Publications by authors named "Dag Jacobsen"

94 Publications

Long Term Cognitive Function After Cardiac Arrest: A Mini-Review.

Front Aging Neurosci 2022 26;14:885226. Epub 2022 May 26.

Department of Medical Research, Baerum Hospital Vestre Viken Hospital Trust, Drammen, Norway.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality worldwide. With better pre- and inhospital treatment, including cardiopulmonary resuscitation (CPR) as an integrated part of public education and more public-access defibrillators available, OHCA survival has increased over the last decade. There are concerns, after successful resuscitation, of cerebral hypoxia and degrees of potential acquired brain injury with resulting poor cognitive functioning. Cognitive function is not routinely assessed in OHCA survivors, and there is a lack of consensus on screening methods for cognitive changes. This narrative mini-review, explores available evidence on hypoxic brain injury and long-term cognitive function in cardiac arrest survivors and highlights remaining knowledge deficits.
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http://dx.doi.org/10.3389/fnagi.2022.885226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204346PMC
May 2022

Fomepizole dosing during continuous renal replacement therapy - an observational study.

Clin Toxicol (Phila) 2022 Apr 29;60(4):451-457. Epub 2021 Sep 29.

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

Background: Fomepizole is the preferred antidote for treatment of methanol and ethylene glycol poisoning, acting by inhibiting the formation of the toxic metabolites. Although very effective, the price is high and the availability is limited. Its availability is further challenged in situations with mass poisonings. Therefore, a 50% reduced maintenance dose for fomepizole during continuous renal replacement therapy (CRRT) was suggested in 2016, based on pharmacokinetic data only. Our aim was to study whether this new dosing for fomepizole during CRRT gave plasma concentrations above the required 10 µmol/L. Secondly, we wanted to study the elimination kinetics of fomepizole during CRRT, which has never been studied before.

Methods: Prospective observational study of adult patients treated with fomepizole and CRRT. We collected samples from arterial line (pre-filter) = plasma concentration, post-filter and dialysate for fomepizole measurements. Fomepizole was measured using high-pressure liquid chromatography with a reverse phase column.

Results: Ten patients were included in the study. Seven were treated with continuous veno-venous hemodialysis (CVVHD) and three with continuous veno-venous hemodiafiltration (CVVHDF). Ninety-eight percent of the plasma samples were above the minimum plasma concentration of 10 µmol/L. Fomepizole was removed during CRRT with a median saturation/sieving coefficient of 0.85 and dialysis clearance of 28 mL/min.

Conclusion: Fomepizole was eliminated during CCRT. The new dosing recommendations for fomepizole and CRRT appeared safe, by maintaining the plasma concentration above the minimum value of 10 µmol/L. Based on these data, the fomepizole maintenance dose during CRRT could be reduced to half as compared to intermittent hemodialysis.
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http://dx.doi.org/10.1080/15563650.2021.1980581DOI Listing
April 2022

Quality of care, resource use and patient outcome by use of emergency response team compared with standard care for critically ill medical patients in the emergency department: a retrospective single-centre cohort study from Norway.

BMJ Open 2021 08 12;11(8):e047264. Epub 2021 Aug 12.

Joint Medical Services, Norwegian Armed Forces, Sessvollmoen, Norway.

Objective: The study aimed to investigate quality of care, resource use and patient outcome in management by an emergency response team versus standard care for critically ill medical patients in the emergency department (ED). The emergency response team was multidisciplinary and had eight members, with a registrar in internal medicine as team leader.

Design: Register-based retrospective cohort study.

Setting: Tertiary hospital in Norway.

Participants: The study included 1120 patients with National Early Warning Score 2 (NEWS2) 5-10 points from 2015 and 2016. Patients missing ≥3 NEWS2 part scores, <18 years and with orders 'Not for ICU' or 'Not for resuscitation' were excluded.

Outcome Measures: Quality of care: pain assessment documented, analgesics given within 20 min, complete set of vital signs documented and antibiotics within 60 min if sepsis. Resource use: >3 diagnostic interventions, critical care in the ED and ED length of stay (LOS) <180 min. Patient outcome: intensive care unit (ICU) admission, ICU LOS <66 hours, hospital LOS <194 hours and mortality.

