BackgroundThis Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research.MethodsThe RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities.ResultsData from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied.ConclusionThe RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

BACKGROUND: Severe traumatic brain injury (sTBI) can be divided into primary and secondary injuries. Intensive care protocols focus on preventing secondary injuries. This prospective cohort study was initiated to investigate outcome, including mortality, in patients treated according to the Lund Concept after a sTBI covering 10-15 years post-trauma.

METHODS: Patients were included during 2000-2004 when admitted to the neurointensive care unit, Sahlgrenska University Hospital. Inclusion criteria were: Glasgow coma scale score of ≤8, need for artificial ventilation and intracranial monitoring. Glasgow Outcome Scale (GOS) was used to evaluate outcome both at 1-year and 10-15 years post-trauma.

RESULTS: Ninety-five patients, (27 female and 68 male), were initially included. Both improvement and deterioration were noted between 1- and 10-15 years post-injury. Mortality rate (34/95) was higher in the studied population vs. a matched Swedish population, (Standard mortality rate (SMR) 9.5; P < 0.0001). When dividing the cohort into Good (GOS 4-5) and Poor (GOS 2-3) outcome at 1-year, only patients with Poor outcome had a higher mortality rate than the matched population (SMR 7.3; P < 0.0001). Further, good outcome (high GOS) at 1-year was associated with high GOS 10-15 years post-trauma (P < 0.0001). Finally, a majority of patients demonstrated symptoms of mental fatigue.

CONCLUSION: This indicates that patients with severe traumatic brain injury with Good outcome at 1-year have similar survival probability as a matched Swedish population and that high Glasgow outcome scale at 1-year is related to good long-term outcome. Our results further emphasise the advantage of the Lund concept.

Background: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. Methods: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. Results: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. Conclusions: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appears considerable.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease with high mortality and morbidity. Patients with aSAH in Sweden are cared for at one of six neuro intensive care units (NICU) or at a general intensive care unit (ICU).This study aimed to describe the incidence, length of stay, time in ventilator and mortality for these patients. Methods: This is a retrospective, descriptive study of patients with aSAH, registered in the Swedish Intensive care Registry between 2017 and 2019. The cohort was divided in sub-cohorts (NICU and general ICU) and regions. Mortality was analysed with logistic regression. Results: A total of 1520 patients with aSAH from five regions were included in the study. Mean age of the patients were 60.6 years and 58% were female. Mortality within 180 days of admission was 30% (n = 456) of which 17% (n = 258) died during intensive care. A majority of the patients were treated at one hospital and in one ICU (70%, n = 1062). More than half of the patients (59%, n = 897) had their first intensive care admission at a hospital with a NICU. Patients in the North region had the lowest median GCS (10) and the highest SAPS3 score (60) when admitted to NICU. Treatment with invasive mechanical ventilation differed significantly between regions; 91% (n = 80) in the region with highest proportion versus 56% (n = 94) in the region with the lowest proportion, as did mortality; 16% (n = 44) versus 8% (n = 23). No differences between regions were found regarding age, sex and length of stay. Conclusions: Patients with aSAH treated in a NICU or in an ICU in Sweden differs in characteristics. The study further showed some differences between regions which might be reduced if there were national consensus and treatment guidelines implemented.

The long-term properties of commercially available ECG-electrodes were studied by investigating the parameters: polarization potential, electrical impedance, adhesion, and skin reactions during a period of 7 days. As expected, the most stable polarization potentials were obtained for Ag/AgCl electrodes. Certain simple disposable electrodes showed large polarization potential variations. The most stable electrode impedance was obtained for disposable electrodes with stable adhesion and equipped with an electrode cup or similar. Unchanged adhesion and mechanical properties during the test period were shown by the disposable electrodes with a large self-adhesive collar.

BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Background: Corticosteroids reduce the incidence of PONV but the mode of action is not known. The purpose of this study was to evaluate if betamethasone has serotonin (5-HT) antagonistic effects. Ipecacuanha is known to release serotonin and therefore it was used to induce nausea and vomiting. The 5-HT3 antagonist ondansetron was used as a control substance. Methods: In a randomized, double-blind, cross-over, placebo-controlled study 10 healthy male and female volunteers (6 M/4F), mean age 19.5 (18-23) years, mean weight 69.7 (53-84) kg, were studied on three occasions separated by at least 1 week. They were randomly allocated to receive pretreatment with betamethasone 8 mg, ondansetron 8 mg, or normal saline 2 ml as placebo on each occasion, 15 min before oral ingestion of 30 ml of Ipecacuanha syrup. After ingestion of ipecacuanha, vomitings were recorded and the intensity of nausea was estimated with a visual analog scale during 2 h. Results: During the first 2 h after ingestion of ipecacuanha nine of the 10 volunteers vomited both after betamethasone and placebo. No volunteer vomited after ondansetron (P < 0.01 vs. betamethasone and placebo). The max VAS for nausea was significantly higher after betamethasone and placebo compared to ondansetron (P < 0.01). There were no statistically significant differences of the max VAS for nausea between betamethasone and placebo. Conclusion: This study in volunteers has shown that betamethasone does not prevent nausea and vomiting induced by oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamin, it can be concluded that betamethasone does not have 5-HT3 antagonistic effects.

