Opposite effects of fasting on TGF-beta 3 and T beta RI distribution in the gastric mucosa of suckling and early weanling rats

Objective: Our aim was to evaluate the effects of a dietary regimen (suckling or early weaning) and feeding status (fed or fasted) on the distribution of transforming growth factor-beta 3 (TGF-beta 3) and TGF receptor-I (T beta RI) in the gastric epithelium of pups Methods: Wistar rats were used At 15 d, half of the pups were separated from dams and fed with hydrated powered chow On day 17, suckling and early weanling rats were subjected to fasting (17 h). Four different conditions were established. suckling fed and fasted and early weanling fed and fasted At 18 d stomachs were collected under anesthesia and were fixed in 4% formaldehyde for immunohistochemistry The number of immunostained epithelial cells per microscopic field was determined for TGF-beta 3 and T beta RI in longitudinal sections from the gastric mucosa Results: We found that during suckling, fasting reduced the number of immunolabeled cells per field of both molecules when compared with the fed group (P < 0.05), whereas in early weaning, food restriction increased TGF-beta 3 and T beta RI distributions (P < 0.05) We also observed that TGF-beta 3 and T beta RI were more concentrated in parietal cells in the upper gland in suckling pups, whereas after early weaning these were displaced to parietal and chief cells at the bottom of the gland Conclusion: Suckling and early weaning directly influence TGF-beta 3 and T beta RI distributions in the gastric epithelium in response to fasting, such that early weaning anticipates the effects observed in adult rats. Furthermore, the differential concentrations of TGF-beta 3 and T beta RI indicate that they might be important for cell proliferation events in growth control (C) 2010 Elsevier Inc. All rights reserved

EGFR is involved in control of gastric cell proliferation through activation of MAPK and Src signalling pathways in early-weaned rats

Objectives: Early weaning (EW) increases proliferation of the gastric epithelium in parallel with higher expression of transforming growth factor alpha and its receptor epidermal growth factor receptor (EGFR). The primary objective of the present study was to examine involvement of EGFR signalling in regulating mucosal cell proliferation during the early weaning period. Materials and methods: Fifteen-day-old rats were split into two groups: suckling (control) and EW, in which pups were separated from the dam. Animals were killed daily until the 18th day, 3 days after onset of treatment. To investigate the role of EGFR in proliferation control, EW pups were injected with AG1478, an EGFR inhibitor; signalling molecules, proliferative indices and cell cycle-related proteins were evaluated. Results: EW increased ERK1/2 and Src phosphorylation at 17 days, but p-Akt levels were unchanged. Moreover, at 17 days, AG1478 administration impaired ERK phosphorylation, whereas p-Src and p-Akt were not altered. AG1478 treatment reduced mitotic and DNA synthesis indices, which were determined on HE-stained and BrdU-labelled sections. Finally, AG1478 injection decreased p21 levels in the gastric mucosa at 17 days, while no changes were detected in p27, cyclin E, CDK2, cyclin D1 and CDK4 concentrations. Conclusions: EGFR is part of the mechanism that regulates cell proliferation in rat gastric mucosa during early weaning. We suggest that such responses might depend on activation of MAPK and/or Src signalling pathways and regulation of p21 levels.

In vivo effects of TGF beta 1 on the the growth of gastric epithelium in suckling rats

As the content of Transforming Growth Factor-beta (TGF beta) wanes in the milk of lactating rat, an increase in TGF beta is observed in the gastric epithelia concomitant with differentiation of the glands upon weaning. Whereas TGF beta has been shown to inhibit the proliferation of gastrointestinal cells in vitro, its functional significance and mechanisms of action have not been studied in vivo. Therefore, we administered TGF beta 1 (1 ng/g body wt.) to 14-day-old rats in which the gastric epithelium was induced to proliferate by fasting, and determined the involvement of signaling through Smads and the impact on epithelial cell proliferation and apoptosis. After the gavage, we observed the progressive increase of active TGF beta 1 while T beta RII-receptor remained constant in the gastric mucosa. By immunohistochemistry, we showed Smad2/3 increase at 60 min (p < 0.05) and Smad2 phosphorylation/activation and translocation to the nucleus most prominently between 0 and 30 min after treatment (p < 0.05). Importantly, TGF beta 1 inhibited cell proliferation (p < 0.05), which was estimated by BrDU pulse-labeling 12 h after gavage. Lower proliferation was reflected by increased p27(kip1) at 2 h (p < 0.05). Also, TGF beta 1 increased apoptosis as measured by M30 labeling at 60 and 180 min (p < 0.001), and by morphological features at 12 h (p < 0.05). In addition, we observed higher levels of activated caspase 3 (17 kDa) from 0 to 30 min. Altogether, these data indicate a direct effect of TGF beta 1 signaling through Smads on both inhibiting proliferation, through alteration of cycle proteins, and inducing apoptosis of gastric epithelial cells in vivo. Further, the studies suggest a potential role for both milk and tissue-expressed TG beta 1 in gastric growth during postnatal development, (C) 2007 Elsevier B.V. All rights reserved.

