg/dL (< 23.9 mumol/L) (Kaplan-Meier analysis)., Conclusions: Renal and liver dysfunction preceded clinical evidence of lung disease in bone marrow transplant patients who developed respiratory failure. Lung disease leading to respiratory failure and adult respiratory distress syndrome appears to develop as one component of the multiple organ failure syndrome in pediatric bone marrow transplant patients.

Objective: To study the effect of severe prolonged hypoxia combined with ligation of the carotid artery and jugular vein (simulating pre-extracorporeal membrane oxygenation [ECMO] events) on cerebral autoregulation in the newborn lamb., Design: Animal studies, using the newborn lamb, with comparison of two randomized treatment groups., Subjects: Newborn lambs of mixed breed, 1 to 7 days of age, were used for the study. Two groups of animals were studied: a normoxic control group (n = 7) and a hypoxic group (n = 8)., Setting: Work was conducted in the research laboratories of the Department of Anesthesiology, Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD., Interventions: Animals were anesthetized (pentobarbital), intubated, and mechanically ventilated. We examined the effect of prolonged severe hypoxia combined with carotid artery and jugular vein ligation on cerebral autoregulation during recovery from this insult. Control animals were maintained in a normoxic state (3 hrs) without carotid artery or jugular vein ligation. Hypoxic animals with carotid artery and jugular vein ligation were exposed to a 2-hr period of hypoxia (arterial oxygen saturation 44 +/- 14%; PaO2 30 +/- 3 torr [4 +/- 0.4 kPa]) followed by a 1-hr normoxic recovery period. Cerebral autoregulation was evaluated at the end of the 1-hr recovery period in hypoxic animals, and after 3 hrs of normoxia in control animals. Cerebral perfusion pressure was decreased by increasing intracranial pressure, with infusion of artificial cerebrospinal fluid into an intracranial pressure catheter in the lateral ventricle of the brain., Measurements: Studies were taken at four ranges of cerebral perfusion pressure: > 55 mm Hg; 55 to 40 mm Hg; 39 to 26 mm Hg; and < or = 25 mm Hg. Cerebral blood flow was measured using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period., Main Results: Two hours of severe hypoxia increased cerebral blood flow by 110%, whereas cerebral oxygen consumption was unchanged. In hypoxic animals, cerebral autoregulation was altered, with both cerebral blood flow and cerebral oxygen consumption decreasing at a cerebral perfusion pressure of 39 to 26 mm Hg compared with unchanged cerebral blood flow or cerebral oxygen consumption at a cerebral perfusion pressure of < or = 25 mm Hg in control animals. At the point of loss of autoregulation, significant right-to-left hemispheric cerebral blood flow changes occurred in hypoxic animals. In hypoxic animals, cerebellar cerebral blood flow changes were similar to those changes in the total cerebrum, while brain stem and caudate decreased cerebral blood flow only at a cerebral perfusion pressure of < or = 25 mm Hg., Conclusions: These findings indicate that cerebral autoregulation is disrupted during the recovery phase from an insult caused by prolonged, severe hypoxia with carotid artery and jugular vein ligation. This insult results in significant differences in right and left hemispheric cerebral blood flow rates when cerebral autoregulation is lost. If these results can be extrapolated to the human state, they may help to explain the role of pre-ECMO hypoxia combined with vessel ligation as a risk factor in cerebral injury in ECMO patients.

