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.

Gender differences in randomised, controlled trials in intensive care units.

There is a male dominance among patients in intensive care units (ICUs). Potentially, this will increase the risk of a skewed male/female distribution in randomised, controlled trials (RCTs). We have evaluated if this has in fact happened when randomising and whether the authors have been aware of that. We performed a systematic search on PubMed from 1 January 2011 to 31 May 2012 using the mesh terms 'randomized controlled trial' and 'intensive care unit'. Twenty-five RCTs with a total of 12,788 patients met the inclusion criteria, with an overall male dominance of 63.6% (P < 0.0001). Eighteen of the 25 papers had an individually statistically significant gender difference in their total trial population. None of the 18 trials with a significant gender difference in their overall trial population had calculated the P-value for this overall difference. In the randomised groups, there was a significant gender difference in five papers. Seventeen had no significant gender difference in the randomised groups, and three papers did not state gender in the randomised groups. This study show that there is a marked male dominance in RCTs conducted in ICUs. We recommend that when planning future RCTs, the authors contemplate if their results can be used indiscriminately among ICU patients if the distribution of males and females is much skewed. It is relevant to determine if ones endpoint can be influenced by gender differences and if there is a risk of gender influence on data, proportional allocation or stratification should be considered.

Non-invasive ventilation in do-not-intubate patients: five-year follow-up on a two-year prospective, consecutive cohort study.

BACKGROUND: End-of-life decisions are common in intensive care units (ICUs), and increasingly, non-invasive ventilation (NIV) is used as a ceiling of ventilatory care. However, little is known about the outcome following that decision. METHODS: An observational, single-center, retrospective, follow-up study with no interventions, on ICU patients treated with NIV and a do-not-intubate (DNI) order. The patients were followed until a 5-year survival rate could be calculated. RESULTS: One hundred and fifty-seven patients were treated with NIV during 2002 and 2003, and among 38 a DNI order was in effect. Of the 38 DNI patients, 11 died in the ICU, 16 died on the ward and 11 survived the hospital stay. Five of these 11 survivors died within 6 months, two died after 2.7 and 3.3 years, respectively, but four were still alive after 5 years. The long-term (>6 months) survivors have, surprisingly only been admitted to the hospital 0-2 times a year - and seldom with the need for ICU treatment. CONCLUSIONS: According to this study, and previous ones, it seems worthwhile treating DNI patients with NIV. Twenty-five to 35% leave the hospital alive, every 6th patient lives for at least 1 year, and this paper shows that 10% may survive for 5 years or more. However, only chronic obstructive pulmonary disease and chronic heart failure patients (both with a concomitant low APACHE score) seem to have a reasonable outcome, and patients should be informed about this. So far, no study has investigated the quality of life of these survivors.

Experiences from introducing non-invasive ventilation in the intensive care unit: a 2-year prospective consecutive cohort study.

OBJECTIVE: To describe 2 years of experience and staff learning curves after the introduction of non-invasive ventilation (NIV). METHODS: A prospective, consecutive, strictly observational, 2-year cohort study of all patients treated with NIV in a county general hospital intensive care unit (ICU), with no interventions, was performed. RESULTS: One hundred and fifty-seven patients with 15 different diagnoses were treated with NIV. An increasing number of patients were treated in the second year and, probably as a result of increased staff experience, the NIV treatment time and overall time spent in the ICU were less in the second year of the study period (30 h vs. 19 h and 55 h vs. 34 h, respectively; P < 0.05). Patients were also intubated earlier if NIV failed during the second year. Of the 157 patients, 119 had a full treatment option (i.e. including the possibility of invasive mechanical ventilation) and 26% died; their Acute Physiology and Chronic Health Evaluation II (APACHE II)- and Simplified Acute Physiology II (SAPS II)-predicted death rates were 31% and 32% respectively (not significant, NS). The overall mortality rate in all NIV patients was 38%, compared with predicted death rates of 36% and 33%, respectively (NS). 'Do-not-intubate' orders were issued for 38 of the 157 patients, and 11 of these (29%) left the hospital alive. Patients treated successfully with NIV had significantly lower APACHE II scores than those in whom it failed (18.8 vs. 22, P= 0.01). CONCLUSION: With increasing staff experience, more patients may be treated with NIV and the treatment period decreases significantly. Weaning from NIV has almost exclusively been taken over by nurses. Unselected cohorts of patients with chronic obstructive pulmonary disease can be treated successfully with NIV, and NIV offers a treatment option even for some patients with a 'do-not-intubate' order.

Cardiac magnetic resonance imaging: long term reproducibility of the late enhancement signal in patients with chronic coronary artery disease.