Evidensbaserad munvård för att förebygga ventilatorassocierad pneumoni hos ventilatorbehandlande patienter : en systematisk litteraturstudie

Utgångspunkten för denna litteraturstudie är att ventilatorassocierad pneumoni (VAP) går att förebygga. Syftet med detta arbete var att kartlägga olika evidensbaserade munvårdsmetoder som används av intensivvårdssjuksköterskor för att förebygga VAP hos ventilatorbehandlade patienter. Syftet var också att belysa vilka faktorer som påverkar intensivvårdssjuksköterskans utförande av evidensbaserad munvård till ventilatorbehandlade patienter. Studien utfördes som en systematisk litteraturstudie. Till resultatet användes 16 vetenskapliga artiklar. För att kunna bedöma artiklarnas vetenskapliga kvalitet granskades artiklarna utifrån en modifierad granskningsmall. Samtliga artiklar fick höga kvalitetspoäng, vilket innebär hög vetenskaplig relevans. Resultatet av litteraturstudien visar att i flera av de evidensbaserade munvårdsprotokoll som publicerats den senaste tiden finns några återkommande punkter. Dessa punkter är; bedömning av munhålans status, tandborstning med barntandborste, munsköljmedel och att munnen fuktas med ett intervall av två till sex timmar. Flera faktorer påverkar intensivvårdssjuksköterskans utförande av evidensbaserad munvård. Genom att införa ett evidensbaserat munvårdsprotokoll för ventilatorbehandlade intensivvårdspatienter och ge personalen utbildning i munvård kan incidensen av VAP minska. Resultatet visar också att generellt sett är kunskapsnivån låg hos intensivvårdssjuksköterskor gällande förebyggande åtgärder för att förhindra VAP. Om sjuksköterskan anser att hon/han har tid att utföra munvård blir resultatet av högre kvalitet och hon/han upplever också åtgärden som mindre obehaglig. Detta innebär att försök att förbättra omvårdnaden och därmed minska antalet vårdrelaterade infektioner även är en organisatorisk fråga.

The comparative energetics and growth strategies of sympatric Antarctic and subantarctic fur seal pups at Iles Crozet

The period of maternal dependence is a time during which mammalian infants must optimise both their growth and the development of behavioural skills in order to successfully meet the demands of independent living. The rate and duration of maternal provisioning, post-weaning food availability and climatic conditions are all factors likely to influence the growth strategies of infants. While numerous studies have documented differences in growth strategies at high taxonomic levels, few have investigated those of closely related species inhabiting similar environments. The present study examined the body composition, metabolism and indices of physiological development in pups of Antarctic fur seals (Arctocephalus gazella) and subantarctic fur seals (Arctocephalus tropicalis), congeneric species with different weaning ages (4 months and 10 months, respectively), during their overlap in lactation at a sympatric breeding site in the Iles Crozet. Body lipid reserves in pre-moult pups were significantly greater (t₂₈=2.73, P<0.01) in subantarctic (26%) than Antarctic fur seals (22%). Antarctic fur seal pups, however, had significantly higher (t₂₆=3.82, P<0.001) in-air resting metabolic rates (RMR; 17.1±0.6 ml O₂ kg^-1 min^-1) than subantarctic fur seal pups (14.1±0.5 ml O2 kg^-1 min^-1). While in-water standard metabolic rate (SMR; 22.9±2.5 ml O2 kg^-1 min^-1) was greater than in-air RMR for Antarctic fur seal pups (t₉=2.59, P<0.03), there were no significant differences between in-air RMR and in-water SMR for subantarctic fur seal pups (t₁₂=0.82, P>0.4), although this is unlikely to reflect a greater ability for pre-moult pups of the latter species to thermoregulate in water. Pup daily energy expenditure was also significantly greater (t₂₇=2.36, P<0.03) in Antarctic fur seals (638±33 kJ kg^-1 day^-1) than in subantarctic fur seals (533±33 kJ kg^-1 day^-1), which corroborates observations that pups of the former species spend considerably more time actively learning to swim and dive. Consistent with this observation is the finding that blood oxygen storage capacity was significantly greater (t₉=2.81, P<0.03) in Antarctic (11.5%) than subantarctic fur seal (8.9%) pups. These results suggest that, compared with subantarctic fur seals, Antarctic fur seal pups adopt a strategy of faster lean growth and physiological development, coupled with greater amounts of metabolically expensive behavioural activity, in order to acquire the necessary foraging skills in time for their younger weaning age.

