The clinical task force: Improving quality of medical students' internship.

Background: Up to 40% of young medical doctors feel that the internships prepared them insufficiently for the clinical work. This study investigated whether a Clinical Task Force (CTF) could improve internship quality. Methods: The CTF visited internship departments with a triple-targeted approach: first, departments pre-filled a self-evaluating questionnaire; secondly, CTF visited departments to discuss the self-evaluation and previous student evaluations; and thirdly, CTF and departments agreed on several quality-improving focus points to work on after the meeting. Focus points were followed-up after three and 12 months. The impact on internship quality was assessed with departments' student evaluation scores, number of completed focus points, and the effect of completed focus points on a range of learning parameters. The CTF learned several things along the way, that potentially could affect the quality of internships. A shortlist of these was provided to illustrate unmeasurable benefits. Results: The CTF met with 53 out of 60 eligible departments. The CTF and departments agreed upon 197 focus points of which 64% were completed. The three most frequent categories of focus points were Introduction of the students, The departments' evaluation percentage, and The departments' function as an educational site. The mean student evaluation scores did not change significantly, but the individual evaluation parameters changed significantly in two categories. It decreased in the category regarding the students' satisfaction with the clinical lecturers and the scheduled teaching and increased in the category regarding the percentage of students evaluating the department. Conclusion: The CTF's triple-targeted approach did not increase the mean student evaluation score significantly. For departments that completed the agreed focus points, one category increased and another decreased. However, the unmeasurable benefits illustrated that CTF was a good viable linking element between the faculty, departments, and students with the potential of improving other aspects of the quality of internships.

Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients.

BACKGROUND: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors' preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors' preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. METHODS: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. RESULTS: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2 ) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2 ); and 23% preferred SaO2 . Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. CONCLUSION: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.

Hypophosphatemia and duration of respiratory failure and mortality in critically ill patients.

BACKGROUND: Hypophosphatemia has been associated with prolonged duration of respiratory failure and increased mortality in critically ill patients, but there is very limited evidence supporting the negative effects of low phosphate. We examined the association between hypophosphatemia at ICU admission and time to successful weaning and 28-day mortality. METHODS: This was a cohort study that included all mechanically ventilated adult patients admitted to the ICU in 2013 at Nordsjaellands Hospital. Hypophosphatemia was defined as a serum level below 0.80 mmol/L. Multivariate Cox-regression was used to evaluate the effect of hypophosphatemia on mechanical ventilation and 28-day mortality. Multiple imputation was used to adjust for missing values. RESULTS: A total of patients were admitted during the study period, of whom 190 were eligible. 122 (64.2%) had serum phosphate levels measured during the first 24 hours of admission, of whom 25 (20.5%) were found to be hypophosphatemic. About 74% of patients were successfully weaned from the ventilator within 28 days. Hypophosphatemia was not associated with this outcome (HR: 0.56; 95% CI: 0.30-1.04; P = .067). All-cause 28-day mortality was 32.6%. Hypophosphatemia was also not associated with 28-day mortality (HR: 1.64; 95% CI: 0.65-4.17; P = .447). Similar results were present in supplementary analysis where missing data were included by means of multiple imputation. CONCLUSION: Hypophosphatemia at ICU admission was not associated with prolonged respiratory failure nor mortality. Further studies are warranted, where phosphate is measured systematically on all patients to elucidate the effect of low phosphate on relevant outcomes.

Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial.

BACKGROUND: Accumulation of fluids is frequent in intensive care unit (ICU) patients with acute kidney injury and may be associated with increased mortality and decreased renal recovery. We present the results of a pilot trial assessing the feasibility of forced fluid removal in ICU patients with acute kidney injury and fluid accumulation of more than 10% ideal bodyweight. METHODS: The FFAKI-trial was a pilot trial of forced fluid removal vs standard care in adult ICU patients with moderate to high risk acute kidney injury and 10% fluid accumulation. Fluid removal was done with furosemide and/or continuous renal replacement therapy aiming at net negative fluid balance > 1 mL/kg ideal body weight/hour until cumulative fluid balance calculated from ICU admission reached less than 1000 mL. RESULTS: After 20 months, we stopped the trial prematurely due to a low inclusion rate with 23 (2%) included patients out of the 1144 screened. Despite the reduced sample size, we observed a marked reduction in cumulative fluid balance 5 days after randomisation (mean difference -5814 mL, 95% CI -2063 to -9565, P = .003) with forced fluid removal compared to standard care. While the trial was underpowered for clinical endpoints, no point estimates suggested harm from forced fluid removal. CONCLUSIONS: Forced fluid removal aiming at 1 mL/kg ideal body weight/hour may be an effective treatment of fluid accumulation in ICU patients with acute kidney injury. A definitive trial using our inclusion criteria seems less feasible based on our inclusion rate of only 2%.