OBJECTIVE: To determine long term reproducibility of the late enhancement (LE) signal in contrast enhanced magnetic resonance imaging (MRI) and potential changes of the signal after revascularisation. METHODS: 33 patients (29 men, mean (SD) 61 (11) years) with coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30 (7)%) underwent two contrast enhanced MRI procedures within 9 (3) months. Fifteen patients (group A: 14 men, 59 (12) years) had no interventions between the two studies. Eighteen patients underwent revascularisation after MRI 1 (group B: 15 men, 62 (9) years). Changes in the LE signal between the first and second MRIs were investigated in both groups as well as intraobserver and interobserver variabilities for delineation of the signal. RESULTS: The LE signal was highly reproducible in groups A and B for segmental analysis (concordance 86% v 82%, respectively; kappa = 0.70 v 0.67) and summed scores (group A: r = 0.97, p < 0.001; group B: r = 0.93, p < 0.001). The LE signal was quantified as 27 (27) cm3 in group A versus 30 (16) cm3 in group B in the first MRI and 26 (25) cm3 versus 30 (15) cm3, respectively, for the second MRI (both not significant). Moreover, low intraobserver and interobserver variabilities were observed in segmental analysis (kappa = 0.86 and 0.74, respectively, for group A, and kappa = 0.87 and 0.82, respectively, for group B). CONCLUSION: In patients with chronic CAD, the LE signal in contrast enhanced MRI is very stable over an extended time period. These results further characterise contrast enhanced MRI as a useful tool for myocardial viability assessment. Low intraobserver and interobserver variabilities promise robustness of the method for clinical application.

Nuclear cardiology in acute coronary syndromes.

Acute coronary syndromes are a frequent manifestation of coronary artery disease, usually being associated with chest pain and presenting as a medical emergency. Since a considerable number of patients with chest pain, however, have a non cardiac etiology of their pain, properly triaging these patients represents a diagnostic challenge for physicians in the emergency department. As the available diagnostic procedures have limited accuracy, many different diagnostic strategies have been evaluated. Among these, radionuclide myocardial perfusion imaging (MPI) at rest or in combination with stress procedures has been investigated in many trials. MPI has been proven to be useful, especially in a patient population with a low to intermediate probability of an ischemic event. Perfusion scintigraphy has a high sensitivity in the detection of myocardial infarction and reveals an excellent negative predictive value, allowing a safe discharge strategy of patients with a negative scan result. Moreover, it enables risk stratification and provides incremental and independent prognostic information regarding short to long term future cardiac adverse events. Several cost effectiveness studies have shown that perfusion imaging leads to lower overall direct costs, mainly by a reduction of unnecessary hospital admissions and diagnostic angiograms, without worsening of the clinical outcome of these patients. As a possible study endpoint, myocardial perfusion imaging in the acute setting enables the quantification of salvaged myocardium and therefore the evaluation of treatment efficacy. Besides perfusion agents, several infarct avid radiopharmaceuticals have been developed, which in part show promising results. However, larger randomized trials evaluating these tracers in clinical settings are needed to warrant routine clinical application.

Lactic acidosis following convulsions.

Lactic acidosis is a common cause of metabolic acidosis and is usually connected with high mortality. However, changes in the level of lactate and pH can also be seen after generalized epileptic attacks, due to local muscle hypoxia during the seizures. Although these changes can be quite marked, the condition is self-limiting and usually does not call for any specific treatment. We report five cases of lactic acidosis following convulsions from our centre.

Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction.

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (>or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.

[Percutaneous balloon dilatation of discrete subaortic stenosis]. / Perkutane Ballondilatation einer umschriebenen Subaortenstenose.

Discrete subaortic stenosis is an uncommon congenital cardiac disorder in which the left ventricular outflow tract is narrowed. We report about the diagnostic procedures and the successful balloon dilatation of a 49-year old, highly symptomatic male patient suffering from discrete subvalvular aortic stenosis.

Construction and characterization of a catalytic fusion protein system: P-450(11beta)-adrenodoxin reductase-adrenodoxin.

Cortisol is an important intermediate for the production of steroidal drugs and can only be synthesized chemically by rather complicated multi-step procedures. The most critical step is the 11beta-hydroxylation of 11-deoxycortisol, which is catalyzed by a mitochondrial enzyme, P-450(11beta). Various fusion constructs of P-450(11beta) with its electron transfer components, adrenodoxin and adrenodoxin reductase, were produced by cDNA manipulation and were successfully expressed in COS-1 cells from which the hydroxylation activities were assayed. It was demonstrated that the fusion protein required both adrenodoxin reductase and adrenodoxin for its activity and was not able to receive electrons from an external source. The fusion protein with all three components had less activity than P-450(11beta) alone, receiving electrons from coexpressed or internal electron transfer components. The activities of the fusion proteins were determined mainly by the fusion sequence. The fusion protein with a sequence of P-450(11beta)-adrenodoxin reductase-adrenodoxin was more active than that of P-450(11beta)-adrenodoxin-adrenodoxin reductase, 1.5- and 3-fold for bovine and human P-450(11beta), respectively. Modification of the linker region by extending the size of the linker with various peptide sequences in the bovine P-450(11beta)-adrenodoxin reductase-adrenodoxin fusion protein indicated that the linker did not have significant effect on the P-450 activity. Taken together, the fusion protein obtained here can serve as a model for the investigation of electron transfer in P-450 systems and is of potential importance for biotechnological steroid production.

