Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses.

BACKGROUND: Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. METHODS: Extended Cox models with time-varying co-variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. RESULTS: Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause-specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19-0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14-1.82, p = .003), and lower risk of all-cause mortality (HR: 0.22, 95% CI: 0.18-0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21-0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13-0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63-1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all-cause mortality (HR: 1.27, 95% CI: 0.99-1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all-cause mortality was statistically significant (p = .024). CONCLUSIONS: Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study.

Necrotising soft tissue infections. / Nekrotiserende bløtdelsinfeksjoner.

Necrotising soft tissue infections can affect the skin, subcutaneous tissue, superficial fascia, deep fascia and musculature. The infections are severe, they spread quickly and can result in extensive tissue loss. Although rare, morbidity and mortality rates are high. Early clinical identification is crucial for the outcome, and rapid infection control through surgery and targeted antibiotic treatment is needed to save lives. Few prospective clinical trials have been conducted for the treatment of this type of infection. Specific challenges include rapid identification of the condition and the uncertain efficacy of the various treatment options. In this clinical review article, we describe clinical characteristics, diagnostics and treatment.

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Protocol for exploratory post hoc analyses.

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding.

Patients over 75 years admitted to the National Burn Centre, Haukeland University Hospital, 2000-19. / Pasienter over 75 år innlagt ved Brannskadeavdelinga, Haukeland universitetssjukehus 2000­19.

BACKGROUND: The number of burn patients over the age of 75 receiving advanced treatment, including extensive surgery and intensive care, is increasing. We aimed to describe the treatment and outcomes for burn patients over the age of 75 admitted to the National Burn Centre at Haukeland University Hospital. We also wanted to investigate whether frailty scores can be a predictor of the treatment outcome. MATERIAL AND METHOD: All patients ≥ 75 years admitted to the National Burn Centre at Haukeland University Hospital in the period 2000-19 were included in the study. Frailty scores were calculated retrospectively based on patients' medical records. RESULTS: Our study included 101 patients (50 women and 51 men). The number of admissions of older burn patients increased from an average of 3.3 per year in 2000-14 to 10.2 in the period 2015-19. The median total body surface area with burns was 11 % (range 0.9-80 %). Seventeen patients received palliative care, and 12 patients receiving active treatment died in hospital. In 68 of 84 (81 %) actively treated patients, tangential excision and split-thickness skin grafting were performed. The remainder received conservative treatment (non-surgical) with wound care and application of a silver dressing. Patients who died in hospital had a significantly higher total body surface area with burns (p < 0.0001) and higher frailty scores (p = 0.003) than patients who survived. INTERPRETATION: The yearly number of patients over the age of 75 treated at the National Burn Centre tripled during the period. More than two-thirds of the patients were discharged alive. Extent of burn injury and frailty score are associated with mortality and may be useful for adjusting therapy.

Vasoactive and/or inotropic drugs in initial resuscitation of burn injuries: A systematic review.

BACKGROUND: According to current guidelines, initial burn resuscitation should be performed with fluids alone. The aims of the study were to review the frequency of use of vasoactive and/or inotropic drugs in initial burn resuscitation, and assess the benefits and harms of adding such drugs to fluids. METHODS: A systematic literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, UpToDate, and SveMed+ through 3 December 2021. The search included studies on critically ill burn patients receiving vasoactive and/or inotropic drugs in addition to fluids within 48 h after burn injury. RESULTS: The literature search identified 1058 unique publications that were screened for inclusion. After assessing 115 publications in full text, only two retrospective cohort studies were included. One study found that 16 out of 52 (31%) patients received vasopressor(s). Factors associated with vasopressor use were increasing age, burn depth, and % total body surface area (TBSA) burnt. Another study observed that 20 out of 111 (18%) patients received vasopressor(s). Vasopressor use was associated with increasing age, Baux score, and %TBSA burnt in addition to more frequent dialysis treatment and increased mortality. Study quality assessed by the Newcastle-Ottawa quality assessment scale was considered good in one study, but uncertain due to limited description of methods in the other. CONCLUSION: This systematic review revealed that there is a lack of evidence regarding the benefits and harms of using vasoactive and/or inotropic drugs in addition to fluids during early resuscitation of patients with major burns.

Humoral and cellular immune responses in critically ill influenza A/H1N1-infected patients.

