The effect of age on clinical dose equivalency of fentanyl and morphine analgosedation in mechanically ventilated patients: Findings from the ANALGESIC trial.

BACKGROUND: The dose equivalency of fentanyl vs. morphine is widely considered to be approximately 1:100. However, little is known about the effect of age on this ratio when these agents are used as infusions for analgosedation. OBJECTIVES: To assess the impact of age on the clinical dose equivalency of fentanyl and morphine when used as infusions for analgosedation in mechanically ventilated intensive care unit patients. METHODS: We performed a post hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation. Dose and analgosedative clinical equivalency of fentanyl and morphine were assessed by age and by using different body-size descriptors. RESULTS: We studied 663 patients (338 fentanyl, 325 morphine). Median (interquartile range) hourly dose of fentanyl and morphine were 58.1 (40.0-89.2) mcg and 3400 (2200-5000) mcg, respectively. The ratio of total dose of fentanyl:morphine was 1:93 in the 18- to 29-year-old group and 1:25 in the ≥80-year-old group (p = 0.015), respectively, with fentanyl becoming relatively less clinically effective as age increased. This effect was also seen when comparing dosing by different body-size descriptors with the strongest age-related change when using body surface area as body-size descriptor (p = 0.009). CONCLUSION: The analgosedative clinical dose equivalency of fentanyl vs. morphine is heterogeneous when used as infusions for analgosedation, with fentanyl becoming relatively less clinically effective as age increases. This information can help guide prescription of these agents during transition from one agent to the other in critically ill patients.

A Phase II Cluster-Crossover Randomized Trial of Fentanyl versus Morphine for Analgosedation in Mechanically Ventilated Patients.

Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. Objectives: To compare the effect of fentanyl versus morphine on patient-centered outcomes in ventilated patients. Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult ICUs. We compared two continuous infusion regimens (fentanyl versus morphine). One ICU was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator-free days at Day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and ICU-free days at Day 28. Measurements and Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded because of the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [interquartile range] age, 59 [44-69] years). Median ventilator-free days at Day 28 were 26.1 (20.7-27.3) in the fentanyl versus 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% confidence interval, 0.31 to 1.28], P = 0.001). ICU-free days were greater (P < 0.001) and length of stay in the ICU for survivors shorter (P < 0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Conclusions: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator-free days at Day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation.

Hospital and long-term opioid use according to analgosedation with fentanyl vs. morphine: Findings from the ANALGESIC trial.

Objectives: Opioid use disorder is extremely common. Many long-term opioid users will have their first exposure to opioids in hospitals. We aimed to compare long-term opioid use in patients who received fentanyl vs. morphine analgosedation and assess ICU related risk factors for long-term opioid use. Design: We performed a post-hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation in mechanically ventilated patients. Setting: Two mixed, adult, university affiliated intensive care units in Melbourne, Australia. Participants: Adult patients who were mechanically ventilated and received fentanyl or morphine for analgosedation in the ANALGESIC trial. Main outcome measures: We assessed discharge and long-term (90-365 days) opioid use in opioid-naïve patients at hospital admission according to the agent used for analgosedation. Results: We studied 477 patients (242 fentanyl and 235 morphine). There were no differences between discharge (16.5% vs. 14.0%, p = 0.45), 90-180 day post-discharge use (3.7% vs 2.1%, p = 0.30) or 180-365 day post-discharge use (3.4% vs 1.3%, p = 0.22) of opioids when comparing those patients who received fentanyl vs. those who received morphine. Surgical diagnosis and one chronic condition were associated with increased hospital discharge prescription of opioids, whereas increasing APACHE II score was associated with decreased discharge prescription. No ICU-related factors were associated with long-term opioid use. Conclusions: Approximately one in seven opioid-naïve patients who receive analgosedation for mechanical ventilation in ICU will be prescribed opioid medications at hospital discharge. There was no difference in discharge prescription or long-term use of opioids depending on whether fentanyl or morphine was used for analgosedation.