Ontogeny of diving behaviour in the Australian sea lion: trials of adolescence in a late bloomer

1.Foraging behaviours of the Australian sea lion (Neophoca cinerea) reflect an animal working hard to exploit benthic habitats. Lactating females demonstrate almost continuous diving, maximize bottom time, exhibit elevated field metabolism and frequently exceed their calculated aerobic dive limit. Given that larger animals have disproportionately greater diving capabilities, we wanted to examine how pups and juveniles forage successfully.
2.Time/depth recorders were deployed on pups, juveniles and adult females at Seal Bay Conservation Park, Kangaroo Island, South Australia. Ten different mother/pup pairs were equipped at three stages of development (6, 15 and 23 months) to record the diving behaviours of 51 (nine instruments failed) animals.
3. Dive depth and duration increased with age. However, development was slow. At 6 months, pups demonstrated minimal diving activity and the mean depth for 23-month-old juveniles was only 44 ± 4 m, or 62% of adult mean depth.
4. Although pups and juveniles did not reach adult depths or durations, dive records for young sea lions indicate benthic diving with mean bottom times (2·0 ± 0·2 min) similar to those of females (2·1 ± 0·2 min). This was accomplished by spending higher proportions of each dive and total time at sea on or near the bottom than adults. Immature sea lions also spent a higher percentage of time at sea diving.
5. Juveniles may have to work harder because they are weaned before reaching full diving capability. For benthic foragers, reduced diving ability limits available foraging habitat. Furthermore, as juveniles appear to operate close to their physiological maximum, they would have a difficult time increasing foraging effort in response to reductions in prey. Although benthic prey are less influenced by seasonal fluctuations and oceanographic perturbations than epipelagic prey, demersal fishery trawls may impact juvenile survival by disrupting habitat and removing larger size classes of prey. These issues may be an important factor as to why the Australian sea lion population is currently at risk.

Ontogeny of oxygen stores and physiological diving capability in Australian sea lions

1.For air-breathing animals in aquatic environments, foraging behaviours are often constrained by physiological capability. The development of oxygen stores and the rate at which these stores are used determine juvenile diving and foraging potential.
2. We examined the ontogeny of dive physiology in the threatened Australian sea lion Neophoca cinerea. Australian sea lions exploit benthic habitats; adult females demonstrate high field metabolic rates (FMR), maximize time spent near the benthos, and regularly exceed their calculated aerobic dive limit (cADL). Given larger animals have disproportionately greater diving capabilities; we wanted to determine the extent physiological development constrained diving and foraging in young sea lions.
3. Ten different mother/pup pairs were measured at three developmental stages (6, 15 and 23 months) at Seal Bay Conservation Park, Kangaroo Island, South Australia. Hematocrit (Hct), haemoglobin (Hb) and plasma volume were analyzed to calculate blood O2 stores and myoglobin was measured to determine muscle O₂. Additionally, FMR's for nine of the juveniles were derived from doubly-labelled water measurements.
4. Australian sea lions have the slowest documented O₂ store development among diving mammals. Although weaning typically occurs by 17·6 months, 23-month juveniles had only developed 68% of adult blood O₂. Muscle O₂ was the slowest to develop and was 60% of adult values at 23 months.
5. We divided available O₂ stores (37·11 ± 1·49 mL O₂ kg−1) by at-sea FMR (15·78 ± 1·29 mL O₂ min−1 kg−1) to determine a cADL of 2·33 ± 0·24 min for juvenile Australian sea lions. Like adults, young sea lions regularly exceeded cADL's with 67·8 ± 2·8% of dives over theoretical limits and a mean dive duration to cADL ratio of 1·23 ± 0·10.
6. Both dive depth and duration appear impacted by the slow development of oxygen stores. For species that operate close to, or indeed above their estimated physiological maximum, the capacity to increase dive depth, duration or foraging effort would be limited. Due to reduced access to benthic habitat and restricted behavioural options, young benthic foragers, such as Australian sea lions, would be particularly vulnerable to resource limitation.

