Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Perioperative central nervous system injury in neonates.

Anaesthetic-induced developmental neurotoxicity (AIDN) has been clearly established in laboratory animal models. The possibility of neurotoxicity during uneventful anaesthetic procedures in human neonates or infants has led to serious questions about the safety of paediatric anaesthesia. However, the applicability of animal data to clinical anaesthesia practice remains uncertain. The spectre of cerebral injury due to cerebral hypoperfusion, metabolic derangements, coexisting disease, and surgery itself further muddles the picture. Given the potential magnitude of the public health importance of this issue, the clinician should be cognisant of the literature and ongoing investigations on AIDN, and raise awareness of the risks of both surgery and anaesthesia.

Broiler performance and in vivo viscosity as influenced by a range of xylanases, varying in ability to effect wheat in vitro viscosity.

1. Exogenous enzymes such as xylanase are used in diets for broilers to eliminate anti-nutritive effects caused by the presence of non-starch polysaccharides (NSP). It has been proposed that the mechanism by which xylanases exert their effect is through reducing in vivo viscosity within the broiler digestive tract. Previous research has reported that in vitro viscosity was a reasonable predictor of in vivo viscosity and that this method could be used to assess the efficacy of xylanases. 2. The objective of this study was to examine the response of broilers offered a wheat-based diet supplemented with a range of xylanases, varying in ability to reduce in vitro viscosity. 3. A total of 18 xylanases (Syngenta Animal Nutrition) were used to investigate the effect of xylanase on wheat in vitro viscosity. For the in vitro viscosity assay, pepsin was dissolved in either 005 or 01 M hydrochloric acid (HCl). 4. A wheat-based diet was formulated, produced and split into 7 batches; xylanase (500 U/kg) was sprayed onto 6 of the batches and the 7th was the control. This was repeated three times to produce a total of 21 diets, 18 of which contained xylanase. 5. The experiment was conducted in three consecutive trials. Each trial utilised 63 male, Ross broilers from 7 to 28 d of age. Dry matter intake (DMI), liveweight gain (LWG) and gain:feed were determined weekly. Excreta were collected from d 14 to 21 for determination of apparent metabolisable energy (AME). Oil and neutral detergent fibre (NDF) digestibility and ileal digestibility of dry matter (DM) and starch were determined. 6. Regression analyses were applied to the mean intestinal viscosity against DMI, LWG, gain:feed and the ratio of metabolisable energy to gross energy (ME:GE). To compare xylanases across the three trials, the data were subjected to REML analysis (Genstat 5). 7. When 01 M HCl was used for dissolution of pepsin, considerable reductions in in vitro viscosity were achieved for the majority of the xylanases-to values less than 12% of the control treatment. When 005 M HCl was used for the dissolution of pepsin, initial viscosity values were lower and the reduction in in vitro viscosity less dramatic than that observed with 01 M HCl. 8. With the exception of diets containing xylanases 9003 and 7162, significant reductions in in vivo viscosity were observed for diets containing xylanase in comparison to the control diet. 9. In terms of gain:feed, ME:GE and AME the xylanases ranked best were 2230 and 9003. Xylanase 2230 also resulted in the highest values for ileal DM and starch digestibility. 10. There were weak but significant relationships between in vitro viscosity and in vivo jenjunal digesta viscosity when in vitro viscosity was determined using either 01 or 005 M HCl (r(2)= 0287 and 0240, respectively). 11. The relationship between jejunal viscosity and DMI was significant (P < 005) but relatively poor (r(2)= 023). There were also significant (P < 005) relationships between jejunal digestal viscosity and gain:feed and ME:GE (r(2)= 034 and 028, respectively). 12. In conclusion, in vitro viscosity may be of some use in predicating xylanase response in vivo.

Prediction of wheat chemical and physical characteristics and nutritive value by near-infrared reflectance spectroscopy.