Delirium in ventilated patients receiving fentanyl and morphine for Analgosedation: Findings from the ANALGESIC trial.

PURPOSE: The differential effect of fentanyl vs. morphine analgosedation on the development of hospital inpatient delirium in patients receiving mechanical ventilation is unknown. We aimed to compare the incidence of coding for delirium and antipsychotic medication use in patients treated with fentanyl vs. morphine in the ANALGESIC trial. MATERIALS AND METHODS: We obtained data from a cluster randomized, cluster crossover trial of fentanyl vs. morphine for analgosedation on antipsychotic use and coding diagnosis of delirium and compared these outcomes according to treatment allocation. We assessed the relationship between opioid choice and dose, hospital inpatient delirium, and outcomes. RESULTS: Among 681 patients enrolled in the ANALGESIC trial, 160/344 (46.5%) in the fentanyl group vs. 132/337 (39.1%) in the morphine group (absolute difference 7.34% [95% CI -0.9 to 14.78]; RR: 1.19 [95%CI 1.00 to 1.41]; p = 0.053) developed hospital inpatient delirium. Antipsychotic use was linearly related to opioid dose. Antipsychotic use was not associated with increased mortality. CONCLUSIONS: Fentanyl is associated with a higher incidence of hospital inpatient delirium when used for analgosedation compared with morphine, and the dose of opioid is linearly related to the need for antipsychotic medication administration. The role of analgosedation in promoting delirium requires further investigation.

The role of the medical emergency team in end-of-life care: a multicenter, prospective, observational study.

OBJECTIVE: To investigate the role of medical emergency teams in end-of-life care planning. DESIGN: One month prospective audit of medical emergency team calls. SETTING: Seven university-affiliated hospitals in Australia, Canada, and Sweden. PATIENTS: Five hundred eighteen patients who received a medical emergency team call over 1 month. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 652 medical emergency team calls in 518 patients, with multiple calls in 99 (19.1%) patients. There were 161 (31.1%) patients with limitations of medical therapy during the study period. The limitation of medical therapy was instituted in 105 (20.3%) and 56 (10.8%) patients before and after the medical emergency team call, respectively. In 78 patients who died with a limitation of medical therapy in place, the last medical emergency team review was on the day of death in 29.5% of patients, and within 2 days in another 28.2%.Compared with patients who did not have a limitation of medical therapy, those with a limitation of medical therapy were older (80 vs. 66 yrs; p < .001), less likely to be male (44.1% vs. 55.7%; p = .014), more likely to be medical admissions (70.8% vs. 51.3%; p < .001), and less likely to be admitted from home (74.5% vs. 92.2%, p < .001). In addition, those with a limitation of medical therapy were less likely to be discharged home (22.4% vs. 63.6%; p < .001) and more likely to die in hospital (48.4% vs. 12.3%; p < .001). There was a trend for increased likelihood of calls associated with limitations of medical therapy to occur out of hours (51.0% vs. 43.8%, p = .089). CONCLUSIONS: Issues around end-of-life care and limitations of medical therapy arose in approximately one-third of calls, suggesting a mismatch between patient needs for end-of-life care and resources at participating hospitals. These calls frequently occur in elderly medical patients and out of hours. Many such patients do not return home, and half die in hospital. There is a need for improved advanced care planning in our hospitals, and to confirm our findings in other organizations.

Efficacy and safety of ketamine in mechanically ventilated intensive care unit patients: a scoping review.

