Publications by authors named "Espen Rostrup Nakstad"

11 Publications

  • Page 1 of 1

Complement ratios C3bc/C3 and sC5b-9/C5 do not increase the sensitivity of detecting acute complement activation systemically.

Mol Immunol 2022 01 11;141:273-279. Epub 2021 Dec 11.

Department of Immunology, Oslo University Hospital and University of Oslo, Norway; Division of Emergencies and Critical Care, Oslo University Hospital, Norway. Electronic address:

Background: Complement activation plays an important pathogenic role in numerous diseases. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone.

Materials And Methods: Samples from patients with acute heart failure following ST-elevated myocardial infarction (STEMI) and from patients with out-of-hospital cardiac arrest (OHCA) were used. C3, C3bc and C5, sC5b-9 were analysed in 629 and 672 patient samples, respectively. Healthy controls (n = 20) served to determine reference cut-off values for activation products and ratios, defined as two SD above the mean.

Results: Increased C3bc/C3- and sC5b-9/C5 ratios were vastly dependent on C3bc and sC5b-9. Thus, 99.5 % and 98.1 % of the increased C3bc/C3- and sC5b-9/C5 ratios were solely dependent on increased C3bc and sC5b-9, respectively. Significantly decreased C3 and C5 caused increased ratios in only 3/600 (0.5 %) and 4/319 (1.3 %) samples, respectively. Strong correlations between C3bc and C3bc/C3-ratio and between sC5b-9 and sC5b-9/C5-ratio were found in the STEMI- (r = 0.926 and r = 0.786, respectively) and the OHCA-population (r = 0.908 and r = 0.843, respectively; p < 0.0001 for all). Importantly, sC5b-9 identified worse outcome groups better than sC5b-9/C5-ratio.

Conclusion: C3bc and sC5b-9 were sensitive markers of complement activation. The ratios of C3bc/C3 and sC5b-9/C5 did not improve detection of complement activation systemically.
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January 2022

Severe acute respiratory syndrome coronavirus 2 prevalence in 1170 asymptomatic Norwegian conscripts.

Health Sci Rep 2021 Mar 15;4(1):e233. Epub 2021 Jan 15.

Norwegian Armed Forces Joint Medical Services Sessvollmoen Norway.

Background: Accurate estimates of SARS-CoV-2 infection in different population groups are important for the health authorities. In Norway, public infection control measures have successfully curbed the pandemic. However, military training and service are incompatible with these measures; therefore extended infection control measures were implemented in the Norwegian Armed Forces. We aimed to describe these measures, discuss their value, and investigate the polymerase chain reaction (PCR) prevalence and seroprevalence of SARS-CoV-2, as well as changes in antibody titer levels over the 6-week military training period in a young, asymptomatic population of conscripts.

Methods: In April 2020, 1170 healthy conscripts (median age 20 years) enrolled in military training. Extended infection control measures included a pre-enrollment telephone interview, self-imposed quarantine, questionnaires, and serial SARS-CoV-2 testing. At enrollment, questionnaires were used to collect information on symptoms, and SARS-CoV-2 rapid antibody testing was conducted. Serial SARS-CoV-2 PCR and serology testing were used to estimate the prevalence of confirmed SARS-CoV-2 and monitor titer levels at enrollment, and 3 and 6 weeks thereafter.

Results: At enrollment, only 0.2% of conscripts were SARS-CoV-2 PCR-positive, and seroprevalence was 0.6%. Serological titer levels increased nearly 5-fold over the 6-week observation period. Eighteen conscripts reported mild respiratory symptoms during the 2 weeks prior to enrollment (all were PCR-negative; one was serology-positive), whereas 17 conscripts reported respiratory symptoms and nine had fever at enrollment (all were PCR- and serology-negative).

Conclusions: The prevalence of SARS-CoV-2 was less than 1% in our sample of healthy Norwegian conscripts. Testing of asymptomatic conscripts seems of no value in times of low COVID-19 prevalence. SARS-CoV-2 antibody titer levels increased substantially over time in conscripts with mild symptoms.
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March 2021

A survey of the antidote preparedness in Norwegian hospitals.

Eur J Hosp Pharm 2021 Jan 22. Epub 2021 Jan 22.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Objectives: Antidotes are an important part of the emergency preparedness in hospitals. In the case of a major chemical accident or a fire, large quantities of antidotes may be needed within a short period of time. For time-critical antidotes it is therefore necessary that they be immediately available. We wanted to evaluate the antidote preparedness in Norwegian hospitals as regards the national recommendations and compare this with other international guidelines.

Methods: A digital survey was sent to the 50 hospitals in Norway that treat acute poisonings. Of these, four hospitals are categorised as regional hospitals, 15 as large hospitals and 31 as small hospitals. Each hospital was asked which antidotes they stockpiled from a list of 35 antidotes. The financial costs (low, moderate, high) were added to an established efficacy scale to illustrate the cost-effectiveness of the different antidotes.

