Cyclic vomiting syndrome: contribution to dysphagic infant death.

Vomiting involves the simultaneous violent contraction of abdominal and diaphragm muscles to produce a high pressure on the stomach. The heart right atrium forms a through path from IVC to SVC, so the high intra-abdominal pressure will drive blood from abdominal contents into the head. Normally internal viscous drags in organs will limit the volume leaving them during a single vomiting event. However, repetitive vomiting such as occurs in cyclic vomiting syndrome (CVS) may drive sufficient blood into head veins to produce extreme venous hypertension. Dysphagic infant death is essentially a head vein hypertension malady, some features of which match those that are postulated for Shaken Baby Syndrome. CVS was described by Gee in 1882 but is still poorly understood. Recently a consensus statement has been released by the North American Society for Pediatric Gastroenterology Hepatology and Nutrition setting out key issues to be addressed. Understanding CVS may therefore have important implications beyond its gastroenterological aspects. A case demonstrating a sequence of features suggesting CVS and the effects of increasing abdominal muscle strength with age is presented. It showed (1) swallowing dysfunction, (2) grunting and apnoea (surfactant poisoning), (3) reflux, (4) diarrhoea, (5) apparently unprovoked prolonged screaming fits (migraine?), (6) petechiae (local capillary rupture), (7) skull growth abnormalities (hydrocephalus) and (8) unconscious "blank staring spells " (from which the infant would auto-resuscitate). Repetitive vomiting may also sensitise the epiglottis thus increasing the risk of laryngospasm, and making attempts at intubation hazardous, possibly leading to hypoxic brain death.

Shaken baby syndrome: does it exist?

UNLABELLED: The original (1993) definition of Shaken Baby Syndrome (SBS) specifies a group of infants with a history of dysphagia, presenting in a comatose state with respiratory difficulty progressing to apnoea or bradycardia requiring cardiopulmonary resuscitation. It is stated that retinal and vitreous haemorrhages are characteristic of SBS, and that subdural haemorrhage caused by shearing forces disrupting small bridging veins is a common result of shaking, but visible cerebral contusions are unusual. COMMENT: Experimental studies of whiplash injuries in primates in the 1960s showed that when coma was induced cerebral contusions were usually visible, but where the impulse was insufficient to induce coma no damage of any sort was found. Two modes of injury were established, having different impulse thresholds. At the lower threshold it was possible to study injury to axons, e.g. compare the effect of varying the plane of rotation, without inducing subdural bleeding. Contusions were usually observed in this mode, which was considered to be due to separation of the pia mater from the cortex due to trabecular tension. Subdural bleeding could be added by raising the impulse above the second threshold. Thus contusions can occur without subdural bleeding but not vice versa in whiplash injury. HYPOTHESIS: The SBS definition is internally inconsistent. By specifying that contusions are rarely seen it seems to rule out whiplash on which the concept of Shaken Baby Syndrome is based. The definition is consistent with dysphagic accidents leading to aspiration, a Dysphagic Infant Death Syndrome in which the carer plays no part.

Paroxysmal coughing, subdural and retinal bleeding: a computer modelling approach.

Unexplained subdural and retinal haemorrhages in an infant are commonly attributed to 'shaking', the mechanism of which is believed to be traumatic venous rupture. However, the haemorrhagic retinopathy reported as a result of Valsalva manoeuvres and the subdural bleeding that is a rare complication of pertussis together demonstrate that if a sustained rise in intrathoracic pressure is transmitted to cerebral and retinal vessels, it may result in bleeding, similar to that reported in inflicted injury. Such haemorrhages would be expected to occur whenever severe paroxysmal coughing were induced, whatever the cause. This study used a computer modelling approach to investigate feeding accidents as the trigger for bleeding. A dynamic circulatory model of a 3-month-old infant was induced to 'cough', and the response to changes in physiological variables monitored. It showed that coughing causes intracranial pressures to build up exponentially to approach a maximum, proportional to the amount of pressure the musculature of the thorax can produce, as venous return is impeded. They do not have time to become dangerous during individual coughs, as blood quickly returns after the cough is over, reestablishing normal pressures. Paroxysmal coughing, however, does not allow blood to return between coughs, with the result that very high luminal pressures may be generated, sufficient to damage veins. A history of coughing, vomiting or choking is not uncommon in otherwise normal infants with retinal and subdural bleeding. Our findings suggest that paroxysmal coughing could account for such bleeding in some cases.

