Observations on the Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clinical Studies on Healthy Volunteers and Intensive Care Patients

Patients treated in intensive care units require sedation and analgesia. However, sedative drugs also have potential adverse effects, and there is no single ideal sedativeanalgesic drug for these patients. Dexmedetomidine is an apha2-adrenoceptor agonist licenced for sedation of intensive care patients and patients undergoing surgery and other invasive procedures. Several routes of parenteral administration (intravenous, intramuscular, subcutaneous and intranasal) have been utilized. In the present series of studies, the pharmacokinetics and pharmacodynamics of intranasally administered dexmedetomidine as well as the gastrointestinal effects of intravenous dexmedetomidine were determined in healthy volunteers. Pharmacokinetics of dexmedetomidine during long lasting, high-dose infusions were characterized in intensive care patients. The bioavailability of intranasal dexmedetomidine was relatively good (65%), but interindividual variation was large. Dexmedetomidine significantly inhibited gastric emptying and gastrointestinal transit. In intensive care patients, the elimination half-life of dexmedetomidine was somewhat longer than reported for infusions of shorter duration and in less ill patients or healthy volunteers. Dexmedetomidine appeared to have linear pharmacokinetics up to the studied dose rate of 2.5 μg/kg/h. Dexmedetomidine clearance was decreasing with age and its volume of distribution was increased in hypoalbuminaemic patients, resulting in a longer elimination half-life and context-sensitive half-time. Intranasally administered dexmedetomidine was efficacious and well tolerated, making it appropriate for clinical situations requiring light sedation. The clinical significance of the gastrointestinal inhibitory effects of dexmedetomidine should be further evaluated in intensive care patients. The possibility of potentially altered potency and effect duration should be taken into account when administering dexmedetomidine to elderly or hypoalbuminaemic patients.Siirretty Doriast

Predictive value of shock index variants on 30-day mortality of trauma patients in helicopter emergency medical services : a nationwide observational retrospective multicenter study

The original shock index (SI) has been further developed to increase its prognostic value. We aimed to evaluate the predictive value of different SI variants on 30-day mortality among severely injured trauma patients in pre-hospital critical care settings. Adult trauma patients in the national Helicopter Emergency Medical Services (HEMS) registry were evaluated based on the primary outcome of 30-day mortality. SI, SIA (SI multiplied by age), SI/G (SI divided by Glasgow Coma Scale (GCS)), SIA/G (SI multiplied by age and divided by GCS), and SS (SI divided by oxygen saturation) were calculated based on the first vital signs measured at the time of HEMS contact. The area under the receiver operating curve (AUROC) was calculated for each SI variant. In total 4108 patients were included in the study. The overall 30-day mortality was 13.5%. The SIA/G and SI/G had the highest predictive ability (AUROC 0.884 [95% CI 0.869-0.899] and 0.8000 [95% CI 0.7780-0.8239], respectively). The SIA/G yielded good predictive performance between 30-day survivors and non-survivors in the pre-hospital critical care setting.Peer reviewe

The effect of time of measurement on the discriminant ability for mortality in trauma of a pre-hospital shock index multiplied by age and divided by the Glasgow Coma Score : a registry study

Peer reviewe

EMS non-conveyance: A safe practice to decrease ED crowding or a threat to patient safety?

Background: The safety of the Emergency Medical Service's (EMS's) non-conveyance decision was evaluated by EMS re-contacts, primary health care or emergency department (ED) visits, and hospitalization within 48 h. The secondary outcome was 28-day mortality.Methods: This cohort study used prospectively collected data on non-conveyed EMS patients from three different regions in Finland between June 1 and November 30, 2018. The Adjusted International Classification of Primary Care (ICPC2) as the reason for care was compared to hospital discharge diagnoses (ICD10). Multivariable logistic regressions were used to determine factors that were independently associated with adverse outcomes. Results are presented with adjusted odds ratios (aORs) together with 95% confidence intervals (CIs). Data regarding deceased patients were reviewed by the study group.Results: Of the non-conveyed EMS patients (n = 11,861), 6.3% re-contacted the EMS, 8.3% attended a primary health care facility, 4.2% went to the ED, 1.6% were hospitalized, and 0.1% died 0-24 h after the EMS mission. The 0-24 h adverse event rate was higher than 24-48 h. After non-conveyance, 32 (0.3%) patients were admitted to an intensive care unit within 24 h. Primary non-urgent EMS mission (aOR 1.49; 95% CI 1.25 to 1.77), EMS arrival at night (aOR 1.82; 95% CI 1.58 to 2.09), ALS unit type vs BLS (aOR 1.43; 95% CI 1.16 to 1.77), rural area (aOR 1.74; 95% CI 1.51 to 1.99), and older patient age (aOR 1.41; 95% CI 1.20 to 1.66) were associated with subsequent primary health care visits (0-24 h).Conclusions: Four in five non-conveyed patients did not have any re-contact in follow-up period. EMS non-conveyance seems to be a relatively safe method of focusing ED resources and avoiding ED crowding.</p

Accuracy of prehospital clinicians' perceived prognostication of long-term survival in critically ill patients : a nationwide retrospective cohort study on helicopter emergency service patients