Results: The median age was 66 years, 53.5% were male, 44.3% were admitted to the ICU and the mortality rate was 10.6%. Altogether 691 patients received team management and 429 standard care. Team management had a positive association with 'complete set of vital signs documented' (OR 1.720, CI 1.254 to 2.360), 'analgesics given within 20 minutes' (OR 3.268, CI 1.375 to 7.767) and 'antibiotics within 60 minutes if sepsis' (OR 7.880, CI 3.322 to 18.691), but a negative association with ' pain assessment documented' (OR 0.068, CI 0.037 to 0.128). Team management was also associated with 'critical care in the ED' (OR 9.900, CI 7.127 to 13.751), 'ED LOS <180 min' (OR 2.944, CI 2.070 to 4.187), 'ICU admission' (OR 2.763, CI 1.962 to 3.891) and 'mortality' (OR 1.882, CI 1.142 to 3.102).

Conclusions: Team management showed positive results for quality of care and resource use. The results for later outcomes such as mortality, ICU LOS and hospital LOS were more ambiguous.
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http://dx.doi.org/10.1136/bmjopen-2020-047264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362729PMC
August 2021

Treating patients with opioid overdose at a primary care emergency outpatient clinic: a cost-minimization analysis.

Cost Eff Resour Alloc 2021 Aug 4;19(1):48. Epub 2021 Aug 4.

Department of Health Management and Health Economics, University of Oslo, Oslo, Norway.

Background: Treating patients with acute poisoning by substances of abuse in a primary care emergency clinic has previously been shown to be a safe strategy. We conducted an economic evaluation of this strategy compared to hospital treatment, which is the usual strategy.

Methods: Assuming equal health outcomes, we conducted a cost-minimization analysis. We constructed a representative opioid overdose patient based on a cohort of 359 patients treated for opioid overdose at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) from 1.10.2011 to 30.9.2012. Using a health care system perspective, we estimated the expected resources used on the representative patient in primary care based on data from the observed OAEOC cohort and on information from key informants at the OAEOC. A likely course of treatment of the same patient in a hospital setting was established from information from key informants on provider procedures at Drammen Hospital, as were estimates of hospital use of resources. We calculated expected costs for both settings. Given that the treatments usually last for less than one day, we used undiscounted cost values.

Results: The estimated per patient cost in primary care was 121 EUR (2018 EUR 1.00 = NOK 9.5962), comprising 97 EUR on personnel costs and 24 EUR on treatment costs. In the hospital setting, the corresponding cost was 612 EUR, comprising 186 EUR on personnel costs, 183 EUR on treatment costs, and 243 EUR associated with intensive care unit admission. The point estimate of the cost difference per patient was 491 EUR, with a low-difference scenario estimated at 264 EUR and a high-difference scenario at 771 EUR.

Conclusions: Compared to hospital treatment, treating patients with opioid overdose in a primary care setting costs substantially less. Our findings are probably generalizable to poisoning with other substances of abuse. Implementing elements of the OAEOC procedure in primary care emergency clinics and in hospital emergency departments could improve the use of health care resources.
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http://dx.doi.org/10.1186/s12962-021-00303-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335998PMC
August 2021

NEWS2 versus a single-parameter system to identify critically ill medical patients in the emergency department.

Resusc Plus 2020 Sep 6;3:100020. Epub 2020 Aug 6.

Medicine, Health, Patient Safety and Integration, Oslo University Hospital, Postboks 4950 Nydalen, 0424, Oslo, Norway.

Aim: To test National Early Warning Score 2 (NEWS2) versus a single-parameter system to identify critically ill general medical patients in the emergency department (ED), by 1) testing NEWS2s prediction of and association with primary outcome 'mortality' (hospital or 30 day) and secondary outcomes 'intensive care unit (ICU) admission' and 'critical care in ED' and 2) comparing this for different NEWS2 cut-offs and the single-parameter system in use.

Methods: Register-data on adult triage 1 and 2 patients with complete NEWS2 from 2015 and 2016 were retrieved. Prediction was assessed using area under the receiver-operating characteristic curve. Associations were analyzed using multiple logistic regression.

Results: 1586 patients were included. NEWS2 showed poor prediction of 'mortality' (AUC 0.686, CI 0.633-0.739) and adequate prediction of 'ICU admission' (AUC 0.716, CI 0.690-0.742) and 'critical care in ED' (AUC 0.756, CI 0.732-0.780). It was strongly associated with all outcomes (all p<0.001). All NEWS2 cut-offs and the single-parameter system showed poor prediction of all outcomes (all AUCs <0.7). The single-parameter system had the strongest association with 'mortality' (OR 1.688, CI 1.052-2.708, p<0.05) and 'critical care in ED' (OR 3.267, CI 2.490-4.286, p<0.001). NEWS2 > 4 had the strongest association with 'ICU admission' (OR 2.339, CI 1.742-3.141, p<0.001).