Fluid accumulation during acute kidney injury in the intensive care unit.

INTRODUCTION: Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. METHOD: We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. RESULTS: The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. CONCLUSION: Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery.

Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock.

BACKGROUND: The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock. METHODS: This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate, highest dose of noradrenaline, and the urinary output were recorded in five time frames in the first 24 h after randomisation. We used multiple linear mixed effects models to compare the two groups. RESULTS: We included all 151 randomised patients; the cumulated fluid resuscitation volume in the first 24 h after randomisation was median 500 ml (Interquartile range (IQR) 0-1500) and 1250 ml (500-2500) in the fluid restriction group and standard care group, respectively. The estimated differences in the fluid restriction group vs. the standard care group were 0.1 mM (95% confidence interval -0.7 to 0.9; P = 0.86) for lactate, 0.01 µg/kg/min (-0.02 to 0.05; P = 0.48) for dose of noradrenaline, and -0.1 ml/kg/h (-0.3 to 0.2; P = 0.70) for urinary output during the first 24 h after randomisation. CONCLUSIONS: We observed no indications of worsening of measures of circulatory efficacy in the first 24 h of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation.

Impact of follow-up consultations for ICU survivors on post-ICU syndrome: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of routine follow-up consultations versus standard of care for intensive care unit (ICU) survivors. METHODS: Systematic literature review from five databases (Cochrane CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL), reference lists, citation tracking, and ongoing/unpublished trials. Randomized controlled trials investigating post-ICU consultations in adults with outcomes such as quality of life (QOL), anxiety, depression, posttraumatic stress disorder (PTSD), physical ability, cognitive function, and return to work were included. Two reviewers extracted data and assessed quality independently. The mean differences, risk ratios, and 95 % confidence intervals were calculated depending on outcome measures. RESULTS: From 1544 citations, five trials were included (855 patients). The overall risk of bias was low in two trials, unclear in two trials, and high in one trial. The overall quality of evidence was low. The trials assessed follow-up interventions defined as consultations informing survivors about their ICU stay. One trial found no effect on QOL. Pooling data from two trials (n = 374) showed a protective effect on risk of new onset PTSD at 3-6 months after ICU (risk ratio 0.49, 95 % CI 0.26-0.95). There was no effect on other outcomes. CONCLUSIONS: The evidence indicates that follow-up consultations might reduce symptoms of PTSD at 3-6 months after ICU discharge in ICU survivors, but without affecting QOL and other outcomes investigated. This review highlights that planning of future RCTs should aim to standardize interventions and outcome measures to allow for comparisons across studies.

Fluid volume and osmoregulation in humans after a week of head-down bed rest.