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Background: Optimisation of stroke volume using oesophageal Doppler is an established technique to guide intraoperative fluid therapy. The method has practical limitations and therefore alternative indices of fluid responsiveness, such as ventilator-induced variation in the pulse oximetric signal (Pleth Variability Index (PVI)) could be considered. We hypothesised that both methods predict fluid responsiveness in a similar way. Methods: Seventy-five patients scheduled for open major abdominal surgery were randomised to fluid optimisation using fluid bolus algorithms based on either PVI (n = 35) or Doppler (n = 39). All patients were monitored with both methods; the non-guiding method was blind. Primary endpoint was the concordance between the methods to predict fluid responsiveness. We also analysed the ability of each method to predict a stroke volume increase &gt;= 10% after a fluid bolus, as well as the accumulated intraoperative bolus fluid volume. Results: PVI indicated a need for fluid in one-third of the situations when Doppler did so, Cohens kappa = 0.03. A fluid bolus indicated by the PVI algorithm increased stroke volume by &gt;= 10% in half the situations. The same was found for the Doppler algorithm. The mean total bolus volume given was 878 ml when the fluid management was governed by PVI compared to 826 ml with Doppler (P = 0.71). Conclusion: PVI-and Doppler-based stroke volume optimisations agreed poorly, which did not affect the amount of fluid administered. None of the algorithms showed a good ability to predict fluid responsiveness. Our results do not support the fluid responsiveness concept.

Background Identification of surgical populations at high risk for negative outcomes is needed for clinical and research purposes. We hypothesized that combining two classification systems, ASA (American Society of Anesthesiology physical status) and surgical severity, we could identify a high-risk population before surgery. We aimed to describe postoperative outcomes in a population selected by these two classifications system. Methods Data were collected in a Swedish multicentre, time-interrupted prospective, consecutive cohort study. Eligibility criteria were age &gt;= 18 years, ASA &gt;= 3, elective or emergent, major to Xmajor/complex (Specialist Procedure Codes used in United Kingdom), gastrointestinal, urogenital or orthopaedic procedures. Postoperative morbidity was identified by the Postoperative Morbidity Survey on postoperative days 3 +/- 1, 7 +/- 1, 10 + 5 and graded for severity by the Clavien-Dindo system. Mortality was assessed at 30, 180 and 360 days. Results Postoperative morbidity was 78/48/47 per cent on postoperative days 3/7/10. Majority of morbidities (67.5 per cent) were graded as &gt;1 by Clavien-Dindo. Any type of postoperative morbidity graded &gt;1 was associated with increased risk for death up to one year. The mortality was 5.7 per cent (61/1063) at 30 days, 13.3 per cent (142/1063) at 6 months and 19.1 per cent (160/1063) at 12 months. Conclusion Severity classification as major to Xmajor/complex and ASA &gt;= 3 could be used to identify a high-risk surgical population concerning postoperative morbidity and mortality before surgery. Combining the two systems future electronic data extraction is possible of a high-risk population in tertiary hospitals.

Background We have previously reported inconclusive results from a randomized controlled trial in elderly with hip-fracture comparing intra-operative goal-directed therapy with routine fluid treatment. Now we aimed to describe and compare secondary outcomes at 4 months and 1 year follow-up and to analyze the cost-effectiveness. Methods Patients with hip fracture (age amp;gt;= 70) were randomized for GDT or routine fluid treatment (RFT). The secondary outcomes were long-term survival, complications, number of hospital readmissions, and quality of life (EQ-5D) changes. Additionally, cost effectiveness was analyzed by an analytic tool which combines the clinical effectiveness, quality of life changes and costs. Results Patient data (GDT n = 74; RFT n = 75) were analyzed on an intention to treat basis. Statistically significant differences (GDT vs RFT) were not found considering survival (RR 0.76, 95%CI 0.45-1.28) and complications (RR 0.68, 95% CI 0.4-1.10) at 12 months. No statistically significant difference was found between hospital readmissions and quality of life changes. Conclusion The statistical uncertainty of risk reduction of negative outcomes and the large variability of the collected data indicate the need of further research in large sample sizes. To enable future health economic evaluation for decision support surrounding implementation of GDT, we suggest adding patient-oriented outcomes in future trials.

Background: A controversy exists whether beneficial analgesic effects of epidural analgesia over intravenous analgesia influence the rate of post-operative complications and the length of hospital stay. There is some evidence that favours epidural analgesia following major surgery in high-risk patients. However, there is a controversy as to whether epidural analgesia reduces the intensive care resources following major surgery. In this study, we aimed at comparing the post-operative costs of intensive care in patients receiving epidural or intravenous analgesia.

Methods: Clinical data and rates of post-operative complications were extracted from a previously reported trial following thoraco-abdominal oesophagectomy. Cost data for individual patients included in that trial were retrospectively obtained from administrative records. Two separate phases were defined: costs of pain treatment and the direct cost of intensive care.

Results: Higher calculated costs of epidural vs. intravenous pain treatment, 1,037 vs. 410 Euros/patient, were outweighed by lower post-operative costs of intensive care 5,571 vs. 7,921 Euros/patient (NS).

Conclusion: Higher costs and better analgesic effects of epidural analgesia compared with intravenous analgesia do not reduce total costs for post-operative care following major surgery.

Background: Intravascular volume expansion is followed by loss of fluid from the circulation. The extravasation of albumin in this readjustment is insufficiently known. Methods: Twelve male volunteers participated, each in three separate sessions, in a controlled, randomised, open fashion. They received one of the following: albumin 40g/L,(7.1mL/kg, i.e. 500mL per 70kg), Ringer's acetate (21.4mL/kg), or dextran 30g/L (7.1mL/kg). The fluids were infused during 30min and the subjects were followed for 180min. ECG, arterial oxygen saturation and non-invasive arterial pressure were recorded. Haemoglobin, haematocrit, serum albumin and osmolality, plasma colloid osmotic pressure and hyaluronan concentration were determined in venous samples. Results: The serum albumin concentration decreased (P < 0.05, ANOVA) following Ringer's acetate or dextran, whereas serum osmolality was unchanged in all groups. The colloid osmotic pressure decreased (P<0.05) after the Ringer solution. The blood volume increase was estimated from the decrease in haemoglobin concentration and did not differ between the three fluids. The cumulated extravasation of albumin was largest following albumin (10.4 ▒ 5.4g, mean ▒ SD), less following dextran (5.6 ▒ 5.0 g) and negligible in the Ringer group (0.5 ▒ 10.0 g, P < 0.05 against albumin). However, the Ringer solution increased the plasma concentration of hyaluronan drastically. Conclusions: Infusion of hypotonic colloidal solutions entails net loss of albumin from the vascular space. This is not the case after Ringer's acetate. Increased interstitial hydration from the latter fluid is followed by lymphatic wash out of hyaluronan. ⌐ Acta Anaesthesiologica Scandinavica.