Results: The response rate was 100%. Eleven of fifty (22%) hospitals stockpiled all antidotes recommended for their hospital size. All four regional hospitals had all the recommended antidotes. Large hospitals which were not regional hospitals had the least availability of antidotes, and only one large hospital stockpiled all antidotes recommended for this hospital size.

Conclusions: We found varying compliance with the national recommendations for antidote storage in hospitals. To strengthen antidote preparedness, we recommend standardised European guidelines to support national guidelines.
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January 2021

Asymptomatic COVID-19 with ambiguous test results.

Tidsskr Nor Laegeforen 2020 12 14;140(18). Epub 2020 Dec 14.

Background: Testing for SARS-CoV-2 using polymerase chain reaction (PCR) and SARS-CoV-2 antibody tests is a significant part of the effort to combat the COVID-19 pandemic. Mass testing of healthy individuals raises several issues, however, and the results can be challenging to interpret.

Case Presentation: A healthy 19-year-old man entered the military after two weeks of quarantine. The recruit had no respiratory symptoms or fever before, during or after his enrolment, and no history of SARS-CoV-2 exposure. At enrolment, he had a positive rapid test and a venous blood sample showed antibodies against SARS-CoV-2. PCR tests of specimens obtained from the upper respiratory tract were negative at enrolment and at week three, but were positive at week six.

Interpretation: The overall assessment of all the tests indicates a probable asymptomatic infection. This case report illustrates the challenge of interpreting screening results in asymptomatic individuals.
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December 2020

Carbon monoxide and cyanide gas poisoning in fires.

Tidsskr Nor Laegeforen 2020 06 29;140(10). Epub 2020 Jun 29.

Acute poisoning caused by inhalation of carbon monoxide and other toxic substances is the primary cause of death in fires and may occur without signs of external injury. Life-threatening symptoms may arise immediately, as in cyanide poisoning, or over a longer period, as in carbon monoxide poisoning. Severe inhalation injury may also occur independently of systemic poisoning and should always be suspected in patients with soot on their face and in the respiratory tract, or hoarseness and wheezing.
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June 2020

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

Crit Care Res Pract 2019 7;2019:4384796. Epub 2019 May 7.

Institute of Clinical Medicine, University of Oslo, P.O.Box 1072 Blindern, 0316 Oslo, Norway.

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 -2-microglobulin (2M), 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 2M, osteopontin, and TFF3 levels sampled at admission and day three were independent risk factors for AKI, mortality, and PNO. Exceptions were that 2M 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 2M, 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.
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May 2019

Comparison of three haemodynamic monitoring methods in comatose post cardiac arrest patients.

Scand Cardiovasc J 2018 06 16;52(3):141-148. Epub 2018 Mar 16.

d Department of Cardiology, Division of Medicine , Oslo University Hospital , Oslo , Norway.

Objectives: Haemodynamic monitoring during post arrest care is important to optimise treatment. We compared stroke volume measured by minimally-invasive monitoring devices with or without thermodilution calibration, and transthoracic echocardiography (TTE), and hypothesised that thermodilution calibration would give stroke volume index (SVI) more in agreement with TTE during targeted temperature management (TTM).

Design: Comatose out-of-hospital cardiac arrest survivors receiving TTM (33 °C for 24 hrs) underwent haemodynamic monitoring with arterial pulse contour analyses with (PiCCO2®) and without (FloTrac/Vigileo monitor) transpulmonary thermodilution calibration. Haemodynamic parameters were collected simultaneously every fourth hour during TTM (hypothermia) and (normothermia). SVI was measured with TTE during hypothermia and normothermia. Bland-Altman analyses were used for determination of SVI bias (±1SD).

Results: Twenty-six patients were included, of whom 77% had initial shockable rhythm and 52% discharged with good outcome. SVI (bias ±2SD) between PiCCO (after thermodilution calibration) vs FloTrac/Vigileo, TTE vs FloTrac/Vigileo and TTE vs PiCCO were 1.4 (±25.8), -1.9 (±19.8), 0.06 (±18.5) ml/m2 during hypothermia and 9.7 (±23.9), 1.0 (±17.4), -7.2 (±12.8) ml/m2 during normothermia. Continuous SVI measurements between PiCCO and FloTrac/Vigileo during hypothermia at reduced SVI (<35 ml/m2) revealed low bias and relatively narrow limits of agreement (0.5 ± 10.2 ml/m2).

Conclusion: We found low bias, but relatively wide limits of agreement in SV with PiCCO, FloTrac/Vigileo and TTE during TTM treatment. The methods are not interchangeable. Precision was not improved by transpulmonary thermodilution calibration during hypothermia.
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June 2018

Manual ventilation and open suction procedures contribute to negative pressures in a mechanical lung model.

BMJ Open Respir Res 2017 8;4(1):e000176. Epub 2017 May 8.

Department of Pulmonary Medicine, Oslo University Hospital, Ullevaal, Norway.

Introduction: Removal of pulmonary secretions in mechanically ventilated patients usually requires suction with closed catheter systems or flexible bronchoscopes. Manual ventilation is occasionally performed during such procedures if clinicians suspect inadequate ventilation. Suctioning can also be performed with the ventilator entirely disconnected from the endotracheal tube (ETT). The aim of this study was to investigate if these two procedures generate negative airway pressures, which may contribute to atelectasis.