The physiological and behavioural development of diving in Australian fur seal (Arctocephalus pusillus doriferus) pups

The physiological and behavioural development of diving was examined in Australian fur seal (Arctocephalus pusillus doriferus) pups to assess whether animals at weaning are capable of exploiting the same resources as adult females. Haematocrit, haemoglobin and myoglobin contents all increased throughout pup development though total body oxygen stores reached only 71% of adult female levels just prior to weaning. Oxygen storage components, however, did not develop at the same pace. Whereas blood oxygen stores had reached adult female levels by 9 months of age, muscle oxygen stores were slower to develop, reaching only 23% of adult levels by this age. Increases in diving behaviour corresponded to the physiological changes observed. Pups spent little time (<8%) in the water prior to moulting (age 1–2 months) whereas following the moult, they spent >27% of time in the water and made mid-water dives (maximum depth 35.7 ± 2.9 m) with durations of 0.35 ± 0.03 min. By 9 months (just prior to weaning), 30.5 ± 9.3% of all dives performed were U-shaped benthic dives (maximum depth 65.0 ± 6.0 m) with mean durations of 0.87 ± 0.25 min, significantly shorter than those of adult females. These results suggest that while Australian fur seal pups approaching the age of weaning are able to reach similar depths as adult females, they do not have the physiological capacity to remain at these depths for sufficient durations to exploit them to the same efficiency.

Ontogeny of body size and shape of Antarctic and subantarctic fur seals

Pre- and post-weaning functional demands on body size and shape of mammals are often in conflict, especially in species where weaning involves a change of habitat. Compared with long lactations, brief lactations are expected to be associated with fast rates of development and attainment of adult traits. We describe allometry and growth for several morphological traits in two closely related fur seal species with large differences in lactation duration at a sympatric site. Longitudinal data were collected from Antarctic (Arctocephalus gazella (Peters, 1875); 120 d lactation) and subantarctic (Arctocephalus tropicalis (Gray, 1872); 300 d lactation) fur seals. Body mass was similar in neonates of both species, but A. gazella neonates were longer, less voluminous, and had larger foreflippers. The species were similar in rate of preweaning growth in body mass, but growth rates of linear variables were faster for A. gazella pups. Consequently, neonatal differences in body shape increased over lactation, and A. gazella pups approached adult body shape faster than did A. tropicalis pups. Our results indicate that preweaning growth is associated with significant changes in body shape, involving the acquisition of a longer, more slender body with larger foreflippers in A. gazella. These differences suggest that A. gazella pups are physically more mature at approximately 100 d of age (close to weaning age) than A. tropicalis pups of the same age

Omega 6 to omega 3 fatty acid imbalance early in life leads to persistant reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion

Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and  permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2–1.7% of the total fatty acids. The results suggest that omega 6–3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

1-14C-Linoleic Acid distrubution in various tissue lipids of guinea pigs following an oral dose