This study was designed to evaluate the effect of ligation of the carotid artery and/or jugular vein, after exposure to prolonged (4 hours) hypoxia, and the effect of acute normalization of PaO2 after prolonged hypoxia with vessel ligation, on the cerebral circulation. Twelve 1- to 7-day-old lambs were anesthetized with pentobarbital. Catheters were placed in the femoral artery and vein, left ventricle, lingual artery, and sagittal sinus. Cerebral blood flow (CBF) was determined using the radiolabeled microsphere technique. After baseline studies, the animals were made hypoxic with a nitrogen/air mixture, to lower PaO2 to 36 +/- 5 mm Hg for 4 hours, followed by 1 hour of normoxia. After four hours of hypoxia, studies were performed. The animals were divided into two groups to evaluate carotid artery and jugular vein ligation separately. In group I, the carotid artery was ligated first, with studies performed after 5 minutes; this was followed by ligation of the jugular vein, with studies after 5 minutes. In group II, the jugular vein was ligated first, with studies after 5 minutes; this was followed by ligation of the carotid artery, with studies after 5 minutes. With regard to physiological variables, there were no differences between the groups. CBF increased 106% (P < .001 compared with the baseline value) after 4 hours of hypoxia, maintaining cerebral oxygen consumption (CMRO2) and oxygen transport (OT) constant in both groups. Ligation of either the carotid artery or jugular vein after 4 hours of hypoxia, did not alter CBF responses to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine if the institution of extracorporeal membrane oxygenation (ECMO) alters the cerebrovascular response to changes in PaCO2., Design: Prospective, randomized, controlled animal trial., Subjects: Anesthetized 1- to 7-day-old lambs of mixed breed (n = 16)., Setting: University research laboratory., Interventions: The experimental group was placed on ECMO. Both experimental and control groups (n = 8) were exposed to three concentrations of PaCO2 (hypocarbia, normocarbia, and hypercarbia) by varying mechanical ventilation and by adding carbon dioxide to the ventilator gases., Measurements and Main Results: Cerebral blood flow was measured by the radiolabeled microsphere method. Arterial blood gases and sagittal sinus blood gases were drawn at the time of cerebral blood flow measurement so that cerebral metabolism, cerebral oxygen transport, and extraction could be calculated. In the control group, as PaCO2 increased from 34 +/- 2 (SD) to 53 +/- 4 torr (4.5 +/- 0.3 to 7.1 +/- 0.5 kPa), cerebral blood flow increased from 53 +/- 12 to 147 +/- 50 mL/min/100 g. This increase in cerebral blood flow was not different from that of the ECMO group, where PaCO2 increased from 33 +/- 2 to 56 +/- 3 torr (4.4 +/- 0.3 to 7.5 +/- 0.4 kPa) and cerebral blood flow increased from 48 +/- 17 to 106 +/- 38 mL/min/100 g. As PaCO2 decreased from 34 +/- 2 to 19 +/- 2 torr (4.5 +/- 0.27 to 2.5 +/- 0.27 kPa), cerebral blood flow decreased from 53 +/- 12 to 43 +/- 8 mL/min/100 g in the control group. This decrease was not different from that of the ECMO group, where cerebral blood flow decreased from 48 +/- 17 to 39 +/- 10 mL/min/100 g as PaCO2 decreased from 33 +/- 2 to 22 +/- 3 torr (4.4 +/- 0.3 to 2.9 +/- 0.4 kPa). When regional cerebral blood flow was analyzed, no regional differences in the cerebrovascular responses to PaCO2 between ECMO and control groups were found. The cerebral metabolic rate was not different between ECMO and control groups at any level of PaCO2, nor was the cerebral metabolic rate affected by changes in PaCO2. Oxygen extraction increased with hypocarbia and decreased with hypercarbia in a similar fashion in both ECMO and control groups., Conclusion: The cerebrovascular response to changes in PaCO2 was unaffected by ECMO.

This study was designed to evaluate the effect of normothermic partial bypass, or venoarterial extracorporeal membrane oxygenation (ECMO), on cerebral autoregulation. Fourteen newborn lambs, 1-7 d of age, were randomized into two groups: control (ligation of right carotid artery and jugular vein without ECMO; n = 7) and ECMO (ligation with placement on routine venoarterial ECMO at 120-150 mL/kg/min; n = 7). After 1 h of ECMO or stabilization in controls, cerebral autoregulation was evaluated by lowering cerebral perfusion pressure (CPP) by increasing intracranial pressure through infusion of artificial cerebrospinal fluid into the lateral ventricle. Four ranges of CPP were evaluated: 1) baseline, 2) 55-40, 3) 39-25, and 4) < 25 mm Hg. In ECMO animals, cerebral blood flow (CBF) decreased from baseline (39 +/- 7 mL/100 g/min) to 23 +/- 7 and 12 +/- 2 at CPP of 39-25 and < 25 mm Hg. In the control group, CBF was unchanged from baseline (48 +/- 11 mL/100 g/min) until CPP was < 25 mm Hg, at which time it decreased to 27 +/- 16 mL/100 g/min. Cerebral oxygen consumption decreased from baseline (4.2 +/- 1.1 mL/100 g/min) to 4.0 +/- 0.7 and 3.2 +/- 1.3 mL/100 g/min at CPP of 39-25 and < 25 mm Hg, respectively, in the ECMO group. In the control group, cerebral oxygen consumption was unchanged from baseline (4.2 +/- 1.1 mL/100 g/min) until CPP was reduced to < 25 mm Hg (3.2 +/- 1.3 mL/100 g/min). When CBF autoregulation was altered, i.e. when total CBF decreased, right-left hemispheric CBF differences were noted in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