Conclusion: For identification in order to trigger a response in the ED, outcomes closest in time seem most clinically relevant. As such, the single-parameter system had acceptable performance. NEWS2 > 4 should be considered as an additional trigger due to its association with ICU admission.
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http://dx.doi.org/10.1016/j.resplu.2020.100020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244393PMC
September 2020

Formate test for bedside diagnosis of methanol poisoning.

Basic Clin Pharmacol Toxicol 2021 Jul 12;129(1):86-88. Epub 2021 May 12.

Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.
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http://dx.doi.org/10.1111/bcpt.13597DOI Listing
July 2021

Formate test for bedside diagnosis of methanol poisoning.

Basic Clin Pharmacol Toxicol 2021 Jul 12;129(1):86-88. Epub 2021 May 12.

Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.
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http://dx.doi.org/10.1111/bcpt.13597DOI Listing
July 2021

New patient care pathways: You can't please everyone.

Authors:
Dag Jacobsen

Tidsskr Nor Laegeforen 2021 02 1;141(2). Epub 2021 Feb 1.

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http://dx.doi.org/10.4045/tidsskr.21.0014DOI Listing
February 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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http://dx.doi.org/10.1136/ejhpharm-2020-002544DOI Listing
January 2021

Characteristics, management and outcome of critically ill general medical patients in the Emergency Department: An observational study.

Int Emerg Nurs 2021 01 7;54:100939. Epub 2020 Dec 7.

Medicine, Health, Patient Safety and Integration, Oslo University Hospital, Postboks 4950 Nydalen, 0424 Oslo, Norway. Electronic address:

Background: Critically ill general medical patients are an increasing group in the Emergency Department (ED). This register-based cohort study aimed to examine these patients' characteristics, ED management and outcome, and investigate factors associated with ICU admission.

Methods: The study comprised all adult medical triage 1 patients treated by a specialized multidisciplinary team in 2015 and 2016. Univariate and multivariate analysis were used.

Results: 1294 patients were included. Mean age was 59 years, 56% (n = 725) were male, mean National Early Warning Score 2 (NEWS2) was 7, intensive care unit (ICU) admission was 56.8% (n = 735) and mortality rate was 16.8% (n = 217). Median ED length of stay (LOS) was 1.6 h, 1.2 h if admitted to ICU. The most frequent discharge diagnosis was acute poisoning (24.0%, n = 308). Younger age, male gender, arriving at nighttime weekdays, higher NEWS2 at arrival, critical care interventions or medications in the ED was associated with ICU admission.

Conclusion: More than half of the patients were admitted to ICU, and the mortality rate was 16.8%. A large proportion was diagnosed with acute poisoning. Younger age, higher NEWS and critical care in ED were associated with ICU admission. The short ED LOS suggests that management by a multidisciplinary team is beneficial.
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http://dx.doi.org/10.1016/j.ienj.2020.100939DOI Listing
January 2021

Carbon monoxide – the internal strangler.

Authors:
Dag Jacobsen

Tidsskr Nor Laegeforen 2020 11 23;140(17). Epub 2020 Nov 23.

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http://dx.doi.org/10.4045/tidsskr.20.0903DOI Listing
November 2020

Unconscious man in his fifties with elevated anion gap.

Tidsskr Nor Laegeforen 2020 10 26;140(15). Epub 2020 Oct 26.

Background: The use of GHB is still widespread with many hospitalised overdose cases.

Case Presentation: A man in his fifties was found unconscious in the street and brought to our Acute Admissions. When first examined he was still unconscious, hypothermic, had snoring respiration and smelled of alcohol. He was otherwise haemodynamically stable. Blood samples showed elevated osmolal and anion gaps. The increase in the osmol gap could be explained by the ethanol level of 210 mg/dL (46 mmol/L), but the reason for the increased anion gap was unknown. Flumazenil and naloxone were administered without effect. As the ethanol concentration alone was unlikely to explain the clinical picture, extended toxicological tests were performed. GHB in plasma was very high (5.0 mmol/L; 520 mg/L) even though the sample was taken almost 4 hours after admission. The GHB concentration (present as an anion) corresponded to the increased anion gap. The patient was comatose for approximately 12 hours, which is unusually long in GHB poisoning.