Dysphagia as a risk factor for sudden unexplained death in infancy.

The TRIAD of encephalopathy, subdural haemorrhages, and retinal haemorrhages is commonly considered diagnostic of Shaken Baby Syndrome, but the original paper describes a statistically linked QUADRAD of features, the fourth of which is a previous history of feeding difficulties (dysphagia). Recent reviews of giving pacifiers (dummies) to infants during sleeping periods have found a significant reduction in the incidence of Sudden Infant Death Syndrome. Stimulation of swallowing is a possible connection with dysphagia, which is examined here, illustrated by a well documented case. Although amniotic fluid passes freely through the larynx of fetal mammals during fetal breathing, application of pure water to the laryngeal epithelium in infants causes choking and laryngeal closure. "Water sensors" in the surface respond to lack of chloride ions and adapt very slowly or not at all. Others have found in puppies that following application of pure water only 32% resume breathing in less than 30-40s. The rest needed at least one saline flush, and some required artificial ventilation in addition. These receptors also respond to high potassium concentrations and acid or alkaline solutions. Normally, airway closure during swallowing or vomiting prevents entry of feed or oesophageal reflux, but in some forms of dysphagia leakage can occur, causing paroxysmal coughing, reflex laryngeal closure, and so prolonged apnoea. Recently, it has been realised that the TRIAD injuries can also result from high intracranial vascular pressures transmitted from intra-thoracic pressure surges during paroxysmal coughing, choking, etc. Triggering of such pressure surges by dysphagic accidents provides a physiological link to injuries commonly considered diagnostic of Shaken Baby Syndrome, completing the statistically identified QUADRAD of features. Further dysphagic research might reveal predictive factors, and preventative measures such as feeds of optimal pH.

The 'Sutured Skull' and intracranial bleeding in infants.

It is known that retinal haemorrhages can result in adults when elevated intrathoracic pressures due to coughing, cardiopulmonary resuscitation, etc., force blood into the head. In infants under one year of age retinal and intracranial haemorrhage commonly occur together, but the same is not true for the older child and adult. The role of the elasticity of the infant skull (resulting from suture and fontanelle stretching) compared to the rigid mature skull, was investigated in a computer aided method. This showed that although in the event of Valsalva-like situations very high lumen pressures may be present in both groups, in the rigid adult skull an immediate corresponding increase in intracranial pressure is produced which surrounds and supports vascular walls leaving transmural pressures little changed. No such support is provided in the eye, and retinal vessels may rupture. Within the skull there may be drastic effects on brain circulation, but since changes in vascular transmural pressure are minimal vessel distension is not induced. In the infant skull the sutures stretch as pressure rises. Since vascular volume is only about 5% of intracranial volume each 1% increase in skull volume permits a 20% increase in vascular volume. Quite small skull expansions will allow dangerous vascular distension and risk of wall damage. Until skull bones fuse, intra-cranial bleeding will be expected in the soft infant skull in any situation where retinal haemorrhage alone is known to occur in the adult or child.

Paroxysmal cough injury, vascular rupture and 'shaken baby syndrome'.

It is widely assumed that subdural and retinal haemorrhage in infants can only result from traumatic rupture of vulnerable blood vessels. An alternative aetiology, that of vascular rupture resulting from excessive intraluminal pressure, is presented in three disease conditions. (1) Perlman et al., studying premature neonates requiring mechanical ventilation for respiratory distress syndrome, observed "cough-like" fluctuations in oesophageal pressure greater than 18 cms H2O, whose timing matched fluctuations in anterior cerebral artery flow. When 14 out of 24 neonates were paralysed (to prevent abdominal muscle activity) intraventricular haemorrhage developed in all 10 controls but in only one of the paralysed group during paralysis. (2) New analysis of pressure data extracted from a previous study of prolonged expiratory apnoea showed alveolar collapse induced 100 mmHg intrathoracic cough pressure surges. Superior vena cava pressures up to 50 mmHg were implied, and radial artery systolic pressures over 180 mmHg recorded. (3) Bordetella pertussis bacteria attach to cilia in the airways, but do not invade the underlying tissue. The irritation causes the powerful coughing paroxysms of whooping cough. Brain haemorrhages and retinal detachment have been observed to result from the high intravascular pressures produced. The data suggest that any source of intense airway irritation not easily removed (laryngeal infection, inhalation of regurgitated feed, fluff, smoke etc.) could induce similar bleeding, a paroxysmal cough injury (PCI). Additional objective evidence of inflicted trauma is necessary to distinguish between 'shaken baby syndrome' and PCI.

Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention.

OBJECTIVE: To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients. DESIGN: Prospective, interrupted time-series analysis. SETTING: University hospital in the south-eastern United States. SUBJECTS: Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003. INTERVENTION: A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation. MAIN OUTCOME MEASURE: The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention. RESULTS: There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units. CONCLUSIONS: A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability.

Pseudo-arterio-arterial anastomoses in twin-twin transfusion syndrome.

OBJECTIVE: It has recently been claimed that fetoscopic recognition of a haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests minimal net intertwin flow. This was based on blood from one fetus being dark and from the other bright red, the boundary between them reciprocating with the fetal heart beats. However, bright red indicates that the blood had passed through a cotyledon and been freshly oxygenated, which should be impossible in an AAA. We applied a computer model of chorionic vessels to determine a configuration that reproduced this phenomenon. METHODS: A previously published TTTS model was extended to provide placental detail in a segment containing four cotyledons of each placenta supplied by three generations of placental arteries and veins. RESULTS: Reciprocating flow is not unique to AAAs. It also occurs in the chorionic arteries of any cotyledon deprived of its venous outflow, in a similar manner to that in which reverse end-diastolic flow occurs in umbilical arteries when whole placental resistance is high. If venous return from the common chorionic vein in the recipient (draining the venous end of an AVA) is blocked as might happen after laser, there can be bidirectional flow from one umbilical artery insertion, through two cotyledons to the other insertion. We define this phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path means that its resistance cannot match the low flow resistance of a true AAA, and transmission of the contralateral pulsatile pattern is absorbed in the cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two sets of systolic peaks, one forward and one reverse, can be discerned in true AAAs but only one in PAAAs. CONCLUSIONS: We demonstrate how venous occlusion of an arterio-venous anastomosis may produce a pseudo-AAA colour equator at endoscopy. However, visual observation of reciprocating flow is not sufficient to define a vessel as a true AAA which instead requires ultrasonical identification of two systolic patterns.

Spiral artery associated restricted growth (SPAARG): a computer model of pathophysiology resulting from low intervillous pressure having fetal programming implications.

Failure of adequate trophoblastic conversion of maternal spiral arteries is associated with intrauterine growth restriction (IUGR). In addition to poor oxygen delivery, raised spiral artery resistance reduces placental intervillous pressure. An iterative type computer model was formed by linking an existing model of the fetus and a new nine cotyledon placental model. Simulation of compression cuffing of the spiral arteries to progressively restrict uteroplacental flow was performed, while observing various fetal and placental variables. Water moved to the fetus in the cotyledonary core villi, and to the mother in the outer villous layers. While the fetus could match villous capillary pressure to changes in intervillous pressure, net transplacental water movement was minimal, but when spiral artery resistance was increased sufficiently to cause mean intervillous pressure to fall below that which the fetus could match, a net flow to the mother appeared. That continued until the resulting fetal blood hemoconcentration produced a sufficient increase in colloid osmotic pressure to restrict further loss. All cells within the fetal-placental unit are then required to operate in an abnormal ionic environment, which may significantly affect systems such as the renin-angiotensin set-point, with implications for post-natal homeostasis such as control of adult blood pressure. Furthermore, in vivo, cells of the feto-placental unit respond to the increased intravascular osmotic pressure by production of intracellular osmolytes in order to match intracellular and vascular/interstitial osmotic pressures. This may explain the observed effects on postnatal water balance in growth restricted infants and could also provide a possible mechanism for the association of the systemic maternal complications associated with impaired placentation and reduced intervillus flow.