1. The aims of this study were to investigate the potential of near infrared reflectance spectroscopy (NIRS) to predict the chemical and physical characteristics of wheat and also to predict the nutritive value of wheat for broiler chickens. 2. A total of 164 wheat samples, collected from a wide range of different sources (England, Northern Ireland and Canada), varieties and years, were used in this study. 3. Chemical and physical parameters measured included specific weight, thousand grain weight, in vitro viscosity, gross energy, nitrogen, neutral detergent fibre (NDF), starch, total and soluble non-starch polysaccharides (NSP), lysine, threonine, amylose, hardness, rate of starch digestion and protein profiles. 4. A total of 94 wheat samples were selected for inclusion in three bird trials and included at 650 g/kg in a typical UK starter/grower diet. Birds were housed in individual wire metabolism cages from 7 to 28 d and offered water and food ad libitum. Dry matter intake (DMI), live weight gain (LWG) and gain:feed ratio were measured weekly. A balance collection was carried out from d 14 to 21 for determination of apparent metabolisable energy (AME), ME:gain and dry matter retention. At 28 d the birds were humanely killed, the contents of the jejunum removed for determination of in vivo viscosity and the contents of the ileum removed for determination of ileal dry matter, starch and protein digestibility. 5. The wheat samples were scanned as whole and milled wheat, both dried and undried and NIRS calibrations, first excluding and then including the Canadian wheat samples, were developed. 6. NIRS calibrations for milled wheat samples may be useful for determining specific weight (R(cv)(2) = 0.75, for milled wheat dried), nitrogen (R(cv)(2) = 0.983 for milled and dried) and rate of starch digestion (R(cv)(2) = 0.791 for milled, dried and undried). 7. NIRS calibrations for whole wheat samples (undried) may be useful for determining wheat nutritive value, with good predictions for live weight gain (R(cv)(2) = 0.817) and feed conversion efficiency (R(cv)(2) = 0.825). 8. Inclusion of the Canadian wheat samples in the NIRS analysis provided additional robust calibrations for gross energy (R(cv)(2) = 0.86, dried and milled) and starch content (R(cv)(2) = 0.79, undried and milled). 9. This study shows that NIR is a useful tool in the accurate and rapid determination of wheat chemical parameters and nutritive value and could be extremely beneficial to both the poultry and wheat industry. 10. Further extension of the dataset would be recommended to further validate these findings.

Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children.

BACKGROUND AND OBJECTIVES: The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr. METHODS: After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg(-1), was given over 4 min, followed immediately by an infusion of 2 mg mL(-1) ropivacaine 0.4 mg kg(-1) h(-1) for the next 24-72 h. RESULTS: Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L(-1) at 16-31 and 59-72 h, respectively) and alpha1-acid-glucoprotein (mean 13 and 25 micromol L(-1) at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L(-1) at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L(-1)). Apparent unbound clearance (mean 346, range 86-555 mL min(-1) kg(-1)) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine. CONCLUSION: Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg(-1) h(-1) in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.

Fumaric and sorbic acid as additives in broiler feed.

The aim of the experiment was to study the effect of dietary organic acids, fumaric and sorbic, on nitrogen corrected apparent metabolisable energy (AME(N)), metabolisability of nutrients, endogenous losses and performance on young broiler chickens. A total of 56 male Ross broilers were used in a growing experiment from 14 to 30d age. Seven experimental wheat-based (655g/kg) diets were formulated. The control diet did not contain organic acids. The other six diets were produced with the addition of fumaric or sorbic acids, replacing 0.5% , 1.0% or 1.5% of the wheat. The organic acid supplemented diets contained higher levels of AME(N) compared to the control diet. Overall, birds offered organic acids had lower feed intake. Dietary organic acids did not significantly affect weight gain or feed efficiency, however, birds offered supplemented diets had lower numbers of Lactic acid bacteria and Coliforms in the ileum and caeca. Birds offered organic acids had lower levels of endogenous losses compared to control fed birds. There was a negative relationship between AME(N) of the diets and excreted endogenous losses, measured as sialic acid. It can be concluded that the decrease in secretions from the gastrointestinal tract in the presence of fumaric and sorbic acids may be a mechanism involved in the mode of action of dietary organic acids.

Investigation of growth rate variation between commercial pig herds.