Background: Chronic obstructive pulmonary disease (COPD) represents a major and growing health problem. The purpose of this work was to examine characteristics, resource use and long-term survival in patients with an acute exacerbation of COPD that were admitted to Swedish intensive care units (ICU). Methods: Patient characteristics at admission, length of stay (LOS), resource use and outcome were collected for admissions due to COPD during 2002-2006 in the database of the Swedish Intensive Care Registry. Vital status was secured for 99.6% of the patients. Kaplan-Meier survival estimates were computed for index admissions only. Results: We identified 1009 patients with 1199 admissions due to COPD (1.3% of all intensive care admissions). The mean (SD) age was 70.2 (9.1) years and the proportion of women were 61.5%. Mean (SD) Acute Physiology and Chronic Health Evaluation II probability of hospital death was 0.31 (0.19). Median LOS was 28 (interquartile range 52) h. The number of readmissions was 190 during the 5-year study. Older patients had fewer readmissions (OR 0.96, 95% CI: 0.95-0.98/year increase in age). ICU mortality was 7.3% (87 of 1199 admissions) and 30-day mortality was 26.0% (262 of 1009 index admissions). Median survival was 14.5 months and 31% of patients survived 3 years after the index admission. Conclusions: Short (30 days) and long-term survival is poor in acute COPD. Readmissions are frequent reflecting the severity of this chronic illness. Patients are less likely to be readmitted with increasing age which may be due to withholding of further intensive care. © 2008 The Authors.

Background The choice between non-invasive ventilation (NIV) and invasive ventilation in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may be irrational. The aim of this study was to examine those patient characteristics, and circumstances deemed important in the choice made between NIV and invasive ventilation in the intensive care unit (ICU). Methods We first examined 95 admissions of AECOPD patients on nine ICUs and identified variables associated with invasive ventilation. Thereafter, a questionnaire was sent to ICU personnel to study the relative importance of different factors with a possible influence on the decision to use invasive ventilation at once. Results Univariable analysis showed that increasing age [odds ratio (OR) 1.06 per year] and increasing body mass index (BMI) (OR 1.11 per kg/m2) were associated with immediate invasive ventilation, while there was no such association with arterial blood gases or breath rate. BMI was the only factor that remained associated with immediate invasive ventilation in the multivariable analysis [OR 1.12 (95% confidence interval 1.031.23) kg/m2]. Ranking of responses to the questionnaire showed that consciousness, respiratory symptoms and blood gases were powerful factors determining invasive ventilation, whereas high BMI and age were ranked low. Non-patient-related factors were also deemed important (physician in charge, presence of guidelines, ICU workload). Conclusion Factors other than those deemed most important in guidelines appear to have an inappropriate influence on the choice between NIV and immediate intubation in AECOPD in the ICU. These factors must be identified to further increase the appropriate use of NIV.

Background: Propofol is known to interact with the γ-aminobutyric acid_A (GABA_A) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia.

Methods: To compare propofol and GABA, their interaction with the GABA_A receptor β subunit and actin were studied in three cellular fractions of cultured rat neurons using Western blot technique.

Results: Propofol tyrosine phosphorylated the GABA_A receptor β₂ (MW 54 and 56 kDa) and β₃ (MW 57 kDa) subtypes. The increase was shown in both the cytoskeleton (β₂₍₅₄₎ and β₂₍₅₆₎ subtypes) and the cell membrane (β₂₍₅₄₎ and β₃ subtypes). Concurrently the 56 kDa β₂ subtype was reduced in the cytosol. Propofol, but not GABA, also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. Without extracellular calcium available, the amount of actin decreased in the cytoskeleton, but tyrosine phosphorylation was unchanged. GABA caused increased tyrosine phosphorylation of β₂₍₅₆₎ and β₃ subtypes in the membrane and both β₂ subtypes in the cytoskeleton but no cytosolic tyrosine phosphorylation.

Conclusion: The difference between propofol and GABA at the GABA_A receptor was shown to take place in the membrane, where the β₂₍₅₄₎ was increased by propofol and instead the β₂₍₅₆₎ subtype was increased by GABA. Only propofol also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. This interaction between the GABA_A receptor and actin might explain the difference between anaesthesia and physiological neuronal inhibition.

BACKGROUND: It is unknown whether an intra-operative colloid infusion alters the dynamics of a crystalloid load administered post-operatively.

METHODS: Ten patients received 12.5 ml/kg of Ringer's lactate over 30 min 1-3 days before and 4 h after laparoscopic cholecystectomy, during which 10 ml/kg of a colloid solution, hydroxyethylstarch (HES 130/0.4), was infused. The total body clearance of the pre- and post-operative test infusions was taken as the ratio between the urinary excretion and the Hb-derived dilution of venous plasma over 150 min. The plasma clearance of the infused fluid was calculated using volume kinetics based on the plasma dilution alone. The pre-operative plasma clearance was compared with the post-operative plasma clearance and patients served as their own control.