Alveolar septal collapse in the transitional infant lung: a possible common mechanism in sudden unexpected death in infancy.

Sudden unexpected death in infancy (SUDI) is a category used to represent the largest single group of infant deaths. Although there are several theories, the cause of SUDI remains unknown and the mechanism of co-sleeping associated deaths are also undetermined. We investigate a possible biomechanical mechanism which may be common in SUDI and may provide an explanation for the association of the known risk factors for SUDI such as co-sleeping, prematurity, prone sleeping position, overwrapping, overheating and maternal smoking. The neonatal lung has few, if any, true septa but from about four weeks of age, a period of rapid alveolarisation commences. The developing alveolar walls (septae) have little fibre support against surface tension forces as they grow but are supported by a double layer of capillaries. Until the elastin/collagen supporting network is laid down these nascent septal walls are vulnerable to collapse against sac or duct walls during this transitional period. We hypothesise that such collapse will prevent one side of the septa, and the wall it overlays, from alveolar gas exchange and a functional left-right shunt is formed which may result in hypoxia. Furthermore, lung stretch receptors in bronchi running through or adjacent to collapsed regions will be activated, falsely signalling lung inflation to the brain stem with resultant respiratory inhibition, so precipitating further collapse. The process will continue until lung volume falls below residual capacity, when normal tidal breathing efforts will no longer result in significant air flow, even if stretch receptor signals have not produced complete apnoea. Large inspiratory efforts are then required to break the surface tension seal, which damages capillaries to produce petechial haemorrhages. Many epidemiological risk factors for SUDI could influence such a mechanism, leading to the proposal that Alveolar Septal Collapse in Infancy (ASCI) is a core mechanism via which these factors act.

The dynamic placenta: I. Hypothetical model of a placental mechanism matching local fetal blood flow to local intervillus oxygen delivery.

The placenta can be severely infarcted and yet return well oxygenated blood in spite of the potential shunt paths produced. Optimisation of oxygen transport by some form of local flow matching has been suggested, either via a direct action of hypoxia on subchorial vessels, or indirectly by syncytiotrophoblastic metabolic products. Using casts of cotyledonal vessels and software modelling, a mechanism of hypoxic fetoplacental vasoconstriction could be demonstrated. A simple previously described passive placental model was extended to include hypoxic sensitive arteries and dependence of syncytio-trophoblastic metabolism on intervillus (maternal) blood oxygen content. Such a mechanism of placental flow matching could maintain fetal pO2 by reducing flow through inadequately oxygenated cotyledons, therefore optimising pO2 at the expense of flow. A further modification stabilising fetal water transfer was required to avoid changes in intervillus oxygen delivery producing changes in fetal water content via placental capillary pressure alterations. Intervillus/villus flow matching is likely in the human placenta and this study suggests probable biologically plausible mechanisms for such a phenomenon.

The dynamic placenta: II. Hypothetical model of a fetus driven transplacental water balance mechanism producing low apparent permeability in a highly permeable placenta.

In vitro and isotopic studies in vivo have reported the paradox that the human placenta is highly permeable, water exchanging at 3.6 litres per hour at 35 weeks of gestation, but clinical measurements in vivo show net transfer is minimal, around 2 ml/day. Current theories are based on osmotic pressure balances, but changes in maternofetal hydrostatic pressure change much faster than osmotic factors could respond. An alternative explanation might be that net transfer is not in fact the result of passive mechanisms, but is actively controlled by the fetus itself. The fetus is well equipped to monitor changes in blood volume, such as via sensors in venous and atrial stretch receptors to control ANF and hence urine production. Transplacental water regulation requires modification of transvillus pressures. Placental sub-chorial arteries and veins (of extra-embryonic origin) have different sensitivities from fetal body tissues to some vasoactive substances, and stem villous veins have unusually well developed vascular smooth muscle. It is thus theoretically possible for the fetus to modify subchorial venous resistances, and hence villous capillary pressure with a suitable circulating placental venous constrictive agent. A computer modelling study was undertaken using a fictitious placental venous constricting agent "fictensin", considered to be released by the fetus in proportion to disturbance of vascular volume. The effective placental permeability fell in proportion to the tightness of this fetal control mechanism, suggesting that the apparent placental permeability measured in vivo is a measure of fetal control, not true permeability. However, the range of compensatory pressures that the fetus can produce by this means is limited and failure of such a mechanism could allow flooding or dehydration of the feto-placental unit. This may shed new light on disorders such as polyhydramnios and fetal hydrops.