Interpretation: Intoxication with GHB is important to consider in comatose patients where other causes are excluded. Prolonged clinical course may be due to a saturation of the GHB metabolism after a large dose or ingestion of GBL or 1,4-butanediol, both of which are precursors to GHB.
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http://dx.doi.org/10.4045/tidsskr.20.0120DOI Listing
October 2020

Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes.

Basic Clin Pharmacol Toxicol 2020 Jul 5;127(1):47-51. Epub 2020 Feb 5.

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

Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where pharmacogenetic screening was conducted. This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI may add to the risk of toxicity. This case may indicate that pharmacogenetic variability is of potential relevance for the risk of paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of hepatotoxicity in these patients at therapeutic doses of paracetamol and hence provide information for selection of analgesic treatment.
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http://dx.doi.org/10.1111/bcpt.13389DOI Listing
July 2020

Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).

Resuscitation 2020 04 8;149:170-179. Epub 2020 Jan 8.

Department of Anaesthesiology, Oslo University Hospital, Ullevål, Postboks 4956 Nydalen, N-0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Institute of Clinical Medicine, PB 1171 Blindern, N-0318 Oslo, Norway.

Background: Outcome prediction after out-of-hospital cardiac arrest (OHCA) may lead to withdrawal of life-sustaining therapy if the prognosis is perceived negative. Single use of uncertain prognostic tools may lead to self-fulfilling prophecies and death. We evaluated prognostic tests, blinded to clinicians and without calls for hasty outcome prediction, in a prospective study.

Methods: Comatose, sedated TTM 33-treated OHCA patients of all causes were included. Clinical-neurological/-neurophysiological/-biochemical predictors were registered. Patients were dichotomized into good/poor outcome using cerebral performance category (CPC) six months and > four years post-arrest. Prognostic tools were evaluated using false positive rates (FPR).

Results: We included 259 patients; 49 % and 42 % had good outcome (CPC 1-2) after median six months and 5.1 years. Unwitnessed arrest, non-shockable rhythms, and no-bystander-CPR predicted poor outcome with FPR (CI) 0.05 (0.02-0.10), 0.13 (0.08-0.21), and 0.13 (0.07-0.20), respectively. Time to awakening was median 6 (0-25) days in good outcome patients. Among patients alive with sedation withdrawal >72 h, 49 % were unconscious, of whom 32 % still obtained good outcome. Only absence of pupillary light reflexes (PLR) -and N20-responses in somato-sensory evoked potentials (SSEP), as well as increased neuron-specific enolase (NSE) later than 24 h to >80 μg/L, had FPR 0. Malignant EEG (burst suppression/epileptic activity/flat) differentiated poor/good outcome with FPR 0.05 (0.01-0.15).

Conclusion: Time to awakening was over six days in good outcome patients. Most clinical parameters had too high FPRs for prognostication, except for absent PLR and SSEP-responses >72 h after sedation withdrawal, and increased NSE later than 24 h to >80 μg/L.
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http://dx.doi.org/10.1016/j.resuscitation.2019.12.031DOI Listing
April 2020

Reference values for osmolal gap in healthy subjects and in medical inpatients.

Scand J Clin Lab Invest 2020 Feb 6;80(1):1-5. Epub 2019 Dec 6.

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

Methanol and ethylene glycol poisonings are associated with high morbidity and mortality rates if treatment is not initiated early. Since few hospitals measure these toxic alcohols on a 24/7 basis, calculation of the osmolal gap (OG) is an important diagnostic tool. The reference value for the OG lacks consensus. We, therefore, wanted to update the reference value for OG in presumed healthy subjects and study OG values in internal medicine patients. The OG was calculated in 285 patients at the Medical Clinic at Oslo University Hospital, and in 118 healthy blood donors at Vestfold Hospital Trust. OG was calculated by the formula: OG = Measured osmolality - calculated osmolality ((1.86 × s-sodium + s-glucose + s-urea)/0.93) mOsm/kg HO. In the patients, median OG was 0 mOsm/kg HO (interquartile range -3 to 3 mOsm/kg HO, range -16 to103 mOsm/kg HO). When corrected for one outlier, the central 95% interval for OG was -10 to 20. The healthy blood donors had a median OG of -1 mOsm/kg HO (interquartile range -3 to1 mOsm/kg HO, range -13 to 8 mOsm/kg HO). When corrected for outliers, the reference range was -6 to 5 mOsm/kg HO. Based on results from a healthy population, we suggest a reference value for the OG of ≤5 mOsm/kg HO, but also recommend, based on our results from medical inpatients, to keep today's practice for suspecting poisoning with toxic alcohols at an elevated OG of ≥20 mOsm/kg HO.
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http://dx.doi.org/10.1080/00365513.2019.1672086DOI Listing
February 2020

Substance abuse-related admissions in a mixed Norwegian intensive care population.