Body fluid homeostasis was investigated during chronic bed rest (BR) and compared with that of acute supine conditions. The hypothesis was tested that 6 degrees head-down BR leads to hypovolemia, which activates antinatriuretic mechanisms so that the renal responses to standardized saline loading are attenuated. Isotonic (20 ml/kg body wt) and hypertonic (2.5%, 7.2 ml/kg body wt) infusions were performed in eight subjects over 20 min following 7 and 10 days, respectively, of BR during constant sodium intake (200 meq/day). BR decreased body weight (83.0 +/- 4.8 to 81.8 +/- 4.4 kg) and increased plasma osmolality (285.9 +/- 0.6 to 288.5 +/- 0.9 mosmol/kgH(2)O, P < 0.05). Plasma ANG II doubled (4.2 +/- 1.2 to 8.8 +/- 1.8 pg/ml), whereas other endocrine variables decreased: plasma atrial natriuretic peptide (42 +/- 3 to 24 +/- 3 pg/ml), urinary urodilatin excretion rate (4.5 +/- 0.3 to 3.2 +/- 0.1 pg/min), and plasma vasopressin (1.7 +/- 0.3 to 0.8 +/- 0.2 pg/ml, P < 0.05). During BR, the natriuretic response to the isotonic saline infusion was augmented (39 +/- 8 vs. 18 +/- 6 meq sodium/350 min), whereas the response to hypertonic saline was unaltered (32 +/- 8 vs. 29 +/- 5 meq/350 min, P < 0.05). In conclusion, BR elicits antinatriuretic endocrine signals, but it does not attenuate the renal natriuretic response to saline stimuli in men; on the contrary, the response to isotonic saline is augmented.

Gastrointestinal osmoreceptors and renal sodium excretion in humans.

The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogastric tube as isotonic or hypertonic saline (850 mM). In additional experiments, salt loading was replaced by oral water loading (3.5% of total body water). Plasma sodium concentration increased after hypertonic saline (+3.1 +/- 0.7 mM), decreased after water loading (-3.8 +/- 0.8 mM), and remained unchanged after isotonic saline. Oncotic pressure decreased by 9.4 +/- 1.2, 3.7 +/- 1.2, and 10.7 +/- 1.3%, respectively. Isotonic saline induced an increase in renal sodium excretion (104 +/- 15 to 406 +/- 39 micromol/min) that was larger than seen with hypertonic saline (85 +/- 15 to 325 +/- 39 micromol/min) and water loading (88 +/- 11 to 304 +/- 28 micromol/min). Plasma ANG II decreased to 22 +/- 6, 35 +/- 6, and 47 +/- 5% of baseline after isotonic saline, hypertonic saline, and water loading, respectively. Plasma atrial natriuretic peptide (ANP) concentrations and urinary excretion rates of endothelin-1 were unchanged. In conclusion, stimulation of osmoreceptors by intragastric infusion of hypertonic saline is not an important natriuretic stimulus in sodium-replete subjects. The natriuresis after intragastric salt loading was independent of ANP but can be explained by inhibition of the renin-angiotensin system.

Antihypertensive effect of 0.1-Hz blood pressure oscillations to the kidney.

BACKGROUND: Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. METHODS AND RESULTS: Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. CONCLUSIONS: BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Blood pressure and plasma catecholamines in acute and prolonged hypoxia: effects of local hypothermia.

This study measured the pressor and plasma catecholamine response to local hypothermia during adaptation to hypobaric hypoxia. Eight healthy men were studied at rest and after 10 and 45 min of local cooling of one hand and forearm as well as after 30 min of rewarming at sea level and again 24 h and 5 days after rapid, passive transport to high altitude (4,559 m). Acute mountain sickness scores ranged from 5 to 16 (maximal attainable score: 20) on the first day but were reduced to 0-8 by the fifth day. Systolic blood pressure, heart rate, and plasma epinephrine increased on day 1 at altitude compared with sea level but declined again on day 5, whereas diastolic and mean blood pressures continued to rise in parallel with plasma norepinephrine. With local cooling, an increased vasoactive response was seen on the fifth day at altitude. Very high pressures were obtained, and the pressure elevation was prolonged. Heart rate increased twice as much on day 5 compared with the other two occasions. Thoracic fluid index increased with cooling on day 5, suggesting an increase in pulmonary vascular resistance. In conclusion, prolonged hypoxia seems to elicit an augmented pressor response to local cooling in the systemic and most likely also the pulmonary circulation.

Mechanisms of inhibition of vasopressin release during moderate antiorthostatic posture change in humans.