Occlusion of arterio-arterial anastomosis manifesting as acute twin-twin transfusion syndrome.

In vivo, ex vivo and modelling studies suggest that arterio-arterial anastomoses (AAAs) protect against haemodynamic imbalance in monochorionic twins and thus the development of TTTS. We report the acute onset of severe TTTS at 34 weeks' gestation in a patient with an antenatally visualized AAA which was shown at injection studies to have been obliterated, presumably by thrombosis. Computer modelling with the relevant clinical data confirmed that occlusion of the AAA alone was sufficient to reproduce the clinical manifestations. A study of the vascular configuration of AAA in the fixed placenta suggested that its small diameter and turbulent flow may have contributed to its occlusion. This case report shows that the unmasking of unbalanced AVA configurations by occlusion of a protective AAA can manifest as TTTS.

Transmitted arterio-arterial anastomosis waveforms causing cyclically intermittent absent/reversed end-diastolic umbilical artery flow in monochorionic twins.

OBJECTIVES: To characterize the phenomenon of retrograde transmission of arterio-arterial anastomosis (AAA) interference patterns on umbilical artery (UA) waveform by (a) documenting the periodicity, (b) correlation with in vivo and in vitro demonstration of AAAs and (c) reproducing these patterns by computer modelling. METHODS: Monochorionic twins (MC) twins underwent placental and umbilical Doppler studies. AAAs were sought by pulse wave Doppler of their bi-directional interference pattern and confirmed by postnatal injection studies. The periodicity of transmitted patterns in the UA was determined. Determinants of the transmitted patterns were ascertained by computer modelling of physiological and fetal variables. RESULTS: Among 83 prospectively studied MC twin pregnancies; a transmitted pattern was observed in 6 (7 per cent) patients for 15-114 days. This was found in 20 per cent (6/30) of smaller MC twins discordant for growth restriction but in no appropriately grown twins. It was only observed in association with AAAs validated both in vivo and in ex vivo. Computer modelling demonstrated that this pattern could be reproduced by summating end diastolic flow with a high pulsatility index in the UA in the presence of a large AAA. Consistent with this, MC twins with a transmitted pattern had larger AAAs (median diameter 4.3 mm interquartile range 4.1-5.2) compared to MC twins discordant for intrauterine growth restriction (2.1 mm interquartile range 1.5 to 2.8) (P<0.05) without a transmitted pattern. Perinatal mortality was similar in the fetuses with and without transmitted patterns (0/12 vs. 2/48 P=0.7).

Developing a methodology to improve the allocation of specialized health resources for acutely injured persons.

Inappropriate triage following acute injury may result in misallocation of specialized health resources, increased health care costs, reduced or delayed access to care, and increased death and disability. Although triage criteria have been developed, they vary widely, and inappropriate triage rates are high (50% - 85%). The purpose of this project was to evaluate the ability of decision tree induction to predict need for specialized trauma resources in acutely injured persons. We considered any person who was admitted to the trauma center's ICU or died prior to being admitted to the ICU as needing specialized trauma resources.

The role of intraplacental vascular smooth muscle in the dynamic placenta: a conceptual framework for understanding uteroplacental disease.

Although non-innervated, the placenta must continually accommodate changes in uteroplacental pressure (due to spiral artery failure, maternal position, maternal emotional state, etc.), which might otherwise be expected to result in rapid feto-maternal water fluxes in the highly water-permeable human hemochorial placenta. Uteroplacental flow must also be under the same influences, producing temporary, or permanent, regions of poor intervillous flow, yet the reduction of umbilical vein oxygen content that would be expected to be produced by such shunts of feto-placental blood do not occur in the normal fetus. We suggest that there is a local villus tree mechanism matching intravillus flow of fetal blood to local uteroplacental oxygen content. By analogy to ventilation/perfusion (V/Q) matching in the postnatal lung we suggest the term U/Q matching for this mechanism in the placenta. We further suggest that such disturbances in flow matching are compensated for by the fetus, via complementary adjustment of umbilico-chorionic artery and umbilical venous flow resistances, utilizing the differing sensitivities of vascular smooth muscle tissues of embryonic and extra-embryonic origin to vasoactive agents.

