Inter-observer reliability using the General Movement Assessment is influenced by rater experience.

OBJECTIVE: To describe the inter-observer reliability of the General Movement Assessment (GMA) among a sample of infants at high-risk of cerebral palsy (CP) among raters with various levels of experience. METHODS: Video assessments of 150 high-risk infants at 10-15 weeks corrected age were rated by three Prechtl GMA-certified observers with varied experience using the assessment. Videos were scored based on temporal organization of fidgety movements (FMs), presence of abnormal FMs, or absence of FMs. Inter-observer agreements were analyzed with Gwet's AC1 statistic. RESULTS: We found fair to moderate agreement when subcategories of normal FMs (continuous and intermittent) were included (AC1 = 0.32-0.57) and moderate to near perfect agreement when normal categories of FMs were combined (AC1 = 0.60-0.95). Reliability was higher among observers with more experience using the GMA (AC1 = 0.57-0.98) than the observer with less experience (AC1 = 0.32-0.61). CONCLUSIONS: Caution may be warranted when the GMA is used to differentiate "continuous and intermittent" FMs temporal organization. The GMA is highly reliable among experienced raters when comparing normal FMs to other FMs categorizations.

White Matter Injury and General Movements in High-Risk Preterm Infants.

BACKGROUND AND PURPOSE: Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. MATERIALS AND METHODS: In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. RESULTS: Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. CONCLUSIONS: Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays.

Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability.

BACKGROUND: Changes in skin conductance (SC), clinical stress score (CSS), the bispectral index spectroscopy (BIS) index and the variation in the BIS index may be used to monitor responses to nociceptive stimuli. We wanted to examine these methods during noxious stimulation during general anaesthesia and if the responses were associated with variability in genes related to pain. METHODS: Sixty patients, given propofol to a BIS level of 40-50, were stimulated with standardised tetanic electrical stimuli during propofol infusion, plasma level of 3 µg/ml alone, or together with remifentanil target plasma level of 3 ng/ml or 10 ng/ml. The CSS, SC, BIS index and the variability of the BIS index were registered. The inter-individual variation in nociceptive responses was analysed for co-variation with genotypes of 89 single nucleotide polymorphisms from 23 candidate genes. RESULTS: During tetanic stimuli, CSS and SC increased significantly and were attenuated with increasing level of remifentanil, different from the BIS index and the variation in the BIS index. Polymorphisms in the P-glycoprotein (ABCB1), tachykinin 1 receptor (TACR1), dopamine receptor D3 (DRD3) and beta arrestin 2 (ARRB2) genes were associated with the co-variation in SC variables or CSS response or both during standardised nociceptive stimuli (P < 0.05). Because of no corrections for multiple testing, the genetic analyses are explorative, and associations must be tested in further studies. CONCLUSION: This exploratory study suggests genes that may be tested further with relation to nociceptive response during anaesthesia. SC and CSS may be useful tools for monitoring nociceptive response during general anaesthesia.

Hip fracture incidence is decreasing in the high incidence area of Oslo, Norway.

UNLABELLED: This study reports a significant decrease in age-adjusted incidence rates of hip fracture for women in Oslo, Norway, even compared with data from 1978/1979. Use of bisphosphonate may explain up to one third of the decline in the incidence. INTRODUCTION: The aims of the present study were to report the current incidence of hip fractures in Oslo and to estimate the influence of bisphosphonates on the current incidence. METHODS: Using the electronic diagnosis registers and lists from the operating theaters of the hospitals of Oslo, all patients with ICD-10 codes S72.0 and S72.1 (hip fracture) in 2007 were identified. Medical records of all identified patients were reviewed to verify the diagnosis. Age- and gender-specific annual incidence rates were calculated using the population of Oslo on January 1, 2007 as the population at risk. Data on the use of bisphosphonates were obtained from official registers. RESULTS: A total number of 1,005 hip fractures, 712 (71%) in women, were included. The age-adjusted fracture rates per 10,000 for the age group >50 years were 82.0 for women and 39.1 for men in 2007, compared with 110.8 and 41.4 in 1996/1997, 116.5 and 42.9 in 1988/1989, and 97.5 and 34.5 in 1978/1979, respectively. It was estimated that the use of bisphosphonates may explain up to 13% of the decline in incidence in women aged 60-69 years and up to 34% in women aged 70-79 years. CONCLUSIONS: The incidence of hip fractures in women in Oslo has decreased significantly during the last decade and is now at a lower level than in 1978/1979. This reduction was not evident in men. The incidence of hip fractures in Oslo is, however, still the highest in the world.

