Association between protocol change to a higher-protein formula with lower energy targets and nutrient delivery in critically ill patients with COVID-19: A retrospective cohort study.

BACKGROUND: Guidelines recommend prioritizing protein provision while avoiding excessive energy delivery to critically ill patients with coronavirus disease 2019 (COVID-19), but there are no prospective studies evaluating such a targeted approach in this group. We aimed to evaluate the effect of a "higher-protein formula protocol" on protein, energy, and volume delivery when compared with standard nutrition protocol. METHODS: This was a retrospective cohort study of adult patients with COVID-19 who received mechanical ventilation for >72 h and enteral nutrition. Before October 2021, the standard nutrition protocol for patients was 0.7 ml/kg/h ideal body weight (IBW) of a 63 g/L protein and 1250 kcal/L formula. From October 2021, we implemented a higher-protein formula protocol for patients with COVID-19. The initial prescription was 0.5 ml/kg/h IBW of a 100 g/L protein and 1260 kcal/L formula with greater emphasis on energy targets being directed by indirect calorimetry when possible. Measured outcomes included protein, energy, and volume delivered. RESULTS: There were 114 participants (standard protocol, 48; higher-protein protocol, 66) with 1324 days of nutrition support. The median (95% CI) differences in protein, energy, and volume delivery between targeted and standard protocol periods were 0.08 g/kg/day (-0.02 to 0.18 g/kg/day), -1.71 kcal/kg/day (-3.64 to 0.21 kcal/kg/day) and -1.5 ml/kg/day (-2.9 to -0.1 ml/kg/day). Thirty-three patients (standard protocol, 7; higher-protein protocol, 26) had 44 indirect calorimetry assessments. There was no difference in measured energy expenditure over time (increased by 0.49 kcal/kg/day [-0.89 to 1.88 kcal/kg/day]). CONCLUSION: Implementation of a higher-protein formula protocol to patients with COVID-19 modestly reduced volume administration without impacting protein and energy delivery.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Assessing the safety profile of voriconazole use in suspected COVID-19-associated pulmonary aspergillosis-a two-centre observational study.

The decision to use voriconazole for suspected COVID-19-associated pulmonary aspergillosis (CAPA) is based on clinical judgement weighed against concerns about its potential toxicity. We assessed the safety profile of voriconazole for patients with suspected CAPA by conducting a retrospective study of patients across two intensive care units. We compared changes in any liver enzymes or bilirubin and any new or increasing corrected QT interval (QTc) prolongation following voriconazole use to patient baseline to indicate possible drug effect. In total, 48 patients with presumed CAPA treated with voriconazole were identified. Voriconazole therapy was administered for a median of 8 days (interquartile range [IQR] 5-22) and the median level was 1.86 mg/L (IQR 1.22-2.94). At baseline, 2% of patients had a hepatocellular injury profile, 54% had a cholestatic injury profile, and 21% had a mixed injury profile. There were no statistically significant changes in liver function tests over the first 7 days after voriconazole initiation. At day 28, there was a significant increase in alkaline phospahte only (81-122 U/L, P = 0.006), driven by changes in patients with baseline cholestatic injury. In contrast, patients with baseline hepatocellular or mixed injury had a significant decrease in alanine transaminase and aspartate transaminase. Baseline QTc was 437 ms and remained unchanged after 7 days of voriconazole therapy even after sensitivity analysis for concomitantly administered QT prolonging agents. Therefore, at the doses used in this study, we did not detect evidence of significant liver or cardiac toxicity related to voriconazole use. Such information can be used to assist clinicians in the decision to initiate such treatment.

Our study did not show significant voriconazole-related liver or cardiac side effects in a critically ill cohort of patients with suspected COVID-19-associated pulmonary aspergillosis. These findings may allay specific clinician concerns when commencing therapy for such patients.

People in intensive care with COVID-19: demographic and clinical features during the first, second, and third pandemic waves in Australia.

OBJECTIVE: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia. DESIGN, SETTING, AND PARTICIPANTS: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021). MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies. RESULTS: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave. CONCLUSION: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave.

Intensive care unit trainee perception of end-of-life care provided during medical emergency team activation events.

BACKGROUND: Hospital medical emergency team (MET) activation events involving end-of-life care (EOLC) are common. The issues faced by medical staff attending these events are incompletely described. AIMS: The purpose of this study was to measure the perceptions of Victorian hospital medical staff, training in the speciality of intensive care, about multiple aspects of EOLC MET calls. We sought to determine the overall extent of formal training in MET and EOLC and assess the domains of self-perceived confidence, barriers to communication, frequency of clinician agreement and trainee distress. METHODS: We conducted an anonymous, voluntary, Internet-based survey of registered trainees of the College of Intensive Care Medicine of Australia and New Zealand in May 2019. The participants eligible were those trainees working in an adult intensive care unit in Victoria, Australia, during the study period. The main outcome measures were self-reported levels of confidence, barriers to communication, frequency of conflict and distress, senior support, supervision and access to training. RESULTS: Of 124 trainees surveyed, 75 (60%) responded. Overall, 78% of respondents felt confident to manage EOLC MET calls, but the frequently reported barriers to effective patient/next of kin communication included: (i) lack of private meeting rooms; (ii) resource and time constraints; and (iii) lack of patient and family availability during a MET call to discuss medical treatment limitations. Two-thirds of respondents reported emotional distress at least occasionally, this being frequent in one in five. Most (68%) trainees experienced conflict with other medical teams at least occasionally. Factors associated with experiencing distress at least occasionally include greater trainee age, patients' being unable to participate in discussion due to illness, resource and time constraints and negative encounters with other medical teams. CONCLUSIONS: Victorian intensive care trainees were confident managing EOLC MET activation events. However, distress was reported commonly and strategies are required to address the areas of concern.