Improving patient's intensive care admission through multidisciplinary simulation-based crisis resource management: A qualitative study.

AIM: To explore nurses' and physicians' experiences of simulation-based training in a crisis resource management quality improvement intervention on intensive care admission. BACKGROUND: Quantitative studies have documented that staffs' non-technical skills are improved after simulation-based training in crisis resource management interventions. Experienced-based consensus led to development of a quality improvement intervention based on principles of crisis resource management and tested in simulation-based training to enhance staffs' non-technical skills. However, the impact on staff is unexplored, leaving little understanding of the relationship between simulation-based training in crisis resource management interventions and changes in non-technical skills. DESIGN: A qualitative study with a hermeneutical approach. METHODS: Data consisted of semi-structured interviews with physicians (n = 5) and nurses (n = 15) with maximum variation in work experience. Data were collected 3 months after implementation and analysed using thematic analysis. The COREQ guideline was applied. RESULTS: The analysis revealed three themes: prioritising core clinical activities and patient centredness; transition into practice; and reflection on patient safety. These themes reflected staff's experiences of the intervention and implementation process, which evolved through prioritising core clinical activities that facilitated the transition into clinical practice and staff's reflection on patient safety. CONCLUSIONS: Prioritising core clinical activities were facilitated by clear communication, predefined roles and better teamwork. Transition into practice stimulated professional growth through feedback. Reflection on patient safety created a new understanding on how a new structure of intensive care admission could be implemented. Collectively, this indicated a joint understanding of admissions. IMPLICATIONS FOR PRACTICE: Findings enables health care professionals to understand how the intervention can contribute to improve quality of care in management of intensive care admission. Improving non-technical skills are vital in high-quality admissions, which supported a structured process and a collaborative professional standard of admissions. PATIENT AND PUBLIC CONTRIBUTION: None.

Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial.

BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.

Pharmacokinetic-pharmacodynamic modelling of the analgesic and antihyperalgesic effects of morphine after intravenous infusion in human volunteers.

Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15 males). The subjects were chosen based on a previous trial where 100 subjects rated (VAS) their pain during a heat injury (47°C, 7 min., 12.5 cm(2) ). The 33% lowest- and highest pain-sensitive subjects were offered participation in the present study. A two-compartment linear model with allometric scaling for weight provided the best description of the plasma concentration-time profile of morphine. Changes in the EPTo and 2HA responses with time during the placebo treatment were best described by a linear model and a quadratic model, respectively. The model discrimination process showed clear evidence for adding between-occasion variability (BOV) on baseline and the placebo slope for EPTo and 2HA, respectively. The sensitivity covariate was significant on baseline EPTo values and genetics as a covariate on the placebo slope for 2HA. The analgesic and antihyperalgesic effects of morphine were pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo.

Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study.

PURPOSE: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation. SUBJECTS AND METHODS: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli) testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg), buprenorphine (0.3/0.6 mg), or placebo (normal saline) were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm(2)), and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist. RESULTS: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia/heat injury relative to placebo) for low-dose morphine was 0.01 (interquartile range: -6.2; 9.9), 0.00 (-2.4; 2.1) for high-dose morphine, 0.03 (-1.8; 2.1) for low-dose buprenorphine, and 0.00 (-3.2; 1.1) for high-dose buprenorphine (P > 0.466). There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286). High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004). CONCLUSION: The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system.

Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.

The main objective of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the effects of buprenorphine on cognitive functioning in healthy volunteers. Twenty-three male volunteers received 0.6 mg buprenorphine as an intravenous infusion over 150 min. The cognitive and psychomotor performance was evaluated before and at various times after drug administration by a test battery consisting of trail-making test for visual information processing, finger-tapping test for psychomotor speed, and continuous reaction time for attention. Non-linear mixed effect modelling was used in the analysis of the PK/PD relationships. Buprenorphine caused significant deficits in cognitive and psychomotor functioning. The time course of cognitive and psychomotor impairment was found to have a slow distribution to the biophase from plasma with PK/PD models involving an effect compartment providing the best descriptions of the time course of the data. The values for half-life of biophase equilibration were consistent between the neuropsychological tests in the range of 66.6-84.9 min. The time to onset and duration of the cognitive and psychomotor impairment of buprenorphine was determined by a slow distribution to the biophase.

Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers.

OBJECTIVE: The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only. METHODS: Twenty-three healthy male volunteers aged 21-40 years received 0.6 mg buprenorphine by means of an i.v. infusion over a 150-min period. The plasma concentration-time profiles up to 24 h post-administration of the infusion were subjected to population pharmacokinetic modelling using NONMEM: software. RESULTS: A three-compartment model best described the plasma concentration-time course. Body weight was found to be a significant covariate for elimination clearance in a linear fashion. Inter-individual variability (coefficient of variation) was estimable for apparent clearance (CL, 23.5%), central distribution volume (V(1), 81.8%), peripheral distribution volume 1 (V(2), 23.7%) and inter-compartmental clearances between V(1) and V(2) (Q(2), 34.8%). Models using parameters derived from previous published data obtained after an i.v. bolus of buprenorphine were found to overestimate the measured buprenorphine concentrations during the course of the i.v. infusion and to underpredict those following the end of the infusion. CONCLUSION: Most parameters describing the disposition of buprenorphine in the volunteers showed only moderate inter-subject variability. However, the parameters differed from those previously reported for i.v. bolus administration. We conclude that pharmacokinetic parameter estimates obtained from the appropriate study in accordance to the mode of administration should be used in the design of dose regimens of buprenorphine.

Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers.

AIM: After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers. METHODS: The study was conducted accordingly to a nonblinded, randomised, balanced three-way crossover design in eight healthy male subjects. The subjects received 200 mg oral M6G, 50 mg oral M6G and 30 mg oral morphine. Blood samples were collected until 72 h after M6G administration and until 9 h after morphine administration. Paracetamol and sulfasalazine were coadministered with M6G as markers for the gut contents reaching the duodenum and colon, respectively. RESULTS: The plasma concentration peaks of M6G were seen at 4.0 (2.0-6.0) and 18 (12.0-24.0) h after 200 mg M6G and at 3.5 (2.0-6.0) and 21.3 (10.0-23.3) h after 50 mg M6G, which was in agreement with previously published results. The K(M6G_abs)/K(M6G_M6G) ratio was found to be 10. CONCLUSION: The pharmacokinetic profile of M6G after oral administration was confirmed and with the presence of M3G and morphine in plasma after oral administration of M6G, proof seems to be found of the constant and prolonged absorption of M6G. The K(M6G_abs)/K(M6G_M6G) ratio of 10 indicates that the second absorption peak of M6G consists of approximately 10 times more absorbed M6G than reglucuronidated M6G. However, further studies are required to determine the precise kinetics of the second absorption peak.

[What is intensive therapy? Neurointensive therapy]. / Hvad er intensiv terapi? Neurointensiv terapi.

The neurointensive care unit provides observation and treatment of acute, life-threatening disorders of and injuries to the central and peripheral nervous system. The primary aim of care is the prevention of secondary neuronal damage; this requires a highly multidisciplinary approach, involving neuromonitoring as well as management of systemic comorbidity and complications. This article presents major pathophysiological issues specific to neurointensive care, as well as recent advances in the management of the critically-ill neurosurgical and neurological patient.