Coating of titanium with hydroxyapatite leads to decreased bone formation: A study in rabbits.

OBJECTIVES: An experimental rabbit model was used to test the null hypothesis, that there is no difference in new bone formation around uncoated titanium discs compared with coated titanium discs when implanted into the muscles of rabbits. METHODS: A total of three titanium discs with different surface and coating (1, porous coating; 2, porous coating + Bonemaster (Biomet); and 3, porous coating + plasma-sprayed hydroxyapatite) were implanted in 12 female rabbits. Six animals were killed after six weeks and the remaining six were killed after 12 weeks. The implants with surrounding tissues were embedded in methyl methacrylate and grinded sections were stained with Masson-Goldners trichrome and examined by light microscopy of coded sections. RESULTS: Small amounts of bone were observed scattered along the surface of five of the 12 implants coated with porous titanium, and around one out of 12 porous coated surfaces with Bonemaster. No bone formation could be detected around porous coated implants with plasma-sprayed hydroxyapatite. CONCLUSION: Porous titanium coating is to some degree osteoinductive in muscles.

Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study.

AIM: To assess if growth restricted (small for gestational age, SGA) extremely preterm infants have excess neonatal mortality and morbidity. METHODS: This was a cohort study of all infants born alive at 22-27 weeks' post menstrual age in Norway during 1999-2000. Outcomes were compared between those who were SGA, defined as a birth weight less than the fifth percentile for post menstrual age, and those who had weights at or above the fifth percentile. RESULTS: Of 365 infants with a post menstrual age of <28 weeks, 31 (8%) were SGA. Among infants with a post menstrual age of <28 weeks, only chronic lung disease was associated with SGA status (OR 2.7, 95% CI 1.0 to 7.2). SGA infants with a post menstrual age of 26-27 weeks had excess neonatal mortality (OR 3.8, 95% CI 1.3 to 11), chronic lung disease and a significantly higher mean number of days (age) before tolerating full enteral nutrition. SGA infants with a post menstrual age of 22-25 weeks had an excess risk of necrotising enterocolitis. CONCLUSION: Extremely preterm SGA infants had excess neonatal mortality and morbidity in terms of necrotising enterocolitis and chronic lung disease.

The iodinated radiographic contrast medium iohexol mimics the vasodilator effect seen with small increases in extracellular K+ in the isolated rabbit central ear artery.

PURPOSE: To investigate whether iodinated radiographic contrast media (IRCM) mimic the hyperpolarizing and vasodilator effects of K+ by comparing the vasodilator effect of a transient rise in extracellular K+ with that of the IRCM iohexol. MATERIAL AND METHODS: Immersed rabbit central ear arterial rings with and without endothelium and pre-contracted with phenylephrine (PE) were used to investigate the dependency of the endothelium in K+-induced vasodilatation. Perfused rabbit central ear arteries, pre-contracted with PE, were used to study the effects of bolus administrations of the IRCM iohexol or KCl on arterial tone under conditions that mimic those employed during clinical arteriography. RESULTS: A small rise in K+ caused an endothelium-independent and ouabain-sensitive relaxation of PE-constricted rabbit central ear artery rings. The relaxation was not changed in the presence of barium. The IRCM iohexol and KCl, injected as boluses into perfused PE-constricted rabbit ear arteries, caused transient decreases in perfusion pressure. Iohexol- and K+-induced pressure decreases were significantly reduced in the presence of 10 microM ouabain alone or in combination with 30 microM barium. Neither iohexol- nor K+-induced pressure decrease was significantly changed in the presence of barium alone compared to controls. CONCLUSION: The vasodilator effect of IRCM mimics the vasodilator effect seen upon small increase in extracellular K+. Under the experimental conditions employed in the present study, a considerable part of the IRCM-induced vasodilatation appears to be due to activation of Na+/K+-ATPase in the smooth muscle cells.

Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium-dependent vasodilation in the femoral artery of developing piglets.

Mechanisms mediating endothelium-dependent vasodilation were investigated in femoral artery rings from <2-day-old (newborn) and 2-week-old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)-cyclic 3',5'-guanosine monophosphate (cGMP) and K+ channel-activation to acetylcholine (ACh)-induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K+ channel blockade and the intra-arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS-inhibitors N G-monomethyl-L-arginine acetate (L-NMMA; 100 microM) or NG-nitro-L-arginine (L-NOARG; 1-100 microM), however, relaxation was significantly more reduced in femoral artery rings from 2-week-old than from newborn, with lower pD2 values in the older age group. Inhibition of large (BKCa) conductance calcium-sensitive K+ channels with tetraethylammonium chloride (TEA; 1 mM), gave a significant rightward shift in the concentration-response curves to ACh which was of the same magnitude in both age groups. The ACh-induced vasodilation was abolished in both age groups by high K+ (20 mM) in combination with L-NOARG (100 microM). The relative increase in cGMP levels after addition of ACh (10 nM) was significantly larger in rings from newborn compared with 2-week-old piglets (12- vs. four-fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K+ channel blockade with TEA was the same in femoral artery rings from newborn to 2-week-old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.

Postoperative epidural analgesia in children after major orthopaedic surgery. A randomised study of the effect on PONV of two anaesthetic techniques: low and high dose i.v. fentanyl and epidural infusions with and without fentanyl.

BACKGROUND: The study was performed in order to improve postoperative pain management in children after major orthopaedic surgery. Two different anaesthetic techniques (sevoflurane-low fentanyl and propofol-higher fentanyl) and two different epidural mixtures (bupivacaine 1.5 mg ml(-1) and adrenaline 2 microg ml(-1) compared with bupivacaine 1 mg ml(-1), adrenaline 2 microg ml(-1) and fentanyl 2 microg ml(-1)) were investigated with regard to postoperative analgesia and side effects, primarily postoperative nausea and vomiting (PONV). METHODS: Forty-two children were randomised into one of three groups: sevoflurane anaesthesia and epidural solution with fentanyl (SBAF); sevoflurane anaesthesia and epidural solution without fentanyl (SBA); propofol anaesthesia and epidural solution without fentanyl (PBA). RESULTS: Including fentanyl in the epidural mixture resulted in excellent postoperative analgesia without any need of i.v. opioids. However, 7 out of 16 children were nauseated and needed antiemetic drugs. On average, a 55-75% higher dose of bupivacaine was necessary to assure adequate analgesia when an epidural mixture without fentanyl was used. In addition, significantly more children needed i.v. opioids. Under these conditions there was no significant difference in pain scoring between the groups. There was significantly less nausea and less use of antiemetic drugs in children having epidurals without fentanyl in the sevoflurane groups. The same tendency, although not significant, was observed in the whole material. Sevoflurane anaesthesia resulted in less PONV than propofol anaesthesia, probably due to the higher amount of intravenous fentanyl used with the latter. This difference was not significant due to the small number of children included. Incidence of pruritus related significantly to epidural fentanyl. CONCLUSION: A satisfactory postoperative analgesia can be achieved with both epidural mixtures used in the study. Epidural fentanyl results in better analgesia, but significantly more PONV and greater use of antiemetic drugs. Omitting epidural fentanyl results in less PONV, but significantly less profound analgesia and a need for additional treatment with i.v. opioids, in addition to a 55-75% higher epidural bupivacaine infusion. Both epidural treatments result in high and similar patient satisfaction and no serious complications. The study could not show any significant difference between the effect of sevoflurane and propofol anaesthesia on PONV.

