Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

Measurement of renal congestion and compliance following intravenous fluid administration using shear wave elastography.

Objective: Ultrasound shear wave elastography (SWE) is a novel technique that may provide non-invasive measurements of renal compliance. We aimed to investigate the relationship between intravenous (IV) fluid administration and change in SWE measurements. We hypothesised that following IV fluid administration in healthy volunteers, global kidney stiffness would increase and that this increase in stiffness could be quantified using SWE. Our second hypothesis was that graduated doses of IV fluids would result in a dose-dependent increase in global kidney stiffness measured by SWE. Design: Randomised prospective study. Setting: Intensive Care Unit. Participants: Healthy volunteers aged 18-40 years. Interventions: Participants were randomised to receive 20 ml/kg, 30 ml/kg, or 40 ml/kg of normal saline. The volume of fluid infused was based on the actual body weight recorded. Main outcome measures: We recorded average SWE stiffness (kPa with standard deviation of the mean), median SWE stiffness (kPa), and the interquartile range. Results: Ninety-eight percent of participants (44/45) demonstrated an increase in global kidney stiffness following administration of IV fluids. The average SWE pre fluid administration was 7.572 kPa ± 2.38 versus 14.9 kPa ± 4.81 post fluid administration (p < 0.001). In subgroup analysis, there were significant changes in global kidney stiffness pre and post fluid administration with each volume (ml/kg) of fluid administered. Average percentage change in global kidney stiffness from baseline was compared between the three groups. There was no significant difference when comparing groups 1 and 2 (197.1% increase ± 49.5 vs 216.1% ± 72.0, p » 0.398), groups 2 and 3 (216.1% increase ± 72.0 vs 197.8% ± 59.9, p » 0.455), or groups 1 and 3 (197.1% increase ± 49.5 vs 197.8% ± 59.9, p » 0.972). Conclusions: Fluid administration results in immediately visible and quantifiable changes in global kidney stiffness across all infused volumes of fluid.

Automated rapid response system activation-Impact on nurses' attitudes and perceptions towards recognising and responding to clinical deterioration: Mixed-methods study.

AIM: To explore general ward nurses' attitudes and perceptions towards recognising and responding to clinical deterioration in a hospital with automated rapid response system activation. BACKGROUND: There is growing interest in deploying automated clinical deterioration notification systems to reduce delayed or failed recognition and response to clinical deterioration of ward patients. However, little is known about its impact on ward nurses' perspectives and work patterns. DESIGN: A mixed-methods study. METHODS: Online survey of 168 registered nurses and individual interviews with 10 registered nurses in one acute hospital in Singapore. The study adhered to the STROBE checklist for cross-sectional studies and the COREQ guidelines for qualitative studies. RESULTS: Many nurses (38.1%) rarely performed patient assessments or observations other than vital signs assessment to assess for early signs of clinical deterioration. About 30% were worried about being criticised for calling the primary team doctors. Four themes emerged from the qualitative analysis: automated rapid response system activation as a safety net, being more cautious with vital signs monitoring, the NEWS2 alone is inadequate, and ward nurses as the 'middleman' between the intensive care unit outreach nurse and primary team doctors. CONCLUSIONS: Although nurses value the automated rapid response system activation as a safety net to minimise delays in accessing urgent critical care resources, it does not address the sociocultural barriers inherent in escalation of care. Although the automated system led nurses to be more cautious with vital signs monitoring, it does not encourage them to perform comprehensive patient assessments to detect early signs of deterioration. RELEVANCE TO CLINICAL PRACTICE: Nurse education on assessing for clinical deterioration should focus on the use of broader patient assessment skills other than vital signs. Sociocultural barriers to escalation of care remain a key issue that needs to be addressed by hospital management. NO PATIENT OR PUBLIC CONTRIBUTION: No patients, service users, care-givers or members of the public were involved in the study.

Virtual monitoring for stable chronic hepatitis B patients does not reduce adherence to medications: A randomised controlled study.

INTRODUCTION: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB. METHODS: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1-10. RESULTS: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients - 76 (80.9%) in VMC group and 74 (75.5%) in control group - had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group (p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively (p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm. DISCUSSION: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients.