Objectives: Mechanically ventilated patients account for about one-third of all admissions to the intensive care unit (ICU). Ketamine has been conditionally recommended to aid with analgesia in such patients, with low quality of evidence available to support this recommendation. We aimed to perform a narrative scoping review of the current knowledge of the use of ketamine, with a specific focus on mechanically ventilated ICU patients. Methods: We searched MEDLINE and EMBASE for relevant articles. Bibliographies of retrieved articles were examined for references of potential relevance. We included studies that described the use of ketamine for postoperative and emergency department management of pain and in the critically unwell, mechanically ventilated population. Results: There are few randomised controlled trials evaluating ketamine's utility in the ICU. The evidence is predominantly retrospective and observational in nature and the results are heterogeneous. Available evidence is summarised in a descriptive manner, with a division made between high dose and low dose ketamine. Ketamine's pharmacology and use as an analgesic agent outside of the ICU is briefly discussed, followed by evidence for use in the ICU setting, with particular emphasis on analgesia, sedation and intubation. Finally, data on adverse effects including delirium, coma, haemodynamic adverse effects, raised intracranial pressure, hypersalivation and laryngospasm are presented. Conclusions: Ketamine is used in mechanically ventilated ICU patients with several potentially positive clinical effects. However, it has a significant side effect profile, which may limit its use in these patients. The role of low dose ketamine infusion in mechanically ventilated ICU patients is not well studied and requires investigation in high quality, prospective randomised trials.

Erratum.

[This corrects the article DOI: 10.51893/2022.2.L.].

Prediction of tracheostomy in critically ill trauma patients: a systematic review.

BACKGROUND: Tracheostomy is relatively common in mechanically ventilated patients in the intensive care unit (ICU). The prediction of which patients will receive a tracheostomy is crucial to both clinical decision making and the design of targeted interventional trials of its timing. OBJECTIVES: We aimed to systematically review the literature to ascertain whether useful predictors of eventual tracheostomy can be identified, with a particular focus on trauma patients. DATA SOURCES AND REVIEW METHODS: We searched three electronic databases to identify all studies of any design evaluating potential predictors of tracheostomy in mechanically ventilated ICU patients. Bias was assessed using the Quality in Prognosis Studies tool. RESULTS: Of 140 potentially eligible studies, we identified 12 relevant observational studies recruiting a total of 119 945 mechanically ventilated patients, of whom 14 080 (11.7%) received a tracheostomy. Seven studies were performed in trauma populations and included 24 858 patients, of whom 6140 (24.7%) received a tracheostomy. Factors predictive of receiving a tracheostomy in the trauma population included patient factors (age and comorbidities), diagnostic factors (injury type and injury severity score), and intervention factors (craniotomy or laparotomy). Profound clinical and methodological heterogeneity prevented meaningful metaanalysis. Significantly, more predictors were present on the day of admission in trauma populations than in non-trauma patients with brain injury and in other populations (89.7% v 73.3% v 25.0%). CONCLUSION: There are a number of clinical factors associated with subsequent tracheostomy in mechanically ventilated patients, in particular trauma patients. Given the need to prevent patients from receiving an unnecessary tracheostomy, these findings indicate that better predictive models are needed before the conduct of interventional trials. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO registry no. CRD42018084987.

Patient characteristics, incidence, technique, outcomes and early prediction of tracheostomy in the state of Victoria, Australia.

BACKGROUND: Tracheostomy is a relatively common procedure in Intensive Care Unit (ICU) patients. AIMS: To study the patient characteristics, incidence, technique, outcomes and prediction of tracheostomy in the State of Victoria, Australia. METHODS: We used data from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD) and the Victorian Admitted Episode Dataset (VAED) to identify and match patients who had received a tracheostomy from 2004 to 2014. RESULTS: Between 1st January 2004 and 30th June 2014, 9750 patients received a tracheostomy with 7670 available for matching and 6010 (78.4%) successfully matched. Of the matched tracheostomy patients, median age was 61years, median APACHE IIIJ score was 66 and overall hospital mortality was 21%. The incidence of tracheostomy almost halved over the decade with more than half of tracheostomies (53.5%) being percutaneous. Hospital mortality of patients receiving a tracheostomy decreased from 26.5% in 2004 to 16.5% in 2014 by an average decrease of 6%/year. No robust model could be developed to predict tracheostomy. CONCLUSION: The incidence of tracheostomy and the adjusted mortality rate of patients who received a tracheostomy have significantly decreased over a decade. Day of admission information could not be used to predict subsequent tracheostomy.