There is limited knowledge of influenza-specific immune responses and their kinetics in critically ill patients. We investigated humoral and cellular immune responses after critical influenza A/H1N1 infection and hypothesized that dysfunctionality or absence of immune responses could contribute to more severe illness. We followed 12 patients hospitalized with severe influenza infection; the majority admitted to intensive care unit (ICU). Blood samples were collected at days 10 and 19 and at 5 months. Antibody responses to surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) of A/H1N1pdm09 were quantified by haemagglutination inhibition (HAI), microneutralization (MN), Enzyme-linked immunosorbent assay (ELISA) and Enzyme-linked lectin assay (ELLA). Influenza-specific antibody levels and avidity were measured separately for head and stalk domains of H1. Cytokine secreting CD4+ and CD8+ T cell responses to conserved influenza epitopes (M1, NP and PB1) were analysed by FluoroSpot. Overall, the patients retained a high level of functional HA- and NA-specific antibodies over the study period. During the acute phase (up to 3 weeks from symptom onset), antibodies specific to H1 stalk increased earlier and were present in higher amount compared with H1 head-specific antibodies. The NA-specific antibodies and the non-neutralizing HA-specific antibody response for H1 head and H1 full-length showed a significant decline from acute to convalescent phase. Despite high total IgG concentrations, avidity to H1 head and H1 full-length protein remained low at all time points. Similarly, CD8+ T cell responses were continuously measured at low levels. In conclusion, our study found that critically ill patients were characterized by low HA-specific antibody avidity and CD8+ T cell response.

Acute kidney injury in burn patients admitted to the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU) associated with increased morbidity and mortality. Our primary aim was to review incidence, risk factors, and outcomes of AKI in burn patients admitted to the ICU. Secondary aims were to review the use of renal replacement therapy (RRT) and impact on health care costs. METHODS: We conducted a systematic search in PubMed, UpToDate, and NICE through 3 December 2018. All reviews in Cochrane Database of Systematic Reviews except protocols were added to the PubMed search. We searched for studies on AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE); Acute Kidney Injury Network (AKIN); and/or Kidney Disease: Improving Global Outcomes (KDIGO) criteria in burn patients admitted to the ICU. We collected data on AKI incidence, risk factors, use of RRT, renal recovery, length of stay (LOS), mortality, and health care costs. RESULTS: We included 33 observational studies comprising 8200 patients. Overall study quality, scored according to the Newcastle-Ottawa scale, was moderate. Random effect model meta-analysis revealed that the incidence of AKI among burn patients in the ICU was 38 (30-46) %. Patients with AKI were almost evenly distributed in the mild, moderate, and severe AKI subgroups. RRT was used in 12 (8-16) % of all patients. Risk factors for AKI were high age, chronic hypertension, diabetes mellitus, high Total Body Surface Area percent burnt, high Abbreviated Burn Severity Index score, inhalation injury, rhabdomyolysis, surgery, high Acute Physiology and Chronic Health Evaluation II score, high Sequential Organ Failure Assessment score, sepsis, and mechanical ventilation. AKI patients had 8.6 (4.0-13.2) days longer ICU LOS and higher mortality than non-AKI patients, OR 11.3 (7.3-17.4). Few studies reported renal recovery, and no study reported health care costs. CONCLUSIONS: AKI occurred in 38% of burn patients admitted to the ICU, and 12% of all patients received RRT. Presence of AKI was associated with increased LOS and mortality. TRIAL REGISTRATION: PROSPERO (CRD42017060420).

Outcomes of Prophylactic Pantoprazole in Adult Intensive Care Unit Patients Receiving Dialysis: Results of a Randomized Trial.

BACKGROUND: Intensive care unit (ICU) patients with acute kidney injury requiring renal replacement therapy (RRT) are considered at high risk of gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP) is often prescribed. We aimed to assess the incidence of GI bleeding and effects of SUP in these patients. METHODS: We assessed GI bleeding in ICU patients receiving RRT at baseline (and at any time in the ICU) and effects of prophylactic pantoprazole versus placebo in the international SUP in the ICU (SUP-ICU) trial. All analyses were conducted according to a published protocol and statistical analysis plan. RESULTS: Data of 3,291 acutely admitted adult ICU patients with one or more risk factors for GI bleeding randomized to pantoprazole or placebo intravenously once daily during ICU stay (until ICU discharge, death, or a maximum of 90 days) were analyzed. Some 20 out of 258 (7.8%, 95% CI 4.5-11.1%) and 52 out of 568 (9.2%, 95% CI 6.8-11.6%) of the patients receiving RRT at baseline and at any time in ICU, respectively, developed clinically important GI bleeding in the ICU. We did not observe statistically significant differences in the intervention effect (pantoprazole vs. placebo) in the proportion of patients with clinically important GI bleeding, clinically important events, infectious adverse events, use of interventions to stop GI bleeding, or 90-day mortality in patients with versus without RRT at baseline. CONCLUSIONS: In adult ICU patients receiving RRT at baseline, we observed high incidences of clinically important GI bleeding, but did not observe effects of pantoprazole versus placebo in this subgroup.

Use of simulation to improve management of perioperative anaphylaxis: a narrative review.

