Successful haemofiltration therapy in severe phenobarbital overdose

In the 19th century, barbiturates were first-line treatment as hypnotic and anticonvulsants, then gradually replaced by agents with a safer clinical profile. However, its ongoing use in Australian veterinary medicine and steadfast prescriptions in developing countries/our migrant population, still contributes to overdoses.We present a case of a middle-aged man with a life-threatening phenobarbital overdose. Haemofiltration was trialled, causing a rapid fall in phenobarbital levels and a speedy recovery. Through a review of the literature, treatment options of barbiturate overdose presentations will be discussed. It is imperative clinicians are aware of barbiturate’s mechanism and its enhanced elimination through extracorporeal treatment

Medical Emergency Team syndromes and an approach to their management

INTRODUCTION: Most literature on the medical emergency team (MET) relates to its effects on patient outcome. Less information exists on the most common causes of MET calls or on possible approaches to their management. METHODS: We reviewed the calling criteria and clinical causes of 400 MET calls in a teaching hospital. We propose a set of minimum standards for managing a MET review and developed an approach for managing common problems encountered during MET calls. RESULTS: The underlying reasons for initiating MET calls were hypoxia (41%), hypotension (28%), altered conscious state (23%), tachycardia (19%), increased respiratory rate (14%) and oliguria (8%). Infection, pulmonary oedema, and arrhythmias featured as prominent causes of all triggers for MET calls. The proposed minimum requirements for managing a MET review included determining the cause of the deterioration, documenting the events surrounding the MET, establishing a medical plan and ongoing medical follow-up, and discussing the case with the intensivist if certain criteria were fulfilled. A systematic approach to managing episodes of MET review was developed based on the acronym 'A to G': ask and assess; begin basic investigations and resuscitation, call for help if needed, discuss, decide, and document, explain aetiology and management, follow-up, and graciously thank staff. This approach was then adapted to provide a management plan for episodes of tachycardia, hypotension, hypoxia and dyspnoea, reduced urinary output, and altered conscious state. CONCLUSION: A suggested approach permits audit and standardization of the management of MET calls and provides an educational framework for the management of acutely unwell ward patients. Further evaluation and validation of the approach are required

Admissions of Children and Adolescents With Deliberate Self-harm to Intensive Care During the SARS-CoV-2 Outbreak in Australia

Importance: Identification of potential indirect outcomes associated with the COVID-19 pandemic in the pediatric population may be essential for understanding the challenges of the current global public health crisis for children and adolescents. Objective: To investigate whether the SARS-CoV-2 outbreak and subsequent effective public health measures in Australia were associated with an increase in admissions to intensive care units (ICUs) of children and adolescents with deliberate self-harm (DSH). Design, setting, and participants: This national, multicenter cohort study was conducted using the Australian data subset of the binational Australian and New Zealand Paediatric Intensive Care registry, a collaborative containing more than 200 000 medical records with continuous contributions from all 8 Australian specialist, university-affiliated pediatric ICUs, along with 1 combined neonatal-pediatric ICU and 14 general (adult) ICUs in Australia. The study period encompassed 6.5 years from January 1, 2015, to June 30, 2021. Patients aged 12 to 17 years were included. Data were analyzed from December 2021 through February 2022. Exposures: Any of the following admission diagnoses: ingestion of a drug, ingestion of a nondrug, hanging or strangulation, or self-injury. Main outcomes and measures: The primary outcome measure was the temporal trend for national incidence of DSH ICU admissions per 1 million children and adolescents aged 12 to 17 years in Australia. Results: A total of 813 children and adolescents aged 12 to 17 years admitted to ICUs with DSH were identified among 64 145 patients aged 0 to 17 years in the Australian subset of the registry during the study period. Median (IQR) age was 15.1 (14.3-15.8) years; there were 550 (67.7%) female patients, 261 (32.2%) male patients, and 2 (0.2%) patients with indeterminate sex. At the onset of the pandemic, monthly incidence of DSH ICU admissions per million children and adolescents increased from 7.2 admissions in March 2020 to a peak of 11.4 admissions by August 2020, constituting a significant break in the temporal trend (odds ratio of DSH ICU admissions on or after vs before March 2020, 4.84; 95% CI, 1.09 to 21.53; P = .04). This occurred while the rate of all-cause admissions to pediatric ICUs of children and adolescents of all ages (ie, ages 0-17 years) per 1 million children and adolescents decreased from a long-term monthly median (IQR) of 150.9 (138.1-159.8) admissions to 91.7 admissions in April 2020. Conclusions and relevance: This cohort study found that the coronavirus pandemic in Australia was associated with a significant increase in admissions of children and adolescents to intensive care with DSH

Small scale Direct Potable Reuse (DPR) project for a remote area

An Advanced Water Treatment Plant (AWTP) for potable water recycling in Davis Station Antarctica was trialed using secondary effluent at Selfs Point in Hobart, Tasmania, for nine months. The trials demonstrated the reliability of performance of a seven barrier treatment process consisting of ozonation, ceramic microfiltration (MF), biologically activated carbon, reverse osmosis, ultra-violet disinfection, calcite contactor and chlorination. The seven treatment barriers were required to meet the high log removal values (LRV) required for pathogens in small systems during disease outbreak, and on-line verification of process performance was required for operation with infrequent operator attention. On-line verification of pathogen LRVs, a low turbidity filtrate of approximately 0.1 NTU (Nephelometric Turbidity Unit), no long-term fouling and no requirement for clean-in-place (CIP) was achieved with the ceramic MF. A pressure decay test was also reliably implemented on the reverse osmosis system to achieve a 2 LRV for protozoa, and this barrier required only 2-3 CIP treatments each year. The ozonation process achieved 2 LRV for bacteria and virus with no requirement for an ozone residual, provided the ozone dose was > 11.7 mg/L. Extensive screening using multi-residue gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) database methods that can screen for more than 1200 chemicals found that few chemicals pass through the barriers to the final product and rejected (discharge) water streams. The AWTP plant required 1.93 kWh/m3 when operated in the mode required for Davis Station and was predicted to require 1.27 kWh/m3 if scaled up to 10 ML/day. The AWTP will be shipped to Davis Station for further trials before possible implementation for water recycling. The process may have application in other small remote communities

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research