Acta Anaesthesiol Scand 2020 03 29;64(3):329-337. Epub 2019 Nov 29.

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

Background: Alcohol and drug abuse are potentially modifiable risk factors for critical illness. The aims of this study were to describe patients with substance abuse-related admissions (abbreviated SARA) in a mixed intensive care (ICU) population in Oslo, and to compare these patients with patients with non-SARA.

Methods: Cross-sectional prospective study of a mixed medical and surgical ICU-population in Oslo, Norway. Data were collected consecutively using a questionnaire, medical records, and toxicology results. SARA included admissions due to acute or chronic complications of alcohol or drug abuse, as well as substance abuse-related injuries.

Results: Of the 852 patients included, 168 (20%) had SARA; 102 (12%) alcohol-related and 66 (8%) drug-related. Male patients aged 18-39 had the highest proportion of SARA (47/97, 49%). Among the trauma patients, 69/182 (38%) were influenced by alcohol and drugs at the time of injury. Patients with SARA were significantly younger (median age 48 vs 66), had lower Charlson comorbidity index (mean 1.4 vs 2.5) and shorter length of stay (median days 2.4 vs 4.9), than non-SARA patients. Hospital mortality was similar when adjusting for age (OR 0.8, P = .27, non-SARA as reference).

Conclusion: Overall, one in five ICU admissions was associated with substance abuse. For male patients aged 18-39 this ratio was nearly half. More than one third of the trauma patients were influenced by alcohol or drugs at time of injury.
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http://dx.doi.org/10.1111/aas.13506DOI Listing
March 2020

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Clin Toxicol (Phila) 2019 12 22;57(12):1129-1136. Epub 2019 Jul 22.

The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO. We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes. We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient. We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak.
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http://dx.doi.org/10.1080/15563650.2019.1636992DOI Listing
December 2019

Structured evaluation on arrival of patients with sepsis and initiation of antibiotics.

Tidsskr Nor Laegeforen 2019 May 27;139(9). Epub 2019 May 27.

Background: In 2017, Acute Admissions at Oslo University Hospital, Ullevål, introduced a specific protocol for evaluating patients with suspected sepsis on arrival. Patients with suspected sepsis, and all those who fulfilled at least two of three criteria in the Quick Sequential Organ Failure Assessment (qSOFA) screening tool, were to undergo a structured evaluation by a dedicated sepsis team. We have examined whether this initiative improved compliance with national recommendations to initiate antibiotics within one hour in cases of sepsis.

Material And Method: Adult patients with suspected sepsis who underwent a structured team evaluation on arrival in Acute Admissions in the period 15 May to 15 November 2017 were included. A retrospective review was used to determine whether or not those included did in fact have sepsis.

Results: Antibiotics were administered for suspected sepsis following 216 structured evaluations in Acute Admissions (172 by sepsis teams and 44 by general medical teams). In all, 175 (81 %) patients received antibiotics within one hour of arrival in Acute Admissions. Median time from arrival to initiation of antibiotics was 35 minutes. Use of qSOFA alone captured 80 (71 %) of the 112 patients who were subsequently classified as having sepsis.

Interpretation: Following the introduction of a structured evaluation for patients with suspected sepsis, antibiotic treatment was generally initiated within one hour.
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http://dx.doi.org/10.4045/tidsskr.18.0216DOI Listing
May 2019

Acute Dysnatremias - a dangerous and overlooked clinical problem.

Scand J Trauma Resusc Emerg Med 2019 May 28;27(1):58. Epub 2019 May 28.

Department of Acute Medicine, Oslo University Hosptial and University of Oslo, Oslo, Norway.

Background: Dysnatremias are common electrolyte disturbances with significant morbidity and mortality. In chronic dysnatremias a slow correction rate (<10 mmol/L/24 h) is indicated to avoid neurological complications. In acute dysnatremias (occurring <48 h) a rapid correction rate may be indicated. Most guidelines do not differ between acute and chronic dysnatremias. In this review, we focus on the evidence-based treatment of acute dysnatremias.

Methods: A literary search in PubMed and Embase. A total of 72 articles containing 79 cases were included, of which 12 cases were excluded due to lack of information.