RESULTS: The urinary excretion averaged 350 ml for the pre-operative infusion and 612 ml post-operatively, which corresponds to 46% and 68% of the pre- and post-operative infusions, respectively. The total body clearance of the crystalloid fluid was 30 ml/min before surgery and 124 ml/min after surgery (P<0.01). The plasma clearance, as obtained from the plasma dilution alone, was 28 and 412 ml/min, respectively. The maximal increase in plasma volume was 410 ml pre-operatively vs. 220 ml post-operatively.

CONCLUSIONS: Infusion of a colloid solution in combination with a crystalloid during laparoscopic cholecystectomy increased the plasma clearance of a post-operative crystalloid infusion.

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Background: Intrathecal analgesia (ITA) is a valuable treatment option for intractable cancer-related pain. However, the issue of movement-evoked breakthrough pain (BTP) has not been specifically investigated in the ITA setting. The aim of the study was to evaluate the effect of ITA on spontaneous resting pain intensity (SRPI), doses of non-ITA opioids, and specifically on movement-evoked pain intensity (MEPI). less thanbrgreater than less thanbrgreater thanMethods: We prospectively studied 28 consecutive patients who graded SRPI and MEPI on a 0-10 numerical rating scale (NRS) at the time of ITA procedure, after 1 week, and after 1 month. Mild pain was defined as NRS andlt;= 3 and severe pain as NRS andgt;= 7. Concomitant doses of opioids were registered. less thanbrgreater than less thanbrgreater thanResults: After 1 week, no patient had severe SRPI compared with 31% before ITA, and the proportion of patients with mild SRPI had increased from 27% to 76%. Meanwhile, the median daily dose of non-ITA opioids decreased from 575 to 120 mg of oral morphine equivalents. The effect on SRPI and on doses of non-ITA opioids remained essentially unchanged during the study month, but the proportion of patients having severe MEPI did not change significantly: 44% still had severe MEPI after 1 week and 40% after 1 month. less thanbrgreater than less thanbrgreater thanConclusion: Movement-evoked BTP was a major clinical problem throughout the study month despite otherwise successful ITA. Improving the quality of life of patients with intractable cancer-related pain should include developing strategies to better deal with movement-evoked BTP.

Background We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. Methods Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. Results Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. Conclusion There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the ISTH guidelines for antithrombotic treatment in COVID-19. This evidence-based guideline serves as a useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

The Scandinavian Society of Anaesthesiology and Intensive Care Medicine Clinical Practice Committee endorses the recent DASAIM/DSIT guideline for prevention of rhabdomyolysis-induced acute kidney injury. However, we emphasize the low quality of evidence with only weak recommendations for all interventions, highlighting that further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimates.

Background: Myocardial dysfunction occurs commonly in septic shock. It is not known whether this is due to local ischaemia and metabolic disturbances. Our hypothesis was that endotoxaemic myocardial dysfunction may be associated with interstitial ischaemic and metabolic changes, measured using interstitial microdialysis (MD). Methods: Eighteen pigs were randomized to control (n=6) or endotoxin infusion (n=12). MD catheters were inserted into the myocardium for measurement of interstitial glucose, pyruvate and lactate concentrations. Plasma glucose and lactate concentrations and systemic haemodynamic parameters were measured simultaneously. Results: Compared with the control group, the endotoxaemic animals had significantly decreased left ventricular stroke work and venous oxygen saturation (SvO2), and increased mean pulmonary artery pressure and plasma lactate. In the endotoxaemic group, decreases in interstitial glucose were observed, occurring simultaneously with increases in interstitial pruvate. Interstitial lactate : pyruvate ratios decreased with time in all animals. Conclusions: Despite severe systemic and pulmonary haemodynamic changes, interstitial MD measurements revealed no evidence of anaerobic metabolism in the myocardium of endotoxaemic pigs. There were, however, changes in glucose and pyruvate concentrations, suggesting local energy metabolic disturbances. © 2008 The Authors.

Background A major risk with epidural analgesia is accidental dural puncture (ADP), which may result in post-dural puncture headache (PDPH). This survey was conducted to explore the incidence of ADP, the policy for management of PDPH and the educational practices in epidural analgesia during labour in the Nordic countries. Methods A postal questionnaire was sent to the anaesthesiologist responsible for Obstetric anaesthesia service in all maternity units (n=153) with questions relating to the year 2008. Results The overall response rate was 93%. About 32% (22-47%) of parturients received epidural analgesia for labour. There were databases for registering obstetric epidural complications in 13% of Danish, 24% of Norwegian and Swedish, 43% of Finnish and 100% of hospitals in Iceland. The estimated incidence of ADP was 1% (n approximate to 900). Epidural blood patch (EBP) was performed in 86% (n approximate to 780) of the parturients. The most common time interval from diagnosis to performing EBP was 24-48 h. The success rate for EBP was greater than 75% in 67% (62-79%) of hospitals. The use of diagnostic CT/MRI before the first or the second EBP was exceptional. No major complication was reported. Teaching of epidurals was commonest (86%) in the non-obstetric population and 53% hospitals desired a formal training programme in obstetric analgesia. Conclusion We found the incidence of ADP to be approximately 1%. EBP was the commonest method used for its management, and the success rate was high in most hospitals. Formal training in epidural analgesia was absent in most countries and trainees first performed it in the non-obstetric population.

BACKGROUND: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry.

METHODS: A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry.

RESULTS: Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P < 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison.

CONCLUSIONS: There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.

Background:  The perioperative effects of intrathecal and epidural clonidine combined with local anesthetic were evaluated in 60 patients undergoing hip arthroplasty.

