Self-reported symptoms experienced by intensive care unit patients: a prospective observational multicenter study.

PURPOSE: The purpose of this study is to describe the prevalence, intensity and distress of five symptoms in intensive care unit (ICU) patients and to investigate possible predictive factors associated with symptom intensity. METHODS: This is a prospective cohort study of ICU patients. A symptom questionnaire (i.e., Patient Symptom Survey) was used to describe the prevalence, intensity and distress of pain, thirst, anxiousness, tiredness, and shortness of breath over seven ICU days. Associations between symptom intensity and possible predictive factors were assessed using the general estimating equation (GEE) model. RESULTS: Out of 603 eligible patients, 353 (Sample 2) were included in the present study. On the first ICU day, 195 patients (Sample 1) reported thirst as the most prevalent symptom (66%), with the highest mean intensity score (6.13, 95% confidence interval (CI) [5.7-6.56]). Thirst was the most prevalent (64%) and most intense (mean score 6.05, 95%CI [5.81-6.3]) symptom during seven days in the ICU. Anxiousness was the most distressful (mean score 5.24, 95%CI [4.32-6.15]) symptom on the first day and during seven days (mean score 5.46, 95%CI [4.95-5.98]). During seven days, analgesic administration and sepsis diagnosis were associated with increased thirst intensity. Older age and being mechanically ventilated were associated with decreased pain intensity, and analgesic administration was associated with increased pain intensity. Family visits and female gender were associated with increased intensity of anxiousness and shortness of breath, respectively. CONCLUSIONS: Self-reporting ICU patients experienced a high and consistent symptom burden across seven days. Certain variables were associated with the degree of symptom intensity, but further research is required to better understand these associations.

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.

Early activity in mechanically ventilated patients - a meta-analysis. / Tidlig aktivitet hos respiratorpasienter ­ en metaanalyse.

BACKGROUND: In Norway, almost 8 500 patients received mechanical ventilation in 2019. We have investigated the effect of early activity in mechanically ventilated adults in intensive care units on the duration of ventilation, weaning time from mechanical ventilation, mortality, length of stay, and adverse events. METHOD: We conducted a systematic literature search for randomised controlled trials in nine databases. Two authors selected studies, extracted data and then rated the certainty of evidence according to the GRADE framework. RESULTS: A total of 3 270 titles and abstracts were read, and 17 studies with 1 805 patients and a low-to-moderate risk of bias were included. The analyses showed that early mobilisation reduced both the mean duration of ventilation (-1.43 days; 95 % CI -2.68 to -0.18, p = 0.02) and the ICU length of stay (-1.08 days; 95 % CI -1.95 to -0.21, p = 0.02), with the certainty of evidence rated as moderate. Inspiratory muscle training had no effect on the duration of mechanical ventilation (-0.11; 95 % CI -1.76 to 1.53, p = 0.89) or on the weaning time from mechanical ventilation (-0.33; 95 % CI -1.31 to 0.65, p = 0.51), with the certainty of evidence rated as low. Neither early mobilisation nor inspiratory muscle training affected mortality. Few adverse events were reported. INTERPRETATION: The analyses show that early mobilisation is safe and can shorten the duration of mechanical ventilation and the ICU length of stay, but has no effect on mortality. Inspiratory muscle training had no effect on any of the outcome measures.

Utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit patients.

BACKGROUND: The aim of this study was to evaluate the utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit (ICU) patients. METHODS: Prospective observational study of ICU patients receiving dalteparin prophylaxis at Oslo University Hospital in Norway. Trough and peak antithrombin, protein C, anti-factor Xa activity (aFXa), d-dimer, thromboelastography, calibrated automated thrombogram and microparticles were analysed. Levels were compared in patients with and without venous thromboembolism (VTE), major bleeding, acute kidney injury (AKI) with use of renal replacement therapy (RRT) and variable dalteparin dose. RESULTS: Among 50 included patients (76% male, mean age 62 years) five (10%) developed VTE and eight (16%) major bleeding. Median through aFXa level was 0.03 (0.02-0.05) IU/mL, and 48 (96%) of patients were within and two (4%) above target range. Peak aFXa level was 0.21 (0.13-0.29) IU/mL, the number of patients below, within and above prophylactic range were 21 (42%), 25 (50%) and four (8%). Peak aFXa levels were similar in patients with and without VTE (0.18 vs 0.21 IU/L, P = .72), major bleeding (0.22 vs 0.21 IU/mL, P = .38) and AKI with RRT (0.18 vs 0.24, P = .13), but lower in patients receiving dalteparin 5000 IU od compared to 7500 IU od (0.19 vs 0.30 IU/mL, P < .01). CONCLUSIONS: Intensive care unit patients receiving dalteparin prophylaxis had half of patients within prophylactic peak aFXa target range. Peak aFXa levels was affected by administered dalteparin dose, but not presence of VTE, major bleeding or AKI with RRT.