Simulation-based education is often highlighted as a method to prepare health personnel to handle clinical emergencies through repeated training and the design of supports. As one of the most common clinical emergencies in anaesthesia, anaphylaxis is often included in simulation scenarios at both graduate and postgraduate levels. Case reviews of anaphylaxis management continue to identify deficiencies in clinical responses. We evaluated the evidence to support the use of simulation to address these deficiencies. We undertook a comprehensive review of the MEDLINE and Embase databases with MESH terms 'Anaphylaxis', 'Anaesthesia', 'Simulation training', and variations of these terms. Articles were also searched from reference lists in the identified papers. A total of 39 articles on perioperative anaphylaxis simulation were identified, with most focusing on the clinical skills of individuals. However, anaphylaxis scenarios are also being used in assessment of teams and in the evaluation of broader system performance. Many countries mandate simulation training and competency assessment at graduate and postgraduate levels: despite this, none of the articles linked simulation training or assessment with improved patient management or outcomes. We found evidence that in situ simulation and use of cognitive aids lead to improved teamwork and task performace. Quantitative and qualitative evidence for simulation-based perioperative training is limited. Future studies should investigate whether simulation training in perioperative anaphylaxis, particularly in situ simulation, translates into improved patient management and outcomes.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

Iatrogenic cerebral gas embolism-A systematic review of case reports.

BACKGROUND: Cerebral gas embolism is a complication of several medical procedures and occurs when gas enters the cerebral circulation. Knowledge about etiology and outcome in affected patients is limited, and prospective trials on management and treatment are hardly feasible. Case reports are therefore an important source of information. METHODS: A systematic literature search was conducted in June 2016 and May 2018, supplemented by a manual search. Titles and abstracts were systematically assessed for eligibility, followed by full-text screening for included papers. Screening and data extraction were performed independently by two researchers. Cases of cerebral gas embolism due to any iatrogenic cause were included. Criteria for exclusion were: animal studies, non-cerebral localization, extravascular gas only, and non-iatrogenic causes. 264 cases reported in 189 papers were included. RESULTS: A broad range of procedures leading to iatrogenic cerebral gas embolism (ICGE) were identified and a comprehensive list is presented in this article. Procedures were mostly reported as conducted correctly, but procedure related error, patient activity, or defective equipment were also reported as causes. Neurological, neuropsychological, and cardiopulmonary symptoms were common. The diagnosis was frequently based on or confirmed by radiology, usually CT. Hyperbaric oxygen therapy was applied in a large number of cases. CONCLUSION: The reported causes, symptoms and signs, and outcomes of ICGE vary significantly, and awareness of the condition in the medical community is essential. A standardized method of reporting could facilitate higher quality research in the field.

Time to onset of gastrointestinal bleeding in the SUP-ICU trial: A pre-planned substudy.

BACKGROUND: The aetiology and risk factors for clinically important gastrointestinal bleeding (CIB) in adult ICU patients may differ according to the onset of CIB, which could affect the balance between benefits and harms of stress ulcer prophylaxis (SUP). METHODS: We assessed the time to CIB in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. We assessed if associations between baseline characteristics including allocation to SUP and CIB changed during time in the ICU, specifically in the later (after day 2) compared to the earlier (first 2 days) period, using Cox models adjusted for SAPS II and allocation to SUP. Additionally, we described baseline characteristics and CIB episodes stratified by earlier/later/no CIB and 90-day mortality status. RESULTS: Clinically important gastrointestinal bleeding occurred in 110/3291 (3.3%) patients after a median of 6 (interquartile range 2-13) days; 25.5% of the episodes occurred early. Higher SAPS II was consistently associated with increased risk of CIB (hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05 in the earlier period vs HR 1.02, 95% CI 1.01-1.03 in the later period; P = .37); university hospital admission was associated with decreased risk of earlier CIB (HR 0.30, 95% CI 0.14-0.63); this significantly increased in the later period (to HR 0.85, 95% CI 0.53-1.37; P = .02). Patients with later compared to earlier CIB received more transfusions and had more diagnostic/therapeutic procedures for CIB. CONCLUSIONS: Clinically important gastrointestinal bleeding mostly occurred more than 2 days after randomization. University hospital admission was associated with significantly decreased risk of CIB in the earlier period only.

Pantoprazole in ICU patients at risk for gastrointestinal bleeding-1-year mortality in the SUP-ICU trial.

BACKGROUND: The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. METHODS: In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan. RESULTS: A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients. CONCLUSION: We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others; ClinicalTrials.gov number, NCT02467621).

Are participants in the Medical Student Research Programme continuing to engage in research? / Fortsetter forskerlinjestudenter å forske?