Clinical Outcomes of Routine Awake Prone Positioning in COVID-19 Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Before coronavirus disease 2019 (COVID-19) emerged, proning had been demonstrated to improve oxygenation in those with acute hypoxic respiratory failure and be performed in non-intensive care settings. This benefit was further exemplified by the COVID-19 pandemic, leading to awake prone positioning (APP). We assessed the efficacy of routine APP versus standard care in preventing death and invasive mechanical ventilation (IMV) in non-intubated hypoxic COVID-19 patients. PubMed, Cochrane Library, Scopus, and medRxiv databases were used from January 1st, 2020, to January 15th, 2022, to identify randomized controlled trials (RCTs). Routine APP group were encouraged to be self-prone, whereas the standard care group received care according to local clinical practice and allowed APP crossover as rescue therapy. We included eight COVID-19 RCTs assessing 809 APP vs. 822 standard care patients. APP group had less IMV requirement (26.5% vs. 30.9%; OR - odds ratio 0.77; P=0.03) than the standard care group, with subgroup analysis showing greater benefit (32.5% vs. 39.1%; OR 0.75; P=0.02) for those mainly requiring oxygen support of non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC). The time to IMV initiation was similar (mean 8.3 vs. 10.0 days; P=0.66) for patients requiring NIMV and HFNC. Patients mainly receiving supplemental oxygen and non-rebreather masks had improved oxygenation parameters, although not statistically significant. Other outcomes involving all-cause hospital mortality, hospital and ICU (intensive care unit) length of stay, and adverse events were comparable. APP appeared to be an important modality for reducing IMV requirements, especially in those requiring NIMV and HFNC.

Comparison of ROX index (SpO2/FIO2 ratio/respiratory rate) with a modified dynamic index incorporating PaO2/FIO2 ratio and heart rate to predict high flow nasal cannula outcomes among patients with acute respiratory failure: a single centre retrospective study.

BACKGROUND: High flow nasal cannula (HFNC) is increasingly being used to support patients with acute respiratory failure (ARF) and to avoid need for intubation. However, almost one third of the patients do not respond and require escalation of respiratory support. Previously, ROX index (SpO2/FIO2 [SF] ratio/respiratory rate) has been validated among pneumonia patients to facilitate early recognition of patients likely to fail HFNC and therefore, benefit from timely interventions. However, it has been postulated that incorporation of PaO2/FIO2 (PF) ratio from arterial blood gas (ABG) analysis may better predict the outcome of HFNC compared to indices that utilizes SF ratio. Similarly, heart rate increase after HFNC therapy initiation has been found to be associated with HFNC failure. Therefore, we aimed to compare ROX index with a new modified index to predict HFNC outcomes among ARF patients. MATERIALS AND METHODS: This single centre 2-year retrospective study included ARF patients of varying etiologies treated with HFNC. The modified index incorporated heart rate and substituted PF ratio for SF ratio in addition to respiratory rate. We named the index POX-HR and calculated Delta POX-HR index as the difference pre- and post-HFNC initiation POX-HR. We also recorded ROX index at the time when post-HFNC initiation ABG was done ('post-HFNC initiation ROX') and calculated Delta ROX. HFNC success was defined as no need of escalation of respiratory support or discharged to ward within 48 h of HFNC initiation, or successful wean off HFNC for at least 12 h. Evaluation was performed using area under the receiver operating characteristic curve (AUROC) and cut-offs assessed for prediction of HFNC outcomes. RESULTS: One hundred eleven patients were initiated on HFNC for ARF, of whom 72 patients (64.9%) had HFNC success. Patients with HFNC failure had significantly lower values for all the indices. At median of 3.33 h (IQR 1.48-7.24 h), Delta POX-HR demonstrated the best prediction accuracy (AUROC 0.813, 95% CI 0.726-0.900). A Delta POX-HR > 0.1 was significantly associated with a lower risk of HFNC failure. CONCLUSIONS: Our proposed modified dynamic index (Delta POX-HR) may facilitate early and accurate prediction of HFNC outcomes compared to ROX index among ARF patients of varied etiologies.

Clinical Outcomes of Early Versus Late Tracheostomy in Coronavirus Disease 2019 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: A significant proportion of Coronavirus Disease 2019 (COVID-19) patients require admission to the intensive care unit (ICU) and invasive mechanical ventilation (IMV). Tracheostomy is increasingly performed when a prolonged course of IMV is anticipated. OBJECTIVES: To determine clinical and resource utilization benefits of early versus late tracheostomy among COVID-19 patients. METHODS: Pubmed, Cochrane Library, Scopus, and Embase were used to identify relevant studies comparing outcomes of COVID-19 patients undergoing early and late tracheostomy from January 1, 2020, to December 1, 2021. RESULTS: Twelve studies were selected, and 2222 critically ill COVID-19 patients hospitalized between January to December 2020 were included. Among the included patients, 34.5% and 65.5% underwent early and late tracheostomy, respectively. Among the included studies, 58.3% and 41.7% defined early tracheostomy using cutoffs of 14 and 10 days, respectively. All-cause in-hospital mortality was not different between the early and late tracheostomy groups (32.9% vs. 33.1%; OR = 1.00; P = 0.98). Sensitivity analysis demonstrated a similar mortality rate in studies using a cutoff of 10 days (34.6% vs. 35.5%; OR = 0.97; P = 0.89) or 14 days (31.2% vs. 27.7%; OR = 1.05; P = 0.78). The early tracheostomy group had shorter ICU length of stay (LOS) (mean: 23.18 vs. 30.51 days; P < 0.001) and IMV duration (mean: 20.49 vs. 28.94 days; P < 0.001) than the late tracheostomy group. The time from tracheostomy to decannulation was longer (mean: 23.36 vs. 16.24 days; P = 0.02) in the early tracheostomy group than in the late tracheostomy group, but the time from tracheostomy to IMV weaning was similar in both groups. Other clinical characteristics, including age, were similar in both groups. CONCLUSIONS: Early tracheostomy reduced the ICU LOS and IMV duration among COVID-19 patients compared with late tracheostomy, but the mortality rate was similar in both groups. The findings have important implications for the treatment of COVID-19 patients, especially in a resource-limited setting.