A recent study on the metabolism of 1-¹⁴C-α-linolenic acid in the guinea pig revealed that the fur had the highest specific activity of all tissues examined, 48 h after dosing. The present study investigated the pattern of tissue lipid labeling following an oral dose of 1-¹⁴C-linoleic acid after the animals had been dosed for the same time as above. Guinea pigs were fed one of two diets with a constant linoleic acid content (18% total fatty acids) and a different content of α-linolenic acid (0.3 or 17.3%) from weaning for 3 wk and 1-¹⁴C-linoleic acid was given orally to each animal for 48 h prior to sacrifice. The most highly labeled tissues (dpm/mg of linoleic acid) were liver, followed by brain, lung and spleen, heart, kidney and adrenal and intestines, in both diet groups. The liver had almost a three-fold higher specific activity than skin and fur which was more extensively labeled than the adipose and carcass. Approximately two-thirds of the label in skin plus fur was found in the fur which, because of a low lipid mass, would indicate that the fur was highly labeled. All tissues derived from animals on the diet with the low α-linolenic acid level were significantly more labeled than the tissues from the animals on the high α-linolenic acid diet, by a factor of 1.5 to 3. The phospholipid fraction was the most highly labeled fraction in the liver, free fatty acids were the most labeled fraction in skin & fur, while triacyglycerols were the most labeled in the carcass and adipose tissue. In these tissues, more than 90% of the radioactivity was found in fatty acids with 2-double bonds in the tissue lipids. These data indicate that the majority of label found in guinea pig tissues 48 h after dosing was still associated with a fatty acid fraction with 2-double bonds, which suggests there was little metabolism of linoleic acid to more highly unsaturated fatty acids in this time frame. In this study, the labeling of guinea pig tissues with linoleic acid, 48 h after dosing, was quite different from the labeling with α-linolenic acid reported previously. The retention of the administered radioactivity from ¹⁴C-linoleic acid in the whole body lipids was 1.6 times higher in the group fed the low α-linolenic acid diet (diet contained a total of 1.8 g PUFA/100 g diet)compared with the group fed the high α-linolenic acid diet (diet contained 3.6 g PUFA/100 g diet). The lack of retention of ¹⁴C-labeled lipids in the whole body would be consistent with an increased rate of β-oxidation of the labeled fatty acid on the diet rich in PUFA, a result supported by other studies using direct measurement of labeled carbon dioxide.

Does perinatal ω-3 polyunsaturated fatty acid deficiency increase appetite signaling?

Objective: To investigate the effect of maternal dietary ω-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling.
Research Methods and Procedures: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) ω-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking β-oxidation of fatty acids (by β-mercaptoacetate injection).
Results: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to β-mercaptoacetate.
Discussion: These findings indicate that supply of ω-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of ω-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition : a protective effect?

Objective:
Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning.

Design:
This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague–Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow.

Results:
Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle.

Conclusion:
This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.

Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution.

Does an evidence-based sedation protocol improve practice and patient outcomes in critical care?

Learning Objective 1: compare protocol-directed sedation management with traditional non-protocol-directed practice in mechanically ventilated patients in an Australian critical care.

Learning Objective 2: explain the contrasting international research findings on sedation protocol implementation.
Minimization of sedation in critical care patients has recently received widespread support. Professional organizations internationally have published sedation management guidelines for critically ill patients to improve the use of research in practice, decrease practice variability and shorten mechanical ventilation duration. Innovations in practice have included the introduction of decision making protocols, daily sedation interruptions and new drugs and monitoring technologies. The aim of this study was to compare protocol-directed sedation management with traditional non-protocol-directed practice in mechanically ventilated patients in an Australian critical care setting.

A randomized, controlled trial design was used to study 312 mechanically ventilated adult patients in a general critical care unit at an Australian metropolitan teaching hospital. Patients were randomly assigned to receive protocol directed sedation management developed from evidence based guidelines (n=153) or usual clinical practice (n=159).

The median (95% CI) duration of ventilation was 58 hrs (44–78 hrs) for patients in the non-protocol group and 79 hrs (56–93) for those patients in the protocol group (p=0.20). Results were not significant for length of stay in critical care or hospital, the frequency of tracheostomies, and unplanned extubations. A Cox proportional hazards model estimated that protocol directed sedation management was associated with a 22% decrease (95% CI: 40% decrease to 2% increase, p=0.07) in the occurrence of successful weaning from mechanical ventilation.

Few randomized controlled trials have evaluated the effectiveness of protocol-directed sedation outside of North America. This study highlights the lack of transferability between different settings and different models of care. Qualified, high intensity nursing in the Australian critical care setting facilitates rapid, responsive decisions for sedation management and an increased success rate for weaning from mechanical ventilation.