BAKGRUNN: I 2002 ble Forskerlinjen opprettet for tidlig å rekruttere medisinstudenter til forskning. Vi ønsket å kartlegge hvor mange tidligere forskerlinjestudenter fra Universitetet i Bergen som fortsatte å forske og identifisere faktorer som var assosiert med videre forskning. MATERIALE OG METODE: Alle studenter innrullert i forskerlinjeprogrammet ved Universitetet i Bergen siden oppstart i 2002 som var uteksaminert fra medisinstudiet innen juni 2017 ble kontaktet per e-post med en elektronisk spørreundersøkelse. Vi undersøkte om deltagerne holdt på med eller hadde gjennomført doktorgrad, antall publiserte artikler, tid siden siste publisering, akademisk undervisning og veiledning samt nåværende stilling på universitet eller høyskole. RESULTATER: Totalt 102 av 148 (69 %) besvarte spørreundersøkelsen. Av disse hadde 68 % gått videre med doktorgrad, 38 % var involvert i akademisk undervisning eller veiledning og 29 % var ansatt i en akademisk stilling. Samlet hadde deltagerne i median publisert fire artikler. Kvinner hadde større sannsynlighet for å gå videre med doktorgrad enn menn. Det samme hadde de som publiserte minst én artikkel før fullført medisinstudium, og de som ikke hadde mottatt regelmessig veiledning som forskerlinjestudent. Det var ingen sammenheng mellom det å fullføre Forskerlinjen og det å gå videre med doktorgrad. FORTOLKNING: Mange medisinstudenter som har gått Forskerlinjen ved Universitetet i Bergen fortsetter med forskning etter fullført studium. Dette gjelder også de som ikke fullfører linjen.

Patients with burn injuries admitted to Norwegian hospitals - a population-based study. / Brannskadede innlagt i norske sykehus ­ en populasjonsbasert studie.

BACKGROUND: The objective of this article is to elucidate the scope of burn injuries in Norway, on the basis of those patients who had sustained a burn injury that caused hospitalisation through a calendar year. MATERIAL AND METHOD: The article is based on data retrieved from the Norwegian Patient Registry on patients discharged from Norwegian hospitals in 2012 with a burn injury as their main diagnosis, supplemented with activity data for children admitted to the Burn Unit, Haukeland University Hospital, Bergen, during the period 2013 ­ 15. RESULTS: In 2012, altogether 620 people (12.4/100 000 inhabitants) were hospitalised with burn injuries. Of these patients, 393 (63.4 %) were men. A total of 375 patients (60 %) were hospitalised more than once, and 124 (20 %) were admitted to more than one hospital. Altogether 367 patients (59 %) were hospitalised for less than eight days. Average hospitalisation time for the group as a whole was 11.3 days (SD 18.8 days). Many of the burn-injured patients were young: the average age was 27.4 years (SD 26.0 years). As many as 183 patients (30 %) were less than three years old. Children in this age group were admitted for burn injuries 12 times more frequently than children ≥ 5 years and adults. INTERPRETATION: We found no definite reduction in burn injuries as a cause for admission to Norwegian hospitals in 2012 when compared to results from previous studies for the period 1992 ­ 2007. There ought to be a major potential for more effective prevention of burn injuries in the age group < 3 years, in which scalding (78 %) and contact with hot surfaces (most often stoves) (17 %) are the main mechanisms of injury.

COVID-19 and venous thromboembolism - prophylaxis and treatment. / Covid-19 og venøs tromboembolisme ­ profylakse og behandling.

As the pandemic has been unfolding, reports have emerged of a relatively high incidence of coagulopathy and thromboembolic events in connection with COVID-19 infections. Raised awareness surrounding this issue, and appropriate antithrombotic prophylaxis and treatment, are therefore important for this group of patients.

Determining energy requirements in the ICU.

PURPOSE OF REVIEW: Resting energy expenditure in critically ill patients is highly variable depending on the diagnoses, illness severity, nutritional status, and treatments. The main questions are the following: What is the optimal energy target in my critically ill patient in the ICU at a given time point of the ICU stay? Is measured energy expenditure equivalent with energy requirement? RECENT FINDINGS: There is uncertainty on the best way to feed the ICU patient; when to start, and what to give, especially concerning the amount of energy. Recent studies indicate that outcome is dependent on provision, components, and route. Indirect calorimetry is considered the gold standard to measure energy requirement and cannot be replaced by assumptions based on weight, height, sex, age, or minute ventilation. A main concern is that an indirect calorimeter with appropriate specifications to a reasonable cost is not available in the market. There are initiatives to solve this matter. SUMMARY: Nutritionists, intensive care doctors, researchers, and innovators must collaborate to develop an indirect calorimeter to a reasonable cost (less than 10,000 €) that is accurate and handy in the clinical setting. Since this instrument is not yet available, clinicians are left with good clinical practice and predictive formulas.