'Cor placentale': placental intervillus/intravillus blood flow mismatch is the pathophysiological mechanism in severe intrauterine growth restriction due to uteroplacental disease.

The underlying pathophysiology in most cases of severe intrauterine growth restriction and pre-eclampsia is thought to be abnormal and inadequate conversion of the branches of the uterine arteries into low resistance uteroplacental vessels, due to poor extravillous trophoblastic invasion, leading to reduced intervillous blood flow. Since, in most vascular beds the main site of flow resistance is at the level of the small arteries/arterioles rather than the capillary bed itself it is likely that in cases of intrauterine growth restriction due to uteroplacental dysfunction with abnormal fetal umbilical artery flow velocity waveforms, the underlying pathological mechanism is primarily an initial reduction in intervillus flow leading to relative local hypoxia of some villus territories. This results initially in autocrine/paracrine mediated localized stem artery vasoconstriction to minimize intervillus/intravillus flow mismatch which, when widespread, will result in abnormal umbilical artery Doppler waveforms due to the globally increased resistance to fetoplacental flow. Since, a small reduction in vessel radius will result in an exponential increase in flow resistance and reduction in flow, the magnitude of stem vessel constriction need only be small to result in large changes in fetoplacental vascular haemodynamics. Thus, the underlying progressive pathology in this condition may be cardiac failure, secondary to chronic stem vessel vasoconstriction caused by abnormalities in oxygenation of the fetal respiratory system hence the term 'cor placentale' is proposed.

Twin-to-twin transfusion syndrome results from dynamic asymmetrical reduction in placental anastomoses: a hypothesis.

Although placental vascular anastomoses between the fetoplacental circulations are ubiquitous in monochorionic twin pregnancies, the factors regulating their formation and maintenance are not understood. Increasing evidence implicates asymmetric anastomotic patterns in the aetiology of severe twin-to-twin transfusion syndrome (TTTS). The authors propose that anastomoses between placental circulations in monochorionic twins occur in a random manner at the embryological stage of connection of embryonic and extra-embryonic circulations. Placental expansion is then associated with random disruption of anastomoses and regression of their associated villus districts. TTTS develops as discordant loss of anastomoses results in asymmetrical flow resistance. Pregnancies with fetal growth concordance but discordant nuchal translucency at 10-14 weeks are at increased risk of developing subsequent severe TTTS because these clinical features indicate significant pressure differentials in the presence of a placentoplacental circulation, consistent with the presence of numerous, asymmetric anastomoses. However, since the anastomotic pattern is dynamic in the first half of pregnancy this hypothesis predicts that it will not be possible to devise a clinical test at 12 weeks that will predict with certainty the outcome of monochorionic twin pregnancies in relation to TTTS because this depends on random subsequent events.

A computer based intervention on the appropriate use of arterial blood gas.

OBJECTIVE: To evaluate impact of a computer-based intervention on arterial blood gas (ABG) usage in an intensive care setting. DESIGN: Retrospectively examined, via mixed group analysis, the effects of the intervention on ABG usage in the intensive care unit (ICU). SUBJECTS: Included all clinicians who placed ABG orders in an ICU using the computerized physician order-entry system, as well as controls in non-order entry units. METHODS: Computer-based intervention presenting ordering clinician with patient s previous ABG values and limiting forward duration of tests ordered. Study spanned 12 weeks, 5 weeks pre-intervention and 7-weeks post-intervention. Of 8 ICUs, intervention implemented in 6, not implemented in 2. Data analyzed using the repeated measure ANOVA. RESULTS: Physicians entered <40% ABG orders. 376 ABGs per week processed pre-intervention, 387 per week post. Results nonsignificant with a p= 0.09. Orders placed declined from 1039 per week, Jan 2000 to 662 per week, April 2001. DISCUSSION: Study did not demonstrate significant change; limited power. Need longer study periods. Impact improved in the future by targeting physician users and tailoring intervention to specific work flow pattern of high utilization units.