Hospitalisations for COVID-19 - a comparison of different data sources. / Sykehusinnleggelser med covid-19 ‒ en sammenligning av ulike datakilder.

BACKGROUND: Three different data sources exist for monitoring COVID-19-associated hospitalisations in Norway: The Directorate of Health, the Norwegian Intensive Care and Pandemic Registry (NIPaR), and the linking of the Norwegian Patient Registry (NPR) and the Norwegian Surveillance System for Communicable Diseases (MSIS). A comparison of results from different data sources is important to increase understanding of the data and to further optimise current and future surveillance. We compared results from the three data sources from March to June 2020. MATERIAL AND METHOD: We analysed the number of new admissions, as well as the total number of hospitalised patients and those on ventilatory support, reported per day and by regional health authority. The analysis was descriptive. RESULTS: The cumulative number of new admissions according to NPR-MSIS (n=1260) was higher than NIPaR (n=1153). The discrepancy was high early in the epidemic (93 as of 29 March). The trend in the number of hospitalised patients was similar for all three sources throughout the study period. NPR-MSIS overestimated the number of hospitalised patients on ventilatory support. INTERPRETATION: The discrepancy in new admissions between NIPaR and NPR-MSIS is primarily due to missing registrations for some patients admitted before NIPaR became operational. Basic information retrieved daily by the Directorate of Health give comparable results to more comprehensive daily information retrieval undertaken in NIPaR and NPR-MSIS, adjusted retrospectively. Further analysis is necessary regarding whether NIPaR and NPR-MSIS provide timely data and function as required in an emergency preparedness situation.

Barriers and challenges in the process of including critically ill patients in clinical studies.

BACKGROUND: Clinical research in severely ill or injured patients is required to improve healthcare but may be challenging to perform in practice. The aim of this study was to analyse barriers and challenges in the process of including critically ill patients in clinical studies. METHODS: Data from critically ill patients considered for inclusion in an observational study of venous thromboembolism in Norway were analysed. This included quantitative and qualitative information from the screening log, consent forms and research notes. RESULTS: Among 279 eligible critically ill patients, 204 (73%) were omitted from the study due to challenges and barriers in the inclusion process. Reasons for omission were categorised as practical in 133 (65%), medical in 31 (15%), and legal or ethical in 40 (20%) of the patients. Among 70 included patients, 29 (41%) consents were from patients and 41 (59%) from their next of kin. Several challenges were described herein; these included whether patients were competent to give consent, and which next of kin that should represent the patient. Furthermore, some included patients were unable to recall what they have consented, and some appeared unable to separate research from treatment. CONCLUSIONS: Barriers and challenges in the inclusion process led to the omission of near three out of four eligible patients. This analysis provided information about where the problem resides and may be solved. The majority of challenges among included patients were related to issues of autonomy and validity of consent. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03405766).

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).

Urine ß-2-Microglobulin, Osteopontin, and Trefoil Factor 3 May Early Predict Acute Kidney Injury and Outcome after Cardiac Arrest.

PURPOSE: Acute kidney injury (AKI) is a common complication after out-of-hospital cardiac arrest (OHCA), leading to increased mortality and challenging prognostication. Our aim was to examine if urine biomarkers could early predict postarrest AKI and patient outcome. METHODS: A prospective observational study of resuscitated, comatose OHCA patients admitted to Oslo University Hospital in Norway. Urine samples were collected at admission and day three postarrest and analysed for ß-2-microglobulin (ß2M), osteopontin, and trefoil factor 3 (TFF3). Outcome variables were AKI within three days according to the Kidney Disease Improving Global Outcome criteria, in addition to six-month mortality and poor neurological outcome (PNO) (cerebral performance category 3-5). RESULTS: Among 195 included patients (85% males, mean age 60 years), 88 (45%) developed AKI, 88 (45%) died, and 96 (49%) had PNO. In univariate analyses, increased urine ß2M, osteopontin, and TFF3 levels sampled at admission and day three were independent risk factors for AKI, mortality, and PNO. Exceptions were that ß2M measured at day three did not predict any of the outcomes, and TFF3 at admission did not predict AKI. In multivariate analyses, combining clinical parameters and biomarker levels, the area under the receiver operating characteristics curves (95% CI) were 0.729 (0.658-0.800), 0.797 (0.733-0.861), and 0.812 (CI 0.750-0.874) for AKI, mortality, and PNO, respectively. CONCLUSIONS: Urine levels of ß2M, osteopontin, and TFF3 at admission and day three were associated with increased risk for AKI, mortality, and PNO in comatose OHCA patients. This trail is registered with NCT01239420.