Functional expression of the guinea pig 11b-hydroxylase in COS-1 cells.

We expressed a guinea pig 11 beta-hydroxylase cDNA (1) in COS-1 cells. In order to find the optimal expression system we compared three expression plasmids, each driven by a different promoter. Although promoters exhibited different transcriptional activities this did not result in different enzymatic activities. Upon cotransfection with bovine adrenodoxin a 5-fold increase of enzyme activity was achieved. A comparison with the bovine 11 beta-hydroxylase clearly demonstrated that the guinea pig enzyme was not able to produce significant amounts of 18-hydroxylated and 18-oxidized products from deoxycorticosterone under the experimental conditions used.

Expression of cytochrome P45011B1 mRNA in the brain of normal and hypertensive transgenic rats.

Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the brain of male rats by in situ hybridization methods. Normal Sprague-Dawley rats were compared to the transgenic strain TGR(mRen2)27, characterized by the expression of the murine Ren-2d renin gene and the development of severe hypertension. Specific riboprobes were generated by in the vitro transcription of a 152 base-pair long cDNA template 35S-labeled riboprobes were hybridized to cryostat sections from adrenal glands and from two different levels of the brain using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared. Following autoradiography and counterstaining, cytochrome P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis of the adrenal cortex and in distinct layers of the cerebral cortex. High signal densities were obtained in the layers II-IV of the neocortex and in the layer II of the piriform cortex, although the concentrations of cytochrome P45011B1 mRNA were remarkably lower in the central nervous system as compared to adrenal glands. As revealed by the semi-quantitative analysis, there was a slight increase in adrenal 11 beta-hydroxylase mRNA in the transgenic rats, whereas the brain seems to express nearly the same amount of this enzyme in both strains. The cytochrome P45011B1 mRNA expression in distinct cells, probably nerve cells, and especially in regions with high densities of glucocorticoid receptors points to a possible function of brain derived corticosterone in receptor activation.

Management of postoperative pain. An intervention study.

BACKGROUND: In 1989 a study had shown that the quality of postoperative pain treatment (PPT) in a district general hospital was not satisfactory. Therefore, new instructions for PPT were issued, intra-venous medication with morphine was introduced on the wards, and the staff was educated in PPT. The purpose of this study was to investigate the quality of PPT in 1992 compared to the quality in 1989. METHODS: Using identical questionnaires, 191 patients in 1989 and 126 patients in 1992 were interviewed before and 2-5 days after surgery regarding postoperative pain. At the postoperative interview patients in pain also filled out the McGill Pain Questionnaire. A questionnaire was also answered by the nurses regarding PPT in 1989 and in 1992. RESULTS: 1992 compared to 1989 (1992/1989): all patients were now medicated (100%/93%), most of them regularly (79%/ 4%) and the majority (94%/15%) also received non-opioid analgesic. Fewer patients (65%/80%) experienced postoperative pain lasting more than one day following surgery. Analgesic prescription was more standardized. In 1992 the nurses were more satisfied than in 1989 with the PPT and the physicians' prescribing patterns. All the above-mentioned parameters were significantly improved from 1989 to 1992. All the different pain-scores showed a reduction (8-30%) but did not reach statistical significance (P = 0.2). CONCLUSIONS: Our two investigations show that it is possible to improve the quality of pain management with rather simple reforms.

Zone-specific localization of cytochrome P45011B1 in human adrenal tissue by PCR-derived riboprobes.

Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the human adrenal cortex and in human adenomas by in situ hybridization methods. Specific riboprobes were generated by in vitro transcription of 11 beta-hydroxylase--specific synthetic oligonucleotides with attached T7 and SP6 polymerase promotors. [35S]- and digoxigenin-labeled riboprobes were hybridized to sections of an aldosterone-producing adenoma (APA), the non-tumour portion of the corresponding adrenal gland, and two adenomas not related to hyperaldosteronism using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared by statistical tests. Following autoradiography or immunohistochemical detection of the digoxigenin cytochrome P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis of non-tumour portion of an human adrenal with an APA. Zona glomerulosa, medulla and connective tissue were free of label. As revealed by the semi-quantitative analysis, 11 beta-hydroxylase mRNA signals in the APA were significantly lower than those in the attached non-tumour portion and the other two adenomas. The results confirm known observations on the occurrence of cytochrome P45011B1 in the adrenal cortex of other species, but show, contrary to several immunohistochemical studies, that the enzyme is obviously not expressed in the zona glomerulosa.

