Methadone in combination with magnesium, ketamine, lidocaine, and dexmedetomidine improves postoperative outcomes after coronary artery bypass grafting: an observational multicentre study.

BACKGROUND: An optimal pharmacological strategy for fast-track cardiac anesthesia (FTCA) is unclear. This study evaluated the effectiveness and safety of an FTCA program using methadone and non-opioid adjuvant infusions (magnesium, ketamine, lidocaine, and dexmedetomidine) in patients undergoing coronary artery bypass grafting. METHODS: This retrospective, multicenter observational study was conducted across private and public teaching sectors. We studied patients managed by a fast-track protocol or via usual care according to clinician preference. The primary outcome was the total mechanical ventilation time in hours adjusted for hospital, body mass index, category of surgical urgency, cardiopulmonary bypass time and EuroSCORE II. Secondary outcomes included successful extubation within four postoperative hours, postoperative pain scores, postoperative opioid requirements, and the development of postoperative complications. RESULTS: We included 87 patients in the fast-track group and 88 patients in the usual care group. Fast-track patients had a 35% reduction in total ventilation hours compared with usual care patients (p = 0.007). Thirty-five (40.2%) fast-track patients were extubated within four hours compared to 10 (11.4%) usual-care patients (odds ratio: 5.2 [95% CI: 2.39-11.08; p < 0.001]). Over 24 h, fast-track patients had less severe pain (p < 0.001) and required less intravenous morphine equivalent (22.00 mg [15.75:32.50] vs. 38.75 mg [20.50:81.75]; p < 0.001). There were no significant differences observed in postoperative complications or length of hospital stay between the groups. CONCLUSION: Implementing an FTCA protocol using methadone, dexmedetomidine, magnesium, ketamine, lignocaine, and remifentanil together with protocolized weaning from a mechanical ventilation protocol is associated with significantly reduced time to tracheal extubation, improved postoperative analgesia, and reduced opioid use without any adverse safety events. A prospective randomized trial is warranted to further investigate the combined effects of these medications in reducing complications and length of stay in FTCA. TRIALS REGISTRATION: The study protocol was registered in the Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au/ACTRN12623000060640.aspx , retrospectively registered on 17/01/2023).

Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial.

PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

Dose equivalence for metaraminol and noradrenaline - A retrospective analysis.

BACKGROUND: Noradrenaline and metaraminol are commonly used vasopressors in critically ill patients. However, little is known of their dose equivalence. METHODS: We conducted a single centre retrospective cohort study of all ICU patients who transitioned from metaraminol to noradrenaline infusions between August 26, 2016 and December 31, 2020. Patients receiving additional vasoactive drug infusion were excluded. Dose equivalence was calculated based on the last hour metaraminol dose (in µg/min) and the first hour noradrenaline dose (in µg/min) with the closest matched mean arterial pressure (MAP). Sensitivity analyses were performed on patients with acute kidney injury (AKI), sepsis and mechanical ventilation. RESULTS: We studied 195 patients. The median conversion ratio of metaraminol to noradrenaline was 12.5:1 (IQR 7.5-20.0) for the overall cohort. However, the coefficient of variation was 77% and standard deviation was 11.8. Conversion ratios were unaffected by sepsis or mechanical ventilation but increased (14:1) with AKI. One in five patients had a MAP decrease of >10 mmHg during the transition period from metaraminol to noradrenaline. Post-transition noradrenaline dose (p < 0.001) and AKI (p = 0.045) were independently associated with metaraminol dose. The proportion of variation in noradrenaline dose predicted from metaraminol dose was low (R2 = 0.545). CONCLUSIONS: The median dose equivalence for metaraminol and noradrenaline in this study was 12.5:1. However, there was significant variance in dose equivalence, only half the proportion of variation in noradrenaline infusion dose was predicted by metaraminol dose, and conversion-associated hypotension was common.