Objectives Prehospital critical care physicians regularly attend to patients with poor prognosis and may limit the advanced therapies. The aim of this study was to evaluate the accuracy of poor prognosis given by prehospital critical care clinicians. Design Cohort study. Setting We performed a retrospective cohort study using the national helicopter emergency medical services (HEMS) quality database. Participants Patients classified by the HEMS clinician to have survived until hospital admission solely because of prehospital interventions but evaluated as having no long-term survival by prehospital clinician, were included. Primary and secondary outcome The survival of the study patients was examined at 30 days, 1 year and 3 years. Results Of 36 715 patients encountered by the HEMS during the study period, 2053 patients were classified as having no long-term survival and included. At 30 days, 713 (35%, 95% CI 33% to 37%) were still alive and 69 were lost to follow-up. Furthermore, at 1 year 524 (26%) and at 3 years 267 (13%) of the patients were still alive. The deceased patients received more often prehospital rapid sequence intubation and vasoactives, compared with patients alive at 30 days. Patients deceased at 30 days were older and had lower initial Glasgow Coma Scores. Otherwise, no clinically relevant difference was found in the prehospital vital parameters between the survivors and non-survivors. Conclusions The prognostication of long-term survival for critically ill patients by a prehospital critical care clinician seems to fulfil only moderately. A prognosis based on clinical judgement must be handled with a great degree of caution and decision on limitation of advanced care should be made cautiously.Peer reviewe

Is advanced life support better than basic life support in prehospital care? A systematic review

Background -: Prehospital care is classified into ALS- (advanced life support) and BLS- (basic life support) levels according to the methods used. ALS-level prehospital care uses invasive methods, such as intravenous fluids, medications and intubation. However, the effectiveness of ALS care compared to BLS has been questionable. Aim -: The aim of this systematic review is to compare the effectiveness of ALS- and BLS-level prehospital care. Material and methods -: In a systematic review, articles where ALS-level prehospital care was compared to BLS-level or any other treatment were included. The outcome variables were mortality or patient's health-related quality of life or patient's capacity to perform daily activities. Results -: We identified 46 articles, mostly retrospective observational studies. The results on the effectiveness of ALS in unselected patient cohorts are contradictory. In cardiac arrest, early cardiopulmonary resuscitation and defibrillation are essential for survival, but prehospital ALS interventions have not improved survival. Prehospital thrombolytic treatment reduces mortality in patients having a myocardial infarction. The majority of research into trauma favours BLS in the case of penetrating trauma and also in cases of short distance to a hospital. In patients with severe head injuries, ALS provided by paramedics and intubation without anaesthesia can even be harmful. If the prehospital care is provided by an experienced physician and by a HEMS organisation (Helicopter Emergency Medical Service), ALS interventions may be beneficial for patients with multiple injuries and severe brain injuries. However, the results are contradictory. Conclusions -: ALS seems to improve survival in patients with myocardial infarction and BLS seems to be the proper level of care for patients with penetrating injuries. Some studies indicate a beneficial effect of ALS among patients with blunt head injuries or multiple injuries. There is also some evidence in favour of ALS among patients with epileptic seizures as well as those with a respiratory distress.Peer reviewe

Accuracy of prehospital clinicians' perceived prognostication of long-term survival in critically ill patients: a nationwide retrospective cohort study on helicopter emergency service patients

Objectives Prehospital critical care physicians regularly attend to patients with poor prognosis and may limit the advanced therapies. The aim of this study was to evaluate the accuracy of poor prognosis given by prehospital critical care clinicians.Design Cohort study.Setting We performed a retrospective cohort study using the national helicopter emergency medical services (HEMS) quality database.Participants Patients classified by the HEMS clinician to have survived until hospital admission solely because of prehospital interventions but evaluated as having no long-term survival by prehospital clinician, were included.Primary and secondary outcome The survival of the study patients was examined at 30 days, 1 year and 3 years.Results Of 36 715 patients encountered by the HEMS during the study period, 2053 patients were classified as having no long-term survival and included. At 30 days, 713 (35%, 95% CI 33% to 37%) were still alive and 69 were lost to follow-up. Furthermore, at 1 year 524 (26%) and at 3 years 267 (13%) of the patients were still alive. The deceased patients received more often prehospital rapid sequence intubation and vasoactives, compared with patients alive at 30 days. Patients deceased at 30 days were older and had lower initial Glasgow Coma Scores. Otherwise, no clinically relevant difference was found in the prehospital vital parameters between the survivors and non-survivors.Conclusions The prognostication of long-term survival for critically ill patients by a prehospital critical care clinician seems to fulfil only moderately. A prognosis based on clinical judgement must be handled with a great degree of caution and decision on limitation of advanced care should be made cautiously.</p

The development of emergency medical services benefit score : a European Delphi study

Publisher Copyright: © 2021. The Author(s).BACKGROUND: The helicopter emergency services (HEMS) Benefit Score (HBS) is a nine-level scoring system developed to evaluate the benefits of HEMS missions. The HBS has been in clinical use for two decades in its original form. Advances in prehospital care, however, have produced demand for a revision of the HBS. Therefore, we developed the emergency medical services (EMS) Benefit Score (EBS) based on the former HBS. As reflected by its name, the aim of the EBS is to measure the benefits produced by the whole EMS systems to patients. METHODS: This is a four-round, web-based, international Delphi consensus study with a consensus definition made by experts from seven countries. Participants reviewed items of the revised HBS on a 5-point Likert scale. A content validity index (CVI) was calculated, and agreement was defined as a 70% CVI. Study included experts from seven European countries. Of these, 18 were prehospital expert panellists and 11 were in-hospital commentary board members. RESULTS: The first Delphi round resulted in 1248 intervention examples divided into ten diagnostic categories. After removing overlapping examples, 413 interventions were included in the second Delphi round, which resulted in 38 examples divided into HBS categories 3-8. In the third Delphi round, these resulted in 37 prehospital interventions, examples of which were given revised version of the score. In the fourth and final Delphi round, the expert panel was given an opportunity to accept or comment on the revised scoring system. CONCLUSIONS: The former HBS was revised by a Delphi methodology and EBS developed to represent its structural purpose better. The EBS includes 37 exemplar prehospital interventions to guide its clinical use. Trial registration The study permission was requested and granted by Turku University Hospital (decision number TP2/010/18).Peer reviewe