Opioid Use After Intensive Care: A Nationwide Cohort Study.

OBJECTIVE: To describe opioid use after ICU admission, identify factors associated with chronic opioid use after critical care, and determine if chronic opioid use is associated with an increased risk of death. DESIGN: Retrospective cohort study. SETTING: Sweden including all registered ICU admissions between 2010 and 2018. PATIENTS: Adults surviving the first two quarters after ICU admission were eligible for inclusion. A total of 265,496 patients were screened and 61,094 were ineligible. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: Among 204,402 individuals included in the cohort, 22,138 developed chronic opioid use following critical care. Mean opioid consumption peaked after admission followed by a continuous decline without returning to baseline during follow-up of 24 months. Factors associated with chronic opioid use included high age, female sex, presence of comorbidities, preadmission opioid use, and ICU length of stay greater than 2 days. Adjusted hazard ratio for death 6-18 months after admission for chronic opioid users was 1.7 (95% CI, 1.6-1.7; p < 0.001). In the subset of patients not using opioids prior to admission, similar findings were noted. CONCLUSIONS: Mean opioid consumption is increased 24 months after ICU admission despite the lack of evidence for long-term opioid treatment. Given the high number of ICU entries and risk of excess mortality for chronic users, preventing opioid misuse is important when improving long-term outcomes after critical care.

Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.

BACKGROUND: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. METHODS: We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. RESULTS: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups. CONCLUSIONS: The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care. TRIAL REGISTRATION: ISRCTN54917435. Registered 15 June 2020 ( https://doi.org/10.1186/ISRCTN54917435 ).

Antidepressant drug use after intensive care: a nationwide cohort study.

Modern intensive care has improved survival rates, but emerging evidence suggests a high prevalence of post-intensive care unit (ICU) health problems, including post-traumatic stress disorder, depression and anxiety. These symptoms may have a detrimental effect on quality of life and increase mortality. The primary objective of this study is to examine the extent of initiation of antidepressant medication among ICU survivors and identify the factors associated with its usage. The secondary objective is to investigate whether the use of these medications is linked to an increased mortality. The nationwide study cohort included 125,130 ICU survivors admitted between 2010 and 2017. Within the first 3 months after ICU discharge, 7% of patients initiated antidepressant medication, by 1 year 15.5% had started medication. We found no tendency to a decrease during the 2-year follow-up period. Factors associated with antidepressant use included middle age, female sex, psychiatric and somatic comorbid conditions, substance dependence, higher illness severity, and longer ICU stay. Antidepressant users had a higher mortality rate, and deaths due to external causes and suicide were more frequent in this group. This study emphasizes the importance of detecting and addressing depression in ICU survivors to improve their quality of life and reduce mortality rates.

Opioid use following cardio-thoracic intensive care: risk factors and outcomes: a cohort study.

Opioid misuse has become a serious public health problem. Patients admitted to cardio-thoracic critical care are usually exposed to opioids, but the incidence and effects of chronic opioid use are not known. The primary objective was to describe opioid use after admission to a cardio-thoracic intensive care unit. Secondary objectives were to identify factors associated with chronic opioid usage and analyze risk of death. This cohort study included all cardio-thoracic ICU care episodes in Sweden between 2010 and 2018. Among the 34,200 patients included in the final study cohort, 4050 developed persistent opioid use after ICU care. Younger age, preadmission opioid use, female sex, presence of comorbidities and earlier year of ICU admission were all found to be associated with persistent opioid use. The adjusted hazard ratio for mortality between 6 and 18 months after admission among individuals with persistent opioid use was 2.2 (95% CI 1.8-2.6; P < 0.001). For opioid-naïve patients before ICU admission, new onset of chronic opioid usage was significant during the follow-up period of 24 months. Despite the absence of conclusive evidence supporting extended opioid treatment, the average opioid consumption remains notably elevated twelve months subsequent to cardio-thoracic ICU care.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. CONCLUSIONS: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Lung impedance changes during awake prone positioning in COVID-19. A non-randomized cross-over study.