Methods:  This was a double-blinded study and the patients were randomized into three groups, with 20 patients in each group. All patients received spinal anesthesia with 17.5 mg of plain bupivacaine with 15 µg of clonidine (Group BC-RC) or without clonidine (Groups B-R and B-RC). Postoperatively, epidural infusion was administered in the following way: Group B-R – ropivacaine 4 mg h⁻¹; Groups B-RC and BC-RC: ropivacaine 4 mg h⁻¹ and clonidine 40 µg h⁻¹. Sensory block was assessed with light touch, pinprick, transcutaneous electrical stimulation at T12 and L2 dermatomes, and perception of thermal stimuli.

Results:  The maximal upper level of sensory block measured by pin-prick (T6–T7) did not differ between the groups while the partial sensory block for cold and warmth were increased two dermatomes above pin-prick level in the group with intrathecal clonidine compared to the other two groups (P < 0.05). Duration of anesthesia, analgesia and motor block were longer in Group BC-RC compared to Groups B-R and B-RC (P < 0.02). Postoperatively, both VAS score on movement and PCA-morphine consumption were higher in Group B-R than in Groups B-RC and BC-RC (P < 0.01). The arterial pressure and heart rate in Groups B-RC and BC-RC were significantly lower than in Group B-R at 10–24 and 15–24 h, respectively, after spinal injection.

Conclusion:  Low-dose intrathecal clonidine provided a better quality of anesthesia and longer-lasting analgesia. Epidural clonidine-ropivacaine infusion resulted in improved postoperative analgesia but was associated with a moderate decrease in blood pressure.

Background: The purpose of the present study was to evaluate the postoperative analgesic and adverse effects of equal doses of oral or intrathecal clonidine in spinal anaesthesia with bupivacaine plain.

Methods: Forty-five ASA I-III orthopaedic patients scheduled for osteosynthesis of a traumatic femur fracture were randomised in a double-blind fashion to one of 3 groups. Patients received 15 mg of plain bupivacaine intrathecally (group B) or an intrathecal mixture of bupivacaine 15 mg and clonidine 150 mg (group CIT). In group CPO oral clonidine 150 mg was administered 60 min before intrathecal injection of bupivacaine 15 mg.

Results: Oral and intrathecal clonidine prolonged the time until the first request for analgesics, 313 ± 29 and 337 ± 29 min, respectively, vs. 236 ± 27 min in group B (P < 0.01). The total 24- h PCA morphine dose was significantly lower in group CIT(19.3 ± 1.3 mg) compared to groups B and CPO(33.4 ± 2.0 and 31.2 ± 3.1 mg). MAP was decreased significantly during the first hour after intrathecal clonidine(14%) and during the first 5 h after oral clonidine(14–19%). HR decreased in CIT during the 5th and 6th postoperative hours(7–9%) and during the first 2 h(9%) in CPO (P < 0.01). The degree of sedation was more pronounced in group CPO during the first 3 h. Four patients had pruritus in group B.

Conclusions: Addition of intrathecal clonidine prolonged analgesia and decreased morphine consumption postoperatively more than oral clonidine. Hypotension was more pronounced after oral than after intrathecal clonidine. Intrathecal clonidine is therefore recommended.

Background: Enhancement of local anaesthetic-produced regional blocks by clonidine seems well established. There are insufficient data about dose-effect relationship of combinations of clonidine with individual agents, efficiency of local versus systemic administration of clonidine, and comparative evaluation of clonidine with vasoconstrictors. Because of unavailability of long-acting local anaesthetics at the time of study, our aim was to evaluate augmentation of lidocaine spinal block with local or systemic clonidine and to compare the results with the efficacy of intrathecal phenylephrine.

Methods: Ninety pts of age 50–72 yrs with ASA 1–4 physical status, scheduled for open prostatectomies, hysterectomies or ostheosynthesis of fractured hip were randomized to one of 6 treatment groups, 15 pts in each. Patients received intrathecally (L₃–L₄) either 100 mg of plain lidocaine (group L100); or a mixture of lidocaine 40 and 80 mg with clonidine 100 μg (groups L40-C100 and L80-C100); or a combination of lidocaine 40 and 80 mg with clonidine 300 μg orally 60 min before spinal puncture (L40-C300 and L80-C300). Addition of intrathecal phenylephrine 5 mg to 80 mg of lidocaine was also investigated (L80-P5).

Results: There were no significant intergroup differences concerning demographic data or type of surgery. All operations (duration up to 150 min) were completed without need for analgesic supplementation. The addition of clonidine resulted in a significant reduction of the onset time of spinal block and prolongation of the duration of sensory and motor blocks compared to plain lidocaine or lidocaine with phenylephrine. In spite of the well-known hypotensive action of α₂-agonists, haemodynamic depression only in group L80-C300 was significantly more pronounced than in L100 and L80-P5 groups. The least decrease of BP and minimal need of rescue ephedrine among all patients studied were recorded in the group receiving low dosage of lidocaine with intrathecal clonidine (L40-C100). Sedation occurred in most patients receiving clonidine.

Conclusion: Our results indicate that addition of clonidine to lidocaine, irrespective of the route of administration, prolongs the duration of spinal block and permits a reduction of the lidocaine dose needed for a given duration of block. Addition of phenylephrine results in a less pronounced statistically significant prolongation of anaesthesia. The regression of sensory block before restoration of motor function seems to be a specific (and unfortunate) effect of both clonidine and phenylephrine.

BACKGROUND: The fluid absorption that occurs during transurethral resection of the prostate (TURP) can be indicated and quantified by the ethanol method. Recently, nitrous oxide (N(2)O) was tested in animals and volunteers and seemed to be more accurate and safe. The present study compared these two methods in surgical patients.