Results: Of 67 patients (70% women) with acute dysnatremia, 60 had hypo- and 7 had hypernatremia. All patients with hyper- and 88% with hyponatremia had a rapid correction rate (> 10 mmol/L/24 h). The median time of correction was 1 day in patients with hypo- and 2.5 days in patients with hypernatremia. The mortality was 7% in patients with hypo- and 29% in patients with hypernatremia.

Interpretation: Severe acute dysnatremias have significant mortality and require immediate treatment. A rapid correction rate may be lifesaving and is not associated with neurological complications. Chronic dysnatremias, on the other hand, are often compensated and thus less severe. In these cases a rapid correction rate may lead to severe cerebral complications.
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http://dx.doi.org/10.1186/s13049-019-0633-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540386PMC
May 2019

Mortality and repeated poisoning after self-discharge during treatment for acute poisoning by substances of abuse: a prospective observational cohort study.

BMC Emerg Med 2019 01 11;19(1). Epub 2019 Jan 11.

General Practice Research Unit (AFE), University of Oslo, Oslo, Norway.

Background: Though substance use is a known risk factor for self-discharge, patients self-discharging during treatment for acute poisoning have not previously been described. We charted characteristics of patients self-discharging during treatment for acute poisoning by substances of abuse looking for associations between self-discharge, repeated poisoning, and death.

Methods: All patients 12 years and older treated for acute poisoning by substances of abuse at an emergency outpatient clinic in Oslo, Norway, were included consecutively from October 2011 through September 2012. We collected data on gender, age, main toxic agent, suicidal intention, homelessness, history of severe mental illness, and self-discharge. Information on deaths was retrieved from the National Cause of Death Register. We did a multiple logistic regression analysis to look for associations between self-discharge and repeated poisoning and a Cox regression analysis for associations between self-discharge and death.

Results: During one year, 1731 patients were treated for 2343 episodes of acute poisoning by substances of abuse. Two-hundred-and-sixty-six (15%) patients self-discharged during at least one poisoning episode. Self-discharging patients were older, median age 39 years vs 32 years (p <  0.001), more frequently homeless, 20/266 (8%) vs 63/1465 (4%) (p = 0.035), and the main toxic agent more frequently was an opioid, 82/266 (31%) vs 282/1465 (19%) (p <  0.001). Self-discharge was an independent risk factor for repeated poisoning. The adjusted odds ratio for two or more poisoning episodes during one year among self-dischargers was 3.0 (95% CI 2.2-4.1). The association was even stronger for three or more poisoning episodes, adjusted odds ratio 5.0 (3.3-7.5). In total, there were 34 deaths, 9/266 (3.4%) among self-discharging patients and 25/1465 (1.7%) among patients not self-discharging (p = 0.12). The adjusted hazard ratio for death among self-discharging patients was 1.6 (0.75-3.6).

Conclusions: Self-discharge was associated with frequent poisonings by substances of abuse. Short-term mortality was doubled among self-discharging patients, though this increase was not statistically significant. Still, the increased risk of repeated poisoning marks self-discharging patients as a vulnerable group who might benefit from targeted post-discharge follow-up measures.
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http://dx.doi.org/10.1186/s12873-018-0219-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329053PMC
January 2019

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

Acta Anaesthesiol Scand 2019 05 8;63(5):630-638. Epub 2019 Jan 8.

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

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.
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http://dx.doi.org/10.1111/aas.13316DOI Listing
May 2019

Factors associated with rapidly repeated acute poisoning by substances of abuse: a prospective observational cohort study.

BMC Res Notes 2018 Oct 12;11(1):724. Epub 2018 Oct 12.

General Practice Research Unit (AFE), University of Oslo, Oslo, Norway.

Objective: We have previously found that 9% of patients treated for acute poisoning by substances of abuse in a primary care emergency outpatient setting presented with a new poisoning within a week. We now identify factors associated with rapidly repeated acute poisoning by substances of abuse.

Results: In 169/1952 (9%) cases of acute poisoning by substances of abuse included consecutively from October 2011 through September 2012 at a primary care emergency outpatient clinic in Oslo, Norway, the patient re-presented within a week with a new poisoning. Homeless patients were more likely to re-present, adjusted odds ratio (AOR) 2.0 (95% confidence interval (CI) 1.3-3.2, p = 0.003), as were self-discharging patients, AOR 1.7 (95% CI 1.2-2.4, p = 0.007), and patients with an opioid as main toxic agent, AOR 1.5 (95% CI 1.0-2.3, p = 0.028). There was no statistically significant association between rapid re-presentation and severe mental illness or suicidal intention.
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http://dx.doi.org/10.1186/s13104-018-3834-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186040PMC
October 2018

Pneumococcal sepsis requiring mechanical ventilation: Cohort study in 38 patients with rapid progression to septic shock.

