Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review.

BACKGROUND: The use of composite outcome measures (COM) in clinical trials is increasing. Whilst their use is associated with benefits, several limitations have been highlighted and there is limited literature exploring their use within critical care. The primary aim of this study was to evaluate the use of COM in high-impact critical care trials, and compare study parameters (including sample size, statistical significance, and consistency of effect estimates) in trials using composite versus non-composite outcomes. METHODS: A systematic review of 16 high-impact journals was conducted. Randomised controlled trials published between 2012 and 2022 reporting a patient important outcome and involving critical care patients, were included. RESULTS: 8271 trials were screened, and 194 included. 39.1% of all trials used a COM and this increased over time. Of those using a COM, only 52.6% explicitly described the outcome as composite. The median number of components was 2 (IQR 2-3). Trials using a COM recruited fewer participants (409 (198.8-851.5) vs 584 (300-1566, p = 0.004), and their use was not associated with increased rates of statistical significance (19.7% vs 17.8%, p = 0.380). Predicted effect sizes were overestimated in all but 6 trials. For studies using a COM the effect estimates were consistent across all components in 43.4% of trials. 93% of COM included components that were not patient important. CONCLUSIONS: COM are increasingly used in critical care trials; however effect estimates are frequently inconsistent across COM components confounding outcome interpretations. The use of COM was associated with smaller sample sizes, and no increased likelihood of statistically significant results. Many of the limitations inherent to the use of COM are relevant to critical care research.

Extracorporeal Membrane Oxygenation as a Bridge to Surgical Repair of Postinfarct Ventricular Septal Defect.

Postinfarct ventricular septal defect (PIVSD) is associated with high mortality and the management of these patients has been a challenge with little improvement in outcomes. We commenced a protocol of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for those patients who present in cardiogenic shock with the aim to improve end-organ function before definitive surgical repair to reduce postoperative mortality. This study reviewed the results of this strategy. This was a single-center, retrospective review of all patients who were admitted to our institution with PIVSD in cardiogenic shock from September 2015 to November 2019. Clinical and investigative data were evaluated. Eight patients were referred with PIVSD during this period in cardiogenic shock. One patient had an anterior PIVSD and the other seven had inferior PIVSD. Six patients underwent surgical repair at a median (interquartile range, IQR) of 7 (5-8) days after initiation of VA ECMO. Two patients did not undergo surgical repair. Five patients survived after surgery and one patient died postoperatively due to multiorgan failure. Preoperative use of VA ECMO is a feasible strategy for PIVSD and may improve the results of repair.

Outcomes of patients with refractory out-of-hospital cardiac arrest transported to an ECMO centre compared with transport to non-ECMO centres.

Objective: To compare the outcomes of patients with refractory out-of-hospital cardiac arrest (OHCA) transported to a hospital that provides extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) with patients transported to hospitals without ECPR capability. Design, setting: Retrospective review of patient care records in a pre-hospital and hospital setting. Participants: Adult patients with OHCA who left the scene and arrived with cardiopulmonary resuscitation in progress at 16 hospitals in Melbourne, Australia, between January 2016 and December 2019. Intervention: For selected patients transported to the ECPR centre, initiation of ECMO. Main outcome measures: Survival to hospital discharge and 12-month quality of life. Results: There were 223 eligible patients during the study period. Of 49 patients transported to the ECPR centre, 23 were commenced on ECMO. Of these, survival to hospital with good neurological recovery (Cerebral Performance Category [CPC] score 1/2) occurred in 4/23 patients. Four other patients developed return of spontaneous circulation in the ECPR centre before cannulation of whom one survived, giving overall good functional outcome at 12 months survival of 5/49 (10.2%). There were 174 patients transported to the 15 non-ECPR centres and 3/174 (2%) had good functional outcome at 12 months. After adjustment for baseline differences, the odds ratio for good neurological outcome after transport to an ECPR centre compared with a non-ECPR centre was 4.63 (95% CI, 0.97-22.11; P = 0.055). Conclusion: The survival rate of patients with refractory OHCA transported to an ECPR centre remains low. Outcomes in larger cities might be improved with shorter scene times and additional ECPR centres that would provide for earlier initiation of ECMO.

The knowledge of Cormack-Lehane intubation grade and intensive care unit outcome.