In-hospital cardiac arrest incidence and outcomes in the era of COVID-19: an observational study in a Singapore hospital.

BACKGROUND: COVID-19 pandemic has resulted in significant strain on healthcare resources and this requires diligent resource re-allocation. We aim to describe the incidence and outcomes of in-hospital cardiac arrest (IHCA) during this period as compared to non-pandemic period. METHODS: We conducted a retrospective study in a tertiary care hospital in Singapore. The study compared the incidence and outcomes of code blue activations over a 3-month period from March to May 2020 (COVID-19 period) with the same months in 2019 (pre-COVID-19 period). The primary outcome of the study was the rate of survival to hospital discharge for IHCA. The secondary outcomes included incidence of all code blue activation per 1000 hospital admissions, incidence of IHCA per 1000 hospital admissions. OUTCOMES: The rate of survival to hospital discharge for IHCA was 5.88% in the COVID-19 period as compared to 10.0% in the pre-COVID-19 period [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.26-1.95]. Compared to pre-COVID-19 period, there were more IHCA incidences per 1000 hospital admissions in the COVID-19 period (1.86 vs 1.03; OR, 1.81; 95% CI, 0.78-4.41). CONCLUSIONS: The study observed a trend towards higher incidence of IHCA and lower rate of survival to hospital discharge during COVID-19 pandemic compared to pre-COVID-19 period.

Clinical features and predictors of severity in COVID-19 patients with critical illness in Singapore.

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24-6.47) and neutrophil count (aOR 2.39, 95% CI 1.34-4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828-0.979). Median APACHE II score was 19 (IQR 17-22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89-129). Median peak FiO2 was 0.75 (IQR 0.6-1.0), positive end-expiratory pressure 12 (IQR 10-14) and plateau pressure 22 (IQR 18-26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5-13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.

Effective design of barrier enclosure to contain aerosol emissions from COVID-19 patients.

Facing shortages of personal protective equipment, some clinicians have advocated the use of barrier enclosures (typically mounted over the head, with and without suction) to contain aerosol emissions from coronavirus disease 2019 (COVID-19) patients. There is, however, little evidence for its usefulness. To test the effectiveness of such a device, we built a manikin that can expire micron-sized aerosols at flow rates close to physiological conditions. We then placed the manikin inside the enclosure and used a laser sheet to visualize the aerosol leaking out. We show that with sufficient suction, it is possible to effectively contain aerosol from the manikin, reducing aerosol exposure outside the enclosure by 99%. In contrast, a passive barrier without suction only reduces aerosol exposure by 60%.

Point-of-Care Ultrasound Training Among Intensivists in Singapore: A Multicentre Survey.

INTRODUCTION: Point of care ultrasound (POCUS) has become essential in the management of critically ill patients. Multiple POCUS training courses exist, but are not widely adopted in Singapore. Given the discordance between training supply and demand, we aimed to uncover the learning needs and barriers among intensive care medicine (ICM) doctors locally. MATERIALS AND METHODS: An anonymous online survey was carried out from January to April 2019 among ICM doctors from 6 major teaching hospitals in Singapore. RESULTS: 66 out of 160 ICM specialists and trainees responded (41.3%). Although only 6% of respondents had current formal POCUS accreditation, the majority were already using critical care echocardiography (CCE) and pleural/ lung ultrasound. 93% supported having a local training programme. More than 50% of trainees wanted training in CCE, diaphragm/muscle ultrasound, airway ultrasound and ultrasound for neurological disease. More than 50% of specialists wanted training in diaphragm/muscle ultrasound, with mixed interests in other topics. The top 2 obstacles hindering POCUS training were lack of supervisors and locally based programmes. CONCLUSIONS: ICM doctors who responded were supportive of a local POCUS training programme. The programme's curriculum should address the learning needs of the majority of learners, with diaphragm/muscle ultrasound being the top unmet need. The programme would need to develop supervisors and be as affordable as possible.