BACKGROUND: The effects of awake prone positioning (APP) on respiratory mechanics in patients with COVID-19 are not well characterized. The aim of this study was to investigate changes of global and regional lung volumes during APP compared with the supine position using electrical lung impedance tomography (EIT) in patients with hypoxemic respiratory failure due to COVID-19. MATERIALS AND METHODS: This exploratory non-randomized cross-over study was conducted at two university hospitals in Sweden between January and May 2021. Patients admitted to the intensive care unit with confirmed COVID-19, an arterial cannula in place, a PaO2/FiO2 ratio <26.6 kPa (<200 mmHg) and high-flow nasal oxygen or non-invasive ventilation were eligible for inclusion. EIT-data were recorded at supine baseline, at 30 and 60 minutes after APP-initiation, and 30 minutes after supine repositioning. The primary outcomes were changes in global and regional tidal impedance variation (TIV), center of ventilation (CoV), global and regional delta end-expiratory lung-impedance (dEELI) and global inhomogeneity (GI) index at the end of APP compared with supine baseline. Data were reported as median (IQR). RESULTS: All patients (n = 10) were male and age was 64 (47-73) years. There were no changes in global or regional TIV, CoV or GI-index during the intervention. dEELI increased from supine reference value 0 to 1.51 (0.32-3.62) 60 minutes after APP (median difference 1.51 (95% CI 0.19-5.16), p = 0.04) and returned to near baseline values after supine repositioning. Seven patients (70%) showed an increase >0.20 in dEELI during APP. The other EIT-variables did not change during APP compared with baseline. CONCLUSION: Awake prone positioning was associated with a transient lung recruiting effect without changes in ventilation distribution measured with EIT in patients with hypoxemic respiratory failure due to COVID-19.

Benzodiazepine Dependence After Cardiothoracic Intensive Care: A Nationwide Cohort Study.

BACKGROUND: This study aimed to describe benzodiazepine use after cardiothoracic intensive care unit (ICU) care, including factors associated with new long-term high-potency benzodiazepine use after critical care, and to determine whether benzodiazepine use is associated with an increased risk of death. METHODS: A nationwide retrospective cohort study was conducted of all cardiothoracic ICU patients in Sweden between 2010 and 2018. All patients older than 18 years who survived the first 3 months after admission to a cardiothoracic ICU were eligible for inclusion. A total of 36,135 patients were screened, and 4163 were ineligible. RESULTS: In the final study cohort of 31,972 benzodiazepine-naive patients admitted to critical care, 578 patients had persistent high-potency benzodiazepine use. The proportion of new persistent benzodiazepine users was 5% in the first 3 months after ICU care, followed by a decline to a consistent level of 2% at 2 years of follow-up. Factors associated with persistent benzodiazepine use included higher age, female sex, psychiatric and somatic comorbidities, substance abuse, and preadmission opioid and low-potency benzodiazepine use. Adjusted hazard ratio for death 6 to 18 months after admission for new persistent benzodiazepine users was 2.2 (95% CI, 1.5-3.1; P < .001). CONCLUSIONS: High-potency benzodiazepine consumption is increased 2 years after admission to cardiothoracic ICU care despite lack of support for long-term use of benzodiazepines. Being older and female, prior opioid use, and comorbid conditions were among risk factors for persistent benzodiazepine use. Persistent benzodiazepine users had an increased risk of death.

Long-term opioid use following bicycle trauma: a register-based cohort study.

PURPOSE: Chronic opioid use is a significant public health burden. Orthopaedic trauma is one of the main indications for opioid prescription. We aimed to assess the risk for long-term opioid use in a healthy patient cohort. METHODS: In this matched cohort study, bicycle trauma patients from a Swedish Level-I-Trauma Centre in 2006-2015 were matched with comparators on age, sex, and municipality. Information about dispensed opioids 6 months prior until 18 months following the trauma, data on injuries, comorbidity, and socioeconomic factors were received from national registers. Among bicycle trauma patients, the associations between two exposures (educational level and injury to the lower extremities) and the risk of long-term opioid use (> 3 months after the trauma) were assessed in multivariable logistic regression models. RESULTS: Of 907 bicycle trauma patients, 419 (46%) received opioid prescriptions, whereof 74 (8%) became long-term users. In the first quarter after trauma, the mean opioid use was significantly higher in the trauma patients than in the comparators (253.2 mg vs 35.1 mg, p < 0.001) and fell thereafter to the same level as in the comparators. Severe injury to the lower extremities was associated with an increased risk of long-term opioid use [OR 4.88 (95% CI 2.34-10.15)], whereas high educational level had a protecting effect [OR 0.42 (95% CI 0.20-0.88)]. CONCLUSION: The risk of long-term opioid use after a bicycle trauma was low. However, opioids should be prescribed with caution, especially in those with injury to lower extremities or low educational level.

