Risks for impaired cerebral autoregulation during cardiopulmonary bypass and postoperative stroke.

BACKGROUND: Impaired cerebral autoregulation may predispose patients to cerebral hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was to identify risk factors for impaired autoregulation during coronary artery bypass graft, valve surgery with CPB, or both and to evaluate whether near-infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify this condition. METHODS: Two hundred and thirty-four patients were monitored with transcranial Doppler and NIRS. A continuous, moving Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and cerebral blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional autoregulation is indicated by an Mx and COx that approach zero (no correlation between CBF and MAP); impaired autoregulation is indicated by an Mx and COx approaching 1. Impaired autoregulation was defined as an Mx ≥0.40 at all MAPs during CPB. RESULTS: Twenty per cent of patients demonstrated impaired autoregulation during CPB. Based on multivariate logistic regression analysis, time-averaged COx during CPB, male gender, Pa(CO(2)), CBF velocity, and preoperative aspirin use were independently associated with impaired CBF autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with impaired autoregulation compared with five of 187 (2.7%) patients with preserved autoregulation (P=0.011). CONCLUSIONS: Impaired CBF autoregulation occurs in 20% of patients during CPB. Patients with impaired autoregulation are more likely than those with functional autoregulation to have perioperative stroke. Non-invasive monitoring autoregulation may provide an accurate means to predict impaired autoregulation. Clinical trials registration. www.clinicaltrials.gov (NCT00769691).

Evidence for a hypothalamic defect in septo-optic dysplasia.

A 21-year-old man demonstrated septo-optic dysplasia. Optic and retinal colobomas were present and panhypopituitarism was documented. Releasing hormone studies showed partial luteinizing hormone (LH) response and no follicle-stimulating hormone response to administration of gonadorelin (LH-releasing hormone); thyroid-stimulating hormone (TSH) and prolactin levels were increased normally after administration of protirelin (thyrotropin-releasing hormone). The LH, TSH, and prolactin responses are believed to be evidence of intact pituitary function and suggest that a hypothalamic defect accounts for the hypopituitarism.

Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.

Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.

PIP: The effect of fluoxymesterone (9 alpha-fluoro-11 beta, 17 beta-dihydroxy-17 alpha-methyl-4-androstene-3-one) on the pituitary-gonadal axis and the role of testosterone-estradiol-binding globulin (TeBG) were investigated. 4 normal men and 2 agonadal men were given fluoxymesterone for 3 days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and luteinizing hormone (LH) were measured every 30 minutes on a control day and on the 1st day of treatment. T and LH were measured every 6 hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes/day decreased from 10.5 to 6.2 (p less than .01), mean 24-hour LH decreased from 12.6 mIU/ml to 9.3 mIU/ml (p less than .01), and mean 17-OHP decreased from 2.33 ng/ml to 1.18 ng/ml (p less than .01) in all normal subjects. T decreased from 464.5 ng/100 ml to 294.2 ng/100 ml (p less than .01). By the 3rd day of treatment, LH had decreased further in 4 and T in 3 of 4 normals. Mean LH levels and the number of LH spikes did not decrease in the agonadal patients. Fluoxymesterone displaced T in vitro from plasma binding proteins with an apparent equilibrium constant of 1 X 10(8) and 1.9 X 10(7) in female and male plasma, respectively, at 22 degrees C and 5.2 X 10(7) and 8 X 10(6) at 37 degrees C. In polyacrylamide gel electrophoresis a 500-fold more excess of fluoxymesterone decreased the peak of TeBG-bound T significantly (p less than .01, 45%). These in Vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vitro.

Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.

Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative "hyperdynamic beta-adrenergic state."

The ontogeny of cerebrovascular pressure autoregulation in premature infants.

OBJECTIVE: To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle. STUDY DESIGN: The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle. RESULTS: Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=-0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=-0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and 'effective cerebral perfusion pressure' (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx. CONCLUSION: Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation.

Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1ß), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1ß were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

Relationship between cerebrovascular dysautoregulation and arterial blood pressure in the premature infant.

OBJECTIVE: To evaluate cerebrovascular autoregulation as a function of arterial blood pressure (ABP) in the critically ill, premature infant. STUDY DESIGN: A prospective observational pilot study was conducted in two tertiary care Neonatal Intensive-Care Units. Premature infants (n=23, ≤30 weeks estimated gestational age with invasive ABP monitoring) were enrolled and received routine care while undergoing continuous autoregulation monitoring, using the cerebral oximetry index (COx). The COx is a moving, linear correlation coefficient between cortical reflectance oximetry and ABP. COx values were stratified as a function of ABP for individual subject recordings and for the cohort. RESULT: The mean duration of autoregulation monitoring was 3.2 days (median: 2.97, range: 0.61-3.99). A total of 10 of 23 (43%) developed intraventricular hemorrhage and 1 of 23 (4%) developed periventricular leukomalacia by head ultrasound. No association was found between neurologic injury and percentage of the monitoring periods with autoregulation impairment (defined as COx>0.5). Lower ABP was associated with dysautoregulation (higher COx values, P<0.01). The percentage of time with impaired autoregulation was greater with lower ABP (P=0.013, Spearman r=0.51). CONCLUSION: All infants studied had periods with intact and periods with impaired cerebrovascular autoregulation, measured with the COx. Low ABP was associated with impaired autoregulation.