Intensive care implications of epidemic thunderstorm asthma.

OBJECTIVE: To investigate the environmental precipitants, treatment and outcome of critically ill patients affected by the largest and most lethal reported epidemic of thunderstorm asthma. DESIGN, SETTING AND PARTICIPANTS: Retrospective multicentre observational study. Meteorological, airborne particulate and pollen data, and a case series of 35 patients admitted to 15 intensive care units (ICUs) due to the thunderstorm asthma event of 21-22 November 2016, in Victoria, Australia, were analysed and compared with 1062 total ICU-admitted Australian patients with asthma in 2016. MAIN OUTCOME MEASURES: Characteristics and outcomes of total ICU versus patients with thunderstorm asthma, the association between airborne particulate counts and storm arrival, and ICU resource utilisation. RESULTS: All 35 patients had an asthma diagnosis; 13 (37%) had a cardiac or respiratory arrest, five (14%) died. Compared with total Australian ICU-admitted patients with asthma in 2016, patients with thunderstorm asthma had a higher mortality (15% v 1.3%, P < 0.001), were more likely to be male (63% v 34%, P < 0.001), to be mechanically ventilated, and had shorter ICU length of stay in survivors (median, 31.8 hours [interquartile range (IQR), 14.8-43.6 hours] v 40.7 hours [IQR, 22.3-75.1 hours]; P = 0.025). Patients with cardiac arrest were more likely to be born in Asian or subcontinental countries (5/10 [50%] v 4/25 [16%]; relative risk, 3.13; 95% CI, 1.05-9.31). A temporal link was demonstrated between airborne particulate counts and arrival of the storm. The event used 15% of the public ICU beds in the region. CONCLUSION: Arrival of a triggering storm is associated with an increase in respirable airborne particles. Affected critically ill patients are young, have a high mortality, a short duration of bronchospasm, and a prior diagnosis of asthma is common.

Ventilation management in Victorian intensive care unit patients without acute respiratory distress syndrome.

BACKGROUND: The setting of tidal volume (VT) during controlled mechanical ventilation (CMV) in critically ill patients without acute respiratory distress syndrome (ARDS) is likely important but currently unknown. We aimed to describe current CMV settings in intensive care units (ICUs) across Victoria. METHODS: We performed a multicentre, prospective, observational study. We collected clinical, ventilatory and arterial blood gas data twice daily for 7 days. We performed subgroup analysis by sex and assessment of arterial partial pressure of carbon dioxide (PaCO2) management where hypercapnia was potentially physiologically contraindicated. RESULTS: We recorded 453 observational sets in 123 patients across seven ICUs. The most commonly selected initial VT was 500 mL (33%), and this proportion did not differ according to sex (32% male, 34% female). Moreover, 38% of patients were exposed to initial VT per predicted body weight (VT-PBW) > 8.0 mL/kg. VT-PBW in this range were more likely to occur in females, those with a lower height, lower ideal body weight or in those for whom hypercapnia was potentially physiologically contraindicated. As a consequence, females were more frequently exposed to a lower PaCO2 and higher pH. CONCLUSIONS: In adults without ARDS undergoing CMV in Australian ICUs, the initial VT was a stereotypical 500 mL in one-third of participants, irrespective of sex. Moreover, around 40% of patients were exposed to an initial VT-PBW > 8.0 mL/kg. Finally, women were more likely to be exposed to a high VT and hyperventilation.

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Medical emergency team syndromes and an approach to their management.