Characteristics and outcome of traumatic cardiac arrest at a level 1 trauma centre over 10 years in Sweden.

BACKGROUND: Historically, resuscitation in traumatic cardiac arrest (TCA) has been deemed futile. However, recent literature reports improved but varying survival. Current European guidelines emphasise the addressing of reversible aetiologies in TCA and propose that a resuscitative thoracotomy may be performed within 15 min from last sign of life. To improve clinician understanding of which patients benefit from resuscitative efforts we aimed to describe the characteristics and 30-day survival for traumatic cardiac arrest at a Swedish trauma centre with a particular focus on resuscitative thoracotomy. METHODS: Retrospective cohort study of adult patients (≥ 15 years) with TCA managed at Karolinska University Hospital Solna between 2011 and 2020. Trauma demographics, intra-arrest factors, lab values and procedures were compared between survivors and non-survivors. RESULTS: Among the 284 included patients the median age was 38 years, 82.2% were male and 60.5% were previously healthy. Blunt trauma was the dominant injury in 64.8% and median Injury Severity Score (ISS) was 38. For patients with a documented arrest rhythm, asystole was recorded in 39.2%, pulseless electric activity in 24.8% and a shockable rhythm in 6.8%. Thirty patients (10.6%) survived to 30 days with a Glasgow Outcome Scale score of 3 (n = 23) or 4 (n = 7). The most common causes of death were haemorrhagic shock (50.0%) and traumatic brain injury (25.5%). Survivors had a lower ISS (P < 0.001), more often had reactive pupils (P < 0.001) and a shockable rhythm (P = 0.04). In the subset of prehospital TCA, survivors less frequently received adrenaline (epinephrine) (P < 0.001) and in lower amounts (P = 0.02). Of patients that underwent resuscitative thoracotomy (n = 101), survivors (n = 12) had a shorter median time from last sign of life to thoracotomy (P = 0.03), however in four of these survivors the time exceeded 15 min. CONCLUSION: Survival after TCA is possible. Determining futility in TCA is difficult and this study demonstrates survivors outside of recent guidelines.

Blast polytrauma with hemodynamic shock, hypothermia, hypoventilation and systemic inflammatory response: description of a new porcine model.

PURPOSE: In the past decade blast injuries have become more prevalent. Blast trauma may cause extensive injuries requiring improved early resuscitation and prevention of haemorrhage. Randomized prospective trials are logistically and ethically challenging, and large animal models are important for further research efforts. Few severe blast trauma models have been described, which is why we aimed to establish a comprehensive polytrauma model in accordance with the criteria of the Berlin definition of polytrauma and with a survival time of > 2 h. Multiple blast injuries to the groin and abdomen were combined with hypoperfusion, respiratory and metabolic acidosis, hypoventilation, hypothermia and inflammatory response. The model was compared to lung contusion and haemorrhage. METHODS: 16 landrace swine (mean weight 60.5 kg) were randomized to "control" (n = 5), "chest trauma/hem" by lung contusion and class II haemorrhage (n = 5), and "blast polytrauma" caused by multiple blast injuries to the groin and abdomen, class II haemorrhage, lipopolysaccharide (LPS) infusion and hypothermia 32 °C (n = 6). RESULTS: The blast polytrauma group had an Injury Severity Score of 57 which resulted in haemodynamic shock, hypothermia, respiratory and metabolic acidosis and inflammatory response. The chest trauma/hem group had an Injury Severity Score of 9 and less profound physiologic effects. Physiologic parameters presented a dose-response relationship corresponding to the trauma levels. CONCLUSION: A comprehensive blast polytrauma model fulfilling the Berlin polytrauma criteria, with a high trauma load and a survival time of > 2 h was established. A severe, but consistent, injury profile was accomplished enabling the addition of experimental interventions in future studies, particularly of immediate resuscitation efforts including whole blood administration, trauma packing and haemostasis.

The swine as a vehicle for research in trauma-induced coagulopathy: Introducing principal component analysis for viscoelastic coagulation tests.