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries.

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d (7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone (LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

[Mortality and functional disabilities among children with birth weight lower than 1500 g. Changes during 1983-88 at the neonatal unit of the Trondheim regional hospital]. / Mortalitet og funksjonshemning blant barn med fødselsvekt less than or equal to 1,500 g. Endringer i perioden 1983-88 ved neonatalenheten, Regionsykehuset i Trondheim.

The aim of the present study was to evaluate whether increased resources led to a higher rate of survival among infants with a birth weight less than or equal to 1,500 g, admitted to our department during the period 1983-88. During this period both personnel and equipment were upgraded. The number of patients more than doubled from 1983-84 to 1987-88 (37 versus 89). In spite of a significant decrease in gestational age from the first to the last period (29.6 weeks versus 28.2 weeks), the total mortality rate was halved, from 40.5% in 1983-84 to 22.5% in 1987-88. There was no significant increase in disability rate among survivors. The larger increasing number of disabled children was accounted for mainly by mild spastic diplegias.

Thermoregulatory vasoconstriction decreases cutaneous heat loss.

To determine the extent to which thermoregulatory vasoconstriction decreases heat loss to the environment, we measured regional heat flux, average skin temperature, and tympanic membrane temperature before and after thermoregulatory vasoconstriction in five minimally clothed volunteers maintained in a 30.8 +/- 0.1 degrees C environment. Thermoregulatory vasoconstriction was induced by central venous infusion of cooled fluid. Peripheral cutaneous blood flow was evaluated with venous-occlusion volume plethysmography and skin-surface temperature gradients. Laser Doppler flowmetry was used to measure vasoconstriction in centrally located skin. This model mimics the common clinical situation in which patients in a warm environment are centrally cooled by administration of cold intravenous fluids or by lavage of internal cavities with cold fluids. Tympanic membrane temperature decreased 1.5 +/- 0.3 degrees C in the first 15 min after the cold fluid infusion was started and remained approximately 1 degrees C below control values during the rest of the study. Average skin-surface temperature decreased slowly to approximately 0.7 degrees C below control. Flow in capillaries of centrally distributed skin, determined with laser Doppler flowmetry, decreased only approximately 40%. Total heat flux, and flux from the arms and legs decreased approximately 25% (15.5 +/- 0.3 W). Heat loss from the trunk and head decreased only 17%, whereas, loss from the hands and feet (10.5% of the body surface area) decreased approximately 50%. All measured values decreased significantly following vasoconstriction (P less than 0.01). Therefore, thermoregulatory vasoconstriction in a thermoneutral environment appears to decrease cutaneous loss of metabolic heat approximately 25%.

The thermoregulatory threshold is inversely proportional to isoflurane concentration.