The hypothesis was tested that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release. Ten healthy males underwent this posture change for 30 min without or with simultaneous application of lower body negative pressure (LBNP) adjusted to maintain left atrial diameter (LAD) at the Seat level. Throughout Sup, mean arterial pressure and heart rate decreased from 98 +/- 2 to 91 +/- 2 mmHg and from 63 +/- 2 to 55 +/- 2 beats/min (P < 0.05), respectively, whereas the corresponding decreases during Sup + LBNP were attenuated and of shorter duration (98 +/- 2 to 93 +/- 2 mmHg and 62 +/- 2 to 58 +/- 3 beats/min, P < 0.05). During Sup, LAD increased from 30 +/- 1 to 33 +/- 1 mm, and arterial pulse pressure (PP) increased from 40 +/- 2 to 47 +/- 2 mmHg, whereas plasma AVP decreased from 0.9 +/- 0.2 to 0.5 +/- 0.1 pg/ml (P < 0.05), and plasma norepinephrine (NE) decreased from 176 +/- 20 to 125 +/- 16 pg/ml (P < 0.05). During Sup + LBNP, there were no changes in LAD, PP, plasma AVP, or NE. In conclusion, vasopressin secretion is suppressed during an antiorthostatic posture change, which increases carotid sinus pressure, PP, and LAD. The suppression is absent when PP and LAD are prevented from increasing and is thus critically dependent on at least one of these stimuli.

Isotonic and hypertonic sodium loading in supine humans.

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day(-1). Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L(-1)). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 +/- 0.3 mmol L(-1)). Oncotic pressure decreased significantly more with isotonic saline (4.1 +/- 0.3 mmHg) than with hypertonic saline (3.2 +/- 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 +/- 13 mmol) and hypertonic saline (123 +/- 10 mmol) were statistically identical exceeding that of time control (81 +/- 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.

Cardiovascular, endocrine, and renal effects of urodilatin in normal humans.

Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood pressure and heart rate. The two highest doses elicited larger decreases in stroke volume (17 and 21%) but also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%), such that cardiac output remained unchanged. Hematocrit and plasma protein concentration increased with the three highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 +/- 17 micrograms/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (<10 pg/min) and that fractional excretion of urodilatin remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate, and that filtered urodilatin is almost completely removed by the renal tubules.

Ten days of head down tilt: effects of isotonic and hypertonic saline loads in normal man.

The initial response to bed rest involves an increase in central blood volume leading to a an enhanced renal excretion of fluid and electrolytes. Within 24 hours of head-down bed rest a new steady state condition occurs with a sustained reduction of plasma volume, extracellular fluid volume, total body water, and body weight. It was the purpose of the present study to elucidate the volume homeostatic mechanisms during head-down bed rest by investigating the endocrine and renal responses to a load of sodium chloride given as either an isotonic or a hypertonic solution.

Renal effects of urodilatin and atrial natriuretic peptide in volume expanded conscious dogs.

The renal effects of urodilatin and atrial natriuretic peptide (ANP) were examined in conscious dogs during acute volume expansion maintained through independent infusions of water and NaCl. Peptide was infused in a step-up fashion, in 40-min periods at rates of 2.5, 12.5 and 50.0 ng kg-1 min-1 (ANP, urodilatin) or 0.5, 2.5 and 10.0 ng kg-1 min-1 (second series of urodilatin). ANP immunoreactivity (ANPir) in plasma was measured with an antibody showing 100% cross-reactivity with urodilatin. At 50 ng kg-1 min-1, ANP increased plasma ANPir some 10-fold (64 +/- 6 pg ml-1 to 728 +/- 82 pg ml-1) while urodilatin elicited a 25-fold increase in ANPir (78 +/- 13 pg ml-1 to 1645 +/- 204 pg ml-1). ANP doubled sodium excretion (61 +/- 12 to 124 +/- 30 mumol min-1, P < 0.05) while urodilatin increased sodium excretion to 269 +/- 45 mumol min-1. Both peptides approximately doubled urine flow. Urodilatin at 10 ng kg-1 min-1 increased sodium excretion from 57 +/- 17 mumol min-1 to 106 +/- 25 mumol min-1, i.e. similar to the response ANP elicited at 50 ng kg-1 min-1. In the time control series a significant fall in sodium excretion was observed, despite the continuous replacement of sodium and water. The results demonstrate that in identical, relatively high doses, the changes in sodium excretion, diuresis, heart rate (HR) and arterial pressures elicited by urodilatin are more pronounced than those of ANP.(ABSTRACT TRUNCATED AT 250 WORDS)