Impact of implementing novel automated code blue activation system on in-hospital cardiac arrest: A single center study.

BACKGROUND: Prompt identification and management of patients having clinical deterioration on wards is one of the key steps to reduce in-hospital cardiac arrests (IHCA). Our organization implemented a novel Automated Code Blue Alert and Activation (ACBAA) system since 1st March 2018. METHODS: We conducted a retrospective before-and-after ACBAA system implementation study in JurongHealth Campus (JHC) of National University Health system (NUHS), Singapore. In JHC, code blue can be activated by both manual activation and ACBAA system activation from 1st March 2018. The ACBAA system will be activated when any of the pre-defined peri-arrest criteria is met. The primary outcome of the study was the incidence of IHCA. The secondary outcome included return of spontaneous circulation (ROSC) of IHCA and in-hospital survival to home discharge of code blue activation. OUTCOMES: The incidence of IHCA per 1000 hospital admissions after-ACBAA system implementation was 14.6% lower than before-ACBAA system though not statistically significant [relative risk (RR): 0.86, 95% confidence interval (CI) 0.55-1.34, P > 0.05]. Compared to the before-ACBAA system period, the after-ACBAA system period had a trend for higher rate of survival to home discharge after IHCA (RR: 2.13, 95% CI 0.65-6.93, P > 0.05) with good neurological outcome. CONCLUSIONS: Implementation of a novel ACBAA system has shown a trend in reducing IHCA incidence. In the era of digitalised healthcare system, the ACBAA system is practical and advisable to implement in order to reduce IHCA. Further studies are required to validate the criteria for peri-arrest code blue activation.

Characteristics and Outcomes of COVID-19 Patients with Respiratory Failure Admitted to a "Pandemic Ready" Intensive Care Unit - Lessons from Singapore.

INTRODUCTION: Singapore was one of the first countries affected by the coronavirus disease 2019 (COVID-19) pandemic but has been able to prevent its healthcare system and intensive care units (ICU) from being overwhelmed. We describe the clinical features, management and outcomes of COVID-19 patients with respiratory failure admitted to our ICU. MATERIALS AND METHODS: A case series of COVID-19 patients admitted to our ICU for respiratory failure from 7 February, with data censoring at 30 June 2020, was performed from a review of medical records. RESULTS: Twenty-two COVID-19 patients were admitted to our ICU for respiratory failure. The median age was 54.5 years (IQR 30-45.5), 72.7% were male and had at least one comorbidity. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 2.5 (IQR 1.25-7) and 10 (8.25-12) respectively. Thirteen patients required invasive mechanical ventilation (IMV) and had a median PaO2/FiO2 ratio of 194 mmHg (IQR 173-213) after intubation. The 28-day survival was 100%, with 2 patients demising subsequently. The overall ICU mortality rate was 9.1% at the time of data censoring. In IMV survivors, length of IMV and ICU stay were 11 days (IQR 9-17.75) and 16 days (IQR 12-32) respectively. CONCLUSION: Low COVID-19 ICU mortality was observed in our "pandemic-ready" ICU. This was achieved by having adequate surge capacity to facilitate early ICU admission and IMV, lung protective ventilation, and slow weaning. Being able to maintain clinical standards and evidence-based practices without having to resort to rationing contributed to better outcomes.

A patient with thyroid storm presenting with apathetic thyrotoxicosis and features of meningoencephalitis.

BACKGROUND: Apathetic thyrotoxicosis is distinctly unusual in thyroid storm and features of meningoencephalitis are very rare. Here we present such a patient. PATIENT FINDINGS: The patient was a 67-year-old Chinese woman who presented with acute generalized weakness, decreased mentation, fever, and rapid deterioration to coma, accompanied by meningism, initially mimicking meningoencephalitis. Further investigations excluded intracranial lesions. Laboratory findings were consistent with Graves' thyrotoxicosis. She was treated for thyroid storm with antithyroid drugs, Lugol's iodine solution, and other supportive management. Subsequently, her level of consciousness returned to normal and neurological signs resolved. SUMMARY: We report a patient with thyroid storm with an apathetic presentation, manifesting as coma with meningism, that mimicked meningoencephalitis. These resolved after treatment for thyroid storm was instituted. CONCLUSIONS: Apathetic thyrotoxicosis is a rare presentation of thyroid storm. Early recognition and treatment is essential for reducing its morbidity and mortality.