Haemodynamic changes during prone versus supine position in patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Prone positioning improves oxygenation in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. However, its haemodynamic effects are poorly understood. OBJECTIVES: The objective of this study was to investigate the acute haemodynamic changes associated with prone position in mechanically ventilated patients with COVID-19 ARDS. The primary objective was to describe changes in cardiac index with prone position. The secondary objectives were to describe changes in mean arterial pressure, FiO2, PaO2/FiO2 ratio, and oxygen delivery (DO2) with prone position. METHODS: We performed this cohort-embedded study in an Australian intensive care unit, between September and November 2021. We included adult patients with severe COVID-19 ARDS, requiring mechanical ventilation and prone positioning for respiratory failure. We placed patients in the prone position for 16 h per session. Using pulse contour technology, we collected haemodynamic data every 5 min for 2 h in the supine position and for 2 h in the prone position consecutively. RESULTS: We studied 18 patients. Cardiac index, stroke volume index, and mean arterial pressure increased significantly in the prone position compared to supine position. The mean cardiac index was higher in the prone group than in the supine group by 0.44 L/min/m2 (95% confidence interval, 0.24 to 0.63) (P < 0.001). FiO2 requirement decreased significantly in the prone position (P < 0.001), with a significant increase in PaO2/FiO2 ratio (P < 0.001). DO2 also increased significantly in the prone position, from a median DO2 of 597 mls O2/min (interquartile range, 504 to 931) in the supine position to 743 mls O2/min (interquartile range, 604 to 1075) in the prone position (P < 0.001). CONCLUSION: Prone position increased the cardiac index, mean arterial pressure, and DO2 in invasively ventilated patients with COVID-19 ARDS. These changes may contribute to improved tissue oxygenation and improved outcomes observed in trials of prone positioning.

The Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis.

INTRODUCTION: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy. METHODS: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization. RESULTS: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes. CONCLUSIONS: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.

A Multidisciplinary Approach to Verbal Communication Interventions for Mechanically Ventilated Adults With a Tracheostomy.

There is developing evidence with regard to the feasibility, utility, and safety of verbal communication interventions with patients with tracheostomy who are invasively ventilated. In the past 2 decades, research efforts have focused on establishing evidence for communication interventions, including introducing an intentional leak into the ventilatory circuit such as with a fenestrated tube, leak speech or ventilator-adjusted leak speech, the use of a one-way valve in-line with the ventilator, and above cuff vocalization. This narrative review describes the benefits of a multi-disciplinary approach, summarizes verbal communication interventions, and provides guidance on the indications, contraindications and considerations for patient selection. Our clinical procedures based on collective clinical experience are shared. A multidisciplinary team approach enables holistic management across acuity, ventilation, airway, communication, and swallowing parameters. This collaborative approach is recommended to maximize the chance of successful opportunities for patients to communicate safely and effectively.

Early and prolonged continuous hypertonic saline infusion in patients with acute liver failure.

PURPOSE: To study patient characteristics, physiological changes, and outcomes associated with prolonged continuous hypertonic saline (HTS) infusion in acute liver failure (ALF). MATERIALS AND METHODS: Retrospective observational cohort study of adult patients with ALF. We collected clinical, biochemical, and physiological data six hourly for the first week, daily until day 30 or hospital discharge, and weekly, when documented, until day 180. RESULTS: Of 127 patients, 85 received continuous HTS. Compared with non-HTS patients they were more likely to receive continuous renal replacement therapy (CRRT) (p < 0.001) and mechanical ventilation (p < 0.001). Median HTS duration was 150 (Interquartile range (IQR): 84-168) hours, delivering a median 2244 (IQR: 979-4610) mmol sodium load. Median peak sodium concentration was 149 mmol/L vs 138 mmol/L in non-HTS patients (p < 0.001). The median rate of sodium increase with infusion was 0.1 mmol/L/h and median rate of decrease during weaning was 0.1 mmol/L every 6 h. Median lowest pH value was 7.29 vs. 7.35 in non-HTS patients. Survival of HTS patients was 72.9% overall and 72.2% without transplantation. CONCLUSIONS: In ALF patients, the prolonged administration of HTS infusion was not associated with severe hypernatremia or rapid shifts in serum sodium upon commencement, delivery, or weaning.

The PhLIP team: Feasibility of a physiotherapy-led intensive prone positioning team initiative during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in a surge of patients with refractory hypoxaemic respiratory failure being admitted to the intensive care unit (ICU). Prone positioning can improve oxygenation but requires a team of skilled personnel to complete safely. Critical care physiotherapists (PTs) are ideally suited to lead proning teams, due to their expertise in moving critically unwell, invasively ventilated patients. OBJECTIVES: The aim of this study was to describe the feasibility of implementing a physiotherapy-led intensive proning (PhLIP) team to support the critical care team during surges. METHODS: This study involves descriptive evaluation of feasibility and implementation of the PhLIP team, a novel model of care, during the Delta wave of the COVID-19 pandemic, through a retrospective, observational audit of PhLIP team activity, ICU clinical activity, and a description of clinical outcomes. RESULTS: Between 17 September and 19 November 2021, 93 patients with COVID-19 were admitted to the ICU. Fifty-one patients (55%) were positioned prone, a median [interquartile range] 2 [2, 5] times, for a mean (±standard deviation) duration of 16 (±2) h, across 161 episodes. Twenty-three PTs were upskilled and deployed to the PhLIP team, adding 2.0 equivalent full time to the daily service. Ninety-four percent of prone episodes (154) were led by the PhLIP PTs with a median 4 [interquartile range: 2, 8] turns per day. Potential airway adverse events occurred on three occasions (1.8%) and included an endotracheal tube leak, displacement, and obstruction. Each incident was promptly managed without prolonged impact on the patient. No manual handling injuries were reported. CONCLUSION: The implementation of a physiotherapy-led proning team was safe and feasible and can release critical care-trained medical and nursing staff to other duties in the ICU.