METHODS: Eighty-six TURPs were performed at two hospitals using an irrigating fluid that contained 3% mannitol, 1% ethanol and 0.004% N(2)O (40 ml/l). The ethanol concentration was measured by end-expiratory tests every 10 min. The N(2)O concentration was measured by a flared nasal cannula every second. Fluid absorption was calculated based on a regression equation (ethanol method) from the area under the curve based on the samples where CO(2) >median (N(2)O method).

RESULTS: Thirteen patients (15%) absorbed >300 ml of fluid as indicated by the ethanol method. The median volume was 707 ml (range 367-1422). Ethanol yielded higher figures for fluid absorption up to 700-800 ml, whereafter the N(2)O method indicated that the absorption was larger. Over the entire range, the mean difference between the two methods at the end of any 10-min period of TURP was only +45 ml, although the 95% limits of agreement were quite separated (-479 to +569 ml).

CONCLUSIONS: The N(2)O method does not require forced breath sampling and was successfully apply clinically. However, there was a dose-dependent difference in result between the ethanol and N(2)O methods, which markedly separated the limits of agreement for a wider range of fluid absorption events.

Functional coagulation analyses like Sonoclot and thromboelastography have not been evaluated during perioperative autotransfusion. We have prospectively studied three different transfusion regimes in 45 patients undergoing total hip arthroplasty. Blood losses were replaced either with heterologous erythrocyte concentrate (group I), intra- and postoperative autotransfusion of blood salvaged with cellsaver technique (group II) or predonated autologous erythrocyte concentrates together with salvaged blood (group III). Routine and functional coagulation analyses with a Sonoclot were performed preoperatively, 6 hours postoperatively (6 h), day 1–5 and 10. An early postoperative hypo- and late postoperadve hypercoagulative phase could be detected with Sonoclot signs of platelet function and fibrin deposition in all groups. Sonoclot coagulation analyses better correlated to both blood loss and dextran dosage than APTT and platelet count in the routine coagulation analyses. Functional coagulation analysis has a potential use in individualizing plasmasubstitution and thromboprophylaxis regimes during autotransfusion in THR.

Background: Explicit recall (ER) is evident in approximately 0.2% of patients given general anaesthesia including muscle relaxants. This prospective study was performed to evaluate if cerebral monitoring using BIS to guide the conduction of anaesthesia could reduce this incidence significantly. Patients and methods: A prospective cohort of 4945 consecutive surgical patients requiring muscle relaxants and/or intubation were monitored with BIS and subsequently interviewed for ER on three occasions. BIS values between 40 and 60 were recommended. The results from the BIS-monitored group of patients was compared with a historical group of 7826 similar cases in a previous study when no cerebral monitoring was used. Results: Two patients in the BIS-monitored group, 0.04%, had ER as compared with 0.18% in the control group (P < 0.038). Both BIS-monitored patients with ER were aware during intubation when they had high BIS values (>60) for 4 min and more than 10 min, respectively. However, periods with high BIS = 4 min were also evident in other patients with no ER. Episodes with high BIS, 4 min or more, were found in 19% of the monitored patients during induction, and in 8% of cases during maintenance. Conclusions: The use of BIS monitoring during general anaesthesia requiring endotracheal intubation and/or muscle relaxants was associated with a significantly reduced incidence of awareness as compared with a historical control population.

BACKGROUND: Arterial hypotension following induction of spinal anesthesia is difficult to prevent with infusion fluids. In a randomized, unblinded and controlled study we evaluated whether a rapid fluid administration planned according to volume kinetic analysis is followed by a more stable blood pressure.

METHODS: Spinal anesthesia was induced in 75 surgical patients, using one of three different fluid regimens: intravenous 'bolus injection' of 5 ml kg(-1) of Ringer's acetate over 3 min, 2 ml kg(-1) of low-molecular weight (1 kDa) dextran over 3 min, or a constant-rate infusion of 15 ml kg(-1) of Ringer's acetate over 40 min (controls). The kinetics of the fluid was studied in five patients in each group and also in eight volunteers.

RESULTS: The decrease in mean arterial pressure averaged 28%, 27% and 26%, respectively, and was fully developed 16 min after the induction. The height of the block, but not the fluid programme, correlated with the hypotension. Nausea or near-fainting associated with marked hypotension or bradycardia was recorded in none, five (20%) and two (8%) of the patients, respectively. Both bolus injections were followed by translocation of fluid from the peripheral tissues to the bloodstream, which maintained the plasma dilution at about 10% for at least 30 min until surgery began.

CONCLUSION: A brisk infusion of Ringer's solution or dextran 1 kDa over 3 min was followed by the same decrease in arterial pressure as a longer and 3-5-times larger infusion of Ringer's solution over 40 min during induction of spinal anesthesia.

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Background Survival among critically ill COVID-19 patients varies between countries and time periods. Mortality rates up to 60% have been reported in intensive care units (ICUs). Standard-of-care has evolved throughout the pandemic. The purpose of the study was to explore management and mortality of COVID-19 ICU-patients during the first pandemic wave and assess their post-ICU health status. Methods We conducted an exploratory observational ambidirectional population-based study of ICU-patients with COVID-19 in a Swedish county during 1 March-30 June 2020. Primary outcome was 60-day mortality with secondary outcomes including treatments, complications, self-reported general health and dyspnoea post-discharge. Patients were consecutively divided into equal tertiles with cut-offs on April 4 and April 20, 2020, to analyse time trends. Results One hundred patients, median age was 63 years, were included, and 60-day mortality rate was 22%. Ninety-one percent had moderate/severe ARDS and 88% required mechanical ventilation. In the first tertile of patients 60-day mortality was 33%, declining to 15% and 18% in the following two. This reduction paralleled increased use of thromboprophylaxis, less steep rise of treated ICU-patients per day and expanded ICU resources. Four months post-discharge, 63% of survivors reported self-assessed decline in general health retrospectively compared to prior COVID-19. Conclusions In this cohort, the initial 60-day mortality quickly declined, despite continuous admittance of critically ill patients. This was parallel to adaptation to increased workload and more intense thromboembolic prophylaxis. A majority of survivors reported declined general health four months after discharge. Further studies on long-term health status of ICU-survivors are indicated.

Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.Conclusion: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.

Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence-Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow-up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide-bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long-term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long-term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator-assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow-up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.

Background Thoracic epidural analgesia (TEDA) was offered to patients with refractory angina pectoris. Our primary objectives were to evaluate TEDAs influence on quality of life (QoL, base for power analysis), and hypothesising that TEDA with bupivacaine during 1 month counteracts exercise-induced myocardial hypoperfusion and increase physical performance. Methods Patients with refractory angina and exercise inducible hypoperfusion, as demonstrated by myocardial perfusion imaging (MPI), were randomised to 1-month treatment with TEDA with bupivacaine (B-group, n = 9) or saline (P-group, n = 10) in a double-blind fashion. MPI and bicycle ergometry were performed before TEDA and after 1 month while subjective QoL on a visual analogue scale (VAS) reported by the patients was checked weekly. Results During this month VAS (mean [95%CI]) increased similarly in both groups (B-group from 33 [18-50] to 54 [30-78] P P amp;lt; 0.05). The B-group reduced their exertional-induced myocardial hypoperfusion (from 32% [12-52] to 21% [3-39]; n = 9; P amp;lt; 0.05), while the P-group showed no significant change (before 21% [6-35]; at 1 month 23% [6-40]; n = 10). MPI at rest did not change and no improvement in physical performance was detected in neither of the groups. Conclusions In refractory angina, TEDA with bupivacaine inhibits myocardial ischaemia in contrast to TEDA with saline. Regardless of whether bupivacaine or saline is applied intermittently every day, TEDA during 1 month improves the quality of life and reduces angina, even when physical performance remains low. A significant placebo effect has to be considered.

Background: A major problem in pain treatment in the newborn is the ability to assess the degree of experienced pain. Several different methods for estimating pain in the newborn have been introduced in recent years. The objectives of this study were to see whether pain scoring was used in Swedish neonatal units, and by which method, and furthermore to observe whether any changes had occurred between 1993 and 1998.

Method: A questionnaire was distributed to all Swedish neonatal units in 1993 and 1998.

Results: In both 1993 and 1998, 86% of all clinics answered the questionnaire. Two-thirds of these clinics used some method for estimating pain in the newborn at both times. Eight clinics used a structured method in the latter period compared to one in the earlier period. A higher proportion of units having full intensive care measured pain compared to other units.

Conclusion: The study shows that an unchanging low proportion of neonatal units in Sweden attempt to assess pain. There is a minor increase in the number of departments that use a structured method for pain scoring. Documentation of pain intensity is still inadequate and should be improved.

Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

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Background

Patient‐controlled sedation (PCS) with propofol accompanied by a bedside nurse anaesthetist is an alternative sedation method for endoscopic procedures compared with midazolam administered by a nurse or endoscopist. Increasing costs in health care demands an economic perspective when introducing alternative methods. We applied a hospital perspective on a cost analysis comparing different methods of sedation and the resource use that were expected to affect cost differences related to the sedation.

Methods

Based on two randomised previous studies, the direct costs were determined for different sedation methods during two advanced endoscopic procedures: endoscopic retrograde cholangiopancreatography (ERCP) and flexible bronchoscopy including endobronchial ultrasound. ERCP comparisons were made between midazolam sedation by the endoscopic team, PCS with a bedside nurse anaesthetist and propofol sedation administered by a nurse anaesthetist. Bronchoscopy comparisons were made between midazolam sedation by the endoscopic team and PCS with a bedside nurse anaesthetist, categorised by premedication morphine‐scopolamine or glycopyrronium.

Results

Propofol PCS with a bedside nurse anaesthetist resulted in lower costs per patient for sedation for both ERCP (233 USD) and bronchoscopy (premedication morphine‐scopolamine 267 USD, premedication glycopyrronium 269 USD) compared with midazolam (ERCP 425 USD, bronchoscopy 337 USD). Aborted procedures that needed to be repeated and prolonged hospital stays significantly increased the cost for the midazolam groups.

Conclusion

Propofol PCS with a bedside nurse anaesthetist reduces the direct sedation costs for ERCP and bronchoscopy procedures compared with midazolam sedation.

Local anesthetics (LA) are injected via catheters placed in surgical wounds for post-operative analgesia. The primary aim of this systematic review was to assess whether LA reduce pain intensity when injected via wound catheters. A literature search was performed from Medline via PubMed, EMBASE and the Cochrane database from 1966 until November 2009. The search strategy included the following key words: pain, postoperative, catheters and local anesthetics. Two co-authors independently read every article that was initially included and extracted data into a pre-defined study record form. A total of 753 studies primarily fit the search criteria and 163 were initially extracted. Of these, 32 studies were included in the meta-analysis. Wound catheters provided no significant analgesia at rest or on activity, except in patients undergoing gynecological and obstetric surgery at 48 h (P = 0.03). The overall morphine consumption was lower (approximate to 13 mg) during 0-24 h (P less than 0.001) in these patients. No significant differences in side effects were found, except for a lower risk of wound breakdown (P = 0.048) and a shorter length of hospital stay (P = 0.04) in patients receiving LA. A statistically significant heterogeneity was seen between the studies in most end-points. LA injected via wound catheters did not reduce pain intensity, except at 48 h in a subgroup of patients undergoing obstetric and gynecological surgery. Rescue analgesic consumption was also lower in this group at 0-24 h. The magnitude of these effects was small and compounded by pronounced heterogeneity.