Methods: The effects of device insertion and suctioning in ETTs were examined in a mechanical lung model with a pressure transducer inserted distal to ETTs of 9 mm, 8 mm and 7 mm internal diameter (ID). A 16 Fr bronchoscope and 12, 14 and 16 Fr suction catheters were used at two different vacuum levels during manual ventilation and with the ETTs disconnected.

Results: During manual ventilation with ETTs of 9 mm, 8 mm and 7 mm ID, and bronchoscopic suctioning at moderate suction level, peak pressure (P) dropped from 23, 22 and 24.5 cm HO to 16, 16 and 15 cm HO, respectively. Maximum suction reduced P to 20, 17 and 11 cm HO, respectively, and the end-expiratory pressure fell from 5, 5.5 and 4.5 cm HO to -2, -6 and -17 cm HO. Suctioning through disconnected ETTs (open suction procedure) gave negative model airway pressures throughout the duration of the procedures.

Conclusions: Manual ventilation and open suction procedures induce negative end-expiratory pressure during endotracheal suctioning, which may have clinical implications in patients who need high PEEP (positive end-expiratory pressure).
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May 2017

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

Crit Care 2016 10 5;20(1):314. Epub 2016 Oct 5.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

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: NCT01239420 . Registered 10 November 2010.
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October 2016

Post-Resuscitation ECG for Selection of Patients for Immediate Coronary Angiography in Out-of-Hospital Cardiac Arrest.

Circ Cardiovasc Interv 2015 Oct;8(10)

From the Department of Anesthesiology (H.S.-J., K.S.), Institute for Experimental Medical Research (H.S.-J.), Department of Acute Medicine (E.R.N., D.J.), Department of Cardiology (E.F., A.M., J.E., G.Ø.A.), and Department of Research and Development (T.D.), Oslo University Hospital Ulleval, Oslo, Norway; and Center for Heart Failure Research (A.M., J.E., G.Ø.A.), and Insititute of Clinical Medicine (D.J., K.S.), University of Oslo, Norway.

Background: We aimed to investigate coronary angiographic findings in unselected out-of-hospital cardiac arrest patients referred to immediate coronary angiography (ICA) irrespective of their first postresuscitation ECG and to determine whether this ECG is useful to select patients with no need of ICA.

Methods And Results: All resuscitated patients admitted after out-of-hospital cardiac arrest without a clear noncardiac cause underwent ICA. Patients were retrospectively grouped according to the postresuscitation ECG blinded for ICA results: (1) ST elevation or presumably new left bundle branch block, (2) other ECG signs indicating myocardial ischemia, and (3) no ECG signs indicating myocardial ischemia. All coronary angiograms were reevaluated blinded for postresuscitation ECGs. Two hundred and ten patients were included with mean age 62±12 years. Six-months survival with good neurological outcome was 54%. Reduced Thrombolysis in Myocardial Infarction flow (0-2) was found in 55%, 34%, and 18% and a ≥90% coronary stenosis was present in 25%, 27%, and 19% of patients in group 1, 2, and 3, respectively. An acute coronary occlusion was found in 11% of patients in group 3. ST elevation/left bundle branch block identified patients with reduced Thrombolysis in Myocardial Infarction (0-2) flow with 70% sensitivity and 62% specificity. Among patients with initial nonshockable rhythms (24%), 32% had significantly reduced Thrombolysis in Myocardial Infarction flow.

Conclusions: Initial ECG findings are not reliable in detecting patients with an indication for ICA after experiencing a cardiac arrest. Even in the absence of ECG changes indicating myocardial ischemia, an acute culprit lesion may be present and patients may benefit from emergent revascularization. CLINICAL TRIAL REGISTRATIONURL: Unique identifier: NCT01239420.
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October 2015

Bradycardia during therapeutic hypothermia is associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.

Crit Care Med 2014 Nov;42(11):2401-8

1Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital-Ulleval, Oslo, Norway. 2Institute for Experimental Medical Research, Oslo University Hospital-Ulleval, Oslo, Norway. 3Centre of Heart Failure Research, University of Oslo, Oslo, Norway. 4Department of Acute Medicine, Oslo University Hospital-Ulleval, Oslo, Norway. 5Department of Cardiology, Oslo University Hospital-Ulleval, Oslo, Norway.

Objective: Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.

Design: Retrospective cohort study, from January 2009 to January 2011.

Setting: University hospital medical and cardiac ICUs.

Patients: One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia.

Interventions: Patients treated with standardized treatment protocol after cardiac arrest.

Measurements And Main Results: All out-of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32-34°C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had significantly worse outcome than the lower three groups (p = 0.013).

Conclusions: Bradycardia during therapeutic hypothermia was associated with good neurologic outcome at hospital discharge. Our data indicate that bradycardia should not be aggressively treated in this period if mean arterial pressure, lactate clearance, and diuresis are maintained at acceptable levels. Studies, both experimental and clinical, are warranted.
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November 2014