Ammonia and nutritional therapy in the critically ill: when to worry, when to test and how to treat?

PURPOSE OF REVIEW: Hyperammonaemia is almost always develops in patients with severe liver failure and this remains the commonest cause of elevated ammonia concentrations in the ICU. Nonhepatic hyperammonaemia in ICU presents diagnostic and management challenges for treating clinicians. Nutritional and metabolic factors play an important role in the cause and management of these complex disorders. RECENT FINDINGS: Nonhepatic hyperammonaemia causes such as drugs, infection and inborn errors of metabolism may be unfamiliar to clinicians and risk being overlooked. Although cirrhotic patients may tolerate marked elevations in ammonia, other causes of acute severe hyperammonaemia may result in fatal cerebral oedema. Any coma of unclear cause should prompt urgent measurement of ammonia and severe elevations warrant immediate protective measures as well as treatments such as renal replacement therapy to avoid life-threatening neurological injury. SUMMARY: The current review explores important clinical considerations, the approach to testing and key treatment principles that may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes.

What you need to know about: acute liver failure.

Acute liver failure is a rare but important clinical syndrome, with a high mortality rate. Prompt recognition, appropriate management and early referral to a liver transplant centre can lead to good outcomes in these critically unwell patients. This article gives an overview of the key clinical challenges and optimal management of patients with acute liver failure. Acute liver failure is defined and a comprehensive list of aetiologies and suggested investigations is provided. The clinical challenges of sepsis, renal impairment, coagulopathy, hypoglycaemia, haemodynamic instability and cerebral oedema are discussed. Quadruple H therapy, a combination of therapies aimed to reduce cerebral oedema in acute liver failure, is described. A systemic guide to managing patients with acute liver failure is provided, as are indications for referral to a liver transplant centre.

Prevalence, severity, duration and resolution of cholestasis after acute liver failure.

OBJECTIVE: Persistent cholestasis may follow acute liver failure (ALF), but its course remains unknown. We aimed to describe the prevalence, onset, severity, duration and resolution of post-ALF cholestasis. DESIGN: Cohort of 127 adult patients with ALF at a liver transplantation centre identified using electronic databases. We obtained laboratory data every 6 hours for the first week, daily until day 30 and weekly, when documented, until day 180. RESULTS: Median age was 40.7 (IQR 31.0-52.4) years, median peak alanine aminotransferase level was 5494 (2521-8819) U/L and 87 (68.5%) cases had paracetamol toxicity. Overall, 12.6% underwent transplantation (3.4% for paracetamol vs 32.5% for non-paracetamol; p<0.001). Ninety-day mortality was 20.7% for paracetamol versus 30.0% for non-paracetamol patients. All non-transplanted survivors reached a bilirubin level>50 µmol/L, which peaked 3.5 (1.0-10.1) days after admission at 169.0 (80.0-302.0) µmol/L. At hospital discharge, 18.8% of patients had normal bilirubin levels and, at a median follow-up time from admission to last measurement of 16 (10-30) days, 46.9% had normal levels. Similarly, there was an increase in alkaline phosphatase (ALP) (207.0 (148.0-292.5) U/L) and gamma-glutamyl transferase (GGT) (336.0 (209.5-554.5) U/L) peaking at 4.5 days, with normalised values in 40.3% and 8.3% at hospital discharge. CONCLUSION: Post-ALF cholestasis is ubiquitous. Bilirubin, ALP and GGT peak at 3 to 5 days and, return to baseline in the minority of patients at median follow-up of 16 days. These data inform clinical expectations of the natural course of this condition.

Midodrine use in critically ill patients: a narrative review.

Midodrine is a peripherally acting, oral α-agonist that is increasingly used in intensive care units despite conflicting evidence for its effectiveness. It has pharmacological effects on blood vessels as well as pupillary, cardiac, renal, gastrointestinal, genitourinary, lymphatic and skin tissue. It has approval for use as a treatment for orthostatic hypotension, but a surge in interest over the past decade has prompted its use for a growing number of off-label indications. In critically ill patients, midodrine has been used as either an adjunctive oral therapy to wean vasoplegic patients off low dose intravenous vasopressor infusions, or as an oral vasopressor agent to prevent or minimise the need for intravenous infusion. Clinical trials have mostly focused on midodrine as an intravenous vasopressor weaning agent. Early retrospective studies supported its use for this indication, but more recent randomised controlled trials have largely refuted this practice. Key questions remain on its role in managing critically ill patients before intensive care admission, during intensive care stay, and following discharge. This narrative review presents a comprehensive overview of midodrine use for the critical care physician and highlights why lingering questions around ideal patient selection, dosing, timing of initiation, and efficacy of midodrine for critically ill patients remain unanswered.