Respiratory changes during treatment of postoperative pain with high dose transdermal fentanyl.

This study made a longterm (72 hours) evaluation of the efficacy and possible side-effects of transdermal delivery of fentanyl (TTS-system) for post-operative pain relief. The study was double-blind, placebo-controlled with either a TTS-system delivering fentanyl 100 micrograms.h-1 and rescue analgesic on demand or a placebo system and analgesic on demand. Analgesic consumption, pain, general satisfaction, respiratory rate, and levels of SpO2 and tcCO2 (pulse oximetry and transcutaneous CO2 measuring) were evaluated. Recruitment was stopped after enrolment of 24 patients, on safety grounds. The Fentanyl group was more satisfied with postoperative pain relief (P = 0.008); they had a lower analgesic demand (P < 0.05) but also a lower respiratory rate (P < 0.05) and a higher level of tcCO2 23 hours after application (P < 0.05). There were three cases (25%) of increased PaCO2 (> 6.5 kPa) in the Placebo group but without low PaO2 levels, sedation or bradypnoea. Conversely, there were three cases (33%) in the Fentanyl group with bradypnoea (< 10 breaths/minute), two without influence on PaO2 or PaCO2, but one (no. 24) with bradypnoea, heavy sedation, a marked decrease in PaO2 (5.8 kPa) and increased PaCO2 (7.5 kPa). These findings terminated the study. The 100 micrograms transdermal fentanyl system is agreeable to the patients, but apparently too potent for routine postoperative pain relief due to a risk of respiratory depression. Respiratory frequency can not be relied upon as sole indicator of insufficient respiration.

[Quality assurance in postoperative pain treatment]. / Kvalitetsvurdering af postoperativ smertebehandling.

One hundred and ninety-one patients were interviewed before and after surgery about their attitude toward and the quality of received pain relief. The nurses working in the same surgical units answered a questionnaire covering attitudes to postoperative pain and pain treatment. Forty-seven percent of the patients were in pain at the time of the postsurgical interview, 10% had not any analgesic prescribed at all, and 15% had received less than prescribed. Fifty-one nurses (71% of the total nursing staff) answered the questionnaire. Of these, 63% were sometimes in doubt about the physicians' prescriptions, 55% would occasionally refuse to give analgesics for various reasons, and 37% were not satisfied with the routines of pain control in their ward. Knowledge of pain treatment and communication between surgeons, anaesthesiologists, nurses and patients must be improved to make postsurgical pain relief adequate.

[Acupuncture treatment of knee arthrosis. A long-term study]. / Akupunkturbehandling til knaeartrose. Et langtidsstudie.

The purpose of this study was to examine acupuncture treatment of patients with osteoarthrosis of the knee. Twenty-nine patients with a total of 42 osteoarthritic knees were randomized to two groups. Group A was treated while group B served as a no treatment control group for nine weeks. Analgesic consumption, pain and objective measurements were registered. In the second part of the study 17 patients (26 knees) continued with treatments once a months. Registrations were continued for a total study period of 49 weeks. Comparing group A with B, there was a significant reduction in pain, analgesic consumption and in most objective measures. In group A + B combined there was an 80% subjective improvement, and a significantly increased range of movement of the knee. Results were significantly better in those who had not been ill for a long time. The second part of the study showed that it was possible to maintain the improvements.

[Loop diuretics. Rational pharmacotherapy]. / Slyngediuretika. Rationel farmakoterapi.

UNLABELLED: The pharmacodynamics and -kinetics as well as rational pharmacotherapy of furosemide and bumetanide is reviewed. In renal insufficiency, a reduced response to diuretics is due to altered pharmacokinetics. The optimum dose can be determined within three to four hours by titration and the effect is measured by the amount of excreted sodium. In nephrotic syndrome, both pharmaco-kinetics and--dynamics are altered. The optimum dose is established as above. Starting and ceiling doses are given in tables for both drugs in renal insufficiency and nephrotic syndrome. In congestive heart failure, the difference is greater between oral and intravenous doses than apparent from the bioavailability of the drugs. If potent diuretics are without effect, the heart failure must be treated more vigorously or a combination with thiazides tried out. Potent diuretics are seldom used in the treatment of liver cirrhosis, but, if used, large doses are necessary. Non-steroidal antiinflammatory drugs are usually considered contra-indicated in patients with severe renal insufficiency, since the pharmacodynamics of the diuretics are altered. CONCLUSION: The general strategy when using potent diuretics is titration to an effective dose and then using this dose as frequently as needed in order to obtain the desired response.