Open air carbon monoxide poisoning in a child swimming behind a boat.

Carbon monoxide (CO) poisoning is the most common fatal poisoning in the United States. The circumstances often involve an unsuspected increase of CO in an enclosed environment. Victims often are unaware that their activity or environment placed them at risk for CO poisoning. The possibility of open air CO poisonings was first reported in 1987. We present a case of open air CO poisoning resulting in neurologic depression and a markedly elevated carboxyhemoglobin level in a child who had been swimming behind a house boat. Emergency physicians and pediatricians should be aware of the possibility of accidental open air CO poisoning in children and adults who swim around recreational boats.

Central nervous system manifestations of an ibuprofen overdose reversed by naloxone.

Ibuprofen overdose is usually characterized by GI upset, dizziness, and mild sedation. On rare occasions, severe complications such as respiratory failure, metabolic acidosis, renal failure, coma, and death have been reported in both adults and children. Presently, treatment of acute ibuprofen intoxication with complications requires supportive therapy until the symptoms resolve over 24 to 48 hours. We report the case of an 11-month-old female infant with a depressed level of consciousness after ingestion of ibuprofen whose mental status markedly improved with administration of naloxone.

Cat-scratch disease causing status epilepticus in children.

Status epilepticus from cat-scratch encephalopathy is often recalcitrant to usual therapies, causing treatment to focus on critical care management of the patient that may require aggressive interventions, such as continuous pentobarbital administration. We describe two children whose initial clinical presentation of cat-scratch disease was status epilepticus with normal cerebrospinal fluid studies. A history of cat exposure (specifically, kitten and/or fleas), regional lymphadenopathy, and a papule or inoculation site should be sought, but are not essential for diagnosis. The presumptive diagnosis of cat-scratch disease can be made by serology alone even in the absence of classic diagnostic criteria. Our two cases and other reports in the literature show a favorable prognosis in most cases, despite the occurrence of status epilepticus. The diagnosis of cat-scratch disease should be strongly considered in all children with unexplained status epilepticus or encephalopathy and serologic testing for Bartonella henselae should be done.

Prospective study of airway management of children requiring endotracheal intubation before admission to a pediatric intensive care unit.

OBJECTIVE: To prospectively identify complications related to airway management in children before pediatric intensive care unit (ICU) admission. DESIGN: A descriptive, prospective study covering an 18-month period. A survey was completed at the time of admission to obtain demographic data, reason for endotracheal (ET) intubation, medications administered, location of and personnel responsible for ET intubation, and major/minor variances associated with airway management. Major variances were defined as technical problems resulting in a significant risk for airway trauma and increased morbidity. Minor variances were problems that should be avoided, but which do not significantly increase the immediate risk to the patient. Additional information obtained included whether a chest radiograph (CXR) was obtained and if postextubation problems occurred, such as stridor requiring treatment or reintubation. SETTING: Community hospitals, emergency rooms, children's hospital emergency rooms PATIENTS: All children < or =18 yrs of age receiving ET intubation before admission to the pediatric ICU, except those in cardiovascular arrest. MEASUREMENTS AND MAIN RESULTS: Data were collected on 250 consecutive patients. Major or minor variances were noted in 135 (54%) patients and in 66% of patients < or =1 yr of age (p = .02865; odds ratio, 2.0). Twenty-six percent of patients < or =1 yr of age received an anticholinergic agent before ET intubation compared with 40% of older patients (p = .04343; odds ratio, 0.504). Eleven patients received a neuromuscular blocking agent (NMBA) without a sedative/analgesic agent. Major variances occurred in 54% of patients who did not receive a NMBA and in 27% of patients who received a NMBA (p = .00002; odds ratio, 0.307). Forty-one patients (16%) were intubated with an inappropriately sized ET tube. Postintubation CXRs were obtained in 65% of patients managed outside of a children's hospital and in 93% of patients in a children's hospital emergency room (p < .00001; odds ratio, 7.199). Variances detectable by CXR went unrecognized in 40% of patients, despite obtaining a CXR. CONCLUSIONS: Emergency airway management in children can be fraught with problems. Most variances could be avoided by improved education regarding appropriate ET tube size, appropriate medication use, and improved training for evaluation of ET tube placement.

A family of concanavalin A-binding peptides from a hexapeptide epitope library.

The lectin concanavalin A (Con A) binds methyl alpha-D-mannopyranoside (Me alpha Man) as well as alpha-D-mannosyl groups at the nonreducing terminus of oligosaccharides. Ligand peptides that mimic the binding of Me alpha Man to Con A were identified from screening an epitope library composed of filamentous phage displaying random hexapeptides. A consensus sequence was identified among affinity-purified phage; Con A binds phage bearing this sequence and is inhibited from doing so by Me alpha Man. When tested for binding against a panel of lectins, phage bearing this sequence bind only weakly to a closely related D-mannose-binding lectin, indicating that binding to Con A is highly selective. A synthetic peptide bearing the consensus sequence blocks the precipitation of Con A by dextran with an inhibition strength equivalent to that of methyl alpha-D-glucopyranoside. These results demonstrate that the specificity of Con A is not limited to carbohydrates and that highly selective sugar-mimics for lectins of plant, animal, or bacterial origin may be identified from epitope libraries.