Service delivery model of extracorporeal membrane oxygenation in an Australian regional hospital

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) for adults in regional centres with low numbers of patients receiving ECMO is unclear. A robust service delivery model may assist in the quality provision of ECMO. OBJECTIVE: To describe a novel ECMO service delivery model in a regional Australian hospital, reporting on patient characteristics and outcomes before and after its implementation. METHODS: An observational cohort study of all patients receiving ECMO at the University Hospital Geelong intensive care unit before and after implementation of a new ECMO clinical service model. The program included intensivist training in cannulation and care for ECMO patients, nurse accreditation in ECMO maintenance, and establishing a relationship with an ECMO centre caring for a high number of patients. Data included ECMO caseload, circuit configuration, complications, durations of therapy, and survival to ECMO weaning and ICU and hospital discharge. RESULTS: During the 14-year period for which we collected data, 61 adults received ECMO: 21 (35%) before and 40 (65%) after implementation of the structured program. The median annual case rate increased significantly between periods from two (range, 0-5 cases) to 10 (range, 5-13 cases) (P < 0.01). Other changes from before to after implementation included more medical indications for ECMO (48% v 80%; P < 0.01), higher peripheral cannulation configuration (57% v 98%; P < 0.01) and greater intensivist involvement as cannulation proceduralists (29% v 80%; P < 0.01). There were no significant differences between cohorts in ECMO weaning or duration, complication rates or ICU or in-hospital mortality. CONCLUSIONS: Provision of ECMO in a tertiary regional hospital within a multifaceted clinical service model is feasible and safe. Partnership with a centre providing ECMO for a high number of patients during service development and delivery is desirable

The association of time and medications with changes in bone mineral density in the 2 years after critical illness

BackgroundCritical illness is associated with increased risk of fragility fracture and loss of bone mineral density (BMD), although the impact of medication exposures (bone anti-fracture therapy or glucocorticoids) and time remain unexplored. The objective of this study was to describe the association of time after ICU admission, and post-ICU administration of bone anti-fracture therapy or glucocorticoids after critical illness, with change in BMD.MethodsIn this prospective observational study, conducted in a tertiary hospital ICU, we studied adult patients requiring mechanical ventilation for at least 24 hours and measured BMD annually for 2 years after ICU discharge. We performed mixed linear modelling to describe the association of time, and post-ICU administration of anti-fracture therapy or glucocorticoids, with annualised change in BMD.ResultsNinety-two participants with a mean age of 63 (&plusmn;15) years had at least one BMD assessment after ICU discharge. In women, a greater loss of spine BMD occurred in the first year after critical illness (year 1: -1.1&thinsp;&plusmn;&thinsp;2.0% vs year 2: 3.0&thinsp;&plusmn;&thinsp;1.7%, p&thinsp;=&thinsp;0.02), and anti-fracture therapy use was associated with reduced loss of BMD (femur 3.1&thinsp;&plusmn;&thinsp;2.4% vs -2.8&thinsp;&plusmn;&thinsp;1.7%, p&thinsp;=&thinsp;0.04, spine 5.1&thinsp;&plusmn;&thinsp;2.5% vs -3.2&thinsp;&plusmn;&thinsp;1.8%, p&thinsp;=&thinsp;0.01). In men anti-fracture and glucocorticoid use were not associated with change in BMD, and a greater decrease in BMD occurred in the second year after critical illness (year 1: -0.9&thinsp;&plusmn;&thinsp;2.1% vs year 2: -2.5&thinsp;&plusmn;&thinsp;2.1%, p&thinsp;=&thinsp;0.03).ConclusionsIn women a greater loss of spine BMD was observed in the first year after critical illness, and anti-fracture therapy use was associated with an increase in BMD. In men BMD loss increased in the second year after critical illness. Anti-fracture therapy may be an effective intervention to prevent bone loss in women after critical illness.<br /

Prevalence, goals of care and long-term outcomes of patients with life-limiting illness referred to a tertiary ICU

OBJECTIVE: To describe the prevalence, characteristics, long-term outcomes and goals-of-care discussions of patients with objective indicators of life-limiting illnesses (LLIs) referred to the intensive care unit. DESIGN, SETTING AND PATIENTS: A prospective, observational, cohort study of all adult inpatients referred to the ICU by the medical emergency team or by direct referral, during the period 30 August 2012 to 1 February 2013, at a tertiary teaching hospital in Australia. MAIN OUTCOME MEASURES: Mortality, LLIs, discharge destination and documentation on goals of care in medical record. RESULTS: A total of 649 of 1024 patients referred to the ICU had an LLI, and only 34.4% of these patients had goals of care documented. Overall, 49.2% were admitted to the ICU, 48.4% were discharged home, and the 1-year mortality was 35.1%. The most common LLI criteria were heart disease (52.2%), chronic obstructive pulmonary disease (24.8%) and frailty (23.7%). The highest 1-year mortality was associated with pre-hospital residence in a nursing home (64.9%), dementia (63.3%), cancer (60.8%) and frailty (50.6%). Analysis of patients by clinical trajectory showed that 1-year mortality was significantly higher for patients with cancer (59.6%), combined organ failure and frailty (47.3%), frailty (43.8%) and organ failure (23.6%), compared with patients with no LLI (P &lt; 0.0001). CONCLUSIONS: A high proportion of patients referred to the ICU have an LLI, and this is associated with prolonged hospital length of stay and a high 1-year mortality, and only one-quarter have documented discussions on goals of care. Patients with cancer-related and frailty-related LLIs have the worst survival trajectories

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Skeletal morbidity among survivors of critical illness

Objectives: To describe the incident fracture rate in survivors of critical illness and to compare fracture risk with populationmatched control subjects.Design: Retrospective longitudinal case&ndash; cohort study.Setting: A tertiary adult intensive care unit in Australia. Patients: All patients ventilated admitted to intensive care and requiring mechanical ventilation for &gt;48 hrs between January 1998 and December 2005.Interventions: None.Measurements and Main Results: New fractures were identified in the study population for the postintensive care unit period (intensive care unit discharge to January 2008). The incident fracture rate and age-adjusted fracture risk of the female intensive care unit population were compared with the general population adult females derived from the Geelong Osteoporosis Study. Over the 8-yr period, a total of 739 patients (258 women, 481 men) were identified. After a median follow-up of 3.7 yrs (interquartile range, 2.0&ndash;5.9 yrs) for women and 4.0 yrs (interquartile range, 2.1&ndash;6.1 yrs) for men, incident fracture rates (95% confidence interval) per 100 patient years were 3.84 (2.58 &ndash;5.09) for females 2.41 (1.73&ndash;3.09) for males. Compared with an age-matched random population-based sample of women, elderly women were at increased risk for sustaining an osteoporosisrelated fracture after critical illness (hazard ratio, 1.65; 95% confidence interval, 1.08 &ndash;2.52; p .02).Conclusions: The increase in fracture risk observed in postintensive care unit older females suggests an association between critical illness and subsequent skeletal morbidity. The explanation for this association is not explored in this study and includes the effects of pre-existing patient factors and/or direct effects of critical illness. Prospective research evaluating risk factors, the relationship between critical illness and bone turnover, the extent and duration of bone loss, and the associated morbidity in this population is warranted