Registrar triage, communication and moral distress during end-of-life care rapid response team calls in a teaching hospital.

BACKGROUND: Approximately one-third of rapid response teams (RRT) involve end-of-life care (EOLC) issues. Intensive care unit (ICU) registrar experience in such calls is underinvestigated. AIMS: To evaluate the proportion of RRT calls triaged as relating to EOLC issues, issues around communication regarding prognostication, registrar self-reported moral distress and associations between RRT EOLC classification and patient outcomes. METHODS: Prospective observational study of RRT calls in a tertiary referrals hospital between December 2016 and January 2017 using a standardised case report form and data from an electronic RRT database. RESULTS: There were 401 RRT calls in the study period, and data were available for 270 (67%) calls, of which 72%, 10% and 18% were triaged as 'obviously not EOLC call', 'obvious EOLC call' and 'uncertain EOLC call' respectively. Most discussions regarding prognostication occurred between registrars, and more than half (55%) were with a covering doctor. Consensus on prognostication was achieved in 93% cases. Registrars reported distress in 19% of calls that obviously related to EOLC and 22% of calls that were uncertain, compared with <1% of calls that were obviously not relating to EOLC. Inhospital mortality was 6%, 67% and 39% for obviously not EOLC, obvious EOLC and uncertain EOLC calls respectively. CONCLUSIONS: EOLC issues occur commonly in RRT calls and are often associated with moral distress to ICU registrars. Although consensus on prognostication is usually achieved, conversations often involve covering doctors. These issues impact on the ICU registrar experience of RRT calls and require further exploration.

Factors associated with short versus prolonged tracheostomy length of cannulation and the relationship between length of cannulation and adverse events.

BACKGROUND: Tracheostomy management and care is multifaceted and costly, commonly involving complex patients with prolonged hospitalisation. Currently, there are no agreed definitions of short and prolonged length of tracheostomy cannulation (LOC) and no consensus regarding the key factors that may be associated with time to decannulation. OBJECTIVES: The aims of this study were to identify the factors associated with short and prolonged LOC and to examine the number of tracheostomy-related adverse events of patients who had short LOC versus prolonged LOC. METHODS: A retrospective observational study was undertaken at a large metropolitan tertiary hospital. Factors known at the time of tracheostomy insertion, including patient, acuity, medical, airway, and tracheostomy factors, were analysed using Cox proportional hazards model and Kaplan-Meier survival curves, with statistically significant factors then analysed using univariate logistic regression to determine a relationship to short or prolonged LOC as defined by the lowest and highest quartiles of the study cohort. The number of tracheostomy-related adverse events was analysed using the Kaplan-Meier survival curve. RESULTS: One hundred twenty patients met the inclusion criteria. Patients who had their tracheostomy performed for loss of upper airway were associated with short LOC (odds ratio [OR]: 2.30 (95% confidence interval [CI]: 1.01-5.25) p = 0.049). Three factors were associated with prolonged LOC: an abdominal/gastrointestinal tract diagnosis (OR: 5.00 [95% CI: 1.40-17.87] p = 0.013), major surgery (OR: 2.51 [95% CI: 1.05-6.01] p = 0.038), and intubation for >12 days (OR: 0.30 [95% CI: 0.09-0.97] p = 0.044). Patients who had one or ≥2 tracheostomy-related adverse events had a high likelihood of prolonged LOC (OR: 5.21 [95% CI: 1.95-13.94] p = ≤0.001 and OR: 12.17 [95% CI: 2.68-55.32] p ≤ 0.001, respectively). CONCLUSION: Some factors that are known at the time of tracheostomy insertion are associated with duration of tracheostomy cannulation. Tracheostomy-related adverse events are related to a high risk of prolonged LOC.

Fast-track recovery program after cardiac surgery in a teaching hospital: a quality improvement initiative.

OBJECTIVE: Fast-track cardiac anesthesia (FTCA) is a technique that may improve patient access to surgery and maximize workforce utilization. However, feasibility and factors impacting FTCA implementation remain poorly explored both locally and internationally. We describe the specific intraoperative and postoperative protocols for our FTCA program, assess protocol compliance and identify reasons for FTCA failure. RESULTS: We tested the program in 16 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. There was 100% compliance with the FTCA protocols. Four (25%) patients successfully completed the FTCA protocol (extubated < 4 h postoperatively and discharged from the intensive care unit on the same operative day).