Acta Anaesthesiol Scand 2018 11 21;62(10):1428-1435. Epub 2018 Aug 21.

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

Background: The aim was to study the course of severe pneumococcal sepsis in patients who rapidly developed septic shock with multiorgan failure.

Methods: Combined retrospective and prospective cohort study of all patients with pneumococcal sepsis requiring mechanical ventilation admitted to our Medical Intensive Care Unit at Oslo University Hospital Ullevaal, during an 8-year period (01 January 2006 to 31 December 2013). The inclusion criteria were growth of Streptococcus pneumoniae in blood culture and respiratory failure treated with invasive mechanical ventilation.

Results: Thirty-eight patients were included. Median age was 57 years (interquartile range 49-68, range 22-79). For 84% (32/38), it took <24 hours from the first medical evaluation until they were in septic shock. Initial clinical features were variable; none were treated with antibiotics before hospital admission. Median Sequential Organ Failure Assessment (SOFA) score at admission was 11 (range 1-15) and maximum 15 (range 5-22), all patients developed multiorgan failure. Mutilating complications were seen in 47% (18/38) of the patients: six with amputations, 11 had adverse neurological complications and one patient both. In-hospital mortality was 40% (15/38), 20% (8/38) survived with sequelae and 40% (15/38) returned to their habitual state. Poor outcome was associated with meningitis, disseminated intravascular coagulation, and gastrointestinal symptoms.

Conclusion: In this patient cohort with pneumococcal sepsis and respiratory failure rapid development of septic shock was seen in all cases, even in young healthy individuals. Initial clinical features were variable; none were treated with antibiotics before admission. Mortality was high (40%), as was morbidity with limb amputations and neurological complications.
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http://dx.doi.org/10.1111/aas.13236DOI Listing
November 2018

The Hypothesis of Circulus Hypoxicus and Its Clinical Relevance in Patients With Methanol Poisoning - An Observational Study of 35 Patients.

Basic Clin Pharmacol Toxicol 2018 Dec 23;123(6):749-755. Epub 2018 Jul 23.

Department of Acute Medicine, Division of Medicine, Oslo University Hospital, Oslo, Norway.

Methanol mass poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following methanol poisoning as a self-enhancing hypoxic circle responsible for methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in methanol poisoning, namely the 'Circulus hypoxicus'.
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http://dx.doi.org/10.1111/bcpt.13074DOI Listing
December 2018

Mortality, morbidity and follow-up after acute poisoning by substances of abuse: A prospective observational cohort study.

Scand J Public Health 2019 Jun 11;47(4):452-461. Epub 2018 Jun 11.

1 Department of General Practice, University of Oslo, Norway.

Aims: Despite the excess mortality and morbidity associated with acute poisoning by substances of abuse, follow-up is frequently not organised. We assessed morbidity, including repeated poisoning, and follow-up after acute poisoning by substances of abuse through charting contacts with health services. We also charted short-term mortality.

Methods: Patients 12 years and older treated for acute poisoning by substances of abuse at a primary care emergency outpatient clinic in Oslo, Norway, were included consecutively from October 2011 through September 2012. We retrieved information from national registers on fatalities, hospital admissions, and contacts at outpatient specialist health services and with general practitioners (GPs), during the 90 days following a poisoning episode.

Results: We included 1731 patients treated for 2343 poisoning episodes. During the 90 days following the poisoning, 31% of the patients were treated at somatic hospitals, 9% admitted to psychiatric hospitals, 37% in treatment at outpatient psychiatric/addiction specialist health services, 55% saw their GP, while 34% had no follow-up. The short-term mortality rate was 2.0%, eight times higher than expected. Increasing age, suicidal intention, opioid poisoning, and severe mental illness were associated with increased risk of death. Increasing age, male gender, opioid poisoning, and severe mental illness were associated with repeated poisoning. Patients with increased risk of repeated poisoning were more likely to be in follow-up at outpatient specialist psychiatric/addiction services and in contact with their GP.

Conclusions: Follow-up measures seem targeted to those most in need, though one out of three had none. The mortality rate calls for concern.
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http://dx.doi.org/10.1177/1403494818779955DOI Listing
June 2019

Mortality, morbidity and follow-up after acute poisoning by substances of abuse: A prospective observational cohort study.