BACKGROUND: For patients on invasive mechanical ventilation (MV), it is unclear if knowledge of intubation grade influences intensive care unit (ICU) outcome. We aimed to determine if there was an independent relationship between knowledge of intubation grade during ICU admission and in-hospital mortality. METHODS: We performed a retrospective cohort study of all patients receiving invasive MV at the Alfred ICU between December 2011 and February 2015. Demographics, details of admission, the severity of illness, chronic health status, airway detail (unknown or known Cormack-Lehane (CL) grade), MV duration and in-hospital mortality data were collected. Univariable and multivariable analyses were conducted to assess the relationship. The primary outcome was in-hospital mortality, and the secondary outcome was the duration of MV. RESULTS: Amongst 3556 patients studied, 611 (17.2%) had an unknown CL grade. Unadjusted mortality was higher in patients with unknown CL grade compared to known CL grade patients (21.6% vs. 9.9%). After adjusting for age, sex, severity of illness, type of ICU admission, cardiac arrest, limitations to treatment and diagnosis, having an unknown CL grade during invasive MV was independently associated with an increase in mortality (adjusted OR 1.5, 95% CI 1.14-1.98, p < 0.01). CONCLUSION: Amongst ICU patients receiving MV, not knowing CL grade appears to be independently associated with increased mortality. This information should be communicated and documented in all patients receiving MV in ICU.

Arterio-VENouS Intra Subject agreement for blood gases within intensive care: The AVENSIS study.

BACKGROUND: In critically ill patients, who require multiple blood gas assessments, agreement between arterial and venous blood gas values for pH and partial pressure of carbon dioxide, is not clear. Good agreement would mean that venous values could be used to assess ventilation and metabolic status of patients in intensive care unit. METHODS: All adult patients admitted to Alfred intensive care unit, Melbourne, from February 2013 to January 2014, who were likely to have arterial and central venous lines for three days, were enrolled. Patients on extra-corporeal life support and pregnant women were excluded. After enrolment, near simultaneous arterial and central venous sampling and analysis were performed at least once per nursing shift till the lines were removed or the patient died. Bland-Altman analysis for repeated measures was performed to assess the agreement between arterio-venous pH and partial pressure of carbon dioxide. RESULTS: A total of 394 paired blood gas analyses were performed from 59 participants. The median (IQR) number of samples per patient was 6 (5-9) with the median (IQR) sampling interval 9.4 (5.2-18.5) h. The mean bias for pH was + 0.036 with 95% limits of agreement ranging from - 0.005 to + 0.078. For partial pressure of carbon dioxide, the values were -2.58 and -10.43 to + 5.27 mmHg, respectively. CONCLUSIONS: The arterio-venous agreement for pH in intensive care unit patients appears to be acceptable. However, the agreement for partial pressure of carbon dioxide was poor.

Levels of training in critical care echocardiography in adults. Recommendations from the College of Intensive Care Medicine Ultrasound Special Interest Group.

Critical care echocardiography (CCE) is commonly performed in many intensive care units across Australia and New Zealand (ANZ). The scope of practice ranges from Basic CCE through to Advanced CCE and includes the use of transthoracic echocardiography and transoesophageal echocardiography. Many training and qualification pathways exist with no standardisation of education goals. This document defines different levels of CCE expertise and recommends minimum training standards for each level of adult CCE in ANZ. Guidelines committee of College of Intensive Care Medicine's Ultrasound Special Interest Group held multiple face to face meetings, organised teleconferences, conducted a survey of the Fellows of the college and reviewed the international CCE training pathways prior to writing these guidelines.

Predictors of mortality after extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a promising adjunct to cardiopulmonary resuscitation (CPR) in refractory cardiac arrest (CA). Factors associated with outcome are incompletely characterised. The aim of our study was to identify pre-ECMO factors associated with in-hospital mortality after extracorporeal CPR (ECPR). DESIGN: Retrospective analysis of a prospective cohort of patients. SETTING: Academic quaternary referral hospital. PARTICIPANTS: All patients who underwent ECPR from January 2012 through April 2017. INTERVENTIONS: A retrospective chart review was performed for CPR and ECMO. A multivariable logistic regression was performed to identify factors associated with mortality after ECPR. MAIN OUTCOME MEASURES: Primary outcome was in-hospital mortality. Secondary outcomes included survival with favourable neurologic outcome, days on ECMO, and intensive care unit (ICU) length of stay. RESULTS: During the study period, 75 patients received ECPR. Median age was 59 years, 81% were male, 51% had out-of-hospital CA, and 57% had an initial shockable rhythm. Median time from arrest to ECMO was 91 minutes (IQR, 56-129) for non-survivors and 51 minutes (IQR, 37-84) for survivors (P =0.02). Twenty-six patients (39%) were successfully separated from ECMO, with 31% surviving to hospital discharge and 29% with a cerebral performance category score of 1 or 2. In multivariable analysis, significant predictors of in-hospital mortality were ongoing CPR at the time of ECMO initiation (P < 0.01) and arrest to ECMO cannulation time (P =0.02). CONCLUSION: Following ECPR, the factors most strongly associated with mortality were ongoing CPR at the time of ECMO initiation and arrest to ECMO cannulation time. Interventions aimed at reducing time to ECMO initiation may lead to improved outcomes.