This study tested the hypothesis that the threshold for thermoregulatory vasoconstriction is lowered as isoflurane concentration increases, but the intensity of vasoconstriction, once triggered, is well preserved during isoflurane anesthesia. The thermoregulatory threshold was prospectively defined as the central temperature at which vasoconstriction occurred, and significant vasoconstriction was defined as a skin-surface temperature gradient (forearm-fingertip) greater than or equal to 4 degrees C. The threshold for thermoregulatory vasoconstriction and the intensity of vasoconstriction, measured as maximum skin-temperature gradient, was determined in six unpremedicated patients electively donating a kidney during isoflurane anesthesia, and in four healthy, awake volunteers. All anesthetized patients were deliberately cooled and became hypothermic. Vasoconstriction occurred in five of six at central temperatures between 35.3 and 32.4 degrees C, at end-tidal isoflurane concentrations between 0.74 and 1.65%. The patient who did not vasoconstrict received the highest isoflurane concentration (approximately 2.5%) and reached a central temperature of 31 degrees C. Unanesthetized volunteers also were exposed to cold and each vasoconstricted at a temperature near 37 degrees C. The threshold for thermoregulatory cutaneous vasoconstriction was inversely correlated with anesthetic dose, the thermoregulatory threshold decreasing approximately 3 degrees C/% isoflurane concentration. There were no statistically significant differences between maximum skin-surface temperature gradients in awake volunteers and patients given isoflurane, or between any of the groups when patients from previous studies given halothane or nitrous oxide/fentanyl anesthesia were included in the comparison. These data indicate that the intensity of vasoconstriction, once triggered, is similar during several different types of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Atracurium, vecuronium, and pancuronium do not alter the minimum alveolar concentration of halothane in humans.

The authors studied 64 unpremedicated, healthy surgical patients, aged 42 +/- 14 yr, to determine the effects of atracurium, vecuronium, and pancuronium on the minimum alveolar concentration (MAC) of halothane. Anesthesia was induced using halothane/nitrous oxide/oxygen via a mask without the administration of other drugs. Nitrous oxide was discontinued, the trachea was intubated without prior administration of neuromuscular blocking drugs, and anesthesia was maintained with halothane in oxygen. Participating patients were assigned to one of five groups: 1) no neuromuscular blocking drug (control group, n = 9); 2) atracurium 0.5 mg/kg (n = 10); 3) atracurium 1.0 mg/kg (n = 15); 4) vecuronium 0.1 mg/kg (n = 20); or, 5) pancuronium 0.1 mg/kg (n = 10). Tourniquets, inflated to 300 mmHg immediately before iv administration of neuromuscular blocking drug and 15-30 min prior to skin incision, were used to isolate extremities from circulating neuromuscular blocking drug in all patients. A positive response to stimulation was defined as movement of at least one extremity occurring distal to the tourniquet within 1 min following skin incision. The first patients in the control and atracurium groups were studied at an end-tidal halothane concentration of 0.95%. The first patient in the pancuronium group was studied at a halothane concentration of 0.75%, and the first patient in the vecuronium group at 0.70%. Subsequent patients were studied at end-tidal halothane concentrations 0.10% above or below that of the preceding patient, depending on the presence or absence of movement with skin incision. Control MAC for halothane was 0.74% +/- 0.09% (mean +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)

Lower esophageal contractility predicts movement during skin incision in patients anesthetized with halothane, but not with nitrous oxide and alfentanil.

The frequency of spontaneous lower esophageal contractions (SLEC) has been proposed as one measure of anesthetic depth. The authors tested the hypothesis that SLEC frequency can predict movement in response to skin incision during halothane or nitrous oxide/alfentanil anesthesia. The incidence of movement during skin incision was compared with the frequency of spontaneous lower esophageal contractions in 20 healthy patients anesthetized with halothane. Esophageal contractility was determined using the Lectron 302, which senses the pressure in a water-filled balloon positioned in the distal esophagus. Absence of SLEC in the 6 min preceding incision correlated with no movement, with one exception (n = 9). All but one patient having greater than or equal to 2 SLEC in the 6 min preceding skin incision moved (n = 8) (P less than 0.01). Sixteen additional patients anesthetized with nitrous oxide (70%) and alfentanil demonstrated no correlation between SLEC frequency and movement. These data suggest that the frequency of spontaneous lower esophageal contractions, and its ability to predict movement, depends on anesthetic type.

Airway obstruction associated with an endotracheal tube.

A case of endotracheal tube obstruction with fatal outcome is presented. The obstruction was caused by the endotracheal tube bevel lying against the tracheal wall, the trachea being excessively displaced by the aorta at the level of the aortic knuckle.