There is little information regarding alterations in cerebral venous flow related to ligation of the right jugular vein in newborns treated with extracorporeal membrane oxygenation (ECMO). The authors performed duplex and color Doppler sonographic evaluations of the intracranial venous system in 23 consecutive newborns during ECMO. The superior sagittal sinus (SSS) was visualized in every newborn, and the left transverse sinus was seen in 14 newborns (61%). The relative contribution of a jugular bulb catheter was evaluated in 16 newborns by measuring average blood flow velocities in the SSS with the catheter open (baseline) and with the catheter temporarily occluded. Occlusion of the catheter resulted in significantly reduced SSS blood flow velocities (P = .01). Persistent reductions in SSS flow velocity were associated with a significantly higher risk of cerebrovascular injury (P = .002). These results show that alterations in cerebral venous drainage are not uncommon in newborns treated with venoarterial ECMO and suggest a possible association between abnormal venous drainage and cerebrovascular injury in these newborns.

Extracorporeal membrane oxygenation (ECMO) supplies respiratory support to term or near-term infants with respiratory failure. Although infants requiring this therapy may have already sustained significant hypoxia and/or ischemia predisposing them to neurologic injury, the high incidence of neuroimaging abnormalities in the ECMO population raises concerns about the additional neurologic risk associated with the ECMO procedure itself. Our study was undertaken to evaluate the effects of ECMO on the normal neonatal cerebral circulation. Thirteen newborn lambs (1-7 d of age) were placed on normothermic venoarterial ECMO using a silicone membrane oxygenator and roller occlusion pump. Regional brain blood flows, cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport were determined 30 and 120 min after initiation of ECMO. Neither cerebral blood flow (baseline, 60.2 +/- 23.6; 30 min, 56.1 +/- 18.1; 120 min 56.1 +/- 12.9 mL/100 g/min) nor oxygen metabolism (cerebral oxygen consumption: baseline, 4.48 +/- 1.48; 30 min, 3.86 +/- 1.53; 120 min, 4.10 +/- 1.32 mL/100 g/min and oxygen extraction: baseline, 0.52 +/- 0.09; 30 min, 0.47 +/- 0.14; 120 min, 0.46 +/- 0.14 mL/100 g/min) changed after the initiation of ECMO. Regional and left/right blood flow differences were not noted. These findings suggest that in healthy newborn lambs, initiation of ECMO does not alter cerebral blood flow or oxygen metabolism.

The authors compared changes in cerebral blood flow (CBF), determined by means of injection of radiolabeled microspheres, with Doppler blood flow measurements obtained simultaneously in the middle (n = 9) and anterior cerebral arteries (n = 3) in 12 newborn lambs. Doppler estimates of blood flow and mean blood flow velocity correlated well with changes in CBF. However, with changes in mean blood flow velocity, the degree of change in CBF tended to be underestimated. The resistive index correlated well with perfusion pressure but correlated weakly with cerebrovascular resistance and poorly with changes in CBF. Doppler blood flow estimates and mean blood flow velocities correlate well with changes in CBF and allow significant improvement in accuracy over instantaneous velocity or pulsatility measurements alone. Determination of absolute blood flow remains difficult due to systolic and diastolic differences in vessel diameter and intrinsic error in true diameter measurement with currently available color flow technology.