The study was designed to provide quantifiable information on both within- and between-herd variation in pig growth rate from birth to slaughter and to examine how this was influenced by moving pigs at a common age to a common environment. Five litters were selected from each of eight pig herds in Northern Ireland with varying growth performance. All eight herds were offered the same nutritional regime. Five pigs (three boars and two gilts) were selected from each litter. In each herd, 22 pigs (12 boars and 10 gilts) were weighed individually, every 4 weeks, from 4 to 20 weeks of age. At 4 weeks of age (weaning) three non-sibling boars were taken from each herd and brought to a common environment where they received medication, were housed individually from 6 weeks of age and offered the same dietary regime. They were weighed and feed intakes were recorded twice weekly. A growth rate difference of 61 g/day (P < 0.001), 112 g/day (P < 0.01) and 170 g/day (P < 0.001) was observed on farm, between the top and bottom quartile of herds during 4 to 8, 8 to 12 and 12 to 20 weeks of age, respectively. This difference in growth rate equated to an average difference in cost of production of ¢13/kg carcass on a birth to bacon unit. When pigs from the different herds were housed in the common environment, large variation in growth performance (143 g/day (P < 0.01) and 243 g/day (P < 0.001) for 8 to 12 and 12 to 20 weeks, respectively) was also observed between the top and bottom quartile of herds. Although feed efficiency was similar, a significant feed intake difference of 329 g/day (P < 0.01) and 655 g/day (P < 0.001) between 8 to 12 and 12 to 20 weeks of age was observed. The variation in growth rate between pigs whether managed on farm or in the common environment was similar (variation in days to 100 kg on farm and in the common environment was 18 and 19 days, respectively). When housed in the common environment, although the top and bottom quartile of pigs converted feed equally efficiently, pigs in the top quartile had significantly higher feed intakes suggesting greater appetites. It is difficult to assess the extent to which these differences can be attributed to genetic effects or pre-weaning environment, and how much the effects of management, disease or genetics contributed to the variation between and within herds.

The pharmacokinetics of epidural ropivacaine in infants and young children.

UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.

The differences in the bispectral index between infants and children during emergence from anesthesia after circumcision surgery.

UNLABELLED: The bispectral index (BIS) correlates with consciousness during adult anesthesia. In this prospective, blinded study of children (n = 24) and infants (n = 25) undergoing elective circumcision, we evaluated BIS and consciousness level during emergence from anesthesia. Anesthesia was maintained with sevoflurane, and a penile nerve block was performed in each patient before surgical stimulation. At the completion of surgery, the sevoflurane was decreased stepwise from 0.9% in increments of 0.2%, and arousal was tested with a uniform auditory stimulus given after a steady state of end-tidal sevoflurane concentration was achieved at each step. The BIS increased significantly as the sevoflurane concentrations decreased in children (0.9%, 62.5 +/- 8.1; 0.7%, 70.8 +/- 7.4; and 0.5%, 74.1 +/- 7.1; P < 0.001 for 0.7% and 0.5% compared with 0.9%), but a similar relationship was not demonstrated in infants. The BIS values at 0.7% and 0.5% sevoflurane were significantly higher in children than infants (P < 0.02 and P < 0.002, respectively). In both children and infants, the BIS increased significantly from pre- to postarousal (children, 73.5 +/- 7 to 83.1 +/- 12, P = 0.01; infants, 67.8 +/- 10 to 85.6 +/- 13.6, P < 0.001). The BIS at which arousal was possible with the stimulus tended to be higher in children than in infants (P = 0.06). IMPLICATIONS: In this study comparing the Bispectral index (BIS) in infants and children undergoing circumcision surgery by use of a standardized surgical and anesthetic technique, a significant decrease in BIS was detected in children during a stepwise decrease in end-tidal sevoflurane concentration. A similar relationship was not demonstrated in infants less than 1 yr old. In both children and infants, BIS increased significantly from pre- to postarousal. Additional studies are necessary to determine changes in BIS with maturational changes in the electroencephalogram.

Effect of intravenous infusion of omega-3 and omega-6 lipid emulsions on equine monocyte fatty acid composition and inflammatory mediator production in vitro.

The effect of intravenous administration of lipid emulsions enriched with omega-3 (n3) and omega-6 (n6) fatty acids on equine monocyte phospholipid fatty acid composition and the synthesis of inflammatory mediators in vitro was evaluated. In a randomized crossover design, horses were infused intravenously with 20% lipid emulsions containing n3 or n6 fatty acids. Monocytes were isolated from the horses before and 0 h, 8 h, 24 h, and 7 days after lipid infusion. Monocyte fatty acid analysis demonstrated incorporation of the parenteral n3 and n6 fatty acids in monocyte phospholipids immediately after infusion, with changes in the fatty acid composition persisting for up to 7 days after infusion. In vitro production of the inflammatory mediators thromboxane B2/thromboxane B3 (TXB(2/3)) and tumor necrosis factor-alpha (TNFalpha) by peripheral blood monocytes was diminished by n3 lipid infusion and was unchanged or increased by n6 lipid infusion. The results of this study demonstrate that short-term infusions of n3 and n6 fatty acid-enriched lipid emulsions alter the fatty acid composition of equine monocyte phospholipids and modify the inflammatory response of these cells in vitro. These results also support further investigation into the use of parenteral n3 fatty acids as part of the supportive therapy of patients with multiple organ dysfunction (MODS) or systemic inflammatory response syndrome (SIRS).