BACKGROUND: Uncontrolled bleeding is the leading cause of potentially preventable deaths among trauma patients. Tissue injury and shock result in trauma-induced coagulopathy (TIC). There are still uncertainties regarding detection methods and best practice management for TIC, and a deeper understanding of the pathophysiology requires robust animal models. The applicability of swine in coagulation studies, particularly after trauma has not been sufficiently elucidated. We, therefore, evaluated the swine as a vehicle for TIC research in a selection of trauma modalities. METHODS: Twenty-six landrace swine (3 females/23 males) (mean weight, 60.0 kg) were anesthetized and randomized to negative controls, receiving no manipulation (n = 5), positive controls by hemodilution (n = 5), pulmonary contusion without hemorrhage (n = 5), pulmonary contusion with hemorrhage (n = 5), and blast polytrauma with hypothermia, hypoperfusion, hypoventilation, and systemic inflammation (n = 6). A comprehensive coagulation panel was analyzed at baseline, 20 minutes and 120 minutes after trauma. RESULTS: PT(INR), aPTT, thrombocytes, and fibrinogen did not change after trauma. D-dimer increased (p < 0.0001), prothrombin decreased (p < 0.05) and aPC decreased (p < 0.01) after polytrauma. PAI-1 decreased after pulmonary contusion with hemorrhage (p < 0.05). Positive controls displayed changes in PT(INR), thrombocytes, fibrinogen, prothrombin, aPC (p < 0.05). Principal Component Analysis of rotational thromboelastometry presented pathologic coagulation profiles in both polytrauma and positive control groups with vectors extending outside the 95% confidence interval, which were not detected in negative controls. CONCLUSION: Coagulopathy was induced after severe porcine blast polytrauma, specifically detected in rotational thromboelastometry. A novel method for principal component analysis of viscoelastic tests was introduced which may increase the detection sensitivity and differentiation of TIC phenotypes and should be further investigated in trauma populations.

Predicting prolonged sick leave among trauma survivors.

Many survivors after trauma suffer from long-term morbidity. The aim of this observational cohort study was to develop a prognostic prediction tool for early assessment of full-time sick leave one year after trauma. Potential predictors were assessed combining individuals from a trauma register with national health registers. Two models were developed using logistic regression and stepwise backward elimination. 4458 individuals were included out of which 488 were on sick leave full-time 12 months after the trauma. One comprehensive and one simplified model were developed including nine and seven predictors respectively. Both models showed excellent discrimination (AUC 0.81). The comprehensive model had very good calibration, and the simplified model good calibration. Prediction models can be used to assess post-trauma sick leave using injury-related variables as well as factors not related to the trauma per se. Among included variables, pre-injury sick leave was the single most important predictor for full-time sick leave one year after trauma. These models could facilitate a more efficient use of resources, targeting groups for follow-up interventions to improve outcome. External validation is necessary in order to evaluate generalizability.

Post-trauma morbidity, measured as sick leave, is substantial and influenced by factors unrelated to injury: a retrospective matched observational cohort study.

BACKGROUND: Mortality as an endpoint has been the focus of trauma research whereas few studies investigate long-term outcomes in terms of morbidity. An adequate analysis of post-injury morbidity includes several dimensions, for this reason sick leave has been used as a proxy for morbidity in the current study. The aim of this retrospective matched observational cohort study was to investigate sick leave before and after trauma and factors associated with prolonged sick leave. METHODS: Patients from a level one trauma centre 2005-2010 were matched in a 1:5 ratio with uninjured controls. By linkage to national registries, sick leave rates were compared. The association between potential risk factors and full-time sick leave at twelve months post injury, the primary end-point, was examined in trauma patients by logistic regression. RESULTS: Four thousand seven hundred twelve patients and 25,013 controls aged 20-63 were included. Trauma patients had more sick leave both before and after trauma. Age, psychiatric disease, low level of education, serious injury, spinal injury, reduced consciousness at admission, discharge destination other than home, and hospital length of stay >7 days were all associated with the primary end-point. The strongest risk factor was sick leave before trauma; this was also noted in the most seriously injured patients. DISCUSSION: In this retrospective matched observational cohort study we found a significant long-term morbidity, measured as sick leave, among trauma patients. Compared to controls the difference was maximal early after trauma and sustained throughout the follow up period. In the logistic regression, factors associated with the traumatic injury as well as host factors increased the probability of not returning to work. Full sick leavemonth twelve post injury was strongly associated with pre-injury sick leave but also with age, psychiatric comorbidity, level of education, injury severity, spinal injury, low GCS at admission, length of stay at hospital and discharge to other destination than home. CONCLUSIONS: Trauma patients suffer from significant long-term morbidity. The sustained post-trauma morbidity is largely influenced by factors not related to injury per se. These insights enable identification of patients at risk for prolonged sick leave after trauma.