Acute kidney injury in trauma patients admitted to the ICU: a systematic review and meta-analysis.

PURPOSE: To perform a systematic review and meta-analysis of acute kidney injury (AKI) in trauma patients admitted to the intensive care unit (ICU). METHODS: We conducted a systematic literature search of studies on AKI according to RIFLE, AKIN, or KDIGO criteria in trauma patients admitted to the ICU (PROSPERO CRD42017060420). We searched PubMed, Cochrane Database of Systematic Reviews, UpToDate, and NICE through 3 December 2018. Data were collected on incidence of AKI, risk factors, renal replacement therapy (RRT), renal recovery, length of stay (LOS), and mortality. Pooled analyses with random effects models yielded mean differences, OR, and RR, with 95% CI. RESULTS: Twenty-four observational studies comprising 25,182 patients were included. Study quality (Newcastle-Ottawa scale) was moderate. Study heterogeneity was substantial. Incidence of post-traumatic AKI in the ICU was 24% (20-29), of which 13% (10-16) mild, 5% (3-7) moderate, and 4% (3-6) severe AKI. Risk factors for AKI were African American descent, high age, chronic hypertension, diabetes mellitus, high Injury Severity Score, abdominal injury, shock, low Glasgow Coma Scale (GCS) score, high APACHE II score, and sepsis. AKI patients had 6.0 (4.0-7.9) days longer ICU LOS and increased risk of death [RR 3.4 (2.1-5.7)] compared to non-AKI patients. In patients with AKI, RRT was used in 10% (6-15). Renal recovery occurred in 96% (78-100) of patients. CONCLUSIONS: AKI occurred in 24% of trauma patients admitted to the ICU, with an RRT use among these of 10%. Presence of AKI was associated with increased LOS and mortality, but renal recovery in AKI survivors was good.

Venous thromboembolism in the critically ill: A prospective observational study of occurrence, risk factors and outcome.

BACKGROUND: The aim of the study was to explore occurrence, risk factors and outcome of venous thromboembolism (VTE) in intensive care unit (ICU) patients. METHODS: Prospective observational study of ICU patients receiving thromboprophylaxis at Oslo University Hospital in Norway. Adult medical and surgical patients with ICU length of stay (LOS) longer than 48 hours were included. For detection of VTE, Doppler ultrasound screening of neck, upper and lower extremity veins was used, and computed tomography angiography when clinically indicated for any medical reason. RESULTS: Among 70 included patients, 79% were males and mean age was 62 (±12.1) years. All received thromboprophylaxis with dalteparin, and 44 (63%) used graduated compression stockings. VTE was found in 19 (27%) patients; deep vein thrombosis in 15 (21%) and pulmonary embolism in 4 (6%). Among the VTEs, 11 (58%) presented within the first 48 hours after admission, two (11%) were located in the lower limbs and five (26%) were symptomatic. Risk factors for VTE in multivariable analyses were malignancy, abdominal surgery and SAPS II score <41 with an AuROC (95% CI) of 0.72 (0.58-0.85, P = 0.01). Patients with and without VTE had comparable ICU LOS (13 vs 11 days, P = 0.27) and mortality (16% vs 20%, P = 0.72). CONCLUSION: Venous thromboembolism was observed in 27% of ICU patients receiving thromboprophylaxis. Factors associated with increased risk of VTE were malignancy, abdominal surgery and SAPS II score <41. Presence of VTE did not impact on patient outcome.

Urine biomarkers give early prediction of acute kidney injury and outcome after out-of-hospital cardiac arrest.