Scand J Public Health 2019 Jun 11;47(4):452-461. Epub 2018 Jun 11.

1 Department of General Practice, University of Oslo, Norway.

Aims: Despite the excess mortality and morbidity associated with acute poisoning by substances of abuse, follow-up is frequently not organised. We assessed morbidity, including repeated poisoning, and follow-up after acute poisoning by substances of abuse through charting contacts with health services. We also charted short-term mortality.

Methods: Patients 12 years and older treated for acute poisoning by substances of abuse at a primary care emergency outpatient clinic in Oslo, Norway, were included consecutively from October 2011 through September 2012. We retrieved information from national registers on fatalities, hospital admissions, and contacts at outpatient specialist health services and with general practitioners (GPs), during the 90 days following a poisoning episode.

Results: We included 1731 patients treated for 2343 poisoning episodes. During the 90 days following the poisoning, 31% of the patients were treated at somatic hospitals, 9% admitted to psychiatric hospitals, 37% in treatment at outpatient psychiatric/addiction specialist health services, 55% saw their GP, while 34% had no follow-up. The short-term mortality rate was 2.0%, eight times higher than expected. Increasing age, suicidal intention, opioid poisoning, and severe mental illness were associated with increased risk of death. Increasing age, male gender, opioid poisoning, and severe mental illness were associated with repeated poisoning. Patients with increased risk of repeated poisoning were more likely to be in follow-up at outpatient specialist psychiatric/addiction services and in contact with their GP.

Conclusions: Follow-up measures seem targeted to those most in need, though one out of three had none. The mortality rate calls for concern.
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http://dx.doi.org/10.1177/1403494818779955DOI Listing
June 2019

Treningsindusert rabdomyolyse.

Tidsskr Nor Laegeforen 2018 01 8;138(1). Epub 2018 Jan 8.

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http://dx.doi.org/10.4045/tidsskr.17.1079DOI Listing
January 2018

Rhabdomyolysis: a 10-year retrospective study of patients treated in a medical department.

Eur J Emerg Med 2019 Jun;26(3):199-204

Department of Acute Medicine, Oslo University Hospital Ulleval.

Background: Rhabdomyolysis is a common and potentially life-threatening syndrome, and acute kidney injury (AKI) is a serious complication. We performed a 10-year retrospective study that included all patients treated for rhabdomyolysis in a medical clinic. We examined the relationships between the levels of creatine kinase (CK), myoglobin, and creatinine (as a marker of renal function and thereby AKI), and whether the myoglobin/CK ratio could be a valuable tool in the clinical evaluation of this patient group. Clinical characteristics were noted.

Patients And Methods: The study included all patients treated for rhabdomyolysis in the Department of Medicine, Oslo University Hospital Ulleval, from 2003 to 2012. Rhabdomyolysis was defined as a serum CK activity more than five times the upper reference limit.

Results: A total of 341 patients were included in the study; 51% developed AKI, and 20% of those required dialysis. Logistic regression showed that myoglobin concentration [P < 0.001, odds ratio (OR) = 6.24] was a better predictor than CK activity (P = 0.001, OR = 3.45) of the development of AKI. The myoglobin/CK ratio was a good predictor of AKI (P < 0.001, OR = 5.97). The risk of developing AKI increased with increasing myoglobin/CK ratio (P < 0.001); a ratio more than 0.2 was associated with an increased likelihood of developing AKI.

Conclusion: Serum myoglobin concentration was a better predictor of AKI than was serum CK activity. The myoglobin/CK ratio may be useful for assessing the likelihood of developing AKI.
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http://dx.doi.org/10.1097/MEJ.0000000000000510DOI Listing
June 2019

Dekkende litteratur, men begrenset nytteverdi.

Authors:
Dag Jacobsen

Tidsskr Nor Laegeforen 2017 Jun 26;137(12-13):927. Epub 2017 Jun 26.

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http://dx.doi.org/10.4045/tidsskr.17.0335DOI Listing
June 2017

[A well-trained man with mechanical aortic valve and leg pain].

Tidsskr Nor Laegeforen 2017 01 24;137(2):113-116. Epub 2017 Jan 24.

Akuttmedisinsk avdeling Oslo universitetssykehus, Ullevål og Institutt for klinisk medisin Universitetet i Oslo.

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http://dx.doi.org/10.4045/tidsskr.15.1337DOI Listing
January 2017
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