Background: Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringers acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids. Methods: Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringers acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects. Results: The micro-constants describing distribution (k(12)) and elimination (k(10)) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k(21)) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V-c) doubled. Conclusion: The return of Ringers acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid.

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BackgroundFluid absorption is a well-known complication of endoscopic surgeries, such as transurethral prostatic resection and transcervical endometrial resection. Absorption of electrolyte-free fluid in excess of 1L, which occurs in 5% to 10% of the operations, markedly increases the risk of adverse effects from the cardiovascular and neurological systems. Absorption of isotonic saline, which is used with the new bipolar resection technique, will change the scenario of adverse effects in a yet unknown way. Hyponatremia no longer occurs, but marking the saline with ethanol reveals that fluid absorption occurs just as much as with monopolar prostate resections. MethodsEthanol monitoring is a method for non-invasive indication and quantification of fluid absorption that has been well evaluated. By using an irrigating fluid that contains 1% of ethanol, updated information about fluid absorption can be obtained at any time perioperatively by letting the patient breathe into a hand-held alcolmeter. ResultsRegression equations and nomograms with variable complexity are available for estimating how much fluid has been absorbed, both when the alcolmeter is calibrated to show the blood ethanol level and when it is calibrated to show the breath ethanol concentration. Examples of how such estimations should be performed are given in this review article. ConclusionsThe difficulty is that the anesthesiologist must be aware of how the alcolmeter is calibrated (for blood or breath) and be able to distinguish between the intravascular and extravascular absorption routes, which give rise to different patterns and levels of breath ethanol concentrations.

Introduction: Assessment of dehydration in the preoperative setting is of potential clinical value. The present study uses urine analysis and plasma volume kinetics, which have both been validated against induced changes in body water in volunteers, to study the incidence and severity of dehydration before open abdominal surgery begins. Methods: Thirty patients (mean age 64 years) had their urine analysed before major elective open abdominal surgery for colour, specific weight, osmolality and creatinine. The results were scored and the mean taken to represent a dehydration index. Thereafter, the patients received an infusion of 5ml/kg of Ringers acetate intravenously for over 15min. Blood was sampled for 70min and the blood haemoglobin concentration used to estimate the plasma volume kinetics. Results: Distribution of fluid occurred more slowly (Pless than0.01) and the elimination half-life was twice as long (median 40min, not significant) in the 11 patients (37%) diagnosed to be moderately dehydrated as compared with euhydrated patients. The dehydration index indicated that the fluid deficit in these patients corresponded to 2.5% of the body weight, whereas the deficit in the others was 1%. In contrast, the 11 patients who later developed postoperative nausea and vomiting had a very short elimination half-life, only 9min (median, Pless than0.01). These patients were usually euhydrated but had microalbuminuria (Pless than0.03) and higher natriuresis (Pless than0.01). Conclusions: The degree of dehydration before major surgery was modest as evidenced both by urine sampling and volume kinetic analysis.

Intravenous fluid is life-saving in hypovolemic shock, but fluid sometimes aggravates the bleeding. During the past 25 years, animal models have helped our understanding of the mechanisms involved in this unexpected effect. A key issue is that vasoconstriction is insufficient to arrest the bleeding when damage is made to a major blood vessel. ‘Uncontrolled hemorrhage’ is rather stopped by a blood clot formed at the outside surface of the vessel, and the immature clot is sensitive to mechanical and chemical interactions. The mortality increases if rebleeding occurs. In the aortic tear model in swine, hemorrhage volume and the mortality increase from effective restoration of the arterial pressure. The mortality vs. amount of fluid curve is U-shaped with higher mortality at either end. Without any fluid at all, irreversible shock causes death provided the hemorrhage is sufficiently large. Crystalloid fluid administered in a 3 : 1 proportion to the amount of lost blood initiates serious rebleeding. Hypertonic saline 7.5% in 6% dextran 70 (HSD) also provokes rebleeding resulting in higher mortality in the recommended dosage of 4 ml/kg. Uncontrolled hemorrhage models in rats, except for the ‘cut-tail’ model, confirm the results from swine. To avoid rebleeding, fluid programs should not aim to fully restore the arterial pressure, blood flow rates, or blood volume. For a hemorrhage of 1000 ml, computer simulations show that deliberate hypovolemia (−300 ml) would be achieved by infusing 600–750 ml crystalloid fluid over 20–30 min or 100 ml of HSD over 10–20 min in an adult male.

The Revised (or "Extended") Starling principle is based on highly controlled laboratory-based frog and rodent experiments and remains a hypothesis awaiting clinical validation. A key point is that the endothelial glycocalyx layer moves the oncotic gradient from being between the plasma and the interstitium to between the plasma and a virtually protein-free space between the glycocalyx and the endothelial cell membrane, which dramatically changes the prerequisites for fluid absorption from tissue to plasma. However, many experimental and clinical observations in humans agree poorly with the new microcirculatory proposals. The most troubling aspect of the explanation regarding the role of the glycocalyx in the Revised Starling principle is the effective reabsorption of fluid by skeletal muscle when the capillary filtration pressure is acutely reduced. Other issues include the plasma volume effects of hypertonic saline, iso-oncotic and hyper-oncotic albumin, fluid distribution during cardio-pulmonary bypass, and the virtually identical capillary leakage of plasma and albumin despite marked inflammation found in our fluid therapy studies. The Revised Starling principle deals mainly with steady-state conditions, but the circulatory system is highly dynamic. Second to second vasomotion is always operational and must be considered to understand what we observe in humans.