INTRODUCTION: Most literature on the medical emergency team (MET) relates to its effects on patient outcome. Less information exists on the most common causes of MET calls or on possible approaches to their management. METHODS: We reviewed the calling criteria and clinical causes of 400 MET calls in a teaching hospital. We propose a set of minimum standards for managing a MET review and developed an approach for managing common problems encountered during MET calls. RESULTS: The underlying reasons for initiating MET calls were hypoxia (41%), hypotension (28%), altered conscious state (23%), tachycardia (19%), increased respiratory rate (14%) and oliguria (8%). Infection, pulmonary oedema, and arrhythmias featured as prominent causes of all triggers for MET calls. The proposed minimum requirements for managing a MET review included determining the cause of the deterioration, documenting the events surrounding the MET, establishing a medical plan and ongoing medical follow-up, and discussing the case with the intensivist if certain criteria were fulfilled. A systematic approach to managing episodes of MET review was developed based on the acronym 'A to G': ask and assess; begin basic investigations and resuscitation, call for help if needed, discuss, decide, and document, explain aetiology and management, follow-up, and graciously thank staff. This approach was then adapted to provide a management plan for episodes of tachycardia, hypotension, hypoxia and dyspnoea, reduced urinary output, and altered conscious state. CONCLUSION: A suggested approach permits audit and standardization of the management of MET calls and provides an educational framework for the management of acutely unwell ward patients. Further evaluation and validation of the approach are required.

A comparison of therapeutic hypothermia and strict therapeutic normothermia after cardiac arrest.

BACKGROUND AND AIMS: In a recent high-quality randomised controlled trial (RCT), strict therapeutic normothermia (STN) following cardiac arrest with coma resulted in similar outcomes to therapeutic hypothermia (TH). We aimed to test the feasibility, reproducibility, and safety of the STN protocol outside of its RCT context. METHODS: In two teaching hospital ICUs, we performed a before-and-after study comparing the previously International Liaison Committee on Resuscitation (ILCOR)-endorsed TH protocol to the recently studied STN protocol. The primary feasibility end point was the percentage of temperature recordings in the prescribed range in the first 24h of treatment. Secondary end points included pharmacological management and complications. RESULTS: We studied 69 similar patients in each group. We found no difference in feasibility as shown by the proportion of within range temperatures. However, the median doses of midazolam (37mg vs. 9mg, p=0.02), fentanyl (883µg vs. 310µg, p=0.01) and the use of muscle relaxants (84.1% vs. 59.4%, p=0.001) was greater with the TH protocol. Furthermore, shivering (52.2% vs. 18.8%, p<0.001), a composite of other pre-defined complications (66.7% vs. 47.8%, p<0.03) and fever in the first 96h (55.1% vs. 33.3%, p=0.01) were also more common with the TH protocol. CONCLUSIONS: The STN protocol was successfully reproduced outside of an RCT and appeared associated with fewer complications than the TH protocol. Our findings imply that the STN protocol may offer clinical advantages over the TH protocol.

Improving the documentation of medical emergency team reviews.

OBJECTIVES: To improve the documentation of events surrounding medical emergency team (MET) calls and to audit the incidence of MET calls and subsequent patient outcomes. METHODS: Prospective audit and patient chart review before and after three simultaneous interventions: medical team education, addition of intensive care personnel to the MET and introduction of a dedicated medical documentation pro forma. Data collected included patient demographics (including outcomes), features of each MET call (criteria, timing and treatment) and the completeness of medical documentation using nine predetermined criteria. Baseline data were collected over 5 months, April to August 2005. Following a 2-week education period, data were collected for a further 4 months, September to December 2005. Apart from the principal investigators, medical and nursing staff were not aware of this research during either data collection period. RESULTS: There were 94 MET calls (10.3 per 1000 admissions) during the baseline period and 101 (14.2 per 1000 admissions) after the interventions. MET calls were more common in medical than surgical patients (34.9 v 12.9 calls per 1000 admissions; P < 0.001). Sixty of the 195 calls (30.7%) resulted in patients being transferred to a critical care area, and the overall in-hospital mortality following a MET call was 31.8%. The interventions resulted in a significant increase in the overall quantity and quality of medical documentation (in seven out of the nine criteria). The interventions were not associated with an increase in hospital resource utilisation, in particular hospital bed days or admissions to critical care areas. CONCLUSIONS: Critical-care resource utilisation and inhospital mortality risk following a MET call at our institution is high. Three simple interventions improved the quality of medical documentation but did not significantly increase overall resource utilisation or improve patient outcomes.