BACKGROUND: Post-resuscitation care after out-of-hospital cardiac arrest (OHCA) is challenging due to the threat of organ failure and difficult prognostication. Our aim was to examine whether urine biomarkers could give an early prediction of acute kidney injury (AKI) and outcome. METHODS: This was a prospective observational study of comatose OHCA patients at Oslo University Hospital Ullevål, Norway. Risk factors were clinical parameters and biomarkers measured in spot urine (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and the product of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7)) at admission and day 3. Outcome variables were AKI within 3 days using the Kidney Disease Improving Global Outcomes definition, 6-month mortality, and poor neurological outcome (PNO) defined as cerebral performance category 3-5. RESULTS: Among 195 included patients (85 % males, mean age 60 years), 88 (45 %) died, 96 (49 %) had PNO, and 88 (45 %) developed AKI. In univariate analysis, increased urine cystatin C and NGAL concentration sampled at admission and day 3 were independent risk factors for AKI, mortality and PNO. Increased urine TIMP-2 × IGFBP7 levels was associated with AKI only at admission. In multivariate analyses combining clinical parameters and biomarker concentrations, the area under the receiver operating characteristics curve (AuROC) with 95 % confidence interval (CI) were 0.774 (0.700-0.848), 0.812 (0.751-0.873), and 0.819 (0.759-0.878) for AKI, mortality and PNO, respectively. CONCLUSIONS: In comatose OHCA patients, urine levels of cystatin C and NGAL at admission and day 3 were independent risk factors for AKI, 6-month mortality and PNO. TRIAL REGISTRATION: Clinicaltrials.gov NCT01239420 . Registered 10 November 2010.

Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis.

PURPOSE: To compare benefits and harms of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit (ICU) patients. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International Network, PROSPERO and the metaRegister of Controlled Trials through 3 December 2014. Random effects risk ratios (RR) and 95% confidence intervals (CI) were derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, mortality and net clinical benefit (any DVT, any PE, major bleeding and/or mortality). RESULTS: Eight RCTs (5567 patients) were included, whereof two were considered to have overall low risk of bias. Pooled analyses showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95% CI 0.71-0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95% CI 0.83-0.97, p = 0.01). There was no statistically significant difference in the risk of any PE (RR 0.65, 95% CI 0.41-1.03, p = 0.06), major bleeding (RR 0.99, 95% CI 0.77-1.28, p = 0.96) or mortality (RR 0.93, 95% CI 0.78-1.12, p = 0.43). TSA supported the results of the conventional analysis on the outcome net clinical benefit but not on risk of any DVT. CONCLUSIONS: Evidence from this systematic review revealed a beneficial effect of LMWH compared with UFH when used as thromboprophylaxis in ICU patients.

Primary injuries and secondary organ failures in trauma patients with acute kidney injury treated with continuous renal replacement therapy.

Background. Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is a severe complication in trauma patients. The aim of the study was to assess primary traumatic injuries and secondary organ failures in severe posttraumatic AKI. Methods. Retrospective review of adult trauma patients admitted to the trauma centre at Oslo University Hospital Ullevål. Injury severity score (ISS) was used to assess the severity of primary injuries, and sequential organ failure assessment (SOFA) score was utilized to measure secondary organ failures. Results. Forty-two (8%) of 506 trauma patients admitted to intensive care unit developed AKI treated with CRRT, whereof 40 (95%) suffered blunt trauma mechanisms. Patients had extensive primary organ injuries with median (interquartile range) ISS 36 (27-49). The majority of the patients had respiratory (93% intubated) and cardiovascular (67% with inotropic and/or vasoactive medication) failure within 24 hours after admission. AKI was often part of multiple organ failure, most frequently respiratory and cardiovascular failure, affecting 33 (75%) and 30 (71%) of the patients, respectively. Conclusion. Trauma patients with AKI undergoing CRRT often had severe primary injuries due to blunt trauma. Most of them suffered from secondary multiple organ failure concomitant to AKI.

Variability in Uremic Control during Continuous Venovenous Hemodiafiltration in Trauma Patients.

Introduction. Acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT) is a severe complication in trauma patients (TP). We wanted to assess daily duration of CRRT and its impact on uremic control in TP. Material and Methods. We retrospectively reviewed adult TP, with or without rhabdomyolysis, with AKI undergoing CRRT. Data on daily CRRT duration and causes for temporary stops were collected from the first five CRRT days. Uremic control was assessed by daily changes in serum urea (Δurea) and creatinine (Δcreatinine) concentrations. Results. Thirty-six TP were included with a total of 150 CRRT days, 17 (43%) with rhabdomyolysis. The median (interquartile range (IQR)) time per day with CRRT was 19 (15-21) hours. There was a significant correlation between daily CRRT duration and Δurea (r = 0.60, P≤0.001) and Δcreatinine (r = 0.43; P = 0.012). CRRT pauses were caused by filter clotting (54%), therapeutic interventions (25%), catheter related problems (10%), filter timeout (6%), and diagnostic procedures (6%). Rhabdomyolysis did not affect the CRRT data. Conclusions. TP undergoing CRRT had short daily CRRT duration causing reduced uremic control. Clinicians should modify their daily clinical practice to improve technical skills and achieve sufficient dialysis dose.