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.

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.

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.

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.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Characteristics of 24-hour ambulatory blood pressure monitoring in a COVID-19 survivor.

COVID-19 infection primarily causes severe pneumonia complicated by acute respiratory distress syndrome and multiorgan failure requiring a ventilator support. We present a case of a 55-year-old male, admitted with COVID-19. He was obese but had no other medical conditions. His blood pressure was measured by his general physician on several occasions in the past, all values being normal (<140/90 mmHg). He developed multiorgan failure, requiring vasopressor and ventilator support for 17 days. A prone positioning improved the arterial oxygenation, and reduced the need for supplemental oxygen. After recovery, he showed persistently elevated blood pressure and sinus tachycardia both in clinic and out-of-clinic. The activation of the renin-angiotensin-aldosterone and sympathetic systems, volume-overload, hyperreninemia and cytokine storm might have contributed to the exaggerated cardiovascular response.

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.

Spontaneous Splenic Artery Rupture as the First Symptom of Systemic Amyloidosis.

Spontaneous splenic rupture is a life-threatening condition leading to a rapidly progressing hypovolemic shock due to intra-abdominal blood loss, with a mortality rate of about 10%. Spontaneous splenic rupture can be caused by widely different disorders including acute and chronic infections, neoplastic disorders, and inflammatory noninfectious disorders. In this case report, we present a 67-year-old male patient with hemorrhagic shock caused by an acute bleeding from the splenic artery. The patient was massively transfused with blood products and fluids and underwent laparotomy for hemostatic control and clinical stabilization. Multiorgan involvement by amyloid light-chain amyloidosis (AL-amyloidosis) caused by plasma cell dyscrasia, specifically with infiltration of the spleen artery, was found to be the underlying cause of his life-threatening bleeding. Based on this case, we discuss the features of serious spleen bleeding, massive transfusion therapy in the intensive care setting, and AL-amyloidosis pathophysiology and treatment.

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.

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).

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses.

TRIAL REGISTRATION: ClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751.

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.

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).

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.

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.

Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial.

PURPOSE: In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further. METHODS: The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53. RESULTS: A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00-1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96-1.22 and 1.10; 95% CI 0.97-1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes. CONCLUSIONS: In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. CLINICALTRIALS.GOV: ClinicalTrials.gov No. NCT02467621.