Electrocardiographic inscription of diaphragmatic contractions during anaesthesia.

An electrocardiographic artifact was noted on a child under general anaesthesia. The artifact was caused by rhythmic diaphragmatic contractions. A systematic approach to distinguish an artifact from a cardiac electrophysiological event is presented.

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.

Effects of acetylpromazine, xylazine, and vertical load on digital arterial blood flow in horses.

Palmar digital arterial blood flow was measured in 6 conscious, standing horses, using surgically placed perivascular ultrasonic flow probes. The effects of 2 dosages of xylazine (0.55 and 1.1 mg/kg of body weight) and of 3 dosages of acetylpromazine (0.01, 0.02, and 0.04 mg/kg), as well as the effect of vertical load, on digital blood flow were evaluated. Intravenous administration of xylazine induced a significant (P < 0.05), transient decrease in digital blood flow. Intravenous administration of acetylpromazine induced a significant (P < 0.05), prolonged increase in digital blood flow. Correlation between vertical load and digital blood flow was found. The results of this study indicate that use of acetylpromazine may be beneficial in clinical treatment of horses with reduced digital blood flow. Xylazine, on the other hand, may exacerbate ischemic conditions of the digit and should be used with caution.

Conservative management of femoral diaphyseal fractures in four foals.

Femoral fractures in young horses can occur as a result of severe trauma and generally have a poor prognosis despite treatment. Four young horses with femoral diaphyseal fractures were managed with conservative treatment consisting of prolonged rest, analgesics, hind limb support, and corrective farriery. A favorable outcome in the form of pasture soundness with potential for limited athletic usefulness was obtained in 3 out of the 4 cases. This report supports the use of conservative treatment of selected diaphyseal femoral fractures in young horses.

Sound levels in the human uterus.

OBJECTIVE: We sought to determine the degree to which noises and voices are attenuated or enhanced as they pass into the uterus. METHODS: In eight parturients, a hydrophone in the uterus was used to measure sound pressure levels for externally generated one-third-octave band noises, male and female voices, and the subject's voice. RESULTS: Low-frequency sounds (0.125 kHz) generated outside the mother were enhanced by an average of 3.7 dB. There was a gradual increase in attenuation for increasing frequencies, with a maximum attenuation of 10.0 dB at 4.0 kHz. Sound attenuation was slightly less if the insonation was from in front of the woman rather than behind. Intrauterine sound levels of the mother's voice were enhanced by an average of 5.2 dB, whereas external male and female voices were attenuated by 2.1 and 3.2 dB, respectively. The effect of frequency on attenuation, the differences between front and back insonation, and the differences between speakers in attenuation were all statistically significant. CONCLUSIONS: The intrauterine environment is rich with externally generated sounds. This may imply fetal risk from maternal noise exposure and may aid in understanding fetal imprinting from prenatal exposure to voices.

Effects of vibration frequency and tissue thickness on intrauterine sound levels in sheep.

Pure-tone sinusoidal mechanical vibratory stimuli ranging in frequency from 4 to 4000 Hz were applied to the ventral abdominal wall of pregnant ewes, and intrauterine sound pressure levels were recorded with a hydrophone 5, 10, 15, and 20 cm from the surface. There were significant decreases in sound pressure levels with increasing frequencies (p less than 0.0001) and increasing depth (p = 0.01). There was no significant interaction between these two variables. An electronic artificial larynx was also activated on the abdominal wall, resulting in quite high sound pressure levels (mean, 119 dB) measured 5 cm from the surface, with a significant decrease in sound pressure levels as the thickness of the intervening maternal tissues increased (p = 0.005). These results suggest that the frequency of vibratory stimulus used and the thickness of the maternal abdominal wall could influence fetal response to the vibroacoustic stimulation test by affecting intrauterine sound pressure levels.